Hyperinsulinism, glucose-dependent insulinotropic polypeptide, and the enteroinsular axis in morbidly obese patients before and after gastric bypass

The role of glucose-dependent insulinotropic polypeptide (GIP) in the hyperinsulinism of morbid obesity and its correction after gastric bypass was studied in 12 morbidly obese (150 +/- 15 kg) patients. After oral glucose, significant increases in serum glucose, insulin, and GIP levels occurred both before and after gastric bypass. Compared with preoperative values, fasting concentrations and integrated incremental areas for glucose, insulin, and GIP were decreased after a 25% weight loss after gastric bypass. The hyperinsulinism of morbid obesity and its amelioration after gastric bypass may be caused by markedly elevated levels of GIP before surgery and its reduced release after bypass. Reduced release of GIP after gastric bypass may partly occur because of exclusion of ingested glucose from contact with the mucosa of the duodenum and proximal jejunum, sites with the highest concentration of GIP.     

Restoration of euglycemia and normal acute insulin response to glucose in obese subjects with type 2 diabetes following bariatric surgery

Insulin resistance and loss of glucose-stimulated acute insulin response (AIR) are the two major and earliest defects in the course of type 2 diabetes. We investigated whether weight loss after bariatric surgery in patients with morbid obesity and type 2 diabetes could restore euglycemia and normal AIR to an intravenous glucose tolerance test (IVGTT). We studied 25 morbidly obese patients-12 with type 2 diabetes, 5 with impaired glucose tolerance, and 8 with normal glucose tolerance (NGT)-before and after a biliopancreatic diversion (BPD) with Roux-en-Y gastric bypass (RYGBP). Twelve individuals with normal BMI served as control subjects. Twelve months after surgery, in the diabetes group, BMI decreased from 53.2 +/- 2.0 to 29.2 +/- 1.7 kg/m(2), fasting glucose decreased from 9.5 +/- 0.83 to 4.5 +/- 0.13 mmol/l, and fasting insulin decreased from 168.4 +/- 25.9 to 37.7 +/- 4.4 pmol/l (mean +/- SE; P < 0.001). AIR, the mean of insulin concentration at 2, 3, and 5 min over basal in the IVGTT, increased by 770 and 935% at 3 and 12 months after surgery, respectively (from 24.0 +/- 22.7 to 209 +/- 43.4 and 248 +/- 33.1 pmol/l, respectively; P < 0,001). Conversely, in the NGT group, the AIR decreased by 40.5% (from 660 +/- 60 to 393 +/- 93 pmol/l; P = 0.027) 12 months after surgery. BPD with RYGBP performed in morbidly obese patients with type 2 diabetes leads to significant weight loss, euglycemia, and normal insulin sensitivity; but most importantly, it restores a normal beta-cell AIR to glucose and a normal relationship of AIR to insulin sensitivity. This is the first study to demonstrate that the lost glucose-induced AIR in patients with type 2 diabetes of mild or moderate severity is a reversible abnormality.     

Impact of gastric restrictive surgery on hypertension in the morbidly obese.

Hypertension is a major health risk factor in patients who are morbidly obese. Two hundred eighty-nine morbidly obese patients undergoing gastric restrictive surgery were evaluated for the presence of hypertension (blood pressure greater than or equal to 160/90 mm Hg or currently undergoing antihypertensive therapy) pre- and postoperatively. Of 74 (26%) preoperatively hypertensive patients, 67 (91%) were available for follow-up. Preoperative hypertension resolved in 66% (44 of 67) of patients following gastric restrictive surgery. Superobese and morbidly obese patients had similar reductions in hypertension after surgery (69% versus 63%). Patients not receiving antihypertensives preoperatively had a greater reduction of hypertension than those medically treated preoperatively (78% versus 58%). The amount of weight loss significantly predicted the reduction of hypertension, whereas follow-up weight achieved did not. The amounts of weight loss for patients with resolved and persistent hypertension were 89.3 +/- 5.6 lbs (mean +/- standard error of the mean +ADSEM+BD) and 66.0 +/- 8.3 lbs, respectively (p less than 0.02). For patients with resolved hypertension, follow-up weights for the morbidly obese and superobese were 162.0 +/- 10.8 lbs (133% +/- 4% ideal body weight +ADIBW+BD) and 220.4 +/- 9.5 lbs (170% +/- 7% IBW). Gastric restrictive surgery is effective therapy for hypertension in morbidly obese patients. Patients need not achieve weights approaching IBW to enjoy the benefits of gastric restrictive surgery on hypertension.     

