Normal Glucose Tolerance Group Research Articles

First-Trimester Triglyceride-Glucose Index and Triglyceride/High-Density Lipoprotein Cholesterol are Predictors of Gestational Diabetes Mellitus Among the Four Surrogate Biomarkers of Insulin Resistance.

This study seeks to assess the potential of early pregnancy Triglyceride Glucose Index (TyG), triglyceride to High-Density Lipoprotein Cholesterol ratio (TG/HDL-c), Low-Density Lipoprotein Cholesterol to High-Density Lipoprotein Cholesterol ratio (LDL-C/HDL-C), and Total Cholesterol to High-Density Lipoprotein Cholesterol ratio (TC/HDL-C) in predicting Gestational Diabetes Mellitus (GDM). A total of 1073 adults singleton pregnant women were enrolled from June 2017 to September 2019. Complete anthropometric data and lipid profiles were measured in the first trimester (before 12 weeks gestation) and a 75g oral glucose tolerance test (OGTT) at 24-28 weeks was performed. Based on OGTT results, participants were categorised into Normal Glucose Tolerance (NGT) group (n=872) and GDM group (n=201). General data, laboratory test results, and surrogate insulin resistance indicators such as TyG index, TG/HDL-C, LDL-C/HDL-C, and TC/HDL-C were documented and compared. To compare differences between the two groups, t-test was used, Spearman correlation analysis and linear regression analysis were performed to establish associations between these indicators and insulin resistance in GDM. Receiver Operating Characteristic (ROC) curves were generated to compare the thresholds of these indicators for predicting GDM during pregnancy and to quantify overall diagnostic accuracy. Individuals with GDM had higher TyG, TG/HDL-C, and LDL-C/HDL-C levels (P < 0.001), but with no significant difference observed in TC/HDL-C. All four ratios were positively correlated with Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), yet only TyG emerged as an independent risk factor for HOMA-IR. The Area under the Curve (AUC) of TyG index (0.692) was comparable to that of HOMA-IR (0.703). The cut-off points for TyG index, TG/HDL-C, and HOMA-IR in predicting GDM were 7.088, 0.831, and 1.8, respectively. HOMA-IR exhibited the highest sensitivity (79.1%), while TyG index (64.3%) and TG/HDL-C ratio (64.3%) demonstrated better specificity compared to HOMA-IR (56.3%). LDL-C/HDL-C and TC/HDL-C offered no discernible predictive advantage. Early pregnancy TyG index and TG/HDL-C can aid in identifying pregnant women at risk for GDM, potentially facilitating early and effective intervention to improve prognosis. TyG index exhibited superior predictive capability compared to TG/HDL-C.

Changes in isoleucine, sarcosine, and dimethylglycine during OGTT as risk factors for diabetes.

Current metabolomics studies in diabetes have focused on the fasting state, while only few addressed the satiated state. We combined oral glucose tolerance test (OGTT) and metabolomics to examine metabolite level changes in populations with different glucose tolerance statuses and evaluate the potential risk of these changes for diabetes. We grouped participants into those with normal glucose tolerance (NGT), impaired glucose regulation (IGR), and newly diagnosed type 2 diabetes (NDM). During the OGTT, serum was collected at 0, 30, 60, 120, and 180 min. We evaluated the changes in metabolite levels during OGTT and compared metabolic profiles among the three groups. The relationship between metabolite levels during the OGTT and risk of diabetes and prediabetes was analyzed using generalized estimating equation (GEE). The regression results were adjusted for sex, body mass index, fasting insulin levels, heart rate, smoking status, and blood pressure. Glucose intake altered metabolic profile and induced an increase in glycolytic intermediates and decrease in amino acids, glycerol, ketone bodies, and triglycerides. Isoleucine levels differed between NGT and NDM groups and between NGT and IGR groups. Changes in sarcosine levels during OGTT in diabetes groups were opposite to those in glycine levels. GEE analysis revealed that during OGTT, isoleucine, sarcosine, and acetic acid levels were associated with NDM risks, while isoleucine and acetate levels with IGR risks. Metabolic profiles differ after glucose induction in individuals with different glucose tolerance statuses. Changes in metabolite levels during OGTT are potential risk factors for diabetes development.

