Elevated Plasma SPARC Levels Are Associated with Insulin Resistance,Dyslipidemia, and Inflammation in Gestational Diabetes Mellitus

Objective

Recent studies suggested that secreted protein acidic and rich in cysteine (SPARC), a novel adipokine, is a key player in the pathology of obesity and type 2 diabetes. We aimed to determine whether concentrations of SPARC were altered in patients with gestational diabetes mellitus (GDM) compared to normal glucose tolerance (NGT) controls and to investigate the relationships between SPARC and metabolic parameters in pregnant women.

Design/Methods

Cross-sectional study of 120 pregnant women with GDM and 60 controls with NGT, in a university hospital setting. Plasma levels of SPARC, adiponectin, fibroblast growth factor 21 (FGF21), insulin and proinsulin were determined by ELISA.

Results

GDM women had higher SPARC and lower adiponectin than NGT subjects; no difference was found in FGF21. SPARC levels were the lowest in subjects in the third tertile of insulin sensitivity index (ISI_OGTT) and correlated positively with pre-pregnant BMI, insulin and 3 h glucose during 100-g OGTT, HOMA-IR, fasting proinsulin, hsCRP and white blood cells count, and negatively with ISI_OGTT, when adjusting for gestational age. Triglyceride (TG), Apolipoprotein A1, apolipoprotein B and lipoprotein (a) correlated with SPARC in partial Pearson correlation. Correlations between SPARC with adiponectin, systolic blood pressure and TG were marginally significant in partial Spearman correlation analysis. In multivariate regression analysis, SPARC was an independent negative indicator of ISI_OGTT.

Conclusions

SPARC levels are correlated significantly with inflammation and may also be correlated with dyslipidemia and represent an independent determinant of insulin resistance in late pregnancy, indicating a potential role of SPARC in the pathophysiology of GDM.     

Insulin Dynamics in Young Women with Polycystic Ovary Syndrome and Normal Glucose Tolerance across Categories of Body Mass Index

Background

Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls.

Research Design and Methods

Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method).

Results

Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons).

Conclusion

Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls.     

Lower Cerebrospinal Fluid/Plasma Fibroblast Growth Factor 21 (FGF21) Ratios and Placental FGF21 Production in Gestational Diabetes

Objectives

Circulating Fibroblast Growth Factor 21 (FGF21) levels are increased in insulin resistant states such as obesity, type 2 diabetes mellitus and gestational diabetes mellitus (GDM). In addition, GDM is associated with serious maternal and fetal complications. We sought to study human cerebrospinal fluid (CSF) and corresponding circulating FGF21 levels in women with gestational diabetes mellitus (GDM) and in age and BMI matched control subjects. We also assessed FGF21 secretion from GDM and control human placental explants.

Design

CSF and corresponding plasma FGF21 levels of 24 women were measured by ELISA [12 GDM (age: 26–47 years, BMI: 24.3–36.3 kg/m²) and 12 controls (age: 22–40 years, BMI: 30.1–37.0 kg/m²)]. FGF21 levels in conditioned media were secretion from GDM and control human placental explants were also measured by ELISA.

Results

Glucose, HOMA-IR and circulating NEFA levels were significantly higher in women with GDM compared to control subjects. Plasma FGF21 levels were significantly higher in women with GDM compared to control subjects [234.3 (150.2–352.7) vs. 115.5 (60.5–188.7) pg/ml; P<0.05]. However, there was no significant difference in CSF FGF21 levels in women with GDM compared to control subjects. Interestingly, CSF/Plasma FGF21 ratio was significantly lower in women with GDM compared to control subjects [0.4 (0.3–0.6) vs. 0.8 (0.5–1.6); P<0.05]. FGF21 secretion into conditioned media was significantly lower in human placental explants from women with GDM compared to control subjects (P<0.05).

