Neuropeptide Y, galanin, and leptin release in obese women and in women with anorexia nervosa

The study objective was to determine circulating levels of the appetite-controlling neuropeptides, neuropeptide Y (NPY), galanin, and leptin, in subjects with eating disorders. The study group consisted of 48 obese women aged 19 to 45 years, 15 women with anorexia nervosa aged 18 to 23 years, and 19 lean healthy women aged 18 to 42 years (control group). The obese women were divided into four groups: (A) body mass index (BMI) = 25 to 30 kg/m², N = 9 (overweight); (B) BMI = 31 to 40 kg/m², N = 23 (moderate obesity); (C) BMI greater than 40 kg/m², N = 9 (severe obesity); and (D) BMI = 31 to 40 kg/m², N = 7 (moderate obesity + non—insulin-dependent diabetes mellitus [NIDDM]). Plasma NPY, galanin, and leptin concentrations were measured in peripheral blood samples with radioimmunoassay methods. Plasma NPY levels in obese women (groups A, B, C, and D) were significantly higher as compared with the control group (P < .01, P < .001, P < .001, and P < .001, respectively). The highest plasma NPY concentrations were observed in obese women with NIDDM. Plasma galanin levels were significantly higher in groups B, C, and D (P < .001, P < .001, and P < .001, respectively). Plasma leptin concentrations were significantly higher in groups C and D as compared with the control group (P < .001 and P < .001, respectively). Plasma NPY and galanin concentrations in women with anorexia nervosa did not differ from the levels in the control group. However, plasma leptin concentrations were significantly lower in anoractic women than in the control group (P < .01). Our results indicate that inappropriate plasma concentrations of NPY, galanin, and leptin in obese women may be a consequence of their weight status, or could be one of many factors involved in the pathogenesis of obesity.     

Circulating leptin and insulin in obese patients with and without type 2 diabetes mellitus: relation to ghrelin and oxidative stress

Aim

This case control study aimed to investigate relationship between appetite hormones (ghrelin and leptin) and body mass index (BMI), insulin and oxidative stress in simple obese and type 2 diabetes (T2DM) obese patients.

Methods

Thirty healthy controls; 30 simple obese and 30 T2DM obese patients were enrolled. Demographic and clinical data of all participants were reported. Serum levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), lipid peroxide (LPO) and nitric oxide (NO) were measured by chemical methods while, insulin, leptin and ghrelin by ELISA kits.

Results

Serum levels of insulin, leptin, LPO were significantly higher while, ghrelin was significantly lower in simple obese and obese patients with diabetes versus controls. Insulin resistance was found in 76.67% simple obese and 93.33% obese patients with diabetes. Ghrelin showed a positive correlation with PBG in controls; but negative correlation with BMI in simple obese and with NO in obese patients with diabetes. Positive correlations were found between LPO and FBG, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and between leptin and FBG in obese patients with diabetes.

Conclusions

Our results suggested that hyperinsulinemia and hyperleptinemia may be most important mechanisms in decreasing ghrelin and inducing oxidative stress in simple obese and T2DM obese patients.     

Circulating leptin and insulin in obese patients with and without type 2 diabetes mellitus: Relation to ghrelin and oxidative stress

AimThis case control study aimed to investigate relationship between appetite hormones (ghrelin and leptin) and body mass index (BMI), insulin and oxidative stress in simple obese and type 2 diabetes (T2DM) obese patients.MethodsThirty healthy controls; 30 simple obese and 30 T2DM obese patients were enrolled. Demographic and clinical data of all participants were reported. Serum levels of fasting blood glucose (FBG), postprandial blood glucose (PBG), lipid peroxide (LPO) and nitric oxide (NO) were measured by chemical methods while, insulin, leptin and ghrelin by ELISA kits.ResultsSerum levels of insulin, leptin, LPO were significantly higher while, ghrelin was significantly lower in simple obese and obese patients with diabetes versus controls. Insulin resistance was found in 76.67% simple obese and 93.33% obese patients with diabetes. Ghrelin showed a positive correlation with PBG in controls; but negative correlation with BMI in simple obese and with NO in obese patients with diabetes. Positive correlations were found between LPO and FBG, insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and between leptin and FBG in obese patients with diabetes.ConclusionsOur results suggested that hyperinsulinemia and hyperleptinemia may be most important mechanisms in decreasing ghrelin and inducing oxidative stress in simple obese and T2DM obese patients.     

