Occurrence Of Type 2 Diabetes Research Articles

Association of circulating inflammatory proteins with type 2 diabetes mellitus and its complications: a bidirectional Mendelian randomization study.

Increasing evidence indicates that immune response underlies the pathology of type 2 diabetes (T2D). Nevertheless, the specific inflammatory regulators involved in this pathogenesis remain unclear. We systematically explored circulating inflammatory proteins that are causally associated with T2D via a bidirectional Mendelian randomization (MR) study and further investigated them in prevalent complications of T2D. Genetic instruments for 91 circulating inflammatory proteins were derived from a genome-wide association study (GWAS) that enrolled 14,824 predominantly European participants. Regarding the summary-level GWASs of type 2 diabetes, we adopted the largest meta-analysis of European population (74,124 cases vs. 824,006 controls) and a prospective nested case-cohort study in Europe (9,978 cases vs. 12,348 controls). Summary statistics for five complications of T2D were acquired from the FinnGen R9 repository. The inverse variance-weighted method was applied as the primary method for causal inference. MR-Egger, weighted median and maximum likelihood methods were employed as supplementary analyses. Results from the two T2D studies were combined in a meta-analysis. Sensitivity analyses and phenotype-wide association studies (PheWAS) were performed to detect heterogeneity and potential horizontal pleiotropy in the study. Genetic evidence indicated that elevated levels of TGF-α (OR = 1.16, 95% CI = 1.15-1.17) and CX3CL1 (OR = 1.30, 95% CI = 1.04-1.63) promoted the occurrence of T2D, and increased concentrations of FGF-21 (OR = 0.87, 95% CI = 0.81-0.93) and hGDNF (OR = 0.96, 95% CI = 0.95-0.98) mitigated the risk of developing T2D, while type 2 diabetes did not exert a significant influence on said proteins. Elevated levels of TGF-α were associated with an increased risk of ketoacidosis, neurological complications, and ocular complications in patients with T2D, and increased concentrations of FGF-21 were potentially correlated with a diminished risk of T2D with neurological complications. Higher levels of hGDNF were associated with an increased risk of T2D with peripheral vascular complications, while CX3CL1 did not demonstrate a significant association with T2D complications. Sensitivity analyses and PheWAS further ensure the robustness of our findings. This study determined four circulating inflammatory proteins that affected the occurrence of T2D, providing opportunities for the early prevention and innovative therapy of type 2 diabetes and its complications.

Using data on biomarkers and siblings to study early-life economic determinants of type-2 diabetes.

We study the effect of economic conditions early in life on the occurrence of type-2 diabetes in adulthood using contextual economic indicators and within-sibling pair variation. We use data from Lifelines: a longitudinal cohort study and biobank including 51,270 siblings born in the Netherlands from 1950 onward. Sibling fixed-effects account for selective fertility. To identify type-2 diabetes we use biomarkers on the hemoglobin A1c concentration and fasting glucose in the blood. We find that adverse economic conditions around birth increase the probability of type-2 diabetes later in life both in males and in females. Inference based on self-reported diabetes leads to biased results, incorrectly suggesting the absence of an effect. The same applies to inference that does not account for selective fertility.

The rest-activity rhythm, genetic susceptibility and risk of type 2 diabetes: A prospective study in UK Biobank.