New perspective on first-trimester serum uric acid level in predicting the risk of gestational diabetes mellitus

This study aimed to investigate the correlation between serum uric acid (UA) and gestational diabetes mellitus (GDM) during the first trimester and provide a new perspective for the prevention and treatment of GDM. Based on the diagnostic criteria of gestational diabetes of the International Association of Diabetes and Pregnancy Study Groups, 1744 and 4256 patients were enrolled in the GDM and normal glucose tolerance (NGT) groups. Four groups were constituted based on the quartile of first-trimester serum UA (UA) level, and the differences in each indicator between groups were compared. Logistic regression was used to analyze the effects of UA level on GDM risk. The rate of GDM in the UA quartile changed from low to high. Significant differences were also observed in fasting plasma glucose level, 1 h post glucose and 2 h post glucose levels, in all the groups (P < 0.05), which increased with the UA level. UA level were independent risk factors for GDM. The best threshold of GDM predicted by the first-trimester UA level was 226.55 μmol/L. The first-trimester UA level in patients with GDM was relatively higher and was an independent risk factor for GDM.

Relationship between serum NLRP3 along with its effector molecules and pregnancy outcomes in women with hyperglycemia

Objective The study aims to investigate the levels of serum NLRP3 along with its effector molecules (Caspase-1, IL-1β, and IL-18) in the mid-pregnancy in pregnant women with hyperglycemia, and explore the relationship between NLRP3, along with its effector molecules (Caspase-1, IL-1β, and IL-18) and insulin resistance, as well as pregnancy outcomes. Methods The levels of serum NLRP3 along with its effector molecules (Caspase-1, IL-1β, and IL-18) in three groups of pregnant women with gestational diabetes mellitus (GDM), pregestational diabetes mellitus (PGDM) and normal glucose tolerance (NGT) were measured in mid-pregnancy, and their relationship with insulin resistance and pregnancy outcomes was analyzed. The ROC curve was also used to evaluate the predictive value of serum NLRP3 inflammasome and its effector molecules for pregnancy outcomes. Results There were no statistical differences in the general clinical data of the three groups, and the concentrations of serum NLRP3 along with its effector molecules were higher in the GDM and PGDM groups than in the NGT group, and NLRP3 along with its effector molecules were positively correlated with fasting blood glucose, fasting insulin, and insulin resistance index in both groups (r > 0, p < .05). The incidence of preterm delivery, hypertensive disorders of pregnancy, premature rupture of membranes, neonatal hypoglycemia and macrosomia was significantly higher in both groups than in the NGT group (p < .05). The value of the combined serum NLRP3 and its effector molecules in mid-pregnancy to predict adverse pregnancy outcomes was highest, and the AUCs for the combined prediction of late hypertensive disorders of pregnancy, premature rupture of membranes, preterm delivery, neonatal hypoglycemia and macrosomia were 0.84 (95% CI 0.79–0.88, p < .001), 0.81 (95% CI 0.75–0.85, p < .001), 0.76 (95% CI 0.70–0.81, p < .001), 0.76 (95% CI 0.70–0.81, p < .001) and 0.72 (95% CI 0.63–0.81, p < .001), respectively. Conclusions Increased serum NLRP3 along with its effector molecules in pregnant women with hyperglycemia are associated with the levels of insulin resistance and the subsequent development of adverse pregnancy outcomes.

Association between Transcription Factor 7-Like 2 Gene Polymorphisms rs7903146 and rs12255372 with the Risk of Diabetic Nephropathy among South Indian Population

Abstract Introduction: Transcription factor 7-like 2 (TCF7L2) gene has been associated with the genetic predisposition of type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN) in different populations. The study aimed to explore the correlation between rs7903146 and rs12255372 polymorphisms of TCF7L2 gene and DN among the South Indian population. Methods: Polymerase chain reaction (PCR)-based direct sequencing method and allele-specific PCR were used to determine the genotypes of TCF7L2 polymorphisms in 20 normal glucose tolerance (NGT) participants, 35 T2DM patients without DN and 35 T2DM patients with DN. The differences in genotype and allelic distribution between the study groups were analyzed by Chi-square test and odds ratio (OR) with 95% confidence interval (CI) which were used to indicate the relative risk of DN. Results: The distribution of TCF7L2 gene polymorphism rs7903146 prevalence was as follows: in the NGT group, CC, 65%; CT, 30%; TT, 5%; in the T2DM without DN group, CC, 25.71%; CT, 62.86%; TT, 11.43%; and in the T2DM with DN group, CC, 31.43%; CT, 60.0%; TT, 8.57%. The distribution of rs12255372 was as follows: in the NGT group, GG, 80%; GT, 15%; TT, 5%; in the T2DM without DN group, GG, 42.86%; GT, 41.46%; TT, 8.57%; and in the T2DM with DN group, GG, 48.57%; GT, 40%; TT, 5.71%. The T allele of rs7903146 polymorphism was associated with an increased risk of T2DM without DN (OR = 3.0; 95% CI = 1.21–7.437; P = 0.010) and T2DM with DN (OR = 2.51; 95% CI = 1.00–6.252; P = 0.04), and the T allele of rs12255372 polymorphism was also associated with increased risk of T2DM without DN (OR = 3.42; 95% CI = 1.18–9.902; P = 0.018) and not with T2DM with DN when compared with NGT individuals. Conclusion: In our study, the T allele of the rs7903146 single-nucleotide polymorphism in the TCF7L2 gene confers the risk of developing DN in diabetes patients, but the T allele of the rs12255372 polymorphism in the TCF7L2 gene is associated with T2DM and its association with DN is arbitrated through T2DM.

