Diabetes Hub

 

Areas with a high density of fast food outlets are associated with a greater prevalence of type 1 diabetes but not type 2 diabetes, according to new research.

These findings come from an analysis of emergency claims data for 5 million adults and 1.6 million children in New York who visited an emergency department at least once during 2009-2013. Researchers also looked at sociodemographic data for the area from community surveys and used local authorities’ inspection data to characterize local restaurant and retail food environments.

Annbozhko/iStock/Getty Images

The unadjusted analysis suggested a higher prevalence of all types of diabetes in so-called “fast food swamps” – areas with a high prevalence of fast food restaurants.

But when the analysis was adjusted to account for a range of factors, including age, sex, ethnicity, household income, and employment rates, the association between fast food swamps and diabetes was significant for pediatric type 1 diabetes only.

“Given the rising prevalence of type 1 diabetes, there has been increasing belief that certain environmental influences are contributing sharply to these increases,” wrote David C. Lee, MD, New York University Langone Health, and his coauthors. “There is some emerging literature which suggests that pregnant women in adverse food environments may have a higher likelihood of gestational diabetes, which some believe may affect health outcomes in their offspring.”

The study also failed to find an influence of retail food swamps – areas with more bodegas or small convenience stores within a 1-mile radius – on the prevalence of either type 1 or type 2 diabetes, in either adults or children. When researchers extended this to a 2-mile radius, they did find a significantly higher prevalence of pediatric type 1 diabetes associated with retail food swamps but a significantly lower prevalence of adult type 1 diabetes.

“This result may suggest that the retail food environment does not have a strong association with local diabetes prevalence or may be due to how we measured the retail food environment,” they wrote.

 

In general, the study found that the prevalence of adult and pediatric type 1 diabetes was significantly lower in most black neighborhoods, while the prevalence of adult type 1 diabetes was significantly lower in most Hispanic neighborhoods. Higher-income neighborhoods showed a significantly higher prevalence of pediatric type 1 diabetes.

The prevalence of type 2 diabetes in adults was significantly higher in low-income neighborhoods and those with more elderly residents, while the highest rates of pediatric type 2 diabetes were found in black neighborhoods.

The authors commented that they were surprised that their data did not show a higher prevalence of adult type 2 diabetes in black neighborhoods.

“In our multivariate analysis, older age and lower income were the only demographic or socioeconomic factors associated with higher adult type 2 diabetes prevalence,” they wrote.

 

Their use of ED surveillance data may have skewed the findings toward individuals more likely to visit those departments, namely Medicaid patients. But they suggested this would be balanced by the fact that the analysis was based on small geographic areas.

“Overall, our results may suggest that the physical food environment may not play as strong a role in characterizing the risk of type 2 diabetes among children and that other factors such as genetics, health behaviors, environmental exposures, or family influences may play more important roles.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation. No conflicts of interest were declared.

SOURCE: Lee DC et al. J Endocr Soc. 2018. Apr 17. doi: 10.1210/js.2018-00001.

 

Areas with a high density of fast food outlets are associated with a greater prevalence of type 1 diabetes but not type 2 diabetes, according to new research.

These findings come from an analysis of emergency claims data for 5 million adults and 1.6 million children in New York who visited an emergency department at least once during 2009-2013. Researchers also looked at sociodemographic data for the area from community surveys and used local authorities’ inspection data to characterize local restaurant and retail food environments.

Annbozhko/iStock/Getty Images

The unadjusted analysis suggested a higher prevalence of all types of diabetes in so-called “fast food swamps” – areas with a high prevalence of fast food restaurants.

But when the analysis was adjusted to account for a range of factors, including age, sex, ethnicity, household income, and employment rates, the association between fast food swamps and diabetes was significant for pediatric type 1 diabetes only.

“Given the rising prevalence of type 1 diabetes, there has been increasing belief that certain environmental influences are contributing sharply to these increases,” wrote David C. Lee, MD, New York University Langone Health, and his coauthors. “There is some emerging literature which suggests that pregnant women in adverse food environments may have a higher likelihood of gestational diabetes, which some believe may affect health outcomes in their offspring.”

The study also failed to find an influence of retail food swamps – areas with more bodegas or small convenience stores within a 1-mile radius – on the prevalence of either type 1 or type 2 diabetes, in either adults or children. When researchers extended this to a 2-mile radius, they did find a significantly higher prevalence of pediatric type 1 diabetes associated with retail food swamps but a significantly lower prevalence of adult type 1 diabetes.

“This result may suggest that the retail food environment does not have a strong association with local diabetes prevalence or may be due to how we measured the retail food environment,” they wrote.

 

In general, the study found that the prevalence of adult and pediatric type 1 diabetes was significantly lower in most black neighborhoods, while the prevalence of adult type 1 diabetes was significantly lower in most Hispanic neighborhoods. Higher-income neighborhoods showed a significantly higher prevalence of pediatric type 1 diabetes.

The prevalence of type 2 diabetes in adults was significantly higher in low-income neighborhoods and those with more elderly residents, while the highest rates of pediatric type 2 diabetes were found in black neighborhoods.

The authors commented that they were surprised that their data did not show a higher prevalence of adult type 2 diabetes in black neighborhoods.

“In our multivariate analysis, older age and lower income were the only demographic or socioeconomic factors associated with higher adult type 2 diabetes prevalence,” they wrote.

 

Their use of ED surveillance data may have skewed the findings toward individuals more likely to visit those departments, namely Medicaid patients. But they suggested this would be balanced by the fact that the analysis was based on small geographic areas.

“Overall, our results may suggest that the physical food environment may not play as strong a role in characterizing the risk of type 2 diabetes among children and that other factors such as genetics, health behaviors, environmental exposures, or family influences may play more important roles.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation. No conflicts of interest were declared.

SOURCE: Lee DC et al. J Endocr Soc. 2018. Apr 17. doi: 10.1210/js.2018-00001.

 

Areas with a high density of fast food outlets are associated with a greater prevalence of type 1 diabetes but not type 2 diabetes, according to new research.

These findings come from an analysis of emergency claims data for 5 million adults and 1.6 million children in New York who visited an emergency department at least once during 2009-2013. Researchers also looked at sociodemographic data for the area from community surveys and used local authorities’ inspection data to characterize local restaurant and retail food environments.

Annbozhko/iStock/Getty Images

The unadjusted analysis suggested a higher prevalence of all types of diabetes in so-called “fast food swamps” – areas with a high prevalence of fast food restaurants.

But when the analysis was adjusted to account for a range of factors, including age, sex, ethnicity, household income, and employment rates, the association between fast food swamps and diabetes was significant for pediatric type 1 diabetes only.

“Given the rising prevalence of type 1 diabetes, there has been increasing belief that certain environmental influences are contributing sharply to these increases,” wrote David C. Lee, MD, New York University Langone Health, and his coauthors. “There is some emerging literature which suggests that pregnant women in adverse food environments may have a higher likelihood of gestational diabetes, which some believe may affect health outcomes in their offspring.”

The study also failed to find an influence of retail food swamps – areas with more bodegas or small convenience stores within a 1-mile radius – on the prevalence of either type 1 or type 2 diabetes, in either adults or children. When researchers extended this to a 2-mile radius, they did find a significantly higher prevalence of pediatric type 1 diabetes associated with retail food swamps but a significantly lower prevalence of adult type 1 diabetes.

“This result may suggest that the retail food environment does not have a strong association with local diabetes prevalence or may be due to how we measured the retail food environment,” they wrote.

 

In general, the study found that the prevalence of adult and pediatric type 1 diabetes was significantly lower in most black neighborhoods, while the prevalence of adult type 1 diabetes was significantly lower in most Hispanic neighborhoods. Higher-income neighborhoods showed a significantly higher prevalence of pediatric type 1 diabetes.

The prevalence of type 2 diabetes in adults was significantly higher in low-income neighborhoods and those with more elderly residents, while the highest rates of pediatric type 2 diabetes were found in black neighborhoods.

The authors commented that they were surprised that their data did not show a higher prevalence of adult type 2 diabetes in black neighborhoods.

“In our multivariate analysis, older age and lower income were the only demographic or socioeconomic factors associated with higher adult type 2 diabetes prevalence,” they wrote.

 

Their use of ED surveillance data may have skewed the findings toward individuals more likely to visit those departments, namely Medicaid patients. But they suggested this would be balanced by the fact that the analysis was based on small geographic areas.

“Overall, our results may suggest that the physical food environment may not play as strong a role in characterizing the risk of type 2 diabetes among children and that other factors such as genetics, health behaviors, environmental exposures, or family influences may play more important roles.”

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and the Juvenile Diabetes Research Foundation. No conflicts of interest were declared.

SOURCE: Lee DC et al. J Endocr Soc. 2018. Apr 17. doi: 10.1210/js.2018-00001.

 

Three vibration-based detection tools vary widely in their sensitivity for detection of diabetic peripheral neuropathy. Researchers are suggesting that physicians use more than a single vibration-based device when they check the sensitivity of their diabetic patients’ feet.

“This would significantly reduce the proportion of patients with diabetes who would be falsely identified as having no peripheral neuropathy and subsequently denied the benefit of beneficial and effective secondary risk factor control,” said study coauthor Cynthia Formosa, PhD, of the University of Malta, Msida, and Staffordshire University, Stoke-on-Trent, England, in an interview.

Researchers have estimated that 50% of patients with diabetes develop diabetic polyneuropathy over their lives, and that the condition is responsible for more than a quarter of all diabetes spending. “Despite a long history of research in this area, we are only starting to understand the pathophysiology of the disease,” reports a 2016 review of recent findings.

In a previous report, several of the authors of the new study analyzed 10 sets of guidelines regarding diabetic foot and found that some lacked information to back up the recommendations. Guideline limitations “are responsible for the current gaps between guidelines, standard clinical practice, and development of complications,” the researchers wrote (Rev Diabet Stud. 2016, 13[2-3]:158-86).

Most of the guidelines recommended the use of a 10-g monofilament test, in which a monofilament is placed against the skin, plus a vibration-based test, the researchers reported.

For the new study in Primary Care Diabetes, the researchers examined the efficacy of three noninvasive tools that are used to detect neuropathy in the foot: the 128-Hz tuning fork; the VibraTip, a pocket-sized, motorized device; and the neurothesiometer, a 7-pound electromechanical device that comes in a carrying case and includes an attachment that delivers vibrations to the body.

According to Dr. Formosa, the tuning fork is the most commonly used testing device in normal clinical practice.

 

Physicians such as endocrinologists and podiatrists use the vibrations produced by the devices to detect whether patients have normal levels of sensation in various parts of the foot and ankle. “Vibration testing is extremely important,” the study investigators wrote, “since in the initial stages of neuropathy, the vibratory sensory system is amongst the first component of the nervous system to be affected.”

However, research into the accuracy of the devices has been inconsistent, according to the investigators.

The researchers prospectively recruited 100 patients at primary health centers diagnosed with type 2 diabetes for at least 10 years. The subjects included 57 males and 43 females, with a mean age of 73 years (± 7.8 years). Practitioners tested the neuropathy detection tools on the patients and recorded whether they felt vibrations.

The study authors reported that 29% of patients didn’t perceive vibrations produced by the VibraTip, compared with 21% for the neurothesiometer and 12% for the 128-Hz tuning fork (P less than .001).

 

The VibraTip device is available for about $90 on Amazon. The cost of a neurothesiometer is listed by one medical supply company as $2,850. Prices for 128-Hz tuning forks vary on Amazon, with prices listed from $6 to $40.

The study researchers did not confirm neuropathy via more sophisticated neurologic testing, so it remains unclear which device is actually the most accurate at detecting cases of neuropathy.

Still, “the findings of this study suggest that use of only one screening tool to assess vibration perception is likely to yield high false negative results,” the researchers wrote. “We recommend that peripheral neuropathy in patients with diabetes should be assessed utilizing two or more modalities.”

If results don’t concur, neurologic testing may be appropriate, study senior author Nachiappan Chockalingam, PhD, also of the University of Malta and Staffordshire University, said in an interview.

Moving forward, Dr. Chockalingam said, the research team plans to launch “a structured clinical trial using a gold-standard tool such as nerve conduction testing to confirm which simple screening method best detects neuropathy.”

No study funding was reported. The authors reported no relevant disclosures.
 

SOURCE: Azzopardia K et al. Prim Care Diabetes. 2018 Apr;12(2):111-5.

 

Three vibration-based detection tools vary widely in their sensitivity for detection of diabetic peripheral neuropathy. Researchers are suggesting that physicians use more than a single vibration-based device when they check the sensitivity of their diabetic patients’ feet.

“This would significantly reduce the proportion of patients with diabetes who would be falsely identified as having no peripheral neuropathy and subsequently denied the benefit of beneficial and effective secondary risk factor control,” said study coauthor Cynthia Formosa, PhD, of the University of Malta, Msida, and Staffordshire University, Stoke-on-Trent, England, in an interview.

Researchers have estimated that 50% of patients with diabetes develop diabetic polyneuropathy over their lives, and that the condition is responsible for more than a quarter of all diabetes spending. “Despite a long history of research in this area, we are only starting to understand the pathophysiology of the disease,” reports a 2016 review of recent findings.

In a previous report, several of the authors of the new study analyzed 10 sets of guidelines regarding diabetic foot and found that some lacked information to back up the recommendations. Guideline limitations “are responsible for the current gaps between guidelines, standard clinical practice, and development of complications,” the researchers wrote (Rev Diabet Stud. 2016, 13[2-3]:158-86).

