Understanding the Diabetes Patient

Endocrinologists and retina specialists find common ground for treating these complex patients.

Dr. Boyer: Dr. Peters, please give us a brief overview of your goals when treating patients who have diabetes.

Dr. Peters: First, I’d like to take a step back. All of the early clinical trials in diabetes looked at microvascular endpoints. The Diabetes Control and Complications Trial (DCCT)¹ and the United Kingdom Prospective Diabetes Study (UKPDS)^2-5 showed the benefits of tight glycemic control to prevent microvascular complications. More recent studies have looked at macrovascular endpoints, which can be somewhat more complicated.^6-7 Basically, as a diabetologist, I try to reduce microvascular complications by reducing blood sugar levels.

Dr. Boyer: One of the challenges we have is communicating to endocrinologists the importance of seeing patients early, especially in light of the new treatments we have available. Dr. Peters, you’ve written that vision loss is one of the complications that patients fear most. How do you talk to them about this?

Dr. Peters: My patients are concerned about their quality of life, as am I, and they particularly want to preserve their vision. They want to avoid diabetic retinopathy at all costs, but if they get it, they want to deal with it. So when I talk to patients about glucose control, I talk to them about reducing the risk of retinopathy, nephropathy and neuropathy. I also discuss the need for screening. The problem for many is that they don’t understand what a retina eye exam entails, that it’s not just a vision screening. Even in an educated population, I see a lack of knowledge as to why managing glucose levels is so important and why patients should have eye examinations. I have to make an effort to be sure patients follow through with screening and treatment.

A patient can be virtually asymptomatic with 20/20 vision and have significant treatable maculopathy. So when someone says to the endocrinologist or the internist, “My vision is fine. I can read, and I can drive,” that doesn’t make him fine. Patients with diabetes need to be evaluated in a careful, precise manner, so that we can begin treatment, if necessary. — Steven Schwartz, MD

WHEN TO REFER TO A RETINA SPECIALIST

Dr. Handelsman: When a patient is newly diagnosed with diabetes, I tell him to see his eye doctor, because I assume he has one. If he doesn’t have an eye doctor, I want to recommend one. Are all eye doctors equal? To whom should I refer my patients?

Dr. Schwartz: We would like you to send them to a general ophthalmologist, an eye MD, unless they have vision loss, in which case they should go directly to a retina specialist.

Dr. Peters: What about patients who have floaters and the like?

Dr. Schwartz: If a patient has flashes, floaters or distortion or is having trouble driving, reading and functioning, then referral to a retina specialist is reasonable.

Dr. Boyer: All of those scenarios warrant a thorough examination. Patients who are managing their diabetes well and who have no leakage can be followed by a general ophthalmologist. If there is leakage, then we need to treat it.

Dr. Handelsman: The leaking is determined by the retina specialist, not the diabetologist, correct?

Dr. Boyer: That is correct. We will look for subtle changes and identify clinically significant macular edema, which we now call center-involving or noncenter-involving macular edema.

Dr. Schwartz: Diagnosis of retinal pathology has become much more efficient and precise. We have a variety of imaging techniques, such as optical coherence tomography, ultra widefield angiography and autofluorescence, that help us diagnose, prognosticate and make treatment decisions.

Dr. Boyer: Dr. Gonzalez, when do you want to see a patient who has diabetes?

Dr. Gonzalez: Ideally, I should see a patient at the time of diagnosis before irreversible structural changes have occurred. If a patient has a large accumulation of lipids in the central fovea, it doesn’t matter if I use laser or pharmacotherapy, chances are he will not recover as much vision as he would have if I’d been able to treat him earlier.

Dr. Schwartz: Dr. Gonzalez makes a key point. A patient can be virtually asymptomatic with 20/20 vision and have significant treatable maculopathy. So when someone says to the endocrinologist or the internist, “My vision is fine. I can read, and I can drive,” that doesn’t make him fine. Patients with diabetes need to be evaluated in a careful, precise manner, so that we can begin treatment, if necessary.

Dr. Handelsman: Of the newly diagnosed patients referred to you, how many have severe retinopathy? I understand patients with a new diagnosis — let’s say their hemoglobin A1c (HbA1c) is 11 or 12 and glucose is 300 or 400 — may have changes in vision but not necessarily retinopathy. Is that correct?

Dr. Schwartz: Yes. That is correct. Typically, those changes are lenticular. I believe we have statistics showing about 15% of patients with newly diagnosed type 2 diabetes and HbA1c readings above 9 have discernible retinopathy.⁸

That’s a fairly high number that were missed by direct ophthalmoscopy in the internist’s office or during other types of screening.