Effect of laparoscopic Roux-en Y gastric bypass on type 2 diabetes mellitus

OBJECTIVE: To evaluate pre- and postoperative clinical parameters associated with improvement of diabetes up to 4 years after laparoscopic Roux-en-Y gastric bypass (LRYGBP) in patients with type 2 diabetes mellitus (T2DM). SUMMARY BACKGROUND DATA: The surgical treatment of morbid obesity leads to dramatic improvement in the comorbidity status of most patients with T2DM. However, little is known concerning what preoperative clinical factors are associated with postoperative long-term improvement in diabetes in the morbidly obese patient with diabetes.METHODS We evaluated pre- and postoperative data, including demographics, duration of diabetes, metabolic parameters, and clinical outcomes, in all patients with impaired fasting glucose (IFG) and type T2DM undergoing LRYGBP from July 1997 to May 2002. RESULTS: During this 5-year period, 1160 patients underwent LRYGBP and 240 (21%) had IFG or T2DM. Follow up was possible in 191 of 240 patients (80%). There were 144 females (75%) with a mean preoperative age of 48 years (range, 26-67 years). After surgery, weight and body mass index decreased from 308 lbs and 50.1 kg/m2 to 211 lbs and 34 kg/m2 for a mean weight loss of 97 lbs and mean excess weight loss of 60%. Fasting plasma glucose and glycosylated hemoglobin concentrations returned to normal levels (83%) or markedly improved (17%) in all patients. A significant reduction in use of oral antidiabetic agents (80%) and insulin (79%) followed surgical treatment. Patients with the shortest duration (<5 years), the mildest form of T2DM (diet controlled), and the greatest weight loss after surgery were most likely to achieve complete resolution of T2DM. CONCLUSION: LRYGBP resulted in significant weight loss (60% percent of excess body weight loss) and resolution (83%) of T2DM. Patients with the shortest duration and mildest form of T2DM had a higher rate of T2DM resolution after surgery, suggesting that early surgical intervention is warranted to increase the likelihood of rendering patients euglycemic.     

Changes in hormones and biomarkers in polycystic ovarian syndrome treated with gastric bypass

BackgroundSmall retrospective studies have demonstrated reduction in weight and co-morbid hirsutism and diabetes in women with polycystic ovary syndrome (PCOS) treated with Roux-en-Y gastric bypass. The objective of this study was to prospectively determine clinical improvements in obese women with PCOS treated with gastric bypass and identify postoperative biomarker changes.MethodsData were collected on obese women with PCOS undergoing Roux-en-Y gastric bypass over 1 year. Testosterone, follicle stimulating hormone, lutenizing hormone, insulin, fasting glucose, and lipid levels were obtained preoperatively at baseline, and 6 and 12 months after surgery. Testosterone was used as the primary hormonal biomarker. A physical examination for body mass index (BMI) and hirsutism, and information on menstrual pattern were collected at baseline and 3, 6, and 12 months after surgery.ResultsData were available for 14 women. Mean BMI decreased from 44.8±5.9 kg/m² at baseline to 29.2±5.9 kg/m² at 12 months postoperatively. Significant improvements were seen in testosterone, fasting glucose, insulin, cholesterol, and triglyceride at 12 months (P<.05). At baseline, irregular menses were reported in 10 patients; all patients were experiencing regular menses 6 and 12 months after surgery. Hirsutism was present in 11 patients at baseline and only 7 patients at 12 months. Improvements in biomarkers, menstrual cycling, and hirsutism was not correlated with degree of weight change.ConclusionGastric bypass achieved significant reductions in BMI, testosterone, and markers of glucose and lipid metabolism. These data confirm reports of previous retrospective studies showing weight reduction and health improvement in women with PCOS treated with gastric bypass.     