Conclusions

The central actions of FGF21 in GDM subjects maybe pivotal in the pathogenesis of insulin resistance in GDM subjects. The significance of FGF21 produced by the placenta remains uncharted and maybe crucial in our understanding of the patho-physiology of GDM and its associated maternal and fetal complications. Future research should seek to elucidate these points.     

Circulating fibroblast growth factor 21 levels are closely associated with hepatic fat content: a cross-sectional study

Background and Aims

Fibroblasts growth factor 21 (FGF21), a liver-secreted endocrine factor involved in regulating glucose and lipid metabolism, has been shown to be elevated in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to evaluate the quantitative correlation between serum FGF21 level and hepatic fat content.

Methods

A total of 138 subjects (72 male and 66 female) aged from 18 to 65 years with abnormal glucose metabolism and B-ultrasonography diagnosed fatty liver were enrolled in the study. Serum FGF21 levels were determined by an in-house chemiluminescence immunoassay and hepatic fat contents were measured by proton magnetic resonance spectroscopy.

Results

Serum FGF21 increased progressively with the increase of hepatic fat content, but when hepatic fat content increased to the fourth quartile, FGF21 tended to decline. Serum FGF21 concentrations were positively correlated with hepatic fat content especially in subjects with mild/moderate hepatic steatosis (r = 0.276, p = 0.009). Within the range of hepatic steatosis from the first to third quartile, FGF21 was superior to any other traditional clinical markers including ALT to reflect hepatic fat content. When the patients with severe hepatic steatosis (the fourth quartile) were included, the quantitative correlation between FGF21 and hepatic fat content was weakened.

Conclusions

Serum FGF21 was a potential biomarker to reflect the hepatic fat content in patients with mild or moderate NAFLD. In severe NAFLD patients, FGF21 concentration might decrease due to liver inflammation or injury.     

Serum Levels of Fibroblast Growth Factor 19 Are Inversely Associated with Coronary Artery Disease in Chinese Individuals

Background

The fibroblast growth factor 19 (FGF19) has been implicated in recent studies as a potential regulator of glucose and lipid metabolism, which may lead to atherosclerosis. Here, we investigated the association of FGF19 with the presence and severity of coronary artery disease (CAD) in a Chinese population.

Methods

A total of 315 patients with suspected or established CAD, including 205 males and 110 postmenopausal females, were enrolled and assessed by coronary angiography. CAD severity was determined by the Gensini score. Serum FGF19 was measured by quantitative sandwich ELISA.

Results

FGF19 levels were not significantly different between male and female patients (median [interquartile range], 143.40 [87.96–250.80] vs. 141.60 [87.13–226.32] pg/mL, P = 0.773). CAD patients had lower levels of FGF19 than those without CAD (128.20 [80.62–226.58] vs. 188.00 [105.10–284.70] pg/mL, P = 0.007). FGF19 was negatively correlated with 2hPG (r = –0.150, P = 0.008), FINS (r = –0.169, P = 0.004), HOMA-IR (r = –0.171, P = 0.004), and the Gensini score (r = –0.141, P = 0.012), but positively correlated with HDL-c (r = 0.116, P = 0.041) and adiponectin (r = 0.128, P = 0.024). Moreover, FGF19 was found to be independently correlated with 2hPG (β = –0.146, P = 0.022) and adiponectin (β = 0.154, P = 0.016). After adjusting for other CAD risk factors, FGF19 was demonstrated to be an independent factor for Gensini score (β = –0.140, P = 0.019) and the presence of CAD (β = –1.248, P = 0.036).

Conclusions

Serum FGF19 is associated with the presence and severity of CAD in a Chinese population.     

Higher Fetal Insulin Resistance in Chinese Pregnant Women with Gestational Diabetes Mellitus and Correlation with Maternal Insulin Resistance

Objective

The aim of this study was to determine the effect of gestational diabetes mellitus (GDM) on fetal insulin resistance or β-cell function in Chinese pregnant women with GDM.

