Association Of Type 2 Diabetes Research Articles

Gut Microbiota in the Progression of Type 2 Diabetes and the Potential Role of Exercise: A Critical Review.

Type 2 diabetes (T2D) is the predominant metabolic epidemic posing a major threat to global health. Growing evidence indicates that gut microbiota (GM) may critically influence the progression from normal glucose tolerance, to pre-diabetes, to T2D. On the other hand, regular exercise contributes to the prevention and/or treatment of the disease, and evidence suggests that a possible way regular exercise favorably affects T2D is by altering GM composition toward health-promoting bacteria. However, research regarding this potential effect of exercise-induced changes of GM on T2D and the associated mechanisms through which these effects are accomplished is limited. This review presents current data regarding the association of GM composition and T2D and the possible critical GM differentiation in the progression from normal glucose, to pre-diabetes, to T2D. Additionally, potential mechanisms through which GM may affect T2D are presented. The effect of exercise on GM composition and function on T2D progression is also discussed.

Type 2 Diabetes and Risk Factors in an Adult Population in Oujda, Eastern Morocco: A Cross-Sectional Observational Study.

Objectives The rapidly increasing prevalence of diabetes makes it a public health concern. Adopting a healthier lifestyle can prevent or delay the onset of type 2 diabetes (T2D), the most common type of diabetes, and its complications. The aim of this study is to determine the prevalence of diabetes at the level of local health centers in the prefecture of Oujda, Morocco, and its relationship with obesity, physical activity, and sociodemographic factors. Methodology In a cross-sectional study in first-line health centers, sociodemographic and bioclinical data were collected through convenient purposive sampling using anthropometric and blood glucose measurements and structured, comprehensible interview questionnaires. The International Physical Activity Questionnaire (IPAQ) questionnaire was used to measure the physical activity of the patients. The association of T2D with age, gender, education, occupation, obesity, and physical activity was analyzed. Results Out of 535 observed patients, 510 were included, mostly female with a minimum age of 18 years, with a prevalence of T2D of 16%. More than half of the patients were illiterate (56%) and 83% had no occupation. Obesity was prevalent, especially among diabetics, and only a minority were physically active according to WHO targets. Thirty-six percent of all patients and 46% of diabetics reported low levels of physical activity. Age and obesity were the main factors associated with T2D. Conclusion Obesity and T2D have a high prevalence in the Oujda region. A balanced diet and regular physical activity remain our best recommendations for preventing this disease. Special attention should be paid to women with diabetes in Arab countriesso that they can actively participate in prevention activities.

Type 2 Diabetes, Circulating Metabolites, and Calcific Aortic Valve Stenosis: A Mendelian Randomization Study.

Epidemiological studies have shown an association between type 2 diabetes (T2D) and calcific aortic valve stenosis (CAVS), but the potential causal relationship and underlying mechanisms remain unclear. Therefore, we conducted a two-sample and two-step Mendelian randomization (MR) analysis to evaluate the association of T2D with CAVS and the mediating effects of circulating metabolites and blood pressure using genome-wide association study (GWAS) summary statistics. The inverse variance weighted (IVW) method was used for the primary MR analysis, and comprehensive sensitivity analyses were performed to validate the robustness of the results. Our results showed that genetically predicted T2D was associated with increased CAVS risk (OR 1.153, 95% CI 1.096-1.214, p < 0.001), and this association persisted even after adjusting for adiposity traits in multivariable MR analysis. Furthermore, the two-step MR analysis identified 69 of 251 candidate mediators that partially mediated the effect of T2D on CAVS, including total branched-chain amino acids (proportion mediated: 23.29%), valine (17.78%), tyrosine (9.68%), systolic blood pressure (8.72%), the triglyceride group (6.07-11.99%), the fatty acid group (4.78-12.82%), and the cholesterol group (3.64-11.56%). This MR study elucidated the causal impact of T2D on CAVS risk independently of adiposity and identified potential mediators in this association pathways. Our findings shed light on the pathogenesis of CAVS and suggest additional targets for the prevention and intervention of CAVS attributed to T2D.

Type 2 diabetes increase the risk of arteriovenous fistula non-maturation, mediated by postoperative vascular hemodynamics.

