- Original investigation
- Open Access
Estimated incidence of cardiovascular complications related to type 2 diabetes in Mexico using the UKPDS outcome model and a population-based survey
© Reynoso-Noverón et al; licensee BioMed Central Ltd. 2011
- Received: 17 November 2010
- Accepted: 7 January 2011
- Published: 7 January 2011
To estimate the incidence of complications, life expectancy and diabetes related mortality in the Mexican diabetic population over the next two decades using data from a nation-wide, population based survey and the United Kingdom Prospective Diabetes Study (UKPDS) outcome model
The cohort included all patients with type 2 diabetes evaluated during the National Health and Nutrition Survey (ENSANut) 2006. ENSANut is a probabilistic multistage stratified survey whose aim was to measure the prevalence of chronic diseases. A total of 47,152 households were visited. Results are shown stratified by gender, time since diagnosis (> or ≤ to 10 years) and age at the time of diagnosis (> or ≤ 40 years).
The prevalence of diabetes in our cohort was 14.4%. The predicted 20 year-incidence for chronic complications per 1000 individuals are: ischemic heart disease 112, myocardial infarction 260, heart failure 113, stroke 101, and amputation 62. Furthermore, 539 per 1000 patients will have a diabetes-related premature death. The average life expectancy for the diabetic population is 10.9 years (95%CI 10.7-11.2); this decreases to 8.3 years after adjusting for quality of life (CI95% 8.1-8.5). Male sex and cases diagnosed after age 40 have the highest risk for developing at least one major complication during the next 20 years.
Based on the current clinical profile of Mexican patients with diabetes, the burden of disease related complications will be tremendous over the next two decades.
- Ischemic Heart Disease
- Average Life Expectancy
- United Kingdom Prospective Diabetes Study
- Diabetes Related Complication
- Family Health History
Diabetes is the principal cause of death in Mexico . Its prevalence in adults over the age of 20 has grown from 6.7% in 1993 to nearly 14% in 2006 [2–4]. Nationwide population based surveys providing unbiased information regarding the prevalence and clinical characteristics of persons with diabetes are scant [5, 6]. In Mexico, three nationwide surveys have shown that adults with type 2 diabetes have a high prevalence of co-morbid conditions which contribute to the high incidence of macrovascular and microvascular complications. Regrettably, the incidence of chronic complications is unknown.
Simulation modeling is gaining acceptance as a valuable tool for providing long-term information regarding prognosis; such information is often unavailable from clinical studies. Several simulation models [7–12] are available for estimating the incidence of diabetic complications. The United Kingdom Prospective Diabetes Study (UKPDS) outcome model is the most popular. This model was developed using data obtained from patients who participated in the UKPDS. In this study the medical history, biochemical variables and diabetes related complications were documented in the vast majority of patients, with very few patients lost during follow-up [13, 14].
Since predictions using validated tools and population representative data have not been published in Latin American countries, the objective of this report is to estimate the incidence of complications, life expectancy, quality-adjusted life expectancy and diabetes related mortality in the Mexican diabetic population over the next two decades. This will allow us to simulate the challenges that the Mexican health system will face in the next 20 years.
The 2006 National Health and Nutrition Survey (ENSANut) was a cross sectional study including individuals representative of those living in Metropolitan, urban and rural areas. A multistage, stratified and probabilistic sampling procedure was used to collect information. A random sample of Basic Geographical Statistical Units was obtained in all states of Mexico, and neighborhood blocks were randomly selected. In every home, a randomly selected adult, adolescent, child and health service user were invited to participate. A target of 4731 individuals and 1476 households was estimated per state. The total number of households visited was 48600. A sample of this size is capable of detecting risk factors that have a state-wide prevalence of at least 8.1% with a relative error of estimation of 0.25, a design effect of 1.7 and a non-response rate of 20%. The study was carried out in accordance with the Helsinki Declaration of Human Studies. Informed consent was obtained from each participant. A separate consent form was signed by participants who provided blood samples. The study was approved by the Research and Ethics committees of the Instituto Nacional de Salud Pública.
The procedures of the study are reported in detail elsewere [15, 16]. Briefly, a structured interview was conducted and a previously standardized questionnaire was used to obtain demographic, socioeconomic, family health history, past medical history and lifestyle information (e.g. smoking). Diabetes was considered present if subjects referred to a previous diagnosis or if the fasting plasma glucose was ≥ 126 mg/dl . Type 1 diabetes was diagnosed if insulin treatment was required during the first two months after the diagnosis or if the patient had history of ketoacidosis. Fasting blood samples were obtained in approximately 30% of the adult population (n = 6613). These cases were randomly distributed among study subjects. This subsample has a statistical power to detect conditions with a nation-wide prevalence ≥ 8%. The response rate was 85%. Detailed information about the methods used for the collection of the data is published elsewhere . The socio-demographic parameters (age, gender, socioeconomic status and body mass index) of the subsample were not different from the rest of the population. The sampling procedure was standardized during a two week training course. The subjects were sampled at their homes; they remained seated for five minutes before the blood sample was drawn. All analytical measurements were carried out in the laboratories of the Instituto Nacional de Salud Pública using commercial reagents described in detail elsewere .
