Diabetes Glucose Tolerance Research Articles

Influence of impaired glucose tolerance and type 2 diabetes on the multimorbidity cluster of cardiovascular disease and cancer: a post hoc analysis of the Da Qing Diabetes Prevention Outcome Study

BackgroundThis study explored the influence of type 2 diabetes and impaired glucose tolerance (IGT) on the risk of the multimorbidity cluster of cardiovascular disease (CVD) and cancer.MethodsA total of 1629 participants in the Da Qing Diabetes Prevention Outcome Study were recruited in the present analysis, including normal glucose tolerance (NGT, N = 492), IGT (N = 540), and newly diagnosed type 2 diabetes (N = 597) groups. Cox proportional hazards analyses were performed to assess the relationship between NGT, IGT, and newly diagnosed type 2 diabetes and the risk of the multimorbidity cluster of CVD and cancer.ResultsThe incidence rates for multimorbidity cluster CVD and cancer were 1.25, 3.17, and 3.23 per 1000 person-years in people with NGT, IGT, and the newly diagnosed type 2 diabetes groups, respectively, over 34-year follow-up. Cox analysis revealed that diabetes status (as time-dependent variable) was significantly associated with the subsequent increased risk of multimorbidity cluster of CVD and cancer compared with non-diabetes (hazard ratios [HR] = 2.55, 95% confidence interval [CI] 1.51–4.31) after adjustment of potential confounders. Similar analysis showed that this risk was significantly higher in the IGT and newly diagnosed type 2 diabetes groups compared with NGT, with HR of 3.28 (95% CI 1.83–5.87) and HR of 3.90 (95% CI 2.14–7.09), respectively. Whereas compared diabetes with IGT group, this risk was not significantly different.ConclusionsSimilar to newly diagnosed type 2 diabetes, IGT is significantly associated with an increased risk of the multimorbidity cluster of CVD and cancer compared with NGT. This finding highlights the urgent need for an active detection of IGT and effective prevention and management of diabetes.

Glucose inhibitor tubes in Croatian laboratories: are we doing well?

Reliable and accurate measurement of blood glucose concentration is of crucial importance for making clinical decisions in diagnosis diabetes, gestational diabetes and impaired fasting glucose tolerance. Survey was performed in form of questionnaire. Questionnaire was sent to all Croatian laboratories (N = 204) in electronic form using SurveyMonkey cloud-based software (SurveyMonkey, Inc., San Mateo, USA) as an extra-analytical module of the Croatian EQA (External Quality Assessment) provider Croatian center for external quality assessment (CROQALM) in June 2023. In total 148 (73%) of laboratories responded to the survey. Large proportion of laboratories never use glucose inhibitor tubes for random glucose measurement (more than half) or for glucose function tests (one quarter). Only three laboratories use recommended glycolysis inhibitor citrate. Many other inhibitors are also used, even if some of them are not recommended for plasma glucose measurement. Glucose is almost never (93%) sampled on ice when glucose inhibitor tube is not available. Laboratories in Croatia do not follow the recommended procedures regarding glycolysis inhibitors for glucose determination.

Arsenic exposure and measures of glucose tolerance in Bangladeshi adults: A cross-sectional study.

Arsenic has been associated with diabetes and impaired glucose tolerance in many studies, although some reports have shown null findings. We conducted a cross-sectional study among 300 adults in Bangladesh. Participants were randomly selected from a roster of 1800 people who previously participated in studies of arsenic and skin lesions. We measured fasting glucose and insulin levels. We assessed drinking water arsenic concentration using graphite furnace atomic absorption spectrophotometry (GF-AAS) and toenail arsenic concentration using inductively coupled mass spectrometry (ICP-MS). We ran covariant-adjusted, linear regression and spline models to examine associations of arsenic concentrations with the homeostatic model assessment of insulin resistance (HOMA-IR), a marker of insulin resistance, and HOMA of beta-cell function (HOMA-β), a marker of beta-cell function. Among 285 participants with complete data, the median (IQR) arsenic concentration was 4.0 (6.9) μg/g in toenails and 39.0 (188.5) μg/L in drinking water. Arsenic concentrations were not associated with insulin resistance or beta-cell function. HOMA-IR was 0.67% lower and HOMA-β was 0.28% lower per µg/g increment in toenail arsenic, but these effect estimates were small, and confidence intervals crossed the null value. Although arsenic exposure has been associated with diabetes, we found no evidence of an adverse effect on insulin resistance or beta-cell function.

