Association Between Hemoglobin A1c and All-Cause Mortality: Results of the Mortality Follow-up of the German National Health Interview and Examination Survey 1998

Abstract

OBJECTIVEThis study examined the association of HbA 1c -defined glycemic status and continuous HbA 1c with all-cause mortality. RESEARCH DESIGN AND METHODSThe study population comprised 6,299 participants (aged 18-79 years) of the German National Health Interview and Examination Survey 1998, who were followed up for mortality for an average of 11.6 years. Glycemic status was defined as known diabetes (self-reported diagnosis or intake of antidiabetic medication) and based on Spline models revealed a U-shaped association, with lowest risk at HbA 1c levels 5.4-5.6% (36-38 mmol/mol) and a significantly increased risk at £5.0% (£31 mmol/mol) and ‡6.4% ( ‡46 mmol/mol). CONCLUSIONSUnlike known and undiagnosed diabetes, HbA 1c levels in the prediabetic range were not associated with an increased mortality risk. The observed U-shaped relationship adds to existing evidence that not only high but also low HbA 1c levels might be associated with all-cause mortality.

The Highs and Lows of Hemoglobin A_1c

“…In this report, as has been found in previous studies on nondiabetic individuals with coronary artery disease [3], type 2 diabetes mellitus [4] and in the general population [5,6], there was a progressively increasing risk of death with increasing HbA 1c over about 7%. The extent to which hyperglycemia itself mediates this association is unclear.…”

“…Similar findings have been reported in population-based studies, so the relationship of low HbA 1c to mortality seems not to be confined to people at high risk for coronary artery disease [5,6]. This level of HbA 1c is below the physiologic range for nonpregnant adults, so the reader wonders what was going on in those individuals.…”

Mean HbA1c, HbA1c variability, and mortality in people with diabetes aged 70 years and older: a retrospective cohort study

“…Exceptionally low HbA1c levels have previously been linked to mortality. Paprtot et al 13 analysed data on patients with diabetes (n=6,299) over an 11 year period and found a 70% increased risk of mortality in diabetes subjects with HbA1c ≤5%(31mmol/mol), compared with a reference group of HbA1c, 5(31mmol/mol)-5·7%(39mmol/mol). Low HbA1c levels have been associated with increased inflammatory activity and altered liver function, 12 and in an older population this may be linked to the physical and metabolic decline observed in frailty.…”

“…Having reviewed the previous studies we further refined our analysis, by: considering the impact of very low HbA1c values (<5%,31mmol/mol), which may be associated with elevated mortality hazard independent of diabetes; 12,13 and introducing more granularity in the exposure thresholds for glycaemic targets, to provide more precise estimations of the hazard distribution.…”

Claimed effects, outcome variables and methods of measurement for health claims proposed under European Community Regulation 1924/2006 in the area of blood glucose and insulin concentrations

“…HbA1c is also linearly related to the risk of CVD and diabetes in non-diabetic individuals [61,62]. The mortality curve associated with HbA1c levels is U-shaped, with the lowest death rates for values between 5.0 and 5.5% [63]. No intervention studies have targeted HbA1c for the prevention of cardiovascular morbidity/mortality in people with normal glucose regulation.…”