Increased Fasting Plasma Glucose Research Articles

The Plasma Glucose Threshold Values Associated with Adverse Pregnancy Outcomes Among Asian Indian Pregnant Women: MAASTHI Birth Cohort Analysis.

To assess the association of adverse pregnancy and infant outcomes with different cut-off levels of glucose intolerance during pregnancy in the MAASTHI cohort. Pregnant women (n = 1470) underwent Oral glucose tolerance test between 24 and 36 weeks using a 75-g oral glucose load, with plasma glucose estimations measured at fasting and two hours later. Follow-up was done within 72 hours of delivery for recording type of delivery, infant weight, mid-upper arm circumference, and skinfold thickness. The odds of having higher skinfold thickness (>90th percentile) were 43% higher (AOR = 1.43; 95% CI: 1.18, 1.74) and the odds of being overweight at birth was 34% higher (AOR = 1.34; 95% CI: 1.09, 1.62) for every 1 standard deviation (9.9 mg/dL) increase in fasting plasma glucose (FPG) in male infants. The odds of delivering via caesarean section were 45% higher in women with female foetus (1.45,95% CI 1.15,1.82) for every one SD (23.4 mg/dl) increase in 2-h post-load Glucose. The impact of maternal glucose levels on infant and maternal outcomes differed notably between sex of the child. Compared to female infants, male infants exhibited a stronger association with elevated risks for adverse outcomes, including higher infant weight and increased skinfold thickness.

Patients with autoimmune liver disease have glucose disturbances that mechanistically differ from steatotic liver disease.

Autoimmune liver diseases are associated with an increased risk of diabetes, yet the underlying mechanisms remain unknown. In this cross-sectional study, we investigated the glucose-regulatory disturbances in patients with autoimmune hepatitis (AIH, n = 19), primary biliary cholangitis (PBC, n = 15), and primary sclerosing cholangitis (PSC, n = 6). Healthy individuals (n = 24) and patients with metabolic dysfunction-associated steatotic liver disease (MASLD, n = 18) were included as controls. Blood samples were collected during a 120-min oral glucose tolerance test. We measured the concentrations of glucose, C-peptide, insulin, glucagon, and the two incretin hormones, glucose insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1). We calculated the homeostasis model assessment of insulin resistance (HOMA-IR), whole body insulin resistance (Matsuda index), insulin clearance, and insulinogenic index. All patient groups had increased fasting plasma glucose and impaired glucose responses compared with healthy controls. Beta-cell secretion was increased in AIH, PBC, and MASLD but not in PSC. Patients with AIH and MASLD had hyperglucagonemia and hepatic, as well as peripheral, insulin resistance and decreased insulin clearance, resulting in hyperinsulinemia. Patients with autoimmune liver disease had an increased GIP response, and those with AIH or PBC had an increased GLP-1 response. Our data demonstrate that the mechanism underlying glucose disturbances in patients with autoimmune liver disease differs from that underlying MASLD, including compensatory incretin responses in patients with autoimmune liver disease. Our results suggest that glucose disturbances are present at an early stage of the disease.NEW & NOTEWORTHY Patients with autoimmune liver disease but without overt diabetes display glucose disturbances early on in their disease course. We identified pathophysiological traits specific to these patients including altered incretin responses.

Mean platelet volume (MPV) as new marker of diabetic macrovascular complications in patients with different glucose homeostasis

BackgroundPlatelets play an important role in the development of cardiovascular disease (CVD). Mean platelet volume (MPV) is considered as biological marker of platelets activity and function. The aim of the present study was to evaluate MPV values and its possible correlation with arterial stiffness and subclinical myocardial damage, in normal glucose tolerance patients (NGT), in newly diagnosed type 2 diabetic (T2DM) patients and in individuals with pre-diabetes.MethodsWe enrolled 400 newly diagnosed hypertensive patients. All patients underwent an Oral Glucose Tolerance test (OGTT). Arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV), augmentation pressure (AP) and augmentation index (AI). Echocardiographic recordings were performed using an E-95 Pro ultrasound system.ResultsAmong groups there was an increase in fasting plasma glucose (FPG) (p < 0.0001), fasting plasma insulin (FPI) (p < 0.0001), high sensitivity c reactive protein (hs-CRP) levels (p < 0.0001) and a decrease in renal function as demonstrated by e-GFR values (p < 0.0001). From the NGT group to the T2DM group there was a rise in MPV value (p < 0.0001). Moreover, in the evaluation of arterial stiffness and subclinical myocardial damage, MPV showed a positive correlation with these parameters.ConclusionsIn the present study we highlighted that MPV is significantly increased, not only in newly diagnosed T2DM patients, but also in early stage of diabetes, indicating that subjects with pre-diabetes present increased platelets reactivity. Moreover, our results suggest that MPV is associated with increased arterial stiffness and subclinical myocardial damage, indicating MPV as new marker of CV risk.