The United Kingdom Prospective Diabetes (UKPDS) outcome model was used to estimate life expectancy, quality-adjusted life years (QALY), risk for the development of fatal and non fatal myocardial infarction, ischemic heart disease, cerebrovascular event, cardiac failure, amputation and death in the diabetic population. The model was developed based on observations and follow up over 10 years of 5102 patients with newly diagnosed type 2 diabetes. It considers four risk factors (HbA1c, HDL-cholesterol, total cholesterol, systolic blood pressure and smoking) as longitudinal data and adjusts a model of random effects to estimate the pattern over time. Equations for HbA1c, systolic blood pressure, total cholesterol and HDL-cholesterol are based on annual changes of each risk factor, while change in smoking habit is calculated in three-year time periods from the diagnosis of diabetes. With respect to diabetic complications, Weibull proportional risks regression model was used to estimate occurrence of a compound result for fatal and non-fatal events. In this simulation model, ischemic heart disease and congestive heath failure events are registered only if they occurred prior to a myocardial infarction event. Separate equations were used to model diabetes and diabetes related mortality using a combination of Gompertz regression equations and logistic regression models. The impact of different complications was obtained through the EQ-5D health condition questionnaire given to patients free of complications. It is assumed that multiple complications have an additive effect on quality of life. The simulations are carried out in annual cycles. A combination of bootstrap methods and multiple attribution were used to handle uncertainty, such that confidence intervals reflect uncertainty of the parameter in the model . Missing data were attributed considering the mean values of the conditions according to age (< 40, 40-60 and > 60 years), gender and time of diagnosis (< 10 and > 10 years). A license was obtained for the use of the UKPDS outcome model (Serial 1896, July 21,2005). The UKPDS Results Model version 1.1 was run with 1000 Monte Carlo essays per subject and with 10 re-samplings (bootstraps) to handle uncertainty. It was assumed that clinical variables remained unchanged over time. The model's three ethnic groups do not include the Mexican population, therefore, the group most closely related to our study population was selected (Asian Indians). Native American and Asian populations share peculiarities in their body composition. In these populations, the mean body mass index (BMI) and height are lower than that observed for Caucasians, although the tendency towards abdominal obesity may be greater [17, 18]. Life expectancy, quality-adjusted life expectancy, expected incidence of chronic complications were calculated for a 20 year period. Results are presented by gender, time of diagnosis (> or ≤ to 10 years) and age of diagnosis (> or ≤ 40 years).
Validation of the UKPDS outcome model for cardiovascular (CVD) events in Mexicans
The UKPDS outcome model has not been applied previously in Mexicans. As a consequence, we run a separate study to validate the estimates. For this purpose, a retrospective study based on the medical charts of patients with type 2 diabetes treated for at least 10 years at the Instituto Nacional de Ciencias Médicas y Nutrición was performed. Patients lost to follow up for more than one year were excluded. Predicted (using baseline variables at diagnosis) and observed proportions of primary cardiovascular events were compared. The discrimination (c-statistic) and calibration (Hosmer-Lemeshow χ2) of the UKPDS outcome model were calculated. A total of 1089 records were reviewed. Of these 654 records were excluded for the following reasons: 35 patients with type 1 diabetes mellitus, 13 patients with secondary diabetes, 379 without HbA1c results, 42 without a lipid profile, 2 patients were younger than age 20 at the time of diagnosis and 182 patients had cardiovascular disease diagnosed in the initial visit. Thus, the study sample was composed of 436 patients (217 men and 219 women). The mean age at diagnosis of diabetes was 48.7 years. One hundred and one (23.1%) died during the follow-up period. Cardiovascular disease was the cause of death in 52 patients (51.4%). In addition, 260 cardiovascular events were recorded (coronary events = 45, stroke = 45). Discrimination of the UKPDS outcome model for CVD events was 0.66 (IC 95% 0.59-0.72). The calibration was poor (Hosmer-Lemeshow χ2 = 23.8, p = 0.03), but of the same magnitude as that reported by Guzder . The sensitivity and specificity for an estimated 10-year CVD risk of 20% was 89% and 36%, respectively.
Description of the diabetic population included in the Encuesta Nacional de Salud y Nutrición 2006
Population of 20 years or older
n = 56,745,719
Diagnosed during the survey
Time from diagnosis (years)
Total Cholesterol (mmol/l)
HDL cholesterol (mmol/l)
Systolic blood pressure (mmHg.)
