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Reduction in Glycosylated Hemoglobin Urged for All

Am Fam Physician. 2001 Sep 1;64(5):841-844.

Mortality rates in men with diabetes are more than double the rates in other men. For some causes of death, such as cardiovascular and ischemic heart disease, the rates are three to four times higher, independent of age and other risk factors. Based on studies of microvascular complications such as retinopathy, a “threshold” of glycosylated hemoglobin (HbA1c) of 5 percent has been thought to determine the risk of mortality. Studies indicate that the relationship between glycemic control and macrovascular mortality is direct and continuous; therefore, control of blood sugar is important in all men, not just those with diabetes. Khaw and associates conducted a prospective population study to examine the value of HbA1c concentration as a predictor of death from cardiovascular disease and all causes in men.

The authors used data from a large study of general practices in eastern England. Beginning in 1993, data from more than 25,600 men and women 45 to 79 years of age were collected from questionnaires, physical examinations and laboratory tests. Regular monitoring of this population included reporting of all deaths by cause. By 1999, follow-up data were available on 4,662 men whose early profiles included HbA1c testing.

Age-Adjusted Rates for All-Cause, Cardiovascular, Ischemic Heart Disease and Noncardiovascular Death by Glycosylated Hemoglobin Concentration and Self-Reported Diabetes*

Glycosylated hemoglobin (%)
Cause of death < 5 (n = 1,204) 5 to 5.4 (n = 1,606) 5.5 to 6.9 (n = 1,611) ≥ 7 (n = 81) Self-reported diabetes (n = 160)

All causes (n = 135):

Age adjusted rate/100 (no. of events)

1.65 (18)

2.33 (35)

3.43 (61)

4.35 (5)

5.92 (16)

Relative risk

1.00

1.41

2.07

2.64

3.59

Cardiovascular disease (n = 60):

Age-adjusted rate/100 (no. of events)

0.50 (5)

1.27 (19)

1.24 (22)

2.54 (3)

4.11 (11)

Relative risk

1.00

2.53

2.46

5.04

8.16

Ischemic heart disease (n = 42)

Age-adjusted rate/100 (no. of events)

0.31 (3)

0.86 (13)

0.87 (15)

1.63 (2)

3.43 (9)

Relative risk

1.00

2.74

2.77

5.20

10.91

Noncardiovascular disease (n = 75):

Age-adjusted rate/100 (no. of events)

1.15 (13)

1.06 (16)

2.19 (39)

1.81 (2)

1.82 (5)

Relative risk

1.00

0.92

1.91

1.58

1.58


*— In men aged 45 to 79 years, 1995 to 1999.

Adapted with permission from Khaw K, 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;322:16.

Age-Adjusted Rates for All-Cause, Cardiovascular, Ischemic Heart Disease and Noncardiovascular Death by Glycosylated Hemoglobin Concentration and Self-Reported Diabetes*

View Table

Age-Adjusted Rates for All-Cause, Cardiovascular, Ischemic Heart Disease and Noncardiovascular Death by Glycosylated Hemoglobin Concentration and Self-Reported Diabetes*

Glycosylated hemoglobin (%)
Cause of death < 5 (n = 1,204) 5 to 5.4 (n = 1,606) 5.5 to 6.9 (n = 1,611) ≥ 7 (n = 81) Self-reported diabetes (n = 160)

All causes (n = 135):

Age adjusted rate/100 (no. of events)

1.65 (18)

2.33 (35)

3.43 (61)

4.35 (5)

5.92 (16)

Relative risk

1.00

1.41

2.07

2.64

3.59

Cardiovascular disease (n = 60):

Age-adjusted rate/100 (no. of events)

0.50 (5)

1.27 (19)

1.24 (22)

2.54 (3)

4.11 (11)

Relative risk

1.00

2.53

2.46

5.04

8.16

Ischemic heart disease (n = 42)

Age-adjusted rate/100 (no. of events)

0.31 (3)

0.86 (13)

0.87 (15)

1.63 (2)

3.43 (9)

Relative risk

1.00

2.74

2.77

5.20

10.91

Noncardiovascular disease (n = 75):

Age-adjusted rate/100 (no. of events)

1.15 (13)

1.06 (16)

2.19 (39)

1.81 (2)

1.82 (5)

Relative risk

1.00

0.92

1.91

1.58

1.58


*— In men aged 45 to 79 years, 1995 to 1999.

Adapted with permission from Khaw K, 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;322:16.

Although only 5 percent of the population is diabetic, about 70 percent have HbA1c levels between 5 and 6.9 percent. The age-adjusted death rate for all causes was more than 2.5 times higher in men with HbA1c levels of at least 7 percent than in men with HbA1c levels of less than 5 percent (see accompanying table). Death rates from cardiovascular disease and ischemic heart disease were increased 8.16 and 10.91 times, respectively. The risk of death from these causes was directly related to HbA1c concentration. The authors calculate that each 1 percent increase in the HbA1c level was associated with an increase of 29 percent in all-cause mortality, 38 percent in cardiovascular mortality and 44 percent in ischemic heart-disease mortality, after adjustment for age, blood pressure, cholesterol level, body mass index, smoking status and history of myocardial infarction or stroke. About 37 percent of the total deaths in the entire study population were attributed to excess mortality in men with HbA1c concentrations of 5 percent or more.

The authors conclude that HbA1c concentration significantly predicts mortality and that there is no threshold effect. Independent of other risk factors, lowering HbA1c levels has great potential to reduce mortality in men regardless of diabetic status. The authors calculate that reducing the average HbA1c level by just 0.2 percent could lower mortality by 10 percent. They point out that very small changes in HbA1c levels in very large numbers of men would have great impact, but that achieving these changes requires reversing the current population trends of obesity and an increasing rate of diabetes.

Khaw K, et al. Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European Prospective Investigation of Cancer and Nutrition (EPIC-Norfolk). BMJ. January 6, 2001;322:15–8.

editor's note: The authors of this article speculate that screening HbA1c concentration could become routine and that intervention to reduce levels in all patients, regardless of diabetic status, could become standard of care. As they point out, even small changes in the very large number of patients with HbA1c levels that are currently considered borderline could have substantial benefits for the general population. Unfortunately, the prevalence of diabetes is increasing, and most middle-age Americans are steadily growing in weight and girth. Intervening to promote better nutrition and increased exercise is neither easy nor, often, rewarding for most physicians. However, we used to have similar hesitations and lack of confidence when speaking with patients about smoking cessation. We can and should help patients lower their HbA1c levels and increase their well-being through exercise and nutrition. If we do not, we are the ones who must help them through the consequences.—a.d.w.

 

Copyright © 2001 by the American Academy of Family Physicians.
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