Supplementation of papaya leaf juice has beneficial effects on glucose homeostasis in high fat/high sugar-induced obese and prediabetic adult mice

Prediabetes is characterized by a cluster of glycemic parameters higher than normal but below the threshold of type 2 diabetes mellitus (T2DM). In recent years, phytochemical-rich plant extracts have gained popularity as therapeutic agents for metabolic disorders. This study investigated the effects of papaya leaf (PL) juice supplementation on blood glucose levels in diet-induced obese and prediabetic adult mice. B65JL F1 mice (n = 20) at 12–14 months old were fed a high fat/sugar diet (HFHS) for 120 days. Mice were switched to restricted rodent chow of 3 g feed/30 g body weight/day, supplemented with 3 g/100 mL PL juice for 30 days. HFHS diet remarkably increased fasting plasma glucose levels from 114 ± 6.54 mg/dL to 192.7 ± 10.1 mg/dL and body weight from 32.5 ± 1.6 to 50.3 ± 4.1 g. HFHS diet results in hyperglycemia, insulin resistance, hyperlipidemia, and liver steatosis. The combination of PL juice and restricted diet significantly reduced body weight and fasting blood glucose levels to 43.75 ± 1.4 g and 126.25 ± 3.2 mg/dl, respectively. Moreover, PL juice with a restricted diet significantly improved lipid profile: cholesterol from 204 to 150 mg/dL, LDL-c from 110.4 to 50 mg/dL, and triglyceride from 93.7 to 60 mg/dL. Additionally, PL juice combined with a restricted diet significantly reduced adiposity, reversed fatty liver, and restored skeletal muscle Glut4 and phosphorylated (p-AKT (ser473). This study demonstrated that supplementation of PL juice with a restricted diet was more effective than a restricted diet alone in reversing major symptoms related to prediabetic and obesity conditions.

Association of Dietary Patterns with Metabolic Syndrome among Middle-Aged Adults in Shiraz, Iran: Shiraz Heart Study (SHS).

Metabolic syndrome (MetS) is a noncommunicable disease with a high burden, including the development of type 2 diabetes mellitus, cardiovascular events, and death. It is characterized by abdominal obesity, elevated blood pressure, increased fasting plasma glucose levels, hypertriglyceridemia, and reduced levels of high-density lipoprotein (HDL) cholesterol. MetS is preventable by modifying lifestyle and dietary patterns, which are major contributing factors. This research aimed to investigate the dietary patterns of the Shiraz Heart Study (SHS) and their associations with the occurrence of MetS and its components among middle-aged residents of Shiraz. Based on data from the Shiraz Heart Study (SHS), a prospective cohort study, the nutritional status of 1,675 participants was assessed using a food frequency questionnaire (FFQ). Three food patterns were extracted from the analysis named as vegan, western, and carbohydrate. Subjects were categorized into three levels for three major dietary patterns: low, moderate, and high, based on their adherence to each pattern. After adjusting the effect of co-founder variables, the relationship between dietary patterns, and the risk of developing MetS was analyzed. Of the 1,675 participants, 728 (43.5%) of them were male. The prevalence of MetS was 47.2%. Multivariate logistic regression analysis showed that high adherence to the vegan pattern was negatively associated with the occurrence of MetS (P value <0.001), while low adherence to the western pattern was also negatively associated (P value <0.05). Healthier diets, such as vegan diets, are significantly related to lower rates of MetS among the 40-70-year-old people in Shiraz, Iran.

Association of Chronic Hyperglycemia With the Risk of Urolithiasis.