The progression of atherosclerosis in small and medium-sized vessels has been associated with Type 2 diabetes (T2D). However, the influence of T2D on postoperative vascular remodeling and arteriovenous fistula (AVF) maturation is inconclusive. Besides, hemodynamic changes of postoperative vessel are also associated with AVF maturation. This study is intended to investigate the link between T2D and the occurrence of AVF non-maturation, as well as to delve into the impact of postoperative vascular hemodynamic parameters in this process. A total of 477 hemodialysis patients, with or without type 2 diabetes, underwent AVF creation at Beijing Haidian Hospital (Haidian Section of Pecking University Third Hospital) from August 2018 to March 2022 were collected, and were followed for 1-5years. Logistic regression was applied to analyze the association of T2D, postoperative vascular hemodynamic parameters with the risk of AVF non-maturation. To verify the stability of the results, the sensitivity analyses were performed using propensity scores to match patients. We further investigated the regulatory role of the postoperative vascular hemodynamics. There were 173 patients with T2D and 304 patients without T2D in this study. The maturation rate in T2D and non-T2D group was 47.977% and 63.816%, respectively. The findings of logistic regression analysis suggested that T2D significantly increased the risk of AVF immaturity [OR 1.716 (1.019-2.890), P = 0.042]. Besides, T2D was associated with the restriction of postoperative vascular hemodynamic parameters changes, including with decreased diameter of forearm cephalic radial artery and dilation rate of radial artery. The result of logistic regression analysis indicated that cephalic vein diameter at 1-month [0.402 (0.237-0.681), P = 0.001] and cephalic vein diameter at 2-month [0.501 (0.355-0.708), P < 0.001] were independently correlated with AVF maturation. Besides, the results of sensitivity analysis were consistent with that of logistic regression analysis. Moreover, the mediating effects of cephalic vein diameter were significant. Our findings discovered that T2D significantly increased the risk of arteriovenous fistula non-maturation, which was mainly mediated by the changes of cephalic vein diameter.

Assessment of genetic and clinical factors in T2D susceptibility among patients with hypertension.

Hypertension (HTN) and Type 2 Diabetes (T2D) often coexist, therefore understanding the relationship between both diseases is imperative to guide targeted prevention/therapy. This study aims to explore the relationship between HTN and T2D using genome-wide association study (GWAS) analysis and biochemical data to understand the implication of both clinical and genetic factors in these pathologies. A total of 2,876 patients were enrolled. Using GWAS and biochemical data, patients with both T2D and HTN were compared to patients with only HTN. Specificity was confirmed by testing the detected genetic variants for associations with HTN development in T2D patients, or with HTN in healthy subjects. Regression models were applied to examine the association of T2D in patients with HTN with cardiovascular risk factors. Replication was performed using UK Biobank dataset with 31,170 subjects. Data showed that females with HTN are at higher risk of developing T2D due to dyslipidemia, while males faced higher risk due to high BMI (body mass index) and family history of T2D. GWAS identified Single Nucleotide Polymorphisms (SNPs) linked to T2D in patients with HTN. Notably, rs7865889, rs7756992, and rs10896290 were positively associated with T2D, whereas rs12737517 yielded negative association. Three SNPs were replicated in the UK Biobank (rs10896290, rs7865889, and rs7756992). Incorporating clinical and genetic screening into risk assessment is important for the detection and prevention of T2D in patients with HTN. The detected SNPs (rs7865889, rs12737517, and rs10896290), especially the protective SNP (rs12737517), provide an opportunity for better diagnosis, prevention, and therapy of patients with T2D and HTN.

Abstract P496: Proteomic BMI Signature and Incidence of Type 2 Diabetes

Background: Obesity exhibits heterogeneity in physiological states and metabolic phenotypes cross individuals. A recent study identified a proteomics signature of obesity which better captures such heterogeneity than classical Body Mass Index (BMI). Aims: We aimed to create a proteomics-inferred BMI signature and investigate whether the proteomic-inferred BMI was associated with incident Type 2 Diabetes (T2D). Methods: This study included 34,317 adults in the UK Biobank who were free of T2D and had complete data on proteomics metrics assessed by antibody-based Olink assay. Sixty-seven pre-identified proteins were available and used to create the proteomic BMI signature. Cox proportional models were used to estimate the association between proteomic BMI signature and incident T2D. Results: The proteomic BMI signature was strongly correlated with actual BMI (Pearson correlation coefficients=0.75, P &lt;0.001). During a mean follow-up of 13.2 years, a total of 1,651 T2D events were documented. We observed that per standard deviation increase in proteomic BMI signature was significantly associated with a 250% higher risk of T2D (HR, 2.50, 95%CI, 2.37, 2.64). Compared with the lowest Quartile, the HR (95%CI) for the Quartile 2 to the Quartile 4 of proteomic BMI signature were 2.06 (1.61, 2.64), 3.56 (2.83, 4.48), and 10.0 (8.08, 12.4), respectively ( P -trend&lt;0.001). Also, we observed that the associations between proteomic BMI signature and incident T2D were stronger in women than men ( P for interaction &lt; 0.001). Compared with the lowest Quartile, the HR (95%CI) for highest Quartile of proteomic BMI signature were 16.63 (9.75, 28.36) for women and 8.06 (6.37, 10.19) for men. Conclusions: Higher proteomics-inferred BMI was significantly associated with higher risk of incident T2D, and such association was stronger in women than men. Our results suggest that proteomic BMI signature may serve as a surrogate metabolic indicator to better understand the mechanism underlying the association of BMI and T2D.

