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AMSTERDAM – People infected with HIV had a 66% increased rate of developing heart failure – compared with matched, uninfected people – that was independent of any other cardiovascular disease risk factor in a study of roughly 425,000 individuals from a large U.S. health care system.

“HIV infection is independently associated with a higher risk for developing heart failure, and this excess risk does not appear mediated through atherosclerotic disease pathways or differential use of cardioprotective medications,” Alan S. Go, MD, said at the 22nd International AIDS Conference.

The finding sends two important messages to physicians who care for people living with HIV, Dr. Go said in a video interview. First, have “greater awareness for the risk of heart failure” in people living with HIV, even in those who have excellent [HIV] treatment. Be on the lookout, he recommended, for classic symptoms of heart failure like dyspnea and fatigue, and if found follow-up with an assessment of heart function, usually by echocardiography. The second message is to pay attention to and aggressively treat risk factors for heart failure, such as hypertension, smoking, obesity, diabetes, and hypercholesterolemia, said Dr. Go, director of the Comprehensive Clinical Research Unit of Kaiser Permanente in Oakland, Calif.

Results from a small number of prior studies also suggested an increased heart failure rate in people infected with HIV, but those reports had not been able to untangle this observed increase from a possible relationship to the elevated rate of MIs among people living with HIV. The study led by Dr. Go adjusted for acute coronary syndrome events that occurred during follow-up in the analysis and this showed that the increased incidence of heart failure occurred independently of any preceding MI or unstable angina event.

Dr. Go proposed several potential mechanisms that could tie HIV infection to an elevated heart failure risk that was not linked to a prior ischemic heart disease event. The virus could directly damage cardiac myocytes to produce fibrosis, the virus could trigger cardiac inflammation, and the infected person could have an increased susceptibility to infection by a pathogen know to potentially cause cardiac damage and myocarditis such as coxsackievirus.

For the time being, patients infected by HIV who develop heart failure should receive the same treatments that are recommended for the general population, Dr. Go said, but he also highlighted the need for further study to determine the effectiveness of standard heart failure treatments specifically in people living with HIV. He and his associates are also currently analyzing the relationship of several other variables to the risk for heart failure in HIV-infected people, such as the degree of HIV control, and the types of antiretroviral therapy that patients receive. So far the study has not shown a relationship between HIV infection and any specific type of heart failure. About a quarter of the HIV-infected people who developed heart failure in this study had reduced left ventricular ejection fraction, about a quarter had preserved ejection fraction, and for the remaining patients information on their left ventricular ejection fraction was not available, Dr. Go said.

The Kaiser Permanente HIV Heart Study used data from health records from about 13.5 million people enrolled in the health system during 2000-2016 at locations in northern California, southern California, or the mid-Atlantic region. From these records the researchers identified 38,868 people diagnosed with an HIV infection, free of a heart failure diagnosis, and at least 21 years old, and matched them by age, sex, and race with 386,586 people in the health system who were both uninfected and free of heart failure. At “baseline” in the analysis the two study groups had very similar rates of smoking, but those with HIV had somewhat more alcohol abuse and nearly twice the rate of illicit drug use, although even among those with HIV this rate was low at 4%.

Some clinical characteristics at baseline showed significant differences between the two groups. People living with HIV had substantially less hypertension, 7% compared with 12% in those without HIV; half the rate of dyslipidemia, 8% compared with 16% among the control group; and nearly half the prevalence of diabetes, 3% versus 5% among those without HIV. On the other hand, certain other clinical characteristics were more common among those with HIV. The prevalence at baseline of diagnosed dementia was 15% among people infected with HIV and essentially nonexistent (less than 1%) among controls, and the prevalence of diagnosed depression was 8% among people with HIV and 5% among those without the infection.

Baseline parameters also showed that at the time this review first identified a person with HIV and without heart failure in the system records only 18% of the HIV-infected individuals were on an antiretroviral therapy regimen. Dr. Go said that the study is currently analyzing subsequent HIV treatments that these patients may have received. Also at “baseline” 13% of people with documented HIV infection had a CD4 cell count of fewer than 200 cell/mm³, with 4% having fewer than 50 CD4 cells/mm³, and 29% of those with HIV had a blood level of at least 500 copies of HIV RNA/mL. In addition, information on CD4 cell counts was unavailable for 43% of these people, and information on viral load was unavailable for about half.

During “follow-up” in the system’s medical records for a period of up to 17 years, diagnoses of incident heart failure accumulated significantly faster among people with HIV compared to those without HIV. After adjustment for demographic differences, the time of entry into the health system, cardiovascular and other medical differences, and differences in medication use, people living with HIV had a 75% higher rate of incident heart failure compared with those without HIV. Further adjustment based on incident first episodes of acute coronary syndrome during “follow-up” brought the excess rate of heart failure to 66% higher among people infected by HIV, Dr. Go reported. He cautioned that the findings came from a U.S. population that had access to comprehensive health care.

[email protected]

SOURCE: Go AS et al. AIDS 2018, Abstract 2778, THAB0103.

AMSTERDAM – People infected with HIV had a 66% increased rate of developing heart failure – compared with matched, uninfected people – that was independent of any other cardiovascular disease risk factor in a study of roughly 425,000 individuals from a large U.S. health care system.

“HIV infection is independently associated with a higher risk for developing heart failure, and this excess risk does not appear mediated through atherosclerotic disease pathways or differential use of cardioprotective medications,” Alan S. Go, MD, said at the 22nd International AIDS Conference.

The finding sends two important messages to physicians who care for people living with HIV, Dr. Go said in a video interview. First, have “greater awareness for the risk of heart failure” in people living with HIV, even in those who have excellent [HIV] treatment. Be on the lookout, he recommended, for classic symptoms of heart failure like dyspnea and fatigue, and if found follow-up with an assessment of heart function, usually by echocardiography. The second message is to pay attention to and aggressively treat risk factors for heart failure, such as hypertension, smoking, obesity, diabetes, and hypercholesterolemia, said Dr. Go, director of the Comprehensive Clinical Research Unit of Kaiser Permanente in Oakland, Calif.

Results from a small number of prior studies also suggested an increased heart failure rate in people infected with HIV, but those reports had not been able to untangle this observed increase from a possible relationship to the elevated rate of MIs among people living with HIV. The study led by Dr. Go adjusted for acute coronary syndrome events that occurred during follow-up in the analysis and this showed that the increased incidence of heart failure occurred independently of any preceding MI or unstable angina event.