Measurements

Maternal fasting blood and venous cord blood samples (reflecting fetal condition) were collected in 65 well-controlled Chinese GDM mothers (only given dietary intervention) and 83 control subjects. The insulin, glucose and proinsulin concentrations of both maternal and cord blood samples were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) and the proinsulin-to-insulin ratios (an indicator of fetal β-cell function) were calculated in maternal and cord blood respectively.

Results

Both maternal and fetal levels of insulin, proinsulin and HOMA-IR but not proinsulin-to-insulin ratios were significantly higher in the GDM group than in the control group (maternal insulin, 24.8 vs. 15.4 µU/mL, P = 0.004, proinsulin, 23.3 vs. 16.2 pmol/L, P = 0.005, and HOMA-IR, 5.5 vs. 3.5, P = 0.041, respectively; fetal: insulin, 15.1 vs. 7.9 µU/mL, P<0.001, proinsulin, 25.8 vs. 15.1 pmol/L, P = 0.015, and HOMA-IR, 2.8 vs. 1.4, P = 0.017, respectively). Fetal HOMA-IR but not proinsulin-to-insulin ratios was significantly correlated to maternal HOMA-IR (r = 0.307, P = 0.019), in the pregnant women with GDM.

Conclusions

Fetal insulin resistance was higher in Chinese pregnant women with GDM than control subjects, and correlated with maternal insulin resistance.     

Serum Liver Fatty Acid Binding Protein Levels Correlate Positively with Obesity and Insulin Resistance in Chinese Young Adults

Background

Liver fatty acid–binding protein (FABP1) plays an inconclusive role in adiposity. We investigated the association of serum FABP1 levels with obesity and insulin resistance in Chinese young people under 30 years old.

Methodology and Principal Findings

Cross-sectional analysis including 200 obese and 172 normal-weight subjects matched for age and sex, anthropometric measurements were performed and serum FABP1 and biochemical characteristics were measured. Insulin resistance was determined by homeostasis model assessment of insulin resistance (HOMA-IR) and by the insulin sensitivity index (S_i) derived from Bergman’s minimal model. FABP1 levels in obese subjects were significantly higher than those in normal-weight subjects (p<0.001) and the significance remained after adjustment for age, gender, alanine and aspartate aminotransferases (p<0.001). Serum FABP1 levels were significantly correlated with many metabolic-related parameters, with BMI and triglycerides as the independent determinants. FABP1 levels remained an independent risk factor of insulin resistance assessed by binary S_i (OR = 1.868 per SD unit, 95% CI [1.035–3.373], p = 0.038) after adjustment for age, sex, BMI, waist circumference, systolic blood pressure, serum triacylglycerol, total cholesterol, HDL- and LDL-cholesterol,. FABP1 levels were also elevated with an increasing number of components of the metabolic syndrome (p for trend <0.001). Multiple regression modeling for the MetS and its components demonstrated that hypertriglyceridemia and low HDL-cholesterol were significantly correlated to serum FABP1 levels.

Conclusions and Significance

Serum FABP1 correlates positively with obesity and insulin resistance in Chinese young adults. Our data supports the fact that FABP1 might be an important mediator participating in fatty acid metabolism and energy balance.     

Serum Activin A and Follistatin Levels in Gestational Diabetes and the Association of the Activin A-Follistatin System with Anthropometric Parameters in Offspring

Context

The Activin A-Follistatin system has emerged as an important regulator of lipid and glucose metabolism with possible repercussions on fetal growth.

Objective

To analyze circulating activin A, follistatin and follistatin-like-3 (FSTL3) levels and their relationship with glucose metabolism in pregnant women and their influence on fetal growth and neonatal adiposity.

Design and methods

A prospective cohort was studied comprising 207 pregnant women, 129 with normal glucose tolerance (NGT) and 78 with gestational diabetes mellitus (GDM) and their offspring. Activin A, follistatin and FSTL3 levels were measured in maternal serum collected in the early third trimester of pregnancy. Serial fetal ultrasounds were performed during the third trimester to evaluate fetal growth. Neonatal anthropometry was measured to assess neonatal adiposity.

