Adipocyte factors,high-sensitive C-reactive protein levels and lipoxidative stress products in overweight postmenopausal women with normal and impaired OGTT

Objective

In obese postmenopausal women we assessed leptin and adiponectin, high-sensitive C-reactive protein (hsCRP), serum lipids and lipoxidative stress products: oxidized LDL (oxLDL) and malondialdehyde (MDA), in relation to impaired glucose tolerance (IGT).

Methods

Thirty-eight overweight/obese postmenopausal women were included in the study. Eighteen with normal glucose metabolism (NGT) and twenty with IGT, as it is diagnosed by OGTT. Serum leptin, adiponectin, hsCRP and MDA were measured at time 0 and 120 min of OGTT while total-cholesterol, LDL, HDL, triglycerides, oxLDL and anti-oxLDL autoantibodies at time 0. Insulin resistance (HOMA)/sensitivity (QUICKI) indexes were estimated.

Results

In subjects with NGT, hsCRP was positively correlated with fasting leptin and HOMA, while in subjects with IGT negatively with QUICKI. In both groups, hsCRP was positively correlated with fasting insulin, body mass index and waist circumference. Fasting adiponectin was positively associated with HDL in both groups and negatively with triglycerides in subjects with NGT as well as with serum glucose levels at time 120 min of OGTT in subjects with IGT. No association was observed between oxLDL and adipokines. A significant positive association was found between oxLDL and HOMA in subjects with IGT. During OGTT there was a significant increase of leptin and MDA levels in both groups.

Conclusions

A relationship exists between obesity, insulin and sub-clinical inflammation. Leptin and lipid peroxidation are linked to hyperglycaemic state while oxLDL might be considered as a predictor of insulin resistance. Adiponectin could exert its antiatherogenic effect through HDL independently of the presence of IGT.     

Correlation between estrogens and serum adipocytokines in premenopausal and postmenopausal women

OBJECTIVE: The purpose of this study was to investigate the association between serum adipocytokines (adiponectin, resistin, leptin, and tumor necrosis factor alpha [TNF-alpha]) and endogenous estrogen (estrone and estradiol) levels in healthy premenopausal and postmenopausal women. DESIGN: This study included 53 healthy premenopausal women, 45 healthy postmenopausal women, and 10 postmenopausal women with the metabolic syndrome who were participating in general health examinations. A secondary analysis was performed on levels of adiponectin, resistin, leptin, TNF-alpha, estrone (E1), and estradiol (E2). RESULTS: After accounting for body mass index, TNF-alpha was significantly increased (1.5+/-0.1 vs 2.0+/-0.1 pg/mL, P<0.05) in healthy postmenopausal women as compared with healthy premenopausal women, whereas leptin was decreased (5.6+/-1.1 vs 4.0+/-1.1 ng/mL). Estrogen (E1 and E2) was positively correlated with leptin in only healthy premenopausal women, whereas estrogen did not correlate with any adipocytokine in healthy postmenopausal women. In the multiple regression analysis, only leptin significantly contributed to insulin resistance. Combining healthy premenopausal and postmenopausal women, E1 correlated negatively with TNF-alpha (r=-0.23, P<0.05) and positively with leptin (r=0.35, P<0.01) and did not correlate with resistin. E2 correlated negatively with TNF-alpha (r=-0.24, P<0.05) and positively with leptin (r=0.34, P<0.01); it did not correlate with adiponectin or resistin. Leptin might stimulate the increase of plasma gonadotropin-releasing hormone levels, which could result in a positive correlation with estrogen in premenopausal women but not in postmenopausal women. CONCLUSIONS: Estrogen deficiency resulted in increased TNF-alpha levels. Serum leptin levels correlated positively with estrogen levels in premenopausal women. However, the increase in obesity in postmenopausal women increased leptin, which increases insulin resistance.     

