Diabetic Retinopathy Without Diabetes?

The Diabetes Prevention Program (DPP) showed that lifestyle modification significantly reduces the risk of developing type 2 diabetes in at-risk patients. Specifically, 150 minutes of modest physical activity per week reduced the risk of diagnosis over a three-year period by 58% in patients diagnosed with prediabetes. Prediabetes is defined as impaired fasting glucose (FPG ranging between 100 and 125 mg/dl) and/or impaired glucose tolerance (OGTT values at two hours between 150 and 199 mg/dl). More than 41 million Americans are believed to have prediabetes, so the public health implications of the DPP are truly astounding.

This last month, another astounding statistic came forth from the DPP data: Over three years of subsequent follow-up of 302 DPP participants, 13% of prediabetics who developed type 2 disease were found to have diabetic retinopathy, and nearly 8% of “prediabetics” also were found to have diabetic retinopathy, though they never developed diabetes per diagnostic criteria. What do these data mean?

Of course, the meaning of any data set is subject to any and all kind of clinical interpretation and, yes, even philosophical and political “spin.” In my view, there are two key conclusions that emerge. First, that a significant number of newly diagnosed type 2 patients already have microvascular diabetes complications, most probably as a result of chronic hyperglycemic and, possibly, hypertensive insult. This finding is not all that surprising, as a number of previous studies have shown that up to 35% of newly diagnosed type 2 patients will have at least mild, non-proliferative diabetic retinopathy with meticulous fundus examination. A significant corollary to this conclusion is that patients are not being diagnosed and treated early enough; little surprise, here.

The second key conclusion is that patients are suffering end-organ damage even though they don’t conform to diagnostic criteria, even though they “do not have” the disease that causes such end-organ complications.. Logic aside, we are faced with the relatively untenable position of a new diagnostic category – “prediabetic retinopathy.” The more logical corollary here, of course, is that these patients do, indeed, have diabetes.

There was a time in eye care when intraocular pressure (IOP) was the singular arbiter of glaucoma diagnosis; patients with high eye pressure had glaucoma by definition, whereas patients with normal eye pressure were excluded, by definition, from having glaucoma. We now know that a significant percentage of patients with high IOP never develop optic nerve damage or visual field loss (the sine qua non of glaucoma), whereas another significant minority of patients will, in fact, develop nerve damage and field loss despite normal IOP. This understanding has led to widespread recognition of “normal tension glaucoma” and to the exclusion of reference to intraocular pressure in the very definition of glaucoma by the American Academy of Ophthalmology.

I think this remarkable, historical development in ophthalmic diagnosis and care sheds some interesting light on these remarkable, new findings from the DPP. Recognizing that structural and functional abnormalities in the optic nerve take diagnostic precedence over measurement of eye pressure, ophthalmologists and optometrists have changed totally the way we think about IOP – it no longer makes the diagnosis but is, rather, a modifiable risk factor. Similarly, fasting plasma glucose and measurement of glucose tolerance could be viewed as (environmentally and pharmacologically) modifiable risk factors for the microvascular and macrovascular disease states that diabetes engenders.

Do “prediabetics” with “diabetic retinopathy” really have diabetes? Or do they really have “prediabetic retinopathy”? I suspect it is up to the diabetes care community to settle this language game with both some degree of intellectual honesty and at least a modicum political finesse. It may be no easy task, but the implications for the public health and welfare of our nation are significant.

References

Diabetes Prevention Research Group: Reduction in the evidence of type 2 diabetes with life-style intervention or metformin. N Engl J Med 346:393–403, 2002

ADA 65th Annual Scientific Sessions: Late-breaking trials. Presented June 12, 2005.

Kohner EM et al. United Kingdom Prospective DiabetesStudy, 30: diabetic retinopathy at diagnosis of non-insulin-dependent diabetes mellitus and associated risk factors. Arch Ophthalmol. 1998 Mar;116(3):297-303

Hitchings RA. Chronic glaucoma: definition of the phenotype. Eye. 2000 June 14; 419-21

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Lessons from a Diabetic Eye Doctor:
How to Avoid Blindness and Get Great Eye Care

Dr. Paul Chous received his undergraduate education at Brown University and the University of California at Irvine, where he was elected to Phi Beta Kappa in 1985. He received his Masters Degree in 1986 and his Doctorate of Optometry in 1991, both with highest honors from the University of California at Berkeley. Dr. Chous was selected as the Outstanding Graduating Optometrist in 1991. He has practiced in Renton, Kent, Auburn and Tacoma, Washington for the last 12 years, emphasizing diabetic eye disease and diabetes education. Dr. Chous has been a Type 1 diabetic since 1968. He lives in Maple Valley, Washington with his wife and son. More Info Here