Left ventricular diastolic and systolic function in normotensive obese subjects: influence of degree and duration of obesity.

The present study was carried out to evaluate systolic and diastolic parameters in overweight and moderately obese, but otherwise healthy subjects, and in a lean control group, to determine whether degree and duration of obesity can influence left ventricular function. A total of 27 subjects, 17 overweight or with moderate obesity and 10 lean, healthy subjects were included. Patients were divided into three groups according to their body mass index (BMI) and to Garrow's criteria as follows: lean control group (BMI less than 25 kg.m-2); overweight subjects (BMI from 25 to 30 kg.m-2); moderately obese subjects (BMI greater than 30 less than 40 kg.m-2). Systolic and diastolic parameters were measured using blood pool gated radionuclide angiography. Left ventricular (LV) ejection fraction (EF), peak ejection rate (PER), time to PER (tPER), peak filling rate (PFR) and time to PFR (tPFR) were evaluated. PER and PFR values were normalized for end-diastolic volume (EDV). EF and PFR were significantly lower (P less than 0.05) both in moderately obese and in overweight subjects and tPFR was significantly (P less than 0.05) prolonged in both groups in comparison to lean controls. Only in moderately obese subjects was PER significantly (P less than 0.05) decreased and tPER significantly (P less than 0.05) prolonged in comparison to lean controls. As compared to overweight individuals, moderately obese subjects were characterized by a significant decrease (P less than 0.05) in LVEF and PER and by a significant increase (P less than 0.05) in tPER, without relevant change in PFR and in tPFR.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypertension in obese subjects: distinct hypertensive subgroup

Obesity and hypertension are two closely associated conditions and obesity probably predisposes to hypertension. In this investigation we evaluated central, systemic haemodynamic and intravascular volume characteristics of 51 established hypertensive obese subjects subgrouped for degree of obesity. Subgrouping according to body mass index (BMI) was as follows: lean hypertensives, 17 subjects (BMI 23.00 +/- 0.45 Kg/m2); moderately obese, 19 subjects (BMI 26.92 +/- 0.30 Kg/m2); severely obese, 15 subjects (BMI 32.78 +/- 0.45 Kg/m2). Obese hypertensives were characterised by significantly increased cardiac output and total plasma volume (P less than 0.05) and by decreased total peripheral resistance (not significantly) and left ventricular ejection fraction (P less than 0.01). These changes appear to be related to the degree of obesity. Significant correlation coefficients between body mass index and cardiac output, total blood volume, total peripheral resistance and ejection fraction were also observed. In conclusion, established hypertension in the severely obese patient appears to be a separate haemodynamic entity.     

Promoter polymorphism in the macrophage migration inhibitory factor gene is associated with obesity

OBJECTIVE: To explore the association of promoter polymorphisms of macrophage migration inhibitory factor (MIF) gene with obesity.Subjects:In total, 213 nondiabetic Japanese subjects. They were divided into three groups according to World Health Organization definitions: lean (body mass index (BMI) <25 kg/m2), overweight (25 < or = BMI < 30 kg/m2) and obese (BMI> or = 30 kg/m2). METHODS:We examined two polymorphic loci in the MIF gene in the subjects: a single-nucleotide polymorphism at position -173 (G/C) and a CATT-tetranucleotide repeat polymorphism at position -794, which both can affect promoter activity in different cells. RESULTS: We detected four alleles: 5-, 6-, 7- and 8-CATT at position -794. Genotypes without the 5-CATT allele (X/X, X refers to 6-, 7- or 8-CATT alleles) were more common in obese subjects than in lean or overweight groups (P = 0.013). The X-CATT allele was more frequent in obese subjects than in lean or overweight subjects (P = 0.030). In contrast, -173G/C was not associated with obesity. Among the haplotypes of the two promoter polymorphisms, G/5-CATT ((-173G/C)/(-794[CATT](5-8))) was associated with a decreased risk of obesity (P = 0.025) and G/6-CATT with an increased risk of overweight (P=0.028).Conclusion:Promoter polymorphism in the MIF gene is linked with obesity.     

Glucose uptake and insulin action in human adipose tissue--influence of BMI, anatomical depot and body fat distribution.

