Beating Prediabetes

New research explores the impact of prediabetes on a Mexican population.

According to a study presented at ENDO 2024, prediabetes increases the risk of dying before the age of 75, particularly due to heart disease, kidney disease, and acute diabetic complications in Mexican populations. The study’s author, Carlos A. Fermín-Martínez, MD, discusses his findings and why it’s important for clinicians to screen for prediabetes, especially in susceptible populations.

According to the World Health Organization, more than half a billion people worldwide are living with diabetes, and most of those live in low- and middle-income countries, including Latin America, where the prevalence rate is higher than the global prevalence rate and projected to increase dramatically. Likewise, the global burden of prediabetes is close to a half a billion people and growing, expected to increase to 10% of the worldwide population in less than 20 years, according to the International Diabetes Federation (using the impaired glucose tolerance [IGT] definition).

The urgency here is that, not only are those with prediabetes at high risk of developing type 2 diabetes, but they are also at higher risk for all-cause, cardiovascular, renal, and acute diabetic mortality. Compounding this issue, most people (80%) with prediabetes are unaware of their status and therefore unable to make timely interventions to prevent type 2 diabetes development and other deleterious health effects.

Prediabetes in the Mexico City Prospective Study

Carlos A. Fermín-Martínez, MD, of the National Autonomous University of Mexico and the National Institute of Geriatrics in Mexico City, Mexico, and his research team, seeking to better understand the epidemiology of diabetes and metabolic diseases, identified a lack of evidence regarding the epidemiology of prediabetes in the Mexican population. “We recently described the changes in the prevalence of prediabetes in the last seven years in Mexico and its potential determinants. We figured that the next step should be to describe the long-term effects of this condition, particularly on mortality,” explains Fermín-Martínez.

Importantly, besides that the prevalence is rising in the Latin American population, this population may have other factors that predispose them to the development of prediabetes/diabetes. “Overweight, obesity, and dyslipidemia are also major public health concerns among the Mexican population,” Fermín-Martínez says, “which could be attributed to a detrimental lifestyle (accentuated by socioeconomic health determinants) and genetics (e.g., variants in SLC16A11). All of this in turn predisposes our population to a higher risk of prediabetes and diabetes.”

In the study entitled, “Prediabetes as a Risk Factor for All-Cause and Cause-Specific Mortality in 115,919 Adults Without Diabetes in Mexico City,” the researchers undertook a secondary analysis from the Mexico City Prospective Study (MCPS) examining 110,405 participants ages 35 to 74 years old who did not have diabetes during the study recruitment phase from 1998 to 2004. Exclusion criteria included individuals with previously diagnosed diabetes, individuals who used glucose-lowering pharmacotherapy regardless of prior diagnosis, and individuals with undiagnosed diabetes but a glycosylated hemoglobin (HbA_1c) level 6.5% or higher as well as those with self-reported chronic comorbidities at baseline (e.g., ischemic heart disease, stroke, chronic kidney disease, chronic obstructive pulmonary disease, cirrhosis, or cancer).

Participants were followed up to January 1, 2021. Of these participants, more than a quarter (26%, or 28,852 individuals) met the American Diabetes Association (ADA) criterion for prediabetes of an HbA_1c level between 5.7% and 6.4%. Because there is still controversy regarding the definition of prediabetes, however, Fermín-Martínez also used an HbA_1c level between 6.0% and 6.4% to define prediabetes, which is from the International Experts Committee (IEC) who were asked to adjudicate a definition of A1C use for diagnosing diabetes in 2008. The number of participants meeting the IEC criterion dropped to 7% (7,203 individuals).

“In our study, participants were initially free of diabetes; however, eventual development of diabetes likely accounts for a significant percentage of deaths, further highlighting that early detection and management of prediabetes is crucial to reduce mortality and cardiometabolic disease.” — Carlos A. Fermín-Martínez, MD, PhD student, National Autonomous University of Mexico; National Institute of Geriatrics; Mexico City, Mexico

With these two distinct cutoffs, the team looked for associations with all-cause and cause-specific mortality using Cox regression analysis after adjusting for common confounders (e.g., municipality of residence — Coyoacán or Iztapalapa, education level, physical activity, smoking, alcohol consumption, and adiposity levels).

The sociodemographic, health-related, and lifestyle data were collected by questionnaire under nurse supervision. Height, weight, hip and waist circumference, and blood pressure measurements were obtained using calibrated instruments and standard protocols. Non-fasting venous blood samples were taken, and HbA1c levels were measured using a validated high-performance liquid chromatography method.

Research Findings

Although the team has a preprint of their study pending, Fermín-Martínez presented highlights at ENDO 2024 as part of a press conference devoted to cutting-edge diabetes research. He reported that participants meeting the IEC — the stricter — definition of prediabetes had 3.4 times the risk of dying of acute complications of diabetes at ages 35 to 74, compared to participants with normal blood glucose levels. Their risk of dying prematurely from kidney disease was increased by 1.7 times (70%). When using the ADA definition of prediabetes, the researchers also found significant, but weaker, associations with mortality. In other words, although lower glycemic marker cutoffs may be helpful for screening for prediabetes, they may not fully reflect the associated long-term health risks.

Drilling down a bit, the absolute excess risk associated with ADA- and IEC-defined prediabetes at ages 35 to 74 years accounted for 6% and 3% of cardiovascular deaths, respectively; 10% and 5% of renal deaths; and 31% and 14% of acute diabetic deaths. They found risk ratios (RRs) to be larger at younger ages than at older ages. RRs did not vary significantly between males and females.

Implications

Prediabetes is an early-stage indicator of glycemic dysregulation, which can lead to hyperglycemia and sometimes hyperinsulinemia, which may result in inflammation, impaired lipid metabolism and endothelial dysfunction, explained Fermín-Martínez. “These processes contribute to the development of diabetes, hypertension and dyslipidemia that ultimately culminate in life-threatening conditions such as cardiovascular and kidney disease. In our study, participants were initially free of diabetes; however, eventual development of diabetes likely accounts for a significant percentage of deaths, further highlighting that early detection and management of prediabetes is crucial to reduce mortality and cardiometabolic disease,” he says.

The takeaway is clear: as prediabetes increases the risk of dying from cardiovascular, renal, and acute diabetic causes as well as all causes, clinicians—particularly in Mexico—could significantly reduce premature mortality by identifying and treating prediabetes early on.

“Overweight, obesity, and dyslipidemia are also major public health concerns among the Mexican population, which could be attributed to a detrimental lifestyle (accentuated by socioeconomic health determinants) and genetics (e.g., variants in SLC16A11). All of this in turn predisposes our population to a higher risk of prediabetes and diabetes.” — Carlos A. Fermín-Martínez, MD, PhD student, National Autonomous University of Mexico; National Institute of Geriatrics; Mexico City, Mexico

Look for the results of this important study to publish soon. Meanwhile, looking back to his presentation at ENDO 2024, Fermín-Martínez recalls that: “it was a very exciting and fulfilling experience; the best part was definitely the opportunity to connect with students and early-career researchers like me and having the chance to represent my research team. I am also a Society member, which so far has been very informative, as I often receive updates on conferences and research opportunities. It is undoubtedly worth it.”

Horvath is a freelance writer based in Baltimore, Md. She wrote about oral testosterone replacement therapy for men in the October issue.