Insulin Perturbations Seen in Nondiabetic Patients With NAFLD

LAS VEGAS – Nondiabetic patients with nonalcoholic fatty liver disease already have insulin perturbations putting them on track for a variety of more serious health conditions, new data show.

In a study of 98 consecutive nondiabetic patients with NAFLD referred to a metabolic liver clinic, the mean fasting insulin level was 14.3 microIU/mL, according to data reported at the annual meeting of the American Association of Clinical Endocrinologists.

Additionally, mean insulin levels during an oral glucose tolerance test (OGTT) exceeded the upper limit of normal from 60 minutes after glucose administration onward, with the gap increasing out to 120 minutes.

"Hyperinsulinemia and insulin resistance are already present in patients with NAFLD," commented first author Dr. Leah Folb of Weill Cornell Medical College, Houston Methodist Hospital in Texas. Intervention at this early point might help prevent progression to nonalcoholic steatohepatitis (NASH), diabetes, and cardiovascular disease, she said.

This patient population should be further evaluated, according to Dr. Folb. "Consider OGTT in all patients with persistent abnormal liver function tests if you have ruled out other causes, such as alcoholic [etiology] and hepatitis. And consider NASH FibroSure in all the patients with abnormal liver function tests and/or insulin resistance," she recommended.

The investigators are establishing a registry to follow such patients longitudinally and determine the natural history of insulin resistance. "We want to assess the response to interventions such as pioglitazone [Actos] and vitamin E based on the PIVENS study [Pioglitazone or Vitamin E for NASH Study]," she added.

Session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, Boston, said the findings were "not surprising," as previous studies, especially by investigators in Finland, have shown that higher liver fat content is associated with insulin resistance.

This new study "adds to our understanding that NAFLD is associated with insulin resistance and metabolic abnormalities," he commented in an interview. "We should be treating, and probably the best way to treat this is by dietary restriction and weight loss and lifestyle modifications."

Explaining the study’s rationale, Dr. Folb noted that the risk of cardiovascular death increases with simple steatosis and increases further still with the more advanced NASH. "We’re thinking that insulin resistance and maybe hyperinsulinemia may be the link here," she said.

On average, the patients studied had a body mass index of 30 kg/m², triglyceride level of 149 mg/dL, and HDL cholesterol level of 47 mg/dL. Results of NASH FibroSure testing showed that their mean fibroscore was 0.25 and their mean steatosis score was 0.60.

Fully 40% of the patients overall (48% of women and 28% of men) had prediabetes, Dr. Folb reported.

Analyses showed positive correlations of steatosis score with BMI (P less than .0001); of steatosis score with hemoglobin A_1c (P = .003); of beta-cell function, as ascertained from HOMA-B, with BMI (P = .01); and of insulin resistance, as ascertained from HOMA-IR, with BMI (P = .02).

Dr. Folb disclosed no relevant conflicts of interest.

LAS VEGAS – Nondiabetic patients with nonalcoholic fatty liver disease already have insulin perturbations putting them on track for a variety of more serious health conditions, new data show.

In a study of 98 consecutive nondiabetic patients with NAFLD referred to a metabolic liver clinic, the mean fasting insulin level was 14.3 microIU/mL, according to data reported at the annual meeting of the American Association of Clinical Endocrinologists.

Additionally, mean insulin levels during an oral glucose tolerance test (OGTT) exceeded the upper limit of normal from 60 minutes after glucose administration onward, with the gap increasing out to 120 minutes.

"Hyperinsulinemia and insulin resistance are already present in patients with NAFLD," commented first author Dr. Leah Folb of Weill Cornell Medical College, Houston Methodist Hospital in Texas. Intervention at this early point might help prevent progression to nonalcoholic steatohepatitis (NASH), diabetes, and cardiovascular disease, she said.

This patient population should be further evaluated, according to Dr. Folb. "Consider OGTT in all patients with persistent abnormal liver function tests if you have ruled out other causes, such as alcoholic [etiology] and hepatitis. And consider NASH FibroSure in all the patients with abnormal liver function tests and/or insulin resistance," she recommended.

The investigators are establishing a registry to follow such patients longitudinally and determine the natural history of insulin resistance. "We want to assess the response to interventions such as pioglitazone [Actos] and vitamin E based on the PIVENS study [Pioglitazone or Vitamin E for NASH Study]," she added.

