Kenneth G. MacDonald

Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus.

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 to 615 lb) to 192.2 lb (range, 104 to 466) by 1 year and were maintained at 205.4 lb (range, 107 to 512 lb) at 5 years, 206.5 lb (130 to 388 lb) at 10 years, and 204.7 lb (158 to 270 lb) at 14 years.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.

A multicenter, placebo-controlled, randomized, double-blind, prospective trial of prophylactic ursodiol for the prevention of gallstone formation following gastric-bypass-induced rapid weight loss

BACKGROUND Previous studies have documented a high incidence of gallstone formation following gastric-bypass (GBP)-induced rapid weight loss in morbidly obese patients. This study was designed to determine if a 6-month regimen of prophylactic ursodiol might prevent the development of gallstones. METHODS A multicenter, randomized, double-blind, prospective trial evaluated 3 oral doses of ursodiol: 300, 600, and 1,200 mg versus placebo beginning within 10 days after surgery and continuing for 6 months or until gallstone development, for patients with a body mass index (BMI) > or = 40 kg/m2. All patients had normal intraoperative gallbladder sonography. Transabdominal sonography was obtained at 2, 4, and 6 months following surgery, or until gallstone formation. RESULTS Of 233 patients with at least one postoperative sonogram, 56 were randomized to placebo, 53 to 300 mg ursodiol, 61 to 600 mg ursodiol, and 63 to 1,200 mg ursodiol. Preoperative age, sex, race, weight, BMI, and postoperative weight loss were not significantly different between groups. Gallstone formation occurred at 6 months in 32%, 13%, 2%, and 6% of the patients on the respective doses. Gallstones were significantly (P < 0.001) less frequent with ursodiol 600 and 1,200 mg than with placebo. CONCLUSION A daily dose of 600 mg ursodiol is effective prophylaxis for gallstone formation following GBP-induced rapid weight loss.

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.

Surgical treatment of obesity and its effect on diabetes: 10-y follow-up.

Since 1980 we have performed the identical Greenville gastric bypass (GGB) procedure on 479 morbidly obese patients with an acceptable morbidity and a mortality rate of 1.2%. The weight loss in the series was well maintained over the follow-up period of 10 y. The GGB can control non-insulin-dependent diabetes mellitus (NIDDM) in most patients. The group of 479 patients included 101 (21%) with NIDDM and another 62 (13%) who were glucose impaired. Of these 163 individuals, 141 reverted to normal and only 22 (5%) remained with inadequate control of their carbohydrate metabolism. Those patients who were older or whose diabetes was of longer duration were less likely to revert to normal values. The gastric bypass operation is an effective approach for the treatment of morbid obesity. Along with its control of weight, the operation also controls the hyperglycemia, hyperinsulinemia, and insulin resistance of the majority of patients with either glucose impairment or frank NIDDM.

Weight Loss in Severely Obese Subjects Prevents the Progression of Impaired Glucose Tolerance to Type II Diabetes: A longitudinal interventional study

OBJECTIVE To determine if weight loss may prevent conversion of impaired glucose tolerance (IGT) to diabetes, because weight loss reduces insulin resistance. The prevalence of IGT in the U. S. population is estimated at 11.2%, more than twice that of diabetes. Furthermore, because an oral glucose tolerance test is needed for its detection, most of these patients are undiagnosed. Screening for IGT would be meaningful if progression to diabetes could be delayed or prevented. RESEARCH DESIGN AND METHODS For an average of 5.8 years (range 2–10 years), 136 individuals with IGT and clinically severe obesity (>45 kg excess body weight) were followed. The experimental group included 109 patients with IGT who underwent bariatric surgery for weight loss. The control group was made up of 27 subjects with IGT who did not have bariatric surgery. The criteria of the World Health Organization was used to detect IGT and diabetes in this population. The main outcome measure of this nonrandomized control trial is the incidence density, or number of events (development of diabetes) divided by the time of exposure to risk. RESULTS Of the 27 subjects in the control group, 6 developed diabetes during an average of 4.8 ± 2.5 years of postdiagnosis follow-up, yielding a rate of conversion to diabetes of 4.72 cases per 100 person-years. The 109 individuals of the experimental group were followed for an average of 6.2 ± 2.5 years postbariatric surgery. Based on the 95% confidence interval of the comparison group, we would expect to find that between 22 and 36 subjects in the experimental group developed diabetes over the follow-up period. Only 1 of the 109 experimental-group patients developed diabetes, resulting in a conversion rate of the experimental group of only 0.15 cases per 100 person-years, which is significantly lower (P < 0.0001) than the control group. CONCLUSIONS Weight loss in patients with clinically severe obesity prevents the progression of IGT to diabetes by >30-fold.

Gastrogastric fistulas. A complication of divided gastric bypass surgery.