OBJECTIVE: To examine and compare in vitro basal and insulin-stimulated glucose uptake in human omental and subcutaneous adipose tissue derived from lean, overweight or obese individuals, and in those with central or peripheral obesity. DESIGN: In vitro study of basal and insulin-stimulated 2-deoxyglucose uptake in human omental and subcutaneous adipose tissue explants derived from patients undergoing elective abdominal surgery. SUBJECTS: Fourteen lean (average age 47 y, average body mass index (BMI) 22 kg/m(2)), 12 overweight (average age 51 y, average BMI 27 kg/m(2)), and 15 obese subjects (average age 45 y, average BMI 39 kg/m(2)). Ten peripherally obese (average age 43 y, average WHR 0.76) and 17 centrally obese (average age 50 y, average waist-to-hip ratio (WHR) 0.92). MEASUREMENTS: Fatness and fat distribution parameters (by anthropometry), basal and insulin stimulated [(3)H]-2-deoxyglucose uptake in omental and subcutaneous adipose tissue explants. RESULTS: In adipose tissue from lean subjects transport of 2-deoxyglucose over basal was stimulated approximately two-fold by insulin. In contrast, 2-deoxyglucose transport in adipose tissue of obese or overweight subjects was not responsive to insulin. Following incubation with 100-nM insulin for 35 min, insulin-stimulated 2-deoxyglucose transport was significantly lower in both omental and subcutaneous adipose tissue of obese and overweight compared to lean subjects. Basal 2-deoxyglucose uptake was also significantly reduced in omental and subcutaneous tissue in obese compared to lean subjects. Depot-specific differences in 2-deoxyglucose uptake were also seen. Overall 2-deoxyglucose uptake was greater in omental than subcutaneous adipose tissue but this was due to increased basal levels rather than increased insulin action. The reduction in insulin-stimulated 2-deoxyglucose uptake seen in overweight and obese subjects was relatively similar in both depots. However, insulin responsive 2-deoxyglucose transport was significantly lower in the omental adipose tissue of subjects with central obesity, as compared to that of subjects with peripheral obesity. No difference in insulin induced 2-deoxyglucose transport was observed in the subcutaneous adipose tissue explants of subjects with either central or peripheral obesity. CONCLUSION: In lean individuals insulin responsiveness of omental and subcutaneous adipose tissue was similar, but basal glucose uptake was significantly higher in omental adipose tissue. Adipose tissue obtained from overweight as well as obese individuals is insulin resistant. This insulin resistance occurs at a lower BMI than previously expected and is not adipose-depot specific. However, in obese subjects with a central distribution of adiposity insulin resistance occurs at the site of omental adipose tissue, in contrast to those with peripheral obesity.     

B-type natriuretic peptide levels in obese patients with advanced heart failure.

Although recent studies show that obesity, or elevated body mass index (BMI), is associated with lower levels of B-type natriuretic peptide (BNP), it is unknown whether BMI affects the prognostic value of BNP in heart failure (HF). This study confirms the relationship between high BMI and low BNP in patients with advanced systolic HF. Despite relatively lower levels of BNP in overweight and obesity, BNP predicts worse symptoms, impaired hemodynamics, and higher mortality in HF at all levels of BMI.OBJECTIVES: This study aimed to examine the influence of obesity on the predictive value of the B-type natriuretic peptide (BNP) assay in heart failure (HF). BACKGROUND: Recent studies show that obesity, or elevated body mass index (BMI), is associated with lower circulating levels of BNP both in the general population and in patients with HF. METHODS: We analyzed data from 316 systolic HF (left ventricular ejection fraction [LVEF] < or =40%) patients [age, 53 +/- 13 years; mean LVEF, 24 +/- 7%; 48% ischemic] followed up at a university HF center. Patients were divided into categories of BMI: lean (BMI <25 kg/m2), overweight (BMI = 25 to 29.9 kg/m2), and obese (BMI > or =30 kg/m2). RESULTS: The BNP levels were significantly lower in overweight and obese compared with lean patients (p = 0.0001); median BNP (interquartile range) for the lean (n = 131), overweight (n = 99), and obese (n = 86) groups was 747 (272 to 1,300), 380 (143 to 856), and 332 (118 to 617) pg/ml, respectively. In each BMI category, elevated BNP was significantly associated with worse symptoms and higher pulmonary capillary wedge pressure. Higher BNP was also a significant independent predictor of survival independent of BMI. Optimal BNP cutoff for prediction of death or urgent transplant in lean, overweight, and obese HF patients was 590, 471, and 342 pg/ml, respectively. CONCLUSIONS: Although BNP levels are relatively lower in overweight and obese HF patients, BNP predicts worse symptoms, impaired hemodynamics, and higher mortality at all levels of BMI.     