Twenty year incidence of macrovascular complications
Expected incidence of cardiovascular complications in persons with diabetes in Mexico
Number of expected cases/1000 diabetics
Confidence Interval 95%
Total expected cases (CI95%)
Ischaemic heart disease
Twenty year accumulated probability for having macrovascular complications or death: effect of ethnicity
Ischemic heart disease
Death and life expectancy
Expected mortality in persons with diabetes in Mexico
Number of expected cases/1000 persons with diabetes
95% Confidence Interval
Total expected cases (95% CI)
Expected twenty years incidence of cardiovascular complications and life expectancy by gender, time of evolution and age of diagnosis
Probability (95% CI)
Expected Cases (95% CI)
Probability (95% CI)
Expected Cases (95% CI)
Expected Cases* (CI95%)
n = 3,931,127
≤ 10 years
n = 6,652,964
Age at diagnosis
≤ 40 years
n = 2,590,066
n = 3,961,850
> 10 years
n = 1,240,012
Age at diagnosis
> 40 years
n = 5,302,911
Ischemic heart disease
The results of three population-based nationwide surveys have shown that the prevalence of type 2 diabetes has grown rapidly in México over the past few decades. More than seven million Mexican adults now live with diabetes. This report clearly shows that the burden imposed by diabetes to Mexico will be very high risk over the next twenty years. This report makes emphasis in macrovascular complications, the main cause of death among patients with type 2 diabetes . The UKPDS outcome model estimates that 53.9% (95 CI% 50.8-57%) of currently affected subjects will be dead by the year 2026. Their life expectancy will be reduced to an average of 10.9 years (IC95% 10.7-11.2). The predicted 20 year-incidence of the principal cardiovascular complications per 1000 diabetic individuals are: ischemic heart disease 112, myocardial infarction 260, heart failure 113, stroke 101 and amputation 62. These predictions must urge the Mexican health system to establish effective treatment programs and improve diabetes care. In the absence of such measures, the resources required to manage future diabetes related complications will surpass the capability of the Mexican health system.
Strengths of the study and implications for the Mexican Health system
Limitations of the study
The main disadvantage of simulation models is that estimates are not precise for persons who have characteristics different to that of persons who participated in the original trial. Latino populations, for example, were not included in the UKPDS. Despite this concern, the UKPDS outcome model has been applied in multiethnic study samples [28, 29]. To counter this factor, we treated our study sample as Asian Indians, which is an ethnic group included in the UKPDS study that shares biological and socio-economical characteristics with Latin populations [17, 18]. We re-ran the estimates in order to measure the magnitude of the ethnicity effect among the options provided by the simulation model. Minor, non significant differences were found if an Asian or a Caucasian background was assumed in the modeling process. Thus, the selection of the Asian Indians as the group most closely related to our study population may have minor consequences on the estimates reported here. In addition, we validated the prognostic value for CVD events of the UKPDS outcome model in a group of Mexican patients followed up for over ten years. The discrimination (c = 0.66 (IC 95% 0.59-0.72) for CVD events reported here is similar to that reported in the multiethnic ADVANCE study (c = 0.70 (0.65-0.76))  and in a cohort composed of Caucasians (c = 0.670) . This observation suggests that the UKPDS outcome model estimates may be as valid in Mexicans as in other ethnic groups. Other limitations may affect our ability to predict the CVD outcomes. The UKPDS outcome model measures the probability of presenting the first event, but not subsequent ones. For instance, it does not consider the existence of a double amputation. Also, the model simulates the progression of diabetes under "conventional treatment" within the UKPDS study. Conventional treatment in Mexico is much more varied. In addition, the UKPDS risk engines apply to people with newly diagnosed diabetes. Here, the model was applied to both undiagnosed and diagnosed cases of diabetes. Finally, the estimates are derived from a single measurement. Despite these limitations, the value of the present analysis depends largely on the extent to which the participants of the Encuesta Nacional de Salud y Nutricion are representative of current populations of patients with type 2 diabetes living in México.
The UPKDS outcome model is thought to either overestimate  or underestimate CVD risk  depending on the nature of the population under study. It is probable that the model may overestimate the CVD risk in a population-based sample  like the one reported here. Our CVD estimates are similar to those reported in Mexican-Americans from the 1999-2002 National Health and Nutrition Examination Survey . The 10 year risk of CVD events (ischemic heart disease plus myocardial infarction) estimated in our sample (22.8%) was almost identical (22.5%) to that found in the Mexican Americans.
The impact of type 2 diabetes on the Mexican health system will be significantly greater in the next two decades. Simulation modeling shows that if the clinical characteristics of the diabetic population remain unaltered, a large proportion of the diabetic population will suffer premature mortality and disabilities in the coming years.
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