ABSTRACT Introduction Maternal pre‐pregnancy overweight/obesity and gestational hyperglycemia are linked to adverse offspring neurodevelopment, but the role of oral glucose tolerance test (OGTT) response patterns remains unclear. We investigated the independent and combined effects of maternal pre‐pregnancy BMI and OGTT response patterns on neurodevelopment in 2‐year‐old offspring. Methods This cohort study included 2639 mother–child pairs from Wuhan, China. A 75‐g OGTT was performed at 24–28 gestational weeks, with glucose measured at fasting, 1 and 2 h. Group‐based trajectory modeling identified distinct OGTT response patterns. Offspring neurodevelopment was assessed at 2 years using the Bayley Scales of Infant Development. Associations were examined with generalized linear and logistic regression models, and additive interaction was evaluated using RERI and AP. Results Three OGTT response patterns were identified; pattern 3 showed the most pronounced glycemic response. Maternal pre‐pregnancy overweight/obesity alone showed nominal associations with lower MDI scores in the overall population and in girls, but these associations did not remain significant after FDR correction. In girls exposed to both maternal overweight/obesity and pattern 3, MDI was markedly lower (β = −13.73, 95% CI: −23.06 to −4.39), and the risk of suboptimal mental development was higher (OR = 2.88, 95% CI: 1.03 to 8.09), with significant additive interaction (RERI = 0.76; AP = 0.42). Conclusions Maternal pre‐pregnancy overweight/obesity and OGTT response patterns alone showed limited independent associations with offspring neurodevelopment. However, combined exposure may be associated with poorer mental developmental performance, with more consistent evidence in girls.
ABSTRACT Background Diabetic nephropathy (DN) is a leading cause of end‐stage renal disease. ELAVL1, an RNA‐binding protein, is involved in the regulation of genes closely associated with DN pathogenesis, whereas suPAR acts as a circulating mediator that promotes podocyte damage and contributes to proteinuric kidney disorders. However, whether ELAVL1 regulates suPAR release in DN remains unexplored. Methods Clinical samples from patients with DN were collected and analyzed. In vitro, podocytes were treated with high glucose, and ELAVL1 or PLAUR (encoding uPAR) was knocked down or overexpressed using lentiviral transduction. In db/db mice, podocyte‐specific manipulation of Elavl1 or Plaur was performed via adeno‐associated virus‐mediated delivery. Renal function was assessed by measuring the urinary albumin‐to‐creatinine ratio (UACR) and serum creatinine. Glomerular pathology and inflammatory markers were evaluated histologically and biochemically. Results ELAVL1 was upregulated in DN and positively correlated with podocyte injury. Knockdown of ELAVL1 mitigated hyperglycemia‐induced podocyte damage and inflammatory responses. Mechanistically, ELAVL1 directly bound to and stabilized PLAUR mRNA, leading to increased uPAR protein expression and elevated suPAR secretion. The protective effects of ELAVL1 knockdown were reversed by PLAUR overexpression in podocytes. In diabetic mice, podocyte‐specific knockdown of Elavl1 or Plaur markedly lowered circulating suPAR levels and alleviated renal dysfunction and histopathological injury. Moreover, restoration of the PLAUR‐suPAR axis abolished the renoprotective benefits conferred by Elavl1 knockdown. Conclusion Hyperglycemia‐induced ELAVL1 upregulates PLAUR and suPAR release from podocytes, promoting renal inflammation and injury. Targeting the ELAVL1‐PLAUR‐suPAR axis may offer a therapeutic strategy for DN.
