T2DM Cases Research Articles

National burden and risk factors of diabetes mellitus in China from 1990 to 2021: Results from the Global Burden of Disease study 2021.

In recent years, the prevalence and mortality rates of diabetes have been rising continuously, posing a significant threat to public health and placing a heavy burden on the population. This study was conducted to describe and analyze the burden of diabetes in China from 1990 to 2021 and its attributable risk factors. Utilizing data from the Global Burden of Disease Study 2021, we analyzed the incidence, prevalence, and disability-adjusted life years (DALYs) of type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in China from 1990 to 2021. We extracted sex- and age-specific data on diabetes, focusing on DALYs, years lived with disability, and years of life lost. Bayesian meta-regression and spatiotemporal Gaussian process regression were used to estimate disease parameters. Age-standardized rates (ASRs) and estimated annual percentage changes (EAPC) were calculated using direct standardization and log-linear regression. The population-attributable fractions were also determined for each risk factor. In 2021, the absolute number of incident diabetes mellitus (DM) cases was estimated at 4003543.82, including 32 000 T1DM and 3971486.24 T2DM cases. The ASRs were 244.57 for DM, 2.67 for T1DM, and 241.9 for T2DM (per 100 000 population). The absolute number of prevalent DM cases was 117288553.93, including 1442775.09 T1DM and 115845778.84 T2DM cases. The ASRs were 6142.29 for DM, 86.78 for T1DM, and 6055.51 for T2DM (per 100 000 population). In 2021, there were 178475.73 deaths caused by DM, with an ASR of mortality of 8.98 per 100 000 population. The DALYs due to DM in 2021 were 11713613.86, with an ASR of 585.43 per 100 000 population and an EAPC of 0.57. This increase can be attributed to several factors, including high body mass index, air pollution, and dietary habits. The burden of diabetes is considerable, with high prevalence and incidence rates, highlighting the urgent need for public health interventions. Addressing factors like high fasting plasma glucose, body mass index, air pollution, and dietary risks through effective interventions is critical.

Thyroid Nodules and Insulin Resistance in Type 2 Diabetes Patients

Abstract Background Diabetes mellitus (DM) is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. DM can result from deterioration in function and//or a loss of mass in pancreatic tissue. The disease burden of DM is expected to increase in the next few years and decades. The Atlas of the International DM Federation estimated that 537 million adults (20–79 years) were living with DM in 2022, and this number could increase to 643 million by 2030 and 781 million by 2045 Aim of the Work To find out the association between Insulin resistance and thyroid nodules in T2DM. Patients and Methods This study was a Case-control study that was conducted to find association between insulin resistance and thyroid nodules in T2DM cases. The present study was carried out on 80 patients attending Ain Shams University internal medicine department and endocrinology outpatient clinic during the period from August 2021 to May 2023. Results Therefore, the aim of the current work is to find out the assosciation between insulin resistance and thyroid nodules in T2DM. Our study showed that fasting insulin and HOMI-IR were significantly higher in diabetic patients with nodules than in diabetic patients without nodules (P = 0.029 & P = 0.001 respectively). Our study also showed that fasting insulin and HOMI-IR were predictive risk factors for thyroid nodules. Moreover, our results revealed that fasting insulin & IR were positively correlated with thyroid nodule volume and size. Our study showed that there was a significant increase in the mean of FT4 levels in diabetic patients with thyroid nodules (when compared to diabetic patients without thyroid nodules (P = 0.043). Yet, no significant correlation was found between Thyroid nodule volume, Thyroid nodule size, and IR with FT4. The binary logistic regression analysis showed that FT4 was a risk factors for thyroid nodule in the T2DM patients. Furthermore, the results showed that there was a significant increase in the mean of TPO levels in diabetic patients with thyroid nodules when compared to diabetic patients without thyroid nodules (P = 0.038). The binary logistic regression analysis showed that TPO was risk factor for thyroid nodule in the T2DM patients. There was a significant increase in the mean value of fasting blood glucose level in diabetic groups with thyroid nodules when compared to those without thyroid nodules (P < 0.001). Pearson's correlation test also showed significant positive correlation between thyroid nodule size and fasting blood glucose (r = 0.400, P = 0.010) as well as fasting blood insulin (r = 0.440, P = 0.005). The binary logistic regression analysis showed that FBG, PPGL were risk factors for thyroid nodule in the T2DM patients. Conclusion Our research demonstrates that IR is strong risk factors for thyroid nodule occurrence but its prevalence in diabetic cases is not evaluated in our study. So, it is of great clinical significance to perform thyroid Ultrasonography on patients with T2DM. The independent correlates of TNs were multifactorial, and there existed differences in different physiological states

Summary of the 2023 European Society of Cardiology clinical guidelines on the management of cardiovascular disease in patients with diabetes mellitus

