Tumor necrosis factor system in insulin resistance in gestational diabetes

OBJECTIVE: The aim of the study was to investigate the pathophysiological role of the tumor necrosis factor (TNF) system in insulin resistance in patients with gestational diabetes (GDM) and during the course of normal pregnancy. PATIENTS AND METHODS: Thirty women with GDM (16-39 gestational weeks), 35 healthy pregnant women (15 first, nine second and 11 third trimester) and 25 healthy age-matched non-pregnant women were studied. Serum TNF-alpha, and its soluble receptors 1 and 2 (sTNFR-1 and -2) were measured. RESULTS: In non-diabetic pregnant women in the third trimester all measures were significantly higher (P<0.05 or less) than in the first trimester and in non-pregnant women (BMI 27.6 +/- 4.1 (+/- S.D.), 24.1 +/- 2.6, 22.4 +/- 2.4 kg/m(2)), serum TNF-alpha (4.6 +/- 0.6, 4.1 +/- 0.4, 4.1 +/- 0.4 ng/l), sTNFR-1 (2.7 +/- 0.9, 2.0 +/- 0.5, 2.0 +/- 0.1 microg/l), sTNFR-2 (5.6 +/- 2.6, 4.6 +/- 2.1, 3.3 +/- 0.2 microg/l), C-peptide (3.1 +/- 1.7, 1.1 +/- 0.7, 1.1 +/- 0.8 microg/l), and C-peptide:blood glucose ratio (0.6 +/- 0.2, 0.2 +/- 0.1, 0.2 +/- 0.1 microg/mmol). In GDM these measures were even higher than in any subgroup of healthy pregnant women (BMI) (33.4 +/- 6.4 kg/m(2), TNF-alpha) (6.3 +/- 0.6 microg/l), sTNFR-1 (3.0 +/- 0.5 microg/l), sTNFR-2 (10.0 +/- 6.9 microg/l, C-peptide 6.0 +/- 2.7 microg/l, C-peptide:blood glucose ratio: 1.2 +/- 0.5 microg/mmol, P<0.01). Significant (P<0.01) positive linear correlations were found in gestational diabetic and non-diabetic women between serum TNF-alpha, C-peptide levels, and BMI. In gestational diabetic women, in multivariate analysis studying the dependency of C-peptide only BMI remained significant (r(2)=0.67, P=0.01). CONCLUSIONS: Our observation emphasizes the obesity-related component of insulin resistance driven by adipocytokines, such as TNF-alpha and its receptors during the course of normal pregnancy and GDM.     

瘦素与妊娠糖尿病患者胰岛素抵抗及胎儿发育的相关性

目的 探讨瘦素及可溶性瘦素受体(sLR)在妊娠糖尿病发病及胎儿发育中的作用.方法 选取2014年1月至12月在厦门大学附属成功医院连续产检并分娩的673名孕妇为研究对象,跟踪随访至孕晚期.根据糖耐量试验结果,采用随机抽样法选取50例血糖控制良好的妊娠糖尿病患者纳入妊娠糖尿病组,根据一般资料进行匹配选取50名糖耐量试验结果阴性者纳入正常妊娠组.根据妊娠周数分为孕早期和孕晚期亚组,比较两组不同孕期血清及脐血瘦素、sLR、脂联素、抵抗素及生化指标水平,计算稳态模型评估-胰岛素抵抗指数(HOMA-IR),精确测量新生儿生长发育指标,使用多元Logistic回归分析孕早期胰岛素抵抗的危险因素,同时采用Spearman相关性分析血清瘦素与sLR、脂联素、抵抗素及生化指标水平的相关性.结果 与正常妊娠组相比,妊娠糖尿病组孕早期血清瘦素、甘油三酯、总胆固醇、低密度脂蛋白-胆固醇(LDL-C)、空腹胰岛素(FINS)、HOMA-IR明显升高(t=0.938～6.864,P均＜0.05),sLR、脂联素显著降低(t=9.237、2.216,P均＜0.05),抵抗素、高密度脂蛋白-胆固醇(HDL-C)、空腹血糖差异无统计学意义(P均＞0.05).与正常妊娠组相比,妊娠糖尿病组孕晚期血清瘦素、抵抗素、空腹血糖、FINS、甘油三酯、总胆固醇、LDL-C、HOMA-IR明显升高(t=0.429 ～ 13.787,P均＜0.05),sLR、脂联素显著降低(t=2.216、5.623,P均＜0.05),HDL-C差异无统计学意义(P＞0.05).与正常妊娠组相比,妊娠糖尿病组脐血瘦素、抵抗素明显升高(t=1.007、11.857,P均＜0.05),sLR、脂联素显著降低(t=0.201、4.558,P均＜0.05).多元Logistic回归分析显示,瘦素(OR =1.288,95％ CI:1.137 ～4.370)、抵抗素(OR=1.223,95％CI:1.035～ 1.570)、总胆固醇(OR=1.216,95％CI:1.026 ～1.823)、甘油三酯(OR=1.357,95％CI:1.008～ 3.572)、LDL-C (OR=1.634,95％ CI:1.251～3.764)是妊娠糖尿病组孕早期发生胰岛素抵抗的独立危险因素,sLR (OR =0.714,95％ CI:0.161～0.893)、脂联素(OR =0.352,95％CI:0.112 ～0.510)是妊娠糖尿病组孕早期发生胰岛素抵抗的保护性因素.妊娠糖尿病组孕晚期母体血瘦素含量与sLR、脂联素均呈负相关(r=-0.16、-1.13,P均=0.000),与抵抗素呈正相关(r=0.269,P=0.019).妊娠糖尿病组脐血瘦素含量与sLR、脂联素均呈负相关(r=-0.147、-1.250,P均=0.000),与抵抗素、体重、Ponderal 指数均呈正相关(r =0.410、0.673、0.301,P均＜0.05),与头围、身长无关(P均＞0.05).结论 瘦素及sLR与妊娠糖尿病患者胰岛素抵抗存在相关性,但与胎儿宫内生长和发育无关.     