孕中期血浆脂联素水平与妊娠糖尿病相关性研究

目的探讨孕中期血浆脂联素水平与妊娠糖尿病(GDM)的相关性。方法选取305名孕妇于孕24～28周做75g口服葡萄糖耐量试验,其中218名葡萄糖耐量正常,35名确诊为GDM。空腹血样的检测指标包括血浆脂联素、血糖、胰岛素、游离脂肪酸(FFA)及血脂水平。OGTT1h、2h血样检测指标包括血糖、胰岛素水平。结果GDM孕妇孕中期血浆脂联素浓度明显低于糖耐量正常组(P=0.014);多元Logistic回归分析显示:在排除了血浆脂联素和FFA影响因素外,母亲孕前BMI和GDM仍保留着明显的相关性(P=0.017);肥胖妇女孕中期的脂联素水平明显低于非肥胖组;在正常糖耐量组,血浆脂联素水平与空腹胰岛素浓度、甘油三酯浓度、OGTT1h血糖水平、BMI(孕中期和分娩时)呈显著负相关,而与高密度脂蛋白和胆固醇浓度呈显著正相关;在GDM组,血浆脂联素水平与低密度脂蛋白浓度和新生儿出生体重显著负相关。结论孕中期低脂联素水平与GDM高风险相关。     

Adipocytokine Levels in Obese and Non-obese Subjects: an Observational Study

We evaluated the levels of some inflammatory adipocytokines in 363 obese and 365 non-obese subjects. We measured: body mass index (BMI), waist circumference (WC), fasting plasma glucose, fasting plasma insulin (FPI), homeostasis model assessment (HOMA) index, blood pressure, lipid profile, retinol binding protein-4 (RBP-4), vaspin, omentin-1, leptin, interleukin-6 (IL-6), visfatin, resistin, adiponectin (ADN), adipsin, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (Hs-CRP). We observed higher BMI, WC, FPI, HOMA index, TC, LDL-C, RBP-4, leptin, IL-6, adipsin, Hs-CRP, vaspin, resistin and TNF-α levels, and lower visfatin, and ADN levels in obese compared to non-obese subjects. Higher WC correlated with lower ADN and visfatin levels, and higher vaspin levels. Higher HOMA index correlated with higher resistin, adipsin, RBP-4, and leptin concentrations, while higher leptin levels correlated with higher TNF-α, Hs-CRP, and IL-6 concentration, and lower ADN values. We confirmed obese subjects’ predisposition to develop dysmetabolic disease and hormonal dysfunctions.     

瘦素、脂联素与妊娠期糖尿病胰岛素抵抗关系的研究

目的探讨瘦素、脂联素与妊娠期糖尿病胰岛素抵抗的关系。方法采用稳态模型评估法评估正常糖耐量孕妇（NGT）糖耐量减低孕妇（GIGT）和妊娠期糖尿病孕妇（GDM）的胰岛素抵抗指数,采用放射免疫分析方法检测其血浆瘦素、脂联素、血糖及胰岛素水平。结果 GDM组和GIGT组HOMA-IR显著高于NGT组,GDM组HOMA-IR显著高于GIGT组。血清瘦素水平由NGT组到GIGT组和GDM组呈显著增高,瘦素与空腹胰岛素、孕晚期体重指数、HOMA-IR呈显著正相关;血清脂联素由NGT组到GIGT组和GDM组呈显著下降,脂联素与空腹胰岛素、孕晚期体重指数、HOMA-IR呈显著负相关。结论瘦素、脂联素水平与GDM患者IR程度密切相关,其水平可作为预测妊娠期糖尿病胰岛素敏感性的指标,将来可能是治疗妊娠期糖尿病的新靶点。     

Abnormal glucose tolerance in Chinese women with polycystic ovary syndrome

BACKGROUND: The aims of this study were to analyse the prevalence of impaired glucose tolerance (IGT) and diabetes mellitus (NIDDM) in Chinese polycystic ovary syndrome (PCOS) patients and to assess the ability of screening tests to predict these abnormalities within this population. METHODS: A total of 102 PCOS patients were evaluated. All patients underwent oral glucose tolerance tests (OGTTs) with blood samples taken at 0, 1 and 2 h. The 2-h plasma glucose level was used to categorize subjects as having IGT or NIDDM. RESULTS: The prevalence of IGT was 20.5% and that of NIDDM was 1.9%. There was no significant relationship between BMI and 2-h plasma glucose levels. The areas under the receiver operating characteristic (ROC) curve for glucose to insulin ratio (G:I), homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI) were 0.702, 0.734 and 0.733 respectively. ROC analysis suggested a threshold value of 10.7 in G:I ratio (73.9% sensitivity and 59.5% specificity), a value of 2.14 in HOMA (73.9% sensitivity and 73.4% specificity) and a value of 0.34 in QUICKI (73.9% sensitivity and 73.4% specificity) for the prediction of abnormal glucose tolerance (IGT and NIDDM). CONCLUSIONS: Chinese women with PCOS are at increased risk of IGT and NIDDM. Even though G:I, HOMA and QUICKI are easier than OGTT, they could not replace the role of 2-h post-challenge plasma glucose level in the screening of IGT and NIDDM in PCOS women.     

