Risk and mechanism of dexamethasone-induced deterioration of glucose tolerance in non-diabetic first-degree relatives of NIDDM patients

Diabetologia. 1997 Dec;40(12):1439-48. doi: 10.1007/s001250050847.

Abstract

We tested the hypothesis that glucose intolerance develops in genetically prone subjects when exogenous insulin resistance is induced by dexamethasone (dex) and investigated whether the steroid-induced glucose intolerance is due to impairment of beta-cell function alone and/or insulin resistance. Oral glucose tolerance (OGTT) and intravenous glucose tolerance tests with minimal model analysis were performed before and following 5 days of dex treatment (4 mg/day) in 20 relatives of non-insulin-dependent diabetic (NIDDM) patients and in 20 matched control subjects (age: 29.6 +/- 1.7 vs 29.6 +/- 1.6 years, BMI: 25.1 +/- 1.0 vs 25.1 +/- 0.9 kg/m2). Before dex, glucose tolerance was similar in both groups (2-h plasma glucose concentration (PG): 5.5 +/- 0.2 [range: 3.2-7.0] vs 5.5 +/- 0.2 [3.7-7.4] mmol/l). Although insulin sensitivity (Si) was significantly lower in the relatives before dex, insulin sensitivity was reduced to a similar level during dex in both the relatives and control subjects (0.30 +/- 0.04 vs 0.34 +/- 0.04 10(-4) min(-1) per pmol/l, NS). During dex, the variation in the OGTT 2-h PG was greater in the relatives (8.5 +/- 0.7 [3.9-17.0] vs 7.5 +/- 0.3 [5.7-9.8] mmol/l, F-test p < 0.05) which, by inspection of the data, was caused by seven relatives with a higher PG than the maximal value seen in the control subjects (9.8 mmol/l). These "hyperglycaemic" relatives had diminished first phase insulin secretion (O1) both before and during dex compared with the "normal" relatives and the control subjects (pre-dex O1: 12.6 +/- 3.6 vs 26.4 +/- 4.2 and 24.6 +/- 3.6 (p < 0.05), post-dex O1: 22.2 +/- 6.6 vs 48.0 +/- 7.2 and 46.2 +/- 6.6 respectively (p < 0.05) pmol x l(-1) x min(-1) per mg/dl). However, Si was similar in "hyperglycaemic" and "normal" relatives before dex (0.65 +/- 0.10 vs 0.54 +/- 0.10 10(-4) x min(-1) per pmol/l) and suppressed similarly during dex (0.30 +/- 0.07 vs 0.30 +/- 0.06 10(-4) x min(-1) per pmol/l). Multiple regression analysis confirmed the unique importance of low pre-dex beta-cell function to subsequent development of high 2-h post-dex OGTT plasma glucose levels (R2 = 0.56). In conclusion, exogenous induced insulin resistance by dex will induce impaired or diabetic glucose tolerance in those genetic relatives of NIDDM patients who have impaired beta-cell function (retrospectively) prior to dex exposure. These subjects are therefore unable to enhance their beta-cell response in order to match the dex-induced insulin resistant state.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / metabolism
  • C-Peptide / blood
  • Cholesterol, HDL / blood
  • Dexamethasone*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Glucose Intolerance*
  • Glucose Tolerance Test
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Male
  • Risk Factors

Substances

  • Blood Glucose
  • C-Peptide
  • Cholesterol, HDL
  • Insulin
  • Dexamethasone