Risk Factors For Type 2 Diabetes Research Articles

DNA methylation signatures of youth-onset type 2 diabetes and exposure to maternal diabetes

ObjectiveYouth-onset type 2 diabetes (T2D) is physiologically distinct from adult-onset, but it is not clear how the two diseases differ at a molecular level. In utero exposure to maternal type 2 diabetes (T2D) is known to be a specific risk factor for youth-onset T2D. DNA methylation (DNAm) changes associated with T2D but which differ between youth- and adult-onset might delineate the impacts of T2D development at different ages and could also determine the contribution of exposure to in utero diabetes.MethodsWe performed an epigenome-wide analysis of DNAm on whole blood from 218 youth with T2D and 77 normoglycemic controls from the iCARE (improving renal Complications in Adolescents with type 2 diabetes through REsearch) cohort. Associations were tested using multiple linear regression models while adjusting for maternal diabetes, sex, age, BMI, smoking status, second-hand smoking exposure, cell-type proportions and genetic ancestry.ResultsWe identified 3830 differentially methylated sites associated with youth T2D onset, of which 3794 were moderately (adjusted p-value < 0.05 and effect size estimate > 0.01) associated and 36 were strongly (adjusted p-value < 0.05 and effect size estimate > 0.05) associated. A total of 3725 of these sites were not previously reported in the EWAS Atlas as associated with T2D, adult obesity or youth obesity. Moreover, three CpGs associated with youth-onset T2D in the PFKFB3 gene were also associated with maternal T2D exposure (FDR < 0.05 and effect size > 0.01). This is the first study to link PFKFB3 and T2D in youth.ConclusionOur findings support that T2D in youth has different impacts on DNAm than adult-onset, and suggests that changes in DNAm could provide an important link between in utero exposure to maternal diabetes and the onset of T2D.

The predictive value of plasma uridine for type 2 diabetes and its atherosclerotic complications.

Uridine might be a common link between pathological pathways in diabetes and cardiovascular diseases. This study aimed to investigate the predictive value of plasma uridine for type 2 diabetes and type 2 diabetes with atherosclerosis. Individuals with type 2 diabetes (T2D) and healthy controls (n=218) were randomly enrolled in a cross-sectional study. Patients with T2D were divided into two groups based on carotid ultrasound: patients with carotid atherosclerosis (CA) (group DCA), and patients without CA (group D). Plasma uridine was determined using high-performance liquid chromatography-tandem mass spectrometry. Correlation and logistic regression analyses were used to analyze the results. Fasting and postprandial uridine were significantly increased in patients with T2D compared with healthy individuals. Logistic regression suggested that fasting and postprandial uridine were independent risk factors for T2D. The receiver operating characteristic (ROC) curve showed that fasting uridine had a predictive value on T2D (95% CI,0.686-0.863, sensitivity 74.3%, specificity 71.8%). Fasting uridine was positively correlated with LDL-c, FBG, and PBG, and negatively correlated with CP-0h and HOMA-IS. The change in postprandial uridine from fasting baseline (Δ uridine) was smaller in T2D patients with CA compared with those without (0.80(0.04-2.46) vs. 2.01(0.49-3.15), P=0.010). Δuridine was also associated with T2D with CA and negatively correlated with BMI, CP-0h, and HOMA-IR. Fasting uridine has potential as a predictor of diabetes. Δuridine is closely associated with carotid atherosclerosis in patients with T2D.

Association between liver enzymes and type 2 diabetes: a real-world study.