Dr. Go proposed several potential mechanisms that could tie HIV infection to an elevated heart failure risk that was not linked to a prior ischemic heart disease event. The virus could directly damage cardiac myocytes to produce fibrosis, the virus could trigger cardiac inflammation, and the infected person could have an increased susceptibility to infection by a pathogen know to potentially cause cardiac damage and myocarditis such as coxsackievirus.

For the time being, patients infected by HIV who develop heart failure should receive the same treatments that are recommended for the general population, Dr. Go said, but he also highlighted the need for further study to determine the effectiveness of standard heart failure treatments specifically in people living with HIV. He and his associates are also currently analyzing the relationship of several other variables to the risk for heart failure in HIV-infected people, such as the degree of HIV control, and the types of antiretroviral therapy that patients receive. So far the study has not shown a relationship between HIV infection and any specific type of heart failure. About a quarter of the HIV-infected people who developed heart failure in this study had reduced left ventricular ejection fraction, about a quarter had preserved ejection fraction, and for the remaining patients information on their left ventricular ejection fraction was not available, Dr. Go said.

The Kaiser Permanente HIV Heart Study used data from health records from about 13.5 million people enrolled in the health system during 2000-2016 at locations in northern California, southern California, or the mid-Atlantic region. From these records the researchers identified 38,868 people diagnosed with an HIV infection, free of a heart failure diagnosis, and at least 21 years old, and matched them by age, sex, and race with 386,586 people in the health system who were both uninfected and free of heart failure. At “baseline” in the analysis the two study groups had very similar rates of smoking, but those with HIV had somewhat more alcohol abuse and nearly twice the rate of illicit drug use, although even among those with HIV this rate was low at 4%.

Some clinical characteristics at baseline showed significant differences between the two groups. People living with HIV had substantially less hypertension, 7% compared with 12% in those without HIV; half the rate of dyslipidemia, 8% compared with 16% among the control group; and nearly half the prevalence of diabetes, 3% versus 5% among those without HIV. On the other hand, certain other clinical characteristics were more common among those with HIV. The prevalence at baseline of diagnosed dementia was 15% among people infected with HIV and essentially nonexistent (less than 1%) among controls, and the prevalence of diagnosed depression was 8% among people with HIV and 5% among those without the infection.

Baseline parameters also showed that at the time this review first identified a person with HIV and without heart failure in the system records only 18% of the HIV-infected individuals were on an antiretroviral therapy regimen. Dr. Go said that the study is currently analyzing subsequent HIV treatments that these patients may have received. Also at “baseline” 13% of people with documented HIV infection had a CD4 cell count of fewer than 200 cell/mm³, with 4% having fewer than 50 CD4 cells/mm³, and 29% of those with HIV had a blood level of at least 500 copies of HIV RNA/mL. In addition, information on CD4 cell counts was unavailable for 43% of these people, and information on viral load was unavailable for about half.

During “follow-up” in the system’s medical records for a period of up to 17 years, diagnoses of incident heart failure accumulated significantly faster among people with HIV compared to those without HIV. After adjustment for demographic differences, the time of entry into the health system, cardiovascular and other medical differences, and differences in medication use, people living with HIV had a 75% higher rate of incident heart failure compared with those without HIV. Further adjustment based on incident first episodes of acute coronary syndrome during “follow-up” brought the excess rate of heart failure to 66% higher among people infected by HIV, Dr. Go reported. He cautioned that the findings came from a U.S. population that had access to comprehensive health care.

[email protected]

SOURCE: Go AS et al. AIDS 2018, Abstract 2778, THAB0103.

AMSTERDAM – People infected with HIV had a 66% increased rate of developing heart failure – compared with matched, uninfected people – that was independent of any other cardiovascular disease risk factor in a study of roughly 425,000 individuals from a large U.S. health care system.

“HIV infection is independently associated with a higher risk for developing heart failure, and this excess risk does not appear mediated through atherosclerotic disease pathways or differential use of cardioprotective medications,” Alan S. Go, MD, said at the 22nd International AIDS Conference.

The finding sends two important messages to physicians who care for people living with HIV, Dr. Go said in a video interview. First, have “greater awareness for the risk of heart failure” in people living with HIV, even in those who have excellent [HIV] treatment. Be on the lookout, he recommended, for classic symptoms of heart failure like dyspnea and fatigue, and if found follow-up with an assessment of heart function, usually by echocardiography. The second message is to pay attention to and aggressively treat risk factors for heart failure, such as hypertension, smoking, obesity, diabetes, and hypercholesterolemia, said Dr. Go, director of the Comprehensive Clinical Research Unit of Kaiser Permanente in Oakland, Calif.

Results from a small number of prior studies also suggested an increased heart failure rate in people infected with HIV, but those reports had not been able to untangle this observed increase from a possible relationship to the elevated rate of MIs among people living with HIV. The study led by Dr. Go adjusted for acute coronary syndrome events that occurred during follow-up in the analysis and this showed that the increased incidence of heart failure occurred independently of any preceding MI or unstable angina event.

Dr. Go proposed several potential mechanisms that could tie HIV infection to an elevated heart failure risk that was not linked to a prior ischemic heart disease event. The virus could directly damage cardiac myocytes to produce fibrosis, the virus could trigger cardiac inflammation, and the infected person could have an increased susceptibility to infection by a pathogen know to potentially cause cardiac damage and myocarditis such as coxsackievirus.

For the time being, patients infected by HIV who develop heart failure should receive the same treatments that are recommended for the general population, Dr. Go said, but he also highlighted the need for further study to determine the effectiveness of standard heart failure treatments specifically in people living with HIV. He and his associates are also currently analyzing the relationship of several other variables to the risk for heart failure in HIV-infected people, such as the degree of HIV control, and the types of antiretroviral therapy that patients receive. So far the study has not shown a relationship between HIV infection and any specific type of heart failure. About a quarter of the HIV-infected people who developed heart failure in this study had reduced left ventricular ejection fraction, about a quarter had preserved ejection fraction, and for the remaining patients information on their left ventricular ejection fraction was not available, Dr. Go said.

The Kaiser Permanente HIV Heart Study used data from health records from about 13.5 million people enrolled in the health system during 2000-2016 at locations in northern California, southern California, or the mid-Atlantic region. From these records the researchers identified 38,868 people diagnosed with an HIV infection, free of a heart failure diagnosis, and at least 21 years old, and matched them by age, sex, and race with 386,586 people in the health system who were both uninfected and free of heart failure. At “baseline” in the analysis the two study groups had very similar rates of smoking, but those with HIV had somewhat more alcohol abuse and nearly twice the rate of illicit drug use, although even among those with HIV this rate was low at 4%.