Effects of glucose and insulin on acyl ghrelin and desacyl ghrelin, leptin, and adiponectin in pregnant women with diabetes

The aim of the study was to compare the regulation of ghrelin, leptin, and adiponectin by insulin and glucose during the second and third trimesters of pregnancy in women with diabetes. We studied 9 pregnant women with diabetes. All women were treated with insulin and omitted the morning dose on the day of the test. After collection of baseline fasting samples, we performed 3 successive glucose clamps: 2 euglycemic clamps (glucose, 5 mmol/L; insulin infusion at 20 and 40 mU m⁻² min⁻¹) and 1 hyperglycemic clamp (glucose, 10 mmol/L; insulin infusion at 40 mU m⁻² min⁻¹). We determined concentrations of acyl and desacyl ghrelin (using a double-antibody sandwich assay that recognizes the full-length molecule), leptin, and adiponectin. Fasting desacyl ghrelin concentrations decreased, whereas insulin and leptin concentrations increased, between the second and third trimesters of pregnancy (P ≤ .011). During the clamp studies, desacyl ghrelin concentrations decreased by 33% (second trimester, P = .004) and 27% (third trimester, P = .09) with increasing glucose and insulin concentrations, whereas acyl ghrelin, leptin, and adiponectin concentrations were unaffected. Glucose and insulin regulate desacyl ghrelin concentrations in pregnant women with diabetes. Impaired desacyl ghrelin regulation may affect energy metabolism in pregnant women with poorly controlled diabetes.     

Circulating levels of leptin, adiponectin, resistin, and ghrelin in inflammatory bowel disease

BACKGROUND: There is evidence that adipocytokines play an important role in metabolism and in inflammation. Because human metabolism dramatically changes in inflammatory bowel disease (IBD) and chronic inflammation is the hallmark of the disease, we studied serum levels of leptin, adiponectin, resistin, and ghrelin in patients with ulcerative colitis (UC) and Crohn's disease (CD) in comparison with healthy controls (HC). METHODS: Leptin, adiponectin, resistin, and active ghrelin serum levels were measured in 100 IBD patients (46 UC and 54 CD) and in 60 matched HC using commercially available enzyme-linked immunosorbent assays. Leptin, adiponectin, resistin, and ghrelin levels were correlated with disease activity, type, localization, and treatment. RESULTS: Mean serum leptin levels were 10.6+/-2.0 ng/mL in UC patients, 12.5+/-2.6 ng/mL in CD patients, and 15.0+/-1.8 ng/mL in HC (P=.01). Mean serum adiponectin levels were 9514.8+/-787.8 ng/mL in UC patients, 7651.1+/-613 ng/mL in CD patients, and 7270.6+/-559.4 ng/mL in HC (P=.05). Mean serum resistin levels were 21.2+/-2.2 ng/mL in UC patients, 18.7+/-1.6 ng/mL in CD patients and 11.8+/-0.6 ng/mL in HC (P=.0002). Mean serum ghrelin levels were 48.2+/-4.2 pg/mL in UC patients, 49.4+/-4.6 pg/mL in CD patients and 14.8+/-3.0 pg/mL in HC (P<.0001). Serum levels of these adipocytokines were not correlated with either C-reactive protein levels or the clinical indices of activity. No association between serum adipocytokines levels and disease localization in both UC and CD patients was found. Only serum ghrelin was significantly higher in ileal compared with colonic CD (P=.04). CONCLUSIONS: Serum levels of adiponectin, resistin, and active ghrelin are increased whereas serum levels of leptin are decreased in patients with IBD. Further studies are needed to elucidate the role of adipocytokines in IBD.     

