Impaired Glucose Tolerance Group Research Articles

The association between triglyceride-glucose index and related parameters and risk of cardiovascular disease in American adults under different glucose metabolic states

BackgroundCardiovascular disease (CVD) encompasses an array of cardiac and vascular disorders, posing a significant threat to global health. It remains unclear whether there exists an association between triglyceride-glucose index (TyG) and its derived indices and the incidence of cardiovascular disease, and in particular, the strength of the association in populations with different glucose metabolisms is not known.MethodsData extracted from the National Health and Nutrition Examination Survey (NHANES) covering the period from 1999 to 2020, involving a cohort of 14,545 participants, were leveraged for the analysis. Statistical assessments were executed utilizing R software, employing multivariable logistic regression models to scrutinize the correlation between TyG and its associated parameters with the incidence of cardiovascular disease across diverse glucose metabolism categories. Interaction analyses and restricted cubic splines were applied to evaluate potential heterogeneity in associations and investigate the link between TyG and its derivatives with the occurrence of cardiovascular disease. Furthermore, receiver operating characteristic curves were constructed to evaluate the extent of variability in the predictive performance of TyG and its derived parameters for cardiovascular disease across distinct glucose metabolic statuses.ResultsThis study found that TyG and its related parameters were differentially associated with the occurrence of cardiovascular disease in different glucose metabolic states. Curvilinear correlations were found between TyG in the IFG population and TyG-WC, TyG-BMI, and TyG-WHtR in the impaired glucose tolerance (IGT) population with the occurrence of cardiovascular disease. In addition, the introduction of TyG and its derived parameters into the classical Framingham cardiovascular risk model improved the predictive performance in different glucose metabolism populations. Among them, the introduction of TyG-WHtR in the normal glucose tolerance (NGT), impaired fasting glucose (IFG), IFG & IGT and diabetes groups and TyG in the IGT group maximized the predictive power.ConclusionsThe findings provide new insights into the relationship between the TyG index and its derived parameters in different glucose metabolic states and the risk of cardiovascular disease, offering important reference value for future clinical practice and research. The study highlights the potential for improved risk stratification and prevention strategies based on TyG and its derived parameters.

Oral glucose tolerance test clearance in type 2 diabetes patients who underwent remission following intense lifestyle modification: A quasi-experimental study.

Achieving diabetes remission (HbA1c<48mmol/mol without the use of anti-diabetic medication for 3 months) might not assure restoration of a normal glycemic profile [fasting blood sugar level <5.6 mmol/L and Post-Prandial (PP) blood glucose <7.8mmol/L]. The study investigates the factors associated with OGTT clearance in patients under type 2 diabetes remission. Four hundred participants who achieved remission during a one-year online structured lifestyle modification program, which included a plant-based diet, physical activity, psychological support, and medical management (between January 2021 and June 2022), and appeared for the OGTT were included in the study. OGTT clearance was defined by fasting blood glucose < 5.6 mmol/L and 2-hour post-prandial blood glucose <7.8 mmol/L post-consumption of 75g glucose solution. Of the 400 participants, 207 (52%) cleared OGTT and 175 (44%) had impaired glucose tolerance (IGT). A shorter diabetes duration (<5 years) was significantly associated with OGTT clearance (p<0.05). Pre-intervention use of glucose-lowering drugs showed no association with OGTT clearance (p<0.1). Post-intervention, the OGTT-cleared group showed significantly higher weight loss (p<0.05) and a decrease in HbA1c compared to the IGT group (p<0.05). Improvement in Insulin resistance and β-cell function was also higher in the OGTT-cleared group compared to the IGT group (p<0.05). In conclusion, clearing the OGTT is a possibility for those achieving remission through lifestyle interventions. Higher weight loss, a shorter duration of diabetes, and improvement in insulin resistance were significantly associated with OGTT clearance in participants in remission. Future randomized controlled trials with longer follow-ups may help substantiate our findings.