Some clinical characteristics at baseline showed significant differences between the two groups. People living with HIV had substantially less hypertension, 7% compared with 12% in those without HIV; half the rate of dyslipidemia, 8% compared with 16% among the control group; and nearly half the prevalence of diabetes, 3% versus 5% among those without HIV. On the other hand, certain other clinical characteristics were more common among those with HIV. The prevalence at baseline of diagnosed dementia was 15% among people infected with HIV and essentially nonexistent (less than 1%) among controls, and the prevalence of diagnosed depression was 8% among people with HIV and 5% among those without the infection.

Baseline parameters also showed that at the time this review first identified a person with HIV and without heart failure in the system records only 18% of the HIV-infected individuals were on an antiretroviral therapy regimen. Dr. Go said that the study is currently analyzing subsequent HIV treatments that these patients may have received. Also at “baseline” 13% of people with documented HIV infection had a CD4 cell count of fewer than 200 cell/mm³, with 4% having fewer than 50 CD4 cells/mm³, and 29% of those with HIV had a blood level of at least 500 copies of HIV RNA/mL. In addition, information on CD4 cell counts was unavailable for 43% of these people, and information on viral load was unavailable for about half.

During “follow-up” in the system’s medical records for a period of up to 17 years, diagnoses of incident heart failure accumulated significantly faster among people with HIV compared to those without HIV. After adjustment for demographic differences, the time of entry into the health system, cardiovascular and other medical differences, and differences in medication use, people living with HIV had a 75% higher rate of incident heart failure compared with those without HIV. Further adjustment based on incident first episodes of acute coronary syndrome during “follow-up” brought the excess rate of heart failure to 66% higher among people infected by HIV, Dr. Go reported. He cautioned that the findings came from a U.S. population that had access to comprehensive health care.

[email protected]

SOURCE: Go AS et al. AIDS 2018, Abstract 2778, THAB0103.

AMSTERDAM – An investigational HIV vaccine that recently began testing in a phase IIb trial showed durable safety and anti-HIV immune responses out to 1 year following the final dosage in the initial phase I/IIa trial that had identified the most effective dosing strategy for the vaccine.

The 96-week follow-up data showed durable humoral and cellular immunity induction by the vaccine and its associated booster, a durable breadth of immune responses to the multiple HIV clades that the vaccine targets, and no serious or grade 3 or 4 adverse effects in the 393 people who participated in the early-phase study, Frank L. Tomaka, MD, said at the 22nd International AIDS Conference.

The 96-week results he reported came from follow-up of the 393 people who received one of several different dosing regimens for an engineered, mosaic HIV vaccine. The vaccine incorporates genes for three different HIV envelope antigens that contain components drawn from several different HIV clades (to induce more broadly protective immunity) into a serotype 26 adenovirus. The immunization regimen also includes treatment with HIV glycoprotein 140 as a booster agent. Dr. Tomaka and his associates reported the primary endpoints from this placebo-controlled study, APPROACH, measured just after the fourth and final immunizing regimen at 48 weeks after the first treatment in a recently published article (Lancet. 2018 Jul 21;392[10143]:232-43).

As part of the study, the investigators administered the vaccine and booster to rhesus monkeys and found that the regimens produced a pattern of immune responses in the monkeys similar to that seen in people. When the monkeys that received the regimen that performed best in people received six monthly challenges with a simian-human immunodeficiency virus that’s related to HIV, the researchers found a 67% efficacy for protection against infection. These “very encouraging” findings led the company developing the vaccine to launch in November 2017 a phase IIb trial, named Imbokodo, in five African countries, with a plan to enroll 2,600 people, Dr. Tomaka said.

“What’s unique and very exciting” about the APPROACH findings are the nonhuman primate findings, and the fact that the vaccine was designed to provide protection against several different HIV clades, Dr. Tomaka said in a video interview. The 67% level of protection against viral challenge in the monkeys is at a level that would be clinically meaningful if replicated in people. A vaccine and booster regimen that provided something in the range of 50%-60% protection or better might be an attractive option in a region with relatively low resources, while in a more developed country a vaccine with a protective efficacy of 70% or better would also likely be seen as an attractive intervention, said Dr. Tomaka, clinical leader for HIV/STI vaccines for Janssen in Titusville, N.J.

[email protected]

SOURCE: Tomaka FL et al. AIDS 2018, Abstract TUAA0104.

AMSTERDAM – An investigational HIV vaccine that recently began testing in a phase IIb trial showed durable safety and anti-HIV immune responses out to 1 year following the final dosage in the initial phase I/IIa trial that had identified the most effective dosing strategy for the vaccine.

The 96-week follow-up data showed durable humoral and cellular immunity induction by the vaccine and its associated booster, a durable breadth of immune responses to the multiple HIV clades that the vaccine targets, and no serious or grade 3 or 4 adverse effects in the 393 people who participated in the early-phase study, Frank L. Tomaka, MD, said at the 22nd International AIDS Conference.

The 96-week results he reported came from follow-up of the 393 people who received one of several different dosing regimens for an engineered, mosaic HIV vaccine. The vaccine incorporates genes for three different HIV envelope antigens that contain components drawn from several different HIV clades (to induce more broadly protective immunity) into a serotype 26 adenovirus. The immunization regimen also includes treatment with HIV glycoprotein 140 as a booster agent. Dr. Tomaka and his associates reported the primary endpoints from this placebo-controlled study, APPROACH, measured just after the fourth and final immunizing regimen at 48 weeks after the first treatment in a recently published article (Lancet. 2018 Jul 21;392[10143]:232-43).

As part of the study, the investigators administered the vaccine and booster to rhesus monkeys and found that the regimens produced a pattern of immune responses in the monkeys similar to that seen in people. When the monkeys that received the regimen that performed best in people received six monthly challenges with a simian-human immunodeficiency virus that’s related to HIV, the researchers found a 67% efficacy for protection against infection. These “very encouraging” findings led the company developing the vaccine to launch in November 2017 a phase IIb trial, named Imbokodo, in five African countries, with a plan to enroll 2,600 people, Dr. Tomaka said.

“What’s unique and very exciting” about the APPROACH findings are the nonhuman primate findings, and the fact that the vaccine was designed to provide protection against several different HIV clades, Dr. Tomaka said in a video interview. The 67% level of protection against viral challenge in the monkeys is at a level that would be clinically meaningful if replicated in people. A vaccine and booster regimen that provided something in the range of 50%-60% protection or better might be an attractive option in a region with relatively low resources, while in a more developed country a vaccine with a protective efficacy of 70% or better would also likely be seen as an attractive intervention, said Dr. Tomaka, clinical leader for HIV/STI vaccines for Janssen in Titusville, N.J.