Effects of Obesity Surgery on Type 2 Diabetes Mellitus Asian Patients

Background  Obesity is a major risk factor for the development of type 2 diabetes mellitus (T2DM). Surgery is the most effective treatment for morbid obesity, and it has been shown to lead to dramatic improvement in type T2DM. However, data concerning obese Asian patients have not been reported, and the mechanism of improving T2DM after bariatric surgery in this population remains speculative. Methods  From April 1997 to March 2006, 1,375 patients undergoing obesity surgery were recruited for our study of the effects of weight loss surgery on type 2 diabetes mellitus (T2DM). Laparoscopic vertical banded gastric partition (LVBG) was performed in 552 patients (40.1%), laparoscopic gastric bypass in 660 patients (48.0%), and laparoscopic adjustable gastric banding (LAGB) in 140 patients (10.2%). Another 23 patients (1.7%) received open or revision surgery. We evaluated the clinical data and effect of obesity surgery on T2DM, impaired fasting glucose (IFG) and compared the changes with those with normal fasting glucose. Results  Among all the patients, 166 (12.1%) had impaired fasting glucose (IFG) and 247 (18.0%) had T2DM. Patients with IFG or DM were significantly older, more central obese, and they had higher insulin resistance and a higher HbA1C level than those with normal fasting glucose. The mean total weight loss for the population was 28.6%, 29.1%, 28.5%, 23.8%, and 24.4% (at 1, 2, 3, 5, and 7 years after surgery). There was no increase of surgical risk in T2DM or IFG patients. One year after operation, fasting plasma glucose returned to normal in 78.5% of T2DM patients and 94.7% of IFG patients. The HbA1C level returned to under 7.0 in 81.5% of T2DM and in 100% of IFG patients. Laparoscopic gastric bypass patients had a greater weight loss and a higher rate of glucose normalization (93.1%) than the LVBG patients (85.3%) and LAGB patients (73.9%), but no difference in HbA1C normalization. Conclusions  Obesity surgery resulted in significant and sustained weight loss with a cure rate of T2DM up to 80% in morbidly obese Asian patients. Gastric bypass surgery had a better result in T2DM cure rate than LVBG and LAGB because of better weight reduction.     

Results of teenaged bariatric patients performed in an adult program

BACKGROUND: Morbid obesity is a growing epidemic among adolescents. Bariatric surgery has proven to be the only long-term effective method in treating morbidly obese adults for over a decade. The laparoscopic approach has become a popular option. This study tested the hypothesis that laparoscopic Roux-en-Y gastric bypass is a feasible option in teenaged patients with good results through an adult bariatric program. METHODS: All patients under the age of 20 at the time of surgery were included in this study. Each patient had undergone a laparoscopic Roux-en-Y gastric bypass. Charts were reviewed for preoperative evaluation, operative time, complications, and length of hospital stay. Percentage of excess body weight lost (%EBWL) was calculated at the follow-up. RESULTS: Of the 202 patients who underwent a laparoscopic gastric bypass procedure at our institution, 5 (2%) were teenagers. The mean age was 18 years (range, 17-19). The mean height was 69 inches (range, 61-75). Average weight was 323 lbs (range, 227-394). The mean preoperative body mass index was 48 kg/m2 (range, 44-56). All patients had medical and psychological clearance prior to surgery. Mean operative time was 150 minutes (range, 130-172). There were no complications in this subset of patients. All 5 patients were discharged on postoperative day 2. Follow-up ranged from 17.8 to 44.8 months. The mean %EBWL was 77% (range, 58%-88%). CONCLUSIONS: The laparoscopic gastric bypass procedure is technically feasible in teenaged patients, with excellent results even when performed in an adult bariatric program. Long-term data will be needed to determine its role in the treatment of morbidly obese adolescents.     

A new paradigm for type 2 diabetes mellitus: could it be a disease of the foregut?

