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Kay-Tee Khaw a Department of
Public Health and Primary Care, Institute of Public Health, University
of Cambridge School of Clinical Medicine, Cambridge CB2 2SR, b Medical Research Council Dunn Human Nutrition Unit,
Cambridge CB2 2XY
Correspondence to: K-T Khaw, Clinical Gerontology Unit, Box
251, University of Cambridge School of Clinical Medicine,
Addenbrooke's Hospital, Cambridge CB2 2QQ kk101{at}medschl.cam.ac.uk
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Abstract |
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Objective:
To examine the value of glycated
haemoglobin (HbA1c) concentration, a marker of blood
glucose concentration, as a predictor of death from cardiovascular and
all causes in men.
The global prevalence of diabetes is predicted to rise from 135 million in 1995 to 300 million by 2025.1-3 In the United Kingdom, diabetes and associated complications cost the NHS £4.9bn a
year, about a tenth of its entire budget.
Various blood glucose threshold concentrations have been proposed for
the diagnosis of diabetes,4-7 based on the relation to
risk of microvascular complications of diabetes, particularly retinopathy.8 However, people with diabetes are also at
increased risk of macrovascular diseases such as coronary heart disease and stroke,9 and it is uncertain whether the relation
between blood glucose concentration and such diseases has a threshold or is a continuum.
Glycated haemoglobin (HbA1c) concentration is an indicator
of average blood glucose concentration over three months and has been
suggested as a diagnostic or screening tool for
diabetes.
8 10
Meta-regression analyses of several studies
suggest a continuous relation between fasting or two hour glucose
concentration and macrovascular events even below accepted thresholds
for diabetes, but data for glycated haemoglobin have been limited by
the few prospective studies in which it has been measured in people
without diabetes.
We examined the relation between glycated haemoglobin concentrations,
diabetes, and subsequent mortality in men.
We studied men in the Norfolk cohort of the European
Prospective Investigation into Cancer and Nutrition. The cohort
comprises 25 623 men and women aged 45-79 years resident in Norfolk,
recruited from general practice age-sex registers.11
Additional data were collected for the Norfolk cohort to enable us to
examine the determinants of chronic disease. At the baseline survey
between 1993 and 1997 participants completed a detailed health and
lifestyle questionnaire. People with established diabetes were defined
as those who responded "yes" to the diabetes option of the
question: "Has a doctor ever told you that you have any of the
following?" followed by a list of conditions including diabetes,
heart attack, and stroke. Smoking history was derived from responses to
the questions "Have you ever smoked as much as one cigarette a day
for as long as a year?" and "Do you smoke cigarettes now?"
Participants attended a health examination carried out by trained
nurses. Body mass index was estimated as weight (kg)/(height (m))2. Blood pressure was measured with an Accutorr blood
pressure monitor12 after the participant had been seated
resting for five minutes; the mean of two readings was used for
analysis. Plasma and serum samples were obtained from blood taken by
venepuncture. From November 1995, an additional EDTA-anticoagulated
blood sample was taken for measurement of HbA1c. Blood
samples were assayed at the department of clinical biochemistry,
Cambridge University. Serum total cholesterol, high density lipoprotein
cholesterol, and triglyceride concentrations were measured by
colorimetry (RA 1000, Bayer Diagnostics, Basingstoke), and low density
lipoprotein cholesterol concentrations were calculated by the
Friedewald formula.13 Glycated haemoglobin assays used a
Biorad Diomat high pressure liquid chromatography analyser. The
coefficient of variation was 3.6%.
All participants were flagged for death certification at the Office of
National Statistics. We present results for mortality follow up to
December 1999. Death certificates were coded by trained nosologists at
the Office of National Statistics according to the International
Classification of Disease (ICD), 9th revision. Cardiovascular death was
defined as ICD 400-438 and ischaemic heart disease death as ICD 410-414 anywhere on the death certificate.
The study was approved by the Norwich District Health Authority ethics
committee, and all participants gave signed informed consent.
The analysis reported here includes all men aged 45-79 years who
completed the baseline health examination and had HbA1c
measured. There were not enough events in women with HbA1c
measurements for robust analyses. We divided the men into five
categories: those with established diabetes, those with previously
undiagnosed diabetes (defined as those without a history of diabetes
but with a HbA1c concentration We also calculated the population distribution of
HbA1c concentration and diabetes and estimated the
population attributable risk associated with diabetes or
HbA1c above the lowest category less than 5%, assuming the
death rates for those with a HbA1c concentration less than
5% applied to the whole population.
