Relationship between insulin resistance, weight loss, and coronary heart disease risk in healthy, obese women.

Several popular books have recently been published stating that being insulin-resistant favors weight gain and/or prevents weight loss. Because this view seems to have gained widespread support in the general population, we thought it important to perform the current study testing the hypothesis that differences in insulin-mediated glucose disposal do not affect weight loss in response to calorie-restricted diets. For this purpose, we studied the change in weight and risk factors for coronary heart disease (CHD) in healthy women volunteers, defined as being obese on the basis of a body mass index (BMI) greater than 30.0 kg/m(2). The insulin suppression test was used to stratify obese women at baseline into insulin-resistant and insulin-sensitive subgroups on the basis of their steady-state plasma glucose (SSPG) concentration at the end of a 180-minute infusion of octreotide, exogenous insulin, and glucose. They were then instructed on a calorie-restricted diet plus sibutramine (15 mg/day) for a total period of 4 months. Baseline measurements also included determination of fasting lipid and lipoprotein concentrations, and hourly (8 AM to 4 PM) determinations of plasma glucose and insulin concentrations before and after breakfast and lunch. Twenty-four women completed the 4-month period of calorie restriction: 13 classified as insulin-resistant (SSPG = 219 +/- 7 mg/dL) and 11 as insulin-sensitive (SSPG = 69 +/- 6 mg/dL). The insulin-resistant group also had higher (P =.03) plasma triglyceride (TG) concentrations and a higher ratio of total to high-density lipoprotein (HDL) cholesterol concentration (P =.02) at baseline. Both groups lost a significant amount of weight during the study, and there was no difference between the weight loss in the insulin-resistant (8.6 +/- 1.3 kg) and insulin-sensitive (7.9 +/- 1.4 kg) groups. weight loss in the insulin-resistant group was also associated with a significant decrease in SSPG concentration (219 +/- 7 to 144 +/- 14 mg/dL), associated with significantly lower fasting TG concentrations (P <.001) and day-long concentrations of plasma glucose and insulin (P <.005). None of these variables changed in the insulin-sensitive group. These results indicate that: (1) CHD risk factors in obese women vary as a function of being insulin-resistant or insulin-sensitive; (2) dramatic variations in insulin-mediated glucose disposal do not modulate weight loss in response to calorie-restricted diets, and (3) weight loss is effective in reducing CHD risk in insulin-resistant, obese women. Given these data, it seems obvious that attempts to reduce CHD risk factors by weight loss should focus on obese individuals who are also insulin-resistant. Copyright 2001 by W.B. Saunders Company

The importance of histopathological and clinical variables in predicting the evolution of colon cancer.

It has been a consensus that prognostic factors should always be taken into account before planning treatment in colorectal cancer. AIM: A 5 year prospective study was conducted, in order to assess the importance of several histopathological and clinical prognostic variables in the prediction of evolution in colon cancer. Some of the factors included in the analysis are still subject to dispute by different authors. METHODS: 46 of 53 screened patients qualified to enter the study and underwent a potentially curative resection of the tumor, followed, when necessary, by adjuvant chemotherapy. Univariate and multivariate analyses were carried out in order to identify independent prognostic indicators. The endpoint of the study was considered the recurrence of the tumor or the detection of metastases. RESULTS: 65.2% of the patients had a good evolution during the follow up period. Multivariate survival analysis performed by Cox proportional hazard model identified 3 independent prognostic factors: Dukes stage (p = 0.00002), the grade of differentiation (p = 0.0009) and the weight loss index, representing the weight loss of the patient divided by the number of months when it was actually lost (p = 0.02). Age under 40 years, sex, microscopic aspect of the tumor, tumor location, anemia degree were not identified by our analysis as having prognostic importance. CONCLUSIONS: Histopathological factors continue to be the most valuable source of information regarding the possible evolution of patients with colorectal cancer. Individual clinical symptoms or biological parameters such as erytrocyte sedimentation rate or hemoglobin level are of little or no prognostic value. More research is required relating to the impact of a performance status index (which could include also weight loss index) as another reliable prognostic variable.

Albumin concentrations are primarily determined by the body cell mass and the systemic inflammatory response in cancer patients with weight loss.

The association between hypoalbuminemia and poor prognosis in patients with cancer is well recognized. However, the factors that contribute to the fall in albumin concentrations are not well understood. In the present study, we examined the relationship between circulating albumin concentrations, weight loss, the body cell mass (measured using total body potassium), and the presence of an inflammatory response (measured using C-reactive protein) in male patients (n = 40) with advanced lung or gastrointestinal cancer. Albumin concentrations were significantly correlated with the percent ideal body weight (r = 0.390, p < 0.05), extent of reported weight loss (r = -0.492, p < 0.01), percent predicted total body potassium (adjusted for age, height, and weight, r = 0.686, p < 0.001), and log10 C-reactive protein concentrations (r = -0.545, p < 0.001). On multiple regression analysis, the percent predicted total body potassium and log10 C-reactive protein concentrations accounted for 63% of the variation in albumin concentrations (r2 = 0.626, p < 0.001). The interrelationship between albumin, body cell mass, and the inflammatory response is consistent with the concept that the presence of an ongoing inflammatory response contributes to the progressive loss of these vital protein components of the body and the subsequent death of patients with advanced cancer.

