Associations of Habitual Calcium Supplementation With Risk of Cardiovascular Disease and Mortality in Individuals With and Without Diabetes

Journal of Hypertension

Objective:The evidence regarding the associations of circulating metabolic biomarkers with hypertension risk is scarce. We aimed to examine the associations between circulating metabolites and risk of hypertension.Methods:We included 49 422 individuals free of hypertension at baseline with a mean (SD) age of 53.5 (8.0) years from the UK Biobank. Nuclear magnetic resonance spectroscopy was used to quantify 143 individual metabolites. Multivariable-adjusted Cox regression models were used to estimate hazard ratios and 95% confidence intervals (CIs).Results:During a mean (SD) follow-up of 11.2 (1.8) years, 2686 incident hypertension cases occurred. Out of 143 metabolites, 76 were associated with incident hypertension, among which phenylalanine (hazard ratio: 1.40; 95% CI: 1.24–1.58) and apolipoprotein A1 (hazard ratio: 0.76; 95% CI: 0.66–0.87) had the strongest association when comparing the …

Food Chemistry

This study introduces a multidisciplinary approach to investigate bioactive food metabolites often overlooked due to their low concentrations. We integrated an in-house food metabolite library (n = 494), a human metabolite library (n = 891) from epidemiological studies, and metabolite pharmacological databases to screen for food metabolites with potential bioactivity. We identified six potential metabolites, including meglutol (3-hydroxy-3-methylglutarate), an understudied low-density lipoprotein (LDL)-lowering compound. We further focused on meglutol as a case study to showcase the range of characterizations achievable with this approach. Green pea tempe was identified to contain the highest meglutol concentration (21.8 ± 4.6 mg/100 g). Furthermore, we identified a significant cross-sectional association between plasma meglutol and lower LDL cholesterol in two Hispanic adult cohorts (n = 1,628) (β …

Journal of the American Geriatrics Society

Background Caregiving is commonly undertaken by older women. Research is mixed, however, about the impact of prolonged caregiving on their health, well‐being, and mortality risk. Using a prospective study design, we examined the association of caregiving with mortality in a cohort of older women. Methods Participants were 158,987 postmenopausal women aged 50–79 years at enrollment into the Women's Health Initiative (WHI) who provided information on current caregiving status and caregiving frequency at baseline (1993–1998) and follow‐up (2004–2005). Mortality was ascertained from baseline through March of 2019. Cox regression with caregiving status defined as a time‐varying exposure was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for mortality, adjusting for sociodemographic factors, smoking, and history of diabetes, hypertension, cardiovascular disease (CVD …

The Journal of Nutrition

BackgroundIt remains unclear if adherence to the planetary healthy diet (PHD), designed to improve human and environmental health, is associated with better cognitive function in aging, and if this association differs by apolipoprotein E (APOE) genotype.ObjectivesWe aimed to examine the association between the PHD pattern and risk of poor cognitive function, and to further assess whether the APOE ε4 allele could modify this association.MethodsThe study included 16,736 participants from the Singapore Chinese Health Study. The PHD score was calculated using data from a validated 165-item food frequency questionnaire at baseline (1993–1998), with higher scores indicating greater adherence to the PHD. Cognitive function was assessed by the Singapore-modified Mini-Mental State Examination at follow-up 3 visits (2014–2016). A subset of 9313 participants had APOE genotype data. Logistic regression …

American Journal of Kidney Diseases

Rationale & ObjectiveChronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD has been lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study.Study DesignObservational cohort study.Setting & ParticipantsA total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy.ExposureLevels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers were quantified via NMR spectroscopy.OutcomeIncident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records.Analytical ApproachCox proportional hazards regression …

Metabolism

BackgroundClinical trials and Mendelian randomization (MR) studies reported null effects of high-density lipoprotein cholesterol (HDLsingle bondC) on risk of cardiovascular disease (CVD), which might have overlooked a nonlinear causal association. We aimed to investigate the dose-response relationship between circulating HDL-C concentrations and CVD in observational and MR frameworks.MethodsWe included 348,636 participants (52,919 CVD cases and 295,717 non-cases) of European ancestry with genetic data from the UK Biobank (UKB) and acquired genome-wide association summary data for HDL-C of Europeans from the Global Lipids Genetics Consortium (GLGC). Observational analyses were conducted in the UKB. Stratified MR analyses were conducted combing genetic data for CVD from UKB and lipids from GLGC.ResultsObservational analyses showed L-shaped associations of HDL-C with …

