Klotho levels: association with insulin resistance and albumin-to-creatinine ratio in type 2 diabetic patients

Silva, Ana Paula; Mendes, Filipa; Pereira, Luísa Helena; André, Fabrice; Gonçalves, Rui Baptista; Santos, Nélio; Rato, Fátima; Neves, Pedro Leão

doi:10.1007/s11255-017-1646-3

Cited by 24 publications

(24 citation statements)

References 22 publications

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“…α-Klotho is stimu lated by 1,25(OH) 2 VD 3 and inhibited by FGF-23 thereby creating an endocrine loop, as circulating Klotho can activate FGF-23-FGFR signaling. 42 In the majority of clinical studies CKD has been described has a state of FGF-23 resistance due to endocrine and renal Klotho deficiency. 43 In this study, lower levels of Klotho seem to be an independent pre dictive factor for bone fracture, in T2DM patients with CKD.…”

Section: Discussionmentioning

confidence: 99%

FGF23-klotho axis as predictive factors of fractures in type 2 diabetics with early chronic kidney disease

Ribeiro

Mendes

Carias

et al. 2020

Journal of Diabetes and its Complications

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Background: The aim of our study was to evaluate the relevance of FGF23-klotho axis in the predisposition for bone fractures in type 2 diabetic patients with early chronic kidney disease. Methods: In a prospective study we included 126 type 2 diabetic patients with CKD stages 2-3 (from 2010 to 2017). We used descriptive statistics, ANOVA and chi-square test. Our population was divided into two groups according to the occurrence of a bone fracture event or not, and the groups were compared considering several biological and laboratorial parameters. We employed a multiple regression model to identify risk factors for bone fracture events and hazard ratios (HR) were calculated using a backward stepwise likelihood ratio (LR) Cox regression. Results: Patients with a fracture event displayed higher levels of FGF-23, Phosphorus, PTH, TNF-α, OxLDL, HOMA-IR, calcium × phosphorus product and ACR and lower levels of Osteocalcin, α-Klotho, 25(OH)D3 and eGFR compared with patients without a fracture event (p b 0.001). The number of patients with a fracture event was higher than expected within inclining CKD stages (χ2, p = 0.06). The occurrence of fracture and the levels of TNF-α, klotho, 25(OH)D3 and OxLDL were found to predict patient entry into RRT (p b 0.05). Age, osteocalcin, α-Klotho and FGF-23 independently influenced the occurrence of bone fracture (p b 0.05). Conclusions: α-Klotho and FGF-23 levels may have a good clinical use as biomarkers to predict the occurrence of fracture events.

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Section: Discussionmentioning

confidence: 99%

FGF23-klotho axis as predictive factors of fractures in type 2 diabetics with early chronic kidney disease

Ribeiro

Mendes

Carias

et al. 2020

Journal of Diabetes and its Complications

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“…Klotho is a peptide that affects the parathyroid gland and kidney via FGF23. Recently, klotho has been reported to affect insulin resistance 40 . Inhibition of tyrosine phosphorylation on insulin receptors and enhancement of glucose-induced insulin secretion through transient receptor potential V2 (TRPV2) are regarded as the mechanisms underlying the association between klotho and insulin resistance 41 .…”

Section: Discussionmentioning

confidence: 99%

Association between resistin and fibroblast growth factor 23 in patients with type 2 diabetes mellitus

Nakashima

Yokoyama

Kawanami

et al. 2018

Sci Rep

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Fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease and all-cause mortality in patients with diabetes mellitus. Insulin resistance has recently been reported to increase FGF23 levels, and resistin is a peptide that mainly regulates insulin resistance. However, few studies have investigated the association between FGF23 and resistin. A total of 422 patients with diabetes mellitus were recruited for this cross-sectional study to examine the association between resistin and intact FGF23. The mean ( ± standard deviation) age was 63.1 ± 11.9 years, and the median HbA1c was 6.7% (range, 6.1–7.1%). The mean estimated glomerular filtration rate (eGFR) was 66.2 ± 23.1 mL/min/m2. Multiple regression analysis for resistin showed that logFGF23 (coefficient (Coef): 1.551; standard error (SE): 0.739; P = 0.036), C-peptide (Coef: 0.798; SE: 0.229; P = 0.001), ghrelin (Coef: 1.061; SE: 0.332; P = 0.001), intact parathyroid hormone (Coef: 0.022; SE: 0.099; P = 0.030), and eGFR (Coef: −0.091; SE: 0.017; P < 0.001) were all significantly associated with the resistin level. These associations were modified in patients with higher age, lower body mass index, and higher vitamin D levels. These results suggest that resistin is positively associated with serum FGF23 levels.

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“…The literature reports that protein concentrations from the fibroblast growth factor family are increased in first-degree relatives of DM2 patients with pre-diabetes and that there is a strong association between fibroblast growth factor 21 (FGF 21) and obesity and insulin sensitivity [55]. We know that Klotho levels among patients with type 1 diabetes mellitus might be affected by renal impairment, hyperglycaemia, and high insulin doses [56]. It is possible that the Klotho protein synthesised in the pancreas plays a completely different role from the known one.…”

Section: Discussionmentioning

confidence: 99%

“…Literatura donosi, że stężenia białek z rodziny czynników wzrostu fibroblastów są zwiększone u krewnych pierwszego stopnia chorych na CT2 ze stanem przedcukrzycowym i że istnieje silny związek między stężeniem czynnika wzrostu fibroblastów 21 (FGF21) a otyłością i wrażliwością na insulinę [55]. Wiemy także, że na poziom Klotho u pacjentów z CT1 może wpływać niewydolność nerek, hiperglikemia i wysokie dawki insuliny [56]. Możliwe jest także, że syntetyzowane w trzustce białko Klotho pełni funkcję zupełnie inną od poznanej.…”

Section: Streszczenieunclassified

Klotho protein function among patients with type 1 diabetes

Flotyńska

Uruska

Araszkiewicz

et al. 2018

Endokrynologia Polska

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The fibroblast growth factor 23 (FGF23) and Klotho system play a very important role in the regulation of the human body metabolism. On the one hand, they promote longevity, and on the other hand they promote insulin resistance. Nowadays, accelerated aging in diabetes as the main consequence of chronic complications of the disease is postulated. Signalling pathways induced by insulin, insulin-like growth factor (IGF-1), and their homologues play an important role in controlling the aging process. Because FGF23/Klotho system affects glucose metabolism and gene expression of antioxidant enzymes, changes in its concentration may be a marker of chronic complications of diabetes or a treatment option. Despite huge improvements in the treatment of diabetes, its chronic complications remain an important clinical problem. An interesting issue is the relationship between the concentration of FGF23/Klotho and management of the disease, duration, insulin resistance, and development of complications in type 1 diabetes. (Endokrynol Pol 2018; 69 (6): 696-704)

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Klotho levels: association with insulin resistance and albumin-to-creatinine ratio in type 2 diabetic patients

Abstract: Our results showed that Klotho levels are influenced by FGF23, vitamin D and insulin resistance. This suggests that Klotho levels might be affected by renal function as well as having a relevant role on insulin metabolism and ACR homeostasis.

Cited by 24 publications

References 22 publications

FGF23-klotho axis as predictive factors of fractures in type 2 diabetics with early chronic kidney disease

FGF23-klotho axis as predictive factors of fractures in type 2 diabetics with early chronic kidney disease

Association between resistin and fibroblast growth factor 23 in patients with type 2 diabetes mellitus

Klotho protein function among patients with type 1 diabetes

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