Use of oral glucose tolerance testing and HbA1c at 6-14 gestational weeks to predict gestational diabetes mellitus in high-risk women.

PURPOSE: To study the prediction of gestational diabetes mellitus (GDM) in high-risk pregnant women by testing fasting blood glucose, 1-h(1hPG) and 2-h plasma glucose (2hPG) after an oral glucose tolerance test, and glycated hemoglobin (HbA1c) in early pregnancy (6-14 weeks). METHODS: We recruited 1311 pregnant women at high risk for diabetes from the Obstetrics Clinic of Daxing District People's Hospital between June 2017 and December 2019. The tests performed during the first trimester included fasting blood glucose (FPG), HbA1c, and 75-g oral glucose tolerance test (OGTT) with 1hPG and 2hPG. Seventy-three pregnant women diagnosed with pregestational diabetes mellitus (PGDM) early in pregnancy and 36 who were missed in the second trimester were excluded. A total of 1202 women were followed up until 24-28 weeks for GDM. The receiver operating characteristic (ROC) and area under the ROC curve (AUC) were calculated to determine the predictive values of FPG, 1hPG, 2hPG, and HbA1c for GDM in early pregnancy in high-risk pregnant women. RESULTS: The AUC for 1hPG for the prediction of GDM in high-risk pregnant women was greater than those for FPG, 2hPG, and HbA1c. All differences were significant. The AUCs for the predictive values of FPG, 1hPG, 2hPG, and HbA1c in high-risk pregnant women were 0.63, 0.76, 0.71, and 0.67, respectively. The prevalence of PGDM among pregnant women at high risk of diabetes was 5.6%. CONCLUSION: First-trimester levels of FPG, 1hPG, 2hPG, and HbA1c in high-risk women are significant predictors of GDM, with 1hPG having the most significant predictive value.

Effect of obstructive sleep apnea on glucose metabolism.

BACKGROUND: Obstructive sleep apnea (OSA) is prevalent in people with obesity and is a major risk factor for type 2 diabetes (T2D). The effect of OSA on metabolic function and the precise mechanisms (insulin resistance, ß-cell dysfunction, or both) responsible for the increased T2D risk in people with OSA are unknown. DESIGN AND METHODS: We used a two-stage hyperinsulinemic-euglycemic clamp procedure in conjunction with stable isotopically labeled glucose and palmitate tracer infusions and 18F-fluorodeoxyglucose injection and positron emission tomography to quantify multi-organ insulin action and oral and intravenous tolerance tests to evaluate glucose-stimulated insulin secretion in fifteen people with obesity and OSA and thirteen people with obesity without OSA. RESULTS: OSA was associated with marked insulin resistance of adipose tissue triglyceride lipolysis and glucose uptake into both skeletal muscles and adipose tissue, whereas there was no significant difference between the OSA and control groups in insulin action on endogenous glucose production, basal insulin secretion, and glucose-stimulated insulin secretion during both intravenous and oral glucose tolerance tests. CONCLUSIONS: These data demonstrate that OSA is a key determinant of insulin sensitivity in people with obesity and underscore the importance of taking OSA status into account when evaluating metabolic function in people with obesity. These findings may also have important clinical implications because disease progression and the risk of diabetes-related complications vary by T2D subtype (i.e. severe insulin resistance vs insulin deficiency). People with OSA may benefit most from the targeted treatment of peripheral insulin resistance and early screening for complications associated with peripheral insulin resistance.

Insulin clearance and incretin hormones following oral and "isoglycemic" intravenous glucose in type 2 diabetes patients under different antidiabetic treatments.