Background The incidence of urolithiasis is increasing along with elevated rates of chronic hyperglycemia. Therefore, this study aimed to assess the association between high hemoglobin Alc (HbAlc) levels, in the form of type 2 diabetes mellitus (T2DM), and the risk of kidney stone formation among those living in the Eastern Province of Saudi Arabia. Methodology We conducted a cross-sectional study on a total of 501 patients with known cases of urolithiasis who visited King Fahad University Hospital (Khabar, Saudi Arabia). We calculated odds ratios (ORs) of having stones with respect to three parameters, namely, fasting blood glucose level, random blood glucose level, and glycosylated HbA1c testing. Results Of the 501 cases with urinary stones included in this study, the majority (223, 44.5%) were 41-59 years of age, and 350 (69.9%) were males. Our results showed that T2DM was significantly associated with high stone burden, with increased fasting plasma glucose, increased random blood glucose, and increased HbA1c being strong predictors. The significant associations between glycemic control measures and the risk of urolithiasis remained even after adjusting for factors related to insulin resistance. Conclusions According to our results, glycemiccontrol can be an independent risk factor for urolithiasis. This critical finding demonstrates the need for further studies to investigate this particular group of patients.

Prevalence of metabolic syndrome and metabolic dysfunction-associated fatty liver disease in Malaysia 2023: study protocol for a community-based nationwide cross-sectional survey

IntroductionMetabolic syndrome (MetS) is a cluster of cardio-metabolic dysfunctions characterised by increased fasting plasma glucose, waist circumference, blood pressure, triglycerides and reduction in high-density lipoprotein cholesterol. Meanwhile, metabolic dysfunction-associated fatty...

Prevalence and risk factors for impaired renal function among Asian patients with nonalcoholic fatty liver disease

BackgroundNonalcoholic fatty liver disease (NAFLD) is associated with impaired renal function, and both diseases often occur alongside other metabolic disorders. However, the prevalence and risk factors for impaired renal function in patients with NAFLD remain unclear. The objective of this study was to identify the prevalence and risk factors for renal impairment in NAFLD patients. MethodsAll adults aged 18–70 years with ultrasound-diagnosed NAFLD and transient elastography examination from eight Asian centers were enrolled in this prospective study. Liver fibrosis and cirrhosis were assessed by FibroScan-aspartate aminotransferase (FAST), Agile 3+ and Agile 4 scores. Impaired renal function and chronic kidney disease (CKD) were defined by an estimated glomerular filtration rate (eGFR) with value of < 90 mL/min/1.73 m2 and < 60 mL/min/1.73 m2, respectively, as estimated by the CKD-Epidemiology Collaboration (CKD-EPI) equation. ResultsAmong 529 included NAFLD patients, the prevalence rates of impaired renal function and CKD were 37.4% and 4.9%, respectively. In multivariate analysis, a moderate-high risk of advanced liver fibrosis and cirrhosis according to Agile 3+ and Agile 4 scores were independent risk factors for CKD (P< 0.05). Furthermore, increased fasting plasma glucose (FPG) and blood pressure were significantly associated with impaired renal function after controlling for the other components of metabolic syndrome (P< 0.05). Compared with patients with normoglycemia, those with prediabetes [FPG ≥ 5.6 mmol/L or hemoglobin A1c (HbA1c) ≥ 5.7%] were more likely to have impaired renal function (P< 0.05). ConclusionsAgile 3+ and Agile 4 are reliable for identifying NAFLD patients with high risk of CKD. Early glycemic control in the prediabetic stage might have a potential renoprotective role in these patients.

The Association between Personality Factors and Metabolic Parameters among Patients with Non-Alcoholic-Fatty Liver Disease and Type 2 Diabetes Mellitus-A Cross-Sectional Study.