This study aims to examine the association between the rest-activity rhythm (RAR) and the incidence of type 2 diabetes (T2D). In total, 97 503 participants without diabetes in the UK Biobank cohort were recruited. Wearable accelerometry was used to monitor circadian behaviour. The parameters of RAR including inter-daily stability, intra-daily variability, relative amplitude (RA), most active continuous 10 h period (M10), and least active continuous 5 h period (L5) were calculated to evaluate the robustness and regularity of the RAR. The weighted polygenic risk score for T2D (T2D-PRS) was calculated. Cox proportion hazards models were used to evaluate the survival relationship and the joint and interaction effects of RAR parameters and T2D-PRS on the occurrence of T2D. During 692 257 person-years follow-ups, a total of 2434 participants were documented. After adjustment for potential confounders, compared with participants in the highest quartile of RA and M10, the participants in the lowest quartile had a greater risk of T2D (HRRA = 2.06, 95% CI: 1.76-2.41; HRM10 = 1.33, 95% CI: 1.19-1.49). Meanwhile, the highest quartile of L5 was related to a higher risk of T2D (HR = 1.78, 95% CI: 1.55-2.24). The joint analysis showed that the high T2D-PRS with the lowest quartile of RA and M10, or highest quartile of L5 jointly increased the risk of T2D (HRRA = 4.46, 95% CI: 3.36-6.42; HRM10 = 3.15, 95% CI: 2.29-4.32; HRL5 = 3.09, 95% CI: 2.40-3.99). No modification effects of T2D-PRS on the association between the RAR parameters and risk of T2D were observed (p > .05). The unbalanced RAR are associated with a greater risk of T2D, which are independent of known risk factors of T2D.

Cytokine Gene Polymorphisms in Patients with Chronic Inflammatory Demyelinating Polyneuropathy.

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients (p = 0.049), but the GA genotype prevailed among the patients (p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs (p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 (p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients (p = 0.049) and the CG heterozygote in the HCs (p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier (p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.

Evaluating the Inter Relationship between Obesity and Diabetes Mellitus Type 2: A Clinical Pilot Study

Purpose: This study aims to investigate the effect of anthropometric parameters and clinical indexes on a sample of diabetic patients. Material and Methods: 440 patients with Type 2 diabetes (T2D), with an average age of 49.9 years, who were selected from a sample of 2.500 cases. Entry criteria for the group were the long-term follow-up period of patients and the repeatability of lab tests. Results: A strong effect was observed between Body Mass Index (BMI) and hyperglycemia. The frequency of T2D occurrence, was higher in overweight patients (>25 kg/m²) than in those with normal weight (<25 kg/m²). The mean BMI of newly diagnosed diabetic patients was 30.2 Kg/m². There was found a dependence between BMI and sex with the occurrence of cholelithiasis-cholecystitis, with a higher incidence in the class of obese and women. People with normal weight were found to have T2D at a younger age than the other BMI classes that did not differ from each other. Women show higher glucose concentrations than men with normal body weight. At the same BMI class, blood glucose is higher in women than in overweight class. In men no change in glucose was observed at the different BMI classes. The transition of hemoglobin (HbA1c) from step 2 (>7%) to step 1 (<7%) causes a triglyceride concentration reduction of 14.5%. BMI was recorded as the third factor correlated with hyperglycemia, after predisposition and hyperlipidemia and before diastolic blood pressure and age. Conclusions: At the ascertainment of the newly diagnosed T2D, the presence or not of obesity, determined of BMI, does not affect blood glucose levels in men. In women the normal BMI levels are not deterrent factors of high glucose values, nor age, regardless of gender. BMI is classified as third correlation factor of highglucose values in newly diagnosed diabetics.

Type 2 diabetes with obesity and hypertension: prevalence and sociodemographic risk factors in Yemen

