Differential Effect of Weight Loss on Insulin Resistance in Surgically Treated Obese PatientsPurpose: To compare the effects of equivalent weight loss induced by two bariatric surgical techniques on insulin action in severely obese patients. Methods: Eighteen nondiabetic patients with severe obesity (mean [± SD] body mass index: 53.5 ± 9 kg/m2) and 20 sex- and age-matched lean subjects (body mass index: 23.8 ± 3 kg/m2) underwent metabolic studies, including measurement of insulin sensitivity by the insulin clamp technique. Patients then underwent either vertical banded gastroplasty with Roux-en-Y gastric bypass or biliopancreatic diversion and were restudied at 5–6 months and again at 16–24 months postsurgery. Results: At baseline, patients were hyperinsulinemic (194 ± 47 pmol/L vs 55 ± 25 pmol/L, p < .0001), hypertriglyceridemic (1.56 ± 0.30 mmol/L vs 0.78 ± 0.32 mmol/L, p < .0001), and profoundly insulin resistant (insulin-mediated glucose disposal: 20.8 ± 4.4 µmol/min/kg fat-free mass vs 52 ± 10.1 µmol/min/kg, p < .0001) as compared with controls. Weight loss by the 2 procedures was equivalent in both amount (averaging –53 kg) and time course. In the gastric bypass group, insulin sensitivity improved (23.8 ± 6 µmol/min/kg at 5 months and 33.7 ± 11.3 µmol/min/kg at 16 months, p < .01 vs baseline and controls). In contrast, in the biliopancreatic diversion group, insulin sensitivity was normalized already at 6 months (52.5 ± 12.4 µmol/min/kg, p = .72 vs controls) and increased further at 24 months (68.7 ± 9.5 µmol/min/kg, p < .01 vs controls), despite a persistent obese phenotype (body mass index 33.2 ± 8 kg/m2). Conclusions: In surgically treated obese patients, insulin sensitivity improves in proportion to weight loss with use of predominantly restrictive procedures (gastric bypass) but is reversed completely by predominantly malabsorptive approaches (biliopancreatic diversion) long before normalization of body weight. Selective nutrient absorption and gut hormones may interact with one another in the genesis of the metabolic abnormalities of obesity. COMMENT: The Centers for Disease Control and Prevention reported that the rate of obesity doubled in the United States between 1980 and 2000, with a 44% increase in direct healthcare costs related to obesity (comparing 1993 with 2003).1 As the majority of obese patients attempting weight loss continue to fail diet and exercise programs, the number of bariatric surgeries has grown from 16,000 in the early 1990s to 103,000 in 2003.2 Surgical interventions designed to address morbid obesity can be classified into 3 categories: restrictive, malabsorptive, or a combination of restrictive and malabsorptive procedures.3 Restrictive operations such as vertical banded gastroplasty limit the volume of the stomach and promote weight loss through a decrease in appetite and control of food intake. Malabsorptive interventions include the biliopancreatic diversion (BPD), where a portion of the stomach is removed and the remaining pouch is connected to the distal end of the small intestine, completely bypassing the duodenum and jejunum. Weight loss occurs because the bulk of oral intake is routed into the colon, where little nutrient absorption takes place. Additional surgical procedures such as the Roux-en-Y gastric bypass take advantage of both restrictive and malabsorptive properties to stimulate weight loss following the anatomical modifications. In this study, Muscelli and colleagues4 examined the effects of equivalent weight loss from either vertical banded gastroplasty with a Roux-en-Y gastric bypass (a combination surgical technique that results in a predominantly restrictive weight loss) or BPD on insulin sensitivity in severely obese patients. The investigation was conducted in 2 centers in Italy, comparing 18 obese patients undergoing bariatric procedures (10 vertical banded gastroplasty with Roux-en-Y gastric bypass, 8 BPDs) with controls matched for gender and age. Neither the obese study participants nor the control arm was diabetic or hypertensive. Both patients and controls were white and had normal results reported for liver and renal function tests. Outcomes measured at baseline and during follow-up included fasting and steady-state blood glucose levels, fasting and steady-state insulin levels, serum triglyceride concentration, and glucose disposal. The study participants were 34 years of age (± 8 years) and composed of 5 men and 13 women. The details of their inclusion or exclusion criteria for study eligibility were not cited. The primary endpoints evaluated were weight loss and insulin sensitivity. Magnitude and timing of weight loss were equivalent in both gastric bypass and BPD groups (average of 53 kg); however, "weight stabilization" was believed to occur at different points postoperatively, which explains why the metabolic studies between the 2 groups were not conducted simultaneously. Insulin sensitivity normalized (a reduction of 60%) at a faster rate in the BPD group (6 months postsurgery) compared with the gastric bypass group (16 months postsurgery). The authors suspect that the difference in outcomes from the 2 procedures is related to the higher degree of lipid malabsorption in the BPD patients. This study comparing the outcomes from different bariatric techniques includes a small number of patients and is not weighted equally between genders. Because obesity contributes to a myriad of disease states, comorbidities may have been present. Although the study subjects were listed as normotensive and euglycemic, these characteristics were based on the 1993 Joint National Consensus V and the 1997 American Diabetes Association guidelines. With a large percentage of obese patients displaying hypertension and diabetes in the general population, the clinical applicability of this study sample is questionable. Furthermore, the relatively young age of the study participants does not mirror the demographics of most obese Americans. To quantitatively measure insulin sensitivity, the investigators chose to calculate glucose disposal rates that were normalized per kg of fat-free mass or per kg of body weight. Interestingly, the method to establish fat-free mass for study patients was different between the 2 groups. Those undergoing BPD had fat-free mass determined through the doubly labeled water method, and patients undergoing gastric bypass had fat-free mass calculated from electrical bioimpedance. Both techniques make assumptions to simplify data computation, and each has a significant error rate associated with it that could ultimately have skewed the normalized insulin sensitivity calculation. The relationship of adipose volume to insulin sensitivity is complex and has yet to be completely elucidated. Although the authors of this research conjecture that it is the significant fat malabsorption that occurs after BPD that leads to improved insulin sensitivity, it is likely that additional mechanisms are at play. Further investigation is needed to explore such avenues as an altered humoral component that may occur after surgical manipulation of the gastrointestinal tract.
Todd Canada, PharmD, BCNSP University of Texas MD Anderson, Houston, Texas E Muscelli, G Mingrone, S Camastra, et al. Department of Medicine, State University of Campinas, São Paulo, Brazil; Department of Medicine, Catholic University, Rome, Italy; and Department of Internal Medicine and C.N.R. Institute of Clinical Physiology, University of Pisa, Italy
Nutrition in Clinical Practice, Vol. 21, No. 1,
92-93 (2006)
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