Association Between Uric Acid and Insulin-Like Growth Factor-1 in Type 2 Diabetes Mellitus

Liu, Fang; Wang, Yaru; Zhao, Qiang; Zhang, Mei; Ban, Bo

doi:10.2147/ijgm.s323579

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…[ 14 ] This condition is implicated in the underlying mechanism of hyperuricemia and the occurrence of diabetes, and it plays a crucial role in the pathogenesis of diabetes. [ 8 50 51 52 53 54 55 ] This finding supports the hypothesis that serum UA might be involved in the early stages of impaired glucose metabolism leading to prediabetes and accelerating the development of diabetes.…”

Section: Discussionsupporting

confidence: 75%

Association between serum uric acid with diabetes and other biochemical markers

Alasmary

Alqahtani

Awan³

et al. 2022

Journal of Family Medicine and Primary Care

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Objective: This study aimed to decipher the association between serum uric acid (UA) and glycated hemoglobin (HbA1c) in the population from the southern region of Saudi Arabia. Method: In this retrospective cross-sectional investigation, clinical data obtained from the different commercial laboratories in the Asir region of Saudi Arabia were screened over 2 years. Data were analyzed using standard statistical methods. Results: A total of 1984 laboratory investigations with 1215 females (61.2%) and 769 males (38.6%) were included in the data analysis. In our investigation, the prevalence of hyperuricemia in the study population was 53.5% (41.2% females and 12.3% males) and in the diabetic population was 12.7% (9.47% females and 3.23% males), in prediabetics was 12.65% (9.8% females and 2.85% males), respectively. Prediabetic subjects had higher UA levels than people with diabetes or healthy people. Higher UA quartiles were associated with a high level of urea, blood urea nitrogen (BUN) creatinine, HbA1c, fasting blood sugar (FBS), and total cholesterol (TC) ( P < 0.05). High UA (OR = 1.33 for diabetes; OR = 2.676 for prediabetes), high BUN (OR = 3.05 for diabetes; OR = 2.293 for prediabetes), high TC (OR = 3.75 for diabetes; OR = 1.098 for prediabetes), and high TG (OR = 2.67 for diabetes; OR = 1.943 for prediabetes) parameters are the most influential risk factor in diabetic and prediabetic patients than the people who have normal UA, BUN, TC, and TG value. Conclusion: High UA levels are significantly associated with prediabetes as defined by HbA1c criteria, indicating that UA has a significant role in the disturbance of glucose metabolism. A significant positive association was observed between dyslipidemia and serum UA in the study population.

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Section: Discussionsupporting

confidence: 75%

Association between serum uric acid with diabetes and other biochemical markers

Alasmary

Alqahtani

Awan³

et al. 2022

Journal of Family Medicine and Primary Care

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“…However, we did not find a causal effect of serum urate on the markers of systematic inflammation. Previous studies have observed the associations between serum urate and serum inflammation indicators ( 13 , 61 , 62 ). Our study indicates that these associations are not causal.…”

Section: Discussionmentioning

confidence: 95%

Associations between serum urate and telomere length and inflammation markers: Evidence from UK Biobank cohort

Cui²,

Zhang³

2022

Front. Immunol.

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ObjectiveHyperuricemia and gout have become gradually more common. The effect of serum urate on organism aging and systematic inflammation is not determined. This study aims to evaluate whether serum urate is causally associated with cellular aging markers and serum inflammation markers.MethodsA Mendelian randomization study was performed on summary-level data from the largest published genome-wide association studies. Single nucleotide polymorphisms with a genome-wide significance level were selected as instrumental variables for leukocyte telomere length (LTL), and serum soluble makers of inflammation (CRP, IL-6, TNF-α, and IGF-1). Standard inverse variance weighted (IVW) method was used as the primary statistical method. The weighted median, MR-Egger regression, and MR-PRESSO methods were used for sensitivity analysis.ResultsAn inverse causal association of genetically predicted serum urate levels and LTL was found using IVW method (OR: 0.96, 95%CI 0.95, 0.97; β=-0.040; SE=0.0072; P=4.37×10-8). The association was also supported by MR results using MR-Egger method and weighted median method. The MR-PRESSO analysis and leave-one-out sensitivity analysis supported the robustness of the combined results. In terms of other aging-related serum biomarkers, there was no evidence supporting a causal effect of serum urate on CRP, IL-6, TNF-α, or IGF-1 levels.ConclusionsSerum urate levels are negatively associated with telomere length but are not associated with serum soluble indicators of inflammation. Telomere length may be a critical marker that reflects urate-related organismal aging and may be a mechanism in the age-related pathologies and mortality caused by hyperuricemia.

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“…Negative and nonlinear correlations between IGF-1 and UA levels have however been reported in nondiabetic and T2DM adults. 66,67 IGF-1 also inhibits secretion of insulin, 6 and insulin reduces renal fractional excretion of urate [68][69][70] by stimulating urate transport through GLUT9a and other reabsorptive urate transporters. 65 We hypothesized that IGF-1 also exerts direct effects on urate transport mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Genetic and Physiological Effects of Insulin-Like Growth Factor-1 (IGF-1) on Human Urate Homeostasis

Mandal

Leask

Sumpter

et al. 2023

JASN

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Background Metabolic syndrome and hyperinsulinemia are associated with hyperuricemia. Insulin infusion in healthy volunteers elevates serum urate (SU) by activating net urate reabsorption in the renal proximal tubule, whereas IGF-1 infusion reduces SU by mechanisms unknown. Variation within the IGF1R gene also affects SU levels.Methods Colocalization analyses of a SU genome-wide association studies signal at IGF1R and expression quantitative trait loci signals in cis using COLOC2, RT-PCR, Western blotting, and urate transport assays in transfected HEK 293T cells and in Xenopus laevis oocytes.Results Genetic association at IGF1R with SU is stronger in women and is mediated by control of IGF1R expression. Inheritance of the urate-lowering homozygous genotype at the SLC2A9 locus is associated with a differential effect of IGF1R genotype between men and women. IGF-1, through IGF-1R, stimulated urate uptake in human renal proximal tubule epithelial cells and transfected HEK 293T cells, through activation of IRS1, PI3/Akt, MEK/ERK, and p38 MAPK; urate uptake was inhibited in the presence of uricosuric drugs, specific inhibitors of protein tyrosine kinase, PI3 kinase (PI3K), ERK, and p38 MAPK. In X. laevis oocytes expressing ten individual urate transporters, IGF-1 through endogenous IGF-1R stimulated urate transport mediated by GLUT9, OAT1, OAT3, ABCG2, and ABCC4 and inhibited insulin's stimulatory action on GLUT9a and OAT3. IGF-1 significantly activated Akt and ERK. Specific inhibitors of PI3K, ERK, and PKC significantly affected IGF-1 stimulation of urate transport in oocytes. ConclusionsThe combined results of infusion, genetics, and transport experiments suggest that IGF-1 reduces SU by activating urate secretory transporters and inhibiting insulin's action.

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Association Between Uric Acid and Insulin-Like Growth Factor-1 in Type 2 Diabetes Mellitus

Cited by 7 publications

References 28 publications

Association between serum uric acid with diabetes and other biochemical markers

Association between serum uric acid with diabetes and other biochemical markers

Associations between serum urate and telomere length and inflammation markers: Evidence from UK Biobank cohort

Genetic and Physiological Effects of Insulin-Like Growth Factor-1 (IGF-1) on Human Urate Homeostasis

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