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

Senescent terminal weight loss in the male F344 rat.

Loss of weight, often of unknown cause and culminating in death, commonly occurs in humans at advanced ages. Rats that live to old ages, such as the Fischer 344 (F344) strain, also exhibit a terminal loss in body weight. A presently held hypothesis is that the terminal weight loss in the F344 rat model is due to reduced food intake because of an alteration in hypothalamic function resulting in early satiation. We report findings on terminal weight loss and food intake in male F344 rats fed ad libitum (AL group) or a life-prolonging dietary regimen in which caloric intake was restricted (DR group). Rats in both dietary groups that did not exhibit a terminal weight loss died at younger ages than those exhibiting the loss. Terminal weight loss in the AL group was not associated with decreased food intake; indeed, half of the rats in this group had an increased food intake during the period of terminal weight loss. This finding is not in accord with the presently held hypothesis. In the DR group, terminal weight loss was associated with reduced food intake. Pathology (renal disease and neoplasms) did not explain the presence or absence of the association between reduced food intake and weight loss in either dietary group. The duration of the period of terminal weight loss was similar for the AL and DR groups. Apparently, restricting calories delays the occurrence but does not affect the duration of senescent terminal weight loss.

Obesity is a common and challenging problem that often leads to other medical problems, including type II diabetes, hyperlipidemia, hypertension, coronary artery disease, and degenerative joint disease. Weight loss, which is central to the dietary treatments for obesity, is often of limited success. Recent studies have documented the safety and efficacy of certain appetite suppressants for assisting in long-term weight loss and maintenance of weight loss. Since appetite suppressants, alone or in combination, have been documented to be safe and effective adjuncts for treating obesity and complicated obesity, physicians should consider using these agents in the pharmacotherapy for obese patients.

Effects of intraperitoneal administration of gemcitabine and paclitaxel on hepatic regeneration in rats.

BACKGROUND/AIMS: We aimed to test clinical implications of intra-peritoneally administered gemcitabine and paclitaxel on hepatic regeneration after hepatic resection in rats. METHODS: Fifty male, Swiss albino rats weighing between 200 and 240 g were used. After a 30% partial hepatectomy was performed (except Sham group), animals were divided into five groups as: high-dose gemcitabine, low-dose gemcitabine, paclitaxel, control, and Sham operation groups. In the high-dose and low-dose gemcitabine groups, animals received 200 and 12.5 mg/kg intraperitoneal gemcitabine for five days after partial hepatectomy respectively. In the paclitaxel group, animals were administered 6 mg/kg paclitaxel in the same fashion. Control and Sham groups received intraperitoneal 0.9% NaCl. On the sixth postoperative day, the animals were killed liver tissues were resected, proliferating cell nuclear antigen immunopositivity was determined and weight loss and diarrhea were assessed. Results: Gemcitabine and paclitaxel treated animals lost weight and had more severe diarrhea than control and Sham group animals. No significant difference was observed between treatment groups in terms of weight loss, diarrhea, and proliferating cell nuclear antigen. When treatment groups were compared to the control group in terms of proliferating cell nuclear antigen immunopositivity, no significant differences were detected. CONCLUSIONS: It can be concluded that adjuvant chemotherapy with gemcitabine and paclitaxel is a safe option in terms of liver regeneration and side effects such as diarrhea and weight loss.

Weight Loss readiness in middle-aged women: psychosocial predictors of success for behavioral weight reduction.

Accurate prediction of weight loss success and failure has eluded researchers for many years. Thus, we administered a comprehensive psychometric battery before a 4-month lifestyle behavioral weight reduction program and analyzed weight changes during that period to identify baseline characteristics of successful and unsuccessful participants, among 112 overweight and obese middle-aged women (age, 47.8 +/- 4.4 years; BMI, 31.4 +/- 3.9 kg/m2). Mean weight and percentage fat losses among the 89 completers were -5.4 kg and -3.4%, respectively (p < .001). A higher number of recent dieting attempts and recent weight loss, more stringent weight outcome evaluations, a higher perceived negative impact of weight on quality of life, lower self-motivation, higher body size dissatisfaction, and lower self-esteem were associated with less weight loss and significantly distinguished responders from nonresponders among all participants. These findings are discussed as to their usefulness (i) to screen individuals before treatment, (ii) to provide a better match between interventions to participants, and (iii) to build a weight loss readiness questionnaire.