The increasing prevalence of type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD) states a serious problem for public health. The introduction of effective methods of treatment and prevention is crucial to avoid complications of these diseases. Among them, we can specify psychological factors that affect everyday life and determine the patient's attitude towards therapy, and what follows, their compliance in treatment. The literature indicates these connections in various ways; in our study, we extend this view to include a broader perspective of human personality. We decided to investigate the associations between personality factors and metabolic parameters in patients with NAFLD and T2DM in order to better understand the patient's approach to the treatment of a chronic disease, such as those mentioned, and to establish the basis for further research implementing psychological interventions in the treatment of NAFLD and T2DM. One hundred participants with NAFLD and T2DM underwent blood tests and anthropometric measures. Each of them was asked to complete five questionnaires evaluating their personality properties. We revealed that a rise in body mass index is related to a fall in the emotional intelligence factor of utilizing emotions, and a rise in emotional perception. The decrease in task-oriented coping style and a rise in emotion-oriented coping style are associated with a waist-hip ratio increase. The increase in fasting plasma glucose is predicted by a decrease in task-oriented coping style score. A fall in social diversion coping style score is associated with a high-density lipoprotein increase; in turn, a triglycerides increase is connected with a decline in rhythmicity score. The personality factors are in relationship in the management of NAFLD and T2DM. They affect a patient's approach to treatment, which is very important, because we know lifestyle and dietary interventions are an important part of the treatment of these diseases. The compliance manifests by lifestyle modifications, taking medications regularly, measuring blood glucose, and inspection visits in outpatients' clinics are a large part of a diabetic's life. Future studies introducing psychological intervention to improve, e.g., coping styles or rhythmicity are needed to implement new methods of patient management.

Rare Heterozygous Loss-of-Function Variants in the Human GLP-1 Receptor Are Not Associated With Cardiometabolic Phenotypes.

Lost glucagon-like peptide 1 receptor (GLP-1R) function affects human physiology. This work aimed to identify coding nonsynonymous GLP1R variants in Danish individuals to link their in vitro phenotypes and clinical phenotypic associations. We sequenced GLP1R in 8642 Danish individuals with type 2 diabetes or normal glucose tolerance and examined the ability of nonsynonymous variants to bind GLP-1 and to signal in transfected cells via cyclic adenosine monophosphate (cAMP) formation and β-arrestin recruitment. We performed a cross-sectional study between the burden of loss-of-signaling (LoS) variants and cardiometabolic phenotypes in 2930 patients with type 2 diabetes and 5712 participants in a population-based cohort. Furthermore, we studied the association between cardiometabolic phenotypes and the burden of the LoS variants and 60 partly overlapping predicted loss-of-function (pLoF) GLP1R variants found in 330 566 unrelated White exome-sequenced participants in the UK Biobank cohort. We identified 36 nonsynonymous variants in GLP1R, of which 10 had a statistically significant loss in GLP-1-induced cAMP signaling compared to wild-type. However, no association was observed between the LoS variants and type 2 diabetes, although LoS variant carriers had a minor increased fasting plasma glucose level. Moreover, pLoF variants from the UK Biobank also did not reveal substantial cardiometabolic associations, despite a small effect on glycated hemoglobin A1c. Since no homozygous LoS nor pLoF variants were identified and heterozygous carriers had similar cardiometabolic phenotype as noncarriers, we conclude that GLP-1R may be of particular importance in human physiology, due to a potential evolutionary intolerance of harmful homozygous GLP1R variants.

Association between Maternal Blood Glucose Levels during Pregnancy and Birth Outcomes: A Birth Cohort Study.

This study aimed to investigate the relationship between maternal blood glucose levels during pregnancy and neonatal birth outcomes in Northwest China. This population-based cohort study included 10,010 first-trimester pregnant women who joined the birth cohort of the Northwest Women's and Children's Hospital from July 2018 to July 2020. Basic demographic characteristics, lifestyle and behavior patterns were collected. Oral glucose tolerance test (OGTT) results during the second trimester and pregnancy outcomes after childbirth were also collected. A generalized linear model was constructed to analyze the effects of blood glucose levels on neonatal birth outcomes. We found that every 1 mmol/L increase in fasting plasma glucose (FPG) was associated with an increase in birth weight (β = 100.22 g, 95% confidence interval (95%CI): 81.91, 118.52), birth weight Z score (β = 0.23, 95%CI: 0.19, 0.27) and birth weight Z centile (β = 6.72%, 95%CI: 5.51, 7.94). Moreover, the risk of macrosomia, premature birth and being born large for gestational age (LGA) increased by 2.01 (95%CI: 1.67, 2.43), 1.35 (95%CI: 1.09, 1.66) and 1.80 (95%CI: 1.57, 2.07) times, respectively. Additionally, for every 1 mmol/L increase in FPG associated with a decrease in gestational age (β = -0.12 weeks, 95%CI: -0.19, -0.06), the risk of SGA decreased by 0.70 (OR = 0.70, 95%CI: 0.55, 0.89) times. Every 1 mmol/L increase in 1/2-h PG had similar outcomes as FPG, besides premature birth and SGA. Higher blood glucose in pregnant women may increase neonatal birth weight, decrease gestational age and lead to a higher risk of macrosomia, premature birth and LGA. Mothers should actively prevent and control hyperglycemia to promote maternal and infant health.

