Insulin resistance is of major pathogenic importance in obese DM2 and this can be improved by weight loss. Very low calorie diets (VLCDs) are often used for this purpose. This thesis focused on the... Show moreInsulin resistance is of major pathogenic importance in obese DM2 and this can be improved by weight loss. Very low calorie diets (VLCDs) are often used for this purpose. This thesis focused on the safety and tolerability of a VLCD and on the short-term and long-term effects of a VLCD on glucose and lipid metabolism in obese DM2 on insulin therapy. Firstly, VLCDs are safe in obese DM2, even for up to 8 months. Secondly, all blood-glucose lowering therapy could be withdrawn simultaneously provided that patients still had remaining endogenous insulin secretion (fasting C-peptide >0.8 ng/ml). Thirdly, in these patients, fasting plasma glucose levels decline arter 2 days of a VLCD, due to a decrease in basal endogenous glucose production (EGP, mainly the liver), without an effect on insulin sensitivity. Fourthly, weight loss of 50% of overweight not only normalised basal EGP but also significantly improved insulin sensitivity, especially insulin-stimulated glucose disposal (mainly skeletal muscle, by 107 %). Fiftly, at the myocellular level an improvement in insulin signalling and a tendency to an increase of the glucose transporter GLUT-4 at the cell membrane was found. This is possibly due to the observed decrease in intramyocellular triglycerides. Finally, even a once-only 30-day VLCD had beneficial effects on body weight, glycaemic regulation, blood pressure and dyslipidaemia after 18 months. Show less
