Increased Mortality in Diabetes Patients with Low HbA1c Values Is Found Only in Patients with Haptoglobin Type 2-2  – Paradigm Shift Towards Genetically-Determined Personalized Glycemic Targets

Presentation Number: SAT 599
Date of Presentation: April 1st, 2017

Irit Hochberg*1, Chen Shapira2, Mordechai Alperin2 and Uzi Milman2
1Rambam Health Care Campus, Haifa, Israel, 2Clalit Health Services, Haifa, Israel


The optimal target of glucose and HbA1c for reducing cardiovascular events and mortality in patients with long standing diabetes is not clear. The ACCORD study found higher mortality in the tight control arm in diabetes patients with high cardiovascular risk, and several large retrospective studies have found a J shape of hazard-ratio curve of HbA1c and mortality, with the lowest mortality risk in patients with HbA1c 7.5%, and with increased hazard ratio for mortality in patients with lower or higher HbA1c values(1). Haptoglobin (Hp) type 2-2 is a strong cardiovascular risk factor in diabetes(2), and we hypothesized that Hp type may modify the effect of HbA1c on mortality and cardiovascular events. We followed the ADHOC study cohort, consisting of 3034 type 2 diabetes patients (285 with Hp 1-1, 1248 with Hp 2-1 and 1511 with Hp 2-2), from 2002 to 2014 for cardiovascular events and total mortality. HbA1c distribution was similar between the Hp groups. We found a J shaped curve in patients with Hp 2-2, with the highest rates of mortality and composite outcome of mortality and myocardial infarction in Hp 2-2 patients with HbA1c<6.6% (P<0.0002 for mortality and P<0.015 for the composite outcome). The J shaped curve was not found in patients with Hp 2-1 and 1-1, where HbA1c values of less than 6.6% were associated with lower occurrence of the composite outcome of mortality and myocardial infarction (P<0.033 for Hp 1-1 and P<0.036 for Hp 2-1). Our results shift current clinical paradigms in treating diabetes, utilizing a novel approach to optimize “personalised medicine” based on a genetic characteristic. Determining Hp type for each diabetes patient may be useful for making decisions on the intensity of glycemic treatment.


Nothing to Disclose: IH, CS, MA, UM