The multidirectional assessment of moderate caloric restriction and metformin treatment in obese patients.

Obesity treatment is often burdensome for patients. We used the combination of moderate caloric restriction (CR) with hypoglycemic metformin to assess their multidirectional effect in obese patients. One group was treated only with moderate CR (n=21) the second was treated with moderate CR and 800 mg metformin twice daily (n=23). Serum was drawn before and after treatment. The following parameters were monitored: anthropometric, cardiovascular, inflammatory, metabolic, and markers characteristic for thyroid, liver, pancreas, and kidney functions. Both tested groups did not significantly differ in most tested parameters after the treatment. Two groups reduced anthropometric parameters (body mass, body mass index (BMI), waist circumference) and fat mass but also muscle and fat-free mass, improving systolic blood pressure, insulin and leptin concentration, insulin sensitivity, leptin to adiponectin ratio, and inflammatory markers. Unfortunately, there was little impact on improving dyslipidemia and the thyroid and liver parameters. Free triiodothyronine (fT3) and gamma glutamyl transferase (GGT) activity were decreased in both groups, but triglycerides were reduced only in patients treated with moderate CR. Metformin with CR treatment decreases uric acid and aspartate aminotransferase (AspAT) activity. Metformin treatment with moderate CR in obese patients mainly improved insulin sensitivity, resulting in a reduction of patients with glucose intolerance, improved anthropometric, cardiovascular, and inflammatory mediators, and only slightly enhanced liver and thyroid function. No changes in kidney and pancreas function were observed during the treatment. In conclusion, eight weeks of CR alone and CR with metformin in obese adults improved anthropometric and metabolic markers, reduced muscle mass, fT3, GGT, proinflammatory, and CV parameters, and displayed no changes in kidney and pancreas function. The group treated with metformin after the treatment was still more obese and had higher C-reactive protein (CRP) and homeostasis model assessment-an index of insulin resistance (HOMA-IR), but despite this, considerably reduced the number of patients with glucose intolerance.

Soluble receptor for advanced glycation end products (sRAGE) correlates with obesity-related parameters, and it is not easy to be modified by moderate caloric restriction in obese humans.

Deficiency of a soluble form of the advanced glycation end products receptor (sRAGE) is implicated in obesity-induced complications. Serum sRAGE is inclined to be modified by changes in body weight. We analysed serum sRAGE concentrations in patients with obesity undergoing moderate calorie restriction, which mimics the real-life situation and is not harmful to obese humans. Serum sRAGE was measured by immunoassay in 50 patients with obesity who underwent calorie restriction by 300-500 kcal/day for 8 weeks. In effect calorie restriction resulted in an expected decrease in body weight (by 2.1 kg for an 8-week intervention, p<0.0001), as well as reduced systolic blood pressure, modified dyslipidemia (cholesterol, triglycerides), reduced obesity-related inflammation (tumor necrosis factor-alfa, interleukin-6, C-reactive protein), improved insulin sensitivity. However, it was not accompanied by any significant change in sRAGE concentration. There was a strong negative correlation between BMI and the sRAGE level. Accordingly, the levels of sRAGE were the highest in lean control. In conclusion: a modest weight reduction is unlikely to improve decreased sRAGE levels.

The influence of orlistat, metformin and diet on serum levels of insulin-like growth factor-1 in obeses women with and without insulin resistance.

A range of studies showed confusing data about the relationship between obesity, weight reduction and circulating total insulin-like growth factor -1 (IGF-1). The aim of the study was to compare the influence of orlistat (IO), metformin (IM), or calorie-restricted diet (LC) on IGF-1, with special respect to insulin-resistance status. One hundred and fourteen obese women aged from 18 to 40 years were divided into insulin sensitive (IS) and insulin resistant (IR) groups and received a low calorie diet (LC), or an isocaloric diet and 500 mg metformin twice daily (IM), or isocaloric diet with 120 mg orlistat three times daily (IO). Before and after the intervention anthropometric parameters, serum lipid profile, serum concentrations of alanine aminotransferase, aspartate aminotransferase, insulin, glucose, IGF-1, HOMA-IR (homeostatic model assessment), and visceral adiposity index (VAI), and their changes were registered. Although the reductions in weight and body fat were comparable in IS and IR groups, only women with IR showed a significant increase in IGF-1 concentration as a result of all interventions. We found significant positive correlations of ΔIGF-1 with initial and Δ values of: HOMA-IR, triglyceride/high-density cholesterol ratio, VAI. IR premenopausal women show significant increase in IGF-1 serum concentrations regardless the method of intervention. The increase in IGF-1 was parallel to the improvement of insulin resistance parameters.

