Increased Risk Of Diabetes Research Articles

Association between depression and diabetes among American adults using NHANES data from 2005 to 2020.

Depression impairs self-management in diabetic patients, exacerbates insulin resistance, and elevates glycated hemoglobin (HbA1c) levels, thereby increasing diabetes risk. This study analyzed data from 30,386 participants in the National Health and Nutrition Examination Survey (NHANES), assessing depression severity using the 9-item Patient Health Questionnaire (PHQ-9) and evaluating diabetes status through clinical markers such as HbA1c, random blood glucose, and fasting blood glucose. Participants were stratified by depression severity and diabetes status to examine the relationship between depression and diabetes risk. We applied descriptive statistics, logistic regression models, subgroup analyses, and restricted cubic spline (RCS) modeling to explore this association. The results revealed that greater depression severity was significantly associated with increased diabetes incidence, elevated HbA1c, fasting glucose, and insulin levels. Multivariate regression analysis confirmed a consistent positive correlation between depression severity and diabetes risk. Subgroup analyses further identified significant relationships between depression and various demographic and behavioral factors, including gender, race, BMI, smoking status, and prediabetic conditions. Additionally, the RCS model demonstrated a clear increase in diabetes risk with rising PHQ-9 scores. In conclusion, our study demonstrates that the severity of depression is positively correlated with the risk of diabetes, and this association may be closely linked to various glycemic and lipid metabolic parameters.

Napping and Obesity in Adults - What do we Know?

To review the evidence on the relationship between daytime napping and obesity. There is concern that napping may be harmful to metabolic health. Prospective studies have shown long time daytime napping (> 1h) is associated with increased diabetes risk which may be partly associated with obesity. Evidence from numerous cross-sectional studies and meta-analyses of cross-sectional studies have shown that long time napping (> 1h) but not short time napping is associated with increased risk of obesity, and this is seen worldwide. Inference regarding the nature of association from cross-sectional studies is limited; it is suggested the association is bidirectional. Prospective studies on the association between daytime napping and obesity are few and results unclear. Large longitudinal studies integrating daytime napping duration and night-time sleep behaviour and detailed information on lifestyle influences is needed to help elucidate further the associations of long time napping with obesity.

Cardiometabolic risk assessment in transgender individuals - differential impact of sex hormones and sex chromosomes.

While transgender individuals represent a significant group seeking medical care, the differential effect of sex on cardiometabolic risk metrics is incompletely understood. Therefore, the current study aimed to characterize the impact of sex hormones and chromosomes on a contemporary panel of cardiometabolic risk biomarkers and functional cardiovascular measurements. 17 transmen and 17 transwomen were studied at baseline (T0), 4 weeks (hormonal castration, T1), and 11 months following gender-affirming hormone treatment (T12). We analyzed carotid intima-media thickness (cIMT) and arterial stiffness, lipoproteins and other metabolites comprehensively by nuclear magnetic resonance spectroscopy and HDL-mediated cholesterol efflux capacity (CEC) from macrophages. T0 to T12 comparisons informed the impact of sex hormones, comparisons of genetic XX and XY individuals at T1 the impact of sex chromosomes. Vascular function was comparable at T12 and T0; systolic blood pressure increased in transmen (p=0.002). Transmen developed a pro-atherogenic lipoprotein profile, estrogen treatment in transwomen tended to result in improvements. Several metabolites indicating increased diabetes risk including plasma glucose were changed in transmen (p=0.025), with opposite changes in transwomen (p=0.002). Interestingly, at T1 apparent diabetes risk was lower in XX compared with XY individuals (p=0.002). CEC decreased in transwomen (p<0.01), while remaining unchanged in transmen. However, in both groups the strong positive association of apoA-I with cholesterol efflux observed at T0 was lost at T12. The results are consistent with increased cardiometabolic risk in transmen, while transwomen show beneficial changes early during gender-affirming hormone therapy. Sex chromosomes have less intrinsic effects. XY individuals and transmen display an increased apparent diabetes risk. Further research of cardiometabolic risk is needed for transgender individuals.

