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Abstract: We examined the postprandial glucose regulators nateglinide and GLP-1, separately and in combination, in people with type 2 diabetes. Nateglinide inhibited DPP-4 activity, reduced GLP-1 degradation and enhanced its insulinotropic and blood glucose lowering effect. Combining nateglinide and GLP-1 derivatives may effectively control postprandial glycaemia. [Copyright &y& Elsevier]

Aims: Glycation of insulin has been demonstrated within pancreatic β-cells and the resulting impaired bioactivity may contribute to insulin resistance in diabetes. We used a novel radioimmunoassay to evaluate the effect of nateglinide on plasma concentrations of glycated insulin and glucose tolerance in type 2 diabetes. Methods: Ten patients (5 M/5 F, age 57.8±1.9 years, HbA1c 7.6±0.5%, fasting plasma glucose 9.4±1.2 mmol/l, creatinine 81.6±4.5 μmol/l) received oral nateglinide 120 mg or placebo, 10 min prior to 75 g oral glucose in a random, single blind, crossover design, 1 week apart. Blood samples were taken for glycated insulin, glucose, insulin and C-peptide over 225 min. Results: Plasma glucose and glycated insulin responses were reduced by 9% (P=0.005) and 38% (P=0.047), respectively, following nateglinide compared with placebo. Corresponding AUC measures for insulin and C-peptide were enhanced by 36% (P=0.005) and 25% (P=0.007) by nateglinide. Conclusions: Glycated insulin in type 2 diabetes is reduced in response to the insulin secretagogue nateglinide, resulting in preferential release of native insulin. Since glycated insulin exhibits impaired biological activity, reduced glycated insulin release may contribute to the antihyperglycaemic action of nateglinide. [Copyright &y& Elsevier]