Plasma Adiponectin Levels in Overweight and Obese Asians

Objective: Hypoadiponectin has been documented in subjects with obesity, diabetes mellitus, or coronary heart disease, suggesting a potential use of plasma adiponectin in following the clinical progress in subjects with metabolic syndrome (MS). In this study, we investigated the plasma adiponectin levels in relation to the variables of MS among overweight/obese Asian subjects. Research Methods and Procedures: The plasma adiponectin, anthropometric and biochemical measurements, oral glucose tolerance tests (OGTT), and modified insulin suppression tests were performed on 180 overweight/obese Asian subjects [body mass index (BMI) ≥ 23 kg/m²], including 47 subjects with morbid obesity (BMI ≥ 40 kg/m²). Results: The plasma adiponectin levels negatively correlated with BMI, waist-to-hip ratio, fasting plasma glucose, insulin, triglyceride, uric acid levels, hyperinsulinemia, and glucose intolerance in OGTT, but positively with high-density lipoprotein-cholesterol. In contrast, they were not related to blood pressure and total cholesterol. Moreover, insulin sensitivity, measured by quantitative insulin sensitivity check index (QUICKI) or in insulin suppression tests, significantly correlated with the plasma adiponectin levels. Among morbidly obese subjects, only the waist-to-hip ratio correlated with the plasma adiponectin levels. Using multivariate linear regression models, the area under curve of plasma glucose in OGTT and high-density lipoprotein-cholesterol among the overweight/obese subjects and WHR among the morbidly obese subjects were significantly related to the plasma adiponectin levels after adjustment for other variables. Discussion: In overweight/obese Asians, the plasma adiponectin levels significantly correlated with various indices of MS except hypertension. Whether the plasma adiponectin level could be a suitable biomarker for following the clinical progress of MS warrants further investigation.     

BMI Is the Main Determinant of the Circulating Leptin in Women after Vertical Banded Gastroplasty

Objective: To assess the main determinant of serum leptin concentration changes in morbidly obese patients treated by banded vertical gastroplasty. Research Methods and Procedures: Serum leptin and insulin concentrations, insulin resistance, BMI, body weight, and body fat mass in 18 obese women and 8 obese men treated by vertical banded gastroplasty were studied. Lean women and men subjects were used as controls. Results: Before surgery, serum leptin and insulin concentrations and insulin resistance index were significantly higher in morbidly obese patients than in control subjects. BMI, body fat mass, and serum triacylglycerol concentrations were also significantly higher in obese than in lean subjects. All of these parameters gradually decreased during 50 weeks after surgery. Univariate regression analysis displayed significant correlations between the following: serum leptin concentration and BMI (and body fat mass), serum leptin concentration and serum insulin concentration, and serum leptin concentration and insulin resistance index. Multivariate regression analysis indicated that only BMI was independently correlated with the decrease in serum leptin concentration. Discussion: Obtained data suggest the following: 1) vertical banded gastroplasty causes reduction of body weight, serum leptin and insulin concentration, insulin resistance, and serum triacylglycerol concentration; and 2) BMI is the main determinant of the circulating leptin concentration in morbidly obese women after anti‐obesity surgery.     

Resistin,Adiponectin, Ghrelin,Leptin, and Proinflammatory Cytokines: Relationships in Obesity