Results

Serum follistatin levels were significantly lower in GDM than in NGT pregnant women (8.21±2.32 ng/mL vs 9.22±3.41, P = 0.012) whereas serum FSTL3 and activin A levels were comparable between the two groups. Serum follistatin concentrations were negatively correlated with HOMA-IR and positively with ultrasound growth parameters such as fractional thigh volume estimation in the middle of the third trimester and percent fat mass at birth. Also, in the stepwise multiple linear regression analysis serum follistatin levels were negatively associated with HOMA-IR (β = −0.199, P = 0.008) and the diagnosis of gestational diabetes (β = −0.138, P = 0.049). Likewise, fractional thigh volume estimation in the middle of third trimester and percent fat mass at birth were positively determined by serum follistatin levels (β = 0.214, P = 0.005 and β = 0.231, P = 0.002, respectively).

Conclusions

Circulating follistatin levels are reduced in GDM compared with NGT pregnant women and they are positively associated with fetal growth and neonatal adiposity. These data suggest a role of the Activin-Follistatin system in maternal and fetal metabolism during pregnancy.     

Circulating Complement-C1q TNF-Related Protein 1 Levels Are Increased in Patients with Type 2 Diabetes and Are Associated with Insulin Sensitivity in Chinese Subjects

Background

Complement-C1q TNF-related protein 1 (CTRP1), a member of the CTRP superfamily, possesses anti-inflammatory and anti-diabetic effects in mice. However, the clinical relevance of CTRP1 has been seldom explored. The current study aimed to investigate the association of circulating CTRP1 and type 2 diabetes mellitus (T2DM) in a Chinese population.

Design and Methods

Serum CTRP1 and adiponectin levels of 96 T2DM patients and 85 healthy subjects were determined by ELISA, and their associations with adiposity, glucose and lipid profiles were studied. In a subgroup of this study, the 75-g oral glucose tolerance test (OGTT) was performed in 20 healthy and 20 T2DM subjects to evaluate the relationship among serum levels of CTRP1 and adiponectin, insulin secretion and insulin sensitivity.

Results

Serum CTRP1 levels were significantly increased in patients with T2DM, compared with healthy controls (p<0.001). Similar to adiponectin, serum levels of CTRP1 were significantly correlated to several parameters involved in glucose metabolism and insulin resistance, and independently associated with fasting glucose levels (p<0.05) after BMI and gender adjustments. Furthermore, CTRP1 levels were positively correlated to insulin secretion, while negatively to insulin sensitivity, as measured by OGTT.

Conclusion

CTRP1 is a novel adipokine associated with T2DM in humans. The paradoxical increase of serum CTRP1 levels in T2DM subjects may be due to a compensatory response to the adverse glucose and lipid metabolism, which warrants further investigation.     

Patterns of Circulating Fibroblast Growth Factor 21 in Subjects with and without Type 2 Diabetes

Background

Fibroblast growth factor 21 (FGF21) exerts wide-range effects on carbohydrate and lipid metabolism. However, its perturbation in type 2 diabetes mellitus (T2DM) remains elusive. Besides, previous human studies in T2DM simply investigated fasting or stimulated levels of FGF21. The current study sought to evaluate the temporal changes of circulating FGF21 in subjects with and without T2DM.

Methods

Ten patients with T2DM and 16 normal controls (NC) were recruited. Participants were categorized as obese (BMI≥25 kg/m²) or lean (BMI<25 kg/m²). Blood samples were drawn every 30 min within 7 hours (8 a.m.-3 p.m.). Serum FGF21, blood glucose, insulin, free fatty acids (FFAs) and adiponectin were measured in all subjects.