Neonatal Outcomes in Different Maternal Diabetes Types: Experience from a Tertiary Care Unit

Objective: Infants of mothers with diabetes (IMD) may require hospitalization in neonatal intensive care units (NICU) for various reasons. In our study, our objective was to compare clinical and laboratory findings, as well as malformations and morbidities among IMD based on the types of maternal diabetes. Material and Methods: The diabetic status of mothers of 4713 infants admitted to tertiary neonatal intensive care unit (NICU) at Ankara Bilkent City Hospital between January 1, 2020, and January 1, 2022, was examined. We retrospectively analyzed demographic data, clinical and laboratory characteristics, and morbidities for 616 infants born to mothers with impaired glucose tolerance (IGT), gestational diabetes mellitus (GDM), or pre-existing gestational diabetes mellitus (Pre-GDM). Results: Of the 616 cases, 167 (27.1%) were infants of mothers with IGT, 394 (64%) with GDM and 55 (8.9%) with Pre-GDM. The prevalence of macrosomia was significantly higher in Pre-GDM (30.9%) than in the IGT (15%) and GDM (19.3%) groups (p=0.033). The most common malformations in the cases were related to the cardiovascular system (CVS) (77.4%). The frequency of septal hypertrophy was significantly higher in the Pre-GDM group compared to the IGT and GDM groups, and in the GDM group compared to the IGT group (p&amp;lt;0.001). The rates of septal hypertrophy, CVS malformation, LGA/macrosomia, and hypocalcemia were found to be significantly higher in infants of mothers with insulin requirement and high HbA1c levels, particularly in Pre-GDM group (p&amp;lt;0.001). According to the ROC analysis for the optimum maternal HbA1c value predicting septal hypertrophy, the threshold value was found to be 6% (AUC=0.693) with 62% sensitivity and 66% specificity. In logistic regression analysis, macrosomia and maternal HbA1c ≥6% were determined as independent risk factors for the presence of septal hypertrophy. Conclusion: Despite variations in the type of maternal diabetes, IDM experience significant clinical challenges when hospitalized and monitored in the NICU. Infants born to mothers with IGT may also be subjected to maternal hyperglycemia. The likelihood of certain complications rises in infants born to pregnant women with inadequate glycemic control, particularly those with elevated HbA1c levels. By ensuring maternal glycemic control and closely monitoring these infants, it is possible to reduce both mortality and morbidity.

Impaired Glucose Tolerance and Risk for Mild Cognitive Impairment and Dementia:Results from the SPRINT‐MIND Trial

AbstractBackgroundIn epidemiological studies, persons with a diagnosis of diabetes mellitus (DM), especially those with coexisting hypertension, have been shown to be at increased risk for dementia.[1‐3] However, the relationship between impaired glucose tolerance (IGT) and future risk of Mild Cognitive Impairment (MCI) and dementia is less clear, especially in persons without diagnosed DM . The SPRINT‐MIND trial (4) provides an opportunity to assess the relationship between baseline glucose level and risk for transition to mild cognitive impairment in the context of hypertension control.MethodRandomized clinical trial (n = 9,361) conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diagnosed diabetes or history of stroke. Baseline serum glucose obtained fasting and incidence of adjudicated MCI and probable dementia (PD) was calculated. Results were also stratified by age, baseline cardiovascular disease risk, and baseline systolic blood pressure.ResultAt baseline, 4398 participants (58%) had a serum glucose &amp;lt; 100 mg/dl and 3606 (42%) had a serum glucose &amp;gt;100. Overall, 389 (7.9%) of participants in the normoglycemic group and 250 (6.9%) of participants in the impaired glucose tolerance group developed MCI. For incident PD, 204 (4.1%) and 118 (3.3%) cases occurred in in persons with normal vs. impaired glucose tolerance. Incidence MCI or Dementia did not significantly differ when the results were stratified by baseline age or blood pressure.ConclusionIn persons with hypertension but without diagnosed diabetes, baseline impaired glucose tolerance does not confer elevated risk for MCI or dementia.

Lipidomics analysis of impaired glucose tolerance and type 2 diabetes mellitus in overweight or obese elderly adults.

Aging, obesity, and type 2 diabetes mellitus (T2DM) form a metabolic disease continuum that has a continuously increasing prevalence. Lipidomics explains the complex interactions between lipid metabolism and metabolic diseases. We aimed to systematically investigate the plasma lipidome changes induced by newly diagnosed impaired glucose tolerance (IGT) and T2DM in overweight/obese elderly individuals and to identify potential biomarkers to differentiate between the IGT, T2DM, and control groups. Plasma samples from 148 overweight/obese elderly individuals, including 52 patients with IGT, 47 patients with T2DM, and 49 euglycemic controls, were analyzed using a high-coverage nontargeted absolute quantitative lipidomics approach. We quantified 1840 lipids from thirty-eight classes and seven lipid categories. Among overweight/obese elderly individuals, the lipidomic profiles of IGT and T2DM patients were significantly different from those of controls, while they were similar in the IGT and T2DM groups. The concentrations of diglycerides, triglycerides, phosphatidylcholines, and ceramides were obviously altered in the IGT and T2DM groups. Particularly, IGT and T2DM induced the accumulation of triglycerides with longer carbon atom numbers (C44-50) and saturated or lower double bond numbers (n (C=C) = 0-2). Furthermore, a total of 17 potential lipidic biomarkers were identified to successfully differentiate between the IGT, T2DM, and control groups. In overweight/obese elderly patients, IGT and T2DM induced apparent lipidome-wide changes. This study's results may contribute to explaining the complex dysfunctional lipid metabolism in aging, obesity, and 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.