Most of the guidelines recommended the use of a 10-g monofilament test, in which a monofilament is placed against the skin, plus a vibration-based test, the researchers reported.

For the new study in Primary Care Diabetes, the researchers examined the efficacy of three noninvasive tools that are used to detect neuropathy in the foot: the 128-Hz tuning fork; the VibraTip, a pocket-sized, motorized device; and the neurothesiometer, a 7-pound electromechanical device that comes in a carrying case and includes an attachment that delivers vibrations to the body.

According to Dr. Formosa, the tuning fork is the most commonly used testing device in normal clinical practice.

 

Physicians such as endocrinologists and podiatrists use the vibrations produced by the devices to detect whether patients have normal levels of sensation in various parts of the foot and ankle. “Vibration testing is extremely important,” the study investigators wrote, “since in the initial stages of neuropathy, the vibratory sensory system is amongst the first component of the nervous system to be affected.”

However, research into the accuracy of the devices has been inconsistent, according to the investigators.

The researchers prospectively recruited 100 patients at primary health centers diagnosed with type 2 diabetes for at least 10 years. The subjects included 57 males and 43 females, with a mean age of 73 years (± 7.8 years). Practitioners tested the neuropathy detection tools on the patients and recorded whether they felt vibrations.

The study authors reported that 29% of patients didn’t perceive vibrations produced by the VibraTip, compared with 21% for the neurothesiometer and 12% for the 128-Hz tuning fork (P less than .001).

 

The VibraTip device is available for about $90 on Amazon. The cost of a neurothesiometer is listed by one medical supply company as $2,850. Prices for 128-Hz tuning forks vary on Amazon, with prices listed from $6 to $40.

The study researchers did not confirm neuropathy via more sophisticated neurologic testing, so it remains unclear which device is actually the most accurate at detecting cases of neuropathy.

Still, “the findings of this study suggest that use of only one screening tool to assess vibration perception is likely to yield high false negative results,” the researchers wrote. “We recommend that peripheral neuropathy in patients with diabetes should be assessed utilizing two or more modalities.”

If results don’t concur, neurologic testing may be appropriate, study senior author Nachiappan Chockalingam, PhD, also of the University of Malta and Staffordshire University, said in an interview.

Moving forward, Dr. Chockalingam said, the research team plans to launch “a structured clinical trial using a gold-standard tool such as nerve conduction testing to confirm which simple screening method best detects neuropathy.”

No study funding was reported. The authors reported no relevant disclosures.
 

SOURCE: Azzopardia K et al. Prim Care Diabetes. 2018 Apr;12(2):111-5.

 

Three vibration-based detection tools vary widely in their sensitivity for detection of diabetic peripheral neuropathy. Researchers are suggesting that physicians use more than a single vibration-based device when they check the sensitivity of their diabetic patients’ feet.

“This would significantly reduce the proportion of patients with diabetes who would be falsely identified as having no peripheral neuropathy and subsequently denied the benefit of beneficial and effective secondary risk factor control,” said study coauthor Cynthia Formosa, PhD, of the University of Malta, Msida, and Staffordshire University, Stoke-on-Trent, England, in an interview.

Researchers have estimated that 50% of patients with diabetes develop diabetic polyneuropathy over their lives, and that the condition is responsible for more than a quarter of all diabetes spending. “Despite a long history of research in this area, we are only starting to understand the pathophysiology of the disease,” reports a 2016 review of recent findings.

In a previous report, several of the authors of the new study analyzed 10 sets of guidelines regarding diabetic foot and found that some lacked information to back up the recommendations. Guideline limitations “are responsible for the current gaps between guidelines, standard clinical practice, and development of complications,” the researchers wrote (Rev Diabet Stud. 2016, 13[2-3]:158-86).

Most of the guidelines recommended the use of a 10-g monofilament test, in which a monofilament is placed against the skin, plus a vibration-based test, the researchers reported.

For the new study in Primary Care Diabetes, the researchers examined the efficacy of three noninvasive tools that are used to detect neuropathy in the foot: the 128-Hz tuning fork; the VibraTip, a pocket-sized, motorized device; and the neurothesiometer, a 7-pound electromechanical device that comes in a carrying case and includes an attachment that delivers vibrations to the body.

According to Dr. Formosa, the tuning fork is the most commonly used testing device in normal clinical practice.

 

Physicians such as endocrinologists and podiatrists use the vibrations produced by the devices to detect whether patients have normal levels of sensation in various parts of the foot and ankle. “Vibration testing is extremely important,” the study investigators wrote, “since in the initial stages of neuropathy, the vibratory sensory system is amongst the first component of the nervous system to be affected.”

However, research into the accuracy of the devices has been inconsistent, according to the investigators.

The researchers prospectively recruited 100 patients at primary health centers diagnosed with type 2 diabetes for at least 10 years. The subjects included 57 males and 43 females, with a mean age of 73 years (± 7.8 years). Practitioners tested the neuropathy detection tools on the patients and recorded whether they felt vibrations.

The study authors reported that 29% of patients didn’t perceive vibrations produced by the VibraTip, compared with 21% for the neurothesiometer and 12% for the 128-Hz tuning fork (P less than .001).

 

The VibraTip device is available for about $90 on Amazon. The cost of a neurothesiometer is listed by one medical supply company as $2,850. Prices for 128-Hz tuning forks vary on Amazon, with prices listed from $6 to $40.

The study researchers did not confirm neuropathy via more sophisticated neurologic testing, so it remains unclear which device is actually the most accurate at detecting cases of neuropathy.

Still, “the findings of this study suggest that use of only one screening tool to assess vibration perception is likely to yield high false negative results,” the researchers wrote. “We recommend that peripheral neuropathy in patients with diabetes should be assessed utilizing two or more modalities.”

If results don’t concur, neurologic testing may be appropriate, study senior author Nachiappan Chockalingam, PhD, also of the University of Malta and Staffordshire University, said in an interview.

Moving forward, Dr. Chockalingam said, the research team plans to launch “a structured clinical trial using a gold-standard tool such as nerve conduction testing to confirm which simple screening method best detects neuropathy.”

No study funding was reported. The authors reported no relevant disclosures.
 

SOURCE: Azzopardia K et al. Prim Care Diabetes. 2018 Apr;12(2):111-5.

 

The total direct and indirect costs of diabetes jumped over 25% from 2012 to 2017, which was enough to make it “the most costly chronic illness in the country,” the American Diabetes Association said.

The estimated total economic burden of diabetes went from an inflation-adjusted estimate of $261 billion in 2012 to $327 billion – $237 billion in direct medical costs and $90 billion in indirect costs such as absenteeism, reduced productivity, and premature mortality – in 2017, according to a new report from the ADA published in Diabetes Care.

The $237 billion in direct medical costs attributed to diabetes in 2017 included $34.6 billion for insulin and other mediations and supplies to directly treat diabetes, $71.2 billion for other prescription medications, $69.7 billion for inpatient care, and $30 billion for physician office visits. The total medical cost incurred by the 24.7 million Americans with diabetes was $414 billion, the ADA reported.

“One of every four health care dollars is incurred by someone with diagnosed diabetes, and one of every seven health care dollars is spent directly treating diabetes and its complications,” the ADA said in a written statement.

The study used data from a large number of sources, including the American Community Survey, the OptumInsight de-identified Normative Health Information database, the Medical Expenditure Panel Survey, and the Medicare 5% sample Standard Analytical Files. All cost estimates were extrapolated to the 2017 U.S. population and adjusted to 2017 dollars.

[email protected]

SOURCE: Diabetes Care. 2018 Mar 22. doi: 10.2337/dci18-0007.

 

The total direct and indirect costs of diabetes jumped over 25% from 2012 to 2017, which was enough to make it “the most costly chronic illness in the country,” the American Diabetes Association said.

The estimated total economic burden of diabetes went from an inflation-adjusted estimate of $261 billion in 2012 to $327 billion – $237 billion in direct medical costs and $90 billion in indirect costs such as absenteeism, reduced productivity, and premature mortality – in 2017, according to a new report from the ADA published in Diabetes Care.

The $237 billion in direct medical costs attributed to diabetes in 2017 included $34.6 billion for insulin and other mediations and supplies to directly treat diabetes, $71.2 billion for other prescription medications, $69.7 billion for inpatient care, and $30 billion for physician office visits. The total medical cost incurred by the 24.7 million Americans with diabetes was $414 billion, the ADA reported.

“One of every four health care dollars is incurred by someone with diagnosed diabetes, and one of every seven health care dollars is spent directly treating diabetes and its complications,” the ADA said in a written statement.

The study used data from a large number of sources, including the American Community Survey, the OptumInsight de-identified Normative Health Information database, the Medical Expenditure Panel Survey, and the Medicare 5% sample Standard Analytical Files. All cost estimates were extrapolated to the 2017 U.S. population and adjusted to 2017 dollars.

[email protected]

SOURCE: Diabetes Care. 2018 Mar 22. doi: 10.2337/dci18-0007.

 

The total direct and indirect costs of diabetes jumped over 25% from 2012 to 2017, which was enough to make it “the most costly chronic illness in the country,” the American Diabetes Association said.

The estimated total economic burden of diabetes went from an inflation-adjusted estimate of $261 billion in 2012 to $327 billion – $237 billion in direct medical costs and $90 billion in indirect costs such as absenteeism, reduced productivity, and premature mortality – in 2017, according to a new report from the ADA published in Diabetes Care.

The $237 billion in direct medical costs attributed to diabetes in 2017 included $34.6 billion for insulin and other mediations and supplies to directly treat diabetes, $71.2 billion for other prescription medications, $69.7 billion for inpatient care, and $30 billion for physician office visits. The total medical cost incurred by the 24.7 million Americans with diabetes was $414 billion, the ADA reported.

“One of every four health care dollars is incurred by someone with diagnosed diabetes, and one of every seven health care dollars is spent directly treating diabetes and its complications,” the ADA said in a written statement.

The study used data from a large number of sources, including the American Community Survey, the OptumInsight de-identified Normative Health Information database, the Medical Expenditure Panel Survey, and the Medicare 5% sample Standard Analytical Files. All cost estimates were extrapolated to the 2017 U.S. population and adjusted to 2017 dollars.

[email protected]

SOURCE: Diabetes Care. 2018 Mar 22. doi: 10.2337/dci18-0007.

 

Physicians should aim for hemoglobin A_1c levels between 7% and 8% in patients with type 2 diabetes, according to recommendations by the American College of Physicians.

But the guidance drew strong condemnation from diabetes and endocrinology organizations, which warned the higher target range could do more harm than good.

Evidence presented in the ACP statement shows the intensive therapy commonly used to reach the previous target of 6.5%-7% is likely either to increase risk of adverse cardiovascular and hypoglycemic events or have the same risk as less intensive therapy.

“Treatment with drugs targeted to 7%, in contrast to 8%, does not prevent heart attacks or strokes,” said Jack Ende, MD, president of the ACP. “But it does result in substantial harm, including low blood sugar, increased medication burden, and increased cost.”

The ACP recommends clinicians should talk with patients about creating personalized treatment plans based on the risks and benefits of different drugs, what the patients prefers, life expectancy, and cost of care.

 

Previous guidelines on reaching HbA_1c had been developed to reduce micro- and macrovascular complications; however, evidence that lowering levels also would lower events was not substantial enough to prove correct, as results were limited to reductions in less serious complications, according to Dr. Ende.

Physicians whose patients have HbA_1c levels less than 6.5% are advised to deintensify patients’ pharmacologic therapy by reducing the dosage, or taking a medication out completely.

New guidelines were based on evaluation of four drug-therapy trials, which encompassed long- and short-term effects of intensive pharmacological therapy compared with more moderate treatment.

 

In the Veterans Affairs Diabetes Trial, patients given intensive treatment found no reduction in major cardiovascular, microvascular events, or death in a 5.6-year follow-up. The intensive group did show fewer cardiovascular events after a longer period of time – 12 years – but this difference was small (8.6 events per 1,000 patient-years), according to the investigators.

Because of these long-term improvements, which were found across almost all studies evaluated, the ACP also recommends treatment of symptoms related to hyperglycemia instead of HbA_1c for patients with lower life expectancy, including those older than 80 years, those in nursing homes, and those with chronic conditions such as cancer or dementia.

“Setting stringent targets in these populations is not an optimal approach, and clinicians should instead focus on treating to reduce symptoms from both disease and treatment,” wrote Amir Qaseem, MD, PhD, vice president, Clinical Policy and Center for Evidence Reviews, ACP, and fellow investigators. “The ACP guidance statement in persons with a life expectancy less than 10 years is based on the small death or cardiovascular benefit of lower HbA_1c targets through at least 10 years, which should be balanced with treatment harms.”

The policy implications of these recommendations address physician performance evaluations, which the ACP recommends should not have a target HbA_1c level below 8%, nor any target level for patients with limited life expectancies.

But many diabetes organizations aren't embracing the new target levels. 

The ACP's recommendations could keep many diabetes patients from achieving all the benefits from long-term intensive glucose control, warned the Endocrine Society, the American Diabetes Association, the American Association for Clinical Endocrinologists, and the American Association of Diabetes Educators in a joint statement. And the ACP's recommendations overlook the positive impact that newer diabetes drugs have shown on morbidity and mortality in high-risk type 2 diabetes patients.

