Sex hormone levels are not associated with progression of renal disease in male patients with T2DM - 23/06/16

Doi : 10.1016/j.diabet.2016.05.012

E. Feigerlová ^a,^b,^c,^⁎ , P.-J. Saulnier ^c, P. Gourdy ^d,^e,^f, R. Roussel ^g,^h,ⁱ, J.-M. Halimi ^j,^k, E. Gand ^a, D. Dardari ^l, B. Guerci ^m, P. Sosner ^n,^o, M. Marre ^g,^h,ⁱ, P. Zaoui ^p,^q, S. Ragot ^c, S. Hadjadj ^a,^b,^c
for the DIAB 2 NEPHROGENE, SURDIAGENE Study Groups
^a CHU de Poitiers, Service d’Endocrinologie, Pole DUNE, 86021 Poitiers, France
^b Université de Poitiers, UFR Médecine Pharmacie, 86021 Poitiers, France
^c Inserm, CIC 1402 & U1082, 86021 Poitiers, France
^d CHU de Toulouse, Service de Diabétologie, Maladies Métaboliques et Nutrition, 31059 Toulouse, France
^e Inserm, UMR1048/I2MC, 31059 Toulouse, France
^f Université Paul-Sabatier, UMR1048/I2MC, 31059 Toulouse, France
^g Université Paris Diderot, Sorbonne Paris Cité, 75013 Paris, France
^h Inserm, UMRS1138, Centre de Recherche des Cordeliers, 75006 Paris, France
ⁱ AP–HP, Hôpital Bichat, Diabétologie, Endocrinologie Nutrition, DHU FIRE, 75018 Paris, France
^j CHU de Tours, Service Néphrologie, Dialyse et Transplantation, 37000 Tours, France
^k Inserm, Centre d’Investigation Clinique 0202, 37000 Tours, France
^l Hospital of Sud Francilien, Endocrinology Department, 91100 Corbeil-Essonnes, France
^m CHU de Nancy, Service d’Endocrinologie, 54511 Vandoeuvre-lès-Nancy, France
ⁿ Complexe médico-sportif Mon-Stade, 75013 Paris, France
^o Université de Poitiers, Laboratoire MOVE (EA 6314), 86021 Poitiers, France
^p CHU de Grenoble, Service Néphrologie, Dialyse et Transplantation, 38700 Grenoble, France
^q Université Joseph-Fournier, Faculté de Médecine, 38700 Grenoble, France

^⁎Corresponding author at: CHU de Poitiers, Service d’Endocrinologie, Pole DUNE, 86021 Poitiers, France.

En prensa. Pruebas corregidas por el autor. Disponible en línea desde el Thursday 23 June 2016
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Abstract

Background

Greater renal function decline (RFD) in type 2 diabetes (T2DM) has been suggested in men compared with women, and imbalances in estrogen/androgen levels have been associated with cardiovascular disease mortality in elderly men, but it remains unclear whether sex hormone disequilibrium is related to diabetic nephropathy (DN) in men with T2DM.

Objective

This study examined the relationship between sex steroid concentrations and renal outcomes in male T2DM patients.

Population and methods

Total testosterone (T), total estradiol (E2), sex hormone-binding globulin (SHBG), and total and calculated free (cf) E2/T ratios were compared in 735 male T2DM patients with (n=513) and without (n=222) DN, using a cross-sectional approach. Also, in a pilot complementary prospective nested case-control cohort, total E2/total T and cfE2/cfT were evaluated according to a hard renal outcome (HRO): end-stage renal disease/doubling of baseline serum creatinine (36 HRO cases, 72 HRO controls) and rate of eGFR decline (68 rapid vs 68 slow RFD).

Result

With the cross-sectional approach, E2 and cfE2 were higher in DN cases vs DN controls (95.5 vs 86.8pmol/L [P=0.0246] and 2.59 vs 2.36pmol/L [P=0.005], respectively). The difference in E2 persisted on multivariate analysis. In the prospective approach, E2 and T concentrations, and total E2/total T and cfE2/cfT2 ratios did not differ in HRO cases vs controls or in patients with rapid vs slow RFD.

Conclusion

Although positively related to DN in the cross-sectional analysis, progression of renal disease in male patients with T2DM was not related to either sex hormone levels or aromatase index as reflected by E2/T ratio.

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Keywords : Aromatase index, Diabetic nephropathy, Estradiol, Testosterone, Type 2 diabetes

Abbreviations : cfE2, cfT, E2, ERα, eGFR, ESRD, HRO, RRFD, SHBG, SRFD, T, UAC, uACR, UAE