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Aims: People with type 2 diabetes (T2DM) have an increased risk of cardiovascular disease (CVD). We examined depressive symptoms (DS) and diabetes distress (DD) in relation to the estimated 10-year risk of CVD in adults with T2DM enrolled in the GRADE Emotional Distress Substudy., Methods: Linear regression models examined the associations of baseline DS and DD with estimated 10-year risk of CVD using the Atherosclerotic Cardiovascular Disease (ASCVD) risk score, adjusting for age, sex, race/ethnicity, education, income, diabetes duration, diabetes-related complications, and HbA1c., Results: A total of 1,605 GRADE participants were included: 54% Non-Latino (NL) White, 18% Latino, 19% NL-Black, 66% male, mean age 57.5 (SD = 10.25) years, diabetes duration 4.2 (SD = 2.8) years, and HbA1c 7.5% (SD = 0.5%). After incorporating covariates, only DS, especially cognitive-affective symptoms, were associated with ASCVD risk (estimate = 0.15 [95% CI: 0.04, 0.025], p = 0.006). Higher DS remained significantly associated with higher ASCVD risk when adding DD to covariates (estimate = 0.19 [95% CI: 0.07, 0.30], p = 0.002). DD was not associated with ASCVD risk when accounting for covariates., Conclusions: Depressive symptoms, particularly cognitive-affective symptoms, are associated with increased 10-year predicted ASCVD risk among adults with early T2DM. Diabetes distress is not significantly associated with the predicted ASCVD risk when accounting for covariates., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [GCR reports grants from JDRF outside the submitted work. CJH reports grants from NIH, and JDRF outside the submitted work. CP reports grants/contracts from NIH, outside the submitted work. EW reports grants from NIH, participation in a data safety monitoring board or advisory board for a NIH P20 center grant, and leadership as a board of director for Chronic Care International, outside the submitted work. JSG reports grants from NIH and JDRF, outside the submitted work. AC reports grants from NIH, outside the submitted work. IB, HKS, AND, AC, RF, and DE have nothing to disclose.]., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: We examined emotional distress in relation to metformin adherence, overall diabetes self-management, and glycemic control among adults with early type 2 diabetes (T2DM) enrolled in the GRADE study., Methods: Linear regression models examined cross-sectional associations of baseline depression symptoms and diabetes distress with adherence to metformin, self-management, and HbA1c, adjusting for covariates. Cognitive-affective (e.g., sadness) and somatic (e.g., sleep/appetite disturbance) depression symptoms and diabetes distress subscales were also examined., Results: This substudy of 1,739 GRADE participants (56 % Non-Hispanic White, 18 % Non-Hispanic Black, 17 % Hispanic, 68 % male, mean[SD] age = 57.96[10.22] years, diabetes duration = 4.21[2.81] years, and HbA1c = 7.51[0.48]) found that the prevalence of clinically significant depression and diabetes distress was 8.7 % and 25 %, respectively. Fully adjusted models showed that depression symptoms were associated with lower self-management (p < 0.0001); this effect was only significant for somatic symptoms. Diabetes distress was associated with lower adherence (p = 0.0001) and self-management (p < 0.0001); effects were significant for all subscales, except physician-related distress. No significant relationships of total depression symptom severity or diabetes distress with HbA1c were found., Conclusions: Depression symptoms and diabetes distress were robustly associated with problematic diabetes self-management among participants in GRADE. These findings highlight the need for routine assessment of depression symptoms and diabetes distress early in T2DM care., Competing Interests: Declaration of Competing Interest JSG reports grants from NIH and JDRF, outside the submitted work. CJH reports grants from NIDDK, NIA, and JDRF outside the submitted work. EAW reports grants from NIH/NIDDK, participation in a data safety monitoring board or advisory board for a NIH P20 center grant, and leadership as a board