 

Coauthor Michael J. Barry, MD, reported receiving grants from the nonprofit Healthwise, outside of this statement.

All other authors reported no relevant financial disclosures.

[email protected]

 

Physicians should aim for hemoglobin A_1c levels between 7% and 8% in patients with type 2 diabetes, according to recommendations by the American College of Physicians.

But the guidance drew strong condemnation from diabetes and endocrinology organizations, which warned the higher target range could do more harm than good.

Evidence presented in the ACP statement shows the intensive therapy commonly used to reach the previous target of 6.5%-7% is likely either to increase risk of adverse cardiovascular and hypoglycemic events or have the same risk as less intensive therapy.

“Treatment with drugs targeted to 7%, in contrast to 8%, does not prevent heart attacks or strokes,” said Jack Ende, MD, president of the ACP. “But it does result in substantial harm, including low blood sugar, increased medication burden, and increased cost.”

The ACP recommends clinicians should talk with patients about creating personalized treatment plans based on the risks and benefits of different drugs, what the patients prefers, life expectancy, and cost of care.

 

Previous guidelines on reaching HbA_1c had been developed to reduce micro- and macrovascular complications; however, evidence that lowering levels also would lower events was not substantial enough to prove correct, as results were limited to reductions in less serious complications, according to Dr. Ende.

Physicians whose patients have HbA_1c levels less than 6.5% are advised to deintensify patients’ pharmacologic therapy by reducing the dosage, or taking a medication out completely.

New guidelines were based on evaluation of four drug-therapy trials, which encompassed long- and short-term effects of intensive pharmacological therapy compared with more moderate treatment.

 

In the Veterans Affairs Diabetes Trial, patients given intensive treatment found no reduction in major cardiovascular, microvascular events, or death in a 5.6-year follow-up. The intensive group did show fewer cardiovascular events after a longer period of time – 12 years – but this difference was small (8.6 events per 1,000 patient-years), according to the investigators.

Because of these long-term improvements, which were found across almost all studies evaluated, the ACP also recommends treatment of symptoms related to hyperglycemia instead of HbA_1c for patients with lower life expectancy, including those older than 80 years, those in nursing homes, and those with chronic conditions such as cancer or dementia.

“Setting stringent targets in these populations is not an optimal approach, and clinicians should instead focus on treating to reduce symptoms from both disease and treatment,” wrote Amir Qaseem, MD, PhD, vice president, Clinical Policy and Center for Evidence Reviews, ACP, and fellow investigators. “The ACP guidance statement in persons with a life expectancy less than 10 years is based on the small death or cardiovascular benefit of lower HbA_1c targets through at least 10 years, which should be balanced with treatment harms.”

The policy implications of these recommendations address physician performance evaluations, which the ACP recommends should not have a target HbA_1c level below 8%, nor any target level for patients with limited life expectancies.

But many diabetes organizations aren't embracing the new target levels. 

The ACP's recommendations could keep many diabetes patients from achieving all the benefits from long-term intensive glucose control, warned the Endocrine Society, the American Diabetes Association, the American Association for Clinical Endocrinologists, and the American Association of Diabetes Educators in a joint statement. And the ACP's recommendations overlook the positive impact that newer diabetes drugs have shown on morbidity and mortality in high-risk type 2 diabetes patients.

 

Coauthor Michael J. Barry, MD, reported receiving grants from the nonprofit Healthwise, outside of this statement.

All other authors reported no relevant financial disclosures.

[email protected]

 

Physicians should aim for hemoglobin A_1c levels between 7% and 8% in patients with type 2 diabetes, according to recommendations by the American College of Physicians.

But the guidance drew strong condemnation from diabetes and endocrinology organizations, which warned the higher target range could do more harm than good.

Evidence presented in the ACP statement shows the intensive therapy commonly used to reach the previous target of 6.5%-7% is likely either to increase risk of adverse cardiovascular and hypoglycemic events or have the same risk as less intensive therapy.

“Treatment with drugs targeted to 7%, in contrast to 8%, does not prevent heart attacks or strokes,” said Jack Ende, MD, president of the ACP. “But it does result in substantial harm, including low blood sugar, increased medication burden, and increased cost.”

The ACP recommends clinicians should talk with patients about creating personalized treatment plans based on the risks and benefits of different drugs, what the patients prefers, life expectancy, and cost of care.

 

Previous guidelines on reaching HbA_1c had been developed to reduce micro- and macrovascular complications; however, evidence that lowering levels also would lower events was not substantial enough to prove correct, as results were limited to reductions in less serious complications, according to Dr. Ende.

Physicians whose patients have HbA_1c levels less than 6.5% are advised to deintensify patients’ pharmacologic therapy by reducing the dosage, or taking a medication out completely.

New guidelines were based on evaluation of four drug-therapy trials, which encompassed long- and short-term effects of intensive pharmacological therapy compared with more moderate treatment.

 

In the Veterans Affairs Diabetes Trial, patients given intensive treatment found no reduction in major cardiovascular, microvascular events, or death in a 5.6-year follow-up. The intensive group did show fewer cardiovascular events after a longer period of time – 12 years – but this difference was small (8.6 events per 1,000 patient-years), according to the investigators.

Because of these long-term improvements, which were found across almost all studies evaluated, the ACP also recommends treatment of symptoms related to hyperglycemia instead of HbA_1c for patients with lower life expectancy, including those older than 80 years, those in nursing homes, and those with chronic conditions such as cancer or dementia.

“Setting stringent targets in these populations is not an optimal approach, and clinicians should instead focus on treating to reduce symptoms from both disease and treatment,” wrote Amir Qaseem, MD, PhD, vice president, Clinical Policy and Center for Evidence Reviews, ACP, and fellow investigators. “The ACP guidance statement in persons with a life expectancy less than 10 years is based on the small death or cardiovascular benefit of lower HbA_1c targets through at least 10 years, which should be balanced with treatment harms.”

The policy implications of these recommendations address physician performance evaluations, which the ACP recommends should not have a target HbA_1c level below 8%, nor any target level for patients with limited life expectancies.

But many diabetes organizations aren't embracing the new target levels. 

The ACP's recommendations could keep many diabetes patients from achieving all the benefits from long-term intensive glucose control, warned the Endocrine Society, the American Diabetes Association, the American Association for Clinical Endocrinologists, and the American Association of Diabetes Educators in a joint statement. And the ACP's recommendations overlook the positive impact that newer diabetes drugs have shown on morbidity and mortality in high-risk type 2 diabetes patients.

 

Coauthor Michael J. Barry, MD, reported receiving grants from the nonprofit Healthwise, outside of this statement.

All other authors reported no relevant financial disclosures.

[email protected]

 

ANAHEIM, CALIF. – Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes mellitus in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.

The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A_1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.

Bruce Jancin/Frontline Medical News

In men with T2DM, there was no significant difference in rates of new-onset dementia between the low-dose aspirin and control groups.

JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.

 

In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.

During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.

JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).

Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.

 

She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.

Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”

There are quite a few Western large cohort studies examining the use of low-dose aspirin for prevention of cardiovascular events, and many of them also feature cognitive outcomes. It should be easy to find collaborators from those studies who could cull out the data on participants with type 2 diabetes in order to confirm the JPAD 2 findings, according to Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont in Burlington.

Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.

Dr. Matsumoto reported having no financial conflicts.

[email protected]

SOURCE: Matsumoto C. AHA scientific sessions.

 

ANAHEIM, CALIF. – Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes mellitus in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.

The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A_1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.

Bruce Jancin/Frontline Medical News

In men with T2DM, there was no significant difference in rates of new-onset dementia between the low-dose aspirin and control groups.

JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.

 

In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.

During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.

JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).

Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.

 

She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.

Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”

There are quite a few Western large cohort studies examining the use of low-dose aspirin for prevention of cardiovascular events, and many of them also feature cognitive outcomes. It should be easy to find collaborators from those studies who could cull out the data on participants with type 2 diabetes in order to confirm the JPAD 2 findings, according to Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont in Burlington.

Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.

Dr. Matsumoto reported having no financial conflicts.

[email protected]

SOURCE: Matsumoto C. AHA scientific sessions.

 

ANAHEIM, CALIF. – Daily low-dose aspirin reduced the incidence of dementia by more than one-third in patients with type 2 diabetes mellitus in the randomized JPAD 2 study, Chisa Matsumoto, MD, reported at the American Heart Association scientific sessions.

The benefit was restricted to women with T2DM. During a median 9.7 years of follow-up, the incidence of dementia, as defined by prescription of antidementia drugs or hospitalization for dementia, was 2.7 cases per 1,000 person-years in women randomized to low-dose aspirin and 6 per 1,000 person-years in those assigned to standard care. This translated to a 60% relative risk reduction in a multivariate analysis adjusted for age, hypertension, dyslipidemia, smoking, and hemoglobin A_1c level, according to Dr. Matsumoto of Hyogo (Japan) College of Medicine.

Bruce Jancin/Frontline Medical News

In men with T2DM, there was no significant difference in rates of new-onset dementia between the low-dose aspirin and control groups.

JPAD 2 was a multicenter prospective cohort study of 2,536 Japanese patients with T2DM who previously participated in the open-label randomized Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial, which ran from 2002 to 2008. Patients’ average age at baseline was 64 years; they had a 7-year duration of diabetes and no history of cardiovascular disease or dementia. When JPAD ended, patients continued on in JPAD 2, with follow-up through July 2015.

 

In the overall JPAD 2 population, the dementia incidence rate was 3.6 per 1,000 person-years in the low-dose aspirin group compared with 4.9 per 1,000 person-years in controls, for a highly significant 35% relative risk reduction in a fully adjusted multivariate intention to treat analysis.

During follow-up, 15% of patients switched from low-dose aspirin to no aspirin or vice versa, prompting Dr. Matsumoto and her coinvestigators to perform a per protocol analysis of the data. The results were essentially the same as in the intent-to-treat analysis.

JPAD 2 was the first-ever study to evaluate the long-term efficacy of low-dose aspirin for prevention of dementia specifically in patients with T2DM, a known risk factor for dementia. Other observational and randomized controlled studies have yielded inconsistent results. For example, a recent meta-analysis of five studies with a median 6-year follow-up found an 18% relative risk reduction in onset of dementia or cognitive impairment, a difference that didn’t achieve statistical significance (J Am Geriatr Soc. 2017 Aug;65[8]:1763-8).

Some prior studies have suggested there is a sex-based difference in the risk of dementia, which prompted Dr. Matsumoto and her coinvestigators to analyze the JPAD 2 results separately in men and women.

 

She was quick to acknowledge that the novel JPAD 2 findings cry out for replication in other studies with larger numbers and/or longer follow-up.

Session moderator Mary Cushman, MD, declared, “I think this is really exciting and interesting.”

There are quite a few Western large cohort studies examining the use of low-dose aspirin for prevention of cardiovascular events, and many of them also feature cognitive outcomes. It should be easy to find collaborators from those studies who could cull out the data on participants with type 2 diabetes in order to confirm the JPAD 2 findings, according to Dr. Cushman, professor of medicine and pathology and medical director of the thrombosis and hemostasis program at the University of Vermont in Burlington.

Asked to speculate on the mechanism for the divergent efficacy of low-dose aspirin in men and women with T2DM in JPAD 2, Dr. Matsumoto said play of chance may have had a partial role. The incidence of dementia was roughly 50% greater in the JPAD 2 women than in the men, so the study may have been underpowered to look at the dementia rate in men. But there may be a biologic mechanism at work, as well: Apolipoprotein E4, which is linked to increased risk of dementia, is believed to interact with gender, she said.

Dr. Matsumoto reported having no financial conflicts.

[email protected]

SOURCE: Matsumoto C. AHA scientific sessions.

 

Preoperative weight loss improves bariatric surgery outcomes, according to findings from a single-institution retrospective analysis. The weight loss came from following a 4-week low-calorie diet (LCD) and was of greatest benefit to patients who lost 8% or more of their excess weight. These patients had a greater loss of excess weight in the 12 months following surgery, as well as shorter average hospital length of stay.

Whitestorm/ThinkStock

The results appeared online in the Journal of the American College of Surgeons.

Preliminary studies indicated that short-term weight loss before surgery might reduce surgical complexity by reducing the size of the liver and intra-abdominal fat mass, but it remained uncertain what effect weight loss might have on long-term outcomes.

The LCD included 1,200 kcal/day (45% carbohydrates, 35% protein, 20% fat), which were consumed through five meal-replacement products and one food-based meal. Liquids included at least 80 ounces of calorie-free, caffeine-free, carbonation-free beverages per day. Patients were also instructed to conduct 30 minutes of moderate to vigorous activity per day.

Deborah A. Hutcheon, DCN, and her fellow researchers analyzed data from their own institution, where a presurgical 4-week LCD with a target loss of 8% or more of excess weight had been standard policy already. The population included 355 patients who underwent sleeve gastrectomy (n = 167) or Roux-en-Y gastric bypass (n = 188) between January 2014 and January 2016.

Almost two-thirds (63.3%) of patients achieved the target weight loss before surgery. There were some differences between the two groups. The group that achieved the target contained a greater proportion of men than did the other group (25.5% vs. 13.7%, respectively; P = .013), a higher proportion of white patients (84.8% vs. 74.1%; P = .011), and a higher proportion of patients taking antihypertensive medications (68.3% vs. 57.3%; P = .048). The two groups had similar rates of preoperative comorbidities and surgery types.

