Abstract
BackgroundEffective prevention of type 2 diabetes (T2D) requires early identification of high-risk individuals who might benefit from intervention. We sought to determine whether low serum testosterone, a novel risk factor for T2D in men, adds clinically meaningful information beyond current T2D risk models.MethodsThe Men Androgen Inflammation Lifestyle Environment and Stress (MAILES) study population consists of 2563 community-dwelling men aged 35–80 years in Adelaide, Australia. Of the MAILES participants, 2038 (80.0 %) provided information at baseline (2002–2006) and follow-up (2007–2010). After excluding participants with diabetes (n = 317), underweight (n = 5), and unknown BMI status (n = 11) at baseline; and unknown diabetes status (n = 50) at follow-up; 1655 participants were followed for 5 years. T2D at baseline and follow-up was defined by self-reported diabetes, or fasting plasma glucose (FPG) ≥7.0 mmol/L (126.1 mg/dL), or glycated haemoglobin (HbA1c) ≥6.5 %, or diabetes medications. Risk models were tested using logistic regression models. Sensitivity, specificity, positive predictive values (PPV) were used to identify the optimal cut-off point for low serum testosterone for incident T2D and the area under the receiver operating characteristic (AROC) curve was used to summarise the predictive power of the model. 15.5 % of men had at least one missing predictor variable; addressed through multiple imputation.ResultsThe incidence rate of T2D was 8.9 % (147/1655) over a median follow-up of 4.95 years (interquartile range: 4.35-5.00). Serum testosterone level predicted incident T2D (relative risk 0.96 [95 % CI: 0.92,1.00], P = 0.032) independent of current risk models including the AUSDRISK, but did not improve corresponding AROC statistics. A cut-off point of <16 nmol/L for low serum testosterone, which classified about 43 % of men, returned equal sensitivity (61.3 % [95 % CI: 52.6,69.4]) and specificity (58.3 % [95 % CI: 55.6,60.9) for predicting T2D risk, with a PPV of 12.9 % (95 % CI: 10.4,15.8).ConclusionsLow serum testosterone predicts an increased risk of developing T2D in men over 5 years independent of current T2D risk models applicable for use in routine clinical practice. Screening for low serum testosterone in addition to risk factors from current T2D risk assessment models or tools, including the AUSDRISK, would identify a large subgroup of distinct men who might benefit from targeted preventive interventions.
Highlights
Effective prevention of type 2 diabetes (T2D) requires early identification of high-risk individuals who might benefit from intervention
Additional screening for low serum testosterone would identify a large group of distinct men who might benefit from targeted preventive interventions
It is generally accepted that people with diagnosed T2D have progressed from ‘pre-diabetes’; an intermediate stage of impaired glucose regulation defined by impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) [4]
Summary
Effective prevention of type 2 diabetes (T2D) requires early identification of high-risk individuals who might benefit from intervention. Preventing the rising prevalence of T2D in highincome countries like Australia, where healthcare expenditure for diabetes is among the highest in the world [1], could yield significant health and economic benefits [3]. Effective lifestyle programs targeting modifiable risk factors in people with pre-diabetes may delay or prevent the onset of T2D. Large-scale trials from Finland [10], China [11], and the United States [12] showed that lifestyle intervention can effectively halve the risk of developing T2D in people with pre-diabetes over three to six years
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