DEPRESSED INSULIN-SECRETION IN RESPONSE TO DIFFERENT STIMULI IS A FEATURE OF SECONDARY FAILURE IN NORMAL-WEIGHT NON-INSULIN-DEPENDENT DIABETICS ON SULFONYLUREAS

Insulin secretion following metabolic stimuli (oral glucose tolerance test, mixed meal) and during a pharmacological stimulus (i.v. glibencl amide infusion), together with the hepatic glucose production in basal state were evaluated in a carefully selected group of non-obese NIDDM patients in secondary failure and a matched group of controls still r esponding to sulphonylurea compounds. In the non-responders, the C-pep tide incremental area was reduced in response to both the OGTT (82+/-1 4 vs 143+/-18 nmol . 180 min/l, p=0.015) and the standard mixed meal ( 122+/-21 vs 243+/-41 nmol . 240 min/l, p=0.017); a similar result was obtained in response to the glibenclamide test (7.8+/-1.2 vs 14.6+/-3. 2 nmol . 120 min/l, p=0.054). Hepatic glucose production was significa ntly higher in the non-responders (5.69+/-0.8 vs 2.79+/-0.76 mg . kgLB M(-1). min(-1), p=0.018). In addition, the C-peptide incremental area after the standard meal was directly correlated with the secretory res ponse to glibenclamide (r=0.578, p=0.01), and inversely correlated wit h the duration of diabetes (r=-0.412, p=0.041). In conclusion, any sti mulus (metabolic or pharmacological) was sufficient to reveal the defi cient B-cen function of this carefully selected, non-obese secondary f ailure population compared with a control group of responders. It may also be hypothesized that this deficiency is of primary importance in the onset of secondary failure itself.