This study aimed to examine the association of liver enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl-transferase (GGT), with type 2 diabetes (T2D) risk, particularly their dose-response relationship. This cross-sectional study enrolled participants aged >20 years old who underwent physical examination at our local hospital from November 2022 to May 2023. A generalized additive model (GAM) was fit to assess the dose-response relationship between liver enzymes and T2D risk. Furthermore, data from the UK Biobank (n=217,533) and National Health and Nutrition Examination Survey (NHANES 2011-2018; n= 15,528) were analyzed to evaluate whether the dose-response relationship between liver enzymes and T2D differed by population differences. A total of 14,100 participants were included (1,155 individuals with T2D and 12,945 individuals without diabetes) in the analysis. GAM revealed a non-linear relationship between liver enzymes and T2D risk (P non-linear < 0.001). Specifically, T2D risk increased with increasing ALT and GGT levels (range, <50 IU/L) and then plateaued when ALT and GGT levels were >50 IU/L. Elevated AST within a certain range (range, <35 IU/L) decreased the risk of T2D, whereas mildly elevated AST (>35 IU/L) became a risk factor for T2D. The UK Biobank and NHANES data analysis also showed a similar non-linear pattern between liver enzymes and T2D incidence. Liver enzymes were non-linearly associated with T2D risk in different populations, including China, the UK, and the US. Elevated ALT and GGT levels, within a certain range, could increase T2D risk. More attention should be given to liver enzyme levels for early lifestyle intervention and early T2D prevention. Further studies are necessary to explore the mechanism of the non-linear association between liver enzymes and T2D risk.

Associations of Lifestyle Patterns with Glucose and Lipid Metabolism in Finnish Adults at Increased Risk of Type 2 Diabetes.

Various lifestyle and sociodemographic factors have been associated with risk factors for type 2 diabetes (T2D). However, their combined associations with T2D risk factors have been studied much less. This study investigates cross-sectional associations of lifestyle patterns with T2D risk factors among 2925 adults at increased risk participating in the Stop Diabetes study. Lifestyle patterns are determined using principal component analysis (PCA) with several lifestyle and sociodemographic factors. The associations of lifestyle patterns with measures of glucose and lipid metabolism and serum metabolites analyzed by nuclear magnetic resonance (NMR) spectroscopy are studied using linear regression analysis. "Healthy eating" pattern is associated with better glucose and insulin metabolism, more favorable lipoprotein and fatty acid profiles and lower serum concentrations of metabolites related to inflammation, insulin resistance, and T2D. "High socioeconomic status and low physical activity" pattern is associated with increased serum concentrations of branched-chain amino acids, as are "Meat and poultry" and "Sleeping hours" patterns. "Snacks" pattern is associated with lower serum concentrations of ketone bodies. Our results show, in large scale primary care setting, that healthy eating is associated with better glucose and lipid metabolism and reveal novel associations of lifestyle patterns with metabolites related to glucose metabolism.

The Potential of the Adzuki Bean (Vigna angularis) and Its Bioactive Compounds in Managing Type 2 Diabetes and Glucose Metabolism: A Narrative Review.

Type 2 diabetes (T2D) is a common noncommunicable disease. In the United States alone, 37 million Americans had diabetes in 2017. The adzuki bean (Vigna angularis), a legume, has been reported to possess antidiabetic benefits. However, the extent and specific mechanisms through which adzuki bean consumption may contribute to T2D prevention and management remain unclear. Therefore, the aim of this narrative review is to analyze current evidence supporting the utilization of adzuki beans in the diet as a strategy for preventing and managing T2D. Animal studies have demonstrated a positive impact of adzuki beans on managing T2D. However, supporting data from humans are limited. Conversely, the potential of adzuki bean consumption in preventing T2D via modulating two T2D risk factors (obesity and dyslipidemia) also lacks conclusive evidence. Animal studies have suggested an inconsistent and even contradictory relationship between adzuki bean consumption and the management of obesity and dyslipidemia, in which both positive and negative relationships are reported. In sum, based on the existing scientific literature, this review found that the effects of adzuki bean consumption on preventing and managing T2D in humans remain undetermined. Consequently, human randomized controlled trials are needed to elucidate the potential benefits of the adzuki bean and its bioactive components in the prevention and management of T2D.

Precision prognostics for cardiovascular disease in Type 2 diabetes: a systematic review and meta-analysis.

