Risk Of Type 2 Diabetes Research Articles

The joint effect of cumulative metabolic parameters on the risk of type 2 diabetes: a population-based cohort study

Background and aimsThis study aimed to examine the cumulative effects of body mass index (BMI), body roundness index (BRI), pulse pressure (PP), triglycerides (TG), high-density lipoprotein cholesterol (HDL) and fasting plasma glucose (FPG) on Type 2 diabetes (T2D) morbidity.MethodsA total of 78,456 participants aged older than 45 years were extracted from basic public health services in China. During the 2-year follow-up, 6,942 individuals had developed T2D. The binary logistic regression models and multinomial logistic regression models were conducted to investigate the effects of cumulative metabolic parameters on incident T2D, prediabetes regression and progression.ResultsWe found statistically deleterious impacts of exposure to high cumulative BMI, BRI, PP, TG and low cumulative HDL on T2D morbidity and prediabetes progression. Compared to the group with low cumulative of all five parameters, the adjusted ORs for new-onset T2D for participants presenting with 1–2, 3, and 4–5 elevated metabolic parameters were 1.41(1.31,1.52), 1.93(1.74,2.13) and 2.21(1.94,2.51), respectively. There was additive interaction between FPG level and cumulative metabolic parameters with T2D. Compared with participants with the lowest quartile of FPG and low cumulative of all 5 parameters, those with the highest quartile of FPG and high cumulative of 4–5 parameters had a 14.63 [95% CI (12.27, 17.42)] higher risk of incident T2D.ConclusionsParticipants with more numbers of high-cumulative metabolic parameters were associated with a higher risk of incident T2D and prediabetes progression. A high level of normal FPG could enhance these risks.

Potato Consumption and Risk of Type 2 Diabetes Mellitus: A Harmonized Analysis of 7 Prospective Cohorts.

Data on the relation of potato consumption with risk of type 2 diabetes (T2D) are limited and inconsistent. It is unclear whether the plant-based diet index (PDI), which is a novel and comprehensive tool to assess overall dietary pattern, modifies the association of potato intake with T2D. We examined the association of total, combined baked, boiled, and mashed potatoes and fried potatoes with risk of T2D and test the interaction between PDI score and potato consumption on T2D risk. We conducted a de novo, harmonized, individual-level data from 7 United States cohorts (N = 105,531). Cox regression was used to estimate hazard ratios (HRs) separately in each cohort adjusting for anthropometric, demographic, and lifestyle factors and cohort-specific results were pooled using an inverse-variance weighted method. Mean age ranged from 25 to 72 y, 65% women, and mean consumption of total potatoes ranged from 1.9 to 4.3 times per week. In the primary analysis, total potato intake was not associated with T2D risk: multivariable adjusted HR of 1.01 (95% confidence interval [CI]: 0.95, 1.08) for consumption of 1-2 servings/wk; 1.01 (95% CI: 0.93, 1.10) for >2-3 servings/wk; 1.05 (95% CI: 0.99, 1.12) for >3 to <5 servings/wk; and 1.07 (95% CI: 0.99, 1.16) for 5+ servings/wk compared with no potato intake. In secondary analyses, consumption of combined baked, boiled, and mashed potatoes was not associated with T2D risk, whereas fried potato consumption was positively associated with T2D risk: HR were 1 (ref), 1.07 (95% CI: 1.02, 1.12), and 1.12 (95% CI: 1.03, 1.22) for intake frequency of 0/wk, >0 to 1/wk, and >1/wk, respectively (P-trend = 0.04). There was no significant interaction between PDI score and potato consumption on T2D risk. Although consumption of total potato is not associated with T2D risk, a modest elevated risk of T2D is observed with fried potato consumption.

