Weight loss reduces circulating asymmetrical dimethylarginine concentrations in morbidly obese women

The endogenous nitric oxide-synthase inhibitor asymmetrical dimethyl-L-arginine (ADMA) is elevated in patients with increased risk for arteriosclerosis. Obesity is a risk factor for cardiovascular disease. We measured plasma ADMA concentrations in morbidly obese women before and after weight loss following gastroplastic surgery. ADMA and symmetrical dimethyl-L-arginine concentrations were analyzed by HPLC from 34 female patients (age 41 +/- 7 yr) with a body mass index (BMI) of 49 +/- 1 kg/m2 before and 14 months after vertical ring gastroplasty. Age-matched healthy women (BMI < 25 kg/m2; n = 24) were studied as controls. After gastroplastic surgery, BMI decreased to 34 +/- 1 kg/m2 in obese women (P < 0.00001), and ADMA concentrations were reduced from 1.06 +/- 0.06 micromol/liter at baseline to 0.81 +/- 0.04 micromol/liter after weight loss (P < 0.00001). Symmetrical dimethyl-L-arginine plasma levels were not affected. ADMA correlated with high-sensitivity C-reactive protein at baseline (r = 0.42; P < 0.05) and after weight loss (r = 0.56; P < 0.005). No association with blood pressure or plasma lipids could be observed. ADMA concentrations were lower in controls (0.68 +/- 0.04 micromol/liter; P < 0.05) compared with obese patients before or after weight reduction. The decrease of highly elevated ADMA concentrations in morbidly obese patients is paralleled by improvement of parameters associated with the metabolic syndrome after weight loss.     

Prevalence of impaired glucose tolerance 6 years after gestational diabetes.

AIM: Prevalence of glucose metabolism disorders in women six years after gestational diabetes in the index pregnancy (GDM). METHOD: 227 Caucasian women who developed GDM between 1995 and 1996 were investigated; 173 women (BMI 27.5+/-6.0 kg/m2) received 75 g oGGT on average 5.8+/-2.0 years after delivery. RESULTS: Impaired glucose metabolism was found in 31.2%, IGT or IFG 19.1%, diabetes mellitus type 2 (DM2) 9.2%, diabetes mellitus type 1 (DM1) 2.3%, second GDM 0.6%. 27.2% (BMI 25-29.9 kg/m2) were overweight, 23.1% suffered from obesity (BMI 30-39.9 kg/m2) and 5.2% morbid obesity (BMI>or=40 kg/m2). In comparison to a healthy control group, women with DM2 at re-examination were: older in age (32.1+/-5.9 vs. 29.1+/-4.8 years, p<0.05), had higher BMI (29.4+/-6.9 vs. 24.6+/-4.8 kg/m2, p<0.05), higher fasting blood glucose (6.5+/-1.9 vs. 5.2+/-0.9 mmol/l, p<0.05), earlier diagnosis of GDM (25+/-8 vs. 29+/-5 SSW, p<0.05), more frequent insulin therapy during pregnancy (75 vs. 24%) and had significantly higher insulin- and C-peptide for all measures of the oGTT, whereas HbA1c was not different (4.9+/-0.5 vs. 4.8+/-0.3%, n. s.). CONCLUSION: In an average of 5.8 years after the diagnosis of GDM, the majority of women still have chronic insulin resistance. One third has either IGT, IFG or diabetes mellitus. Therefore, a long term follow-up is strongly recommended for women diagnosed with GDM.     

Unchanged asymmetric dimethylarginine levels in non-diabetic, premenopausal obese women who have common risk factors for cardiovascular disease

This study was performed to test whether plasma asymmetric dimethylarginine (ADMA) concentrations are related to obesity and obesity complications including decrement in insulin sensitivity and adiponectin levels, dyslipidemia and low-grade inflammation. Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) concentrations were analyzed by HPLC in 17 overweight (BMI ≥ 25 kg/m²) and 40 obese (BMI ≥ 30 kg/m²) premenopausal women. Age-matched healthy women were studied as controls. Obesity did not give rise to a significant change in circulating ADMA levels but reduced in SDMA levels. As compared with control subjects (0.441 ± 0.102 μM), ADMA values in overweight and obese subjects were found to be as 0.412 ± 0.102 and 0.436 ± 0.093, respectively. No Pearson’s association of ADMA with relevant risk variables for cardiovascular disease, including blood pressure, insulin sensitivity, inflammatory markers, lipid and adiponectin levels. However, in linear regression analysis, BMI, diastolic blood pressure, glucose, insulin, and IL-8 emerged as significant predictors of ADMA. In spite of obese women have elevated hs-CRP, triglyceride levels and decreased insulin sensitivity, adiponectin and HDL-cholesterol levels, all of which is closely linked risk factors for cardiovascular disease, circulating ADMA levels remained unchanged in obese individuals as compared with controls.     