Sleep Medicine

AimTo evaluate the prospective associations of nighttime sleep duration, midday napping, and sleep quality during early pregnancy with gestational diabetes mellitus (GDM) risk among Chinese pregnant women.MethodsSleep-related information was assessed by the Pittsburgh Sleep Quality Index in baseline surveys during the 6–15 (mean 10.3) gestational weeks. GDM was diagnosed during 24–28 gestational weeks according to the Chinese Guidelines on Diagnosis and Management of Hyperglycemia in Pregnancy (2022). Multivariable logistic regression models with adjustments for socio-demographic and lifestyle factors were used to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the associations of sleep traits with GDM risk.ResultsWe identified 503 incident GDM cases among 6993 participants. Compared with women who slept for 7–9 h/night in early pregnancy, those who slept <7 h …

The Journal of Clinical Endocrinology & Metabolism

Context It is largely unknown whether regional fat accumulation is associated with risk of cardiovascular disease (CVD) and mortality among individuals with type 2 diabetes (T2D), who often exhibit changes in relative fat distribution and have increased CVD risk. Objective To prospectively examine the association between regional body fat and risk of CVD in individuals with T2D and to determine whether the associations are independentof traditional measures of obesity. Methods The main analysis included 21 472 participants with T2D from the UK Biobank. Regional body fat was measured by bioelectric impedance assessment. Cox proportional-hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Results Over a median of 7.7 years of follow-up, 3976 CVD events occurred. After multivariable …

Metabolism

BackgroundClinical trials and Mendelian randomization (MR) studies reported null effects of high-density lipoprotein cholesterol (HDLsingle bondC) on risk of cardiovascular disease (CVD), which might have overlooked a nonlinear causal association. We aimed to investigate the dose-response relationship between circulating HDL-C concentrations and CVD in observational and MR frameworks.MethodsWe included 348,636 participants (52,919 CVD cases and 295,717 non-cases) of European ancestry with genetic data from the UK Biobank (UKB) and acquired genome-wide association summary data for HDL-C of Europeans from the Global Lipids Genetics Consortium (GLGC). Observational analyses were conducted in the UKB. Stratified MR analyses were conducted combing genetic data for CVD from UKB and lipids from GLGC.ResultsObservational analyses showed L-shaped associations of HDL-C with …

Molecular Nutrition & Food Research

Scope Among patients with diabetes, who have modified nutritional behavior and a higher risk of cardiovascular disease (CVD), the influence of ultraprocessed foods (UPFs) on CVD remains unknown. The study aims to evaluate the association between UPF intake and the risk of CVD among individuals with type 2 diabetes (T2D) and further examine the potential biological pathways linking the association. Methods and results This study includes 5405 participants with T2D who provided at least one 24‐h dietary recall from the UK Biobank study. In the fully adjusted models, a 10% increase in the proportion of UPFs is associated with higher hazards of overall CVD (hazard ratio [HR]: 1.10; 95% confidence interval [CI]: 1.04, 1.15), coronary heart disease (HR: 1.10; 95% CI: 1.04, 1.16), heart failure (HR: 1.14; 95% CI: 1.05, 1.25), but not stroke (HR: 1.01; 95% CI: 0.90, 1.12). Cystatin C, high‐density lipoprotein …

Med

BackgroundA healthy lifestyle is associated with a lower premature mortality risk and with longer life expectancy. However, the metabolic pathways of a healthy lifestyle and how they relate to mortality and longevity are unclear. We aimed to identify and replicate a healthy lifestyle metabolomic signature and examine how it is related to total and cause-specific mortality risk and longevity.MethodsIn four large cohorts with 13,056 individuals and 28-year follow-up, we assessed five healthy lifestyle factors, used liquid chromatography mass spectrometry to profile plasma metabolites, and ascertained deaths with death certificates. The unique healthy lifestyle metabolomic signature was identified using an elastic regression. Multivariable Cox regressions were used to assess associations of the signature with mortality and longevity.FindingsThe identified healthy lifestyle metabolomic signature was reflective of lipid …