Changes in calcium, 25(OH) vitamin D3 and other biochemical factors during pregnancy

INTRODUCTION AND AIMS: Calcium and vitamin D play major roles in calcium homeostasis and skeletal development, especially during pregnancy. This study was conducted to determine changes in calcium, 25 hydroxy [25(OH)] vitamin D3 and other biochemical factors (PTH, osteocalcin, alkaline phosphatase, magnesium, phosphorus) related to calcium homeostasis and bone turnover during pregnancy and compare the values to those of non-pregnant women. MATERIALS AND METHODS: In a cohort study, 48 pregnant women, in their first trimester of pregnancy (12+/-2.7 weeks), from 5 prenatal care centers, and 47 non-pregnant women randomly selected from the Tehran Lipid and Glucose Study (TLGS) population were enrolled. These pregnant women were followed in their second (26+/-1.9 weeks) and third trimesters (37+/-3.2 weeks) of pregnancy. Samples were drawn from June 2002 to March 2003. Including criteria were healthy women with no background of disease. Women using photo protection and calcium and vitamin D supplementation were excluded. A questionnaire was used to obtain demographic information for both groups. Venous blood samples were taken after 12-14 h of overnight fasting to measure serum calcium, phosphorus, magnesium, alkaline phosphatase, PTH, 25 (OH) vitamin D3 and serum osteocalcin levels. The repeated measures analysis of variance and t-test were used for statistical analysis. Data were matched for age and weight in both the case (in the first trimester) and control groups. RESULTS: Significant differences were found in the mean serum levels of osteocalcin and alkaline phosphatase between the three trimesters of pregnancy (p< 0.001). Osteocalcin was significantly higher in the first trimester as compared to second and third trimesters of pregnancy. Alkaline phosphatase was significantly lower in the first trimester as compared to the second and third trimesters of pregnancy and their controls. There was also a significant difference in osteocalcin in the second and third trimesters and alkaline phosphatase in the first and third trimesters of pregnancy in comparison to the control group. The mean values of osteocalcin were 12.7+/-8.5, 8.1+/-6.9, 5.6+/-5.0 and 13.9+/-7.9 ng/ml, respectively, and mean values for alkaline phosphatase were 115+/-38, 125+/-37, 174+/-61 and 134+/-35.0 Iu/l, respectively. In the first trimester, alkaline phosphatase was lower and osteocalcin was higher than in the second and third trimesters. In the first trimester of pregnancy, 20 and 40% of women had 25(OH) vitamin D3 < 10 and < 20 ng/ml, respectively, and 19% of women had serum calcium levels < 8.6 mg/dl. CONCLUSION: 60% of women in the first trimester, 48% in the second and 47% in the third trimester had either severe or moderate vitamin D deficiency. It is recommended that the importance of calcium supplements with vitamin D in pregnant women be stressed for these individuals.     

Variations in postprandial ghrelin status following ingestion of high-carbohydrate, high-fat, and high-protein meals in males

AIM: The purpose of this study was to investigate the response of postprandial acylated ghrelin to changes in macronutrient composition of meals in healthy adult males. METHODS: A randomized crossover study was performed. Ten healthy adult males were recruited. All subjects received, on separate occasions, a high-carbohydrate (HC), a high-fat (HF), and a high-protein (HP) meal. Blood samples were collected before and 15, 30, 60, 120, and 180 min following the ingestion of each meal. Plasma acylated ghrelin as well as serum insulin, glucose, and triglycerides were measured. RESULTS: The levels of acylated ghrelin fell significantly following the three meals. The HC meal induced the most significant decrease in postprandial ghrelin secretion (-15.5 +/- 2.53 pg/ml) as compared with HF (-8.4 +/- 2.17 pg/ml) and HP (-10.0 +/- 1.79 pg/ml) meals (p < 0.05). However, at 180 min, the HP meal maintained significantly lower mean ghrelin levels (29.7 +/- 3.56 pg/ml) than both HC (58.4 +/- 5.75 pg/ml) and HF (45.7 +/- 5.89 pg/ml) meals and lower levels than baseline (43.4 +/- 5.34 pg/ml) (p <0.01). The postprandial insulin levels increased to significantly higher levels following the HC meal (+80.6 +/- 11.14 microU/ml) than following both HF (37.3 +/- 4.82 microU/ml) and HP (51.4 +/- 6.00 microU/ml) meals (p < 0.001). However, at 180 min, the mean insulin levels were found to be significantly higher following the HP meal (56.4 +/- 10.80 microU/ml) as compared with both HC (30.9 +/- 4.31 microU/ml) and HF (33.7 +/- 4.42 microU/ml) meals (p < 0.05). Acylated ghrelin was also found to be negatively correlated with circulating insulin levels, across all meals. CONCLUSIONS: These results indicate that the nutrient composition of meals affects the extent of suppression of postprandial ghrelin levels and that partial substitution of dietary protein for carbohydrate or fat may promote longer-term postprandial ghrelin suppression and satiety. Our results also support the possible role of insulin in meal-induced ghrelin suppression.     