Association of MST1 in the First Trimester of Pregnancy with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes.

We investigate the association of mammalian sterile line 20-like kinase 1 (MST1) in the first trimester with the risks of gestational diabetes mellitus (GDM) and adverse pregnancy outcomes. Pregnancies were recruited during their first antenatal care visit between 8 and 12 gestational weeks. These pregnancies underwent an oral glucose tolerance test between 24 and 28 gestational weeks and were followed up until delivery. Serum MST1 levels at 8-12 gestational weeks and 24-28 gestational weeks were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Logistic regression models were used to evaluate the association between MST1 levels in the first trimester and the risks of GDM and adverse pregnancy outcomes. This cohort study enrolled a total of 231 pregnancies. GDM was present in 42 (18.18%) women. Compared to the normal glucose tolerance (NGT) group, the GDM group had higher levels of FPG, HOMA-IR, and MST1 both in the first and second trimesters, but had lower HOMA-β levels only in the second trimester. Then participants were classified according to the median MST1 value in the first trimester. Incidences of GDM, composite adverse pregnancy outcomes, preterm birth, and macrosomia increased in women with higher MST1 values. Serum MST1 in the first trimester was correlated with FPG, 1hr PG, 2hr PG, and HOMA-IR, while inversely correlated with HOMA-β in the second trimester. Furthermore, after adjusting for traditional risk factors, women with higher first-trimester MST1 values had greater odds of GDM, composite adverse pregnancy outcomes, preterm birth, and macrosomia (aOR 2.276, P=0.030; aOR 2.690, P=0.003; aOR 3.210, P=0.048; aOR 5.488, P=0.010). Elevated levels of MST1 in the first trimester of pregnancies are associated with increased risks of GDM and adverse pregnancy outcomes.

Correlation Between Neck Circumference and Gestational Diabetes.

The objective of this study was to explore whether neck circumference can serve as an early predictor of the risk of Gestational Diabetes (GDM). A total of 318 singleton pregnant women who underwent routine prenatal examinations at Qinhuangdao Maternal and Child Health Hospital from September 2017 to September 2020 were selected and categorized into the GDM group and the normal glucose tolerance group (NGT) based on the results of the oral glucose tolerance test (OGTT) conducted during the second trimester. The general information and laboratory test results were compared and analyzed. Inter-group comparison was conducted using the t-test, and multivariate logistic regression analysis was employed to analyze the independent risk factors of GDM. The predictive threshold of various indicators for GDM occurrence during pregnancy was determined using the subject's work curve. The GDM group exhibited significantly higher levels of pre-pregnancy weight, pre-pregnancy BMI, neck circumference, waist circumference, hip circumference, triglycerides (TG), uric acid (UA), TG/HDL-C ratio, and waist-hip ratio compared to the NGT group. Additionally, HDL cholesterol (HDL-C) levels were significantly lower in the GDM group, and blood glucose levels at each point of the OGTT were markedly higher compared to the NGT group (P<0.05). Multivariate logistic regression analysis revealed that neck circumference (OR=1.239, P<0.001) and early pregnancy TG (OR=1.842, P<0.001) were independent risk factors for GDM. The receiver operating characteristic analysis demonstrated that the optimal critical value of neck circumference for predicting GDM was 32.6 cm, with a sensitivity of 50% and specificity of 74.3%. The neck circumference during early pregnancy was found to be related to GDM, and the predictive cutoff point of 32.6 cm for neck circumference could be employed as a simple index to predict GDM in early pregnancy.

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.