Plasma oxysterols and vitamin E concentrations and lipid profile in morbidly obese women

Morbid obesity (BMI > or = 40 kg/m2) is accompanied by lipid disturbances which may be involved in the increased incidence of atherosclerosis, arterial hypertension and non-insulin-dependent diabetes mellitus. The aim of the study was to assess concentrations of total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, triglycerides (TG), products of cholesterol peroxidation--oxysterols, and the major lipophilic antioxidant--vitamin E, in morbidly obese women without coexisting diseases. The study was performed in 11 morbidly obese women (BMI 42.21 +/- 2.21 kg/m2) and 11 healthy volunteers (BMI 23.0 +/- 2.31 kg/m2). Obese women demonstrated higher concentrations of TG (2.03 +/- 0.78 vs. 0.99 +/- 0.37 mmol/l; p < 0.05), 7-ketocholesterol (7-K) (89.85 +/- 63.03 vs. 41.90 +/- 17.33 ng/ml; p < 0.05) and 7-hydroxycholesterol (7-OH) (456.04 +/- 199.22 vs. 132.37 +/- 53.96 ng/ml; p < 0.05), and lower HDL-cholesterol level (0.74 +/- 0.10 vs. 1.30 +/- +/- 0.17 mmol/l; p < 0.05) compared to the control group, while there were no significant differences between the two groups in concentrations of TC, LDL-cholesterol and vitamin E. Plasma vitamin E/(TC + TG) ratio was lower in obese women (6.42 +/- 2.61 vs. 10.76 +/- 4.57 mumol/mmol; p < 0.05). Tocoferols concentration correlated positively with TG (r = 0.45; p < 0.05) and negatively with 7-OH (r = -0.44; p < 0.05) levels. Moreover, concentration of 7-K correlated positively with the level of HDL (r = 0.54; p < 0.05). In conclusion, despite normal TC and LDL-cholesterol concentrations, there are disturbances in cholesterol peroxidation processes, with the rise in oxysterol levels and the decrease in vitamin E concentration in lipoproteins, which may be involved in the increased incidence of cardiovascular diseases in morbidly obese women.     

Fibrinolytic dysfunction after gestation is associated to components of insulin resistance and early type 2 diabetes in latino women with previous gestational diabetes

Among patients with metabolic syndrome (MS), atherosclerosis and abnormal fibrinolytic function are frequently present, mostly owing to an increase in plasminogen activator inhibitor-1(PAI-1). We analyze PAI-1 in pregnant women, both normal and with gestational diabetes (GDM) and postpartum regarding its correlation to MS surrogates. Clinical characteristics, glucose tolerance (100g-OGTT), lipids, PAI-1 antigen, insulin sensitivity (HOMA-S), and pancreatic beta-cell function (HOMA-B) were investigated in 34 women. Eleven had normal glucose tolerance (NGT) during pregnancy and 23 had GDM (all GAD antibodies-negative). All patients were studied at 28-34 weeks of gestation and 16-24 weeks after delivery (75 g-OGTT). Parameters of interest were determined using commercial test systems. During pregnancy, PAI-1 was not statistically different between NGT and GDM (47+/-25 ng/ml versus 47+/-28 ng/ml, p=0.9). After gestation, 19 (56%) women had NGT (11 of them from previous NGT group) and 15 (44%) had impaired glucose tolerance (IGT) or DM. The IGT (IGT+DM) group had higher PAI-1 (p=0.01), which did not decreased after delivery NGT-NGT before and after delivery (47+/-25 ng/ml versus 6+/-5 ng/ml; p<0.001), GDM-NGT (62+/-36 ng/ml versus 14+/-15 ng/ml; p=0.001) and GDM-IGT (39+/-20 ng/ml versus 27+/-23 ng/ml; p=0.15). PAI-1 levels were positively correlated (p<0.05) to total cholesterol (r(s)=0.37), triglycerides (r(s)=0.48), fasting plasma glucose (r(s)=0.52), 2-h plasma glucose in the OGTT (r(s)=0.58) and were negatively correlated (p<0.05) with HOMA-S (r(s)=-0.42) and HOMA-B (r(s)=-0.38). Fibrinolytic dysfunction is still present in GDM women and is associated with early development of IGT or T2DM. PAI correlated with surrogate markers of MS levels and may identify a group of women at risk for macroangiopathy.     