Abstract P432: Validation and Optimization of the American Diabetes Association Score for Undiagnosed Type 2 Diabetes Risk in Hispanic or Latino Adults

Background: The prevalence of type 2 diabetes (T2D) is increasing in Hispanic or Latino adults. The American Diabetes Association (ADA) score to identify current risk of T2D was developed with limited Hispanic or Latino representation. Therefore, we sought to validate the ADA score in a cohort of Hispanic or Latino adults. Methods: At enrollment in the Sangre Por Salud Biobank, 3,625 Hispanic or Latino adults from Phoenix, Arizona completed a baseline questionnaire. Current risk of undiagnosed T2D was based on non-laboratory risk factors and ADA score ≥5 (Table). Participants also completed T2D screening (ie, fasting glucose, 2-hour oral glucose tolerance test, and/or hemoglobin A1c). Undiagnosed T2D was based on 'no self-reported T2D but meeting T2D diagnostic’ criteria. Multivariable logistic regression analyzed associations of ADA risk factors and undiagnosed T2D, and model performance was based on sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results: At enrollment, 7.3% of participants had undiagnosed T2D (n=265/3,625). In multivariable analysis, most risk factors described for the ADA score were significantly associated with T2D, except for sex, which showed no association. ADA score ≥5 had sensitivity 50%, specificity 79%, PPV 18%, and NPV 95%. However, ADA score ≥4 had sensitivity 72%, specificity 61%, PPV 14%, and NPV 96%. ADA score ≥4 vs ≥5 identified 22% (n=59) additional cases of undiagnosed T2D. Furthermore, using the revised definition for elevated blood pressure (&gt;120/80 mmHg) vs ≥140/90 mmHg (current ADA score) further improved the ADA score ≥4 (sensitivity 81%; specificity 52%). Other scores had lower performance using both hypertension definitions. Conclusion: In Hispanic or Latino adults, a lower ADA score than currently recommended identified additional cases of undiagnosed T2D. The ADA score requires validation and recalibration, including for the updated hypertension guidelines.

Abstract P151: Increased Gain of Skeletal Muscle Adiposity in Middle-Aged African Caribbean Men With Type 2 Diabetes

While type 2 diabetes (T2D) is a known risk factor for the acceleration of muscle loss with aging, less is known about the impact of T2D on skeletal muscle fat infiltration (i.e., myosteatosis) and overall adiposity. Myosteatosis increases with aging, is greater in African as compared to European ancestry individuals, and plays an important role in the development of T2D. Thus, we investigated the association of T2D with changes in body adiposity distribution, with a particular interest in myosteatosis. T2D was identified by self-report, use of hypoglycemic agents, or fasting glucose levels of ≥ 126 mg/dL. Longitudinal changes in computed tomography-measured calf skeletal muscle density [as an inverse surrogate measure of intramuscular adiposity (mg/cm 3 )] and dual-energy X-ray absorptiometry-measured regional and whole body fat were examined by T2D status over an average of 6 years in 724 African-Caribbean men aged 40-54 years from the Tobago Health Study. Total body, arm, leg, and trunk adiposity increased to a significantly greater extent among men without compared to with T2D. In contrast, men with T2D had a 1.6 times greater decrease in calf skeletal muscle density compared with their non-diabetic counterparts (p=0.03). T2D is associated with lower gains in general adiposity, but an increased gain in skeletal muscle adiposity among middle aged African Caribbean men. Our novel findings suggest that middle-aged African Caribbean men with T2D might be at especially high risk for increased gain of myosteatosis. Interventions targeted for men in this age group could focus on controlling diabetes, slowing myosteatosis, and promoting healthy aging.

Microvascular disease not type 2 diabetes is associated with increased cortical porosity: A study of cortical bone microstructure and intracortical vessel characteristics