Table 1 shows the characteristics of the 4662 men according to
concentration of HbA1c and self reported diabetes. Men with self reported diabetes or previously undiagnosed diabetes were older
and had higher levels of risk factors for cardiovascular disease than
the rest of the population.
Table 1.
Design:
Prospective population study.
Setting:
Norfolk cohort of European Prospective
Investigation into Cancer and Nutrition (EPIC-Norfolk).
Subjects:
4662 men aged 45-79 years who had had
glycated haemoglobin measured at the baseline survey in 1995-7 who were followed up to December 1999.
Main outcome measures:
Mortality from all causes,
cardiovascular disease, ischaemic heart disease, and other causes.
Results:
Men with known diabetes had increased
mortality from all causes, cardiovascular disease, and ischaemic
disease (relative risks 2.2, 3.3, and 4.2, respectively, P <0.001
independent of age and other risk factors) compared with men without
known diabetes. The increased risk of death among men with diabetes was
largely explained by HbA1c concentration. HbA1c
was continuously related to subsequent all cause, cardiovascular, and
ischaemic heart disease mortality through the whole population
distribution, with lowest rates in those with HbA1c
concentrations below 5%. An increase of 1% in HbA1c was
associated with a 28% (P<0.002) increase in risk of death independent
of age, blood pressure, serum cholesterol, body mass index, and
cigarette smoking habit; this effect remained (relative risk 1.46, P=0.05 adjusted for age and risk factors) after men with known
diabetes, a HbA1c concentration
7%, or history of
myocardial infarction or stroke were excluded. 18% of the population
excess mortality risk associated with a HbA1c concentration
5% occurred in men with diabetes, but 82% occurred in men with
concentrations of 5%-6.9% (the majority of the population).
Conclusions:
Glycated haemoglobin concentration seems
to explain most of the excess mortality risk of diabetes in men and to
be a continuous risk factor through the whole population distribution. Preventive efforts need to consider not just those with established diabetes but whether it is possible to reduce the population
distribution of HbA1c through behavioural means.
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Introduction
Top
Abstract
Introduction
Participants and methods
Results
Discussion
References
![]()
Participants and methods
Top
Abstract
Introduction
Participants and methods
Results
Discussion
References
7%8), and
then the remainder by approximate thirds of HbA1c
concentration using clinically applicable cut off points. We calculated
age adjusted death rates by cause in these categories using
2 for linear trend to assess statistical
significance.14 We used the Cox proportional hazards model
to determine the contribution of risk factors to
mortality.15
![]()
Results
Top
Abstract
Introduction
Participants and methods
Results
Discussion
References
Table 2 shows age adjusted mortality by concentration of HbA1c and self reported diabetes. Men with established or undiagnosed diabetes had greater risk of dying from all causes, cardiovascular disease, or ischaemic heart disease compared with men without diabetes. Risk of death increased through the range of HbA1c concentrations, with lowest rates in those with HbA1c concentrations less than 5% and a gradient of increasing rates through the whole distribution.
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Table 3 shows the independent multivariate relation between
HbA1c concentration or diabetes status and mortality with
the Cox proportional hazards model after adjustment for age alone and
for age, systolic blood pressure, serum cholesterol concentration, body
mass index, cigarette smoking habit, and history of myocardial infarction or stroke. In separate models diabetes status significantly predicted death from all causes, cardiovascular disease, and ischaemic heart disease and HbA1c concentrations predicted all cause,
cardiovascular, ischaemic heart disease, and non-cardiovascular
mortality independently of age and known risk factors. When diabetes
status and HbA1c concentration were both included in the
same model, diabetes no longer significantly independently predicted
mortality. The increased risk of mortality in men with diabetes was
largely mediated through HbA1c concentration. An increase
of 1% in HbA1c concentration was associated with roughly a
30% increase in all cause and 40% increase in cardiovascular or
ischaemic heart disease mortality. After men with a history of diabetes
or with a HbA1c concentration
7% and those with a
history of heart disease and stroke (n=522) were excluded, the relative
risk of all cause mortality for a 1% increase in HbA1c was
1.49 (95% confidence interval 1.03 to 2.17, P=0.03) adjusted for age
and 1.46 (1.00 to 2.12, P=0.05) adjusted for age and risk
factors.