Dysglycaemia screening and its prognostic impact in patients with coronary artery disease: experiences from the EUROASPIRE IV and V cohort studies

Glucose perturbations can be detected by fasting plasma glucose (FPG), HbA1c, and the oral glucose tolerance test (OGTT). The highest yield is provided by OGTT. HbA1c is considered more practical. We compare the diagnostic and predictive performance of these glycaemic indicators based on combined data from the EUROASPIRE IV (EAIV) and V (EAV) studies. This cohort study was conducted in 79 centres in 24 European countries (EAIV) and 131 centres in 27 European countries (EAV). Eligible patients were aged 18-80 years, did not have diabetes, and were diagnosed with coronary artery disease 6-36 months (EAIV) or 6-24 months (EAV) before the investigation. Patients were investigated with OGTT (FPG and 2 h post-load glucose [2-hPG]) and HbA1c. Follow-up of subsequent cardiovascular events was done by means of a questionnaire at least 1 year after the baseline investigation. Analyses were done in patients with both OGTT and HbA1c data available. Outcome analysis in these patients was restricted to those with valid follow-up data available. 16 259 patients were interviewed in EAIV (2012-13) and EAV (2016-17). 8364 patients had both OGTT and HbA1C data and were included in the analysis population (3932 in EAIV and 4432 in EAV). Information on cardiovascular events was available in 7892 patients. Follow-up was for a median 1·6 years (IQR 1·2-2·0). The average patient age was 63·3 years (SD 9·8), and 6346 (75·9%) of 8364 patients were men. At baseline, 1856 (22·5%) of 8263 patients were determined to have newly detected type 2 diabetes using OGTT alone, compared with 346 (4·2%) using HbA1c alone. New dysglycaemia, defined as newly detected type 2 diabetes or impaired glucose tolerance (IGT), was present in 3896 (47·1%) of the patients according to 2hPG. 2hPG 9 mmol/L or greater (162 mg/dL, adjusted hazard ratio [aHR] 1·58; 95% CI 1·27-1·95, p<0·0001), and HbA1c 5·9% or greater (41 mmol/mol, aHR 1·48, 1·19-1·84; p=0·0010) were the strongest predictors of cardiovascular events, while FPG did not predict. A multivariable model showed that the effect of HbA1c on cardiovascular events was mainly explained by 2hPG (aHR for 1 unit increase in HbA1c 1·13, 0·98-1·30; p=0·11; and aHR for 1 unit increase in Ln[2hPG] 1·37, 1·08-1·74; p=0·0042). 2hPG appears better than HbA1c in detecting dysglycaemia and predicting its impact on future cardiovascular events in patients with coronary artery disease and should be recommended as the primary screening tool. Swedish Heart-Lung Foundation, Region Stockholm (ALF), the Erling Persson Foundation, the Baltic Child Foundation.

The gut microbiota intervenes in glucose tolerance and inflammation by regulating the biosynthesis of taurodeoxycholic acid and carnosine.

This study aims to investigate the pathogenesis of hyperglycemia and its associated vasculopathy using multiomics analyses in diabetes and impaired glucose tolerance, and validate the mechanism using the cell experiments. In this study, we conducted a comprehensive analysis of the metagenomic sequencing data of diabetes to explore the key genera related to its occurrence. Subsequently, participants diagnosed with impaired glucose tolerance (IGT), and healthy subjects, were recruited for fecal and blood sample collection. The dysbiosis of the gut microbiota (GM) and its associated metabolites were analyzed using 16S rDNA sequencing and liquid chromatograph mass spectrometry, respectively. The regulation of gene and protein expression was evaluated through mRNA sequencing and data-independent acquisition technology, respectively. The specific mechanism by which GM dysbiosis affects hyperglycemia and its related vasculopathy was investigated using real-time qPCR, Western blotting, and enzyme-linked immunosorbent assay techniques in HepG2 cells and neutrophils. Based on the published data, the key alterable genera in the GM associated with diabetes were identified as Blautia, Lactobacillus, Bacteroides, Prevotella, Faecalibacterium, Bifidobacterium, Ruminococcus, Clostridium, and Lachnoclostridium. The related metabolic pathways were identified as cholate degradation and L-histidine biosynthesis. Noteworthy, Blautia and Faecalibacterium displayed similar alterations in patients with IGT compared to those observed in patients with diabetes, and the GM metabolites, tauroursodeoxycholic acid (TUDCA) and carnosine (CARN, a downstream metabolite of histidine and alanine) were both found to be decreased, which in turn regulated the expression of proteins in plasma and mRNAs in neutrophils. Subsequent experiments focused on insulin-like growth factor-binding protein 3 and interleukin-6 due to their impact on blood glucose regulation and associated vascular inflammation. Both proteins were found to be suppressed by TUDCA and CARN in HepG2 cells and neutrophils. Dysbiosis of the GM occurred throughout the entire progression from IGT to diabetes, characterized by an increase in Blautia and a decrease in Faecalibacterium, leading to reduced levels of TUDCA and CARN, which alleviated their inhibition on the expression of insulin-like growth factor-binding protein 3 and interleukin-6, contributing to the development of hyperglycemia and associated vasculopathy.