Objective: To evaluate interactions among leptin, adiponectin, resistin, ghrelin, and proinflammatory cytokines [tumor necrosis factor receptors (TNFRs), interleukin‐6 (IL‐6)] in nonmorbid and morbid obesity. Research Methods and Procedures: We measured these hormones by immunoenzyme or radiometric assays in 117 nonmorbid and 57 morbidly obese patients, and in a subgroup of 34 morbidly obese patients before and 6 months after gastric bypass surgery. Insulin resistance by homeostasis model assessment, lipid profile, and anthropometrical measurements were also performed in all patients. Results: Average plasma lipids in morbidly obese patients were elevated. IL‐6, leptin, adiponectin, and resistin were increased and ghrelin was decreased in morbidly obese compared with nonmorbidly obese subjects. After adjusting for age, gender, and BMI in nonmorbidly obese, adiponectin was positively associated with HDLc and gender and negatively with weight (β = ?0.38, p < 0.001). Leptin and resistin correlated positively with soluble tumor necrosis factor receptor (sTNFR) 1 (β = 0.24, p = 0.01 and β = 0.28, p = 0.007). In the morbidly obese patients, resistin and ghrelin were positively associated with sTNFR2 (β = 0.39, p = 0.008 and β = 0.39, p = 0.01). In the surgically treated morbidly obese group, body weight decreased significantly and was best predicted by resistin concentrations before surgery (β = 0.45, p = 0.024). Plasma lipids, insulin resistance, leptin, sTNFR1, and IL‐6 decreased and adiponectin and ghrelin increased significantly. Insulin resistance improved after weight loss and correlated with high adiponectin levels. Discussion: TNFα receptors were involved in the regulatory endocrine system of body adiposity independently of leptin and resistin axis in nonmorbidly obese patients. Our results suggest coordinated roles of adiponectin, resistin, and ghrelin in the modulation of the obesity proinflammatory environment and that resistin levels before surgery treatment are predictive of the extent of weight loss after bypass surgery.     

Is endocan a novel potential biomarker of liver steatosis and fibrosis?

BackgroundStudies that evaluated endocan levels in nonalcoholic fatty liver disease (NAFLD) and liver fibrosis are scarce. We aimed to explore endocan levels in relation to different stages of liver diseases, such as NAFLD, as determined with fatty liver index (FLI) and liver fibrosis, as assessed with BARD score.MethodsA total of 147 participants with FLI≥60 were compared with 64 participants with FLI <30. An FLI score was calculated using waist circumference, body mass index, gamma-glutamyl transferase and triglycerides. Patients with FLI≥60 were further divided into those with no/mild fibrosis (BARD score 0-1 point; n=23) and advanced fibrosis (BARD score 2-4 points; n=124). BARD score was calculated as follows: diabetes mellitus (1 point) + body mass index≥28 kg/m2 (1 point) + aspartate amino transferase/alanine aminotransferase ratio≥0.8 (2 points).ResultsEndocan was independent predictor for FLI and BARD score, both in univariate [OR=1.255 (95% CI= 1.104-1.426), P=0.001; OR=1.208 (95% CI=1.029-1.419), P=0.021, respectively] and multivariate binary logistic regression analysis [OR=1.287 (95% CI=1.055-1.570), P=0.013; OR=1.226 (95% CI=1.022-1.470), P=0.028, respectively]. Endocan as a single predictor showed poor discriminatory capability for steatosis/fibrosis [AUC=0.648; (95% CI=0.568-0.727), P=0.002; AUC= 0.667 (95% CI=0.555-0.778), P=0.013, respectively], whereas in a Model, endocan showed an excellent clinical accuracy [AUC=0.930; (95% CI=0.886-0.975), P<0.001, AUC=0.840 (95% CI=0.763-0.918), P<0.001, respectively].ConclusionsEndocan independently correlated with both FLI and BARD score. However, when tested in models (with other biomarkers), endocan showed better discriminatory ability for liver steatosis/fibrosis, instead of its usage as a single biomarker.     

The Effects of Metformin and Diet on Plasma Testosterone and Leptin Levels in Obese Men

Objective: The aim of this study was to investigate the effects of combined hypocaloric diet and metformin on circulating testosterone and leptin levels in obese men with or without type 2 diabetes. Research Methods and Procedures: Twenty obese men with type 2 diabetes (mean body mass index [BMI]: 35.5 ± 1.1 kg/m²) and 20 nondiabetic obese men were enrolled in the study. We measured serum follicle‐stimulating hormone, luteinizing hormone (LH), total testosterone (TT), free testosterone (FT), sex‐hormone‐binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and plasma leptin levels before and 3 months after metformin treatment. Both groups were placed on a hypocaloric diet and 850 mg of metformin taken orally twice daily for 3 months. Results: Metformin and hypocaloric diets led to decreases in BMI and waist and hip circumferences in both groups. A significant decrease in TT levels in the diabetic group and FT levels in the control group was found, whereas follicle‐stimulating hormone, LH, and DHEAS levels were not changed significantly. A significant increase in SHBG levels was observed in the control group but not in the patient group. Leptin levels also decreased after treatment in both groups. Decreased testosterone levels were not correlated to changes in waist and hip circumference, waist‐to‐hip ratio, BMI, and levels of fasting blood glucose, leptin, SHBG, or DHEAS in the diabetic group. However, a decrease in FT was correlated to changes in the levels of SHBG (r = ?0.71, p = 0.001) and LH (r = 0.80, p = 0.001) but not to other parameters. Discussion: We conclude that metformin treatment combined with a hypocaloric diet leads to reduced FT levels in obese nondiabetic men and to reduced TT levels in obese men with type 2 diabetes. Increased SHBG levels may account for the decrease in FT levels in the former group.     