IntroductionFracture risk is elevated in type 2 diabetes (T2D) despite normal or even high bone mineral density (BMD). Microvascular disease (MVD) is a diabetic complication, but also associated with other diseases, for example chronic kidney disease. We hypothesize that increased fracture risk in T2D could be due to increased cortical porosity (Ct.Po) driven by expansion of the vascular network in MVD. The purpose of this study was to investigate associations of T2D and MVD with cortical microstructure and intracortical vessel parameters. MethodsThe study group consisted of 75 participants (38 with T2D and 37 without T2D). High-resolution peripheral quantitative CT (HR-pQCT) and dynamic contrast-enhanced MRI (DCE-MRI) of the ultra-distal tibia were performed to assess cortical bone and intracortical vessels (outcomes). MVD was defined as ≥1 manifestation including neuropathy, nephropathy, or retinopathy based on clinical exams in all participants. Adjusted means of outcomes were compared between groups with/without T2D or between participants with/without MVD in both groups using linear regression models adjusting for age, sex, BMI, and T2D as applicable. ResultsMVD was found in 21 (55 %) participants with T2D and in 9 (24 %) participants without T2D. In T2D, cortical pore diameter (Ct.Po.Dm) and diameter distribution (Ct.Po.Dm.SD) were significantly higher by 14.6 μm (3.6 %, 95 % confidence interval [CI]: 2.70, 26.5 μm, p = 0.017) and by 8.73 μm (4.8 %, CI: 0.79, 16.7 μm, p = 0.032), respectively. In MVD, but not in T2D, cortical porosity was significantly higher by 2.25 % (relative increase = 12.9 %, CI: 0.53, 3.97 %, p = 0.011) and cortical BMD (Ct.BMD) was significantly lower by −43.6 mg/cm3 (2.6 %, CI: −77.4, −9.81 mg/cm3, p = 0.012). In T2D, vessel volume and vessel diameter were significantly higher by 0.02 mm3 (13.3 %, CI: 0.004, 0.04 mm3, p = 0.017) and 15.4 μm (2.9 %, CI: 0.42, 30.4 μm, p = 0.044), respectively. In MVD, vessel density was significantly higher by 0.11 mm−3 (17.8 %, CI: 0.01, 0.21 mm−3, p = 0.033) and vessel volume and diameter were significantly lower by −0.02 mm3 (13.7 %, CI: −0.04, −0.004 mm3, p = 0.015) and − 14.6 μm (2.8 %, CI: −29.1, −0.11 μm, p = 0.048), respectively. ConclusionsThe presence of MVD, rather than T2D, was associated with increased cortical porosity. Increased porosity in MVD was coupled with a larger number of smaller vessels, which could indicate upregulation of neovascularization triggered by ischemia. It is unclear why higher variability and average diameters of pores in T2D were accompanied by larger vessels.

Associations of glycosylated hemoglobin, pre-diabetes, and type 2 diabetes with incident lung cancer: A large prospective cohort study

BackgroundThe association of pre-diabetes and type 2 diabetes (T2D) with incident lung cancer is uncertain, and the incident risk across the glycemic spectrum is unclear. We aimed to explore the associations of glycosylated hemoglobin (HbA1c), pre-diabetes, and T2D with incident lung cancer in a large prospective cohort. MethodsLeveraging a total of 210,779 cancer-free adults recruited in the UK Biobank between 2006 and 2010. We performed multivariable Cox proportional hazards models and restricted cubic spline methods to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations of HbA1c, pre-diabetes, and T2D with incident lung cancer. ResultsDuring a median follow-up of 11.06 years, 1738 incident lung cancer cases were ascertained. The incidence of lung cancer was 20% higher among people with diabetes (HR: 1.20, 95% CI: 1.02 to 1.42) and 38% higher among people with pre-diabetes (HR: 1.38, 95% CI: 1.15 to 1.65). After dividing people with diabetes by whether taking antidiabetic medications, the incidence was 28% higher among people with diabetes without medications (HR: 1.28, 95% CI: 1.02 to 1.61) and 15% higher among people with diabetes with medications (HR: 1.15, 95% CI: 0.93 to 1.41). The increased risk of incident lung cancer for each standard deviation (6.45 mmol/mol) increase in HbA1c was more pronounced across HbA1c values of 32–42 mmol/mol (HR: 1.37, 95% CI: 1.18 to 1.59). The risk was more pronounced among participants <60 years. ConclusionsPre-diabetes and T2D are associated with an increased incidence of lung cancer. The increased risk of incident lung cancer is more pronounced across HbA1c values of 32–42 mmol/mol, which are currently considered normal values.

Transcriptomic Analysis of Type 2 Diabetes Mellitus Combined with Lower Extremity Atherosclerotic Occlusive Disease.