Asymmetric dimethylarginine concentrations are elevated in women with gestational diabetes

As shown in the previous studies, asymmetric dimethylarginine (ADMA) is related to endothelial dysfunction, whereas high-sensitive C-reactive protein (hCRP) is the marker of inflammation. In our study, we investigated ADMA, hCRP, and homocysteine concentrations in women with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) during late pregnancy. Fifty-four women with GDM and 69 women with NGT between 32 and 39 weeks of gestation were included in this study. ADMA, hCRP, homocysteine, lipid parameters, glycated hemoglobin (HbA1c) levels, insulin, and homeostasis model assessment for insulin resistance (HOMA-IR) were measured. The plasma ADMA concentrations were significantly higher in GDM patients than in NGT subjects (P = 0.03) and the hCRP levels were also significantly increased in GDM group when compared with those in the NGT group (P = 0.008). However, plasma homocysteine levels did not differ between the groups (P = 0.4), while HOMA-IR, insulin, and triglyceride levels were higher in the GDM group than in the NGT group (P = 0.001, 0.002, and 0.02, respectively). The ADMA concentrations in the third trimester were positively correlated with the glucose levels the 50-g glucose challenge test (GCT) during 24-28 weeks in the whole group (r = 0.21, P = 0.02). Our results demonstrate that ADMA and hCRP are elevated in women with GDM during late pregnancy. Further studies are needed to clarify the significance and the underlying mechanisms of the elevated ADMA and hCRP levels in women with GDM.     

Insulin resistance and beta-cell dysfunction in normoglycaemic European women with a history of gestational diabetes

OBJECTIVE: Women with previous gestational diabetes (GDM) are at increased risk of subsequent type 2 diabetes. To characterize early metabolic abnormalities associated with this increased risk, we studied normoglycaemic women with a history of GDM. PATIENTS AND MEASUREMENTS: We performed an insulin-modified, frequently sampled intravenous glucose tolerance test (FSIVGTT) in 34 normoglycaemic European women with previous GDM and 44 European control women, deriving measures of insulin sensitivity, glucose effectiveness, glucose disappearance rate and acute insulin response to glucose. RESULTS: Post-GDM women were more obese than controls [body mass index (BMI), geometric mean (95% confidence interval); 25.3 kg/m2 (23.8-27.1 kg/m2) vs. 23.1 kg/m2 (21.9-24.3 kg/m2), P = 0.03]. Evidence of insulin resistance was provided by their lower insulin sensitivity as measured by FSIVGTT [0.6 x 10-4/min/pmol/l (0.3-1.2 x 10-4/min/pmol/l) vs. 1.5 x 10-4/min/pmol/l (1.2-1.8 x 10-4/min/pmol/l), P = 0.01] and by homeostatic model assessment [72% (49-107%) vs. 153% (113-206%), P = 0.004]; and by their higher fasting triglycerides [1.0 mmol/l (0.7-1.5 mmol/l) vs. 0.7 mmol/l (0.6-0.8 mmol/l), P = 0.001]. Though there was no difference between groups in fasting NEFA levels, acute NEFA suppression was diminished in the post-GDM group (P = 0.01). Concomitant beta-cell dysfunction in the post-GDM women was revealed by their lower disposition index [0.05/min (0.02-0.10/min) vs. 0.11/min (0.09-0.14/min), P = 0.02] compared to controls. The differences in insulin sensitivity, but not those of beta-cell function, were partly, though not completely, attributable to differences in regional and total adiposity. CONCLUSIONS: European normoglycaemic women with previous GDM display both glucoregulatory and antilipolytic insulin resistance, reduced beta-cell function and dyslipidaemia. These metabolic abnormalities are likely to contribute to their increased risk of future type 2 diabetes.     

Plasma insulin, cholecystokinin, galanin, neuropeptide Y and leptin levels in obese women with and without type 2 diabetes mellitus