Precision medicine has the potential to improve cardiovascular disease (CVD) risk prediction in individuals with Type 2 diabetes (T2D). We conducted a systematic review and meta-analysis of longitudinal studies to identify potentially novel prognostic factors that may improve CVD risk prediction in T2D. Out of 9380 studies identified, 416 studies met inclusion criteria. Outcomes were reported for 321 biomarker studies, 48 genetic marker studies, and 47 risk score/model studies. Out of all evaluated biomarkers, only 13 showed improvement in prediction performance. Results of pooled meta-analyses, non-pooled analyses, and assessments of improvement in prediction performance and risk of bias, yielded the highest predictive utility for N-terminal pro b-type natriuretic peptide (NT-proBNP) (high-evidence), troponin-T (TnT) (moderate-evidence), triglyceride-glucose (TyG) index (moderate-evidence), Genetic Risk Score for Coronary Heart Disease (GRS-CHD) (moderate-evidence); moderate predictive utility for coronary computed tomography angiography (low-evidence), single-photon emission computed tomography (low-evidence), pulse wave velocity (moderate-evidence); and low predictive utility for C-reactive protein (moderate-evidence), coronary artery calcium score (low-evidence), galectin-3 (low-evidence), troponin-I (low-evidence), carotid plaque (low-evidence), and growth differentiation factor-15 (low-evidence). Risk scores showed modest discrimination, with lower performance in populations different from the original development cohort. Despite high interest in this topic, very few studies conducted rigorous analyses to demonstrate incremental predictive utility beyond established CVD risk factors for T2D. The most promising markers identified were NT-proBNP, TnT, TyG and GRS-CHD, with the highest strength of evidence for NT-proBNP. Further research is needed to determine their clinical utility in risk stratification and management of CVD in T2D.

Association of Protein Tyrosine Phosphatase Receptor Type D and Serine Racemase Genetic Variants with Type 2 Diabetes in Malaysian Indians.

Type 2 diabetes (T2D) candidate genes, protein tyrosine phosphatase receptor type D (PTPRD), and serine racemase (SRR) were suggested by a genome-wide association study (GWAS) in the Chinese population. Association studies have been replicated among East Asian populations. The association of PTPRD and SRR genetic variants with T2D in Southeast Asian populations still needs to be studied. This study aimed to investigate the association of PTPRD and SSR genetic variants with T2D in Malaysian Indian subjects. The single nucleotide polymorphisms (SNPs) of PTPRD (rs649891 and rs17584499) and SRR (rs4523957, rs391300, and rs8081273) were genotyped in 397 T2D and 285 normal Malaysian Indian subjects. The homozygous dominant genotype of rs17584499 is frequent in diabetic patients (56.5%) compared to normal subjects (47.3%). In contrast, the homozygous recessive genotype of rs8081273 is more frequent among normal subjects (12.5%) than diabetic patients (5.6%). The dominant genetic model showed that PTPRD rs17584499 (CC) is a risk factor for T2D (OR = 1.42, P = 0.029), whereas the recessive genetic model showed that SRS SNP rs8081273 was protective for T2D (OR = 0.42, P = 0.003). This study confirmed the association of PTPRD rs17584499 genetic variations with T2D in Malaysian Indians. While the SRR rs8081273 (TT) genotype showed protection against T2D, more investigation in different populations is required to confirm this protection.

Type 2 diabetes metabolomics score and risk of progression to type 2 diabetes among women with a history of gestational diabetes mellitus.

Several metabolites are individually related to incident type 2 diabetes (T2D) risk. We prospectively evaluated a novel T2D-metabolite pattern with a risk of progression to T2D among high-risk women with a history of gestational diabetes mellitus (GDM). The longitudinal Nurses' Health Study II cohort enroled 116,429 women in 1989 and collected blood samples from 1996 to 1999. We profiled plasma metabolites in 175 incident T2D cases and 175 age-matched controls, all with a history of GDM before the blood draw. We derived a metabolomics score from 21 metabolites previously associated with incident T2D in the published literature by scoring according to the participants' quintile (1-5 points) of each metabolite. We modelled the T2D metabolomics score categorically in quartiles and continuously per 1 standard deviation (SD) with the risk of incident T2D using conditional logistic regression models adjusting for body mass index at the blood draw, and other established T2D risk factors. The percentage of women progressing to T2D ranged from 10% in the bottom T2D metabolomics score quartile to 78% in the highest score quartile. Adjusting for established T2D risk factors, women in the highest quartile had more than a 20-fold greater diabetes risk than women in the lowest quartile (odds ratios [OR]=23.1 [95% CI=8.6, 62.1]; p for trend<0.001). The continuous T2D metabolomics score was strongly and positively associated with incident T2D (adjusted OR=2.7 per SD [95% CI=1.9, 3.7], p<0.0001). A pattern of plasma metabolites among high-risk women is associated with a markedly elevated risk of progression to T2D later in life.

