Gestational weight gain and visceral adiposity in adult offspring: Is there a link with the fecal abundance of Acidaminococcus genus?

Intrauterine environment can influence the offspring's body adiposity whose distribution affect the cardiometabolic risk. Underlying mechanisms may involve the gut microbiome. We investigated associations of gestational weight gain with the adult offspring's gut microbiota, body adiposity and related parameters in participants of the Nutritionists' Health Study. METHODS: This cross-sectional analysis included 114 women who had early life and clinical data, body composition, and biological samples collected. The structure of fecal microbiota was analyzed targeting the V4 region of the 16 S rRNA gene. Beta diversity was calculated by PCoA and PERMANOVA used to test the impact of categorical variables into the diversity. Bacterial clusters were identified based on the Jensen-Shannon divergence matrix and Calinski-Harabasz index. Correlations were tested by Spearman coefficient. RESULTS: Median age was 28 (IQR 24-31) years and BMI 24.5 (IQR 21.4-28.0) kg/m2. Fifty-eight participants were assigned to a profile driven by Prevotella and 56 to another driven by Blautia. Visceral adipose tissue was correlated to abundance of Acidaminococcus genus considering the entire sample (r = 0.37; p < 0.001) and the profiles (Blautia: r = 0.35, p = 0.009, and Prevotella: r = 0.38, p = 0.006). In Blautia-driven profile, the same genus was also correlated to maternal gestational weight gain (r = 0.38, p = 0.006). CONCLUSIONS: Association of Acidaminococcus with gestational weight gain could reinforce the relevance with mothers' nutritional status for gut colonization at the beginning of life. Whether Acidaminococcus abundance could be a marker for central distribution of adiposity in young women requires further investigation.

Adiponectin, HOMA-Adiponectin, HOMA-IR in Children and Adolescents: Ouro Preto Study.

OBJECTIVES: To examine the association and predictive capacity of adiponectin levels, HOMA-AD and HOMA-IR indexes with metabolic risk markers in children and adolescents. METHODS: A cross-sectional study was conducted with 691 children and adolescents (7-14 y), of both sexes. Demographic (sex, age), anthropometric (weight, height, body mass index, waist circumference, body fat), biochemical [total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, fasting glycemia, insulin and adiponectin] and clinical parameters (arterial blood pressure) were analyzed. RESULTS: In multiple linear regression models, metabolic risk were analyzed in relation to adiponectin levels, HOMA-AD and HOMA-IR. ROC curve analysis was used to define the cut-off for metabolic syndrome for each method studied. Adiponectin level was inversely correlated with weight (r = -0.12; p = 0.01), waist circumference (WC) (r = -0.12; p = 0.01), and triglycerides (r = -0.11; p = 0.02); it was directly correlated with HDL (r = 0.10; p = 0.03) only in the adolescents. In the final linear regression model, after adjustment, only triglycerides (p = 0.03) and HDL (p = 0.04) remained significant. However, HOMA-AD and HOMA-IR were associated with metabolic risk and were the most suitable methods for metabolic syndrome screening in both age groups. For children, independent variables explained 16.0% and 14.5% of HOMA-AD and HOMA-IR, respectively. For adolescents, R2 was higher in HOMA-AD and HOMA-IR models (R2adjusted = 31.9% and R2adjusted = 29.6%, respectively). CONCLUSIONS: HOMA-AD and HOMA-IR are better explained by metabolic markers than adiponectin levels.

Early Regression of Carotid Intima-Media Thickness after Bariatric Surgery and Its Relation to Serum Leptin Reduction.