Fetal size monitoring in women with gestational diabetes and normal glucose tolerance.

To monitor fetal size and identify predictors for birthweight in women with gestational diabetes (GDM) and normal glucose tolerance (NGT). Cohort study of 1843 women universally screened for GDM, with routine ultrasounds each trimester. Women with GDM and NGT were categorized in subgroups by birthweight centile. Of the total cohort, 231 (12.5%) women were diagnosed with GDM. Fetal size, incidence of large-for-gestational age (LGA: 12.3% of GDM vs. 12.9% of NGT, p = 0.822) and small-for-gestational age (SGA) neonates (4.8% of GDM vs. 5.1% of NGT, p = 0.886) were similar between GDM and NGT. GDM women with LGA neonates were more insulin resistant at baseline and had more often estimated fetal weight (EFW) ≥ P90 on the 28-33 weeks ultrasound (p = 0.033) than those with AGA (appropriate-for-gestational age) neonates. Compared to NGT women with AGA neonates, those with LGA neonates were more often obese and multiparous, had higher fasting glycemia, a worse lipid profile, and higher insulin resistance between 24 -28 weeks, with more often excessive gestational weight gain. On the 28-33 weeks ultrasound, abdominal circumference ≥ P95 had a high positive predictive value for LGA neonates in GDM (100%), whereas, in both GDM and NGT, EFW ≥ P90 and ≤ P10 had a high negative predictive value for LGA and SGA neonates (> 88%), respectively. There were no differences in fetal size throughout pregnancy nor in LGA incidence between GDM and NGT women. EFW centile at 28-33 weeks correlated well with birthweight. This indicates that GDM treatment is effective and targeted ultrasound follow-up is useful. TRIAL REGISTRATION CLINICALTRIALS.GOV: NCT02036619. Registration date: January 15, 2014. https://clinicaltrials.gov/ct2/show/NCT02036619 .

FEATURES OF THE COURSE OF NON-ALCOHOLIC FATTY LIVER DISEASE INTYPE 2 DIABETES MELLITUS AND IMPAIRED GLUCOSE TOLERANCE

Background. Non-alcoholic fatty liver disease and type 2 diabetes mellitus or impaired glucose tolerance are common diseases with a high risk of developing cardiovascular diseases, the leading cause of disability and death. Our aim is to develop new methods for screening, prevention, and treatment of cardiovascular diseases in patients with non-alcoholic fatty liver disease, type 2 diabetes mellitus, and impaired glucose tolerance. Methods and methods. This study is single-center, open-label, uncontrolled, diagnostic study. Between 2023 and February 2024, 216 patients with cardiovascular diseases and concomitant non-alcoholic fatty liver disease, type 2 diabetes, and impaired glucose tolerance were selected at Heart Center “University Medical Center” Corporate Fund. Results. All examined patients with cardiovascular diseases and concomitant non-alcoholic fatty liver disease showed increased liver enzyme activity. Blood lipid profile indicators were significantly higher than optimal levels for patients with cardiovascular diseases. There was also a significant increase in liver enzymes, C-reactive protein, triglycerides, and lipoproteins in patients with cardiovascular diseases and non-alcoholic fatty liver disease combined with type 2 diabetes and impaired glucose tolerance. Conclusion. Liver enzyme activity, C-reactive protein, glucose, and lipid profile analysis showed significant increases in these indicators in patients with cardiovascular diseases and non-alcoholic fatty liver disease, especially in the presence of type 2 diabetes and impaired glucose tolerance. All examined patients showed increased liver enzyme activity and lipid levels, indicating the impact of these diseases on the liver and metabolism

