Transient hyperglycemia, impaired glucose tolerance and gestational diabetes mellitus (GDM) in preterm pregnant women receiving antenatal steroids

OBJECTIVE:To determine the frequency of transient hyperglycemia, impaired glucose tolerance and gestational diabetes mellitus(GDM) in preterm pregnant women receiving antenatal steroids. METHODOLOGY:This descriptive cross-sectional study was carried out in Maternal and Child Health Center unit 1 (MCH-1) at Pakistan Institute of Medical Sciences Islamabad Pakistan from January 2017 till August 2017. A total of 365 pregnant women presenting to emergency and outpatient department with preterm labor (alive morphologically normal babies), with preterm premature rupture of membranes (PPROM) and other conditions which require early delivery including preeclampsia, IUGR requiring preterm delivery, severe oligohydramnios, antepartum hemorrhage(APH), women receiving two doses dexamethasone and all those with BSR>126mg/dl were included in the study. Multiple pregnancies, advanced preterm labor (cervix > 5cm dilated), gestational diabetes mellitus (GDM) or type I/II diabetes mellitus (DM), chorioamnionitis and taking any medication that affects glucose metabolism were excluded from the study. After ethical approval, informed consent was taken from study participants. Blood sugar levels before the commencement of 1st dose of dexamethasone were noted. Blood sugar profile (fasting, 2 hours after lunch, 2 hours after dinner) were carried out. 2nd dose of dexamethasone was given after 12 hours of 1st dose. Profile was carried out till euglycemia or 5 days if sugars remain deranged. Patients having deranged levels for greater than 5 days were advised 75 g oral glucose tolerance test(OGTT) and labelled as having impaired glucose tolerance or gestational diabetes mellitus. RESULTS: In our study, 57.57%(n=213) were between 18-30 years, 42.43%(n=157) were between 31-40 years of age, mean age was calculated as 28.92+5.54 while mean gestational age was 31.19+1.92 weeks. Frequency of transient hyperglycemia, impaired glucose tolerance and gestational diabetes mellitus(GDM) in preterm pregnant women receiving antenatal steroids revealed 62.16%(n=230) had transient hyperglycemia, 9.46%(n=35) had impaired glucose tolerance, 2.16%(n=8) had gestational diabetes and 26.22%(n=97) had no blood glucose abnormality. CONCLUSION: We concluded that the frequency of abnormal glucose levels increases in preterm pregnant women receiving antenatal steroids. Therefore, single blood sugar level done routinely before dexamethasone therapy are insufficient to judge the glucose metabolic status and should be closely monitored during the use of antenatal corticosteroids. KEYWORDS: Preterm delivery, antenatal steroids, transient hyperglycemia, impaired glucose tolerance and gestational diabetes mellitus(GDM)

Screening study of the antihyperglycemic action of new solid quercetin dispersions

The aim – to screen new solid dispersions of quercetin for the presence of antihyperglycemic action and to identify the most active substances that are promising for the creation of antidiabetic drugs. Materials and methods. The object of the study was 4 new solid dispersions of quercetin, developed at the National University of Pharmacy. Solid dispersions of quercetin were prepared by the liquid-phase method; hydroxypropyl methylcellulose (HPMC) or polyvinylpyrrolidone (PVP) in ratios of 1:1 and 1:2 were used as a carrier. The antihyperglycemic effect of the studied substances at a dose of 50 mg / kg was assessed in rats by the ability to lower blood glucose levels after carbohydrate loading in a model of impaired glucose tolerance induced by dexamethasone and in experimental type 2 diabetes mellitus induced by dexamethasone. Results. It was found that with impaired glucose tolerance, a solid dispersion of quercetin with HPMC (1:1) showed a pronounced antihyperglycemic effect – the glucose level 30 minutes after glucose load significantly decreased by 28 % and did not differ from the action of metformin, which was confirmed by the value of the area under glycemic crooked. When solid dispersions with PVP (1:1 and 1:2) were used, the antihyperglycemic effect was less pronounced. In a model of type 2 diabetes mellitus, a significant antihyperglycemic effect was found only in a solid dispersion of quercetin with HPMC (1:1) at the metformin level, which indicates an increase in the solubility and absorption of quercetin. Conclusions. A pronounced antihyperglycemic effect at the metformin level was found in a solid dispersion of quercetin with HPMC in a 1:1 ratio with impaired glucose tolerance and type 2 diabetes mellitus. It has been proven that a solid dispersion of quercetin with HPMC is a promising substance for creating a monocomponent drug or for inclusion in a new antidiabetic combined drug