ABSTRACT Background To analyze the interplay between family history of type 2 diabetes (T2D) and cardiovascular health (CVH) in relation to T2D onset age and subsequent cardiovascular disease (CVD) risk. Methods A total of 79 831 participants were included to investigate the association between family history and T2D onset age. Then, 7387 diagnosed T2D patients were 1:1 matched with non‐T2D individuals to analyze the association of T2D onset age with subsequent CVD risk. The benefit of good CVH was further assessed. Stratified Cox regression and conditional Cox regression were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Family history was associated with younger T2D onset, with an approximately 2.4‐year earlier onset of T2D, which further increased the subsequent risk of CVD. Compared with individuals without family history, those with family history had HRs (95% CIs) of 3.911 (3.041, 5.032), 3.785 (3.385, 4.233), 3.627 (3.340, 3.938), 3.465 (3.189, 3.764), and 3.169 (2.787, 3.603) for T2D onset at < 40, 40–50, 50–60, 60–70, and ≥ 70 years old, respectively (Pinteraction = 0.007). Among individuals with family history, HR (95% CI) for incident CVD was 3.598 (1.372, 9.433) for those diagnosed T2D < 50 years compared with those without T2D, while the HR (95% CI) was 2.336 (1.232, 4.428) among those without family history. However, high CVH could mitigate risk of young‐onset T2D, and could further decrease CVD risk after their T2D diagnosis. Conclusions Having family history of T2D increased susceptibility to young‐onset T2D and subsequent CVD risks, while ideal CVH could counteract these risks, highlighting the necessity of early screening and intervention.
ABSTRACT Background The combined prognostic value of continuous glucose monitoring (CGM) metrics and circulating glucose biomarkers for predicting mortality in type 2 diabetes has not been fully established, particularly regarding residual risk in patients achieving glycemic targets. Methods This cohort study included 3677 patients with type 2 diabetes for a median of 7.4 years follow‐up. Cox proportional hazards models evaluated the associations of baseline CGM‐derived time in range (TIR) (target 70%) and serum 1,5‐anhydroglucitol (1,5‐AG) (threshold 6.0 μg/mL) with all‐cause and cardiovascular mortality in the overall population. We further examined the relationship between 1,5‐AG and mortality within TIR subgroups and compared its performance with metrics of glycemic variability derived from CGM. Results During follow‐up, 522 all‐cause deaths and 181 cardiovascular deaths occurred. TIR and 1,5‐AG were moderately correlated and independently predicted mortality, with concurrent low TIR (≤ 70%) and low 1,5‐AG (< 6.0 μg/mL) yielding the highest risk (hazard ratio [HR] 1.82, 95% CI 1.40–2.37). In stratified analyses, reduced 1,5‐AG was significantly associated with increased mortality risk in patients with TIR > 70% (HR 1.69, 95% CI 1.25–2.28), whereas no significant association was observed in those with TIR ≤ 70%. Adding 1,5‐AG improved traditional risk prediction in the former subgroup. Compared with 1,5‐AG, CGM‐derived glycemic variability indices such as mean amplitude of glycemic excursions, coefficient of variation, and standard deviation of glucose showed no significant association with mortality. Conclusions TIR and serum 1,5‐AG offer independent and complementary value, with low 1,5‐AG identifying residual mortality risk despite achieving TIR targets.
Comparison of percentage total body weight loss (%TWL) between metabolic bariatric surgery and incretin-based pharmacotherapy in adults with type 2 diabetes mellitus. Forest plot showing pooled mean difference in percentage total body weight loss (%TWL) between treatment groups. Positive values favor metabolic bariatric surgery. Random-effects model with Hartung-Knapp adjustment was used.