The pathological damage mechanism of type 2 diabetes (T2D) and macroangiopathy is extremely complex, and T2D and arteriosclerosis obliterans have different biological behaviors and clinical features. To explore the mechanism of lower extremity arteriosclerosis occlusion (LEAOD) in T2D patients, we utilized RNA-seq to identify unique gene expression signatures of T2D and LEAOD through transcriptomic analysis. We obtained blood samples and performed RNA sequencing from four patients with T2D, five of whom had LEAOD. Another six age- and gender-matched blood samples from healthy volunteers were used for control. By exploring the general and specific differential expression analysis after transcriptome sequencing, specific gene expression patterns of T2D and LEAOD were verified. Transcriptome analysis found differentially expressed genes in T2D, and T2D + LEAOD (vs normal) separately, of which 35/486 (T2D/T2D + LEAOD) were up-regulated and 1290/2970 (T2D/T2D + LEAOD) were down-regulated. A strong overlap of 571 genes across T2D, LEAOD, and coexisting conditions was mainly involved in extracellular exosomes and the transcription process. By exploring the sex difference gene expression features between T2D, T2D + LEAOD, and healthy controls, we noticed that sex chromosome-associated genes do not participate in the sexual dimorphism gene expression profiles of T2D and LEAOD. Protein-Protein Interaction Network analysis and drug target prediction provided the drug candidates to treat T2D and LEAOD. This study provides some evidence at the transcript level to uncover the association of T2D with LEAOD. The screened hub genes and predicted target drugs may be therapeutic targets.

Genetic architecture and biology of youth-onset type 2 diabetes

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1, producing a growing public health concern1 that disproportionately affects minority groups2. The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3. Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females. We identify monogenic diabetes variants in 2.4% of individuals and three exome-wide significant (P < 2.6 × 10−6) gene-level associations (HNF1A, MC4R, ATXN2L). Furthermore, we report rare variant association enrichments within 25 gene sets related to obesity, monogenic diabetes and β-cell function. Many youth-onset T2D associations are shared with adult-onset T2D, but genetic risk factors of all frequencies—and rare variants in particular—are enriched within youth-onset T2D cases (5.0-fold increase in the rare variant and 3.4-fold increase in common variant genetic liability relative to adult-onset cases). The clinical presentation of participants with youth-onset T2D is influenced in part by the frequency of genetic risk factors within each individual. These findings portray youth-onset T2D as a heterogeneous disease situated on a spectrum between monogenic diabetes and adult-onset T2D.

Complete HLA genotyping of type 1 diabetes patients and controls from Mali reveals both expected and novel disease associations.

HLA genotyping was performed on 99 type 1 diabetes (T1D) patients and 200 controls from Mali. Next-generation sequencing of the classical HLA-A, -B, -C, -DRB1, -DRB3, -DRB4, -DRB5, -DQA1, -DQB1, -DPA1, and -DPB1 loci revealed strong T1D association for all loci except HLA-C and -DPA1. Class II association is stronger than class I association, with most observed associations predisposing or protective as expected based on previous studies. For example, HLA-DRB1*03:01, HLA-DRB1*09:01, and HLA-DRB1*04:05 predispose for T1D, whereas HLA-DRB1*15:03 is protective. HLA-DPB1*04:02 (OR = 12.73, p = 2.92 × 10-05 ) and HLA-B*27:05 (OR = 21.36, p = 3.72 × 10-05 ) appear highly predisposing, although previous studies involving multiple populations have reported HLA-DPB1*04:02 as T1D-protective and HLA-B*27:05 as neutral. This result may reflect the linkage disequilibrium between alleles on the extended HLA-A*24:02~HLA-B*27:05~HLA-C*02:02~HLA-DRB1*04:05~HLA-DRB4*01:03~HLA-DQB1*02:02~HLA-DQA1*02:01~HLA-DPB1*04:02~HLA-DPA1*01:03 haplotype in this population rather than an effect of either allele itself. Individual amino acid (AA) analyses are consistent with most T1D association attributable to HLA class II rather than class I in this data set. AA-level analyses reveal previously undescribed differences of the HLA-C locus from the HLA-A and HLA-B loci, with more polymorphic positions, spanning a larger portion of the gene. This may reflect additional mechanisms for HLA-C to influence T1D risk, for example, through expression differences or through its role as the dominant ligand for killer cell immunoglobulin-like receptors (KIR). Comparison of these data to those from larger studies and on other populations may facilitate T1D prediction and help elucidate elusive mechanisms of how HLA contributes to T1D risk and autoimmunity.

Abstract 16868: Genetic Regulation of Branched-Chain Amino Acid Levels Does Not Increase Type 2 Diabetes Risk