Laparoscopic reoperative bariatric surgery: experience from 27 consecutive patients.

BACKGROUND: 10 to 25% of patients undergoing bariatric surgery will require a revision, either for unsatisfactory weight loss or for complications. Reoperation is associated with a higher morbidity and has traditionally been done in open fashion. The purpose of this study was to determine the safety and efficacy of reoperative surgery using a laparoscopic approach. METHODS: A retrospective review of medical records over a 22-month period was conducted. 27 consecutive obesity surgery patients, who had undergone a laparoscopic revision, were identified. 26 of the 27 patients were women. The average age was 40.3 years (range 20 to 58 years) and average original preoperative body mass index (BMI) was 51.6 kg/m2 (range 42 to 66.5). The 27 primary bariatric operations consisted of vertical banded gastroplasty (12), gastric band placement (9) and gastric bypass (6). 17 of them were open procedures. After the primary surgery, the lowest average BMI was 37.6 kg/m2 (range 21 to 52), which increased to 42.7 kg/m2 (range 29 to 56) before reoperation. 24 of the 27 reoperations were indicated for insufficient weight loss. On average, revision was undertaken 52 months after the primary procedure (range 12 to 240 months). RESULTS: 24 of the 27 laparoscopic reoperations were conversions to a gastric bypass. A second reoperation was indicated for insufficient weight loss on four occasions. In one case, conversion to open surgery was required. The average operative time was 232 +/- 18.5 minutes (range 120 to 480) and length of hospital stay was 3.7 days (range 1 to 9). 22% percent of patients (6) experienced complications, including pneumothorax, gastric remnant dilation, gastrojejunostomy stenosis, port-site hernia and protein malnutrition. There was no mortality in the study. The average BMI was 35.9 kg/m2 (range 27 to 45.5) 8 months after surgery (range 1 to 22 months). Compared with a preoperative BMI of 42.7 kg/m2, the weight loss was statistically significant (p < 0.001). CONCLUSION: Our results compare favorably with those reported for open reoperative bariatric surgery. A laparoscopic approach may be considered a feasible and safe alternative to an open operation.

The role of proinflammatory cytokines in wasting disease during lymphocytic choriomeningitis virus infection.

Infection with pathogens often leads to loss of body weight, but the cause of weight loss during infection is poorly understood. We used the infection of mice with lymphocytic choriomeningitis virus (LCMV) as a model to study how pathogens induce weight loss. If LCMV is introduced into the CNS of CTL-deficient mice, the immune response against the virus leads to a severe weight loss called wasting disease. We planned to determine what components of this antiviral immune response mediate wasting disease. By adoptive transfer, we show that CD4 T cells activated by LCMV infection are sufficient to cause wasting disease. We examined the role of cytokines in LCMV-induced wasting disease using mice lacking specific cytokines or cytokine receptors. Results of adoptive transfer experiments suggest that TNF-alpha is not involved in LCMV-induced wasting disease and show that IFN-gamma contributes to the disease. Consistent with a role for IFN-gamma in wasting, we find that IFN-gamma is necessary for LCMV-specific CD4 T cell responses in the CNS, most likely because it is required to induce MHC class II expression. Our data also indicate that IL-1 is required for LCMV-induced wasting and that IL-6 contributes to the wasting disease. Additionally, our results identify alpha-melanocyte-stimulating hormone as a potential mediator of the disease. Overall, this work defines the critical role of virus-primed CD4 T cells and of proinflammatory cytokines in the pathogenesis of wasting disease induced by LCMV infection.

Gastric bypass is an effective treatment for obstructive sleep apnea in patients with clinically significant obesity.