[email protected]

SOURCE: Tomaka FL et al. AIDS 2018, Abstract TUAA0104.

AMSTERDAM – An investigational HIV vaccine that recently began testing in a phase IIb trial showed durable safety and anti-HIV immune responses out to 1 year following the final dosage in the initial phase I/IIa trial that had identified the most effective dosing strategy for the vaccine.

The 96-week follow-up data showed durable humoral and cellular immunity induction by the vaccine and its associated booster, a durable breadth of immune responses to the multiple HIV clades that the vaccine targets, and no serious or grade 3 or 4 adverse effects in the 393 people who participated in the early-phase study, Frank L. Tomaka, MD, said at the 22nd International AIDS Conference.

The 96-week results he reported came from follow-up of the 393 people who received one of several different dosing regimens for an engineered, mosaic HIV vaccine. The vaccine incorporates genes for three different HIV envelope antigens that contain components drawn from several different HIV clades (to induce more broadly protective immunity) into a serotype 26 adenovirus. The immunization regimen also includes treatment with HIV glycoprotein 140 as a booster agent. Dr. Tomaka and his associates reported the primary endpoints from this placebo-controlled study, APPROACH, measured just after the fourth and final immunizing regimen at 48 weeks after the first treatment in a recently published article (Lancet. 2018 Jul 21;392[10143]:232-43).

As part of the study, the investigators administered the vaccine and booster to rhesus monkeys and found that the regimens produced a pattern of immune responses in the monkeys similar to that seen in people. When the monkeys that received the regimen that performed best in people received six monthly challenges with a simian-human immunodeficiency virus that’s related to HIV, the researchers found a 67% efficacy for protection against infection. These “very encouraging” findings led the company developing the vaccine to launch in November 2017 a phase IIb trial, named Imbokodo, in five African countries, with a plan to enroll 2,600 people, Dr. Tomaka said.

“What’s unique and very exciting” about the APPROACH findings are the nonhuman primate findings, and the fact that the vaccine was designed to provide protection against several different HIV clades, Dr. Tomaka said in a video interview. The 67% level of protection against viral challenge in the monkeys is at a level that would be clinically meaningful if replicated in people. A vaccine and booster regimen that provided something in the range of 50%-60% protection or better might be an attractive option in a region with relatively low resources, while in a more developed country a vaccine with a protective efficacy of 70% or better would also likely be seen as an attractive intervention, said Dr. Tomaka, clinical leader for HIV/STI vaccines for Janssen in Titusville, N.J.

[email protected]

SOURCE: Tomaka FL et al. AIDS 2018, Abstract TUAA0104.

ORLANDO – Research suggests that HIV-positive people who take the latest generations of AIDS medications are living almost as long as everyone else. But they still face special medical challenges, and an endocrinologist urged colleagues to adjust their approaches to diabetes in these patients.

“The HIV population is indeed aging, diabetes is very common, and there are some unique pathophysiologic and management considerations,” said Todd T. Brown, MD, PhD, of Johns Hopkins Medicine, Baltimore, in a presentation at the annual scientific sessions of the American Diabetes Association.

It’s not just a matter of subbing in an alternate drug here or there. When it comes to diabetes, patients with HIV require significant adjustments to diagnosis and treatment, Dr. Brown said.

In terms of diagnosis, treatment guidelines approved by the Infectious Diseases Society of America and ADA recommend that all HIV-positive patients be tested for diabetes before they begin taking antiretroviral therapy. Then, the guidelines suggest, they should be tested 4-6 weeks after initiation of therapy, and every 6-12 months going forward.

“It’s a bit of overkill to go every 6 months,” said Dr. Brown, who prefers an annual testing approach. He added that research has suggested that the 2-hour postload glucose test is more sensitive than the fasting glucose test in some HIV-positive populations. However, he believes that it’s generally fine to give a fasting glucose test before initiation of therapy – and on an annual basis afterward – rather than the more cumbersome postload test.

Still, he said, the postload test may be appropriate in a patient with impaired glucose tolerance “if you really want to make the diagnosis, and especially if you’ll change your treatment based on it.”

Ongoing treatment of HIV-positive patients also presents unique challenges, he said. For one, antiretroviral therapy seems to affect glucose metabolism and body fat, he said, and findings from a 2016 study suggest HIV-positive people who begin antiretroviral therapy face a higher risk of developing diabetes after weight gain (J Acquir Immune Defic Syndr. 2016 Oct 1;73[2]:228-36).

One option is to switch patients to integrase inhibitors, but findings from a 2017 study suggested that this may also lead to more weight gain, Dr. Brown said.

“This has been an evolving story,” he said. “The clinical consequences of this are unclear. This is a topic that’s being hotly investigated now in the HIV health world” (JAIDS. 2017 Dec 15;76[5]:527-31).

As for other diabetes management issues, Dr. Brown noted that hemoglobin A_1c tests appear to underestimate glycemia in HIV-infected patients. He suggested that goal HbA_1c levels should be lower in diabetic patients with HIV, especially those with CD4+ counts under 500 cells /mm³ and/or mean cell volume over 100 fL.

Research suggests that lifestyle changes seem to work well in HIV-positive patients, he said, and metformin is the ideal first-line drug treatment just as in the HIV-negative population. “It’s a good drug. We all love it,” he said. “It may improve lipohypertrophy and coronary plaque.”

He added that proteinuria and neuropathy are more common in HIV-positive patients with diabetes. He said levels of neuropathy and nephropathy could be related to AIDS drugs.

On the medication front, Dr. Brown cautioned about certain drugs in HIV-positive patients: The HIV drug dolutegravir increases metformin concentrations by about 80%, he said, and there are concerns about bone and cardiac health in HIV-positive patients who take the diabetes medications known as thiazolidinediones (glitazones).

He added that there are sparse data about the use of several types of diabetes drugs – DPP IV inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors – in HIV-positive patients.

Dr. Brown discloses consulting for Gilead Sciences, ViiV, BMS, Merck, Theratechnologies, and EMD Serono.

ORLANDO – Research suggests that HIV-positive people who take the latest generations of AIDS medications are living almost as long as everyone else. But they still face special medical challenges, and an endocrinologist urged colleagues to adjust their approaches to diabetes in these patients.

“The HIV population is indeed aging, diabetes is very common, and there are some unique pathophysiologic and management considerations,” said Todd T. Brown, MD, PhD, of Johns Hopkins Medicine, Baltimore, in a presentation at the annual scientific sessions of the American Diabetes Association.

It’s not just a matter of subbing in an alternate drug here or there. When it comes to diabetes, patients with HIV require significant adjustments to diagnosis and treatment, Dr. Brown said.