SUMMARY BACKGROUND DATA: We previously reported, in a study of 608 patients, that the gastric bypass operation (GB) controls type 2 diabetes mellitus in the morbidly obese patient more effectively than any medical therapy. Further, we showed for the first time that it was possible to reduce the mortality from diabetes; GB reduced the chance of dying from 4.5% per year to 1% per year. This control of diabetes has been ascribed to the weight loss induced by the operation. These studies, in weight-stable women, were designed to determine whether weight loss was really the important factor. METHODS: Fasting plasma insulin, fasting plasma glucose, minimal model-derived insulin sensitivity and leptin levels were measured in carefully matched cohorts: six women who had undergone GB and had been stable at their lowered weight 24 to 30 months after surgery versus a control group of six women who did not undergo surgery and were similarly weight-stable. The two groups were matched in age, percentage of fat, body mass index, waist circumference, and aerobic capacity. RESULTS: Even though the two groups of patients were closely matched in weight, age, percentage of fat, and even aerobic capacity, and with both groups maintaining stable weights, the surgical group demonstrated significantly lower levels of serum leptin, fasting plasma insulin, and fasting plasma glucose compared to the control group. Similarly, minimal model-derived insulin sensitivity was significantly higher in the surgical group. Finally, self-reported food intake was significantly lower in the surgical group. CONCLUSIONS: Weight loss is not the reason why GB controls diabetes mellitus. Instead, bypassing the foregut and reducing food intake produce the profound long-term alterations in glucose metabolism and insulin action. These findings suggest that our current paradigms of type 2 diabetes mellitus deserve review. The critical lesion may lie in abnormal signals from the gut.     

Improvement of Insulin Resistance After Obesity Surgery: A Comparison of Gastric Banding and Bypass Procedures

BACKGROUND: Obesity is a major risk factor for the development of type 2 diabetes mellitus (T2DM). Insulin resistance (IR) is considered the pathologic link between T2DM and obesity. The mechanism in improving T2DM after bariatric surgery remains speculative. This trial assessed the effect of duodenal jejunal exclusion on the resolution of IR in gastric banding and gastric bypass procedures. METHODS: 660 patients with complete biochemical and clinical data at baseline and at 3 years were selected for analysis. There were 197 males and 463 females. The mean age was 31.5 years (18-64) and mean BMI was 41.4 (32-77). There were 544 patients who received laparoscopic gastric bypass, and 116 patients received laparoscopic gastric banding. IR was measured by homeostatic model assessment (HOMA) index (HI), that can be calculated as HI = plasma glucose (mmol/l) x insulin (UI/ml)/22.5. HI was measured before surgery and 1, 3, 6, 12, 24, and 36 months after surgery. RESULTS: Of the 660 individuals, 517 (78.4%) had IR. The mean HI was 7.62 +/- 13.13. The HI was correlated with BMI, waist circumference, insulin resistance, hyperlipidemia, inflammatory indicators, and abnormal liver enzymes. Before surgery, the HI was 7.92 +/- 14.18 for the bypass group and 6.27 +/- 6.47 for the banding group. After surgery, the HI began to lower in both groups, and this reduction was maintained during follow-up. At 36 months after surgery, mean percentage of excess weight loss (%EWL) was 70.5% for the bypass group and 41.9% for the banding group. The HI was 1.00 +/- 0.79 for bypass and 1.51 +/- 1.25 for banding. The bypass patients had a better and faster weight reduction, but the HI was similar between the two groups at the same weight reduction percentage. CONCLUSION: IR is common in morbidly obese patients. Both gastric banding and gastric bypass are effective for the reverse of IR in these patients. It seems that the effect is related to the absolute weight loss rather than different surgical procedures. There is no duodenal jejunal exclusion effect on IR resolution was observed in this study.     

