| 1. |
- Guldstrand, Marie, et al.
(författare)
-
Alteration of the counterregulatory responses to insulin-induced hypoglycemia and of cognitive function after massive weight reduction in severely obese subjects
- 2003
-
Ingår i: Metabolism, Clinical and Experimental. - 1532-8600. ; 52:7, s. 900-907
-
Tidskriftsartikel (refereegranskat)abstract
- The autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis are reported as activated in excess in the morbidly obese state and, therefore, changes after weight loss can be anticipated. The aim of this study was to investigate the impact of a massive (similar to30%) weight reduction on the activation of the HPA axis and the ANS following bariatric surgery. Eight (7 women, 1 man) severely obese (125 +/- 12 kg; body mass index [BMI], 45 +/- 4 kg/m(2)) nondiabetic subjects, underwent a 3-hour hyperinsulinemic (1,034 pmol/kg/h) glucose clamp study at hypoglycemia of arterial B-glucose concentration of 3.4 mmol/L. Cognitive function was evaluated by a visuospatial computerized problem-solving test, the Perceptual Maze Test (PMT). The mean weight loss was 40 +/- 9 kg approximately 12 months postsurgery when their weight was stabilized (85 6 kg; BMI, 31 +/- 3 kg/m(2)), and insulin sensitivity improved to an average increase of 376% +/- 250% (P < .01) of initial value. Before weight reduction, all patients demonstrated brisk peak responses in glucagon, epinephrine, pancreatic polypeptide (PP), norepinephrine, and cortisol, indicative of preserved or exaggerated activation of ANS and HPA axis. In the reduced-obese state, all these responses were attenuated and most markedly so for glucagon, which was totally abolished. In contrast, the growth hormone (GH) response was increased after weight reduction. The cognitive function was clearly modified by weight reduction both during normoglycemia and hypoglycemia and was changed preferentially to a speed-preferring strategy in the reduced-obese state compared with a more accuracy preferred problem-solving process of PMT test presurgery. These results demonstrate a reduction of the glucose counterregulatory hormonal responses, increased insulin sensitivity, and perturbed cognitive function after massive weight reduction. It may be speculated on if the increased insulin sensitivity and reduced counterregulation to hypoglycemia could predispose to low plasma glucose concentrations.
|
|
| 2. |
- Guldstrand, Marie
(författare)
-
Endocrine aspects of obesity and weight reduction by bariatric surgery : with special emphasis on beta cell function
- 2003
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Severe obesity is the most predictive acquired risk factor for the development of type 2 diabetes. Bariatric surgery induces marked weight loss and reverses the diabetic state significantly. This could be explained not only by improved insulin secretion and insulin action, but also by a number of regulatory mechanisms emerging from adipose tissue, the enteroinsular axis, the hypothalamic-pituitary- adrenal (HPA) axis and the autonomic nervous system (ANS). The present research programme was set up to look into various aspects of beta cell function in obesity and to investigate the importance of hyperinsulinemia for glycaemic control and weight development. Emphasis was given to the effects of weight-reducing surgery. In studies I, IV and V, obese women were investigated before and after 30% weight reduction OR) by vertical banded gastroplasty (VBG). Reduction of hyperinsulinemia was associated with a pronounced increase in insulin sensitivity. The fall in circulating leptin was closely related to insulin levels. Increase in hepatic insulin extraction and reduction &circulating leptin, were correlated to increased concentration of insulin-l ike growth factor-binding protein-1 (IGFBP-1) (study V). These findings confirm that a reduction of chronic hyperinsulinemia has an impact on improvements in the regulation of GH/IGF-I during WR in obese subjects. The main finding in study IV, was that of a reduction of glucose counterregulatory responses after WR, consistent with a reduced activation of the vagal and the symphatoadrenergic systems. Most notably, we documented a completely abolished glucagon response. This "defect" may in itself predispose to low plasma glucose concentrations in the weight-reduced state. Cognitive function tested by a perceptual maze test during hypoglycaemic stress, showed differences within the same subjects, consistent with a speed-preferring strategy before vs. a more accuracy preferred problemsolving after WR. In studies II and III, obese women were examined before and after 15% and 25% WR respectively, and 1 and 2 years (study III) after bariatric surgery.Two different procedures were utilized, one gastric restrictive (VBG) and the other one malabsorptive, jejunoileal bypass (JIB). The inverse relationship between insulin sensitivityand insulin secretion resulted in a quantitatively more pronounced improvement in insulin sensitivity than the reduction in insulin secretion after WIZ indicating an improved beta cell function, as verified by the increment of the disposition index and by reduction in proinsulin-to-insulin ratios. The results from the enteroinsular axis showed that a high glucagon-like peptide-1 (GLP-1)and a low gastric inhibitory polypeptide (GIP) response were associated with lower insulin levels, improved glucose tolerance and maintenance of a reduced body weight. In study VI short-term treatment with oral diazoxide improved important parameters of beta cell function in 4 male and 4 female obese subjects with type 2 diabetes, indicating beneficial effects on beta cell function through relief from overstimulation. Conclusions: The improvements in carbohydrate metabolism after surgical treatment for obesity is associated with a more pronounced reduction in insulin resistance than the reduction of the hyperinsulinemia, an increase in IGFBP-1, an abolished glucagon response to hypoglycaemia and a reduced activation of the HPA-axis as well as the ANS. Beta cell rest induced by diazoxide results in improvements of parameters of beta cell function in obese type 2 diabetics. A high GLP-1 and a low GIP response to oral glucose after WR are associated with improved glucose tolerance and maintenance of reduced body weight.
|
|
| 3. |
- Guldstrand, Marie, et al.
(författare)
-
Improved beta -cell function after standardized weight reduction in severely obese subjects.
- 2003
-
Ingår i: American Journal of Physiology: Endocrinology and Metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 284:3, s. 557-565
-
Tidskriftsartikel (refereegranskat)abstract
- Islet function was examined in 13 severely obese women [body mass index 46.4 ± 5.5 (SD) kg/m2] before and after standardized 15 and 25% weight reduction (WR) instituted by bariatric surgery. The insulin response to arginine at fasting (AIR1), at 14 mmol/l, and at >25 mmol/l glucose was reduced by 37–50% after 15 and 25% WR ( P ≤ 0.05). Insulin sensitivity was determined as the amount of glucose infused to reach 14 mmol/l divided by the insulin level (M/I), a measure showing a linear correlation with insulin sensitivity during euglycemic hyperinsulinemic clamps ( r = 0.74, P < 0.001) and a hyperbolic relation to AIR1 ( r = −0.63, P < 0.001) in 169 healthy subjects. M/I was increased by 318 ± 182% after 15% ( P = 0.004) and by 489 ± 276% after 25% WR ( P = 0.007). The reduction in insulin secretion was not as large as anticipated from the increased insulin sensitivity, which resulted in an increased disposition index (DI; AIR1 × M/I). Thus DI increased by 95 ± 24% after 15% ( P = 0.018) and by 176 ± 35% after 25% WR ( P = 0.011). This improved β-cell function correlated independently with reduced glucose, triglycerides, and leptin and increased adiponectin levels and was associated with a reduced proinsulin-to-insulin ratio. In contrast, glucagon secretion was not significantly affected by WR. We conclude that WR results in improved β-cell function when related to insulin sensitivity.
|
|