Session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, Boston, said the findings were "not surprising," as previous studies, especially by investigators in Finland, have shown that higher liver fat content is associated with insulin resistance.

This new study "adds to our understanding that NAFLD is associated with insulin resistance and metabolic abnormalities," he commented in an interview. "We should be treating, and probably the best way to treat this is by dietary restriction and weight loss and lifestyle modifications."

Explaining the study’s rationale, Dr. Folb noted that the risk of cardiovascular death increases with simple steatosis and increases further still with the more advanced NASH. "We’re thinking that insulin resistance and maybe hyperinsulinemia may be the link here," she said.

On average, the patients studied had a body mass index of 30 kg/m², triglyceride level of 149 mg/dL, and HDL cholesterol level of 47 mg/dL. Results of NASH FibroSure testing showed that their mean fibroscore was 0.25 and their mean steatosis score was 0.60.

Fully 40% of the patients overall (48% of women and 28% of men) had prediabetes, Dr. Folb reported.

Analyses showed positive correlations of steatosis score with BMI (P less than .0001); of steatosis score with hemoglobin A_1c (P = .003); of beta-cell function, as ascertained from HOMA-B, with BMI (P = .01); and of insulin resistance, as ascertained from HOMA-IR, with BMI (P = .02).

Dr. Folb disclosed no relevant conflicts of interest.

LAS VEGAS – Nondiabetic patients with nonalcoholic fatty liver disease already have insulin perturbations putting them on track for a variety of more serious health conditions, new data show.

In a study of 98 consecutive nondiabetic patients with NAFLD referred to a metabolic liver clinic, the mean fasting insulin level was 14.3 microIU/mL, according to data reported at the annual meeting of the American Association of Clinical Endocrinologists.

Additionally, mean insulin levels during an oral glucose tolerance test (OGTT) exceeded the upper limit of normal from 60 minutes after glucose administration onward, with the gap increasing out to 120 minutes.

"Hyperinsulinemia and insulin resistance are already present in patients with NAFLD," commented first author Dr. Leah Folb of Weill Cornell Medical College, Houston Methodist Hospital in Texas. Intervention at this early point might help prevent progression to nonalcoholic steatohepatitis (NASH), diabetes, and cardiovascular disease, she said.

This patient population should be further evaluated, according to Dr. Folb. "Consider OGTT in all patients with persistent abnormal liver function tests if you have ruled out other causes, such as alcoholic [etiology] and hepatitis. And consider NASH FibroSure in all the patients with abnormal liver function tests and/or insulin resistance," she recommended.

The investigators are establishing a registry to follow such patients longitudinally and determine the natural history of insulin resistance. "We want to assess the response to interventions such as pioglitazone [Actos] and vitamin E based on the PIVENS study [Pioglitazone or Vitamin E for NASH Study]," she added.

Session comoderator Dr. Edward S. Horton, vice president and director of clinical research at the Joslin Diabetes Center and professor of medicine at Harvard Medical School, Boston, said the findings were "not surprising," as previous studies, especially by investigators in Finland, have shown that higher liver fat content is associated with insulin resistance.

This new study "adds to our understanding that NAFLD is associated with insulin resistance and metabolic abnormalities," he commented in an interview. "We should be treating, and probably the best way to treat this is by dietary restriction and weight loss and lifestyle modifications."

Explaining the study’s rationale, Dr. Folb noted that the risk of cardiovascular death increases with simple steatosis and increases further still with the more advanced NASH. "We’re thinking that insulin resistance and maybe hyperinsulinemia may be the link here," she said.

On average, the patients studied had a body mass index of 30 kg/m², triglyceride level of 149 mg/dL, and HDL cholesterol level of 47 mg/dL. Results of NASH FibroSure testing showed that their mean fibroscore was 0.25 and their mean steatosis score was 0.60.

Fully 40% of the patients overall (48% of women and 28% of men) had prediabetes, Dr. Folb reported.

Analyses showed positive correlations of steatosis score with BMI (P less than .0001); of steatosis score with hemoglobin A_1c (P = .003); of beta-cell function, as ascertained from HOMA-B, with BMI (P = .01); and of insulin resistance, as ascertained from HOMA-IR, with BMI (P = .02).

Dr. Folb disclosed no relevant conflicts of interest.