Hepatic fat content and insulin action on free fatty acids and glucose metabolism rather than insulin absorption are associated with insulin requirements during insulin therapy in type 2 diabetic patients.

• DOI: 10.2337/diabetes.49.5.749
• Publication Date: 2007-03-06T19:04:22Z
• Authors: L Ryysy; A M Häkkinen; T Goto; S Vehkavaara; J Westerbacka; J Halavaara; H Yki-Järvinen
• Keywords: Carbohydrate Metabolism

To determine causes of interindividual variation in insulin requirements, we recruited 20 type 2 diabetic patients with stable glucose control and doses for >1 year on combination therapy bedtime NPH metformin. Insulin absorption (increase free total over 8 h after a subcutaneous dose regular insulin) actions intravenous (6-h 0.3 mU x kg(-1) min(-1) euglycemic clamp combined [3-3H]glucose) (glucose infusion rate required to maintain isoglycemia suppression fatty acids [FFAs]) insulin, liver fat content (proton spectroscopy), visceral (magnetic resonance imaging), weight, body composition were determined. We found the following parameters: range 10-176 U (mean 42 U, fold 17.6x) or 0.13-1.39 U/kg (0.44 U/kg, 10.7x), absorbed 10.6x, action suppress FFAs 7.5 stimulate metabolism (M value) 11.5x, weight 67-127 kg (91 kg, 1.9x), 2-28% (12%, 14x), 179-2,053 ml (1,114 ml, 11.5x). The amount absorbed, measured as either was significantly correlated its ability but not per se. were, other hand, daily (r = 0.70 FFAs, P < 0.001, r -0.61 M value, 0.005). Actions 0.82, R2 67%). Of measures adiposity, percent hepatic parameter best 0.76, 0.001). also endogenous production 0.72, conclude that major reason requirements diabetes is action. Variation may influence via an effect sensitivity insulin.