Central obesity and hypertensive renal disease: association between higher levels of BMI, circulating transforming growth factor beta1 and urinary albumin excretion

OBJECTIVE: In this study, the relationship between circulating transforming growth factor beta1 (TGFbeta1) and urinary albumin excretion (UAE) has been investigated in non-obese and central obese hypertensive patients. DESIGN AND PATIENTS: Fifty-eight consecutive hypertensive outpatients both lean and with central obesity were enrolled and divided in three groups, according to their body mass index (BMI) values. Group A: 16 lean hypertensives (men with BMI < 25 kg/m2 and women with BMI < 24.7 kg/m2); Group B: 16 overweight hypertensives (men with BMI > or = 25 kg/m2 and < 30 kg/m2 and women with BMI > 24.7 kg/m2 and < 27.3 kg/m2); Group C: 26 obese hypertensives (men with BMI > or = 30 kg/m2 and women with BMI > or = 27.3 kg/m2). MEASURES: In all patients, UAE, by immunonephelometric assay, circulating TGFbeta1 by a solid-phase specific sandwich enzyme-linked immunosorbent assay (ELISA) technique, blood urea nitrogen (BUN) and creatinine, by routine laboratory methods, were determined. In addition, left ventricular telediastolic internal diameter (LVIDd), interventricular septum diastolic (IVSTd), posterior wall thickness (PWT), total and normalized to height2.7 left ventricular mass (LVM, LVM/h2.7), relative wall thickness (RWT) and left ventricular ejection fraction (EF) by M-B Mode echocardiography were calculated. RESULTS: Overweight and obese hypertensives had significantly (p < 0.05) higher BMI, waist-hip ratio (WHR), UAE and TGFbeta1 than lean hypertensives. Obese hypertensives had significantly (p < 0.05) higher total and indexed LVM values than lean hypertensives. Obese hypertensives had significantly (p < 0.05) higher BMI, UAE and TGFbeta1 than overweight hypertensives. In all subjects, TGFbeta1 correlated directly with BMI (r = 0.52; p < 0.0001), WHR (r = 0.48; p < 0.003), MBP (r = 0.31; p < 0.02) and UAE (r = 0.57; p < 0.0001). Multiple regression analysis indicated that BMI, MBP and UAE were able to explain the 47.9% TGFbeta1 variability (r = 0.69; p < 0.0001), and that TGFbeta1 was the best predictor of UAE changes (r = 0.60; p < 0.0001). CONCLUSION: Our data suggest that TGFbeta1 levels are positively associated with BMI, MBP and UAE in hypertensive subjects. This also indicates that TGFbeta1 overproduction might be considered a pathophysiology mechanism of progressive renal function impairment in obese hypertensives.     

Enhanced vascular activity of endogenous endothelin-1 in obese hypertensive patients

Hypertensive patients have increased endothelin-1-dependent vasoconstrictor tone. This abnormality, however, might not be uniformly present in all forms of hypertension, as suggested by experimental studies showing that endothelin-1 activity is enhanced predominantly in low-renin, high-volume models and in insulin-resistant states. Because hypertension in obesity is commonly associated with both expanded plasma volume and insulin resistance, this study sought to determine whether increased body mass index (BMI) in hypertensive patients relates to activation of the endothelin-1 system. Forearm blood flow (FBF) responses (plethysmography) to intra-arterial infusion of an ETA receptor blocker (BQ-123) were analyzed in hypertensive patients and normotensive control subjects according to BMI. The vasodilator response to BQ-123 was significantly higher in hypertensive patients than in control subjects (P<0.001). During BQ-123, a significant increase in FBF from baseline was observed in obese (BMI > or =30 kg/m2; P<0.001) and overweight (BMI, 27 to 29.9 kg/m2; P=0.04) but not in lean (BMI <27 kg/m2; P=0.83) hypertensive patients. In contrast, no significant change in FBF was observed during BQ-123 either in obese (P=0.53), overweight (P=0.76), or lean (P=0.93) normotensive subjects. Moreover, a significant correlation between BMI and the vasodilator response to ETA blockade was observed in hypertensive subjects (R=0.53; P=0.005) but not in control subjects (R=0.11; P=0.58). In human hypertension, increased BMI is associated with enhanced ETA-dependent vasoconstrictor activity, suggesting that this abnormality may play a role in the pathophysiology of obesity-related hypertension and that targeting the endothelin-1 system may be useful in the treatment of these patients.     