Genetic architecture of oral glucose-stimulated insulin release provides biological insights into type 2 diabetes aetiology

The genetics of β-cell function (BCF) offer valuable insights into the aetiology of type 2 diabetes (T2D)1,2. Previous studies have expanded the catalogue of BCF genetic associations through candidate gene studies3–7, large-scale genome-wide association studies (GWAS) of fasting BCF8,9 or functional islet studies on T2D risk variants10–14. Nonetheless, GWAS focused on BCF traits derived from oral glucose tolerance test (OGTT) data have been limited in sample size15,16 and have often overlooked the potential for related traits to capture distinct genetic features of insulin-producing β-cells17,18. We reasoned that investigating the genetic basis of multiple BCF estimates could provide a broader understanding of β-cell physiology. Here, we aggregate GWAS data of eight OGTT-based BCF traits from ~26,000 individuals of European descent, identifying 55 independent genetic associations at 44 loci. By examining the effects of BCF genetic signals on related phenotypes, we uncover diverse disease mechanisms whereby genetic regulation of BCF may influence T2D risk. Integrating BCF-GWAS data with pancreatic islet transcriptomic and epigenomic datasets reveals 92 candidate effector genes. Gene silencing in β-cell models highlights ACSL1 and FAM46C as key regulators of insulin secretion. Overall, our findings yield insights into the biology of insulin release and the molecular processes linking BCF to T2D risk, shedding light on the heterogeneity of T2D pathophysiology.

Metabolic Stress Levels Influence the Ability of Myelin Transcription Factors to Regulate β-Cell Identity and Survival.

A hallmark of type 2 diabetes (T2D) is endocrine islet β-cell failure, which can occur via cell dysfunction, loss-of-identity, and/or death. How each is induced remains largely unknown. Here, we use mouse β-cells that are deficient for Myelin transcription factors (Myt TFs, including Myt1, 2, and 3) to address this question. We have reported that inactivating all three Myt genes in pancreatic progenitor cells (MytPancΔ) causes β-cell failure and late onset diabetes in mice. Their lower expression in human β-cells is correlated with β-cell dysfunction and SNPs in MYT2 and MYT3 are associated in higher risk of T2D. We now show that these Myt TF-deficient postnatal β-cells also de-differentiate by reactivating several progenitor markers. Intriguingly, mosaic Myt TF inactivation in only a portion of islet β-cells does not results in overt diabetes, but this creates a condition where Myt TF-deficient β-cells stay alive while activating several markers of Ppy-expressing islet cells. By transplanting MytPancΔ islets into the anterior eye chambers of immune-compromised mice, we directly show that glycemic and obesity-related conditions influence cell fate, with euglycemia inducing several Ppy+ cell markers while hyperglycemia and insulin resistance inducing additional cell death. These findings suggest that the observed β-cell defects in T2D depend on not only their inherent genetic/epigenetic defects, but also the metabolic load.

Loneliness, Discrimination, Stress, and Type 2 Diabetes Risk in Young Adults

IntroductionThe aim of this study was to determine the associations between type 2 diabetes (T2D) or prediabetes and loneliness and related social experiences in young adults, a population at increasingly high risk of T2D. MethodsThis was a cross-sectional analysis using data from adults ages 18-35 enrolled in the All of Us Research Program. Exposures included loneliness, social support, discrimination, neighborhood social cohesion, and stress, measured by standardized surveys. The main outcome was T2D or prediabetes by self-report or linked health record. Logistic regression determined odds of T2D/prediabetes for each survey measure, adjusting for age, sex, race or ethnicity, income, and family history. Latent class analysis (LCA) evaluated clustering of social experiences. Data was collected from 2018-2022 and analyzed May 2023-June 2024. ResultsThe cohort included 14,217 young adults (28.2 ± 4.4 years; 70.3% (n=9,792) women; 64.1% (n=9,111) White, 10.6% (n=1,506) Hispanic, 5.7% (n=806) Black, 9.1% (n=1,299) multiracial). Overall, 5.5% (n=777) had either prediabetes or T2D. The two highest loneliness quartiles were associated with increased odds of prediabetes/T2D (Q3: OR 1.42 [95% CI 1.15-1.76]; Q4: 1.75 [95% CI 1.43-2.16]). Greater stress and discrimination and lower social support and neighborhood social cohesion were also associated with increased odds of prediabetes/T2D. LCA revealed three distinct phenotypes, with elevated odds of prediabetes/T2D in the two with the most adverse social profiles (OR 2.32 [95% CI 1.89-2.84] and OR 1.28 [95% CI 1.04-1.58]). ConclusionsLoneliness and related experiences are strongly associated with T2D and prediabetes in young adults. Whether these factors could be leveraged to reduce T2D risk should be investigated.

