Bayesian network analysis of factors influencing type 2 diabetes, coronary heart disease, and their comorbidities.

OBJECTIVE: Bayesian network (BN) models were developed to explore the specific relationships between influencing factors and type 2 diabetes mellitus (T2DM), coronary heart disease (CAD), and their comorbidities. The aim was to predict disease occurrence and diagnose etiology using these models, thereby informing the development of effective prevention and control strategies for T2DM, CAD, and their comorbidities. METHOD: Employing a case-control design, the study compared individuals with T2DM, CAD, and their comorbidities (case group) with healthy counterparts (control group). Univariate and multivariate Logistic regression analyses were conducted to identify disease-influencing factors. The BN structure was learned using the Tabu search algorithm, with parameter estimation achieved through maximum likelihood estimation. The predictive performance of the BN model was assessed using the confusion matrix, and Netica software was utilized for visual prediction and diagnosis. RESULT: The study involved 3,824 participants, including 1,175 controls, 1,163 T2DM cases, 982 CAD cases, and 504 comorbidity cases. The BN model unveiled factors directly and indirectly impacting T2DM, such as age, region, education level, and family history (FH). Variables like exercise, LDL-C, TC, fruit, and sweet food intake exhibited direct effects, while smoking, alcohol consumption, occupation, heart rate, HDL-C, meat, and staple food intake had indirect effects. Similarly, for CAD, factors with direct and indirect effects included age, smoking, SBP, exercise, meat, and fruit intake, while sleeping time and heart rate showed direct effects. Regarding T2DM and CAD comorbidities, age, FBG, SBP, fruit, and sweet intake demonstrated both direct and indirect effects, whereas exercise and HDL-C exhibited direct effects, and region, education level, DBP, and TC showed indirect effects. CONCLUSION: The BN model constructed using the Tabu search algorithm showcased robust predictive performance, reliability, and applicability in forecasting disease probabilities for T2DM, CAD, and their comorbidities. These findings offer valuable insights for enhancing prevention and control strategies and exploring the application of BN in predicting and diagnosing chronic diseases.

The unique association between the level of plateletcrit and the prevalence of diabetic kidney disease: a cross-sectional study.

Objective: The activation of platelets in individuals with type 2 diabetes mellitus (T2DM) triggers inflammation and hemodynamic abnormalities, contributing to the development of diabetic kidney disease (DKD). Despite this, research into the relationship between plateletcrit (PCT) levels and DKD is sparse, with inconsistent conclusions drawn regarding the connection between various platelet parameters and DKD. This highlights the necessity for comprehensive, large-scale population studies. Therefore, our objective is to explore the association between PCT levels and various platelet parameters in relation to DKD. Methods: In this cross-sectional study, hematological parameter data were collected from a cohort of 4,302 hospitalized Chinese patients. We analyzed the relationships between PCT, platelet count (PLT), mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR), and DKD, along with the urinary albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR). Receiver operating characteristic (ROC) curve analysis was conducted to evaluate the diagnostic potential of these parameters. Results: DKD patients exhibited significantly higher PCT levels compared to those without DKD. Multivariate regression analysis identified elevated PCT and PLT levels as potential independent risk factors for both DKD and UACR, while lower MPV levels might serve as independent protective factors for eGFR. The areas under the ROC curve for PCT in relation to DKD and UACR (≥30 mg/g) were 0.523 and 0.526, respectively. The area under the ROC curve for PLT in relation to UACR (≥30 mg/g) was 0.523. Conclusion: PCT demonstrates a weak diagnostic value for T2DM patients at risk of developing DKD and experiencing proteinuria, and PLT shows a similarly modest diagnostic utility for detecting proteinuria. These insights contribute to a deeper understanding of the complex dynamics involved in DKD. Additionally, incorporating these markers into routine clinical assessments could enhance risk stratification, facilitating early interventions and personalized management strategies.

Prevalence and factors associated with diabetes-related distress in type 2 diabetes patients: a study in Hong Kong primary care setting.

