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

Abstract 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. 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.

[1]  M. Shipley,et al.  CORONARY-HEART-DISEASE RISK AND IMPAIRED GLUCOSE TOLERANCE The Whitehall Study , 1980, The Lancet.

[2]  L. Bouter,et al.  Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study , 1999, Diabetologia.

[3]  E. Feskens,et al.  Glucose tolerance and mortality: comparison of WHO and American Diabetic Association diagnostic criteria , 1999, The Lancet.

[4]  Philip D. Harvey,et al.  Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38 , 1998, BMJ.

[5]  J. Shaw,et al.  Isolated post-challenge hyperglycaemia confirmed as a risk factor for mortality , 1999, Diabetologia.

[6]  P. Zimmet,et al.  The Rising Global Burden of Diabetes and its Complications: Estimates and Projections to the Year 2010 , 1997, Diabetic medicine : a journal of the British Diabetic Association.

[7]  D. E. Lamphiear,et al.  Mortality from coronary heart disease in the Tecumseh study. Long-term effect of diabetes mellitus, glucose tolerance and other risk factors. , 1985, American journal of epidemiology.

[8]  J. Neaton,et al.  Serum cholesterol, blood pressure, cigarette smoking, and death from coronary heart disease. Overall findings and differences by age for 316,099 white men. Multiple Risk Factor Intervention Trial Research Group. , 1992, Archives of internal medicine.

[9]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.

[10]  E. Barrett-Connor,et al.  GHb Is a Better Predictor of Cardiovascular Disease Than Fasting or Postchallenge Plasma Glucose in Women Without Diabetes: The Rancho Bernardo Study , 1996, Diabetes Care.

[11]  D L McGee,et al.  Diabetes and Glucose Tolerance as Risk Factors for Cardiovascular Disease: The Framingham Study , 1979, Diabetes Care.

[12]  A. Krolewski,et al.  Glycosylated hemoglobin and the risk of microalbuminuria in patients with insulin-dependent diabetes mellitus. , 1995, The New England journal of medicine.

[13]  S. Yusuf,et al.  The relationship between glucose and incident cardiovascular events. A metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years. , 1999, Diabetes care.

[14]  M. Wong,et al.  Glucose intolerance and physical inactivity: the relative importance of low habitual energy expenditure and cardiorespiratory fitness. , 2000, American journal of epidemiology.

[15]  R. Holman,et al.  Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. , 1998 .

[16]  J. Haapakoski,et al.  Plasma insulin as coronary heart disease risk factor: relationship to other risk factors and predictive value during 9 1/2-year follow-up of the Helsinki Policemen Study population. , 2009, Acta medica Scandinavica. Supplementum.

[17]  E. Barrett-Connor,et al.  Sex differences in fasting glycemia as a risk factor for ischemic heart disease death. , 1991, American journal of epidemiology.

[18]  W. Bartlett,et al.  Standardization of HbA1c measurements , 2000, Diabetic medicine : a journal of the British Diabetic Association.

[19]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[20]  G. Mancia,et al.  Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention. , 1998, Atherosclerosis.

[21]  Classification and Diagnosis of Diabetes Mellitus and Other Categories of Glucose Intolerance , 1979, Diabetes.

[22]  A. Folsom,et al.  Glycosylated Hemoglobin Level and Carotid Intimal-Medial Thickening in Nondiabetic Individuals: The Atherosclerosis Risk in Communities Study , 1997, Diabetes Care.

[23]  L. Wilhelmsen,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 , 1986, Diabetic medicine : a journal of the British Diabetic Association.

[24]  D. Singer,et al.  Association of HbA1c With Prevalent Cardiovascular Disease in the Original Cohort of the Framingham Heart Study , 1992, Diabetes.

[25]  M. Engelgau,et al.  Screening for type 2 diabetes. , 2000, Diabetes care.

[26]  M. Wiseman,et al.  The dietary and nutritional survey of British adults. , 1990 .

[27]  R. Klein,et al.  The association of glycemia and cause-specific mortality in a diabetic population. , 1994, Archives of internal medicine.

[28]  R. Holman,et al.  Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. , 1998 .

[29]  S. Marshall,et al.  Standardization of HbA1c measurements − a consensus statement , 2000, Annals of clinical biochemistry.

[30]  P Ducimetière,et al.  Coronary heart disease mortality in relation with diabetes, blood glucose and plasma insulin levels. The Paris Prospective Study, ten years later. , 1985, Hormone and metabolic research. Supplement series.

[31]  D. Reed,et al.  Postchallenge Glucose Concentration and Coronary Heart Disease in Men of Japanese Ancestry: Honolulu Heart Program , 1987, Diabetes.