PURPOSE: Bariatric surgery (BS) promotes carotid intima-media thickness (C-IMT) regression as early as 6 months post-surgery. To verify whether C-IMT regression occurs even earlier, we aimed at the effect of Roux-en-Y gastric bypass (RYGBP) and biliopancreatic diversion (BPD) on C-IMT 1-2 months and 12 months post-surgery. SUBJECTS/METHODS: Prospective trial. BS was performed on 109 patients either with (RYGBP = 42; BDP = 40) or without type 2 diabetes (RYGBP = 27). Healthy volunteers served as control group. FOLLOW-UP: baseline, 1-2 months, 12 months post-surgery. ENDPOINTS: changes (∆) in C-IMT, weight, body mass index, fat mass, waist and neck circumferences, blood pressure, HbA1c, glucose, insulin, insulin sensitivity [HOMA-IR; OGIS, from meal tolerance test], lipids, C-reactive protein, leptin, adiponectin, MCP-1. RESULTS: All surgery subgroups had similar levels of ∆-C-IMT. C-IMT in the pooled surgery group reduced from [mean (95% confidence interval)] 0.81 (0.77-0.84) mm to 0.66 (0.63-0.69) mm, p < 0.001 [-17.1 (-20.4 to -13.8)%] at 1-2 months, and to 0.63 (0.59-0.66) mm, p < 0.001 [-21.8 (-25.3 to -18.4)%] at 12 months post-surgery. ∆-C-IMT 1-2 months and 12 months post-surgery correlated to baseline C-IMT, and with ∆-leptin at 1-2 months, but not at 12 months post-surgery. In linear regression analysis, ∆-leptin and baseline C-IMT were predictors of ∆-C-IMT 1-2 months post-surgery. CONCLUSIONS: A remarkable C-IMT regression occurred as early as 1-2 months after BS in obese patients either with or without type 2 diabetes, which was associated to the early reduction in leptin, (at least partially) independent of weight loss. Whether this is a causative or correlative association needs further investigation.

Impairment of body mass reduction-associated activation of brown/beige adipose tissue in patients with type 2 diabetes mellitus.

Backgrounds/Objectives:The activity of brown/beige adipose tissue (B/BAT) is inversely proportional to body adiposity. Studies have shown that obese subjects submitted to distinct approaches aimed at reducing body mass present an increase of B/BAT activation. However, it is unknown if this beneficial effect of body mass reduction applies to patients with type 2 diabetes mellitus. In this study, we evaluated the impact of massive body mass reduction obtained as a consequence of bariatric surgery in the cold-induced activation of B/BAT in obese non-diabetic (OND) and obese diabetic (OD) subjects. SUBJECTS/METHODS: This is an observational study. Fourteen OND, 14 OD and 11 subjects were included in the study. All obese subjects were submitted to Roux-in-Y gastric bypass and measurements were performed before and 8 months after surgery. B/BAT was evaluated by (18F)-FDG-PET/CT scan and determination of signature transcript expression in specimens obtained in biopsies. RESULTS: Before surgery, mean B/BAT activity and the expression of signature transcripts were similar between OND and OD groups. Eight months after surgery, body mass reduction was similar between the obese groups. Nevertheless, the activity of B/BAT was increased in OND and unchanged in OD subjects. This effect was correlated with a more pronounced improvement of insulin resistance, as evaluated by the hyperinsulinemic, euglycemic clamp, in OND subjects as compared with OD subjects. CONCLUSIONS: Body mass reduction has a more efficient effect to induce the activation of B/BAT in non-diabetic than in diabetic subjects. This effect is accompanied by more pronounced insulin sensitivity and serine 473 phosphorylation of Akt in B/BAT of non-diabetic than in diabetic subjects.

Distinct regulation of hypothalamic and brown/beige adipose tissue activities in human obesity.

BACKGROUND/OBJECTIVES: The identification of brown/beige adipose tissue in adult humans has motivated the search for methods aimed at increasing its thermogenic activity as an approach to treat obesity. In rodents, the brown adipose tissue is under the control of sympathetic signals originating in the hypothalamus. However, the putative connection between the depots of brown/beige adipocytes and the hypothalamus in humans has never been explored. The objective of this study was to evaluate the response of the hypothalamus and brown/beige adipose tissue to cold stimulus in obese subjects undergoing body mass reduction following gastric bypass. SUBJECTS/METHODS: We evaluated twelve obese, non-diabetic subjects undergoing Roux-in-Y gastric bypass and 12 lean controls. Obese subjects were evaluated before and approximately 8 months after gastric bypass. Lean subjects were evaluated only at admission. Subjects were evaluated for hypothalamic activity in response to cold by functional magnetic resonance, whereas brown/beige adipose tissue activity was evaluated using a (F 18) fluorodeoxyglucose positron emisson tomography/computed tomography scan and real-time PCR measurement of signature genes. RESULTS: Body mass reduction resulted in a significant increase in brown/beige adipose tissue activity in response to cold; however, no change in cold-induced hypothalamic activity was observed after body mass reduction. No correlation was found between brown/beige adipose tissue activation and hypothalamus activity in obese subjects or in lean controls. CONCLUSIONS: In humans, the increase in brown/beige adipose tissue activity related to body mass reduction occurs independently of changes in hypothalamic activity as determined by functional magnetic resonance.