Obesity is an important factor predisposing to type 2 diabetes mellitus, especially for postmenopausal women. Experimental studies provided evidences that leptin, cholecystokinin (CCK), galanin (GAL), neuropeptide Y (NPY) and insulin are involved in feeding behaviour. The aim of the study was to evaluate their possible relationships in obese and diabetic women. Three groups of postmenopausal women (FSH > 30 mIU/ml) were evaluated: 8 diabetic (mean age 56.6 +/- 6.9 y, BMI 29.8 +/- 5.3 kg/m2), 10 obese non-diabetic (mean age 49.6 +/- 5.4 y, BMI 36.0 +/- 3.7 kg/m2) and 12 non-diabetic controls (mean age 52.7 +/- 3.5 y, BMI 27.3 1.9 kg/m2). For each patient BMI and WHR were measured and calculated. Blood samples were collected at 8:00 a.m. after an overnight fast. Plasma concentrations of FSH, leptin, CCK, GAL, NPY and insulin were determined using commercial RIA kits. Mean plasma NPY concentration was significantly higher in diabetic women than in controls (190.1 pg/ml +/- 85.4 vs 120.4 +/- 36.6). Compared to controls, mean plasma leptin level was significantly higher in obese non-diabetic women (32.9ng/ml +/- 9.2 vs 18.9 +/- 9.1). No significant differences were found between obese non-diabetic and diabetic women. In diabetic subjects positive correlations were found between: CCK and leptin (r= 0.8295; P= 0.011), CCK and insulin (r=0.7832; P=0.022), leptin and insulin (r=0.9302; P=0.001). In obese subjects a positive correlation between WHR and GAL (r= 0.6624; P= 0.037) and a negative between GAL and insulin (r= -0.6795; P= 0.031) were found. In controls positive correlations were found between WHR and CCK (r=0.6412; P=0.025), GAL and insulin (r=0.630; P=0.028) and negative between CCK and NPY (r = -0.6505; P= 0.022). Our results, ie higher mean plasma NPY levels in postmenopausal diabetic women and positive correlation of CCK with leptin and insulin, may suggest the role of these neuropeptides in metabolic disorders leading to type 2 diabetes mellitus.     

Normal serum alanine aminotransferase activity in uncomplicated obesity

AIM: To evaluate serum alanine aminotransferase (ALT) activity in a well-characterized group of uncomplicated obese subjects and its correlation with insulin resistance, plasma adiponectin, and leptin concentrations. METHODS: One hundred and five uncomplicated obese subjects (87 women, 18 men, age 34.3±9.6 years, BMI 39.9±8.3 kg/m2)were studied. Serum ALT activity was evaluated. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp (M index) and fasting insulin. Plasma leptin and adiponectin levels were also measured. RESULTS: Serum ALT concentration in the whole group of uncomplicated obese subjects was 17.73±6.33 U/L with none of the subjects presenting ALT levels greater than 43 U/L and only 9 (11%) women and 3 (19%) men showed ALT levels >19 and >30 U/L for women and men, respectively. No significant difference was detected in serum ALT levels between severe obese subjects (BMI >40 kg/m2) and those with BMI <40 kg/m2 (18.63±6.25 vs 17.26±6.02 U/L). ALT was significantly correlated with fasting insulin (r=0.485, P= 0.02) and triglycerides (r= 0.358, P=0.03). CONCLUSION: Serum ALT activity is practically normal in uncomplicated obese subjects, independently of their obesity degree. These findings suggest the role of obesityrelated comorbidities and not of BMI as main risk factors for elevated ALT levels in obese subjects.     

Influence of insulin treatment on insulin sensitivity in insulin requiring type 2 diabetes patients

Insulin resistance in type 2 diabetes subjects was investigated before and 6 months after insulin administration in 43 type 2 diabetes patients (28 females and 15 males). Their age was 56.1+/-8.6 years, diabetes duration 11.7+/-6.8 years, BMI 29.5+/-5.3 kg/m2. All patients were on maximal dosage of oral hypoglycaemic agents and had poor metabolic control (HbA1c 11.2+/-1.6%). Insulin sensitivity was measured by euglycaemic clamp (insulin infusion rate 1 mU kg-1 min-1). The glucose disposal rate (M-value) was considerably lower in patients (2.4+/-1.6 mg kg-1 min-1, 0.2-8.1) compared with healthy subjects (7.1+/-0.2 mg kg-1 min-1, p<0.01). M-value was strongly associated with WHR (r=-0.41, p<0.05). The patients with poorest insulin sensitivity had the highest level of total cholesterol (r=-0.41, p=0.02) and LDL-cholesterol (r=-0.38, p=0.03). After 6 months of insulin treatment BMI was 30.3+/-4.2 kg/m2 (p<0.05), mean weight increase was 2.7+/-0.8 kg. M-value was substantially increased to 4.5+/-2.3 mg kg-1 min-1 (p<0.001), the degree of improvement depended on basal insulin sensitivity (r=-0.55, p<0.01). HbA1c was reduced to 7.7+/-1.4% (p<0.01), the correlation M-value with change of HbA1c (r=-0.59, p<0.01) was shown. Total cholesterol decreased from 6.3+/-1.1 to 5.4+/-1.1 mmol/l, LDL-cholesterol from 4.1+/-1.1 to 3.4+/-1.0 mmol/l, triglycerides from 2.6+/-1.6 to 1.6+/-0.7 mmol/l (p<0.001). In conclusion, insulin treatment of type 2 diabetes patients leads to decrease in insulin resistance due to reduction in glucose toxicity and plasma atherogenicity despite weight gain.     