Diabetes-related distress (DRD) refers to the psychological distress specific to living with diabetes. DRD can lead to negative clinical consequences such as poor self-management. By knowing the local prevalence and severity of DRD, primary care teams can improve the DRD evaluation in our daily practice. This was a cross-sectional study conducted in 3 General Out-patient Clinics (GOPCs) from 1 December 2021 to 31 May 2022. A random sample of adult Chinese subjects with T2DM, who regularly followed up in the selected clinic in the past 12 months, were included. DRD was measured by the validated 15-item Chinese version of the Diabetes Distress Scale (CDDS-15). An overall mean score ≥ 2.0 was considered clinically significant. The association of DRD with selected clinical and personal factors was investigated. The study recruited 362 subjects (mean age 64.2 years old, S.D. 9.5) with a variable duration of living with T2DM (median duration 7.0 years, IQR 10.0). The response rate was 90.6%. The median HbA1c was 6.9% (IQR 0.9). More than half (59.4%) of the subjects reported a clinically significant DRD. Younger subjects were more likely to have DRD (odds ratio of 0.965, 95% CI 0.937-0.994, p = 0.017). Patients with T2DM in GOPCs commonly experience clinically significant DRD, particularly in the younger age group. The primary care clinicians could consider integrating the evaluation of DRD as a part of comprehensive diabetes care.

Relationship between atherosclerotic cardiovascular disease and diabetic retinopathy in patients with type 2 diabetes mellitus.

This study aimed to explore the potential correlation between atherosclerotic cardiovascular disease (ASCVD) and diabetic retinopathy (DR) in patients with type 2 diabetes mellitus (T2DM). We enrolled 6540 patients with T2DM who were receiving chronic disease management for hypertension, hyperglycemia, and hyperlipidemia in Chengyang District of Qingdao. Among them, 730 had ASCVD (ASCVD group), which 5810 did not (N-ASCVD group). The results showed significantly higher levels of age, blood glucose, glycosylated hemoglobin (HbA1c), systolic blood pressure, ASCVD family history, female proportion, and DR incidence in the N-ASCVD group. Additionally, the glomerular filtration rate was significantly lower in the ASCVD group. Logistic regression analysis revealed a positive correlation between DR and ASCVD risk. DR was further categorized into 2 subtypes, nonproliferative DR (NPDR) and proliferative DR (PDR), based on e lesion severity. Interestingly, only the PDR was associated with ASCVD. Even after accounting for traditional ASCVD risk factors such as age, sex, and family history, PDR remained associated with ASCVD, with a staggering 718% increase in the risk for patients with PDR. Therefore, there is a strong association between ASCVD and DR in individuals with T2DM, with PDR particularly exhibiting an independent and positive correlation with increased ASCVD risk.

Association of dietary nutrient intake with type 2 diabetes: A Mendelian randomization study.

Observational research suggests that the evidence linking dietary nutrient intake (encompassing minerals, vitamins, amino acids, and unsaturated fatty acids) to type 2 diabetes (T2D) is both inconsistent and limited. This study aims to explore the potential causal relationship between dietary nutrients and T2D. Causal estimation utilized Mendelian randomization techniques. Single nucleotide polymorphisms linked to dietary nutrients were identified from existing genome-wide association studies and used as instrumental variables. Genome-wide association studies data pertinent to T2D were sourced from the DIMANTE consortium and the FinnGen database. Techniques including inverse variance weighting (IVW), weighted mode, weighted median, and Mendelian randomization-Egger were employed for causal inference, complemented by sensitivity analysis. Genetically predicted higher phenylalanine (IVW: odds ratio = 1.10 95% confidence interval 1.04-1.17, P = 1.5 × 10-3, q_pval = 3.4 × 10-2) and dihomo-gamma-linolenic acid (IVW: odds ratio = 1.001 95% confidence interval 1.0006-1.003, P = 3.7 × 10-3, q_pval = 4.1 × 10-2) levels were directly associated with T2D risk. Conversely, no causal relationships between other nutrients and T2D were established. We hypothesize that phenylalanine and dihomo-gamma-linolenic acid contribute to the pathogenesis of T2D. Clinically, the use of foods with high phenylalanine content may pose potential risks for patients with a heightened risk of T2D. Our study provides evidence supporting a causal link between dietary nutrient intake and the development of T2D.

Exploring the interconnected between type 2 diabetes mellitus and nonalcoholic fatty liver disease: Genetic correlation and Mendelian randomization analysis.