Risk of fatal and non-fatal cardiovascular events in men aged 25-44 in the city of Novosibirsk. Cohort study

Aim. To study the incidence and risk factors of cardiovascular events (CVEs) during an 8-year follow-up of a cohort of men aged 25-44 years (Novosibirsk).Material and methods. The cohort study included 1415 people aged 37,33 [31,83; 41,92] years (Median, Me [interquartile range, Q25; Q75], of which 670 (47,3%) were men. Median follow-up period was 6,9 [5,8; 7,8] years. CVEs were identified using the "Registry of Acute Myocardial Infarction", fatal cases — from the "Medical Certificates of Cause of Death". The examination program included a questionnaire, anthropometry, biochemical studies. Statistical processing was carried out using SPSS (version 13.0).Results. Thirteen CVEs were identified, of which 6 were fatal. Survival prognosis was more favorable in men without hypertension, with a heart rate (HR) &lt;80 bpm. The risk of CVEs increased by 14% with an increase in fasting plasma glucose by 0,5 mmol/l, by 1,8 times with creatinine increase by 10 pmol/l (decreased by 29% with an increase in glomerular filtration rate by 5 ml/min /1,73 m2); 2 times with a heart rate increase by 10 bpm, regardless of other cardiometabolic risk factors.Conclusion. Significant risk factors for fatal and non-fatal CVEs in men aged 25-44 years are hypertension, heart rate &gt;80 bpm, increased fasting plasma glucose, creatinine levels (or decreased glomerular filtration rate).

Effect of acute TLR4 inhibition on insulin resistance in humans.

BackgroundStudies in cell cultures and rodents suggest that TLR4 is involved in the pathogenesis of insulin resistance, but direct data in humans are limited. We tested the hypothesis that pharmacologic blockade of TLR4 with the competitive inhibitor eritoran would improve insulin resistance in humans.MethodsIn protocol I, 10 lean, healthy individuals received the following 72-hour i.v. infusions in a randomized crossover design: saline (30 mL/h) plus vehicle; Intralipid (30 mL/h) plus vehicle; or Intralipid (30 mL/h) plus eritoran (12 mg i.v. every 12 hours). In protocol II, also a randomized crossover design, 9 nondiabetic individuals with obesity received eritoran or vehicle for 72 hours. The effect of eritoran was assessed with euglycemic hyperinsulinemic clamps.ResultsIn protocol I, lipid infusion significantly decreased peripheral insulin sensitivity (M value) by 14% and increased fasting plasma glucose (FPG) concentrations, fasting plasma insulin (FPI) concentrations, and the homeostatic model assessment of insulin resistance (HOMA-IR) index by 7%, 22%, and 26%, respectively. Eritoran did not prevent lipid-induced alterations of these metabolic parameters. Eritoran also failed to improve any baseline metabolic parameters (M, FPG, FPI, HOMA-IR) in individuals with obesity and insulin resistance (protocol II).ConclusionsAcute TLR4 inhibition with eritoran did not protect against lipid-induced insulin resistance. Short-term eritoran administration also failed to improve obesity-associated insulin resistance. These data do not support a role for TLR4 in insulin resistance. Future studies with a different class of TLR4 inhibitors, longer drug exposure, and/or lipid-enhancing interventions richer in saturated fats may be needed to further clarify the role of TLR4 in metabolic dysfunction in humans.Trial registrationClinicalTrials.gov NCT02321111 and NCT02267317.FundingNIH grants R01DK080157, P30AG044271, P30AG013319, and UL1TR002645.

Impact of Germinated Brown Rice and Brown Rice on Metabolism, Inflammation, and Gut Microbiome in High Fat Diet-Induced Insulin Resistant Mice.