Specific depressive symptoms, body mass index and diabetes in middle-aged and older Chinese adults: Analysis of data from the China Health and Retirement Longitudinal Study (CHARLS)

BackgroundThis study examined the association between specific depressive symptoms and incident diabetes, and whether overweight or obesity mediates this relationship among middle-aged and older adults in China. MethodsIn a nationally representative prospective cohort study of 11,893 middle-aged and older Chinese adults without baseline diabetes, we used Cox models to assess the association between depressive symptoms and diabetes. The quantile g-computation (qgcomp) model evaluated the contribution of 10 specific depressive symptoms to diabetes risk, and a two-stage regression method explored the mediation effect of overweight or obesity. ResultsOver a median follow-up of 7.1 years, 1,314 cases of diabetes were identified. Elevated depressive symptoms were associated with increased diabetes risk (HR 1.23; 95 % CI 1.09–1.38). Eight out of 10 depressive symptoms were significantly associated to diabetes, with loneliness (weight = 18 %; HR 1.23; 95 % CI 1.10–1.39), restless sleep (weight = 17 %; HR 1.16; 95 % CI 1.04–1.29), and bother (weight = 15 %; HR 1.19; 95 % CI 1.07–1.33) being the primary contributors. Mediation analysis showed that overweight and obesity reduced the depression-diabetes risk association by 8.21 % and 12.61 %, respectively. LimitationsDiagnosis of diabetes was self-reported. ConclusionsEight out of ten specific depressive symptoms were associated to diabetes, overweight and obesity may partially mitigate the effect of depressive symptoms on diabetes among middle-aged and older adults in China. Clinical implicationsOur results highlight the importance of tailoring diabetes prevention and management strategies according to specific depressive symptoms among middle-aged and older adults in China.

Relationships among Dioxin-like Mitochondria Inhibitor Substances (MIS)-Mediated Mitochondria Dysfunction, Obesity, and Lung Function in a Korean Cohort.

Mitochondrial dysfunction is closely linked to obesity and diabetes, with declining lung function in aging increasing diabetes risk, potentially due to elevated serum levels of dioxin-like mitochondria inhibitor substances (MIS) from prolonged exposure to environmental pollutants. However, the mechanisms connecting MIS, mitochondria, lung function, and metabolic disorder remain unclear. In this study, we analyzed data from 1371 adults aged 40-69 years in the 2008 Korean Genome Epidemiologic Study (KoGES) Ansung cohort. We indirectly estimated dioxin-like MIS levels by measuring intracellular ATP (MISATP) and reactive oxygen species (MISROS) in cultured cells treated with the serum of participants. Using correlation analysis and structural equation modeling (SEM), we explored the relationships among MIS, mitochondrial function, body mass index (BMI), and lung function (FEV1 and FVC). Our findings revealed that MISATP was associated with BMI in females and with FVC in males, while MISROS correlated with both BMI and FVC in males, not in females. Significant associations between BMI and FVC were found in the highest MIS subgroup in both sexes. SEM analyses demonstrated that MIS negatively influenced mitochondrial function, which in turn affected BMI and lung function. Age-related declines in lung function were also linked to mitochondrial dysfunction. This study underscores the potential of MIS assays as alternatives for assessing mitochondrial function and highlights the importance of mitochondrial health in metabolic disorders and lung function.

Clustering-based risk stratification of prediabetes populations: Insights from the Taiwan and UK Biobanks.

This study aimed to identify low- and high-risk diabetes groups within prediabetes populations using data from the Taiwan Biobank (TWB) and UK Biobank (UKB) through a clustering-based Unsupervised Learning (UL) approach, to inform targeted type 2 diabetes (T2D) interventions. Data from TWB and UKB, comprising clinical and genetic information, were analyzed. Prediabetes was defined by glucose thresholds, and incident T2D was identified through follow-up data. K-means clustering was performed on prediabetes participants using significant features determined through logistic regression and LASSO. Cluster stability was assessed using mean Jaccard similarity, silhouette score, and the elbow method. We identified two stable clusters representing high- and low-risk diabetes groups in both biobanks. The high-risk clusters showed higher diabetes incidence, with 15.7% in TWB and 13.0% in UKB, compared to 7.3% and 9.1% in the low-risk clusters, respectively. Notably, males were predominant in the high-risk groups, constituting 76.6% in TWB and 52.7% in UKB. In TWB, the high-risk group also exhibited significantly higher BMI, fasting glucose, and triglycerides, while UKB showed marginal significance in BMI and other metabolic indicators. Current smoking was significantly associated with increased diabetes risk in the TWB high-risk group (P < 0.001). Kaplan-Meier curves indicated significant differences in diabetes complication incidences between clusters. UL effectively identified risk-specific groups within prediabetes populations, with high-risk groups strongly associated male gender, higher BMI, smoking, and metabolic markers. Tailored preventive strategies, particularly for young males in Taiwan, are crucial to reducing T2D risk.