1270-P: Evolution of Stroke Incidence over 34 Years Follow-up among People with Newly Diagnosed Diabetes and Impaired Glucose Tolerance in the Da Qing Diabetes and Diabetes Prevention Study 1986–2020

1270-P: Evolution of Stroke Incidence over 34 Years Follow-up among People with Newly Diagnosed Diabetes and Impaired Glucose Tolerance in the Da Qing Diabetes and Diabetes Prevention Study 1986–2020

Optimal Glycated Hemoglobin Cutoff for Diagnosis of Diabetes and Prediabetes in Chinese Breast Cancer Women.

Glycated hemoglobin (HbA1c) is widely used in diabetes management and now recommended for diagnosis and risk assessment. Our research focused on investigating the optimal cutoff points of HbA1c for diagnosis of diabetes and prediabetes in Chinese breast cancer women, aiming to enhance early detection and tailor treatment strategies. This study involved 309 breast cancer women without diabetes history in China. Patients were categorized into groups of newly diagnosed diabetes, prediabetes, and normal glucose tolerance using oral glucose tolerance test (OGTT) according to the 2010 ADA criteria. HbA1c data were collected from all patients. Receiver operating characteristic (ROC) curve analysis was used to assess the effectiveness of the HbA1c screening. Among the 309 breast cancer women without diabetes history, 96 (31.0%) were identified with diabetes and 130 (42.1%) had prediabetes according to OGTT, and the incidence of normal glucose tolerance was only 26.9% (83). ROC curve analysis, using OGTT as a reference, revealed that the area under the curve of 0.903 (P<0.001, 95% CI, 0.867-0.938) for HbA1c alone, indicating high accuracy. The optimal HbA1c cutoff for identifying diabetes was determined to be 6.0%, with a sensitivity of 78.1% and specificity of 86.4%. For prediabetes, the ROC curve for HbA1c alone showed that the area under the ROC curve of 0.703 (P<0.001, 95% CI, 0.632-0.774), with an optimal cutoff of 5.5% (sensitivity of 76.9% and specificity of 51.8%). The prevalence of undiagnosed diabetes is very high in breast cancer women without diabetes history in China. The optimal cutoff points of HbA1c for identifying diabetes and prediabetes are 6.0% and 5.5% in Chinese breast cancer women, respectively.

Masked uncontrolled hypertension in patients with impaired carbohydrate metabolism

Aim. To establish the prevalence of masked uncontrolled hypertension (HTN) (MUH) in patients with diabetes or impaired glucose tolerance (IGT) and determine its clinical and hemodynamic characteristics.Material and methods. The study involved 87 patients who received regular antihypertensive therapy for hypertension and had established diabetes or IGT. The mean age of patients was 62,6±9,9 years, of which 51,7% were women, 48,3% — men. Type 2 diabetes was revealed in 77,7%, IGT — 22,8% of patients. For 24-hour blood pressure monitoring, BpLAB system (OOO Petr Telegin) was used; blood pressure (BP) was determined in the brachial artery, central blood pressure — in the aorta. We analyzed risk factors and target organ damage. The results were processed using the Excel Microsoft Office 2007 package and the Statistica 6.0 and 10.0 package from StatSoft, Inc (USA).Results. Uncontrolled hypertension was revealed in 59,8%, MUH — in 18,4%, controlled HTN — 21,8% of patients. Mean daytime and mean nighttime systolic BP in patients with MUH and uncontrolled HTN were comparable. Patients with controlled hypertension compared with MUH had lower mean day- and nighttime aortic BP by 27,1% (p&lt;0,01) and 16,8% (p&lt;0,01), respectively. Aortic BP was comparable in individuals with MUH and uncontrolled HTN. Asymptomatic hyperuricemia was more common in patients with uncontrolled HTN compared with MUH and controlled hypertension by 29,3% and 41,8%, respectively. With MUH, compared with controlled HTN, we revealed a higher incidence of stroke by 18,8%, a decrease in glomerular filtration rate &lt;60 ml/min by 17,5%, albuminuria by 18,8%, left ventricular hypertrophy by 2,6 times.Conclusion. Only 41,2% of patients with diabetes and prediabetes achieve the target office BP level, while every second of these patients has MUH. MUH, compared with controlled HTN, is characterized by a higher incidence of stroke, kidney (decrease in glomerular filtration rate &lt;60 ml/min and albuminuria) and heart damage (left ventricular hypertrophy).