Relative hypoleptinaemia in women with mild gestational diabetes mellitus.

AIMS: There is increasing evidence suggesting that leptin plays a major role in the regulation of energy homeostasis, as well as in the neuroendocrine and reproductive systems. Leptin is synthesized in the human placenta. The aim of this study was to relate serum leptin levels during pregnancy to glucose tolerance, body mass index (BMI) and specific metabolic variables, such as specific insulin and proinsulin. METHODS: A 2-h 75 g oral glucose tolerance test was performed in 221 pregnant women at 22-29 weeks of gestation (median 25th week). Serum leptin was measured using a radioimmunoassay. In 49 women, sequential leptin measurements were performed (during pregnancy and post partum (median 5 months)). RESULTS: During pregnancy serum leptin was significantly related to body weight (r = 0.49), BMI (r = 0.51), fasting immunoreactive insulin (r = 0.46), specific insulin (r = 0.43) and proinsulin (r = 0.29) (all P-values <0.0001). In women with mild gestational diabetes (GDM, n = 55), leptin levels were lower compared to women with normal glucose tolerance (n = 166) after adjusting for BMI and fasting insulin (26.9 vs. 19.4 ng/ml, P = 0.0001). Leptin was significantly higher during pregnancy compared to post partum (mean +/- SE: 24.3+/-1.5 vs. 19.6+/-1.6 ng/ml, P = 0.0003), even after adjustment for changes in BMI and changes in fasting insulin (P = 0.013). CONCLUSIONS: Leptin levels are elevated in pregnancy. Women with mild GDM presented with relative hypoleptinaemia compared to women with normal glucose tolerance.     

Correlation of maternal serum fetuin/alpha2-HS-glycoprotein concentration with maternal insulin resistance and anthropometric parameters of neonates in normal pregnancy and gestational diabetes

OBJECTIVE: Human fetuin/alpha(2)-HS-glycoprotein (AHSG) is a 49 kDa serum and tissue protein which is a natural inhibitor of insulin receptor signaling. We investigated serum AHSG levels during pregnancy and whether the protein is involved in insulin resistance observed in healthy pregnant women and patients with gestational diabetes. DESIGN: One hundred and four healthy pregnant women and 23 of their neonates, 30 patients with gestational diabetes and their neonates and 30 healthy age-matched non-pregnant females as a control group were investigated in a case-control cross-sectional study. METHODS: Serum AHSG was determined by radial immunodiffusion. RESULTS: We observed an increase of serum AHSG concentration in the second and third trimesters. Gestational diabetes patients had significantly higher AHSG levels than healthy pregnant women and non-pregnant controls. There was a highly significant positive correlation between serum AHSG concentration and indirect parameters of insulin resistance, i.e. tumor necrosis factor-alpha (TNF-alpha), leptin, C-peptide and C-peptide/blood glucose ratio. There was also a negative correlation between maternal AHSG, TNF-alpha, leptin levels and head circumference, body length and body weight of newborns. CONCLUSION: AHSG, TNF-alpha and leptin may contribute to insulin resistance during normal pregnancy and gestational diabetes. AHSG along with these cytokines may also negatively regulate neonatal skeletal development.     