Epidemiological and clinical studies have indicated a higher risk of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM), implying a potentially shared genetic etiology, which is still less explored. Genetic links between T2DM and NAFLD were assessed using linkage disequilibrium score regression and pleiotropic analysis under composite null hypothesis. European GWAS data have identified shared genes, whereas SNP-level pleiotropic analysis under composite null hypothesis has explored pleiotropic loci. generalized gene-set analysis of GWAS data determines pleiotropic pathways and tissue enrichment using eQTL mapping to identify associated genes. Mendelian randomization analysis was used to investigate the causal relationship between NAFLD and T2DM. Linkage disequilibrium score regression analysis revealed a strong genetic correlation between T2DM and NAFLD, and identified 24 pleiotropic loci. These single-nucleotide polymorphisms are primarily involved in biosynthetic regulation, RNA biosynthesis, and pancreatic development. generalized gene-set analysis of GWAS data analysis revealed significant enrichment in multiple brain tissues. Gene mapping using these 3 methods led to the identification of numerous pleiotropic genes, with differences observed in liver and kidney tissues. These genes were mainly enriched in pancreas, brain, and liver tissues. The Mendelian randomization method indicated a significantly positive unidirectional causal relationship between T2DM and NAFLD. Our study identified a shared genetic structure between NAFLD and T2DM, providing new insights into the genetic pathogenesis and mechanisms of NAFLD and T2DM comorbidities.

Association between ideal cardiovascular health and abnormal glucose metabolism in the elderly: evidence based on real-world data.

BACKGROUND: Limited information is available on the effect of ideal cardiovascular health (CVH) and abnormal glucose metabolism in elderly people. We aimed to analyze the prevalence of CVH behaviors, abnormal glucose metabolism, and their correlation in 65 and older people. METHODS: In this study, randomized cluster sampling, multivariate logistic regression, and mediating effects analysis were used. Recruiting was carried out between January 2020 and December 2020, and 1984 participants aged 65 years or older completed the study. RESULTS: The prevalence of abnormal glucose metabolism in this group was 26.7% (n = 529), among which the prevalence of impaired fasting glucose (IFG) was 9.5% (male vs. female: 8.7% vs 10.1%, P = 0.338), and the prevalence of type 2 diabetes mellitus (T2DM) was 19.0% (male vs. female: 17.8 vs. 19.8%, P = 0.256). The ideal CVH rate (number of ideal CVH metrics ≥ 5) was only 21.0%. The risk of IFG and T2DM decreased by 23% and 20% with each increase in one ideal CVH metrics, with OR (95%CI) of 0.77(0.65-0.92) and 0.80(0.71-0.90), respectively (P -trend < 0.001). TyG fully mediated the ideal CVH and the incidence of T2DM, and its mediating effect OR (95%CI) was 0.88(0.84-0.91). CONCLUSIONS: Each increase in an ideal CVH measure may effectively reduce the risk of abnormal glucose metabolism by more than 20%.

Contributions of elevated CRP, hyperglycaemia, and type 2 diabetes to cardiovascular risk in the general population: observational and Mendelian randomization studies.

OBJECTIVE: To investigate the contributions of low-grade inflammation measured by C-reactive protein (CRP), hyperglycaemia, and type 2 diabetes to risk of ischemic heart disease (IHD) and cardiovascular disease (CVD) death in the general population, and whether hyperglycaemia and high CRP are causally related. RESEARCH DESIGN AND METHODS: Observational and bidirectional, one-sample Mendelian randomization (MR) analyses in 112,815 individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study, and bidirectional, two-sample MR with summary level data from two publicly available consortia, CHARGE and MAGIC. RESULTS: Observationally, higher plasma CRP was associated with stepwise higher risk of IHD and CVD death, with hazard ratios and 95% confidence intervals (95%CI) of 1.50 (1.38, 1.62) and 2.44 (1.93, 3.10) in individuals with the 20% highest CRP concentrations. The corresponding hazard ratios for elevated plasma glucose were 1.10 (1.02, 1.18) and 1.22 (1.01, 1.49), respectively. Cumulative incidences of IHD and CVD death were 365% and 592% higher, respectively, in individuals with both type 2 diabetes and plasma CRP ≥ 2 mg/L compared to individuals without either. Plasma CRP and glucose were observationally associated (ß-coefficient: 0.02 (0.02, 0.03), p = 3 × 10- 20); however, one- and two-sample MR did not support a causal effect of CRP on glucose (-0.04 (-0.12, 0.32) and - 0.03 (-0.13, 0.06)), nor of glucose on CRP (-0.01 (-0.08, 0.07) and - 0.00 (-0.14, 0.13)). CONCLUSIONS: Elevated concentrations of plasma CRP and glucose are predictors of IHD and CVD death in the general population. We found no genetic association between CRP and glucose, or vice versa, suggesting that lowering glucose pharmacologically does not have a direct effect on low-grade inflammation.

Strengthening the Evidence for a Causal Link between Type 2 Diabetes Mellitus and Pancreatic Cancer: Insights from Two-Sample and Multivariable Mendelian Randomization.