Those who achieved the target weight loss had a shorter hospital length of stay (1.8 days vs. 2.1 days; P = .006). They also had a higher percentage loss of excess weight at 3 months (42.3% vs. 36.1%; P less than .001), 6 months (56.0% vs. 47.5%; P less than .001), and at 12 months (65.1% vs. 55.7%; P = .003).

After controlling for patient characteristics, insurance status, 12-month diet compliance, and surgery type, successful presurgery weight loss was associated with greater weight loss at 12 months.

[email protected]

SOURCE: Hutcheon DA et al. J Am Coll Surgeons. 2018 Jan 31. doi: 10.1016/j.jamcollsurg.2017.12.032.

 

Preoperative weight loss improves bariatric surgery outcomes, according to findings from a single-institution retrospective analysis. The weight loss came from following a 4-week low-calorie diet (LCD) and was of greatest benefit to patients who lost 8% or more of their excess weight. These patients had a greater loss of excess weight in the 12 months following surgery, as well as shorter average hospital length of stay.

Whitestorm/ThinkStock

The results appeared online in the Journal of the American College of Surgeons.

Preliminary studies indicated that short-term weight loss before surgery might reduce surgical complexity by reducing the size of the liver and intra-abdominal fat mass, but it remained uncertain what effect weight loss might have on long-term outcomes.

The LCD included 1,200 kcal/day (45% carbohydrates, 35% protein, 20% fat), which were consumed through five meal-replacement products and one food-based meal. Liquids included at least 80 ounces of calorie-free, caffeine-free, carbonation-free beverages per day. Patients were also instructed to conduct 30 minutes of moderate to vigorous activity per day.

Deborah A. Hutcheon, DCN, and her fellow researchers analyzed data from their own institution, where a presurgical 4-week LCD with a target loss of 8% or more of excess weight had been standard policy already. The population included 355 patients who underwent sleeve gastrectomy (n = 167) or Roux-en-Y gastric bypass (n = 188) between January 2014 and January 2016.

Almost two-thirds (63.3%) of patients achieved the target weight loss before surgery. There were some differences between the two groups. The group that achieved the target contained a greater proportion of men than did the other group (25.5% vs. 13.7%, respectively; P = .013), a higher proportion of white patients (84.8% vs. 74.1%; P = .011), and a higher proportion of patients taking antihypertensive medications (68.3% vs. 57.3%; P = .048). The two groups had similar rates of preoperative comorbidities and surgery types.

Those who achieved the target weight loss had a shorter hospital length of stay (1.8 days vs. 2.1 days; P = .006). They also had a higher percentage loss of excess weight at 3 months (42.3% vs. 36.1%; P less than .001), 6 months (56.0% vs. 47.5%; P less than .001), and at 12 months (65.1% vs. 55.7%; P = .003).

After controlling for patient characteristics, insurance status, 12-month diet compliance, and surgery type, successful presurgery weight loss was associated with greater weight loss at 12 months.

[email protected]

SOURCE: Hutcheon DA et al. J Am Coll Surgeons. 2018 Jan 31. doi: 10.1016/j.jamcollsurg.2017.12.032.

 

Preoperative weight loss improves bariatric surgery outcomes, according to findings from a single-institution retrospective analysis. The weight loss came from following a 4-week low-calorie diet (LCD) and was of greatest benefit to patients who lost 8% or more of their excess weight. These patients had a greater loss of excess weight in the 12 months following surgery, as well as shorter average hospital length of stay.

Whitestorm/ThinkStock

The results appeared online in the Journal of the American College of Surgeons.

Preliminary studies indicated that short-term weight loss before surgery might reduce surgical complexity by reducing the size of the liver and intra-abdominal fat mass, but it remained uncertain what effect weight loss might have on long-term outcomes.

The LCD included 1,200 kcal/day (45% carbohydrates, 35% protein, 20% fat), which were consumed through five meal-replacement products and one food-based meal. Liquids included at least 80 ounces of calorie-free, caffeine-free, carbonation-free beverages per day. Patients were also instructed to conduct 30 minutes of moderate to vigorous activity per day.

Deborah A. Hutcheon, DCN, and her fellow researchers analyzed data from their own institution, where a presurgical 4-week LCD with a target loss of 8% or more of excess weight had been standard policy already. The population included 355 patients who underwent sleeve gastrectomy (n = 167) or Roux-en-Y gastric bypass (n = 188) between January 2014 and January 2016.

Almost two-thirds (63.3%) of patients achieved the target weight loss before surgery. There were some differences between the two groups. The group that achieved the target contained a greater proportion of men than did the other group (25.5% vs. 13.7%, respectively; P = .013), a higher proportion of white patients (84.8% vs. 74.1%; P = .011), and a higher proportion of patients taking antihypertensive medications (68.3% vs. 57.3%; P = .048). The two groups had similar rates of preoperative comorbidities and surgery types.

Those who achieved the target weight loss had a shorter hospital length of stay (1.8 days vs. 2.1 days; P = .006). They also had a higher percentage loss of excess weight at 3 months (42.3% vs. 36.1%; P less than .001), 6 months (56.0% vs. 47.5%; P less than .001), and at 12 months (65.1% vs. 55.7%; P = .003).

After controlling for patient characteristics, insurance status, 12-month diet compliance, and surgery type, successful presurgery weight loss was associated with greater weight loss at 12 months.

[email protected]

SOURCE: Hutcheon DA et al. J Am Coll Surgeons. 2018 Jan 31. doi: 10.1016/j.jamcollsurg.2017.12.032.

 

ANAHEIM, CALIF. – The first large randomized trial to report results on a sodium glucose cotransporter 2 inhibitor for primary prevention of cardiovascular events in patients with type 2 diabetes who are at risk for cardiovascular events or death failed to show a significant benefit in the CANVAS program, Kenneth W. Mahaffey, MD, said at the American Heart Association scientific sessions.

The impressive reductions in cardiovascular and renal events seen in the overall CANVAS (Canagliflozin Cardiovascular Assessment Study) program turned out to be focused in the two-thirds of participants with a prior cardiovascular event at enrollment, according to Dr. Mahaffey, a cardiologist who is professor and vice chair of the department of medicine at Stanford (Calif.) University.

Bruce Jancin/Frontline Medical News

The CANVAS program included 10,142 patients with type 2 diabetes randomized to canagliflozin (Invokana) or placebo and prospectively followed for a mean of 3.6 years. The 66% of subjects with a prior cardiovascular event comprised the secondary prevention cohort. The 34% of CANVAS program participants in the primary prevention cohort all had two or more cardiovascular risk factors at baseline.

The primary outcome has previously been reported: The canagliflozin group had a highly significant 14% reduction in the risk of the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (N Engl J Med. 2017 Aug 17;377[7]:644-57).

At the AHA scientific sessions, Dr. Mahaffey presented a prespecified subgroup analysis comparing the impact of SGLT2 inhibitor for primary versus secondary cardiovascular prevention. Canagliflozin proved to be a big win for secondary prevention: The composite primary endpoint was reduced by 18%, compared with placebo; the composite renal outcome of worsening estimated glomerular filtration rate (eGFR), renal replacement, or renal death was reduced by 41%; and heart failure hospitalizations were reduced by 32%.

All of those benefits were strongly statistically significant. They came at the cost of roughly a fourfold increase in readily treatable male and female genital infections – a known class effect of the SGLT2 inhibitors – as well as an unexpected twofold increase in lower extremity amputations, which fortunately were uncommon. Of the amputations, 29% were above the ankle; the other 71% were less drastic toe or transmetatarsal procedures.

Dr. Mahaffey estimated that for every 1,000 patients with type 2 diabetes who were taking canagliflozin for secondary cardiovascular prevention for 5 years, there would be 36 fewer cardiovascular deaths, nonfatal MIs, or nonfatal strokes; 20 fewer hospitalizations for heart failure; 21 fewer patients who experienced the composite renal outcome; and 21 additional patients with a lower extremity amputation.

Rates of cardiovascular and renal endpoints were at least twofold higher in the secondary prevention group than in the primary prevention cohort. For prevention, the size of the relative risk reductions in heart failure hospitalizations and renal outcomes with canagliflozin, compared with placebo, were similar to the secondary prevention experience. So was the magnitude of the increased risk of lower extremity amputation. However, none of these differences achieved statistical significance, perhaps because of the lower absolute event rates in the primary prevention group.

Moreover, there was no signal of benefit for canagliflozin in terms of the composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke in the primary prevention group; those event rates were virtually identical to those seen in the placebo-treated controls.

That being said, the CANVAS Program wasn’t designed with sufficient statistical power to draw definitive conclusions regarding outcome differences in the primary and secondary prevention groups, Dr. Mahaffey noted.
 

Putting the SGLT2 cardiovascular prevention results in perspective

Discussant Angelyn Bethel, MD, said the impressive outcomes for canagliflozin for secondary prevention in the CANVAS Program are consistent with the results of the earlier 7,020-patient EMPA-REG trial of the SGLT2 inhibitor empagliflozin (Jardiance) versus placebo for secondary prevention in type 2 diabetes (N Engl J Med. 2015 Nov 26;373[22]:2117-28). The relative risk reductions in the primary composite endpoint, as well as in heart failure hospitalizations and renal outcomes, were quite similar in the secondary prevention setting in the two large trials.

The one difference was in all-cause mortality: a striking 32% reduction with empagliflozin, compared with placebo, versus a more modest 11% relative risk reduction in the CANVAS program, which narrowly missed statistical significance.

The mechanisms for the important cardiovascular benefits seen in the secondary prevention setting in the two large SGLT2 trials are still under debate, according to Dr. Bethel, an endocrinologist who is deputy director of the diabetes trial unit at the University of Oxford (England).

“I think what’s obvious to most of us is that we’ve moved now beyond the conventional risk factors. These drugs cause only very small reductions in weight, systolic blood pressure, and diastolic blood pressure; they result in small increases in LDL and HDL; and the timeline of the impact that we see for the SGLT2 inhibitors on the cardiovascular outcomes in particular is much too short to be looking for glucose- or atherosclerotic-mediated processes,” she said.

“The mechanisms probably involve invoking the cardiorenal axis in some way,” Dr. Bethel speculated. “We know these drugs have a diuretic effect and we believe that some of the mortality benefit is probably mediated by heart failure outcomes, with changes in volume status. And there’s also a drive toward ketone metabolism, which is more efficient for the compromised heart.”

As for canagliflozin’s lack of significant benefit for primary prevention in the CANVAS program, it’s possible that this was a statistical power problem, Dr. Bethel said, but she has her doubts.

“If we had more people followed for longer in the primary prevention cohort, would we get there? I think it’s a big ask, but we do have more data coming,” she noted.

Indeed, two major phase 3 clinical trials of SGLT2 inhibitors for both primary and secondary cardiovascular prevention in mixed populations are due to report results in 2019: the roughly 4,500-patient CREDENCE trial of canagliflozin and the 17,0000-patient DECLARE trial, featuring dapagliflozin. Both involve about 5 years of follow-up.

Dr. Bethel advocated waiting until those studies report their primary prevention outcomes before introducing SGLT2-inhibitor therapy for primary cardiovascular prevention in clinical practice.

“In this instance, we do have some evidence that there may be a difference in the way that various events behave in the primary and secondary prevention settings, and we may have an overestimate of the benefits for primary prevention if we were to put this stuff in the water and give it to everybody,” she cautioned.

The CANVAS program analysis of primary versus secondary prevention has been published (Circulation. 2018 Jan 23;137[4]:323-34).

The CANVAS program was supported by Janssen. Dr. Mahaffey reported receiving research grants from and serving as a consultant to Janssen and numerous other companies.

 

[email protected]

SOURCE: Mahaffey KW et al. AHA Scientific Sessions.

 

ANAHEIM, CALIF. – The first large randomized trial to report results on a sodium glucose cotransporter 2 inhibitor for primary prevention of cardiovascular events in patients with type 2 diabetes who are at risk for cardiovascular events or death failed to show a significant benefit in the CANVAS program, Kenneth W. Mahaffey, MD, said at the American Heart Association scientific sessions.

The impressive reductions in cardiovascular and renal events seen in the overall CANVAS (Canagliflozin Cardiovascular Assessment Study) program turned out to be focused in the two-thirds of participants with a prior cardiovascular event at enrollment, according to Dr. Mahaffey, a cardiologist who is professor and vice chair of the department of medicine at Stanford (Calif.) University.

Bruce Jancin/Frontline Medical News

The CANVAS program included 10,142 patients with type 2 diabetes randomized to canagliflozin (Invokana) or placebo and prospectively followed for a mean of 3.6 years. The 66% of subjects with a prior cardiovascular event comprised the secondary prevention cohort. The 34% of CANVAS program participants in the primary prevention cohort all had two or more cardiovascular risk factors at baseline.

The primary outcome has previously been reported: The canagliflozin group had a highly significant 14% reduction in the risk of the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (N Engl J Med. 2017 Aug 17;377[7]:644-57).

At the AHA scientific sessions, Dr. Mahaffey presented a prespecified subgroup analysis comparing the impact of SGLT2 inhibitor for primary versus secondary cardiovascular prevention. Canagliflozin proved to be a big win for secondary prevention: The composite primary endpoint was reduced by 18%, compared with placebo; the composite renal outcome of worsening estimated glomerular filtration rate (eGFR), renal replacement, or renal death was reduced by 41%; and heart failure hospitalizations were reduced by 32%.