Unveiling the influence of circulating immune cells count on type 1 diabetes: Insight from bidirectional Mendelian randomization.

Observational studies have demonstrated an association between circulating immune cell and type 1 diabetes (T1D) risk. However, it is unknown whether this relationship is causal. Herein, we adopted a 2-sample bidirectional Mendelian randomization study to figure out whether circulating immune cell profiles causally impact T1D liability. Summary statistical data were obtained from genome-wide association study (GWAS) to investigate the causal relationship between white cell (WBC) count, 5 specific WBC count, and lymphocyte subtypes cell count and T1D risk. After false discovery rate (FDR) correction, the results indicated that lower lymphocyte cell count (odds ratio [OR] per 1 standard deviation [SD] decrease = 0.746, 95% confidence interval (CI): 0.673-0.828, PFDR = 0.036), and basophil cell count (OR per 1 SD decrease = 0.808, 95% CI: 0.700-0.932, PFDR = 0.010) were causally associated with T1D susceptibility. However, the absolute count of WBC, monocyte, neutrophil, eosinophil, and lymphocyte subtypes cell had no statistically significant effect on T1D risk. Taken together, this study indicates suggestive association between circulating immune cell count and T1D. Moreover, lower numbers of circulating lymphocyte and basophil cell were associated with the increased risk of T1D, which confirmed the immunity predisposition for T1D.

Thyroid Function, Diabetes, and Common Age-Related Eye Diseases: A Mendelian Randomization Study.

Background: Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap. Methods: We examined the causality and directionality of the associations of AITD, and FT4 and TSH within the reference range with common age-related eye diseases (diabetic retinopathy, cataract, early and late AMD, and primary open-angle glaucoma). We conducted a bidirectional two-sample MR study utilizing publicly available genome-wide association study (GWAS) summary statistics from international consortia (ThyroidOmics, International AMD Genetics Consortium, deCODE, UK Biobank, FinnGen, and DIAGRAM). Bidirectional MR tested directionality, whereas MVMR estimated independent causal effects. Furthermore, we investigated type 1 diabetes (T1D) and type 2 diabetes (T2D) as potential mediators. Results: Genetic predisposition to AITD was associated with increased risk of diabetic retinopathy (p = 3 × 10-4), cataract (p = 3 × 10-3), and T1D (p = 1 × 10-3), but less likely T2D (p = 0.01). MVMR showed attenuated estimates for diabetic retinopathy and cataract when adjusting for T1D, but not T2D. We found pairwise bidirectional associations between AITD, T1D, and diabetic retinopathy. Genetic predisposition to both T1D and T2D increased the risk of diabetic retinopathy and cataract (p < 4 × 10-4). Moreover, genetically predicted higher FT4 within the reference range was associated with an increased risk of late AMD (p = 0.01), particularly in women (p = 7 × 10-3). However, we neither found any association between FT4 and early AMD nor between TSH and early and late AMD. No other associations were observed. Conclusions: Genetic predisposition to AITD is associated with risk of diabetic retinopathy and cataract, mostly mediated through increased T1D risk. Reciprocal associations between AITD, diabetic retinopathy, and T1D imply a shared autoimmune origin. The role of FT4 in AMD and potential sex discrepancies needs further investigation.

Continuous Glucose Monitoring With Geriatric Principles in Older Adults With Type 1 Diabetes and Hypoglycemia: A Randomized Controlled Trial.

