medwireNews: Adults with younger-onset type 2 diabetes are at increased risk for complications, excess mortality, and poorer glycemic control than those who develop the condition later in life, show data from a long-term follow-up of the UK Prospective Diabetes Study (UKPDS) cohort.
Amanda Adler (University of Oxford, UK) and co-investigators say their findings highlight “a need to develop services that proactively identify and manage these individuals over their lifetimes.”
Their analysis included 4550 UKPDS participants aged 25–65 years with newly diagnosed type 2 diabetes without diabetes autoantibodies who were randomly assigned to receive intensive versus conventional glycemic control between 1977 and 1991.
Of these, 429 (9.4%) individuals were diagnosed before 40 years of age (mean 35.1 years) and were classed as having younger-onset type 2 diabetes. The remainder had later-onset type 2 diabetes, diagnosed at a mean age of 53.8 years.
At the time of diagnosis, participants with younger-onset diabetes had a significantly higher mean BMI than their older counterparts (30.6 vs 29.0 kg/m2), a significantly lower mean glycated hemoglobin (HbA1c) level (8.7 vs 9.2%; 71.6 vs 77.1 mmol/mol), and significantly higher median insulin resistance (HOMA2-IR 1.8 vs 1.6 units).
Adler and co-authors report in The Lancet Diabetes & Endocrinology that, during a median 18.0 years of follow-up, just under half (47.1%) of participants with younger-onset diabetes experienced a diabetes-related endpoint, namely sudden death, death from hyperglycemia or hypoglycemia, fatal or non-fatal myocardial infarction, angina, heart failure, fatal or nonfatal stroke, renal failure, amputation, vitreous hemorrhage, retinal photocoagulation, blindness in one eye, or cataract extraction.
The rate was 73.2% during a median 17.4 years of follow-up among those with later-onset diabetes, with adjusted incidence rates for any diabetes-related complication of 38.0 and 57.8 cases per 1000 person–years, respectively.
However, the researchers observed that “at any given age during follow-up, the 5-year incidence of all aggregate clinical outcomes, particularly all-cause mortality, diabetes-related mortality, and microvascular disease, was higher with younger age at diagnosis.”
During follow-up, the crude mortality rate was lower in participants with younger-onset diabetes than later-onset disease (10.4 vs 29.2 deaths per 1000 person–years) but the excess mortality associated with type 2 diabetes relative to the general population was higher in the younger versus older subgroups, at standardized mortality ratios of 3.72 versus 1.54.
The researchers also found that annual mean HbA1c, fasting plasma glucose, BMI, and insulin resistance was higher in the first 20 years of follow-up in people with younger- versus later-onset type 2 diabetes.
Of note, there was “no difference in the magnitude of the treatment effect among participants with young-onset versus later-onset diabetes,” the researchers remark.
In an accompanying comment, Soon Song (Sheffield Teaching Hospital NHS Foundation Trust, UK) and Brian Frier (University of Edinburgh, UK) say: “Although younger-onset type 2 diabetes was an uncommon diagnosis when the UKPDS was undertaken, it confirms that in young adults, type 2 diabetes presents a much more serious biological phenotype than when it develops later in life, being associated with the combination of failing insulin secretion, increasing insulin resistance, and greater obesity.”
They also note that the BMI of the younger-onset cohort was lower at diagnosis than has been documented in more recent studies, which highlights “the temporal progression of obesity in young adults over four decades.”
Song and Frier believe the current study has a clear message that “aggressive management is imperative in young adult-onset type 2 diabetes.”
They conclude: “Formulation of national guidelines to inform clinicians of evidence-based and cost-effective interventions for young people with type 2 diabetes is urgently needed since complications are occurring at an economically productive age.”
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Lancet Diabetes Endocrinol 2024; doi:10.1016/ S2213-8587(24)00242-0
Lancet Diabetes Endocrinol 2024; doi:10.1016/ S2213-8587(24)00282-1