All of those benefits were strongly statistically significant. They came at the cost of roughly a fourfold increase in readily treatable male and female genital infections – a known class effect of the SGLT2 inhibitors – as well as an unexpected twofold increase in lower extremity amputations, which fortunately were uncommon. Of the amputations, 29% were above the ankle; the other 71% were less drastic toe or transmetatarsal procedures.

Dr. Mahaffey estimated that for every 1,000 patients with type 2 diabetes who were taking canagliflozin for secondary cardiovascular prevention for 5 years, there would be 36 fewer cardiovascular deaths, nonfatal MIs, or nonfatal strokes; 20 fewer hospitalizations for heart failure; 21 fewer patients who experienced the composite renal outcome; and 21 additional patients with a lower extremity amputation.

Rates of cardiovascular and renal endpoints were at least twofold higher in the secondary prevention group than in the primary prevention cohort. For prevention, the size of the relative risk reductions in heart failure hospitalizations and renal outcomes with canagliflozin, compared with placebo, were similar to the secondary prevention experience. So was the magnitude of the increased risk of lower extremity amputation. However, none of these differences achieved statistical significance, perhaps because of the lower absolute event rates in the primary prevention group.

Moreover, there was no signal of benefit for canagliflozin in terms of the composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke in the primary prevention group; those event rates were virtually identical to those seen in the placebo-treated controls.

That being said, the CANVAS Program wasn’t designed with sufficient statistical power to draw definitive conclusions regarding outcome differences in the primary and secondary prevention groups, Dr. Mahaffey noted.
 

Putting the SGLT2 cardiovascular prevention results in perspective

Discussant Angelyn Bethel, MD, said the impressive outcomes for canagliflozin for secondary prevention in the CANVAS Program are consistent with the results of the earlier 7,020-patient EMPA-REG trial of the SGLT2 inhibitor empagliflozin (Jardiance) versus placebo for secondary prevention in type 2 diabetes (N Engl J Med. 2015 Nov 26;373[22]:2117-28). The relative risk reductions in the primary composite endpoint, as well as in heart failure hospitalizations and renal outcomes, were quite similar in the secondary prevention setting in the two large trials.

The one difference was in all-cause mortality: a striking 32% reduction with empagliflozin, compared with placebo, versus a more modest 11% relative risk reduction in the CANVAS program, which narrowly missed statistical significance.

The mechanisms for the important cardiovascular benefits seen in the secondary prevention setting in the two large SGLT2 trials are still under debate, according to Dr. Bethel, an endocrinologist who is deputy director of the diabetes trial unit at the University of Oxford (England).

“I think what’s obvious to most of us is that we’ve moved now beyond the conventional risk factors. These drugs cause only very small reductions in weight, systolic blood pressure, and diastolic blood pressure; they result in small increases in LDL and HDL; and the timeline of the impact that we see for the SGLT2 inhibitors on the cardiovascular outcomes in particular is much too short to be looking for glucose- or atherosclerotic-mediated processes,” she said.

“The mechanisms probably involve invoking the cardiorenal axis in some way,” Dr. Bethel speculated. “We know these drugs have a diuretic effect and we believe that some of the mortality benefit is probably mediated by heart failure outcomes, with changes in volume status. And there’s also a drive toward ketone metabolism, which is more efficient for the compromised heart.”

As for canagliflozin’s lack of significant benefit for primary prevention in the CANVAS program, it’s possible that this was a statistical power problem, Dr. Bethel said, but she has her doubts.

“If we had more people followed for longer in the primary prevention cohort, would we get there? I think it’s a big ask, but we do have more data coming,” she noted.

Indeed, two major phase 3 clinical trials of SGLT2 inhibitors for both primary and secondary cardiovascular prevention in mixed populations are due to report results in 2019: the roughly 4,500-patient CREDENCE trial of canagliflozin and the 17,0000-patient DECLARE trial, featuring dapagliflozin. Both involve about 5 years of follow-up.

Dr. Bethel advocated waiting until those studies report their primary prevention outcomes before introducing SGLT2-inhibitor therapy for primary cardiovascular prevention in clinical practice.

“In this instance, we do have some evidence that there may be a difference in the way that various events behave in the primary and secondary prevention settings, and we may have an overestimate of the benefits for primary prevention if we were to put this stuff in the water and give it to everybody,” she cautioned.

The CANVAS program analysis of primary versus secondary prevention has been published (Circulation. 2018 Jan 23;137[4]:323-34).

The CANVAS program was supported by Janssen. Dr. Mahaffey reported receiving research grants from and serving as a consultant to Janssen and numerous other companies.

 

[email protected]

SOURCE: Mahaffey KW et al. AHA Scientific Sessions.

 

ANAHEIM, CALIF. – The first large randomized trial to report results on a sodium glucose cotransporter 2 inhibitor for primary prevention of cardiovascular events in patients with type 2 diabetes who are at risk for cardiovascular events or death failed to show a significant benefit in the CANVAS program, Kenneth W. Mahaffey, MD, said at the American Heart Association scientific sessions.

The impressive reductions in cardiovascular and renal events seen in the overall CANVAS (Canagliflozin Cardiovascular Assessment Study) program turned out to be focused in the two-thirds of participants with a prior cardiovascular event at enrollment, according to Dr. Mahaffey, a cardiologist who is professor and vice chair of the department of medicine at Stanford (Calif.) University.

Bruce Jancin/Frontline Medical News

The CANVAS program included 10,142 patients with type 2 diabetes randomized to canagliflozin (Invokana) or placebo and prospectively followed for a mean of 3.6 years. The 66% of subjects with a prior cardiovascular event comprised the secondary prevention cohort. The 34% of CANVAS program participants in the primary prevention cohort all had two or more cardiovascular risk factors at baseline.

The primary outcome has previously been reported: The canagliflozin group had a highly significant 14% reduction in the risk of the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke (N Engl J Med. 2017 Aug 17;377[7]:644-57).

At the AHA scientific sessions, Dr. Mahaffey presented a prespecified subgroup analysis comparing the impact of SGLT2 inhibitor for primary versus secondary cardiovascular prevention. Canagliflozin proved to be a big win for secondary prevention: The composite primary endpoint was reduced by 18%, compared with placebo; the composite renal outcome of worsening estimated glomerular filtration rate (eGFR), renal replacement, or renal death was reduced by 41%; and heart failure hospitalizations were reduced by 32%.

All of those benefits were strongly statistically significant. They came at the cost of roughly a fourfold increase in readily treatable male and female genital infections – a known class effect of the SGLT2 inhibitors – as well as an unexpected twofold increase in lower extremity amputations, which fortunately were uncommon. Of the amputations, 29% were above the ankle; the other 71% were less drastic toe or transmetatarsal procedures.

Dr. Mahaffey estimated that for every 1,000 patients with type 2 diabetes who were taking canagliflozin for secondary cardiovascular prevention for 5 years, there would be 36 fewer cardiovascular deaths, nonfatal MIs, or nonfatal strokes; 20 fewer hospitalizations for heart failure; 21 fewer patients who experienced the composite renal outcome; and 21 additional patients with a lower extremity amputation.

Rates of cardiovascular and renal endpoints were at least twofold higher in the secondary prevention group than in the primary prevention cohort. For prevention, the size of the relative risk reductions in heart failure hospitalizations and renal outcomes with canagliflozin, compared with placebo, were similar to the secondary prevention experience. So was the magnitude of the increased risk of lower extremity amputation. However, none of these differences achieved statistical significance, perhaps because of the lower absolute event rates in the primary prevention group.

Moreover, there was no signal of benefit for canagliflozin in terms of the composite outcome of cardiovascular death, nonfatal MI, or nonfatal stroke in the primary prevention group; those event rates were virtually identical to those seen in the placebo-treated controls.

That being said, the CANVAS Program wasn’t designed with sufficient statistical power to draw definitive conclusions regarding outcome differences in the primary and secondary prevention groups, Dr. Mahaffey noted.
 

Putting the SGLT2 cardiovascular prevention results in perspective

Discussant Angelyn Bethel, MD, said the impressive outcomes for canagliflozin for secondary prevention in the CANVAS Program are consistent with the results of the earlier 7,020-patient EMPA-REG trial of the SGLT2 inhibitor empagliflozin (Jardiance) versus placebo for secondary prevention in type 2 diabetes (N Engl J Med. 2015 Nov 26;373[22]:2117-28). The relative risk reductions in the primary composite endpoint, as well as in heart failure hospitalizations and renal outcomes, were quite similar in the secondary prevention setting in the two large trials.

The one difference was in all-cause mortality: a striking 32% reduction with empagliflozin, compared with placebo, versus a more modest 11% relative risk reduction in the CANVAS program, which narrowly missed statistical significance.

The mechanisms for the important cardiovascular benefits seen in the secondary prevention setting in the two large SGLT2 trials are still under debate, according to Dr. Bethel, an endocrinologist who is deputy director of the diabetes trial unit at the University of Oxford (England).

“I think what’s obvious to most of us is that we’ve moved now beyond the conventional risk factors. These drugs cause only very small reductions in weight, systolic blood pressure, and diastolic blood pressure; they result in small increases in LDL and HDL; and the timeline of the impact that we see for the SGLT2 inhibitors on the cardiovascular outcomes in particular is much too short to be looking for glucose- or atherosclerotic-mediated processes,” she said.

“The mechanisms probably involve invoking the cardiorenal axis in some way,” Dr. Bethel speculated. “We know these drugs have a diuretic effect and we believe that some of the mortality benefit is probably mediated by heart failure outcomes, with changes in volume status. And there’s also a drive toward ketone metabolism, which is more efficient for the compromised heart.”

As for canagliflozin’s lack of significant benefit for primary prevention in the CANVAS program, it’s possible that this was a statistical power problem, Dr. Bethel said, but she has her doubts.

“If we had more people followed for longer in the primary prevention cohort, would we get there? I think it’s a big ask, but we do have more data coming,” she noted.

Indeed, two major phase 3 clinical trials of SGLT2 inhibitors for both primary and secondary cardiovascular prevention in mixed populations are due to report results in 2019: the roughly 4,500-patient CREDENCE trial of canagliflozin and the 17,0000-patient DECLARE trial, featuring dapagliflozin. Both involve about 5 years of follow-up.

Dr. Bethel advocated waiting until those studies report their primary prevention outcomes before introducing SGLT2-inhibitor therapy for primary cardiovascular prevention in clinical practice.

“In this instance, we do have some evidence that there may be a difference in the way that various events behave in the primary and secondary prevention settings, and we may have an overestimate of the benefits for primary prevention if we were to put this stuff in the water and give it to everybody,” she cautioned.

The CANVAS program analysis of primary versus secondary prevention has been published (Circulation. 2018 Jan 23;137[4]:323-34).

The CANVAS program was supported by Janssen. Dr. Mahaffey reported receiving research grants from and serving as a consultant to Janssen and numerous other companies.

 

[email protected]

SOURCE: Mahaffey KW et al. AHA Scientific Sessions.

 

LAS VEGAS – Higher body mass index among inflammatory bowel disease patients is independently associated with an increased risk of treatment failure and IBD-related surgery or hospitalization, a single-center, retrospective cohort study demonstrated.

“The problem of IBD and obesity is on the rise,” Soumya Kurnool said at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Today, 15%-40% of IBD patients are obese. This is significant because there is a decreased prevalence of remission and an increased risk of relapse in obese IBD patients. These patients also have a higher annual burden of hospitalization.”

Doug Brunk/Frontline Medical News

Obesity also is associated with increased drug clearance for all biologic agents and higher odds of failing anti-TNF therapy in other immune-mediated inflammatory diseases, said Ms. Kurnool, a second-year student at the University of California, San Diego. “However, the research on the impact of obesity on treatment response to biologic agents in IBD is sparse and conflicting.”

She and her associates set out to evaluate the effect of obesity on response to biologic therapy in patients with ulcerative colitis (UC). They conducted a single-center, retrospective cohort study of biologic-treated adults with UC who started therapy during 2011-2016. The researchers excluded patients who had undergone a prior colectomy, as well as those who were underweight at the time of starting a biologic agent and those who had fewer than 6 months of follow-up data.

The primary outcome was time to treatment failure, defined as a composite of IBD-related surgery, hospitalization, and/or treatment modification. Secondary outcomes were time to IBD-related surgery and/or hospitalization and whether the patient achieved endoscopic remission within 1 year of starting biologic therapy. They conducted multivariate Cox proportional hazard analyses after adjusting for key confounders.

Ms. Kurnool reported results from 160 patients with a median age of 36 years. Half were male, and the mean follow-up was 24 months. The median BMI of the cohort was 24.3 kg/m²; 26% were overweight and 18% were obese. More than half of patients (55%) were on infliximab with weight-based dosing and 45% were on other fixed-dosing regimens, including 19% on vedolizumab. In terms of outcomes, 68% of patients experienced treatment failure. All who failed treatment underwent treatment modifications; 15% had IBD-related surgery, and 19% had IBD-related hospitalization.

After adjusting for age, sex, disease duration, prior hospitalization, prior anti-TNF therapy, steroid use, and albumin level, Ms. Kurnool and her associates found that every 1-kg/m² increase in BMI was associated with a 4% higher risk of treatment failure (adjusted hazard ratio, 1.04), an 8% higher risk of surgery or hospitalization (adjusted HR, 1.08), and a 6% lower risk of achieving endoscopic remission (adjusted HR, 0.94).