Association between neuromedin U gene variants and overweight and obesity

BACKGROUND: Neuromedin U (NMU) is an anorexic neuropeptide expressed in the hypothalamus. Mice lacking the NmU gene are hyperphagic and obese, whereas mice overexpressing Nmu are hypophagic and lean. OBJECTIVE: Our objective was to investigate whether variants in NMU are associated with human obesity. DESIGN: The coding region of NMU was analyzed for variants in obese Czech children and obese Danish adults. Identified missense variants were investigated for cosegregation with obesity in families or association with obesity in the general population. SETTING: The study was performed at Steno Diabetes Center, Denmark, and Department of Pediatrics, Charles University, Czech Republic. SUBJECTS AND METHODS: A total of 289 Czech children and adolescents with early-onset obesity and 84 Danish obese adults were analyzed for variants in NMU. A NMU Ala19Glu polymorphism was genotyped in 5851 Danish subjects of the Inter99 cohort, and a rare NMU Arg165Trp mutation was sequenced in the proband family and in 53 lean and unrelated Czech subjects. RESULTS: The rare NMU Arg165Trp variant cosegregated with childhood obesity in a Czech family. Homozygous carriers of the Glu allele of the NMU Ala19Glu polymorphism were more common in the overweight and obese subjects; the Glu/Glu frequency was 0.4 (95% confidence interval, 0.2-0.6) among 2586 lean subjects (BMI < 25 kg/m2) and 0.9 (95% confidence interval, 0.7-1.1) among 3265 overweight and obese subjects (body mass index >or= 25 kg/m2) [odds ratio, 2.5 (1.2-5.3); P = 0.01]. CONCLUSION: Amino acid variants in NMU associate with overweight and obesity, suggesting that NMU is involved in energy regulation in humans.     

Left ventricular function response to exercise in normotensive obese subjects: influence of degree and duration of obesity.

This study has been designed to evaluate whether duration and severity of obesity can influence left ventricular function response to exercise in obese subjects without other known cardiovascular risk factors such as hypertension, diabetes or hyperlipoproteinemia. A total of 29 obese subjects were included and they were divided, according to their body mass index and to Garrow's criteria as follows: Overweight or mildly obese subjects: body mass index from 25 to 30 kg/m2; moderately obese subjects: body mass index > 30 and < 40 kg/m2. Both obese groups were further subdivided according to their duration of obesity evaluated by accurate anamnesis in subgroup A (duration of obesity less than 120 months) and subgroup B (duration of obesity more than 120 months). Left ventricular ejection fraction was detected by blood pool gated radionuclide angiocardiography both at rest and after symptom-limited bicycle ergometer procedure. At peak exercise left ventricular ejection fraction increased significantly (p < 0.05) only in overweight subjects. Exercise produced an increase of left ventricular ejection fraction in 14 overweight and in 5 moderately obese subjects and a decrease in 2 moderately obese subjects. At peak exercise mean heart rate and mean blood pressure increased significantly (p < 0.001) in both groups. When obese subjects were subgrouped according to duration of obesity, left ventricular ejection fraction increased significantly (p < 0.05) only in overweight subjects with duration of obesity less than 120 months. Duration of obesity correlated inversely with percent change in left ventricular ejection fraction (EF) at peak exercise (delta EF) (r = -0.59; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

G-protein beta3 subunit gene splice variant in obesity and overweight.

OBJECTIVE: To determine whether the C825T polymorphism of the G-protein beta3 subunit gene (GNB3) is associated with overweight and obesity. This polymorphism leads to a splice variant (Gbeta3-s) with higher activity and very strong association with essential hypertension. DESIGN: A cross-sectional case-control study. SUBJECTS: The sets of affected and control British/European Caucasian subjects used were: (i) an obesity clinic group most of whom had "morbid obesity" (mean body mass index (BMI) for group=43+/-8 kg/m(2)) and non-obese controls (BMI< or =30); (ii) a group of overweight/obese healthy normotensive community volunteers (BMI>25; mean 29+/-5) and controls (BMI< or =25; mean 23+/-1); (iii) a group of overweight/obese hypertensive patients (BMI>25; mean 30+/-4) and lean hypertensive controls (BMI< or =25; mean=23+/-2). MEASUREMENTS: BMI, blood pressure, serum lipids, alleles of GNB3 polymorphism. RESULTS: Compared with control, frequency of the T allele in obese subjects was higher by 12% in (i), 17% in (ii) and 28% in (iii), but the differences were not statistically significant. Slight tracking of the T allele with elevation in BMI was, however, observed, in the obesity clinic group (P=0.018). CONCLUSION: The C825T splice variant of GNB3 makes little if any contribution to obesity in the groups we tested.     