ObjectiveThis report warns that gastrogastric fistulas may follow the division of the stomach in bariatric surgery. Summary Background DataAlthough surgery is the most effective therapy for morbid obesity, the procedures are still undergoing evolution. One of the key elements in bariatric surgery is the partition of the stomach to develop a much smaller reservoir. The partition has been done with single layers of staples with almost universal failure and with double layers of staples with a failure rate of 11.8% when observed for a 12-year follow-up. MethodsThis report details the experience with a series of 100 consecutive patients in whom the partition was created by dividing the stomach. ResultsThe course of six patients was complicated by gastrogastric fistulas. One of the patients had the gastric bypass as the initial bariatric operation; in the other five, the gastric bypasses were carried out to revise failed staple lines. Although one of the patients required drainage for a subphrenic abscess, two had only self-limited signs of infection. In the remaining three patients, there was no evidence of any complication. ConclusionGastrogastric fistulas followed division of the stomach in 6% of our gastric bypass operations. Methods for avoiding this complication include oversewing staple lines, using strong bites of tissue during the anastomosis, avoiding obstruction of the Roux-en-Y jejunal segment, and testing of the integrity of the anastomosis with methylene blue dyes. The ideal method for partition of the stomach remains to be developed.

Muscle insulin receptor concentrations in obese patients post bariatric surgery: relationship to hyperinsulinemia

OBJECTIVE: Obesity results in insulin resistance. Bariatric surgery for obese individuals induces weight loss, improves insulin sensitivity, and lowers insulin levels. We investigated the mechanisms of this improvement.DESIGN: Insulin receptor (IR) content, IR signaling, and adiponectin levels were measured in nine morbidly obese subjects before and after bariatric surgery.SUBJECTS: Seven female and two male, average age 44±2y, BMI >40 kg/m2 and/or at least 100 lbs over ideal body weight, undergoing elective bariatric surgery.MEASUREMENTS: Before surgery BMI, fasting plasma glucose, adiponectin, and insulin levels were measured. A fasting muscle biopsy was obtained from the vastus lateralis for IR concentration and autophosphorylation activity measurements. These procedures were repeated 1 y after surgery.RESULTS: At 1 y after surgery, the subjects had lost an average of 48.3±5.6 kg (P<0.001), insulin sensitivity had significantly increased as determined by the minimal model (SI 0.72±0.18 vs 3.86±1.43, P<0.05), and IR content had increased two-fold in muscle (2.1±0.4 vs 4.3±0.7 ng/mg protein, P<0.01). The increase in IR content was related to fasting insulin levels. In the subjects with the lowest IR function, there was also an increase in IR function. Plasma adiponectin increased by 40% following weight loss (7.4±1.6 pre vs 10.3±1.3 mg/ml post, P<0.05). There was no significant change in muscle content of the IR inhibitor, PC-1.CONCLUSION: Increased IR content, most likely regulated by insulin levels, may be one contributor to the increased insulin sensitivity that occurs when morbidly obese patients undergo bariatric surgery.

Intraoperative video panendoscopy for diagnosing sites of chronic intestinal bleeding

Intraoperative video panendoscopy was performed in 14 patients with chronic, recurrent gastrointestinal bleeding. All of the study patients had undergone extensive and expensive diagnostic testing including multiple radiographic contrast studies of the gastrointestinal tract, upper and lower endoscopy, nuclear bleeding scans, and selective mesenteric angiography without definition of the bleeding source. Intraoperative video panendoscopy, employing a segmental advance and look technique, allowed visualization and transillumination of the entire gut and identified mucosal disease in 13 patients (93 percent). Angiodysplasia of the colon and small intestine was the most common pathologic finding. Intraoperative video panendoscopy significantly influenced the operation performed in 13 patients (93 percent). Postoperative complications were minimal, with none being directly attributable to intraoperative video panendoscopy. Bleeding was totally controlled in 10 patients (71 percent) during a mean follow-up period of 25 months. Intraoperative video panendoscopy is a valuable technique for assisting in the management of the patient with recurrent gastrointestinal bleeding.

The Workup for Bariatric Surgery Does Not Require a Routine Upper Gastrointestinal Series

Background: Morbid obesity is a serious disease that afflicts over five million Americans, threatening their health with such co-morbidities as diabetes, arthritis, pulmonary failure and stroke. Surgery is the only effective therapy, providing long-term control of weight, diabetes, pulmonary failure, and hypertension for as long as 14 years. Because the operation presents a major expense, this study examined whether X-ray examination of the gut could be omitted safely as a cost-saving measure. Methods: The records of 814 consecutive morbidly obese patients who underwent gastric bypass were reviewed to determine: (1) whether these individuals had undergone an upper gastro-intestinal (GI) series, and (2) if these studies influenced therapy or caused cancellation or postponement of surgery. Results: Of the 814 patients, 657 (80.7%) underwent a preoperative GI radiography. Of these examinations, 393 (59.8%) were normal, with the following abnormalities in the remaining 264: hiatal hernia, 164; esophageal reflux, 39; Schatzkis ring, 18; small bowel diverticula, four; renal stones, four; malrotation, three; gall stones, two; pyloric ulcer, one; possible pelvic mass, one; calcified leiomyoma, one; and dysphagial lusoria, one. None of these findings resulted in cancellation or a delay in surgery. Conclusions: The upper GI series can be safely omitted from the routine preoperative evaluation of patients undergoing gastric bypass. At a cost of

Fatty Acid Oxidation by Skeletal Muscle Homogenates From Morbidly Obese Black and White American Women

741.00 per examination, this change represents significant potential savings. Similar evaluations of other routine preoperative tests may well provide a better basis for the evaluation of these complex patients.