“This increase in the risk of treatment failure and IBD-related surgery or hospitalization was consistent across strata of patients treated with infliximab and fixed-dosing regimens,” she said. “Based on these findings, physicians should consider proactive monitoring in obese patients treated with biologic agents.”

Ms. Kurnool reported having received a National Institutes of Health Short Term Training Grant from the University of California, San Diego.

*This story was updated on 3/26.

[email protected]

SOURCE: Kurnool S et al. Crohn’s & Colitis Congress, Clinical Abstract 24.

 

LAS VEGAS – Higher body mass index among inflammatory bowel disease patients is independently associated with an increased risk of treatment failure and IBD-related surgery or hospitalization, a single-center, retrospective cohort study demonstrated.

“The problem of IBD and obesity is on the rise,” Soumya Kurnool said at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Today, 15%-40% of IBD patients are obese. This is significant because there is a decreased prevalence of remission and an increased risk of relapse in obese IBD patients. These patients also have a higher annual burden of hospitalization.”

Doug Brunk/Frontline Medical News

Obesity also is associated with increased drug clearance for all biologic agents and higher odds of failing anti-TNF therapy in other immune-mediated inflammatory diseases, said Ms. Kurnool, a second-year student at the University of California, San Diego. “However, the research on the impact of obesity on treatment response to biologic agents in IBD is sparse and conflicting.”

She and her associates set out to evaluate the effect of obesity on response to biologic therapy in patients with ulcerative colitis (UC). They conducted a single-center, retrospective cohort study of biologic-treated adults with UC who started therapy during 2011-2016. The researchers excluded patients who had undergone a prior colectomy, as well as those who were underweight at the time of starting a biologic agent and those who had fewer than 6 months of follow-up data.

The primary outcome was time to treatment failure, defined as a composite of IBD-related surgery, hospitalization, and/or treatment modification. Secondary outcomes were time to IBD-related surgery and/or hospitalization and whether the patient achieved endoscopic remission within 1 year of starting biologic therapy. They conducted multivariate Cox proportional hazard analyses after adjusting for key confounders.

Ms. Kurnool reported results from 160 patients with a median age of 36 years. Half were male, and the mean follow-up was 24 months. The median BMI of the cohort was 24.3 kg/m²; 26% were overweight and 18% were obese. More than half of patients (55%) were on infliximab with weight-based dosing and 45% were on other fixed-dosing regimens, including 19% on vedolizumab. In terms of outcomes, 68% of patients experienced treatment failure. All who failed treatment underwent treatment modifications; 15% had IBD-related surgery, and 19% had IBD-related hospitalization.

After adjusting for age, sex, disease duration, prior hospitalization, prior anti-TNF therapy, steroid use, and albumin level, Ms. Kurnool and her associates found that every 1-kg/m² increase in BMI was associated with a 4% higher risk of treatment failure (adjusted hazard ratio, 1.04), an 8% higher risk of surgery or hospitalization (adjusted HR, 1.08), and a 6% lower risk of achieving endoscopic remission (adjusted HR, 0.94).

“This increase in the risk of treatment failure and IBD-related surgery or hospitalization was consistent across strata of patients treated with infliximab and fixed-dosing regimens,” she said. “Based on these findings, physicians should consider proactive monitoring in obese patients treated with biologic agents.”

Ms. Kurnool reported having received a National Institutes of Health Short Term Training Grant from the University of California, San Diego.

*This story was updated on 3/26.

[email protected]

SOURCE: Kurnool S et al. Crohn’s & Colitis Congress, Clinical Abstract 24.

 

LAS VEGAS – Higher body mass index among inflammatory bowel disease patients is independently associated with an increased risk of treatment failure and IBD-related surgery or hospitalization, a single-center, retrospective cohort study demonstrated.

“The problem of IBD and obesity is on the rise,” Soumya Kurnool said at the Crohn’s & Colitis Congress, a partnership of the Crohn’s & Colitis Foundation and the American Gastroenterological Association. “Today, 15%-40% of IBD patients are obese. This is significant because there is a decreased prevalence of remission and an increased risk of relapse in obese IBD patients. These patients also have a higher annual burden of hospitalization.”

Doug Brunk/Frontline Medical News

Obesity also is associated with increased drug clearance for all biologic agents and higher odds of failing anti-TNF therapy in other immune-mediated inflammatory diseases, said Ms. Kurnool, a second-year student at the University of California, San Diego. “However, the research on the impact of obesity on treatment response to biologic agents in IBD is sparse and conflicting.”

She and her associates set out to evaluate the effect of obesity on response to biologic therapy in patients with ulcerative colitis (UC). They conducted a single-center, retrospective cohort study of biologic-treated adults with UC who started therapy during 2011-2016. The researchers excluded patients who had undergone a prior colectomy, as well as those who were underweight at the time of starting a biologic agent and those who had fewer than 6 months of follow-up data.

The primary outcome was time to treatment failure, defined as a composite of IBD-related surgery, hospitalization, and/or treatment modification. Secondary outcomes were time to IBD-related surgery and/or hospitalization and whether the patient achieved endoscopic remission within 1 year of starting biologic therapy. They conducted multivariate Cox proportional hazard analyses after adjusting for key confounders.

Ms. Kurnool reported results from 160 patients with a median age of 36 years. Half were male, and the mean follow-up was 24 months. The median BMI of the cohort was 24.3 kg/m²; 26% were overweight and 18% were obese. More than half of patients (55%) were on infliximab with weight-based dosing and 45% were on other fixed-dosing regimens, including 19% on vedolizumab. In terms of outcomes, 68% of patients experienced treatment failure. All who failed treatment underwent treatment modifications; 15% had IBD-related surgery, and 19% had IBD-related hospitalization.

After adjusting for age, sex, disease duration, prior hospitalization, prior anti-TNF therapy, steroid use, and albumin level, Ms. Kurnool and her associates found that every 1-kg/m² increase in BMI was associated with a 4% higher risk of treatment failure (adjusted hazard ratio, 1.04), an 8% higher risk of surgery or hospitalization (adjusted HR, 1.08), and a 6% lower risk of achieving endoscopic remission (adjusted HR, 0.94).

“This increase in the risk of treatment failure and IBD-related surgery or hospitalization was consistent across strata of patients treated with infliximab and fixed-dosing regimens,” she said. “Based on these findings, physicians should consider proactive monitoring in obese patients treated with biologic agents.”

Ms. Kurnool reported having received a National Institutes of Health Short Term Training Grant from the University of California, San Diego.

*This story was updated on 3/26.

[email protected]

SOURCE: Kurnool S et al. Crohn’s & Colitis Congress, Clinical Abstract 24.

 

LOS ANGELES – Heart failure in the presence of type 2 diabetes has a 5-year survival rate on par with some of the worst diseases, such as lung cancer, because diabetes makes the pathophysiology of heart failure worse, according to Mark Kearney, MD.

“Diabetes amplifies the neurohormonal response to heart failure, so it drives progressive heart failure and increases the risk for sudden death,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “As left ventricular function goes down, patients with diabetes have heightened activation of the renin angiotensin system. They have increased left ventricular hypertrophy, and they have increased sympathetic nervous system activation.”

Dr. Kearney, a cardiologist who directs the Leeds Institute of Cardiovascular & Metabolic Medicine at Leeds (England) University, offered a “four Ds” framework that clinicians can use to improve prognosis in these patients.

The four Ds include:

1. Use a loop diuretic to control symptoms. “If the patient has fluid retention, it’s important to get them out of congestive cardiac syndrome as quickly as possible,” he said.

2. Disease modification with beta-blockers and ACE inhibitors, to the maximal dose tolerated. “These are still the mainstays of treatment for patients with heart failure, and they’re even more important in patients with diabetes and heart failure,” he said.

3. Consider device therapy, including defibrillators and resynchronization therapy.4. Optimize diabetes management.

“If you keep these things in your mind as you see a patient with heart failure and diabetes, it will give you a guide to approaching these patients,” said Dr. Kearney, who is also research lead for heart failure services at the University of Leeds. “When I see patients, I’ll check for edema right away. If they have it, I’ll increase the diuretic, and I’ll think about the different steps in the treatment pathway.”

He described heart failure due to systolic dysfunction as a reduction in cardiac output that doesn’t meet the demands of the body, the endpoint of a whole range of insults to the left ventricle.

“The most common cause today is ischemic heart disease; it used to be hypertension,” he said. “People over 40 have a one in five chance of developing heart failure, so it’s really important for all of us to improve outcomes in this terrible syndrome.”

According to a study of nearly 2,000 unselected patients conducted by Dr. Kearney and his associates, those with diabetes and heart failure are more likely to have ischemia, compared with those who have heart failure and no diabetes (75% vs. 58%, respectively), lower hemoglobin (13 g/dL vs. 13.7 g/dL), and worse renal function (eGFR of 51 mL/min per 1.73² m² vs 57 mL/min per 1.73² m²) (Diab Vasc Dis Res. 2013 Jul;10[4]:330-6).

He added that type 2 diabetes is a sudden death risk equivalent to patients with ischemic heart disease and left ventricular systolic dysfunction (Heart 2016 May 15;102[10]:735-40).

“So, if you have diabetes and the U.K. National Institute for Health and Care Excellence guidelines indication for a defibrillator, your risk of sudden death in 5 years is probably 50%,” Dr. Kearney said. “The best treatment in this case is a prophylactic defibrillator.”

ACE inhibitors are used to protect these patients against cardiac myocyte cell death and vasoconstriction, while beta-blockers are used to protect against the activation of the sympathetic nervous system.

“Often, patients don’t like taking beta-blockers because they say they make them feel tired – when in fact they don’t realize it’s their heart failure that’s making them feel tired,” Dr. Kearney said.

He and his associates examined the effect of different drugs doses on all-cause mortality at 5 years. They found that, among patients with heart failure, reduced ejection fraction, and no diabetes, ramipril conferred a 3% improvement in mortality per milligram. At the same time, the mortality among patients with diabetes and heart failure who did not receive a beta-blocker was about 7%.

However, the absolute gain from beta-blocker use in patients with diabetes and heart failure was three times that of patients without diabetes.

“So, every milligram you increase the dose by, there’s an associated improvement in risk,” Dr. Kearney said. “Over 5 years, comparing the lowest beta-blocker dose to the highest beta-blocker dose, it was 1 year of life gained. So, when I see my patients and they ask about side effects of beta-blockers, I now say to them, ‘The side effects actually make you live longer.’”

He concluded his remarks by noting that while he is not a diabetes expert, it’s clear that diabetes is intimately linked to the pathophysiology of heart failure.

“If you’re insulin resistant, you have hypertension, hyperglycemia, you have inflammation and bone marrow dysfunction – all of which can exacerbate left ventricle dysfunction,” he said. “You have a syndrome in which you have cardiac dysfunction and metabolic dysfunction that conspire to lead to worsening of left ventricular dysfunction.”

Dr. Kearney disclosed that he has been a speaker for Merck.

[email protected]

 

LOS ANGELES – Heart failure in the presence of type 2 diabetes has a 5-year survival rate on par with some of the worst diseases, such as lung cancer, because diabetes makes the pathophysiology of heart failure worse, according to Mark Kearney, MD.

“Diabetes amplifies the neurohormonal response to heart failure, so it drives progressive heart failure and increases the risk for sudden death,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “As left ventricular function goes down, patients with diabetes have heightened activation of the renin angiotensin system. They have increased left ventricular hypertrophy, and they have increased sympathetic nervous system activation.”

Dr. Kearney, a cardiologist who directs the Leeds Institute of Cardiovascular & Metabolic Medicine at Leeds (England) University, offered a “four Ds” framework that clinicians can use to improve prognosis in these patients.

The four Ds include:

1. Use a loop diuretic to control symptoms. “If the patient has fluid retention, it’s important to get them out of congestive cardiac syndrome as quickly as possible,” he said.

2. Disease modification with beta-blockers and ACE inhibitors, to the maximal dose tolerated. “These are still the mainstays of treatment for patients with heart failure, and they’re even more important in patients with diabetes and heart failure,” he said.

3. Consider device therapy, including defibrillators and resynchronization therapy.4. Optimize diabetes management.

“If you keep these things in your mind as you see a patient with heart failure and diabetes, it will give you a guide to approaching these patients,” said Dr. Kearney, who is also research lead for heart failure services at the University of Leeds. “When I see patients, I’ll check for edema right away. If they have it, I’ll increase the diuretic, and I’ll think about the different steps in the treatment pathway.”

He described heart failure due to systolic dysfunction as a reduction in cardiac output that doesn’t meet the demands of the body, the endpoint of a whole range of insults to the left ventricle.

“The most common cause today is ischemic heart disease; it used to be hypertension,” he said. “People over 40 have a one in five chance of developing heart failure, so it’s really important for all of us to improve outcomes in this terrible syndrome.”

According to a study of nearly 2,000 unselected patients conducted by Dr. Kearney and his associates, those with diabetes and heart failure are more likely to have ischemia, compared with those who have heart failure and no diabetes (75% vs. 58%, respectively), lower hemoglobin (13 g/dL vs. 13.7 g/dL), and worse renal function (eGFR of 51 mL/min per 1.73² m² vs 57 mL/min per 1.73² m²) (Diab Vasc Dis Res. 2013 Jul;10[4]:330-6).