Association between body mass index and core components of metabolic syndrome in 1486 patients with type 1 diabetes mellitus in Japan (JDDM 13)

There is no recent study on the prevalence of overweight and obesity in patients with type 1 diabetes mellitus (T1DM) in Japan. Being overweight has a significant effect on the metabolic condition and glycemic control of such patients. In the present cross-sectional study, we investigated the effects of body mass index (BMI) on lipid profile, blood pressure, and glycemic control in patients with T1DM. In total, 1486 patients with T1DM (including 401 patients with early onset T1DM who were <20 years of age at diagnosis) were included. Patients were divided into four groups according to their BMI, and glycosylated hemoglobin (HbA1c), daily insulin dose per kg body weight, lipid profile, and blood pressure were compared between groups. We found that 15.7% of all patients were overweight (BMI >or= 25.0 kg/m(2)) and 2.0% were obese (BMI >or= 30.0 kg/m(2)), compared with 17.5% and 2.0%, respectively, in the early onset T1DM subgroup. Significant changes in lipid profiles and blood pressure were found with increasing BMI in both the entire population and the early onset T1DM subgroup. In the entire study population HbA1c and the body weight-adjusted daily insulin dose were significantly higher in patients with a BMI >or= 23 kg/m(2) compared with those with a BMI<23 kg/m(2); however, this was not the case in the early onset T1DM subgroup. This difference may be due to the relatively small number of patients in that subgroup. In conclusion, the prevalence of overweight and obesity in patients with T1DM was less than that in the normal Japanese population. For patients with T1DM, being overweight was associated with higher blood pressure and dyslipidemia. Furthermore, we cannot exclude an association between being overweight and the need for higher daily doses of insulin.     

Obesity and suppressed B-type natriuretic peptide levels in heart failure

OBJECTIVES: This investigation evaluated the relationship between obesity and B-type natriuretic peptide (BNP) in heart failure. BACKGROUND: Obesity is a major risk factor for the development of heart failure, but the precise mechanisms remain uncertain. Physiologically, natriuretic peptides and lipolysis are closely linked. METHODS: A total of 318 patients with heart failure were evaluated between June 2001 and June 2002. Levels of BNP were compared in obese (body mass index [BMI] > or =30 kg/m(2)) and nonobese (BMI <30 kg/m(2)) patients with respect to New York Heart Association functional class and lean body weight-adjusted peak aerobic oxygen consumption. In a subset of 36 patients, plasma levels of tumor necrosis factor-alpha, interleukin-6, and soluble intercellular adhesion molecule-1 were measured. RESULTS: The population's BMI was 29.4 +/- 6.6 kg/m(2); 24% were lean (BMI <25 kg/m(2)), 31% overweight (BMI > or =25 to 29.9 kg/m(2)), and 45% obese (BMI > or =30 kg/m(2)). Obese patients were younger, more often African American, and more likely to have a history of antecedent hypertension, but less likely to have coronary artery disease and with only a trend toward diabetes mellitus. Levels of BNP were significantly lower in obese than in nonobese subjects (205 +/- 22 and 335 +/- 39 pg/ml, respectively; p = 0.0007), despite a similar severity of heart failure and cytokine levels. Multivariate regression analysis identified BMI as an independent negative correlate of BNP level. There were no differences in emergency department visits, heart failure hospitalization, or death between the obese and nonobese patients at 12-month follow-up. CONCLUSIONS: Our investigation indicates that a state of reduced natriuretic peptide level exists in the obese individual with heart failure.     

Impaired activation of skeletal muscle glycogen synthase in non-insulin-dependent diabetes mellitus is unrelated to the degree of obesity