Continuous glucose monitoring (CGM) use in older adults with type 1 diabetes (T1D) has shown benefits. However, the impact of CGM use, coupled with simplified treatment regimens and personalized glycemic goals that are better suited for older patients with multiple comorbidities and hypoglycemia, is not known. Older adults (≥65 years) with T1D with hypoglycemia (two or more episodes of hypoglycemia [blood glucose <70 mg/dL for ≥20 min over 2 weeks]) who were CGM naïve or CGM users were randomized to intervention and control groups. The intervention consisted of the combined use of CGM with geriatric principles (i.e., adjusting goals based on overall health, and simplification of regimens based on CGM patterns and clinical characteristics) over 6 months. The control group received usual care by their endocrinologist. The primary end point was change in time when blood glucose was <70 mg/dL from baseline to 6 months. Cost-effectiveness was calculated using a health care sector perspective. We randomized 131 participants (aged 71 ± 5 years; 21% ≥75 years old) to the intervention (n = 68; CGM users = 33) or the control (n = 63; CGM users = 40) group. The median change in hypoglycemia from baseline to 6 months was -2·6% in the intervention group and -0.3% in the control group (median difference, -2.3% [95% CI -3.7%, -1.3%]; P < 0.001). This improvement was seen in both CGM naïve (-2.8%; 95% CI -5.6%, -0.8%) and CGM users (-1.2%; 95% CI -2.7%, -0.1%). The HbA1c did not differ between the groups (7.5% vs 7.3%). The intervention was cost-effective (incremental cost-effectiveness ratio $71,623 per quality adjusted life-year). In older adults with T1D and high risk of hypoglycemia, CGM use enhanced by geriatric principles can lower hypoglycemia without worsening glycemic control in a cost-effective fashion.

Integrated clinical risk prediction of type 2 diabetes with a multifactorial polygenic risk score.

Combining information from multiple GWASs for a disease and its risk factors has proven a powerful approach for development of polygenic risk scores (PRSs). This may be particularly useful for type 2 diabetes (T2D), a highly polygenic and heterogeneous disease where the additional predictive value of a PRS is unclear. Here, we use a meta-scoring approach to develop a metaPRS for T2D that incorporated genome-wide associations from both European and non-European genetic ancestries and T2D risk factors. We evaluated the performance of this metaPRS and benchmarked it against existing genome-wide PRS in 620,059 participants and 50,572 T2D cases amongst six diverse genetic ancestries from UK Biobank, INTERVAL, the All of Us Research Program, and the Singapore Multi-Ethnic Cohort. We show that our metaPRS was the most powerful PRS for predicting T2D in European population-based cohorts and had comparable performance to the top ancestry-specific PRS, highlighting its transferability. In UK Biobank, we show the metaPRS had stronger predictive power for 10-year risk than all individual risk factors apart from BMI and biomarkers of dysglycemia. The metaPRS modestly improved T2D risk stratification of QDiabetes risk scores for 10-year risk prediction, particularly when prioritising individuals for blood tests of dysglycemia. Overall, we present a highly predictive and transferrable PRS for T2D and demonstrate that the potential for PRS to incrementally improve T2D risk prediction when incorporated into UK guideline-recommended screening and risk prediction with a clinical risk score.

Family History of Diabetes and Clinical Characteristics in Children at Diagnosis of Type 1 Diabetes-A Swedish Population-Based Study.

To compare the prevalence of parental diabetes between children with and without type 1 diabetes (T1D), and to compare clinical characteristics at diagnosis of T1D in children with, versus without, a family history of diabetes. Parental diabetes among children with T1D was compared with a general population cohort. Clinical characteristics were compared by family history of diabetes in parents and grandparents of 3,603 children with T1D using relative risk (RR) and ANOVA. Children with T1D more often had parents with type 2 diabetes (T2D) (RR 1.88; P < 0.001) than did children without diabetes. Children with T1D and a family history of T2D were more likely to be overweight or obese (P = 0.002). A family history of T2D and being overweight may contribute to increased risk of T1D.

Testosterone and the prevention of type 2 diabetes mellitus: therapeutic implications from recent trials.