Jejunal wall triglyceride concentration of morbidly obese persons is lower in those with type 2 diabetes mellitus

The overproduction of intestinal lipoproteins may contribute to the dyslipidemia found in diabetes. We studied the influence of diabetes on the fasting jejunal lipid content and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of these lipoproteins. The study was undertaken in 27 morbidly obese persons, 12 of whom had type 2 diabetes mellitus (T2DM). The morbidly obese persons with diabetes had higher levels of chylomicron (CM) triglycerides (P < 0.001) and apolipoprotein (apo)B48 (P = 0.012). The jejunum samples obtained from the subjects with diabetes had a lower jejunal triglyceride content (P = 0.012) and angiopoietin-like protein 4 (ANGPTL4) mRNA expression (P = 0.043). However, the apoA-IV mRNA expression was significantly greater (P = 0.036). The jejunal triglyceride content correlated negatively with apoA-IV mRNA expression (r = −0.587, P = 0.027). The variables that explained the jejunal triglyceride content in a multiple linear regression model were the insulin resistance state and the apoA-IV mRNA expression. Our results show that the morbidly obese subjects with diabetes had lower jejunal lipid content and that this correlated negatively with apoA-IV mRNA expression. These findings show that the jejunum appears to play an active role in lipid homeostasis in the fasting state.     

Plasma visfatin concentrations in severely obese subjects are increased after intestinal bypass

Objective: Visfatin has shown to be increased in obesity and in type 2 diabetes. The aim of this study was to determine the change in plasma visfatin in severely obese (SO) persons after weight loss following bariatric surgery in relation to glucose concentration. Research Methods and Procedures: Visfatin and leptin were studied in 53 SO persons (BMI, 54.4 ± 6.8 kg/m²) before and 7 months after bariatric surgery and in 28 healthy persons (BMI, 26.8 ± 3.8 kg/m²). All of the patients underwent bariatric surgery with biliopancreatic diversion or gastric bypass. Results: The pre‐surgery levels of visfatin in the SO group were greater than in the control group (55.9 ± 39.9 vs. 42.9 ± 16.6 ng/mL, p = 0.024). This increase was significant in the SO group with impaired fasting glucose (63.4 ± 36.6 ng/mL) and diabetes (60.0 ± 46.0 ng/mL). SO patients with normal fasting glucose had similar levels of visfatin to the controls. Seven months after surgery, visfatin levels were significantly increased (84.8 ± 32.8 ng/mL, p < 0.001). This increase was independent of the pre‐surgical glucose levels. The type of bariatric surgery had no influence on visfatin levels. Post‐surgical visfatin was significantly correlated with the post‐surgery plasma concentrations of leptin (r = 0.39, p = 0.014). Discussion: Plasma levels of visfatin in the SO group were increased but only when accompanied by high glucose levels, even in the range of impaired fasting glucose. Bariatric surgery causes an increase in visfatin, which is correlated mainly with the changes produced in the leptin concentration.     

Change in Vascular Adhesion Protein‐1 and Metabolic Phenotypes after Vertical Banded Gastroplasty for Morbid Obesity

