减重治疗对肥胖患者血清C反应蛋白水平的影响

肥胖患者常伴有胰岛素抵抗 ,与糖尿病、高血压和脂代谢紊乱构成代谢综合征 (ＭＳ)。许多证据表明ＭＳ明显增加心血管疾病的危险性〔1,2〕。研究发现肥胖患者血清中Ｃ反应蛋白 (ＣＲＰ)的水平与动脉粥样硬化、缺血性心血管疾病的患病率、死亡率相关。本研究旨在观察减重治疗是否可以改变患者血清ＣＲＰ水平 ,并且了解与体重变化以及与胰岛素敏感性的关系。一、对象和方法1.对象 :研究对象与全国 6家医院进行的奥利司他有效性和安全性分析研究为同一批病人。我中心共 72人入选。入选标准与排除标准见文献〔3〕。2 .试验方法 :入选的肥胖患者按…     

Effect of orlistat-induced weight loss on blood pressure and heart rate in obese patients with hypertension

OBJECTIVE: To investigate the effects of long-term weight management with orlistat on blood pressure in obese hypertensive patients. DESIGN: A meta-analysis of data from five multicenter, randomized, placebo-controlled studies, conducted in Europe and the USA, was performed. PATIENTS: Obese adults [body mass index (BMI) 28-43 kg/m(2) ] with uncontrolled diastolic hypertension or isolated systolic hypertension (ISH) were eligible for inclusion. INTERVENTIONS: Following a 4-week placebo lead-in period, patients were randomized to orlistat 120 mg or placebo three times daily, in conjunction with a mildly reduced calorie diet for 1 year. MAIN OUTCOME MEASURES: Change in body weight was the primary efficacy parameter. Blood pressure, heart rate and systolic workload were assessed as secondary efficacy parameters. RESULTS: A total of 628 patients were included in the intent-to-treat (ITT) analysis. After 56 weeks, orlistat-treated patients had lost significantly more body weight than placebo recipients (8.0 versus 4.0%; P<0.001). Among patients with ISH, mean systolic pressure was reduced to a significantly greater degree after 1 year with orlistat compared to placebo (-9.4 versus -4.6 mmHg; P= 0.022). Similarly, reductions in mean diastolic pressure in patients with diastolic hypertension were greater with orlistat than with placebo (-7.7 versus -5.6 mmHg; P= 0.017). Weight loss of >or= 10% was associated with significant reductions in blood pressure, heart rate and systolic workload. CONCLUSIONS: Orlistat promotes clinically meaningful weight loss that is associated with significant reductions in blood pressure and heart rate, and may therefore have a role in the management of hypertension in overweight and obese patients.     

The effect of weight loss on C-reactive protein: a systematic review

BACKGROUND: Several studies suggest that weight loss reduces C-reactive protein (CRP) level; however, the consistency and magnitude of this effect has not been well characterized. Our objective was to test the hypothesis that weight loss is directly related to a decline in CRP level. DATA SOURCES: We searched the Cochrane Controlled Trials Register and MEDLINE databases and conducted hand searches and reviews of bibliographies to identify relevant weight loss intervention studies. STUDY SELECTION: We included all weight loss intervention studies that had at least 1 arm that was a surgical, lifestyle, dietary, and/or exercise intervention. Abstracts were independently selected by 2 reviewers. DATA EXTRACTION: Two reviewers independently abstracted data on the characteristics of each study population, weight loss intervention, and change in weight and CRP level from each arm of all included studies. DATA SYNTHESIS: We analyzed the mean change in CRP level (milligrams per liter) and the mean weight change (kilograms), comparing the preintervention and postintervention values from each arm of 33 included studies using graphical displays of these data and weighted regression analyses to quantify the association. RESULTS: Weight loss was associated with a decline in CRP level. Across all studies (lifestyle and surgical interventions), we found that for each 1 kg of weight loss, the mean change in CRP level was -0.13 mg/L (weighted Pearson correlation, r = 0.85). The weighted correlation for weight and change in CRP level in the lifestyle interventions alone was 0.30 (slope, 0.06). The association appeared roughly linear. CONCLUSION: Our results suggest that weight loss may be an effective nonpharmacologic strategy for lowering CRP level.     