Plasma asymmetric dimethylarginine concentrations are elevated in obese insulin-resistant women and fall with weight loss

CONTEXT: Plasma asymmetric dimethylarginine (ADMA) concentrations are higher in apparently healthy, insulin-resistant (IR) individuals and decrease in response to thiazolidenedione treatment. OBJECTIVE: The objective of the study was to determine whether ADMA concentrations would also fall when insulin sensitivity is enhanced with weight loss in obese individuals. DESIGN/SETTING/PATIENTS/INTERVENTION: Twenty obese women classified as IR or insulin sensitive (IS) on the basis of their steady-state plasma glucose (SSPG) concentration during the insulin suppression test underwent 12 wk of dietary weight loss. OUTCOME MEASURES: Plasma glucose, insulin, and ADMA were measured at baseline and after weight loss; change in insulin resistance was quantified by repeating the SSPG after the dietary intervention. RESULTS: Although weight loss was similar in the two groups, significant improvements in SSPG, glucose, and insulin concentrations were confined to the IR group. Baseline plasma ADMA concentrations (mean +/- sd) were higher in IR subjects (1.69 +/- 0.44 vs. 1.18 +/- 0.45 micromol/liter, P = 0.02) and decreased to 1.20 +/- 0.22 micromol/liter (P < 0.001) with weight loss. In contrast, ADMA levels did not change with a similar extent of weight loss in the IS group. CONCLUSION: Plasma ADMA levels are higher in obese, IR women than in equally obese, IS women and decrease in response to weight loss when associated with enhancement of insulin sensitivity.     

Serum homocysteine levels are increased in women with gestational diabetes mellitus

Serum homocysteine (sHcy) has been found to be elevated in patients with type 2 diabetes mellitus, as well as in other clinical conditions associated with insulin resistance and/or vascular diseases. The aims of this study were to measure the relationship between sHcy with biohumoral markers of insulin resistance in pregnant women affected with gestational diabetes mellitus (GDM). We studied 2 groups of pregnant women categorized, after a 100-g, 3-hour oral glucose tolerance test (OGTT) as nondiabetic (n = 78) or affected with GDM (n = 15), by measuring sHcy, serum folate, albumin, vitamin B(12), uric acid, and lipids. In both groups, peripheral insulin sensitivity was measured by using the OGTT-derived index of Matsuda and DeFronzo (ISI(OGTT)). Serum homocysteine was significantly higher in the group with GDM compared with nondiabetic women (5.88 +/- 2.26 micromol/L v 4.45 +/- 1.52 micromol/L; P =.003); was inversely related to serum folate (r = -.48; P =.0001), and was significantly related to serum albumin (r =.27; P =.009), 2-hour plasma glucose (r =.25; P =.01), as well as to serum uric acid (r =.23; P =.03). No relationship was observed between sHcy and serum vitamin B(12), serum triglycerides, total, or high-density lipoprotein (HDL) cholesterol, mean blood pressure and ISI(OGTT). Vitamin B(12) was correlated with ISI(OGTT) (r =.36; P =.0005) and inversely with mean blood pressure (r = -.24; P =.02). GDM remained significantly associated with higher sHcy concentrations also after adjusting for age, serum folate, albumin, uric acid, ISI(OGTT), and vitamin B(12) (P =.006). In conclusion, we found that sHcy is significantly increased in women with GDM, independently of other confounding variables, is significantly related to 2-hour OGTT plasma glucose, and seems unrelated to insulin resistance in these subjects.     

Effect of angiotensin-converting enzyme inhibitor on serum asymmetric dimethylarginine and coronary circulation in patients with type 2 diabetes mellitus

Measurements of serum asymmetric dimethylarginine (ADMA), an endogenous nitric oxide synthase inhibitor, and coronary flow velocity reserve (CFVR) using transthoracic Doppler echocardiography were performed at baseline and after 4 weeks of temocapril therapy (2 mg/day) in 18 patients with type 2 diabetes. Although blood pressure, fasting blood sugar and lipid profiles remained unchanged, serum ADMA concentrations decreased significantly (0.51+/-0.08 to 0.46+/-0.07 micromol/l, p<0.01) and CFVR increased significantly (2.78+/-0.36 to 3.35+/-0.46, p<0.001) after the treatment. Moreover, a strong correlation was observed between the difference of ADMA and that of CFVR (r=-0.80, p<0.001). Temocapril reduced serum ADMA concentrations, improved CFVR beyond its blood pressure lowering effect. Our results suggest that decrease in ADMA by temocapril treatment is related to improvement of coronary circulation as determined by CFVR in patients with type 2 diabetes.     