In terms of diagnosis, treatment guidelines approved by the Infectious Diseases Society of America and ADA recommend that all HIV-positive patients be tested for diabetes before they begin taking antiretroviral therapy. Then, the guidelines suggest, they should be tested 4-6 weeks after initiation of therapy, and every 6-12 months going forward.

“It’s a bit of overkill to go every 6 months,” said Dr. Brown, who prefers an annual testing approach. He added that research has suggested that the 2-hour postload glucose test is more sensitive than the fasting glucose test in some HIV-positive populations. However, he believes that it’s generally fine to give a fasting glucose test before initiation of therapy – and on an annual basis afterward – rather than the more cumbersome postload test.

Still, he said, the postload test may be appropriate in a patient with impaired glucose tolerance “if you really want to make the diagnosis, and especially if you’ll change your treatment based on it.”

Ongoing treatment of HIV-positive patients also presents unique challenges, he said. For one, antiretroviral therapy seems to affect glucose metabolism and body fat, he said, and findings from a 2016 study suggest HIV-positive people who begin antiretroviral therapy face a higher risk of developing diabetes after weight gain (J Acquir Immune Defic Syndr. 2016 Oct 1;73[2]:228-36).

One option is to switch patients to integrase inhibitors, but findings from a 2017 study suggested that this may also lead to more weight gain, Dr. Brown said.

“This has been an evolving story,” he said. “The clinical consequences of this are unclear. This is a topic that’s being hotly investigated now in the HIV health world” (JAIDS. 2017 Dec 15;76[5]:527-31).

As for other diabetes management issues, Dr. Brown noted that hemoglobin A_1c tests appear to underestimate glycemia in HIV-infected patients. He suggested that goal HbA_1c levels should be lower in diabetic patients with HIV, especially those with CD4+ counts under 500 cells /mm³ and/or mean cell volume over 100 fL.

Research suggests that lifestyle changes seem to work well in HIV-positive patients, he said, and metformin is the ideal first-line drug treatment just as in the HIV-negative population. “It’s a good drug. We all love it,” he said. “It may improve lipohypertrophy and coronary plaque.”

He added that proteinuria and neuropathy are more common in HIV-positive patients with diabetes. He said levels of neuropathy and nephropathy could be related to AIDS drugs.

On the medication front, Dr. Brown cautioned about certain drugs in HIV-positive patients: The HIV drug dolutegravir increases metformin concentrations by about 80%, he said, and there are concerns about bone and cardiac health in HIV-positive patients who take the diabetes medications known as thiazolidinediones (glitazones).

He added that there are sparse data about the use of several types of diabetes drugs – DPP IV inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors – in HIV-positive patients.

Dr. Brown discloses consulting for Gilead Sciences, ViiV, BMS, Merck, Theratechnologies, and EMD Serono.

ORLANDO – Research suggests that HIV-positive people who take the latest generations of AIDS medications are living almost as long as everyone else. But they still face special medical challenges, and an endocrinologist urged colleagues to adjust their approaches to diabetes in these patients.

“The HIV population is indeed aging, diabetes is very common, and there are some unique pathophysiologic and management considerations,” said Todd T. Brown, MD, PhD, of Johns Hopkins Medicine, Baltimore, in a presentation at the annual scientific sessions of the American Diabetes Association.

It’s not just a matter of subbing in an alternate drug here or there. When it comes to diabetes, patients with HIV require significant adjustments to diagnosis and treatment, Dr. Brown said.

In terms of diagnosis, treatment guidelines approved by the Infectious Diseases Society of America and ADA recommend that all HIV-positive patients be tested for diabetes before they begin taking antiretroviral therapy. Then, the guidelines suggest, they should be tested 4-6 weeks after initiation of therapy, and every 6-12 months going forward.

“It’s a bit of overkill to go every 6 months,” said Dr. Brown, who prefers an annual testing approach. He added that research has suggested that the 2-hour postload glucose test is more sensitive than the fasting glucose test in some HIV-positive populations. However, he believes that it’s generally fine to give a fasting glucose test before initiation of therapy – and on an annual basis afterward – rather than the more cumbersome postload test.

Still, he said, the postload test may be appropriate in a patient with impaired glucose tolerance “if you really want to make the diagnosis, and especially if you’ll change your treatment based on it.”

Ongoing treatment of HIV-positive patients also presents unique challenges, he said. For one, antiretroviral therapy seems to affect glucose metabolism and body fat, he said, and findings from a 2016 study suggest HIV-positive people who begin antiretroviral therapy face a higher risk of developing diabetes after weight gain (J Acquir Immune Defic Syndr. 2016 Oct 1;73[2]:228-36).

One option is to switch patients to integrase inhibitors, but findings from a 2017 study suggested that this may also lead to more weight gain, Dr. Brown said.

“This has been an evolving story,” he said. “The clinical consequences of this are unclear. This is a topic that’s being hotly investigated now in the HIV health world” (JAIDS. 2017 Dec 15;76[5]:527-31).

As for other diabetes management issues, Dr. Brown noted that hemoglobin A_1c tests appear to underestimate glycemia in HIV-infected patients. He suggested that goal HbA_1c levels should be lower in diabetic patients with HIV, especially those with CD4+ counts under 500 cells /mm³ and/or mean cell volume over 100 fL.

Research suggests that lifestyle changes seem to work well in HIV-positive patients, he said, and metformin is the ideal first-line drug treatment just as in the HIV-negative population. “It’s a good drug. We all love it,” he said. “It may improve lipohypertrophy and coronary plaque.”

He added that proteinuria and neuropathy are more common in HIV-positive patients with diabetes. He said levels of neuropathy and nephropathy could be related to AIDS drugs.

On the medication front, Dr. Brown cautioned about certain drugs in HIV-positive patients: The HIV drug dolutegravir increases metformin concentrations by about 80%, he said, and there are concerns about bone and cardiac health in HIV-positive patients who take the diabetes medications known as thiazolidinediones (glitazones).

He added that there are sparse data about the use of several types of diabetes drugs – DPP IV inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors – in HIV-positive patients.

Dr. Brown discloses consulting for Gilead Sciences, ViiV, BMS, Merck, Theratechnologies, and EMD Serono.

ORLANDO – New research suggests it’s feasible for hospitals to use an automated closed-loop insulin delivery system – free of prandial boluses and carbohydrate counts – to improve glucose control in noncritical patients with type 2 diabetes mellitus (T2DM).