BACKGROUND: Diabetes Mellitus is a rapidly growing and challenging health issue of the 21st century. Type 2 diabetes (T2D) is a major risk factor for obesity and hypertension (HTN). The prevalence of HTN and obesity in T2D patients is not well documented in the country of Yemen. AIM: The focus of this study was to assess the prevalence of hypertension and obesity in patients with type 2 diabetes mellitus in Yemen.METHODS: A cross-sectional study was carried out in Dhamar city hospitals. Patients diagnosed with diabetes (300 males and females: 30 years old and/or above) visiting an endocrinology and diabetes clinic in Dhamar city hospital for the first time were examined and evaluated for blood glucose levels, mode of treatment, duration of the disorder and body mass index. Socio-demographic and clinical data were collected using pretested questionnaires. Ethical approval was obtained from corresponding ethical committees from Dhamar University and hospitals. Data were analyzed using SPSS 23 version.RESULTS: The prevalence of overweight and/or obesity in T2D was 60.67%, and hypertension was 35.66%. The occurrence of T2D was predominant in females (56.33%), patients with an age over 50 years (61%), and rural dwellers (74%). The mode of treatment was mainly through oral antihyperglycemic and hypoglycemic agents (79.3%). A large population (66.3%) showed poor control of blood glucose levels ranging from more than 131 to 500 mg/dL and the type of work these patients were involved in was mostly physically inactive (64%). The body mass index revealed that more than 35% were found to be overweight and 23% to be obese. Patients with hypertension and undergoing treatment for the same showed a significant (P < 0.001) increase in blood glucose level compared to those who were not diagnosed with HTN.CONCLUSION: The prevalence of obesity, HTN, and poor glycemic control in patients with T2D is high, especially in females.

Abstract P346: Adherence to the French Dietary Guidelines and Type 2 Diabetes Risk: The E3n-Epic Prospective Cohort Study

Background: Recently, a dietary index reflecting adherence to the 2017 French food-based dietary guidelines, the Programme National Nutrition Santé - guidelines score 2 (PNNS-GS2), has been developed, but evidence on its level of adherence and incident type 2 diabetes (T2D) risk is limited. Objective: We aimed to investigate the association between adherence to the simplified PNNS-GS2 (sPNNS-GS2) and the risk of incident T2D in a French cohort of women. Methods: Between 1993 and 2014, 71,450 women aged over 18 years were examined, and thereafter followed up for the occurrence of T2D within the E3N-EPIC prospective cohort. Dietary data were collected at baseline via a food frequency questionnaire, and the sPNNS-GS2 was derived for each participant. Multivariable Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) of T2D for continuous and quintile groups of the sPNNS-GS2. Effect modification by body mass index (BMI) and mediation by BMI and waist-hip ratio (WHR) were explored. Results: The mean age was 52.9 years (SD 6.7). During a mean follow-up of 19 years, 3679 incident T2D cases were identified and validated. There was a linear association between adherence to sPNNS-GS2 and T2D risk (P non-linear = 0.85). In the fully adjusted model, each 1-SD increase in the sPNNS-GS2 was associated with a 8% decrease risk of T2D [HR (95% CI), 0.92 (0.89, 0.95)]. Compared to those with the lowest adherence (first quintile), the third [HR (95% CI), 0.91 (0.82, 1.00)] up to the fifth quintile group [HR (95% CI), 0.79 (0.71, 0.88)] had a lower T2D risk. There was a sPNNS-GS2 x BMI interaction on T2D risk (P interaction < 0.01) but not with WHR. The overall association was partly mediated by BMI (18%) and WHR (59%). Conclusion: Higher adherence to the 2017 French food-based dietary guidelines was associated with a lower risk of T2D in women. Furthermore, our mediation analysis suggests that the lower risk of T2D in women associated with adherence to the sPNNS-GS2 is partly mediated by obesity measured by BMI or WHR.

Rheumatoid Arthritis Treatment Options and Type 2 Diabetes: Unravelling the Association.

Multiple lines of evidence have increasingly suggested a pathogenic connection between rheumatoid arthritis (RA) and the mechanisms of type 2 diabetes (T2D) in a vicious circle perpetuated by glucose derangement and inflammatory mediators. These findings have been further reinforced by clinical studies showing that the inhibition of interleukin (IL)-1 and IL-6 may allow the treatment of RA and concomitant T2D at the same time. Interestingly, IL-1 inhibition induced a more evident reduction of glycated haemoglobin (HbA1c) in patients with concomitant RA and T2D than in previous studies on IL-1 inhibition in patients with this metabolic disease alone. Thus, the inflammatory pathogenic mechanisms of T2D could be exaggerated in the context of a rheumatic disease, possibly explaining these findings. In fact, IL-1 inhibition could not only palliate glycaemia, but also decrease the progressive decline in insulin secretion associated with T2D, interfering with apoptosis of β-cells, improving their function, and ameliorating the peripheral insulin resistance. Moreover, the maintenance of clinical remission of rheumatic disease could further improve the glucose derangement and reduce the occurrence of T2D in RA. On these bases, the presence of T2D may allow the physicians to perform a better profile of patients with RA according to the principles of precision medicine, tailoring the medical treatment to the individual characteristics. In this context, the benefits of targeting the inflammatory process, mainly by IL-1 inhibition, may be suggested in patients with RA and concomitant T2D.

