Schmidt, Wolfgang E.

Aim Postprandial insulin pulsatility is impaired in patients with type 2 diabetes, but the effects of exogenous insulin therapy on pulsatile insulin secretion are not known. We addressed, whether pulsatile insulin secretion is related to glycaemic control, whether basal insulin supplementation increases postprandial insulin secretion, and if so, is this accomplished by a specific improvement in pulsatile insulin secretion? Methods Fourteen patients with type 2 diabetes underwent a mixed meal test before and after an 8‐week treatment period with insulin glargine. Glucose, insulin and C‐peptide levels were measured, and insulin pulsatility was determined by deconvolution analysis. Results Insulin treatment lowered fasting glycaemia from 179.6 ± 7.5 mg/dl to 117.6 ± 6.5 mg/dl (p < 0.001). Postprandial insulin and C‐peptide levels increased significantly after the treatment period (p < 0.0001). The total calculated insulin secretion rate increased with insulin treatment (p = 0.0039), with non‐significant increases in both pulsatile and non‐pulsatile insulin secretion. Insulin pulse frequency was unchanged by the intervention. There was an inverse relationship between fasting and postprandial glycaemia and insulin pulse mass ( r 2 = 0.51 and 0.56, respectively), whereas non‐pulsatile insulin secretion was unrelated to either fasting or postprandial glucose concentrations ( r 2 = 0.0073 and 0.031). Conclusions Hyperglycaemia in type 2 diabetes is associated with a reduction in postprandial insulin secretion, specifically through a reduction in insulin pulsatility. Reducing chronic hyperglycaemia by basal insulin therapy enhances endogenous β‐cell function in the postprandial state. These data support the use of basal insulin regimens in the pharmacotherapy of overtly hyperglycaemic patients with type 2 diabetes.

OBJECTIVE In patients with type 2 diabetes, glucagon levels are often increased. Furthermore, pulsatile secretion of insulin is disturbed in such patients. Whether pulsatile glucagon secretion is altered in type 2 diabetes is not known. RESEARCH DESIGN AND METHODS Twelve patients with type 2 diabetes and 13 nondiabetic individuals were examined in the fasting state and after mixed meal ingestion. Deconvolution analyses were performed on insulin and glucagon concentration time series sampled at 1-min intervals. RESULTS Both insulin and glucagon were secreted in distinct pulses, occurring at ∼5-min intervals. In patients with diabetes, postprandial insulin pulse mass was reduced by 74% (P &lt; 0.001). Glucagon concentrations were increased in the patients during fasting and after meal ingestion (P &lt; 0.05), specifically through an increased glucagon pulse mass (P &lt; 0.01). In healthy subjects, the increase in postprandial insulin levels was inversely related to respective glucagon levels (P &lt; 0.05). This relationship was absent in the fasting state and in patients with diabetes. CONCLUSIONS Glucagon and insulin are secreted in a coordinated, pulsatile manner. A plausible model is that the postprandial increase in insulin burst mass represses the corresponding glucagon pulses. Disruption of the insulin–glucagon interaction in patients with type 2 diabetes could potentially contribute to hyperglucagonemia.