Researchers shed light on risk factor and diabetes development interplay

Study reveals a 12.8% 10-year risk of diabetes in a cohort of 44,992 individuals, highlighting the role of fasting plasma glucose, body mass index, age, and sex in predicting risk—even among those with normal FPG levels

Study: Baseline Fasting Glucose Level, Age, Sex, and Body Mass Index and the Development of Diabetes in US Adults. Image Credit: Anatoliy Cherkas/Shutterstock.com

In a recent study published in the JAMA Network Open, a group of researchers assessed how fasting plasma glucose (FPG) levels, age, sex, and body mass index (BMI) influence the progression to diabetes, enabling targeted prevention strategies.

Background

The progression from normal fasting glucose and normal glucose tolerance to type 2 diabetes often involves an intermediate stage of impaired fasting glucose or impaired glucose tolerance, known as prediabetes. Lifestyle and pharmacologic interventions can significantly lower diabetes risk for high-risk individuals.

The American Diabetes Association recommends clinical risk assessments to guide diagnostic testing for prediabetes or diabetes using FPG, 2-hour plasma glucose during a 75-g oral glucose tolerance test, or hemoglobin A1c (HbA1c). Further research is essential to explore interactions between FPG, age, sex, BMI, and other variables to refine risk prediction.

About the study 

The Rochester Epidemiology Project (REP) is a medical records-linkage system that identifies unique individuals across multiple healthcare organizations in Olmsted County, Minnesota. In this retrospective cohort study, data from the REP were used to identify individuals aged 18 to 65 who had at least two FPG tests between January 1, 2005, and December 31, 2017. Based on specific ordering codes, only fasting samples were included, and samples collected during inpatient hospitalizations were excluded.

Individuals with preexisting diabetes, those prescribed glucose-lowering medications, or those with an initial FPG level of 126 mg/dL or more were also excluded. The accuracy of electronically retrieved data was verified by manually reviewing a subset of records.

Study results

A total of 44,992 individuals were included in the cohort, with a mean (SD) age of 43.7 (11.8) years and an age range of 18 to 65 years. The cohort comprised 26,025 women (57.8%) and 18,967 men (42.2%), including 1,844 Asian participants (4.1%), 1,934 Black participants (4.3%), 39,178 White participants (87.1%), and 2,036 individuals of other races or ethnicities (4.5%). The mean (SD) BMI was 28.9 (6.6).

Over a median follow-up of 6.8 years (IQR, 3.6-9.7 years), 3,879 individuals (8.6%) developed diabetes, with 7.1% of women (1,847 of 26,025) and 10.7% of men (2,032 of 18,967) affected. The Kaplan-Meier 10-year cumulative risk of diabetes was 12.8% (95% CI, 12.4%-13.2%).

Cox proportional hazards regression analysis identified significant risk factors, including FPG levels, sex, age, and BMI. Individuals with FPG levels outside the reference range (80-94 mg/dL) faced increased risk, with an HR of 3.49 (95% CI, 2.19-5.57) for FPG <70 mg/dL and HR of 12.47 (95% CI, 10.84-14.34) for FPG 120-125 mg/dL. Male sex increased diabetes risk compared with females (HR, 1.31 [95% CI, 1.22-1.40]). Abnormal BMI categories also elevated risk, with HRs ranging from 2.42 (95% CI, 1.77-3.29) for underweight (BMI <18.5) to 4.03 (95% CI, 3.56-4.56) for class III obesity (BMI ≥40). Age ≥60 years was associated with nearly double the risk (HR, 1.97 [95% CI, 1.71-2.28]).

The additive model provided interpretable risk estimates and highlighted the combined effects of FPG, BMI, age, and sex. For example, a 55- to 59-year-old woman with a BMI of 18.5 to 24.9 and an FPG level of 95-99 mg/dL had a 10-year diabetes risk of 7.0%. This risk increased to 13.0% with a BMI of 30-34.9 and 28.0% with both a higher BMI and FPG level of 105-109 mg/dL.

Across all age groups, individuals with BMI <18.5 or FPG <80 mg/dL faced elevated risks compared to those in the lowest-risk categories. The risk of diabetes rose steadily with increasing FPG levels above 80 mg/dL, but no sharp inflection was observed at the prediabetes cutoff of 100 mg/dL.

The nomogram, based on cumulative points assigned to FPG, age, sex, and BMI categories, stratified individuals into four 10-year risk groups: minimal (0-3 points, 5% risk), low (4-6 points, 12% risk), moderate (7-9 points, 26% risk), and high (≥10 points, 56% risk).

Conclusions

To summarize, in this cohort study of individuals without diabetes at baseline, 8.6% developed diabetes over a median follow-up of 6.8 years, with a 10-year cumulative risk of 12.8%. Risk increased with higher baseline FPG levels, even within the normal range, alongside additive contributions from the male sex, increasing age, and BMI.

Notably, both underweight BMI and FPG levels below 80 mg/dL were associated with higher diabetes risk, likely reflecting poor nutritional status or sarcopenia. While FPG testing is widely available, its limitations underscore the growing role of HbA1c testing for improved diagnostic accuracy and intervention targeting.