8723 Glucose Metabolism Disturbances in Non-Classic Adrenal Hyperplasia (NCAH)

Abstract Disclosure: B. Domagała: None. A. Gamrat: None. A. Skalniak: None. E. Przybylik-Mazurek(†): None. M. Trofimiuk-Muldner: None. A. Hubalewska-Dydejczyk: None. Introduction: There is data reporting an increased risk of cardiovascular and metabolic complications in patients with NCAH. This is frequently attributed to glucocorticoid (over)use or misdosing. It seems that long-term exposure to increased androgens concentrations may also itself lead to diminished insulin sensitivity and increased risk of prediabetes and diabetes. Aim: The study aimed to assess the link between NCAH diagnosis and glucose metabolism disturbances. Material and methods: The study included 327 subjects (315 females and twelve males, median age 25 years) referred for a cosyntropin stimulation test due to the suspected NCAH. Serum 17-OH-progesterone (17-OHP) was assessed with an ELISA assay. The diagnosis of NCAH was confirmed if the initial or stimulated 17-OHP concentration exceeded 10.0 ng/mL. None of the tested subjects was treated with glucocorticoids. A history of preexisting prediabetes or diabetes was recorded. Anthropometric measurements were obtained to calculate body mass index (BMI). Fasting glucose was measured in each subject. Mann-Whitney U and Yates’ χ2 tests were used in statistical analyses, with p&amp;lt;0.05 as the cut-off value of statistical significance. Results: 62 patients (60 females, two males; median age 26 years) were diagnosed with NCAH; the rest of the tested subjects were considered the control group. Preexisting type 2 diabetes was recorded in ten subjects in the entire study group (6 of them were diagnosed with NCAH). There was no significant difference in the fasting glucose levels (p=0.08) and BMI (p=0.32) between subjects with and without NCAH diagnosis (median fasting glucose: 4.96 mmol/L and 4.86 mmol/L, respectively; median BMI: 23.82 kg/m2 and 23.26 kg/m2, respectively). Diabetes was significantly more frequent in patients with NCAH diagnosis (p = 0.004; power: 0.74). The median 17-OHP was higher in patients with diabetes compared to those without it at both 30 (12.25 ng/mL vs 3.25 ng/mL; p=0.003) and 60 minutes (14.93 ng/mL vs 3.95 ng/mL; p=0.046) after stimulation. Conclusions: NCAH seems to be linked to increased diabetes risk, even in glucocorticoid-naïve patients. It seems advisable to screen NCAH patients for glucose metabolism disorders. Presentation: 6/1/2024

Diabetes and Dietary Proteins-Protein Supplement Intake

Diabetes is a growing global health issue, with diet playing a crucial role in prevention and management. Protein, an essential nutrient for growth, repair, and metabolism, can significantly influence diabetes risk and control. High-protein diets, especially those rich in animal proteins, have been linked to increased risk of type 2 diabetes, while plant-based proteins may offer protective benefits. Studies suggest that excessive animal protein intake, particularly from red and processed meats, can increase diabetes risk due to higher saturated fat content. Conversely, plant-based proteins, such as soy, tofu, and nuts, are associated with improved insulin sensitivity and reduced inflammation. Protein supplements—especially whey and soy proteins—are known to help maintain muscle mass and improve metabolic indicators. However, the evidence supporting these benefits remains limited, and excessive protein intake may increase risks of other negative effects, such as impaired kidney function. Therefore, caution is advised when using these supplements. A balanced approach that emphasizes plant-based proteins while moderating animal protein intake is recommended for diabetes prevention and management. Future research should focus on personalized dietary strategies for optimal health outcomes.

Deficiency of the hemoglobin-haptoglobin receptor, CD163, worsens insulin sensitivity in obese male mice.