Objective: The association between circulating vascular adhesion protein‐1 (VAP‐1) and metabolic phenotypes has been shown to be inconsistent. The current study explored whether the changes in serum VAP‐1 levels correlate with the changes in metabolic phenotypes after weight reduction surgery. Research Methods and Procedures: Clinical characteristics and serum VAP‐1 levels in 20 morbidly obese subjects (mean BMI 38.84 kg/m²) were measured before and after vertical banded gastroplasty. Results: Before surgery, serum VAP‐1 levels correlated positively with fasting plasma glucose (γ = 0.56, p = 0.01) and negatively with insulin levels (γ = ?0.51, p = 0.021). After surgery, the changes in serum VAP‐1 levels were negatively correlated with the changes in waist circumference (γ = ?0.57, p = 0.011), diastolic blood pressure (DBP) (γ = ?0.56, p = 0.015), and mean arterial pressure (γ = ?0.46, p = 0.055). In multivariate regression, serum VAP‐1 levels were negatively correlated with waist circumference (β = ?2.36, p = 0.014) and DBP (β = ?3.02, p = 0.017) after adjusting for age and gender. The change in DBP was negatively correlated with the change in VAP‐1 levels after adjusting for age, gender, and steady‐state plasma glucose. Discussion: The results suggest that VAP‐1 levels are correlated with fasting glucose and insulin levels in morbidly obese subjects. After surgery, the changes in VAP‐1 levels were associated with changes in visceral adiposity and DBP. Serum VAP‐1 might modulate DBP independently from the changes in insulin resistance in morbidly obese people.     

Markers for the gene ob and serum leptin levels in human morbid obesity

Leptin, the product of the ob gene, reduces body fat in genetically obese animals and circulates in elevated concentrations in the blood of obese patients. Polymorphic markers situated in the proximity of the human ob gene have recently been suggested to be linked to morbid obesity. We have studied the possible association between the microsatellite markers near the ob gene and morbid obesity in 252 morbidly obese patients with a mean body mass index (BMI) of 43 ± 7 kg/m², and 151 lean controls with a mean BMI of 22 ± 2 kg/m², and searched for linkage of these gene markers to obesity in 76 affected sib-pairs (BMI ≥ 32). No significant association was observed between any of the eight microsatellite markers and morbid obesity, and affected-sib-pair analysis failed to show linkage of three selected ob gene markers to obesity in the sibships. There was a strong positive correlation between serum leptin levels and BMI in morbidly obese patients; a carrier status for either of the two most prevalent alleles of the microsatellite marker D7S530 in the vicinity of the ob gene was associated with serum leptin levels in the obese subjects. Two of the markers (D7S2519, D7S649) showed a significant relation to the weight-losing response to a 16-week very-low-calorie dietary intervention. We have thus been able to confirm a tight relationship between serum leptin and body mass but have found no evidence for genetic linkage of the ob gene markers to morbid obesity in a population considered to represent a genetic isolate and to be an ideal model for studies of complex disorders. Received: 25 October 1996 / Revised: 4 December 1996     

Gastric Pacing for Morbid Obesity: Plasma Levels of Gastrointestinal Peptides and Leptin

Objective: A gastric pacemaker has been developed to treat morbid obesity. Patients experience increased satiety, the ability to reduce food intake, and a resultant weight loss. However, the mechanism behind the changed eating behavior in paced patients is still under investigation. Research Methods and Procedures: This study was performed on 11 morbidly obese patients (mean BMI, 46.0 kg/m²) treated with gastric pacing. The peripheral blood levels of satiety signals of cholecystokinin (CCK), somatostatin, glucagon‐like peptide‐1 (GLP‐1), and leptin were studied 1 month before gastric pacer implantation, 1 month after implantation, and 6 months after activation of electrical stimulation. Blood samples were drawn 12 hours after fasting and in response to a hypocaloric meal (270 kcal). Patients were followed monthly for vital signs and weight level. Results: Gastric pacing resulted in a significant weight loss of a mean of 10.4 kg (4.4 BMI units). No negative side effects or complications were observed during the treatment. After activation of the pacemaker, meal‐related response of CCK and somatostatin and basal levels of GLP‐1 and leptin were significantly reduced (p < 0.05) compared with the tests before gastric pacing. The weight loss correlated significantly with a decrease of leptin levels (R = 0.79, p < 0.01). Discussion: Gastric pacing is a novel and promising therapy for morbid obesity. Activation of the gastric pacer was associated with a decrease in plasma levels of CCK, somatostatin, GLP‐1, and leptin. More studies are necessary to elucidate the correlations between satiety, weight loss, and digestive neuro‐hormone changes.     