He added that type 2 diabetes is a sudden death risk equivalent to patients with ischemic heart disease and left ventricular systolic dysfunction (Heart 2016 May 15;102[10]:735-40).

“So, if you have diabetes and the U.K. National Institute for Health and Care Excellence guidelines indication for a defibrillator, your risk of sudden death in 5 years is probably 50%,” Dr. Kearney said. “The best treatment in this case is a prophylactic defibrillator.”

ACE inhibitors are used to protect these patients against cardiac myocyte cell death and vasoconstriction, while beta-blockers are used to protect against the activation of the sympathetic nervous system.

“Often, patients don’t like taking beta-blockers because they say they make them feel tired – when in fact they don’t realize it’s their heart failure that’s making them feel tired,” Dr. Kearney said.

He and his associates examined the effect of different drugs doses on all-cause mortality at 5 years. They found that, among patients with heart failure, reduced ejection fraction, and no diabetes, ramipril conferred a 3% improvement in mortality per milligram. At the same time, the mortality among patients with diabetes and heart failure who did not receive a beta-blocker was about 7%.

However, the absolute gain from beta-blocker use in patients with diabetes and heart failure was three times that of patients without diabetes.

“So, every milligram you increase the dose by, there’s an associated improvement in risk,” Dr. Kearney said. “Over 5 years, comparing the lowest beta-blocker dose to the highest beta-blocker dose, it was 1 year of life gained. So, when I see my patients and they ask about side effects of beta-blockers, I now say to them, ‘The side effects actually make you live longer.’”

He concluded his remarks by noting that while he is not a diabetes expert, it’s clear that diabetes is intimately linked to the pathophysiology of heart failure.

“If you’re insulin resistant, you have hypertension, hyperglycemia, you have inflammation and bone marrow dysfunction – all of which can exacerbate left ventricle dysfunction,” he said. “You have a syndrome in which you have cardiac dysfunction and metabolic dysfunction that conspire to lead to worsening of left ventricular dysfunction.”

Dr. Kearney disclosed that he has been a speaker for Merck.

[email protected]

 

LOS ANGELES – Heart failure in the presence of type 2 diabetes has a 5-year survival rate on par with some of the worst diseases, such as lung cancer, because diabetes makes the pathophysiology of heart failure worse, according to Mark Kearney, MD.

“Diabetes amplifies the neurohormonal response to heart failure, so it drives progressive heart failure and increases the risk for sudden death,” Dr. Kearney said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “As left ventricular function goes down, patients with diabetes have heightened activation of the renin angiotensin system. They have increased left ventricular hypertrophy, and they have increased sympathetic nervous system activation.”

Dr. Kearney, a cardiologist who directs the Leeds Institute of Cardiovascular & Metabolic Medicine at Leeds (England) University, offered a “four Ds” framework that clinicians can use to improve prognosis in these patients.

The four Ds include:

1. Use a loop diuretic to control symptoms. “If the patient has fluid retention, it’s important to get them out of congestive cardiac syndrome as quickly as possible,” he said.

2. Disease modification with beta-blockers and ACE inhibitors, to the maximal dose tolerated. “These are still the mainstays of treatment for patients with heart failure, and they’re even more important in patients with diabetes and heart failure,” he said.

3. Consider device therapy, including defibrillators and resynchronization therapy.4. Optimize diabetes management.

“If you keep these things in your mind as you see a patient with heart failure and diabetes, it will give you a guide to approaching these patients,” said Dr. Kearney, who is also research lead for heart failure services at the University of Leeds. “When I see patients, I’ll check for edema right away. If they have it, I’ll increase the diuretic, and I’ll think about the different steps in the treatment pathway.”

He described heart failure due to systolic dysfunction as a reduction in cardiac output that doesn’t meet the demands of the body, the endpoint of a whole range of insults to the left ventricle.

“The most common cause today is ischemic heart disease; it used to be hypertension,” he said. “People over 40 have a one in five chance of developing heart failure, so it’s really important for all of us to improve outcomes in this terrible syndrome.”

According to a study of nearly 2,000 unselected patients conducted by Dr. Kearney and his associates, those with diabetes and heart failure are more likely to have ischemia, compared with those who have heart failure and no diabetes (75% vs. 58%, respectively), lower hemoglobin (13 g/dL vs. 13.7 g/dL), and worse renal function (eGFR of 51 mL/min per 1.73² m² vs 57 mL/min per 1.73² m²) (Diab Vasc Dis Res. 2013 Jul;10[4]:330-6).

He added that type 2 diabetes is a sudden death risk equivalent to patients with ischemic heart disease and left ventricular systolic dysfunction (Heart 2016 May 15;102[10]:735-40).

“So, if you have diabetes and the U.K. National Institute for Health and Care Excellence guidelines indication for a defibrillator, your risk of sudden death in 5 years is probably 50%,” Dr. Kearney said. “The best treatment in this case is a prophylactic defibrillator.”

ACE inhibitors are used to protect these patients against cardiac myocyte cell death and vasoconstriction, while beta-blockers are used to protect against the activation of the sympathetic nervous system.

“Often, patients don’t like taking beta-blockers because they say they make them feel tired – when in fact they don’t realize it’s their heart failure that’s making them feel tired,” Dr. Kearney said.

He and his associates examined the effect of different drugs doses on all-cause mortality at 5 years. They found that, among patients with heart failure, reduced ejection fraction, and no diabetes, ramipril conferred a 3% improvement in mortality per milligram. At the same time, the mortality among patients with diabetes and heart failure who did not receive a beta-blocker was about 7%.

However, the absolute gain from beta-blocker use in patients with diabetes and heart failure was three times that of patients without diabetes.

“So, every milligram you increase the dose by, there’s an associated improvement in risk,” Dr. Kearney said. “Over 5 years, comparing the lowest beta-blocker dose to the highest beta-blocker dose, it was 1 year of life gained. So, when I see my patients and they ask about side effects of beta-blockers, I now say to them, ‘The side effects actually make you live longer.’”

He concluded his remarks by noting that while he is not a diabetes expert, it’s clear that diabetes is intimately linked to the pathophysiology of heart failure.

“If you’re insulin resistant, you have hypertension, hyperglycemia, you have inflammation and bone marrow dysfunction – all of which can exacerbate left ventricle dysfunction,” he said. “You have a syndrome in which you have cardiac dysfunction and metabolic dysfunction that conspire to lead to worsening of left ventricular dysfunction.”

Dr. Kearney disclosed that he has been a speaker for Merck.

[email protected]

 

LOS ANGELES – For every 10 of your adult patients with type 2 diabetes, three are likely to have moderate to severe liver fibrosis, according to Kenneth Cusi, MD, FACP, FACE.

“If in the last 10 patients, you didn’t diagnose anybody with fibrosis, you probably missed it,” he said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The question is, How are we going to tackle this problem? My academic goal is that we incorporate screening for NASH [nonalcoholic steatohepatitis], or for fibrosis more specifically, in the same way we do for retinopathy or nephropathy, because we do have a way to treat it.”

Doug Brunk/Frontline Medical News

Dr. Cusi, chief of the division of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, predicted that obesity will become the No. 1 cause of liver transplantation. “It’s a real epidemic; you’re not seeing it because the inflexion of obesity happened just 2 decades ago,” he said. “Patients with diabetes face the greatest risk of fatty liver and of fibrosis. Untreated, it’s the equivalent of having macroalbuminuria. If you do nothing and they don’t die of cardiovascular disease, they’re going to have a good chance of getting fibrosis.”

As part of the large population-based Rotterdam study of individuals aged 45 years and older, researchers found that liver stiffness of 8 kPa or more by transient elastography was present in 5.6% of the study participants and was strongly associated with steatosis and diabetes (Hepatology. 2016;63:138-47). According to Dr. Cusi, individuals who have steatosis without diabetes face a 5%-10% risk of fibrosis, while those with steatosis and diabetes face a 15%-20% risk.

“It’s well established in a number of studies that if you have fibrosis, you’re at high risk not only of cirrhosis, but also of hepatocellular carcinoma,” he said. “The key thing is not detecting fat, which is not really the target. The target is if there’s fibrosis or not.” Three ways to assess for fibrosis include MR elastography, transient elastography (which is the most commonly used), and fibrosis marker panels.

Liver fibrosis likely starts with adipose tissue dysfunction, said Dr. Cusi, who authored a review on the pathophysiology of interactions between adipose tissue and target organs in obesity and the resulting clinical implications for the management of nonalcoholic steatohepatitis (Gastroenterology. 2012;142[4]:711-25.e6).

“When you have insulin-resistant, sick adipose tissue, that leads to the accumulation of fat in the liver,” he said. “Steatosis happens in about 70% of patients who are obese and have type 2 diabetes. The dilemma is how to know who is going down the path to fibrosis. Even if you get people who are matched for BMIs [body mass indexes] between 30 and 35 kg/m², there is a spectrum in which some individuals have very insulin-resistant adipose tissue and others less so. I would say that 1 out of 10 are metabolically healthy, and we don’t understand exactly why.”

In a recent cross-sectional analysis of 352 healthy individuals, Dr. Cusi and his associates found that intrahepatic triglyceride (IHTG) accumulation is strongly associated with adipose tissue insulin resistance, supporting the current theory of lipotoxicity as a driver of IHTG accumulation (Hepatology. 2017;65[4]:1132-44). The researchers observed that once IHTG accumulation reaches about 6%, skeletal muscle insulin resistance, hypertriglyceridemia, and low HDL cholesterol become fully established.

“The next question is, How does this correlate with NASH?” Dr. Cusi said. “Our take is that there is a threshold effect. Once you have a critical amount of triglycerides in your liver, some individuals are going to activate pathways that are harmful. NASH is not something exclusive to individuals who are obese. Lean people can also develop NASH. The key feature is insulin resistance, not metabolic syndrome. Once you develop a fatty liver, your chances of NASH are comparable to that of an obese individual. The paradox is that lean individuals get a fatty liver, but when they get a fatty liver, they are at risk for NASH and for fibrosis.”

Why lean individuals develop NASH is not fully understood, but Dr. Cusi said he suspects that the problem develops at the mitochondrial level.

Results from an unpublished animal model in which mice were fed a high–trans-fat diet for 24 weeks showed that the mice developed steatosis by week 8 and NASH by week 24. The mice had an increase in the tricarboxylic acid (TCA) cycle, which is typical of the NASH period, as well as an increase in ceramides.

“Perhaps a unifying hypothesis would be that the development of NASH is linked to inflammation and to insulin signaling,” Dr. Cusi said. “Not surprisingly, it had a number of effects on the mitochondria, and in this animal model it decreases the TCA.” He noted that the biology of fibrosis remains unknown in humans. “What we have been familiar with is the high-triglyceride, low-HDL pattern,” he said. “If you look at how that correlates with the amount of liver fat, it is basically a threshold effect. Once you have steatosis, you don’t see much worse dyslipidemia, which is typical of these patients.”

Recently published guidance from the American Association for the Study of Liver Diseases on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) suggests that patients require a weight loss of 3%-5% to improve steatosis, but a loss of 7%-10% to improve most histologic features of NASH, including fibrosis (Hepatology. 2018;67[1]:328-57). Exercise alone may prevent or reduce steatosis, but its ability to improve other aspects of liver histology remains unknown. Bariatric surgery can be considered in otherwise eligible obese individuals with NAFLD or NASH. The procedure’s impact on fibrosis is unknown.

The AASLD practice guideline notes that metformin is not recommended for treating NASH in adult patients, but pioglitazone improves liver histology in patients with and without type 2 diabetes with biopsy-proven NASH.

“Pioglitazone has had the greatest benefit in terms of treatment effect, compared to placebo,” Dr. Cusi said. “It’s a generic drug; at the VA [Veterans Affairs], it costs 8 cents per tablet. I think that pioglitazone will be to NASH what metformin has been to type 2 diabetes. The most common side effect is weight gain, typically between 4 and 9 lb. Risks and benefits should be discussed with each patient. It should not be used for NAFLD without biopsy-proven NASH.”

The guideline goes on to say that it’s currently premature to consider GLP-1 (glucagonlike peptide–1) agonists for treating liver disease in patients with NAFLD or NASH. Meanwhile, vitamin E at 800 IU has been shown to improve liver histology in nondiabetic adults with NASH, but the risks and benefits should be discussed with each patient. Vitamin E is not recommended for NASH in diabetic patients, NAFLD without a liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.

The AASLD practice guideline also states that the best evidence for using SGLT2 (sodium-glucose cotransporter–2) inhibitors in NAFLD comes from animal studies, which report a reduction in steatosis with and without weight loss. Clinical studies reporting a reduction in steatosis are limited. There are positive observational studies with a reduction in alanine aminotransferase and some studies that have shown a reduction in liver fat. “For me, the best option is to tailor treatment to the pathophysiology of the disease,” Dr. Cusi said. “You reduce fat by weight loss in some way, or you change the biology of fat with a thiazolidinedione.”

Dr. Cusi reported that he has received grant support from the Burroughs Wellcome Fund, the American Diabetes Association, and the National Institutes of Health.

 

[email protected]

 

LOS ANGELES – For every 10 of your adult patients with type 2 diabetes, three are likely to have moderate to severe liver fibrosis, according to Kenneth Cusi, MD, FACP, FACE.