Sleep and insulin sensitivity in adolescents at risk of type 2 diabetes: the Sleep Manipulation in Adolescents at Risk of Type 2 Diabetes randomized crossover study.

To investigate the effect of increasing sleep duration for 1 week, compared to a week of habitual and decreased sleep, on insulin sensitivity (IS) in adolescents at risk for type 2 diabetes (T2D). Adolescents, 13-18 years old, at risk for T2D, with obesity and other risk factors, were recruited for a randomized (1:1), open-label, sex-stratified crossover study, that manipulated time-in-bed to modify sleep duration (measured by actigraphy). Following a week of habitual (HB) sleep, time-in-bed was increased (IN) and decreased (DE) by 1 hour 30 min/night for 1 week, counterbalanced across participants (HBINDE or HBDEIN), and separated by a week of washout sleep. The main outcome measure was IS, obtained via 2-hour oral-glucose-tolerance-test conducted after each sleep week. Of the 43 participants recruited, 36 (84%) completed all sleep interventions (52.8% female, age = 15.1 years, body mass index = 99.9th percentile, order: HBINDE = 18 and HBDEIN = 18). On average, during the HB week, participants slept 7 hours 31 min/night; sleep duration was 1 hour 02 min/night higher during the IN week and 1 hour 19 min/night lower during the DE week. We found a significant effect of sleep week on IS with a large effect size. Following the IN sleep week, IS was 20% higher compared to after the HB and DE sleep weeks, but there was no significant difference in IS following HB versus DE sleep weeks. Whenever possible, clinicians should empower youth at risk of T2D to improve their sleep duration, since even a modest increase in sleep duration of 1 h/night for 1 week can have a positive impact on IS in this population. Sleep Extension and IS in Adolescents, https://clinicaltrials.gov/study/NCT03754036, November 23rd, 2018. ClinicalTrials.gov (ID:NCT03754036).

Sick individuals, sick populations revisited: a test of the Rose hypothesis for type 2 diabetes disparities

IntroductionThe Rose hypothesis predicts that since genetic variation is greater within than between populations, genetic risk factors will be associated with individuals’ risk of disease but not population disparities, and...

Native low-density lipoproteins are priming signals of the NLRP3 inflammasome/interleukin-1β pathway in human adipose tissue and macrophages

Elevated plasma numbers of atherogenic apoB-lipoproteins (apoB), mostly as low-density lipoproteins (LDL), predict diabetes risk by unclear mechanisms. Upregulation of the NLRP3 inflammasome/interleukin-1 beta (IL-1β) system in white adipose tissue (WAT) is implicated in type 2 diabetes (T2D); however, metabolic signals that stimulate it remain unexplored. We hypothesized that (1) subjects with high-apoB have higher WAT IL-1β-secretion than subjects with low-apoB, (2) WAT IL-1β-secretion is associated with T2D risk factors, and (3) LDL prime and/or activate the WAT NLRP3 inflammasome. Forty non-diabetic subjects were assessed for T2D risk factors related to systemic and WAT glucose and fat metabolism. Regulation of the NLRP3 inflammasome was explored using LDL without/with the inflammasome’s priming and activation controls (LPS and ATP). LDL induced IL1B-expression and IL-1β-secretion in the presence of ATP in WAT and macrophages. Subjects with high-apoB had higher WAT IL-1β-secretion independently of covariates. The direction of association of LDL-induced WAT IL-1β-secretion to T2D risk factors was consistently pathological in high-apoB subjects only. Adjustment for IL-1β-secretion eliminated the association of plasma apoB with T2D risk factors. In conclusion, subjects with high-apoB have higher WAT IL-1β-secretion that may explain their risk for T2D and may be related to LDL-induced priming of the NLRP3 inflammasome.ClinicalTrials.gov (NCT04496154): Omega-3 to Reduce Diabetes Risk in Subjects With High Number of Particles That Carry "Bad Cholesterol" in the Blood—Full Text View—ClinicalTrials.gov.

