Weight Reduction In Patients Research Articles

PDB5 GLYCAEMIC AND WEIGHT EFFECTS OF EXENATIDE FOR DIFFERENT AGE GROUPS

GLYCAEMIC ANDWEIGHT EFFECTS OF EXENATIDE FOR DIFFERENT AGE GROUPS Wintle M, Guan X, Brodows R, Mac S Amylin Pharmaceuticals, Inc, San Diego, CA, USA, Eli Lilly and Company, Indianapolis, IN, USA OBJECTIVES: The incretin mimetic exenatide improves glycaemic control with associated weight reduction in patients with type 2 diabetes (T2DM) treated with metformin (MET) and/or a sulphonylurea (SU), or MET and/or a thiazolidinedione. As a drug’s pharmacokinetics and pharmacodynamics can vary with age, we explored exenatide’s efficacy and safety for patients 0.1). In patients completing 3.5 y of exenatide, changes in lipids for the 0.2). Nausea and hypoglycaemia, themost common adverse events, occurred at similar rates in both subgroups. The only case of severe hypoglycaemia occurred in a patient <65 y whose background therapies were MET and an SU. CONCLUSION: In summary, in this open-label extension study of T2DM patients treated with MET and/or an SU, exenatide exposure 3 y resulted in similar safety profiles and improvements in glycaemic control and lipid concentrations, with associated weight reductions for patients 65 y and <65 y.

Weight Management Program for Treatment-Emergent Weight Gain in Olanzapine-Treated Patients With Schizophrenia or Schizoaffective Disorder

The main objective was to assess the efficacy of a weight management program designed for outpatients taking olanzapine for schizophrenia or schizoaffective disorder and to compare these patients with a randomized control group. The effects of the weight management program were also assessed with regard to safety and quality of life. Forty-eight patients were enrolled in a 12-week, randomized, multicenter weight management study. Thirty-three patients were randomly allocated to an intervention group in which they received olanzapine within a weight management program. Fifteen patients were allocated to a control group in which they were given olanzapine treatment as usual outpatients. Weight, body mass index (BMI), and measurements of safety and quality of life were evaluated. The study was conducted from January 7, 2003, to September 16, 2003. Thirty-six patients (75%) completed this study. We found significant differences in weight (-3.94 +/- 3.63 kg vs. -1.48 +/- 1.88 kg, p = .006) and BMI (-1.50 +/- 1.34 vs. -0.59 +/- 0.73, p = .007) change from baseline to endpoint between the intervention and control groups, respectively. Significant differences in weight reduction were initially observed at week 8 (p = .040). No significant differences were found with regard to the safety outcomes. When the ratio of low-density lipoproteins to high-density lipoproteins was calculated, change from baseline was greater in the intervention group than the control group (-0.19 vs. -0.04), but the difference was not statistically significant (p = .556). After the completion of the weight management program, there was a trend toward statistical difference in the physical health score changes between the weight management and control groups (1.12 in the intervention group vs. -0.93 in the control group, p = .067). The weight management program was effective in terms of weight reduction in patients with schizophrenia or schizoaffective disorder taking olanzapine and was also found to be safe in terms of psychiatric symptoms, vital signs, and laboratory data. In addition, such a weight management program might improve quality of life in patients with schizophrenia or schizoaffective disorder with respect to their physical well-being.