[32]  H. Gerstein.  Glucose: a Continuous Risk Factor for Cardiovascular Disease , 1997, Diabetic medicine : a journal of the British Diabetic Association.

[33]  A. Green,et al.  The rising global burden of diabetes: estimates for the year 2000 , 2000 .

[34]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[35]  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) , 1998, The Lancet.

[36]  N. Day,et al.  Vitamin C and hyperglycemia in the European Prospective Investigation into Cancer--Norfolk (EPIC-Norfolk) study: a population-based study. , 2000, Diabetes care.

[37]  W. Haenszel,et al.  Statistical aspects of the analysis of data from retrospective studies of disease. , 1959, Journal of the National Cancer Institute.

[38]  James D. Neaton,et al.  Serum Cholesterol, Blood Pressure, Cigarette Smoking, and Death From Coronary Heart Disease Overall Findings and Differences by Age for 316099 White Men , 1992 .

[39]  N. Day,et al.  EPIC-Norfolk: study design and characteristics of the cohort. European Prospective Investigation of Cancer. , 1999, British journal of cancer.

[40]  Dang Qing,et al.  Effects of Diet and Exercise in Preventing NIDDM in People With Impaired Glucose Tolerance The , 2022 .

[41]  N. Ahmed,et al.  Glycation and diabetic complications. , 1991, JPMA. The Journal of the Pakistan Medical Association.

[42]  R. Tisch,et al.  Insulin-Dependent Diabetes Mellitus , 1996, Cell.

[43]  B. Howard,et al.  Effects of Diet and Exercise in Preventing NIDDM in People With Impaired Glucose Tolerance: The Da Qing IGT and Diabetes Study , 1997, Diabetes Care.

[44]  P. Zimmet,et al.  Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus. Provisional report of a WHO Consultation , 1998, Diabetic medicine : a journal of the British Diabetic Association.

[45]  O. Meyer.  [Definition, diagnosis, and classification of lupus]. , 1998, La Revue du praticien.

[46]  N. Day,et al.  Frequent salad vegetable consumption is associated with a reduction in the risk of diabetes mellitus. , 1999, Journal of clinical epidemiology.

[47]  R. Hamman.  Genetic and environmental determinants of non-insulin-dependent diabetes mellitus (NIDDM). , 1992, Diabetes/metabolism reviews.

[48]  J. Segall.  Strategy of prevention: lessons from cardiovascular disease , 1981, British medical journal.

[49]  G. Rose,et al.  Strategy of prevention: lessons from cardiovascular disease. , 1981, British medical journal.

[50]  J. Neaton,et al.  Diabetes, Other Risk Factors, and 12-Yr Cardiovascular Mortality for Men Screened in the Multiple Risk Factor Intervention Trial , 1993, Diabetes Care.

[51]  P. Poole‐Wilson,et al.  Prevention of coronary heart disease in clinical practice: recommendations of the Task Force of the European Society of Cardiology, European Atherosclerosis Society and European Society of Hypertension. , 1994, Atherosclerosis.

[52]  D.,et al.  Regression Models and Life-Tables , 2022 .

[53]  M. Goklany.  Report of Study Group I , 1973 .

[54]  Teven,et al.  MORTALITY FROM CORONARY HEART DISEASE IN SUBJECTS WITH TYPE 2 DIABETES AND IN NONDIABETIC SUBJECTS WITH AND WITHOUT PRIOR MYOCARDIAL INFARCTION , 2000 .

[55]  The Absence of a Glycemic Threshold for the Development of Long-Term Complications: The Perspective of the Diabetes Control and Complications Trial , 1996, Diabetes.

[56]  R. Hanson,et al.  Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes , 1994, BMJ.

[57]  V. Barriales,et al.  [Heart disease and diabetes]. , 1991, Medicina clinica.

[58]  Richard Barnett,et al.  Diabetes mellitus. , 1993, The Medical journal of Australia.

[59]  S. Colagiuri,et al.  The Diabetes Control and Complications Trial , 1983, Henry Ford Hospital medical journal.

[60]  P. Savage,et al.  Cardiovascular disease in older adults with glucose disorders: comparison of American Diabetes Association criteria for diabetes mellitus with WHO criteria , 1999, The Lancet.

[61]  H. King,et al.  Global Burden of Diabetes, 1995–2025: Prevalence, numerical estimates, and projections , 1998, Diabetes Care.

[62]  P. Poole‐Wilson,et al.  Prevention of coronary heart disease in clinical practice , 1994 .