Adiponectin and resistin serum levels in women with polycystic ovary syndrome during oral glucose tolerance test: a significant reciprocal correlation between adiponectin and resistin independent of insulin resistance indices

Polycystic ovary syndrome (PCOS) is associated with an increased incidence of insulin resistance (IR), obesity, and type 2 diabetes. Resistin, an adipocytokine, may represent a link between obesity, and these metabolic disorders. There is also evidence that inflammation is a hyperresistinemic state in humans, and cytokine induction of resistin may contribute to insulin resistance in endotoxemia, obesity, and other inflammatory states. In contrast, adiponectin, increases insulin sensitivity, improves glucose tolerance, inhibits inflammatory pathways, while adenovirus-expressed adiponectin reduces atherosclerotic lesions in a mouse model of atherosclerosis. We aimed to assess, in women with PCOS, whether there is a relationship between adiponectin and resistin and the indices of IR, and whether serum levels of these adipocytokines are altered by glucose-induced hyperinsulinaemia. Serum levels of resistin and adiponectin were measured at 0, 60, and 120 min during 75 g oral glucose tolerance test (OGTT), in 19 women with PCOS, age 36.3+/-11.4 years (mean+/-SD), body mass index (BMI) 29.3+/-7.7 kg/m2, and correlated with the indices of IR, such as HOMA-IR, QUICKI, and the insulin resistance index calculated from glucose and insulin levels obtained during OGTT. There was no change in resistin concentrations (7.31+/-4.58, 7.47+/-5.40, 7.22+/-5.12 pg/ml, at 0, 60, and 120 min of OGTT, respectively, P = 0.77), but there was an increase in adiponectin from 11.32+/-4.64 microg/ml at baseline to 14.78+/-7.41 microg/ml, at 120 min of OGTT (P < 0.01). The magnitude of the overall rise in adiponectin was greater from 60 to 120 min (from 12.31+/-5.72 to 14.78+/-7.41 microg/ml, P < 0.006). Neither resistin, nor adiponectin correlated with the indices of IR, lipids, or other hormonal parameters of the PCOS. There was, however, a significant negative correlation between serum resistin and adiponectin (P = 0.001). In conclusion, we observed a strong negative correlation between serum adiponectin and resistin, despite the lack of direct correlation with the indices of IR. Given the opposite effects of resistin and adiponectin on the inflammatory process, we speculate that relative proportion of adiponectin-to-resistin might potentially influence cardiometabolic risk in women with the PCOS independently of IR parameters. The observed increase in adiponectin during OGTT requires further study.     

Prevalence of diabetes and pre‐diabetes in a cohort of Italian young adults with Williams syndrome

Williams syndrome (WS) is a rare, multisystemic genomic disorder showing a high prevalence of impaired glucose metabolism in adulthood. The reason for this association is unknown, though hemizygosity for genes mapping to the WS chromosome region has been implicated. Twenty‐two Italian young adults with WS (13 females, 9 males) were studied. A 75 g oral glucose tolerance test (OGTT) was performed and β‐cell function was estimated with Homeostasis Model Assessment (HOMA)‐B%, Insulinogenic Index, and corrected insulin response whereas insulin sensitivity was assessed with HOMA‐Insulin Resistance Index, Quantitative Insulin Check Index, and composite Insulin Sensitivity Index. One patient had known diabetes mellitus (DM), whereas impaired glucose tolerance (IGT) was diagnosed in 12 patients and DM in one (63.6% prevalence of impaired glucose metabolism). IGT patients were more insulin resistant than those with normal glucose tolerance (NGT), whereas β‐cell function was unchanged or increased. Islet autoimmunity was absent. Logistic regression showed that impaired glucose metabolism was not associated with age, body mass index (BMI), or family history of DM. β‐cell function, insulin sensitivity, and post‐load insulin levels did not differ between WS patients with NGT and healthy controls comparable for gender, age, and BMI, though WS–NGT patients had higher post‐load glucose values. These data confirm the high prevalence of impaired glucose metabolism in WS young adults, thus suggesting the need for screening these patients with OGTT. IGT is associated with reduced insulin sensitivity, but not with impaired β‐cell function, islet autoimmunity, and traditional risk factors for type 2 DM. © 2013 Wiley Periodicals, Inc.     