C-reactive protein and tumor necrosis factor-alpha in gestational hyperglycemia

OBJECTIVES AND STUDY DESIGN: Increasing evidences support an inflammatory origin for gestational hyperglycemia. This paper aims at investigating, cross-sectionally and prospectively, the relationships between tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein (CRP) levels in normoglycemic and hyperglycemic pregnancies of women with and without conventional risk factors for gestational diabetes (GDM). RESULTS: Both at simple and multiple correlations TNF-alpha levels are associated to fasting insulin, homeostasis model assessment-insulin resistance (HOMA-IR) values and gestational hyperglycemia, while high sensitivity CRP (hsCRP) levels to body mass index (BMI). Furthermore, the TNF-alpha levels of the second trimester and their increments in the third trimester are significant predictors of insulin levels measured at 32-36 weeks in the subgroup of hyperglycemic women with < or = 35 yr, BMI <25 kg/m2 and the absence of a first-degree relative with Type 2 diabetes (respectively, beta=1.1; 95%CI 0.66-1.48; p=0.002 and beta=1.0; 95%CI 0.36-1.66; p=0.02), in a multiple regression model, after multiple adjustments. In a second cohort of women at low risk for GDM (<25 yr, BMI <25 kg/m2 and absence of a first-degree relative with Type 2 diabetes), 24-28 weeks TNF-alpha levels are highly associated with corresponding insulin and HOMA values in the same model (respectively, beta=0.27; 95%CI 0.11-0.43; p=0.001 and beta=0.30; 95%CI 0.14-0.46; p<0.001). CONCLUSIONS: The data support the developing hypothesis that low-grade systemic inflammation is associated to GDM, in particular for pregnant women without conventional risk factors for gestational hyperglycemia, whose insulin resistance seems less explainable.     

Effect of small doses of dexamethasone on plasma leptin levels in normal and obese subjects: a dose-response study

To further elucidate the role of glucocorticoids in the regulation of leptin secretion, we studied the effects of overnight small doses of dexamethasone on plasma leptin levels in normal weight controls and in obese patients and correlated the results with indexes of insulin sensitivity and body fat distribution. In 114 subjects (81 obese patients, 49 women and 32 men, BMI 37.4 +/- 0.77 kg/m2 and 33 normal-weight subjects, 17 women and 16 men, BMI 22.1 +/- 0.41 kg/m2) plasma F and leptin levels were measured at 08:00 h basally and after the administration of different doses of dexamethasone (a fixed dose of 1-mg and 0.0035, 0.007, 0.015-mg/kg bw, given po at 23:00 h the night before). Tests were performed one week apart with bw remaining stable over the study period. Basal leptin levels were significantly higher in obese than in normal subjects (31.9 +/- 2.41 vs 7.7 +/- 0.93 ng/ml, p<0.0001). In obese patients, leptin levels increased significantly by 1-mg (from 31.9 +/- 2.41 to 35.0 +/- 2.59 ng/ml, p<0.005) and the 0.015-mg/kg bw dose (from 31.5 +/- 2.34 to 33.7 +/- 2.44 ng/ml, p<0.05), while they were unaffected by each dose of dexamethasone in normal subjects. However, after splitting subjects by gender, mean leptin levels rose from 39.3 +/- 2.97 to 43.3 +/- 3.12 ng/ml after the 1-mg dose, p<0.005, from 39.1 +/- 2.87 to 43.6 +/- 2.91 ng/ml after the 0.015-mg/kg bw dose, p<0.005, from 39.3 +/- 2.90 to 42.2 +/- 2.90 ng/ml after the 0.007-mg/kg bw dose, p<0.05 and from 38.8 +/- 2.66 to 41.1 +/- 2.87 ng/ml after the 0.0035-mg/kg bw dose, p=0.055, only in obese women. Conversely, no leptin changes were seen in the other groups and no differences were observed in the leptin response between groups. After the 1-mg dose, in the whole group, the absolute leptin variation was weakly but significantly related to BMI values (r=0.231, p<0.02) while in all sessions the percent leptin changes over baseline were not significantly correlated with age, BMI, waist, WHR, insulin, HOMA index, a marker of insulin sensitivity, plasma dexamethasone concentrations and to the percent cortisol variation following dexamethasone. In conclusion, in obese women but not in obese men and in normal weight subjects, small overnight increases in plasma glucocorticoid concentrations induced gender-related plasma leptin elevations that were unrelated to body fat distribution and insulin sensitivity. A greater sensitivity of female adipose tissue to glucocorticoids probably underlies this sexually dimorphic pattern of leptin response. These findings provide an additional piece of information on the regulation of leptin secretion exerted by glucocorticoids.     

