Role of glucose and insulin resistance in development of type 2 diabetes mellitus: results of a 25-year follow-up study

Type 2 diabetes mellitus is characterised by resistance of peripheral tissues to insulin and a relative deficiency of insulin secretion. To find out which is the earliest or primary determinant of disease, we used a minimum model of glucose disposal and insulin secretion based on intravenous glucose tolerance tests to estimate insulin sensitivity (S I), glucose effectiveness (ie, insulin-independent glucose removal rate, S G), and first-phase and second-phase beta-cell responsiveness in normoglycaemic offspring of couples who both had type 2 diabetes. 155 subjects from 86 families were followed-up for 6-25 years. More than 10 years before the development of diabetes, subjects who developed the disease had lower values of both S I (mean 3·2 [SD 2·4] vs 8·1 [6·7] 10 -3 I min -1 pmol -1 insulin; p