瘦素、抵抗素、2型糖尿病间的相关性研究

目的：研究血浆瘦素与抵抗素、体重指数、腰围、腰臀比、血脂、胰岛素敏感性指数等的关系。方法：对43例新诊断2型糖尿病患者及37例糖耐量正常者，测定空腹血浆瘦素、胰岛素、血糖、血脂及抵抗素浓度。结果：相关分析显示性别、体重指数（BMI）、腰围、腰臀比、胰岛素与瘦素呈显著正相关（r分别为0.623,0.534，0.516，0.302，0.354，均P<0.01），IAI与瘦素呈显著负相关(r=-0.373,P<0.01),甘油三酯、胆固醇空腹血糖与瘦素无明显相关。瘦素与抵抗素无相关性（r=0.101,P>0.05）结论：空腹血浆瘦素水平与肥胖程度、胰岛素抵抗呈显著正相关，与抵抗素无关。瘦素可能与2型糖尿病的发病有关。     

Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome

BACKGROUND: The aim of the present study was to evaluate insulin resistance (IR), glucose tolerance status and cardiovascular risk factors in first degree relatives of patients with polycystic ovary syndrome (PCOS). METHODS: A total of 120 family members [Mothers(PCOS) (n = 40), Fathers(PCOS) (n = 38), Sisters(PCOS) (n = 25) and Brothers(PCOS) (n = 17)] of 55 patients with PCOS and 75 unrelated healthy control subjects without a family history of diabetes or PCOS (four age- and weight-matched subgroups, i.e. Control(Mothers), Control(Fathers), Control(Sisters) and Control(Brothers)) were studied. IR was assessed by homeostatic model assessment (HOMA IR), log HOMA, insulin sensivity index (ISI), the quantitative insulin sensitivity check index (QUICKI) and area under the curve for insulin during the oral glucose tolerance test (AUCI, AUCG) in with normal glucose tolerance (NGT) subjects and controls. Serum adiponectin, resistin, homocysteine and lipid levels were measured. RESULTS: The prevalence of any degree of glucose intolerance was 40% in Mothers(PCOS) and 52% in Fathers(PCOS). In total, six (15%) glucose tolerance disorders were identified in the Control(Mothers) and Control(Fathers) in first degree relatives of control subjects. The first degree relatives of PCOS patients had significantly higher serum fasting insulin, HOMA-IR, Log HOMA and AUCI levels in all subgroups than the control subjects. The control subjects had significantly elevated QUCKI, ISI levels and serum adiponectin levels compared to the first degree relatives of PCOS subjects in all subgroups. The serum Hcy and resistin levels increased significantly in both Fathers(PCOS) and Mothers(PCOS) groups but not Brothers(PCOS) and Sister(PCOS). CONCLUSION: The results of the present study support the finding that the first degree relatives of PCOS patients carry an increased risk of cardiovascular disease, as do PCOS patients.     

空腹血糖受损患者脂联素水平的临床观察

目的探讨空腹血糖受损（IFG）患者脂联素水平的变化。方法入选糖耐量正常（NGT）、孤立性空腹血糖受损（I-IFG）、孤立性糖耐量低减（I-IGT）、空腹血糖受损并糖耐量低减（IFG／IGT）、新发2型糖尿病（T2DM）各30例，采用酶联免疫吸附法（ELISA）测定血清脂联素，同时检测胰岛素水平及血糖、血脂，计算胰岛素抵抗指数（HOMA．IR）。结果I-IFG组、1-IGT组、IFG／IGT组及新发T2DM组脂联素均明显低于NGT组（P均〈0．01）；新发T2DM组和IFG／IGT组的HOMA-IR均〉I-IGT组〉I-IFG组〉NGT组，各组间差异有统计学意义（P均〈0．05或P〈0．01）；脂联素与空腹血糖（FBG）、餐后2h血糖（2HBG）及HOMA-IR呈负相关（Pa〈0．01）。结论在I-IFG阶段已存在脂联素水平降低，胰岛素抵抗增加，具有向糖尿病转化及并发大血管病变的风险，提高脂联素水平可为糖尿病及其并发症的防治提供一条新的思路。     