Is dermolipectomy effective in improving insulin action and lowering inflammatory markers in obese women?

OBJECTIVE: Obesity is a major risk factor for coronary heart disease, and surgical treatment of obese patients as part of a multidisciplinary approach seems to provide faster results than diet therapy. The aim of this study was to evaluate the effect of dermolipectomy on insulin action and inflammatory markers in 20 obese women. PATIENTS: At baseline and 40 days after dermolipectomy, 20 obese women underwent indirect calorimetry and hyperinsulinaemic glucose clamp. Twenty obese nonsmoking females (age range 25--40 years) volunteered for the study. All subjects had a stable body weight for 2 months before the study. No patient was affected by cardiovascular and/or pulmonary disease, type 2 diabetes, thyroid dysfunction, acute or chronic hepatitis, renal insufficiency or cancer. No patients was receiving any drug therapy and all measurements were made during the follicular phase of the menstrual cycle. RESULTS: At baseline, fat mass (FM) correlated with plasma triglycerides (r=.58, P<0.009), free fatty acids (FFA) (r=0.73, P<0.001), insulin (r=0.70, P<0.002), leptin (r=0.55, P<0.01), adiponectin (r=-0.32, P<0.02) and resistin (r=0.31, P<0.01), insulin sensitivity (IS) (r=-0.59, P<0.005) and respiratory quotient (Rq) (r=0.62, P<0.002). With regard to inflammatory markers, FM was significantly correlated with plasma interleukin (IL)-6 (r=0.71, P<0.001), IL-10 (r=-0.67, P<0.002), tumour necrosis factor-alpha (TNF-alpha) (r=0.78, P<0.001) and soluble IL-6 receptor (sIL-6r) (r=-0.65, P<0.003). Dermolipectomy resulted in a significant decline in total FM of 2.3+/- 0.2 kg. A significant decline in BMI was also observed (30.0+/- 0.08 vs. 31.1+/- 0.7 kg/m(2)). After 40 days a significant decline in plasma resistin (P<0.001) and inflammatory markers and an increase in plasma adiponectin (P<0.03) were observed. Those metabolic changes were accompanied by a significant improvement in insulin-mediated glucose uptake (P<0.001), substrate oxidation and degree of inflammation. Changes in FM following dermolipectomy correlated with the changes in IS (P<0.01), substrate oxidation and FFA (P<0.001). CONCLUSIONS: In obese patients, dermolipectomy is associated with weight lost, improved glucose handling and lower inflammatory markers.     

Endothelial microparticles correlate with endothelial dysfunction in obese women

CONTEXT: Cell-derived microparticles are supposed to be involved in atherogenesis. OBJECTIVE: This study aimed to evaluate circulating microparticles in obese women and their relation with anthropometric measures and endothelial dysfunction. DESIGN, SETTING, AND PARTICIPANTS: Forty-one obese [body mass index (BMI) > 30 kg/m(2)] women and 40 normal weight (BMI < 25 kg/m(2)) age-matched women were studied. Flow cytometry was used to assess microparticles by quantification of circulating endothelial microparticles (EMP, CD31+/CD42b-) and platelet microparticles (PMP, CD31+/CD42b+) in peripheral blood; endothelium-dependent flow-mediated vasodilation (FMD) was evaluated in the right brachial artery after reactive hyperemia. RESULTS: Compared with lean women, obese women presented significantly higher numbers of EMP and PMP, and reduced FMD. BMI did not correlate with either EMP (r = 0.02, P = 0.9) or PMP (r = -0.07, P = 0.645), whereas waist-to-hip ratio (WHR) showed significant correlation with both microparticles (r = 0.699, P < 0.001; r = 0.373, P = 0.016, respectively). Both EMP and PMP counts positively correlated with impairment of FMD in obese women. Multivariate analysis correcting for age, anthropometric indices, lipid parameters, and PMP identified EMP as the only independent predictor for impaired endothelial-dependent vasodilation (P = 0.003). CONCLUSIONS: EMP are elevated in obese women and independently involved in the pathogenesis of endothelial dysfunction. WHR is the anthropometric measure more closely related to EMP and endothelial dysfunction.     

