title: Predictive value of serum testosterone for type 2 diabetes risk assessment in men.
abstract: BACKGROUND
  Effective 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.
  
  
  METHODS
  The 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.
  
  
  RESULTS
  The 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).
  
  
  CONCLUSIONS
  Low 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.
authors.affiliation: School of Nursing and Midwifery, Western Sydney University, Sydney, NSW, Australia. e.atlantis@westernsydney.edu.au.|School of Medicine, University of Adelaide, Adelaide, South Australia, Australia. e.atlantis@westernsydney.edu.au.
authors.forename: Evan
authors.initials: E
authors.lastname: Atlantis
authors.affiliation: School of Science and Health, Western Sydney University, Sydney, NSW, Australia.
authors.forename: Paul
authors.initials: P
authors.lastname: Fahey
authors.affiliation: School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.|Freemasons Foundation Centre for Men's Health, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Sean
authors.initials: S
authors.lastname: Martin
authors.affiliation: Chemical Pathology, SA Pathology, Adelaide, South Australia, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: O'Loughlin
authors.affiliation: Population Research and Outcome Studies, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Anne W
authors.initials: AW
authors.lastname: Taylor
authors.affiliation: School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Adams
authors.affiliation: Population Research and Outcome Studies, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Zumin
authors.initials: Z
authors.lastname: Shi
authors.affiliation: School of Medicine, University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: Gary
authors.initials: G
authors.lastname: Wittert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D001786:Blood Glucose; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis* / Q000453:epidemiology; D042241:Early Diagnosis; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D012680:Sensitivity and Specificity; D013739:Testosterone / Q000097:blood*
chemical_list: D001786:Blood Glucose; D013739:Testosterone
keywords: Cohort; Diabetes; Incidence; Prognosis; ROC; Screening; Testosterone