Mexico City Prospective Study
Established in 1998
CTSU study in collaboration with Mexican Ministry of Health and the National Autonomous University of Mexico
Between 1998 and 2004, CTSU, in collaboration with the Mexican Ministry of Health, established a study in Mexico City, in which over 150,000 middle-aged adults (including 100,000 women and 50,000 men) provided information about their lifestyle and disease history, had physical measurements recorded (including weight, waist and hip circumference, blood pressure) and had a blood sample taken.
All participants are now being tracked for mortality through linkage to Mexican national mortality databases; by January 2018, over 20,000 were confirmed to have died. By relating participants' characteristics at recruitment to death over the following decades, this study is now investigating the main environmental and biological causes of premature death in Mexico.
A resurvey of 10,000 surviving participants (2015 - 2019) captured how lifestyles, physical and biological measurements and treatments for disease (e.g. diabetes) have changed over time. The resurvey also allowed us to better assess the relevance to premature death of characteristics that can vary over time (such as adiposity, diabetes, blood pressure, smoking and alcohol consumption). It also included various ‘enhancements’ (such as bioimpedance, lung function and the collection of a urine sample).
The Mexico City Prospective Study offers an opportunity to study within a single large cohort the social, lifestyle, physical, metabolic and genetic causes of disease in a Latin-American population. The study is being done in collaboration with the National Autonomous University of Mexico in Mexico City and has received funding from the Mexican Ministry of Health (Secretaria de Salud), the Mexican National Council of Science and Technology (Consejo Nacional de Ciencia y Tecnologia), the British Heart Foundation, the UK Medical Research Council, and the UK Wellcome Trust (grant number 058299/Z/99).
discovery of link between gpr75 and obesity
In collaboration with scientists at the Regeneron Genetics Center® (RGC), we combined exome sequence data from the 150,000 participants in the MCPS with data from a further 500,000 people in the UK and the US. We discovered rare genetic mutations in the GPR75 gene that were associated with protection against obesity. Protective ‘loss of function’ mutations were found in about one of every 3,000 people sequenced. People with this genetic ‘superpower’ had 1.8 kg/m2 lower BMI on average and a 54% reduced risk of obesity. The link between the mutations and lower BMI was cemented by studying mice in which the GPR75 gene had been disabled. The results suggest for the first time that pharmacological inhibition of GPR75 may be a therapeutic target both for obesity and the many diseases that result from obesity. Read full paper and press release.
Diabetes and cause-specific mortality
At recruitment, nearly half of women and one-third of men aged 50-59 were obese (ie, had a BMI ≥30 kg/m2) and by age 60 more than 1-in-5 had a confirmed diagnosis of diabetes. Of those with previously-diagnosed diabetes, analysis of blood samples revealed that blood sugar was on average poorly controlled. Over the next 12 years, those with diabetes had four times the overall death rate at ages 35-74 compared with people without diabetes. (In comparison, in high-income countries people with diabetes have been found to have only about twice the death rate of other people.) The biggest excess risk of death among people with diabetes was from kidney disease, followed by heart and other vascular disease, infection and acute diabetic crises (also reflecting poor blood sugar control).
Overall, the excess mortality among people with diabetes accounted for at least one-third of all deaths between the ages 35-74 years, which is twice what previous studies had suggested. Read full paper.
Adiposity and cause-specific mortality
Obesity makes diabetes and several other chronic diseases more common, but these diseases may then result in substantial weight loss, thereby hiding the reason why they arose in the first place. To avoid being misled by this reversal of causality, we looked at the association between adiposity and mortality excluding people who at the time of recruitment already had evidence of any chronic disease, and concentrated our attention on deaths more than 5 years after recruitment.
We found that both general obesity and carrying excess fat around the waist were major risk factors for premature death, with strengths of association that were similar to those observed in high-income populations. Among those with BMI>25 kg/m2, each increase of 5 kg/m2 was associated with a 30% increase in mortality.
In addition, among people whose BMI was similar, waist circumference was of additional relevance to mortality, suggesting that central obesity is particularly harmful. Read full paper.
Blood pressure and cause-specific mortality
Although elevated blood pressure is known to be a major cause of premature death in high-income populations, there is little direct evidence in studies of Hispanic populations. In our analysis, we confirmed that blood pressure was a major risk factor for death from a range of diseases among Mexicans. It was especially strongly related to death from vascular and kidney disease, with no ‘threshold’ levels below which lower blood pressure was not associated with lower risk.
Because those with diabetes were at substantially higher risk than those without diabetes, the absolute excess mortality rates associated with elevated blood pressure were much higher in individuals with diabetes. Read full paper.