Type 2 diabetes (T2D) is increasing to epidemic proportions and frequently associated with obesity and a low serum testosterone concentration in men. This review valuates recent randomized controlled trials (RCTs) investigating the effect of testosterone treatment on glycemic control and T2D prevention. The 2-year Testosterone for the Prevention of Type 2 diabetes Trial (T4DM) study showed that in men aged 50 years and over with visceral obesity and impaired glucose tolerance, testosterone treatment on the background of a lifestyle intervention reduced T2D risk by 40%. The Testosterone Effects on Atherosclerosis Progression in Aging Men and Testosterone Trials demonstrated modest improvements in insulin sensitivity and body composition. However, the Testosterone Replacement Therapy for Assessment of Long-Term Vascular Events and Efficacy Response in Hypogonadal Men trial found no significant glycemic benefits over 2 years. Recent data from the Diabetes Prevention Program Outcome Study support the cost efficacy and durability of metformin. In men at high risk of T2D, treatment with testosterone prevents the disease; however, there are caveats to its use and other approaches may be more applicable. Differences in trial designs, age groups, and outcome measures contribute to varying results. HbA1C is a suboptimal outcome measure. Future research should explore potential synergies between testosterone and GLP-1 receptor agonists in T2D management, while considering cost-effectiveness.

The Effect of Vitamin D Deficiency on Immune-Related Hub Genes: A Network Analysis Associated With Type 1 Diabetes.

Background Type 1 diabetes (T1D) is an autoimmune disorder that results in the destruction of pancreatic beta cells, causing a shortage of insulin secretion. The development of T1D is influenced by both genetic predisposition and environmental factors, such as vitamin D. This vitamin is known for its ability to regulate the immune system and has been associated with a decreased risk of T1D. However, the specific ways in which vitamin D affects immune regulation and the preservation of beta cells in T1D are not yet fully understood. Gaining a better understanding of these interactions is essential for identifying potential targets for preventing and treating T1D. Methods The analysis focused on two Gene Expression Omnibus (GEO) datasets, namely, GSE55098 and GSE50012, to detect differentially expressed genes (DEGs). Enrichr (Ma'ayan Laboratory, New York, NY) was used to perform enrichment analysis for the Gene Ontology (GO) biological process and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The Search Tool for the Retrieval of Interacting Genes 12.0 (STRING) database was used to generate a protein-protein interaction (PPI) network. The Cytoscape 3.10.1 (Cytoscape Team, San Diego, CA) was used to analyze the PPI network and discover the hub genes. Results The DEGs in both datasets were identified using the GEO2R tool, with a particular focus on genes exhibiting contrasting regulations. Enrichment analysis unveiled the participation of these oppositely regulated DEGs in processes relevant to the immune system. Cytoscape analysis of the PPI network revealed five hub genes, MNDA, LILRB2, FPR2, HCK, and FCGR2A, suggesting their potential role in the pathogenesis of T1D and the response to vitamin D. Conclusion The study elucidates the complex interaction between vitamin D metabolism and immune regulation in T1D. The identified hub genes provide important knowledge on the molecular pathways that underlie T1D and have the potential to be targeted for therapeutic intervention. This research underscores the importance of vitamin D in the immune system's modulation and its impact on T1D development.

A functional variant rs912304 for late-onset T1D risk contributes to islet dysfunction by regulating proinflammatory cytokine-responsive gene STXBP6 expression

BackgroundOur previous genome‑wide association studies (GWAS) have suggested rs912304 in 14q12 as a suggestive risk variant for type 1 diabetes (T1D). However, the association between this risk region and T1D subgroups and related clinical risk features, the underlying causal functional variant(s), putative candidate gene(s), and related mechanisms are yet to be elucidated.MethodsWe assessed the association between variant rs912304 and T1D, as well as islet autoimmunity and islet function, stratified by the diagnosed age of 12. We used epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to prioritize the most likely functional variant and potential causal gene. We also performed functional experiments to evaluate the role of the causal gene on islet function and its related mechanisms.ResultsWe identified rs912304 as a risk variant for T1D subgroups with diagnosed age ≥ 12 but not < 12. This variant is associated with residual islet function but not islet-specific autoantibody positivity in T1D individuals. Bioinformatics analysis indicated that rs912304 is a functional variant exhibiting spatial overlaps with enhancer active histone marks (H3K27ac and H3K4me1) and open chromatin status (ATAC-seq) in the human pancreas and islet tissues. Luciferase reporter gene assays and eQTL analyses demonstrated that the biallelic sites of rs912304 had differential allele-specific enhancer activity in beta cell lines and regulated STXBP6 expression, which was defined as the most putative causal gene based on Open Targets Genetics, GTEx v8 and Tiger database. Moreover, Stxbp6 was upregulated by T1D-related proinflammatory cytokines but not high glucose/fat. Notably, Stxbp6 over-expressed INS-1E cells exhibited decreasing insulin secretion and increasing cell apoptosis through Glut1 and Gadd45β, respectively.ConclusionsThis study expanded the genomic landscape regarding late-onset T1D risk and supported islet function mechanistically connected to T1D pathogenesis.

