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Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and microalbuminuria.

ABSTRACT: AIMS/HYPOTHESIS:Patients with type 1 diabetes and microalbuminuria are at high risk of cardiovascular disease (CVD) and end-stage renal disease. Soluble Klotho is an anti-ageing circulating hormone involved in phosphate metabolism and vascular homeostasis through protective effects on the endothelium and antioxidant actions. The role of soluble Klotho in patients with type 1 diabetes and microalbuminuria is unknown. METHODS:In a cross-sectional single-centre study we evaluated the levels of circulating serum soluble Klotho in 33 participants with type 1 diabetes and a history of microalbuminuria (receiving renin-angiotensin system [RAS] inhibitors) and 45 participants with type 1 diabetes without a history of microalbuminuria (not receiving RAS or other antihypertensive drugs). All participants had an eGFR >45 ml/min, duration of diabetes >20 years and no history of CVD. Serum soluble Klotho levels were measured by a validated immunoassay. RESULTS:Participants with microalbuminuria had significantly lower levels of serum Klotho compared with those without microalbuminuria (median [interquartile range], 659.3 [525.3, 827.6] vs 787.7 [629.5, 1007]; p?=?0.023). This difference persisted after adjustment for variables including age and eGFR. In a subgroup of 30 individuals with and without microalbuminuria, other markers of phosphate balance were not significantly different. CONCLUSIONS/INTERPRETATION:In individuals with type 1 diabetes, microalbuminuria is associated with soluble Klotho deficiency. Further studies are required to determine whether soluble Klotho is causally related to the development of cardio-renal disease in type 1 diabetes.

SUBMITTER: Maltese G

PROVIDER: S-EPMC6518370 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and microalbuminuria.

Maltese Giuseppe G Fountoulakis Nikolaos N Siow Richard C RC Gnudi Luigi L Karalliedde Janaka J

Diabetologia 20170213 5

<h4>Aims/hypothesis</h4>Patients with type 1 diabetes and microalbuminuria are at high risk of cardiovascular disease (CVD) and end-stage renal disease. Soluble Klotho is an anti-ageing circulating hormone involved in phosphate metabolism and vascular homeostasis through protective effects on the endothelium and antioxidant actions. The role of soluble Klotho in patients with type 1 diabetes and microalbuminuria is unknown.<h4>Methods</h4>In a cross-sectional single-centre study we evaluated the ...[more]

PMID: 28194484

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Project description:Aims/hypothesisGiven its role in ovarian follicle development, circulating anti-Müllerian hormone (AMH) is considered to be a marker of reproductive ageing. Although accelerated reproductive ageing has been associated with a higher risk of type 2 diabetes, research on the relationship between AMH and type 2 diabetes risk is scarce. Therefore, we aimed to investigate whether age-specific AMH levels and age-related AMH trajectories are associated with type 2 diabetes risk in women.MethodsWe measured AMH in repeated plasma samples from 3293 female participants (12,460 samples in total), aged 20-59 years at recruitment, from the Doetinchem Cohort Study, a longitudinal study with follow-up visits every 5 years. We calculated age-specific AMH tertiles at baseline to account for the strong AMH-age correlation. Cox proportional hazards models adjusted for confounders were used to assess the association between baseline age-specific AMH tertiles and incident type 2 diabetes. We applied linear mixed models to compare age-related AMH trajectories for women who developed type 2 diabetes with trajectories for women who did not develop diabetes.ResultsDuring a median follow-up of 20 years, 163 women developed type 2 diabetes. Lower baseline age-specific AMH levels were associated with a higher type 2 diabetes risk (HRT2vsT3 1.24 [95% CI 0.81, 1.92]; HRT1vsT3 1.62 [95% CI 1.06, 2.48]; ptrend = 0.02). These findings seem to be supported by predicted AMH trajectories, which suggested that plasma AMH levels were lower at younger ages in women who developed type 2 diabetes compared with women who did not. The trajectories also suggested that AMH levels declined at a slower rate in women who developed type 2 diabetes, although differences in trajectories were not statistically significant.Conclusions/interpretationWe observed that lower age-specific AMH levels were associated with a higher risk of type 2 diabetes in women. Longitudinal analyses did not show clear evidence of differing AMH trajectories between women who developed type 2 diabetes compared with women who did not, possibly because these analyses were underpowered. Further research is needed to investigate whether AMH is part of the biological mechanism explaining the association between reproductive ageing and type 2 diabetes. Graphical abstract.

Dataset Information

Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and microalbuminuria.

Publications

Perturbations of the anti-ageing hormone Klotho in patients with type 1 diabetes and microalbuminuria.

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