ObjectiveThis report documents that the gastric bypass operation provides long-term control for obesity and diabetes. Summary Background DataObesity and diabetes, both notoriously resistant to medical therapy, continue to be two of our most common and serious diseases. MethodsOver the last 14 years, 608 morbidly obese patients underwent gastric bypass, an operation that restricts caloric intake by (1) reducing the functional stomach to approximately 30 mL, (2) delaying gastric emptying with a c. 0.8 to 1.0 cm gastric outlet, and (3) excluding foregut with a 40 to 60 cm Roux-en-Y gastrojejunostomy. Even though many of the patients were seriously ill, the operation was performed with a perioperative mortality and complication rate of 1.5% and 8.5%, respectively. Seventeen of the 608 patients (<3%) were lost to follow-up. ResultsGastric bypass provides durable weight control. Weights fell from a preoperative mean of 304.4 lb (range, 198 The operation provides long-term control of non-insulin-dependent diabetes mellitus (NIDDM). In those patients with adequate follow-up, 121 of 146 patients (82.9%) with NIDDM and 150 of 152 patients (98.7%) with glucose impairment maintained normal levels of plasma glucose, glycosylated hemoglobin, and insulin. These antidiabetic effects appear to be due primarily to a reduction in caloric intake, suggesting that insulin resistance is a secondary protective effect rather than the initial lesion. In addition to the control of weight and NIDDM, gastric bypass also corrected or alleviated a number of other comorbidities of obesity, including hypertension, sleep apnea, cardiopulmonary failure, arthritis, and infertility. 339

; 10.1152/ajpendo.00416.2001.-The purpose of this study was to test the hypothesis that muscle fiber type is related to obesity. Fiber type was compared 1) in lean and obese women, 2) in Caucasian (C) and African-American (AA) women, and 3) in obese individuals who lost weight after gastric bypass surgery. When lean (body mass index 24.0 Ϯ 0.9 kg/m 2 , n ϭ 28) and obese (34.8 Ϯ 0.9 kg/m 2 , n ϭ 25) women were compared, there were significant (P Ͻ 0.05) differences in muscle fiber type. The obese women possessed fewer type I (41.5 Ϯ 1.8 vs. 54.6 Ϯ 1.8%) and more type IIb (25.1 Ϯ 1.5 vs. 14.4 Ϯ 1.5%) fibers than the lean women. When ethnicity was accounted for, the percentage of type IIb fibers in obese AA was significantly higher than in obese C (31.0 Ϯ 2.4% vs. 19.2 Ϯ 1.9%); fewer type I fibers were also found in obese AA (34.5 Ϯ 2.8% vs. 48.6 Ϯ 2.2%). These data are consistent with the higher incidence of obesity and greater weight gain reported in AA women. With weight loss intervention, there was a positive relationship (r ϭ 0.72, P Ͻ 0.005) between the percentage of excess weight loss and the percentage of type I fibers in morbidly obese patients. These findings indicate that there is a relationship between muscle fiber type and obesity. adiposity; African-American; insulin resistance; morbid obesity; skeletal muscle SKELETAL MUSCLE IS A HETEROGENEOUS organ consisting of different muscle fiber phenotypes. In human skeletal muscle, histochemical staining for pH-sensitive myosin ATPase activity has revealed two major classifications of fiber type, the type I and type II fibers (3,28,31). The fast-twitch, type II fibers can be broadly categorized into type IIa and type IIb fibers, although other subclasses exist (3,29,31). The type I, or slow-twitch, muscle fibers tend to be oxidative and vascularized, whereas the type IIb fibers (fast twitch) are glycolytic in nature (28, 31). The type I fibers are also insulin sensitive compared with type II muscle (8,13,17).In humans, there can be substantial heterogeneity of muscle fiber types within a given mixed muscle group. Simoneau and Bouchard (32) concluded that, in the vastus lateralis, Ն25% of the North American Caucasian population possessed either less than 35% or more than 65% type I fibers; a range of 13-98% type I fibers has been reported (31). Several factors may be linked with such variance. We have observed that obese individuals exhibit fewer type I and more type IIb muscle fibers than lean subjects (9). Other research has reported a negative relationship between adiposity and the relative percentage of type I muscle fibers (9, 21, 36) and an increased percentage of type IIb muscle fibers in patients with type 2 diabetes (9, 23), in their insulin-resistant offspring (27), and in obese subjects (18,19,21,23). Such findings make it tempting to speculate that there is a relationship between muscle fiber composition and obesity.The purpose of the current study was to test the hypothesis that muscle fiber type is related to obesity. We tested this hypothesis in...