Microbiome and metabolome dysbiosis analysis in impaired glucose tolerance for the prediction of progression to diabetes mellitus

Gut microbiota and circulating metabolite dysbiosis predate important pathological changes in glucose metabolic disorders; however, comprehensive studies on impaired glucose tolerance (IGT), a diabetes mellitus (DM) precursor, are lacking. Here, we perform metagenomic sequencing and metabolomics on 47 pairs of individuals with IGT and newly diagnosed DM and 46 controls with normal glucose tolerance (NGT); patients with IGT are followed up after 4 years for progression to DM. Analysis of baseline data reveals significant differences in gut microbiota and serum metabolites among the IGT, DM, and NGT groups. In addition, 13 types of gut microbiota and 17 types of circulating metabolites showed significant differences at baseline before IGT progressed to DM, including higher levels of Eggerthella unclassified, Coprobacillus unclassified, Clostridium ramosum, L-valine, L-norleucine, and L-isoleucine, and lower levels of Eubacterium eligens, Bacteroides faecis, Lachnospiraceae bacterium 3_1_46FAA, Alistipes senegalensis, Megaspaera elsdenii, Clostridium perfringens, α-linolenic acid, 10E,12Z-octadecadienoic acid, and dodecanoic acid. A random forest model based on differential intestinal microbiota and circulating metabolites can predict the progression from IGT to DM (AUC = 0.87). These results suggest that microbiome and metabolome dysbiosis occur in individuals with IGT and have important predictive values and potential for intervention in preventing IGT from progressing to DM.

Regional differences in islet amyloid deposition in the residual pancreas with new-onset diabetes secondary to pancreatic ductal adenocarcinoma.

Islet amyloid deposition and reduced β-cell mass are pathological hallmarks in type 2 diabetes mellitus subjects. To date, the pathological features of the islets in diabetes secondary to pancreatic ductal adenocarcinoma (PDAC) have not been specifically addressed. To provide further insight into the relationship between islet amyloid deposition of the residual pancreas in PDAC patients and to explore whether regional differences (proximal vs distal residual pancreas) are associated with islet amyloid deposition. We retrospectively collected clinical information and pancreatic tissue removed from tumors of 45 PDAC patients, including 14 patients with normal glucose tolerance (NGT), 16 patients with prediabetes and 15 new-onset diabetes (NOD) patients diagnosed before surgery by an oral glucose tolerance test at West China Hospital from July 2017 to June 2020. Pancreatic volume was calculated by multiplying the estimated area of pancreatic tissue on each image slice by the interval between slices based on abdominal computer tomography scans. Several sections of paraffin-embedded pancreas specimens from both the proximal and/or distal regions remote from the tumor were stained as follows: (1) Hematoxylin and eosin for general histological appearance; (2) hematoxylin and insulin for the determination of fractional β-cell area (immunohistochemistry); and (3) quadruple insulin, glucagon, thioflavin T and DAPI staining for the determination of β-cell area, α-cell area and amyloid deposits. Screening for pancreatic histologic features revealed that duct obstruction with islet amyloid deposition, fibrosis and marked acinar atrophy were robust in the distal pancreatic regions but much less robust in the proximal regions, especially in the prediabetes and NOD groups. Consistent with this finding, the remnant pancreatic volume was markedly decreased in the NOD group by nearly one-half compared with that in the NGT group (37.35 ± 12.16 cm3 vs 69.79 ± 18.17 cm3, P < 0.001). As expected, islets that stained positive for amyloid (islet amyloid density) were found in the majority of PDAC cases. The proportion of amyloid/islet area (severity of amyloid deposition) was significantly higher in both prediabetes and NOD patients than in NGT patients (P = 0.002; P < 0.0001, respectively). We further examined the regional differences in islet amyloid deposits. Islet amyloid deposit density was robustly increased by approximately 8-fold in the distal regions compared with that in the proximal regions in the prediabetes and NOD groups (3.98% ± 3.39% vs 0.50% ± 0.72%, P = 0.01; 12.03% vs 1.51%, P = 0.001, respectively). In conclusion, these findings suggest that robust alterations of the distal pancreas due to tumors can disturb islet function and structure with islet amyloid formation, which may be associated with the pathogenesis of NOD secondary to PDAC.

