Letter

Glycated haemoglobin, diabetes, and mortality in men

BMJ 2001; 322 doi: 10.1136/bmj.322.7292.996 (Published 21 April 2001)
Cite this as: BMJ 2001;322:996

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Maybe disturbance in physiological mechanisms regulating blood glucose is risk factor for cardiovascular death

  1. R J Jarrett, emeritus professor of clinical epidemiology, University of London
  1. 45 Bishopsthorpe Road, London SE26 4PA
  2. East Kent Hospitals NHS Trust, Kent and Canterbury Hospitals, Canterbury CT1 3NG
  3. Institute of Public Health, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ
  4. Saratov State Medical University, PO Box 1528, Saratov, 410601 Russia

    EDITOR—Khaw et al contribute to the substantial literature showing an association between measures of glycaemia and subsequent morbidity and mortality.1 They suggest that “preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population distribution of HbA1c [glycated haemoglobin].” This implies that the determinant is the degree of hyperglycaemia.

    In the non-diabetic population, glycated haemoglobin principally reflects the fasting blood glucose concentration, which has been shown by several groups to predict morbidity and mortality. One of these groups, the DECODE (diabetes epidemiology: collaborative analysis of diagnostic criteria in Europe) Study Group, also measured the blood glucose concentration two hours after a load and found that fasting concentrations were not additionally predictive within two hour blood glucose categories.2

    In a cross sectional study with carotid intima media thickness as a marker of atherosclerosis, blood glucose concentrations after a load (in particular the two hour value) and incremental values (that is, above fasting) were more strongly related to intima media thickness than were fasting glucose or glycated haemoglobin concentrations.3 Furthermore, in a population based study in Italy instability of fasting blood glucose concentrations over the years of observation was an independent predictor of cardiovascular mortality.4

    Clearly there are several possible interpretations of these findings. One is that it is not glycaemia itself that is the risk factor but the disturbance(s) in the physiological mechanisms that regulate the blood glucose concentration. This explanation would agree with the disappointing results of hypoglycaemic treatment in type 2 diabetes, commented on by Barrett-Connor and Wingard.5

    References

    1. 1.↵
      1. Khaw KT,
      2. Wareham N,
      3. Luben R,
      4. Bingham S,
      5. Oakes S,
      6. Welch A,
      7. et al
      .Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European prospective investigation of cancer and nutrition (EPIC-Norfolk).BMJ2001; 322:15–18. (6 January.)
      OpenUrlFREE Full Text
    2. 2.↵
      1. DECODE Study Group
      .Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria.Lancet1999; 354:617–621.
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    3. 3.↵
      1. Temelkova-Kurktschiev TS,
      2. Koehler C,
      3. Henkel E,
      4. Leonhardt W,
      5. Fuecker K,
      6. Hanefeld M
      .Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbAlc level.Diabetes Care2000; 23:1830–1834.
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    4. 4.↵
      1. Muggeo M,
      2. Verlato G,
      3. Boncra E,
      4. Zoppini G,
      5. Corbellini M,
      6. de Marco R
      .Long-term instability of fasting plasma glucose, a novel predictor of cardiovascular mortality in elderly patients with non-insulin-dependent diabetes mellitus: the Verona diabetes study.Circulation1997; 96:1750–1754.
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    5. 5.↵
      1. Barrett-Connor E,
      2. Wingard DL
      .“Normal” blood glucose and coronary risk.BMJ2001; 322:5–6. (6 January.)
      OpenUrlFREE Full Text

    Analytical information is required for generalisation of data

    1. Edmund Lamb (edmund.lamb@kch-tr.sthames.nhs.uk), consultant clinical biochemist
    1. 45 Bishopsthorpe Road, London SE26 4PA
    2. East Kent Hospitals NHS Trust, Kent and Canterbury Hospitals, Canterbury CT1 3NG
    3. Institute of Public Health, University of Cambridge, Addenbrooke's Hospital, Cambridge CB2 2QQ
    4. Saratov State Medical University, PO Box 1528, Saratov, 410601 Russia

      EDITOR—Analytical information is required before data can be generalised. Khaw et al's data suggesting that the relation between cardiovascular disease and glycaemia is a continuum extending throughout the non-diabetic …

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