Influence of obesity, impaired glucose tolerance, and NIDDM on LDL structure and composition. Possible link between hyperinsulinemia and atherosclerosis

The possible causes of the enhanced risk for coronary heart disease (CHD) were examined in morbidly obese women with normoglycemia, impaired glucose tolerance (IGT), and non-insulin-dependent diabetes mellitus (NIDDM) before and after gastric bypass surgery. Compared with age-matched lean women, plasma lipid and apolipoprotein concentrations of the obese women before surgery favored atherogenesis. The risk for CHD may further be exacerbated in the IGT and NIDDM groups by the prevalence of smaller and denser low-density-lipoprotein (LDL) particles. LDL size correlated negatively with plasma insulin levels independent of triglyceride levels, age, or body mass index (BMI). After surgery, BMI, plasma insulin, and triglyceride levels decreased, but LDL size increased, and LDL density decreased. Neither cholesterol nor LDL cholesterol levels were affected after surgery, but high-density-lipoprotein cholesterol was increased in all patients after surgery. Although the mechanisms underlying the changes in the properties of LDL could not be determined from this study, these changes appear to be of benefit in reducing CHD risk in these patients.     

Outcome Following Bariatric Surgery in Super versus Morbidly Obese Patients: Does Weight Matter?

Background: Numerous investigators have attempted to identify prognostic indicators for successful outcome following bariatric surgery. The purpose of this study was to determine whether degree of obesity affects outcome in super obese [>225% ideal body weight (IBW)] versus morbidly obese patients (160-225% IBW) undergoing gastric restrictive/bypass procedures. Methods: Since 1984, 157 patients underwent either gastric bypass or vertical banded gastroplasty. Super obese (78) and morbidly obese (79) patients were followed prospectively, documenting outcome and complications. Results: Super obese patients reached maximum weight loss 3 years following bariatric surgery, exhibiting a decrease in body mass index (BMI) from 61 to 39 kg/m² and an average loss of 42% excess body weight (EBW). Morbidly obese patients had a decrease in BMI from 44 to 31 kg/m² and carried 39% EBW at 1 year. After their respective nadirs, each group began to regain the lost weight with the super obese exhibiting a current BMI of 45 kg/m² (61% EBW) versus 34 kg/m² (52% EBW) in the morbidly obese at 72 months cumulative follow-up. Currently, loss of 50% or more of EBW occurred in 53% of super obese patients versus 72% of morbidly obese (P < 0.01). Twenty-six percent of super obese patients returned to within 50% of ideal body weight (IBW) while 71% of morbidly obese were able to reach this goal (P < 0.01). Co-morbidities and complications related to surgery were similar in each group. Conclusions: Super obese patients have a greater absolute weight loss after bariatric surgery than do morbidly obese patients. Using commonly utilized measures of success based on weight, morbidly obese patients tend to have better outcomes following bariatric surgery.     

Is roux-en-y gastric bypass surgery the most effective treatment for type 2 diabetes mellitus in morbidly obese patients?

Type 2 diabetes mellitus (T2DM) has a very strong association with obesity. The aim of our study was to analyze the effects of Roux-en-Y gastric bypass (RYGB) surgery on the glucose metabolism in morbidly obese patients with T2DM. Morbidly obese patients (n = 117) with T2DM underwent measurements of fasting serum glucose and glycosylated hemoglobin (HbA1C) at baseline, 6 months, and 12 months after laparoscopic RYGB surgery. Logistic regression was used in both univariate and multivariate modeling to identify independent variables associated with complete resolution of T2DM. Twelve months after surgery, fasting plasma glucose decreased from a preoperative mean of 164 ± 55 mg/dL to 101 ± 38 mg/dL (P = .001) and HbA1C decreased from a preoperative mean of 7.7% ±1.5% to 6.0% ± 1.1% (P = .001). Resolution of T2DM was achieved in 72 patients (74%). All of the remaining 25 patients decreased the daily medication requirements. On univariate analysis, preoperative variables associated with resolution of T2DM were waist circumference, HbA1C, and absence of insulin treatment. Waist circumference (odds ratio 2.4; 95% confidence interval 1.4- 4.1; P = .001) and treatment without insulin (odds ratio 42.2; 95% confidence interval 4.3-417.3; P = .002) remained significant predictors of T2DM resolution in the multivariate logistic regression model after adjusting for covariates. Laparoscopic RYGBP resulted in significant resolution of T2DM. Peripheral fat distribution (smaller waist circumference) and absence of insulin treatment were independent and significant predictors of complete resolution of T2DM. Presented at the plenary session of the Forty-Sixth Annual Meeting of The Society for Surgery of the Alimentary Tract, Chicago, Illinois, May 19, 2005 Dr. Torquati is supported by the Vanderbilt Clinical Research Award (NIH-K12RR017697-03).     