Excessive iron accumulation in metabolic organs such as the adipose tissue, liver, and skeletal muscle is associated with increased diabetes risk. Tissue-resident macrophages serve multiple roles including managing inflammatory tone and regulating parachymal iron homeostasis; thus protecting against metabolic dysfunction upon iron overload. The scavenger receptor CD163 is uniquely present on tissue-resident macrophages, and plays a significant role in iron homeostasis by clearing extracellular hemoglobin-haptoglobin complexes, thereby limiting oxidative damage caused by free hemoglobin in metabolic tissues. We show that the absence of CD163 exacerbates glucose intolerance and insulin resistance in male mice with obesity. Additionally, loss of CD163 reduced the expression of iron regulatory genes (Tfr1, Cisd1, Slc40a1) in adipose tissue macrophages and anti-inflammatory (M2-like) bone marrow-derived macrophages (BMDMs). Further, CD163 deficiency mediated a pro-inflammatory shift and limited hemoglobin scavenging specifically in M2-like BMDMs. To this end, iron buffering was diminished in inguinal white adipose tissue (iWAT) macrophages in vivo, which culminated in iron spillover into adipocytes and CD45+CD11B- non-myeloid immune cells in iWAT. These findings show that CD163 on tissue-resident macrophages is critical for their anti-inflammatory and hemoglobin scavenging roles, and its absence results in impaired systemic insulin action in an obese setting.

The Association Between Vitamin D Deficiency and Diabetes in Adult African Americans and Whites: An NHANES Study

Abstract Objective The primary objective of this cross-sectional study is to investigate the association between vitamin D deficiency (VDD) and diabetes and see if this association is the same for adult (age ≥ 20) African Americans (AAs) and Whites. The secondary objective is to examine the distribution of the 25-hydroxyvitamin D test among AAs and Whites and to evaluate the appropriateness of using the same cut-off point for both groups to diagnose VDD. Methods Our analysis is based on the 2011–2014 National Health and Nutrition Examination Surveys (NHANES). We used two common propensity score adjustment methods to analyze the data—propensity score matching (PSM) and the inverse probability of treatment weighting (IPTW). Results The prevalence of diabetes for AAs and Whites was 12.27% (95% CI, 10.47–14.07%) and 7.24% (95% CI, 6.35–8.13%), respectively. The prevalence of VDD for AAs and Whites was 65.29% (95% CI, 62.01–68.58%) and 19.49% (95% CI, 16.53–22.45%), respectively. Under PSM, the odds ratios for the diabetes-VDD association for AAs and Whites were 0.94 (95% CI, 0.70–1.27) and 2.16 (95% CI, 1.49–3.13), respectively. Under IPTW, the VDD-diabetes odds ratios for AAs and Whites were 0.83 (95% CI, 0.64–1.10) and 2.35 (95% CI, 1.67–3.30), respectively. Our results further demonstrate that the 25-hydroxyvitamin D measurements are significantly different for AAs and Whites across the general population, as well as the vitamin D–sufficient and vitamin D–deficient populations. Conclusion The prevalence of VDD and diabetes was higher for AAs compared to Whites. However, VDD was associated with increased diabetes risk for Whites but not for AAs. Though more research is needed to explain why this is the case, a reason for this may be that the 25-hydroxyvitamin D test or its associated cut-off point for defining VDD may not accurately reflect the vitamin D status among AAs.

Impact of Statin Therapy on Diabetes Incidence: Implications for Primary Prevention

Abstract Purpose of Review The present review aims to summarize current evidence, explore underlying mechanisms, and help guide clinicians regarding statin therapy and diabetes risk in primary prevention. Recent Findings The observational and genetic epidemiology, as well as evidence from randomized controlled trials and meta-analyses, illustrate a modest, dose-dependent increase in risk of diabetes from statin therapy. Summary Risk of new onset diabetes from statins appears to be greatest in those near the diagnostic threshold for diabetes or with diabetes risk factors prior to statin initiation. The risk of incident diabetes is vastly offset by the cardiovascular protection offered from statin therapy and should not deter guideline recommended statin initiation in primary prevention.

