Twenty-four-hour insulin secretion rates, circulating concentrations of fuel substrates and gut incretin hormones in healthy offspring of Type II (non-insulin-dependent) diabetic parents: evidence of several aberrations

Aims/hypothesis. Insulin resistance is a common feature in relatives of pat ients with Type II (non-insulin-dependent) diabetes mellitus and abnormalit ies in beta-cell function can also exist. Insight into nonfasting carbohydr ate metabolism in these potentially prediabetic subjects relies almost excl usively on studies in which glucose is infused or ingested or both. We aime d to characterize insulin secretion and aspects of hormonal. and metabolic patterns in relatives using a physiological approach. Methods. We examined profiles of insulin, C peptide, proinsulin, gut incret in hormones and fuel substrates in 26 glucose tolerant but insulin resistan t (clamp) relatives and 17 control subjects during a 24-hour period includi ng three meals. Results. During the day plasma glucose was slightly raised in relatives (p < 0.05). Overall insulin secretion calculated on the basis of C peptide kin etics were increased in relatives (p < 0.0005) whereas incremental insulin secretion after all three meals were similar. Peak incremental insulin secr etion tended, however, to be reduced in relatives (p < 0.10). Despite consi derably increased insulin concentrations in relatives (70%, p < 0.001), ser um NEFA did not differ. Postprandial proinsulin concentrations (p < 0.05), but not proinsulin:insulin ratios, were increased in relatives. After meals concentrations of glucose-dependent-insulinotropic polypeptide (p < 0.05) were increased in relatives. Glucagon-like peptide-1 concentrations were si milar. Conclusion/interpretation. Several hormonal and metabolic aberrations are p resent in healthy relatives of Type II diabetic patients during conditions that simulate daily living. Increased concentrations of glucose-dependent-i nsulinotropic polypeptide could indicate a beta-cell receptor defect for gl ucose-dependent-insulinotropic polypeptide in the prediabetic stage of Type II diabetes. Incremental insulin secretion after mixed meals appear normal in relatives, although a trend towards diminished peak values possibly sig nifies early beta-cell dysfunction.