Transcript of "Association of birth weight and risk factors for renal disease in a rural Canadian cohort of mixed ethnicity"
Association of birth weight and risk factors for renal disease in a rural Canadian cohort of mixed ethnicityValerie A. Luyckx MBBCh1, Samantha L. Bowker PhD2, Alison Miekle3, Ellen L. Toth, MD3. 1Division ofNephrology, 2 School of Public Health and 3Division of Endocrinology,University of Alberta, Edmonton, Alberta, CanadaIntroduction1160 Canadians (ages 6 – 90 years) from off reserve Aboriginal communities or rural towns participated in 2 voluntary programs screening for diabetes risk factors and diabetes and its complications. Individuals gave consent for aggregate analysis of their data. Participants underwent a 2 hour visit with a trained heath care worker. Data was recorded for demographic factors, measured anthropomorphic factors, blood pressure, blood glucose, hemoglobin A1c, lipid panel, urine protein and medication usage. Birth weights were recalled by the subject or their parent. Recalled birth weights have been validated in several populations (Curhan et al., 1996). Subject ethnicity was self‐defined. The status/non‐status group contains individuals from remote communities. Metis and non‐aboriginal groups were still rural but lived closer to larger towns. High blood pressure was defined as a value above the normal for age, in adults a systolic or a diastolic blood pressure ≥ 140/90 and or the use of antihypertensive medication. Diabetes was defined as a positive history of diabetes and or use of insulin or hypoglycaemic medication. Statistical Analysis: Descriptive analyses were stratified by Aboriginal Status. Subjects were grouped as Non‐Aboriginals, Status/Non‐Status, or Métis. Comparisons between the three groups were evaluated using univariate analysis of variance (ANOVA) for continuous variables and Chi square tests for categorical variables; all tests of statistical significance were two‐sided. Logistic Regression was then used to evaluate the relationship between: 1) Birth weight and Diabetes (Yes vs. No) and 2) Birth weight and Blood Pressure (Hypertensive vs. Normal). Birth weight was collapsed into: low (<2500 grams), reference group (2500‐4499 grams), and high (4500 grams). In multivariate Logistic regression models, the following potential confounding variables were included: age, sex, Aboriginal status, Metabolic Syndrome (Yes vs. No), blood pressure (in the diabetes model) (hypertensive vs. normal), waist circumference (high vs. normal), and diabetes status (in the blood pressure model) (Yes vs. No). Interaction terms between birth weight and each variable in the model were also examined. None of these interaction terms were statistically significant (at the p <0.10 level), however, so no interaction terms were included in the final model. All statistics were performed using Predictive Analytics Software (PASWStatistics; v18.0, Chicago, IL).Individuals who are identified as Indian (First Nations), Métis and Inuit are recognized in the Canadian Constitution. North American Indian is the term used for those persons who self‐identity as such, and generally refers to persons who consider themselves as part of the First Nations in Canada, whether or not they have legal Indian Status (“Registered Indians”) according to the Indian Act of Canada. Inuit is the term for Aboriginal people who originally lived north of the tree line in Canada and who self‐identify as such.Status Indians ‐ Status Indians are people who are entitled to have their names included on the Indian Register, an official list maintained by the federal government. Certain criteria determine who can be registered as a Status Indian. Only Status Indians are recognized as Indians under the Indian Act and are entitled to certain rights and benefits under the law.NonStatus Indians ‐ Non‐Status Indians are people who consider themselves Indians or members of a First Nation but whom the Government of Canada does not recognize as Indians under the Indian Act, either because they are unable to prove their Indian status or have lost their status rights. Non‐Status Indians are not entitled to the same rights and benefits available to Status Indians.Métis ‐ The word Métis is French for "mixed blood." The Constitution Act of 1982 recognizes Métis as one of the three Aboriginal Peoples. Today, the term is used broadly to describe people with mixed First Nations and European ancestry who identify themselves as Métis.NonAboriginal subjects in this cohort were Caucasian, largely from Mennonite communities.Low (LBW) and high (HBW) birth weight are emerging as consistent risk factors for adult cardiovascular and renal disease. Since the 1980’s, when the inverse correlation between LBW and hypertension was reported, numerous studies in humans and animal models have supported this observation. It is important to note that in LBW children, blood pressures tend to be higher than those of normal birth weight (NBW) children, but are not in the hypertensive range, although with time, blood pressures increase and LBW individuals become overtly hypertensive with age. A recent systematic review found a significantly increased risk of chronic kidney disease with LBW in various populations (White et al., 2009). Among Pima Indians and subjects from the Southern United States, a U‐ shaped association, i.e. both LBW and HBW were associated with increased albumin excretion and end‐stage renal disease, especially among diabetic subjects (Nelson et al, 1998, Lackland et al, 2000). A similar association has been found between birth weight and type 2 diabetes in a systematic review incorporating 31 studies(Whincup et al., 2008). The relationship between birth weight, hypertension, diabetes and renal disease has not been well studied among Canadian populations thus far, although high birth weights are associated with increased prevalence of Type 2 diabetes in Native North Americans (Dyck et al., 2001). We investigated the relationship between birth weight and risk factors for renal disease among a cohort of rural Canadians of varied ethnicity.ResultsIn univariate analysis, stratified by ethnicity, Diabetes was significantly associated with birth weight among Aboriginal subjects (12.2% of LBW, 5.3 % of NBW, 7.9% of HBW, p = 0.035). Hypertension was associated with birth weight among Non‐Aboriginal subjects (37% of LBW, 20.8% of NBW, 29% of HBW, p = 0.028). Proteinuria data was missing in 80% of the cohort. In those where it was measured, proteinuria the prevalence was 32.6% of LBW, 19.9% of NBW and 7% of HBW subjects.LBW and HBW are both associated with hypertension in this rural Canadian cohort comprised of subjects of various ethnicitiesLBW, but not HBW, is significantly associated with later life Diabetes in the cohort as a whole, including the Aboriginal subgroup. The latter finding is in contrast to prior published data (Dyck et al., 2001) and may reflect the fact that the status/non‐status group contains an over‐representation of individuals from remote communities. As expected, diabetes, hypertension and metabolic syndrome are all associated with each other and therefore may confound the relationship with birth weight, however each may be independently programmed during fetal development and may compound each other’s impact on subsequent cardiovascular risk.These data are in general agreement with reports from other populations around the world supporting the role of developmental programming in adult diseaseTable 1. Descriptive Analyses by Aboriginal Status*Denominators different for these two variables (i.e. missing data)Table 2. Logistic regression with Diabetes as dependent variableTable 3. Logistic regression with Blood Pressure as dependent variableMethodsSubject ethnicityResultsResultsConclusions