Adiponectin is an adipocytokine that is hypothesized to be involved in the regulation of insulin action. The purpose of the present investigation was to determine whether plasma adiponectin is altered in conjunction with enhanced insulin action with exercise training. An insulin sensitivity index (SI) and fasting levels of glucose, insulin, and adiponectin were assessed before and after 6 mo of exercise training (4 days/wk for ∼45 min at 65–80% peak O2 consumption) with no loss of body mass (PRE, 91.9 ± 3.8 kg vs. POST, 91.6 ± 3.9 kg) or fat mass (PRE, 26.5 ± 1.8 kg vs. POST, 26.7 ± 2.2 kg). Insulin action significantly ( P < 0.05) improved with exercise training (SI +98%); however, plasma adiponectin concentration did not change (PRE, 6.3 ± 1.5 μg/ml vs. POST, 6.6 ± 1.8 μg/ml). In contrast, in a separate group of subjects examined before and after weight loss, there was a substantial increase in adiponectin (+281%), which was accompanied by enhanced insulin action (SI, +432%). These data suggest that adiponectin is not a contributory factor to the exercise-related improvements in insulin sensitivity.

. Skeletal muscle lipid metabolism with obesity. Am J Physiol Endocrinol Metab 284: E741-E747, 2003. First published December 27, 2002 10.1152/ajpendo.00514.2002The objectives of this study were to 1) examine skeletal muscle fatty acid oxidation in individuals with varying degrees of adiposity and 2) determine the relationship between skeletal muscle fatty acid oxidation and the accumulation of long-chain fatty acyl-CoAs. Muscle was obtained from normal-weight [n ϭ 8; body mass index (BMI) 23.8 Ϯ 0.58 kg/m 2 ], overweight/obese (n ϭ 8; BMI 30.2 Ϯ 0.81 kg/m 2 ), and extremely obese (n ϭ 8; BMI 53.8 Ϯ 3.5 kg/m 2 ) females undergoing abdominal surgery. Skeletal muscle fatty acid oxidation was assessed in intact muscle strips. Long-chain fatty acyl-CoA concentrations were measured in a separate portion of the same muscle tissue in which fatty acid oxidation was determined. Palmitate oxidation was 58 and 83% lower in skeletal muscle from extremely obese (44.9 Ϯ 5.2 nmol ⅐ g Ϫ1 ⅐ h Ϫ1 ) patients compared with normal-weight (71.0 Ϯ 5.0 nmol ⅐ g Ϫ1 ⅐ h Ϫ1 ) and overweight/obese (82.2 Ϯ 8.7 nmol ⅐ g Ϫ1 ⅐ h Ϫ1 ) patients, respectively. Palmitate oxidation was negatively (R ϭ Ϫ0.44, P ϭ 0.003) associated with BMI. Long-chain fatty acyl-CoA content was higher in both the overweight/obese and extremely obese patients compared with normal-weight patients, despite significantly lower fatty acid oxidation only in the extremely obese. No associations were observed between long-chain fatty acyl-CoA content and palmitate oxidation. These data suggest that there is a defect in skeletal muscle fatty acid oxidation with extreme obesity but not overweight/obesity and that the accumulation of intramyocellular long-chain fatty acyl-CoAs is not solely a result of reduced fatty acid oxidation.long-chain fatty acyl-coenzyme A; intramyocellular triacylglycerol; fatty acids THE PREVALENCE OF OVERWEIGHT/OBESITY and insulin resistance is continually increasing and is associated with increased risk for the development of non-insulin-dependent diabetes mellitus (NIDDM), hypertension, and cardiovascular disease (5,11,24). The cellular mechanisms responsible for insulin resistance with overweight and obesity are not yet clear. Data have shown that intramyocellular triacylglycerols (IMTG) are increased with obesity and NIDDM (14,19,21). In addition, the accumulation of IMTG is associated with skeletal muscle insulin resistance (3,13,15,19,23,28,29,31,36,39). It is believed, however, that the accumulation of IMTG is not the direct cause of the development of insulin resistance but that IMTG is an inert marker for the presence of other lipid intermediates (diacylglycerol, fatty acyl-CoAs, or ceramide, etc.), which have been directly linked to defects in insulin signaling (8,17,25,32,37).To date, the mechanism(s) responsible for the accretion of IMTG and intermediates of lipid metabolism in intact skeletal muscle are not evident. Two possibilities include an increase in lipid synthesis and/or a reduction in fatty acid oxidation, both of which may res...

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