Diabetes, prediabetes, and atrial fibrillation-A population-based cohort study based on national and regional registers.

Previous studies have shown an increased risk for atrial fibrillation and atrial flutter (AF) in people with type 2 diabetes and prediabetes. It is unclear whether this increase in AF risk is independent of other risk factors for AF. To investigate the association between diabetes and different prediabetic states, as independent risk factors for the onset of AF. We performed a population-based cohort study in Northern Sweden, including data on fasting plasma glucose, oral glucose tolerance test, major cardiovascular risk factors, medical history, and lifestyle factors. Participants were divided into six groups depending on glycemic status and followed through national registers for AF diagnosis. Cox proportional hazard model was used to assess the association between glycemic status and AF, using normoglycemia as reference. The cohort consisted of 88,889 participants who underwent a total of 139,661 health examinations. In the model adjusted for age and sex, there was a significant association between glycemic status and development of AF in all groups except the impaired glucose tolerance group, with the strongest association for the group with known diabetes (p-value <0.001). In a model adjusted for sex, age, systolic blood pressure, body mass index, antihypertensive drugs, cholesterol, alcohol, smoking, education level, marital status, and physical activity, there was no significant association between glycemic status and AF. The association between glycemic status and AF disappears upon adjustment for potential confounders. Diabetes and prediabetes do not appear to be independent risk factors for AF.

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.

A Study to Evaluate the Role of Secreted Frizzled-Related Protein 4 (SFRP4) as a Potential Novel Biomarker of Type 2 Diabetes Mellitus

ABSTRACT Background: A new inflammation mediator called secreted frizzled-related protein 4 (SFRP4), was recently found, the secretion of which is regulated by interleukin-1β. SFRP4 as a potential biomarker of early β-cell dysfunction can help to identify high-risk individuals who are going to develop diabetes in the future. It is highly expressed in β-cells of islets and its levels increase several years before diabetes diagnosis. Objectives: This study was conducted with an objective to estimate and correlate SFRP4 in pre-diabetes, type 2 diabetes, and non-diabetes persons, and evaluate the predictive risk assessment of SFRP4 as a novel biomarker. Materials and Methods: In this cross-sectional observational study, a total of 300 human participants were included among which 100 were prediabetic, 100 were diabetic, and 100 were age- and gender-matched control individuals from a community, all of whom were selected through a predesigned screening questionnaire and inclusion and exclusion criteria from January 2020 to January 2022 in Banke district, Nepal. Serum SFRP4 and IL-1β levels were determined by ELISA. Results: There was a statistically significant difference in body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), fasting insulin, fasting plasma glucose (FPG), two-hour post-load plasma glucose (2hPG), glycosylated hemoglobin (HbA1c), insulin resistance (HOMA-IR), Homeostasis model assessment of β cell function (HOMA-β%), high-sensitivity C-reactive protein (hs-CRP), total cholesterol (TC), triglyceride (TG), and low-density lipoprotein (LDL) between the three groups, with a progressive increase from the normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) groups and with the highest value in the type 2 diabetes mellitus (T2DM) groups (P &lt; 0.05). However, diastolic blood pressure (DBP) and IL-1β showed a significant difference between the NGT and T2DM groups (P &lt; 0.001) and the NGT and IGT groups (P &lt; 0.001). The median serum SFRP4 concentrations showed a significant difference among three groups (all P &lt; 0.05) and were positively correlated with FPG, HbA1c, hs-CRP, and IL-1 β (P &lt; 0.05). Conclusion: Our study presumes importance as we report increased SFRP4 levels in Asian Nepalis even at the stage of IGT. These findings propose that the increased serum SFRP4 may be a good biomarker of decline in β-cell function and insulin resistance.

Can orbital artery resistive indexes detect complications of diabetes in the prediabetic phase?