The findings, released at the annual scientific sessions of the American Diabetes Association and via simultaneous publication in The New England Journal of Medicine, don’t examine cost or clinical outcomes. However, “our results suggest this new technology might be another approach to manage in-patient hypoglycemia in a safe and effective way, lead author Lia Bally, MD, PhD, of the division of endocrinology, diabetes, and clinical nutrition, Bern (Switzerland ) University Hospital, said in an interview.

For the open-label trial, the researchers recruited 136 adults with T2DM under noncritical care at two hospitals (one in the England and the other in Switzerland). Some patients had undergone surgery, Dr. Bally said, and some others were being treated for systemic infections. Comorbidities were significantly more severe in the closed-loop group, and 43% had sepsis.

All of the subjects required subcutaneous insulin therapy.

From 2016 to 2017, patients were randomly assigned to receive normal subcutaneous insulin therapy (n = 70) or closed-loop insulin delivery (n = 66).

It took about 15 minutes to perform the procedure to implement the closed-loop insulin delivery system, Dr. Bally said. It featured a subcutaneous cannula inserted into the abdomen, a continuous glucose monitor (a device also used in the control group), and a trial insulin pump.

This was not a hybrid system, and it did not include prandial insulin boluses or input of the timing and carbohydrate content of meals. One reason behind the choice to adopt a fully automated system was to relieve the burden on both health care professionals and patients, coauthor Hood Thabit, PhD, of Wellcome Trust–MRC Institute of Metabolic Science, the Manchester Academic Health Science Center, and University of Manchester, said in an interview.

For up to 15 days or until discharge, researchers tracked how much of the time sensor glucose measurements were in a target range of 100 mg/dL to 180 mg/dL.

In the closed-loop group, glucose measurements were in the target range 66 mg/dL ± 17% of the time compared to 42 mg/dL ± 17% in the control group, a difference of 24 mg/dL ± 3% (95% confidence interval, 19-30; P less than .001).

For the closed-loop group, the average glucose level was 154 mg/dL, and it was 188 mg/dL in the control group (P less than .001).

The researchers didn’t find a statistically significant difference between the groups in duration of hypoglycemia or amount of insulin delivered.

None of the patients suffered from severe hypoglycemia or clinically significant hyperglycemia with ketonemia.

There were 18 incidents of clinically significant hyperglycemia events (capillary glucose levels of more than 360 mg/dL) in the closed-loop group, compared with 41 such events in the control group. (P = .03)

Three patients in each group had adverse trial-related device effects.

Of 62 patients in the closed-loop group who completed the trial, 87% reported being pleased by their glucose levels, and all but one reported being happy to have their levels monitored automatically. All 62 patients said they’d recommend the system to others.

Going forward, the researchers hope to launch a multicenter trial that will examine clinical outcomes such as postoperative complications, infections, mortality, and glucose control after hospital discharge, according to Dr. Bally.

The study was supported by Diabetes UK, the Swiss National Science Foundation, the European Foundation for the Study of Diabetes, the JDRF, the National Institute for Health Research Cambridge Biomedical Research Center, and a Wellcome Strategic Award. Abbott Diabetes Care supplied equipment and guidance regarding connectivity, and representatives reviewed the manuscript before submission.

Dr. Bally reported funding from the University Hospital Bern, University of Bern and the Swiss Diabetes Foundation. Dr. Thabit reported no disclosures. Other authors report no disclosures or various disclosures.

SOURCE: Bally L et al. ADA 2018 Abstract 350-OR. Published simultaneously in The New England Journal of Medicine. June 25, 2018

ORLANDO – New research suggests it’s feasible for hospitals to use an automated closed-loop insulin delivery system – free of prandial boluses and carbohydrate counts – to improve glucose control in noncritical patients with type 2 diabetes mellitus (T2DM).

The findings, released at the annual scientific sessions of the American Diabetes Association and via simultaneous publication in The New England Journal of Medicine, don’t examine cost or clinical outcomes. However, “our results suggest this new technology might be another approach to manage in-patient hypoglycemia in a safe and effective way, lead author Lia Bally, MD, PhD, of the division of endocrinology, diabetes, and clinical nutrition, Bern (Switzerland ) University Hospital, said in an interview.

For the open-label trial, the researchers recruited 136 adults with T2DM under noncritical care at two hospitals (one in the England and the other in Switzerland). Some patients had undergone surgery, Dr. Bally said, and some others were being treated for systemic infections. Comorbidities were significantly more severe in the closed-loop group, and 43% had sepsis.

All of the subjects required subcutaneous insulin therapy.

From 2016 to 2017, patients were randomly assigned to receive normal subcutaneous insulin therapy (n = 70) or closed-loop insulin delivery (n = 66).

It took about 15 minutes to perform the procedure to implement the closed-loop insulin delivery system, Dr. Bally said. It featured a subcutaneous cannula inserted into the abdomen, a continuous glucose monitor (a device also used in the control group), and a trial insulin pump.

This was not a hybrid system, and it did not include prandial insulin boluses or input of the timing and carbohydrate content of meals. One reason behind the choice to adopt a fully automated system was to relieve the burden on both health care professionals and patients, coauthor Hood Thabit, PhD, of Wellcome Trust–MRC Institute of Metabolic Science, the Manchester Academic Health Science Center, and University of Manchester, said in an interview.

For up to 15 days or until discharge, researchers tracked how much of the time sensor glucose measurements were in a target range of 100 mg/dL to 180 mg/dL.

In the closed-loop group, glucose measurements were in the target range 66 mg/dL ± 17% of the time compared to 42 mg/dL ± 17% in the control group, a difference of 24 mg/dL ± 3% (95% confidence interval, 19-30; P less than .001).

For the closed-loop group, the average glucose level was 154 mg/dL, and it was 188 mg/dL in the control group (P less than .001).

The researchers didn’t find a statistically significant difference between the groups in duration of hypoglycemia or amount of insulin delivered.

None of the patients suffered from severe hypoglycemia or clinically significant hyperglycemia with ketonemia.

There were 18 incidents of clinically significant hyperglycemia events (capillary glucose levels of more than 360 mg/dL) in the closed-loop group, compared with 41 such events in the control group. (P = .03)

Three patients in each group had adverse trial-related device effects.

Of 62 patients in the closed-loop group who completed the trial, 87% reported being pleased by their glucose levels, and all but one reported being happy to have their levels monitored automatically. All 62 patients said they’d recommend the system to others.

Going forward, the researchers hope to launch a multicenter trial that will examine clinical outcomes such as postoperative complications, infections, mortality, and glucose control after hospital discharge, according to Dr. Bally.

The study was supported by Diabetes UK, the Swiss National Science Foundation, the European Foundation for the Study of Diabetes, the JDRF, the National Institute for Health Research Cambridge Biomedical Research Center, and a Wellcome Strategic Award. Abbott Diabetes Care supplied equipment and guidance regarding connectivity, and representatives reviewed the manuscript before submission.

