The young T2D – more trouble ahead than you think

13th May 2019, Dr Chee L Khoo

You are already seeing the worrying trend of younger and younger patients being diagnosed with type 2 diabetes (T2D). My youngest is 25 years old when first diagnosed with T2D. I am sure many of you have patients younger than that. Of course, we need to make sure that these are not patients with type 1 diabetes. Unfortunately, these patients have a much greater loss of life expectancy because of the associated poorer risk factor profiles and they have a longer lead time to cause damage. How bad are these patients’ long-term clinical trajectory? How aggressive should we be in managing these patients?

Risk of cardiovascular disease (CVD) and mortality for patients with versus without type 2 diabetes mellitus (T2DM) appears to vary by the age at T2D diagnosis, but few population studies have analysed mortality and CVD outcomes associations across the full age range. All patients registered as T2D with the Swedish National Diabetes Register (NDR) were included in a recent study to evaluate the life expectancy and excess risk of cardiovascular disease and death in patients with T2D across a range of ages (1).

All patients with records with the NDR between 1998 and 2012 were evaluated. For each patient diagnosed with T2D, 5 matched controls were identified, matched for age, sex, and county, randomly selected from the general population. To reflect current conditions and management of T2D, the analysis was restricted to persons with a diabetes mellitus duration of <10 years when first registered in the NDR. assessed all-cause mortality, cardiovascular mortality, acute myocardial infarction, stroke, CHD, hospitalization for HF, and AF.

214 278 patients with T2D without previous CVD and 1 363 612 controls matched on age, sex, and county of residence. The mean age at diagnosis of 61.79 years and a spread of ages spanning from 9 to 101 years of age. Patients with T2D in comparison with controls had lower average income, were more commonly born beyond the European Union, had higher prevalence of amputation and of previous cancer but lower prevalence of dementia at baseline.

Body mass index (BMI) in those diagnosed with diabetes mellitus at <40 years of age being around 8 points higher than if they developed diabetes mellitus in their 90s. The HbA1c at diagnosis is higher the younger the age at diagnosis is with 0.47% higher in those <40 years of age in comparison with those 71 to 80 years of age. Median follow-up was 5.63 years.

Those with T2D diagnosed at ≤40 years had the highest excess relative risk for most outcomes:

  • 2.05 (1.81–2.33) for total mortality
  • 2.72 (2.13–3.48) for cardiovascular-related mortality
  • 1.95 (1.68–2.25) for noncardiovascular mortality
  • 4.33 (3.82–4.91) for CHD
  • 3.41 (2.88–4.04) for acute myocardial infarction
  • 3.58 (2.97–4.32) for stroke
  • 4.77 (3.86–5.89) for HF
  • 1.95 (1.56–2.44) for AF

Beyond 40 years, incremental risks generally declined with each higher decade age at diagnosis of T2D. For those diagnosed with T2D when > 80 years, adjusted relative risks reversed with most <1.0 for T2D versus controls for all 3 of total mortality (0.83), cardiovascular mortality (0.75), and non-cardiovascular mortality (0.87) outcomes. In those with T2D diagnosis at age >90, the only outcome for which risk seemed to be appreciably higher for those with T2D versus controls was stroke (HR, 1.56).

The median loss of life was close to 12 years when T2D was diagnosed at 15 years of age, 6 years when diagnosed at 45 years of age, 2 years when diagnosed at 65 years of age, and no accelerated loss of life after 80 years or so.

Previous studies performed in the 1990s before the advent of statins and new anti-hypertensives found a 14 fold higher myocardial infarction risk in those diagnosed with diabetes at <45 years old (2). In a more recent study, prevalent diabetes mellitus at younger ages (<55) was associated with ≈3-fold greater mortality risks, whereas such risks were null in patients with diabetes mellitus over the age of 75 (3).

These findings have important clinical implications for CVD and diabetes management and prevention guidelines:

  1. We need to be more aggressive in screening for patients who at high risk of developing diabetes at a young age (overweight or obese from young, strong family history of T2D, non-Caucasian ethnicity). Early diagnosis of diabetes allows us for diabetes remission. The longer we can delay the diabetes onset, the better the prognosis is for cardiovascular complications.
  2. Younger persons diagnosed with T2D needs aggressive cardiovascular risk management.
  3. On the other hand, we need to reassess and discuss treatment goals and aggressiveness of interventions in people diagnosed after 80 years of age, in particular, in asymptomatic individuals.

Access the abstract here.

References:

  1. Naveed Sattar, Araz Rawshani, Stefan Franzén, et al. Age at Diagnosis of Type 2 Diabetes Mellitus and Associations With Cardiovascular and Mortality Risks Findings From the Swedish National Diabetes Registry. Circulation. 2019;139:2228–2237. DOI: 10.1161/CIRCULATIONAHA.118.037885
  2. Hillier TA, Pedula KL. Complications in young adults with early-onset type 2 diabetes: losing the relative protection of youth. Diabetes Care. 2003;26:2999–3005. doi: 10.2337/diacare.26.11.2999
  3. Tancredi M, Rosengren A, Svensson AM, Kosiborod M, Pivodic A, Gudbjörnsdottir S, Wedel H, Clements M, Dahlqvist S, Lind M. Excess mortality among persons with type 2 diabetes. N Engl J Med. 2015;373:1720–1732. doi: 10.1056/NEJMoa1504347