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Relationship Between Risk Factors, Age, and Mortality in Type 1 Diabetes Patients

Management of non-glycemic cardiovascular disease risk factors may have increasing benefits in an aging type 1 diabetes patient population with long-term hyperglycemia.

The duration of diabetes and how well it is controlled are important factors for preventing type 1 diabetes complications and mortality. Evidence-based therapy and improvement in technology has led to a significantly higher life expectancy among T1D patients. As these patients live longer, risk for cardiovascular disease complications has increased. CVD is the major cause of death in patients with type 1 diabetes and accounts for approximately half of all deaths while the other half is as a result of non-CVD and other causes. Risk factors that lead to insulin resistance, such as high triglyceride, high LDL-cholesterol, low HDL cholesterol, high waist-to-hip ratio (WHR), and albuminuria are strong indicators of CVD in type 1 diabetes patients.

In the EURODIAB Prospective Cohort Study, 2,787 type 1 diabetes patients were studied over a 7-year period. Mortality causes were categorized as CVD, non-CVD and unknown. The analyses were adjusted for age and the length of time since diabetes was diagnosed and the most important risk factors were determined using a simultaneous and stepwise approach. Non-CVD causes had a higher annual mortality rate at 1.9 per 1,000 person-years [1.4–2.6], while mortality rate due to CVD causes was 1.4 per 1,000 person-years [1.01–2.08], and 1.7 [1.3–2.4] per 1,000 person-years for unknown causes. The results of the study showed that for younger diabetes age, non-CVD risk factors and other unknown factors contributed more to mortality rate compared to CVD risk factors.

In the DCCT/EDIC study, 1441 participants were followed for a 27-year period and their HbA1c  and other risk factors measured over time. This study determined changes in HbA1c proportion over time and its effect on risk of CVD as observed through changes in systolic blood pressure (SBP), pulse rate, triglycerides and LDL-cholesterol (LDL-c) levels. The results of this study showed that HbA1c did not have any significant influence on CVD outcomes over time. On the other hand, conventional risk factors such as SBP, pulse rate, high triglycerides and high LDL-c had an increased effect on CVD outcomes. The effect of HbA1c on CVD risk at 10 years as shown by SBP was a minimal increase of 2.7% compared to an increase of 26% at 20 years while the effect of HbA1c  on CVD risk displayed by pulse rate increased from 6.3% over 10 years to 29.3% over 20 years. The same effects were observed for triglycerides and LDL-c.

The Joslin 50-Year Medalist Study showed that glycemic control was not a significant factor in the development of microvascular complications among the participants who had lived with T1D for 5 decades. CVD prevalence was proportional to the duration and this demonstrated an age-related effect or the influence of another factor. The main cause of mortality among participants was CVD (55·0%) followed by cancer (16·3%). The age at study entry (HR 1·1, 95% CI: 1·08, 1·14) and presence of CVD (HR=2·29, 95% CI: 1·50, 3·49) were significantly associated with increased mortality risk.

These studies show that while glycemic control is very important for patients with T1D, cardiovascular risk factor become more prevalent and more significant as they grow older when compared to non-cardiovascular disease risk factors. Treatment for this patient population should therefore be directed toward cardiac-related risk factors such as high blood pressure, heart rate, and dyslipidemia.

Practice Pearls:

  • Age of diabetes and glycemic control are the most recognized factors associated with type 1 diabetes complications and mortality.
  • Risk factors such as dyslipidemia, obesity, and albuminuria lead to insulin resistance and are also strong indicators of CVD in type 1 diabetes patients.
  • Treatment for long-standing uncontrolled T1D should be directed to traditional risk factors such as high blood pressure, heart rate and dyslipidemia.

References:

Soedamah-Muthu SS, Chaturvedi N, Witte DR, et al. Relationship Between Risk Factors and Mortality in Type 1 Diabetic Patients in Europe: The EURODIAB Prospective Complications Study (PCS). Diabetes Care. 2008;31(7):1360-1366. doi:10.2337/dc08-0107.

Bebu I. Braffett BH. Pop-Busui R. Orchard TJ. Nathan DM. Lachin JM. DCCT/EDIC Research Group. The relationship of blood glucose with cardiovascular disease is mediated over time by traditional risk factors in type 1 diabetes: the DCCT/EDIC study. Diabetologia. 2017 Jul 16. doi: 10.1007/s00125-017-4374-4.

Tinsley LJ. Kupelian V. D’Eon SA. Et al. Association of glycemic control with reduced risk of large vessel disease after more than 50 years of type 1 diabetes. The Journal of Clinical Endocrinology & Metabolism. 2017. DOI: 10.1210/jc.2017-00589

 

Josephat Macharia, PharmD candidate, Lecom School of Pharmacy class of 2018