Introduction: The branched-chain amino acids (BCAAs) valine, leucine, and isoleucine are associated with incident type 2 diabetes (T2D). Prior genetic studies have provided conflicting results as to whether the BCAAs are causally related to T2D but are limited by a small number of genetic instruments associated with BCAA levels. Hypothesis: We hypothesized that polygenic predictors that capture a broad set of genetic mechanisms regulating BCAA levels would clearly define the etiological relationship with T2D. Methods: We constructed and validated instrumental variables for each BCAA using well-powered datasets and tested their association with T2D using two-sample inverse variance weighted (IWV) Mendelian randomization (MR). Sensitivity analyses were performed to ensure the accuracy of the findings. We also tested whether instrumental variables for T2D, fasting insulin, and body mass index (BMI) were associated with BCAA levels. Finally, logistic regression was used to test whether a polygenic risk score (PRS) for T2D was associated with measured BCAA levels among 1220 participants in the Framingham offspring study (FOS) without prevalent T2D. Results: There were no significant associations with T2D for valine (beta=0.17 change in log-odds per standard deviation change in valine, [95% CI, -0.28 - 0.62], p=0.45), leucine (beta=0.19 [-0.30 - 0.68] p=0.45) or isoleucine (beta=0.02 [-0.54 - 0.59], p=0.94). In contrast, T2D was associated with each BCAA (valine: beta=0.08 per standard deviation change in levels per log-odds change in type 2 diabetes, [0.05 - 0.10], p=1.8x10 -9 ), (leucine: beta= 0.06 [0.04 - 0.09], p=4.5x10 -8 ) and isoleucine (beta= 0.06 [0.04 - 0.08], p=2.8x10 -8 ). The T2D associations were replicated in an independent population but not in a second population where T2D cases were removed. Similarly, a T2D PRS was associated with measured BCAA levels in the FOS study but not when incident T2D cases were removed. Positive associations were seen for fasting insulin and BMI, and the BCAAs by MR, and, in multivariable MR analyses, T2D and fasting insulin had independent associations with each BCAA. Conclusions: These data suggest that BCAAs are not mediators of T2D risk but may rather serve as biomarkers of T2D and higher insulin levels.

Impact of Type 2 Diabetes on the Outcomes of Solid Organ Transplantations in the U.S.: Data From a National Registry.

Type 2 diabetes (T2D) is a major driver of chronic diseases around the globe. The aim was to assess the impact of T2D on the outcomes of solid organ transplantations. We used the Scientific Registry of Transplant Recipients from 2006 to 2021 to collect data for all patients age ≥18 years who received a lung, heart, liver, or kidney transplant in the U.S. We included 462,692 solid organ transplant recipients: 31,503 lung, 38,004 heart, 106,639 liver, and 286,440 kidney transplantations. The prevalence of pretransplantation T2D was 15% in lung, 26% in heart, 25% in liver, and 30% in kidney transplant recipients, increasing over time. Posttransplantation mortality was significantly higher among transplant recipients with T2D versus those without T2D (lung 32.1% vs. 29.3% [3 years], 46.4% vs. 42.6% [5 years]; P < 0.01; heart 11.2% vs. 9.1% [1 year], 24.4% vs. 20.6% [5 years]; P < 0.0001; liver 10.6% vs. 8.9% [1 year], 26.2% vs. 22.0% [5 years]; P < 0.0001; kidney 5.3% vs. 2.5% [1 year], 20.8% vs. 10.1% [5 years]; P < 0.0001). Independent association of pretransplantation T2D with higher posttransplantation mortality was significant after adjustment for clinicodemographic confounders (adjusted hazard ratio in lung transplant recipients 1.08 [95% CI 1.03-1.13]; heart 1.26 [1.20-1.32]; liver 1.25 [1.21-1.28]; kidney 1.65 [1.62-1.68]; P < 0.01). The prevalence of T2D in solid organ transplantation candidates is increasing. In all solid organ transplantations, pretransplantation T2D was independently associated with higher posttransplantation mortality, most profoundly in kidney transplantations.

Association between maternal hyperglycemia in pregnancy and offspring anthropometry in early childhood: the pandora wave 1 study.

In-utero hyperglycemia exposure influences later cardiometabolic risk, although few studies include women with pre-existing type 2 diabetes (T2D) or assess maternal body mass index (BMI) as a potential confounder. To explore the association of maternal T2D and gestational diabetes mellitus (GDM) with childhood anthropometry, and the influence of maternal BMI on these associations. The PANDORA cohort comprises women (n = 1138) and children (n = 1163). Women with GDM and T2D were recruited from a hyperglycemia in pregnancy register, and women with normoglycemia from the community. Wave 1 follow-up included 423 children, aged 1.5-5 years (median follow-up age 2.5 years). Multivariable linear regression assessed associations between maternal antenatal variables, including BMI and glycemic status, with offspring anthropometry (weight, height, BMI, skinfold thicknesses, waist, arm and head circumferences). Greater maternal antenatal BMI was associated with increased anthropometric measures in offspring independent of maternal glycemic status. After adjustment, including for maternal BMI, children exposed to maternal GDM had lower mean weight (-0.54 kg, 95% CI: -0.99, -0.11), BMI (-0.55 kg/m2, 95% CI: -0.91, -0.20), head (-0.52 cm, 95% CI: -0.88, -0.16) and mid-upper arm (-0.32 cm, 95% CI: -0.63, -0.01) circumferences, and greater mean suprailiac skinfold (0.78 mm, 95% CI: 0.13, 1.43), compared to children exposed to normoglycemia. Adjustment for maternal BMI strengthened the negative association between GDM and child weight, BMI and circumferences. Children exposed to maternal T2D had smaller mean head circumference (-0.82 cm, 95% CI: -1.33, -0.31) than children exposed to normoglycemia. Maternal T2D was no longer associated with greater child mean skinfolds (p = 0.14) or waist circumference (p = 0.18) after adjustment for maternal BMI. Children exposed to GDM had greater suprailiac skinfold thickness than unexposed children, despite having lower mean weight, BMI and mid-upper arm circumference, and both GDM and T2D were associated with smaller mean head circumference. Future research should assess whether childhood anthropometric differences influence lifetime cardiometabolic and neurodevelopmental risk.

