Association of a Biomarker of Glucose Peaks, 1,5-Anhydroglucitol, With Subclinical Cardiovascular Disease

Abstract

OBJECTIVE1,5-Anhydroglucitol (1,5-AG) is a biomarker of glucose peaks and has been associated with clinical cardiovascular disease. However, the association between 1,5-AG and subclinical cardiovascular disease is unknown. We investigated the association of 1,5-AG with subclinical myocardial damage (assessed by high-sensitivity cardiac troponin T [hs-cTnT]) and atherosclerosis (assessed by carotid intima-media thickness [CIMT] and carotid plaque).RESEARCH DESIGN AND METHODSWe measured 1,5-AG, hs-cTnT, CIMT, and carotid plaque among 10,072 people without diabetes and 681 with diabetes who attended the second examination of the Atherosclerosis Risk in Communities (ARIC) Study (baseline, 1990–1992). We used Poisson regression to characterize the associations between 1,5-AG and prevalent elevated hs-cTnT, thick CIMT, or carotid plaque. Among 9,145 people with a second hs-cTnT measurement 6 years later, we used multinomial logistic regression to assess associations with incident elevation in hs-cTnT.RESULTSWe found that in people with diabetes, lower 1,5-AG (<6 μg/mL) was cross-sectionally associated with elevated hs-cTnT (prevalence ratio 2.06, 95% CI 1.23–3.46) compared with higher 1,5-AG (≥10 μg/mL). Associations in people without diabetes and with thick CIMT or the presence of carotid plaque were less robust. Low 1,5-AG was prospectively associated with the 6-year incident elevation in hs-cTnT (relative risk 2.90, 95% CI 1.23–6.85) in people with diabetes. All associations were strongly attenuated with further adjustment for HbA1c.CONCLUSIONSIn people with diabetes, 1,5-AG was associated with subclinical cardiovascular disease, particularly chronic subclinical myocardial damage. Nonetheless, whether observed associations are truly independent of average glycemia is unclear.

Response of 1,5‐anhydroglucitol level to intensive glucose‐ and blood‐pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial

“…Our results for the observational analysis of baseline 1,5‐AG with microvascular and macrovascular events in the ADVANCE trial is consistent with previous studies in populations with type 2 diabetes . In analyses of the Atherosclerosis Risk in Communities (ARIC) study, we previously reported that 1,5‐AG was inversely associated with prevalent retinopathy and incident chronic kidney disease, incident end‐stage renal disease, and incident cardiovascular disease and mortality .…”

“…Low 1,5‐AG is thought to be a useful biomarker to monitor glycosuric hyperglycaemia. 1,5‐AG has been linked to complications of diabetes in previous observational studies, but few reports have examined how 1,5‐AG may respond to an intensive glucose‐lowering intervention. Previous trials have been small and or of short duration (a few weeks or less) …”

Orthostatic Hypotension and Risk of Clinical and Subclinical Cardiovascular Disease in Middle‐Aged Adults

“…We defined an elevated NT‐proBNP as ≥100 pg/mL. We used a detectable hs‐cTnT and elevated NT‐proBNP on the basis of prior literature, suggesting that detectable hs‐cTNT is associated with underlying cardiac damage, whereas elevated NT‐proBNP is associated with cardiac wall strain 28, 29, 30…”

“…Covariates were selected a priori to examine the independent association between OH and CVD 28, 29, 31. We specifically examined established cardiovascular risk factors on the basis of demographic information, self‐reported behaviors, body mass index, cholesterol, and comorbid conditions (diabetes mellitus, hypertension, and chronic kidney disease).…”

Effects of dietary carbohydrate on 1,5‐anhydroglucitol in a population without diabetes: results from the OmniCarb trial

“…l,5-AG is inversely associated with blood glucose concentrations as a result of competitive inhibition by glucose in the proximal tubule [4] and is thought to be useful for intermediate-term monitoring of glycaemic variability in people with diabetes [5]. In epidemiological studies, low concentrations have been associated with greater diabetes risk [6,7] and, in the setting of diabetes with retinopathy, chronic kidney disease [7][8][9] and cardiovascular disease [10,11]. In people without diabetes, 1,5-AG may reflect carbohydrate digestion [12,13].…”