We seek to provide evidence that prolonged, continuous, tight glycemic control, initiated when type 2 diabetes (DM) is first diagnosed and maintained throughout patients'DM lifetime, can reduce the risk of cardiovascular disease (CVD). Current recommendations on care for persons with DM include tight glycated hemoglobin (A1C) control (<7%) as a means to reduce risk of CVD and other complications. Recent studies raised questions about this recommendation by failing to demonstrate that tight A1C control provides CV benefit in persons with DM, but these studies could not account for glycemic control prior to trial initiation. Other research supports the benefit of tight glycemic control over time, and suggests that even moderately elevated A1C levels in the 'normal'range indicate long-term CVD risk. To address these seemingly contradictory perspectives on how to optimize DM care, we propose to test the hypothesis that tight glycemic control does indeed reduce CVD risk, if begun early and continued throughout the course of DM. We will also assess whether cumulative glycemic burden over time, predict long-term CVD risk better than current A1C level or mean A1C over time, and to identify threshold levels of cumulative glycemic burden at which CVD risk becomes markedly elevated, among persons with DM. We will conduct the proposed analyses using data from the Kaiser Permanente Northwest Diabetes Registry. Since 1988, KPNW has developed and maintained this highly specific, sensitive, data-rich registry of members with DM;as of December 2009, it contained data on >70,000 persons. Among adults who joined the registry in 1995-2010, we will identify individuals who experienced a CVD event and match them to 5 controls who did not. We will then conduct multivariate logistic regression analyses of the extent to which A1C, mean A1C, and cumulative A1C burden predict time until first CVD event, and describe differences in the odds of CVD from date of DM diagnosis through 2010, to identify cut-points (of A1C, mean A1C over time, and cumulative glycemic burden levels) where CVD risk increases. The clinical application of such findings would lie in proving what has long been suspected - that cumulative glycemic burden is a critical CVD risk factor - thus providing critical support for the importance of initiating tight glycemic control immediately upon DM diagnosis and maintaining such control rigorously. No previous studies have evaluated cumulative glycemic burden as an indicator of CVD risk in DM, alone or in comparison to mean A1C over time, despite cumulative burden's biological plausibility as a CVD risk factor. The proposed work builds on our previous development of methods for measuring cumulative glycemic burden.

Public Health Relevance

This study will use existing data on Kaiser Permanente Northwest members with diabetes from 1995- 2010 to assess whether control of high blood sugar, if begun early and continued over time, reduces cardiovascular disease risk. We will use a novel measure of high blood sugar, glycemic burden, which accounts for how high blood sugar is and how long it has been high. Our results would show the importance of treating blood sugar aggressively immediately upon diabetes diagnosis and maintaining such aggressive treatment rigorously.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Exploratory/Developmental Grants (R21)
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Kidney, Nutrition, Obesity and Diabetes (KNOD)
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Savage, Peter J
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Kaiser Foundation Research Institute
United States
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Nichols, Gregory A; Rosales, A Gabriela; Perrin, Nancy A et al. (2014) The association between different A1C-based measures of glycemia and risk of cardiovascular disease hospitalization. Diabetes Care 37:167-72