Importance of Studying Non-Coding RNA in Children and Adolescents with Type 1 Diabetes.

Type 1 diabetes (T1D) mellitus is a chronic illness in children and teens, with rising global incidence rates. It stems from an autoimmune attack on pancreatic β cells, leading to insufficient insulin production. Genetic susceptibility and environmental triggers initiate this process. Early detection is possible by identifying multiple autoantibodies, which aids in predicting future T1D development. A new staging system highlights T1D's onset with islet autoimmunity rather than symptoms. Family members of T1D patients face a significantly increased risk of T1D. Italy recently passed a law mandating national T1D screening for pediatric populations. Measurements of β cell function continue to be essential in assessing efficacy, and different models have been proposed, but more appropriate biomarkers are mandatory for both progression studies before the onset of diabetes and during therapeutic monitoring. Biomarkers like microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) play key roles in T1D pathogenesis by regulating gene expression. Understanding their roles offers insights into T1D mechanisms and potential therapeutic targets. In this review, we summarized recent progress in the roles of some non-coding RNAs (ncRNAs) in the pathogenesis of T1D, with particular attention to miRNAs, lncRNAs, and circRNAs.

Genetic Associations of Lipids and Lipid-Modifying Drug Targets With Type 2 Diabetes in the Chinese Population

BackgroundDyslipidemia is a recognized risk factor for type 2 diabetes (T2D), yet the genetic basis and causal nature remain unclear, particularly in Chinese populations. ObjectivesThe authors investigated the causal effects of genetically predicted lipid levels on T2D risk and explored the potential effects of lipid-modifying drugs. MethodsLeveraging data from the Kunshan Community cohort in China, we analyzed the associations between low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, and triglycerides (TGs) with T2D risk using genetic risk scores, 1-sample univariable, multivariable, and nonlinear Mendelian randomization (MR) analyses. Two-sample MR using summary-level data from Global Lipid Genetics Consortium and Biobank Japan was used for validation. Drug-target MR was used to examine the impact of lipid-modifying drug targets on T2D. ResultsLower genetic risk scores of LDL-C (OR per SD: 0.97 [95% CI: 0.95-0.99]; P = 0.010) and TGs (0.96 [95%CI: 0.94-0.98]; P = 0.002) were associated with increased T2D risk. Univariable MR revealed that genetically predicted lower LDL-C (0.78 [95% CI: 0.65-0.93]; P = 0.006) and TG levels (0.76 [95% CI: 0.66-0.89]; P < 0.001) were linked to a higher T2D risk, validated by 2-sample MR. Multivariable MR demonstrated a direct inverse association between LDL-C (0.80 [95% CI: 0.66-0.97]; P = 0.020) and TG (0.80 [95% CI: 0.66-0.97]; P = 0.022) with T2D. No evidence was found for nonlinearity. Among lipid-modifying drugs, genetic mimicry of apolipoprotein C3 (APOC3) inhibition increased T2D risk (OR per 1 mmol/L reduction in TG: 1.38 [95% CI: 1.10-1.75]; P = 0.007). ConclusionsOur findings suggested potential adverse effects of lower LDL-C, TG levels, as well as long-term use of APOC3 inhibitors on T2D risk in Chinese populations. These findings highlight the need for cautious lipid management strategies in T2D prevention.