Results

The peak levels of FGF21 were observed in the fasting state (8 a.m.) both in T2DM and NC groups (267.35 ±158.72 ng/L vs. 178.93±121.37 ng/L, P = 0.096). FGF21 AUC did not differ significantly between the two groups (T2DM: 949.4±471.47 ng/L; NC: 883.13±561.40 ng/L, P = 0.770). Obese subjects had higher FGF21 levels than lean ones in patients either with or without T2DM. The pattern of FFAs closely resembled that of FGF21. Correlation analysis showed that temporal levels of FGF21 were significantly related to FFAs (r = 0.749, P = 0.002),but not blood glucose, insulin or adiponectin (all P> 0.05).

Conclusions

These findings suggest that the pattern of circulating FGF21 does not differ significantly between T2DM and NC,although T2DM patients showed a trend toward higher fasting FGF21 than healthy subjects. The pattern of circulating FFAs is significantly associated with that of FGF21.     

Cytokeratin19-2g2, a Novel Fragment of Cytokeratin19 in Serum,Indicating a More Invasive Behavior and Worse Prognosis in Breast Cancer Patients

Background

Various studies have been searching for new tumor biomarkers for breast cancer for years. However, so far, few markers have been proved clinically useful except CA153. Based on knowledge that most adenocarcinomas including breast carcinoma expressed Cytokeratin19, the authors studied CK19-2G2,a novel fragment of cytokeratin19 shedding into serum in breast cancer patients.

Patients and Methods

The serum samples of four hundred and seventeen patients including three hundred and three (fifty-four DCIS and two hundred and forty-nine stage I-III) PBC patients and one hundred and fourteen MBC patients, eighty-one healthy controls and twenty-one breast benign disease patients were provided for measurement of CK19-2G2, CEA and CA153.The correlation between clinicopathological characters, prognosis and CK19-2G2 levels was further studied.

Results

The serum CK19-2G2 levels in breast cancer patients were significantly higher than that in healthy and benign controls. For breast cancer patients, CK19-2G2 levels in MBC were significantly higher than that in PBC patients. The sensitivities of CK19-2G2 for breast carcinoma are as high as CEA and CA153, and up to 71% in MBC patients. Serum CK19-2G2 levels (≥2 mU/mL) were associated with pathological stages, tumor size (≥2 cm), lymph node involvement, and HER2 status. Multivariate analysis revealed that high serum CK19-2G2 level was an independent factor for relapse (P = 0.029) and death (P = 0.040) in breast cancer patients.

Conclusion

Serum CK19-2G2 may be an independent indicator for prognosis and a candidate marker for monitoring metastasis in breast cancer.     

Total and high molecular weight adiponectin and hepatocellular carcinoma with HCV infection

Background

Adiponectin is shown to be inversely associated with development and progression of various cancers. We evaluated whether adiponectin level was associated with the prevalence and histological grade of hepatocellular carcinoma (HCC), and liver fibrosis in patients with hepatitis C virus (HCV) infection.

Methods

A case-control study was conducted on 97 HCC patients (cases) and 97 patients (controls) matched for sex, Child-Pugh grade and platelet count in patients with HCV infection. The serum total and high molecular weight (HMW) adiponectin levels were measured by enzyme-linked immunosorbent assays and examined in their association with the prevalence of HCC. In addition, the relationship between these adiponectin levels and body mass index (BMI), progression of liver fibrosis, and histological grade of HCC was also evaluated. Liver fibrosis was assessed using the aspartate aminotransferase to platelet ratio index (APRI).

Results

There were no significant differences in the serum total and HMW adiponectin levels between cases and controls. Moreover, there were no inverse associations between serum total and HMW adiponectin levels and BMI in both cases and controls. On the other hand, serum total and HMW adiponectin levels are positively correlated with APRI in both cases (r = 0.491, P<0.001 and r = 0.485, P<0.001, respectively) and controls (r = 0.482, P<0.001 and r = 0.476, P<0.001, respectively). Interestingly, lower serum total (OR 11.76, 95% CI: 2.97–46.66 [P<0.001]) and HMW (OR 10.24, CI: 2.80–37.40 [P<0.001] adiponectin levels were independent risk factors of worse histological grade of HCC.