瘦素、脂联素、抵抗素、内肥素与妊娠糖尿病胰岛素抵抗的相关性研究

目的:探讨脂肪因子瘦素、脂联素、抵抗素、内肥素与妊娠糖尿病(GDM)胰岛素抵抗的相关性.方法:实验分为正常育龄妇女组(44例)、正常妊娠妇女组(62例)和妊娠糖尿病患者组(63例),用ELISA方法分别检测3组瘦素(Leptin),脂联素(Adiponectin),抵抗素(Resistin),内肥素(Visfatin)的水平,用葡萄糖氧化酶法检测血糖水平,免疫发光法检测胰岛素水平,用HOMA-IR(稳态模型胰岛素抵抗指数)表示胰岛素抵抗状态,HOMA-IR=空腹血糖×空腹血胰岛素÷22.5,用SPSSll.5统计软件进行统计分析.结果:妊娠糖尿病患者组的瘦素水平明显高于正常妊娠妇女组[(13.50±7.14)ng/ml、(7.78±3.82)ng/ml,P<0.001],正常妊娠妇女组明显高于正常育龄妇女组[(7.78±3.82)ng/ml、(1.73±0.70)ng/ml,P<0.001]差异具有统计学意义;GDM 组的内肥素水平明显低于正常妊娠妇女组[(15.67±5.78)ng/ml、(22.43±5.68)ng/ml,P<0.001],正常妊娠妇女组明显低于正常育龄妇女组[(22.43±5.68)ng/ml、(36.46±13.34)ng/ml,P<0.001],差异具有统计学意义;GDM 组的脂联素水平低于正常妊娠妇女组[(5 491.71±2 986.00)ns/ml、(6 692.34±2 583.51)ng/ml,P=O.029],差异有统计学意义,正常妊娠妇女组明显低于正常育龄妇女组[(6 692.34±2 583.51)ng/ml、(11 076.82±3 694.75)ng/ml,P<0.1301],差异具有统计学意义;GDM组抵抗素水平与正常妊娠妇女组比较差异没有统计学意义.在妊娠糖尿病患者组,HOMA-IR与瘦素(r=0.352,P=0.005)正相关,与内肥素(,=-0.255,P=0.046)呈负相关.结论:妊娠糖尿病患者瘦素水平升高,内肥素和脂联素水平降低,瘦素和内肥素与胰岛素抵抗有关,瘦素和内肥素参与了妊娠糖尿病胰岛素抵抗的发生发展;脂联素和抵抗素与胰岛素抵抗不具有相关性,脂联素和抵抗素可能与妊娠糖尿病胰岛素抵抗的发生无关.     

Insulin resistance and obesity-related factors in Prader-Willi syndrome: comparison with obese subjects

Prader-Willi syndrome (PWS), the most common genetic cause of marked obesity in humans, is usually due to a de novo paternally derived chromosome 15q11-q13 deletion or maternal disomy 15 [(uniparental disomy (UPD)]. Obesity is due to energy imbalance, but few studies have examined fat patterning and obesity-related factors in subjects with PWS (deletions and UPD) compared with subjects with simple obesity. We examined for differences in fatness patterning and lipid, leptin, and glucose and insulin levels in subjects with simple obesity and PWS and adjusted for gender, age, and body mass index (BMI). Fasting peripheral blood samples and cross-sectional magnetic resonance image scans at the level of the umbilicus were obtained in 55 subjects ranging in age from 10.4 to 49 years: 20 PWS deletion, 17 PWS UPD, and 18 obese controls. Subcutaneous fat area (SFA) and intra-abdominal visceral fat area (VFA) were calculated. No significant difference was seen between the PWS deletion subjects or PWS UPD subjects for fatness measurements or leptin levels. Twenty-three of 37 PWS subjects met the criteria for obesity (BMI > 95th percentile). No significant differences were observed for SFA and VFA between the PWS subjects judged to be obese and control subjects with simple obesity. There was an overall trend for decreased VFA in the PWS subjects but not significantly different. VFA was significantly positively correlated with both fasting insulin and total cholesterol in PWS deletion subjects but not in PWS UPD subjects or obese controls. Fasting insulin level was significantly lower in the obese PWS subjects compared with subjects with simple obesity, and insulin sensitivity (QUICKI) was significantly higher in PWS subjects with obesity. Homeostasis model assessment (HOMA) and QUICKI values were correlated and in opposite directions with triglycerides in the obese PWS subjects but not in the obese controls. Subjects in each group were stratified according to published criteria on the basis of their level of visceral fat (e.g. > or = 130 cm(2)) to assess the influence of VFA on metabolic abnormalities. In the obese PWS subjects, the fasting triglyceride, glucose, and insulin levels, and HOMA value were significantly elevated, while the QUICKI value was significantly lower in those with VFA > or = 130 cm(2). Such significant differences were not seen in the obese control group. Our results indicate that VFA may be regulated differently in PWS subjects compared to individuals with simple obesity. Insulin resistance is lower in PWS subjects and insulin sensitivity is higher compared with obese controls. PWS subjects with increased VFA may be at a higher risk of obesity-related complications compared to PWS subjects without increased VFA.     