A Resampling Approach for Causal Inference on Novel Two-Point Time-Series with Application to Identify Risk Factors for Type-2 Diabetes and Cardiovascular Disease

A Resampling Approach for Causal Inference on Novel Two-Point Time-Series with Application to Identify Risk Factors for Type-2 Diabetes and Cardiovascular Disease

Obstructive sleep apnea and type 2 diabetes: a bidirectional Mendelian randomization study

Objective: This study aims to explore the causal relationship between obstructive sleep apnea (OSA) and type 2 diabetes (T2D) using bidirectional Mendelian randomization (MR). Methods: The genetic data related to OSA were obtained from the FinnGen Biobank (Ncase=16, 761, Ncontrol=201, 194) in the Genome-wide association study (GWAS). Three single nucleotide polymorphism (SNP) were screened out as instrumental variable (IV) of OSA. The genetic data related to T2D were derived from a large Meta-analysis of GWAS (Ncase=62, 892, Ncontrol=596, 424), 114 SNP were selected as IV of T2D. Multiple MR methods were used for analysis and inverse variance weighted (IVW) was performed as main method. The sensitivity of MR analytic results was analyzed using MR-Egger and other methods, and the IV was evaluated using F-value statistics. Results: MR analysis showed that OSA was significantly associated with increased risk of T2D (OR=2.016, 95%CI: 1.185-3.429, P<0.05). There was no significant relationship between T2D and OSA risk (OR=1.030, 95%CI: 0.980-1.082, P=0.238). There was heterogeneity in both-way results (OSA➝T2D, P=1.808×10-11; T2D➝OSA, P=1.729×10-7), and no horizontal pleiotropy (OSA➝T2D, P=0.477; T2D➝OSA, P=0.349). IV of OSA and T2D-selected in the study were strong instrumental variables (F statistics of OSA=20.543; F statistics of T2D=30.117). Conclusion: Our results supported that OSA was a risk factor for T2D, but T2D had no significant impact on the incidence of OSA. Blood glucose monitoring and diabetes screening in OSA patients might be beneficial to the early detection and intervention of T2D.

Ethnic Differences in the Association Between Age at Natural Menopause and Risk of Type 2 Diabetes Among Postmenopausal Women: A Pooled Analysis of Individual Data From 13 Cohort Studies.

To investigate associations between age at natural menopause, particularly premature ovarian insufficiency (POI) (natural menopause before age 40 years), and incident type 2 diabetes (T2D) and identify any variations by ethnicity. We pooled individual-level data of 338,059 women from 13 cohort studies without T2D before menopause from six ethnic groups: White (n = 177,674), Chinese (n = 146,008), Japanese (n = 9,061), South/Southeast Asian (n = 2,228), Black (n = 1,838), and mixed/other (n = 1,250). Hazard ratios (HRs) of T2D associated with age at menopause were estimated in the overall sample and by ethnicity, with study as a random effect. For each ethnic group, we further stratified the association by birth year, education level, and BMI. Over 9 years of follow-up, 20,064 (5.9%) women developed T2D. Overall, POI (vs. menopause at age 50-51 years) was associated with an increased risk of T2D (HR 1.31; 95% CI 1.20-1.44), and there was an interaction between age at menopause and ethnicity (P < 0.0001). T2D risk associated with POI was higher in White (1.53; 1.36-1.73), Japanese (4.04; 1.97-8.27), and Chinese women born in 1950 or later (2.79; 2.11-3.70); although less precise, the risk estimates were consistent in women of South/Southeast Asian (1.46; 0.89-2.40), Black (1.72; 0.95-3.12), and mixed/other (2.16; 0.83-5.57) ethnic groups. A similar pattern, but with a smaller increased risk of T2D, was observed with early menopause overall (1.16; 1.10-1.23) and for White, Japanese, and Chinese women born in 1950 or later. POI and early menopause are risk factors for T2D in postmenopausal women, with considerable variation across ethnic groups, and may need to be considered in risk assessments of T2D among women.

A Longitudinal Clinical Trajectory Analysis Examining the Accumulation of Co-morbidity in People with Type 2 Diabetes (T2D) Compared with Non-T2D Individuals.