Weight loss-dependent and -independent effects of moderate calorie restriction on endothelial cell markers in obesity.

Endothelial cell dysfunction in obesity can be reduced by calorie restriction (CR), however it is unclear whether this benefit requires a concomitant weight loss or is it simply related to the reduced calorie intake per se. In our study serum was drawn from 41 obese women who were undergoing an 8-week dietary intervention with 15 - 30% energy deficit, and from 48 age- and sex-matched controls of normal weight. Serum was analysed for biomarkers of endothelial cell function, oxidative stress and inflammation. Compared with non-obese individuals, the obese patients had lower serum levels of nitric oxide (NO), adiponectin, and decreased serum antioxidant status. They also had significantly higher levels of adhesive molecules, thrombomodulin (TM), von Wilebrand factor (vWF), asymmetric dimethylarginine (ADMA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and leptin. To further characterize the effect of moderate CR, the patients were ranked into two comparable groups according to the extent of weight loss - below and above the median (-5.8 kg). A moderate dietary intervention did not correct adiponectin, antioxidant status, vWF, TM, and plasminogen activator inhibitor-1 (PAI-1) but ameliorated changes in other parameters. Only changes in NO and - to a lesser degree - in sE-selectin showed a clear relationship with the magnitude of weight reduction. By contrast, a beneficial reduction in TNF-α occurred equally in patients who lost more or less weight after caloric restriction. We concluded that moderate calorie restriction could still improve several parameters of endothelial cell function irrespective of whether it was accompanied by changes in body mass. However, a significant improvement in nitric oxide, a key mediator of endothelial well-being, requires a substantial reduction in body weight.

Improvement of serum adiponectin and leptin concentrations: effects of a low-calorie or isocaloric diet combined with metformin or orlistat - a prospective randomized open-label trial.

OBJECTIVE: We compared the effects of three weight loss interventions on serum concentrations of adiponectin and leptin in obese premenopausal women. PATIENTS AND METHODS: 114 obese Caucasian women were randomized into three groups receiving a low-calorie diet (LC; n = 39), an isocaloric diet with 500 mg of metformin twice a day (IM; n = 38), and an isocaloric diet with 120 mg of orlistat three times a day (IO; n = 37), for three months. Serum concentrations of adiponectin and leptin were evaluated, along with anthropometric and body composition parameters, at baseline and after the study. RESULTS: Both IO and LC, but not IM, caused an increase in serum adiponectin concentration (p < 0.01, p < 0.05 respectively). A decrease in serum leptin level was documented in the LC (p < 0.001), IM (p < 0.01), and IO group (p < 0.01). Beneficial changes in anthropometric and body composition values were observed following all interventions with the greatest advantage seen in the IO group. The strongest correlations, of Δadiponectin with Δbody weight (r = -0.54), ΔBMI (r = -0.49), ΔFAT [%] (r = -0.48), ΔFAT [kg] (r = -0.48), and Δlean [%] (r = 0.48); and of Δleptin with Δbody weight, ΔBMI, Δwaist, Δfat, and Δlean, were documented in the IO group. CONCLUSIONS: Beneficial effects were observed on serum leptin concentration, weight loss, and body composition for all interventions and in all examined groups, with the greatest advantage being associated with the orlistat treatment. Improvements in serum adiponectin concentrations resulted from the low-calorie and isocaloric diets with orlistat, but not from the isocaloric diet with metformin. We find these strategies more promising for the treatment of obesity and its related complications in obese premenopausal women.