One abnormal value or vomiting after oral glucose tolerance test in pregnancy: incidence and impact on maternal-fetal outcomes

Objective To analyze pregnancy outcomes of women with one abnormal value (OAV) during oral glucose tolerance test (OGTT) or OGTT-intolerance, compared with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT) pregnant women, according to whether they received any health intervention or not. Methods An observational retrospective study was designed including pregnant women who gave birth at Hospital del Mar, Barcelona (Spain) during December/2014–July/2018. Baseline characteristics, pregnancy outcomes and health interventions were obtained from a database collected previously for other study. Inclusion criteria were singleton pregnancies with OAV or OGTT-intolerants who gave birth at the Hospital. GDM screening followed a two-step approach: 50 g O’Sullivan test and 100 g 3-hour OGTT if the former was abnormal. Results From a total of 2,662 pregnancies, 326 (12.2%) had GDM, 87 OAV (3.3%), 65 OGTT intolerance (2.4%) and 2,184 were NGT women. First trimester HbA1c in both OAV and OGTT-intolerant women was significantly higher than in NGT group, and significantly lower than in GDM pregnants. No differences in obstetric outcomes were found between OGTT-intolerants and NGT/GDM groups. Treated OGTT-intolerants had greater gestational age at delivery than non-treated ones (weeks, 39.6 ± 1.2 vs 38.0 ± 4.0, respectively). In OAV women, significant differences were observed in newborns’ birthweight (g, 3227.3 ± 500.8 vs 3351.1 ± 436.7, vs GDM) and gestational age at birth (weeks, 38.7 ± 1.8 vs 39.3 ± 1.9, vs NGT), but not in macrosomia/pre-eclampsia. No differences were found according to treatment in OAV. Conclusions OAV and OGTT-intolerants account for a third of pregnant women referred to Diabetes Unit. Their rates of preterm birth, pre-eclampsia and macrosomia were not different from NGT or GDM women.

Interaction of Iron Homeostasis and Fatty Acid Metabolism in the Development of Glucose Intolerance in Women with Previous Gestational Diabetes Mellitus.

A gestational diabetes mellitus (GDM) diagnosis during pregnancy means an increased risk of developing type 2 diabetes later in life. By following up with women after GDM we aimed to examine the relationship between iron parameters, individual fatty acids (FAs) and desaturases in the development of impaired glucose metabolism (IGM). Based on an oral glucose tolerance test (OGTT), six years after GDM, 157 women were grouped as having normal glucose tolerance (NGT) or IGM. Fasting serum FAs, activity of desaturases and iron parameters (ferritin, transferrin, iron, soluble transferrin receptor, total iron binding capacity, hepcidin) were measured, and clinical and anthropometric measurements taken. Soluble transferrin receptor was higher in the IGM group compared to the NGT group (3.87 vs. 3.29 mg/L, p-value = 0.023) and associated positively with saturated FAs and negatively with monounsaturated FAs in the IGM group (adjusted for BMI, age and high sensitivity C-reactive protein; p-value < 0.05). Iron, as well as transferrin saturation, showed a positive association with MUFAs and desaturase activity. These associations were not seen in the NGT group. These results suggest that iron homeostasis and FA metabolism interact in the development of glucose intolerance in women with previous GDM.

1585-P: MAFLD in Obesity with Deteriorating Glucose Control

The incidence of metabolic dysfunction-associated fatty liver disease (MAFLD) is rising in parallel with increasing bodyweight and loss of glucose control, implicating a high risk of hepatic and extra-hepatic complications. This longitudinal observational study analysed several indicators for MAFLD in 240 overweight subjects (body mass index (BMI) &amp;gt; 28 kg/m²) at 2 visits within in average 16 months. Subjects were categorised according to their insulin sensitivity (HOMAIR) and diabetic status. Liver fat and liver stiffness were measured with sonographic elastography (FibroScan®), and by calculation of Fatty Liver Index (FLI), and NAFLD Fibrosis Score (NFS). Parameters indicative for liver steatosis, i.e., the controlled attenuation parameter (CAP) and the FLI, were significantly higher in the T2DM group compared to the normal glucose tolerance (NGT) and impaired glucose tolerance (IGT) groups (p&amp;lt;0.05). FLI values and the HOMAIR significantly correlated with sonographic liver fat content (CAP) (r=0.53, p&amp;lt;0.0001; r=0.34, p&amp;lt;0.001, respectively). An inverse correlation was observed between serum adiponectin levels and CAP (r=-0.20; p&amp;lt;0.019) and adiponectin levels and FLI (r=-0.37; p&amp;lt;0.0001). Over 16 months, fasting insulin levels and HOMAIR score increased mainly driven by the group of obese subjects with T2DM. No significant change in liver fat or stiffness was observed that period. In subjects with a BMI ≥ 28kg/m², the prevalence of MAFLD increases in line with increasing insulin resistance and loss of glucose control. Despite some further deterioration in insulin sensitivity, liver fat content appeared relatively unchanged over 16 months. Disclosure T.Forst: Consultant; Pfizer Inc., Speaker's Bureau; Amarin Corporation, AstraZeneca, Boehringer Ingelheim Inc., Cipla Inc., Daiichi Sankyo, Eli Lilly and Company, MSD Life Science Foundation, Novo Nordisk, Sanofi. I.Botz: None. M.Berse: None. S.K.Baumann: None. A.Schultz: None.