It has not been elucidated whether incretins affect insulin clearance in type 2 diabetes (T2D). We aimed exploring possible associations between insulin clearance and endogenously secreted or exogenously administered incretins in T2D patients. Twenty T2D patients were studied (16 males/4 females, 59 ± 2 years (mean ± standard error), BMI = 31 ± 1 kg/m2, HbA1c = 7.0 ± 0.1%). Patients were treated with metformin, sitagliptin, metformin/sitagliptin combination, and placebo (randomized order). On each treatment period, oral and isoglycemic intravenous glucose infusion tests were performed (OGTT, IIGI, respectively). We also studied twelve T2D patients (9 males/3 females, 61 ± 3 years, BMI = 30 ± 1 kg/m2, HbA1c = 7.3 ± 0.4%) that underwent infusion of GLP-1(7-36)-amide, GIP, GLP-1/GIP combination, and placebo. Plasma glucose, insulin, C-peptide, and incretins were measured. Insulin clearance was assessed as insulin secretion to insulin concentration ratio. In the first study, we found OGTT/IIGI insulin clearance ratio weakly inversely related to OGTT/IIGI total GIP and intact GLP-1 (R2 = 0.13, p < 0.02). However, insulin clearance showed some differences between sitagliptin and metformin treatment (p < 0.02). In the second study we found no difference in insulin clearance following GLP-1 and/or GIP infusion (p > 0.5). Thus, our data suggest that in T2D there are no relevant incretin effects on insulin clearance. Conversely, different antidiabetic treatments may determine insulin clearance variations.

Obstetric and neonatal outcomes of gestational diabetes mellitus in twin pregnancies according to changes in its diagnostic criteria from National Diabetes Data Group criteria to Carpenter and Coustan criteria: a retrospective cohort study.

BACKGROUND: To compare obstetric and neonatal outcomes in twin pregnancies with or without gestational diabetes mellitus (GDM) before and after changes in GDM diagnostic criteria. METHODS: This was a retrospective cohort study of 1,764 twin pregnancies including 130 women with GDM (GDM group) and 1,634 women without GDM (non-GDM group). Patients with pregestational diabetes, unknown GDM status, and fetal death at < 24 gestational weeks were excluded. Obstetric and neonatal outcomes were compared between the two groups by two periods: period 1 (1995-2005) and period 2 (2005-2018) when National Diabetes Data Group criteria and Carpenter and Coustan criteria were used for diagnosis of GDM, respectively. RESULTS: The incidence of GDM in twin pregnancies increased from 4.0% in period 1 to 9.3% in period 2. Composite obstetric complications rate was significantly higher in the GDM group than that in the non-GDM group during period 1 (72.0% vs. 45.5%, P = 0.009). However, it became comparable during period 2 (60.0% vs. 57.4%, P = 0.601). Interaction between GDM and period indicated a significant differential effect of GDM by period on the rate of composite obstetric complications. The rate of composite neonatal complications was similar between the two groups during both periods. The interaction between GDM and period was not significant. CONCLUSION: After changes of GDM diagnostic criteria, the incidence of GDM increased more than twice, and the rate of composite obstetric complications decreased, but the rate of composite neonatal complications did not change significantly.

Comparison of insulin sensitivity between healthy neonatal foals and horses using minimal model analysis.

The equine neonate is considered to have impaired glucose tolerance due to delayed maturation of the pancreatic endocrine system. Few studies have investigated insulin sensitivity in newborn foals using dynamic testing methods. The objective of this study was to assess insulin sensitivity by comparing the insulin-modified frequently sampled intravenous glucose tolerance test (I-FSIGTT) between neonatal foals and adult horses. This study was performed on healthy neonatal foals (n = 12), 24 to 60 hours of age, and horses (n = 8), 3 to 14 years of age using dextrose (300 mg/kg IV) and insulin (0.02 IU/kg IV). Insulin sensitivity (SI), acute insulin response to glucose (AIRg), glucose effectiveness (Sg), and disposition index (DI) were calculated using minimal model analysis. Proxy measurements were calculated using fasting insulin and glucose concentrations. Nonparametric statistical methods were used for analysis and reported as median and interquartile range (IQR). SI was significantly higher in foals (18.3 L·min-1· µIU-1 [13.4-28.4]) compared to horses (0.9 L·min-1· µIU-1 [0.5-1.1]); (p < 0.0001). DI was higher in foals (12 × 103 [8 × 103-14 × 103]) compared to horses (4 × 102 [2 × 102-7 × 102]); (p < 0.0001). AIRg and Sg were not different between foals and horses. The modified insulin to glucose ratio (MIRG) was lower in foals (1.72 µIUinsulin2/10·L·mgglucose [1.43-2.68]) compared to horses (3.91 µIU insulin2/10·L·mgglucose [2.57-7.89]); (p = 0.009). The homeostasis model assessment of beta cell function (HOMA-BC%) was higher in horses (78.4% [43-116]) compared to foals (23.2% [17.8-42.2]); (p = 0.0096). Our results suggest that healthy neonatal foals are insulin sensitive in the first days of life, which contradicts current literature regarding the equine neonate. Newborn foals may be more insulin sensitive immediately after birth as an evolutionary adaptation to conserve energy during the transition to extrauterine life.

