Glycemic Control and Potential Complications in Patients with Diabetes Mellitus

CARLOS R. HAMILTON, JR., MD, FACE: Hello, I'm Dr. Carlos Hamilton and welcome to the AACE Clinical Conversations. In this program, we're going to discuss glycemic control and the potential complications in patients with diabetes mellitus.

Joining me today is Dr. Philip Orlander, Professor and Director of the Division of Endocrinology, Diabetes and Metabolism at the University of Texas Medical School at Houston.

And also with us is Dr. Dale Hamilton, attending physician with the Methodist Academic Associates and Diabetes Clinical Service Chief at the Methodist Hospital in Houston. Thank you both of you for joining us today.

Our topic today of glycemic control and potential complications in diabetes really raises two somewhat distinct issues. First, let's talk a little bit about glycemic control.

Philip, what constitutes good control and how do you measure that in your patients?

PHILIP R. ORLANDER, MD: Well, Carlos, as you know, we would all like to have patients who have normal blood sugars, and the normal glycohemoglobin is probably less than 6%, probably less than 5.8%. But in order to attain that, there may be an unacceptable amount of hyperglycemia.

So various organizations have come up with recommendations that are all slightly different. The ADA would like it to be less than 7%, but there is really an action point at 8%. The AACE wants it to be less than 6.5%, and the VA has a variety of different numbers based on what the life expectancy of the patient is and how long they've had diabetes going up to even 9% in patients who are older or don't have more than five years of life expectancy.

So there is a variety of different numbers based on concern of hyperglycemia, which is really the limiting factor in terms of controlling blood sugar.

Personally, I think that trying to get it as low as possible in a way that's safe for the patient is probably best, and certainly the 6.5% would be the first aim, especially since if you look across all the studies, very few people are less than 7%, even with multiple doses of different medications.

CARLOS R. HAMILTON, JR., MD, FACE: So especially in younger patients, the goal of 6.5% for the hemoglobin-A1c is reasonable.

PHILIP R. ORLANDER, MD: Yes.

CARLOS R. HAMILTON, JR., MD, FACE: Now the blood glucose measurements, which both we do in the office and in the outpatient -- and the patients do them themselves, what sort of ranges do you like for those to be Dale?

DALE J. HAMILTON, MD, FACE: Yes, when looking at the blood glucose fasting, we prefer to have it as close to normal as possible, especially in the younger patient, but acceptable values between 90 and 130 mg/dL with comparable levels before meals.

After meals, we target it to less than 180 mg/dL.

CARLOS R. HAMILTON, JR., MD, FACE: There are some people that would suggest that a fasting glucose of 120 or less is a reasonable goal and that a two hour postprandial of 140 or less would be really constituting almost ideal management. Would both of you agree with that as a reasonable goal?

DALE J. HAMILTON, MD, FACE: Yes. That would reflect near normal glycemia and would be a reasonable goal on a motivated patient.

PHILIP R. ORLANDER, MD: It's interesting that in patients with diabetes and pregnancy, we frequently can get much better control than that. At least over a short period of time, again, there is an added motivation of the pregnancy.

CARLOS R. HAMILTON, JR., MD, FACE: Absolutely. How often Philip do you recommend that your patients test, both type 1s and type 2s?

PHILIP R. ORLANDER, MD: I think for type 2 diabetic patients who are not on insulin, I'm not sure how much benefit they get out of multiple testing per day. I think the evidence seems to suggest that if they're using that information for something, they're changing their lifestyle, they're going out and walking or doing other things and changing their diet, that there is a nice feedback in terms of what the blood sugar is.

If all they're doing is collecting the information, then it really doesn't serve much good, and the physician can get as much information with relatively few checks, maybe just one check a day on someone on oral agents and with the glycohemoglobin.

We can get back to some of these issues related to postprandial blood sugars and cardiovascular disease.

CARLOS R. HAMILTON, JR., MD, FACE: Patients with type 1 diabetes or type 2s that are on insulin...