The prevalence of cardiovascular diseases (CVDs) is well known. According to the World Health Organization (WHO), almost 18 million people die from CVDs worldwide every year, accounting for 31% of all causes of death [1]. CVDs often develop concomitantly with diabetes mellitus (DM), with approximately 20% of cardiovascular deaths attributed to elevated blood glucose levels [2]. Notably, CVDs are the leading cause of death among patients with type 2 diabetes (T2DM). Based on data from the Federal Register of Diabetes 2022 in Russia, chronic heart failure was the direct cause of death in 24.2% of T2DM cases, followed by acute heart failure (13.1%), cerebrovascular events (10.0%), and myocardial infarction (3.7%) [3].The pathophysiological interplay between atherosclerotic cardiovascular disease and DM has led to a situation where cardiologists are increasingly involved in the treatment of patients with DM, while endocrinologists are encountering a growing number of patients with CVDs. This association has become so apparent that in a recent article published in the European Journal of Cardiology, Yu. Braunwald speculated about the emergence of a new subspecialty - diabetocardiology [4]. Unfortunately, experts predict that the global number of diabetic patients will reach 783 million [5].Recent data on the CV benefits of certain hypoglycemic drugs (primarily, certain SGLT2 inhibitors, several GLP-1 receptor agonists, and a novel non-steroidal mineralocorticoid receptor antagonist finerenone) prove the need for a unified interdisciplinary approach to managing CVDs and DM.Given the importance of integrated and coordinated efforts in managing patients with CVD and DM, the Task Force of the -European Society of Cardiology (ESC) updated, formulated, and published clinical guidelines on the treatment of CVD in diabetic patients in 2023 [6]. This article provides a concise overview of the key provisions outlined in the guidelines.

Cognitive decline and diabetes in the clinical setting

Objective. The aim of our study was to evaluate the prevalence of cognitive decline in patients with diabetes in the clinical setting and to identify patient characteristics directly associated with this condition. patients with diabetes in the clinical setting and to identify patient characteristics directly associated with this condition.
 Methods. In our cross-sectional study, we applied the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) to determine cognitive function in 172 diabetic patients, in the clinical setting. We included 120 patients with type 2 diabetes (T2DM), 42 cases with type 1 diabetes (T1DM) and 10 patients with confirmed secondary diabetes (SDM). The mean age of the participants was 62.4 years (±1.01, min: 26 years, Max: 87 years), with median diabetes duration of 15±11.8 years.
 Results. More than half (55.23%) of the subjects presented cognitive deterioration, which was diabetes type-specific (p<0.05). Mild forms affected mostly T1DM and SDM cases (31.5% and 30% vs. T2DM: 14.5%, p=0.00), whereas moderate cognitive decline was more predominant in T2DM (21.9% vs. T1DM: 7.1%, p=0.1). A higher prevalence of severe cognitive impairment was present in T1DM (14.5% vs. T2DM: 8.7%, p=0.1).
 The middle-aged category (40-64 years) was characterized by a more significant reduction of cognitive function in comparison with other age groups (p=0.02).
 No gender-related difference in the prevalence of cognitive decline was found (female: 45.83% vs male: 45.71%, p=0.98), although severe forms were significantly more suggestive for men (15.27% vs. 4.18%, p=0.04).
 Diabetic ketoacidosis (DKA) at admission was more frequently associated with cognitive deterioration, in comparison with hypoglycemic events (p=0.03).
 In T2DM, cognitive decline (p=0.006, r=-0.342) was associated with the presence of anemia.
 In T2DM women, treatment with calcium-channel blockers facilitated cognitive decrement (p=0.01, r=-0.339), whereas in men, therapy for distal symmetric polyneuropathy resulted in higher MMSE/ MoCA test scores (p=0.00, r=0.72).
 In T1DM, a higher glycemic burden evidenced by increased HbA1c (p=0.03, r=- 0.364) and glycemia at admission (p=0.01, r=-0.389) was suggestive to a more severe form of cognitive impairment. Distal symmetrical polyneuropathy (p=0.05, r=-0.305) and diabetic retinopathy (p=0.03, r=-0.102) was often co-occurring with cognitive decline.
 Cognitive deterioration was associated with insulin therapy (p=0.05, r=-0.232).
 Conclusion. The prevalence of cognitive decline is high in the diabetic population. Risk stratification must start at diagnosis and physicians should follow disease progression periodically, with special attention attributed to T1DM and the middle-aged population.