The constituents of germinated brown rice (GBR), brown rice (BRR), and white rice (WHR) and their impact on metabolism, inflammation, and gut microbiota in high fat (HF) diet-fed mice were examined. The contents of total fiber and γ-aminobutyric acid in BRR and GBR were higher than that in WHR (p < 0.05). Male C57 BL/6J mice received HF diet+26 g% of WHR, BRR, or GBR for 12 weeks. BRR and GBR comparably reduced HF diet-induced increases in fasting plasma glucose, lipids, insulin resistance, and inflammatory markers compared to WHR (p < 0.01). The abundance of fecal Bacteroidetes in mice fed HF+GBR or HF+BRR was higher than in HF+WHR-fed mice (p < 0.05). The abundance of fecal Lactobacillus gasseri in GBR-fed mice was greater than that in WHR- or BRR-fed mice (p < 0.05). The results indicated that GBR or BRR attenuated hyperglycemia, insulin resistance, and inflammation in mice. HF+GBR, but not HF+BRR, increased a probiotic bacteria in the gut.

Increased Fasting Plasma Glucose and Breast Cancer Risk in Sudanese Women: Association with Premenopausal Status and High Body Mass Index

Background: Female breast cancer is the most common cancer in Sudan, however little data is available about breast cancer in Sudanese. We aimed to assess whether fasting glucose and insulin levels are associated with the risk of having breast cancer in Sudanese women.Methods: This study was conducted at the National Cancer Institute – University of Gezira (NCI-UG), Sudan. A total of 174 females were enrolled, the patient group included 77 newly diagnosed untreated breast cancer women and a control group of 97 healthy women. Overnight fasting blood samples were collected to measure fasting plasma glucose and serum insulin levels. Results: The fasting plasma glucose level was significantly increased in the breast cancer patients (101.94±2.94 mg/dL) than the controls (90.75±2.02 mg/dL), p=0.002. Overweight-obese and premenopausal breast cancer patient’s subgroups revealed significant elevation of fasting glucose levels (105.35±4.06 mg/dL); (99.64±4.06 mg/dL) compared to controls (89.44±2.62 mg/dL), p=0.001; and (86.38±2.44 mg/dL), p=0.007 respectively. Only in the non-obese patients the insulin level was significantly lower (3.76±0.40 µU/ml) than in the control (6.11±1.00 µU/ml) p=0.034. The patient group was more likely to have 2.5 times higher fasting glucose level than the control (p=0.005). Moreover, the overweight-obese and premenopausal breast cancer patients subgroups were more likely to have 4.4 times and 4.5 times respectively elevated fasting blood glucose level, both with p=0.002. The non-obese breast cancer patients were tended to have 4.3 times decreased insulin level (p=0.019). Conclusion: The elevated fasting plasma glucose levels are associated with high risk of breast cancer in Sudanese women especially in the premenopausal individuals and those having BMI more than or equal to 25 kg/m2. Consequently, adjusting blood glucose level and controlling body weight by changing the lifestyle are suggested to reduce the risk of breast cancer in Sudanese women.

Smoking causes the disorder of glucose metabolism under different levels of blood pressure in male occupational population.

Smoking is an important modifiable factor in the risk of type 2 diabetes. Type 2 diabetes and hypertension overlap in the population. The present study investigated effects of smoking on glucose metabolism under different blood pressure (BP) levels in occupational population. A smoking survey among occupational groups was conducted in 2018. The general linear model was used to analyze the differences of glucose metabolism indexes and BP indexes influenced by different smoking intensity (never 0, mild <10, moderate <20, heavy ≥20 pack‐years). Odds ratios of developing diabetes and β‐cell deficiency were analyzed by using logistic regression model. BP was further taken into account in the relationship between smoking and glucose metabolism. As a result, 1730 male workers aged 21 to 60 years were included in the analysis finally. Compared to never smokers, heavy smokers had significantly increased fasting plasma glucose. Moderate and above smokers had significantly increased glycosylated hemoglobin, decreased fasting plasma insulin and β‐cell function, after adjustment for covariates. Further, smoking intensity was found to have a dose‐dependent relationship with impaired β‐cell function and diabetes. In conclusion, smoking has a positive dose‐dependent relationship with β‐cell deficiency and diabetes. Male smoking workers, especially the moderate or higher smoking, with high‐normal and high BP levels are at high risk of abnormal glucose metabolism.