Novel association of SNP rs2297828 in PRDM16 gene with predisposition to type 2 diabetes

ObjectivesTranscriptional regulator PRD1-BF-1-RIZ1 homology (PR) domain containing protein-16 (PRDM16) has a fundamental function in maintaining energy homeostasis and regulating glucose and lipid metabolism, which are responsible for the development of type 2 diabetes (T2D). However, the impact of genetic variation of PRDM16 gene on T2D risk remains to be investigated. Thus, we evaluated the possible association between genetic variants within PRDM16 region and T2D development in Chinese individuals. MethodsA total of 427 T2D patients and 408 healthy controls were enrolled. Ten single-nucleotide variants across PRDM16 gene were screened with the SNaPshot assay. The effect of genotypes and alleles of different variant on the T2D risk was examined under diverse genetic models. The impact of genetic variant on promoter activity was determined using an in vitro luciferase reporter gene assay. ResultsGenotypic frequency of rs2297828 in the PRDM16 promoter region was significantly different between patients with T2D and controls (P = 0.004). The minor allele A of rs2297828 was potentially associated with a higher T2D susceptibility in a dominant model (AG + AA vs GG: OR = 1.54, 95 % CI: 1.12–1.12; P = 0.007), and the subjects with either an AA homozygote or an AG heterozygote displayed increased fasting blood levels of glucose and lipids. Reporter gene assays demonstrated that rs2297828 can influence the activity of the PRDM16 promoter. ConclusionsWe firstly observed that PRDM16 variation might influence T2D occurrence, and rs2297828 might be a functional variant that can influence the expression of PRDM16.

The mitochondrial NAD kinase functions as a major metabolic regulator upon increased energy demand

ObjectiveThe mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (MNADK) mediates de novo mitochondrial NADP biosynthesis by catalyzing the phosphorylation of NAD to yield NADP. In this study, we investigated the function and mechanistic basis by which MNADK regulates metabolic homeostasis. MethodsGeneralized gene set analysis by aggregating human patient genomic databases, metabolic studies with genetically engineered animal models, mitochondrial bioenergetic analysis, as well as gain- and loss- of-function studies were performed to address the functions and mechanistic basis by which MNADK regulates energy metabolism and redox state associated with metabolic disease. ResultsHuman MNADK common gene variants or decreased expression of the gene are significantly associated with the occurrence of type-2 diabetes, non-alcoholic fatty liver disease (NAFLD), or hepatocellular carcinoma (HCC). Ablation of the MNADK gene in mice led to decreased fat oxidation, coincident with increased respiratory exchange ratio (RER) and decreased energy expenditure upon energy demand triggered by endurance exercise or fasting. On an atherogenic high-fat diet (HFD), MNADK-null mice exhibited hepatic insulin resistance and glucose intolerance, indicating a type-2 diabetes-like phenotype in the absence of MNADK. MNADK deficiency led to a decrease in mitochondrial NADP(H) but an increase in cellular reactive oxygen species (ROS) in mouse livers. Consistently, protein levels of the major metabolic regulators or enzymes were decreased, while their acetylation modifications were increased in the livers of MNADK-null mice. Feeding mice with a HFD caused S-nitrosylation (SNO) modification, a posttranslational modification that represses protein activities, on MNADK protein in the liver. Reconstitution of an SNO-resistant MNADK variant, MNADK-S193, into MNADK-null mice mitigated hepatic steatosis induced by HFD. ConclusionMNADK, the only known mammalian mitochondrial NAD kinase, plays important roles in preserving energy homeostasis to mitigate the risk of metabolic disorders.