American Journal of Kidney Diseases

Rationale & ObjectiveChronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD has been lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study.Study DesignObservational cohort study.Setting & ParticipantsA total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy.ExposureLevels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers were quantified via NMR spectroscopy.OutcomeIncident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records.Analytical ApproachCox proportional hazards regression …

The Journal of Clinical Endocrinology & Metabolism

Context Evidence linking glucose metabolism status with brain macro- and microstructure is limited and inconsistent. Objective We aim to investigate the associations of glucose metabolism status with brain macrostructure and microstructure, including brain volumes, subcortical gray matter volumes, and white matter microstructural metrics. Methods This study enrolled 29 251 participants from the UK Biobank. Glucose metabolism status was classified into normal glucose metabolism (NGM), prediabetes, type 2 diabetes (T2D) with HbA1c <7%, and T2D with HbA1c ≥7%. Brain macrostructural metrics included volumes of total and subcortical gray matter, white matter, white matter hyperintensity (WMH), cerebrospinal fluid, and brain stem. Brain microstructural metrics included fractional anisotropy (FA) and mean diffusivity in white matter tracts. Multivariable …

Journal of Affective Disorders

BackgroundDepression is a global health issue, associated with increased risk of cardiovascular disease (CVD) and premature death, but whether the association varied across different socioeconomic status (SES), and mechanisms responsible for this association is unclear. We aimed to evaluate the association of depressive symptoms with the risk of incident CVD and mortality in people of low, medium, and high SES, and determine the extent to which lifestyle behaviors could explain the association.MethodsThis study included 314,800 participants from the UK Biobank. Depressive symptoms were assessed using the Patient Health Questionnaire-2 (PHQ-2). Information on socioeconomic status and lifestyle was obtained from baseline assessment.ResultsDuring 12 years of follow-up, 29,074 incident CVD cases and 16,673 deaths were documented. The increased CVD risk in participants with depressive …

The American Journal of Clinical Nutrition

BackgroundAlthough low-carbohydrate and low-fat diets are beneficial in short-term metabolic improvement, the associations of these dietary patterns, particularly with different food sources and quality of macronutrients, with mortality remain unclear among people with prediabetes.ObjectivesWe aimed to examine the associations of different types of lower-carbohydrate diets (LCDs) and lower-fat diets (LFDs) with mortality among individuals with prediabetes.MethodsThis study included 9793 adults with prediabetes from the NHANES 1999–2014. Mortality status was linked to National Death Index mortality data through 31 December, 2015. Overall, unhealthy, and healthy LCD and LFD scores were determined based on the percentages of energy from total and subtypes of carbohydrate, fat, and protein. Cox proportional hazards regression models were applied to calculate HRs and 95% CIs.ResultsHigher healthy …

The Journal of Clinical Endocrinology & Metabolism

Aims To investigate the association of individual beverage consumption, including artificially sweetened beverages (ASBs), sugar-sweetened beverages (SSBs), tea, coffee, natural juice, and yogurt, with the risk of microvascular complications (including diabetic retinopathy, diabetic kidney diseases, and diabetic neuropathy) in adults with T2D. Methods This cohort study included 6,676 participants with T2D who were free of macro- and microvascular complications at baseline in the UK Biobank. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Results During a median follow-up of 11.7 years, 1,116 cases of composite microvascular complications were documented. After multivariable adjustment, a linear dose-response relationship was demonstrated between the consumption of ASBs and …

Journal of Affective Disorders

BackgroundDepression is a global health issue, associated with increased risk of cardiovascular disease (CVD) and premature death, but whether the association varied across different socioeconomic status (SES), and mechanisms responsible for this association is unclear. We aimed to evaluate the association of depressive symptoms with the risk of incident CVD and mortality in people of low, medium, and high SES, and determine the extent to which lifestyle behaviors could explain the association.MethodsThis study included 314,800 participants from the UK Biobank. Depressive symptoms were assessed using the Patient Health Questionnaire-2 (PHQ-2). Information on socioeconomic status and lifestyle was obtained from baseline assessment.ResultsDuring 12 years of follow-up, 29,074 incident CVD cases and 16,673 deaths were documented. The increased CVD risk in participants with depressive …