Type 2 diabetes mellitus (T2D) is commonly associated with an increasing complexity of multimorbidity. While some progress has been made in identifying genetic and non-genetic risk factors for T2D, understanding the longitudinal clinical history of individuals before/after T2D diagnosis may provide additional insights. In this study, we utilised longitudinal data from the DARE (Diabetes Alliance for Research in England) study to examine the trajectory of clinical conditions in individuals with and without T2D. Data from 1932 individuals (T2D n = 1196 vs. matched non-T2D controls n = 736) were extracted and subjected to trajectory analysis over a period of up to 50years (25years pre-diagnosis/25years post-diagnosis). We also analysed the cumulative proportion of people with diagnosed coronary artery disease (CAD) in their general practice (GP) record with an analysis of lower respiratory tract infection (RTI) as a comparator group. The mean age of diagnosis of T2D was 52.6 (95% confidence interval 52.0-53.4)years. In the years leading up to T2D diagnosis, individuals who eventually received a T2D diagnosis consistently exhibited a considerable increase in several clinical phenotypes. Additionally, immediately prior to T2D diagnosis, a significantly greater prevalence of hypertension (35%)/RTI (34%)/heart conditions (17%)/eye, nose, throat infection (19%) and asthma (12%) were observed. The corresponding trajectory of each of these conditions was much less dramatic in the matched controls. Post-T2D diagnosis, proportions of T2D individuals exhibiting hypertension/chronic kidney disease/retinopathy/infections climbed rapidly before plateauing. At the last follow-up by quintile of disadvantage, the proportion (%) of people with diagnosed CAD was 6.4% for quintile 1 (least disadvantaged) and 11% for quintile 5 (F = 3.4, p = 0.01 for the difference between quintiles). These findings provide novel insights into the onset/natural progression of T2D, suggesting an early phase of inflammation-related disease activity before any clinical diagnosis of T2D is made. Measures that reduce social inequality have the potential in the longer term to reduce the social gradient in health outcomes reported here.

Assessment of common risk factors of diabetes and chronic kidney disease: a Mendelian randomization study.

The increasing prevalence of diabetes and its significant impact on mortality and morbidity rates worldwide has led to a growing interest in understanding its common risk factors, particularly in relation to chronic kidney disease (CKD). This research article aims to investigate the shared risk factors between type 1 diabetes (T1D), type 2 diabetes (T2D), and CKD using a Mendelian randomization (MR) design. The study utilized genome-wide association study (GWAS) datasets for T1D, T2D, and CKD from the FinnGen research project. GWAS summary statistics datasets for 118 exposure traits were obtained from the IEU OpenGWAS database. MR analyses were conducted to examine the causal relationships between exposure traits and each of the three outcomes. Multiple methods, including inverse-variance weighted, weighted median, and MR-Egger, were employed for the MR studies. Phenome-wide MR analyses revealed that eosinophil percentage exhibited a significant and suggestive causal association with T1D and CKD, respectively, suggesting its potential as a shared risk factor for T1D and CKD. For T2D, 34 traits demonstrated significant associations. Among these 34 traits, 14 were also significantly associated with CKD, indicating the presence of common risk factors between T2D and CKD, primarily related to obesity, height, blood lipids and sex hormone binding globulin, blood pressure, and walking pace. This research has uncovered the eosinophil percentage as a potential common risk factor for both T1D and CKD, while also identifying several traits, such as obesity and blood lipids, as shared risk factors for T2D and CKD. This study contributes to the understanding of the common risk factors between diabetes and CKD, emphasizing the need for targeted interventions to reduce the risk of these diseases.

Denture use and risk for cardiometabolic disease: observational and Mendelian randomization analyses.