Defective regulation of adipose tissue autophagy in obesity.

OBJECTIVES: Autophagy is a highly regulated process that has an important role in the control of a wide range of cellular functions, such as organelle recycling, nutrient availability and tissue differentiation. A recent study has shown an increased autophagic activity in the adipose tissue of obese subjects, and a role for autophagy in obesity-associated insulin resistance was proposed. Body mass reduction is the most efficient approach to tackle insulin resistance in over-weight subjects; however, the impact of weight loss in adipose tissue autophagy is unknown. SUBJECTS: Adipose tissue autophagy was evaluated in mice and humans. RESULTS: First, a mouse model of diet-induced obesity and diabetes was maintained on a 15-day, 40% caloric restriction. At baseline, markers of autophagy were increased in obese mice as compared with lean controls. Upon caloric restriction, autophagy increased in the lean mice, whereas it decreased in the obese mice. The reintroduction of ad libitum feeding was sufficient to rapidly reduce autophagy in the lean mice and increase autophagy in the obese mice. In the second part of the study, autophagy was evaluated in the subcutaneous adipose tissue of nine obese-non-diabetic and six obese-diabetic subjects undergoing bariatric surgery for body mass reduction. Specimens were collected during the surgery and approximately 1 year later. Markers of systemic inflammation, such as tumor necrosis factor-1α, interleukin (IL)-6 and IL-1ß were evaluated. As in the mouse model, human obesity was associated with increased autophagy, and body mass reduction led to an attenuation of autophagy in the adipose tissue. CONCLUSION: Obesity and caloric overfeeding are associated with the defective regulation of autophagy in the adipose tissue. The studies in obese-diabetic subjects undergoing improved metabolic control following calorie restriction suggest that autophagy and inflammation are regulated independently.

Cerebrospinal fluid xenin levels during body mass reduction: no evidence for obesity-associated defective transport across the blood-brain barrier.

CONTEXT: Recent studies have shown that xenin can act in the hypothalamus, reducing food intake through a leptin- and melanocortin system-independent mechanism. OBJECTIVE: To evaluate the impact of body mass reduction on the blood and cerebrospinal fluid (CSF) levels of xenin. DESIGN AND SETTING: Thirteen obese patients (11 women) selected for roux-in-Y gastric bypass surgery were evaluated before and approximately 8 months after surgery. Xenin was determined in serum and CSF by radioimmunoassay. RESULTS: As compared with lean subjects, obese patients have increased blood levels of xenin, which reduce after surgery. There are significant correlations between blood xenin and blood leptin and insulin levels. CSF concentration of xenin is ∼10-fold lower than blood levels, and is significantly higher in obese subjects as compared with lean ones, returning to normal levels after body mass reduction. There is a significant linear correlation between CSF and blood levels of xenin. CONCLUSION: Xenin is present in the human CSF in a concentration ∼10-fold lower than the blood. Both blood and CSF xenin are correlated with blood levels of important markers of adiposity, leptin and insulin. The levels of CSF xenin are linearly correlated with blood xenin, independently of patient body mass, suggesting that either its transport across the blood-brain barrier is not saturated in the concentration range detected in this study or that there is a coordinated release of xenin from the periphery and the CNS.

The newly identified anorexigenic adipokine nesfatin-1 in hemodialysis patients: Are there associations with food intake, body composition and inflammation?

Nesfatin-1 is a recently identified anorexigenic peptide that has been implicated in appetite regulation, weight loss and/or malnutrition. Anorexia and malnutrition are common features of chronic kidney disease (CKD) that predispose patients to worse outcomes. However, the reasons for the occurrence of anorexia in CKD patients are not fully elucidated. The aim of this study was to investigate the association between nesfatin-1 and protein intake and body composition in patients undergoing hemodialysis (HD). Twenty five HD patients from a private Clinic in Rio de Janeiro, Brazil were studied and compared with 15 healthy subjects that were matched for body mass index (BMI), % body fat mass (by anthropometrics) and age. Appetite was measured using a specific questionnaire, and food intake was evaluated based on 3-day food records. Nesfatin-1 levels were measured by ELISA and leptin, TNF-α and IL-6 levels were determined by a multiplex assay kit. Serum nesfatin-1 levels did not differ between HD patients (0.16±0.07ng/mL) and healthy subjects (0.17±0.10ng/mL). Nesfatin-1 levels showed significant negative correlations with protein intake (r=-0.42; p=0.03), but did not associate with inflammatory markers or appetite scores. Combining patients and controls, we observed positive correlations with BMI (r=0.33; p=0.03), % body fat (r=0.35; p=0.03), leptin (r=0.45; p=0.006) and the triceps skinfold thickness (r=0.36; p=0.02). In multivariate analysis % body fat was the main determinant of nesfatin-1 variance. In conclusion, nesfatin-1 levels did not differ between HD patients and healthy subjects and negatively correlated with protein intake. This pathway is likely not dysregulated in uremia.

