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Hemoglobin Levels Predict Diabetic Retinopathy

Posted: Monday, November 23, 2009

An already routine blood test may identify juvenile-onset diabetic patients at heightened risk for proliferative retinopathy, researchers said.

In a multivariate analysis, each increment of 1 g/dL in hemoglobin was associated with a linear 29% increase in risk for retinopathy in men with Type 1 diabetes (95% CI 8% to 54%), and a quadratic 10% risk increase in women (95% CI 0% to 20%), reported Trevor Orchard, MD, of the University of Pittsburgh, and colleagues.

"This is the first study, to our knowledge, to show high hemoglobin levels to be predictive of the long-term incidence of proliferative diabetic retinopathy," the researchers wrote.

Their study analyzed data on 426 participants in the Pittsburgh Epidemiology of Diabetes Complications Study, which began in the late 1980's. Some 18 years of follow-up were thus available. At enrollment, participants were about 25 years old on average, and had had diabetes for a mean of 17 years. During the study, 48% of both men and women were diagnosed with proliferative diabetic retinopathy.

Mean hemoglobin levels were 16.5 g/dL in those who went on to develop retinopathy, compared with 16.1 g/dL in those who did not (P=0.009).

Other baseline factors that differed between the eventual retinopathy cases and those who remained free of the disorder included presence of overt nephropathy, albumin excretion rate, total and non-HDL cholesterol, diastolic (but not systolic) blood pressure, and glycated hemoglobin levels.

Of those, only diastolic pressure and glycated hemoglobin were predictive of retinopathy in multivariate analysis for both sexes. The multivariate analysis controlled for all these factors as well as diabetes duration, body mass index, white blood cell count, fibrinogen, and hypertension medication.

Each 1% increment in glycated hemoglobin was associated with a hazard ratio of 1.30 in men (95% CI 1.14 to 1.49) and 1.32 in women (95% CI 1.26 to 1.50). The hazard ratio for retinopathy associated with each 1 mm Hg in diastolic pressure was 1.03 in men (95% CI 1.00 to 1.05) and 2.28 in women (95% CI 1.02 to 5.07), Orchard and colleagues said.

Systolic pressure predicted retinopathy in women (HR 1.03 per mm Hg) but not in men. Albumin excretion rate was a significant predictor in men (HR 1.34 per ěg/min) but not in women.

The researchers said that most attention to hemoglobin in the context of diabetes has focused on low levels -- that is, anemia -- in late-stage kidney disease.

They said their findings on high hemoglobin levels and retinopathy "may have important clinical relevance, as they may both identify new pathogenetic pathways to proliferative diabetic retinopathy and influence clinical treatment." Increased hemoglobin could be related to a number of factors potentially influencing retinopathy development, they said, such as testosterone levels, hypoxia, abnormalities in growth factors, and blood viscosity.

The researchers noted that the difference in the nature of the relationship between hemoglobin and retinopathy risk between sexes -- linear in men, quadratic in women -- may just be a statistical fluke, arising from the small number of men with hemoglobin levels below 13.5 g/dL.

A U-shaped relationship, indicating increased retinopathy risk for both low and high levels of hemoglobin, is likely to apply to both sexes, they said.

Source: Diabetes In Control: Conway B, et al "Prediction of proliferative diabetic retinopathy with hemoglobin level" Arch Ophthalmol Nov,2009; : 1494-99.

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