Selenium and Selenoproteins at the Intersection of Type 2 Diabetes and Thyroid Pathophysiology.

Type 2 diabetes (T2D) is considered one of the largest global public-health concerns, affecting approximately more than 400 million individuals worldwide. The pathogenesis of T2D is very complex and, among the modifiable risk factors, selenium (Se) has recently emerged as a determinant of T2D pathogenesis and progression. Selenium is considered an essential element with antioxidant properties, and is incorporated into the selenoproteins involved in the antioxidant response. Furthermore, deiodinases, the enzymes responsible for homeostasis and for controlling the activity of thyroid hormones (THs), contain Se. Given the crucial action of oxidative stress in the onset of insulin resistance (IR) and T2D, and the close connection between THs and glucose metabolism, Se may be involved in these fundamental relationships; it may cover a dual role, both as a protective factor and as a risk factor of T2D, depending on its basal plasma concentration and the individual’s diet intake. In this review we discuss the current evidence (from experimental, observational and randomized clinical studies) on how Se is associated with the occurrence of T2D and its influence on the relationship between thyroid pathophysiology, IR and T2D.

182-LB: Delayed Onset of Parkinson’s Disease among Type 2 Diabetes Subjects—Data from an Observational Study

Background and aim: Parkinson's disease (PD) is a common neurodegenerative movement disorder. Treatment aims at symptoms control and prevention of complications. Although type 2 diabetes (T2D) is a well-established risk factor for cerebrovascular diseases, evidence is lacking with regards to the possible association between T2D and PD. With the present study we aimed at investigating the prevalence and relative time of occurrence of T2D in a cohort of PD patients from an Italian tertiary level center and compare it with the Italian general population. Methods: For this retrospective observational study, the database of the Parkinson Institute ASST Pini-CTO in Milan was queried. We have selected from the database to include and analyze in the study the records of consecutive patients with an established diagnosis of PD based on the UK Parkinson disease Brain Bank criteria followed at our Institute over a 10-year period, from January 2010 to December 2019. Results: A total of 8380 patients were included in the study. At the last follow-up visit, 673 (8.4%) PD patients had T2D. Standardized prevalence of T2D was lower among PD patients compared to the Italian general population (3.8 % vs. 5.3%, p<.05) . Age at PD onset was approximately 67 years in those who had already diagnosed with T2D, a higher mean onset age of 7 years compared with both PD patients with later occurrence of T2D and PD patients without T2D (p<.001) . A multivariate regression analysis showed that PD onset in patients who had T2D for seven years or less was delayed by an average of 2.7 years, while patients with a T2D duration for over seven years displayed a mean delay of 5.7 years compared with patients without T2D before PD onset (p<.001) . Discussion: As per our knowledge so far no other conditions or agents are associated with a delay in the onset of PD. Data from this study show that patients with T2D have a significant delay in PD onset. Causes may be further investigated looking at treatments, hormones, metabolic changes and dietary regimen of T2D. Whether this delay has an impact on the prevalence of PD in the T2D population, remains unclear and need to be studied. Disclosure S. Colosimo: None. E. Cereda: None. F. Del Sorbo: None. D. Calandrella: None. M. Barichella: None. G. Pezzoli: None. Funding Fondazione Grigioni per il Parkinson, Brain and Malnutrition in Chronic Diseases Association

The Kynurenine Pathway in Obese Middle-Aged Women with Normoglycemia and Type 2 Diabetes.

