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Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk)

BMJ 2001; 322 doi: (Published 06 January 2001) Cite this as: BMJ 2001;322:15

Rapid Response:

Psychosocial stress may be a cause of increased HbA1c

Editor - The paper of Prof Khaw's and colleagues' very important
study on the relationship between percentage of glycated haemoglobin and
mortality in diabetic and non-diabetic men [1] mentions at best by way of
intimation a very likely cause of elevated HbA1c: psychosocial stress.

Activation of both the corticoid system from the hypothalamic-pituitary-
adrenal axis and the epinephrine system from the sympathetic-adrenal
medullary axis increases blood glucose.

Environmental circumstances e.g. such as job strain or belonging to
indigenous populations, stressed by westernised living conditions, were
associated with higher proportions of glycated haemoglobin [2, 3]. Longer
examination periods increased significantly HbA1c percentage in healthy
medical students; several months after the stressful examinations the
values were significantly lower [4].

Elevated extra- and intra-cellular glucose concentrations result in what
biochemists call "oxidative stress", defined as imbalance between
prooxidants and antioxidants [5]. Glucose autoxidation, formation of
usually irreversible, so-called "advanced glycation endproducts" (ACEs),
and the polyol pathway, seem to be involved in the genesis of this
oxidative stress, which is reported both in experimental diabetes in
animals as well as in type 1 and type 2 diabetic patients [5].

Many secondary diseases of diabetes are nowadays explained by these
mechanisms. HbA1c is one of these ACEs; and the observed positive
correlation between glycated haemoglobin concentration and mortality below
the diabetic threshold [1] might perhaps be explained by the same
mechanisms as in diabetics.

Peter Schuck, MD, PhD

Egerstr. 19,
D-08258 Markneukirchen, Germany.


1 Khaw KT, Wareham N, Luben R, Bingham S, Oakes S, Welch A, et al.
Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of
European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk).
BMJ 2001;322:1-6.

2 Netterstrøm B, Kristensen TS, Damsgaard MT, Olsen O, Sjol A. Job
strain and cardiovascular risk factors: a cross sectional study of
employed Danish men and women. Br J Ind Med 1991;48:684-9.

3 Daniel M, O'Dea K, Rowley KG, McDermott R, Kelly S. Glycated
hemoglobin as an indicator of social environmental stress among indigenous
versus westernized populations. Prev Med 1999;29:405-13.

4 Schuck P. Glycated hemoglobin as a physiological measure of stress
and its relation to some psychological stress indicators. Behav Med

5 Bonnefont-Russelot D, Bastard JP, Jaudon MC, Delattre J.
Consequences of the diabetic status on the oxidant/antioxidant balance.
Diabetes Metab 2000;26:163-76.

Competing interests: No competing interests

18 January 2001
Peter Schuck