The studies described in this thesis explored the effects of nutritional, exercise and pharmacological interventions on ectopic triglyceride accumulation in obese patients and/or patients with type... Show moreThe studies described in this thesis explored the effects of nutritional, exercise and pharmacological interventions on ectopic triglyceride accumulation in obese patients and/or patients with type 1 or type 2 diabetes mellitus (T2DM). Ectopic fat is defined as triglyceride (TG) storage in tissues, other than adipose tissue, such as the liver, heart and skeletal muscle. The focus of this thesis is on ectopic fat accumulation in two important organs: the liver and the heart. Studies in current thesis indeed have shown that lifestyle and pharmacological interventions can change ectopic triglyceride accumulation in (advanced) T2DM and is associated with changes in function. However, the notion emerges that the different fat compartments have differential regulation in relation to exercise, nutrition and pharmacological interventions. This points to different regulatory mechanisms involved in the accumulation and/or lipolysis of these fat compartments. Alternatively, it is possible that similar mechanisms are involved but with different dose-response relationships. These cannot be derived from the studies described in the current thesis because the aims of these studies were not focussed at these mechanisms underlying the dynamics of the individual fat depots. As patients with obesity and T2DM may have different ectopic fat distribution, this may also affect their (cardiac) risk profile. Manchann et al. already studied the effect of lifestyle intervention versus antidiabetic medication in patients with different fat distribution and found that this could predict intervention failure. More studies in these dynamics will hopefully lead to understanding from which treatments specific patient groups will benefit most. Show less
Snel, M.; Sleddering, M.A.; Peijl, I.D. van der; Romijn, J.A.; Pijl, H.; Meinders, A.E.; Jazet, I.M. 2012
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
