Association between serum Klotho levels and the prevalence of diabetes among adults in the United States

Wang, Kai; Mao, Yu; Lu, Miao; Liu, Xianling; Sun, Yan V.; Li, Zhong‐Ming; Li, Yansong; Ding, Yongfang; Zhang, Jing; Hong, Jian; Xu, Di

doi:10.3389/fendo.2022.1005553

Cited by 32 publications

(22 citation statements)

References 49 publications

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“…However, only a few clinical studies have shown associations between FGF23, α-klotho and various indexes related to T2DM, including insulin resistance (measured by homeostasis model assessment of insulin resistance), dyslipidemia, resistin levels, and obesity status, suggesting that an imbalance in the FGF23/α-klotho axis may result in an unfavorable lipid profile, which could contribute to the development or progression of both T2DM and atherosclerosis [ 31 – 33 ]. Although several studies have shown a negative correlation between α-klotho and diabetes [ 34 , 35 ], recent published studies have ruled out this association [ 28 , 36 ]. The present study demonstrated positive correlations between serum FGF23 levels and FGF23/α-klotho ratio with T2DM and a negative correlation between serum α-klotho levels and T2DM.…”

Section: Discussionmentioning

confidence: 99%

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus

Bi,

Zheng,

et al. 2024

Cardiovasc Diabetol

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Background Compelling evidence suggests that calcium/phosphorus homeostasis-related parameters may be linked to diabetes mellitus and cardiovascular events. However, few studies have investigated the association of fibroblast growth factor 23 (FGF23), α-klotho and FGF23/α-klotho ratio with atherosclerosis in patients with type 2 diabetes mellitus (T2DM). Objective This study was designed to evaluate whether FGF23, α-klotho and FGF23/α-klotho ratio are associated with T2DM and further to explore the relationships between these three factors and atherosclerosis in Chinese patients with T2DM. Methods Serum FGF23 and α-klotho levels were measured via an enzyme-linked immunosorbent assay (ELISA) kit, and the carotid intima-media thickness (CIMT) was assessed via high-resolution color Doppler ultrasonography. The associations of serum FGF23, α-klotho and FGF23/α-klotho ratio with atherosclerosis in T2DM patients were evaluated using multivariable logistic regression models. Results This cross-sectional study involved 403 subjects (207 with T2DM and 196 without T2DM), 41.7% of the patients had atherosclerosis, and 67.2% of the carotid intima were thickened to a thickness greater than 0.9 mm. Compared with those in the lowest tertile, higher tertiles of FGF23 levels and FGF23/α-klotho ratio were positively associated with T2DM after adjusting for covariates, and serum α-klotho concentration was inversely correlated with T2DM (all P values < 0.01). Moreover, elevated serum FGF23 levels and FGF23/α-klotho ratio were positively associated with CIMT and carotid atherosclerosis in T2DM patients (all P values < 0.01). Further spline analysis similarly revealed linear dose‒response relationship (all P values < 0.01). And there was still significant differences in CIMT and carotid atherosclerosis between the highest group of α-klotho and the reference group in T2DM patients (P values = 0.05). Conclusions T2DM was positively linearly related to serum FGF23 concentration and FGF23/α-klotho ratio, and negatively correlated with serum α-klotho concentration. Furthermore, both FGF23 and FGF23/α-klotho ratio were positively correlated with CIMT and atherosclerosis in T2DM patients, while α-klotho was inversely correlated with both CIMT and atherosclerosis, although the associations were not completely significant. Prospective exploration and potential mechanisms underlying these associations remain to be further elucidated.

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Section: Discussionmentioning

confidence: 99%

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus

Bi,

Zheng,

et al. 2024

Cardiovasc Diabetol

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“…In mobile examination centers (MECs), blood samples of participants with obtained consent were collected in the morning after fasting for at least 9 h [ 16 ]. The samples were packaged on dry ice and then stored at -80 °C for further analysis.…”

