A1C Variability Predicts Incident Cardiovascular Events, Microalbuminuria, and Overt Diabetic Nephropathy in Patients With Type 1 Diabetes

Abstract

OBJECTIVERecent data from the Diabetes Control and Complications Trial (DCCT) indicated that A1C variability is associated with the risk of diabetes microvascular complications. However, these results might have been influenced by the interventional study design. Therefore, we investigated the longitudinal associations between A1C variability and diabetes complications in patients with type 1 diabetes in the observational Finnish Diabetic Nephropathy (FinnDiane) Study.RESEARCH DESIGN AND METHODSA total of 2,107 patients in the FinnDiane Study had complete data on renal status and serial measurements of A1C from baseline to follow-up (median 5.7 years), and 1,845 patients had similar data on cardiovascular disease (CVD) events. Intrapersonal SD of serially measured A1C was considered a measure of variability.RESULTSDuring follow-up, 10.2% progressed to a higher albuminuria level or to end-stage renal disease, whereas 8.6% had a CVD event. The SD of serial A1C was 1.01 versus 0.75 (P < 0.001) for renal status and 0.87 versus 0.79 (P = 0.023) for CVD in progressors versus nonprogressors, respectively. In a Cox regression model, SD of serial A1C was independently associated with progression of renal disease (hazard ratio 1.92 [95% CI 1.49–2.47]) and of a CVD event (1.98 [1.39–2.82]) even when adjusting for mean A1C and traditional risk factors. Interestingly for CVD, mean serial A1C itself was not predictive even though SD of A1C was.CONCLUSIONSIn patients with type 1 diabetes, A1C variability was not only predictive of incident microalbuminuria and progression of renal disease but also of incident CVD events.

Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis

“…Twenty studies in 87,641 participants met the inclusion criteria. Ten studies included participants from Europe (10,11,14,(16)(17)(18)(19)26,29,35,36), eight from Asia (12,13,15,18,20,24,27,28), four from North America (6,18,23, 25), and one from Australasia (18). The number of participants in each study ranged from 234 to 35,891.…”

“…Seven studies included 44,021 participants with type 1 diabetes (6,10,11,14,25,29,35). These comprised three retrospective cohort studies (11,14,25), two prospective cohort studies (10,29), one post hoc analysis of a randomized controlled trial (6), and one cross-sectional study (35).…”

“…A recent meta-analysis concluded that HbA 1c variability, assessed by the SD, is associated with renal disease in type 1 and type 2 diabetes (9). However, no systematic reviews or meta-analyses have evaluated the relationship between long-term glycemic variability and other complications in diabetes, despite contradictory literature providing evidence in support (6,(10)(11)(12)(13)(14)(15) and against (16)(17)(18)(19)(20) such a relationship.…”

“…First, unlike short-term glycemic variability, longterm glycemic variability may predict complications in both type 1 and type 2 diabetes (6,(10)(11)(12)(13)(14)(15)(21)(22)(23)(24)(25)(26)(27)(28)(29). Second, HbA 1c is routinely recorded in primary care for both types of diabetes, whereas measures of short-term variability are not (30,31).…”

The study of correlation of silent myocardial ischemia with microalbuminuria in patients of type 2 diabetes mellitus

“…15 Muggeo M et al in the Verona Diabetes study found long-term instability of fasting plasma glucose an independent cardiovascular risk factor in type 2 diabetics. 16 In our study 25 out of 29 (86 .2%) patients with Hba1c > 9 had positive treadmill test.…”