内脂素、抵抗素在妊娠期糖尿病发病中的作用

目的探讨新近发现的两种脂肪细胞因子——内脂素和抵抗素,与胰岛素抵抗的关系及其在妊娠期糖尿病(GDM)发病中的作用。方法采用病例对照的研究方法,通过检测40例GDM孕妇和40例正常孕妇的血清内脂素(Visfa-tin)、抵抗素(Resistin)空腹血糖(FPG)和空腹胰岛素(FINS)水平,计算HOMA稳态模型胰岛素抵抗指数(IRI),比较两组胰岛素抵抗程度的差异,并进一步分析内脂素、抵抗素与胰岛素抵抗之间的关系及其在GDM发生过程中所起的作用。结果 (1)GDM组的血清内脂素、抵抗素、空腹血糖(FPG)、空腹胰岛素(FINS)和胰岛素抵抗指数(IRI)均明显高于对照组(P<0.01)。(2)相关分析表明:GDM孕妇的血清内脂素、抵抗素均与胰岛素抵抗指数(IRI)呈显著正相关(r=0.568,0.618,P=0.000),而内脂素与抵抗素之间亦呈密切正相关(r=0.919,P=0.000)。结论 (1)GDM孕妇的血清内脂素、抵抗素水平较正常孕妇明显增高。(2)内脂素、抵抗素均与胰岛素抵抗呈正相关。(3)血清内脂素、抵抗素水平增高以及二者对胰岛素敏感性调节所产生的综合效应是诱导妊娠期糖尿病发生或促进其发展的重要因素。     

Serum levels of ischemia modified albumin in overweight/obese postmenopausal women: a potential biomarker of atherosclerotic burden associated with oxidative stress

Objective

Menopause is associated with weight gain and an increase of cardiovascular risk. The aim of the present study was to estimate serum ischemia-modified albumin (IMA) levels in postmenopausal women and evaluate their association with body mass index (BMI) and coronary artery disease (CAD).

Methods

The study included 130 non-smoker postmenopausal women aged 43–80: 40 with BMI 26–32 kg/m² (Group A), 60 with BMI 21–25 kg/m² (Group B), and 30 with documented CAD and BMI 23–29 kg/m² (Group C). Serum IMA, albumin, hsCRP and NT-proBNP, glucose and insulin were measured. Homeostasis assessment model score (HOMA) and Quantitative insulin sensitivity index (QUICKI) were co-estimated.

Results

Serum IMA and IMA to albumin ratio were significantly elevated in Group A as compared to Group B (p < 0.001) and similar to those of Group C. hsCRP and NT-proBNP did not differ between Groups A and B while they were lower in comparison to Group C (p < 0.001). Glucose, insulin and HOMA were elevated in Group A compared to Group B (p < 0.001) while QUICKI was lower (p < 0.001). In Group A, IMA was positively correlated with BMI, hsCRP, insulin, HOMA and negatively with QUICKI. In postmenopausal women, multivariable regression analysis revealed that obesity was the strongest significant determinant of circulating IMA levels (p < 0.001) contributing, therefore, to the elevated serum IMA concentration.

Conclusions

Postmenopausal obesity is associated with elevated serum IMA possibly due to obesity associated oxidative stress. IMA measurement could provide an assessment of atherosclerotic burden in postmenopausal women. Further clinical evaluation is under investigation.     