PGC1α gene Gly482Ser polymorphism predicts improved metabolic, inflammatory and vascular outcomes following bariatric surgery.

AIMS/HYPOTHESIS: Bariatric surgery is currently employed as an effective approach to treat class III obesity and class II obesity with co-morbidities. Unfortunately, the general anthropometric and metabolic outcomes of the surgery are not homogeneous, and defining the eligibility criteria that allow for a more precise prediction of the outcomes of this invasive procedure will refine the selection of patients. Here we tested the hypothesis that the Gly482Ser polymorphism of the ppargc1a gene would predict different outcomes following bariatric surgery. METHODS: Fifty-five patients (26 Gly/Gly and 29 Gly/Ser+Ser/Ser) selected for the Roux-en-Y gastric bypass according to the National Institutes of Health Consensus Statement criteria were followed up for 1 year, monitoring their anthropometric, metabolic and inflammatory parameters. RESULTS: Patients with the Gly482Ser polymorphism had significantly improved reductions in the waist/hip ratio, fasting blood glucose, C-reactive protein, blood leukocyte count, serum interleukin-6 and intima-media thickness of the carotid artery, as compared with Gly/Gly patients. CONCLUSIONS/INTERPRETATION: Thus, the Gly482Ser polymorphism may predict a more favorable metabolic and inflammatory outcome for obese patients submitted to bariatric surgery, leading to a reduced atherosclerotic risk.

Hip circumference is associated with high density lipoprotein cholesterol response following statin therapy in hypertensive subjects.

AIM: This report investigated the relationship between anthropometric measurements of body fat distribution and lipid response to statins in hypercholesterolemic hypertensive patients. METHODS: We prospectively examined 129 subjects who used either simvastatin 20 mg/day (no.=83) or atorvastatin 10 mg/day (no.=46) for 3 months. Anthropometry included evaluation of body mass index, waist and hip circumferences, and waist-to-hip-ratio. RESULTS: Significant decreases in LDL (p<0.001), total cholesterol (p<0.001), and triglycerides (p=0.04) levels were detected after 3 months of therapy in the whole sample. At baseline, only an inverse correlation between waist circumference and HDLcholesterol levels was detected (r=-0.18; p=0.04). Conversely, a direct relationship between hip circumference and HDLcholesterol response to statins was found in the whole sample (r=0.24; p=0.006), while no other anthropometric measurement displayed significant correlation with lipid changes. The association between HDL-cholesterol response and hip circumference was further confirmed by stepwise regression analysis adjusted for baseline HDL-cholesterol levels, metabolic syndrome, body mass index, and waist circumference. CONCLUSIONS: Hip circumference, a surrogate marker of peripheral adiposity, is associated with HDL-cholesterol changes following statin therapy in hypertensive patients.

Rosiglitazone decreases intra- to extramyocellular fat ratio in obese non-diabetic adults with metabolic syndrome.