Comment on: Physical function improvements after laparoscopic Roux-en-Y gastric bypass surgery

BackgroundObesity is a risk factor for impaired physical function and disability, with the degree of impairment most compromised in extreme obesity. Mild-to-moderate weight loss has been shown to improve function in older adults. The impact of laparoscopic Roux-en-Y gastric bypass surgery on weight loss and physical function in morbidly obese individuals was assessed.MethodsThis longitudinal, observational study followed up 28 morbidly obese men and women (body mass index ≥40.0 kg/m²) for 12 months after laparoscopic Roux-en-Y gastric bypass. Physical function (self-report using the Fitness Arthritis and Seniors Trial disability questionnaire; performance tasks using the Short Physical Performance Battery and a lateral mobility task); strength (maximal isometric knee torque); and body composition measured using bioelectrical impedance were determined before surgery (baseline) and at 3 weeks, 3 months, 6 months, and 12 months after surgery.ResultsThe 12-month weight loss was 34.2% (excess weight loss 59.8%), with a mean fat mass loss of 46 kg and a loss of fat free mass of 6.6 kg. The performance tasks and self-reported questionnaire scores had improved by 3 months after surgery compared with baseline, with selected measures showing less impairment and disability in as few as 3 weeks after surgery. Muscle quality, as measured using the maximal torque per kilogram body weight, was greater at 6 months than at baseline.ConclusionThe results of our study have shown that in morbidly obese individuals with a high risk of mobility impairments, surgical procedures to reduce body weight increase mobility and improve performance of daily activities in as few as 3 weeks after gastric bypass surgery.     

Is type II diabetes mellitus (NIDDM) a surgical disease?

Since February 1, 1980, 515 morbidly obese patients have undergone the Greenville gastric bypass (GGB) operation. Of these, 212 (41.2%) were euglycemic, 288 (55.9%) were either diabetic or had glucose intolerance, and 15 (2.9%) were unable to complete the evaluation. After the operation, only 30 (5.8%) patients remained diabetic (and 20 of these improved), 457 (88.7%) became and have remained euglycemic, and inadequate data prevented classification of the other 28 (5.4%). The patients who failed to return to normal glucose values were older and their diabetes was of longer duration than those who did. The effect of the GGB was not only limited to the correction of abnormal glucose levels. The GGB also corrected the abnormal levels of fasting insulin and glycosylated hemoglobin in a cohort of 52 consecutive severely obese patients with non-insulin-dependent diabetes. The GGB effectively controls weight. If morbid obesity is defined as 100 pounds over ideal body weight, 89% of the patients are no longer "morbidly" obese within 2 years. In most patients, the control of the weight has been well maintained during the 11 years of follow-up; most of the upward creep in weight of 20.8% between 24 and 132 months was from the 49 (9.5%) patients who had staple line breakdowns between the large and small gastric pouches. Non-insulin-dependent diabetes, previously considered a chronic unrelenting disease, can be controlled in the severely obese by the gastric bypass. Whether the correction of glucose metabolism affects the complications of diabetes is unknown. Whether the gastric bypass should be considered for patients with advanced non-insulin-dependent diabetes but who are not severely obese deserves consideration. The GGB has an unacceptably high rate of staple line failure. Accordingly, the authors have recently changed their procedure to one that divides the stomach rather than partitions it with staples.     