Plasma adiponectin and insulin resistance in Korean type 2 diabetes mellitus

Insulin resistance, which implies impairment of insulin signaling in the target tissues, is a common cause of type 2 diabetes. Adipose tissue plays an important role in insulin resistance through the dysregulated production and secretion of adipose-derived proteins, including tumor necrosis factor-alpha, plasminogen activator inhibitor-1, leptin, resistin, angiotensinogen, and adiponectin. Adiponectin was estimated to be a protective adipocytokine against atherosclerosis, and also to have an anti-inflammatory effect. In this study, the relationship between fasting plasma adiponectin concentration and adiposity, body composition, insulin sensitivity (ITT, HOMAIR, QUICK), lipid profile, fasting insulin concentration were examined in Korean type 2 diabetes. The difference in the adiponectin concentrations was also examined in diabetic and non-diabetic subjects, with adjustment for gender, age and body mass index. 102 type 2 diabetics and 50 controls were examined. After a 12-h overnight fast, all subjects underwent a 75 gram oral glucose tolerance test. Baseline blood samples were drawn for the determinations of fasting plasma glucose, insulin, adiponectin, total cholesterol, triglyceride, LDL-cholesterol, and HDL-cholesterol. The body composition was estimated using a bioelectric impedance analyzer (Inbody 2.0). The insulin sensitivity was estimated using the insulin tolerance test (ITT), HOMAIR and QUICK methods. In the diabetic group, the fasting adiponectin concentrations were significantly lower in men than in women. They were negatively correlated with BMI (r=-0.453), hip circumference (r=-0.341), fasting glucose concentrations (r=-0.277) and HOMAIR (r= -0.233). In addition, they were positively correlated with systolic blood pressure (r=0.321) and HDL-cholesterol (r= 0.291). The systolic blood pressure and HDL-cholesterol were found to be independent variables, from a multiple logistic regression analysis, which influenced the adiponectin concentration. Compared with the non-diabetic group, the adiponectin concentrations were significantly lower in the diabetic group, with the exception of obese males. In conclusion, the plasma adiponectin concentrations were closely related to the insulin resistance parameters in Korean type 2 diabetic patients.     

Should we consider performing oral glucose tolerance tests more frequently in postmenopausal women for optimal screening of impaired glucose tolerance?

OBJECTIVE: To investigate an optimal screening protocol for impaired glucose tolerance (IGT) and type II or non-insulin-dependent diabetes mellitus (DM) by using fasting plasma glucose (FPG) and oral glucose tolerance test (OGTT) in postmenopausal women. DESIGN: One hundred consecutive postmenopausal women were screened with FPG determination, and then all underwent an OGTT. Basal serum lipid and insulin levels of these women were also determined. Insulin sensitivity was determined by using the homeostasis model assessment. Receiver operating characteristic analysis was performed to determine the efficacy of these variables in detecting women with IGT and DM, and optimal cutoff values were determined. RESULTS: FPG with a cutoff value of 98 mg/dL had the best combination of sensitivity (71%) and specificity (76%) for the detection of IGT and DM. Combined FPG and body mass index screening (with the optimal cutoff value of 26.5 kg/m2) improved the sensitivity to 96% but decreased the specificity to 47%. This combined screening protocol detected 94% of the women with IGT and all diabetic women. CONCLUSIONS: Given that IGT and DM are common among postmenopausal women and DM can be prevented by nonpharmacologic interventions in women with IGT, OGTT may be used more frequently among these women. Our data indicate that for optimal screening of non-insulin-dependent DM and IGT, OGTT should be considered in postmenopausal women, especially when risk factors in addition to age are present. This model may detect most of the women with IGT and almost all diabetic women.     

Impaired Secretion of Total Glucagon-like Peptide-1 in People with Impaired Fasting Glucose Combined Impaired Glucose Tolerance