Characteristics Associated With Fasting Appetite Hormones (Obestatin,Ghrelin, and Leptin)

Obestatin, derived from the same gene as the hunger hormone ghrelin, may reduce food intake in animals. The role of obestatin in human physiology is unclear. We evaluated cross‐sectional associations between participant characteristics and fasting levels of obestatin as well two other hormones associated with energy balance, ghrelin and leptin. Data are from the baseline visit of the Optimal Macronutrient Intake Trial to Prevent Heart Disease (OMNI‐Heart) Trial that enrolled adults with elevated blood pressure (systolic 120–159 mm Hg or a diastolic of 80–99 mm Hg) but who were otherwise healthy. Partial Spearman's correlations and linear regression models estimated the association between age, gender, BMI, physical activity, and smoking with fasting hormones. Obestatin was directly associated with ghrelin (r = 0.45, P < 0.05). On average, overweight (BMI 25–30) and obese (BMI > 30) individuals had obestatin concentrations that were 12.6 (s.d. 8.8) and 25.4 (s.d. 8.4) pg/ml lower compared to normal weight (BMI < 25) individuals, respectively (P for trend = 0.002). Overweight (BMI 25–30) and obese (BMI > 30) individuals had ghrelin concentrations that were 161.7 (s.d. 69.6) and 284.7 (s.d. 66.5) pg/ml lower compared to normal weight (BMI < 25) individuals, respectively (P for trend <0.0001). A 5 unit increase in BMI was associated with 41.3% (s.d. 4.3%) (P < 0.0001) higher leptin. Obestatin and ghrelin are directly correlated and share the same patterns of association with participant characteristics. Modifiable risk factors for chronic diseases, such as BMI, are associated with fasting levels of leptin, obestatin, and ghrelin.     

Serum amyloid A: a marker of adiposity-induced low-grade inflammation but not of metabolic status

Objective: Adipocytes secrete a series of acute phase proteins including serum amyloid A (SAA); the link with metabolic status is unknown. We studied the variations of expression of the SAA gene in adipose and liver tissues and of SAA serum levels, as well as their relationships with metabolic features during weight loss. Research Methods and Procedures: Plasmatic variations of SAA, inflammatory markers (high sensitivity C‐reactive protein, interleukin‐6, fibrinogen, and orosomucoid), and adipokines (adiponectin, leptin) were studied in 60 morbidly obese patients before and after gastric surgery. For 10 subjects, SAA mRNA expression was measured at baseline in subcutaneous white adipose tissue (scWAT) and visceral white adipose tissue (vWAT) and in the liver. The evolution of SAA mRNA expression was also studied after surgery in scWAT. Results: SAA serum concentration displayed a significant reduction 3 months after surgery and remained stable beyond 6 months. mRNA expression of inducible SAA isoforms (SAA 1 and 2) in scWAT was higher than in vWAT (p = 0.01) and the liver (p < 0.01) and correlated significantly with BMI, SAA, and high sensitivity C‐reactive protein serum concentrations but not with metabolic markers (glucose, insulin, lipid parameters, adiponectin). SAA serum level and its variation during weight loss significantly correlated with adiposity markers (BMI and adipocyte volume, p < 0.01) and inflammatory markers but not with variations of metabolic parameters. The variations of SAA expression in scWAT after surgery correlated with changes in BMI and SAA protein serum levels (p < 0.05). Discussion: SAA can be considered as a marker of adiposity‐induced low‐grade inflammation but not of the metabolic status of obese subjects.     

Triglyceride Levels and Not Adipokine Concentrations Are Closely Related to Severity of Nonalcoholic Fatty Liver Disease in an Obesity Surgery Cohort