Rosiglitazone improves insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus

Rosiglitazone (RSG) is known to be an agonist for the peroxisome proliferator-activated receptor-γ (PPARγ) and promotes differentiation of pre-adipocytes into adipocytes. Leptin is highly correlated with adiposity, while the activation of PPARγ is known to inhibit Lep gene expression and leptin release. This study was performed to evaluate the relationship between changes in circulating leptin levels, insulin sensitivity and regional adiposity after RSG treatment. Two hundred fifty-one type 2 diabetic patients (176 men and 75 women) who had been treated with sulfonylurea and/or metformin received 4 mg of RSG daily, in addition to the previous medications. Before and after RSG treatment (average duration 5.6 ± 0.9 months), indices of insulin resistance, metabolic parameters, and serum leptin and adiponectin levels were measured. Abdominal subcutaneous fat thickness (SFT_max) and visceral fat thickness were measured by sonography. After RSG treatment, HOMA-IR index decreased significantly (2.82 ± 1.94 vs. 2.01 ± 1.58), while BMI and SFT_max increased, and leptin (4.72 ± 3.77 vs. 5.69 ± 4.30 ng/ml) and adiponectin levels (7.54 ± 10.20 vs. 12.89 ± 10.13 μg/ml) increased. The increase in serum leptin correlated with an increase in SFT_max (r = 0.511, p < 0.001) and with a reduction in HOMA-IR (r = −0.368, p < 0.001). The correlation of Δleptin with ΔHOMA-IR and with ΔSFT_max was higher in females and among insulin-resistant subjects. In conclusion, RSG improves the insulin sensitivity with increased serum leptin levels in patients with type 2 diabetes mellitus, which is related to an increase in subcutaneous adiposity.     

Eating behavior in obese patients with and without type 2 diabetes mellitus

OBJECTIVE: Aim of this study was the assessment of the prevalence of eating disorders, and of eating disorder symptoms, in obese patients with type 2 diabetes, compared to non-diabetic subjects. DESIGN: Three samples of individuals were studied: a series of 156 (76 male, 80 female) overweight and obese type 2 diabetic patients, aged 30-65 y, with a body mass index (BMI)>28 kg/m(2) (DM); a series of 192 (20 male, 172 female) obese (BMI>30 kg/m(2)) non-diabetic patients aged 30-65 y seeking treatment for weight loss (OC); and a non-clinical sample of 48 (22 male, 26 female) obese (BMI>30 kg/m(2)) subjects aged 30-65 y selected from the lists of two general practices (OP). Eating behavior was assessed using the Eating Disorder Examination (EDE 12.0D). RESULTS: The prevalence of Binge Eating Disorder was lower than 5% in all the three samples. Median EDE scores in females were significantly higher in OC (3.0) and OP (3.4) than in DM (1.7), while diabetic patients showed higher scores on Restraint than both non-diabetic samples. Among diabetic patients, a significant correlation of EDE scores with HbA(1)c was observed. CONCLUSIONS: Type 2 diabetes is unlikely to induce relevant eating disturbances in obese patients, apart from an increase in restraint. Abnormalities of eating attitudes and behavior are associated with an impairment of metabolic control.     

Plasma leptin levels are associated with coronary atherosclerosis in type 2 diabetes

Leptin signaling may promote atherothrombosis and lead to cardiovascular disease. However, whether leptin is associated with human atherosclerosis, distinct from thrombosis, is unknown. We determined the association of plasma leptin levels with coronary artery calcification (CAC), a measure of coronary atherosclerosis, in a cross-sectional study of type 2 diabetes. Leptin levels were associated with CAC after adjusting for established risk factors [odds ratio (95% confidence interval) for 5 ng/ml leptin increase: 1.31 (1.10-1.55); P = 0.002]. Leptin remained associated with CAC after further controlling for body mass index (BMI) [1.29 (1.07-1.55); P = 0.008], waist circumference [1.30 (1.09-1.57); P = 0.003], C-reactive protein (CRP) levels [1.28 (1.07-1.55); P = 0.008], and subclinical vascular disease [1.30 (1.08-1.57); P = 0.006]. Addition of BMI (P = 0.97), waist (P = 0.55), or CRP (P = 0.39) to a model with leptin failed to improve the model's explanatory power, whereas addition of leptin to a model with BMI (P = 0.029), waist (P = 0.006), or CRP (P = 0.005) improved the model significantly. Plasma leptin levels were associated with CAC in type 2 diabetes after controlling adiposity and CRP. Whether leptin signaling promotes atherosclerosis directly or represents a therapeutic target for the prevention of atherosclerotic cardiovascular disease remains to be explored.     