Objective: We assessed the serum glucagon-like peptide-1 (GLP-1) levels for Chinese adults with pre-diabetes (PD) and newly-diagnosed diabetes mellitus (NDDM) during oral glucose tolerance test (OGTT). The relationships between total GLP-1 level and islet β cell function, insulin resistance (IR) and insulin sensitivity (IS) were also investigated.Methods: A 75g glucose OGTT was given to 531 subjects. Based on the results, they were divided into groups of normal glucose tolerance (NGT), isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT), IFG combined IGT (IFG+IGT) and NDDM. Total GLP-1 levels were measured at 0- and 2-hour during OGTT. Homeostasis model assessment of β cell function (HOMA-β), HOMA of insulin resistance (HOMA-IR), Gutt and Matsuda indexes were calculated. The relationships between GLP-1 level and β cell function, IR and IS were analyzed.Results: The levels of total fasting GLP-1 (FGLP-1), 2h GLP-1 (2hGLP-1) and 2hGLP-1 increments (∆GLP-1) following OGTT reduced significantly in IFG+IGT and NDDM groups (P<0.005). HOMA-β , HOMA-IR, Gutt and Matsuda indexes demonstrated various patterns among NGT, isolated IFG, isolated IGT, IFG+IGT and NDDM groups (P<0.05). Spearman rank correlation analysis and multivariable linear regression model suggested that some levels of correlation between GLP-1 levels, ∆GLP-1 and β cell function, IR (P<0.05).Conclusions: The total GLP-1 levels and its response to glucose load decreased significantly in IFG+IGT group, compared to isolated IFG or IGT group. They were even similar to that of NDDM group. Moreover, there were observable correlations between impaired GLP-1 secretion and β cell function, IR and IS.     

The role of adipokines as regulators of skeletal muscle fatty acid metabolism and insulin sensitivity

Several adipose-derived cytokines (adipokines) have been suggested to act as a link between accumulated fat mass and altered insulin sensitivity. Resistin and tumour necrosis factor-alpha (TNF-alpha) have been implicated in impairing insulin sensitivity in rodents; conversely, two other adipokines, leptin and adiponectin, increase insulin sensitivity in lean and obese rodents. Currently, there is considerable focus on the concept that lipid accumulation in skeletal muscle leads to the development of insulin resistance. Adiponectin and leptin have each been demonstrated to increase rates of fatty acid (FA) oxidation and decrease muscle lipid content, which may in part be the underlying mechanism to their insulin sensitizing effect. These effects on FA metabolism appear to be mediated in part through the activation of AMP-activated protein kinase. Evidence derived from animal and human studies suggests that the ability of leptin and adiponectin to stimulate FA oxidation in muscle is impaired in the obese condition. Thus, leptin and adiponectin resistance may be an initiating factor in the accumulation of intramuscular lipids, such as diacylglycerol and ceramide, and the ensuing development of insulin resistance. Lifestyle factors such as diet and exercise are able to restore the sensitivity of muscle to leptin. The actual physiological roles of resistin and TNF-alpha in altering muscle lipid metabolism are more controversial, but each has been shown to directly impair insulin signalling and consequently, insulin stimulated glucose uptake in muscle. However, the possibility that resistin and TNF-alpha reduces insulin sensitivity in muscle by directly impairing FA metabolism in this tissue leading to lipid accumulation, has been virtually unexamined. Thus, the contribution of various adipokines to the development of insulin resistance is complex and not fully understood. Finally, the effects of these adipokines on metabolism and insulin sensitivity are generally studied in isolation, making it difficult to predict the interactive effects and the net impact on insulin sensitivity.     

Adipokine signatures of subcutaneous and visceral abdominal fat in normal-weight and obese women with different metabolic profiles

IntroductionMetabolic syndrome arises from abnormal adipose function accompanied by insulin resistance. As early factors reflecting/impacting lipid storage dysfunction of adipose tissues, we sought to determine adipokine levels in subcutaneous and visceral adipose tissues (SAT and VAT).Material and methodsGene and protein expression levels of leptin, adiponectin, and resistin were analysed in SAT and VAT of normal-weight and overweight/obese women, subclassified according to insulin resistance index, triglyceride, total, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels into metabolically healthy and “at risk” groups.ResultsCompared with normal-weight women, obese women had higher serum leptin levels (p < 0.05), as well as increased leptin gene and protein expression in VAT. Conversely, expression levels of leptin were lower in SAT of obese women, and minor in the SAT of “at risk” groups of women, compared with weight-matched healthy groups. In addition, lower adiponectin levels were detected in SAT of metabolically healthy obese women (p < 0.01), and lower in SAT and VAT (p < 0.05) of “at risk” obese women compared to healthy, obese women. Significant differences in resistin levels were only observed in obese women; resistin gene expression was higher in VAT and SAT of obese, compared to normal-weight women. However, higher gene expression was not consistent with protein expression of resistin.ConclusionsLow adiponectin in both examined adipose tissues and inappropriate leptin expression levels in SAT appear to be important characteristics of obesity-related metabolic syndrome. Intriguingly, this adipokine dysregulation is primary seen in SAT, suggesting that endocrine dysfunction in this abdominal depot may be an early risk sign of metabolic syndrome.