Although nonalcoholic fatty liver disease (NAFLD) is frequent in obesity, the metabolic determinants of advanced liver disease remain unclear. Adipokines reflect inflammation and insulin resistance associated with obesity and may identify advanced NAFLD. At the time of obesity surgery, 142 consecutive patients underwent liver biopsy and had their preoperative demographic and clinical data obtained. Liver histology was scored by the NAFLD activity score, and patients subdivided into four groups. Concentrations of retinol‐binding protein 4 (RBP4), adiponectin, tumor necrosis factor‐α (TNF‐α), and leptin were determined ～1 week prior to surgery and results were related to liver histology. The prevalence of no NAFLD was 30%, simple steatosis 23%, borderline nonalcoholic steatohepatitis (NASH) 28%, and definitive NASH 18%. Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MS) prevalence were 39 and 75%, respectively, and did not differ across the four histological groups (P = NS). Triglyceride (TG) and alanine transaminase (ALT) levels, strongly associated with advanced stages of NAFLD and NASH (P = 0.04). TG levels >150 mg/dl, increased the likelihood of NASH 3.4‐fold, whereas high‐density lipoprotein (HDL) levels predicted no NAFLD (P < 0.01). Concentrations of TNF‐α, leptin, and RBP4 did not differ among histological groups and thus did not identify NASH; however, there was a trend for adiponectin to be lower in NASH vs. no NAFLD (P = 0.061). In summary, both TG and ALT levels assist in identification of NASH in an obesity surgery cohort. These findings underscore the importance of fatty acid delivery mechanisms to NASH development in severely obese individuals.     

Type 2 diabetes in non-obese Indian subjects is associated with reduced leptin levels: Study from Mumbai, Western India

Objective: Asian Indian subjects have a high tendency to develop Type 2 diabetes even though obesity is relatively uncommon. We evaluated the serum leptin levels in a group of non-obese Type 2 diabetic patients from Mumbai, Western India.Design: Cross sectional study.Methods: A total of 104 subjects consisting of 28 with Type 2 diabetes, 16 with impaired glucose tolerance and 60 age and sex-matched control subjects were given 75 g oral glucose tolerance test. Fasting serum leptin (IRMA), insulin and C-peptide were measured along with fasting and 2 h plasma glucose. The relation between these variables was studied by univariate and multiple regression analysis.Results: Type 2 diabetes was associated with marked (50–60%) reduction in serum leptin levels, in both men and women. Women, but not men, with impaired glucose tolerance exhibited 60% lower leptin. Serum leptin levels were positively correlated to body mass index (BMI; r = 0.501, p = 0.001) and calculated body fat percent (r = 0.525, p = 0.001) in all the study subjects with a better correlation in the normal subjects (r = 0.562 for BMI and 0.735 for body fat). On the other hand, serum leptin showed significant correlation to serum insulin (r = 0.362, p = 0.008) only in subjects with diabetes or IGT. In the multiple regression model, BMI was the only independent predictor of leptin, in all the subjects. However, in subjects with diabetes or impaired glucose tolerance, waist circumference (p = 0.003), gender (p = 0.007) and body fat (p = 0.009) were significant predictors of leptin, besides BMI. Gender-specific multiple regression revealed serum insulin as an independent predictor of leptin in men (p = 0.026). Therefore, lower serum leptin levels in diabetes is partly due to increased waist circumference, decreased BMI and male sex. These observations are consistent with the view that leptin levels in this cohort of non-obese Indians from Mumbai exhibit gender-specific relationship partly attributed to changes in serum insulin and waist circumference in men and to changes in BMI, in women.     

Impact of Type 2 Diabetes on Nonalcoholic Steatohepatitis and Advanced Fibrosis in Patients with Nonalcoholic Fatty Liver Disease