Risk Factors for CAD Among the Patients with Ischemie Heart Disease- A Cross Sectional Study

Introduction: Coronary heart disease (CHD) is an impairment of heart function due to inadequate blood flow to the heart compared to its needs, caused by obstructive changes in the coronary circulation to the heart. It is a common multifarious public health crisis today and a leading cause of morbidity and mortality in both developing and developed countries. Objective: To analyses the risk factors for coronary artery disease (CAD) for patients with ischemia heart disease. Methods: A cross sectional study was conducted at Department of Cardiology, Bangladesh Medical College Hospital, Dhaka, Bangladesh from January to December 2022. Total 150 with acute coronary syndrome or coronary angiographic or Electrocardiography evidence of ischemic heart disease. Risk factors studied were the conventional risk factors for coronary artery disease- hypertension, diabetes mellitus, dyslipidemia, body mass index (BMI), smoking, and family history of coronary artery disease Data are collected from the patients, old medical records, Clinical Examination and Laboratory results of the patients were analyzed for the study. Results: A total of 100 (66.6%) patients in the study gave a positive family history for CAD. Based on the blood 'pressure monitoring, the patients were classified according to JNC 7 (reviewed) classification for hypertension as normotensive 78 (78.0%), pre-hypertensive 4(4.0%), stage 1 hypertension was found in 18 patients (18.0%). There was no gender difference noted in the occurrence of hypertension. From the study, diabetes or impaired glucose tolerance (79%) and dyslipidemia (71%) are the major risk factor for Coronary artery disease as only a minority of the study population had hypertension or gives a history of cigarette smoking. 57% of the study population had a family history of coronary artery disease. Among the studied population, 55% of females are with increased BMI, whereas only 16% of males with CAD were with BMI above 30. Conclusion: Among diabetes mellitus and dyslipidemia are the major Risk factor for Coronary artery disease. So early detection of diabetes mellitus and dyslipidemia and proper treatment of both, before developing the end organ damage, play a vital role for the prevention of coronary artery disease.

Glycemic Trends in Patients with Thyroid Eye Disease Treated with Teprotumumab in 3 Clinical Trials

ObjectiveAssess incidence, severity, and outcomes of serum glucose excursions in patients with thyroid eye disease who received the insulin-like growth factor-1 receptor inhibitor, teprotumumab, during pivotal clinical trials. DesignAnalysis of pooled glycemic data and longitudinal trends. Subjectsphase 2 and phase 3 (OPTIC) pooled analysis: 170 patients (84 teprotumumab, 86 placebo); OPTIC-X: 51 patients from OPTIC. MethodsTeprotumumab administered as 8 intravenous infusions over 21 weeks. In the phase 2 trial, serum glucose was measured at weeks 1, 4, 15, and 21, with fasting blood collections weeks 1 and 4. In OPTIC and OPTIC-X, serum glucose was measured at each study visit, with fasting draws weeks 1 and 4 (non-diabetic patients) or all visits (diabetic patients). In all studies, hemoglobin A1c (HbA1c) was measured at baseline, 12, and 24 weeks plus weeks 36 and 48 of OPTIC-X. Main Outcome MeasuresSerum glucose and HbA1c over time. ResultsIn the pooled analysis, 9 hyperglycemic episodes were reported in 8 teprotumumab patients; mean HbA1c in teprotumumab patients increased 0.22% from baseline to week 24 (to 5.8%, range 5.0%–7.9%) versus 0.04% in placebo patients (to 5.6%, range 4.6%–8.1%). At study end, 78% of teprotumumab and 87% of placebo patients were normoglycemic. Normoglycemia was maintained from baseline to week 24 in 84% (57/68) of teprotumumab and 93% (64/69) of placebo patients. Of prediabetic patients, 43% (3/7) remained prediabetic in both groups and 29% (2/7) of teprotumumab and 14% (1/7) of placebo patients were diabetic at week 24. OPTIC-X showed a trend toward increased fasting glucose and HbA1c during teprotumumab retreatment and initial therapy (placebo patients from OPTIC). Fasting glucose commonly rose following the first 2-3 infusions and stabilized over subsequent infusions. Most hyperglycemic incidents occurred in patients with baseline prediabetes or diabetes and were controlled with medication. There was no evidence of progression or increased incidence of hyperglycemia with subsequent doses. ConclusionsSerious glycemic excursions are uncommon in patients who are normoglycemic before teprotumumab therapy. Patients with controlled diabetes or impaired glucose tolerance can be treated safely if baseline screening, regular monitoring of glycemic control, and treatment of hyperglycemia are ensured.