We examined the relationships of tryptophan (Trp) and the metabolites of the kynurenine pathway (KP) to the occurrence of type 2 diabetes (T2D) and metabolic risk factors in obese middle-aged women. The study included 128 obese women divided into two subgroups: a normoglycemic group (NG, n = 65) and a T2D group (n = 63). The concentrations of serum tryptophan (Trp), kynurenine (Kyn), 3-hydroxykynurenine (3HKyn), quinolinic acid (QA), and kynurenic acid (Kyna) were analyzed using ultra-high-performance liquid chromatography coupled with electrospray ionization/triple quadrupole mass spectrometry. Blood biochemical parameters and anthropometric parameters were measured. The women with T2D had significantly higher Trp, Kyna, Kyna/QA ratio, and Kyna/3HKyn ratio values than the NG women. Logistic regression analysis showed that the concentrations of Trp and Kyna and the values of the Kyna/3HKyn ratio were most strongly associated with T2D occurrence, even after controlling for confounding factors. The model with Trp level and Kyna/3HKyn ratio accounted for 20% of the variation in the presence of T2D. We also showed a different pattern of correlations between kynurenines and metabolic factors in the NG and T2D women, which was mostly reflected in the stronger relationship between BMI and KP metabolites in the NG obese women. An increase in Trp and Kyna levels with an accompanying increase in Kyna/3HKyn ratio value is associated with the occurrence of T2D in obese middle-aged women.

Multiomics Integrated Analysis Identifies SLC24A2 as a Potential Link between Type 2 Diabetes and Cancer.

Background So far, type 2 diabetes (T2D) is considered as an independent risk factor for various cancers, but the underlying mechanism remains unclear. Methods. SLC24A2 was first identified as a key gene strongly associated with fasting plasma glucose (FPG). Then, overlapped differentially expressed genes (DEGs) between T2D verse control and SLC24A2-high verse SLC24A2-low were extracted and imported into weighted correlation network analysis. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and gene set enrichment analysis were used for functional enrichment analysis of DEGs. Least absolute shrinkage and selection operator was utilized to build a T2D prediction model. Timer and K-M plotters were employed to find the expression and prognosis of SLC24A2 in pan cancer. Results Interestingly, both DEGs between T2D verse control and SLC24A2-high verse SLC24A2-low enriched in cancer-related pathways. Moreover, a total of 3719 overlapped DEGs were divided into 8 functional modules. Grey module negatively correlated with T2D and FPG and was markedly involved in ribosome biogenesis. Ten SLC24A2-related genes (RRP36, RPF1, GRWD1, FBL, EXOSC5, BCCIP, UTP14A, TWISTNB, TBL3, and SKIV2L) were identified as hub genes, based on which the LASSO model accurately predicts the occurrence of T2D (AUC = 0.841). In addition, SLC24A2 was only expressed in islet β cells and showed abnormal expression in 17 kinds of cancers and significantly correlated with the prognosis of 10 kinds of cancers. Conclusion Taken together, SLC24A2 may link T2D and cancer by influencing the ribosome function of islet β cells and play different prognostic roles in different cancers.

The protease SENP2 controls hepatic gluconeogenesis by regulating the SUMOylation of the fuel sensor AMPKα

Uncontrolled gluconeogenesis results in elevated hepatic glucose production in type 2 diabetes (T2D). The small ubiquitin-related modifier (SUMO)-specific protease 2 (SENP2) is known to catalyze deSUMOylation of target proteins, with broad effects on cell growth, signal transduction, and developmental processes. However, the role of SENP2 in hepatic gluconeogenesis and the occurrence of T2D remain unknown. Herein, we established SENP2 hepatic knockout mice and found that SENP2 deficiency could protect against high-fat diet–induced hyperglycemia. Pyruvate- or glucagon-induced elevation in blood glucose was attenuated by disruption of SENP2 expression, whereas overexpression of SENP2 in the liver facilitated high-fat diet–induced hyperglycemia. Using an in vitro assay, we showed that SENP2 regulated hepatic glucose production. Mechanistically, the effects of SENP2 on gluconeogenesis were found to be mediated by the cellular fuel sensor kinase, 5′-AMP-activated protein kinase alpha (AMPKα), which is a negative regulator of gluconeogenesis. SENP2 interacted with and deSUMOylated AMPKα, thereby promoting its ubiquitination and reducing its protein stability. Inhibition of AMPKα kinase activity dramatically reversed impaired hepatic gluconeogenesis and reduced blood glucose levels in SENP2-deficient mice. Our study highlights the novel role of hepatic SENP2 in regulating gluconeogenesis and furthers our understanding of the pathogenesis of T2D.