Plasma relaxin concentration is related to beta-cell function and insulin sensitivity in women with type 2 diabetes mellitus

The aim of the study was to assess whether HbA_1c levels reflected mean blood glucose (MBG) levels in Type 2 diabetes. Despite the good correlation between HbA_1c and MBG, one-third of the patients had consistently higher HbA_1c or lower HbA_1c levels than that expected under the hypothesis that HbA_1c is solely determined by MBG, suggesting the existence of different haemoglobin glycation phenotypes. The use of HbA_1c alone for glycemic control monitoring in these patients could be insufficient to clearly trace their risk of complications.     

2型糖尿病Leptin与胰岛素抵抗的关系

目的　研究新诊断非肥胖 2型糖尿病患者血清leptin水平与胰岛素抵抗的相关关系。方法　以空腹血浆胰岛素与血糖乘积的倒数作为胰岛素抵抗程度的指标 ,采用酶联免疫法测定 31名正常人、2 9例新诊断非肥胖 2型糖尿病患者的血清leptin水平。 结果　新诊断非肥胖 2型糖尿病患者 ,血清leptin浓度与胰岛素敏感性指数有显著负相关 (r =-0 .37,P <0 .0 5 ) ,主要表现在男性 (r =-0 .6 6 ,P <0 .0 1)。leptin与空腹血胰岛素 (r =-0 .45 ,P <0 .0 5 )、空腹血糖(r =-0 .37,P <0 .0 5 )有正相关关系。男性患者leptin血清水平比正常男性有显著性升高 (P<0 .0 5 )。结论　新诊断非肥胖 2型糖尿病患者血清leptin水平与胰岛素抵抗程度有显著正相关关系 ,leptin与 2型糖尿病的发病有关     

Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance

OBJECTIVE: Adipose tIssue regulates insulin sensitivity via the circulating adipocytokines, leptin, resistin and adiponectin. The objective of this study was to compare the levels of resistin, adiponectin and leptin in lean and obese subjects and determine the relationship between circulating adipocytokines and insulin resistance. METHODS: We examined plasma levels of resistin, adiponectin and leptin in 17 lean subjects with a mean body mass index (BMI) of approximately 23 and 34 non-diabetic obese individuals with a mean BMI approximately 33. Insulin resistance was assessed using the homeostasis model assessment ratio (HOMA-R) formula derived from fasting insulin and glucose levels. RESULTS: Resistin levels were not significantly different between the two groups but were significantly higher in women compared with men, 35.4+/-6.5 (s.e.) vs 15.4+/-2.9 microg/L, P<0.01. Resistin did not correlate with BMI but did significantly correlate with HOMA-R, P<0.01, and this correlation remained significant after adjustment for gender and BMI. Adiponectin levels were significantly lower in obese compared with lean subjects, P<0.005, and higher in women, P<0.001, but showed no significant correlation with HOMA-R. Leptin levels were significantly higher in obese subjects and women and correlated with HOMA-R and resistin. DISCUSSION: In this small group of patients we demonstrated that insulin resistance correlated most strongly with leptin levels. A significant correlation between resistin levels and insulin resistance was also observed. Although a similar trend was apparent for adiponectin, the correlation with insulin resistance did not achieve statistical significance.     

糖尿病一级亲属脂联素和瘦素与胰岛素抵抗的相关性

目的　了解2型糖尿病(T2DM)患者一级亲属非糖尿病个体中瘦素、脂联素水平的变化,研究瘦素、脂联素与胰岛素抵抗(IR)的相关性。　方法　选取 153 例糖耐量正常者,其中无家族史的正常对照(NC)者41例,单纯父亲为糖尿病的一级亲属 36 例,单纯母亲为糖尿病的一级亲属 45例,双亲均为糖尿病的一级亲属31例。测定所有受试者血脂、血糖、胰岛素、瘦素、脂联素。　结果　T2DM患者一级亲属中3个亚组瘦素水平[(11±6)μg/L、(10±5)μg/L、(11±9)μg/L]高于 NC组[(8±6)μg/L](P<0 05),胰岛素抵抗指数(IRI)[(3.0±1.4)、(2.9±1.5)、(3 3±1 5)]高于 NC组[(2.0±0.8)](P<0.05),脂联素水平[(11±6)g/L、(10±6)g/L、(12±8) g/L]低于 NC组[(17±11)g/L](P<0.05)。一级亲属各组间的代谢指标差异无统计学意义。体质指数、瘦素、腰围、腰臀比、脂联素是 IRI的独立危险因素。　结论　T2DM患者一级亲属 IR程度显著高于无家族史者。脂联素与瘦素可能联合影响T2DM患者一级亲属的 IR程度。     