Systematic immune cell dysregulation and molecular subtypes revealed by single-cell RNA-seq of subjects with type 1 diabetes

BackgroundType 1 diabetes mellitus (T1DM) is a prototypic endocrine autoimmune disease resulting from an immune-mediated destruction of pancreatic insulin-secreting β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta$$\\end{document} cells. A comprehensive immune cell phenotype evaluation in T1DM has not been performed thus far at the single-cell level.MethodsIn this cross-sectional analysis, we generated a single-cell transcriptomic dataset of peripheral blood mononuclear cells (PBMCs) from 46 manifest T1DM (stage 3) cases and 31 matched controls.ResultsWe surprisingly detected profound alterations in circulatory immune cells (1784 dysregulated genes in 13 immune cell types), far exceeding the count in the comparator systemic autoimmune disease SLE. Genes upregulated in T1DM were involved in WNT signaling, interferon signaling and migration of T/NK cells, antigen presentation by B cells, and monocyte activation. A significant fraction of these differentially expressed genes were also altered in T1DM pancreatic islets. We used the single-cell data to construct a T1DM metagene z-score (TMZ score) that distinguished cases and controls and classified patients into molecular subtypes. This score correlated with known prognostic immune markers of T1DM, as well as with drug response in clinical trials.ConclusionsOur study reveals a surprisingly strong systemic dimension at the level of immune cell network in T1DM, defines disease-relevant molecular subtypes, and has the potential to guide non-invasive test development and patient stratification.

Longitudinal assessment of classic and 11-oxygenated androgen concentrations and their association with type 2 diabetes mellitus development: the Tromsø study

AimWe aimed to investigate changes in pre-diagnostic concentrations of classic and 11-oxygenated androgens in type 2 diabetes (T2DM) cases and healthy controls, associations between androgen concentrations and T2DM, and the potential for androgens to improve the prediction of T2DM when considered in combination with established risk factors.MethodsAndrogen concentrations were analysed in serum samples from 116 T2DM cases and 138 controls at 3, pre-diagnostic time-points: 1986/87 (T1), 1994/95 (T2), and 2001 (T3). Generalised estimating equations were used to longitudinally examine androgen concentrations, and logistic regression models were used to estimate the odds ratios (OR) of T2DM at each time-point. Logistic regression models were also used to calculate area under the receiver operating characteristics curve (AROC) from models including established risk factors alone (ERF model) and established risk factors plus each androgen, respectively, which were compared to identify improvements in predictive ability.ResultsFor women, no significant associations were observed between any of the investigated androgens and T2DM after adjusting for confounders. For men, after adjusting for confounders, concentrations of all investigated 11-oxygenated androgens were higher in cases than controls at one or several time-points. We observed associations between T2DM and concentrations of 11-ketoandrostenedione (OR: 1.59) and 11-ketotestosterone (OR: 1.62) at T1; and 11-hydroxyandrostenedione (OR: 2.00), 11-hydroxytestosterone (OR: 1.76), 11-ketoandrostenedione (OR: 1.84), 11-ketotestosterone (OR: 1.78) and testosterone (OR: 0.45) at T3 in men. The addition of these androgens (including 11-hydroxytestosterone at T2) to the ERF model resulted in an improved ability to predict T2DM in men (AROC: 0.79–0.82). We did not observe significant differences in changes in androgen concentrations over time between cases and controls in either sex.ConclusionOur results demonstrate that testosterone and 11-oxygenated androgens are associated with T2DM in men before diagnosis and may be potential biomarkers in T2DM risk assessment.

Association of phthalate exposure with type 2 diabetes and the mediating effect of oxidative stress: A case-control and computational toxicology study

Phthalic acid esters (PAEs) are widely used as plasticizers and have been suggested to engender adverse effects on glucose metabolism. However, epidemiological data regarding the PAE mixture on type 2 diabetes (T2DM), as well as the mediating role of oxidative stress are scarce. This case-control study enrolled 206 T2DM cases and 206 matched controls in Guangdong Province, southern China. The concentrations of eleven phthalate metabolites (mPAEs) and the oxidative stress biomarker 8-hydroxy-2′-deoxyguanosine (8-OHdG) in urine were determined. Additionally, biomarkers of T2DM in paired serum were measured to assess glycemic status and levels of insulin resistance. Significantly positive associations were observed for mono-(2-ethylhexyl) phthalate (MEHP) and Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP) with T2DM (P < 0.001). Restricted cubic spline modeling revealed a non-linear dose-response relationship between MEHHP and T2DM (Pnon-linear = 0.001). The Bayesian kernel machine regression and quantile g-computation analyses demonstrated a significant positive joint effect of PAE exposure on T2DM risk, with MEHHP being the most significant contributor. The mediation analysis revealed marginal evidence that oxidative stress mediated the association between the mPAEs mixture and T2DM, while 8-OHdG respectively mediated 26.88 % and 12.24 % of MEHP and MEHHP on T2DM risk individually (Pmediation < 0.05). Di(2-ethylhexyl) phthalate (DEHP, the parent compound for MEHP and MEHHP) was used to further examine the potential molecular mechanisms by in silico analysis. Oxidative stress may be crucial in the link between DEHP and T2DM, particularly in the reactive oxygen species metabolic process and glucose import/metabolism. Molecular simulation docking experiments further demonstrated the core role of Peroxisome Proliferator Activated Receptor alpha (PPARα) among the DEHP-induced T2DM. These findings suggest that PAE exposure can alter oxidative stress via PPARα, thereby increasing T2DM risk.