Weight gain after short- and long-limb gastric bypass in patients followed for longer than 10 years

OBJECTIVE: To complete a long-term (>10 years) follow-up of patients undergoing isolated roux-en-Y gastric bypass for severe obesity. BACKGROUND: Long-term results of gastric bypass in patients followed for longer than 10 years is not reported in the literature. METHODS: Accurate weights were recorded on 228 of 272 (83.8%) of patients at a mean of 11.4 years (range, 4.7-14.9 years) after surgery. Results were documented on an individual basis for both long- and short-limb gastric bypass and compared with results at the nadir BMI and % excess weight loss (%EWL) at 5 years and >10 years post surgery. RESULTS: There was a significant (P < 0.0001) increase in BMI in both morbidly obese (BMI < 50 kg/m) and super obese patients (BMI > 50 kg/m) from the nadir to 5 years and from 5 to 10 years. The super obese lost more rapidly from time zero and gained more rapidly after reaching the lowest weight at approximately 2 years than the morbidly obese patients. There was no difference in results between the long- and short-limb operations. There was a significant increase in failures and decrease in excellent results at 10 years when compared with 5 years. The failure rate when all patients are followed for at least 10 years was 20.4% for morbidly obese patients and 34.9% for super obese patients. CONCLUSIONS: The gastric bypass limb length does not impact long-term weight loss. Significant weight gain occurs continuously in patients after reaching the nadir weight following gastric bypass. Despite this weight gain, the long-term mortality remains low at 3.1%.     

Entero-endocrine changes after gastric bypass in diabetic and nondiabetic patients: a preliminary study

INTRODUCTION: Alterations in entero-endocrine signaling may play a role in improvements in satiety and glucose tolerance after Roux-en-Y gastric bypass (RYGB). We report our findings of gut hormone secretion in a cohort of diabetic and nondiabetic morbidly obese patients. MATERIALS AND METHODS: Ten morbidly obese subjects who underwent uncomplicated RYGB were studied: 5 were diabetic and 9 were female. Nonfasting plasma levels of glucagon-like peptide-1 (GLP-1), insulin, desacyl ghrelin, active ghrelin, neuropeptide Y (NPY), and gastric inhibitory polypeptide (GIP) were determined preoperatively and 6 months postoperatively. RESULTS: Mean patient age was 42 +/- 11 years, and the mean preoperative body mass index was 50 +/- 6 kg/m(2). At 6 months mean BMI fell to 33 +/- 5 kg/m(2) (P < 0.0001), and there were no differences between diabetics and nondiabetics with respect to amount of weight loss. In non-diabetics, compared to preoperative levels, there were significant increases in GLP-1 and desacyl-ghrelin in the nondiabetic patients (P = 0.046 and P = 0.016, respectively); no change in plasma insulin, active ghrelin, NPY, or GIP was demonstrated. In contrast, when compared to preoperative levels, there were no significant changes in entero-endocrine hormone levels in the diabetic cohort postoperatively. CONCLUSIONS: At 6 months postoperation, RYGB significantly alters the hormone levels for GLP-1 and desacyl-ghrelin in morbidly obese nondiabetic patients. No significant change was noted in a matched cohort of diabetic patients. Weight loss was similar in diabetics and nondiabetics, suggesting that GLP-1 and ghrelin are not the only mechanisms producing weight loss after RYGB.     

Changes in Insulin Resistance Following Bariatric Surgery: Role of Caloric Restriction and Weight Loss

The prevalence of type 2 diabetes mellitus (T2DM) and obesity in the western world is steadily increasing. Bariatric surgery is an effective treatment of T2DM in obese patients. The mechanism by which weight loss surgery improves glucose metabolism and insulin resistance remains controversial. In this review, we propose that two mechanisms participate in the improvement of glucose metabolism and insulin resistance observed following weight loss and bariatric surgery: caloric restriction and weight loss. Nutrients modulate insulin secretion through the entero-insular axis. Fat mass participates in glucose metabolism through the release of adipocytokines. T2DM improves after restrictive and bypass procedures, and combinations of restrictive and bypass procedures in morbidly obese patients. Restrictive procedures decrease caloric and nutrient intake, decreasing the stimulation of the entero-insular axis. Gastric bypass (GBP) operations may also affect the entero-insular axis by diverting nutrients away from the proximal GI tract and delivering incompletely digested nutrients to the distal GI tract. GBP and biliopancreatic diversion combine both restrictive and bypass mechanisms. All procedures lead to weight loss and decrease in the fat mass. Decrease in fat mass significantly affects circulating levels of adipocytokines, which favorably impact insulin resistance. The data reviewed here suggest that all forms of weight loss surgery lead to caloric restriction, weight loss, decrease in fat mass and improvement in T2DM. This suggests that improvements in glucose metabolism and insulin resistance following bariatric surgery result in the short-term from decreased stimulation of the entero-insular axis by decreased caloric intake and in the long-term by decreased fat mass and resulting changes in release of adipocytokines. Observed changes in glucose metabolism and insulin resistance following bariatric surgery do not require the posit of novel regulatory mechanisms.     