Section: Methodsmentioning

confidence: 99%

Correlation between serum α-Klotho levels and different stages of periodontitis

Bao

Yan

et al. 2023

BMC Oral Health

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Background Periodontitis is an inflammatory disease characterized by inflammation and progressive destruction of periodontal tissues including alveolar bone. α-klotho protein is a multifunctional protein related to age-related diseases, inflammatory diseases, and bone metabolism-related diseases. However, large-sample epidemiological research evidence on the correlation between α-Klotho and the aggravation of periodontitis stages is still lacking. Methods Cross-sectional study data of participants aged between 40 and 79 years in the National Health and Nutrition Examination Survey 2013‒2014 were selected and analyzed. The stages of periodontitis of the participants were determined according to the 2018 World Workshop Classification of Periodontal and Peri-implant Diseases. The serum α-Klotho levels in people with periodontitis in different stages were evaluated. Then the correlation between serum α-Klotho levels and different stages of periodontitis was analyzed by multiple linear regression (stepwise regression method). Results A total of 2378 participants were included in the study. The serum α-Klotho levels in people with stage I/II, III and IV periodontitis were 896.16 ± 304.84, 871.08 ± 266.42 and 840.52 ± 286.24 pg/mL, respectively. The levels of α-Klotho in people with stage IV periodontitis were significantly lower than those in people with stage I/II and III periodontitis. Linear regression analysis results showed that compared to stage I/II periodontitis, serum α-Klotho levels were significantly negatively correlated with stage III (B ± SE = -37.28 ± 16.00, 95% CI: -68.66 ~ -25.91, P = 0.020) and stage IV (B ± SE = -69.37 ± 16.11, 95% CI: -100.97 ~ -37.77, P < 0.001) periodontitis. Conclusion The serum α-Klotho levels were negatively correlated with the severity of periodontitis. With the aggravation of periodontitis stages, the serum α-Klotho levels gradually decreased.

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“…[6][7][8][9][10] It also contributes to the regulation of glucose metabolism and holds promise as a new therapeutic target for diabetes. [11,12] Although numerous studies suggest a close relationship between Klotho and the progression of T2DM and insulin sensitivity impairment, [13][14][15] the connection between Klotho and insulin resistance remains incompletely elucidated. Therefore, the objective was to explore the link between serum Klotho levels and insulin resistance, utilizing data from the National Health and Nutrition Examination Survey (NHANES) covering the years 2007 to 2016.…”

Section: Introductionmentioning

confidence: 99%

Serum Klotho and insulin resistance: Insights from a cross-sectional analysis

Yan,

Hu,

et al. 2024

Medicine

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The prevalence of diabetes has surged globally, posing significant health and economic burdens. Insulin resistance underlies the initiation and development of type 2 diabetes. Klotho is a crucial endogenous antiaging factor, associated with atherosclerotic cardiovascular diseases, cancer, neurological disorders, and renal diseases. It additionally has a function in controlling glucose metabolism and holds promise as a new therapeutic target for diabetes. However, its relationship with insulin resistance remains unclear. This study utilizes the National Health and Nutrition Examination Survey (NHANES) 2007 to 2016 data to investigate the relationship between serum Klotho concentrations and insulin resistance. In this observational study, information from the NHANES spanning 2007 to 2016 was employed. The sample consisted of 6371 participants. Weighted linear regression model and chi-square tests were utilized to assess differences in continuous and categorical variables, respectively, among groups categorized by Klotho quartiles. The relationship between Klotho and HOMA-IR (homeostatic model assessment of insulin resistance) was studied using multiple linear regression. Smooth curve fitting was used to analyze nonlinear relationships and the inflection point was determined through a 2-stage linear regression method. After adjusting for multiple confounding factors, serum Klotho levels were found to be positively correlated with insulin resistance [0.90 (0.68, 1.13)]. This correlation is nonlinear and exhibits a saturation effect, with the inflection point identified at 1.24 pg/µL. When Klotho levels are below 1.24 pg/µL, for every unit increase in Klotho, HOMA-IR increases by 1.30 units. Conversely, when Klotho levels exceed 1.24 pg/µL, there is no correlation between HOMA-IR and Klotho. Subgroup analysis reveals that the relationship between HOMA-IR and Klotho varies depending on diabetes and body mass index (BMI). This positive correlation was most prominent in the obese nondiabetic population. There is a positive correlation between serum Klotho and insulin resistance.

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Association between serum Klotho levels and the prevalence of diabetes among adults in the United States

Cited by 32 publications

References 49 publications

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus

Relationships of serum FGF23 and α-klotho with atherosclerosis in patients with type 2 diabetes mellitus

Correlation between serum α-Klotho levels and different stages of periodontitis

Serum Klotho and insulin resistance: Insights from a cross-sectional analysis

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