Serum Levels of Plasmalogens and Fatty Acid Metabolites Associate with Retinal Microangiopathy in Participants from the Finnish Diabetes Prevention Study

Diabetic retinopathy (DR) is the most common microvascular complication of diabetes, and retinal microaneurysms (MA) are one of the first detected abnormalities associated with DR. We recently showed elevated serum triglyceride levels to be associated with the development of MA in the Finnish Diabetes Prevention Study (DPS). The purpose of this metabolomics study was to assess whether serum fatty acid (FA) composition, plasmalogens, and low-grade inflammation may enhance or decrease the risk of MA. Originally, the DPS included 522 individuals (mean 55 years old, range 40–64 years) with impaired glucose tolerance who were randomized into an intervention (n = 265) or control group (n = 257). The intervention lasted for a median of four years (active period), after which annual follow-up visits were conducted. At least five years after stopping the intervention phase of DPS, participants classified as MA negative (n = 115) or MA positive (n = 51) were included in the current study. All these participants were free of diabetes at baseline (WHO 1985) and had high-sensitive C-reactive protein (hs-CRP), serum FA composition, and selected lipid metabolites measured during the active study period. Among the markers associated with MA, the serum plasmalogen dm16:0 (p = 0.006), the saturated odd-chain FA 15.0 (pentadecanoic acid; p = 0.015), and omega-3 very long-chain FAs (p < 0.05) were associated with a decreased occurrence of MA. These associations were independent of study group and other risk factors. The association of high serum triglycerides with the MA occurrence was attenuated when these MA-associated serum lipid markers were considered. Our findings suggest that, in addition to n-3 FAs, odd-chain FA 15:0 and plasmalogen dm16:0 may contribute to a lower risk of MA in individuals with impaired glucose tolerance. These putative novel lipid biomarkers have an association with MA independently of triglyceride levels.

Kyushu and Okinawa Population Study (KOPS): a large prospective cohort study in Japan

PurposeThe Kyushu and Okinawa Population Study (KOPS) was established to investigate gene–environmental interactions in non-communicable diseases in Japan. Besides collecting blood samples and anthropometric measurements, we also obtained medical histories, psychological status and lifestyle habits, including physical activities and dietary patterns.ParticipantsKOPS is a community-based prospective cohort study and consists of participants from four southwestern areas in Japan. Baseline surveys were conducted between 2004 and 2007 (wave 1), and 2009 and 2012 (wave 2) at the sites of municipality-based health check-ups. A total of 17 077 participants were included, comprising 10 697 participants of wave 1 and 6380 participants of wave 2; the median age in both groups was 61 years. Among them, 3006 individuals participated in both wave 1 and wave 2 surveys.Findings to dateWe have focused on either risk or confounding factors for non-communicable diseases. We have assessed the clinical utility of the newly developed biomarkers for impaired glucose tolerance, such as urinary myo-inositol and glycated albumin, and atherosclerosis, such as small dense low-density lipoprotein cholesterol. We have conducted an international collaborative study with Framingham Offspring Study to investigate ethnic differences in impaired glucose tolerance and cardiovascular diseases. We have found that insulin resistance and deficiency might account for the ethnic differences in impaired glucose tolerance and cardiovascular disease risks. As gene–environmental interaction analyses, we found a synergic effect of interleukin 28B single nucleotide polymorphisms (SNPs) and gender on the spontaneous elimination of hepatitis C, and a beneficial interaction of SNPs of high-density lipoprotein cholesterol and gender on the impact of physical activity. In addition, we reported eight novel loci contributing to the development and severity of coronary artery disease from a large genome-wide association study.Future plansWe plan to investigate further the clinical utility of the newly developed biomarkers and the gene–environmental interactions using prospective data.

