Haemoglobin glycation index and risk for diabetes-related complications in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial

Abstract

Aims/hypothesis Previous studies have suggested that the haemoglobin glycation index (HGI) can be used as a predictor of diabetes-related complications in individuals with type 1 and type 2 diabetes. We investigated whether HGI was a predictor of adverse outcomes of intensive glucose lowering and of diabetes-related complications in general, using data from the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Methods We studied participants in the ADVANCE trial with data available for baseline HbA 1c and fasting plasma glucose (FPG) (n = 11,083). HGI is the difference between observed HbA 1c and HbA 1c predicted from a simple linear regression of HbA 1c on FPG. Using Cox regression, we investigated the association between HGI, both categorised and continuous, and adverse outcomes, considering treatment allocation (intensive or standard glucose control) and compared prediction of HGI and HbA 1c .Results Intensive glucose control lowered mortality risk in individuals with high HGI only (HR 0.74 [95% CI 0.61, 0.91]; p = 0.003), while there was no difference in the effect of intensive treatment on mortality in those with high HbA 1c . Irrespective of treatment allocation, every SD increase in HGI was associated with a significant risk increase of 14-17% for macrovascular and microvascular disease and mortality. However, when adjusted for identical covariates, HbA 1c was a stronger predictor of these outcomes than HGI. Conclusions/interpretation HGI predicts risk for complications in ADVANCE participants, irrespective of treatment allocation, but no better than HbA 1c . Individuals with high HGI have a lower risk for mortality when on intensive treatment. Given the discordant results and uncertain relevance beyond HbA 1c , clinical use of HGI in type 2 diabetes cannot currently be recommended. Diabetologia (2018) 61:780-789 https://doi

Observational analyses from ADVANCE and ADVANCE‐ON

“…As with SBP, visit‐to‐visit variability of glucose and HbA1c was found to be an independent risk factor, implying that stability of both SBP and glycaemia will improve outcomes. A novel measure of glycaemia, the haemoglobin glycation index, was found to predict diabetic complications, although with no apparent advantage over HbA1c . Epidemiological analyses of HbA1c as a risk factor in diabetes suggested a nadir in the relationship with key outcomes: we concluded that HbA1c levels: “were associated with lower risks of macrovascular events and death down to a threshold of 7.0% and microvascular events down to a threshold of 6.5%.…”

“…A novel measure of glycaemia, the haemoglobin glycation index, was found to predict diabetic complications, although with no apparent advantage over HbA1c. 17 Epidemiological analyses of HbA1c as a risk factor in diabetes suggested a nadir in the relationship with key outcomes: we concluded 11 that HbA1c levels: "were associated with lower risks of macrovascular events and death down to a threshold of 7.0% and microvascular events down to a threshold of 6.5%. There was no evidence of lower risks below these levels but neither was there clear evidence of harm."…”

Association of hemoglobin glycation index and its interaction with obesity/family history of hypertension on hypertension risk: a community-based cross-sectional survey

“…Enhanced HGI levels represented a higher sensitivity to protein glycosylation and increased accumulation of advanced glycation end products (AGEs) [ 11 ]. In diabetic subjects, HGI was reported to be independently associated with a higher risk of diabetic complications like diabetic retinopathy and nephropathy [ 12 ]. For every standard increase in HGI, the risk of diabetic microvascular complications would increase by 14% [ 12 ].…”

Association of hemoglobin glycation index and its interaction with obesity /family history of hypertension on hypertension risk: a community-based cross-sectional survey

“…In diabetic subjects, HGI was reported to be independently associated with a higher risk of diabetic complications like diabetic retinopathy and nephropathy [12]. For every standard increase in HGI, the risk of diabetic microvascular complications would increase by 14% [12]. Moreover, in nondiabetic individuals, a signi cantly positive relationship between HGI and cardiometabolic risk factors clustering was observed [13].…”