Objective: Type 2 diabetes mellitus (T2DM) is a risk factor for nonalcoholic fatty liver disease (NAFLD). The aim of this study was to investigate the effect of T2DM on nonalcoholic steatohepatitis (NASH) and advanced fibrosis.Methods: A total of 221 NAFLD patients who had undergone a liver biopsy were included in this study. Subjects were divided into a non-T2DM group and a T2DM group based on glycemic control. NASH was diagnosed by the joint presence of steatosis, ballooning, and lobular inflammation. The steatosis, activity, and fibrosis (SAF) score and NAFLD activity score (NAS) were used to evaluate the severity of NAFLD. The severity of liver fibrosis was evaluated based on the fibrosis stage.Results: The total percentages of NASH and advanced fibrosis in this study were 95.0% and 50.2%, respectively. The percentages of NASH and advanced fibrosis in NAFLD patients with T2DM were 96.1% and 56.5%, respectively, which were higher than those in the non-T2DM group. SAF score (especially activity and fibrosis stage) and NAS (especially ballooning) were higher in NAFLD patients with T2DM than in NAFLD patients without T2DM. Glycemic control and insulin resistance were positively associated with SAF, NAS, and fibrosis stage. Additionally, T2DM elevated the risk of a high NAS and advanced fibrosis.Conclusion: T2DM increases the risk of serious NASH and advanced fibrosis in patients with NAFLD. Liver biopsy can be performed in NAFLD patients with T2DM to confirm the stage of NAFLD. Screening of NASH and advanced fibrosis in NAFLD patients with T2DM is needed.Abbreviations: ALT = alanine aminotransferase; APO = apolipoprotein; AST = aspartate aminotransferase; BMI = body mass index; CI = confidence interval; FPG = fasting plasma glucose; GGT = gamma-glutamyl transferase; HbA1c = hemoglobin A1c; HDL-c = high-density-lipoprotein cholesterol; ¹H-MRS = proton magnetic resonance spectroscopy; HOMA-IR = homeostasis model assessment of insulin resistance; 2hPG = postprandial plasma glucose at 2 hours; LDL-c = low-density-lipoprotein cholesterol; LFC = liver fat content; NAFLD = nonalcoholic fatty liver disease; NAS = NAFLD activity score; NASH = nonalcoholic steatohepatitis; OGTT = oral glucose tolerance test; OR = odds ratio; T2DM = type 2 diabetes mellitus; TC = total cholesterol; TG = triglyceride; SAF = steatosis, activity, and fibrosis; US-FLI = ultrasonographic fatty liver indicator     

Is Leptin Concentration Associated with the Insulin Resistance Syndrome in Nondiabetic Men?

HAFFNER, STEVEN M., LEENA MYKKÄNEN, DAVID L. RAINWATER, PAULI KARHAPÄÄ, AND MARKU LAAKSO. Is leptin concentration associated with the insulin resistance syndrome in nondiabetic men? Obes Res. Objective Insulin resistance has been strongly associated with cardiovascular risk. Recently, leptin, a hormone that regulates appetite, has been associated with both obesity and insulin resistance. However, the possible relation of leptin to the insulin resistance syndrome has been controversial. Research Methods and Procedures To explore this issue, we examined the relation of leptin to blood pressure, lipid levels, low density lipoprotein (LDL) size, and glucose levels in 87 normoglycemic men. Results Leptin levels were significantly correlated with body mass index (BMI) (r = 0.494), fasting insulin (r = 0.576), whole-body glucose disposal rate (GDR) (r = ?0.566), fasting glucose (r = 0.510), total triglycerides (r= 0.294), apolipoprotein B 0 = 0.223), systolic blood pressure (r= O.223), and LDL size (r = ?0.244). After adjustment for BMI and GDR, leptin levels remained significantly correlated with fasting insulin, fasting glucose, triglyceride, apolipoprotein B, and systolic blood pressure. Leptin levels were also correlated with the number of metabolic risk factors (dyslipidemia, systolic blood pressure, and fasting glucose). Discussion We conclude that leptin concentrations may be associated with several cardiovascular risk factors related to insulin resistance syndrome. These associations are only partly explained by leptin's relationship with BMI and GDR.     

Serum adipokine and ghrelin levels in nonalcoholic steatohepatitis

Adipokines and ghrelin play role in insulin resistance, the key pathophysiological abnormality in patients with nonalcoholic fatty liver diseases. In the present study, relationship between nonalcoholic steatohepatitis (NASH) and serum adipokine and ghrelin levels was investigated. Thirty seven patients with biopsy-proven NASH and 25 age- and sex-matched controls were enrolled. Ten of NASH patients (27%) had diabetes mellitus (n = 5) or impaired glucose tolerance (n = 5). Body mass index (BMI) was less than 30 kg/m(2) in 67.6% of patients, while in the remaining 32.4% it was more than 30 kg/m(2). Serum adiponectin, leptin, TNF-alpha, and ghrelin were determined. Serum leptin (15.49 +/- 4.84 vs 10.31 +/- 2.53) and TNF-alpha (12.1 +/- 2.7 vs 10.31 +/- 2.56) levels were significantly higher in the NASH group compared to in the control group (P < .001 for each). Nevertheless, adiponectin (11.1 +/- 2.1 vs 17.3 +/- 2.8) and ghrelin (6.46 +/- 1.1 vs 7.8 +/- 1.1) levels were lower in the NASH group than in the control group (P < .001 for each). Serum levels of the adipokines and ghrelin, however, were comparable in the subgroups of patients regardless of whether BMI was < 30 or > 30 or glucose tolerance was impaired or not (P > .05). Additionally, neither adipokines nor ghrelin was correlated with histopathological grade and stage (P > .05). In conclusion; there is a significant relationship between NASH and adipokines and ghrelin independent from BMI and status of the glucose metabolism. These cytokines that appear to have role in the pathogenesis of NASH, however, do not have any effect upon the severity of the histopathology.     