Twenty-five newly presenting, untreated, white, non-insulin-dependent diabetic (NIDDM) subjects were studied within 72 hours of diagnosis. They were allocated to three groups according to their body mass index [BMI] (lean BMI less than 25.0, n = 9; overweight BMI 25.0 to 30.0, n = 6; obese BMI greater than .30.0 kg/m2, n = 10). All three groups exhibited equivalent hyperglycemia. Eleven normal control subjects were also studied. The degree of activation of skeletal muscle glycogen synthase (GS) was used as an intracellular marker of insulin action, before and during a 240-minute insulin infusion (100 mU/kg/h). Fractional GS activity did not increase in the lean (change, -0.9 +/- 3.3%), the overweight (-1.9 +/- 2.7%), or the obese (+2.2 +/- 1.6%) NIDDM subjects during the insulin infusion and was markedly decreased compared with the control subjects (change, +14.6 +/- 2.4%, all P less than .001). Glucose requirement was also significantly decreased in all three NIDDM groups (103 +/- 23 v 81 +/- 14 v 53 +/- 14 mg/m2/min, respectively) compared with the control subjects (319 +/- 18 mg/m2/min, all P less than .001). There was a significant negative correlation with BMI (r = -.51, P less than .01), but the difference in glucose requirement between the lean and obese NIDDM groups was not significant. Muscle GS activity at the end of the euglycemic clamp correlated with glucose requirement (r = .53, P less than .001), and a similar correlation was observed between the insulin-induced change in muscle GS activity from basal and glucose requirement (r = .47, P less than .005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum concentrations of nitric oxide, tumor necrosis factor (TNF)-alpha and TNF soluble receptors in women with overweight and obesity

The aims of the present study was to examine how overweight and obesity affect serum concentrations nitric oxide (NO) metabolites and to determine whether there is association between serum concentrations tumor necrosis factor (TNF)-alpha and TNF soluble receptors (sTNF-R) in subjects with overweight and obesity. The study groups involved 154 women: 102 obese (81 obese with body mass index [BMI] 30 to 40 kg/m2 and 21 obese with BMI > 40 kg/m2), 24 overweight patients, and 28 lean controls. Serum concentrations of NO metabolites and of TNF-alpha and its soluble receptors (sTNF-R1, sTNFR-2) were measured by enzyme-linked immunosorbent assay (ELISA) kits. Serum concentration of insulin was measured by radioimmunoassay (RIA). Plasma glucose, cholesterol, high-density lipoprotein (HDL)-cholesterol, and triglicerydes were determined by enzymatic procedure. Body composition was determined by impedance analysis using Bodystat (Douglas, British Isles). Serum concentrations of NO in the overweight group (35.1 +/- 12.1 micromol/L) and the obese groups with BMI 30 to 40 kg/m2 (32.8 +/- 9.3 micromol/L) and with BMI greater than 40 kg/m2 (33.3 +/- 8.5 micromol/L) were significantly higher when compared to controls (28.2 +/- 8.1 micromol/L): P < .05; P < .01, and P < .01, respectively. There was no difference in levels of NO between the overweight group and both obese groups. Serum concentration of TNF-alpha was also significantly higher in the group with overweight (6.5 +/- 3.1 pg/mL), in the obese group with BMI 30 to 40 kg/m2 (6.8 +/- 3.1 pg/mL), and in the obese group with BMI greater than 40 kg/m2 (7.4 +/- 2.6 pg/mL) when compared to controls (2.9 +/- 2.2 pg/mL): P < .00005; P < .00005, and P < .0000001, respectively. However, serum concentrations of sTNF-R1 and -R2 did not differ significantly between the overweight group, both obese groups, and controls. In conclusion, we observed increased serum concentrations of TNF-alpha and NO in overweight and obese women. It seems that there is an association between serum concentrations of TNF-alpha and NO; however, this relationship depends on the degree of obesity.     

The associations of body mass index, C-peptide and metabolic status in Chinese Type 2 diabetic patients.

BACKGROUND: Chinese Type 2 diabetic subjects are generally less obese than their Caucasian counterparts. We hypothesized that lean and obese Chinese Type 2 diabetic subjects have different metabolic and insulin secretory profiles. We compared the clinical features, C peptide and metabolic status between lean/normal weight and obese diabetic subjects. STUDY DESIGN: We conducted a cross-sectional study on 521 consecutive diabetic subjects newly referred to a Diabetes Clinic in 1996. The subjects were categorized into underweight (< 18.5 kg/m(2)), normal weight (18.5-23 kg/m(2)) and overweight (>/= 23 kg/m(2)) according to the re-defined WHO criterion for obesity in Asia Pacific Region. Metabolic and anthropometric parameters were compared between groups with different levels of obesity. RESULTS: In this cohort, 5.8, 30.6 and 63.7% of subjects were underweight, normal weight and overweight, respectively, using the 'Asian' criteria. Of these 521 subjects, 20% had fasting C-peptide less than 0.2 nmol/l, suggesting insulin deficiency. Fasting C-peptide showed linear increasing trend (P < 0.001) while HbA(1c) showed decreasing trend (P = 0.001) with BMI after adjustment for duration of disease. There were more subjects in the underweight group who were treated with insulin (41.3% vs. 13.9 and 8.2%, P < 0.001). Although homeostasis model assessment was similar amongst the three groups, systolic (P = 0.006) and diastolic blood pressure (P < 0.001) and triglyceride (P < 0.001) showed increasing, while HDL-C (P < 0.001) showed decreasing, trends across different BMI groups. The underweight patients had the lowest C-peptide and highest HbA(1c) while overweight patients had the highest C-peptide, blood pressure, triglyceride but lowest HbA(1c) levels. CONCLUSION: In Chinese Type 2 diabetic patients, lean subjects had predominant insulin deficiency and obese subjects had features of metabolic syndrome. Clinicians should have low threshold to initiate insulin therapy in lean Type 2 diabetic patients with suboptimal glycaemic control. In obese diabetic patients, aggressive control of multiple cardiovascular risks is of particular importance.     