The American Journal of Clinical Nutrition

BackgroundEvidence regarding the relationships of serum 25-hydroxyvitamin D (25[OH]D) with cardiovascular diseases (CVD) and mortality among patients with chronic kidney disease (CKD) is limited and inconsistent.ObjectiveThis study aimed to investigate the associations between serum 25(OH)D and CVD incidence and mortality among patients with CKD.MethodsThis prospective study included 21,507 participants with CKD and free of CVD in the UK Biobank. Incidences of total and subtypes of CVD and mortality were ascertained via electronic health records. Cox proportional hazards regression models were used to estimate the hazard ratios (HRs) and 95% confidential intervals (CIs) for CVD incidence and mortality.ResultsThe median serum 25(OH)D concentration was 44.0 nmol/L (interquartile range: 30.1, 60.6 nmol/L). After multivariable adjustment, compared with CKD patients with serum 25(OH)D …

Diabetes Care

OBJECTIVE To prospectively examine the associations of habitual calcium supplementation with cardiovascular disease (CVD) events and mortality in individuals with and without diabetes. RESEARCH DESIGN AND METHODS The main analysis included 434,374 participants from the UK Biobank. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. Interactions of calcium supplement use with diabetes status were tested on multiplicative and additive scales. RESULTS Over a median follow-up of 8.1 and 11.2 years, 26,374 incident CVD events and 20,526 deaths were documented, respectively. After multivariable adjustment, habitual calcium supplementation was significantly associated with higher risks of CVD incidence (HR 1.34; 95% CI 1.14, 1.57), CVD mortality (HR 1.67; 95% CI 1.19, 2.33), and all-cause …

Diabetes/Metabolism Research and Reviews

Aims To examine the prospective association between fibroblast growth factor 21 (FGF21) and risk of gestational diabetes mellitus (GDM) and the modifying effect of overweight/obesity for this association. Methods Serum FGF21 levels were measured at 6–15 weeks of gestation among 332 GDM cases and 664 matched controls. Conditional logistic regression was used to evaluate its association with GDM risk. Interaction analyses on multiplicative and additive scales were conducted to investigate the modifying effect of overweight/obesity. Results Elevated FGF21 levels were associated with a higher risk of GDM in multivariable models, but the positive association was attenuated after further adjustment for pre‐pregnancy body mass index (BMI). A significant multiplicative interaction was noted between FGF21 (both continuous and dichotomous) and pre‐pregnancy BMI (p for interaction = 0.049 and 0.03), and …

Diabetes Care

OBJECTIVE Breastfeeding duration is inversely associated with risks of cardiovascular disease (CVD) and type 2 diabetes in parous women. However, the association among women at high risk, including women with type 2 diabetes or gestational diabetes (GDM) is unclear. RESEARCH DESIGN AND METHODS We included 15,146 parous women with type 2 diabetes from the Nurses’ Health Study I and II (NHS, NHS II) and 4,537 women with a history of GDM from NHS II. Participants reported history of breastfeeding via follow-up questionnaires. Incident CVD by 2017 comprised stroke or coronary heart disease (CHD: myocardial infarction, coronary revascularization). Adjusted hazard ratios (aHRs) and 95% CIs were estimated using Cox models. RESULTS We documented 1,159 incident CVD cases among women with type 2 diabetes in both cohorts during …

Diabetes care

OBJECTIVE Patients with diabetes and end-stage kidney disease (ESKD) may experience “burnt-out diabetes,” defined as having an HbA1c value <6.5% without antidiabetic therapy for >6 months. We aim to assess glycemic control by continuous glucose monitoring (Dexcom G6 CGM) metrics and glycemic markers in ESKD patients on hemodialysis with burnt-out diabetes. RESEARCH DESIGN AND METHODS In this pilot prospective study, glycemic control was assessed by continuous glucose monitoring (CGM), HbA1c measures, and glycated albumin and fructosamine measurements in patients with burnt-out diabetes (n = 20) and without a history of diabetes (n = 20). RESULTS Patients with burnt-out diabetes had higher CGM-measured daily glucose levels, lower percent time in the range 70–180 mg/dL, higher percent time above range (>250 mg/dL), and …

