Association between Inflammation and Biological Variation in Hemoglobin A1c in U.S. Nondiabetic Adults

Abstract

Context: Inflammation is associated with higher glycated hemoglobin (HbA1c) levels. Whether the relationship is independent of blood glucose concentration remains unclear.

Objective: The hemoglobin glycation index (HGI) was used to test the hypothesis that interindividual variation in HbA1c is associated with inflammation.

Participants: This study used nondiabetic adults from the National Health and Nutrition Examination Survey (1999-2008).

Main outcome measures: A subsample of participants was used to estimate the linear regression relationship between HbA1c and fasting plasma glucose (FPG). Predicted HbA1c were calculated for 7323 nondiabetic participants by inserting FPG into the equation, HbA1c = 0.017 × FPG (mg/dL) + 3.7. HGI was calculated as the difference between the observed and predicted HbA1c and the population was divided into low, moderate, and high HGI subgroups. Polymorphonuclear leukocytes (PMNL), monocytes, and C-reactive protein (CRP) were used as biomarkers of inflammation.

Results: Mean HbA1c, CRP, monocyte, and PMNL levels, but not FPG, progressively increased in the low, moderate, and high HGI subgroups. There were disproportionately more Blacks than whites in the high HGI subgroup. CRP (ß, 0.009; 95% confidence interval [CI], 0.0001-0.017), PMNL (ß, 0.036; 95% CI, 0.010-0.062), and monocyte count (ß, 0.072; 95% CI, 0.041-0.104) were each independent predictors of HGI after adjustment for age, sex, race, triglycerides, hemoglobin level, mean corpuscular volume, red cell distribution width, and obesity status.

Conclusions: HGI reflects the effects of inflammation on HbA1c in a nondiabetic population of U.S. adults and may be a marker of risk associated with inflammation independent of FPG, race, and obesity.

Figure 1.

Effect of inflammation on metrics of metabolic control after full adjustment including obesity. y-axis, from left to right: FPG (mg/dL), HbA1c (%), HGI (%). x-axis, upper panel: C-reactive protein (mg/dL); lower panel: monocyte count (k/μl). Groups: Upper panel, Group 1: blank bar (CRP < 0.3 mg/dL); Group 2: shaded bar (0.3 ≤ CRP < 1.0 mg/dL); Group 3: black bar (CRP ≥ 1.0 mg/dL). Lower panel: Group 1: blank bar (monocyte count < 0.8 k/μl); Group 2: black bar (monocyte count ≥ 0.8 k/μl). ^a,b,c, means ± SE with different characters are significantly different within CRP or monocyte count subgroups; P < .05.