Insulin resistant subjects lack islet adaptation to short-term dexamethasone-induced reduction in insulin sensitivity

To establish whether islet compensation to deterioration of insulin action depends on inherent insulin sensitivity.

We examined insulin and glucagon secretion after i.v. arginine (5 g) at fasting, 14 and greater than 25 mmol/l glucose concentrations before and after lowering of insulin sensitivity by oral dexamethasone (3 mg twice daily for 2 1/2 days) in 10 women with normal glucose tolerance, aged 58 or 59 years. Five women had high insulin sensitivity as shown by euglycaemic, hyperinsulinaemic clamp (99 +/- 12 nmol glucose.kg body weight-1.min-1/pmol insulin.l-1; means +/- SD) whereas five women had low insulin sensitivity (34 +/- 15 nmol glucose.kg body weight-1.min-1/pmol insulin.l-1).

Dexamethasone reduced insulin sensitivity in both groups. Fasting insulin concentration increased by dexamethasone in high insulin sensitivity (72 +/- 10 vs 49 +/- 9 pmol/l, p = 0.043) but not in low insulin sensitivity (148 +/- 63 vs 145 +/- 78 pmol/l) whereas the fasting glucose concentration increased in low insulin sensitivity (6.5 +/- 0.8 vs 5.8 +/- 0.6 mmol/l, p = 0.043) but not in high insulin sensitivity (5.3 +/- 0.8 vs 5.3 +/- 0.6 mmol/l). Fasting glucagon concentration was not changed. Plasma insulin concentrations after raising glucose to 14 and more than 25 mmol/l and the insulin response to arginine at more than 25 mmol/l glucose were increased by dexamethasone in high insulin sensitivity (p < 0.05) but not changed by dexamethasone in low insulin sensitivity. Furthermore, in high but not in low insulin sensitivity, dexamethasone reduced the glucagon response to arginine (p = 0.043).

The results show that adaptation in islets function to dexamethasone-induced short-term reduction in insulin sensitivity is lacking in subjects with low inherent insulin sensitivity.