1093-P: Incretins and Cardiac Autonomic Function in Youth with Obesity across the Glycemia Spectrum

Incretins, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) have been related to vascular function with variable effects depending on obesity status in adults. The relationship of incretins to vascular function in youth is unclear. We hypothesized that endothelial and cardiac autonomic dysfunction (CAD) are related to lower GLP-1 and GIP in response to glucose ingestion in youth with dysglycemia compared with those with overweight (OW) or normal weight (NW) and normal glucose tolerance (NGT). Adolescents [50 male/52 female; 15.6±1.8 yrs; 24 NW-NGT, 22 OW-NGT, 27 prediabetes and 29 with type 2 diabetes (T2D)] underwent assessment of body composition (DXA scan), 2-hour oral glucose tolerance test (OGTT) with calculation of whole body insulin sensitivity index (WBISI), area under the curve (AUC) of glucose (BG), GLP-1 and GIP. Reactive hyperemia index (RHI), and heart rate variability (HRV), were measured by peripheral arterial tonometry. For HRV, a higher LF/HF (low frequency to high frequency ratio) is indicative of CAD with loss of parasympathetic tone and decreased HRV. The ratios of AUC-GLP-1 and AUC-GIP to AUC-BG were lower in the groups with dysglycemia compared NGT groups (p=0.016 and 0.001, respectively). GLP-1 and GIP were not related to RHI. Fasting and AUC-GLP-1, but not GIP, negatively related to LF/HF (r=-0.37, p=0.002 and r=-0.43, p&amp;lt;0.001 respectively). In a linear regression model with LnLF/HF as the dependent variable, AUC-BG (β=0.31, p=0.04) and AUC-GLP-1 (β=-0.44, p=0.002) contributed to the variance in LnLF/HF independent of %body fat, hs-CRP, WBISI, age, sex, race-ethnicity and Tanner stage (R2= 0.27, p=0.04). Youth with obesity and dysglycemia have impaired incretin response. Glycemia is negatively, whereas GLP-1 is positively associated with HRV after accounting for adiposity, WBIS and inflammation. GLP-1 may be an important determinant of CA function in youth with obesity across the glycemia spectrum. Disclosure H.El ayash: None. F.Bacha: Other Relationship; Takeda Pharmaceutical Co., Ltd., AstraZeneca. Funding U.S. Department of Agriculture-Agricultural Research Service

Association of abnormal glucose tolerance with liver-related disease and cardiovascular diseases in patients with chronic hepatitis C.

Hepatitis C complicated by diabetes mellitus (DM) is considered a risk factor for the progression of fibrosis and development of hepatocellular carcinoma (HCC) and cardiovascular diseases. However, several studies may have lacked appropriate diagnosis of glucose intolerance. We aimed to examine the risk associated with abnormal glucose intolerance in the development of liver-related diseases, including HCC and complications of liver cirrhosis, such as ascites, esophageal and gastric varices, and hepatic encephalopathy, and cardiovascular diseases in patients with hepatitis C accurately diagnosed with impaired glucose tolerance. This longitudinal retrospective study included 365 patients with chronic hepatitis C admitted to Ehime University Hospital for anti-hepatitis C therapy between September 1991 and January 2015. Patients were classified into normal glucose tolerance (NGT), prediabetes, and DM groups based on 75-g oral glucose tolerance test results. Both univariate and multivariate (adjusted for potential confounders) analyses revealed a significantly higher risk of developing HCC and cardiovascular events in the DM group than in the NGT group. However, in multivariate analysis, liver-related events, particularly liver cirrhosis complications, revealed no significant association. In addition, the prediabetes group had no significant risk of any outcome. Patients with hepatitis C complicated by DM, compared with patients with hepatitis C with NGT or complicated with prediabetes, have a higher risk ofHCC and cardiovascular disease events, but not liver-related events, particularlyin not developing liver cirrhosis complications. Therefore, appropriate follow-up is required for patients with hepatitis C based on their glucose tolerance status.

Soluble TNFR1 Levels in Type 2 Diabetes and its Association with Stages of Proteinuria.