Prediabetic patients have generalized microvascular dysfunction, which leads to end-organ damage, just like diabetes. Therefore, prediabetes is not just a mild elevation in blood sugar, and early detection and prevention of possible complications should be the main goal. Color Doppler imaging (CDI) provides morphologic and vascular information on various diseases. The Resistive Index (RI) is a widely used measure of resistance to arterial flow and is calculated from the CDI. CDI evaluation of vessels in the retrobulbar region may be the first sign of micro- and macrovascular complications. Consecutively, 55 prediabetic patients and 33 healthy subjects were recruited for the study. Prediabetic patients were divided into three groups according to their fasting and postprandial blood glucose values. The groups included an impaired fasting glucose (IFG) group (n = 15), an impaired glucose tolerance (IGT) group (n = 13), and an IFG+IGT group (n = 27). The RI of the ophthalmic artery, posterior ciliary artery, and central retinal artery were measured in all patients. The orbital artery, central retinal artery, and posterior cerebral artery mean RI of prediabetic patients (0.76 ± 0.06, 0.69 ± 0.03, and 0.69 ± 0.04, respectively) were significantly higher than those of the healthy group (0.66 ± 0.04, 0.63 ± 0.04, and 0.66 ± 0.04, respectively; p < 0.001; Student's t-test). The mean ophthalmic artery RI of the healthy, IFG, IGT, and IFG+IGT groups were 0.66 ± 0.39, 0.7 ± 0.27, 0.72 ± 0.29, and 0.82 ± 0.16, respectively, with a significant difference between the groups (p < 0.001, ANOVA). The mean central retinal artery RI of the healthy, IFG, IGT, and IFG+IGT groups were 0.63 ± 0.04, 0.66 ± 0.02, 0.7 ± 0.02, and 0.71 ± 0.02, respectively (p < 0.001, post-hoc Tukey). The mean posterior cerebral artery RI of the healthy, IFG, IGT, and IFG+IGT groups were 0.66 ± 0.04, 0.66 ± 0.04, 0.69 ± 0.03, and 0.71 ± 0.03, respectively, with a significant difference between the groups (p < 0.001 Fisher ANOVA). Increased RI may be the first sign of developing retinopathy, as well as the first sign of microangiopathies occurring simultaneously in the coronary, cerebral, and renal vessels. Precautions to be taken during the prediabetic stage can prevent many possible complications.

The Relationship Between Dietary Patterns and Glycemic Variability in People with Impaired Glucose Tolerance

BackgroundDiurnal glucose fluctuations are increased in prediabetes and might be affected by specific dietary patterns. ObjectivesThe present study assessed the relationship between glycemic variability (GV) and dietary regimen in people with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT). MethodsForty-one NGT (mean age: 45.0 ± 9.0 y, mean BMI: 32.0 ± 7.0 kg/m2) and 53 IGT (mean age: 48.4 ± 11.2 y, mean BMI: 31.3 ± 5.9 kg/m2) subjects were enrolled in this cross-sectional study. The FreeStyleLibre Pro sensor was used for 14 d, and several parameters of GV were calculated. The participants were provided with a diet diary to record all meals. ANOVA analysis, Pearson correlation, and stepwise forward regression were performed. ResultsDespite no difference in diet patterns between the 2 groups, GV parameters were higher in IGT than in NGT. GV worsened with an increase in overall daily carbohydrate and refined grain consumption and improved with the increase in whole grain intake in IGT. GV parameters were positively related [r = 0.14–0.53; all P < 0.02 for SD, continuous overall net glycemic action 1 (CONGA1), J-index, lability index (LI), glycemic risk assessment diabetes equation, M-value, and mean absolute glucose (MAG)], and low blood glucose index (LBGI) inversely (r = −0.37, P = 0.006) related to the total percentage of carbohydrate, but not to the distribution of carbohydrate between the main meals in the IGT group. A negative relationship existed between total protein consumption and GV indices (r = −0.27 to −0.52; P < 0.05 for SD, CONGA1, J-index, LI, M-value, and MAG). The total EI was related to GV parameters (r = 0.27–0.32; P < 0.05 for CONGA1, J-index, LI, and M-value; and r = −0.30, P = 0.028 for LBGI). ConclusionsThe primary outcome results showed that insulin sensitivity, calories, and carbohydrate content are predictors of GV in individuals with IGT. Overall, the secondary analyses suggested that carbohydrate and daily consumption of refined grains might be associated with higher GV, whereas whole grains and daily protein intake were related to lower GV in people with IGT.