“If in the last 10 patients, you didn’t diagnose anybody with fibrosis, you probably missed it,” he said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The question is, How are we going to tackle this problem? My academic goal is that we incorporate screening for NASH [nonalcoholic steatohepatitis], or for fibrosis more specifically, in the same way we do for retinopathy or nephropathy, because we do have a way to treat it.”

Doug Brunk/Frontline Medical News

Dr. Cusi, chief of the division of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, predicted that obesity will become the No. 1 cause of liver transplantation. “It’s a real epidemic; you’re not seeing it because the inflexion of obesity happened just 2 decades ago,” he said. “Patients with diabetes face the greatest risk of fatty liver and of fibrosis. Untreated, it’s the equivalent of having macroalbuminuria. If you do nothing and they don’t die of cardiovascular disease, they’re going to have a good chance of getting fibrosis.”

As part of the large population-based Rotterdam study of individuals aged 45 years and older, researchers found that liver stiffness of 8 kPa or more by transient elastography was present in 5.6% of the study participants and was strongly associated with steatosis and diabetes (Hepatology. 2016;63:138-47). According to Dr. Cusi, individuals who have steatosis without diabetes face a 5%-10% risk of fibrosis, while those with steatosis and diabetes face a 15%-20% risk.

“It’s well established in a number of studies that if you have fibrosis, you’re at high risk not only of cirrhosis, but also of hepatocellular carcinoma,” he said. “The key thing is not detecting fat, which is not really the target. The target is if there’s fibrosis or not.” Three ways to assess for fibrosis include MR elastography, transient elastography (which is the most commonly used), and fibrosis marker panels.

Liver fibrosis likely starts with adipose tissue dysfunction, said Dr. Cusi, who authored a review on the pathophysiology of interactions between adipose tissue and target organs in obesity and the resulting clinical implications for the management of nonalcoholic steatohepatitis (Gastroenterology. 2012;142[4]:711-25.e6).

“When you have insulin-resistant, sick adipose tissue, that leads to the accumulation of fat in the liver,” he said. “Steatosis happens in about 70% of patients who are obese and have type 2 diabetes. The dilemma is how to know who is going down the path to fibrosis. Even if you get people who are matched for BMIs [body mass indexes] between 30 and 35 kg/m², there is a spectrum in which some individuals have very insulin-resistant adipose tissue and others less so. I would say that 1 out of 10 are metabolically healthy, and we don’t understand exactly why.”

In a recent cross-sectional analysis of 352 healthy individuals, Dr. Cusi and his associates found that intrahepatic triglyceride (IHTG) accumulation is strongly associated with adipose tissue insulin resistance, supporting the current theory of lipotoxicity as a driver of IHTG accumulation (Hepatology. 2017;65[4]:1132-44). The researchers observed that once IHTG accumulation reaches about 6%, skeletal muscle insulin resistance, hypertriglyceridemia, and low HDL cholesterol become fully established.

“The next question is, How does this correlate with NASH?” Dr. Cusi said. “Our take is that there is a threshold effect. Once you have a critical amount of triglycerides in your liver, some individuals are going to activate pathways that are harmful. NASH is not something exclusive to individuals who are obese. Lean people can also develop NASH. The key feature is insulin resistance, not metabolic syndrome. Once you develop a fatty liver, your chances of NASH are comparable to that of an obese individual. The paradox is that lean individuals get a fatty liver, but when they get a fatty liver, they are at risk for NASH and for fibrosis.”

Why lean individuals develop NASH is not fully understood, but Dr. Cusi said he suspects that the problem develops at the mitochondrial level.

Results from an unpublished animal model in which mice were fed a high–trans-fat diet for 24 weeks showed that the mice developed steatosis by week 8 and NASH by week 24. The mice had an increase in the tricarboxylic acid (TCA) cycle, which is typical of the NASH period, as well as an increase in ceramides.

“Perhaps a unifying hypothesis would be that the development of NASH is linked to inflammation and to insulin signaling,” Dr. Cusi said. “Not surprisingly, it had a number of effects on the mitochondria, and in this animal model it decreases the TCA.” He noted that the biology of fibrosis remains unknown in humans. “What we have been familiar with is the high-triglyceride, low-HDL pattern,” he said. “If you look at how that correlates with the amount of liver fat, it is basically a threshold effect. Once you have steatosis, you don’t see much worse dyslipidemia, which is typical of these patients.”

Recently published guidance from the American Association for the Study of Liver Diseases on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) suggests that patients require a weight loss of 3%-5% to improve steatosis, but a loss of 7%-10% to improve most histologic features of NASH, including fibrosis (Hepatology. 2018;67[1]:328-57). Exercise alone may prevent or reduce steatosis, but its ability to improve other aspects of liver histology remains unknown. Bariatric surgery can be considered in otherwise eligible obese individuals with NAFLD or NASH. The procedure’s impact on fibrosis is unknown.

The AASLD practice guideline notes that metformin is not recommended for treating NASH in adult patients, but pioglitazone improves liver histology in patients with and without type 2 diabetes with biopsy-proven NASH.

“Pioglitazone has had the greatest benefit in terms of treatment effect, compared to placebo,” Dr. Cusi said. “It’s a generic drug; at the VA [Veterans Affairs], it costs 8 cents per tablet. I think that pioglitazone will be to NASH what metformin has been to type 2 diabetes. The most common side effect is weight gain, typically between 4 and 9 lb. Risks and benefits should be discussed with each patient. It should not be used for NAFLD without biopsy-proven NASH.”

The guideline goes on to say that it’s currently premature to consider GLP-1 (glucagonlike peptide–1) agonists for treating liver disease in patients with NAFLD or NASH. Meanwhile, vitamin E at 800 IU has been shown to improve liver histology in nondiabetic adults with NASH, but the risks and benefits should be discussed with each patient. Vitamin E is not recommended for NASH in diabetic patients, NAFLD without a liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.

The AASLD practice guideline also states that the best evidence for using SGLT2 (sodium-glucose cotransporter–2) inhibitors in NAFLD comes from animal studies, which report a reduction in steatosis with and without weight loss. Clinical studies reporting a reduction in steatosis are limited. There are positive observational studies with a reduction in alanine aminotransferase and some studies that have shown a reduction in liver fat. “For me, the best option is to tailor treatment to the pathophysiology of the disease,” Dr. Cusi said. “You reduce fat by weight loss in some way, or you change the biology of fat with a thiazolidinedione.”

Dr. Cusi reported that he has received grant support from the Burroughs Wellcome Fund, the American Diabetes Association, and the National Institutes of Health.

 

[email protected]

 

LOS ANGELES – For every 10 of your adult patients with type 2 diabetes, three are likely to have moderate to severe liver fibrosis, according to Kenneth Cusi, MD, FACP, FACE.

“If in the last 10 patients, you didn’t diagnose anybody with fibrosis, you probably missed it,” he said at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease. “The question is, How are we going to tackle this problem? My academic goal is that we incorporate screening for NASH [nonalcoholic steatohepatitis], or for fibrosis more specifically, in the same way we do for retinopathy or nephropathy, because we do have a way to treat it.”

Doug Brunk/Frontline Medical News

Dr. Cusi, chief of the division of endocrinology, diabetes, and metabolism at the University of Florida, Gainesville, predicted that obesity will become the No. 1 cause of liver transplantation. “It’s a real epidemic; you’re not seeing it because the inflexion of obesity happened just 2 decades ago,” he said. “Patients with diabetes face the greatest risk of fatty liver and of fibrosis. Untreated, it’s the equivalent of having macroalbuminuria. If you do nothing and they don’t die of cardiovascular disease, they’re going to have a good chance of getting fibrosis.”

As part of the large population-based Rotterdam study of individuals aged 45 years and older, researchers found that liver stiffness of 8 kPa or more by transient elastography was present in 5.6% of the study participants and was strongly associated with steatosis and diabetes (Hepatology. 2016;63:138-47). According to Dr. Cusi, individuals who have steatosis without diabetes face a 5%-10% risk of fibrosis, while those with steatosis and diabetes face a 15%-20% risk.

“It’s well established in a number of studies that if you have fibrosis, you’re at high risk not only of cirrhosis, but also of hepatocellular carcinoma,” he said. “The key thing is not detecting fat, which is not really the target. The target is if there’s fibrosis or not.” Three ways to assess for fibrosis include MR elastography, transient elastography (which is the most commonly used), and fibrosis marker panels.

Liver fibrosis likely starts with adipose tissue dysfunction, said Dr. Cusi, who authored a review on the pathophysiology of interactions between adipose tissue and target organs in obesity and the resulting clinical implications for the management of nonalcoholic steatohepatitis (Gastroenterology. 2012;142[4]:711-25.e6).

“When you have insulin-resistant, sick adipose tissue, that leads to the accumulation of fat in the liver,” he said. “Steatosis happens in about 70% of patients who are obese and have type 2 diabetes. The dilemma is how to know who is going down the path to fibrosis. Even if you get people who are matched for BMIs [body mass indexes] between 30 and 35 kg/m², there is a spectrum in which some individuals have very insulin-resistant adipose tissue and others less so. I would say that 1 out of 10 are metabolically healthy, and we don’t understand exactly why.”

In a recent cross-sectional analysis of 352 healthy individuals, Dr. Cusi and his associates found that intrahepatic triglyceride (IHTG) accumulation is strongly associated with adipose tissue insulin resistance, supporting the current theory of lipotoxicity as a driver of IHTG accumulation (Hepatology. 2017;65[4]:1132-44). The researchers observed that once IHTG accumulation reaches about 6%, skeletal muscle insulin resistance, hypertriglyceridemia, and low HDL cholesterol become fully established.

“The next question is, How does this correlate with NASH?” Dr. Cusi said. “Our take is that there is a threshold effect. Once you have a critical amount of triglycerides in your liver, some individuals are going to activate pathways that are harmful. NASH is not something exclusive to individuals who are obese. Lean people can also develop NASH. The key feature is insulin resistance, not metabolic syndrome. Once you develop a fatty liver, your chances of NASH are comparable to that of an obese individual. The paradox is that lean individuals get a fatty liver, but when they get a fatty liver, they are at risk for NASH and for fibrosis.”

Why lean individuals develop NASH is not fully understood, but Dr. Cusi said he suspects that the problem develops at the mitochondrial level.

Results from an unpublished animal model in which mice were fed a high–trans-fat diet for 24 weeks showed that the mice developed steatosis by week 8 and NASH by week 24. The mice had an increase in the tricarboxylic acid (TCA) cycle, which is typical of the NASH period, as well as an increase in ceramides.

“Perhaps a unifying hypothesis would be that the development of NASH is linked to inflammation and to insulin signaling,” Dr. Cusi said. “Not surprisingly, it had a number of effects on the mitochondria, and in this animal model it decreases the TCA.” He noted that the biology of fibrosis remains unknown in humans. “What we have been familiar with is the high-triglyceride, low-HDL pattern,” he said. “If you look at how that correlates with the amount of liver fat, it is basically a threshold effect. Once you have steatosis, you don’t see much worse dyslipidemia, which is typical of these patients.”

Recently published guidance from the American Association for the Study of Liver Diseases on the diagnosis and management of nonalcoholic fatty liver disease (NAFLD) suggests that patients require a weight loss of 3%-5% to improve steatosis, but a loss of 7%-10% to improve most histologic features of NASH, including fibrosis (Hepatology. 2018;67[1]:328-57). Exercise alone may prevent or reduce steatosis, but its ability to improve other aspects of liver histology remains unknown. Bariatric surgery can be considered in otherwise eligible obese individuals with NAFLD or NASH. The procedure’s impact on fibrosis is unknown.

The AASLD practice guideline notes that metformin is not recommended for treating NASH in adult patients, but pioglitazone improves liver histology in patients with and without type 2 diabetes with biopsy-proven NASH.

“Pioglitazone has had the greatest benefit in terms of treatment effect, compared to placebo,” Dr. Cusi said. “It’s a generic drug; at the VA [Veterans Affairs], it costs 8 cents per tablet. I think that pioglitazone will be to NASH what metformin has been to type 2 diabetes. The most common side effect is weight gain, typically between 4 and 9 lb. Risks and benefits should be discussed with each patient. It should not be used for NAFLD without biopsy-proven NASH.”

The guideline goes on to say that it’s currently premature to consider GLP-1 (glucagonlike peptide–1) agonists for treating liver disease in patients with NAFLD or NASH. Meanwhile, vitamin E at 800 IU has been shown to improve liver histology in nondiabetic adults with NASH, but the risks and benefits should be discussed with each patient. Vitamin E is not recommended for NASH in diabetic patients, NAFLD without a liver biopsy, NASH cirrhosis, or cryptogenic cirrhosis.

The AASLD practice guideline also states that the best evidence for using SGLT2 (sodium-glucose cotransporter–2) inhibitors in NAFLD comes from animal studies, which report a reduction in steatosis with and without weight loss. Clinical studies reporting a reduction in steatosis are limited. There are positive observational studies with a reduction in alanine aminotransferase and some studies that have shown a reduction in liver fat. “For me, the best option is to tailor treatment to the pathophysiology of the disease,” Dr. Cusi said. “You reduce fat by weight loss in some way, or you change the biology of fat with a thiazolidinedione.”

Dr. Cusi reported that he has received grant support from the Burroughs Wellcome Fund, the American Diabetes Association, and the National Institutes of Health.

 

[email protected]