BACKGROUND: We have demonstrated that obstructive sleep apnea (OSA) is prevalent in 60% of patients undergoing bariatric surgery. A study was conducted to determine whether weight loss following bariatric surgery ameliorates OSA. METHODS: All 100 consecutive patients with symptoms of OSA were prospectively evaluated by polysomnography before gastric bypass. Preoperative and postoperative scores of Epworth Sleepiness Scale (ESS), Respiratory Disturbance Index (RDI), and other parameters of sleep quality were compared using t-test. RESULTS: Preoperative RDI was 40 +/- 4 (normal 5 events/hour, n = 100). 13 patients had no OSA, 29 had mild OSA, while the remaining 58 patients were treated preoperatively for moderate-severe OSA. At a median of 6 months follow-up, BMI and ESS scores improved (38 +/- 1 vs 54 +/- 1 kg/m2, 6 +/- 1 vs 12 +/- 0.1, P < 0.001, postoperatively vs preoperatively). To date, 11 patients have completed postoperative polysomnography (3-21 months) after losing weight (BMI 40 +/- 2 vs 62 +/- 3 kg/m2, P < 0.001). There was significant improvement in ESS (3 +/- 1 vs 14 +/- 2), minimum O2 saturation (SpO2 86 +/- 2 vs 77 +/- 5), sleep efficiency (85 +/- 2% vs 65 +/- 5%), all P < 0.001, postop vs preop; and RDI (56 +/- 13 vs 23 +/- 7, P = 0.041). Regression analysis demonstrated no correlation between preoperative BMI, ESS score and the severity of OSA; and no correlation between % excess body weight loss and postoperative RDI. CONCLUSION: weight loss following gastric bypass results in profound improvement in OSA.The severity of apnea cannot be reliably predicted by preoperative BMI and ESS; therefore, patients with symptoms of OSA should undergo polysomnography.

Solubility of root-canal sealers in water and artificial saliva.

AIM: To compare the weight loss of eight different root-canal sealers in water and in artificial saliva with different pH values. METHODOLOGY: For standardized samples (n = 12 per group), ring moulds were filled with epoxy resin (AH 26, AH Plus)-, silicone (RSA RoekoSeal)-, calcium hydroxide (Apexit, Sealapex)-, zinc oxide-eugenol (Aptal-Harz)-, glass-ionomer (Ketac Endo)- and polyketone (Diaket)-based sealers. These samples were immersed in double-distilled water or artificial saliva with different pH values (7.0, 5.7 and 4.5) for 30 s, 1 min, 2 min, 5 min, 10 min, 20 min, 1 h, 2 h, 10 h, 24 h, 48 h, 72 h, 14 days and 28 days. Mean loss of weight was determined and analysed statistically using a one-way anova and Student-Newman-Keuls test for all pairwise comparisons. RESULTS: Most sealers were of low solubility, although Sealapex, Aptal-Harz and Ketac Endo showed a marked weight loss in all liquids. Even after 28 days of storage in water, AH 26, AH Plus, RSA RoekoSeal, and Diaket showed less than 3% weight loss. At exposure times greater than 14 days, Sealapex showed the significantly greatest weight loss of all sealers tested (P < 0.05). Aptal-Harz and Ketac Endo were significantly more soluble in saliva (pH 4.5) than in water (P < 0.05). CONCLUSIONS: Under the conditions of the present study, AH Plus showed the least weight loss of all sealers tested, independent of the solubility medium used. Sealapex, Aptal-Harz and Ketac Endo had a marked weight loss in all liquids.

Reductions in plasma cytokine levels with weight loss improve insulin sensitivity in overweight and obese postmenopausal women.

OBJECTIVE: The purpose of this study was to determine whether improvements in insulin sensitivity with weight loss are mediated by changes in inflammation in obese, postmenopausal women. RESEARCH DESIGN AND METHODS: We studied 58 sedentary, overweight, and obese (BMI 33 +/- 1 kg/m(2), means +/- SEM) postmenopausal (58 +/- 1 year) women at baseline and 37 women who completed 6 months of weight loss induced by diet and exercise. The women underwent 3-h hyperinsulinemic-euglycemic clamps (40 mU x m(-2) x min(-1)) to determine glucose utilization (M). Insulin sensitivity was determined as M/I, the amount of glucose metabolized per unit of plasma insulin (I). Visceral adipose tissue (VAT) and plasma concentrations of C-reactive protein (CRP), cytokines interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha, as well as their soluble receptors, were measured. RESULTS: At baseline, CRP concentration was a predictor of both glucose utilization and insulin sensitivity, independent of adiposity, race, and aerobic fitness (M: partial r = -0.30, P = 0.03, and M/I: partial r = -0.32, P = 0.02). weight loss resulted in significant reductions in body weight, fat mass, VAT, and fasting glucose and insulin levels (P < 0.05). Both glucose utilization and insulin sensitivity increased by 16% (P < 0.05). CRP, IL-6, and soluble TNF receptor (sTNFR)-1 concentrations decreased (P < 0.05), but concentrations of TNF-alpha, sTNFR-2, and soluble IL-6 receptor (IL-6sR) did not change. In stepwise regression models to predict changes in glucose homeostasis, changes in VAT and sTNF-R1 independently predicted changes in glucose utilization (r = -0.49 and cumulative r = -0.64, P < 0.01), while changes in VAT and IL-6 were both independent predictors of changes in insulin sensitivity (r = -0.57 and cumulative r = -0.68, P < 0.01). CONCLUSIONS: Improvements in glucose metabolism with weight loss programs are independently associated with decreases in cytokine concentrations, suggesting that a reduction in inflammation is a potential mechanism that mediates improvements in insulin sensitivity.