Insulin Resistance Is Better Estimated by Using Fasting Glucose, Lipid Profile, and Body Fat Percent Than by HOMA-IR in Japanese Patients with Type 2 Diabetes and Impaired Glucose Tolerance: An Exploratory Study.

Aims: The aim of the present study is to estimate insulin resistance (IR) using clinically available parameters except for serum insulin or C-peptide concentration to overcome the limitation of homeostasis model assessment of IR (HOMA-IR), which has been widely used in clinical practice. Patients and Methods: Fifty-two admitted patients with type 2 diabetes or impaired glucose tolerance were enrolled, and steady state plasma glucose (SSPG) method and cookie meal tolerance test were performed together with fasting blood sampling and anthropometric measurements. Insulin sensitivity measured by SSPG was estimated as glucose clearance corrected by the excretion of glucose into urine (C-GC). Results: Log-transformed (C-GC) was negatively correlated with fasting plasma glucose (FPG), log (Fasting triglyceride: TG), log (Fasting TG/Fasting high-density lipoprotein cholesterol: HDLC), and their area under the curves (AUCs). Fasting and AUC-HDLC was positively and fasting free fatty acid (FFA) was negatively correlated with log (C-GC). Body fat (%) was negatively correlated with log (C-GC). Multiple regression analysis on log (C-GC) as an outcome variable revealed that FPG, log (AUC-TG/AUC-HDLC), body fat (%), and fasting FFA were selected as significant predictive variables and contributed to log (C-GC) by 60% (adjusted R2). Replacing log (AUC-TG/AUC-HDLC) with its fasting value, log (Fasting TG/Fasting HDLC), this model still showed a strong contribution to log (C-GC) by 57% (adjusted R2). These contributions were stronger than those in log (HOMA-IR) (52.5%), log (Fasting C-peptide) (45.7%) to log (C-GC). Conclusions: It is plausible that our estimation for IR without the inclusion of plasma insulin concentration can be applied in Japanese patients whose HOMA-IR is not appropriately available. The model using fasting values is less complicated and could be the best way for the estimation of IR.

Zinc Alpha-2 Glycoprotein, Acylated Ghrelin, and Zinc Levels in Prediabetics.

Prediabetic stages of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) exhibit differences in the sites of insulin resistance. Serum Zinc α-2 glycoprotein (ZAG), acylated ghrelin (AG), and zinc (Zn) levels can affect IFG, IGT, and diabetic glucose tolerance (DGT) differently. This study examined the importance of ZAG, AG, and serum Zn levels in prediabetic individuals with IFG, IGT, and DGT, compared to those with normal glucose levels. The study was conducted at İstanbul University Cerrahpaşa-Cerrahpaşa Faculty of Medicine. A total of n=151 volunteers were classified according to the WHO criteria for diabetes after undergoing an oral glucose tolerance test. Plasma and serum samples were measured by Inductively Coupled Plasma Optical Emission Spectroscopy, ELISA, and immunoassay. Prediabetic conditions became more prominent with the decrease in ZAG levels. ZAG levels showed a negative correlation with acylated ghrelin and Homeostatic Model Assessment for assessing beta-cell function and insulin resistance. Zinc levels were significantly lower in DGT. ZAG levels have regulatory effects on insulin resistance and plasma glucose levels are mediated by zinc and acylated ghrelin.

Regulation of Intestinal Flora and Immune Response by Cyanidin Exhibits Protective Effect against Type-2 Diabetes in Rat Model.