Association between serum S100A11 levels and glucose metabolism in diabetic process

BackgroundDiabetes mellitus (DM) is a prevalent non-communicable metabolic disease, and S100A11 is a newly identified gene closely related to metabolism. The association of S100A11 with diabetes is unclear. This study aimed to assess the relationship between S100A11 and markers of glucose metabolism in patients with different glucose tolerance and gender.MethodsThis study included 97 participants. Baseline data were obtained, and the serum levels of S100A11 and metabolic markers (glycated hemoglobin [HbA1c], insulin release test, and oral glucose tolerance test) were measured. Linear and nonlinear correlations between serum S100A11 levels and HOMA-IR, HOMA of β, HbA1c, insulin sensitivity index (ISI), corrected insulin response (CIR), and oral disposition index (DIo) were analyzed. The expression of S100A11 was also detected in mice.ResultsSerum S100A11 levels increased in patients with impaired glucose tolerance (IGT) of both genders. S100A11 mRNA and protein expression increased in obese mice. There were nonlinear correlations between S10011 levels and CIR, FPI, HOMA-IR, whole-body ISI in the IGT group. S100A11 was nonlinearly correlated with HOMA-IR, hepatic ISI, FPG, FPI, and HbA1c in the DM group. In the male group, S100A11 was linearly correlated with HOMA-IR and nonlinearly correlated with DIo (derived from hepatic ISI) and HbA1c. In the female population, S100A11 was nonlinearly correlated with CIR.ConclusionsSerum S100A11 levels were highly expressed in patients with IGT and in the liver of obese mice. In addition, there were linear and nonlinear correlations between S100A11 and markers of glucose metabolism, demonstrating that S100A11 has a role in diabetes.Trial registration ChiCTR1900026990

Association between microbial composition, diversity, and function of the maternal gastrointestinal microbiome with impaired glucose tolerance on the glucose challenge test.

Over the last two decades, the incidence of gestational diabetes (GDM) has almost doubled resulting in almost 9% of pregnant women diagnosed with GDM. Occurring more frequently than GDM is impaired glucose tolerance (IGT), also known as pre-diabetes, but it has been understudied during pregnancy resulting in a lack of clinical recommendations of maternal and fetal surveillance. The purpose of this retrospective, cross-sectional study was to examine the association between microbial diversity and function of the maternal microbiome with IGT while adjusting for confounding variables. We hypothesized that reduced maternal microbial diversity and increased gene abundance for insulin resistance function will be associated with IGT as defined by a value greater than 140 mg/dL on the glucose challenge test. In the examination of microbial composition between women with IGT and those with normal glucose tolerance (NGT), we found five taxa which were significantly different. Taxa higher in participants with impaired glucose tolerance were Ruminococcacea (p = 0.01), Schaalia turicensis (p<0.05), Oscillibacter (p = 0.03), Oscillospiraceae (p = 0.02), and Methanobrevibacter smithii (p = 0.04). When we further compare participants who have IGT by their pre-gravid BMI, five taxa are significantly different between the BMI groups, Enterobacteriaceae, Dialister micraerophilus, Campylobacter ureolyticus, Proteobacteria, Streptococcus Unclassified (species). All four metrics including the Shannon (p<0.00), Simpson (p<0.00), Inverse Simpson (p = 0.04), and Chao1 (p = 0.04), showed a significant difference in alpha diversity with increased values in the impaired glucose tolerance group. Our study highlights the important gastrointestinal microbiome changes in women with IGT during pregnancy. Understanding the role of the microbiome in regulating glucose tolerance during pregnancy helps clinicians and researchers to understand the importance of IGT as a marker for adverse maternal and neonatal outcomes.