A longitudinal study on the impact of the TyG Index and TG/HDL-C ratio on the risk of type 2 diabetes in Chinese patients with prediabetes

ObjectiveTo elucidate the impact and predictive value of the Triglyceride Glucose Index (TyG) and the ratio of Triglycerides to High-Density Lipoprotein Cholesterol (TG/HDL-C) in identifying the risk of diabetes progression in Chinese individuals with prediabetes.MethodsThis longitudinal study enrolled 15,012 prediabetic adults from the Rich Healthcare Group between 2010 and 2016. Diabetes was defined as self-reported diabetes or a fasting glucose level ≥ 7.0 mmol/L. The Cox proportional hazards models was utilized to assess the relationship between the two indices and the risk of developing diabetes. The predictive efficacy of the two markers was gauged by the area under the curve (AUC).ResultsOver a median follow-up period of 2.87 years, 1,730 (11.5%) prediabetic participants developed diabetes. The adjusted hazard ratios for the top quartile of the TyG index and the TG/HDL-C ratio were 2.03 (95% confidence interval [CI]: 1.71–2.40) and 2.59 (95% CI: 2.20–3.05), respectively, compared to the lowest quartile. A significant trend of increasing diabetes risk with higher quartiles of both indices was observed. The AUC for the adjusted prediction model for prediabetes-to-diabetes transition was 0.726 for the TyG index and 0.710 for the TG/HDL-C ratio. The difference in AUCs was statistically significant (P = 0.03).ConclusionsThe baseline TyG index or TG/HDL-C ratio was significantly associated with an increased risk of diabetes in prediabetic individuals. The TyG index demonstrated superior predictive accuracy, underscoring its importance in preventing diabetes in prediabetic individuals.

High-Fat Feeding Alters Circulating Triglyceride Composition: Roles of FFA Desaturation and ω-3 Fatty Acid Availability.

Hypertriglyceridemia is a risk factor for type 2 diabetes and cardiovascular disease (CVD). Plasma triglycerides (TGs) are a key factor for assessing the risk of diabetes or CVD. However, previous lipidomics studies have demonstrated that not all TG molecules behave the same way. Individual TGs with different fatty acid compositions are regulated differentially under various conditions. In addition, distinct groups of TGs were identified to be associated with increased diabetes risk (TGs with lower carbon number [C#] and double-bond number [DB#]), or with decreased risk (TGs with higher C# and DB#). In this study, we examined the effects of high-fat feeding in rats on plasma lipid profiles with special attention to TG profiles. Wistar rats were maintained on either a low-fat (control) or high-fat diet (HFD) for 2 weeks. Plasma samples were obtained before and 2.5 h after a meal (n = 10 each) and subjected to lipidomics analyses. High-fat feeding significantly impacted circulating lipid profiles, with the most significant effects observed on TG profile. The effects of an HFD on individual TG species depended on DB# in their fatty acid chains; an HFD increased TGs with low DB#, associated with increased diabetes risk, but decreased TGs with high DB#, associated with decreased risk. These changes in TGs with an HFD were associated with decreased indices of hepatic stearoyl-CoA desaturase (SCD) activity, assessed from hepatic fatty acid profiles. Decreased SCD activity would reduce the conversion of saturated to monounsaturated fatty acids, contributing to the increases in saturated TGs or TGs with low DB#. In addition, an HFD selectively depleted ω-3 polyunsaturated fatty acids (PUFAs), contributing to the decreases in TGs with high DB#. Thus, an HFD had profound impacts on circulating TG profiles. Some of these changes were at least partly explained by decreased hepatic SCD activity and depleted ω-3 PUFA.

Machine Learning Analysis of Health and Lifestyle Factors in Understanding Diabetes

Diabetes poses a significant global health challenge, with approximately 537 million adults living with the condition in 2021, a number expected to rise to 783 million by 2045. To enhance predictive accuracy and gain deeper insights into the factors contributing to diabetes, this study employed machine learning algorithms to predict diabetes risk factors using a dataset encompassing health and lifestyle variables. Six supervised machine learning algorithms, including Gradient Boosting, Logistic Regression, and Random Forest, among others, were assessed for their effectiveness in classifying diabetes status into two categories: diabetes and no diabetes. The study found that Gradient Boosting achieved the highest overall accuracy at 85%, demonstrating the best recall for diabetic cases at 57%. Meanwhile, Logistic Regression excelled in precision for non-diabetic cases at 94%. Key risk factors identified include general health status, blood pressure, body mass index, cholesterol levels, and age. Notably, the study uncovered that higher income and education levels were associated with increased diabetes risk, contradicting some existing literature and indicating the potential impact of lifestyle factors.

