By Tarun Sai LomteReviewed by Danielle Ellis, B.Sc.Nov 4 2024

New research highlights that early-onset type 2 diabetes significantly increases mortality risk compared to later diagnoses. 

In a recent study published in The Lancet Diabetes & Endocrinology, researchers evaluated whether mortality and complications differed for younger- and later-onset type 2 diabetes (T2D).

Background

Although T2D has been conventionally regarded as a disease of older and middle age, its onset in younger ages is recognized as a distinct non-autoimmune phenotype. There are concerns that early exposure to hyperglycemia in younger-onset T2D may elevate the risk of complications and reduce life expectancy. Moreover, younger-onset T2D is more aggressive than later-onset T2D, with a greater excess risk of complications and accelerated deterioration of β-cell function.

About the study

In the present study, researchers investigated whether mortality rates and complications differ between younger- and later-onset T2D. This study was an observational analysis of the United Kingdom prospective diabetes study (UKPDS) data collected between 1977 and 2007. The UKPDS was a randomized trial of glucose-lowering therapy in people aged 25–65 with newly diagnosed diabetes.

Participants with fasting plasma glucose (FPG) between 6 mmol/L and 15 mmol/L were randomized to a conventional glycemic control strategy (mainly diet) or an intensive strategy (insulin, metformin, or sulfonylurea). Individuals with FPG > 15 mmol/L were assigned to the intensive strategy, while those with FPG < 6 mmol/L were assigned to diet. This study included participants who tested negative for all diabetes-related autoantibodies.

T2D diagnosis before the age of 40 was defined as younger-onset T2D, whereas diagnosis at the age of 40 or above was defined as later-onset T2D. Seven aggregate outcomes were assessed: diabetes-related endpoints, diabetes-related death, any-cause death, myocardial infarction, peripheral vascular disease, stroke, and microvascular disease. The absolute and adjusted incidence risk of each outcome over the follow-up was estimated.

Further, standardized mortality ratios (SMRs) were calculated by onset and 10-year age intervals at diagnosis. The absolute risk was calculated as incidence rates per 1000 person-years. Follow-up was calculated from diagnosis to endpoint occurrence. Poisson regression was used to estimate incidence rates adjusted for body mass index (BMI), sex, ethnicity, glycated hemoglobin (HbA1c), smoking, systolic blood pressure, and low-density lipoprotein.

Findings

The present study included 4,550 participants from the UKPDS trial with T2D who did not possess diabetes-related autoantibodies. Of these, 429 had younger-onset T2D at an average age of 35.1, while the remainder had later-onset T2D at 53.8 years, on average. At diagnosis, younger-onset T2D participants were more likely to be Indian or Asian; they also had higher mean BMI, median fasting triglycerides, and lower mean HbA1c than later-onset T2D subjects.

Any diabetes-related endpoint occurred in 47.1% and 73.2% of participants with younger- and later-onset T2D over a median of 18 and 17.4 years of follow-up, respectively. The adjusted and absolute incidence rates were higher in the later-onset T2D group for all outcomes except for microvascular disease. In total, 2,048 deaths were recorded over a follow-up of 74,979 person-years.

Younger-onset T2D subjects had a lower crude mortality rate than their later-onset counterparts. However, the younger-onset group had higher excess mortality associated with T2D relative to the general public than the later-onset group. When stratified by 10-year age intervals, the youngest age group (24–35) had the highest SMR. Moreover, SMR attenuated with increasing age at T2D diagnosis.

One year after diagnosis, all age groups showed significant improvements in FPG, BMI, HbA1c, and estimated β-cell function compared to baseline. Thereafter, the average FPG, BMI, insulin resistance and HbA1c were elevated in younger-onset T2D subjects in the first 20 years of follow-up. At 10 years of follow-up, BMI, FPG, and HbA1c increased more in younger-onset T2D subjects.

Notably, estimated β-cell function in the younger-onset group, which was higher at diagnosis, decreased more in the first 10 years post-diagnosis. Overall, 75.1% and 85.2% of younger- and later-onset T2D subjects were randomized to glycemic control strategies. There were no differences in treatment effect between younger- and later-onset groups.

Among those allocated to receive insulin or sulfonylurea compared to conventional therapy, the risk of any-cause death, microvascular disease, myocardial infarction, and diabetes-related death was significantly reduced in the later-onset group. However, there were no significant risk elevations or reductions in the younger-onset T2D group. Similar results were observed among metformin recipients in the later-onset T2D group.

Conclusions

Taken together, the findings reveal that younger-onset T2D was associated with a greater risk of diabetes complications, poor glycemic control, and excess mortality compared to people with later-onset T2D. At any given age, the five-year incidence rate of all aggregate outcomes was greater in younger-onset T2D subjects than in the later-onset group. Overall, these findings warrant the development of services and interventions that identify and manage these individuals.