The incretin mimetic, exenatide: a novel treatment option for type 2 diabetes

Exenatide, (BYETTA TM), is the first in a new class of agents termed incretin mimetics, which replicate several glucoregulatory effects of the endogenous incretin hormone, glucagon-like peptide-1 (GLP-1). Currently approved (April 2005) in the United States as an injectable adjunct to metformin and/or sulphonylurea therapy, exenatide improves glycaemic control through multiple mechanisms of action including: enhancement of glucose-dependent insulin secretion, restoration of first-phase insulin response, suppression of inappropriately elevated glucagon secretion, slowing of gastric emptying and reduction in food intake. Subcutaneous exenatide injected twice-daily before morning and evening meals shows immediate and sustained effects on both postprandial and fasting glucose concentrations and is accompanied by reductions in body weight. Since the actions of exenatide on insulin and glucagon secretion are glucose dependent, the risk of hypoglycaemia is minimised except when exenatide is used in conjunction with agents that induce hypoglycaemia, such as sulphonylureas. Mild-to-moderate nausea is the most common side effect, which can be reduced with dose titration upon initiation of therapy. The incretin mimetic, exenatide, is a novel therapeutic option to improve glycaemic control with potential weight reduction in patients with type 2 diabetes suboptimally controlled with metformin or a sulphonylurea.

Prevention of hepatic steatosis and hepatic insulin resistance in mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 knockout mice

In order to investigate the role of mitochondrial acyl-CoA:glycerol-sn-3-phosphate acyltransferase 1 (mtGPAT1) in the pathogenesis of hepatic steatosis and hepatic insulin resistance, we examined whole-body insulin action in awake mtGPAT1 knockout (mtGPAT1(-/-)) and wild-type (wt) mice after regular control diet or three weeks of high-fat feeding. In contrast to high-fat-fed wt mice, mtGPAT1(-/-) mice displayed markedly lower hepatic triacylglycerol and diacylglycerol concentrations and were protected from hepatic insulin resistance possibly due to a lower diacylglycerol-mediated PKC activation. Hepatic acyl-CoA has previously been implicated in the pathogenesis of insulin resistance. Surprisingly, compared to wt mice, mtGPAT1(-/-) mice exhibited increased hepatic insulin sensitivity despite an almost 2-fold elevation in hepatic acyl-CoA content. These data suggest that mtGPAT1 might serve as a novel target for treatment of hepatic steatosis and hepatic insulin resistance and that long chain acyl-CoA's do not mediate fat-induced hepatic insulin resistance in this model.

Adipositaschirurgie: Patientenselektion und Indikationsstellung

Successful reduction of body weight in patients with morbid obesity (BMI >40 kg/m(2)) is difficult and on a long-term basis nearly impossible with non-interventional treatment modalities. Surgical therapy is an efficient alternative for these patients. Potential surgical treatment should be carefully evaluated during a 6-month preoperative treatment phase during which indications and contraindications should be evaluated. Qualified postoperative care must be provided.

Reversal of Nonalcoholic Hepatic Steatosis, Hepatic Insulin Resistance, and Hyperglycemia by Moderate Weight Reduction in Patients With Type 2 Diabetes

To examine the mechanism by which moderate weight reduction improves basal and insulin-stimulated rates of glucose metabolism in patients with type 2 diabetes, we used (1)H magnetic resonance spectroscopy to assess intrahepatic lipid (IHL) and intramyocellular lipid (IMCL) content in conjunction with hyperinsulinemic-euglycemic clamps using [6,6-(2)H(2)]glucose to assess rates of glucose production and insulin-stimulated peripheral glucose uptake. Eight obese patients with type 2 diabetes were studied before and after weight stabilization on a moderately hypocaloric very-low-fat diet (3%). The diabetic patients were markedly insulin resistant in both liver and muscle compared with the lean control subjects. These changes were associated with marked increases in IHL (12.2 +/- 3.4 vs. 0.6 +/- 0.1%; P = 0.02) and IMCL (2.0 +/- 0.3 vs. 1.2 +/- 0.1%; P = 0.02) compared with the control subjects. A weight loss of only approximately 8 kg resulted in normalization of fasting plasma glucose concentrations (8.8 +/- 0.5 vs. 6.4 +/- 0.3 mmol/l; P < 0.0005), rates of basal glucose production (193 +/- 7 vs. 153 +/- 10 mg/min; P < 0.0005), and the percentage suppression of hepatic glucose production during the clamp (29 +/- 22 vs. 99 +/- 3%; P = 0.003). These improvements in basal and insulin-stimulated hepatic glucose metabolism were associated with an 81 +/- 4% reduction in IHL (P = 0.0009) but no significant change in insulin-stimulated peripheral glucose uptake or IMCL (2.0 +/- 0.3 vs. 1.9 +/- 0.3%; P = 0.21). In conclusion, these data support the hypothesis that moderate weight loss normalizes fasting hyperglycemia in patients with poorly controlled type 2 diabetes by mobilizing a relatively small pool of IHL, which reverses hepatic insulin resistance and normalizes rates of basal glucose production, independent of any changes in insulin-stimulated peripheral glucose metabolism.