Hyperbaric oxygen treatment improves pancreatic ß­cell function and hepatic gluconeogenesis in STZ­induced type­2 diabetes mellitus model mice.

Type­2 diabetes mellitus (T2DM) causes several complications that affect the quality of life and life span of patients. Hyperbaric oxygen therapy (HBOT) has been used to successfully treat several diseases, including carbon monoxide poisoning, ischemia, infections and diabetic foot ulcer, and increases insulin sensitivity in T2DM. The present study aimed to determine the effect of HBOT on ß­cell function and hepatic gluconeogenesis in streptozotocin (STZ)­induced type­2 diabetic mice. To establish a T2DM model, 7­week­old male C57BL/6J mice were fed a high­fat diet (HFD) and injected once daily with low­dose STZ for 3 days after 1­week HFD feeding. At the 14th week, HFD+HBOT and T2DM+HBOT groups received 1­h HBOT (2 ATA; 100% pure O2) daily from 5:00 to 6:00 p.m. for 7 days. The HFD and T2DM groups were maintained under normobaric oxygen conditions and used as controls. During HBOT, the 12­h nocturnal food intake and body weight were measured daily. Moreover, blood glucose was measured by using a tail vein prick and a glucometer. After the final HBO treatment, all mice were sacrificed to conduct molecular biology experiments. Fasting insulin levels of blood samples of sacrificed mice were measured by an ultrasensitive ELISA kit. Pancreas and liver tissues were stained with hematoxylin and eosin, while immunohistochemistry was performed to determine the effects of HBOT on insulin resistance. TUNEL was used to determine the effects of HBOT on ß­cell apoptosis, and immunoblotting was conducted to determine the ß­cell apoptosis pathway. HBOT notably reduced fasting blood glucose and improved insulin sensitivity in T2DM mice. After HBOT, ß­cell area and ß­cell mass in T2DM mice were significantly increased. HBOT significantly decreased the ß­cell apoptotic rate in T2DM mice via the pancreatic Bcl­2/caspase­3/poly(ADP­ribose) polymerase (PARP) apoptosis pathway. Moreover, HBOT improved the morphology of the liver tissue and increased hepatic glycogen storage in T2DM mice. These findings suggested that HBOT ameliorated the insulin sensitivity of T2DM mice by decreasing the ß­cell apoptotic rate via the pancreatic Bcl­2/caspase­3/PARP apoptosis pathway.

Detecting dysglycaemia in compensated liver cirrhosis: Comparison of oral glucose tolerance test and glycated haemoglobin, with continuous glucose monitoring.

AIMS: Liver cirrhosis increases the risk of developing dysglycaemia (pre-diabetes and diabetes), thus people with cirrhosis should undergo regular screening for dysglycaemia. The utility of screening using the laboratory glycated haemoglobin (HbA1c ) test has been questioned in this setting. This study examines the relationship between different potential screening modalities: 75 g oral glucose tolerance test (OGTT) and HbA1c , using continuous glucose monitoring (CGM) as a comparator. METHODS: Participants ≥18 years with no known diabetes, were recruited from a gastroenterology cirrhosis surveillance register. Study measurements included a 75 g OGTT, laboratory HbA1c and two weeks of 'blinded' CGM (Freestyle Libre Pro). The possibility of intravascular haemolysis affecting HbA1c interpretation was also assessed. RESULTS: All 20 participants had compensated cirrhosis. OGTT tended to diagnose more dysglycaemia (N = 7) than did HbA1c (N = 4). Bland-Altman analysis showed laboratory and CGM-estimated HbA1c were broadly comparable, with a difference of 4mmol/mol (95% CI -3 to 12), or 0.4% (95% CI -0.3 to 1.1). Laboratory HbA1c tended to be higher than the CGM-estimated HbA1c , perhaps reflecting positive lifestyle changes in participants during their two weeks of wearing 'blinded' CGM (Hawthorne effect). In the population studied, there was no evidence that haemolysis affected interpretation of HbA1c results. CONCLUSIONS: In the setting of compensated cirrhosis, the OGTT and HbA1c remain standard screening test for diabetes, but multiple studies show the OGTT diagnoses more people with dysglycaemia than does the HbA1c . Blinded CGM in an ambulatory, real world setting provides additional insights into glycaemic excursions but cannot be used to diagnose dysglycaemia.