This two-sample Mendelian randomization (MR) study was conducted to investigate the causal associations between type 2 diabetes mellitus (T2DM) and the risk of pancreatic cancer (PaCa), as this causal relationship remains inconclusive in existing MR studies. The selection of instrumental variables for T2DM was based on two genome-wide association study (GWAS) meta-analyses from European cohorts. Summary-level data for PaCa were extracted from the FinnGen and UK Biobank databases. Inverse variance weighted (IVW) and four other robust methods were employed in our MR analysis. Various sensitivity analyses and multivariable MR approaches were also performed to enhance the robustness of our findings. In the IVW and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) analyses, the odds ratios (ORs) for each 1-unit increase in genetically predicted log odds of T2DM were approximately 1.13 for PaCa. The sensitivity tests and multivariable MR supported the causal link between T2DM and PaCa without pleiotropic effects. Therefore, our analyses suggest a causal relationship between T2DM and PaCa, shedding light on the potential pathophysiological mechanisms of T2DM's impact on PaCa. This finding underscores the importance of T2DM prevention as a strategy to reduce the risk of PaCa.

Sensorineural hearing loss among type 2 diabetic patients and its association with peripheral neuropathy: a cross-sectional study from a lower middle-income country.

INTRODUCTION: Despite potential links between diabetes and sensorineural hearing loss (SNHL), routine hearing assessments for diabetic patients are not standard practice. Our study aimed to investigate the prevalence of SNHL and its association with diabetes-related factors among patients with type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: This cross-sectional study was conducted at the Diabetes Clinic, Jinnah Postgraduate Medical Centre, Karachi, Pakistan, from May to September 2021. A total of 396 patients fulfilling the inclusion criteria participated after informed consent. Data collection involved a sociodemographic profile, Michigan Neuropathy Screening Instrument examination followed by pure-tone audiometry and laboratory tests including haemoglobin A1C (HbA1c). HL was defined using better ear four-frequency pure-tone average of ≥26 dB HL and graded as per WHO criteria. Statistical analyses were performed using SPSS. χ2, independent t-test and multinomial logistic regression analyses were applied. P<0.05 at 95% CI was considered significant. RESULTS: Our study revealed a high prevalence of SNHL among patients with T2DM. Mild HL was seen in 55.8%, while 18.7% suffered from moderate HL. Common audiological symptoms included difficulty understanding speech in noisy surroundings (44.2%), balance problems (42.9%), sentence repetition (35.9%), tinnitus (32.3%) and differentiating consonants (31.1%). Hearing impairment predominantly affected low (0.25-0.5 kHz) and high (4-8 kHz) frequencies with a significant difference at 4 kHz among both sexes (t (394)=2.8, p=0.004). Peripheral neuropathy was significantly associated with SNHL on multinomial logistic regression after adjusting with age, sex, body mass index and the presence of any comorbidities. Diabetes duration, HbA1c or family history of diabetes was found unrelated to SNHL severity. CONCLUSIONS: The study highlights the substantial prevalence of SNHL among patients with T2DM and emphasises the importance of targeted audiological care as part of a holistic approach to diabetes management. Addressing HL early may significantly improve communication and overall quality of life.

Evaluating the correlation of sclerostin levels with obesity and type 2 diabetes in a multiethnic population living in Kuwait.

Obesity and Type 2 Diabetes Mellitus (T2DM) are intricate metabolic disorders with a multifactorial etiology, often leading to a spectrum of complications. Recent research has highlighted the impact of these conditions on bone health, with a particular focus on the role of sclerostin (SOST), a protein molecule integral to bone metabolism. Elevated circulating levels of SOST have been observed in patients with T2DM compared to healthy individuals. This study aims to examine the circulating levels of SOST in a multiethnic population living in Kuwait and to elucidate the relationship between SOST levels, obesity, T2DM, and ethnic background. The study is a cross-sectional analysis of a large cohort of 2083 individuals living in Kuwait. The plasma level of SOST was measured using a bone panel multiplex assay. The study found a significant increase in SOST levels in individuals with T2DM (1008.3 pg/mL, IQR-648) compared to non-diabetic individuals (710.6 pg/mL, IQR-479). There was a significant gender difference in median SOST levels, with males exhibiting higher levels than females across various covariates (diabetes, IR, age, weight, and ethnicity). Notably, SOST levels varied significantly with ethnicity: Arabs (677.4 pg/mL, IQR-481.7), South Asians (914.6 pg/mL, IQR-515), and Southeast Asians (695.2 pg/mL, IQR-436.8). Furthermore, SOST levels showed a significant positive correlation with gender, age, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, HbA1c, insulin, total cholesterol, triglycerides, HDL, LDL, ALT, and AST (p-Value ≥0.05). South Asian participants, who exhibited the highest SOST levels, demonstrated the most pronounced associations, even after adjusting for age, gender, BMI, and diabetes status (p-Value ≥0.05). The observed correlations of SOST with various clinical parameters suggest its significant role in the diabetic milieu, particularly pronounced in the South Asian population compared to other ethnic groups.