Early identification of at-risk individuals for diabetic nephropathy would help in preventing or delaying end-stage renal failure. We measured the levels of circulating soluble tumor necrosis factor receptor 1 (sTNFR1) in various stages of proteinuria (MAC) to determine the association of this marker with diabetic nephropathy. The study was performed on 160 subjects, and a case-control methodology was employed. Type 2 diabetic subjects were recruited based on albuminuria and were grouped as (1) normoalbuminuria (NA); (2) microalbuminuria (MIC); (3) MAC; (4) normal glucose tolerance (NGT) subjects who served as healthy controls. sTNFR1 levels were measured by quantitative enzyme-linked immunosorbent assay (ELISA). Soluble tumor necrosis factor receptor 1 (sTNFR1) levels were highest in the MAC group, followed by the microMAC group. The sTNFR1 levels were not statistically different between the NGT and NA groups. On regression models, sTNFR1 was associated with MIC [odds ratio (OR)- 6.491, 95% confidence interval (CI)-1.868-22.55] and MAC (OR per standard deviation-15.28; 95% CI-3.76-62.15; p &lt; 0.001) even after controlling for all the possible confounding factors. Receiver operator curve (ROC) analysis revealed sTNFR1 cut-point of 1832 pg/mL had a C-statistic of 0.685 to discriminate MI from NA with 52% sensitivity. Whereas the sTNFR1 cut-point of 2050 pg/mL with a C-statistic of 0.8177 had 77% sensitivity for identifying MAC. Soluble tumor necrosis factor receptor 1 (sTNFR1) is significantly associated with MIC and MAC group in type 2 diabetes, and this suggests a potential early diagnostic biomarker role of sTNFR1 for MAC among Asian Indians.

Prevalence of glucose metabolism disorders and its association with left atrial remodelling before and after catheter ablation in patients with atrial fibrillation

To investigate the exact prevalence of glucose metabolism disorders, and their impact on left atrial (LA) remodelling and reversibility in patients with atrial fibrillation (AF). We examined 204 consecutive patients with AF who underwent their first catheter ablation (CA). Oral glucose tolerance test was used to evaluate glucose metabolism disorders in 157 patients without known diabetes mellitus (DM). Echocardiography was performed before and 6 months after CA. Oral glucose tolerance test identified abnormal glucose metabolism in 86 patients [11 with newly diagnosed DM, 74 with impaired glucose tolerance (IGT) and 1 with impaired fasting glucose (IFG)]. Ultimately, 65.2% of patients had abnormal glucose metabolism. Diabetes mellitus group had the worst LA reservoir strain and LA stiffness (both P < 0.05), while there was no significant difference in baseline LA parameters between normal glucose tolerance (NGT) group and IGT/IFG group. The prevalence of LA reverse remodelling (≥15% decrease in the LA volume index at 6 months after CA) was significantly higher in NGT group compared with IGT/IFG and DM group (64.1 vs. 38.6 vs. 41.5%, P = 0.006). Both DM and IFG/IGT carry a significant risk of lack of LA reverse remodelling independent of baseline LA size and AF recurrence. Approximately 65% of patients with AF who underwent their first CA had abnormal glucose metabolism. Patients with DM had significantly impaired LA function compared with non-DM patients. Impaired glucose tolerance/IFG as well as DM carries significant risk of unfavourable LA reverse remodelling. Our observations may provide valuable information regarding the mechanisms and therapeutic strategies of glucose metabolism-related AF.

The effect of impaired glucose metabolism on IVF-ET pregnancy outcome with endometrial hyperplasia and early-stage endometrial cancer