Effects of Behavioral Therapy on Weight Loss in Overweight and Obese Patients With Schizophrenia or Schizoaffective Disorder

Obesity is common in persons with schizophrenia. Besides its adverse health effects, obesity reduces quality of life and contributes to the social stigma of schizophrenia. This 14-week, multicenter, open-label, rater-blinded, randomized study evaluated the effects of a group-based behavioral treatment (BT) for weight loss in overweight and obese stable patients with DSM-IV schizophrenia or schizoaffective disorder who had been switched from olanzapine to risperidone. Participants were randomly assigned to receive BT or usual clinical care (UC). BT included 20 sessions during which patients were taught to reduce caloric intake. In UC, patients were encouraged to lose weight but received no special advice about weight reduction. The primary outcome measure was change in body weight. Seventy-two patients were enrolled. The mean +/- SD weight loss at endpoint was significant in both groups (p < .05) and numerically greater in patients receiving BT than in those receiving UC (-2.0 +/- 3.79 and -1.1 +/- 3.11 kg, respectively). More patients in the BT group than in the UC group had lost > or = 5% of their body weight at endpoint (26.5% [9/34] and 10.8% [4/37], respectively; p = .082). A post hoc analysis of patients attending at least 1 BT session showed that significantly more patients in the BT than the UC group had lost > or = 5% of their body weight at endpoint (32.1% [9/28] vs. 10.8% [4/37], respectively, p = .038) and at week 14 (complete population; 40.9% [9/22] and 14.3% [4/28], respectively, p = .027). BT may be an effective method for weight reduction in patients with chronic psychotic illness.

Risk factors for the intermediate outcome of morbid obesity after laparoscopically placed adjustable gastric banding

Background The overall long-term results of medical treatment for morbid obesity are poor. Surgery is the only treatment option to obtain long-term weight reduction. Analysis of risk factors for treatment success of laparoscopically placed gastric banding (LGB) has not been available until now. Methods Prospective study with 99 patients with LGB between January 1997 and July 2003. The parameters assessed as risk factors included onset of obesity, feeling of postprandial satiety, and initial body mass index (BMI). Results Median follow-up was 36 months (3 to 72). Independent prognostic factors of excess body weight reduction (>25%) were for the first postoperative year: onset of obesity as an adolescent (relative risk [RR] 0.21), an initial BMI <45 kg/m 2 (RR 4.76), and a BMI between 45.1 and 50 kg/m 2 (RR 3.23). After the second year, independent prognostic factors were as follows: feeling of postprandial satiety (RR 5.26) and an initial BMI <45 kg/m 2 (RR 3.03). Conclusion LGB is suitable to achieve intermediate weight reduction in patients with morbid obesity. To obtain the best results, patients should be treated before they achieve a BMI >45 kg/m 2. Additionally a postprandial feeling of satiety after LGB is mandatory for good long-term results.