Effect of increased body mass index on accuracy of two-dimensional echocardiography for measurement of left ventricular volume, ejection fraction, and mass

We used 2- and 3-dimensional echocardiography to determine left ventricular volume, mass, and ejection fraction in overweight (body mass index [BMI] > or = 25 kg/m2), obese (BMI > or = 30 kg/m2), and control (BMI < 25 kg/m2) subjects. Compared with corresponding magnetic resonance imaging measurements, 3-dimensional echocardiography is more accurate than 2-dimensional echocardiography in all patients, but particularly in overweight and obese subjects.     

Obesity is associated with decreasing levels of the circulating soluble leptin receptor in humans

OBJECTIVE: Leptin plays a major role in the regulation of body weight. It circulates in both free and bound form. One of the leptin receptor isoforms exists in a circulating soluble form that can bind leptin. In the present study, we measured the soluble leptin receptor (SLR) levels in lean and obese humans. We investigated the relationship between plasma SLR levels, plasma leptin levels and the degree of obesity. We also examined whether SLR concentrations could be modulated by fat mass loss induced by a 3 month weight-reducing diet. SUBJECTS: A total of 112 obese (age 18-50 y; body mass index (BMI) 30-44 kg/m2; 23 men and 89 women), 38 overweight (age 19-48 y; BMI 25-29 kg/m2; 10 men and 28 women) and 63 lean (age 18-50 y; BMI 17-24 kg/m2; 16 men and 47 women) humans. MEASUREMENTS: A direct double monoclonal sandwich enzyme-linked immunosorbent assay (ELISA) was used for the quantitative measurement of the soluble human leptin receptor. Leptin was measured by radioimmunoassay (RIA). Body composition was assessed by biphotonic absorptiometry DEXA (dual energy X-ray absorptiometry). RESULTS: We observed that the SLR is present in human plasma (range 10-100 ng/ml). SLR levels were lower in obese and overweight than lean subjects (28.7+/-8.8, 40.2+/-14.9, 51.2+/-12.5 ng/ml, respectively) and were inversely correlated to leptin and percentage of body fat (r=-0.74 and r=-0.76; respectively; P<0.0001). The ratio of circulating leptin to SLR was strongly related to the percentage of body fat (r=0.91; P<0.0001). Interestingly a gender difference was observed in SLR levels, which were higher in obese and overweight men than in obese and overweight women. In obese subjects after a 3 month low-calorie diet, SLR levels increased in proportion to the decrease in fat mass. In the gel filtration profile, SLR coeluted exactly with the bound leptin fractions. CONCLUSION: Obesity, in humans is associated with decreasing levels of the circulating soluble leptin receptor (SLR). The relationship of SLR with the degree of adiposity suggests that high SLR levels may enhance leptin action in lean subjects more than in obese subjects.     

Familial obesity, sympathetic activation and blood pressure level.

This study was conducted to evaluate the relative contributions of existing obesity and a family history of obesity (FHOB) to blood pressure (BP) level, sympathetic activity, plasma leptin and insulin levels in young men without a family history of hypertension. The study was of "four-corner" design according to body mass index (BMI). A positive FHOB (FHOB+) was defined as both parents being obese (BMI >26.0 kg/m2), and a negative FHOB (FHOB-) was defined as both parents being lean (BMI <22.0 kg/ m2). The cutoff limits of BP for the subjects and their parents enrolled in present study was defined as a supine reading of <140/90 mmHg. In 12 lean young subjects with FHOB-, 9 obese young subjects with FHOB-, 8 lean young subjects with FHOB+ and 16 obese young subjects with FHOB+, BMI, BP, plasma norepinephrine (NE), insulin and leptin were measured. All subjects were men and non-diabetic. Obese subjects, irrespective of FHOB, had higher levels of BMI, BP, plasma NE, leptin and insulin compared to lean subjects. In subjects with FHOB+, regardless of their current degree of adiposity, there was a higher level of BP and plasma NE than in subjects with FHOB-. In lean subjects, FHOB+ was associated with a higher plasma NE level and BP, but similar levels of plasma leptin and insulin were found when compared with FHOB- subjects. These results suggest that existing obesity and a positive family history of obesity appear to have an association with sympathetic overactivity and BP elevation.     