ABSTRACT Background The prognostic value of the hemoglobin glycation index (HGI) in patients with acute myocardial infarction (AMI) without reduced left ventricular ejection fraction (LVEF) remains unclear. Methods This multicenter retrospective cohort study included 1706 patients with AMI without reduced LVEF. HGI was calculated as measured HbA1c minus predicted HbA1c. Restricted cubic spline (RCS) analysis was used to evaluate nonlinear associations between HGI and outcomes and identify the cutoff value. Piecewise Cox regression and subgroup analyses were also performed. The primary endpoint was major adverse cardiovascular events (MACEs), defined as a composite of rehospitalization for heart failure (HF), recurrent myocardial infarction (MI), and cardiovascular death. Results The median follow‐up was 3.86 (2.30–4.98) years. RCS analysis showed a non‐linear association between HGI and adverse outcomes, with a cutoff at −0.174. In patients with HGI ≤ −0.174, higher HGI was associated with lower risks of rehospitalization for HF (HR = 0.600, 95% CI: 0.464–0.776), recurrent MI (HR = 0.599, 95% CI: 0.365–0.983), cardiovascular death (HR = 0.627, 95% CI: 0.458–0.859), all‐cause death (HR = 0.552, 95% CI: 0.428–0.713), and MACEs (HR = 0.603, 95% CI: 0.483–0.753) after multivariable adjustment. In contrast, no significant associations were observed in patients with HGI > −0.174 after adjustment. Within the lower‐HGI subgroup, severely low HGI was associated with a higher risk of rehospitalization for HF and MACEs compared with mildly low HGI. Subgroup analyses were generally consistent with the main results. Conclusions In AMI patients without reduced LVEF, HGI showed a non‐linear association with adverse outcomes, mainly in the lower‐HGI range. These exploratory findings require prospective validation before clinical application. Trial Registration: ClinicalTrials.gov Identifier: NCT04485988 and NCT04564365
This 14-day multicenter study assessed CT3 CGM accuracy and safety in 71 adults with diabetes. Key results: overall MARD 9.1% (median 7.1%), 82.4%-98.2% met %15/15-%30/30 criteria, 99.7% values in CEG zones A/B. CT3 showed strong performance, suitable for reliable 14-day wear.
ABSTRACT Background The precise link between diabetic retinopathy and incident heart failure remains unclear, largely limited by a lack of echocardiographic data. This study evaluated how the clinical severity of retinopathy relates to incident heart failure and baseline cardiac function in individuals with type 2 diabetes. Methods This retrospective cohort study (2005–2021) included adults with type 2 diabetes receiving structured management and color fundus imaging. Retinopathy was classified as absent, mild nonproliferative, or moderate‐to‐severe nonproliferative to proliferative. A specific subcohort received baseline transthoracic echocardiography. Relationships between cardiac function parameters and retinal damage were assessed using ordinal logistic regression with inverse probability weighting. Incident heart failure risk was determined utilizing Cox proportional hazards and Poisson regression models. Results Among 21 773 participants, heart failure was independently associated with advanced retinopathy (OR, 1.23). After inverse probability weighting (IPW), associations with systolic dysfunction (unweighted OR, 1.96; IPW‐adjusted OR, 2.01) and diastolic dysfunction were significant, with the latter explicitly unmasked by IPW (unweighted OR, 1.08 vs. IPW‐adjusted OR, 1.17). The risk for incident heart failure escalated alongside progressive retinal damage. Compared to patients presenting without retinopathy, the adjusted incidence rate ratios were 1.64 for the mild group and 1.86 for those with moderate‐to‐severe or proliferative disease, an association partially mediated by renal function decline. Conclusions Diabetic retinopathy severity associates with systolic and diastolic dysfunction and is an independent risk factor for incident heart failure in type 2 diabetes. Routine retinal evaluation serves as a practical clinical indicator for assessing systemic microvascular damage and cardiovascular risk.
ABSTRACT Clonal hematopoiesis (CH) refers to an expanded clonal hematopoietic cell population due to acquired mutations conferring a selective growth advantage. Once considered a premalignant hematological state, CH has now been causally associated with cardiovascular diseases (CVDs) and several aging‐related clinical conditions. Emerging evidence suggests that CH is at the intersection of aging and metabolic disorders. CH carriers exhibit a higher risk of Type 2 diabetes, potentially through the obesity–inflammation–insulin resistance axis. Moreover, CH confers a higher risk of CVD and is associated with a poorer prognosis in patients with diabetes compared to noncarriers. In addition, CH has been associated with the development of microvascular complications, including retinopathy and kidney disease in patients with diabetes, although inconsistent findings exist. Preclinical studies found that antidiabetic medication metformin might slow down clonal expansion of CH, while clinical data suggest that anti‐inflammatory medications confer better clinical outcomes for certain CH carriers, although their relevance for patients with diabetes remains to be elucidated. In this narrative review, we also briefly discuss the barriers to clinical adoption of CH detection and highlight the knowledge gaps that should be addressed in future work.