Dr. Bally reported funding from the University Hospital Bern, University of Bern and the Swiss Diabetes Foundation. Dr. Thabit reported no disclosures. Other authors report no disclosures or various disclosures.

SOURCE: Bally L et al. ADA 2018 Abstract 350-OR. Published simultaneously in The New England Journal of Medicine. June 25, 2018

ORLANDO – New research suggests it’s feasible for hospitals to use an automated closed-loop insulin delivery system – free of prandial boluses and carbohydrate counts – to improve glucose control in noncritical patients with type 2 diabetes mellitus (T2DM).

The findings, released at the annual scientific sessions of the American Diabetes Association and via simultaneous publication in The New England Journal of Medicine, don’t examine cost or clinical outcomes. However, “our results suggest this new technology might be another approach to manage in-patient hypoglycemia in a safe and effective way, lead author Lia Bally, MD, PhD, of the division of endocrinology, diabetes, and clinical nutrition, Bern (Switzerland ) University Hospital, said in an interview.

For the open-label trial, the researchers recruited 136 adults with T2DM under noncritical care at two hospitals (one in the England and the other in Switzerland). Some patients had undergone surgery, Dr. Bally said, and some others were being treated for systemic infections. Comorbidities were significantly more severe in the closed-loop group, and 43% had sepsis.

All of the subjects required subcutaneous insulin therapy.

From 2016 to 2017, patients were randomly assigned to receive normal subcutaneous insulin therapy (n = 70) or closed-loop insulin delivery (n = 66).

It took about 15 minutes to perform the procedure to implement the closed-loop insulin delivery system, Dr. Bally said. It featured a subcutaneous cannula inserted into the abdomen, a continuous glucose monitor (a device also used in the control group), and a trial insulin pump.

This was not a hybrid system, and it did not include prandial insulin boluses or input of the timing and carbohydrate content of meals. One reason behind the choice to adopt a fully automated system was to relieve the burden on both health care professionals and patients, coauthor Hood Thabit, PhD, of Wellcome Trust–MRC Institute of Metabolic Science, the Manchester Academic Health Science Center, and University of Manchester, said in an interview.

For up to 15 days or until discharge, researchers tracked how much of the time sensor glucose measurements were in a target range of 100 mg/dL to 180 mg/dL.

In the closed-loop group, glucose measurements were in the target range 66 mg/dL ± 17% of the time compared to 42 mg/dL ± 17% in the control group, a difference of 24 mg/dL ± 3% (95% confidence interval, 19-30; P less than .001).

For the closed-loop group, the average glucose level was 154 mg/dL, and it was 188 mg/dL in the control group (P less than .001).

The researchers didn’t find a statistically significant difference between the groups in duration of hypoglycemia or amount of insulin delivered.

None of the patients suffered from severe hypoglycemia or clinically significant hyperglycemia with ketonemia.

There were 18 incidents of clinically significant hyperglycemia events (capillary glucose levels of more than 360 mg/dL) in the closed-loop group, compared with 41 such events in the control group. (P = .03)

Three patients in each group had adverse trial-related device effects.

Of 62 patients in the closed-loop group who completed the trial, 87% reported being pleased by their glucose levels, and all but one reported being happy to have their levels monitored automatically. All 62 patients said they’d recommend the system to others.

Going forward, the researchers hope to launch a multicenter trial that will examine clinical outcomes such as postoperative complications, infections, mortality, and glucose control after hospital discharge, according to Dr. Bally.

The study was supported by Diabetes UK, the Swiss National Science Foundation, the European Foundation for the Study of Diabetes, the JDRF, the National Institute for Health Research Cambridge Biomedical Research Center, and a Wellcome Strategic Award. Abbott Diabetes Care supplied equipment and guidance regarding connectivity, and representatives reviewed the manuscript before submission.

Dr. Bally reported funding from the University Hospital Bern, University of Bern and the Swiss Diabetes Foundation. Dr. Thabit reported no disclosures. Other authors report no disclosures or various disclosures.

SOURCE: Bally L et al. ADA 2018 Abstract 350-OR. Published simultaneously in The New England Journal of Medicine. June 25, 2018

ORLANDO – Neither metformin nor insulin glargine followed by metformin improved beta cell function in adolescents with impaired glucose tolerance or early type 2 diabetes mellitus (T2DM) in the pediatric medication portion of the Restoring Insulin Secretion (RISE) study.

The treatments, including either metformin for 12 months in 47 participants or insulin glargine for 3 months followed by metformin for 9 months in 44 participants, were not associated with improvement in beta cell function at 12 months, compared with baseline, according to reports from members of the RISE Consortium at the annual scientific sessions of the American Diabetes Association.

Furthermore, measures of beta cell function worsened in both groups at 15-month follow-up, and the same was true for participants with impaired glucose tolerance only; the outcomes in that subset of patients were similar to the entire group, including patients with early T2DM.

“Beta cell failure progressed despite that intervention, and though both [metformin and insulin glargine] were effective for lowering glucose – and metformin for lowering weight ... it had nothing to do with the natural history of the disease, and that’s really quite disappointing,” John B. Buse, MD, said in a video interview.

But that’s not to say the findings weren’t of value.

“The exciting bit was our greater understanding of what’s different about diabetes in youth, and basically [the findings] showed that, both in the setting of impaired glucose tolerance and early diabetes, youth have more insulin resistance than adults, they have relatively more well-preserved beta cell function – they’re secreting more insulin at both impaired glucose tolerance and diabetes, and they have lesser hepatic insulin clearance,” said Dr. Buse, professor, chief of the division of endocrinology, and director of the Diabetes Center at the University of North Carolina, Chapel Hill.

Dr. Buse provided invited commentary on the findings at the ADA scientific sessions and elaborated on those comments in this interview, noting that, in addition to identifying important differences between children and adults with impaired glucose tolerance and diabetes, the RISE study demonstrated that the numerous challenges associated with conducting a major study involving children with impaired glucose tolerance or T2DM can be overcome.

“It’s a really heartwarming story,” he said of the efforts and successes of the RISE investigators in completing the pediatric medication portion of the study. “It at least gives us hope that, even if we haven’t found a cure for type 2 diabetes in children, we at least know we can do the studies.”

Dr. Buse also provided his take on what the future holds for both parts of the RISE study (findings from the adult medication and adult surgery portions are expected to be reported within the next year) and for other studies in children and youth with diabetes; he noted that the current findings and successes in enrolling and completing the pediatric portion of the study highlight multiple opportunities for future research.