The effect of orlistat-induced weight loss,without concomitant hypocaloric diet,on cardiovascular risk factors and insulin sensitivity in young obese Chinese subjects with or without type 2 diabetes

BACKGROUND: We examined the weight-losing effect of orlistat treatment on insulin sensitivity and cardiovascular risk factors in a group of severely obese young Chinese patients with or without type 2 diabetes mellitus. METHODS: Obese patients with diabetes (n = 33) and obese nondiabetic patients (n = 27) were given orlistat, 120 mg 3 times daily, without a concomitant hypocaloric diet for 6 months (body mass index [calculated as weight in kilograms divided by the square of height in meter; kg/m2] range, 27.8-47.4). The efficacy measures were (1) insulin sensitivity indices derived from the homeostasis model assessment and a composite measure of whole-body insulin sensitivity index; (2) glycemic control; (3) cardiovascular risk factors, including anthropometry, blood pressure, lipid profiles, and albuminuria; and (4) body composition determined by dual-energy x-ray absorptiometry. RESULTS: At baseline, patients with diabetes had lower body mass index and percentage of body fat but higher waist-hip ratios and were more insulin resistant. Orlistat therapy reduced body weight, waist and hip circumferences, percentage of total body fat, blood pressure, fasting plasma glucose and lipid levels, albuminuria, and insulin sensitivity indices in both groups (all, P<.05). Despite less weight reduction, we found a greater percentage of reduction from baseline in glycosylated hemoglobin level (-11.6% vs -3.6%; P<.001), fasting plasma glucose level (-18.2% vs -5.0%; P<.001), and systolic blood pressure (-7.1% vs -3.1%; P =.02) in patients with diabetes. Obese subjects without diabetes had greater improvements in triglyceride levels, albuminuria, and the homeostasis model assessment (all, P<.01). CONCLUSION: Short-term orlistat treatment without the use of a hypocaloric diet significantly improved insulin sensitivity and cardiovascular risk profiles in severely obese Chinese patients with or without type 2 diabetes.     

Cardiovascular risk evaluated by C-reactive protein levels in diabetic and obese Mexican subjects.

BACKGROUND: Previous studies have reported elevated levels of C-reactive protein (CRP) in obese and diabetic subjects, but it is unclear whether both these conditions have an additive effect on the variability of serum CRP levels. METHODS AND RESULTS: The study enrolled 385 men and women who were classified into 4 groups: (1) diabetes (n=97), (2) obesity (n=108), (3) diabetes/obesity (n=78), and (4) healthy (n=102). All were Mexican subjects from Guerrero State. Serum high-sensitivity CRP (hs-CRP) levels were higher in both type 2 diabetes mellitus (T2DM)/obesity and obesity (5.1 mg/L) groups than in the diabetics (1.8 mg/L) without obesity. Only the measurements of obesity were strongly related to hs-CRP (body mass index, r=0.46 and waist circumference, r=0.41). The presence of T2DM and obesity explain 20% of the circulating hs-CRP level, following waist circumference (16%), leukocyte count (10%), diastolic blood pressure (6%), and female gender (4%). Obese subjects (odds ratio (OR)=6.3) and T2DM/obesity patients (OR=6.9) showed high risk for coronary disease and this effect was increased in T2DM/obesity women (OR=9.9). Also, abdominal obesity was associated with high coronary disease risk (OR=5.4), showing an increase in women (OR=7.3). CONCLUSION: High hs-CRP levels are related to obesity and central distribution of body fat, leading to a higher cardiovascular risk among Mexican subjects.     