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Table 4 shows the distribution of HbA1c concentration
and self reported diabetes in these men. It also shows the population attributable risk, an estimate of the excess mortality associated with
diabetes or HbA1c concentration
5%. About 37% (48/131)
of the total deaths in this population could be attributed to excess mortality in men with HbA1c concentrations
5%. The
prevalence of established or newly diagnosed diabetes was about 5% in
the study population. Although this group had greatly increased
relative risk of mortality, they contributed only 18% of the excess
deaths from all causes relating to HbA1c >5%; men with
HbA1c concentrations of 5%-6.9%, who form the majority of
the population, contributed about 82% of the excess mortality. Table 4
also shows the estimated effect on prevalence distributions if
HbA1c concentrations were lowered by 0.1% or 0.2% in
everyone in the population (excluding those with self reported
diabetes). An estimated 12% (6/48) of the excess deaths could
potentially be prevented by lowering the population mean
HbA1c concentration by 0.1%, and 25% (13/48) could be
prevented by lowering the population mean by 0.2%. The reduction in
total deaths would be 5% (6/131) and 10% (13/131)
respectively.
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Discussion |
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Glycated haemoglobin concentration significantly predicted mortality, with increasing risk throughout the whole range of concentrations, even below the threshold commonly accepted for diagnosis of diabetes. This effect was independent of known risk factors and consistent after men with existing diabetes, heart disease, and stroke were excluded. The predictive value of HbA1c for total mortality was stronger than that documented for cholesterol concentration, body mass index, and blood pressure. The mortality risk of established diabetes seemed to be mediated largely through HbA1c concentration.
People with diabetes have increased risk of vascular disease, 9 16-18 and in these people blood concentration of glucose or HbA1c predicts subsequent microvascular and macrovascular events. 19 20 High glucose concentrations might accelerate atherosclerotic processes through several plausible mechanisms such as oxidative stress and protein glycation of vessel walls.21 Reductions in blood glucose or HbA1c concentrations through tight blood glucose control in people with diabetes also reduces the risk of microvascular disease.22-25 However, whether the relation of increasing blood glucose with adverse clinical outcomes exists only above a threshold or is a continuous relation across the whole population distribution is still debated.26-32 For microvascular complications, studies report a flat relation below a threshold for fasting and post challenge glucose concentration as well as for HbA1c.8 The relation with macrovascular outcomes, coronary heart disease, and stroke, is less clear.26-32 A review33 and meta-regression analysis of 20 prospective studies34 (94% male) concluded that the progressive relation between glucose concentrations and cardiovascular disease extends below the diabetic threshold.
Importance of glycated haemoglobin in people without diabetes
HbA1c concentration is related to prevalent coronary
disease or carotid intimal thickening in non-diabetic people.
35 36
Two prospective studies reported that
HbA1c predicts cardiovascular disease in non-diabetic
people, but they focused on the top end of the distribution, which may
contain people with undiagnosed diabetes.
37 38
In the
Norfolk cohort, the effect of HbA1c concentration on
mortality was evident even at the lower end of the population
distribution, and there was no apparent threshold effect: men with
HbA1c concentrations above 5% had greater risk than men
with concentrations below 5%. Glycated haemoglobin seems to
resemble blood pressure and blood cholesterol in terms of the
continuous relation with cardiovascular risk.39
Clinical implications
Clinical attention has focused on microvascular complications of
diabetes. However, rates of myocardial infarction and stroke in
diabetic people are about twice the rates of microvascular events,40 and control of other cardiovascular risk factors
such as hypertension is particularly beneficial.41
Treatment trials have shown the effectiveness of lowering blood
pressure and cholesterol concentration in reducing cardiovascular
events. Since blood pressure and cholesterol are continuously related
to mortality,39 prevention of cardiovascular disease has
moved from single risk factor intervention at fixed thresholds to
identifying overall cardiovascular risk in individuals. Lower treatment
thresholds are recommended for people at high absolute risk, as
estimated by age, sex, and cardiovascular risk factors such as
diabetes, blood pressure, blood cholesterol, smoking, and family
history.