PHILIP R. ORLANDER, MD: Then clearly they need to test more often. There, they hopefully will be making decisions on how much insulin to take based on what they're eating and what their blood sugar is. In those patients, we would teach them carbohydrate counting. We would have them adjust their insulin based on what they're eating and what their blood sugar is, so they need to know what the blood sugar is. So you would say at least three to four times day.

CARLOS R. HAMILTON, JR., MD, FACE: But checking before meals and then perhaps even at bedtime would be an appropriate time. A lot of my patients tell me that they also test whenever they feel like something is out of line, which they can oftentimes sense.

PHILIP R. ORLANDER, MD: And now we have the capability of even having some kind of a trend with some of the newer devices so they can actually see what their blood sugars are doing between meals. That has some pros and cons related to it.

CARLOS R. HAMILTON, JR., MD, FACE: Well, in the type 2 diabetics, of course, the big limiting factor is the patient's willingness and ability to keep a good record of what these blood sugars are. Some do much better than others. But I like testing once a day, I think, is perfectly reasonable, but I often ask them, especially if they are good record keepers, to test it at different times of day and keep a record so we can kind of look at it. And sometimes patients can do that. Sometimes they can't.

PHILIP R. ORLANDER, MD: I would agree with that, especially if you're concerned about the postprandial blood sugars if they're not correlating with either the fasting or the glycohemoglobins.

CARLOS R. HAMILTON, JR., MD, FACE: Dale, there is a lot of interest in different sites of testing for blood sugar measurement, especially in the outpatient situation. What sort of differences and what are some of these different sites that you had some experience with?

DALE J. HAMILTON, MD, FACE: Yes. Traditionally, the site has been the fingertip that measures the blood glucose concentration in the capillary blood. That measurement correlates fairly well with arterial blood, the blood that is bathing the brain.

Now technology is such that we can measure blood glucose in the forearm or in the abdominal wall. These blood glucose measurements though are looking at the concentration of interstitial fluid, rather than capillary blood. And the interstitial fluid glucose concentrations tend to vary more slowly than they do in blood.

So, for example, if they blood glucose concentration should decline by 40 or 50 points, say from 120 to 80 mg/dL, the finger stick glucose would reflect that almost immediately. Measurements in the forearm and the abdominal wall, however, might not show that change for 20 minutes.

Consequently, if the blood glucose were to drop abruptly from 80 to 40, the patient or the meter may not sense it for 20 minutes. And the patient could suffer the consequences of low blood glucose.

CARLOS R. HAMILTON, JR., MD, FACE: So the finger stick is still the gold standard for monitoring blood glucose levels, but the forearm and the abdominal wall with the more continuous glucose monitoring devices may be user-friendly but are certainly not as accurate for very labile or brittle diabetics.

DALE J. HAMILTON, MD, FACE: That is correct. And the finger stick glucose is accurate enough that that is the standard use in most inpatient ICU protocols using IV insulin.

PHILIP R. ORLANDER, MD: Dale, there are alternatives to use the palms, which a lot of patients don't like to use the fingertips, and the palms will give you pretty much as accurate as the fingertips without some of the concerns in terms of the upper part of the forearm, and it's less painful, since there are less nerve endings there.

CARLOS R. HAMILTON, JR., MD, FACE: Well that's good. You know, it always worries me when patients say, "Well, I don't mind sticking myself in the finger because I don't feel it anyway," because that implies that they have some neurological problems.

But generally, the fingertips are pretty sensitive and patients are somewhat resistant to sticking themselves there. You're quite right.

Now we've talked a little bit about the measurement of the blood glucose and how this can be effectively done. Dale, tell us a little bit about the complications of diabetes and how you feel that this relates to the diabetic, diabetic control and to the blood sugar levels.

DALE J. HAMILTON, MD, FACE: Now, the complications of diabetes are usually divided into those involving the large arteries, so-called macrovascular complications, and those involving the smaller arteries and nerves, so-called microvascular complications.

The incidence of the complications, both in the small and large vessels is directly related to the level of blood glucose control. There is very compelling evidence from large studies supporting that argument, and the need for tight control then is justified to prevent these complications.