ABSTRACT Background Multimorbidity in type 1 diabetes has previously not been studied in detail. Therefore, we aimed to assess the prevalence of multimorbidity and its association with mortality in type 1 diabetes. Methods This observational follow‐up study includes 4069 individuals with type 1 diabetes from the Finnish Diabetic Nephropathy study. The prevalence of multimorbidity (coexistence of two or more chronic conditions) was based on 32 conditions at baseline. Conditions were grouped into three subcategories: vascular comorbidities, autoimmune disorders, and other conditions. Hazard ratios (HR) for all‐cause mortality were calculated. Results The prevalence of multimorbidity was 60.4% and increased with age and especially diabetes duration. Multimorbidity was associated with increased risk of mortality, HR 6.0 (95% CI 4.6–7.8), p < 0.001. The HR for mortality increased by each additional condition and was 37.9 (95% CI 25.7–56.0) in those with ≥eight conditions. Vascular comorbidities and other conditions were associated with increased mortality, HRs 5.9 (4.4–7.9) and 3.8 (2.4–5.9), p < 0.001, separately, and in combination, HR 11.2 (8.3–15.2), p < 0.001. Autoimmune disorders did not influence mortality. Conclusions Multimorbidity in type 1 diabetes is common and is associated with increased mortality. Comprehensive evaluation of all additional conditions is needed to tailor treatment individually.
ABSTRACT Background To investigate whether diabetic foot (DF) is associated with a higher prevalence and severity of coronary artery calcification (CAC) in patients with type 2 diabetes (T2DM) using low‐dose computed tomography (LDCT). Methods This cross‐sectional study included 710 patients with DF and 1176 patients with T2DM but without DF who had undergone LDCT recruited in the Diabetic Foot Care Center of West China Hospital, Sichuan University. The severity of CAC was evaluated using a length‐based grading method. The independent association between DF and CAC was evaluated using multivariable logistic regression and propensity score matching (PSM). Results The overall prevalence of CAC among individuals with DF was 71.9%, compared to 46.1% in those without DF. DF was independently associated with CAC; an association remained statistically significant after PSM (adjusted OR 1.72; 95% CI [1.28–2.32]; p < 0.001). This association was particularly strong in patients with preserved renal function, irrespective of the presence of peripheral artery disease (PAD). In contrast, among individuals with impaired renal function, no significant differences were observed in the prevalence of mild, moderate, or severe CAC between those with DF and those without DF. However, the overall prevalence of CAC across all severity levels was higher in the renal‐impaired group than in those with preserved renal function. Conclusions DF is independently associated with the presence and severity of CAC in patients with T2DM, particularly among those with preserved renal function, irrespective of the presence of concomitant PAD. This association is not statistically significant in individuals with impaired renal function.