In the current study the effects of metformin and cyanidin on the immune system and intestinal flora in rats with type-2 diabetes was investigated. The findings showed that metformin or cyanidin treatment considerably reduced the rise in body weight and glucose levels induced by type-2 diabetes. The type-2 diabetic rats' glucose tolerance was significantly increased by cyanidin administration comparable to that of metformin. Cyanidin administration resulted in a significant reduction in serum cholesterol and low-density lipoprotein (LDL) levels in rats with type-2 diabetes. Treatment with cyanidin significantly increased the ratio of high-density lipoprotein to low-density lipoprotein in type-2 diabetes rats. Cyanidin administration significantly raised the ratio of Firmicutes to Bacteroidetes in the fecal samples of type-2 diabetic rats compared to the model group. In comparison to the model group, it also significantly raised the levels of Lactobacillus intestinalis, Lactobacillus gasseri, and Lactobacillus reuteri in the type-2 diabetes rats. In type-2 diabetes rat fecal samples, the abundance of Christensenellaceae significantly increased while Enterobacteriaceae and Proteobacteria were found to decrease upon cyanidin administration. Furthermore, cyanidin administration to the rats with type-2 diabetes significantly improved the glucose homeostasis. In conclusion, the study demonstrates that cyanidin enhances glucose homeostasis in rats with type-2 diabetes, potentially through controlling intestinal flora. Thus, cyanidin may be looked into more as a possible therapeutic agent for type 2 diabetes.

Changes in Soluble Serum CD81 Concentration during an Oral Glucose Tolerance Test in Patients with Diabetes Mellitus and Individuals with Normal Glucose Tolerance

Aim: Cluster of differentiation 81 (CD81) is a cell surface protein involved in cell development, activation, growth, and motility. Recent studies have suggested that CD81 is a marker of dedifferentiated β-cells under conditions of metabolic stress, such as progressive diabetes. However, the clinical significance of changes in soluble serum CD81 (sCD81) in diabetic individuals remains unknown. The aim of this study was to investigate whether serum sCD81 concentrations differ between subjects with diabetes and normal glucose tolerance (NGT), and whether sCD81 changes during a 75 g oral glucose tolerance test (OGTT). Materials and methods: We recruited 101 subjects who had completed an OGTT. According to the test results, the participants were divided into diabetes mellitus (DM) and NGT groups. Participants with prediabetes were excluded from the analysis. During the OGTT, sCD81 levels were measured at 0 and 120 min. We compared changes in sCD81 between the groups. Results: In the DM group, soluble sCD81 levels were significantly higher at baseline and 120 min in the OGTT compared with the normal group (0.59 (0.22–1.05) ng/mL vs. 0.25 (0.81–0.67) ng/mL, 0.55 (0.17–0.96) ng/mL vs. 0.21 (0.92–0.78) ng/mL, p = 0.006 and 0.029, respectively). The soluble sCD81 levels in the NGT group remained unchanged (p = 0.658), while those in the DM group were significantly decreased during the OGTT (p = 0.003). Conclusion: Soluble sCD81 levels were elevated in individuals with type 2 diabetes, such that changes in sCD81 were only observed during the OGTT in the DM group. Soluble sCD81 may have potential as a new diagnostic marker for type 2 diabetes.

OP-08 The effect of maternal metabolic factors and lipid profile on birth weight in pregnants with gestational diabetes and normal glucose tolerance

OP-08 The effect of maternal metabolic factors and lipid profile on birth weight in pregnants with gestational diabetes and normal glucose tolerance

Failure to replicate the diabetes alleviating effect of a maternal gluten-free diet in non-obese diabetic mice.

Type 1 diabetes (T1D) is an autoimmune disease with an unexplained rising incidence for which environmental factors like gluten may play a role. Previously, we showed that a gluten-free (GF) diet provided strictly in utero reduces the autoimmune diabetes incidence in Non-Obese Diabetic (NOD) mice compared to a gluten-containing standard (STD) diet. The current study was initiated to elucidate possible mechanisms behind the diabetes-alleviating effect of the same diet intervention. NOD mice received either a GF Altromin diet or a STD Altromin diet during pregnancy. Female offspring from both groups were fed a STD diet throughout life and their diabetes incidence was recorded for 200 days. The following parameters were measured in 13-week-old female offspring: insulitis degree, glucose and insulin tolerance, and plasma insulin autoantibody titer. The diet intervention showed no reduction in autoimmune diabetes incidence, insulitis degree, glucose nor insulin tolerance and plasma insulin autoantibody titer. In conclusion, this study could not replicate the previously observed diabetes alleviative effects of a maternal gluten-free diet in NOD mouse offspring and could therefore not further elucidate potential mechanisms.