Beta cell function, incretin hormones, and incretin effect in obese children and adolescents with prediabetes.

BACKGROUND: Defects of incretin hormones and incretin effect may be underlying mechanisms of abnormal glucose metabolism in youth. OBJECTIVE: To assess incretin hormone dynamics during an oral glucose tolerance test (OGTT) and incretin effect in obese children with prediabetes in comparison with those with normal glucose tolerance (NGT). METHODS: Overweight and obese children were enrolled and classified according to OGTT results as NGT and prediabetes. Insulin sensitivity, insulin secretion, incretin hormone concentrations during OGTT; and incretin effect derived from OGTT and intravenous glucose tolerance test were determined and compared between NGT and prediabetes groups. RESULTS: Sixty-three patients (43 NGT and 20 prediabetes) were enrolled. Their median (interquartile range) age was 12.5 (11.1, 13.8) years. Peak glucagon-like peptide-1 (GLP-1) was demonstrated at 30 min during OGTT and was higher in the prediabetes group (49.2 [35.6, 63.6] versus 36.5 [27.6, 44.2] pmol/L, p = 0.009). However, incremental areas under the curves (iAUCs) of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) were not different between the two groups. There was no difference in incretin effect between NGT and prediabetes (NGT: 66.5% [60.2%, 77.5%] vs. prediabetes: 70.0% [61.5%, 75.0%], p = 0.645). Incretin effect had positive correlations with iAUCs of both GLP-1 and GIP (GLP-1: r = 0.40, p = 0.004 and GIP: r = 0.37, p = 0.009). CONCLUSIONS: Comparing between obese children with prediabetes and NGT, there were no differences in overall incretin hormone changes during OGTT and incretin effect. Incretin effect was positively correlated with iAUCs of GLP-1 and GIP.

16S rRNA gene amplicon sequencing of gut microbiota in gestational diabetes mellitus and their correlation with disease risk factors.

PURPOSE: Although the gut microbiota (GM) are associated with various diseases, their role in gestational diabetes mellitus (GDM) remains uncharacterized. Further study is urgently needed to expose the real relationship between GM and GDM. METHODS: We performed a prospective study in 33 pregnant Chinese individuals [15, GDM; 18, normal glucose tolerance (NGT)] to observe the fecal microbiota by 16S rRNA gene amplicon sequencing at 24-28 weeks of gestational age after a standard 75 g oral glucose tolerance test. Linear regression analysis was employed to assess the relationships between the GM and GDM clinical parameters. RESULTS: Sequencing showed no difference in the microbiota alpha diversity but a significant difference in the beta diversity between the GDM and NGT groups, with the relative abundances of Ruminococcus bromii, Clostridium colinum, and Streptococcus infantis being higher in the GDM group (P < 0.05). The quantitative PCR results validated the putative bacterial markers of R. bromii and S. infantis. Moreover, a strong positive correlation was found between S. infantis and blood glucose levels after adjusting for body mass index (P < 0.05). CONCLUSION: Three abnormally expressed intestinal bacteria (R. bromii, C. colinum, and S. infantis) were identified in GDM patients. S. infantis may confer an increased risk of GDM. Hence, the GM may serve as a potential therapeutic target for GDM.