Relationship between adiponectin levels, acylated ghrelin levels, and short-term body mass index changes in children with diabetes mellitus type 1 at diagnosis and after insulin therapy

OBJECTIVE: To determine the effect of the initial metabolic imbalance and its restoration after insulin therapy on adiponectin and acylated ghrelin levels in children with type 1 diabetes mellitus (T1DM). Study design: Twenty prepubertal children with newly diagnosed T1DM were prospectively studied at diagnosis and after 1 and 4 months of therapy. Body mass index (BMI) and serum levels of adiponectin, resistin, total and acylated ghrelin, leptin, tumor necrosis factor alpha (TNF-alpha), and interleukin-6 (IL-6) were determined. The control group comprised 40 healthy prepubertal children. RESULTS: BMI was decreased at diagnosis, normalized at 1 month, and remained so thereafter. Adiponectin levels at diagnosis were similar to controls, increasing significantly after 1 month and normalizing at 4 months. Acylated ghrelin levels were lower at diagnosis, with a significant increase at 1 month and normalizing at 4 months. Resistin levels were normal at all time points. Leptin levels were decreased, while TNF-alpha and IL-6 were increased at diagnosis and normalized at 1 month. CONCLUSIONS: These findings suggest that BMI is not the main predictor of acylated ghrelin or adiponectin levels in newly diagnosed T1DM subjects and that these peptides may play an important role in the metabolic adaptation in this disease.     

The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men

OBJECTIVE: Body weight is a significant predictor of bone mass. Hormonal factors such as sex hormones, insulin, leptin and adiponectin are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. However, contradictory results have been reported for the association between serum adipocytokines and bone mineral density (BMD). We therefore examined whether the serum adipocytokine and ghrelin levels, markers of fat metabolism, are associated with BMD in male adults. PATIENTS AND MEASUREMENTS: For 80 male adults (average age 54.5 +/- 6.4 years; average body mass index (BMI) 24.4 +/- 2.5 kg/m2), the correlations between serum resistin, leptin, adiponectin and ghrelin levels with BMD were investigated. RESULTS: Among the adipocytokines, serum resistin levels were negatively correlated with lumbar spine BMD (r = -0.237, P = 0.05). After adjustment was made for age and BMI, log-transformed serum leptin showed a significant negative correlation with lumbar spine BMD, which was not seen on bivariate analysis (r = -0.237, P = 0.039). Femoral neck BMD was marginally associated only with serum adiponectin levels (r = -0.226, P = 0.062). In multiple regression analyses, among the adipokines, only resistin was a significant determinant of lumbar spine BMD, although the variance was small (R2 = 0.256). Serum ghrelin levels were not correlated with the BMD of either body site. CONCLUSIONS: Serum resistin level showed a significant negative correlation with lumbar spine BMD, although the variance was small. Further studies are needed to elucidate the role of adipocytokines in bone metabolism.     

Ghrelin and its relationship to growth hormones during normal pregnancy

OBJECTIVE: Ghrelin and GH secretagogue receptors have been found in reproductive organs, including the placenta. The physiology of ghrelin in pregnancy has not been explored. In human pregnancy, pituitary GH is gradually replaced by placental GH (PGH). The present study was undertaken to examine serum ghrelin levels during normal pregnancy and to determine to what extent changes in ghrelin levels coincide with changes in serum levels of free and total GH and PGH. Design Prospective study with blood sampling from pregnant women in gestational weeks 8, 18, 26 and 36 and postpartum. PATIENTS: Eleven nondiabetic pregnant women with singleton pregnancies. MEASUREMENTS: Serum ghrelin was determined using an in-house radioimmunoassay. Serum PGH was determined in a solid-phase immunoradiometric assay, serum GH and insulin in a time-resolved immunofluorometric assay, and serum GHBP in an in-house immunofunctional assay. RESULTS: Serum ghrelin levels peaked in week 18 (1.20 +/- 0.09 microg/l) and the lowest levels were observed in late third trimester (0.87 +/- 0.06 microg/l), corresponding to a mean decrease of 27.7% (P < 0.001) from peak levels. An increase was observed again postpartum. Serum GH diminished throughout pregnancy to low third-trimester values (0.12 +/- 0.03 microg/l; P < 0.001), and PGH increased to 25.7 +/- 2.86 microg/l (P < 0.001) in week 36. Neither total nor calculated free levels of growth hormones correlated to ghrelin levels, and no significant correlations were observed between ghrelin and maternal body mass index (BMI) or fasting insulin levels. CONCLUSIONS: Serum ghrelin levels peak around mid-gestation in human pregnancy. Ghrelin levels during pregnancy are at their lowest in the third trimester at a time of increased body weight, development of insulin resistance and high serum levels of PGH. However, no associations were observed between ghrelin and the two growth hormones.     