Diabetes Care

OBJECTIVE Previous studies suggested that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may initially worsen and possibly increase the risk of diabetic retinopathy. However, data on this possible association remain limited. Thus, this population-based study aimed to determine whether use of GLP-1 RAs is associated with an increased risk of incident diabetic retinopathy. RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink (CPRD), we conducted a cohort study among 77,115 patients with type 2 diabetes initiating antidiabetic drugs between January 2007 and September 2015. Adjusted hazard ratios (HRs) and 95% CIs of incident diabetic retinopathy were estimated using time-dependent Cox proportional hazards models, comparing use of GLP-1 RAs with current use of two or more oral antidiabetic drugs. In an ancillary analysis …

Diabetes Care

OBJECTIVE To assess self-reported awareness of diabetic retinopathy (DR) and concordance of eye examination follow-up compared with findings from concurrent retinal images. RESEARCH DESIGN AND METHODS We conducted a prospective observational 10-year study of 26,876 consecutive patients with diabetes who underwent retinal imaging during an endocrinology visit. Awareness and concordance were evaluated using questionnaires and retinal imaging. RESULTS Awareness information and gradable images were available in 25,360 patients (94.3%). Severity of DR by imaging was as follows: no DR (n = 14,317; 56.5%), mild DR (n = 6,805; 26.8%), or vision-threatening DR (vtDR; n = 4,238; 16.7%). In the no, mild, and vtDR groups, 96.7%, 88.5%, and 54.9% of patients, respectively, reported being unaware of any prior DR. When DR was …

Diabetes Care

Women with gestational diabetes mellitus (GDM) continue to face challenges in initiating breastfeeding despite its many benefits (1). Neonatal intensive care unit/special care nursery (NICU/SCN) admission is particularly associated with reduced breastfeeding uptake (2). In the recent Treatment of Booking Gestational Diabetes Mellitus (TOBOGM) randomized controlled trial (RCT), early diagnosis and immediate management of GDM control (deferred treatment) decreased the risk of adverse neonatal outcomes by 1.2–10.1% and reduced NICU/SCN duration of stay (3). It is unclear whether early diagnosis and treatment of GDM influences breastfeeding uptake. We have now compared breastfeeding initiation as the first step toward longer-term breastfeeding within the TOBOGM cohort. The RCT study design was reported previously (3). The protocol was approved by local ethics committees in each country …

Diabetes Care

OBJECTIVE We report mortality outcomes in GRADE among people with type 2 diabetes diagnosed within 10 years and no recent history of cardiovascular events or cancer. RESEARCH DESIGN AND METHODS Overall mortality rates and major causes of death were assessed over an average of 5 years of follow-up. Cause of death was adjudicated centrally by a committee masked to treatment assignment. We examined baseline covariates and the 10-year Framingham Risk Score for associations. RESULTS Mortality rate was low (0.59 per 100 participant-years). Participants who died during follow-up were likely to be older, male, have a history of hypertension, smoking, and have moderate albuminuria. The two most common underlying causes of death were “cardiovascular-cause” (a composite of underlying causes) (38.6%) and cancer (26.8%). There were …

Diabetes Care

OBJECTIVE Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery …

Diabetes Care

OBJECTIVE To determine whether adiposity depots modulate vaspin levels and whether vaspin predicts type 2 diabetes (T2D) risk, through epidemiological and genetic analyses. RESEARCH DESIGN AND METHODS We assessed the relationship of plasma vaspin concentration with incident and prevalent T2D and adiposity-related variables in 1) the Prospective Urban and Rural Epidemiology (PURE) biomarker substudy (N = 10,052) and 2) the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial (N = 7,840), using regression models. We then assessed whether vaspin is causally associated with T2D and whether genetic variants associated with MRI-measured adiposity depots modulate vaspin levels, using two-sample Mendelian randomization (MR). RESULTS A 1-SD increase in circulating vaspin levels was associated with a 16% increase …