Preventing diabetes: What overweight and obese adults with prediabetes in the United States report about their providers’ communication and attempted weight loss

ObjectiveTo investigate what overweight or obese adults with prediabetes in the United States report being told by providers about 1)havingprediabetes, 2) diabetes risk, and3) losingweight and the associations of these communications with attempted weight loss. MethodsData from 2015 to 2018 National Health and Nutrition Examination Surveys (NHANES) for adults with a body mass index in the overweight or obesity ranges and HbA1c in the prediabetes range were examined (n = 2085). Patient reported data on what providers told them about having prediabetes, being at risk for diabetes, and losing weight were compared with attempted weight loss. ResultsMost participants (66.4%) reported never being told they had prediabetes nor being at risk for diabetes, 13.0% reported being told they had prediabetes, 10.6% at risk for diabetes, and 8.0% both messages. 18.3% of participants reported being told to lose weight. Participants who reported being told they had prediabetes and at increased diabetes risk were more likely to report attempted weight loss (adjusted odds ratio (AOR) 1.8, 95% confidence interval (CI) 1.1–3.2). Reporting that they were told to lose weight was not significantly associated with an increase in reported weight loss attempts. ConclusionsIn this cohort of individuals with overweight/obesity and prediabetic HbA1c values, low rates communications with providers about prediabetes and diabetes risk were reported. When both were discussed, patients reported greater attempted weight loss. These findings draw attention to the potential impact that provider communications about prediabetes and diabetes risk may have on lifestyle behavior change.

The lasting effects of famine.

Early exposure to food scarcity in Ukraine increases diabetes risk in later life.

Associations of muscle mass, strength, and quality with diabetes and the mediating role of inflammation in two National surveys from China and the United states

AimsThe evidence for joint and independent associations of low muscle mass and low muscle strength with diabetes is limited and mixed. The study aimed to determine the associations of muscle parameters (muscle mass, strength, quality, and sarcopenia) and sarcopenia obesity with diabetes, and the previously unstudied mediating effect of inflammation. Materials and MethodsA total of 13,420 adults from the 2023 China National Health Survey (CNHS) and 5,380 adults from the 2011–2014 National Health and Nutrition Examination Survey (NHANES) were included in this study. Muscle mass was determined using bioelectrical impedance analysis (BIA) in the CNHS, and whole-body dual X-ray absorptiometry (DXA) in the NHANES. Muscle strength was assessed using digital hand dynamometer. Multivariate logistic regression models were used to evaluate the associations of muscle parameters and sarcopenia obesity with diabetes. Inflammatory status was assessed using blood cell counts and two systemic inflammation indices (platelet-to-lymphocyte ratio (PLR) and system inflammation response index (SIRI)). Mediation analysis was conducted to examine inflammation’s role in these associations. ResultsLow muscle mass and strength were independently related to diabetes. Low muscle quality was associated with elevated diabetes risk. Sarcopenia has a stronger association with diabetes compared to low muscle strength alone or mass alone (CNHS, odds ratio (OR) = 1.93, 95 % confidence interval (CI):1.64–2.27; NHANES, OR = 3.80, 95 %CI:2.58–5.58). Participants with sarcopenia obesity exhibit a higher risk of diabetes than those with obesity or sarcopenia alone (CNHS, OR = 2.21, 95 %CI:1.72–2.84; NHANES, OR = 6.06, 95 %CI:3.64–10.08). Associations between muscle parameters and diabetes were partially mediated by inflammation (mediation proportion: 1.99 %-36.64 %, P < 0.05). ConclusionLow muscle mass and muscle strength are independently or jointly associated with diabetes, and inflammation might be a potential mechanism underlying this association. Furthermore, the synergistic effects of sarcopenia and obesity could significantly increase diabetes risk.

Efficacy and Safety of Bempedoic Acid in Patients with High Cardiovascular Risk: An Update.