Patients with type 2 diabetes suffer by and large from complications involving the large arteries, at least serious complications. Most patients with type 2 diabetes will succumb to complications from large vessel disease, either heart attack, heart failure, stroke, peripheral vascular disease.

These patients suffer microvascular complications too, but it's these large vessel complications that by and large lead to life ending events for these patients.

CARLOS R. HAMILTON, JR., MD, FACE: The small vessel disease affects obviously the eyes and the kidneys and so forth. Is there good evidence that diabetic control, blood sugar control has a similar effect there Philip?

PHILIP R. ORLANDER, MD: Well certainly from the diabetes control and complication trial, the landmark study, there is no question that retinopathy is very strongly linked to glucose control. Multiple studies have also shown all of the microvascular complications to be so linked.

As Dale had said, there is now good evidence that macrovascular is also linked based on some of the followup studies from the DCCT, but of course, patients without diabetes also get heart disease, so blood sugar by itself won't get rid of all of the heart disease.

The issue in terms of nephropathy is a little bit different between patients with type 1 and type 2 diabetes, as the patients with type 1 diabetes have a relatively clean model, so that if you can control the blood sugar well, you can see that there is a reduction in terms of frequency of microalbuminuria and progression onto renal disease.

In patients with type 2 diabetes, as Dale has mentioned with the cardiovascular disease, these patients come with much more baggage. They have lipid disorders. They have hypertension, so it's a little harder to sort that out. And microalbuminuria is a risk factor not only for renal disease, but also for heart disease as well.

CARLOS R. HAMILTON, JR., MD, FACE: I think this brings us to another issue that's worth mentioning Dale. That is that the macrovascular disease in diabetics is certainly related to the blood sugar, but it's also very importantly related to blood pressure and cholesterol. I know that you have a lot of experience and opinions about that. Could you share that with us.

DALE J. HAMILTON, MD, FACE: Yes. We have to view it as not just a blood glucose problem, but blood pressure, blood lipid and a coagulation problem. But evidence from the UKPDS study, for example, showed that by controlling the blood pressure you can prevent as many heart attacks as you can by controlling the blood glucose, if not more.

So that endocrinologists and diabetologists need to take a multifactorial approach to the prevention of these complications and focus not only on blood glucose control, but blood pressure control, blood lipid control and prevention of platelet aggregation and thrombosis.

CARLOS R. HAMILTON, JR., MD, FACE: So what you're saying is that if you're going to take good care of your diabetic patients, you have to be a complete physician and not just focus on the blood sugar. I think that all of us know that, and it's worth reemphasizing that.

You know, one of the other complications of diabetes that we haven't mentioned is the effects in pregnant women. That is certainly an issue that is of great interest to those individuals that are involved in that. Philip, do you have any particular opinions about how pregnancy ought to be managed from a blood sugar standpoint?

PHILIP R. ORLANDER, MD: Well, of course, it's of ultimate importance to make sure that the blood sugars are in good control prior to pregnancy. So ideally, it should be a planned pregnancy, and any patient that comes to me, I always refer them to preconceptual counseling to review what the high risks will be in terms of what the risks to both the mother and the fetus are in terms of glucose control and attempt to get the glycohemoglobin as well controlled as possible prior to the pregnancy because there are multiple risks during pregnancy, again, both to the mother and the fetus.

Early on, poor blood sugar control is associated with congenital malformations. Later on, it's associated with large babies and obstetrical complications. Then, of course, the increased stress to the hemodynamic system of the mother puts her at risk of progression of retinopathy, nephropathy and some of the other complications of diabetes.

CARLOS R. HAMILTON, JR., MD, FACE: Well certainly in my experience, these patients are the most highly motivated of any of the diabetic patients that I deal with, at least on a regular basis, and taking care of them has great challenges, but great benefits to everyone involved.

I appreciate both of you being with us today. This has been very helpful and I think a very useful conversation. And I just would like to thank you for sharing your time and your expertise with us.

Again, I'm Dr. Carlos Hamilton, and I thank all of you for watching us today.