Conclusions

Our results suggested that serum total and HMW adiponectin levels were predictors of liver fibrosis, but not prevalence of HCC in patients with HCV infection. Moreover, low these adiponectin levels were significantly associated with worse histological grades.     

Effects of inhibition of interleukin-6 signalling on insulin sensitivity and lipoprotein (a) levels in human subjects with rheumatoid diseases

Background

Interleukin-6 (IL-6) is a pro-inflammatory cytokine that has been found to be increased in type 2 diabetic subjects. However, it still remains unclear if these elevated IL-6 levels are co-incidental or if this cytokine is causally related to the development of insulin resistance and type 2 diabetes in humans. Therefore, in the present study we examined insulin sensitivity, serum adipokine levels and lipid parameters in human subjects before and after treatment with the IL-6 receptor antibody Tocilizumab.

Methodology/Principal Findings

11 non-diabetic patients with rheumatoid disease were included in the study. HOMA-IR was calculated and serum levels for leptin, adiponectin, triglycerides, LDL-cholesterol, HDL-cholesterol and lipoprotein (a) (Lp (a)) were measured before as well as one and three months after Tocilizumab treatment. The HOMA index for insulin resistance decreased significantly. While leptin concentrations were not altered by inhibition of IL-6 signalling, adiponectin concentrations significantly increased. Thus the leptin to adiponectin ratio, a novel marker for insulin resistance, exhibited a significant decrease. Serum triglycerides, LDL-cholesterol and HDL-cholesterol tended to be increased whereas Lp (a) levels significantly decreased.

Conclusions/Significance

Inhibition of IL-6 signalling improves insulin sensitivity in humans with immunological disease suggesting that elevated IL-6 levels in type 2 diabetic subjects might be causally involved in the pathogenesis of insulin resistance. Furthermore, our data indicate that inhibition of IL-6 signalling decreases Lp (a) serum levels, which might reduce the cardiovascular risk of human subjects.     

Causal Relationship between Adiponectin and Metabolic Traits: A Mendelian Randomization Study in a Multiethnic Population

Background

Adiponectin, a secretagogue exclusively produced by adipocytes, has been associated with metabolic features, but its role in the development of the metabolic syndrome remains unclear.

Objectives

We investigated the association between serum adiponectin level and metabolic traits, using both observational and genetic epidemiologic approaches in a multiethnic population assembled in Canada.

Methods

Clinical data and serum adiponectin level were collected in 1,157 participants of the SHARE/SHARE-AP studies. Participants were genotyped for the functional rs266729 and rs1260326 SNPs in ADIPOQ and GCKR genes.

Results

Adiponectin level was positively associated with HDL cholesterol and negatively associated with body mass index, waist-to-hip ratio, triglycerides, fasting glucose, fasting insulin, systolic and diastolic pressure (all P<0.002). The rs266729 minor G allele was associated with lower adiponectin and higher HOMA-IR (P = 0.004 and 0.003, respectively). The association between rs266729 SNP and HOMA-IR was no longer significant after adjustment for adiponectin concentration (P = 0.10). The rs266729 SNP was associated with HOMA-IR to an extent that exceeded its effect on adiponectin level (0.15 SD 95% C.I. [0.06, 0.24], P<0.001). There was no significant interaction between rs266729 SNP and ethnicity on adiponectin or HOMA-IR. In contrast, the SNP rs1260326 in GCKR was associated with HOMA-IR (P<0.001), but not with adiponectin level (P = 0.67).

Conclusion

The association of the functional promoter polymorphism rs266729 with lower serum adiponectin and increased insulin resistance in diverse ethnic groups may suggest a causal relationship between adiponectin level and insulin resistance.     

