1828-P: Diurnal Pattern of Hepatic Insulin Extraction in Healthy and Type 2 Diabetes

Hepatic extraction of insulin is associated with insulin sensitivity in humans. It is unknown if a diurnal pattern of HE exists and if this differs between nondiabetic (ND) and type 2 diabetes (T2D) subjects. Here are data presented for 10 ND (BMI 29.4±1.3 kg/m², age 57±3 yrs) and 9 T2D subjects (BMI 33±2 kg/m², age 58±4 yrs, HbA1c 57±4 mM/mol) studied thus far. They ingested identical mixed meals (75 g carbs; 8 kcal/kg) at either breakfast (B), lunch (L) or dinner (D) in randomized Latin square order on three consecutive days with frequent sampling of plasma glucose (G), insulin (I) and C-peptide (C) concentrations. Fasting and post-meal glucose concentrations were higher while fasting and post-meal insulin, C-peptide concentrations were lower during meals in T2D as compared to ND subjects. Total and basal hepatic insulin extraction (HE and HE_b, respectively) were estimated using the Oral Insulin and C-peptide Minimal Models. Differences with B, L and D and between ND and T2D were assessed by N-way ANOVA (a p-value<0.05 was considered statistically significant). Results show that both HE and HE_b were significantly lower (p=0.009, p=0.011, respectively) throughout the day in T2D than ND subjects (Fig 1). Our initial results suggest an emerging diurnal pattern of HE in T2D subjects with D being lower than other meals. These observations provide novel insights into the diurnal pattern of hepatic extraction throughout the day in T2D subjects.

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