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HbA1c in nondiabetic Dutch infants aged 8-12 months: the GECKO-Drenthe birth cohort study.
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MedLine Citation:
PMID:  21270198     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: An international committee of experts recommended using HbA(1c) for diagnostic testing for diabetes. Little is known about normal values of HbA(1c) in infants. The aim of this study is to describe the distribution of HbA(1c) in 8- to 12-month-old nondiabetic infants.
RESEARCH DESIGN AND METHODS: HbA(1c) was measured in 86 infants participating in the Groningen Expert Center for Kids with Obesity (GECKO)-Drenthe birth cohort study. Anthropometric measurements were performed at Well Baby Clinics. Data on parents and children were collected prospectively using questionnaires.
RESULTS: HbA(1c) was normally distributed with a mean (SD) HbA(1c) level of 5.38% (0.24), range 4.8-6.0% or 35.29 mmol/mol (2.65), range 29.1-42.1 mmol/mol. Age, sex, birth weight, duration of breastfeeding, anthropometric measurements, and maternal BMI were not associated with HbA(1c).
CONCLUSIONS: We found a normal distribution of HbA(1c) with a relatively high mean HbA(1c) of 5.38%. No significant association between risk factors for type 2 diabetes and HbA(1c) levels was found.
Hanneke Jansen; Haika G Huiting; Salome Scholtens; Pieter J J Sauer; Ronald P Stolk
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Publication Detail:
Type:  Journal Article; Validation Studies    
Journal Detail:
Title:  Diabetes care     Volume:  34     ISSN:  1935-5548     ISO Abbreviation:  Diabetes Care     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-28     Completed Date:  2011-04-25     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  7805975     Medline TA:  Diabetes Care     Country:  United States    
Other Details:
Languages:  eng     Pagination:  403-5     Citation Subset:  IM    
Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
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MeSH Terms
Analysis of Variance
Chemistry, Clinical / standards*
Cohort Studies
Diabetes Mellitus, Type 2 / epidemiology*
Hemoglobin A, Glycosylated / metabolism*
Netherlands / epidemiology
Predictive Value of Tests
Reference Values
Risk Factors
Reg. No./Substance:
0/Hemoglobin A, Glycosylated; 0/hemoglobin A1c protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Diabetes Care
Journal ID (hwp): diacare
Journal ID (pmc): dcare
Journal ID (publisher-id): Diabetes Care
ISSN: 0149-5992
ISSN: 1935-5548
Publisher: American Diabetes Association
Article Information
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© 2011 by the American Diabetes Association.
Received Day: 9 Month: 6 Year: 2010
Accepted Day: 21 Month: 11 Year: 2010
Print publication date: Month: 2 Year: 2011
Electronic publication date: Day: 20 Month: 1 Year: 2011
Volume: 34 Issue: 2
First Page: 403 Last Page: 405
ID: 3024357
PubMed Id: 21270198
Publisher Id: 1100
DOI: 10.2337/dc10-1100

HbA1c in Nondiabetic Dutch Infants Aged 8–12 Months : The GECKO-Drenthe birth cohort study
Hanneke Jansen, MD1
Haika G. Huiting, MD12
Salome Scholtens, PHD1
Pieter J.J. Sauer, MD, PHD2
Ronald P. Stolk, MD, PHD1
1Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
2Department of Pediatrics, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Correspondence: Corresponding author: Hanneke Jansen,

An international committee of experts recommended using HbA1c as an indicator for diagnosing diabetes, and, with the prevalence of type 2 diabetes rising, an increase in use of HbA1c can be expected (1). Accordingly, reference levels for HbA1c will need to be developed for all age groups. This study’s aim is to describe the distribution of HbA1c in nondiabetic infants aged 8–12 months, and to investigate predictors of HbA1c.


The study population consisted of 86 Dutch infants participating in the Groningen Expert Center for Kids with Obesity (GECKO)-Drenthe study. This population-based birth cohort study within the GECKO was designed to examine risk factors for developing childhood obesity (2). A random subgroup (N = 100) of this study population, aged about 8 months, was invited to participate in the current study. Eighty-seven parents agreed to participate, and in eighty-six infants, an HbA1c value could be assessed. This study was approved by the Medical Ethics Committee of the University Medical Center Groningen.

HbA1c was measured in a capillary blood sample using a turbidimetric inhibition immunoassay on a Cobas Integra 800 CTS analyzer (Roche Diagnostics, Nederland BV, Almere, the Netherlands). This method has been standardized against the reference method of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Results (mmol HbA1c/mol Hb) were converted to units (% HbA1c) traceable to the Diabetes Control and Complications Trial/National Glycohemoglobin Standardization Program (DCCT/NGSP) using the Roche master-equation. Between-batch imprecision (coefficient of variation) was 2.1% for a mean HbA1c of 5.5% and 1.9% for a mean HbA1c of 10.6%.

