Improvement in Peripheral Glucose Uptake After Gastric Bypass Surgery Is Observed Only After Substantial Weight Loss Has Occurred and Correlates with the Magnitude of Weight Lost

Department of Surgery, University of California San Francisco, San Francisco, CA, USA.
Journal of Gastrointestinal Surgery (Impact Factor: 2.8). 10/2009; 14(1):15-23. DOI: 10.1007/s11605-009-1060-y
Source: PubMed


Altered gut and pancreatic hormone secretion may bolster resolution of insulin resistance after Roux-en-Y gastric bypass (RYGB), but the independent effects of weight loss and hormonal secretion on peripheral glucose disposal are unknown.
Two groups of nondiabetic morbidly obese patients were studied: RYGB followed by standardized caloric restriction (RYGB, n = 12) or caloric restriction alone (diet, n = 10). Metabolic evaluations (euglycemic-hyperinsulinemic clamp, meal tolerance test) were done at baseline and 14 days (both groups) and 6 months after RYGB.
At baseline, body composition, fasting insulin, and glucose and peripheral glucose disposal did not differ between groups. At 14 days, excess weight loss (EWL) was similar (RYGB, 12.7% vs. diet, 10.9%; p = 0.12), fasting insulin and glucose decreased to a similar extent, and RYGB subjects had altered postmeal patterns of gut and pancreatic hormone secretion. However, peripheral glucose uptake (M value) was unchanged in both groups. Six months after RYGB, EWL was 49.7%. The changes in fasting glucose and insulin levels and gut hormone secretion persisted. M values improved significantly, and changes in M values correlated with the % EWL (r = 0.68, p = 0.02).
Improvement in peripheral glucose uptake following RYGB was observed only after substantial weight loss had occurred and correlated with the magnitude of weight lost.

