The methods of the Sandy Lake Health and Diabetes Project have previously been described in detail.5,8,13
In brief, between July 1993 and December 1995, 728 (71.5%) of 1018 eligible residents (aged 10–79 years) of Sandy Lake, an Aboriginal community in northwestern Ontario, participated in a population-based cross-sectional survey to determine the prevalence of type 2 diabetes and its associated risk factors. The analyses in this report are based on the subgroup of 236 youths aged 10–19 years at the time of the survey, who represented 72.6% of the eligible population in this age range. Signed, informed consent was obtained from all participants or their parents or guardians, and the study was approved by the Sandy Lake First Nation Band Council and the University of Toronto Ethics Review Committee. All interviews and examinations were conducted by trained community members working with the Sandy Lake Health and Diabetes Project.
Study participants underwent oral glucose tolerance testing, with measurement of blood pressure (using an appropriately sized pediatric cuff) and body anthropometry (height, weight and waist-circumference measurement), as previously described.8,13
Diabetes and impaired glucose tolerance were diagnosed according to 1985 World Health Organization criteria.15
Measurements of fasting glucose, insulin, total cholesterol, triglycerides, HDL cholesterol, low-density lipoprotein (LDL) cholesterol, C-reactive protein, adiponectin and vitamin B6
were obtained, as previously described.9,10
Serum levels of vitamin B12
and folate were measured using the Quantaphase II radioassay (Bio-Rad Laboratories, Mississauga, Ont.). Plasma homocysteine levels were measured using the fluorescence polarization immunoassay (Abbott IMx Homocysteine, Abbott Laboratories, Abbott Park, Ill.; reagent no. 69-4242/R4, Axis-Shield ASA, Oslo). Apolipoprotein B levels were determined using nephelometry.16
Insulin resistance was estimated using the homeostasis model assessment index (HOMA-IR).17
“Current smoking” was defined in the interviewer-administered questionnaire as current use, at the time of the survey, of cigarettes, cigars, pipes or chewing tobacco. Because the use of cigars, pipes and chewing tobacco was rare in this pediatric population, the current analysis was restricted to cigarette smoking. “Ever smoking” was defined by any history of ever using cigarettes, pipes, cigars or chewing tobacco on a daily basis. “Cigarettes per day” was defined as the number of cigarettes currently smoked per day (current exposure). “Pack-years,” a measure of cumulative smoking exposure, was defined as the product of the number of years of smoking and the number of packs of cigarettes smoked per day.
The distributions of continuous variables were assessed for normality, and the natural log-transformations of skewed variables (C-reactive protein level, homocysteine level, vitamin B12 level, number of cigarettes per day and HOMA-IR) were used in subsequent analyses, with back-transformed results from multivariate analyses presented in tables. In analyses restricted to normoglycemic participants (because of the potential confounding effects of glucose intolerance), univariate associations of smoking exposure with traditional and nontraditional cardiovascular risk factors were assessed using Spearman correlation analysis. Differences in cardiovascular risk factors between participants with low (≤ 5 cigarettes per day) and high (≥ 6 cigarettes per day) current smoking exposure were assessed by analysis of variance, with adjustment for age, sex and body mass index (BMI). We chose this smoking exposure threshold of 5 cigarettes per day by rounding up from the mean exposure of 4.2 cigarettes per day in this population. Multiple linear regression analysis was used to determine the factors that were significantly and independently associated with variation in systolic blood pressure and log-transformed homocysteine level. A forward selection approach was used with a p value threshold of 0.1 for entry into the model. For the systolic blood pressure model, the following independent variables were considered: age, sex, BMI, total cholesterol:HDL ratio, LDL cholesterol level, HOMA-IR, C-reactive protein, adiponectin, folate, vitamin B12 and homocysteine levels, and number of cigarettes per day. For the homocysteine model, the following independent variables were considered: age, sex, BMI, systolic blood pressure, total cholesterol:HDL ratio, LDL cholesterol level, HOMA-IR, C-reactive protein, adiponectin, folate, vitamin B12 and vitamin B6 levels, and number of cigarettes per day.