Ultra-processed food, genetic risk, and the risk of cardiometabolic diseases and cardiometabolic multimorbidity: A prospective study

Background and aimsThis study aims to evaluate the impact of ultra-processed food (UPF) on type 2 diabetes (T2D), cardiovascular disease (CVD), hypertension, and cardiometabolic multimorbidity (CMM), and to explore the role of genetic susceptibility in these associations. Methods and results90 631 participants from the UK Biobank were included (collected between 2006 and 2010). The outcomes assessed included T2D, CVD, hypertension and CMM. The Cox proportional hazards model was used to evaluate their associations and the potential modification by genetic risk, which was estimated using the polygenic risk score (PRS). Participants with high UPF consumption had a higher risk of T2D, CVD, and CMM, with the adjusted hazard ratio (HR) of 1.36 (95 % confidence interval [CI]: 1.15, 1.61), 1.13 (95%CI: 1.03, 1.23), and 1.14 (95%CI: 1.05, 1.24), respectively. Those with high UPF consumption and high PRS for T2D, CVD, and hypertension had the highest risk of T2D (HR: 4.01; 95%CI: 2.83, 5.69), CVD (HR: 2.18; 95%CI: 1.86, 2.56), and hypertension (HR: 1.79; 95%CI: 1.61, 1.99), respectively. In participants with one cardiometabolic disease (CMD), those with high UPF consumption and high PRST2D or PRSCVD had the highest risk of developing CMM. A significant additive interaction was observed between PRST2D and UPF consumption on the risk of T2D. ConclusionOur study underscored the importance of identifying individuals with high UPF consumption for targeted dietary interventions to mitigate the risk of CMDs and CMM, particularly among those with a high genetic risk of CMDs.

Multi-level Analysis of HbA1c in Diagnosis and Prognosis of Diabetic Patients.

Type 2 diabetes (T2D), a multifaceted metabolic disorder, may cause health tribulations and changes in biochemical blood markers. Other research has examined the relationships between several biomarkers and the risk of T2D. Few studies have examined the relationships between these biomarkers and potential changes to the network of biomarkers associated with diabetes. Glycated hemoglobin, or HbA1c, is used to evaluate and track the blood glucose history throughout the previous two to three months of testing. The ability to reflect the cumulative glycemic history of the previous two to three months makes HbA1c an essential biomarker of long-term glycemic control. HbA1c offers a trustworthy indicator of chronic hyperglycemia and strongly correlates with the likelihood of long-term consequences from diabetes. Additionally, elevated HbA1c has been recognized as a stand-alone risk factor for patients with and without diabetes developing coronary heart disease and stroke. One HbA1c test offers a wealth of information that makes it a reliable biomarker for the diagnosis and prognosis of diabetes. A clinical examination may be required to establish the connection between diabetes, prediabetes, biochemical blood indicators, age, and body mass index (BMI). We observed that diabetes, BMI, age, HbA1c, cholesterol, triglycerides, LDL, VLDL, and HDL were all linked using multivariate analysis.

Enzymatic and Non-enzymatic Collagen Cross-Links and Fracture Occurrence in Type 1 Diabetes Patients.

Increased fracture risk in type 1 diabetes (T1D) patients is not fully captured by bone mineral density (BMD) by DXA. Advanced glycation end-products (AGEs) have been implicated in the increased fracture risk in T1D, yet recent publications question this. To test the hypothesis that enzymatic collagen cross-links rather than AGEs correlate with fracture incidence in T1D, we analyzed iliac crest biopsies from sex-matched, fracturing T1D patients (N = 5; T1DFx), 6 non-fracturing T1D patients (T1DNoFx), and 6 healthy subjects, by Raman microspectroscopy as a function of tissue age (based on double fluorescent labels), in intracortical and trabecular bone, to determine pyridinoline (Pyd), ε-N-Carboxymethyl-L-lysine, and pentosidine (PEN)). There were no differences in the clinical characteristics between the T1DFx and T1DNoFx groups. At trabecular forming surfaces, T1DFx patients had higher PEN and Pyd content compared to T1DNoFx ones. Previous studies have shown that elevated PEN does not necessarily correlate with fracture incidence in postmenopausal, long-term T1D patients. On the other hand, the elevated Pyd content in the T1DFx patients would be consistent with published studies showing a significant correlation between elevated trivalent enzymatic collagen cross-links and fracture occurrence independent of BMD. Collagen fibers with high Pyd content are more brittle. Thus, a plausible suggestion is that it is the enzymatic collagen cross-links that either by themselves or in combination with the adverse effects of increased AGE accumulation that result in fragility fracture in T1D.

