Diversity in Clinical Trials: A Complicated Issue, Not a Simple Solution.

This article is adapted from a speech Ms. Brown-Friday delivered in June 2023 as President, Health Care & Education, of the American Diabetes Association. She delivered her address at the Association's 83rd Scientific Sessions in San Diego, CA. A webcast of this speech is available for viewing on the DiabetesPro website (https://events.diabetes.org/live/25/page/186).

Emotional Distress Predicts Reduced Type 2 Diabetes Treatment Adherence in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE).

OBJECTIVE: We examined longitudinal associations between emotional distress (specifically, depressive symptoms and diabetes distress) and medication adherence in Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study (GRADE), a large randomized controlled trial comparing four glucose-lowering medications added to metformin in adults with relatively recent-onset type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: The Emotional Distress Substudy assessed medication adherence, depressive symptoms, and diabetes distress in 1,739 GRADE participants via self-completed questionnaires administered biannually up to 3 years. We examined baseline depressive symptoms and diabetes distress as predictors of medication adherence over 36 months. Bidirectional visit-to-visit relationships were also examined. Treatment satisfaction, beliefs about medication, diabetes care self-efficacy, and perceived control over diabetes were evaluated as mediators of longitudinal associations. RESULTS: At baseline, mean ± SD age of participants (56% of whom were White, 17% Hispanic/Latino, 18% Black, and 66% male) was 58.0 ± 10.2 years, diabetes duration 4.2 ± 2.8 years, HbA1c 7.5% ± 0.5%, and medication adherence 89.9% ± 11.1%. Higher baseline depressive symptoms and diabetes distress were independently associated with lower adherence over 36 months (P < 0.001). Higher depressive symptoms and diabetes distress at one visit predicted lower adherence at the subsequent 6-month visit (P < 0.0001) but not vice versa. Treatment assignment did not moderate relationships. Patient-reported concerns about diabetes medications mediated the largest percentage (11.9%-15.5%) of the longitudinal link between emotional distress and adherence. CONCLUSIONS: Depressive symptoms and diabetes distress both predict lower adherence to glucose-lowering medications over time among adults with T2DM. Addressing emotional distress and concerns about anticipated negative effects of taking these treatments may be important to support diabetes treatment adherence.

Study Protocol Using Cohort Data and Latent Variable Modeling to Guide Sampling Women With Type 2 Diabetes and Depressive Symptoms.

BACKGROUND: Depression affects one in three women with Type 2 diabetes, and this concurrence significantly increases the risks of diabetes complications, disability, and early mortality. Depression is underrecognized because of wide variation in presentation and the lack of diagnostic biomarkers. Converging evidence suggests inflammation is a shared biological pathway in diabetes and depression. Overlapping epigenetic associations and social determinants of diabetes and depression implicate inflammatory pathways as a common thread. OBJECTIVES: This article describes the protocol and methods for a pilot study aimed to examine associations between depressive symptoms, inflammation, and social determinants of health among women with Type 2 diabetes. METHODS: This is an observational correlational study that leverages existing longitudinal data from the Women's Interagency HIV Study (WIHS), a multicenter cohort of HIV seropositive (66%) and HIV seronegative (33%) women, to inform purposive sampling of members from latent subgroups emergent from a prior retrospective cohort-wide analysis. Local active cohort participants from the Bronx study site are then selected for the study. The WIHS recently merged with the Multicenter Aids Cohort Study (MACS) to form the MACS/WIHS Combined Cohort Study. Latent subgroups represent distinct symptom trajectories resultant from a growth mixture model analysis of biannually collected depressive symptom data. Participants complete surveys (symptom and social determinants) and provide blood samples to analyze plasma levels and DNA methylation of genes that encode for inflammatory markers (CRP, IL-6, TNF-α). Correlation and regression analysis will be used to estimate the effect sizes between depressive symptoms and inflammatory markers, clinical indices (body mass index, hemoglobin A1C, comorbidities), and social determinants of health. RESULTS: The study began in January 2022, and completed data collection is estimated by early 2023. We hypothesize that depressive symptom severity will associate with higher levels of inflammation, clinical indices (e.g., higher hemoglobin A1C), and exposure to specific social determinants of health (e.g., lower income, nutritional insecurity). DISCUSSION: Study findings will provide the basis for future studies aimed at improving outcomes for women with Type 2 diabetes by informing the development and testing of precision health strategies to address and prevent depression in populations most at risk.

Emotional distress, self-management, and glycemic control among participants enrolled in the glycemia reduction approaches in diabetes: A comparative effectiveness (GRADE) study.

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.