Dr. Buse reported financial relationships with Adocia, AstraZeneca, Dexcom, Elcelyx, Eli Lilly, Fractyl Laboratories, Intarcia Therapeutics, Lexicon Pharmaceuticals, Metavention, NovaTarg Therapeutics, Novo Nordisk, Sanofi, VTV Therapeutics, Boehringer Ingelheim, Johnson & Johnson Services, Theracos, Shenzhen Hightide Biopharmaceutical, National Heart Lung and Blood Institute, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association, Patient-Centered Outcomes Research Institute, and the National Institute of Environmental Health Sciences.

[email protected]

ORLANDO – Neither metformin nor insulin glargine followed by metformin improved beta cell function in adolescents with impaired glucose tolerance or early type 2 diabetes mellitus (T2DM) in the pediatric medication portion of the Restoring Insulin Secretion (RISE) study.

The treatments, including either metformin for 12 months in 47 participants or insulin glargine for 3 months followed by metformin for 9 months in 44 participants, were not associated with improvement in beta cell function at 12 months, compared with baseline, according to reports from members of the RISE Consortium at the annual scientific sessions of the American Diabetes Association.

Furthermore, measures of beta cell function worsened in both groups at 15-month follow-up, and the same was true for participants with impaired glucose tolerance only; the outcomes in that subset of patients were similar to the entire group, including patients with early T2DM.

“Beta cell failure progressed despite that intervention, and though both [metformin and insulin glargine] were effective for lowering glucose – and metformin for lowering weight ... it had nothing to do with the natural history of the disease, and that’s really quite disappointing,” John B. Buse, MD, said in a video interview.

But that’s not to say the findings weren’t of value.

“The exciting bit was our greater understanding of what’s different about diabetes in youth, and basically [the findings] showed that, both in the setting of impaired glucose tolerance and early diabetes, youth have more insulin resistance than adults, they have relatively more well-preserved beta cell function – they’re secreting more insulin at both impaired glucose tolerance and diabetes, and they have lesser hepatic insulin clearance,” said Dr. Buse, professor, chief of the division of endocrinology, and director of the Diabetes Center at the University of North Carolina, Chapel Hill.

Dr. Buse provided invited commentary on the findings at the ADA scientific sessions and elaborated on those comments in this interview, noting that, in addition to identifying important differences between children and adults with impaired glucose tolerance and diabetes, the RISE study demonstrated that the numerous challenges associated with conducting a major study involving children with impaired glucose tolerance or T2DM can be overcome.

“It’s a really heartwarming story,” he said of the efforts and successes of the RISE investigators in completing the pediatric medication portion of the study. “It at least gives us hope that, even if we haven’t found a cure for type 2 diabetes in children, we at least know we can do the studies.”

Dr. Buse also provided his take on what the future holds for both parts of the RISE study (findings from the adult medication and adult surgery portions are expected to be reported within the next year) and for other studies in children and youth with diabetes; he noted that the current findings and successes in enrolling and completing the pediatric portion of the study highlight multiple opportunities for future research.

Dr. Buse reported financial relationships with Adocia, AstraZeneca, Dexcom, Elcelyx, Eli Lilly, Fractyl Laboratories, Intarcia Therapeutics, Lexicon Pharmaceuticals, Metavention, NovaTarg Therapeutics, Novo Nordisk, Sanofi, VTV Therapeutics, Boehringer Ingelheim, Johnson & Johnson Services, Theracos, Shenzhen Hightide Biopharmaceutical, National Heart Lung and Blood Institute, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association, Patient-Centered Outcomes Research Institute, and the National Institute of Environmental Health Sciences.

[email protected]

ORLANDO – Neither metformin nor insulin glargine followed by metformin improved beta cell function in adolescents with impaired glucose tolerance or early type 2 diabetes mellitus (T2DM) in the pediatric medication portion of the Restoring Insulin Secretion (RISE) study.

The treatments, including either metformin for 12 months in 47 participants or insulin glargine for 3 months followed by metformin for 9 months in 44 participants, were not associated with improvement in beta cell function at 12 months, compared with baseline, according to reports from members of the RISE Consortium at the annual scientific sessions of the American Diabetes Association.

Furthermore, measures of beta cell function worsened in both groups at 15-month follow-up, and the same was true for participants with impaired glucose tolerance only; the outcomes in that subset of patients were similar to the entire group, including patients with early T2DM.

“Beta cell failure progressed despite that intervention, and though both [metformin and insulin glargine] were effective for lowering glucose – and metformin for lowering weight ... it had nothing to do with the natural history of the disease, and that’s really quite disappointing,” John B. Buse, MD, said in a video interview.

But that’s not to say the findings weren’t of value.

“The exciting bit was our greater understanding of what’s different about diabetes in youth, and basically [the findings] showed that, both in the setting of impaired glucose tolerance and early diabetes, youth have more insulin resistance than adults, they have relatively more well-preserved beta cell function – they’re secreting more insulin at both impaired glucose tolerance and diabetes, and they have lesser hepatic insulin clearance,” said Dr. Buse, professor, chief of the division of endocrinology, and director of the Diabetes Center at the University of North Carolina, Chapel Hill.

Dr. Buse provided invited commentary on the findings at the ADA scientific sessions and elaborated on those comments in this interview, noting that, in addition to identifying important differences between children and adults with impaired glucose tolerance and diabetes, the RISE study demonstrated that the numerous challenges associated with conducting a major study involving children with impaired glucose tolerance or T2DM can be overcome.

“It’s a really heartwarming story,” he said of the efforts and successes of the RISE investigators in completing the pediatric medication portion of the study. “It at least gives us hope that, even if we haven’t found a cure for type 2 diabetes in children, we at least know we can do the studies.”

Dr. Buse also provided his take on what the future holds for both parts of the RISE study (findings from the adult medication and adult surgery portions are expected to be reported within the next year) and for other studies in children and youth with diabetes; he noted that the current findings and successes in enrolling and completing the pediatric portion of the study highlight multiple opportunities for future research.

Dr. Buse reported financial relationships with Adocia, AstraZeneca, Dexcom, Elcelyx, Eli Lilly, Fractyl Laboratories, Intarcia Therapeutics, Lexicon Pharmaceuticals, Metavention, NovaTarg Therapeutics, Novo Nordisk, Sanofi, VTV Therapeutics, Boehringer Ingelheim, Johnson & Johnson Services, Theracos, Shenzhen Hightide Biopharmaceutical, National Heart Lung and Blood Institute, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, American Diabetes Association, Patient-Centered Outcomes Research Institute, and the National Institute of Environmental Health Sciences.

[email protected]