Association of low birth weight and prematurity with blood pressure and biomarkers of renal and endocrine-pancreatic functions in adults without nephropathy or diabetes

• Ano de defesa: 2022
• Autor(a) principal: Branda, Julia Ines Fleitas
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: Albumin-Creatinine Ratio; Baixo Peso ao Nascer; DOHaD; Glomerular Filtration Rate; HOMA-β Insulin Resistance; Low Birth Weight; Razão Albumina-Creatinina; Resistência à Insulina; Taxa de Filtração Glomerular
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/6/6141/tde-19092022-142414/

Introduction: Low birth weight (LBW), a proxy for hostile intrauterine environment, has been associated with these diseases in adulthood. In Brazil, there is scarce literature on the association of LBW with blood pressure (BP) or kidney and pancreatic functions in adults. The big ELSA-Brasil database allowed to explore whether: 1) pre-diabetic individuals could have kidney function impairment, detectable by renal biomarkers; 2) LBW is associated with less favorable BP levels and kidney and pancreatic function in adulthood compared to normal birth weight. Objectives: To analyze the association of LBW with BP and biomarkers of kidney and endocrine-pancreatic function in adults without DM or nephropathy. The specific objectives were: Paper 1: to review the literature on the prevalence of diabetic kidney disease (DKD) in pre-diabetic individuals. Paper 2: to assess serum Cystatin C (sCys C) as an early marker of kidney dysfunction in individuals without DM. Paper 3: to compare BP levels and kidney function biomarkers (estimated glomerular filtration rate - eGFR, albumin-creatinine ratio - ACR and sCys C) according to the presence of LBW and to analyze their associations with BP and kidney function biomarkers in individuals without DM or nephropathy. Paper 4: to compare markers of &beta;-cell function and insulin sensitivity (HOMA-&beta;, HOMA-IR, HOMA-AD, QUICKI, TyG and TG/HDL) according to the presence of LBW and to analyze LBW associations with markers of &beta;-cell function and insulin sensitivity. Methods: Cross-sectional analysis of ELSA-Brasil data includes 2 fronts: assessment of the LBW associations with BP and kidney function and with endocrine-pancreatic function. Individuals aged > 60 years, BMI < 18.5 kg/m², DM, kidney, thyroid and liver dysfunction were excluded. Sociodemographic data, lifestyle, birth weight and previous diseases were collected by questionnaires, and clinical and laboratory data in the HU/USP. Dependent variables were BP, biomarkers of kidney and pancreatic functions, and independent variable was LBW. Categorical variables were compared using the chi-squared test and continuous variables by Student t test or the Wilcoxon test. Multiple linear regression models were employed to analyze associations between LBW and the outcome variables. Directed acyclic graph (DAG) was used to make the minimum necessary adjustment to the models. The propensity score method was applied to homogenize differences in sample size. Results: Paper 1: Prevalence of DKD ranged from 4.5 to 26.0% in pre-diabetic individuals. Considering eGFR in isolation, the prevalence rates varied from 4.5 to 21.3%, based only on ACR from 7.0 to 26.0% and based on combined criteria the prevalence was between 12.3 and 17.7%. Paper 2: Pre-diabetic individuals had higher sCys C levels than normoglycemic ones [0.67 (0.41-0.95) vs 0.48 (0.31-0.81) mg/L, p<0.001] and lower eGFR (96.3±17.4 vs 100.6±17.1 mL/min/1.73m², p<0.001). Normoglycemic hyperfiltrating individuals had lower sCys C than normofiltrating ones (p=0.035). Comparing eGFR levels between groups, this gradually decreased as the sCys C and ACR parameters worsened (p-trend=0.06). Paper 3: The LBW group had higher systolic (p=0.015) and diastolic BP (p=0.014) and ACR values (p=0.031), and lower eGFR (p=0.015) than normal birth weight. The preterm group had higher mean BP levels, but no difference in kidney function was detected. In a regression model, BP levels were associated with LBW, but this association disappeared after adding prematurity, which remained associated with BP (p=0.017). Having applied propensity score matching, LBW was associated with ACR (p=0.003), but not with eGFR or BP levels. Paper 4: Individuals with LBW or normal birth weight reported similar BMI at the age 20 years and current BMI was slightly lower in the LBW group. Cardiometabolic and endocrine-pancreatic function parameters were within normal ranges. In regression analysis, log-transformed HOMA-&beta;, but not the other indexes, was associated with LBW (p=0.014) independent of sex, skin color, prematurity, and family history of DM. After applying propensity score matching LBW was associated with HOMA-AD and TG/HDL indexes. Discussion: Our findings suggest that individuals with near-normal glucose metabolism disturbance could have some impaired kidney function. Looking at early-life risk factors is relevant since their associations with BP and renal and pancreatic function biomarkers could already be identified even in healthy individuals, without DM and nephropathy. Prospective studies are needed to assess the predictive value aiming at proposing prevention measures.