THE RELATIONSHIP BETWEEN APOB AND APOA1 WITH INSULINEMIC STATUS IN PREDIABETIC SUBJECTS

The present study was mainly aimed at exploring the causal association of the atherogenic (ApoB) and antiatherogenic apolipoproteins (ApoA1) and their ratio in the basic defects of pancreatic β cell dysfunction and insulin resistance in type 2 Diabetes Mellitus (T2DM). An intermediate stage towards diabetes, the prediabetic stage, was chosen to explore the association. Following a standardized selection process, 131 subjects were purposefully recruited for the study, including 18 with impaired fasting glucose (IFG), 56 with impaired glucose tolerance (IGT), and 57 with type 2 diabetes (T2DM). Fifty-nine healthy subjects served as controls. Glucose, lipid and insulin were estimated by glucose-oxidase, enzymatic colorimetric assay and enzyme linked immunosorbent assay (ELISA) respectively. Serum ApoB and ApoA1 were estimated by immuno-nephelometric method. Appropriate statistical tools were used to calculate statistical differences using Statistical Package for Social studies (SPSS) for Windows V12. Absolute insulin (mIU) levels were significantly higher in the IGT and T2DM groups compared to controls (p 0.001 and p = 0.001, respectively). HOMA%B (meanSD) was significantly lower in T2DM groups (p=&lt;0.001) and higher in IGT compared to the controls although it is significantly lower in IFG compared to the controls but mean value is about 90%. HOMA%S was significantly lower in IGT and T2DM group (p=0.001 and 0.002 respectively). ApoA1 levels were significantly higher only in the T2DM group (p = 0.027), whereas ApoB levels were higher in both the IGT and T2DM groups (p = 0.026-0.001).. Neither ApoB nor ApoA1 showed any significant difference in the IFG group as compared to control. ApoB-ApoA1 ratio did not show significant difference among the groups. ApoB showed significant positive correlation with both fasting and postprandial glucose (p=0.006 and 0.040 respectively). In IGT group ApoB was positively correlated with absolute insulin (p=0.025) and HOMA%B (p=0.049) and negatively with HOMA%S (p=0.026). ApoB, but not ApoA1 or the ApoB and ApoA1 ratio, seem to have a causal association with insulin resistance, and elevation of ApoB is also modulated by obesity and atherogenic lipids. Bioresearch Commu. 9(1): 1170-1176, 2023 (January)

Cardiovascular Risk Predictors High Sensitivity C-Reactive Protein and Plasminogen Activator Inhibitor-1 in Women with Lean Phenotype of Polycystic Ovarian Syndrome: A Prospective Case-Control Study.

Objective Accumulating evidence suggests increased cardiovascular risk in women with polycystic ovarian syndrome (PCOS) due to a cluster of factors, such as obesity, lipid abnormalities, impaired glucose tolerance (IGT), and hypertension. Markers such as high-sensitivity C-reactive protein (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) can provide an adjunctive method for the assessment of cardiovascular risk and can indicate future coronary heart diseases in women with lean PCOS. Materials and Methods In this prospective case-control study, women clinically diagnosed with PCOS ( n = 25) with normal body mass index (BMI) and age and BMI-matched healthy controls ( n = 75) were enrolled. The quantitative data were expressed as mean ± standard deviation (SD). Unpaired Student's t -test was used to compare the values (PCOS vs. controls) and Pearson's correlation coefficient was used to elucidate the relationship between the variables. Results The mean level of fasting blood sugar, serum total cholesterol, low-density lipoprotein (LDL), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), hs-CRP, and PAI-1 were significantly increased in PCOS patients ( p < 0.000) compared with the control patients. Of the reported cases, 54.16% had hs-CRP levels greater than 3 mg/L. When the cases were further divided into normal ( n = 20) and IGT ( n = 5), hs-CRP values were significantly higher in IGT group as compared with normal glucose tolerance (NGT) group. On bivariate correlation analysis, hs-CRP had significant correlations with PAI-1 ( r = 0.41, p < 0.000), waist-to-hip ratio (WHR; r = 0.23, p = 0.02), fasting blood sugar (FBS; r = 0.26, p = 0.009), LDL ( r = 0.20, p = 0.03), TSH ( r = 0.42, p < 0.000), and LH-to-FSH ratio ( r = 0.24, p = 0.01). Conclusion Women with lean phenotype of PCOS suffer from many metabolic abnormalities such as abdominal obesity, dyslipidemia, hyperandrogenemia, and insulin resistance. The findings of the study suggest that environment of ongoing low-grade inflammation due to infiltration further exacerbates the metabolic derangements and cardiovascular risk. The investigations as hs-CRP and PAI-1 will help in early identification, diagnosis, and management of cardiovascular diseases associated with lean type of PCOS. These markers can prove to be beneficial in monitoring any unfavorable changes in cardiometabolic profile of such patients.

Metformin Influence on the Intestinal Microbiota and Organism of Rats with Metabolic Syndrome.

