RESUMO
Type 1 Diabetes Mellitus (T1DM) can generate severe complications, such as Diabetic Kidney Disease (DKD) or Diabetic Nephropathy (DN), with it emerging as the leading cause of terminal (end-stage) renal disease all over the world. For T1DM, the clinical evaluation of DKD uses markers like the Glomerular Filtration Rate (GFR) and the Urinary Albumin Excretion (UAE). However, early diagnosis of DKD is still a challenge. For this reason, investigating molecular markers, such as microRNAs (miRNAs), offers a promising perspective to an early diagnosis, highlighting the stability and the ability to reflect incipient molecular manifestations. Thus, here we investigated four miRNAs (hsa-let-7i-5p, hsa-miR-143-3p, hsa-miR-501-3p, and hsa-miR-100-5p) regarding nephropathy in patients with T1DM, considering the albuminuria (micro and macro) as a standard to evaluate the groups. As a result, we found a reduced expression of miR-100-5p in patients with MIC, indicating a protective role in nephropathy. Beyond that, expression levels between the groups (Non vs. UAE) were not significant when comparing the miRNAs miR-501-3p and miR-143-3p. Finally, miR-143-3p and miR-100-5p were linked to some target genes such as AKT1, MMP13, and IGF1R, that are connected to signal pathways and cellular metabolism.
Assuntos
Biomarcadores , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , MicroRNAs , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Albuminúria/genética , Biomarcadores/análise , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/complicações , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Regulação para Baixo/genética , Taxa de Filtração Glomerular , MicroRNAs/genética , Receptor IGF Tipo 1/genética , Receptor IGF Tipo 1/metabolismoRESUMO
BACKGROUND: Peripheral arterial disease in patients with type 2 diabetes mellitus is an important risk factor for vascular events. Recommendations about whether ankle-brachial index should be performed differ depending on the source; therefore, it is necessary to re-evaluate the most important risk factors associated with peripheral arterial disease and whether it is useful to perform ankle-brachial index in newly diagnosed and drug-naïve patients with diabetes, independent of age or peripheral arterial disease symptoms. METHODS: A total of 711 subjects were divided into groups: group 1, 600 type 2 diabetes mellitus patients, symptomatic or not for peripheral arterial disease; group 2, 61 type 2 diabetes mellitus patients newly diagnosed and drug naïve; and group 3, 50 subjects without diabetes. Ankle-brachial index, medical records and physical examination were performed in all patients, accessing cardiovascular risk factors. RESULTS: Analysing group 1 asymptomatic patient to peripheral arterial disease, we found abnormal ankle-brachial index in 49% (77/156) ⩾50 years and 42% (16/38) <50 years (p = not significant). Considering drug-naïve patients, a peripheral arterial disease prevalence of 39% (24/61) was found; among these, 48% (13/27) were <50 years and 32% (11/34) were ⩾50 years (p = not significant). A forward stepwise regression model was developed, with type 2 diabetes mellitus duration (r2 = 0.12) and sedentary lifestyle (r2 = 0.14) found as independent variable predictors of severity of peripheral arterial disease, related to ankle-brachial index. CONCLUSION: We suggest that, in type 2 diabetes mellitus, ankle-brachial index should be measured at diagnosis. In addition, sedentary lifestyle was strongly associated with presence and severity of peripheral arterial disease.