Differential patterns of insulin secretion and sensitivity in patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease versus patients with type 2 diabetes mellitus alone

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) often coexist and have adverse outcomes. The aim of our study was to elucidate metabolic abnormalities in patients with DM-NAFLD versus those with T2DM alone. METHODS: Patients were divided into two groups: 26 T2DM patients with NAFLD and 26 gender-, age-, and body mass index-matched patients with T2DM alone. Patients took a 75-g oral glucose tolerance test (OGTT), which measured serum insulin and C-peptide (C-p) levels at baseline (0 min), 30 min, 60 min, and 120 min after glucose challenge. RESULTS: Patients with DM-NAFLD or T2DM alone had similar blood glucose levels. β-cell hypersecretion was more obvious in patients with DM-NAFLD. In addition, fasting, early-phase, and late-phase C-peptide levels were significantly increased in patients with DM-NAFLD (ΔC-p 0–30 min, P < 0.05; Area Under the Curve (AUC) C-p/PG 30–120 min ratio, P < 0.01; and AUC C-p 30–120 min, P < 0.01). Hepatic and extrahepatic insulin resistance during the OGTT did not differ significantly between groups. Hepatic insulin sensitivity independently contributed to the early phase (0–30 min) of the OGTT in patients with T2DM and NAFLD, whereas a significant deficit in late insulin secretion independently contributed to the 30–120 min glucose status in patients with T2DM only. CONCLUSIONS: In patients with similar levels of insulin resistance and hyperglycemia, DM-NAFLD was associated with higher serum insulin levels than T2DM alone. Hyperinsulinemia is caused mainly by β-cell hypersecretion. The present study demonstrates pathophysiological differences in mechanisms of insulin resistance in patients with DM-NAFLD versus T2DM alone.