Eight-year nationwide study of the bidirectional association between type 2 diabetes and depression in nearly 8 million German outpatients.

INTRODUCTION: Research linking type 2 diabetes and depression mostly relied on hospital-based diagnoses or prescription data, overlooking many outpatient diagnoses. We aimed to quantify the risks of depression in individuals newly diagnosed with type 2 diabetes, and type 2 diabetes in those newly diagnosed with depression, while exploring potential risk differences depending on age, sex, and follow-up time. RESEARCH DESIGN AND METHODS: We conducted a matched cohort study using German nationwide outpatient claims data from 2012 to 2022. Participants were individuals newly diagnosed with type 2 diabetes (N=294 642) or depression (N=1 271 537) in 2015, matched in a 1:4 ratio to controls without these conditions by age, sex, and region. The bidirectional risk was evaluated over an 8-year period using mixed-effects Cox proportional hazards models, adjusting for the Charlson Comorbidity Index, urbanicity, and area-level deprivation. RESULTS: New type 2 diabetes diagnosis was associated with higher depression risk over 8 years (N=54 561 with depression, HR=1.23, 99% CI=1.21 to 1.24). Similarly, depression diagnosis was linked to an increased type 2 diabetes risk (N=71 848 with type 2 diabetes, HR=1.15, 99% CI=1.14 to 1.17). The association between depression and type 2 diabetes was stronger in younger age groups, especially under 34 years. Findings held across sex-stratified analyses. Time stratification showed a more pronounced association between type 2 diabetes and depression risk during the earlier follow-up quarters, whereas the risk of developing type 2 diabetes after depression diagnosis remained constant throughout the follow-up period. CONCLUSIONS: Our findings confirm a bidirectional link between type 2 diabetes and depression, particularly in younger individuals. As type 2 diabetes and depression are frequent, future research needs to study whether preventive approaches can reduce the risk of developing this comorbidity.

Incident Diabetes in Women With Patterns of Gestational Diabetes Occurrences Across 2 Pregnancies.

Importance: Gestational diabetes is a type 2 diabetes risk indicator, and recurrence further augments risk. In women with a single occurrence across 2 pregnancies, it is unclear whether first- vs second-pregnancy gestational diabetes differ in terms of risk. Objective: To compare the hazards of incident diabetes among those with gestational diabetes in the first, in the second, and in both pregnancies with women without gestational diabetes in either. Design, Setting, and Participants: This was a retrospective cohort study with cohort inception from April 1, 1990, to December 31, 2012. Follow-up was April 1, 1990, to April 1, 2019. Participants were mothers with 2 singleton deliveries between April 1, 1990, and December 31, 2012, without diabetes before or between pregnancies, who were listed in public health care insurance administrative databases and birth, stillbirth, and death registries in Quebec, Canada. Data were analyzed from July to December 2023. Exposure: Gestational diabetes occurrence(s) across 2 pregnancies. Main outcomes and measures: Incident diabetes from the second delivery until a third pregnancy, death, or the end of the follow-up period, whichever occurred first. Results: The 431 980 women with 2 singleton deliveries studied had a mean (SD) age of 30.1 (4.5) years at second delivery, with a mean (SD) of 2.8 (1.5) years elapsed between deliveries; 373 415 (86.4%) were of European background, and 78 770 (18.2%) were at the highest quintile of material deprivation. Overall, 10 920 women (2.5%) had gestational diabetes in their first pregnancy, 16 145 (3.7%) in their second, and 8255 (1.9%) in both (12 205 incident diabetes events; median [IQR] follow-up 11.5 [5.3-19.4] years). First pregnancy-only gestational diabetes increased hazards 4.35-fold (95% CI, 4.06-4.67), second pregnancy-only increased hazards 7.68-fold (95% CI, 7.31-8.07), and gestational diabetes in both pregnancies increased hazards 15.8-fold (95% CI, 15.0-16.6). Compared with first pregnancy-only gestational diabetes, second pregnancy-only gestational diabetes increased hazards by 76% (95% CI, 1.63-1.91), while gestational diabetes in both pregnancies increased it 3.63-fold (95% CI, 3.36-3.93). Conclusions and relevance: In this retrospective cohort study of nearly half a million women with 2 singleton pregnancies, both the number and ordinal pregnancy of any gestational diabetes occurrence increased diabetes risk. These considerations offer greater nuance than an ever or never gestational diabetes dichotomy.