AIMS:The revised diagnostic criteria for gestational diabetes (GDM) in New Zealand include lowering the fasting glucose from the current ≥ 5.5 to ≥ 5.3 mmol/L and replacing the current 2-h post-load glucose (≥ 9.0 mmol/L) with a 1-h glucose (≥ 10.6 mmol/L). We assessed the effects of these changes on the demographics of those diagnosed and their perinatal outcomes. MATERIALS AND METHODS:Participants in the GEMS trial were grouped as meeting only the revised criteria (Additional group), only the current criteria (Missed group), both criteria (Both-Criteria group), and neither criteria (Non-GDM group). RESULTS:GDM prevalence among 3921 participants was 6.8% using the revised criteria and 5.8% using the current criteria (risk ratio 1.18, 95% CI 1.00-1.40). Women in the Additional (n = 125) and Missed groups (n = 83), who would be affected by the changes, were more likely to be overweight/obese, have a family history of diabetes, and have Asian ethnicity than women in the Non-GDM group (n = 3562). They also had less gestational weight gain and more induced labors, while their infants were born earlier, had lower birthweight, and more neonatal hypoglycemia (all p < 0.001). Women in the Missed group had lower BMI and fewer were of Pacific ethnicity than the Both-Criteria group (n = 151). They also had less pharmacotherapy use and postpartum hemorrhage. CONCLUSIONS:Using the revised criteria will increase GDM diagnoses by identifying a high-risk group of women likely to benefit from treatment, but 35.5% of women currently treated for GDM will no longer be diagnosed, potentially compromising their health.
BACKGROUND:Previous studies have reported that insulin resistance (IR), blood pressure, body mass index (BMI), and dyslipidemia are associated with arterial stiffness. However, limited evidence exists regarding these relationships in prediabetes patients. The purpose of this study was to investigate the longitudinal associations between cardiometabolic risk markers and progression of arterial stiffness. METHODS:This study included 5771 adults with prediabetes at baseline from the Shougang cohort study. Cardiometabolic risk markers included the triglyceride glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, mean arterial pressure (MAP), BMI, and dyslipidemia. Arterial stiffness was assessed using brachial-ankle pulse wave velocity (baPWV), and its progression was defined as the annual change in baPWV between baseline and the last visit. Multivariate linear and logistic regression models were used to investigate the associations. RESULTS:Multivariate linear regression analyses showed TyG index, TG/HDL-C ratio, MAP, and dyslipidemia were significantly associated with baseline baPWV. Over a mean follow-up of 3.24 years, each one-unit increase in the MAP was significantly associated with a faster progression of baPWV (difference, 0.72 cm/s per year; 95% CI, 0.40 to 1.04 cm/s per year). After adjusting for all covariates, the risk for arterial stiffness increased 3% with each one-unit increase of MAP. CONCLUSION:Among individuals with prediabetes, MAP showed consistent longitudinal associations with arterial stiffness, highlighting the importance of early blood pressure management for vascular protection prior to the onset of diabetes.
BACKGROUND:Diabetic neuropathy (DN) is the most common chronic complication of Type 2 diabetes mellitus (T2DM), with reported prevalence ranging from 23% to 54.5%. This study evaluated the prevalence, clinical characteristics, and treatments of DN using Korean National Health Insurance Service (NHIS) data from 2012 to 2017. METHODS:We analyzed NHIS sample data for 8.7 million individuals stratified by age, sex, eligibility, and income. DN was defined using ICD-10 codes (E10.4-E14.4, G59.0, G63.2, G99.0) and concurrent prescriptions for diabetes and DN. Annual DN prevalence among diabetes patients was calculated, and treatment patterns and patient characteristics were compared between those with and without DN. RESULTS:DN prevalence declined from 23.4% in 2012 to 21.5% in 2017. About half of DN patients received pharmacologic treatment-mainly monotherapy (up to 82%), followed by dual (15%) and triple therapy (3%). The most prescribed drugs were α-lipoic acid (52.1%-55.0%), anticonvulsants (30.4%-34.5%), tricyclic antidepressants, SNRIs, and γ-linolenic acid. DN patients were generally older, more often female, and had more comorbidities such as hypertension, dyslipidemia, cardiovascular disease, diabetic foot, and amputations. They were also more likely to use insulin or multiple oral agents. CONCLUSION:About one-quarter of patients with T2DM had DN, and half received treatment, mostly α-lipoic acid monotherapy. DN patients tended to be older and had multiple comorbidities, resulting in higher hospitalization rates.
