Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids

Abstract

It has been shown in a large sample of the general population, that obesity itself represents an independent risk factor for increased mortality [1,2].Therefore, obesity and its related disorders constitute one of the most relevant health and social problems of the present era because of the high cost and disability which it imposes on the individual and the community [3][4][5].Insulin resistance is a prominent biological marker of obesity. In particular, it is a phenomenon represented by high plasma insulin levels, both in the fasting state and postprandially, and is associated with normal levels of blood glucose. In other words an obese individual needs more insulin to reach a euglycaemic state. This condition is more pronounced in obese Diabetologia (1997) Summary The aim of the present study was to measure whole body glucose uptake (M) and oxidation rate by euglycaemic hyperinsulinaemic clamp and indirect calorimetry in 7 morbidly obese subjects (BMI > 40 kg/m 2 ) at three time points: before biliopancreatic diversion (BPD) surgery (Ob); 3 months after surgery (PO I ); and after reaching stable body weight, at least 2 years after surgery (PO II ). A group of 7 control subjects (C), matched groupwise for sex, age and BMI with PO II patients, was also studied. The M value at PO I was significantly higher than at Ob (49.12 ± 8.57 vs 18.14 ± 8.57 ). Weight decreased mainly in the late postoperative period (PO I to PO II 124.28 ± 11.22 to 69.71 ± 11.78, 83 % of total decrement), rather than in the early postoperative period (Ob to PO I 135.25 ± 14.99 to 124.28 ± 11.22 kg, 17 % of total decrement). We also report the clinical case of a young woman of normal weight, who underwent BPD for chylomicronaemia (secondary to familial lipoprotein lipase deficiency), whose M value, plasma insulin and blood glucose levels were normalized upon normalization of serum NEFA and triglyceride levels as determined by the therapeutic lipid malabsorption. In conclusion, in obese diabetic patients lipid malabsorption induced by BPD causes a definite enhancement of insulin sensitivity and glucose tolerance. This improvement in metabolism is noticeable before the surgery has major effects on body weight. These observations suggest that lowered plasma lipids, rather than weight loss per se, are the cause of the reversibility of insulin resistance. [Diabetologia (1997) 40: 599-605]

Restoration of normal glucose tolerance in severely obese patients after bilio-pancreatic diversion: role of insulin sensitivity and beta cell function

“…Glucose tolerance and insulin sensitivity were significantly heightened post-surgery, even in patients who were NGT at baseline. Previous studies [4][5][6][7] have shown that bariatric surgery is extremely effective in improving glucose tolerance, insulin sensitivity and, to some extent, insulin secretion (as inferred from homeostasis model assessment estimates or the acute insulin response to i.v. glucose).…”

“…In morbidly obese patients undergoing bariatric surgery, one factor contributing to the restoration of normal glucose tolerance is the surgery-induced increase in insulin sensitivity [4][5][6][7]. Although some data are available [5,[7][8][9], the role of beta cell function, its relationship with insulin sensitivity, and the contribution of either factor to the improvement in glucose tolerance are not clearly established.…”

Circadian rhythms of GIP and GLP1 in glucose-tolerant and in type 2 diabetic patients after biliopancreatic diversion

“…We have previously demonstrated that insulin resistance and type 2 diabetes are reversible after malabsorptive bariatric surgery [16][17][18]. However, we are far from understanding the mechanisms involved.…”

Skeletal muscle triglycerides lowering is associated with net improvement of insulin sensitivity, TNF-α reduction and GLUT4 expression enhancement

“…In fact, the skeletal muscle, which represents the principal site of insulin-mediated glucose disposal, 4 shows an increased content of triglycerides in obesity. 5,6 In turn, both circulating 7 and muscle levels of triglycerides are strictly related to the whole body glucose uptake in an inverse fashion. 8 Furthermore, a marked lowering of plasma TG brough about by bariatric surgery (ie bilio-pancreatic diversion, BPD), which in all likelihood reflects the decrease of tissue TG levels, led to the reversibility of diabetes mellitus in two normal-weight young sisters with a genetic defect of lipoprotein lipase (LPL) activity and with ensuing chylomicronemia.…”