Diabetes mellitus in pregnancy across Canada.

BACKGROUND: Contemporary estimates of diabetes mellitus (DM) rates in pregnancy are lacking in Canada. Accordingly, this study examined trends in the rates of type 1 (T1DM), type 2 (T2DM) and gestational (GDM) DM in Canada over a 15-year period, and selected adverse pregnancy outcomes. METHODS: This study used repeated cross-sectional data from the Canadian Institute of Health Information (CIHI) hospitalization discharge abstract database (DAD). Maternal delivery records were linked to their respective birth records from 2006 to 2019. The prevalence of T1DM, T2DM and GDM were calculated, including relative changes over time, assessed by a Cochrane-Armitage test. Also assessed were differences between provinces and territories in the prevalence of DM. RESULTS: Over the 15-year study period, comprising 4,320,778 hospital deliveries in Canada, there was a statistically significant increase in the prevalence of GDM and T1DM and T2DM. Compared to pregnancies without DM, all pregnancies with any form of DM had higher rates of hypertension and Caesarian delivery, and also adverse infant outcomes, including major congenital anomalies, preterm birth and large-for-gestational age birthweight. CONCLUSION: Among 4.3 million pregnancies in Canada, there has been a rise in the prevalence of DM. T2DM and GDM are expected to increase further as more overweight women conceive in Canada.

Causal relationship between air pollution, lung function, gastroesophageal reflux disease, and non-alcoholic fatty liver disease: univariate and multivariate Mendelian randomization study.

Background: The association between air pollution, lung function, gastroesophageal reflux disease, and Non-alcoholic fatty liver disease (NAFLD) remains inconclusive. Previous studies were not convincing due to confounding factors and reverse causality. We aim to investigate the causal relationship between air pollution, lung function, gastroesophageal reflux disease, and NAFLD using Mendelian randomization analysis. Methods: In this study, univariate Mendelian randomization analysis was conducted first. Subsequently, Steiger testing was performed to exclude the possibility of reverse association. Finally, significant risk factors identified from the univariate Mendelian analysis, as well as important factors affecting NAFLD from previous observational studies (type 2 diabetes and body mass index), were included in the multivariable Mendelian randomization analysis. Results: The results of the univariable Mendelian randomization analysis showed a positive correlation between particulate matter 2.5, gastroesophageal reflux disease, and NAFLD. There was a negative correlation between forced expiratory volume in 1 s, forced vital capacity, and NAFLD. The multivariable Mendelian randomization analysis indicated a direct causal relationship between gastroesophageal reflux disease (OR = 1.537, p = 0.011), type 2 diabetes (OR = 1.261, p < 0.001), and NAFLD. Conclusion: This Mendelian randomization study confirmed the causal relationships between air pollution, lung function, gastroesophageal reflux, and NAFLD. Furthermore, gastroesophageal reflux and type 2 diabetes were identified as independent risk factors for NAFLD, having a direct causal connection with the occurrence of NAFLD.

LXR signaling pathways link cholesterol metabolism with risk for prediabetes and diabetes.

BACKGROUNDPreclinical studies suggest that cholesterol accumulation leads to insulin resistance. We previously reported that alterations in a monocyte cholesterol metabolism transcriptional network (CMTN) - suggestive of cellular cholesterol accumulation - were cross-sectionally associated with obesity and type 2 diabetes (T2D). Here, we sought to determine whether the CMTN alterations independently predict incident prediabetes/T2D risk, and correlate with cellular cholesterol accumulation.METHODSMonocyte mRNA expression of 11 CMTN genes was quantified among 934 Multi-Ethnic Study of Atherosclerosis (MESA) participants free of prediabetes/T2D; cellular cholesterol was measured in a subset of 24 monocyte samples.RESULTSDuring a median 6-year follow-up, lower expression of 3 highly correlated LXR target genes - ABCG1 and ABCA1 (cholesterol efflux) and MYLIP (cholesterol uptake suppression) - and not other CMTN genes, was significantly associated with higher risk of incident prediabetes/T2D. Lower expression of the LXR target genes correlated with higher cellular cholesterol levels (e.g., 47% of variance in cellular total cholesterol explained by ABCG1 expression). Further, adding the LXR target genes to overweight/obesity and other known predictors significantly improved prediction of incident prediabetes/T2D.CONCLUSIONThese data suggest that the aberrant LXR/ABCG1-ABCA1-MYLIP pathway (LAAMP) is a major T2D risk factor and support a potential role for aberrant LAAMP and cellular cholesterol accumulation in diabetogenesis.FUNDINGThe MESA Epigenomics and Transcriptomics Studies were funded by NIH grants 1R01HL101250, 1RF1AG054474, R01HL126477, R01DK101921, and R01HL135009. This work was supported by funding from NIDDK R01DK103531 and NHLBI R01HL119962.