Quality and quantity of macronutrients, and their joint associations with the incidence of type 2 diabetes over a nine-year follow-up

BackgroundThe association between macronutrient consumption and the risk of type 2 diabetes (T2D) remains equivocal. Here, we investigated whether the quantity and quality of macronutrient intake are associated with T2D incidence in a West Asian population.MethodsT2D-free adults (n = 2457, mean age 38.5 ± 13.6 years, 54.2% women) who participated in the third examination cycle (2005–2008) of the Tehran Lipid and Glucose Study were followed for a median of 8.6 years. We estimated the macronutrient quality index (MQI), its individual sub-indices (carbohydrate quality index (CQI), fat quality index (FQI), and healthy plate protein quality index (HPPQI)), as well as the macronutrient quantity. The risk of T2D in relation to macronutrient quantity, quality, and their combined effects was examined using Cox proportional hazard models adjusted for known risk factors for T2D.ResultsDuring the study follow-up, 257 incident cases of T2D were documented. Individuals in the highest tertiles of MQI and CQI had a 27% (HR = 0.73, 95% CI = 0.54, 0.98) and 29% (HR = 0.71, 95% CI = 0.51–0.99) lower T2D risk than those in the lowest tertiles. The T2D incidence was 35% lower in the middle HPPQI tertile than in the lowest (HR = 0.65, 95% CI = 0.47, 0.89). The multivariable adjusted model showed that individuals in the middle and highest tertiles of carbohydrate intake had 32% (HR = 0.68, 95% CI = 0.49–0.95) and 26% (HR = 0.74, 95% CI = 0.55–1.00) lower risks of T2D than individuals in the lowest tertile. A high-quantity, high-quality carbohydrate diet (≥ 58.5% of energy from carbohydrate with a CQI ≥ 13) and a low-glycemic index (GI), high-fiber diet (GI < 55 and fiber ≥ 25 g/d) were related to a reduced risk of T2D by 34% (HR = 0.66, 95% CI = 0.47, 0.93) and 42% (HR = 0.58, 95% CI = 0.38, 0.90), respectively.ConclusionA diet with a higher carbohydrate quality may be associated with a lower T2D incidence, particularly when the carbohydrate quantity is also high.

Insulin sensitivity and skeletal muscle mitochondrial respiration in Black and White women with obesity.

Non-Hispanic black women (BW) have a greater risk of type 2 diabetes (T2D) and insulin resistance (IR) compared to non-Hispanic white women (WW). The mechanisms leading to these differences are not understood, and it is unclear whether synergistic effects of race and obesity impact disease risk. To understand the interaction of race and weight, hepatic and peripheral IR were compared in WW and BW with and without obesity. Hepatic and peripheral IR was measured by a labeled, hyperinsulinemic-euglycemic clamp in BW (n=32) and WW (n=32) with and without obesity. Measurements of body composition, cardiorespiratory fitness, and skeletal muscle (SM) respiration were completed. Data were analyzed by mixed model ANOVA. Subjects with obesity had greater hepatic and peripheral IR and lower SM respiration (P<0.001). Despite 14% greater insulin (P=0.066), BW tended to have lower peripheral glucose disposal (Rd; P=0.062), which was driven by women without obesity (P=0.002). BW had significantly lower glucose production (P=0.005), hepatic IR (P=0.024), and maximal coupled and uncoupled respiration (P<0.001) than WW. Maximal coupled and uncoupled SM mitochondrial respiration was strongly correlated with peripheral and hepatic IR (P<0.01). While BW without obesity had lower Rd than WW, race and obesity did not synergistically impact peripheral IR. Paradoxically, WW with obesity had greater hepatic IR compared to BW. Relationships between SM respiration and IR persisted across a range of body weight. These data provide support for therapies in BW, like exercise, that improve SM mitochondrial respiration to reduce IR and T2D risk.