The effects of a glucose load and sympathetic challenge on autonomic function in obese women with and without type 2 diabetes mellitus

This study examined the effect of glucose ingestion on cardiac autonomic function in nonobese women and obese women with and without type 2 diabetes mellitus. Heart rate variability was measured via continuous electrocardiogram, and beat-by-beat blood pressure was recorded using finger photoplethysmography (Portapres, TNO Biomedical Instrumentation, Amsterdam, The Netherlands) in a fasted state and in response to a 75-g glucose load in 42 middle-aged women (40-60 years). Upright tilt was also used as an orthostatic stress to provide a clinically relevant challenge to the cardiovascular system. Significant main effects for log-transformed (Ln) total power (TP, square milliseconds) were observed with upright tilt (P < .01) and glucose challenge (P < .05). LnTP decreased in all groups in both the fasted and fed state with upright tilt (P < .01), but glucose ingestion resulted in higher LnTP in the supine position only (P = .008). Tilt resulted in a significant main effect for low-frequency (LFnu, calculated in normalized units) and high-frequency (HFnu, calculated in normalized units) power (P < .000), whereas the glucose challenge had no effect on LFnu or HFnu power. LFnu approached significance for group differences (P = .07), such that the nonobese had lower LF power than either of the obese groups. Sympathovagal balance (LnLF/HF ratio) was affected by position (P < .000) and group (P < .05), with a lower LnLF/HF in the nonobese than in the obese women. Baroreceptor sensitivity decreased (P < .01) during upright tilt but was not changed by the glucose challenge. In conclusion, basal sympathovagal balance is higher in obese individuals with and without type 2 diabetes mellitus. Women with type 2 diabetes mellitus showed no differences in autonomic function with an orthostatic challenge or glucose load than nondiabetic, obese women. The glucose load did alter total spectral power in all of these middle-aged women but had no impact on baroreceptor sensitivity.     

The effect of metformin on leptin in obese patients with type 2 diabetes mellitus and nonalcoholic fatty liver disease

Insulin resistance is a major feature of type 2 diabetes mellitus, obesity and nonalcoholic fatty liver disease (NAFLD). Several studies pointed out the possible role of increased leptin in NAFLD in humans. The aim of this study is to determine the effect of metformin on plasma leptin levels in obese patients with type 2 diabetes mellitus and NAFLD compared with lifestyle interventions. Thirty-four obese patients with newly diagnosed type 2 diabetes mellitus were prospectively followed for 6 months. All patients had ultrasonographic evidence of NAFLD at baseline. The patients were randomized into two groups: group 1 (n = 15) followed lifestyle changes only and group 2 (n = 19) received metformin (1,700 mg/day). At the end of treatment, BMI, WHR, HbA1c, fasting glucose, leptin, HOMA-IR, alanine aminotransferase values decreased in both groups. No significant difference in the end-points was observed between two groups. Only in group 2, LDL decreased and HDL increased significantly. Liver echogenity decreased significantly at the end of study in both groups. The percentage of patients who no longer had evidence of NAFLD was not significantly different between the groups (20% of patients on lifestyle intervention vs. 16% of patients on metformin). The data demonstrate that, metformin and lifestyle interventions equally affected the plasma leptin levels, BMI and degree of NAFLD in obese patients with type 2 diabetes mellitus. In addition, the effects of metformin on the variables were not found to be mediated by leptin.     