BACKGROUND: Insulin resistance is intrinsically related to intramyocellular (IMCL) rather than extramyocellular (EMCL) triglyceride content. Conflicting results have been reported on the ability of insulin sensitizer agents, such as thiazolidinediones, to modify muscle fat distribution. The aim of this study was to investigate the role of rosiglitazone on muscle fat compartment distribution in an adult population of obese non-diabetic metabolic syndrome patients. PATIENTS AND METHODS: Fifteen obese, non-diabetic, metabolic syndrome patients were studied by means of proton nuclear magnetic resonance ((1)H-NMR) spectroscopy before and after treatment with rosiglitazone 8 mg/day for 6 months. Anthropometrical and metabolic variables were assessed. RESULTS: After rosiglitazone, body weight and hip circumference increased [100.9 (91.12-138.7) vs. 107.0 (79.6-142.8) kg and 118 (107-126) vs. 122 (110-131) cm]; while waist-hip ratio (WHR) decreased from 0.93 (0.87-1.00) to 0.89 (0.82-0.97) (P < 0.001 for all). Additionally, fasting plasma glucose, insulin and homeostatis model assessment of insulin resistance (HOMA-IR) significantly decreased while adiponectin increased over threefold [9.7 (3.7-17.7) vs. 38.0 (19.3-42.4) microg/ml] without any changes in resistin. Finally, the IMCL did not change [267.54 (213.94-297.94) vs. 305.75 (230.80-424.75) arbitrary units (AU), P = 0.15] while the EMCL increased [275.53 (210.39-436.66) vs. 411.39 (279.92-556.59) AU; P < 0.01] therefore decreasing the IMCL-to-EMCL (IMCL/EMCL) ratio [1.07 (0.78-1.23) vs. 0.71 (0.53-0.96); P < 0.01]. CONCLUSION: Rosiglitazone treatment increased body weight and hip circumference and decreased WHR. More importantly, it decreased the IMCL/EMCL ratio by increasing the EMCL without any significant change on the IMCL.

Adiponectin is related to intramyocellular lipid content in non-diabetic adults.

OBJECTIVE: Insulin resistance (IR) is associated with intramyocellular lipid (IMCL) content and low serum adiponectin (ADP) levels and ADP is also involved in muscle fat oxidation. However, the relationship between ADP and IMCL content is still controversial and in this study we explored it further in non-diabetic adults. DESIGN: Cross-sectional clinical study. SUBJECTS: Thirty-three adult subjects, 24 obese non-diabetic patients with metabolic syndrome (MS) and 9 lean healthy controls. MEASUREMENTS: Proton nuclear magnetic resonance spectroscopy (1H-NMRS) was performed to quantify IMCL content. The latter plus serum ADP, anthropometrics and biochemical parameters were evaluated and compared in these 2 groups. RESULTS: MS patients had higher body mass index, waist, waist-to- hip ratio, glucose, insulin, and triglycerides and lower HDL cholesterol (HDLc) compared to controls. Homeostasis model assessment of IR (HOMA-IR) [3.25 (2.58-4.13) vs 1.02 (0.73- 1.29); p<0.0001] and IMCL content [266.1 (189.9-296.3) vs 72.85 (55.3-109.4) AU, p<0.0001] were higher, and quantitative insulin-sensitivity check index (QUICKI) [0.32 (0.31-0.33) vs 0.38 (0.37-0.40); p<0.0001] and ADP [8.6 (4.05-15.95) vs 21.1 (12.9- 24.4) microg/ml; p=0.02] were lower in MS subjects compared to controls. IMCL content was directly associated to glucose, insulin, triglycerides, and HOMA-IR and inversely to HDLc, QUICKI and, more importantly, to ADP (r=-0.41; p<0.05). Only in the MS group, ADP partially influenced IMCL content. CONCLUSION: ADP is inversely related to IMCL content in non-diabetic adults. This finding has possible implications for the role of ADP in muscle fat oxidation, IR, and MS.

Atherogenic lipid profile of Brazilian near-term newborns.

Cardiovascular disease is the primary cause of death in Brazil. Recent studies have shown that low birth weight and preterm birth are linked to a higher prevalence of cardiovascular disease. The aim of the present study was to compare the levels of lipids and apolipoproteins and atherogenic indexes between term and near-term newborn infants. A sample of umbilical cord blood was obtained from 135 newborns (66 males) divided into two groups: 25 near-term neonates (35-36.6 weeks of gestational age) and 110 term neonates (37-42 weeks of gestational age). The total cholesterol concentrations were higher in the near-term neonates than in the term group (94.04 +/- 8.02 vs 70.42 +/- 1.63 mg/dl, P < 0.01), due to an increase in the LDL-cholesterol fraction in the near-term group (57.76 +/- 6.39 vs 34.38 +/- 1.29 mg/dl, P < 0.001). The atherogenic indexes (total cholesterol/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol and apolipoprotein B/apolipoprotein A-I) were higher in the near-term group (P < 0.001, P < 0.001, and P < 0.05, respectively). The gestational age of the newborns was inversely correlated with total cholesterol and LDL-cholesterol, and also with the total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol indexes. These findings demonstrate that the lipid profile is worse in the group of near-term neonates compared with the term group. Future studies are needed to determine if this atherogenic profile in near-term neonates can affect body metabolism, increasing the risk for cardiovascular diseases in adult life.