High protein weight loss diets in obese subjects with type 2 diabetes mellitus

Background and aimDiets where carbohydrate has been partially exchanged for protein have shown beneficial changes in persons with type 2 diabetes but no studies have enrolled people with albuminuria. We aim to determine if a high protein to carbohydrate ratio (HPD) in an energy reduced diet has a beneficial effect on metabolic control and cardiovascular risk factors without negatively affecting renal function.Method and resultsAdult, overweight participants with type 2 diabetes, with albuminuria (30–600 mg/24 h or an albumin-to-creatinine ratio of 3.0–60 mg/mmol), and estimated GFR of >40 ml/min/1.73 m² were enrolled. Participants were randomized to an HPD or an SPD. Protein:fat:carbohydrate ratio was 30:30:40% of energy for the HPD and 20:30:50% for the SPD. Main outcomes were renal function, weight loss, blood pressure, serum lipids and glycaemic control. We recruited 76 volunteers and 45 (35 men and 10 women) finished. There were no overall changes in renal function at 12 months and no significant differences in weight loss between groups (9.7 ± 2.9 kg and 6.6 ± 1.4 kg HPD and SPD group respectively; p = 0.32). Fasting blood glucose decreased significantly with no treatment effect. The decrease in HbA1c differed between treatments at 6 months (HPD −0.9 vs. SPD −0.3%; p = 0.039) but not at 12 months. HDL increased significantly with no treatment effects. There were no changes in LDL or blood pressure overall but DBP was lower in the HPD group (p = 0.024) at 12 months.ConclusionWeight loss improved overall metabolic control in this group of well controlled participants with type 2 diabetes regardless of diet composition.     

Serum retinol-binding protein 4 is reduced after weight loss in morbidly obese subjects

CONTEXT: Administration of retinol-binding protein 4 (RBP-4) impairs insulin sensitivity in animals, and elevated serum concentrations have been associated with insulin resistance in humans. OBJECTIVE: We have studied whether weight loss influences RBP-4. PATIENTS AND METHODS: Fasting serum concentrations of RBP-4 were measured before and 6 months after gastric banding surgery in 33 morbidly obese patients aged 40 +/- 11 yr with a body mass index (BMI) of 46 +/- 5 kg/m(2). Fourteen healthy subjects aged 29 +/- 5 yr with a BMI less than 25 kg/m(2) served as controls. To characterize the association of weight loss with central and peripheral appetite regulation, the signaling protein agouti-related protein (AGRP), the orexigenic hormone ghrelin, and its recently identified antagonist obestatin were determined. RESULTS: At baseline, RBP-4 levels were markedly higher in obese than in lean subjects (2.7 +/- 0.5 vs. 0.9 +/- 0.5 microg/ml; P < 0.001). In contrast, AGRP and obestatin were lower in obese subjects compared with lean controls (all P < 0.001). Six months after gastric banding, BMI was reduced to 40 +/- 5 kg/m(2), RBP-4 was reduced to 2.0 +/- 0.7 microg/ml, AGRP increased from 1.8 +/- 1.1 to 3.4 +/- 1.1 ng/ml, ghrelin increased from 93 +/- 58 to 131 +/- 70 pg/ml, and obestatin increased from 131 +/- 52 to 173 +/- 35 pg/ml (all P < 0.05). Individual changes of RBP-4 were associated with changes of BMI (r = 0.72), the homeostasis model assessment insulin resistance-index (r = 0.53), and total cholesterol (r = 0.42, for all P < 0.05). CONCLUSION: Reductions in circulating RBP-4 may contribute to improved insulin resistance in morbidly obese subjects after weight loss. This is accompanied by favorable changes in appetite-regulating hormones, which might support the sustained weight loss after obesity surgery.     

