IMPACT OF FAMILY HISTORY OF DIABETES ON THE ASSESSMENT OF BETA-CELL FUNCTION

Numerous factors impinge on beta-cell function, and include the geneti c background and insulin sensitivity of the individual. The aim of the present study was to evaluate the impact of a family history of non-i nsulin-dependent diabetes mellitus (NIDDM) on beta-cell function and t o determine whether the relationships between beta-cell function and i nsulin sensitivity and age are influenced by a family history of diabe tes. Thirty-three healthy control subjects (CON), 20 normal glucose-to lerant first-degree relatives of known NIDDM patients (REL), and 12 no ndiabetic identical twins with an identical twin with known NIDDM were studied. Insulin and C-peptide responses to an acute intravenous gluc ose (AIRS) and glucagon bolus (at euglycemia [AIR([G.GON])]) were meas ured, as well as each individual's insulin sensitivity. Fasting insuli n and C-peptide levels were similar in all groups. AIRS was significan tly reduced by 65% in the nondiabetic twins compared with the CON and REL groups, with the latter group being similar to CON, whereas for th e AIR([G.GON]), the insulin responses in the twin subjects were reduce d only by 35% compared with CON. Following stepwise (default) multiple regression analysis, three independent variables (insulin sensitivity , 23%; family history of NIDDM, 20%; and fasting glucose, 7%) were ide ntified, and these combined to fit a model for prediction of acute bet a-cell responses to glucose that yielded an R-2 (adjusted) value of 50 %. Following analysis of covariance (ANCOVA), a positive family histor y of NIDDM and insulin sensitivity but not the age of the subject were confirmed as separate factors affecting AIRS. In conclusion, in subje cts with normal or mild glucose intolerance, the individual's genetic background and insulin sensitivity are important determinants of insul in secretion. Copyright (C) 1998 by W.B. Saunders Company.