Effect of weight loss on QTc dispersion in obese subjects.

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

Increased cholesterol intake in women with gestational diabetes mellitus

AIM: Cholesterol intake is associated with the risk for type 2 diabetes mellitus, but no previous studies have evaluated its role regarding the risk of gestational diabetes mellitus (GDM). We investigate the relation between cholesterol intake and GDM. METHODS: At screening for GDM, 335 pregnant women were evaluated for dietary intake (including cholesterol) during the previous year (validated food-frequency questionnaire). RESULTS: Forty-one women were diagnosed with GDM and 294 did not meet the GDM criteria. Women with GDM were older (32.8+/-0.7 vs. 30.2+/-0.3 years; P=0.01) and had a higher body mass index (27.3+/-0.7 vs. 24.3+/-0.3 kg/m2; P=0.01) than women without GDM. They also had more frequently a family history of type 2 diabetes mellitus (51.2% vs. 40.0%; P=0.02) and history of previous GDM (14.6% vs. 1.7%; P=0.01), and were evaluated earlier in pregnancy (22.1+/-1.2 vs. 24.9+/-0.5 weeks; P=0.03). There were no significant differences between groups in smoking habit, and alcohol, total energy, protein, carbohydrate, fats and fiber intake. Women with GDM had a higher cholesterol intake than women without GDM (145.3+/-4.5 mg/1000 kcal vs. 134.5+/-1.6 mg/1000 kcal; P=0.03). In a multiple logistic regression model, previous GDM, BMI, age and cholesterol intake (OR=1.88; 95% CI: 1.09-3.23 for each increase of 50 mg/1000 kcal) were independently and positively associated with GDM. CONCLUSION: We conclude that cholesterol intake is independently associated with GDM and that it could be involved in the pathogenesis of GDM.     

Postprandial lipoprotein metabolism in normal and obese subjects: comparison after the vitamin A fat-loading test

Abnormalities in fasting lipid and lipoprotein levels are known to occur in obesity and other hyperinsulinemic states. However, postprandial lipoprotein metabolism has not been studied systematically in obese subjects using sensitive techniques to distinguish between triglyceride-rich lipoprotein particles derived from the intestine and the liver. In the present study the vitamin A fat-loading test was used to label intestinally derived triglyceride-rich lipoprotein particles in the postprandial state. Lipid parameters in seven normolipidemic obese subjects [body mass index, 43.7 +/- 2.81 kg/m2 (mean +/- SEM)] were compared to those in eight matched normal weight controls (body mass index, 23.6 +/- 0.72 kg/m2) during the 24-h period following ingestion of a mixed meal with a high fat content to which vitamin A had been added. Although subjects were selected for normal fasting lipid levels, in the obese group fasting triglycerides were significantly higher (1.35 +/- 0.12 vs. 0.68 +/- 0.08 mmol/L; P less than 0.0005) and high density lipoprotein (HDL) cholesterol was lower (0.94 +/- 0.08 vs. 1.35 +/- 0.11 mmol/L; P less than 0.01). The obese subjects had a greater postprandial triglyceride response to the test meal (P less than 0.05). The cumulative increment in total plasma triglycerides was 3.35-fold greater in obese than control subjects, while that of retinyl ester was only 1.63-fold greater, suggesting that a significant portion of the postprandial triglyceride response is due to endogenous hepatic lipoproteins. Postprandial plasma triglyceride and retinyl ester increment correlated with basal triglycerides (r = 0.72; P less than 0.005 and r = 0.57; P less than 0.03, respectively) and negatively with fasting HDL (r = -0.51; P less than 0.05 and r = -0.60; P less than 0.02, respectively). In the obese, the HDL triglyceride content increased maximally 4 h postprandially (4.1% to 6.1%; P less than 0.005) and phospholipid at 12 h (25.8% to 28.7%; P less than 0.05), with lower cholesteryl ester (21.1% to 17.5%; P less than 0.002) at 8 h, reflecting exchange of surface and core lipids with triglyceride-rich particles after the meal. In obese and control subjects the magnitude of HDL triglyceride enrichment after the meal correlated positively with the postprandial triglyceride increment (r = 0.74; P less than 0.007) and negatively with the fasting HDL cholesterol concentration (r = -0.80; P = 0.002). We conclude that even normolipidemic obese subjects have greater postprandial lipemia and triglyceride enrichment of HDL after ingestion of a high fat meal.(ABSTRACT TRUNCATED AT 400 WORDS)