42 43
Our data indicate that raised glycated
haemoglobin concentration, even in men without diabetes, is a marker of
greater absolute risk, and preventive treatment with blood pressure or
cholesterol lowering drugs should be considered in such patients.
Public health implications
Concentrations of glycated haemoglobin are roughly normally
distributed in the population. The lowest death rates were in men with
HbA1c concentrations below 5% (25% of our population).
Established diabetes is associated with increased mortality, but the
prevalence of diabetes is low (5% in the population), whereas about
70% of the population have HbA1c concentrations between
5% and 6.9%. As table 4 shows, 82% of the population excess
mortality occurred in this large group of the population compared with
18% in those with diabetes. Large numbers of people exposed to a small
increase in risk contribute more events to the population than a small
number of people exposed to a large increase in
risk.47 The intensive individual medical management and
tight glucose control that has been achieved in treatment trials for
diabetic patients would not be feasible, or necessarily beneficial, in
people who do not have diabetes. However, if it were possible to lower
the population mean distribution of HbA1c concentration by
lifestyle means such as diet or physical activity, many people could
shift into lower risk categories. As shown in table 4, after men with
diabetes are excluded, a reduction of just 0.1% HbA1c in
the whole population would reduce the prevalence of men with
concentrations of 5%-6.9% from 79% to 63%, and a population reduction of 0.2% HbA1c would reduce the prevalence to
57%. If the same death rates are assumed to apply, these reductions in population prevalence would reduce total mortality by 5% and 10% respectively.
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What is already known on this topic
Diabetes mellitus increases cardiovascular disease risk HbA1c concentrations predict cardiovascular risk in people with diabetes What this study addsHbA1c concentrations predict mortality continuously across the whole population distribution in people without diabetes and at concentrations below those used to diagnose diabetes People with high HbA1c concentration may benefit from control of blood pressure and cholesterol concentration HbA1c may provide a practical screening tool for diabetes or impaired glucose tolerance Over 80% of the population excess mortality associated with HbA1c concentrations above 5% occurred in 70% of the population with HbA1c concentrations of 5%-6.9% |
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Acknowledgments |
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We thank the participants and general practitioners who took part in EPIC-Norfolk.
Contributors: K-TK, ND, and SB originated and designed the EPIC-Norfolk population study. NW introduced the glycated haemoglobin measurements and diabetes component. SO is study coordinator and organised data collection including quality control of blood samples and measurement procedures. AW contributed to data collection and analysis. RL was responsible for data management and computing and assisted with analyses. K-TK conducted the data analyses and wrote the paper with NW and ND. K-TK is guarantor for this paper.
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Footnotes |
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Funding: EPIC-Norfolk is supported by programme grants from the Cancer Research Campaign and Medical Research Council with additional support from the Stroke Association, British Heart Foundation, Department of Health, and the Wellcome Trust.
Competing interests: None declared.
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References |
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|
|---|
| 1. | King H, Aubert RE, Herman WH. Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care 1998; 21: 1414-1431[Abstract]. |
| 2. | Amos AF, McCarty DJ, Zimmet P. The rising global burden of diabetes and its complications: estimates and projections to the year 2010. Diabet Med 1997; 14(suppl 5): S1-85. |
| 3. | American Diabetes Association. Screening for type 2 diabetes. Diabetes Care 2000; 23(suppl 1): S20-S23. |
| 4. | National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes 1979; 28: 1039-1057[Medline]. |
| 5. | Report of a WHO Study Group. Diabetes mellitus. World Health Org Tech Rep Ser 1985; 727: 9-17. |
| 6. | Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provision report of a WHO consultation. Diabet Med 1998; 15: 539-553[CrossRef][Medline]. |
| 7. | Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 1997; 20: 1183-1197[Medline]. |
| 8. |
McCance DR, Hanson RL, Charles M-A, Jacobsson LTH, Pettitt DJ, Bennett PH, et al.
Comparison of tests for glycated hemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes.
BMJ
1994;
308:
1323-1328 |
| 9. |
Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Lakkso M.
Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction.
N Engl J Med
1998;
339:
229-234 |
| 10. |
Marshall SM, Barth JH.
Standardization of HbA1c measurements a consensus statement.