Electroacupuncture Therapy for Weight Loss Reduces Serum Total Cholesterol, Triglycerides, and LDL Cholesterol Levels in Obese Women

Our purpose in this study was to investigate the effect of acupuncture therapy on body weight and on levels of the serum total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol in obese women. Fifty-five women were studied in three groups as follows: (1) control group (n = 12; mean age = 43.3 +/- 4.3, and mean body mass index {BMI} = 32.2 +/- 3.4); (2) electroacupuncture (EA) (n = 22; mean age = 39.8 +/- 5.3, and BMI = 34.8 +/- 3.3); and (3) diet restriction (n = 21; mean age = 42.7 +/- 3.9, and BMI = 34.9 +/- 3.3). EA was performed using the ear points, Sanjiao (Hungry) and Shen Men (Stomach), and the body points, LI 4, LI 11, St 25, St 36, St 44 and Liv 3, once daily, for 30 minutes, for 20 days, whereas patients on diet restriction had a 1425 Kcal diet program, that consisted of 1425 Kcal daily for 20 days. There was a 4.8% weight reduction in patients with EA application, whereas patients on diet restriction had a 2.5% weight reduction. There were significant decreases in total cholesterol and triglyceride levels in EA and diet groups compared with the control group (p < 0.05 in both cases). Furthermore, there was a decrease in LDL levels in the EA group compared with the control group (p < 0.05). No significant changes could be found in HDL levels among the three groups. Our results suggest that EA application in obese women may decrease the serum total cholesterol, triglyceride, and LDL cholesterol levels by increasing the serum beta endorphin level. This lipolytic effect of EA may also reduce the morbidity of obesity by mobilizing the energy stores that result in weight reduction.

Weight reduction in patients with chronic HCV reduces circulating insulin levels

Steatosis occurs in >50% of patients with chronic HCV. In patients with viral genotype 3, steatosis may be a cytopathic effect of the virus. However in many patients with HCV, the pathogenesis of steatosis appears to be the same as for patients with non-alcoholic fatty liver disease (NAFLD) ie related to increased body mass index (BMI). We studied the effect of a 12 week weight reduction program on metabolic parameters in subjects with chronic HCV genotype 1 (Group 1, n = 16), genotype 3 (Group 2, n = 13) and patients with NAFLD (Group 3, n = 13). A liver biopsy was performed prior to and 3-6 months after the intervention period in 15 patients. The mean (SD) BMI of subjects in groups 1, 2 and 3 was 30.7 (4.0), 29.0 (5.2) and 33.3 (7.7), respectively. There was no significant difference in the amount of weight loss, change in waist circumference, change in ALT or reduction in steatosis between the 3 groups. Mean (SD) weight loss was 5.1 (3.7) kg. In those patients who lost weight, serum insulin (mean (SD) mU/L) changed from 17.8 (7.8) to 11.5 (4.8) (p = 0.003), 12.4 (5.0) to 8.4 (4.3) (p = 0.02), and 16.9 (7.3) to 17.8 (8.1) (p = 0.76) in Groups 1, 2 and 3, respectively. A small amount of weight loss is associated with a reduction in circulating insulin levels in patients with chronic HCV, particularly in genotype 1. In patients with NAFLD, the lack of a significant decrease in circulating insulin with weight reduction may reflect the higher initial BMI or may be due to the pathogenesis of this disorder.

Diet and exercise in addition to psychotherapy, in the treatment of patients suffering from eating disorders with obesity.

Treating patients with eating disorders is often a controversial issue, and obesity adds another difficulty to the treatment regimen. In this study we wanted to evaluate the outcome on body weight in patients suffering from eating disorders with obesity, by adding dietary treatment and exercise to ongoing psychotherapy. The prospective intervention study included 18 obese, female patients in primary health care and outpatient clinic with a BMI > or = 27 kg/m2 with eating disorders, nine of whom were diagnosed with bulimia according to the American Psychiatric Association. The patients had had psychotherapy for at least 2 years in a treatment programme which was chosen by a psychologist. This had had no influence on the patients' weight problem, and an additional diet and exercise regime was added to the ongoing psychotherapy through an eight-week very low calorie diet (VLCD) treatment (Nutrilett), during which the patients also participated in weekly group exercise. The patients were followed-up regularly during a 6-month period. During the 8-week VLCD treatment, which was completed by 16 patients (89%), mean body weight in the group decreased significantly from 98.8 kg to 88.6 kg. Six months after the initial treatment, average weight loss was further significantly reduced to 82.5 kg. The findings of the present study suggest that by combining ongoing psychotherapy with a well-balanced VLCD treatment and exercise it is possible to achieve substantial weight reduction in patients suffering from eating disorders with obesity.