Acute neurological presentation due to copper deficiency in a hemodialysis patient following gastric bypass surgery

Acquired copper deficiency has been recently recognized as a cause of myelopathy, and has been reported to occur many years after gastric bypass surgery performed to aid weight reduction in morbidly obese patients. We report a case of a young woman treated by hemodialysis who presented with acute neurological symptoms 5 months after gastric bypass surgery for severe obesity. She had symptoms and signs of cerebellar, spinal cord and peripheral nerve disease, which improved following parenteral copper supplementation. Now that gastric bypass surgery is being offered to morbidly obese hemodialysis patients, this case highlights the importance of monitoring copper levels in hemodialysis patients following gastric bypass surgery.     

Gastric bariatric operation in insulin-treated adults

Gastric bariatric operation has been advocated to ameliorate adult-onset diabetes mellitus in the morbidly obese patient. However, there are few data to support this. In this clinical study we report the cases of 23 insulin-treated, morbidly obese, adult-onset diabetes (type II) patients who underwent gastric bariatric operations for weight reduction. Preoperative insulin requirements ranged from 10 to 230 U/day (mean 74 U/day). After operation, 14 patients discontinued insulin, and seven patients decreased their insulin requirement by 72% (100 to 28 U/day). Two patients were lost to follow-up. Six patients were admitted to the Clinical Research Unit before and after operation to evaluate the effects of surgically induced weight loss on fasting blood glucose levels, hemoglobin A1C insulin resistance, and glucose tolerance. Weight loss at the time of postoperative studies ranged between 22.5 and 49.1 kg (mean 30.6 kg). Fasting blood glucose levels decreased 48% (mean 321 mg/dl before operation to 166 mg/dl after operation). Hemoglobin A1C levels improved from a mean of 11.8% to 7.9%. Insulin resistance assessed in four patients by measurement of glucose clearance during insulin and glucose infusion improved from a mean of 77 ml/min before operation to 228 ml/min after operation. Glucose tolerance was quantitated by determination of glucose disappearance during intravenous glucose tolerance test. The mean glucose disappearance improved from 0.176% to 0.385%/min following operation. This study provides clinical and laboratory evidence indicating significant improvement of insulin-treated diabetes mellitus in morbidly obese patients who have lost weight following gastric bariatric operation.     

Composition of weight loss in morbidly obese patients after gastric bypass

Optimal treatment of morbid obesity requires reduction of excess body fat while minimizing lean tissue loss. In order to determine if gastric bypass surgery satisfies both these requirements, we have studied changes in body composition and weight loss in adult (mean age = 33 years) morbidly obese patients (14 males, 68 females) after gastric bypass surgery. The preoperative weight of this cohort was 136 ± 27 (SD) kg, which was 228 ± 37% of ideal body weight by actuarial standards. Lean body mass (LBM) was estimated from potassium-40 measurements obtained from a wholebody potassium-40 counter and by urine creatinine excretion on a subgroup of 20 patients. The average weight loss at 3, 6, and 12 months after surgery was 25, 35, and 46 kg, respectively. The weight loss phase lasted approximately 1 year, at which time 34% of the initial weight was lost and the percentage of loss of excess weight above ideal body weight plateaued at 61%. LBM accounted for 32% of the total weight loss at 1 month, 11% at 6 months, and only 3% at the end of 1 year. The percentage of body weight represented by LBM increased from 35% prior to surgery to 51% by 18 months after gastric bypass. Actual LBM content increased steadily after the first month following surgery. Mean total weight loss following three different surgical procedures for gastric bypass did not differ significantly. Gastric bypass surgery appears to satisfy the objectives of reducing excess weight contributed by fat while minimizing lean tissue loss in morbidly obese patients.