321-OR: Differential Associations of Obesity and Metabolic Syndrome with Polyneuropathy in Early Type 2 Diabetes and Normal Glucose Tolerance

There is increasing evidence for a role of the metabolic syndrome (MetS) during development of distal sensorimotor polyneuropathy (DSPN). We hypothesized that MetS components are differentially associated with measures of DSPN in individuals with normal glucose tolerance (NGT) and early type 2 diabetes (T2D). Electrophysiological and quantitative sensory testing was performed in 180 participants with NGT and 355 with recent-onset T2D (known diabetes duration &amp;lt;1 year) matched for age from the German Diabetes Study (NGT/T2D [mean±SD]: age: 43.9±14.0/45.1±7.7 years; sex: 61/65% male; BMI: 26.8±5.0/32.3±6.5 kg/m²; HbA1c: 5.2±0.3/6.5±1.0%). Intraepidermal nerve fiber density (IENFD) was assessed in 218 individuals (NGT/T2D: n=117/101). Subsets of participants were followed for 5 years (NGT/T2D: n=48/53). MetS was defined according to International Diabetes Federation (2006) and DSPN according to Toronto consensus criteria (2011). After adjustment for age, sex, height, smoking and HbA1c, a lower IENFD was associated with higher weight (β=-0.306), number of MetS components (NMetSC; β=-0.222) and presence of central obesity (β=-0.292), while higher malleolar vibration perception threshold was associated with weight (β=0.219) in NGT (P&amp;lt;0.05), but not in T2D. Median motor nerve conduction velocity and sural sensory nerve action potential were inversely associated with weight (β=-0.182/-0.286), NMetSC (β=-0.127/-0.128), presence of central obesity (β=-0.163/-0.165), and MetS (β=-0.169/-0.203) in T2D (P&amp;lt;0.05). Higher weight predicted the presence of DSPN at 5 years (β=0.652, P=0.001) in NGT, while increasing NMetSC and MetS prevalence predicted a decline in IENFD over 5 years (β=-0.533/-0.388, P=0.001/0.013) in T2D. This suggests that obesity indices can predict DSPN over 5 years in NGT, while MetS and its components are differentially associated with measures of DSPN in early, well-controlled type 2 diabetes compared with NGT. Disclosure G.Sipola: None. A.Strom: None. M.Bombrich: None. R.Wagner: Advisory Panel; Daiichi Sankyo, Speaker's Bureau; Novo Nordisk, Sanofi. D.Ziegler: None. M.Roden: Advisory Panel; Eli Lilly and Company, Consultant; TARGET PharmaSolutions, Inc., Research Support; Boehringer-Ingelheim, Novo Nordisk, Novartis, Sanofi. G.J.Bönhof: None. Gds group: n/a. Funding German Federal Ministry of Health; Ministry of Innovation, Science, Research and Technology of the state North Rhine-Westphalia; German Federal Ministry of Education and Research

314-OR: The Triglyceride–Glucose Index May be a Surrogate for Both Insulin Resistance and Atherogenic Lipid Profile in Africans

As the insulin assay is expensive and often unavailable in low income countries, the triglyceride-glucose index (TyG) is undergoing global evaluation as both a surrogate marker of insulin resistance (IR) and predictor of cardiovascular disease (CVD). Yet the value of the TyG in African-born populations is uncertain. Therefore, in 555 African-born Blacks currently living in the Washington, DC area (Age: 39±0.4y (mean±SE), Male: 65% (358/555), BMI: 27.7±0.2 kg/m2) we determined: 1) ability of TyG to predict the presence of IR; and 2) correlations between TyG and four lipid parameters, specifically HDL-C and LDL-C, LDL-particle size and LDL-number. Fasting lipid profiles and OGTT were performed. IR was defined by the lowest quartile of the Matsuda Index (≤2.85). Ability of TyG to predict IR was assessed with AUC-ROC curve. Pearson correlations were performed between the lipids and both TyG and Matsuda Index. Diabetes, prediabetes and normal glucose tolerance occurred in 7% (37/555), 31% (173/555) and 62% (345/555) resp. AUC-ROC for the prediction of IR by TyG was 0.75±0.02. Correlations between the lipids and both TyG and Matsuda Index were highly significant (Table). But correlations with each lipid were stronger with TyG than Matsuda Index. Overall, TyG is marker of IR in Africans and may be better than Matsuda Index in predicting CVD because of stronger correlations with atherogenic lipids. Disclosure C.Worthy: None. J.Gatete: None. J.Hurston: None. B.R.Schenk: None. L.Mabundo: None. C.Dubose: None. R.Jagannathan: None. A.E.Sumner: None.