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The risk of type 2 diabetes associated with overweight/obesity appears to be influenced by the co-existence of other metabolic
abnormalities. We compared the risk for diabetes in each of 4 categories of metabolic health and BMI. Participants were drawn
from the Cameron County Hispanic Cohort, a randomly selected Mexican American cohort in Texas on the US-Mexico border.
Subjects were divided into 4 phenotypes according to metabolic health and BMI: metabolically healthy normal weight, metabolically
healthy overweight/obese, metabolically unhealthy normal weight and metabolically unhealthy overweight/obese. Metabolic health
was defined as having less than 2 metabolic abnormalities. Overweight/obese status was assessed by BMI higher than 25 kg/m2.
Diabetes was defined by the 2010 ADA definition or by being on a diabetic medication. Among 3,247 participants, 878 were diagnosed
with diabetes. The odds ratio for diabetes risk was 2.25 in the metabolically healthy overweight/obese phenotype (95% CI 1.34, 3.79),
3.78 (95% CI 1.57, 9.09) in the metabolically unhealthy normal weight phenotype and 5.39 (95% CI 3.16, 9.20) in metabolically
unhealthy overweight/obese phenotype after adjusting for confounding factors compared with the metabolically healthy normal
weight phenotype. Cubic spline modeling showed that the risk of diabetes with age was higher in the metabolically unhealthy than
the metabolically healthy phenotype regardless of overweight/obesity status. Metabolically unhealthy subjects showed significantly
increased risk for diabetes compared with metabolically healthy subjects, regardless of their weight. Greater focus on metabolic health
appears to be a more effective target for prevention and control of diabetes than emphasis on weight loss alone.