Atherogenic lipid profile of Brazilian near-term newborns

Cardiovascular disease is the primary cause of death in Brazil. Recent studies have shown that low birth weight and preterm birth are linked to a higher prevalence of cardiovascular disease. The aim of the present study was to compare the levels of lipids and apolipoproteins and atherogenic indexes between term and near-term newborn infants. A sample of umbilical cord blood was obtained from 135 newborns (66 males) divided into two groups: 25 near-term neonates (35-36.6 weeks of gestational age) and 110 term neonates (37-42 weeks of gestational age). The total cholesterol concentrations were higher in the near-term neonates than in the term group (94.04 ± 8.02 vs 70.42 ± 1.63 mg/dl, P < 0.01), due to an increase in the LDL-cholesterol fraction in the near-term group (57.76 ± 6.39 vs 34.38 ± 1.29 mg/dl, P < 0.001). The atherogenic indexes (total cholesterol/HDL-cholesterol, LDL-cholesterol/HDL-cholesterol and apolipoprotein B/apolipoprotein A-I) were higher in the near-term group (P < 0.001, P < 0.001, and P < 0.05, respectively). The gestational age of the newborns was inversely correlated with total cholesterol and LDL-cholesterol, and also with the total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol indexes. These findings demonstrate that the lipid profile is worse in the group of near-term neonates compared with the term group. Future studies are needed to determine if this atherogenic profile in near-term neonates can affect body metabolism, increasing the risk for cardiovascular diseases in adult life.

Inverse relationship between cord blood adiponectin concentrations and the number of cigarettes smoked during pregnancy.

BACKGROUND: Maternal smoking is linked with several neonatal metabolic disorders. Adiponectin is an adipose-specific hormone with anti-inflammatory and antiatherogenic properties. AIM: The aim of this study was to evaluate the effect of maternal smoking on cord blood adiponectin concentrations. METHODS: We evaluate the effect of maternal smoking on cord blood adiponectin concentrations comparing 14 full-term and seven preterm newborns born to mothers who smoked during pregnancy with 77 full-term and 10 preterm neonates born to non-smokers mothers. RESULTS: Maternal smoking during pregnancy was significantly associated with decreased adiponectin levels of preterm newborns (p < 0.05). CONCLUSIONS: Our findings also reveal a significant relationship between the reported number of cigarettes smoked during pregnancy and cord blood adiponectin concentrations (p = 0.01), suggesting that this association could have a causal relationship.

Does maternal smoking influence leptin levels in term, appropriate-for-gestational-age newborns?

OBJECTIVES: Leptin, a hormone produced in adipose tissue and the placenta, is correlated with neonatal growth. The aim of this study was to investigate the effect of maternal smoking during pregnancy on cord blood leptin concentrations in term, appropriate-for-gestational-age infants. METHODS: Two groups of term, appropriate-for-gestational-age newborns were selected: 19 infants of smoking mothers and 91 infants of non-smoking mothers. Neonatal anthropometric measurements were taken and leptin levels were measured by radioimmunoassay. RESULTS: Leptin concentrations were similar (p=0.915) between the groups. Leptin levels correlated only with ponderal index (p < 0.01) and gestational age of the newborns (p < 0.05). CONCLUSIONS: This study indicates that maternal smoking during pregnancy does not affect cord blood leptin levels in term, appropriate-for-gestational-age infants.

Sibutramine enhances insulin sensitivity ameliorating metabolic parameters in a double-blind, randomized, placebo-controlled trial.