Dr. Gonzalez: I believe the percentage of patients who present with significant retinopathy varies by region and the makeup of your population. In South Texas, where I practice, about 20% to 25% of our population have diabetes. Unfortunately, many of these people have not had access to proper medical care, so as many as 20% to 25% of newly diagnosed patients may have significant retinopathy. I’ve seen patients whose first diagnosis of retinopathy is a vitreous hemorrhage, and that’s when they learned they have diabetes. So, the statistics vary depending on where you practice. It’s important for us to know that we will be seeing more people of color, who have a much higher incidence of diabetes and retinopathy, as the minority populations in this country continue to grow.⁹

Dr. Boyer: I think the take-home message is that anyone who is newly diagnosed with type 2 diabetes should be evaluated by a retina specialist at the time of diagnosis. We can wait several years before seeing a patient newly diagnosed with type 1 diabetes.

Dr. Peters: One exception would be patients newly diagnosed with adult-onset type 1 diabetes. I tend to refer them earlier, because I’m not exactly sure how long they’ve had the disease.

Dr. Schwartz: I stratify the disease based on insulin-dependence, because the demographics of diabetes are changing. I’m seeing 30- and 40-year-old newly diagnosed type 2 patients using insulin, which I never saw before, and I see young, obese people taking oral hypoglycemics, which I never saw before.

Although certain racial groups have been identified as having a higher risk for diabetes, I believe the risk is more genetic than racial. It’s just that the genetic factors tend to cluster within a race. I believe as more research is done, we’ll learn that certain genotypes and phenotypes will develop retinopathy, while others will not. There’s no question that heavier, underserved people have worse diabetes. I agree that any adult who has a new diagnosis should be seen immediately by a retina specialist, while prepubescent patients do not need to be seen immediately.

Dr. Peters: I agree.

Dr. Handelsman: I look at insulin resistance. If patients are overweight or obese and they have signs of insulin resistance, I refer them to a retina specialist immediately. For the typical type 1 diagnosis, I agree with Dr. Boyer that we can wait several years before referring that patient to a retina specialist.

DELAYED TREATMENT EFFECT

Dr. Boyer: Dr. Handelsman, in my experience, if a patient’s blood sugar is poorly controlled and we treat him for diabetic retinopathy, it can take 2 years or more before we see a treatment effect; and sometimes the retinopathy will worsen before we see an improvement. Is there an explanation for that?

Dr. Handelsman: Part of the issue is that we don’t know when retinopathy starts. When do those changes start? Do they start when we diagnose diabetes? Do they start when glucose levels increase, or do they start years before that? We believe the moment a patient is diagnosed with type 2 diabetes, he is already at risk for retinopathy.

In my experience, if a patient’s blood sugar is poorly controlled and we treat him for diabetic retinopathy, it can take 2 years or more before we see a treatment effect; and sometimes the retinopathy will worsen before we see an improvement. — David Boyer, MD

REDUCING HBA1C: IS SLOWER BETTER?

Dr. Boyer: Often, when we see patients, their diabetes is not well controlled. Dr. Schwartz, is there any recommendation to reduce HbA1c slowly?

Dr. Schwartz: Early studies demonstrated a worsening of retinopathy with rapid normalization of HbA1c. Eva Kohner, MD, was an advocate of slowly normalizing glucose. That was probably a smart thing to do in that era, when our ability to diagnose retinopathy was imprecise, and many diabetes patients also had hypertension and renal failure. At that time, we saw rapid normalization, drying of the retina, decreased edema and precipitation of exudates in the macula. We don’t see that any more. With the vascular endothelial growth factor (VEGF) inhibitor we are using now, the rapid drying effect is so precise physiologically and pathologically, that we can target that hyperleakage state, so to speak. We can dry the leakage pharmacologically and then send the patient back to the endocrinologist. The truth is, if a patient’s HbA1c is 11 or 12, that reading won’t be less than 7 for a while, even under the best conditions.

Dr. Handelsman: What do you consider rapid reduction? Is it a day, a week, a month?

Dr. Schwartz: If a patient’s HbA1c drops more than 3 points over one quarter, I consider that rapid normalization. I reinforce the need for patients to hit the three or four targets (sugar, blood pressure, lipids and anemia) given to them by their endocrinologist or internist. I tell them if they can get those three or four targets under control in the next couple of quarters, that’s great.

I also explain to patients that what’s happening in their eyes wasn’t caused by yesterday’s or today’s sugar. That’s another misconception patients have. I tell them, “What happens in your eyes reflects what happened 5 years ago or 3 years ago. Even if your sugar is normal today, if it was uncontrolled a couple of years ago, you may have a rocky road going forward.”

The most important advice I can give patients is to hit their targets. When they do that, we can manage the retina. Nine times out of 10, we can honestly tell a patient he will not go blind. We couldn’t say that with certainty just a few years ago.