Pitavastatin improves serum resistin levels in patients with hypercholesterolemia

AIM: Resistin in serum is associated with high risk in patients with atherosclerosis. This clinical study aimed to investigate whether pitavastatin can regulate the serum level of resistin, together with levels of other inflammatory cytokines and adipocytokines. METHODS: Forty two outpatients (mean age 65.2 +/- 12.6 yr, M/F: 21/21) with hypercholesterolemia were administered 2 mg of pitavastatin and serum levels of resistin, together with serum levels of adiponectin, leptin, TNF-alpha and hsCRP, were measured before, and 12 weeks after enrollment. RESULTS: There was no significant gender-related difference in initial serum resistin levels. Pitavastatin significantly decreased LDL-cholesterol after 12 weeks. Initial levels of resistin showed a significant correlation with those of hsCRP (r=0.38, p=0.013), but not TNF-alpha or HOMA-R. Serum resistin, but not adiponectin and leptin, levels were significantly decreased, dropping from 17.1 +/- 9.9 ng/ dL to 15.2+/-10.0 (p=0.001) after 12 weeks of administration. The patient group with a baseline hsCRP > or = 0.1 at enrollment (n=17) had decreased levels of both resistin and hsCRP (p=0.011 and p=0.022, respectively). CONCLUSION: This study showed the pleiotropic effect of pitavastatin on the serum resistin concentration, suggesting that it may assist in the prevention of atherosclerosis.     

Rosiglitazone treatment increases plasma levels of adiponectin and decreases levels of resistin in overweight women with PCOS: a randomized placebo-controlled study

OBJECTIVE: Abdominal obesity, insulin resistance and compensatory hyperinsulinaemia play a central role in the pathogenesis of the polycystic ovary syndrome (PCOS). Abdominal adipose tissue is a source of adipokines, such as adiponectin and resistin, both of which may be involved in the development of insulin resistance and chronic inflammation in PCOS. Ghrelin, an important regulatory peptide of food intake, may also play a role in metabolic disturbances related to PCOS. The aim of this study was to examine the effects of 4 months of treatment with the insulin sensitizer rosiglitazone on plasma adiponectin, resistin and ghrelin levels in overweight women with PCOS. DESIGN: A randomised placebo-controlled study. METHODS: Thirty overweight/obese women with PCOS (body mass index>25 kg/m(2), mean age 29.1+/- 1.2 (S.E.M.) years) were randomly allocated to either rosiglitazone (Avandia, 4 mg twice a day) or placebo treatment. Plasma levels of adiponectin, resistin and ghrelin and their correlation to serum levels of insulin, C-peptide and steroid hormones, and insulin sensitivity (euglycaemic hyperinsulinaemic clamp) were assessed. RESULTS: Adiponectin and ghrelin levels correlated significantly with most metabolic markers of insulin resistance and with serum levels of DHEA and 17-hydroxyprogesterone. Plasma levels of adiponectin increased from 9.26+/-0.90 (S.E.M.) to 22.22+/-3.66 microg/ml (P<0.001) and those of resistin decreased from 12.57+/-1.63 to 9.21+/-0.53 ng/ml (P=0.009) at 4 months of treatment, but plasma ghrelin levels did not change. CONCLUSIONS: Rosiglitazone had beneficial effects on serum levels of adiponectin and resistin, suggesting that these adipocytokines may contribute to the improvement in insulin sensitivity observed during the treatment.     

慢性阻塞性肺疾病患者血清抵抗素和瘦素水平及其与营养状况的关系

目的探讨慢性阻塞性肺疾病(COPD)患者血清抵抗素、瘦素水平及其与营养状况的关系。方法用酶联免疫吸附测定(ELISA)和放射免疫法检测57例稳定期COPD患者和31名健康对照者血清抵抗素、瘦素水平,分析相关因素。结果COPD患者血清抵抗素、瘦素水平[(2·1±1·2)、(0·65±0·41)μg/L]与对照组[(3·6±2·3)、(1·03±0·71)μg/L]比较差异均有统计学意义(P均<0·01)。COPD营养不良患者抵抗素、瘦素水平[(1·7±0·7)、(0·43±0·16)μg/L]显著低于非营养不良患者[(2·2±1·2)、(0·73±0·48)μg/L,P均<0·05]。COPD患者抵抗素与瘦素、第一秒用力呼气容积(FEV1)及FEV1/用力肺活量(FVC)显著正相关(r=0.426~0.531,P均<0·01),瘦素与体重指数(BMI)、胸围、腹围、抵抗素及FEV1/FVC显著正相关(r=0.371~0.580,P均<0·01)。结论COPD稳定期患者血清抵抗素、瘦素水平下降,合并营养不良时下降更显著。     

Resistin levels in human immunodeficiency virus-infected patients with lipoatrophy decrease in response to rosiglitazone