Diabetes Care

OBJECTIVE Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery …

Diabetes Care

OBJECTIVE Hispanics/Latinos in the United States have the highest prevalence of undiagnosed and untreated diabetes and are at increased risk for cognitive impairment. In this study, we examine glycemic control in relation to cognitive aging and impairment in a large prospective cohort of middle-aged and older Hispanics/Latinos of diverse heritages. RESEARCH DESIGN AND METHODS Study of Latinos–Investigation of Neurocognitive Aging (SOL-INCA) is a Hispanic Community Health Study/Study of Latinos (HCHS/SOL) ancillary study. HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability sampled prospective cohort study. SOL-INCA enrolled 6,377 diverse Hispanics/Latinos age 50 years and older (2016–2018). The primary outcomes were cognitive function, 7-year cognitive decline and mild cognitive impairment (MCI). The primary …

Diabetes Care

In the abstract of the article cited above, the clinical trial number for DISCHARGE (NCT02400229) was inadvertently omitted. The abstract has been revised to include the ClinicalTrials.gov identification. The editors apologize for the error. The online version of the article (https://doi.org/10.2337/dc23-0710) has been updated to correct the error.

Diabetes Care

OBJECTIVE Prediabetes in young people is an emerging epidemic that disproportionately impacts Hispanic populations. We aimed to develop a metabolite-based prediction model for prediabetes in young people with overweight/obesity at risk for type 2 diabetes. RESEARCH DESIGN AND METHODS In independent, prospective cohorts of Hispanic youth (discovery; n = 143 without baseline prediabetes) and predominately Hispanic young adults (validation; n = 56 without baseline prediabetes), we assessed prediabetes via 2-h oral glucose tolerance tests. Baseline metabolite levels were measured in plasma from a 2-h postglucose challenge. In the discovery cohort, least absolute shrinkage and selection operator regression with a stability selection procedure was used to identify robust predictive metabolites for prediabetes. Predictive performance was evaluated in the discovery …

Diabetes Care

OBJECTIVE To assess leisure-time physical activity (LTPA) as a modifier of the diabetes/cognitive decline association in middle-aged and older participants in the Estudo Longitudinal de Saude do Adulto (ELSA-Brasil) study. RESEARCH DESIGN AND METHODS ELSA-Brasil is a cohort of 15,105 participants (age 35–74 years) enrolled between 2008 and 2010. We evaluated global cognitive function, summing the scores of six standardized tests evaluating memory and verbal fluency, including the Trail-Making Test, at baseline and follow-up. Incident cognitive impairment was defined as a global cognitive function score at follow-up lower than −1 SD from baseline mean. Participants reporting ≥150 min/week of moderate to vigorous LTPA at baseline were classified as physically active. We assessed the association of LTPA with global cognition change in those with diabetes in the …

Diabetes Care

OBJECTIVE To understand preferences for features of weight loss programs among adults with or at risk of type 2 diabetes in the U.K. RESEARCH DESIGN AND METHODS We conducted a discrete choice experiment with 3,960 U.K. adults living with overweight (n = 675 with type 2 diabetes). Preferences for seven characteristics of weight loss programs were analyzed. Simulations from choice models using the experimental data predicted uptake of available weight loss programs. Patient groups comprising those who have experience with weight loss programs, including from minority communities, informed the experimental design. RESULTS Preferences did not differ between individuals with and without type 2 diabetes. Preferences were strongest for type of diet. Healthy eating was most preferred relative to total diet replacement (odds ratio [OR] 2.24; 95 …

Diabetes Care

OBJECTIVE To examine the association between diabetes stigma, socioeconomic status, psychosocial variables, and substance use in adolescents and young adults (AYAs) with type 1 or type 2 diabetes. RESEARCH DESIGN AND METHODS This is a cross-sectional analysis of AYAs from the SEARCH for Diabetes in Youth study who completed a survey on diabetes-related stigma, generating a total diabetes stigma score. Using multivariable modeling, stratified by diabetes type, we examined the relationship of diabetes stigma with variables of interest. RESULTS Of the 1,608 AYAs who completed the diabetes-related stigma survey, 78% had type 1 diabetes, and the mean age was 21.7 years. Higher diabetes stigma scores were associated with food insecurity (P = 0.001), disordered eating (P < 0.0001), depressive symptoms (P < 0.0001), and decreased …

