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We investigated type 2 diabetes (T2D) genetic susceptibility in a multi-ethnic meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP) and other biobanks. We identified 558 autosomal and 10 X-chromosome T2D-associated variants, of which 286 autosomal and 7 X-chromosome variants were previously unreported. Ancestry-specific analyses identified 25 additional novel T2D-susceptibility variants. Transcriptome-wide association analysis detected 3,568 T2D-associations with T2D-colocalized genetically predicted gene expression of 804 genes in 52 tissues, of which 687 are novel. Fifty-four of these genes are known to interact with FDA-approved drugs and chemical compounds. T2D polygenic risk score was strongly associated with increased the risk of T2D-related retinopathy, and additionally showed evidence for association with chronic kidney disease (CKD), neuropathy, and peripheral artery disease (PAD). We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including 3 for coronary heart disease, 1 for PAD, 2 for stroke, 4 for retinopathy, 2 for CKD, and 1 for neuropathy. Our findings may identify potential novel therapeutic targets for T2D and genomic pathways that link T2D and its vascular outcomes.

Exercise treadmill test is interpreted as positive or negative for ischemia in the presence or absence of ST depression respectively. This study was conducted to evaluate the diagnostic value of chest pain without ST depression during exercise treadmill test.A total of 180 patients who had abnormal exercise treadmill test result and subsequently underwent coronary angiography were studied. Patients were categorised as having ST depression and angina (group A), only ST depression (group B) and only angina (group C). Coronary angiograms of all patients were assessed and compared.Out of 180 patients [159 (88.3%) men and 21 (11.7%) women], 84 patients were in Group A, 64 in Group B and 32 in Group C. Characteristics like age, sex distribution and risk factors were similar in three groups. Significant coronary artery disease was seen in 77 (91.7%), 40 (62.5%) and in 25 (78.1%) patients in groups A, B and C respectively (p=0.02). Triple vessel disease was seen in 21 (25%), 11 (17.2%) and 5 (15.6%) patients in groups A, B and C respectively. Significant disease of left anterior descending artery was seen in 61 (72.6%), 26 (40.6%) and 23 (71.9%) in groups A, B and C respectively (p=0.001).Occurrence of both ST depression and angina during exercise treadmill test has strong association with angiographic coronary artery disease whereas occurrence of either of the two has similar association with angiographic coronary artery disease with a trend towards more disease in the latter.

To assess long-term survival and anticoagulant-related complications after mechanical valve replacement in adolescents with rheumatic heart disease, 88 patients aged ≤ 18 years were prospectively followed up for 10 years (404.2 patient-years). There were 58 (65.9%) boys and 30 (34.1%) girls, with a mean age of 15.4 ± 2.1 years. Mitral regurgitation was detected in 39 (44.3%) patients, and both mitral and aortic regurgitation in 15 (17%). Ball valves were inserted in 52 (59.1%) patients, bileaflet valves in 31 (35.2%), and single-disc valves in 5 (5.7%). There were 4 (4.5%) hospital deaths and 11 late deaths. Patient survival at 30 days, 3 months, 1, 5, and 10 years was 95.5%, 93.2%, 87.5%, 82.9%, and 82.9%, respectively. Mechanical valve thrombosis occurred in 4 patients; it was fatal in 3 of them. Three patients died from stroke. Severe hemorrhage required hospital admission in 4 (4.5%) patients. Mechanical valve replacement in adolescents, with careful follow-up and anticoagulation, has acceptable long-term results.