Serum adiponectin is positively associated with lung function in young adults,independent of obesity: The CARDIA study

Rationale

Adipose tissue produces adiponectin, an anti-inflammatory protein. Adiponectin deficiency in mice is associated with abnormal post-natal alveolar development.

Objective

We hypothesized that lower serum adiponectin concentrations are associated with lower lung function in humans, independent of obesity. We explored mediation of this association by insulin resistance and systemic inflammation.

Methods and Measurements

Spirometry testing was conducted at years 10 and 20 follow-up evaluation visits in 2,056 eligible young adult participants in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Body mass index, serum adiponectin, serum C-reactive protein (a marker of systemic inflammation), and insulin resistance were assessed at year 15.

Main Results

After controlling for body mass index, years 10 and 20 forced vital capacity (FVC) were 81 ml and 82 ml lower respectively (p = 0.004 and 0.01 respectively) in the lowest vs. highest adiponectin quartiles. Similarly, years 10 and 20 forced expiratory volume in one second (FEV₁) were 50 ml and 38 ml lower (p = 0.01 and 0.09, respectively) in the lowest vs. highest adiponectin quartiles. These associations were no longer significant after adjustment for insulin resistance and C-reactive protein. Serum adiponectin was not associated with FEV₁/FVC or peak FEV₁.

Conclusions

Independent of obesity, lower serum adiponectin concentrations are associated with lower lung function. The attenuation of this association after adjustment for insulin resistance and systemic inflammation suggests that these covariates are on a causal pathway linking adiponectin and lung function.     

Efficacy and Safety of Oral Antidiabetic Drugs in Comparison to Insulin in Treating Gestational Diabetes Mellitus: A Meta-Analysis

Objective

To assess the efficacy and safety of oral antidiabetic drugs (OADs) in gestational diabetes mellitus (GDM) in comparison to insulin.

Methods

A meta-analysis of randomized controlled trials was conducted. The efficacy and safety of OADs in comparison to insulin in GDM patients were explored. Studies were identified by conducting a literature search using the electronic databases of Medline, CENTRAL, CINAHL, LILACS, Scopus and Web of Science in addition to conducting hand search of relevant journals from inception until October 2013.

Results

Thirteen studies involving 2,151 patients met the inclusion criteria. These studies were randomized controlled trials of metformin and glyburide in comparison to insulin therapy. Our results indicated a significant increase in the risk for preterm births (RR, 1.51; 95% CI, 1.04–2.19, p = 0.03) with metformin compared to insulin. However, a significant decrease in the risk for gestational hypertension (RR, 0.54; 95% CI, 0.31–0.91, p = 0.02) was found. Postprandial glucose levels also decreased significantly in patients receiving metformin (MD, −2.47 mg/dL; 95% CI, −4.00, −0.94, p = 0.002). There was no significant difference between the two groups for the remaining outcomes. There were significant increases in the risks of macrosomia (RR, 2.34; 95% CI, 1.18–4.63, p = 0.03) and neonatal hypoglycemia (RR, 2.06; 95% CI, 1.27–3.34, p = 0.005) in the glyburide group compared to insulin whereas results for the other analyzed outcomes remained non-significant.

Conclusion

The available evidence suggests favorable effects of metformin in treating GDM patients. Metformin seems to be an efficacious alternative to insulin and a better choice than glyburide especially those with mild form of disease.     

Inverse correlation between serum levels of selenoprotein P and adiponectin in patients with type 2 diabetes

Background

We recently identified selenoprotein P (SeP) as a liver-derived secretory protein that causes insulin resistance in the liver and skeletal muscle; however, it is unknown whether and, if so, how SeP acts on adipose tissue. The present study tested the hypothesis that SeP is related to hypoadiponectinemia in patients with type 2 diabetes.