Trends of type 2 diabetes with pulmonary tuberculosis patients,2013–2022, and changes after the coronavirus disease 2019 (COVID-19) pandemic

BackgroundTo describe the trends of Type 2 Diabetes with Pulmonary Tuberculosis (T2DM-TB) patients from 2013 to 2022 and to investigate the impact of COVID-19 lockdown on glycemic control and associated factors in T2DM-TB. MethodsIn this population-based study of the First Affiliated Yijishan Hospital of Wannan Medical College in China, we described the 10-year trends of patients diagnosed with T2DM-TB. We included patients diagnosed with TB, T2DM-TB and T2DM-TB patients for comparative analysis, aged 15 years or older. Data were missing, and both multidrug-resistant (MDR) TB patients and non-T2DM patients were excluded from our study. ResultsWe pooled Type 2 Diabetes (T2DM) and Tuberculosis (TB) data from The First Affiliated Yijishan Hospital of Wannan Medical College in China, gathered between January 1, 2013, and December 31, 2022. The data included 14,227 T2DM patients, 6130 TB patients, and 982 T2DM-TB patients. During the past 10 years, the number of inpatients with TB decreased, while the number of patients with T2DM and T2DM-TB increased year by year. To rule out any influence factors, we analyzed the ratio of the three groups. The ratio of TB/T2DM decreased year by year (p < 0.05), while the ratio of TB-T2DM/TB increasing year by year (p = 0.008). During the COVID-19 epidemic period, there was no significant change in the ratio of TB-T2DM/T2DM (p = 0.156). There was no significant change in the proportion of male patients with TB and TB-T2DM (p = 0.325; p = 0.190), but the proportion of male patients with T2DM showed an increasing trend (p < 0.001). The average age of TB patients over the past 10 years was 54.5 ± 18.4 years and showed an increasing trend year by year (p < 0.001). However, there was no significant change in the age of T2DM or TB-T2DM patients (p = 0.064; p = 0.241). Patients data for the first (2013–2017) and the last (2018–2022) five years were compared. We found that the number of T2DM and TB-T2DM in the last five years was significantly higher than in the first five years, but the number of TB was significantly lower than in the first five years. There is a significant statistical difference in the proportion of TB/T2DM and TB-T2DM/TB, which is similar to the previous results. The average age (56.0 ± 17.6 years) of TB patients in the last five years is significantly higher than in the first five years (53.1 ± 18.9) (p < 0.001). The number of male patients with T2DM in the last five years is higher than that in the first five years, with significant difference (p < 0.001). ConclusionThe trends of T2DM-TB among hospitalized TB patients have increased significantly over the past 10 years, which may be related to the increase in the number of T2DM cases. The COVID-19 pandemic has been effective in controlling the transmission of TB, but it has been detrimental to the control of T2DM. Male patients with T2DM and elderly TB patients are the key populations for future prevention and control efforts.

Association between irisin and vascular complications of type 2 diabetic patients: a prospective case–control study

BackgroundDiabetes vascular complications are classified as either macrovascular (cardiovascular disease) or microvascular (nephropathy). These complications considerably raise the risk of morbidity and death. Irisin is a myokine that has been linked to metabolic disorders and cardiovascular disease. The purpose of this study was to look at the relationship between irisin and vascular complications among type 2 diabetic (T2DM) individuals. In this case–control study, the patients were put into four groups based on the occurrence of a diabetic cardiovascular complications and the presence of diabetic nephropathy into group 1: twenty T2DM cases without complications, group 2: twenty T2DM cases with diabetic nephropathy, group 3: twenty T2DM cases with cardiovascular complications, and group 4: thirty controls. History was taken, and clinical examination was done. Laboratory investigations (fasting blood glucose, 2-h postprandial blood glucose, HbA1C, cholesterol, triglycerides, HDL-C and LDL-C, serum urea and creatinine, albumin/creatinine ratio, eGFR, serum irisin) were analyzed.ResultsSerum level of irisin was significantly lower in T2DM patients than in control. Also, irisin level was significantly lower in diabetic cases with vascular complications versus those without complications. Irisin level had a negative correlation to BMI and lipid profile in diabetic cases and had a positive correlation to eGFR in diabetic patients with cardiovascular complications.ConclusionsIrisin level was significantly lower in T2DM patients than control and in diabetic patients with vascular complications than patients without complications. So, irisin may have a role as a marker of vascular complications in T2DM.

Association between a polygenic lipodystrophy genetic risk score and diabetes risk in the high prevalence Maltese population.