Predicting progression from gestational diabetes to impaired glucose tolerance using peri-delivery data: an observational study

Objective: To develop a predictive model to identify women with recent gestational diabetes (GDM) most likely to progress to impaired glucose tolerance postpartum. Design: Observational study. Setting: Academic medical center in the United States. Population: Postpartum women with recent GDM, defined by Carpenter-Coustan criteria & 1-year postpartum HbA1c assessment. Methods: We used lasso regression with k-fold cross validation to develop a multivariable model to predict progression to impaired glucose tolerance, defined as HbA1c ≥ 5.7%, by 1 year postpartum. Predictive ability was assessed by the area under the curve, sensitivity, specificity, positive and negative predictive values. Main Outcome Measures: Impaired glucose tolerance. Results: Of 203 women, 71(35%) had impaired glucose tolerance at 1 year postpartum. The final model had an AUC of 0.81 (95% CI 0.74, 0.87) and included eight indicators of weight, body mass index, Hispanic ethnicity, GDM in a prior pregnancy, GDM diagnosis < 24 weeks’ gestation, and fasting and 2-hour plasma glucose at 2 days postpartum. A cut-point of ≥ 0.24 predicted probability had sensitivity 80% (95% CI 69, 89), specificity 58% (95% CI 49, 66), PPV 57% (95% CI 46, 68) and NPV 83% (95% CI 74, 89) to identify women with impaired glucose tolerance at 1 year postpartum. Conclusions: Our predictive model had reasonable ability to predict impaired glucose tolerance around delivery for women with recent GDM. Funding: National Institute of Mental Health and American Diabetes Association. Keywords: gestational diabetes, impaired glucose tolerance, type 2 diabetes prevention; predictive model

SUR1-E1506K mutation impairs glucose tolerance and promotes vulnerable atherosclerotic plaque phenotype in hypercholesterolemic mice

Background and aims Diabetes is a major risk factor of atherosclerosis and its complications. The loss-of-function mutation E1506K in the sulfonylurea receptor 1 (SUR1-E1506K) induces hyperinsulinemia in infancy, leading to impaired glucose tolerance and increased risk of type 2 diabetes. In this study, we investigate the effect of SUR1-E1506K mutation on atherogenesis in hypercholesterolemic LDLR-/- mice. Methods SUR1-E1506K mutated mice were cross-bred with LDLR-/- mice (SUR1Δ/LDLR-/-), 6 months old mice were fed a western-diet (WD) for 6 months to induce advanced atherosclerotic plaques. At the age of 12 months, atherosclerosis and plaque morphology were analyzed and mRNA gene expression were measured from aortic sections and macrophages. Glucose metabolism was characterized before and after WD. Results were compared to age-matched LDLR-/- mice. Results Advanced atherosclerotic plaques did not differ in size between the two strains. However, in SUR1Δ/LDLR-/- mice, plaque necrotic area was increased and smooth muscle cell number was reduced, resulting in higher plaque vulnerability index in SUR1Δ/LDLR-/- mice compared to LDLR-/- mice. SUR1Δ/LDLR-/- mice exhibited impaired glucose tolerance and elevated fasting glucose after WD. The positive staining area of IL-1β and NLRP3 inflammasome were increased in aortic sections in SUR1Δ/LDLR-/- mice compared to LDLR-/- mice, and IL-18 plasma level was elevated in SUR1Δ/LDLR-/- mice. Finally, the mRNA expression of IL-1β and IL-18 were increased in SUR1Δ/LDLR-/- bone marrow derived macrophages in comparison to LDLR-/- macrophages in response to LPS. Conclusions SUR1-E1506K mutation impairs glucose tolerance and increases arterial inflammation, which promotes a vulnerable atherosclerotic plaque phenotype in LDLR-/- mice.