of director for Chronic Care International, outside the submitted work. HKS, IB, GCR, AND, AW, DE, JBF and AC have nothing to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: We assessed whether and to what extent established cardiovascular disease (CVD) risk factors moderate (enhance/reduce) the effect of hyperglycemia on CVD outcomes in the long-term follow-up of the Diabetes Control and Complications Trial type 1 diabetes (T1D) cohort (N = 1441)., Methods: Moderation of the effect of glycemia on subsequent risk of major adverse cardiovascular events (MACE: fatal or non-fatal myocardial infarction or stroke) and any-CVD (MACE plus confirmed angina, silent MI, revascularization, or congestive heart failure) was assessed separately using interaction terms between HbA1c and other risk factors in Cox proportional hazards models., Results: Over a median follow-up of 29 years, there were 120 MACE cases and 239 any-CVD cases. Higher pulse, higher triglycerides, use of calcium channel blockers, and presence of neuropathy individually enhanced (p < 0.01) the effect of glycemia on any-CVD. Higher pulse and triglyceride levels, albumin excretion rate, hypertension, and no family history of type 2 diabetes enhanced (p < 0.01) the effect of glycemia on MACE., Conclusions: Such moderation analyses identify subgroups with increased CVD risk who might especially benefit from earlier and/or more intensive glycemic control. Interventions treating modifiable moderating factors may independently reduce the risk of CVD and also reduce the risk associated with a higher HbA1c., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: The Glycemia Reduction Approaches in Diabetes - A Comparative Effectiveness (GRADE) trial is a randomized clinical trial comparing glycemic effects of four diabetes medications added to metformin in type 2 diabetes (T2D). Microvascular and macrovascular diseases are secondary outcomes. We evaluated the prevalence and risk factor relationships for microvascular and macrovascular complications in the GRADE cohort at study entry., Methods: Complication prevalence and risk factors were analyzed based on data from screening in all consenting participants meeting GRADE eligibility. Logistic regression and Z-statistics were used to assess risk factor relationships with complications., Results: We enrolled 5047 T2D participants [mean age 57 years; 36% female; mean known T2D duration 4 years (all < 10 years); mean HbA1c 8.0% (∼64 mmol/mol) at screening]. Urinary albumin/creatinine ratio (ACR) ≥ 30 mg/gram was present in 15.9% participants; peripheral neuropathy (by Michigan Neuropathy Screening Instrument) in 21.5%; cardiovascular autonomic neuropathy by electrocardiography-derived indices in 9.7%; self-reported retinopathy in 1.0%. Myocardial infarction ascertained by self-report or electrocardiogram was present in 7.3%, and self-reported history of stroke in 2.0%., Conclusions: In the GRADE cohort with < 10 years of T2D and a mean HbA1c of 8.0%, diabetes complications were present in a substantial fraction of participants, more so than might otherwise have been expected., Competing Interests: Contribution statement All authors affirm that authorship is merited based on the ICMJE authorship criteria. IB, JPC, CD, JBG, HKS, MEL, KJM, RP-B, EBS, and DJW contributed to the conception and design of this manuscript. IB, JPS, CD, JBG, HKS, KJM, JP, ERS, RP-B and EZS contributed to the acquisition of data for this manuscript. IB contributed to the statistical analysis of data for this manuscript. CB, IB, RMC, JPC, CD, JBG, MSK, HKS, KJM, RP-B, ERS, EBS, EZS, and DJW contributed to the interpretation of data and results for this manuscript. CD, KJM, RP-B, and ERS contributed to the supervision and management of research for this manuscript. IB, CD, HKS, HKS, MEL, KJM, and RP-B contributed to the drafting of this manuscript. CB, IB, RMC, JPC, CD, JBG, MSK, HKS, KJM, JP, RP-B, ERS, EBS, EZS, and DJS contributed to the critical review of this manuscript. IB, KJM and RP-B are guarantors of this work, and as such, had full access to all the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis., (Copyright © 2020 Elsevier B.V. All rights reserved.)