Resistin is a recently recognized adipocytokine thought to contribute to insulin resistance. We determined resistin levels and metabolic parameters in 24 HIV-infected men and women with lipoatrophy and hyperinsulinemia and studied the effect of 12 wk of the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone (4-8 mg/d) on resistin in these subjects. Participants completed metabolic testing before and after rosiglitazone including fasting determination of resistin, adiponectin, and leptin levels, serum inflammatory markers, and hyperinsulinemic euglycemic clamp testing. Resistin concentration decreased significantly after rosiglitazone (12.17 +/- 1.15 ng/ml to 10.23 +/- 1.05 ng/ml; P = 0.02), in conjunction with significant increases in adiponectin- (P < 0.001) and insulin- stimulated glucose disposal (P = 0.004). Leptin levels, as well as TNF-alpha, did not change with rosiglitazone. In summary, among HIV-infected subjects with insulin resistance and lipoatrophy, resistin levels decreased significantly after rosiglitazone. Further investigation into the physiological role of this peroxisome proliferator-activated receptor-gamma-responsive adipocytokine in the metabolic abnormalities associated with HIV is warranted.     

Serum amylase and lipase activities in normal pregnancy: a prospective case-control study

OBJECTIVE: The diagnosis of acute pancreatitis during pregnancy is usually based on the association of upper abdominal pain, nausea or vomiting, and elevated serum amylase or lipase activities. The changes in these enzymatic activities have not been clearly established during normal pregnancy. The aim of this study was therefore to evaluate serum amylase and lipase activities in healthy pregnant women. METHODS: Serum amylase and lipase activities were measured in 103 pregnant women (first trimester, n = 34; second trimester, n = 36; third trimester, n = 33) and in 103 nonpregnant women matched for age and not receiving oral contraception. RESULTS: Serum amylase activity was similar in pregnant women and nonpregnant women during all trimesters of pregnancy. Serum lipase activity was significantly lower during the first trimester of pregnancy compared to nonpregnant women (48.6+/-27.6 vs 59.2+/-29.3 IU/L, p < 0.05) and compared to the third trimester (48.6+/-27.6 vs 76.3+/-35.8 IU/L, p < 0.001). Serum lipase activity was not statistically different between pregnant and nonpregnant women during the second and third trimesters. CONCLUSION: An increase in serum amylase and lipase activities during pregnancy should be taken into account, as in nonpregnant women.     

Do adiponectin,TNFα, leptin and CRP relate to insulin resistance in pregnancy? Studies in women with and without gestational diabetes,during and after pregnancy

BACKGROUND: The role of adiponectin, tumour necrosis factor alpha (TNFalpha), leptin and C-reactive protein in the insulin resistance of pregnancy is not clear. We measured their levels in women with gestational diabetes (GDM) and in controls, during and after pregnancy, and related them to insulin secretion and action. METHODS: Nineteen women with GDM and 19 BMI-matched healthy pregnant women underwent intravenous glucose tolerance tests in the third trimester of pregnancy and 4 months postpartum to determine insulin sensitivity (SI) and insulin secretion. Adiponectin, TNFalpha, leptin and high sensitivity CRP (hsCRP) were measured in fasted blood. RESULTS: Of the circulating factors, only leptin (r = -0.41, p = 0.01) correlated with SI in pregnancy. Leptin and hsCRP levels were elevated in pregnancy compared to postpartum (leptin (mean +/- SEM): 27.8 +/- 2.4 vs 19.3 +/- 2.1 ng/mL, p < 0.001; hsCRP: 5.2 +/- 0.7 vs 3.2 +/- 0.6 mg/L, p < 0.001). Adiponectin levels did not change from pregnancy to postpartum, despite a marked increase in SI. All four factors correlated with SI postpartum (adiponectin: r = 0.38, p = 0.01; TNFalpha: r = -0.48, p = 0.002; Leptin: r = -0.61, p = 0.001; hsCRP: r = -0.48, p = 0.002). TNFalpha correlated inversely with insulin secretion in pregnancy (r = -0.35, p = 0.03) and was significantly higher in the GDM group (2.62 +/- 0.3 vs 1.88 +/- 0.3 pg/mL, p = 0.01) in pregnancy. CONCLUSION: In our study, the influence of adiponectin, TNFalpha and hsCRP upon SI is overwhelmed by other factors in pregnancy. While leptin and SI correlated in pregnancy, it is unclear whether this represents cause or effect. Finally, TNFalpha may exert an inhibitory effect on insulin secretion in GDM, contributing to the associated hyperglycaemia.     

