Mediation analysis of the testosterone treatment effect to prevent type 2 diabetes in the Testosterone for Prevention of Type 2 Diabetes Mellitus trial

被引:13
|
作者
Robledo, Kristy P. [1 ,18 ]
Marschner, Ian C. [1 ]
Handelsman, David J. [2 ,3 ]
Bracken, Karen [1 ]
Stuckey, Bronwyn G. A. [4 ,5 ]
Yeap, Bu B. [6 ,7 ]
Inder, Warrick [8 ,9 ]
Grossmann, Mathis [10 ,11 ]
Jesudason, David [12 ,13 ]
Allan, Carolyn A. [14 ,15 ,16 ]
Wittert, Gary [17 ]
机构
[1] Univ Sydney, NHMRC Clin Trials Ctr, Locked bag 77, Camperdown, NSW 1450, Australia
[2] Univ Sydney, ANZAC Res Inst, Androl Lab, Concord, NSW 2139, Australia
[3] Concord Hosp, Androl Dept, Concord, NSW 2139, Australia
[4] Univ Western Australia, Keogh Inst Med Res, Med Sch, Perth, WA 6009, Australia
[5] Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia
[6] Univ Western Australia, Med Sch, Perth, WA 6009, Australia
[7] Fiona Stanley Hosp, Dept Endocrinol & Diabet, Murdoch, WA 6150, Australia
[8] Princess Alexandra Hosp, Diabet & Endocrinol Dept, Woolloongabba, Qld 4102, Australia
[9] Univ Queensland, Sch Med, St Lucia, Qld 4072, Australia
[10] Austin Hosp, Dept Endocrinol, Heidelberg, Vic 3084, Australia
[11] Univ Melbourne, Dept Med, Parkville, Vic 3010, Australia
[12] Univ Adelaide, Sch Med, Adelaide, SA 5005, Australia
[13] Queen Elizabeth Hosp, Endocrinol Unit, Woodville South, SA 5011, Australia
[14] Hudson Inst Med Res, Ctr Endocrinol & Metab, Clayton, Vic 3168, Australia
[15] Monash Univ, Sch Clin Sci, Clayton, Vic 3800, Australia
[16] South Australian Hlth Med Res Inst, Freemasons Ctr Male Hlth & Wellbeing, Adelaide, SA 5000, Australia
[17] Univ Adelaide, Sch Med, Adelaide, SA 5005, Australia
[18] 92-94 Parramatta Rd, Camperdown, NSW 2050, Australia
基金
英国医学研究理事会;
关键词
mediation analysis; testosterone; diabetes; glucose; NATURAL DIRECT; GLUCOSE-METABOLISM; DOUBLE-BLIND; MUSCLE; STRENGTH; LIFE; MEN; 17-BETA-ESTRADIOL; BINDING; MASS;
D O I
10.1093/ejendo/lvad074
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective To determine if testosterone treatment effect on glycaemia is mediated through changes in total fat mass, abdominal fat mass, skeletal muscle mass, non-dominant hand-grip, oestradiol (E2), and sex hormone-binding globulin (SHBG). Design Mediation analysis of a randomised placebo-controlled trial of testosterone. Methods Six Australian tertiary care centres recruited 1007 males, aged 50-74 years, with waist circumference & GE;95 cm, serum total testosterone & LE;14 nmol/L (immunoassay), and either impaired glucose tolerance or newly diagnosed type 2 diabetes on an oral glucose tolerance test (OGTT). Participants were enrolled in a lifestyle programme and randomised 1:1 to 3 monthly injections of 1000 mg testosterone undecanoate or placebo for 2 years. Complete data were available for 709 participants (70%). Mediation analyses for the primary outcomes of type 2 diabetes at 2 years (OGTT & GE; 11.1 mmol/L and change in 2-h glucose from baseline), incorporating potential mediators: changes in fat mass, % abdominal fat, skeletal muscle mass, non-dominant hand-grip strength, E2, and SHBG, were performed. Results For type 2 diabetes at 2 years, the unadjusted OR for treatment was 0.53 (95% CI:.35-.79), which became 0.48 (95% CI:.30-.76) after adjustment for covariates. Including potential mediators attenuated the treatment effect (OR 0.77; 95% CI:.44-1.35; direct effect) with 65% mediated. Only fat mass remained prognostic in the full model (OR: 1.23; 95% CI: 1.09-1.39; P < .001). Conclusion At least part of the testosterone treatment effect was found to be mediated by changes in fat mass, abdominal fat, skeletal muscle mass, grip strength, SHBG, and E2, but predominantly by changes in fat mass.
引用
收藏
页码:613 / 620
页数:8
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