Neighbourhood deprivation and type 2 diabetes in patients with bipolar disorder: A nationwide follow-up study.

Patients with bipolar disorder have higher rates of type 2 diabetes (T2D) compared to the general population. Neighbourhood deprivation is associated with T2D and bipolar disorder. The aim of this study was to explore the potential effect of neighbourhood deprivation on incident T2D in patients with bipolar disorder. This nationwide open cohort study (1997-2018) included adults in Sweden ≥20years with bipolar disorder (90,780 patients) to examine the subsequent risk of T2D. The association between neighbourhood deprivation and T2D was explored using Cox regression analysis, with hazard ratios (HRs) and 95% confidence intervals (95% CIs). All models were conducted in both men and women and adjusted for individual-level sociodemographic factors and comorbidities. Neighbourhood deprivation was significantly associated with T2D in patients with bipolar disorder. The HRs were 1.61 (95% CI 1.40-1.86) for men and 1.83 (1.60-2.10) for women living in high deprivation neighbourhoods compared to those from low deprivation neighbourhoods. After adjustment, these results remained significant: 1.35 (1.17-1.56) in men and 1.39 (1.20-1.60) in women living in high deprivation neighbourhoods. The suggested graded association of higher incident T2D among patients with bipolar disorder, observed when levels of neighbourhood deprivation increased, raises important clinical and public health concerns. The results may help develop a contextual approach to prevention of T2D in patients with bipolar disorder that includes the neighbourhood environment.

Association of Obesity and Type 2 Diabetes with Non-Hodgkin Lymphoma: The Multiethnic Cohort.

Given the role of the immune system in non-Hodgkin lymphoma (NHL) etiology, obesity and type 2 diabetes (T2D) may impact NHL development. We examined the association of body mass index (BMI) and T2D with NHL in the multiethnic cohort (MEC). The MEC recruited >215,000 participants in Hawaii and Los Angeles from five racial/ethnic groups; NHL cases were identified through cancer registry linkages. T2D status, and BMI at age 21 and cohort entry were derived from repeated self-reports; for T2D, Medicare claims were also applied. HRs and 95% confidence intervals (CI) for BMI and T2D as predictors of NHL were determined using Cox regression adjusted for relevant covariates. Among 192,424 participants, 3,472 (1.8%) with NHL and 68,850 (36%) with T2D after 19.2±6.6 years follow-up, no significant association between T2D and NHL (HR, 1.04; 95% CI, 0.96-1.13) was observed. Stratification by BMI at cohort entry showed a significant association of T2D with NHL among individuals with normal weight only (HR, 1.18; 95% CI, 1.03-1.37). In a model with both BMI values plus T2D, only overweight (HR, 1.13; 95% CI, 1.01-1.26) and obesity (HR, 1.25; 95% CI, 0.99-1.59) at age 21 were associated with NHL incidence. Stratification by sex, race/ethnicity, and NHL subtype indicated no differences. Our findings suggest an association between T2D and NHL incidence in several subgroups but not in the total population and an elevated risk related to early-life BMI. Excess body weight in early life, rather than T2D, may be a predictor of NHL incidence.

Type 2 Diabetes and Its Association With Psychiatric Disorders in Young Adults in South Korea