Resilience and Optimism as Moderators of the Negative Effects of Stigma on Women Living with HIV.

Resilience and optimism may not only have main effects on health outcomes, but may also moderate and buffer negative effects of stressors. We examined whether dispositional resilience and optimism moderate the associations between HIV-related stigma in health care settings and health-related outcomes (trust in HIV health care providers and depression symptoms) among women living with HIV (WLHIV). One thousand four hundred five WLHIV in nine US cities completed validated questionnaires for cross-sectional analyses. Higher self-reported experienced and anticipated stigma and lower resilience and optimism were associated with higher depression symptoms and with lower trust in HIV providers. Importantly, resilience moderated the effects of experienced stigma (but not of anticipated stigma): When resilience was high, the association of experienced stigma with higher depression symptoms and lower trust in HIV providers was weaker compared with when resilience was low. Further, significant moderation effects suggested that when optimism was high, experienced and anticipated stigma was both less strongly associated with depression symptoms and with lower trust in one's HIV care providers compared with when optimism was low. Thus, the effects of experienced stigma on depression symptoms and provider trust were moderated by both resilience and optimism, but the effects of anticipated stigma were moderated only by optimism. Our findings suggest that in addition to their main effects, resilience and optimism may function as buffers against the harmful effects of stigma in health care settings. Therefore, optimism and resilience may be valuable intervention targets to reduce depression symptoms or improve trust in providers among populations that experience or anticipate stigma, such as WLHIV.

Predictors of sustained reduction in energy and fat intake in the Diabetes Prevention Program Outcomes Study intensive lifestyle intervention.

BACKGROUND: Few lifestyle intervention studies examine long-term sustainability of dietary changes. OBJECTIVE: To describe sustainability of dietary changes over 9 years in the Diabetes Prevention Program and its outcomes study, the Diabetes Prevention Program Outcomes Study, among participants receiving the intensive lifestyle intervention. DESIGN: One thousand seventy-nine participants were enrolled in the intensive lifestyle intervention arm of the Diabetes Prevention Program; 910 continued participation in the Diabetes Prevention Program Outcomes Study. Fat and energy intake derived from food frequency questionnaires at baseline and post-randomization Years 1 and 9 were examined. Parsimonious models determined whether baseline characteristics and intensive lifestyle intervention session participation predicted sustainability. RESULTS: Self-reported energy intake was reduced from a median of 1,876 kcal/day (interquartile range [IQR]=1,452 to 2,549 kcal/day) at baseline to 1,520 kcal/day (IQR=1,192 to 1,986 kcal/day) at Year 1, and 1,560 kcal/day (IQR=1,223 to 2,026 kcal/day) at Year 9. Dietary fat was reduced from a median of 70.4 g (IQR=49.3 to 102.5 g) to 45 g (IQR=32.2 to 63.8 g) at Year 1 and increased to 61.0 g (IQR=44.6 to 82.7 g) at Year 9. Percent energy from fat was reduced from a median of 34.4% (IQR=29.6% to 38.5%) to 27.1% (IQR=23.1% to 31.5%) at Year 1 but increased to 35.3% (IQR=29.7% to 40.2%) at Year 9. Lower baseline energy intake and Year 1 dietary reduction predicted lower energy and fat gram intake at Year 9. Higher leisure physical activity predicted lower fat gram intake but not energy intake. CONCLUSIONS: Intensive lifestyle intervention can result in reductions in total energy intake for up to 9 years. Initial success in achieving reductions in fat and energy intake and success in attaining activity goals appear to predict long-term success at maintaining changes.

10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study.

