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Background & objectives: With increasing number of people with diabetes worldwide, particularly in India, it is necessary to search for low cost screening methods. We compared the effectiveness and costs of screening for undiagnosed type 2 diabetes mellitus (T2DM), using oral glucose tolerance testing (OGTT) alone, or following a positive result from the Indian Diabetes Risk Score (IDRS) or following a positive result from genotyping of the TCF7L2 polymorphisms in Asian Indians. Methods: In subjects without known diabetes (n=961) recruited from the Chennai Urban Rural Epidemiology Study (CURES), OGTT, IDRS, and genotyping of rs12255372 (G/T) and rs7903146(C/T) of TCF7L2 polymorphisms were done. IDRS includes four parameters: age, abdominal obesity, family history of T2DM and physical activity. Results: OGTT identified 72 subjects with newly diagnosed diabetes (NDD), according to the World Health Organization criteria of fasting plasma glucose ≥ 126 mg/dl or a plasma glucose ≥ 200 mg/dl, 2 h after 75 g oral glucose load. IDRS screening (cut-off ≥ 60) yielded 413 positive subjects, which included 54 (75%) of the 72 NDD subjects identified by OGTT. Genotyping yielded 493 positive subjects which only included 36 (50%) of the 72 NDD subjects showing less discriminatory power. Screening with both SNPs missed 27 (37.5%) NDD subjects identified by IDRS. In contrast, IDRS missed only 9 (12.5%) of the NDD subjects identified by genotyping. Total screening cost for OGTT alone, or with IDRS were 384,400 and 182,810 respectively. Comparing OGTT alone to IDRS followed by OGTT, the incremental cost per additional NDD subject detected by doing OGTT on everyone was 11,199 (201,590 for detecting additional 18 NDD subjects). Interpretation & conclusions: For screening a population of subjects without diagnosed diabetes in India, a simple diabetes risk score is more effective and less expensive than genotyping or doing OGTT on the whole population. [ABSTRACT FROM AUTHOR]