Diabetes and Cause-Specific Mortality in Mexico City

Abstract

Background: Most large, prospective studies of the effects of diabetes on mortality have focused on high-income countries where patients have access to reasonably good medical care and can receive treatments to establish and maintain good glycemic control. In those countries, diabetes less than doubles the rate of death from any cause. Few large, prospective studies have been conducted in middle-income countries where obesity and diabetes have become common and glycemic control may be poor.

Methods: From 1998 through 2004, we recruited approximately 50,000 men and 100,000 women 35 years of age or older into a prospective study in Mexico City, Mexico. We recorded the presence or absence of previously diagnosed diabetes, obtained and stored blood samples, and tracked 12-year disease-specific deaths through January 1, 2014. We accepted diabetes as the underlying cause of death only for deaths that were due to acute diabetic crises. We estimated rate ratios for death among participants who had diabetes at recruitment versus those who did not have diabetes at recruitment; data from participants who had chronic diseases other than diabetes were excluded from the main analysis.

Results: At the time of recruitment, obesity was common and the prevalence of diabetes rose steeply with age (3% at 35 to 39 years of age and >20% by 60 years of age). Participants who had diabetes had poor glycemic control (mean [±SD] glycated hemoglobin level, 9.0±2.4%), and the rates of use of other vasoprotective medications were low (e.g., 30% of participants with diabetes were receiving antihypertensive medication at recruitment and 1% were receiving lipid-lowering medication). Previously diagnosed diabetes was associated with rate ratios for death from any cause of 5.4 (95% confidence interval [CI], 5.0 to 6.0) at 35 to 59 years of age, 3.1 (95% CI, 2.9 to 3.3) at 60 to 74 years of age, and 1.9 (95% CI, 1.8 to 2.1) at 75 to 84 years of age. Between 35 and 74 years of age, the excess mortality associated with previously diagnosed diabetes accounted for one third of all deaths; the largest absolute excess risks of death were from renal disease (rate ratio, 20.1; 95% CI, 17.2 to 23.4), cardiac disease (rate ratio, 3.7; 95% CI, 3.2 to 4.2), infection (rate ratio, 4.7; 95% CI, 4.0 to 5.5), acute diabetic crises (8% of all deaths among participants who had previously diagnosed diabetes), and other vascular disease (mainly stroke). Little association was observed between diabetes and mortality from cirrhosis, cancer, or chronic obstructive pulmonary disease.

Conclusions: In this study in Mexico, a middle-income country with high levels of obesity, diabetes was common, glycemic control was poor, and diabetes was associated with a far worse prognosis than that seen in high-income countries; it accounted for at least one third of all deaths between 35 and 74 years of age. (Funded by the Wellcome Trust and others.).

Figure 1. Prevalence of Previously Diagnosed Diabetes and Its Relevance to Rates of Death from Any Cause during 12-Year Follow-up.

Panel A shows the prevalence of previously diagnosed diabetes among all study participants. I bars represent 95% confidence intervals. The dashed lines indicate the age at which the prevalence of diabetes was 20%. Panel B shows the rate ratios for death from any cause among participants with and participants without previously diagnosed diabetes at recruitment. The rate ratios for death exclude data from any participants who had previously diagnosed chronic disease other than diabetes (chronic kidney disease, ischemic heart disease, stroke, cirrhosis, cancer, or emphysema) and are adjusted for standard features (age, smoking status, district, educational level, height, weight, and waist and hip circumferences). The size of each square is proportional to the amount of data available, and unshaded diamonds represent the values for men and women combined. Horizontal lines represent 95% confidence intervals.

Figure 2. Relevance of Previously Diagnosed Diabetes to Cause-Specific Mortality during 12-Year Follow-up.

Shown are the numbers of deaths and disease-specific rate ratios for death among participants with versus participants without previously diagnosed diabetes at recruitment, according to age group and to the disease to which the participant’s death was attributed. The rate ratios for death exclude data from any participants who had previously diagnosed chronic disease other than diabetes (chronic kidney disease, ischemic heart disease, stroke, cirrhosis, cancer, or emphysema) and are adjusted for standard features (age, smoking status, district, educational level, height, weight, and waist and hip circumferences). Rate ratios are not shown for deaths attributed to acute diabetic crises because all such deaths were due to diabetes, irrespective of whether diabetes was diagnosed before recruitment. The size of each square is proportional to the amount of data available. Horizontal lines represent 95% confidence intervals. Of the 393 participants who died from an acute diabetic crisis, baseline glycated hemoglobin levels were available for 389 participants, of whom 332 (85%) either had diabetes diagnosed before recruitment or had a baseline glycated hemoglobin level of at least 6.5% and 57 (15%) had no diagnosis of diabetes before recruitment and had a baseline glycated hemoglobin level of less than 6.5%. Numerical values for the rate ratios may vary slightly from the position of the squares because of rounding.

Figure 3. Mortality Rates for Each Cause of Death Among Participants with and Participants without Previously Diagnosed Diabetes.

Shown are the absolute estimated disease-specific rates of deaths according to the cause of death among persons with and persons without previously diagnosed diabetes. The analysis combines the percentages of participants in the current study who died between 35 and 74 years of age from particular diseases, the disease-specific rate ratios for death at 35 to 74 years of age, and 2012 national mortality rates in Mexico. The rates for all bars sum to the rates of death from any cause. The unshaded portions of the bars represent the mortality rate for the specific cause of death among participants without previously diagnosed diabetes. The shaded portions of the bars represent excess risk of death that was either associated with previously diagnosed diabetes or that was due to acute diabetic crises. The weighted average of the death rates shown (for 16% of persons with diabetes plus 84% of persons without diabetes) match uniformly age-standardized 2012 Mexican national rates at 35 to 74 years of age for 50% men plus 50% women. Infective diseases include peptic ulcer disease and exclude any infection in another plotted category. For stroke alone, annual rates of death were 0.05% among persons without previously diagnosed diabetes and 0.19% among persons with previously diagnosed diabetes.