scholarly journals Relationship between the FTO Genotype and Early Chronic Kidney Disease in Type 2 Diabetes: The Mediating Role of Central Obesity, Hypertension, and High Albuminuria

2021 ◽  
pp. 1-8
Author(s):  
Júlia Marchetti ◽  
Karla P. Balbino ◽  
Helen Hermana M. Hermsdorff ◽  
Leidjaira L. Juvanhol ◽  
José Alfredo Martinez ◽  
...  

<b><i>Introduction:</i></b> Single nucleotide polymorphisms (SNP) in the fat mass and obesity-associated (<i>FTO</i>) gene have been associated with type 2 diabetes (T2D) and its complications. The aim of the present research was to investigate which and how (directly or indirectly) clinical and metabolic variables mediate the association between fat mass and the <i>FTO</i> gene and early chronic kidney disease (CKD) in individuals with T2D. <b><i>Methods:</i></b> This cross-sectional study was conducted in a sample of 236 participants with T2D (53.4% women, mean age 60 ± 10 years). DNA samples were genotyped for the rs7204609 polymorphism (C/T) in the <i>FTO</i> gene. Clinical, anthropometric, and metabolic data were collected. Path analysis was used to evaluate the associations. <b><i>Results:</i></b> Of the sample, 78 individuals with T2D had CKD (33%). Presence of the risk allele (<i>C</i>) was higher among participants with CKD (21.8 vs. 10.8%; <i>p</i> = 0.023). This polymorphism was positively associated with higher waist circumference, which in turn was associated with higher glycated hemoglobin and higher blood pressure. A higher blood-pressure level was associated with higher urinary albumin excretion (UAE) and as expected, higher UAE was associated with CKD. Path analysis showed an indirect relationship between the <i>FTO</i> gene and early CKD, mediated by waist circumference, blood-pressure levels, and UAE. <b><i>Conclusions:</i></b> These findings suggest that the <i>C</i> allele may contribute to genetic susceptibility to CKD in individuals with T2D through the presence of central obesity, hypertension, and high albuminuria.

2017 ◽  
Vol 19 (11) ◽  
pp. 1570-1578 ◽  
Author(s):  
Antonio Ceriello ◽  
Salvatore De Cosmo ◽  
Maria Chiara Rossi ◽  
Giuseppe Lucisano ◽  
Stefano Genovese ◽  
...  

2019 ◽  
Vol 37 (4) ◽  
pp. 805-813 ◽  
Author(s):  
Francesca Viazzi ◽  
Barbara Bonino ◽  
Antonio Mirijello ◽  
Paola Fioretto ◽  
Carlo Giorda ◽  
...  

2020 ◽  
Vol 17 (4) ◽  
pp. 147916412094591
Author(s):  
Ji Hyun Lee ◽  
Ye An Kim ◽  
Young Lee ◽  
Woo-Dae Bang ◽  
Je Hyun Seo

Background: The effect of interarm blood pressure difference on the development of diabetic retinopathy, proteinuria and chronic kidney disease remains unknown. We investigated to determine the impact of interarm blood pressure difference on the prevalence of diabetic retinopathy, proteinuria and chronic kidney disease in patients with type 2 diabetes. Methods: The study included 563 patients with diabetes, who were evaluated with a simultaneous bilateral blood pressure measurement. The cutoff values for interarm blood pressure difference were 5, 10 and 15 mmHg. Logistic regression analysis was used to explore the relation between interarm blood pressure difference and diabetic retinopathy, proteinuria and chronic kidney disease. Results: Diabetic patients with systolic interarm blood pressure difference ⩾5, ⩾10 and ⩾15 mmHg showed an increased risk of diabetic retinopathy [adjusted odds ratio = 1.48 (95% confidence interval = 1.01–2.18), odds ratio = 1.80 (95% confidence interval = 0.99–3.22), odds ratio = 2.29 (95% confidence interval = 1.00–5.23)] after adjustment. There were significant associations between interarm blood pressure difference ⩾5 and ⩾10 mmHg and proteinuria [odds ratio = 1.68 (95% confidence interval = 1.15–2.44), 1.89 (95% confidence interval = 1.05–3.37)]. Conclusion: The association between interarm blood pressure difference and the presence of diabetic retinopathy emerged even for systolic interarm blood pressure difference ⩾5 mmHg without interaction of systolic blood pressure. Systolic interarm blood pressure difference should be considered a surrogate marker for vascular complication in patients with type 2 diabetes.


Author(s):  
Nan Ye ◽  
Meg J. Jardine ◽  
Megumi Oshima ◽  
Carinna Hockham ◽  
Hiddo J.L. Heerspink ◽  
...  

Background: People with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) experience a high burden of hypertension but the magnitude and consistency of blood pressure (BP) lowering with canagliflozin in this population is uncertain. Whether the effects of canagliflozin on kidney and cardiovascular outcomes vary by baseline BP or BP lowering therapy is also unknown. Methods: The CREDENCE trial randomized people with T2DM and CKD to canagliflozin or placebo. Post-hoc, we investigated the effect of canagliflozin on systolic BP across subgroups defined by baseline systolic BP, number of BP lowering drug classes, and history of apparent treatment-resistant hypertension (BP ≥130/80 mmHg while receiving ≥3 classes of BP lowering drugs, including a diuretic). We also assessed whether effects on clinical outcomes differed across these subgroups. Results: The trial included 4,401 participants of whom 3,361 (76.4%) had baseline systolic BP ≥130 mmHg, and 1371 (31.2%) had resistant hypertension. By week 3, canagliflozin reduced systolic BP by 3.50mmHg (95% CI, -4.27 to -2.72), an effect maintained over the duration of the trial, with similar reductions across BP and BP lowering therapy subgroups (all P-interaction ≥0.05). Canagliflozin also reduced the need for initiation of additional BP lowering agents during the trial (HR 0.68, 95% CI 0.61-0.75). The effect of canagliflozin on kidney failure, doubling of serum creatinine, or death due to kidney or cardiovascular disease (HR 0.70, 95% CI 0.59-0.82) was consistent across BP and BP lowering therapy subgroups (all P-interaction ≥0.35), as were effects on other key kidney, cardiovascular and safety outcomes. Conclusions: In people with T2DM and CKD, canagliflozin lowers systolic BP across all BP defined subgroups and reduces the need for additional BP lowering agents. These findings support use of canagliflozin for end-organ protection and as an adjunct BP lowering therapy in people with CKD. Clinical Trial Registration: URL: https://clinicaltrials.gov. Unique Identifier: NCT02065791.


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