Type 2 diabetes (T2DM) is genetically heterogenous, driven by beta cell dysfunction and insulin resistance. Insulin resistance drives the development of cardiometabolic complications and is typically associated with obesity. A group of common variants at eleven loci are associated with insulin resistance and risk of both type 2 diabetes and coronary artery disease. These variants describe a polygenic correlate of lipodystrophy, with a high metabolic disease risk despite a low BMI. In this cross-sectional study, we sought to investigate the association of a polygenic risk score composed of eleven lipodystrophy variants with anthropometric, glycaemic and metabolic traits in an island population characterised by a high prevalence of both obesity and type 2 diabetes. 814 unrelated adults (n = 477 controls and n = 337 T2DM cases) of Maltese-Caucasian ethnicity were genotyped and associations with phenotypes explored. A higher polygenic lipodystrophy risk score was correlated with lower adiposity indices (lower waist circumference and body mass index measurements) and higher HOMA-IR, atherogenic dyslipidaemia and visceral fat dysfunction as assessed by the visceral adiposity index in the DM group. In crude and covariate-adjusted models, individuals in the top quartile of polygenic risk had a higher T2DM risk relative to individuals in the first quartile of the risk score distribution. This study consolidates the association between polygenic lipodystrophy risk alleles, metabolic syndrome parameters and T2DM risk particularly in normal-weight individuals. Our findings demonstrate that polygenic lipodystrophy risk alleles drive insulin resistance and diabetes risk independent of an increased BMI.

Type 2 Diabetes Mellitus and Non-Metastatic Colorectal Cancer: A Retrospective Study on Survival and Toxicity Profiles.

Being one of the most common cancers accounting for approximately 185 million cases globally, colorectal cancer (CRC) is one of the leading derivers of cancer-related mortalities. A high prevalence of Type 2 diabetes mellitus and CRC was noted, together with a causal link between diabetes and CRC development. Thereby, the goal of this study was to properly evaluate type 2 Diabetes mellitus in non-metastatic colorectal cancer patients, and to highlight its impacts on patient's outcome. Patients with non-metastatic colorectal cancer diagnosed between January 2016 and December 2020 were studied retrospectively. Patients were divided into two groups based on whether or not they had type II diabetes. The clinico-pathological, laboratory, treatment and survival data were gathered. A total of 318 patients were included in this study. The toxicity of the drugs used in CRC patients receiving the treatment protocols (169 in non-T2DM group and 39 in T2DM group), both groups reported close percentage of side effects and a similar frequency of drug toxicity occurrence as well as grade of toxicity, with the exception of neuropathy, which was more common in the T2DM group (33.3% vs 11.2%). As for prognosis, non-T2DM and T2DM patients had a mean progression free survival of (71.4 and 60.83 months, respectively) (p = 0.019). Overall survival was 73.1% for T2DM and 85.3% for non T2DM cases. The median overall survival was not reached for both groups in terms of overall survival. T2DM is considered a risk factor for poor survival among CRC patients. Treatment related toxicity is not affected by the presence or absence of diabetes, yet neuropathy needs further studies for diabetic patients receiving oxaliplatin.

Aberrant DNA methylation of CDKN2B gene in the Type 1 diabetes mellitus and analysis of epigenetic markers

IntroductionAberrant DNA methylation is one of the important molecular markers in acute lymphoblastic leukemia (ALL). ObjectivesTo determine Aberrant DNA methylation profiles of the CDKN2A and CDKN2B genes in ALL samples from T1DM cases. ResultsAberrant hypermethylation of CDKN2B gene and cytogenetic abnormalities were analyzed in >60% of subjected cases. Total cholesterol, triglycerides and low-density lipoprotein cholesterol were not significantly varied between experimental and control (p >0.05). Expression analysis of human peripheral blood mononuclear cells revealed decreased mRNA levels of CDKN2B. The decreased level of p21 and CDK4 expression in the T1DM cases than control. The number of monocytes, lymphocytes and neutrophils significantly varied in T1DM samples and control (p < 0.05). ConclusionsAberrant methylation is one of the important mechanisms involved in the expression of CDKN2B genes and is an important prognostic marker for the early detection of ALL risks.

Schizophrenia polygenic risk score and type 2 diabetes onset in older adults with no schizophrenia diagnosis.

An association between type 2 diabetes (T2DM) and schizophrenia has long been observed, and recent research revealed presence of shared genetic factors. However, epidemiological evidence was inconsistent, some reported insignificant contribution of genetic factors to T2DM-schizophrenia comorbidity. Prior works studied people with schizophrenia, particularly, antipsychotic-naive patients, or those during the first psychotic experience to limit schizophrenia-related environmental factors. In contrast, we controlled such factors by utilizing a general population sample of individuals undiagnosed with schizophrenia. We hypothesized that if schizophrenia genetics impact T2DM development and such impact is not fully mediated by schizophrenia-related environment, people with high polygenic schizophrenia risk would exhibit elevated T2DM incidence. Using a population-representative sample of adults aged ≥50 from English Longitudinal Study of Ageing ( n = 5968, 493 T2DM cases, average follow-up 8.7 years), we investigated if schizophrenia polygenic risk score (PGS-SZ) is associated with T2DM onset. A proportional hazards model with interval censoring was adjusted for age and sex (Model 1), and age, sex, BMI, hypertension, cardiovascular diseases, exercise, smoking, depressive symptoms and T2DM polygenic risk score (Model 2). According to the power calculations, hazard rates > 1.14 per standard deviation in PGS-SZ could be detected. We did not observe a significant association between PGS-SZ and T2DM incidence (hazard ratio 1.04; 95% CI 0.93-1.15; and 1.01, 95% CI 0.94-1.09). Our results suggest low contribution of the intrinsic biological mechanisms driven by the polygenic risk of schizophrenia on future T2DM onset. Further research is needed.