106-OR: Fetal Sex Influences Maternal Insulin and Glucose Metabolism in Pregnancy

Aims and Hypothesis: Women carrying a male fetus are suggested to have altered maternal glucose and insulin dynamics and increased rates of GDM, but current literature remains inconclusive. We aimed to determine the relationship between fetal sex and maternal glucose and insulin metabolism and assess whether inclusion of fetal sex improves prediction of IADPSG GDM. Methods: Using blinded data from five Hyperglycaemia and Adverse Pregnancy Outcome study centres, we examined maternal metabolic data at mean gestational week 28 in 6337 untreated women. Stratifying women by either male (n = 3273) or female fetus (n = 3064) we analysed data from the 75g OGTT, estimates of insulin secretion (Stumvoll first phase) and sensitivity (Matsuda index) and their product (oral Disposition index) using multiple linear regression analysis. To assess the relationship and predictive ability of fetal sex and GDM we utilised multiple logistic regression and receiver operating characteristic curve analysis. Results: Women carrying a male fetus were found to have a modest increase in fasting plasma glucose (4.52 vs. 4.44 mmol/L; P=0.008) and 1 h glucose (7.57 vs. 7.46 mmol/L; P=0.015) during OGTT which translated into an overall increase in the OGTT z score (0.vs. 0.02; P=0.005) . The Matsuda (β: -0.06; 95% CI [-0.10, -0.02]; P=0.008) and oral Disposition index (β: -0.07; 95% CI [-0.11, -0.02]; P=0.005) were significantly reduced in women carrying a male fetus after correction for established maternal clinical risk factors. Women carrying a male fetus were not at higher odds of developing GDM in adjusted (aOR: 1.04; 95% CI [0.9, 1.19]; P=0.6) or unadjusted (OR: 1.09; 95% CI [0.96, 1.25]; P=0.16) models. Conclusion/interpretation: The male fetus is associated with increased maternal fasting and postprandial glucose with concomitant decreased insulin sensitivity and β-cell compensation. The alterations in maternal glucose and insulin dynamics associated with having a male fetus does not translate into a clinical diagnosis of GDM. Disclosure T.P.Mullins: None. K.S.Gibbons: None. L.R.Madsen: None. R.C.Ma: Other Relationship; Bayer AG, Boehringer Ingelheim International GmbH, Research Support; AstraZeneca, Bayer AG, Novo Nordisk A/S, Pfizer Inc., Tricida, Inc. W.H.Tam: None. P.Catalano: None. D.A.Sacks: None. H.L.Barrett: None. D.Mcintyre: None.

206-LB: Increase of Hexokinase-2 Protein without Increase of Other Glycolytic Enzymes in Myotubes with High Glucose Concentration Supports the Hypothesis of Hexokinase-2-Linked Unscheduled Glycolysis as a Driver of Insulin Resistance

Insulin resistance in skeletal muscle is the major metabolic defect leading to the development of type 2 diabetes. The initiating dysfunction driving development of insulin resistance has not been disclosed. Recently, stabilization of hexokinase-2 (HK2) to proteolysis by increased glucose concentration, increasing flux through early-stage glycolysis without increase in expression and activity of other glycolytic enzymes, was identified as the initiator of metabolic dysfunction in hyperglycemia. This creates a wave of increased glycolytic intermediates activating hexosamine and protein kinase C pathways and increasing formation of methylglyoxal. Increased glucose-6-phosphate displaces HK2 from mitochondria, producing mitochondrial hyperpolarization and dysfunction. This is termed HK2-linked unscheduled glycolysis. Skeletal muscle exposed to increased fasting plasma glucose may stimulate this. To test this, we studied glycolytic enzyme abundance in murine C2C12 myotubes incubated with 5.5 and 25 mM glucose for 5 days, determining HK2 protein changes by Western blotting, normalized to ß-actin. Protein abundances in C2C12 myotube cultures with 5.5, 11.1 and 25.0 mM glucose determined by label-free quantitative mass spectrometry proteomics were mined from published data. In C2C12 myotubes, HK2 protein increased 46 ± 5 % in 25 mM glucose (P&amp;lt;0.001, n = 3; Western blotting) . Proteomics corroborated this with 1.5 and 1.8 fold increase of HK2 in 11.1 and 25.0 mM glucose cultures, compared to 5.5. mM glucose control (P&amp;lt;0.01, n = 3) . Abundances of other glycolytic enzymes, hexokinase-1, glucose-6-phosphate isomerase, phosphofructokinase, aldolase, triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase, were unchanged. This establishes the conditions for HK2-linked glycolytic overload. We conclude that high glucose concentration in C2C12 myotubes in vitro exhibits conditions producing hexokinase-2-linked unscheduled glycolysis Disclosure M. Xue: None. N. Rabbani: None. P. Thornalley: None. Funding Qatar Foundation, QB14Qatar University, QUHI-CMED-21_22-1

