ISSN 1662-4009 (Online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 10.17 | DOI: 10.1530/ey.16.10.17

Relative prognostic importance and optimal levels of risk factors for mortality and cardiovascular outcomes in type 1 diabetes mellitus

Rawshani A, Rawshani A, Sattar N, Franzén S, McGuire DK, Eliasson B, Svensson AM, Zethelius B, Miftaraj M, Rosengren A & Gudbjörnsdottir S

Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden

To read the full abstract: Circulation. 2019;139:1900–1912

Numerous publications have reported that higher HbA1c levels relate to higher cardiovascular disease (CVD) risk in people with type 1 diabetes (T1D). However, the strength of association and optimal HbA1c levels are not established.

This analysis of T1D patients recorded in the Swedish National Diabetes Register from 1998 to 2014 examined the prognostic importance of 17 risk factors for death and CVD. Cox regression and machine learning techniques were used to identify optimal cut point levels for HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL) in relation to all-cause mortality, fatal/nonfatal acute myocardial infarction, fatal/nonfatal stroke, and hospitalization for heart failure. Of 32,611 patients with T1D, 1809 (5.5%) died during follow-up over 10.4 years.

The strongest predictors for death and CVD outcomes were: high HbA1c; renal disease as indicated by albuminuria; duration of T1D; higher SBP; and higher LDL. Risk of death increased by: ~2% per 1-mmol/mol higher HbA1c (~22% per 1% HbA1c); and 35% to 50% per 1-mmol/L higher LDL. Micro- or macroalbuminuria was associated with 2 to 4-times higher risk for CVD complications and death. HbA1c <53 mmol/mol (7.0%), SBP <140 mmHg, and LDL <2.5 mmol/l were identified as optimal thresholds associated with better health across the outcomes.

In summary, the study confirms that high HbA1c levels, albuminuria, duration of T1D, SBP, and LDL are the most important predictors for mortality and CVD in patients with T1D. Furthermore, it seems to be justified that levels for HbA1c, SBP, and LDL that are even lower than current guideline recommendations appear to be associated with significantly lower disease risks. This study clearly shows that it is very well worthwhile to do the utmost to achieve good metabolic control in people with T1D.