LCF showed a trend toward a modestly reduced mean glucose and significantly lower insulin requirements as compared with standard feeding but had no effect on glucose variability or time in target range.

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

The haemoglobin glycation index (HGI) quantifies the interindividual variation in the propensity for glycation and is a predictor of diabetes complications and adverse effects of intensive glucose lowering. We investigated the relevance of HGI as independent predictor of complications by using data of the AleCardio trial. The AleCardio trial randomized 7226 type 2 diabetes patients with an acute coronary syndrome to aleglitazar or placebo. From 6458 patients with baseline glycated haemoglobin (HbA) and fasting plasma glucose (FPG), a linear regression equation, HbA (%) = 5.45 + 0.0158 * FPG (mg/dl), was used to calculate predicted HbA and derive HGI (= observed - predicted HbA). With multivariate Cox regression we examined the association with major adverse cardiac events, cardiovascular mortality, total mortality and hypoglycaemia, irrespective of treatment allocation, using HGI subgroups (low, intermediate and high) and HGI as continuous variable. Patients with high HGI were younger, more often non-Caucasian, had a longer duration of diabetes, showed more retinopathy and used insulin more often. Hypoglycaemia occurred less often in the low HGI subgroup, but this difference disappeared after adjustment for duration of diabetes, insulin and sulphonylurea use. Low HGI patients were at lower risk for cardiovascular mortality (hazard ratio 0.64; 95% confidence interval 0.44-0.93, p = 0.020) and total mortality (hazard ratio 0.69; 95% confidence interval 0.50-0.95, p = 0.025), as compared with high HGI patients. Every percentage increase in HGI was associated with a 16% increase in the risk for cardiovascular mortality ( p = 0.005). The association between HGI and mortality disappeared with additional adjustment for HbA. HGI predicts mortality in diabetes patients with acute coronary syndromes, but no better than HbA.