Leptin and Its Relation to Obesity and Insulin in the SHR/N-corpulent Rat,A Model of Type II Diabetes Mellitus

The spontaneously hypertensive/NIH-corpulent (SHR/N-cp) rat is a genetic animal model that exhibits obesity, metabolic features of hyperinsulinemia, hyperglycemia, and hyperlipidemia, which are characteristic of type II diabetes and mild hypertension. To determine the role of leptin, the protein product of the ob gene, in the development of obesity and diabetes in this model, we measured steady-state circulating levels of leptin in obese and lean SHR/N-cp rats and examined the relation between plasma leptin levels and metabolic variables at the stage of established obesity in these animals. Mean fasting plasma leptin concentration was 8-fold higher in obese than in lean rats (p<0.01). This was associated with a 6-fold elevation in plasma insulin in the obese group. Fasting levels of plasma glucose, cholesterol, and triglyceride were all significantly higher in obese rats than in lean controls. Spearman correlation analysis showed a significant positive correlation between plasma leptin concentration and body weight among the animals (r=0.73, p<0.01). Similarly, plasma insulin concentration was significantly correlated with BW in all animals (r=0.54, p<0.05). There was also a significant positive.correlation between plasma leptin and plasma insulin in the entire group (r=0.70, p<0.01). However, this relationship was significant only for lean rats but not for obese rats (r=0.59, p<0.05 for lean rats, and r=0.23, p=NS, for obese rats). Plasma leptin also correlated positively with fasting plasma glucose (r=0.75, p<0.05), total cholesterol (r=0.63, p<0.05), and triglyceride (r=0.67, p <0.05). The marked elevation of plasma leptin in obese SHR/N-cp rats suggests that obesity in this animal model is related to up-regulation of the ob gene. Circulating leptin appears to be one of the best biological markers of obesity and that hyperleptinemia is closely associated with several metabolic risk factors related to insulin resistance in the diabesity syndrome.     

Are Elevated Aminotransferases and Decreased Bilirubin Additional Characteristics of the Metabolic Syndrome?

Abnormal liver tests, as well as morphological changes in the liver, are frequent among obese patients. Other frequent disturbances are visceral fat accumulation, insulin resistance, non-insulin-dependent diabetes mellitus (NIDDM), hypertriglyceridemia, and hypertension; these are a set of aberrations known as the metabolic syndrome. In order to investigate a possible relationship between the metabolic syndrome and impaired liver status we examined associations between liver tests, metabolic variables (insulin, glucose, and triglycerids), body composition and nutrition in 1083 men (BMI 28.8–63.8 kg/m²) and 1367 women (BMI 26.7–68.0 kg/m²) in the ongoing intervention study of Swedish Obese Subjects (SOS). Standard biochemical techniques were used to assess liver status and metabolic variables. Lean body mass (LBM) and masses of visceral and subcutaneous adipose tissue (AT) were estimated by means of computed tomography (CT) calibrated anthropometric equations. In both genders aspartate aminotransferase and alanine aminotransferase were, or tended to be, positively correlated to fasting serum insulin, visceral AT (women), and alcohol intake. In women, the aminotransferases were also correlated with fasting blood glucose. In both genders alkaline phosphatase was, or tended to be, positively associated with visceral AT, insulin (women), and glucose. Bilirubin was negatively correlated to insulin and visceral AT in men and women. Additional multivariate analyses indicated that alcohol had less explanatory power than serum insulin for the examined liver tests, especially among women. These results suggest that pathological liver tests in the obese may represent an expression of the metabolic syndrome.