Diabetes Care

OBJECTIVE Previous studies suggested that glucagon-like peptide 1 receptor agonists (GLP-1 RAs) may initially worsen and possibly increase the risk of diabetic retinopathy. However, data on this possible association remain limited. Thus, this population-based study aimed to determine whether use of GLP-1 RAs is associated with an increased risk of incident diabetic retinopathy. RESEARCH DESIGN AND METHODS Using the U.K. Clinical Practice Research Datalink (CPRD), we conducted a cohort study among 77,115 patients with type 2 diabetes initiating antidiabetic drugs between January 2007 and September 2015. Adjusted hazard ratios (HRs) and 95% CIs of incident diabetic retinopathy were estimated using time-dependent Cox proportional hazards models, comparing use of GLP-1 RAs with current use of two or more oral antidiabetic drugs. In an ancillary analysis …

Diabetes Care

OBJECTIVE Intensive glycemic control reduced coronary artery disease (CAD) events among the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study participants with the haptoglobin (Hp)2-2 phenotype but not in participants without the Hp2-2 phenotype. It is unknown whether and how these results translate across different demographic/clinical characteristics and treatment strategies. RESEARCH DESIGN AND METHODS Haptoglobin phenotype was measured in available samples from the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) biomarker case-cohort study. Weighted multivariable-adjusted Cox regression models were used to evaluate the association between intensive glycemic control (HbA1c target of ≤6.5%) versus standard therapy (based on local guidelines) and major CAD events among …

Diabetes Care

OBJECTIVE To characterize high type 1 diabetes (T1D) genetic risk in a population where type 2 diabetes (T2D) predominates. RESEARCH DESIGN AND METHODS Characteristics typically associated with T1D were assessed in 109,594 Million Veteran Program participants with adult-onset diabetes, 2011–2021, who had T1D genetic risk scores (GRS) defined as low (0 to <45%), medium (45 to <90%), high (90 to <95%), or highest (≥95%). RESULTS T1D characteristics increased progressively with higher genetic risk (P < 0.001 for trend). A GRS ≥ 90% was more common with diabetes diagnoses before age 40 years, but 95% of those participants were diagnosed at age ≥40 years, and they resembled T2D in mean age (64.3 years) and BMI (32.3 kg/m2). Compared with the low risk group, the highest-risk group was more likely to have diabetic ketoacidosis …

Diabetes Care

We read with great interest the study by Chen et al.(1), which adds further robust evidence that dietary patterns based on ultra-processed products (UPP) increase the risk for incident type 2 diabetes (T2D). However, as for the attempt to investigate the associations of specific groups and subgroups of UPP with T2D, here we argue that methodological artifacts may explain the findings on putative protective associations of some UPP groups and subgroups with T2D. First, the multivariable models have ignored the evident multicollinearity between total UPP, UPP group, and UPP subgroup intake added to models, particularly in food frequency questionnaires studies (2). Multicollinearity can obscure true relationships between exposure and outcome variables. It can lead to unreliable estimates, making it difficult to adequately determine individual associations of each correlated exposure variable (eg, total UPP, UPP …

Diabetes Care

OBJECTIVE We evaluated whether adding basal insulin to metformin in adults with early type 2 diabetes mellitus (T2DM) would increase emotional distress relative to other treatments. RESEARCH DESIGN AND METHODS The Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE) of adults with T2DM of <10 years’ duration, HbA1c 6.8–8.5%, and taking metformin monotherapy randomly assigned participants to add insulin glargine U-100, sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or the dipeptidyl peptidase 4 inhibitor sitagliptin. The Emotional Distress Substudy enrolled 1,739 GRADE participants (mean [SD] age 58.0 [10.2] years, 32% female, 56% non-Hispanic White, 18% non-Hispanic Black, 17% Hispanic) and assessed diabetes distress and depressive symptoms every 6 months. Analyses examined …