Factors affecting the serum levels of adipokines in Korean male patients with nonalcoholic fatty liver disease

BACKGROUND/AIMS: Adipokines are associated with various metabolic disorders including insulin resistance, obesity, and dyslipidemia. Metabolic disorders have also been reported to be associated with nonalcoholic fatty liver disease (NAFLD). The aim of this study was to determine the relationship between the serum adipokine levels and the degrees of hepatic fat infiltration in NAFLD. This study also attempted to determine the independent factors influencing the serum adipokine levels in NAFLD. METHODOLOGY: Sixty-five Korean male patients were enrolled in this study. The degree of hepatic fat infiltration was classified into the following three groups according to the ultrasonographic findings: Group I, normal liver; Group II, mild fatty liver; and Group III, moderate to severe fatty liver. The anthropometric parameters, fasting serum adipokine levels including leptin, adiponectin and resistin were measured in all subjects. The level of insulin resistance was estimated using the HOMA-IR. RESULTS: The serum leptin levels increased with increasing degree of hepatic fat infiltration (mean +/- SD: Group I, 2.052 +/- 1.071; Group II, 2.879 +/- 1.016; and Group III, 4.457 +/- 1.965 ng/mL, P < 0.001). However, the serum adiponectin and resistin levels were similar. The fasting serum insulin level was only a related factor for the changes in the serum leptin levels (P = 0.004). There were no related factors for the change in the serum adiponectin and resistin levels. CONCLUSIONS: This study suggests an indirect role for leptin in the pathogenesis of NAFLD by inducing insulin resistance, resulting in increased fasting serum insulin level.     

Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor,free leptin index,adiponectin, and resistin concentrations in healthy humans

The adipocyte-derived hormones leptin [which circulates in a free form and bound to a soluble leptin receptor (sOB-R)], adiponectin, and resistin play a key role in regulating energy homeostasis and metabolism. We assessed the association between body composition, total energy, and macronutrient intake and serum leptin, sOB-R, free leptin index, adiponectin, and resistin concentrations in 61 female and 53 male consecutively enrolled healthy Greek students. In this cross-sectional study, total energy and macronutrient intake were determined using 3-d food records. Body composition was assessed by bioelectrical impedance analysis; fasting blood samples were taken for the measurement of total leptin, sOB-R, adiponectin, and resistin; and the ratio leptin/sOB-R was used as an index of free leptin. Serum sOB-R concentrations were lower in the female subjects compared with the males (27.24 +/- 29.06 vs. 50.14 +/- 39.74 ng/ml, P < 0.001), whereas leptin, adiponectin, and resistin concentrations were significantly higher in females (leptin: 9.93 +/- 6.01 vs. 3.27 +/- 2.54 ng/ml, P < 0.001; adiponectin: 11.40 +/- 6.73 micro g/ml vs. 4.90 +/- 2.79 micro g/ml; P < 0.001; resistin: 16.86 +/- 5.39 ng/ml in females vs. 14.00 +/- 7.16 ng/ml in males, P < 0.02). Simple regression analysis showed that, in both genders, leptin, free leptin index, adiponectin, and resistin correlated positively with body fat mass and negatively with waist to hip ratio. sOB-R correlated negatively with body fat mass and positively with waist to hip ratio. Multiple regression analysis models controlling for gender, body fat, and total energy intake demonstrated that sOB-R is positively associated with energy intake from carbohydrates and negatively with energy intake from dietary fat, whereas free leptin index is negatively associated with energy intake from carbohydrates and positively with energy intake from dietary fat. No statistically significant correlations were observed between serum adiponectin or resistin concentrations and total energy or macronutrient intake. Thus, total energy intake and macronutrient composition of the diet are associated with sOB-R and free leptin index but do not play a role of comparable significance in predicting adiponectin and resistin concentrations in healthy young subjects.     

Ethnic differences in C-peptide/insulin/glucose dynamics in young pregnant women

There are ethnic differences in insulin secretion and resistance in healthy nondiabetic adults, children, and adolescents. It is not known whether these ethnic differences are also detectable during normal pregnancy. The objective of this study was to examine whether ethnic differences in glucose homeostasis (C-peptide/insulin/glucose dynamics) are present in nondiabetic pregnant women. Fasting serum C-peptide, insulin, and plasma glucose were measured in the second and third trimesters in 773 pregnant women (343 African-Americans, 312 Hispanics, and 118 Caucasians), and a 50-g oral glucose challenge test was performed in the third trimester. Significantly reduced C-peptide levels and C-peptide to insulin ratio and elevated fasting insulin to glucose ratios were observed in African-American women compared with Caucasians and/or Hispanics. Similar results were found after a 50-g glucose load. In addition, African-Americans had greater insulin and lower glucose levels at glucose challenge test. There were ethnic differences in insulin production and resistance in both fasting and glucose-stimulated conditions in normal young nondiabetic pregnant women.