The effect of fenofibrate on the levels of high sensitivity C-reactive protein in dyslipidemic obese patients

It is now well documented that obesity is associated with a chronic low-grade inflammatory state. Levels of high-sensitivity C-reactive protein, a marker of systemic inflammation and a mediator of atherothrombotic disease, have been shown to correlate with cardiovascular disease risk. Our objective was to evaluate the effect of fenofibrate on the levels of high-sensitivity C-reactive protein in dyslipidemic obese patients. We selected 30 dyslipidemic obese patients (body mass index > or = 30 kg/m2) and 20 normolipidemic, nonobese healthy subjects. Dyslipidemic obese patients were treated with fenofibrate 200 mg/day for 3 months. Serum high-sensitivity C-reactive protein and metabolic parameters were evaluated at baseline in both groups and after fenofibrate treatment in dyslipidemic obese patients. At baseline, significantly higher high-sensitivity C-reactive protein levels were found in dyslipidemic obese patients than normal subjects (0.58+/-0.3 vs 0.14+/-0.1 mg/dL, P < 0.01). Total cholesterol, low-density lipoprotein cholesterol, and triglyceride decreased significantly (P < 0.05, P < 0.05, and P < 0.01, respectively), and levels of high-density lipoprotein cholesterol significantly increased (P < 0.05) after treatment with fenofibrate in the dyslipidemic obese group. Levels of high-sensitivity C-reactive protein decreased significantly (approximately 74.1%) after fenofibrate treatment from a mean of 0.58+/-0.3 mg/dL to 0.15+/-0.2 mg/dL, P < 0.01. Our findings suggest that fenofibrate may be used as a first-line therapy for improving the plasma lipids profile, as well as the chronic low-grade inflammatory state in dyslipidemia and obesity.     

Energy restriction and weight loss on very-low-fat diets reduce C-reactive protein concentrations in obese, healthy women

C-reactive protein (CRP) is an inflammatory-response protein that is a strong, independent predictor of cardiovascular mortality. CRP is positively associated with body mass index (BMI). In this study, we investigated the effects of dynamic weight loss on CRP in 83 healthy, obese women (mean BMI, 33.8+/-0.4 kg/m(2); range, 28.2 to 43.8 kg/m(2)). Subjects were placed on very-low-fat, energy-restricted diets (5700 kJ, 15% fat) for 12 weeks. Weight, waist and hip circumferences, plasma lipids, glucose, and CRP were measured at baseline and after 12 weeks. CRP was positively associated with BMI (r=0.281, P=0.01) and waist circumference (r=0.278, P=0.01) but was not related to other atherosclerosis risk factors. BMI was significantly different between groups split above or below the median for CRP (34.8+/-0.6 kg/m(2) vs 33.0+/-0.5 kg/m(2), P=0.02). After 12 weeks, weight loss was 7.9+/-0.3 kg. CRP was significantly decreased by 26% (P<0.001), and a correlation was observed between weight loss and the change in CRP (r=0.309, P=0.005). The variance in the change in CRP was partly explained by initial CRP (13.6%), energy intake (5.4%), and percentage weight loss (4.6%, P=0.001). This study confirms recent observations that BMI is associated with CRP, a marker for low-grade systemic inflammation. Furthermore, we observed that CRP was lowered in proportion to weight loss.     

Diet-induced weight loss is associated with decreases in plasma serum amyloid a and C-reactive protein independent of dietary macronutrient composition in obese subjects

Elevated levels of serum amyloid A (SAA) and C-reactive protein (CRP) have been associated with increased cardiovascular risk. Although levels of CRP decrease with weight loss, it is not known whether SAA decreases with weight loss or whether dietary macronutrient composition affects levels of either SAA or CRP. SAA and CRP levels were measured retrospectively on baseline and 3-month plasma samples from 41 obese (mean body mass index 33.63 +/- 1.86 kg/m2) women completing a randomized trial comparing a low-fat diet (n = 19) and a very low-carbohydrate diet (n = 22). For the 41 participants, there were significant decreases from baseline to 3 months in both LogSAA (P = 0.049) and LogCRP (P = 0.035). The very low-carbohydrate dieters had a significantly greater decrease in LogSAA (P = 0.04), but their weight loss also was significantly greater (-7.6 +/- 3.2 vs. -4.3 +/- 3.5 kg, P < 0.01). In this study, the decreases in inflammatory markers correlated significantly with weight loss (r = 0.44, P = 0.004 vs. LogSAA and r = 0.35, P = 0.03 vs. LogCRP). Also, change in LogSAA correlated with change in insulin resistance (r = 0.35, P = 0.03). Thus, in otherwise healthy, obese women, weight loss was associated with significant decreases in both SAA and CRP. These effects were proportional to the amount of weight lost but independent of dietary macronutrient composition.     