Patient and clinician preferences for diabetes management among older adults with co-morbid HIV: A qualitative exploration.

BACKGROUND: Older adults with HIV are at increased risk of developing certain chronic health conditions including type 2 diabetes mellitus (T2DM). As the number and complexity of conditions increases, so do treatment and health care needs. We explored patient and clinician preferences for HIV+T2DM care and perceived solutions to improving care. METHODS: We conducted an exploratory qualitative study comprised of individual in-depth interviews. Participants included English-speaking patients aged 50 and older living with HIV and T2DM and infectious disease (ID) and primary care (PC) clinicians from a large academic health center in Chicago. Thematic analysis drew from the Framework Method. RESULTS: A total of 19 patient and 10 clinician participants were interviewed. Many patients reported seeking HIV and T2DM care from the same clinician; they valued rapport and a 'one-stop-shop'. Others reported having separate clinicians; they valued perceived expertise and specialty care. Nearly all clinicians reported comfort screening for T2DM and initiating first line oral therapy; ID clinicians reported placing referrals for newer, complex therapies. Patients would like educational support for T2DM management; clinicians would like to learn more about newer therapies and easier referral processes. CONCLUSIONS: Patient-centered care includes managing T2DM from a variety of clinical settings for individuals with HIV, yet strategies are needed to better support clinicians. Future research should examine how best to implement these strategies.

Association of type 2 diabetes with family history of diabetes, diabetes biomarkers, mental and physical disorders in a Kenyan setting.

This study aimed to determine the degree of family relations and associated socio-demographics characteristics, clinical/physical and mental disorders in type 2 diabetes mellitus in a Kenyan diabetes clinic. This study was part of a large multicentre study whose protocol and results had been published. It took place at the outpatient diabetes clinic at a County Teaching and Referral Hospital in South East Kenya involving 182 participants. We used a socio-demographic questionnaire, the Hamilton Depression (HAM-D) and PHQ-9 rating scales for depression, the MINI International Neuropsychiatric Interview (MINI; V5 or V6) for DSM-5 diagnoses, the WHO-5 Well-being scale and Problem Areas in Diabetes Scale (PAID). We extracted from the notes all physical conditions. We enquired about similar conditions in 1st and 2nd degree relatives. Descriptive, Chi-square test, Fisher's exact test, one way ANOVA, and Multinomial logistic regression analysis were conducted to test achievements of our specific aims. Of the 182 patients who participated in the study, 45.1% (82/182) reported a family history of diabetes. Conditions significantly (p < 0.05) associated with a degree of family history of diabetes were retinopathy, duration of diabetes (years), hypertension, and depressive disorder. On average 11.5% (21/182) scored severe depression (≥ 10) on PHQ-9 and 85.2% (115/182) scored good well-being (≥ 13 points). All DSM-5 psychiatric conditions were found in the 182 patients in varying prevalence regardless of relations. In addition, amongst the 182 patients, the highest prevalence was poor well-being on the WHO quality of life tool. This was followed by post-traumatic disorders (current), suicidality, and psychotic lifetime on DSM-5. The least prevalent on DSM-5 was eating disorders. Some type 2 diabetes mellitus physical disorders and depression have increased incidence in closely related patients. Overall, for all the patients, the prevalence of all DSM-5 diagnoses varied from 0.5 to 9.9%.

Diabetes mellitus in older persons with neurocognitive disorder: overtreatment prevalence and associated structural brain MRI findings.