Metformin is a first-line drug for DM2 treatment and prevention, but its complex effect on impaired glucose tolerance (IGT), including its influence on myocardial resistance to ischemia-reperfusion injury, is not completely studied. We aimed to evaluate the influence of metformin on the intestinal microbiota (IM), metabolism, and functional and morphological characteristics of myocardium in rats with IGT. IGT was modelled in SPF Wistar rats with a high-fat diet and streptozotocin and nicotinamide injection. Rats were divided into three groups: IGT (without treatment), IGT MET (metformin therapy), and CRL (without IGT induction and treatment). IGT group was characterized by: higher body weight, increased serum glucose and total cholesterol levels, atherogenic coefficient, impairment in the functional parameters of the isolated heart during perfusion, and larger myocardium infarction (MI) size in comparison with the CRL group. IM of IGT rats differed from that of CRL: an increase of Bacteroides, Acinetobacter, Akkermansia, Roseburia, and a decrease of Lactobacillus genera representation. Metformin therapy led to the diminishing of metabolic syndrome (MS) symptoms, which correlated with IM restoration, especially with the growth of Akkermansia spp. and decline of Roseburia populations and their influence on other members of IM. The obtained results allow us to consider from a new point of view the expediency of probiotic A. muciniphila use for MS treatment.

The Effect of Aerobic Exercise on the Oxidative Capacity of Skeletal Muscle Mitochondria in Mice with Impaired Glucose Tolerance.

Methods Male C57BL/6J mice were randomly divided into six different experimental groups (8 animals/group): (1) normal group (NOR), (2) normal control group (NC), (3) normal + exercise group (NE), (4) IGT group (IGT), (5) IGT control group (IC), and (6) IGT+ exercise group (IE).The exercise group received aerobic exercise for 8 weeks. After the intervention, a blood glucose meter was used to detect the level of glucose tolerance in the mouse's abdominal cavity; a biochemical kit was used to detect serum lipid metabolism indicators, malondialdehyde, and superoxide dismutase levels; the ELISA method was used to detect serum insulin and mouse gastrocnemius homogenate LDH, PDH, SDH, and CCO levels. Western blot method was used to detect the protein expression levels of NOX4, PGC-1α, and Mfn2 in the gastrocnemius muscle of mice. Results (1) Mice with high-fat diet for 30 weeks showed impaired glucose tolerance, insulin resistance, and lipid metabolism disorders. The level of LDH, PDH, SDH, and CCO in the gastrocnemius homogenate of mice was reduced. The expressions of NOX4 protein were significantly upregulated, while the expressions of PGC-1α and Mfn2 proteins were significantly downregulated. (2) 8-week aerobic exercise improved the disorders of glucose and lipid metabolism in IGT mice and increased homogenized LDH, PDH, SDH, and CCO levels, and the expressions of NOX4, PGC-1α, and Mfn2 proteins in the gastrocnemius muscle of mice were reversed. It is speculated that aerobic exercise can accelerate energy metabolism. Conclusion (1) C57BL/6 mice were fed high fat for 30 weeks and successfully constructed a mouse model of reduced diabetes; the mice with reduced diabetes have impaired glucose tolerance, insulin resistance, and lipid metabolism disorders; (2) 8 weeks of aerobic exercise improve glucose tolerance, reduce glucose tolerance in mice, reduce insulin resistance, improve lipid metabolism disorders, and reduce oxidative stress; (3) 8-week aerobic exercise reduces skeletal muscle NOX4 expression and increases glucose tolerance; reduces the expression of LDH, PDH, SDH, and CCO in mouse skeletal muscle; increases the expression level of mitochondrial fusion protein 2 and PGC-1α; improves glucose tolerance; reduces energy metabolism of mouse skeletal muscle; reduces oxidative stress; and reduces insulin resistance. It is speculated that aerobic exercise can accelerate energy metabolism. This process may involve two aspects: firstly, increase the expression level of oxidative metabolism enzymes and promote the tricarboxylic acid cycle; secondly, increase the expression of Mfn2 and accelerate mitochondria fission or fusion to regulate energy metabolism, thereby reducing oxidative stress and insulin resistance.

Clinical and MRI features about two types of silent cerebral small-vessel disease in type-2 diabetes mellitus: a retrospective cross-sectional study in a tertiary hospital.