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    • "Studies using the hyperinsulinemic euglycemic clamp technique to measure peripheral glucose disposal have shown that insulin sensitivity is improved after BS. This improvement seems to be in proportion to the amount of weight loss [10] [11]. Since insulin resistance occurs in different tissues, BS may have tissue-specific effects on insulin resistance. "
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    ABSTRACT: Bariatric surgery reduces weight and improves glucose metabolism in obese patients. We investigated the effects of bariatric surgery on hepatic insulin sensitivity. Twenty-three morbidly obese (nine diabetic and fourteen non-diabetic) patients and ten healthy, lean control subjects were studied using positron emission tomography to assess hepatic glucose uptake in the fasting state and during euglycemic hyperinsulinemia. Magnetic resonance spectroscopy was performed to measure liver fat content and magnetic resonance imaging to obtain liver volume. Obese patients were studied before bariatric surgery (either sleeve gastrectomy or Roux-en-Y gastric bypass) and six months after surgery. Insulin-induced hepatic glucose uptake was increased by 33% in non-diabetic and by 36% in diabetic patients at follow-up compared with at baseline, but not totally normalized. The liver fat content was reduced by 76%, liver volume by 26% and endogenous glucose production by 19% in non-diabetic patients. The respective changes in diabetic patients were 73%, 24% and 25%. Postoperatively, liver fat content and endogenous glucose production were almost normalized to lean controls, but liver volume remained greater than in control subjects. This study shows that bariatric surgery leads to a significant improvement in hepatic insulin sensitivity: insulin-stimulated hepatic glucose uptake was improved and endogenous glucose production reduced when measured, six-months, after surgery. These metabolic effects were accompanied by a marked reduction in hepatic volume and fat content. Overall, the gain in hepatic insulin sensitivity in diabetic patients was quite similar to non-diabetic patients for the same weight reduction.
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    • "Both studies compared a diet intervention with surgery in two distinct groups of obese participants, but the patients’ baseline characteristics were not well-matched. Campos et al. (15) randomized some, but not all, of a cohort of obese patients without diabetes to undergo RYGB (n = 12) or diet (n = 10). Two weeks postoperatively or after being placed on the diet, patients lost similar amounts of weight (9.9 ± 2.4 kg for RYGB patients and 8.2 ± 2.3 kg for controls). "
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    ABSTRACT: OBJECTIVE Improvements in diabetes after Roux-en-Y gastric bypass (RYGB) often occur days after surgery. Surgically induced hormonal changes and the restrictive postoperative diet are proposed mechanisms. We evaluated the contribution of caloric restriction versus surgically induced changes to glucose homeostasis in the immediate postoperative period.RESEARCH DESIGN AND METHODS Patients with type 2 diabetes planning to undergo RYGB participated in a prospective two-period study (each period involved a 10-day inpatient stay and periods were separated by a minimum of 6 weeks of wash-out) in which patients served as their own controls. The presurgery period consisted of diet alone. The postsurgery period was matched in all aspects (daily matched diet) and included RYGB surgery. Glucose measurements were performed every 4 h throughout the study. A mixed meal challenge test was performed before and after each period.RESULTSTen patients completed the study and had the following characteristics: age, 53.2 years (95% CI, 48.0-58.4); BMI, 51.2 kg/m(2) (46.1-56.4); diabetes duration, 7.4 years (4.8-10.0); and HbA1c, 8.52% (7.08-9.96). Patients lost 7.3 kg (8.1-6.5) during the presurgery period versus 4.0 kg (6.2-1.7) during the postsurgery period (P = 0.01 between periods). Daily glycemia in the presurgery period was significantly lower (1,293.58 mg/dL*day [1,096.83-1,490.33) vs. 1,478.80 mg/dL*day [1,277.47-1,680.13]) compared with the postsurgery period (P = 0.02 between periods). The improvements in the fasting and maximum poststimulation glucose and 6-h glucose area under the curve (primary outcome) were similar during both periods.CONCLUSIONS Glucose homeostasis improved in response to a reduced caloric diet, with a greater effect observed in the absence of surgery as compared with after RYGB. These findings suggest that reduced calorie ingestion can explain the marked improvement in diabetes control observed after RYGB.
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    • "This relates also to post-OP. Thus, our findings are completely in line with that of Campos et al. (9), who showed an improvement of insulin sensitivity after substantial weight loss in post-RYGB patients after 6 months, but not 2 weeks. However, the changes observed may not only be attributed to the sole loss of body fat mass but could also be related to a negative energy balance. "
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    ABSTRACT: OBJECTIVES Obesity leads to severe long-term complications and reduced life expectancy. Roux-en-Y gastric bypass (RYGB) surgery induces excessive and continuous weight loss in (morbid) obesity, although leading to several abnormal anatomical and physiological conditions.RESEARCH DESIGN AND METHODS To distinctively unveil effects of RYGB surgery on β-cell function and glucose turnover in skeletal muscle, liver, and gut, nondiabetic, morbidly obese patients were studied before (pre-OP, five female/one male, BMI: 49 ± 3 kg/m(2), 43 ± 2 years of age) and 7 ± 1 months after (post-OP, BMI: 37 ± 3 kg/m(2)) RYGB surgery, compared with matching obese (CON(ob), five female/one male, BMI: 34 ± 1 kg/m(2), 48 ± 3 years of age) and lean controls (CON(lean), five female/one male, BMI: 22 ± 0 kg/m(2), 42 ± 2 years of age). Oral glucose tolerance tests (OGTTs), hyperinsulinemic-isoglycemic clamp tests, and mechanistic mathematical modeling allowed determination of whole-body insulin sensitivity (M/I), OGTT and clamp test β-cell function, and gastrointestinal glucose absorption.RESULTSPost-OP lost (P < 0.0001) 35 ± 3 kg body weight. M/I increased after RYGB, becoming comparable to CON(ob), but remaining markedly lower than CON(lean) (P < 0.05). M/I tightly correlated (τ = -0.611, P < 0.0001) with fat mass. During OGTT, post-OP showed ≥15% reduced plasma glucose from 120 to 180 min (≤4.5 mmol/L), and 29-fold elevated active glucagon-like peptide-1 (GLP-1) dynamic area under the curves, which tightly correlated (r = 0.837, P < 0.001) with 84% increased β-cell secretion. Insulinogenic index (0-30 min) in post-OP was ≥29% greater (P < 0.04). At fasting, post-OP showed approximately halved insulin secretion (P < 0.05 vs. pre-OP). Insulin-stimulated insulin secretion in post-OP was 52% higher than before surgery, but 1-2 pmol/min(2) lower than in CON(ob)/CON(lean) (P < 0.05). Gastrointestinal glucose absorption was comparable in pre-OP and post-OP, but 9-26% lower from 40 to 90 min in post-OP than in CON(ob)/CON(lean) (P < 0.04).CONCLUSIONSRYGB surgery leads to decreased plasma glucose concentrations in the third OGTT hour and exaggerated β-cell function, for which increased GLP-1 release seems responsible, whereas gastrointestinal glucose absorption remains unchanged, but lower than in matching controls.
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