A bioinformatics analysis of the contribution of m6A methylation to the occurrence of diabetes mellitus.

N6-methyladenosine (m6A) methylation has been reported to play a role in type 2 diabetes (T2D). However, the key component of m6A methylation has not been well explored in T2D. This study investigates the biological role and the underlying mechanism of m6A methylation genes in T2D. The Gene Expression Omnibus (GEO) database combined with the m6A methylation and transcriptome data of T2D patients were used to identify m6A methylation differentially expressed genes (mMDEGs). Ingenuity pathway analysis (IPA) was used to predict T2D-related differentially expressed genes (DEGs). Gene ontology (GO) term enrichment and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to determine the biological functions of mMDEGs. Gene set enrichment analysis (GSEA) was performed to further confirm the functional enrichment of mMDEGs and determine candidate hub genes. The least absolute shrinkage and selection operator (LASSO) regression analysis was carried out to screen for the best predictors of T2D, and RT-PCR and Western blot were used to verify the expression of the predictors. A total of 194 overlapping mMDEGs were detected. GO, KEGG, and GSEA analysis showed that mMDEGs were enriched in T2D and insulin signaling pathways, where the insulin gene (INS), the type 2 membranal glycoprotein gene (MAFA), and hexokinase 2 (HK2) gene were found. The LASSO regression analysis of candidate hub genes showed that the INS gene could be invoked as a predictive hub gene for T2D. INS, MAFA,and HK2 genes participate in the T2D disease process, but INS can better predict the occurrence of T2D.

The Relationship Between Menopause and Metabolic Syndrome: Experimental and Bioinformatics Analysis.

Menopausal hormonal changes have been associated with the emergence of the metabolic syndrome (MetS) and its consequences such as type 2 diabetes (T2D) and cardiovascular diseases (CVD). The common gene signature and the associated signaling pathways of MetS, T2D, CVD and menopause status have not been widely studied. We analyzed a total of 314 women aged between 35 and 75years. The sample was divided into two groups: Group I, including women in the premenopausal period and Group II, comprising women in the post-menopausal period. The presence of MetS and its components were evaluated, as well as occurrence of T2D and CVD in both groups. We also exploited the translational bioinformatics approach to choose the common gene signatures for MetS, T2D, CVD and the menopause status. The frequency of the MetS was significantly higher in postmenopausal women than in premenopausal ones (67.1 vs. 27.2%, p < 0.001). Gene mining analysis revealed that a total of 47 genes were commonly associated with MetS, T2D, CVD and the menopausal changes. The gene enrichment analysis showed that these genes were markedly enriched in biological processes, including positive regulation of binding, positive regulation of leukocyte cell-cell adhesion, regulation of lipid localization. Furthermore, P53 signaling pathway, prolactin signaling pathway, parathyroid hormone synthesis, secretion and action were the top enriched pathways. Additionally, network analysis revealed TGFB1, SPP1, MMP2, MMP9, CCL2, IGF1, EGFR, ICAM1, TNF and IL6 as important hub genes with significant interacting partners. These hub genes identified in our study may play key role in menopausal changes and influence the risks of MetS, T2D and CVD.

Early Life Exposure to Food Contaminants and Social Stress as Risk Factor for Metabolic Disorders Occurrence?-An Overview.