The effects of weight loss on normal transaminase levels in obese patients

BACKGROUND: Obesity is associated with insulin resistance, which is the main pathogenic factor for nonalcoholic fatty liver disease (NAFLD). NAFLD can progress without associated elevations in liver enzymes. Therefore, we investigated the effects of weight loss on normal transaminase levels in obese subjects who are at risk for NAFLD. METHODS: Thirty-seven obese patients with normal ALT levels were evaluated. All patients received an individualized low-calorie diet over at least 6 months. Twenty-two patients who achieved weight loss of at least 5% body weight were identified as the study group and the others as the control group. Transaminases, insulin resistance, and body mass index were compared before and after the intervention. RESULTS: Hepatic steatosis was found in 83.8% of obese patients. ALT was correlated with HOMA-IR in all patients at baseline (r = 0.363, P = 0.027). At the end of the follow-up, mean weight loss achieved in the study and control groups were 9.2% (8.7 +/- 3.0 kg) and 0.3% (0.5 +/- 2.8 kg), respectively. In the study group, HOMA-IR and ALT decreased from 4.0 +/- 1.8 to 2.4 +/- 0.9 and from 21.4 +/- 6.6 IU/L to 16.8 +/- 5.5 IU/L, respectively (P = 0.005 and P = 0.044). CONCLUSIONS: The results demonstrate that weight loss results in a decrease in normal ALT levels as well as insulin resistance. Therefore, the normal range for ALT may need to be reassessed.     

Effect of weight loss on QTc dispersion in obese subjects.

OBJECTIVE: Increased QTc dispersion is a predictor for ventricular arrhythmias. The aim of this study was to investigate whether QTc dispersion decreases after weight loss program with diet and medical treatment. METHODS: Total 30 (24 women and 6 men, mean age: 44+/-8 years) obese subjects who lost at least 10% of their original weight after 12 week weight loss program were included in present study. Obesity was defined as > or =30 kg/m(2) of body mass index (BMI). Normal weight was defined as < or = 25 kg/m(2) of BMI. RESULTS: After 12 week weight loss program, BMI decreased from 42+/-5 kg/m(2) to 36+/-4 kg/m(2) (p<0.001) and mean weight of obese subjects decreased from 110+/-17 kg to 95+/-15 kg (p<0.001). The mean amount of weight loss was 14.5+/-5.0 kg (range 9-32 kg). The average percent of weight loss was 13% (10.0%-20.3%). Maximum QTc interval (from 446+/-19 ms to 433+/-27 ms, p=0.024) and QTc dispersion (from 66+/-18 ms to 52+/-25 ms, p=0.024) significantly decreased after weight loss program. A statistically significant correlation was found between decrease in level of QTc dispersion and amount of weight loss (r=0.487, p=0.007). CONCLUSION: Substantial weight loss in obese subjects is accompanied by significantly decreased QTc dispersion. The degree of QTc dispersion reduction is associated with amount of weight loss.     

Serum lipase, C-reactive protein, and interleukin-6 levels in ERCP-induced pancreatitis