Persistence of abnormalities in metabolism of apolipoproteins B-100 and A-I after weight reduction in patients with primary hypertriglyceridemia.

Obesity commonly accompanies hypertriglyceridemia, and weight reduction is widely recommended for treatment of elevated triglyceride levels. To determine whether weight reduction will normalize lipoprotein metabolism in overweight, hypertriglyceridemic patients, 10 such male patients underwent weight loss until their body weights were within the desirable range. After reestablishment of a steady state in body weight at the lower level, measurements were made of plasma lipid, lipoprotein, and apolipoprotein levels and the kinetics of low density lipoprotein (LDL) apolipoprotein B-100 (apo B) and apolipoprotein A-I (apo A-I). The patients lost an average of 10.6 +/- 2.1 kg (mean +/- SEM). Plasma triglyceride concentrations fell from 431 +/- 42 mg/dl to 248 +/- 27 mg/dl (p less than 0.001), whereas concentrations of total cholesterol, LDL cholesterol, total apo B, and high density lipoprotein (HDL) cholesterol were unchanged after weight loss. On average, the fractional catabolic rates (FCRs) for LDL were much higher in the patients after weight loss than in 16 normal control subjects (0.55 +/- 0.06 versus 0.31 +/- 0.06 pool/day), and input rates for LDL also were higher for hypertriglyceridemic patients after weight loss (22.2 +/- 2.4 versus 12.8 +/- 2.3 mg/kg.day). Compared with 20 normal control subjects, hypertriglyceridemic patients after weight reduction had persistent low HDL cholesterol levels (32 +/- 2 versus 54 +/- 3 mg/dl) as well as low apo A-I levels (99 +/- 5 versus 122 +/- 4 mg/dl).(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of weight reduction on hepatic abnormalities in overweight patients

The effects of weight reduction on hepatic test results and physical findings related to the liver were retrospectively evaluated in 39 overweight patients screened to exclude other factors affecting the liver. An additional 11 overweight patients with primary liver disease were retrospectively evaluated to compare the effect of weight reduction in patients with liver disease with its effect in those without primary liver disease. This study showed that in overweight adults without primary liver disease, a weight reduction of ≥ 10% corrected abnormal hepatic test results, decreased hepatosplenomegaly, and resolved some stigmata of liver disease. In similarly studied overweight patients with primary liver disease, some findings improved, but the changes did not correlate with a ≥ 10% weight loss. Increased alanine aminotransferase activity was the most frequent hepatic enzyme abnormality in this population. For every 1% reduction in body weight, alanine aminotransferase activity improved by 8.1%. After other causes of liver disease are eliminated by clinical and biochemical parameters, weight reduction should be tried for overweight patients with abnormal hepatic test results in the absence of obvious primary liver disease as judged by clinical and biochemical parameters before extensive and expensive studies are undertaken.

Demineralization in Cystic Fibrosis

Bone mineral content, bone width, and their ratio were measured in patients with cystic fibrosis (CF) using monoenergetic photon absorptiometry. Serial measurements of the radius and ulna were made in 27 patients with CF and were compared with 968 age-matched controls. Demineralization was found in 37% of the boys and 63% of the girls. Patients under age 10 years had normal bone mineral content and nine of 15 patients aged 13 or older were demineralized (P less than .01). Demineralization correlated with the extent of weight reduction in patients (P less than .001). Patients most likely to be demineralized were adolescent girls. To our knowledge, this is the first report of bone mineral status of children with CF, and the results indicate that a sizable proportion of these patients may be demineralized without overt rickets.