Association of subclinical right ventricular dysfunction with obesity.

OBJECTIVES: The purpose of this research was to identify the determinants of right ventricular (RV) dysfunction in overweight and obese subjects. BACKGROUND: Right ventricular dysfunction in obese subjects is usually ascribed to comorbid diseases, especially obstructive sleep apnea. We used tissue Doppler imaging to identify the determinants of RV dysfunction in overweight and obese subjects. METHODS: Standard and tissue Doppler echocardiography was performed in 112 overweight (body mass index [BMI] 25 to 29.9 kg/m2) or obese (BMI >30 kg/m2) subjects and 36 referents (BMI <25 kg/m2), including 22 with obstructive sleep apnea but no obesity. Tissue Doppler was used to measure RV systolic (s(m)) and diastolic (e(m)) velocities and strain indexes. RESULTS: Obese subjects with BMI >35 kg/m2 had reduced RV function compared with referent subjects, evidenced by reduced s(m) (6.5 +/- 2.4 cm/s vs. 10.2 +/- 1.5 cm/s, p < 0.001), peak strain (-21 +/- 4% vs. -28 +/- 4%, p < 0.001), peak strain rate (-1.4 +/- 0.4 s(-1) vs. -2.0 +/- 0.5 s(-1), p < 0.001), and e(m) (-6.8 +/- 2.4 cm/s vs. -10.3 +/- 2.5 cm/s, p < 0.001), irrespective of the presence of sleep apnea. Similar but lesser degrees of reduced systolic function (p < 0.05) were present in overweight (BMI 25 to 29.9 kg/m2) and mildly obese (BMI 30 to 35 kg/m2) groups. Differences in RV e(m), s(m), and strain indexes were demonstrated between the severely versus overweight and mildly obese groups (p < 0.05). Body mass index remained independently related to RV changes after adjusting for age, log insulin, and mean arterial pressures. In obese patients, these changes were associated with reduced exercise capacity but not the duration of obesity and presence of sleep apnea or its severity. CONCLUSIONS: Increasing BMI is associated with increasing severity of RV dysfunction in overweight and obese subjects without overt heart disease, independent of sleep apnea.     

Body composition, fat distribution and metabolic characteristics in lean and obese women with polycystic ovary syndrome

The polycystic ovary syndrome (PCOS), characterized by chronic anovulation and hyperandrogenism, has many features of metabolic syndrome and can be considered a metabolic disease. Approximately 50% of patients with PCOS are overweight or obese with abdominal fat accumulation. Some metabolic alterations and abdominal fat distribution have also been reported in lean women with PCOS. The aim of this study was to evaluate the effect, if any, of obesity on metabolic features, body composition and fat distribution in patients with PCOS. Body composition and abdominal fat distribution (evaluated by DEXA), waist circumference, blood pressure, lipid profile, glucose tolerance and homeostasis model assessment index were determined in 23 lean [mean age 23 +/- 5 yr, mean body mass index (BMI) 22 +/- 2 kg/m2] and 27 overweight-obese (mean age 21 +/- 5 yr, mean BMI 32 +/- 5 kg/m2) patients with PCOS and in 20 age- and weight-matched eumenorrhoic women. Patients exhibited slight but non-significant differences in metabolic parameters, waist circumference, blood pressure and total and abdominal fat content compared with weight-matched controls. None of the lean subjects suffered from metabolic syndrome according to the National Cholesterol Education Program--Adult Treatment Panel III (NCEP-ATPIII) criteria as opposed to 10 overweight-obese patients and three overweight-obese control subjects (37% and 33.3% of each subgroup, respectively). Our data do not show significant metabolic alterations in lean PCOS women. Results indicate that obesity seems to underpin the metabolic alterations exhibited by the overweight-obese patients. However, since women with PCOS are at increased cardiovascular risk, further studies are needed to evaluate metabolic alterations and body composition in these patients.