BACKGROUND: C-reactive protein (CRP) and interleukin-6 (IL-6) are elevated in acute pancreatitis. Limited studies have evaluated their role in ERCP-induced pancreatitis. The aim of this study was to assess the role of serum lipase, CRP, and IL-6 in ERCP-induced pancreatitis. METHODS: Eighty-five patients (62 women, 23 men; mean age 43 years; range 16-85 years) who underwent ERCP were entered in a prospective trial. ERCP-induced pancreatitis was classified as mild, moderate, or severe. Serum levels of lipase, CRP, and IL-6 were measured before ERCP and at 12 to 24 hours and 36 to 48 hours after ERCP. RESULTS: Mild, moderate, and severe pancreatitis occurred, respectively, in 9, 7, and 4 patients after ERCP. There were significant differences in levels of CRP and IL-6 but not lipase for patients with mild versus moderate and moderate versus severe pancreatitis. The mean CRP levels (mg/dL) at 12 to 24 hours were 0.98 +/- 0.24 in mild pancreatitis, 3.89 +/- 0.32 in moderate pancreatitis, and 12.0 +/- 1.60 in severe pancreatitis. The levels, respectively, at 36 to 48 hours were 1.60 +/- 0.31, 7.60 +/- 0.74, and 25.0 +/- 2.9. The mean IL-6 levels (pg/mL) at 12 to 24 hours were 16.6 +/- 2.06 in mild pancreatitis, 73.0 +/- 15.60 in moderate pancreatitis, and 235.5 +/- 26.31 in severe pancreatitis. The levels at 36 to 48 hours were, respectively, 18.92 +/- 3.28, 100.17 +/- 11.56, and 438.2 +/- 71.50. CONCLUSIONS: Serum CRP and IL-6 levels may be useful early markers for predicting the severity of ERCP-induced pancreatitis.     

Effects of sibutramine-induced weight loss on cardiovascular system in obese subjects

BACKGROUND AND AIM: To assess efficacy of sibutramine in obese subjects, and influence on hemodynamics, valve function and left ventricular (LV) geometry and performance. METHODS AND RESULTS: Three-month double-blind, parallel groups, randomized, placebo-controlled of 15 mg o.i.d. sibutramine administration combined with diet. Twenty-five to 65 year-old males or postmenopausal females, were enrolled if their BMI was between 30 and 40 kg/m(2), without evidence of concomitant diseases. Body weight, BMI, blood pressure (BP), echocardiographic LV mass, cardiac output, and diastolic function were measured. Body weight and BMI were better reduced with sibutramine (weight loss of 5% or more in 9 of 11 patients) than placebo group (weight loss of 5% or more in 5 of 9 patients; all p<0.05). Systolic and diastolic BP decreased similarly in both arms. No difference in mean heart rate was detected between treatments. The two groups had slightly different LV geometry at baseline. LV mass decreased with weight loss, more in the sibutramine group (p<0.05), due to reduction in LV chamber size. Stroke volume tended to be reduced in the sibutramine group, influencing diastolic pattern. E/A ratio tended to decrease in the sibutramine group without changes in isovolumic relaxation time and deceleration time of E velocity. No onset or increased severity of valve regurgitation was detected. CONCLUSIONS: Combined to hypocaloric diet, sibutramine increases weight loss in obese individuals. Weight changes have positive effect on reduction of BP and contribute to reduce LV mass, the hallmark of markers of preclinical cardiovascular disease and most powerful predictor of adverse outcome.     

The effect of pegylated recombinant human leptin (PEG-OB) on weight loss and inflammatory status in obese subjects

OBJECTIVE: To investigate whether weekly subcutaneous administration of 60 mg of long-acting pegylated human leptin (PEG-OB) for 8 weeks was able to influence weight loss, metabolic profile and inflammatory status of obese subjects on a mildly hypoenergetic diet (deficit: 3.2 MJ/day). DESIGN: A prospective, randomized, double-blind and placebo-controlled single-center trial. SUBJECTS: Twenty-eight healthy, obese subjects (16 women, 12 men; age 22-65 y; body mass index 27.7-38.7 kg/m2). MEASUREMENTS: Bodyweight, metabolic profile (including lipids), C-reactive protein (CRP) and soluble TNF alpha-receptor (sTNF-R) 55 and 75 levels. RESULTS: At the end of the study no significant differences in the delta or percentage weight loss between the placebo (n = 14) and PEG-OB (n = 14) groups was observed. Also the changes in metabolic profile, CRP, sTNF-R55 and R75 concentrations between the two groups after 8 weeks of treatment did not differ. CONCLUSION: Weekly injection of 60 mg PEG-OB did not lead to additional weight loss after 8 weeks of treatment. Furthermore, PEG-OB administration did not affect the changes in metabolic profile and the inflammatory status of obese subjects.