Association of serum leptin and insulin levels among type 2 diabetes mellitus patients: A case–control study

Secretion of insulin is compromised in type 2 diabetes (T2DM) individuals and inadequate to accommodate for insulin resistance (IR) in peripheral tissue. Hyperleptinemia reflects leptin resistance, which is a key factor in the production of IR in T2DM patients, making leptin a potential biomarker for evaluating IR levels. The objective of the study was to assess the association of serum leptin and insulin levels among T2DM patients. This case-control research was carried out on T2DM patients. A total of 73 patients diagnosed with T2DM (the case group) and 40 healthy participants (control; group 3) were enrolled according to the American Diabetes Association (ADA) criteria. In the case group, T2DM patients were enrolled with metabolic syndrome (group 1, n = 38) or without metabolic syndrome (group 2, n = 35) according to the WHO criteria. Metabolic profiles of T2DM patients with or without metabolic syndrome were evaluated, and compare these two groups with healthy controls. The subjects of all groups were age- and gender-matched. Body mass index (BMI, P < .01), fasting (P = .0133) and postprandial (P < .01) blood sugar levels, % glycated hemoglobin (HbA1c, P < .01), and lipid profile (P < .01) were found significantly different and higher in group 1 as compared to groups 2 and 3. Serum leptin and insulin levels were found higher and significant in patients with metabolic syndrome (P < .01 for both). The values of serum leptin levels were 10.01 ± 2.7 ng/mL, 6.9 ± 2.4 ng/mL, and 4.11 ± 1.8 ng/mL, and those of serum insulin 120 ± 40.7 µIU/mL, 20.43 ± 5.2 µIU/mL, and 11.4 ± 2.5 µIU/mL in groups 1, 2, and 3, respectively. There was a positive linear correlation between BMI, blood sugar, HbA1c, serum cholesterol (TC), and triglycerides (TG) with serum insulin and leptin levels in the case group. An extremely significant correlation (R = 0.74, P < .001) was found in BMI and serum leptin level in the case group. Serum leptin and insulin levels have a positive association, with serum leptin being a significant predictor of IR syndrome (Evidence Level: 5; Technical Efficacy: Stage 3).     

丝胶对糖尿病大鼠胰岛细胞神经肽Y表达的影响

目的观察丝胶对2型糖尿病大鼠胰岛细胞神经肽Y(NPY)表达的影响。方法 36只雄性SD大鼠随机分为正常对照组、糖尿病模型组和丝胶治疗组,每组12只。链脲佐菌素腹腔注射建立2型糖尿病大鼠模型并给予丝胶(2.4 g/kg)灌胃。SP免疫组织化学染色法观察大鼠胰岛细胞NPY的表达。结果 NPY蛋白阳性产物位于胰岛α细胞细胞质,呈棕黄色颗粒状。糖尿病模型组大鼠胰岛α细胞NPY蛋白的表达明显高于正常对照组大鼠(P<0.01);丝胶治疗组大鼠胰岛α细胞NPY蛋白的表达明显低于糖尿病模型组大鼠(P<0.01)。结论丝胶可通过降低神经肽Y的表达保护糖尿病时胰岛细胞损伤。     

Behaviour modification in obese subjects with type 2 diabetes mellitus.

We have followed prospectively, 46 obese, type 2 diabetic patients for a 55-week period, in order to evaluate the efficiency of an educational programme based on behaviour modification to enhance weight loss and changes of other cardiovascular risk factors. No patient received pharmacological treatment during the study. At the end of the follow-up the patients obtained an average weight loss of 9.250 kg (range: 0.500-17.500 kg); the BMI was reduced from 34.2 +/- 0.8 kg/m2 to 30.6 +/- 1.1 kg/m2 (P less than 0.01); fasting serum glucose descended from 7.9 +/- 0.4 to 6.1 +/- 0.5 mM (P less than 0.05); SBP (systolic blood pressure) decreased from 145.7 +/- 3 to 126.4 +/- 5.1 mmHg (P less than 0.01); DBP (diastolic blood pressure) decreased from 83.5 +/- 2.5 to 65 +/- 2.6 mmHg (P less than 0.01); triglyceride levels were lowered from 164.5 +/- 12 to 109.7 +/- 10 mg/dl (P less than 0.01); HDL-cholesterol levels increased from 1.27 +/- 0.05 to 1.53 +/- 0.12 mM (P less than 0.01). Serum glucose 2 h after a 75 g glucose oral load decreased from 14.9 +/- 0.6 to 12.7 +/- 0.9 mM (P less than 0.05) on week 35 of follow-up. Twelve patients no longer presented a diabetic curve (8 normal oral glucose tolerance test (OGTT) curves, and 4 impaired glucose tolerance (IGT) curves). No significant changes in the parameters studied were obtained in the group of patients on conventional treatment.(ABSTRACT TRUNCATED AT 250 WORDS)