Endocrine Abstracts

Aims: Glycated insulin exhibits impaired glucose-lowering ability and increasing evidence supports a role for glycation of insulin in the insulin resistant state of Type 2 diabetes. We used a novel radioimmunoassay to evaluate the effect of the insulin secretagogue nateglinide on plasma glycated insulin in Type 2 diabetes. Methods: Ten patients (5M/5F, age 57.8±1.9 years, HbA1c 7.6±0.5%, fasting plasma glucose 9.4±1.2millimols per litre, creatinine 81.6±4.5micromols per litre) received oral nateglinide 120mg or placebo in a random, single blind design, ten minutes prior to a 75g oral glucose tolerance test. Venous blood samples were taken for glucose, plasma glycated insulin (GI), insulin (I) and C-peptide over 225 minutes. Results: The patient characteristics on the nateglinide and placebo study mornings were similar (P=NS) with fasting plasma glucose (9.6±1.4;9.1±1.0 millimols per litre), GI(4.4±1.9;4.8±2.2 picomols per litre), insulin (99.8±17.7;108.9±19.8 picomols per litre), C-peptide (3.3±0.4;3.5±0.5 micrograms per litre) and GI:I ratio (0.04±0.02;0.05±0.02) concentrations respectively. Peak plasma glycated insulin concentrations of 12.7± 4.9 and 20.9±6.6 picomols per litre were measured at t10 and t5 minutes following drug ingestion, reaching basal levels of 3.2±1.6 and 5.9±2.1 picomols per litre at t70 minutes for nateglinide and placebo respectively. Total AUC measures following nateglinide and placebo respectively were: Plasma glucose (2985.6±326.4; 3270.0±307.7 millimols per litre per min P=0.005), GI(1097.9±406.3; 1764.4±506.6 picomols per litre per min, P=0.047), Insulin(106338.5.2±28896.8; 68628.6±16544.8 picomols per litre per min P=0.005), C-peptide (2075.3±212.0; 1556.7±176.4 micrograms per litre per minute, P=0.007) and GI:I ratio (4.5±1.49; 11.9±4.4, P=0.022). Conclusions: Secretion of glycated insulin is rapid with an early and late phase. Stimulation of beta-cells by nateglinide leads to a reduction in secretion of glycated insulin, probably reflecting a decrease in the storage and process time of insulin in beta-cells, which may have benefits in insulin action beyond its secretagogue activity in Type 2 diabetes.