Hemoglobin within normal range is negatively related to hemoglobin A1c in a nondiabetic American population aged 16 years and older

Table 1 Characteristics of participants in the present work

	Male (n = 22255)	Female (n = 22305)	P value
Age (yr)	42.12 ± 16.96	43.92 ± 17.71	< 0.0001
Race/ethnicity (%)			< 0.0001
Non-Hispanic White	68.87	70.50
Non-Hispanic Black	9.90	9.51
Mexican American	9.07	7.61
Other race/ethnicity	12.16	12.38
Education level (%)			< 0.0001
Less than high school	15.25	13.56
High school	22.89	21.07
More than high school	53.71	58.36
Others	8.15	7.01
Marital status			< 0.0001
Never married	22.22	17.57
Married	61.53	57.48
Divorced	10.22	19.85
Others	6.03	5.10
Smoked at least 100 cigarettes in life (%)			< 0.0001
Yes	48.27	37.03
No	44.76	56.91
Others	6.97	6.06
Body mass index (kg/m2)	27.91 ± 5.70	27.95 ± 7.01	0.4535
Alanine aminotransferase (U/L)	29.29 ± 22.06	20.74 ± 20.30	< 0.0001
Serum creatinine (μmol/L)	85.93 ± 26.19	66.31 ± 18.96	< 0.0001
Blood glucose (mmol/L)	5.08 ± 0.61	4.95 ± 0.59	< 0.0001
Total protein (g/L)	72.34 ± 4.53	71.24 ± 4.62	< 0.0001
Uric acid (μmol/L)	361.26 ± 72.02	277.45 ± 68.64	< 0.0001
Cholesterol (mmol/L)	5.0 ± 1.1	5.1 ± 1.1	< 0.0001
White blood cell count (109/L)	7.10 ± 2.30	7.30 ± 2.21	< 0.0001
Red blood cell count (1012/L)	4.99 ± 0.41	4.48 ± 0.36	< 0.0001
Platelet count (109/L)	240.75 ± 57.14	266.28 ± 64.99	< 0.0001
Hemoglobin (g/dL)	15.28 ± 1.02	13.64 ± 0.93	< 0.0001
Hemoglobin A1c (%)	5.34 ± 0.36	5.32 ± 0.37	< 0.0001

Data are show in mean ± SD, including age, body mass index, alanine aminotransferase, cholesterol, creatinine, blood glucose, red/white blood cell count, platelet count, total protein, serum uric acid, hemoglobin, and hemoglobin A1c. Weighted linear regression model was employed to compute the P value. Categorical variables are represented in percentage (%), including race, educational level, marital status, smoking (> 100 cigarettes in life), while weighted chi-square test was employed to compute the P value.

Table 2 Relation between hemoglobin (1 g/dL) and hemoglobin A1c level (%)

	Unadjusted model β (95%CI)	Minimally adjusted model β (95%CI)	Fully adjusted model β (95%CI)
Hemoglobin	-0.01 (-0.01, -0.01)c	-0.01 (-0.01, -0.00)c	-0.08 (-0.08, -0.07)c
Hemoglobin (Quartile)
Q1	Reference	Reference	Reference
Q2	0.01 (0.00, 0.02)	0.01 (-0.00, 0.01)	-0.06 (-0.07, -0.05)c
Q3	0.02 (0.01, 0.03)b	0.01 (-0.00, 0.02)	-0.12 (-0.13, -0.11)c
Q4	-0.04 (-0.05, -0.03)c	-0.02 (-0.03, -0.01)c	-0.23 (-0.24, -0.22)c
P for trend	< 0.001	< 0.001	< 0.001

^aP< 0.01.

^bP< 0.001.

^cP< 0.0001.

Three models were employed to analyze the relation in this work, namely, unadjusted model, minimally adjusted model, and fully adjusted model. No covariates were regulated in unadjusted model. Only age and gender were regulated in minimally adjusted model. Lastly, in fully adjusted model, all parameters were adjusted, including age, gender, ethnicity, educational level, marital status, smoking behavior, body mass index, uric acid, total protein, serum creatinine, blood glucose, alanine aminotransferase, cholesterol, platelet count, and red/ white blood cell count.

Table 3 Age- and sex-stratified analysis of correlation for hemoglobin (g/dL) and hemoglobin A1c (%)

	Unadjusted model β (95%CI)	Minimally adjusted model β (95%CI)	Fully adjusted model β (95%CI)
Stratified by age
16-29	-0.011 (-0.015, -0.008)a	-0.054 (-0.059, -0.048)a	-0.104 (-0.110, -0.097)a
30-51	-0.004 (-0.008, 0.001)	-0.037 (-0.042, -0.031)a	-0.090 (-0.097, -0.083)a
52-85	-0.021 (-0.025, -0.016)a	-0.023 (-0.028, -0.017)a	-0.084 (-0.091, -0.077)a
Stratified by sex
Men	-0.057 (-0.062, -0.052)a	-0.031 (-0.036, -0.027)a	-0.085 (-0.091, -0.080)a
Women	-0.012 (-0.017, -0.007)a	-0.033 (-0.038, -0.029)a	-0.091 (-0.096, -0.085)a

^aP < 0.0001.

Three models were employed to analyze the relation in this work, namely, unadjusted model, minimally adjusted model, and fully adjusted model. No covariates were regulated in unadjusted model. Only age was regulated in minimally adjusted model. Lastly, in fully adjusted model, all parameters were regulated, including age, gender, ethnicity, educational level, marital status, smoking behavior, body mass index, uric acid, total protein, serum creatinine, blood glucose, alanine aminotransferase, cholesterol, platelet count, and red/ white blood cell count.

Table 4 Threshold effect analysis of hemoglobin-on-hemoglobin A1c using piecewise linear regression

Point of hemoglobin (g/dL)	Odd ratio (95%CI)	P value
< 13.2	-0.04 (-0.05, -0.03)	< 0.0001
> 13.2	-0.10 (-0.10, -0.09)	< 0.0001

A threshold of 13.2g/dL for the hemoglobin existed for hemoglobin A1c. Parameters were adjusted, including age, race, body mass index, smoking (> 100 cigarettes in life), educational level, marital status, serum uric acid, alanine aminotransferase, creatinine, blood glucose, total protein, cholesterol, red/white blood cell count, and platelet count.