ObjectiveImpaired glucose metabolism, including insulin resistance, diabetes, and obesity, is a high-risk factor for the development of endometrial cancer (EC). Most previous studies evaluated the safety and effectiveness of fertility preservation (FP) for endometrial hyperplasia (EH) and EC patients were from the perspective of oncology or case reports. The study aims to evaluate the effect of glucose metabolic status on clinical pregnancy outcome of in vitro fertilization and embryo transfer (IVF-ET) in infertile patients with endometrial hyperplasia and early-stage endometrial cancer. MethodsThis retrospectively analysis included the data from patients who underwent IVF-ET after fertility preservation (FP) with endometrial hyperplasia and early-stage endometrial carcinoma, and primary infertile patients with normal endometrium (NE) but the fallopian tubal factors or pelvic adhesions who underwent IVF-ET during the same period as control group. All the patients were further divided into the following four subgroups: A: FP+ impaired glucose metabolism (IGM) (N = 20); B: FP+ normal glucose tolerance (NGT) (N = 29); C: NE+ IGM (N = 130); and D: NE+ NGT (N = 98). The main research outcome measure was the live birth rate (LBR) per embryo transfer (ET) cycle. Student's t-test or analysis of variance (ANOVA) was used for intergroup comparisons. The least significant difference (LSD) test was used for pairwise comparison between multiple groups. ResultsThe differences in anti-Mullerian hormones (AMH) and body mass index (BMI) between the four groups were significant. As BMI increased, the total dose of gonadotropin (Gn) during the controlled ovarian stimulation in the IGM group was significantly higher than that in the NGT group. The LBR was 16.7%, 26.3%, 41.6%, and 45.3% in the four subgroups (p = 0.033), respectively. By multivariate Logistic analysis, it was found that in FP group, IGM (OR = 1.501, 95% CI: 1.045–2.154, p = 0.028) was an independent risk factor for IVF-ET. ConclusionIGM was negatively affected by the LBR after endometrial complete response (CR) from early-stage endometrial cancer and endometrial hyperplasia. It was essential for the early detection and control of insulin resistance with metformin.

Biomarker screening in children and adolescents reveals that CUB domain-containing protein 1 is associated with obesity and that hepatocyte growth factor is associated with weight gain

Low-grade inflammation is a hallmark of obesity, hyperinsulinemia and type 2 diabetes (T2D), although its role in adolescent T2D and impaired glucose tolerance (IGT) is less known. To identify novel inflammatory protein biomarkers related to childhood obesity, IGT, hyperinsulinemia and hyperglucagonemia and increase in age-adjusted BMI over time. Children and adolescents with obesity (n = 137; eight with T2D, 45 with IGT, 84 with normal glucose tolerance (NGT)), and with normal weight (n = 34) were included. Study subjects were 5–18 years old. In the obesity group the majority were above the 99th BMI percentile. Protein biomarker identification in plasma was performed using proximity extension assay with a 92-plex inflammation-related protein panel. The biomarkers were tested for their association with childhood obesity, IGT, hyperinsulinemia, hyperglucagonemia by t-tests and with increased BMI SDS by linear regression. Six protein biomarkers not previously studied in childhood obesity were elevated in pediatric obesity, among these CUB domain containing protein 1 (CDCP1). Plasma TNF-related Weak Inducer of Apoptosis (TWEAK) was lower in the IGT than in the NGT group. Five protein biomarkers were elevated in hyperinsulinemia and two were elevated in hyperglucagonemia. A high baseline HGF was associated with increased BMI SDS after a follow-up period of on average 1.8 years (B = 0.008, 95% CI 0.005–0.011). Six protein biomarkers not previously described in childhood obesity were identified, among these CDCP-1. A high HGF is associated with increased BMI over time in children and adolescents with obesity.

Association between glucose tolerance and mortality among Japanese community-dwelling older adults aged over 75 years: 12-year observation of the Tosa Longitudinal Aging Study.

Although the relationship between impaired glucose tolerance (IGT) and mortality has been investigated in diverse populations, few studies have focused on older populations. This study aimed to investigate the relationship between glucose tolerance and overall mortality among populations aged ≥75 years. Data were obtained from the Tosa Longitudinal Aging Study, a community-based cohort survey conducted in Kochi, Japan. According to the results of a 75-g oral glucose tolerance test conducted in 2006, the participants were classified into four categories: normal glucose tolerance (NGT), impaired fasting glucose (IFG)/IGT, newly diagnosed diabetes mellitus (NDM), and known diabetes mellitus (KDM). The primary endpoint was overall mortality. Differences in overall mortality among the four categories were evaluated using the Cox proportional hazards model. During a median of 11.5 years of observation, 125 deaths of the 260 enrolled participants were recorded. The cumulative overall survival rate was 0.52, and the survival rates of NGT, IFG/IGT, NDM, and KDM were 0.48, 0.49, 0.49, and 0.25, respectively (log-rank test, P = 0.139). Adjusted hazard ratios (HRs) for mortality in the IFG/IGT and NDM groups compared with the NGT group were 1.02 (95% confidence interval [CI], 0.66-1.58) and 1.11 (95% CI, 0.56-2.22), while mortality in the KDM group was significantly higher than that in the NGT group (HR, 2.43; 95% CI, 1.35-4.37). Mortality did not differ significantly between the IFG/IGT, NDM, and NGT groups, but was higher in the KDM group than in the NGT group. Geriatr Gerontol Int 2023; 23: 341-347.