Younger age at type 2 diabetes diagnosis increases mortality risk

Discover why early diabetes detection could be a lifesaver: New study reveals alarming mortality trends in younger patients

Study: Age at type 2 diabetes diagnosis and the risk of mortality among US population. Image Credit: Eviart / Shutterstock

In a recent study published in the journal Scientific Reports, researchers investigated the relationship between age at the diagnosis of type 2 diabetes (T2D) and mortality.

T2D is a prevalent public health concern, characterized by hyperglycemia due to the destruction of β-cells and insulin resistance. In 2021, 537 million people had T2D, which is projected to reach 783 million by 2045.

Historically observed in middle-aged and older populations, T2D has increasingly become prevalent in younger age groups. Early-onset T2D is more aggressive, with a higher relative risk of diabetes-related complications and mortality and poorer outcomes.

About the study

In the present study, researchers assessed the relationship between age at T2D diagnosis and cardiovascular disease (CVD) and all-cause mortality. They used data from the National Health and Nutrition Examination Surveys (NHANES), which is representative of the United States population (US), conducted between 1999 and 2018, covering more than 101,000 individuals.

Diabetes was defined as 1) a self-reported history, 2) taking diabetes medicines to lower blood glucose, 3) glycated hemoglobin (HbA1c) ≥ 6.5%, and 4) fasting plasma glucose levels ≥ 126 mg/dL. Age at T2D diagnosis was self-reported and was stratified into three categories: < 40, 40–59, and ≥ 60 years. Standardized household questionnaires were administered to collect sociodemographic information.

A linear regression model and chi-squared test compared continuous and categorical variables. Multivariate Cox regression models were used to investigate associations between age at T2D diagnosis and (all-cause and cardiovascular) mortality. One model was adjusted for age, sex, and race; another was additionally adjusted for marital status and education. The third model was additionally adjusted for alcohol consumption, smoking status, body mass index (BMI), estimated glomerular filtration rate (eGFR), hyperuricemia, hypertension, CVD, and diabetes duration.

Further, propensity score matching was used to calculate standardized mortality rates; each diagnostic age group was matched 1:1 to a corresponding non-diabetic group based on age, sex, and race.

Restricted cubic spline regression analysis assessed potential exposure-effect relationships between mortality and age at T2D diagnosis.

Further, subgroup analyses investigated potential modifications of the association across several variables. Sensitivity analyses were performed in subjects with a prior diagnosis of diabetes to ensure robustness of results.

Findings

The study included 8,654 participants aged 59.61 years, on average. The mean age at T2D diagnosis was 51.7 years. Most participants were male (51.59%) and non-Hispanic White (35.19%). The three age groups (< 40, 40–59, and ≥ 60) were followed up for 67,554, 67,609, and 67,625 person-years, respectively. Their median age at T2D diagnosis was 44.04, 57.5, and 72.2 years, respectively.

Participants diagnosed at younger ages were more likely to be current smokers, females, Mexican Americans, non-Hispanic Blacks, and have a higher rate of insulin usage and longer diabetes duration. These subjects had lower levels of education and income and higher HbA1c, BMI, eGFR, and fasting plasma glucose levels. Notably, there was a lower prevalence of complications (CVD, hyperuricemia, or hypertension) among participants diagnosed at younger ages.

Overall, 722 cardiovascular and 2,582 all-cause deaths were recorded. In the unadjusted model, older age at T2D diagnosis was associated with higher all-cause and cardiovascular mortality. Nonetheless, after adjustments, older age at diagnosis was associated with lower cardiovascular and all-cause mortality. This meant that mortality risk increased as the age at diagnosis decreased. For instance, the hazard ratio (HR) for all-cause mortality in the <40 age group compared to the ≥60 age group was 2.72 (95% CI: 1.83-4.05) after full adjustments.

In sensitivity analyses, younger age at T2D diagnosis was associated with higher cardiovascular and all-cause mortality. Restricted cubic spline regression analysis revealed a linear relationship between age at diagnosis and all-cause death.

Interestingly, the analysis also revealed a turning point in cardiovascular mortality at age 54, where the risk decreased until age 54 and then gradually increased.

Subgroup analysis found no significant interactions based on sex, race, eGFR, BMI, CVD, and alcohol consumption. However, the association between age at diagnosis and mortality was significantly stronger in hypertensive individuals and current smokers.

Conclusions

Taken together, the findings illustrate that a younger age at T2D diagnosis was associated with a higher risk of both cardiovascular and all-cause death. This association was significantly stronger in current smokers and people with hypertension.

The study’s findings underscore the importance of early diagnosis and intervention strategies for T2D, particularly in younger populations. The results also highlight the need for personalized risk prediction and management, especially for individuals with hypertension or who are current smokers.

The study’s limitations include reliance on questionnaire data, which are subject to recall bias, non-recording of the type of diabetes in NHANES, and limited generalizability due to a US-based sample.