Diabet Med
2000;
17:
5-6[CrossRef][Medline].
|
| 11. | Day NE, Oakes S, Luben R, Khaw KT, Bingham S, Welch A, et al. EPIC-Norfolk: study design and characteristics of the cohort. Br J Cancer 1999; 80(suppl 1): 95-103. |
| 12. | Gregory J, Foster K, Tyler H, Wiseman M. The dietary and nutritional survey of British adults. London: HMSO, 1990. |
| 13. | Friedewald WT, Levy RI, Frederickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502[Abstract]. |
| 14. | Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959; 22: 719-748. |
| 15. | Cox DR. Regression models and life tables. J R Stat Soc B 1972; 34: 187-220. |
| 16. | Kannel WB, McGee DL. Diabetes and glucose tolerance as risk factors for cardiovascular disease: the Framingham Study. Diabetes Care 1979; 2: 120-126[Abstract]. |
| 17. | Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors and 12 year cardiovascular mortality for men screened in the multiple risk factor intervention trial. Diabetes Care 1993; 16: 434-444[Abstract]. |
| 18. | Wingard DL, Barrett-Connor E. Heart disease and diabetes. In: National Diabetes Data Group,ed. Diabetes in America. 2nd ed. Washington, DC: Government Printing Office, 1995:429-448. (NIH publication No 95-1468.) |
| 19. | Moss SE, Klein R, Klein BEK, Meuer MS. The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med 1994; 154: 2473-2479[Abstract]. |
| 20. |
Krolewski AS, Laffel LMB, Krolewski M, Quinn M, Warram JH.
Glycosylated hemoglobin and the risk of microalbuminuria in patients with insulin-dependent diabetes mellitus.
N Engl J Med
1995;
332:
1251-1255 |
| 21. | Brownlee M. Glycation and diabetic complications. Diabetes 1994; 43: 836-841[Medline]. |
| 22. |
Diabetes Control and Complications Trial Research Group.
The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus.
N Engl J Med
1993;
329:
977-986 |
| 23. | Diabetes Control and Complications Trial Research Group. The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes 1995; 44: 968-983[Abstract]. |
| 24. | Diabetes Control and Complications Trial Research Group. The absence of a glycemic threshold for the development of long term complications: the perspective of the diabetes control and complications trial. Diabetes 1996; 45: 1289-1298[Abstract]. |
| 25. | UK Prospective Diabetes Study Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853[CrossRef][Medline]. |
| 26. | Donahue RP, Abbott RD, Reed DM, Yano K. Post challenge glucose level and coronary heart disease in men of Japanese ancestry. Diabetes 1987; 36: 689-692[Abstract]. |
| 27. |
Butler WJ, Ostrander Jr LD, Carman WJ, Lamphiear DE.
Mortality from coronary heart disease in the Tecumseh study: long-term effect of diabetes mellitus, glucose tolerance and other risk factors.
Am J Epidemiol
1985;
121:
541-547 |
| 28. | Eschwege E, Richard JL, Thibult N, Ducimetiere P, Warner JM, Claude JR, et al. Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin concentrations. The Paris prospective study, ten years later. Horm Metab Res 1985; 15(suppl series): 41-45. |
| 29. | Pyorala K, Savolainen E, Kaukola S, Haapgoski J. Plasma insulin as a coronary heart disease risk factor: relationship to other risk factors and predictive value during 91/2 year follow up of the Helsinki policemen study population. Acta Med Scand 1985; (suppl)701: 38-52. |
| 30. | Ohlson LO, Svardsudd K, Welin L, Eriksson H, Wilhelmsen L, Tibblin G, et al. Fasting blood glucose and risk of coronary heart disease, stroke, and all cause mortality: a 17 year follow up study of men born in 1913. Diabet Med 1986; 3: 33-37[Medline]. |
| 31. | Fuller JH, Shipley MJ, Rose G, Jarrett RJ, Keen H. Coronary heart disease risk and impaired glucose tolerance. The Whitehall study. Lancet 1980; i: 1373-1376. |
| 32. |
Scheidt-Nave C, Barrett-Connor E, Wingard DL, Cohn BA, Edelstein SL.
Sex differences in fasting glycemia as a risk factor of ischemic heart disease death.
Am J Epidemiol
1991;
133:
565-576 |
| 33. | Gerstein HC. Glucose: a continuous risk factor for cardiovascular disease. Diabet Med 1997; 14: S25-S31. |
| 34. |
Coutinho M, Gerstein HC, Wang Y, Yusuf S.