The global prevalence of obesity has been increasing in recent years and is now the major public health challenge worldwide. While the risks of developing metabolic disorders (MD) including obesity and type 2 diabetes (T2D) have been historically thought to be essentially driven by increased caloric intake and lack of exercise, this is insufficient to account for the observed changes in disease trends. Based on human epidemiological and pre-clinical experimental studies, this overview questioned the role of non-nutritional components as contributors to the epidemic of MD with a special emphasis on food contaminants and social stress. This overview examines the impact of early life adverse events (ELAE) focusing on exposures to food contaminants or social stress on weight gain and T2D occurrence in the offspring and explores potential mechanisms leading to MD in adulthood. Indeed, summing up data on both ELAE models in parallel allowed us to identify common patterns that appear worthwhile to study in MD etiology. This overview provides some evidence of a link between ELAE-induced intestinal barrier disruption, inflammation, epigenetic modifications, and the occurrence of MD. This overview sums up evidence that MD could have developmental origins and that ELAE are risk factors for MD at adulthood independently of nutritional status.

Prediction of Type 2 Diabetes Based on Machine Learning Algorithm.

Prediction of type 2 diabetes (T2D) occurrence allows a person at risk to take actions that can prevent onset or delay the progression of the disease. In this study, we developed a machine learning (ML) model to predict T2D occurrence in the following year (Y + 1) using variables in the current year (Y). The dataset for this study was collected at a private medical institute as electronic health records from 2013 to 2018. To construct the prediction model, key features were first selected using ANOVA tests, chi-squared tests, and recursive feature elimination methods. The resultant features were fasting plasma glucose (FPG), HbA1c, triglycerides, BMI, gamma-GTP, age, uric acid, sex, smoking, drinking, physical activity, and family history. We then employed logistic regression, random forest, support vector machine, XGBoost, and ensemble machine learning algorithms based on these variables to predict the outcome as normal (non-diabetic), prediabetes, or diabetes. Based on the experimental results, the performance of the prediction model proved to be reasonably good at forecasting the occurrence of T2D in the Korean population. The model can provide clinicians and patients with valuable predictive information on the likelihood of developing T2D. The cross-validation (CV) results showed that the ensemble models had a superior performance to that of the single models. The CV performance of the prediction models was improved by incorporating more medical history from the dataset.

Occurrence and predictive factors of high blood pressure, type 2 diabetes, and metabolic syndrome in rheumatoid arthritis: findings from a 3-year, multicentre, prospective, observational study.

In rheumatoid arthritis (RA), "traditional" cardiovascular (CV) risk factors continue to be underdiagnosed and undertreated, thus increasing the risk of developing atherosclerosis. In this work, we evaluated the occurrence and predictive factors of "traditional" cardiovascular risk factors, with a focus on high blood pressure (HBP), type 2 diabetes (T2D), and metabolic syndrome (MetS), in participants with RA, in a 3-year, multicentre, prospective, observational study. To assess the occurrence and predictive factors of HBP, T2D, and MetS, consecutive participants with RA, admitted to Italian Rheumatology Units, were evaluated in the GIRRCS (Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale) cohort, a 3-year, multicentre, prospective, observational study. In the present evaluation, 841 participants, who were fully followed up with 3-year of prospective follow-up were assessed. At the end of follow-up, a significant increased incidence of HBP, T2D, and MetS was recorded. Assessing predictive factors, the mean values of C-reactive protein during the follow-up were independent predictors of occurrence of those comorbidities, whereas participants maintaining remission showed a significant lower risk. Furthermore, therapy with hydroxychloroquine (HCQ) reduced the risk of occurrence of T2D and MetS. An increased incidence of HBP, T2D, and MetS was observed in assessed participants, prospectively followed-up. Furthermore, the analysis of predictive factors suggested that the rheumatoid pro-inflammatory process could increase the occurrence of these comorbidities. Conversely, metabolic and cardiovascular benefits of maintaining remission as well as of therapy with HCQ were reported.