|
 |
|
|||||||
|
|||||||||
© 2001 by the American Diabetes Association, Inc.
HbA1c Levels Are Genetically Determined Even in Type 1 Diabetes
Evidence From Healthy and Diabetic Twins
1 Twin Research and Genetic Epidemiology Unit, St Thomas’ Hospital, London, U.K.
2 Georgia Prevention Institute, Medical College of Georgia, Augusta, Georgia
3 Unit of Diabetes and Immunology, St Bartholomew’s Hospital, London, U.K.
4 Department of Diabetes, Royal Infirmary, Edinburgh, U.K.
HbA1c, a measure of blood glucose regulation, reflects glucose levels in the preceding months. In diabetes, HbA1c levels predict the risk of microvascular complications. The aim of this study was to determine whether genetic factors could influence HbA1c levels in normal subjects and type 1 diabetic patients. We performed a classical twin study of HbA1c in healthy nondiabetic female twins and 42 monozygotic (MZ) and 47 dizygotic (DZ) pairs. Interclass correlations (r) were higher in MZ (r = 0.77) compared with DZ (r = 0.53) twin pairs, suggesting a substantial genetic effect; this was confirmed by quantitative genetic model fitting. Additive genetic effects (heritability) explained 62% (95% CI 47–75) of population variance in HbA1c; the remainder was attributable to the influence of unique environment (23% [15–36]) and age (14% [5–28]). Multivariate modeling showed that genetic factors also have a substantial influence on fasting glucose levels (51%). However, HbA1c heritability could not be explained by genes in common with fasting glucose. In the patients with type 1 diabetes, HbA1c levels were correlated in 33 MZ twins concordant for diabetes (r = 0.68; P < 0.001) but also in 45 MZ twins discordant for the disease (r = 0.52; P < 0.001). These significant correlations for HbA1c in both concordant and discordant pairs indicate a diabetes-independent familial effect. Thus, HbA1c levels are largely genetically determined and independent of the genes influencing fasting glucose. Even in type 1 diabetes, familial (i.e., diabetes-independent) factors influence protein glycation, implying that familial factors may explain, in part, the risk for microvascular complications, as indicated by high HbA1c levels.
CiteULike 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  P. K. Khera, C. H. Joiner, A. Carruthers, C. J. Lindsell, E. P. Smith, R. S. Franco, Y. R. Holmes, and R. M. Cohen Evidence for Interindividual Heterogeneity in the Glucose Gradient Across the Human Red Blood Cell Membrane and Its Relationship to Hemoglobin Glycation Diabetes, September 1, 2008; 57(9): 2445 - 2452. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Cohen A1C: Does One Size Fit All? Diabetes Care, October 1, 2007; 30(10): 2756 - 2758. [Full Text] [PDF]
|
|
|
|
|
|
W. H. Herman, Y. Ma, G. Uwaifo, S. Haffner, S. E. Kahn, E. S. Horton, J. M. Lachin, M. G. Montez, T. Brenneman, E. Barrett-Connor, et al. Differences in A1C by Race and Ethnicity Among Patients With Impaired Glucose Tolerance in the Diabetes Prevention Program Diabetes Care, October 1, 2007; 30(10): 2453 - 2457. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Lachin, S. Genuth, D. M. Nathan, and B. N. Rutledge The Hemoglobin Glycation Index Is Not an Independent Predictor of the Risk of Microvascular Complications in the Diabetes Control and Complications Trial Diabetes, July 1, 2007; 56(7): 1913 - 1921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. S. Kilpatrick, A. S. Rigby, and S. L. Atkin Variability in the Relationship between Mean Plasma Glucose and HbA1c: Implications for the Assessment of Glycemic Control Clin. Chem., May 1, 2007; 53(5): 897 - 901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Cohen, H. Snieder, C. J. Lindsell, H. Beyan, M. I. Hawa, S. Blinko, R. Edwards, and R. D. G. Leslie Evidence for Independent Heritability of the Glycation Gap (Glycosylation Gap) Fraction of HbA1c in Nondiabetic Twins: Response to Nuttall Diabetes Care, April 1, 2007; 30(4): e15 - e15. [Full Text] [PDF]
|
|
|
|
|
|
R. M. Cohen, H. Snieder, C. J. Lindsell, H. Beyan, M. I. Hawa, S. Blinko, R. Edwards, T. D. Spector, and R. D. G. Leslie Evidence for Independent Heritability of the Glycation Gap (Glycosylation Gap) Fraction of HbA1c in Nondiabetic Twins Diabetes Care, August 1, 2006; 29(8): 1739 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. McCarter, J. M. Hempe, and S. A. Chalew Mean Blood Glucose and Biological Variation Have Greater Influence on HbA1c Levels Than Glucose Instability: An analysis of data from the Diabetes Control and Complications Trial Diabetes Care, February 1, 2006; 29(2): 352 - 355. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Katoh, M. Lehtovirta, J. Kaprio, V. Harjutsalo, M. Koskenvuo, J. Eriksson, N. Tajima, and J. Tuomilehto Genetic and Environmental Effects on Fasting and Postchallenge Plasma Glucose and Serum Insulin Values in Finnish Twins J. Clin. Endocrinol. Metab., May 1, 2005; 90(5): 2642 - 2647. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Misciagna, G. De Michele, A. M. Cisternino, V. Guerra, G. Logroscino, and J. L. Freudenheim Dietary Carbohydrates and Glycated Proteins in the Blood in Non Diabetic Subjects J. Am. Coll. Nutr., February 1, 2005; 24(1): 22 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Harjutsalo, S. Katoh, C. Sarti, N. Tajima, and J. Tuomilehto Population-Based Assessment of Familial Clustering of Diabetic Nephropathy in Type 1 Diabetes Diabetes, September 1, 2004; 53(9): 2449 - 2454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. J. McCarter, J. M. Hempe, R. Gomez, and S. A. Chalew Biological Variation in HbA1c Predicts Risk of Retinopathy and Nephropathy in Type 1 Diabetes Diabetes Care, June 1, 2004; 27(6): 1259 - 1264. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. M. Cohen, R. S. Franco, and C. H. Joiner Is Poor Glycemic Control Associated With Reduced Red Blood Cell Lifespan? Diabetes Care, April 1, 2004; 27(4): 1013 - 1014. [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Lobo, R. C. Bernardes, J. P. Figueira, J. R. F. de Abreu, and J. G. Cunha-Vaz Three-Year Follow-up Study of Blood-Retinal Barrier and Retinal Thickness Alterations in Patients With Type 2 Diabetes Mellitus and Mild Nonproliferative Diabetic Retinopathy Arch Ophthalmol, February 1, 2004; 122(2): 211 - 217. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. D. G. Leslie, H. Beyan, P. Sawtell, B. O. Boehm, T. D. Spector, and H. Snieder Level of an Advanced Glycated End Product Is Genetically Determined: A Study of Normal Twins Diabetes, September 1, 2003; 52(9): 2441 - 2444. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Diabetes | Diabetes Care | Clinical Diabetes | Diabetes Spectrum |