232-LB: Transcriptional Regulation of Adipocyte Insulin and Inflammatory Signaling by Early B-Cell Factor-1 (Ebf1)

Overnutrition is causally associated with many chronic diseases, including insulin resistance and diabetes, heart disease, hypertension, and cancer. Chronic activation of the innate immune system may lie at the heart of a majority of T2DM cases; the bulk of the evidence suggests that a litany of inflammatory cytokines and toxic lipid species released from irritated adipocytes contribute significantly to disrupted insulin signaling in metabolic tissues and may eventually lead to frank type 2 diabetes. However, the molecular mechanisms that initiate these inflammatory events in adipocytes remain unknown, particularly at the transcriptional level. Our previous work showed that the transcription factor Ebf1 regulates insulin signaling and promotes inflammation in adipocytes; however, the precise molecular mechanisms through which Ebf1 regulates the expression of inflammatory loci remain unknown (as evidence had suggested Ebf1 regulates these genes indirectly). We have recently discovered that Ebf1 can physically interact with multiple subunits of the well-known inflammatory transcription factor NF-κB, and many of the critical inflammatory loci showing impaired expression in Ebf1-deficient 3T3-L1 adipocytes also happen to be well-established NF-κB target genes. This striking result likely explains our paradoxical observations that EBF1 directly (and positively) regulates several core insulin signaling genes (Pik3r1, Akt, etc.) but also promotes insulin resistance in adipocytes—apparently without directly occupying inflammatory loci. We are currently working on physically and functionally characterizing these interactions and propose a model to explain the previously-mentioned paradox. If our hypothesis is correct, we anticipate that the eventual development of pharmaceutical agents designed to interfere with EBF1-NF-κB protein-protein interactions may represent a viable treatment for overnutrition-associated diabetes. Disclosure A. Gutierrez: None. Y. Martinez: None. K. Ibarra: None. Z. Bailey: None. M. Griffin: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases

0826 Chronotype, unhealthy lifestyle, and diabetes risk in middle-aged US women: A prospective cohort study in Nurses’ Health Study II

Abstract Introduction Chronotype refers to one’s inclination to earlier or later sleeping times. Late chronotype has been linked to increased diabetes risk, which may be mediated through adherence to unhealthy lifestyle. This study aimed to evaluate the interplay among chronotype, lifestyle factors, and diabetes risk. Methods In 2009, 63,594 diabetes-free women (mean age=54 yrs) from the Nurses’ Health Study II self-reported their chronotype using a validated question from the Morningness-Eveningness Questionnaire and were prospectively followed for incident type 2 diabetes (T2DM) until June 2017. Unhealthy lifestyle was defined by having &amp;lt; 4 of the following 6 healthy lifestyle factors: high diet quality (AHEI≥49), physical activity (≥3.5 MET-hours/week), moderate alcohol intake (≥5 and &amp;lt; 15 g/day), normal body mass index (≥18.5 and &amp;lt; 25 kg/m2), non-current smoking, and 7-9 hours of sleep. T2DM was self-reported and confirmed using a validated supplementary questionnaire. We used modified Poisson regression models to estimate the cross-sectional associations between chronotype and unhealthy lifestyle. Cox proportional hazards models were used to estimate the adjusted hazard ratios (aHR) for incident diabetes risk according to chronotype and assess the proportion of the association explained by lifestyle factors (mediation analyses). Results Participants reporting a “definitely-evening” type were 55% (95% CI: 1.51-1.60) more likely to have an unhealthy lifestyle compared with participants reporting a “definitely-morning” type. We documented 1,921 T2DM cases over 468,555 person-years of follow-up. With increasing eveningness, the risk of T2DM became significantly higher (Ptrend&amp;lt; 0.0001). Compared with the “definitely-morning” type, the aHR (95% CI) for T2DM was 1.10 (0.97-1.24) for “more-morning”, 1.01 (0.81-1.27) for “intermediate”, 1.26 (1.11-1.42) for “more-evening”, and 1.65 (1.44-1.90) for “definitely-evening” chronotypes, after adjusting for sociodemographic factors, shift-work, depression and family history of diabetes. Additional adjustment of unhealthy lifestyle explained 56.8% (95% CI: 39.4%-72.6%) of the association [aHR (95% CI) for “definitely-evening” versus “definitely-morning”: 1.27 (1.10-1.46)]. Conclusion Women with a late chronotype are more likely to engage in unhealthy lifestyle behaviors. Late chronotype is prospectively associated with increased diabetes risk, which is partly explained by unhealthy lifestyle behaviors. Our results suggest that lifestyle interventions may potentially reduce the adverse impact of late chronotype on diabetes risk. Support (if any) R01HL155395, K01HL143034, U01CA176726