Because type 2 diabetes (T2D) has become increasingly prevalent among young adults, the study of the association of T2D with psychiatric disorders in young adults is important for early detection and timely intervention. To determine whether a diagnosis of a psychiatric disorder is associated with increased risk of developing T2D in young adults. This large-scale prospective cohort study used data collected by the South Korean National Health Insurance Service between 2009 and 2012, representing 97% of the South Korean population. Young adults aged 20 to 39 years with and without diagnoses of psychiatric disorders were included in the study. Young adults with missing data and those with a history of T2D were excluded from the study. The cohort was followed up to monitor development of T2D until December 2018. Data were analyzed from March 2021 to February 2022. Diagnosis of 1 of 5 psychiatric disorders, including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder. The primary outcome was newly diagnosed T2D during a follow-up period of 7.59 years. The incidence rate of T2D was calculated as the number of new cases per 1000 person-years during the follow-up period. The Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% CIs for T2D incidence. Exploratory analyses were performed for subgroups stratified by age and sex. In total, 6 457 991 young adults (mean [SD] age, 30.74 [4.98] years; 3 821 858 men [59.18%]) were followed up, including 658 430 individuals with psychiatric disorders. The cumulative incidence of T2D differed significantly between individuals with and without psychiatric disorders (log-rank test, P < .001). Incidence rates of T2D for individuals with and without psychiatric disorders were 2.89 and 2.56 per 1000 person-years, respectively. Individuals with a diagnosis of any psychiatric disorder showed a higher risk of developing T2D than those without a diagnosis (adjusted HR, 1.20; 95% CI, 1.17-1.22). The adjusted HRs for T2D were 2.04 (95% CI, 1.83-2.28) for individuals with schizophrenia, 1.91 (95% CI, 1.73-2.12) for individuals with bipolar disorder, 1.24 (95% CI, 1.20-1.28) for individuals with depressive disorder, 1.13 (95% CI, 1.11-1.16) for individuals with anxiety disorder, and 1.31 (95% CI, 1.27-1.35) for individuals with sleep disorder. In this large-scale prospective cohort study of young adults, 5 psychiatric disorders were significantly associated with an increased risk of developing T2D. Young adults with schizophrenia and bipolar disorder in particular were at a higher risk of T2D. These results have important implications for early detection of and timely intervention in T2D for young adults with psychiatric disorders.

1395-P: The Impact of Type 2 Diabetes on the Outcomes of Solid Organ Transplants in the U.S.

Background and Aim: Type 2 Diabetes (T2D) is a major driver of chronic diseases across the globe. The aim of this study was to assess the impact of T2D on the outcomes of solid organ transplantations. Method: We used Scientific Registry of Transplant Recipients (SRTR) 2006-2021 to collect data for all patients ≥18 years who received a lung, heart, liver, or kidney single organ transplant in the U.S. Results: We included 442,100 solid organ transplant recipients: 31,503 lung, 38,004 heart, 86,153 liver, 286,440 kidney transplants. The prevalence of pre-transplant T2D was 15% in lung (increased from 12% in 2006 to 15% in 2021), 26% in heart (22% in 2006 to 28% in 2021), 26% in liver (23% in 2008 to 28% in 2019), and 30% in kidney (26% in 2006 to 34% in 2021). In all organs, post-transplant mortality was significantly higher among transplant recipients with vs. without T2D [lung transplant: 14.2% vs. 13.1% (1 year), 46.4% vs. 42.6% (5 years), p&amp;lt;0.05; heart transplant: 11.2% vs. 9.1% (1 year), 24.4% vs. 20.6% (5 years), all p&amp;lt;0.0001; liver transplant: 10.3% vs. 8.4% (1 year), 25.4% vs. 21.1% (5 years), all p&amp;lt;0.0001; kidney transplant: 5.3% vs. 2.5% (1 year), 20.8% vs. 10.1% (5 years), all p&amp;lt;0.0001]. Independent association of pre-transplant T2D with higher post-transplant mortality was significant after adjustment for clinico-demographic confounders (calendar year, age, sex, race, education, insurance, functional status, obesity, history of cancer, listing diagnosis, donor-related parameters): adjusted hazard ratio (aHR) for T2D in lung transplant recipients =1.08 (1.03-1.13), in heart transplant aHR = 1.26 (1.20-1.32), in liver transplant recipients aHR = 1.26 (1.22-1.30), and in kidney transplant recipients aHR = 1.65 (1.62-1.68) (all p&amp;lt;0.01). Conclusions: The prevalence of T2D is rapidly increasing in solid organ transplant candidates. In all solid organ transplants, pre-transplant T2D is independently associated with an increased risk of post-transplant mortality, the most profoundly in kidney transplants. Disclosure M.Stepanova: None. A.Kumar: None. P.Brandt: None. N.Gundurao: None. K.Cusi: Consultant; Poxel SA, Altimmune, Arrowhead Pharmaceuticals, Inc., AstraZeneca, 89bio, Inc., Bristol-Myers Squibb Company, Lilly, Madrigal Pharmaceuticals, Inc., Merck &amp; Co., Inc., Medscape, Myovant, Novo Nordisk, ProSciento, Quest Diagnostics, Sagimet, Sonic Incytes, Terns, Research Support; Echosens, Inventiva, LabCorp, Zydus. Z.Younossi: Consultant; AbbVie Inc., BMS, Gilead Sciences, Inc., Novo Nordisk, Merck &amp; Co., Inc., Quest Diagnostics, Siemens, Intercept Pharmaceuticals, Inc., Viking Therapeutics.