Denture use may potentially increase the risk of cardiometabolic diseases (CMDs), but the casual relevance and strength of the associations are currently unknown. A total of 495 938 participants from the UK Biobank were included in the observational analyses. Linkage disequilibrium score (LDSC) regression and Mendelian randomization analyses were employed to estimate genetic correlation and the associations between the genetic liability for denture use with coronary artery disease, myocardial infarction, heart failure (HF), any stroke (AS), ischaemic stroke, haemorrhagic stroke, type 2 diabetes (T2D), and related clinical risk factors. In observational analysis, denture use was associated with 14-25% higher risks of various CMDs. The LDSC analysis found that denture use showed a positive genetic correlation with CMDs (rg 0.21-0.38). Genetic liability for denture use was associated with an elevated risk of HF [odds ratio: 1.49 (1.20-1.83)] and T2D [1.11 (1.01-1.24)]. By integrating genetic summary data of denture use with the sum of decayed, missing, and filled tooth surfaces (DMFS), a clinical measure of dental caries obtained from an independent source, genetically determined denture use/DMFS was also associated with an elevated risk of AS [1.21 (1.04-1.40)]. Furthermore, genetically predicted denture use/DMFS was significantly associated with established cardiometabolic risk factors, including HDL cholesterol, triglycerides, waist circumference, waist-to-hip ratio, and height. Our study supported potential causal associations between the genetic liability for denture use and risks for HF, AS, T2D, and related clinical risk factors. These findings may inform prevention and intervention strategies targeting dental diseases and CMDs.

A Comparison of the Effects of Empagliflozin and Sitagliptin, When Combined With Metformin, on Lipid Levels in Patients with Type 2 Diabetes: A Clinical Investigation.

Introduction Type 2 diabetes (T2D) is emerging as a major global health concern. An associated condition, dyslipidemia, which acts as a significant modifiable risk factor for T2D, exhibits variations across different ethnicities and socioeconomic backgrounds. While many patients rely on metformin as their primary treatment, it does not always effectively control hyperglycemia. As a result, there is a growing need for adjunctive treatments, including sodium-glucose cotransporter-2 (SGLT2) and dipeptidyl peptidase-4 (DPP-4) inhibitors. This study evaluated the comparative effects of empagliflozin (an SGLT2 inhibitor) and sitagliptin (a DPP-4 inhibitor), both combined with metformin, on the lipid profiles of individuals with T2D. Methods Over six months at the Federal Government Polyclinic Hospital in Islamabad, we enrolled 126 participants diagnosed with T2D. Using a nonprobability consecutive sampling technique, we divided them into two groups. Group A received metformin and empagliflozin, while Group B was administered metformin and sitagliptin. We assessed their fasting lipid profiles three months into the treatment. Results Both groups consisted of 63 patients each. We observed that those in Group B, treated with sitagliptin and metformin, demonstrated a more significant reduction in total cholesterol and low-density lipoprotein-C levels than those in Group A, treated with empagliflozin and metformin. This difference proved to be statistically meaningful. Conclusion The combination of sitagliptin and metformin showed enhanced benefits in lipid profile management compared to the combination of empagliflozin and metformin in patients with T2D. This discovery underscores the need for holistic treatment modalities that factor in blood glucose levels and cardiovascular health.

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.

Erectile dysfunction associated with undiagnosed prediabetes and type 2 diabetes in young adult males: A retrospective cohort study

Erectile dysfunction (ED) is a common comorbidity in type 2 diabetes (T2D). ED has been studied as an outcome in diabetes, but it is not known if ED is a risk factor for T2D. We determined if patients with ED have an increased risk for prediabetes and/or T2D and measured the duration between ED and prediabetes/T2D diagnosis. Retrospective cohort study using de-identified medical record data from a large mid-western health care system to measure ED, T2D and potential confounding factors. Patients were 18 to 40 years of age because we were interested in early onset pre-diabetes/T2D. Eligible patients had ED and were free of prediabetes, hyperglycemia and T2D at index. Entropy balancing controlled for confounding. Modified Poisson regression models with robust error variances calculated relative risk (RR) and 95% confidence intervals for the association of ED and pre-diabetes/T2D. Patients' mean age was 28.3 (±7.0) years, 81.7% were White and 14.0% were Black. After controlling for confounding, ED was associated with increased risk for prediabetes/T2D (RR = 1.34; 95%CI:1.16–1.55). This association was similar to that between ED and T2D alone (RR = 1.38; 95% CI: 1.10–1.74). About 30% had ED and prediabetes/T2D diagnosed on the same day and nearly 75% were diagnosed within a year of ED. ED is a marker for undiagnosed prediabetes/T2D and a risk factor for near term onset of prediabetes/T2D. ED may offer the opportunity for earlier detection and diagnoses of T2D, particularly in younger men. Younger patients presenting with ED should be screened for hyperglycemia.