Vitamin D Levels and Microvascular Complications in Type 2 Diabetes Mellitus Patients: A Study from North Keral

Introduction: Vitamin D plays an important role in glucose metabolism. Several pleiotropic effects of Vitamin D have been studied like regulation of cell proliferation, suppression of cell mediated immunity, Glial cell line-derived neurotrophic factor, stimulation of nerve growth factor, suppression of Renin-angiotensin-aldosterone system (RAAS), reduction of albuminuria, immunomodulatory effects, and anti-inflammatory effects.(1)Thus, vitamin D is implicated in the pathogenesis of retinopathy, neuropathy and nephropathy.&#x0D; Materials and Methods: A Cross-sectional case-control study of 206 patients (&gt;30 years), who met the American Diabetes Association, 2011 criteria (2) for type 2 DM, was conducted. Subjects were evaluated for the presence of microvascular complications by clinical evaluation, urine examination, fundus examination, clinical neuropathy scoring, and various biochemical tests. 25-OH cholecalciferol levels were done and cut off level for vitamin D deficiency was 30 ng/ml. 72 Vitamin D sufficient and 134 Vitamin D deficient cases were studied.&#x0D; Results: A total of 134 T2DM cases with Vitamin D deficiency were studied. 72 age matched T2DM patients with sufficient Vitamin D levels served as controls. The mean age of cases under study was 47.58 ± 9.63 years compared to 51.24 ± 8.75 years of controls. 61.2% were females, whereas 38.8% were males in the case group while in the control group, 69.4% were males, and 30.5% were females. The mean duration of diabetes in the cases studied was 57.08 ± 18.13 months. It was 52.69 ± 17.98 months in the Vitamin D sufficient controls. Significant statistical associations were established using Chi square test between Vitamin D status and development of microvascular complications like Diabetic nephropathy, retinopathy and neuropathy in Type 2 Diabetes Mellitus at p &lt; 0.05.&#x0D; Conclusion and Implication: Vitamin D is an important factor in modifying the risk of Type 2 DM and its microvascular complications, especially Diabetic retinopathy, neuropathy and nephropathy. Administration of vitamin D supplements may prove to be a beneficial adjuvant therapy in mitigating microvascular complications. Frequent Monitoring of Vitamin D status can decrease the burden of co-morbidities in T2DM and thus can decrease the mortality rate associated with T2DM. However; the exact role of vitamin D in these processes requires further investigations.&#x0D; Keywords:&#x0D; Diabetes, Nephropathy, Neuropathy, Retinopathy, Vitamin D

Role of glucagon-like peptide 1 (GLP-1) and its association with inflammatory markers in the pathogenesis of type 2 diabetes mellitus

Background: Diabetes mellitus is a multifactorial disease associated with hyperglycemia and increased risk of progression of vascular complications. Stimulation of insulin secretion by the incretin hormone glucagon-like peptide 1 (GLP-1) has been found to be diminished in hyperglycemia. We hypothesized that this impairment is due to defect at the receptor level induced by the diabetic state. Inflammatory markers like TNF-α and IL-6 plays a potential role in the pathogenesis of T2DM. Therefore, the present study aims to evaluate whether GLP-1 plays a role in the development of T2DM by modulating the balance between pro and anti-inflammatory markers. Material and methods: A total of 60 subjects were recruited in this study among them 30 were T2DM cases and 30 were healthy controls. m-RNA expression and protein level of GLP-1 receptor, TNF-α and IL-6 in peripheral blood lymphocytes were determined by real time PCR and ELISA respectively. Results: We observed plasma level of GLP-1 was significantly lower in diabetic subjects while serum level of IL-6 and TNF-α were significantly higher level in diabetic subjects (p &lt; 0.05). We found significant down regulation of GLP-1 receptor m-RNA expression in diabetic subjects while expression level of IL-6 and TNF-α were 5.8 and 4 folds respectively higher in diabetic subjects. We found significant negative correlation of m-RNA expression of GLP-1 with protein level while IL-6 and TNF-α showed significant positive correlation. Conclusion: Inflammation plays an important role in the pathogenesis of diabetes mellitus and low GLP-1 levels may promote expression of inflammatory markers due to lack of anti-inflammatory effects of GLP-1

Association between serum complement 1q and the associated factors of acute ischemic stroke in patients with type 2 diabetes.