Do East Asians With Normal Glucose Tolerance Have Worse ß-Cell Function? A Meta-Analysis of Epidemiological Studies.

Background: The difference in the relationship between ß-cell function and insulin resistance among Africans, Caucasians and East Asians with normal glucose tolerance (NGT) was not well investigated. Methods: We searched PubMed and Web of Science with keywords and identified studies that used the homeostasis model assessment (HOMA) model to evaluate ß-cell function (HOMA-B) and insulin sensitivity/resistance (HOMA-S/HOMA-IR) in certain ethnic groups. We used random-effect model to pool data of HOMAs and compared the combined data among the three ethnic groups using subgroup analysis. Linear regression analysis was used to estimate the coefficient of HOMA-S on HOMA-B in these ethnic groups. Results: We evaluated pooled data of HOMAs in eight African, 26 Caucasian, and 84 East Asian cohorts with NGT, and also 2,392, 6,645 and 67,317 individuals, respectively. The three ethnic groups had distinct HOMA-B but similar HOMA-IR. The regression coefficient of lnHOMA-B on lnHOMA-S was different between Africans and Caucasians (-1.126 vs -0.401, P = 0.0006) or East Asian (-1.126 vs -0.586, P = 0.0087), but similar between Caucasians and East Asians (-0.401 vs -0.586, P = 0.1282). The coefficient in all ethnic groups was similar when age, BMI, and gender were adjusted (African vs Caucasian P = 0.0885, African vs East Asian P = 0.1092, and Caucasian vs East Asian P = 0.6298). Conclusions: In subjects with NGT, East Asians had lower HOMA-B but similar ß-cell response relative to insulin resistance with Caucasians and Africans when age, BMI, and gender were controlled. This result may challenge the allegation that there was an Asian-specific diabetes phenotype with worse ß-cell function.

Fluvastatin Reduces Glucose Tolerance in Healthy Young Individuals Independently of Cold Induced BAT Activity.

Background: Statins are commonly prescribed for primary and secondary prevention of atherosclerotic disease. They reduce cholesterol biosynthesis by inhibiting hydroxymethylglutaryl-coenzyme A-reductase (HMG-CoA-reductase) and therefore mevalonate synthesis. Several studies reported a small, but significant increase in the diagnosis of diabetes mellitus with statin treatment. The molecular mechanisms behind this adverse effect are not yet fully understood. Brown adipose tissue (BAT), which plays a role in thermogenesis, has been associated with a reduced risk of insulin resistance. Statins inhibit adipose tissue browning and have been negatively linked to the presence of BAT in humans. We therefore speculated that inhibition of BAT by statins contributes to increased insulin resistance in humans. Methods: A prospective study was conducted in 17 young, healthy men. After screening whether significant cold-induced thermogenesis (CIT) was present, participants underwent glucose tolerance testing (oGTT) and assessment of BAT activity by FDG-PET/MRI after cold-exposure and treatment with a ß3-agonist. Fluvastatin 2x40mg per day was then administered for two weeks and oGTT and FDG-PET/MRI were repeated. Results: Two weeks of fluvastatin treatment led to a significant increase in glucose area under the curve (AUC) during oGTT (p=0.02), reduction in total cholesterol and LDL cholesterol (both p<0.0001). Insulin AUC (p=0.26), resting energy expenditure (REE) (p=0.44) and diet induced thermogenesis (DIT) (p=0.27) did not change significantly. The Matsuda index, as an indicator of insulin sensitivity, was lower after fluvastatin intake, but the difference was not statistically significant (p=0.09). As parameters of BAT activity, mean standard uptake value (SUVmean) (p=0.12), volume (p=0.49) and total glycolysis (p=0.74) did not change significantly during the intervention. Matsuda index, was inversely related to SUVmean and the respiratory exchange ratio (RER) (both R2 = 0.44, p=0.005) at baseline, but not after administration of fluvastatin (R2 = 0.08, p=0.29, and R2 = 0.14, p=0.16, respectively). Conclusions: Treatment with fluvastatin for two weeks reduced serum lipid levels but increased glucose AUC in young, healthy men, indicating reduced glucose tolerance. This was not associated with changes in cold-induced BAT activity.

