EYES2019 7th ESE Young Endocrinologists and Scientists (EYES) Meeting Oral Presentations (67 abstracts)
Objective: Insulin clearance can be lower in longstanding insulin-resistant states, whereas hepatic insulin kinetics are not yet clear in newly diagnosed diabetes mellitus.
Methods: Volunteers with type 1 (T1D; n=276, 66% male) or type 2 diabetes (T2D; n=451, 69%) and glucose-tolerant humans (CON; n=143, 65%) underwent hyperinsulinemic-euglycemic clamps to assess whole-body insulin sensitivity (M-value) and whole-body insulin clearance (ICWBIC, ml*kg−1*min−1). Hepatic insulin clearance was calculated from the areas under the curve of plasma C-peptide and insulin during intravenous glucose tolerance (ICIVGTT, 060 min) and mixed-meal tolerance tests (ICMMT, 0180 min). Hepatocellular lipid content (HCL) was measured by 1H-magnetic resonance spectroscopy. Analyses were adjusted for age, sex and BMI.
Results: Compared to T2D and CON, T1D had a lower ICIVGTT (7.9±5.4 vs. 10.6±3.6 and 10.7±3.1, all P < 0.05) as well as ICMMT (5.9±2.8 vs. 9.9±31.4 and 8.6±2.3, all P < 0.05), which in turn correlated negatively with HbA1c (r=−0.234 and r=−0.029, both P < 0.05). In T2D, ICIVGTT was positively correlated with M-value (r=0.379, P < 0.05). T2D patients with hepatic steatosis (n=76) had 8% and 7% lower ICWBIC and ICIVGTT (both P < 0.05) compared to T2D without (n=56). CON with steatosis (n=21) showed a trend towards impaired ICWBIC (P=0.059) than those without (n=94). ICMMT positively correlated with M-value (r=0.289 and r=0.272, both P < 0.05) in T1D and T2D, but not in CON.
Conclusion: Glycemic control impairs insulin clearance in T1D patients, whereas steatosis reduces clearance in T2D suggesting different compensatory mechanisms of insulin kinetics.