Where do the areas of hematology and endocrinology intersect in diabetes management?
I have found that, in order to do the endocrinology work that I do, I needed to start thinking about hematologic questions. I saw patients who had hemoglobin A1c (HbA1c) levels that did not line up with their blood sugar levels, and I became interested in recognizing those patients and identifying the mechanisms behind that disagreement.
Over the past 10 years, my collaborators in hematology, Robert Franco, PhD, and in pediatric hematology, Clinton Joiner, MD, PhD, have looked at glucose metabolism in red cells and their life span.
In particular, while most of us were taught the importance of red blood cell life spans, the mean age of the red blood cell is the real determinant of what fraction of the hemoglobin has attached glucose.
What can hematologists learn from the research you and your team are conducting in the field of diabetes?
Hematologists should be aware of newer techniques for measuring red blood cell age, and of the very small differences in red blood cell age that may go unnoticed. People might assume that red cell life spans are essentially uniform in people without obvious hematologic disease, but there are subtle differences that can affect HbA1c – and could lead to over- or under-treatment of diabetes.
So, how much of a difference matters? Major studies of blood sugar control and its effects on diabetic complications have identified differences in HbA1c of one or two percentage points as the criterion for “clinically important differences” that may impact patient outcomes and the frequency of complications.
We are now using state-of-the-art techniques to measure red cell life span – some of which may be unfamiliar to many hematologists. For instance, we label red blood cells with the vitamin biotin, which allows us to precisely determine red cell life spans. We have also adopted some of the life-span measurement techniques developed in the 1950s, using a labeled amino acid that is eventually incorporated – into the “hemo” portion of the hemoglobin molecule and detected with a mass spectrometer.
Overall, we cannot rely solely on HbA1c to make clinical decisions – we need additional information from blood glucose measurements. Several blood sugar control markers could be compared with HbA1c – synchronistic blood sugars or fructosamine levels, for instance.
The basic question is, “When I look at the measurements from these two different methods, do I get similar or conflicting answers?” It’s a very simple, scientific principle we can apply to this particular clinical problem.
When should a hematologist consult an endocrinologist? When should the endocrinologist consult the hematologist?
Obviously, hematologists are familiar with the most common measurement for determining a diagnosis of diabetes: the HbA1c test. People may take the HbA1c as a measure of blood sugar control by itself but, in fact, HbA1c measure depends on both blood sugar control and the average time that the red blood cell has spent in the circulation.
Endocrinologists and primary care doctors may need some guidance from hematologists for those red blood cell measures – even in the absence of hemoglobinopathies.
We are also looking at certain common measures from usual blood count tests to correct for the red cell life span differences, and the possibility of developing a simple technique for measuring life span that can correct HbA1c.
For diabetic patients who have cancer, how can the endocrinologist and hematologist work together to optimize patient outcomes?
The question in this situation is, “How do I alter management of diabetes differently because of the presence of cancer?” On the other side, “What ‘tricks’ can hematologists use if they are trying to control blood sugar when the patient is undergoing chemotherapy?”
As endocrinologists, we plan forward-thinking regimens that anticipate how a patient’s blood sugar might change and how to prevent those changes – rather than responding to changes after they have happened. Many hematologists may be familiar with the idea of “carbohydrate
counting,” where patients estimate the amount of carbohydrate in their diet and adjust their insulin according to the amount of food they are about to eat. When treating diabetic patients with cancer, that same principle could be extended to patients who are about to receive chemotherapy.
Endocrinologists will plan to omit insulin for a diabetic patient about to have chemotherapy – a patient may have a poor appetite and not be eating as much. For patients repeatedly receiving courses of certain steroids like prednisone or dexamethasone as part of their chemotherapy, though, we know their blood sugars are going to rise in response. In those cases, we will try to adjust the diabetes
management based on what we learn about blood sugar response from one course of chemotherapy; as the patient receives subsequent treatments, the endocrinologist can alter the insulin dose or other diabetic medications to anticipate and prevent those rises in blood sugar.
Preventing elevated blood sugar, in turn, reduces patients’ dehydration and may help people feel a little bit better as they are going through chemotherapy. Patients have so many stresses and strains as they undergo chemotherapy, so we are always looking for ways to alleviate some of that burden.
Before a patient starts a steroid-containing regimen, the hematologist and endocrinologist can work with the patient to plan for the response to treatment and individualize the courses of diabetes and cancer management – and, really, give the patients more control over the situation.