BACKGROUND: In the 2.8 years of the Diabetes Prevention Program (DPP) randomised clinical trial, diabetes incidence in high-risk adults was reduced by 58% with intensive lifestyle intervention and by 31% with metformin, compared with placebo. We investigated the persistence of these effects in the long term. METHODS: All active DPP participants were eligible for continued follow-up. 2766 of 3150 (88%) enrolled for a median additional follow-up of 5.7 years (IQR 5.5-5.8). 910 participants were from the lifestyle, 924 from the metformin, and 932 were from the original placebo groups. On the basis of the benefits from the intensive lifestyle intervention in the DPP, all three groups were offered group-implemented lifestyle intervention. Metformin treatment was continued in the original metformin group (850 mg twice daily as tolerated), with participants unmasked to assignment, and the original lifestyle intervention group was offered additional lifestyle support. The primary outcome was development of diabetes according to American Diabetes Association criteria. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00038727. FINDINGS: During the 10.0-year (IQR 9.0-10.5) follow-up since randomisation to DPP, the original lifestyle group lost, then partly regained weight. The modest weight loss with metformin was maintained. Diabetes incidence rates during the DPP were 4.8 cases per 100 person-years (95% CI 4.1-5.7) in the intensive lifestyle intervention group, 7.8 (6.8-8.8) in the metformin group, and 11.0 (9.8-12.3) in the placebo group. Diabetes incidence rates in this follow-up study were similar between treatment groups: 5.9 per 100 person-years (5.1-6.8) for lifestyle, 4.9 (4.2-5.7) for metformin, and 5.6 (4.8-6.5) for placebo. Diabetes incidence in the 10 years since DPP randomisation was reduced by 34% (24-42) in the lifestyle group and 18% (7-28) in the metformin group compared with placebo. INTERPRETATION: During follow-up after DPP, incidences in the former placebo and metformin groups fell to equal those in the former lifestyle group, but the cumulative incidence of diabetes remained lowest in the lifestyle group. Prevention or delay of diabetes with lifestyle intervention or metformin can persist for at least 10 years. FUNDING: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

Alcohol consumption and diabetes risk in the Diabetes Prevention Program.

BACKGROUND: Moderate alcohol consumption is associated with a decreased risk of type 2 diabetes in the general population, but little is known about the effects in individuals at high risk of diabetes. OBJECTIVES: The objectives were to determine associations between alcohol consumption and diabetes risk factors and whether alcohol consumption was a predictor of incident diabetes in individuals enrolled in the Diabetes Prevention Program (DPP). DESIGN: DPP participants (n = 3175) had impaired glucose tolerance (2-h glucose: 7.8-11.1 mmol/L), elevated fasting glucose (5.3-7.0 mmol/L), and a body mass index (in kg/m(2)) > or =24. Participants were randomly assigned to placebo, metformin, or lifestyle modification and were followed for a mean of 3.2 y. Alcohol intake was assessed at baseline and year 1 by using a semiquantitative food-frequency questionnaire. Diabetes was diagnosed by annual oral-glucose-tolerance testing and semiannual fasting plasma glucose measurement. RESULTS: Participants who reported higher alcohol consumption tended to be male, older, white, and less obese and to have a higher calorie intake and a higher HDL-cholesterol concentration. Higher alcohol consumption was associated with lower insulin secretion at any level of insulin sensitivity. We found lower incidence rates of diabetes with higher alcohol consumption in the metformin (P < 0.01 for trend) and lifestyle modification (P = 0.02 for trend) groups, which remained significant after adjustment for multiple baseline covariates. No similar association was observed in the placebo group. CONCLUSIONS: Despite overall low rates of alcohol consumption, there was a reduced risk of incident diabetes in those who reported modest daily alcohol intake and were assigned to metformin or lifestyle modification. Moderate daily alcohol intake is associated with lower insulin secretion-an effect that warrants further investigation. This trial was registered at clinicaltrials.gov as NCT00038727.

Evaluating the accuracy of an aneroid sphygmomanometer in a clinical trial setting.

BACKGROUND: The mercury sphygmomanometer, the "gold" standard for blood pressure measurements, has been gradually phased out in many institutions because of environmental concerns. Our on-going clinical trial compared the use of mercury vs. aneroid sphygmomanometers, before implementing a study-wide transition to the aneroid sphygmomanometer. METHODS: The Diabetes Prevention Program Outcomes Study (DPPOS) studied the accuracy of the Welch Allyn Tycos 767-Series Mobile aneroid sphygmomanometer from 20 March 2006 to 21 June 2006 at multiple clinic centers. We compared readings from 997 participants in 24 clinic centers using both mercury and aneroid sphygmomanometers. RESULTS: The study found no statistically significant difference for systolic blood pressure (SBP) (P > 0.05) and a small but significantly (P < 0.0001) lower (0.8 mm Hg) reading for diastolic blood pressure (DBP) using the aneroid sphygmomanometer. Regression analysis of aneroid vs. mercury showed regression lines (Y = 4.8 + 0.96X for SBP, Y = 3.1 + 0.95X for DBP) slightly but statistically significantly different from the line of equality (P < 0.001). Participants' age, sex, race/ethnicity, body mass index, blood pressure, and clinical center together explain about 8-10% of the variation of the difference between readings from the two sphygmomanometers. Based on the above result, on 1 August 2006, DPPOS clinics began the conversion from mercury to aneroid sphygmomanometers. CONCLUSIONS: The Welch Allyn Tycos 767-Series Mobile Aneroid model 7670-04 tested in this validation study can be used to replace mercury model in clinical trials.