Worsening Glycemia Increases the Odds of Intermittent but Not Persistent Staphylococcus aureus Nasal Carriage in Two Cohorts of Mexican American Adults.

ABSTRACTNumerous host and environmental factors contribute to persistent and intermittent nasal Staphylococcus aureus carriage in humans. The effects of worsening glycemia on the odds of S. aureus intermittent and persistent nasal carriage was established in two cohorts from an adult Mexican American population living in Starr County, Texas. The anterior nares were sampled at two time points and the presence of S. aureus determined by laboratory culture and spa-typing. Persistent carriers were defined by the presence of S. aureus of the same spa-type at both time points, intermittent carriers were S. aureus-positive for 1 of 2 swabs, and noncarriers were negative for S. aureus at both time points. Diabetes status was obtained through personal interview and physical examination that included a blood draw for the determination of percent glycated hemoglobin A1c (%HbA1c), fasting plasma glucose, and other blood chemistry values. Using logistic regression and general estimating equations, the odds of persistent and intermittent nasal carriage compared to noncarriers across the glycemic spectrum was determined controlling for covariates. Increasing fasting plasma glucose and %HbA1c in the primary and replication cohort, respectively, were significantly associated with increasing odds of S. aureus intermittent, but not persistent nasal carriage. These data suggest that increasing dysglycemia is a risk factor for intermittent S. aureus nasal carriage potentially placing those with poorly controlled diabetes at an increased risk of acquiring an S. aureus infection.IMPORTANCE Factors affecting nasal S. aureus colonization have been studied primarily in the context of persistent carriage. In contrast, few studies have examined factors affecting intermittent nasal carriage with this pathogen. This study demonstrates that the odds of intermittent but not persistent nasal carriage of S. aureus significantly increases with worsening measures of dysglycemia. This is important in the context of poorly controlled diabetes since the risk of becoming colonized with one of the primary organisms associated with diabetic foot infections can lead to increased morbidity and mortality.

Metabolic syndrome and underlying genetic determinants-A systematic review.

The metabolic syndrome is a cluster of heritable and related traits which has been associated with a range of pathophysiological factors including dyslipidaemia, abdominal obesity, increased fasting plasma glucose (FPG) and hypertension. The documented genetic basis of the metabolic syndrome include several chromosomal positions, numerous candidate gene-associated polymorphisms, different genetic variants, which are linked to the syndrome either as a trait or entities mainly linked to metabolic process. Additionally, the latest findings related to the contribution of epigenetic mechanisms, microRNAs, sporadic variants, non-coding RNAs, and assessing the role of genes in molecular systems has enhanced our understanding of the syndrome. Considerable work has been done to understand the underlying disease mechanisms by elucidating its genetic etiology. Nonetheless, a common shared genetic cause has not been established to clarify the coexistence of their components and further investigation is required. While mostly neglected and rarely known, hereditary predisposition needs to be studied, including with the current defective phenotypic condition descriptions. Metabolic syndrome is a multi-faceted characteristic with abundant properties and the condition can arise from interactions between environmental variables such as physical inactivity, caloric obesity and genetic susceptibility. Although there is support for genetic determinants from family and twin research, there is still no recognised genomic DNA marker for genetic association and linkages with quite a long way off potential for clinical application. In the present review efforts have been made to through light on the various genetic determinants with large effects that underlie with the association of these traits to this syndrome. The heterogeneity and multifactorial heritability of MetS, however, has been a challenge towards understanding the factors underlying the association of these traits.