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We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p<5x10-8), including 237 attaining a more stringent trans-ancestry threshold (p<5x10-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health.

IntroductionDespite availability of screening for diabetic retinopathy, testing is underused by many low-income and racial/ethnic minority patients with diabetes. We examined perceived barriers to diabetic retinopathy screening among low-income patients and their health care providers and provider staffers.MethodsWe collected survey data from 101 patients with diabetes and 44 providers and staffers at a safety-net clinic where annual diabetic retinopathy screening rates were low. Barriers specified in the survey were derived from the literature.ResultsPatients surveyed (mean [standard deviation] age, 54.0 [7.7] y; 41% were male) were primarily Hispanics (70%) and African Americans (27%) of low socioeconomic status. Overall, 55% of patients received diabetic retinopathy screening in the previous year. Patients who could not explain why this screening is needed reported more barriers than patients who could (2.5 vs 1.4 barriers, P = .02). Fewer patients reported that they experienced barriers such as transportation (15%), language issues (15%), cultural beliefs or myths (4%), denial (8%), and fear (5%), which providers and staffers considered very or extremely important (all P < .001). Financial burdens (26%) and depression (22%) were most commonly reported by patients as barriers, yet providers and staffers did not rate these barriers as important, P < .001. ConclusionPatients and health care providers had markedly divergent perceptions of barriers to diabetic retinopathy screening. Patients with poor understanding of the need for screening were more likely to report such barriers. These results suggest a need for active community engagement to find key elements for education programs and other interventions to increase rates of diabetic retinopathy screening, particularly among low-income, minority populations.

Aims In type 2 diabetes, early effects of strict near-normalization of glucose control on macrovascular and microvascular disease are still uncertain. We evaluated the effects of early dramatic improvement in glycemia on retinal disease in poorly controlled diabetes. Methods A retrospective, case-control study in public hospital patients with type 2 diabetes, who had annual retinal imaging as part of a case management program or standard diabetes care. Patients included had ≥2 two retinal images ≥1 one year apart, and at least 3 HbA1C measurements. Retinal images were graded using a modified Scottish Diabetic Retinopathy grading scheme. An ‘intensive’ group (n=34) with HbA1C decrease >1.5% was compared with randomly chosen patients (n=34) with minimal HbA1C changes. Results Mean HbA1C (±SEM) over two years was similar in intensive (8.5±0.21%) and control groups (8.1±0.28%, p=NS). However, the intensive group had higher baseline HbA1C and a mean maximal decrease of 4.0±0.41% in contrast to the control group (0.2±0.11%). Retinopathy grade progressed +0.7±0.25 units from baseline in the intensive group (p = 0.015), a 22.6% worsening. The control group changed minimally from baseline (0.03±0.14 units, p=NS). Change in retinopathy grade was significantly different between groups (p=0.02). More eyes worsened by ≥1 retinal grade (p=0.0025) and developed sight-threatening retinopathy (p=0.003) in the intensive group. Visual acuity was unchanged. Conclusions Diabetic retinopathy significantly worsened in poorly controlled type 2 diabetes after early intensification of glycemic control and dramatic HbA1C change. Retinal status should be part of risk-factor evaluation in patients likely to experience marked reductions in HbA1C in poorly controlled diabetes.