The aim of this study was to examine the association between serum complement 1q (C1q) and the associated factors of acute ischemic stroke in patients with type 2 diabetes (T2DM). The baseline clinical variables of the participants were collected, and the levels of blood lipids, blood sugar, inflammatory cytokines, and C1q in the three groups were then compared. The variables which affected the associated factors of acute ischemic stroke in T2DM cases were determined. The levels of C1q in the DAIS group were increased significantly compared with those in the T2DM group. Receiver operating characteristic curve analyses showed that the AUC for C1q and the combined diagnosis of acute ischemic stroke were 0.830 (95%CI 0.747-0.914), with a sensitivity of 0.854 and specificity of 0.780. The results of Pearson's correlation analyses demonstrated that C1q was associated positively with low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (PBG), 2-h postprandial blood glucose (2h PG), and high-sensitive C reaction protein (hs-CRP) (all p < .05). Stratified analysis showed that there was a positive relationship between C1q and the associated factors of acute ischemic stroke for partial LDL-C, and hs-CRP strata. Logistic model analysis suggested that C1q was an independent risk factor for acute ischemic stroke in patients with T2DM. After adjusting for potential confounders, a one-standard deviation (SD) increase in C1q level was strongly related to an approximately 1.5-fold increased risk of acute ischemic stroke in cases with a hs-CRP ≥1.78mg/L. In DAIS patients, the levels of C1q were increased significantly and were an independent associated factor which affected the occurrence of acute ischemic stroke.

Predicting type 2 diabetes prevalence for people with severe mental illness in a multi-ethnic East London population

Background and aimsPrevalence of type two diabetes mellitus (T2DM) in people with severe mental illness (SMI) is 2–3 times higher than in general population. Predictive modelling has advanced greatly in the past decade, and it is important to apply cutting-edge methods to vulnerable groups. However, few T2DM prediction models account for the presence of mental illness, and none seemed to have been developed specifically for people with SMI. Therefore, we aimed to develop and internally validate a T2DM prevalence model for people with SMI. MethodsWe utilised a large cross-sectional sample representative of a multi-ethnic population from London (674,000 adults); 10,159 people with SMI formed our analytical sample (1,513 T2DM cases). We fitted a linear logistic regression and XGBoost as stand-alone models and as a stacked ensemble. Age, sex, body mass index, ethnicity, area-based deprivation, past hypertension, cardiovascular diseases, prescribed antipsychotics, and SMI illness were the predictors. ResultsLogistic regression performed well while detecting T2DM presence for people with SMI: area under the receiver operator curve (ROC-AUC) was 0.83 (95 % CI 0.79–0.87). XGBoost and LR-XGBoost ensemble performed equally well, ROC-AUC 0.83 (95 % CI 0.79–0.87), indicating a negligible contribution of non-linear terms to predictive power. Ethnicity was the most important predictor after age. We demonstrated how the derived models can be utilised and estimated a 2.14 % (95 %CI 2.03 %-2.24 %) increase in T2DM prevalence in East London SMI population in 20 years’ time, driven by the projected demographic changes. ConclusionsPrimary care data, the setting where prediction models could be most fruitfully used, provide enough information for well-performing T2DM prevalence models for people with SMI. We demonstrated how thorough internal cross-validation of an ensemble of a linear and machine-learning model can quantify the predictive value of non-linearity in the data.

Decoding type 2 diabetes mellitus genetic risk variants in Pakistani Pashtun ethnic population using the nascent whole exome sequencing and MassARRAY genotyping: A case-control association study.

Genome-wide association studies have greatly increased the number of T2DM associated risk variants but most of them have focused on populations of European origin. There is scarcity of such studies in developing countries including Pakistan. High prevalence of T2DM in Pakistani population prompted us to design this study. We have devised a two stage (the discovery stage and validation stage) case-control study in Pashtun ethnic population in which 500 T2DM cases and controls each have been recruited to investigate T2DM genetic risk variants. In discovery stage Whole Exome Sequencing (WES) was used to identify and suggest T2DM pathogenic SNPs, based on SIFT and Polyphen scores; whereas in validation stage the selected variants were confirmed for T2DM association using MassARRAY genotyping and appropriate statistical tests. Results of the study showed the target positive association of rs1801282/PPARG (OR = 1.24, 95%Cl = 1.20-1.46, P = 0.010), rs745975/HNF4A (OR = 1.30, 95%Cl = 1.06-1.38, P = 0.004), rs806052/GLIS3 (OR = 1.32, 95%Cl = 1.07-1.66, P = 0.016), rs8192552/MTNR1B (OR = 1.53, 95%Cl = 0.56-1.95, P = 0.012) and rs1805097/IRS-2 (OR = 1.27, 95%Cl = 1.36-1.92, P = 0.045), with T2DM; whereas rs6415788/GLIS3, rs61788900/NOTCH2, rs61788901/NOTCH2 and rs11810554/NOTCH2 (P>0.05) showed no significant association. Identification of genetic risk factors/variants can be used in defining high risk subjects assessment, and disease prevention.