Background: Effective prevention of type 2 diabetes (T2D) requires early identification of high-risk individuals who\nmight benefit from intervention. We sought to determine whether low serum testosterone, a novel risk factor for\nT2D in men, adds clinically meaningful information beyond current T2D risk models.\nMethods: The Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study population consists of\n2563 community-dwelling men aged 35ââ?¬â??80 years in Adelaide, Australia. Of the MAILES participants, 2038 (80.0 %)\nprovided information at baseline (2002ââ?¬â??2006) and follow-up (2007ââ?¬â??2010). After excluding participants with\ndiabetes (n = 317), underweight (n = 5), and unknown BMI status (n = 11) at baseline; and unknown diabetes\nstatus (n = 50) at follow-up; 1655 participants were followed for 5 years. T2D at baseline and follow-up was\ndefined by self-reported diabetes, or fasting plasma glucose (FPG) ââ?°Â¥7.0 mmol/L (126.1 mg/dL), or glycated\nhaemoglobin (HbA1c) ââ?°Â¥6.5 %, or diabetes medications. Risk models were tested using logistic regression\nmodels. Sensitivity, specificity, positive predictive values (PPV) were used to identify the optimal cut-off point for\nlow serum testosterone for incident T2D and the area under the receiver operating characteristic (AROC) curve\nwas used to summarise the predictive power of the model. 15.5 % of men had at least one missing predictor\nvariable; addressed through multiple imputation.\nResults: The incidence rate of T2D was 8.9 % (147/1655) over a median follow-up of 4.95 years (interquartile\nrange: 4.35-5.00). Serum testosterone level predicted incident T2D (relative risk 0.96 [95 % CI: 0.92,1.00], P = 0.032)\nindependent of current risk models including the AUSDRISK, but did not improve corresponding AROC\nstatistics. A cut-off point of <16 nmol/L for low serum testosterone, which classified about 43 % of men,\nreturned equal sensitivity (61.3 % [95 % CI: 52.6,69.4]) and specificity (58.3 % [95 % CI: 55.6,60.9) for predicting\nT2D risk, with a PPV of 12.9 % (95 % CI: 10.4,15.8).\nConclusions: Low serum testosterone predicts an increased risk of developing T2D in men over 5 years\nindependent of current T2D risk models applicable for use in routine clinical practice. Screening for low\nserum testosterone in addition to risk factors from current T2D risk assessment models or tools, including the\nAUSDRISK, would identify a large subgroup of distinct men who might benefit from targeted preventive\ninterventions.
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