Effects of acute starvation on insulin resistance in obese patients with and without type 2 diabetes mellitus

Background & Aims Starvation decreases insulin sensitivity and glucose tolerance in both lean and obese (OB) non-diabetic subjects. Influence of drastic calorie reduction on insulin resistance in patient with type 2 diabetes (T2DM) is not known. Methods We enrolled 10 T2DM (diabetes duration 11.1±7.9 years) and 10 OB age and weight-matched subjects and performed isoglycaemic hyperinsulinaemic clamp (two 120 min phases of 60 and 120 mIU min−1 m−2 i.v. insulin) with indirect calorimetry at baseline and after 60 h of fasting. Results After starvation insulin-mediated glucose disposal decreased significantly in both hyperinsulinaemic phases in T2DM (phase 1: from 46±28 to 33±17, P<0.04; phase 2 from 122±47 to 80±30 μg kg−1 min−1, P<0.01) as well as in OB (phase 1: from 94±52 to 52±24, P<0.04; phase 2: from 131±46 to 106±43 μg kg−1 min, P<0.01). Both oxidative and non-oxidative components of glucose disposal tended to be reduced after fasting. A change of insulin sensitivity was found to be highly dependent upon pre-starvation conditions: more insulin resistant subjects tended to maintain (or modestly improve) insulin resistance whilst subjects with better insulin sensitivity tended to worse it. Conclusion Insulin sensitivity worsens similarly in both T2DM and OB subjects during 60-h fast. The change is probably predictable according to pre-starvation insulin sensitivity.