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Prediabetes is associated with elevated risk of clinical outcomes even without progression to diabetes
Mary R Rooney1,2, Amelia S Wallace3,4, Justin B Echouffo Tcheugui4,5
1Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. mroone12@jhu.edu.
Insights
Prediabetes significantly increases risks for complications like heart failure and kidney disease, even if diabetes doesn't develop. Most of this elevated risk persists even after accounting for progression to diabetes.
Area of Science:
- Endocrinology
- Cardiovascular Disease Epidemiology
- Nephrology
Background:
- Prediabetes is linked to increased risks of microvascular and macrovascular complications.
- The extent to which these risks persist after accounting for progression to diabetes is not well understood.
Purpose of the Study:
- To investigate the association between prediabetes and the incidence of major clinical outcomes.
- To determine the proportion of these risks attributable to progression to diabetes.
Main Methods:
- Analysis of 10,310 participants from the Atherosclerosis Risk in Communities (ARIC) Study.
- Cox regression used to assess associations between prediabetes and ~30-year incidence of complications (ASCVD, heart failure, CKD, mortality).
- Time-varying variable approach to account for intervening diabetes incidence.
Main Results:
- Prediabetes was associated with a modest increased risk of any complication (HR 1.21).
- This association remained significant after accounting for diabetes progression (HR 1.18).
- 85% of the excess risk of complications in prediabetes persisted even after accounting for progression to diabetes.
Conclusions:
- Progression to diabetes accounted for less than one-quarter of the clinical outcome risks associated with prediabetes.
- Prediabetes independently contributes to the risk of clinical outcomes, irrespective of progression to diabetes.
Aims/Hypothesis:
Prediabetes (HbA1c 39-47 mmol/mol [5.7-6.4%] or fasting glucose 5.6-6.9 mmol/l) is associated with elevated risks of microvascular and macrovascular complications. It is unknown to what extent these risks in prediabetes remain after accounting for progression to diabetes.
Methods:
In 10,310 participants from the Atherosclerosis Risk in Communities (ARIC) Study (aged 46-70 years, ~55% women, ~20% Black adults) without diabetes at baseline (1990-1992), we used Cox regression to characterise age- and sex-adjusted associations of prediabetes with ~30 year incidence of complications (composite and separately), including atherosclerotic CVD (ASCVD), heart failure, chronic kidney disease (CKD) and all-cause mortality before and after accounting for intervening incidence of diabetes, modelled as a time-varying variable. We calculated the excess risk of complications in prediabetes remaining after accounting for progression to diabetes.
Results:
Of the 60% of adults with prediabetes at baseline, ~30% progressed to diabetes (median time to diabetes, 7 years). Over the maximum follow-up of ~30 years, there were 7069 events (1937 ASCVD, 2109 heart failure, 3288 CKD and 4785 deaths). Prediabetes was modestly associated with risk of any complication (HR 1.21 [95% CI 1.15, 1.27]) vs normoglycaemia. This association remained significant after accounting for progression to diabetes (HR 1.18 [95% CI 1.12, 1.24]) with 85% (95% CI 75, 94%) of the excess risk of any complication in prediabetes remaining. Results were similar for the individual complications.
Conclusions/Interpretation:
Progression to diabetes explained less than one-quarter of the risks of clinical outcomes associated with prediabetes. Prediabetes contributes to the risk of clinical outcomes even without progression to diabetes.
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