AIM: To assess the effect of sibutramine-assisted weight reduction program on insulin sensitivity and metabolic parameters in obese normal glucose tolerant individuals over a period of 24 weeks. RESEARCH DESIGN AND METHODS: A double-blind, placebo-controlled, parallel, prospective clinical trial was carried out at our medical centre. Forty female normal glucose tolerant patients, body mass index: 34.3 +/- 2.9 kg/m2 and age: 41.1 +/- 9.9 (range: 19-58 years), were randomized to placebo or sibutramine, 10 mg once daily. RESULTS: Seventeen patients from sibutramine group and 14 placebo had completed the study protocol. Significant weight change was seen in sibutramine (p < 0.01) (-5.6 kg or -6.1% vs. +0.9 kg or +1.1% in placebo). Insulin sensitivity enhanced in sibutramine group (Kitt: from 4.03 +/- 1.97 to 5.09 +/- 2.48%/min; p < 0.05). Homeostasis model assessment-IR (HOMA-IR) decreased from 7.8 +/- 6.9 to 5.6 +/- 4.5 (p < 0.05). HOMA-beta also decreased from 508 +/- 381 to 374 +/- 256 (p < 0.05). No changes were observed in the placebo control group regarding insulin sensitivity or secretion. Concomitant reductions were observed in the sibutramine group in lipid parameters (triglycerides and high-density lipoprotein-cholesterol), uric acid and gamma-glutamyl transferase (p < 0.05). CONCLUSIONS: Sibutramine has demonstrated efficacy in reducing weight in non-diabetic women along with amelioration in insulin sensitivity and additional improvement in metabolic parameters.

The insulin tolerance test in morbidly obese patients undergoing bariatric surgery.

OBJECTIVE: To assess the effect of massive weight loss in relation to insulin resistance and its correlation to changes in glycemic homeostasis and lipid profile in severely obese patients. RESEARCH METHODS AND PROCEDURES: A prospective clinical intervention study was carried out with 31 morbidly obese women (body mass index: 54.2 +/- 8.8 kg/m(2)) divided into three groups according to their glucose tolerance test: 14 normal, 8 impaired glucose tolerance, and 9 type 2 diabetes. All subjects underwent an insulin tolerance test with intravenous bolus of 0.1 U insulin/kg body weight before silastic ring vertical gastroplasty Roux-en-Y gastric bypass surgery, and again at 2, 4, 6, and 12 months postoperatively. Fasting plasma glucose, hemoglobin A1c, and lipid profile were also evaluated. RESULTS: A reduction of 68 +/- 15% in initial excess body weight was evident within 1 year. Along with weight loss, the following statistically significant changes were found: an increase in the insulin-sensitivity index (Kitt) and a decrease in fasting plasma glucose and hemoglobin A1c, most notably in the type 2 diabetes group. An overall improvement in lipid profile was observed in all three groups. DISCUSSION: Bariatric surgery was an effective therapeutic approach for these obese patients because it reduced both weight and insulin resistance, along with improving metabolic parameters. Significant correlations were found between insulin resistance and metabolic improvements. Weight loss after bariatric surgery induced an improvement in metabolic fitness, related to the reduction in insulin resistance over a range of glucose tolerance statuses from normal to diabetic.

Serum leptin levels after bariatric surgery across a range of glucose tolerance from normal to diabetes.

BACKGROUND: A longitudinal, clinical intervention study with bariatric surgery was done to investigate the relationship between leptin levels, BMI, and insulin during weight loss across a range of glucose tolerance from normal to diabetes. METHODS: 43 morbidly obese patients (BMI: 42-75 kg/m2) undergoing vertical banded gastroplasty Roux-en-Y gastric bypass (VBG-RGB), were divided into 3 groups: 21 normal (NGT), 12 impaired glucose tolerance (IGT) and 10 type 2 diabetes (DM). Leptin, insulin, glucose, lipids and uric acid were measured at baseline and 2, 4, 6, and 12 months following surgery. RESULTS: BMI fell from 54.1 +/- 9.1 to 34.6 +/- 6.3 kg/m2, similarly in all groups. Leptin decreased from 73.9 +/- 8.7 to 16.9 +/- 10.2 ng/ml and was strongly correlated with BMI during 1-year follow-up (r = 0.78; p < 0.001). Linear univariate analysis for repeated evaluation showed a positive correlation between leptin and glucose, triglycerides, uric acid, and insulin. Multivariate regression analysis indicated that BMI was independently correlated with the decrease in leptin (p < 0.001), accounting for 66% of the variance in leptin levels during weight loss. These results were found in the NGT and IGT groups. In the DM group, a small additional influence in leptin levels was attributed to glucose decrease. CONCLUSIONS: A strong link between leptin and BMI was found after surgery. BMI was the main determinant of the decrease of leptin. In these patients submitted to bariatric surgery, ranging from normal glucose tolerance to diabetes, changes in insulin levels and metabolic parameters, except for glucose in the DM group, did not appear to be correlated with changes in leptin levels.