Secondary failure of oral hypoglycaemic agents in lean patients with Type 2 diabetes mellitus: Insulin sensitivity, insulin response to different stimuli, and the role of cyclic-AMP

A. E. Pontiroli, F. Caviezel, M. Alberetto, A. Sechhi, F. Capra, L. Bonisolli, A. Calderara, G. Pozza

Research output: Contribution to journalArticle

Abstract

The aim of this study was to evaluate the insulin (IRI) response to different stimuli and insulin sensitivity in Type 2 diabetic patients responsive to oral hypoglycaemic agents (OHA) and in Type 2 diabetic patients with secondary failure of OHA (SF), all patients being of normal body weight (relative body weight <120%), and the possible role of cyclic AMP in the reduced IRI release. SF patients, without islet cell antibodies (ICA), with hyperglycaemia lasting more than 3 months, underwent tests with i.v. tolbutamide (n = 21), i.v. glucose (n = 14), i.v. glucagon (n = 19), i.v. arginine infusion (n = 18); the arginine infusion was repeated in 12 patients during administration of aminophylline, an inhibitor of phosphodiesterase. The same tests were performed in groups of 8 to 15 OHA patients and in groups of 6 to 17 healthy subjects. During all the tests, blood glucose levels were higher in SF patients, than in OHA patients and in healthy subjects. Both SF patients and OHA patients had no IRI response to glucose; SF patients, in contrast to OHA patients, had a reduced IRI response to tolbutamide and to glucagon. The IRI response to arginine was not different in OHA, in SF patients and in healthy controls, but was significantly enhanced by aminophylline only in healthy controls. Insulin infusions (1.66 mU/Kg/min for 90 min) were performed in OHA patients and in SF patients at blood glucose levels of 150 and of 250 mg/dl: during the last 60 min, the amount of glucose metabolized (M), and the insulin sensitivity (M/I) index were greater in OHA than in SF patients. These data indicate that secondary failure of OHA in Type 2 diabetic patients of normal body weight is accompanied by reduced, but not exhausted IRI release, and by reduced insulin sensitivity. Further studies are required to elucidate whether the reduced IRI release and the reduced insulin sensitivity are secondary to hyperglycaemia or if they in fact cause hyperglycaemia. A defect of cyclic-AMP-mediated IRI release seems to be a feature of Type 2 diabetes, but not of secondary failure of oral hypoglycaemic agents.

Original languageEnglish
Pages (from-to)25-31
Number of pages7
JournalDiabete et Metabolisme
Volume18
Issue number1
Publication statusPublished - 1992

Keywords

  • aminophylline
  • arginine
  • cyclic-AMP
  • glucagon
  • insulin
  • insulin sensitivity
  • secondary failure
  • sulfonylureas
  • tolbutamide
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

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