Statins play a significant role in the prevention of cardiovascular (CV) diseases (CVDs); however, non-adherence with statin treatment or statin intolerance (mainly attributed to muscleassociated side effects) is not uncommon. New agents such as bempedoic acid (BA) can provide more treatment options. BA is administered orally, once daily, at a dose of 180 mg in current clinical practice. It can decrease circulating low-density lipoprotein cholesterol (LDL-C) levels by nearly 30% as monotherapy or by 20% as an add-on to statins. CV outcome studies have shown that BA decreases major adverse CV event risk in patients with established CVD or high CV risk by 13%. When patients with high CV risk were analyzed alone, the risk reduction was 30%. Its side effects include a rise in serum uric acid levels and liver enzyme activity, whereas it does not increase diabetes risk as statins do. BA can be used as adjunctive therapy to statins in patients at high CV risk in whom lipid targets cannot be achieved or as an alternative to statins in patients with statin intolerance.

Assessing the causal association of pregnancy complications with diabetes and cardiovascular disease.

To the best of our knowledge, numerous observational studies have linked pregnancy complications to increased risks of diabetes and cardiovascular disease (CVD), causal evidence remains lacking. Our aim was to estimate the association of adverse pregnancy outcomes with diabetes and cardiovascular diseases. A two-sample Mendelian randomization (MR) analysis was employed, which is not subject to potential reverse causality. Data for pregnancy complications were obtained from the FinnGen consortium. For primary analysis, outcome data on diabetes, related traits, stroke, and coronary heart disease (CHD) were extracted from the GWAS Catalog, MAGIC, MEGASTROKE, and CARDIoGRAMplusC4D consortium. The MAGIC and UKB consortium datasets were used for replication and meta-analysis. Causal effects were appraised using inverse variance weighted (IVW), weighted median (WM), and MR-Egger. Sensitivity analyses were implemented with Cochran's Q test, MR-Egger intercept test, MR-PRESSO, leave-one-out (LOO) analysis and the funnel plot. Genetically predicted gestational diabetes mellitus (GDM) was causally associated with an increased diabetes risk (OR=1.01, 95% CI=1-1.01, P<0.0001), yet correlated with lower 2-hour post-challenge glucose levels (OR=0.89, 95% CI=0.82-0.97, P=0.006). Genetic liability for pregnancy with abortive outcomes indicated decreased fasting insulin levels (OR=0.97, 95% CI=0.95-0.99, P=0.02), but potentially elevated glycated hemoglobin levels (OR=1.02, 95% CI=1.01-1.04, P=0.01). Additionally, hypertensive disorders in pregnancy was tentatively linked to increased risks of stroke (OR=1.11, 95% CI=1.04-1.18, P=0.002) and CHD (OR=1.3, 95% CI=1.2-1.4, P=3.11E-11). Gestational hypertension might have a potential causal association with CHD (OR=1.11, 95% CI=1.01-1.22, P=0.04). No causal associations were observed between preterm birth and diabetes, stroke, or CHD. The findings of this study provide genetic evidence that gestational diabetes, pregnancy with abortive outcomes, and hypertensive disorders in pregnancy may serve as early indicators for metabolic and cardiovascular risks. These insights are pivotal for the development of targeted screening and preventive strategies.

Deficiency of the hemoglobin-haptoglobin receptor, CD163, worsens insulin sensitivity in obese male mice.

Excessive iron accumulation in metabolic organs such as the adipose tissue, liver, and skeletal muscle is associated with increased diabetes risk. Tissue-resident macrophages serve multiple roles including managing inflammatory tone and regulating parachymal iron homeostasis; thus protecting against metabolic dysfunction upon iron overload. The scavenger receptor CD163 is uniquely present on tissue-resident macrophages, and plays a significant role in iron homeostasis by clearing extracellular hemoglobin-haptoglobin complexes, thereby limiting oxidative damage caused by free hemoglobin in metabolic tissues. We show that the absence of CD163 exacerbates glucose intolerance and insulin resistance in male mice with obesity. Additionally, loss of CD163 reduced the expression of iron regulatory genes (Tfr1, Cisd1, Slc40a1) in adipose tissue macrophages and anti-inflammatory (M2-like) bone marrow-derived macrophages (BMDMs). Further, CD163 deficiency mediated a pro-inflammatory shift and limited hemoglobin scavenging specifically in M2-like BMDMs. To this end, iron buffering was diminished in inguinal white adipose tissue (iWAT) macrophages in vivo, which culminated in iron spillover into adipocytes and CD45+CD11B- non-myeloid immune cells in iWAT. These findings show that CD163 on tissue-resident macrophages is critical for their anti-inflammatory and hemoglobin scavenging roles, and its absence results in impaired systemic insulin action in an obese setting.