Preference of Women for Gestational Diabetes Screening Method According to Tolerance of Tests and Population Characteristics.

Aims: To determine the preferred method of screening for gestational diabetes mellitus (GDM). Methods: 1804 women from a prospective study (NCT02036619) received a glucose challenge test (GCT) and 75g oral glucose tolerance test (OGTT) between 24-28 weeks. Tolerance of screening tests and preference for screening strategy (two-step screening strategy with GCT compared to one-step screening strategy with OGTT) were evaluated by a self-designed questionnaire at the time of the GCT and OGTT. Results: Compared to women who preferred one-step screening [26.2% (472)], women who preferred two-step screening [46.3% (834)] were less often from a minor ethnic background [6.0% (50) vs. 10.7% (50), p=0.003], had less often a previous history of GDM [7.3% (29) vs. 13.8% (32), p=0.008], were less often overweight or obese [respectively 23.1% (50) vs. 24.8% (116), p<0.001 and 7.9% (66) vs. 18.2% (85), p<0.001], were less insulin resistant in early pregnancy (HOMA-IR 8.9 (6.4-12.3) vs. 9.9 (7.2-14.2), p<0.001], and pregnancy outcomes were similar except for fewer labor inductions and emergency cesarean sections [respectively 26.6% (198) vs. 32.5% (137), p=0.031 and 8.2% (68) vs. 13.0% (61), p=0.005]. Women who preferred two-step screening had more often complaints of the OGTT compared to women who preferred one-step screening [50.4% (420) vs. 40.3% (190), p<0.001]. Conclusions: A two-step GDM screening involving a GCT and subsequent OGTT is the preferred GDM screening strategy. Women with a more adverse metabolic profile preferred one-step screening with OGTT while women preferring two-step screening had a better metabolic profile and more discomfort of the OGTT. The preference for the GDM screening method is in line with the recommended Flemish modified two-step screening method, in which women at higher risk for GDM are recommended a one-step screening strategy with an OGTT, while women without these risk factors, are offered a two-step screening strategy with GCT. Clinical Trial Registration: NCT02036619 https://clinicaltrials.gov/ct2/show/NCT02036619.

Evaluation of antihyperglycemic activity of plants in northeast mexico.

iabetes mellitus is one of the most common non-contagious diseases. In 2017, The International Diabetes Federation reported that around 425 million people suffer from diabetes worldwide. Medications used for the treatment of diabetes lead to unwanted side effects, and thus, new safe drugs are necessary. Some natural plant-based products exhibit anti hyperglycemic activity and low toxicity. The aim of this study was to evaluate the antihyperglycemic activity (using both in vitro and in vivo models) as well as cytotoxicity of the extracts obtained from various plants. Nine extracts from a total of eight plant species were subjected to in vitro α-amylase and α-glucosidase inhibition assays. Subsequently, they were assessed through the ex vivo everted sac assay, and finally, the in vivo antihyperglycemic activity was evaluated. The extracts obtained from Ceanothus coeruleus, Chrysactinia mexicana and Zanthoxylum fagara inhibited the activities of α-amylase and α-glucosidase in the in vitro assays. Ethyl acetate and hydroalcoholic extracts from Jatropha dioica, hydroalcoholic extract from Salvia ballotaeflora and Chrysactinia mexicana, as well as methanolic extract from Ricinus communis and Zanthoxylum fagara significantly reduced the glucose uptake in the ex vivo everted intestinal sac test. All the eight extracts showed antihyperglycemic effect through the in vivo model of the Glucose Tolerance Test, using starch as the carbohydrate source.  The antihyperglycemic effect of the extracts could be mediated through the inhibition of digestive enzymes and/or the absorption of glucose through the intestine. However, the mechanism of action for the hydroalcoholic extract of Salvia texana and the methanolic extract of Turnera diffusa, which showed a strong in vivo antihyperglycemic effect, is unclear.

d-Allulose Ameliorates Skeletal Muscle Insulin Resistance in High-Fat Diet-Fed Rats.