The present study aimed to evaluate the frequency of silent cerebral small-vessel disease, especially lacunes and white matter hyperintensities, in patients with or without the impaired glucose tolerance (IGT) and type-2 diabetes mellitus, and to characterize the diabetes-correlated factors related to silent cerebral small-vessel disease. This is a retrospective cross-sectional study. Totally 698 patients were included in this study, from January 2014 to December 2019, among which 270 patients were included in the diabetes mellitus group, 106 patients were included in the IGT group, and 322 patients were included in the Control group. All patients underwent magnetic resonance imaging to investigate the silent cerebral small-vessel disease: the lacunes and the white matter hyperintensities. All the baseline information and diabetes-related factors, such as glycated hemoglobin level, insulin usage, etc., were collected. Then correlation analysis and regression analysis were used to explore the correlation between diabetes with related risk factors and silent cerebral small-vessel disease. Lacunes and white matter hyperintensities were more common in the diabetes mellitus group than in the IGT group and the Control group, with an occurrence of lacunes of 83.3% vs. 70.8% vs. 70.4% (P=0.003), respectively, and an occurrence of white matter hyperintensities of 41.1% vs. 24.5% vs. 31.1% (P=0.003), respectively. The occurrence of lacunes was correlated with the duration of diabetes mellitus [odds ratio (OR) =1.483, 95% confidence interval (CI): 1.082-2.031, P=0.009] and the age (OR =1.141, 95% CI: 1.102-1.180, P<0.001), while white matter hyperintensities were independently correlated only with the age (OR =1.124, 95% CI: 1.094-1.155, P<0.001). Lacunes and white matter hyperintensities, are more common in the diabetes mellitus patients than in the IGT patients or in the other patients. The occurrence of lacunes was correlated with the duration of diabetes mellitus and the age, while the occurrence of white matter hyperintensities was independently correlated with the age.

Cancer and its predictors in Chinese adults with newly diagnosed diabetes and impaired glucose tolerance (IGT): a 30-year follow-up of the Da Qing IGT and Diabetes Study

BackgroundWe aimed to explore if hyperglycaemia and hyperinsulinemia in the diabetes and prediabetes population were associated with increased risk of cancer occurence.MethodsOverall, 1700 participants with different glycaemic statuses were screened from the 110,660 residents of Da-Qing, China, in 1985. They were followed up to 30 years to access cancer outcomes.ResultsCancer was identified in 15.2% (259/1700) of the participants. The incidence of cancer in the normal glucose tolerance (NGT), impaired glucose tolerance (IGT) and diabetes groups was 6.06, 6.77, and 7.18 per 1000 person-years, respectively (P = 0.02). In the Fine-Gray model with all cause death as competing risk, compared with the NGT controls, both IGT and diabetes groups demonstrated significantly higher risk of cancer (for the IGT group, adjusted hazard ratio (aHR) = 1.77, 95% CI 1.38–2.27, P < 0.0001; for the diabetes, aHR = 3.34, 95% CI 2.64–4.22, P < 0.0001). Among the IGT participants, progress to diabetes (aHR = 2.28, 95%CI 1.24–4.20, P = 0.008) and insulin-area under the curve at baseline (for 1 SD increase, aHR = 1.39, P = 0.02) were also associated with the risk of cancer after adjustment of covariables.ConclusionsHyperglycaemia in patients with diabetes, hyperinsulinemia, and progression to diabetes in people with IGT is significantly associated with the long-term increased risk of cancer occurrence.

Role of Betatrophin and Inflammation Markers in Type 2 Diabetes Mellitus, Prediabetes and Metabolic Syndrome.

To determine the association of betatrophin and inflammation factors in metabolic diseases such as diabetes, impaired fasting glucose, impaired glucose tolerance and metabolic syndrome. A cross-sectional, analytical study. Fırat University Medical School between April 2017 and December 2020. The study included 20 patients with type 2 diabetes mellitus, 20 patients with impaired fasting glucose (IFG), 20 patients with impaired glucose tolerance (IGT), 20 patients with metabolic syndrome (MetS), and a control group consisting of 20 healthy individuals. Anthropometric, fasting serum biochemical data were collected. Circulating betatrophin, and inflammation markers were measured by enzyme-linked immunosorbent assay (ELISA). The association of betatrophin, TNF-alpha, and IL-6 levels between groups were performed with One-way ANOVA and post-hoc Tukey HSD test. Significantly higher levels of circulating betatrophin were observed in IFG, IGT, And MetS groups compared to healthy controls (p=0.017). There were significantly difference TNF-α levels in IFG, IGT, and MetS groups compared to healthy controls (p<0.001). The levels of IL-6 were significantly higher in MetS group than healthy controls (p=0.007). The circulating betatrophin and TNF-α levels were increased in MetS, IFG and IGT. IL-6 was decreased in MetS compared to the healty controls. Further studies are needed to elucidate the role of betatrophin and inflammatory parameters in the development of T2DM and prediabetic syndromes, whether betatrophin could have clinical applications in the development of new antidiabetic agents. Key Words: Betatrophin, IL-6, TNF-alpha, Metabolic syndrome, Insulin resistance, Diabetes mellitus type 2.