Anthropometric measurements were performed by trained staff at Well Baby Clinics (2). Forty-eight percent of the infants did not visit the Well Baby Clinic within 2 weeks around blood sampling. For these infants, weight, length, and waist circumference were determined by linear interpolation. Weight, waist circumference, and weight-for-length z-scores were calculated using Growth Analyzer 3.5 (Growth Analyzer B.V., Rotterdam, the Netherlands), based on Dutch reference values (3,4). Growth velocity was defined as increase in weight between birth and time of blood sampling, in grams per week.

Data on gestational age, birth weight, infant feeding, gestational diabetes, maternal BMI, and parental educational level were obtained through questionnaires, and missing data was obtained from Well Baby Clinic files. Small for gestational age (SGA) and large for gestational age (LGA) were defined as birth weight below the 10th percentile and above the 90th percentile, respectively, for gestational age compared with Dutch reference values by parity and sex (5).

We used ANOVA to test for differences in mean HbA1c between groups and linear regression to test the relationship between continuous variables and HbA1c. For all analyses, a level of significance of P < 0.05 was applied. Statistical analyses were performed using SPSS 16.0 for Windows (SPSS, Chicago, IL).


Of the 86 infants included, 43 were girls and 43 were boys, with a mean (SD) age of 9.42 months (1.14). Mean (SD) HbA1c was 5.38% (0.24), range was 4.8–6.0%, with a skewness (SE) of 0.215 (0.260) and a kurtosis (SE) of −0.004 (0.514). According to IFCC values, mean (SD) HbA1c was 35.29 mmol/mol (2.65), range 29.1–42.1 mmol/mol (Fig. 1).

HbA1c was unrelated to age or sex. Birth weight, growth velocity, anthropometric measurements, duration of breastfeeding, gestational diabetes, maternal BMI, and parental educational level were all unassociated with HbA1c. HbA1c did not differ between infants born SGA and infants not born SGA, or between infants born LGA and those not born LGA.


In this nondiabetic infant population, aged 8–12 months, HbA1c was normally distributed, with a mean (SD) HbA1c of 5.38% (0.24), range 4.8–6.0%.

The mean HbA1c of 5.38% observed in the current study is higher than that found by studies in adults and older children (69). Because HbA1c below 6% is considered normal, the clinical relevance of the difference between an HbA1c level of 4.9% seen in adults and children, compared with 5.4% in our study population, is arguable. However, because the rate of formation of HbA1c is directly proportional to ambient glucose concentration, our results could indicate higher glucose levels in 8- to 12-month-old infants. The predominant fuel for human cells is glucose, and survival of the brain depends on a continuous supply, yet the brain cannot synthesize glucose nor store more than a few minutes supply as glycogen. The infant brain is large relative to body mass and, especially in this period, rapid brain growth and differentiation takes place. To meet the high demand for glucose, the rate of glucose production in infants and young children is two to three times that of older children and mature adults (10). This high demand for glucose by the brain and the subsequent higher rate of glucose production might explain the higher HbA1c levels observed in this study. Another explanation for the relatively high HbA1c levels might be the higher percentage of infant fat mass compared with older children; fat mass is known to be positively related to insulin resistance (11,12). Unfortunately, glucose and insulin levels were not assessed, so we could not test these hypotheses.

At birth, between 55 and 65% of total hemoglobin synthesis consists of HbF. After birth, the production of the γ-chain declines to values of <5% by the age of 6 months; normal adult HbF values of <1% are usually reached by age 1 year (13). Because our study population’s age ranged from 8.1–12.3 months, somewhat higher levels of HbF might be expected. Glycated HbF is not detected by the turbidimetric inhibition immunoassay we used; HbF, however, is included in total hemoglobin determination. Because HbA1c is expressed as a proportion, infants with high amounts of HbF (>10%) may have lower than expected HbA1c values (14). However, this does not explain the relatively high HbA1c levels found in our study.

The life span of a fetal erythrocyte is approximately 60–80 days, and the life span of erythrocytes in infants is still less than the 120-day life span of erythrocytes in adults (15). A shorter life span for erythrocytes should show lower HbA1c levels instead of the higher levels we found.

To our knowledge, this is the first study describing the distribution of HbA1c in nondiabetic infants. Compared with known HbA1c levels in older children, we found a relatively high mean HbA1c of 5.38%. No significant association between known risk factors for type 2 diabetes and HbA1c was found.


No potential conflicts of interest relevant to this article were reported.

H.J. researched data, wrote and edited the manuscript, and contributed to the discussion. H.G.H. researched data, wrote and edited the manuscript, and contributed to the discussion. S.S. and R.P.S. contributed to the discussion and wrote, reviewed, and edited the manuscript. P.J.J.S. contributed to the discussion.

Parts of this study were presented in poster form at the 45th Annual Meeting of the European Diabetes Epidemiology Group, Porto Heli, Greece, 15–18 May 2010.

The authors are indebted to the children and their parents for their cooperation. The authors thank Ulf Ekelund and his team at the MRC Epidemiology Unit, Institute of Metabolic Science Cambridge, United Kingdom, for supportive collaboration.

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[Figure ID: F1]
Figure 1 

Distribution of HbA1c in infants aged 8–12 months. Mean (SD): 5.38% (0.24) or 35.29 mmol/mol (2.65).

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    • Epidemiology/Health Services Research

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