Methodology/Principal Findings

We compared serum levels of SeP with those of adiponectin and other clinical parameters in 36 patients with type 2 diabetes. We also measured levels of blood adiponectin in SeP knockout mice. Circulating SeP levels were positively correlated with fasting plasma glucose (r = 0.35, P = 0.037) and negatively associated with both total and high-molecular adiponectin in patients with type 2 diabetes (r = −0.355, P = 0.034; r = −0.367, P = 0.028). SeP was a predictor of both total and high-molecular adiponectin, independently of age, body weight, and quantitative insulin sensitivity index (β = −0.343, P = 0.022; β = −0.357, P = 0.017). SeP knockout mice exhibited an increase in blood adiponectin levels when fed regular chow or a high sucrose, high fat diet.

Conclusions/Significance

These results suggest that overproduction of liver-derived secretory protein SeP is connected with hypoadiponectinemia in patients with type 2 diabetes.     

Role of Haptoglobin in Polycystic Ovary Syndrome (PCOS), Obesity and Disorders of Glucose Tolerance in Premenopausal Women

Background

Hp² alleles of the haptoglobin α–chain polymorphism reduce the anti-oxidant properties and increase the pro-inflammatory actions of this acute-phase protein in a gene-dosage fashion. We hypothesized that the haptoglobin polymorphism might contribute to the increased oxidative stress and low-grade chronic inflammation frequently associated with polycystic ovary syndrome, obesity, and abnormalities of glucose tolerance.

Methodology/Principal Findings

Serum haptoglobin and the haptoglobin α–chain polymorphism were determined in 141 patients with polycystic ovary syndrome and 102 non-hyperandrogenic women. Of the whole group of 243 premenopausal women, 117 were obese and 51 showed abnormal glucose tolerance. Although serum haptoglobin concentrations were similar in PCOS patients and controls, the former presented with an increased frequency of Hp² alleles (62% vs. 52%, P = 0.023). Circulating haptoglobin levels increased with obesity (P<0.001), yet no association was found between obesity and haptoglobin genotypes. No differences were observed in haptoglobin levels or genotype frequencies depending on glucose tolerance. Fifty percent of the variation in serum haptoglobin concentrations was explained by the variability in serum C-reactive protein concentrations, BMI, insulin sensitivity and haptoglobin genotypes.

Conclusions/Significance

Serum haptoglobin concentrations in premenopausal women are largely dependent on the haptoglobin polymorphism and on the presence of obesity, with insulin resistance and chronic inflammation possibly modulating this relationship. The association of polycystic ovary syndrome with Hp² alleles suggests that the anti-oxidant and anti-inflammatory properties of haptoglobin may be reduced in these patients.     

Serum Cytokeratin 19 Fragment,CK19-2G2, as a Newly Identified Biomarker for Lung Cancer

Background

CK19-2G2, a new fragment of cytokeratin 19, is a potential tumor marker for diagnosing lung cancer. The preoperative level of serum CK19-2G2 has been demonstrated to be associated with tumor metastasis and survival of breast cancer patients. This study investigated the postoperative dynamic changes in serum CK19-2G2 levels and its clinical significance in lung cancer patients.

Materials and Methods

Preoperative serum CK19-2G2 levels were measured in 630 lung cancer patients and were compared with individuals with benign pulmonary diseases (n = 134) and healthy volunteers (n = 263). In 352 cases, the patients underwent surgery. In these patients, in addition to preoperative assays, serum CK19-2G2 was also monitored at 1 week and 1 month after the operation.

Results

The preoperative baseline levels of serum CK19-2G2 was significantly higher in lung cancer patients than patients with benign diseases and healthy controls (P<0.001). The postoperative levels of CK19-2G2 declined significantly within 1 week after tumor resection. Hereafter, a further decrease was observed in the patients who underwent palliative operations, while for the patients in the radical resection group, their CK19-2G2 levels stabilized.

Conclusion

CK19-2G2 may be a candidate marker for diagnosing and monitoring a patient''s response to lung cancer treatment. In addition, CK19-2G2 may be an indicator for micrometastases in lung cancer patients.