The relationship between glucose and incident cardiovascular events.
Diabetes Care
1999;
22:
233-240 |
| 35. | Singer DE, Nathan DM, Keaven MA, Wilson PWF, Evans JC. Association of HbA1c with prevalent cardiovascular disease in the original cohort of the Framingham Heart Study. Diabetes 1992; 41: 202-208[Abstract]. |
| 36. | Vitelli LL, Shahar E, Heiss G, McGovern PG, Brancati FL, Eckfeldt JH, et al. Glycosylated hemoglobin level and carotid intimal-medial thickening in non-diabetic individuals. Diabetes Care 1997; 20: 1454-1458[Abstract]. |
| 37. | Park S, Barrett-Connor E, Wingard DL, Shan J, Edelstein S. Ghb is a better predictor of cardiovascular disease than fasting or postchallenge plasma glucose in women without diabetes. The Rancho Bernardo study. Diabetes Care 1996; 19: 450-456[Abstract]. |
| 38. | De Vegt F, Dekker JM, Ruhe HG, Stehouwer CD, Nijpels G, Bouter LM, et al. Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia 1999; 42: 926-931[CrossRef][Medline]. |
| 39. | Neaton JD, Wentworth D. Serum cholesterol, blood pressure, cigarette smoking and death from coronary heart disease. Overall findings and differences by age for 316099 white men. Multiple Risk Factor Intervention Trial Research Group. Arch Intern Med 1992; 152: 56-64[Abstract]. |
| 40. | UK Prospective Diabetes Study (UKPDS) Group. Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-853. |
| 41. |
UK Prospective Diabetes Study Group.
Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes (UKPDS 38)
BMJ
1998;
317:
703-713 |
| 42. |
Wood DA, DE Backer G, Faergeman O, Graham J, Mancia G, Pyorala K.
Prevention of coronary heart disease in clinical practice. Recommendations of the second joint task force of the European Society of Cardiology, European Atherosclerosis Society, and European Society of Hypertension.
Eur Heart J
1998;
19:
1434-1503 |
| 43. | British Cardiac Society, British Hyperlipidaemia Association, British Hypertension Society. Joint British recommendations on prevention of coronary heart disease in clinical practice. Heart 1998; (suppl 2): S1-29. |
| 44. | DECODE Study Group, on behalf of the European Diabetes Epidemiology Group. Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria. Lancet 1999; 354: 617-621[CrossRef][Medline]. |
| 45. | Barzilay JI, Speikerman CF, Wahl PH, Kuller LH, Cushman M, Furberg CD, et al. Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria. Lancet 1999; 354: 622-625[CrossRef][Medline]. |
| 46. | Shaw JE, Hodge Am, de Gurter M, Chitson P, Zimmet PZ. Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality. Diabetologia 1999; 42: 1050-1054[CrossRef][Medline]. |
| 47. | Hamman RF. Genetic and environmental determinants of non-insulin dependent diabetes. Diabetes Metab Rev 1992; 8: 287-338[Medline]. |
| 48. | Pan XR, Cao HB, Li GW, Hu YH, Wang JX, Yang WY, et al. Effects of diet and exercise in preventing NIDDM in people with impaired glucose tolerance. Diabetes Care 1997; 20: 537-544[Abstract]. |
| 49. | Rose G. Strategy of prevention: lessons from cardiovascular disease. BMJ 1981; 282: 1847-1851. |
| 50. |
Sargeant L, Wareham N, Bingham S, Day N, Luben R, Oakes S, et al.
Vitamin C and glucose tolerance in a EPIC-Norfolk: a population study.
Diabetes Care
2000;
23:
726-732 |
| 51. | Williams DE, Wareham NE, Cox BD, Byrne CD, Hales CN, Day NE. Frequent salad consumption is associated with a reduction in the risk of diabetes mellitus. J Clin Epidemiol 1999; 52: 329-335[CrossRef][Medline]. |
| 52. |
Wareham NJ, Wong MY, Day NE.
Glucose intolerance and physical inactivity: the relative importance of low habitual energy expenditure and cardiorespiratory fitness.
Am J Epidemiol
2000;
152:
132-139 |
(Accepted 11 October 2000)
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