COMMUNICATION IS KEY

Dr. Boyer: What information should ophthalmologists be conveying to diabetologists to help manage patients?

Dr. Peters: Ideally, our communication would begin with a note from me to you saying, “Mrs. Smith is doing better, but her HbA1c is still 9, and she really could use more encouragement,” because what you say to my patients really influences them and vice versa.

It’s important that ophthalmologists and diabetologists communicate directly because sometimes what patients tell us isn’t accurate. For example, I may receive a form from your office that says the patient told you his/her HbA1c is 7, and I know it’s actually 10. I know it’s more work, but somehow if there were an easier way to have a referral from me to you, or some communication about how the patient is doing, especially those who are difficult, then you would be aware of the challenges I’m facing, and you could talk to patients in the context of their eyes. You’re the experts on that. We need a system so that I can help you so we can better serve patients.

It’s important for us to know that we will be seeing more people of color, who have a much higher incidence of diabetes and retinopathy, as the minority populations in this country continue to grow. — Victor Gonzalez, MD

Dr. Gonzalez: That’s important because the real problem right now — and I have been working with the ADA and the American Academy of Ophthalmology on this — is that only about 50% of the people who should be screened by a retina specialist are screened. There’s obviously a problem, and I don’t think it’s a problem with knowledge on either side. We all agree that patients with diabetes need to be screened. The problem is with our mechanisms, so we’re looking at some programs to address that issue. When I go to Europe, I see their screening statistics, and in some places, they’re screening more than 90% of patients. One of the reasons is that patients are being screened in their primary care offices, which is probably something we need to consider.

To address your issue, Dr. Peters, there are programs now where you take a photograph in your office and send it electronically to the retina doctor for evaluation. Although it’s not a perfect system, it’s a way to get more access to patients. Unfortunately, what often happens now is the doctor refers patients to a retina specialist, and half of them don’t go.

Dr. Handelsman: In addition to one-on-one communication among consultants, we also need to communicate more in terms of professions, as we’re doing today. When you offer treatment options to a patient whom we share, she’ll likely come to me and ask my opinion. I need to be educated about those options, so I can help her make an informed decision. I know you’ll send me a report, but we need more general knowledge and interaction. In Los Angeles, for example, a small group of diabetologists meets every few months. I think that would be a great forum to share interdisciplinary news.

The issue of day-to-day communication may be more difficult to resolve because of the sheer numbers of patients that we see. We need to develop systems for efficient communication.

Dr. Schwartz: One currently available patient-empowered mobile health application called Sight Book, is a free downloadable application into which pictures and office notes can be dropped, allowing patients to reliably measure their visual function and facilitate communication between patient and all of their doctors. The patient’s doctors can see the results and manage visits remotely or instruct patients to come in for an evaluation. Importantly, both the retina doctor and the endocrinologist can see the data. It’s the beginning of a new era, because you’re exactly right, doctors can’t do it all. Patients have to take some responsibility.

Dr. Boyer: An application such as the one Dr. Schwartz described would provide open access for any of the consultants. We could see a patient’s true blood sugar, as reported by the diabetologist, as well as his lipid and blood pressure readings. We could enter our data, and patients could check their own vision.

Dr. Schwartz: It’s also important for retina specialists to stay current with diabetes research, so we can advise patients appropriately. Recently, for example, a major study was published suggesting that high fructose corn syrup may be one of the culprits in terms of the risk for diabetes.¹⁰ According to the researchers, countries that have high fructose corn syrup in their food chain have approximately a 20% higher rate of type 2 diabetes than those developing countries that do not have it in their food chain. Passing along that type of information is a simple step we can take to intervene when making dietary suggestions to our patients with diabetes.

References

1. 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.

2. 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.

3. UK Prospective Diabetes Study Group: Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352:854-865.

4. 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.

5. UK Prospective Diabetes Study Group: Efficacy of atenolol and captopril in reducing risk of both macrovascular and microvascular complications in type 2 diabetes (UKPDS 39). BMJ 1998;317:713-720.

6. Gerstein HC, Riddle MC, Kendall DM et al. Effects of intensive glucose lowering in Type 2 diabetes. The Action to Control Cardiovascular Risk in Diabetes Study Group N Engl J Med 2008;358:2545-2559.

7. Duckworth W, Abraira C, Moritz Tet al. VADT Investigators: Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009;360(2):129-139.

8. The American Academy of Ophthalmology. Diabetic Retinopathy: Medical Therapy and Surgery. http://one.aao.org/CE/PracticeGuidelines/default.aspx. Accessed Jan.31, 2013.

9. American Diabetes Association.diabetes.org. Accessed on Jan. 31, 2013.

10. Goran MI, Ulijaszek SJ, Ventura EE. High fructose corn syrup and diabetes prevalence: A global perspective. Glob Public Health. 2013;8(1):55-64.