BACKGROUND: d-Allulose is a rare sugar with antiobesity and antidiabetic activities. However, its direct effect on insulin sensitivity and the underlying mechanism involved are unknown. OBJECTIVE: This study aimed to investigate the effect of d-allulose on high-fat diet (HFD)-induced insulin resistance using the hyperinsulinemic-euglycemic (HE)-clamp method and intramuscular signaling analysis. METHODS: Wistar rats were randomly divided into three dietary groups: chow diet, HFD with 5% cellulose (HFC), and HFD with 5% d-allulose (HFA). After four weeks of feeding, the insulin tolerance test (ITT), intraperitoneal glucose tolerance test (IPGTT), and HE-clamp study were performed. The levels of plasma leptin, adiponectin, and tumor necrosis factor (TNF)-α were measured using the enzyme-linked immunosorbent assay. We analyzed the levels of cell signaling pathway components in the skeletal muscle using Western blotting. RESULTS: d-allulose alleviated the increase in HFD-induced body weight and visceral fat and reduced the area under the curve as per ITT and IPGTT. d-Allulose increased the glucose infusion rate in the two-step HE-clamp test. Consistently, the insulin-induced phosphorylation of serine 307 in the insulin receptor substrate-1 and Akt and expression of glucose transporter 4 (Glut-4) in the muscle were higher in the HFA group than HFC group. Furthermore, d-allulose decreased plasma TNF-α concentration and insulin-induced phosphorylation of stress-activated protein kinase/Jun N-terminal kinase in the muscle and inhibited adiponectin secretion in HFD-fed rats. CONCLUSIONS: d-allulose improved HFD-induced insulin resistance in Wistar rats. The reduction of the proinflammatory cytokine production, amelioration of adiponectin secretion, and increase in insulin signaling and Glut-4 expression in the muscle contributed to this effect.

Prediction of insulin treatment in women with gestational diabetes mellitus.

INTRODUCTION: The identification of pregnant women with Gestational Diabetes Mellitus (GDM) who will require insulin therapy, may modify their management to closer monitoring and probable early interventions. The aim of the study was to develop a predictive model for the necessity of insulin treatment in women with GDM. MATERIALS AND METHODS: This was a prospective cohort study. Data from 775 women diagnosed with GDM per the IADPSG criteria were analyzed using logistic regression and a machine learning algorithm, the Classification and Regression Trees (CART). Potential predictors routinely recorded at follow-up visits were tested and used for the development of the model. The resultant model was externally validated using the data from two different perinatology clinics. RESULTS: Preconceptional maternal BMI and morning fasting blood glucose levels at baseline and at 1 h during an Oral Glucose Tolerance Test (OGTT) were independent significant predictors for the treatment modality of GDM. Baseline blood glucose greater than 98 mg/dl and preconceptional maternal Body Mass Index (BMI) between 26 and 31 kg/height2 increased substantially the probability of insulin therapy (odds ratio [OR] 4.04, 95% confidence interval [CI] CI 2.65-6.17 and 2.21, 95%CI 1.42-3.43, respectively). The area under the curve (AUC) for the internal and external validation of the predictive model was 0.74 and 0.77, respectively. CONCLUSIONS: A simple model based on maternal characteristics and the values of an OGTT can predict the need for insulin treatment with accuracy. Overweight women with an abnormal baseline blood glucose at OGTT are at high likelihood for insulin treatment. KEY MESSAGE: Fifteen to 30% of women with Gestational Diabetes Mellitus (GDM) require insulin therapy. Overweight women with baseline blood glucose greater than 98 mg/dl at OGTT are at increased risk for insulin treatment and close monitoring and increased physical exercise are required.

A new mouse model of type 2 diabetes mellitus established through combination of high-fat diet, streptozotocin and glucocorticoid.