BACKGROUND: Tight diabetes control is often applied in older persons with neurocognitive disorder resulting in increased hypoglycemic episodes but little is known about the pattern of brain injury in these overtreated patients. This study aims to: (a) quantify the prevalence of diabetes overtreatment in cognitively impaired older adults in a clinical population followed in an academic memory clinic (b) identify risk factors contributing to overtreatment; and (c) explore the association between diabetes overtreatment and specific brain region volume changes. METHODS: Retrospective study of older patients with type 2 diabetes and cognitive impairment who were diagnosed in a memory clinic from 2013 to 2020. Patients were classified into vulnerable and dependent according to their health profile. Overtreatment was defined when glycated hemoglobin was under 7% for vulnerable and 7.6% for dependent patients. Characteristics associated to overtreatment were examined in multivariable analysis. Grey matter volume in defined brain regions was measured from MRI using voxel-based morphometry and compared in patients over- vs. adequately treated. RESULTS: Among 161 patients included (median age 76.8 years, range 60.8-93.3 years, 32.9% women), 29.8% were considered as adequately treated, 54.0% as overtreated, and 16.2% as undertreated. In multivariable analyses, no association was observed between diabetes overtreatment and age or the severity of cognitive impairment. Among patients with neuroimaging data (N = 71), associations between overtreatment and grey matter loss were observed in several brain regions. Specifically, significant reductions in grey matter were found in the caudate (adj ß coeff: -0.217, 95%CI: [-0.416 to -0.018], p = .033), the precentral gyri (adj ßcoeff:-0.277, 95%CI: [-0.482 to -0.073], p = .009), the superior frontal gyri (adj ßcoeff: -0.244, 95%CI: [-0.458 to -0.030], p = .026), the calcarine cortex (adj ßcoeff:-0.193, 95%CI: [-0.386 to -0.001], p = .049), the superior occipital gyri (adj ßcoeff: -0.291, 95%CI: [-0.521 to -0.061], p = .014) and the inferior occipital gyri (adj ßcoeff: -0.236, 95%CI: [-0.456 to - 0.015], p = .036). CONCLUSION: A significant proportion of older patients with diabetes and neurocognitive disorder were subjected to excessively intensive treatment. The association identified with volume loss in several specific brain regions highlights the need to further investigate the potential cerebral damages associated with overtreatment and related hypoglycemia in larger sample.

Prevalence of diabetic cardiomyopathy in patients with type 2 diabetes in a large academic medical center.

BACKGROUND: Diabetic cardiomyopathy (DbCM) is characterized by asymptomatic stage B heart failure (SBHF) caused by diabetes-related metabolic alterations. DbCM is associated with an increased risk of progression to overt heart failure (HF). The prevalence of DbCM in patients with type 2 diabetes (T2D) is not well established. This study aims to determine prevalence of DbCM in adult T2D patients in real-world clinical practice. METHODS: Retrospective multi-step review of electronic medical records of patients with the diagnosis of T2D who had echocardiogram at UC San Diego Medical Center (UCSD) within 2010-2019 was conducted to identify T2D patients with SBHF. We defined "pure" DbCM when SBHF is associated solely with T2D and "mixed" SBHF when other medical conditions can contribute to SBHF. "Pure" DbCM was diagnosed in T2D patients with echocardiographic demonstration of SBHF defined as left atrial (LA) enlargement (LAE), as evidenced by LA volume index ≥ 34 mL/m2, in the presence of left ventricular ejection fraction (LVEF) ≥ 45%, while excluding overt HF and comorbidities that can contribute to SBHF. RESULTS: Of 778,314 UCSD patients in 2010-2019, 45,600 (5.9%) had T2D diagnosis. In this group, 15,182 T2D patients (33.3%) had echocardiogram and, among them, 13,680 (90.1%) had LVEF ≥ 45%. Out of 13,680 patients, 4,790 patients had LAE. Of them, 1,070 patients were excluded due to incomplete data and/or a lack of confirmed T2D according to the American Diabetes Association recommendations. Thus, 3,720 T2D patients with LVEF ≥ 45% and LAE were identified, regardless of HF symptoms. In this group, 1,604 patients (43.1%) had overt HF and were excluded. Thus, 2,116 T2D patients (56.9% of T2D patients with LVEF ≥ 45% and LAE) with asymptomatic SBHF were identified. Out of them, 1,773 patients (83.8%) were diagnosed with "mixed" SBHF due to comorbidities such as hypertension (58%), coronary artery disease (36%), and valvular heart disease (17%). Finally, 343 patients met the diagnostic criteria of "pure" DbCM, which represents 16.2% of T2D patients with SBHF, i.e., at least 2.9% of the entire T2D population in this study. CONCLUSIONS: Our findings provide insights into prevalence of DbCM in real-world clinical practice and indicate that DbCM affects a significant portion of T2D patients.