Behavior and lifestyle: approaches to treatment of obesity.

The increasing prevalence of overweight and obesity in adults and children demonstrates a steadily growing epidemic. This rising rate of obesity is associated with obesity related comorbidities including cardiovascular disease, hypertension, some cancers, joint disease, and particularly, type 2 diabetes. Modest weight loss (5% to 10% of total body weight) through lifestyle intervention approaches has been found to have a beneficial effect on comorbid conditions, particularly hypertension and type 2 diabetes. Effective behavioral treatment of obesity involves modification of eating and physical activity patterns to yield negative energy balance. Research studies have found that interventions that combine a low-calorie diet, increased physical activity, and behavior therapy are most effective for weight loss and maintenance. Furthermore, extended length of treatment contact, weight loss satisfaction, and social support may promote positive long-term outcomes in obese adults and children.

Energy restriction reduces fractional calcium absorption in mature obese and lean rats.

weight loss is associated with bone loss and the risk may be greater in lean than heavier individuals, but the mechanisms involved remain unclear. We hypothesized that energy restriction (EnR) would decrease true fractional Ca absorption (TFCA) and be mediated by Ca-regulating hormones, but differently in obese and lean rats. Rats were fed a high fat (47% energy) or low fat (16% energy) diet for 4 mo. At 6 mo of age, the resulting lean [284 +/- 28g (mean +/- SD, n = 18)] and obese (319 +/- 34g, n = 20) groups (P < 0.005) were divided into controls (CTL, ad libitum) and energy-restricted (40% restriction) groups. At baseline, bone resorption (urinary crosslinks) was higher and bone formation (serum osteocalcin) was lower in obese than in lean rats, whereas Ca balance components and Ca-regulating hormones did not differ. EnR for 10 wk reduced body weight by 25 +/- 7% compared with a 6 +/- 6% gain in CTL rats (P < 0.001). For both lean and obese rats, TFCA (5-d measurement, (45)Ca radioisotope) decreased from 30 +/- 9% to 24 +/- 9% with EnR, compared with 25 +/- 10% to 29 +/- 11% in controls (P < 0.05). weight loss was directly correlated with the decrease in TFCA (r = 0.34, P < 0.05). Uterine weights indicated a reduced estrogenic activity in energy-restricted rats (P < 0.0001). In lean, but not obese rats, serum estradiol (E(2)) correlated with weight loss (r = 0.52, P < 0.05), and tended to correlate with the decrease in TFCA (r = 0.48, P = 0.06). At the end of the study, serum 25-hydroxyvitamin-D was lower and urinary Ca was higher in lean than obese energy-restricted rats. Distinct endocrine profiles during weight loss in obese and lean rats suggest that the susceptibility of bone and Ca metabolism to EnR could differ depending on initial body weight.

Assessing clinical probability of organic disease in patients with involuntary weight loss: a simple score.

BACKGROUND: Involuntary weight loss (IWL) is a frequent complaint with a difficult diagnosis. Any one of a number of different diseases may be the source of the symptom. However, there is no universal clinical protocol that can help physicians study this complex syndrome. METHODS: In March 1998, we defined a diagnostic protocol for the study of IWL. IWL was defined as an involuntary and documented weight loss of at least 5% of the usual body weight in the previous 3 months. We analyzed 78 consecutive patients with IWL who came to our clinic between March 1998 and December 2000. RESULTS: An organic disease was found in 56% of cases; cancer, metabolic and digestive diseases were the most common entities. Psychiatric problems were found in 33% of cases. After extensive study, an idiopathic group of 11% was identified. The variables that were independently predictive of a final diagnosis of organic disease were: age>50 years (OR: 8.6, CI 95%: 1.7-43.6), psychiatric symptoms (OR: 0.2, CI 95%: 0.1-0.8), smoking (OR: 14.3, CI 95% 2.3-74), the presence of guide symptoms (OR: 8.0, CI 95%: 1.8-34.4), and anemia (OR: 3.1, CI 95%: 2.5-387). Sixteen percent of the patients died, more often those suffering from organic diseases. Based on multivariate regression coefficients, a clinical risk score was established. CONCLUSIONS: IWL is a complex and frequent syndrome with a 16% rate of mortality during the first year. A protocol based on clinical data can help in the management of IWL. Our clinical prediction rule may help physicians to identify those patients with IWL who are likely to have an underlying organic disease.