AIM: A stable induced type 2 diabetes model (T2DM) still needs to be explored for basic and clinical research, due to nonuniform model methods and unstable consequences. Our aims were to explore and establish an optimized induced T2DM model in mice that exhibits insulin resistance and ß-cell damage. MATERIALS AND METHODS: C57BL/6 mice were treated with a high-fat diet (HFD), streptozotocin (STZ) and dexamethasone (DEX) at different doses and in combination. The general growth status, blood glucose and fasting insulin were detected, and the success rate and insulin sensitivity indices were calculated. KEY FINDING: Low-dose STZ injection multiple times was more secure in the process of T2DM model production. Combined intervention was more efficient in reducing insulin sensitivity and improving the success rate of T2DM model construction. SIGNIFICANCE: Combined with a high-fat diet, glucocorticoids and streptozotocin, a new mouse model of T2DM with insulin resistance and ß-cell damage could be established. The optimized experimental method can serve as a stable model for further studies on the mechanisms and therapy of T2DM.

Distribution of normal and pathological OGTTs among pregnant population and non-pregnant women with PCOS - the cross-sectional study.

ABSTRACT: Both pregnancy, as physiological, and polycystic ovary syndrome (PCOS), as a pathological condition, carry the risk for developing glucose metabolism abnormalities. In this retrospective cross-sectional study, we hypothesized that pregnancy as a physiological condition carries a higher likelihood for abnormal oral glucose tolerance test (OGTT) results than PCOS as a pathological condition.We have compared the prevalence and likelihood ratios for abnormal OGTT results between non-pregnant women with PCOS (Group A) and pregnant women at 24 to 28 weeks of gestation (Group B). Participants of both study groups underwent glucose tolerance testing with 75 g glucose OGTT. During the study period, 7411 women were tested, 3932 women encompassed Group A, and 3479 women comprised Group B.The numbers of yearly tested pregnant women and the corresponding proportion of tested women among all study participants have decreased during the study period, from 766 to 131 and 89.1% to 20.5%, respectively. Group A had a significantly lower prevalence (4.4%) of pathological OGTT results compared to Group B (8.1%). This has resulted in a 45.427 likelihood ratio (P < .001) for abnormal OGTT results in pregnant women compared to non-pregnant women with PCOS.We might conclude that pregnancy could have a more challenging influence on glucose metabolism and that carries higher risks for abnormal glucose metabolism than PCOS. The awareness of obstetricians regarding physiological changes during pregnancy that predisposes abnormal glucose metabolism is decreasing over time and the compliance concerning OGTT testing of pregnant women is decreasing too.

First trimester glycosylated hemoglobin for gestational diabetes mellitus screening.

OBJECTIVE: Our aim in this study is to evaluate the efficacy of HbA1c in screening for GDM during the first trimester of pregnancy. MATERIALS AND METHODS: In this retrospective cohort study, we evaluated the first trimester HbA1c (ft-HbA1c) levels of 195 pregnant women who attended our university hospital's obstetrics clinic. Blood samples were drawn from patients during 11-14 weeks of gestation. After that, all patients were screened using standardized one-step 75gr OGTT between 24 and 28 weeks of pregnancy. RESULTS: In this study, 195 pregnant women were included. Thirty-two (16.4%) of the women included in this study were diagnosed with GDM. The mean ft-HbA1c level was 5.52% in those who developed GDM and 5.21% in those who did not develop GDM (p = 0.000). Only seven (3.6%) of the women included in this study had an ft-HbA1c level above the prediabetes limit of 5.7%. All these women with prediabetes developed GDM. The cut-off value for ft-HbA1c to distinguish GDM was 5,33%. For this cut-off value, the sensitivity was 71.9%, and the specificity was 82.8%. CONCLUSION: The findings suggest that ft-HbA1c level is a promising biomarker for GDM screening. Especially, patients with ft-HbA1c level ≥5.33% are at increased risk for developing GDM.

The 1-Hour Plasma Glucose: Common Link Across the Glycemic Spectrum.

Evidence from populations at risk for type 1 diabetes, type 2 diabetes or gestational diabetes substantiates the 1-hour plasma glucose as a sensitive alternative marker for identifying high-risk individuals when ß-cell function is relatively more functional. An elevated 1-hour plasma glucose could therefore diagnose dysglycemia and risk for complications across the glycemic spectrum. Reducing the 2-hour oral glucose tolerance test to 1-hour would reduce the burden on patients, likely reduce costs, and enhance its accessibility in practice.