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Diabetes Care in the Elderly (Slides with Transcript)

Posted: 8/24/2007

Diabetes Care in the Elderly

Dr. Meneghini set out some myths of diabetes, so maybe I could pick up on that and start with a myth or 2. The first is that nobody
here is ever going to get old and be called elderly. I guess like me, you look in the mirror every morning and you see a 25-year-old.
Plus a few wrinkles. The second myth, of course, is that when we're treating diabetes in the elderly, we feel that they're not going to
live very long, that they're not going to have time to develop complications, that all we have to do is keep them symptom free. We
don't have to treat to target. I want to show you that that is a myth.

Introduction
Life Expectancy at Birth, Age 65, and Age 75

This is life expectancy in the United States, at birth and at age 65 and at age 75. You'll see that at age 65, there is still between 17
and 20 years of life expectancy for an average individual. Even at 75, people are still looking forward to 10 years of life.

Projected Life Expectancy (UK)

Here are some figures from the United Kingdom; what we have here is projected life expectancy. This is not historical life
expectancy; this is life expectancy that you can realistically expect, taking into account medical advances. If you look at the age of
70, you see people still have more than 15 years of life expectancy. It's not until you get to the age of 90 that your life expectancy
comes down to around 5 years. So there is still plenty of time when you become designated as elderly for you to develop diabetic
complications if your diabetes is poorly controlled.
Diabetes Prevalence Increases With Age

Now let's look at the prevalence of diabetes by age group, particularly when you get to 60-plus years, where 20% of the population
has diabetes. One in 5 people at the age of 60 has diabetes. And those are historical figures. We do not know the impact upon those
figures of the epidemic of obesity, for example.

Age and Comorbidities Decrease the Likelihood of Therapy Advancement

The other problem, of course, is that as you get old, you're likely to have comorbidity, other illnesses to go with your diabetes. Some
might be diabetes related, but they might be unrelated to your diabetes. It's clear that if you have comorbidity, there is a reluctance
by the physician and by the patient to advance treatment, to go from tablets to more tablets or from tablets to insulin. We can assess
this by something called the Charlson score, a summary measure of the burden of comorbidity. At the age of less than 65, if there is
no comorbidity, about 25% of patients advance their treatment option, but only around 22% if there is comorbidity. If you look down
the slide, you'll see that the percentages decrease as you get older. So having comorbidity — having other illnesses — means
there's more reluctance to advance treatment. And as you get older, there's also a greater reluctance to advance treatment.

Case Study: Mildred

Let's take a look at a typical elderly person who is having problems with her diabetic control.

Mildred is a 70-year-old white female with type 2 diabetes for 4 years who lives with family. She has been treated with sulfonylurea
therapy since her diagnosis. She has several comorbid conditions, including hypertension, New York Heart Association class II heart
failure, and compromised renal function. She is here for a 3-month follow-up visit. At her last visit, her A1C was 8.5% and her self-
monitored PPG was 220 mg/dL. At that time, the need to intensify her treatment regimen, if glycemic control did not improve, was
discussed. She is still moderately active and enjoys shopping with her daughter.

DOCTOR: Mildred, how are you today?

MILDRED: Okay, I suppose. You know how it is when you get to be my age. A little tired sometimes and it makes it hard to go out
shopping with my daughter. We go shopping every Tuesday and Thursday and I like my routine, but with all this tiredness, I'm afraid
my heart might be getting worse.

DOCTOR: Well, there are a lot of reasons you might be getting tired lately. Let's try to figure out what's going on. Why don't we start
by talking about your medications. Are you taking all of your pills?

MILDRED: My daughter helps me with the pills. She makes sure I take everything when I'm supposed to. I take a lot of pills, so it's
hard to remember. But she helps me split them out by meals and I always have breakfast at 7, lunch at noon, and dinner at 5 and I
like my routine.

DOCTOR: So you're taking your diabetes pill at every meal?

MILDRED: Yes.

DOCTOR: Well, we talked about this at our last visit. Your A1C did not get better since then. It's now 8.8%. I think we're going to
have to change your diabetes medication to help you get to your target.

MILDRED: Does this mean I'll have to take more medications?

DOCTOR: Well, you've got a decision to make.

We do indeed. We have a decision to make. To summarize, her A1C is 8.8%, her FPG is 199 mg/dL, and the most recent self-
monitored PPG is 260 mg/dL.

Audience Response Question

Which of the following treatment regimens would you select for Mildred?

1. Continue sulfonylurea therapy tid (3 times daily), and add a single daily injection of a basal insulin analog
2. Reduce sulfonylurea therapy to bid (twice daily), and add a single daily injection of a biphasic insulin analog with dinner
3. Discontinue sulfonylurea therapy, and add 2 daily injections of a biphasic insulin analog
4. Discontinue sulfonylurea therapy, and initiate full basal-bolus therapy with multiple daily injections.
Audience Response Question

So, 45% of you are going to discontinue sulfonylurea therapy and add 2 daily injections of a biphasic insulin analog. The addition of
a basal insulin analog to sulfonylurea therapy — only 23% of you are going to do.

Treatment Options

News You Can Use: Treatment Options Explored

Let's explore the options in a little more detail.

What do the guidelines recommend? The ADA would say to add metformin or a TZD or basal insulin. The AACE, to initiate
combination therapy with metformin plus a sulfonylurea or meglitinide; metformin plus a TZD or alpha-glucosidase inhibitor; a TZD
plus a sulfonylurea; an incretin mimetic plus metformin and/or a sulfonylurea; a basal, rapid-acting, or biphasic insulin analog; or any
other approved combination. Guidelines can be helpful, but I sometimes feel that the more difficult we make our subject, the less
success we'll have in treating people. These guidelines are fine, but they are all-embracing guidelines. They don't actually help, I
think, when you're faced with a specific patient such as Mildred.

What Are the Treatment Considerations for This Patient?

Because then you have to take other things into account. Mildred is elderly. What is the glycemic target that we're going to set for
her? Seven percent or lower in healthy adults in good functional status, and 8% for frail, older adults or persons with a life
expectancy of less than 5 years. But only people over 90 have a life expectancy of less than 5 years. Of course, we must modify our
treatment on the basis of comorbidity, especially when other illnesses might be present that raise difficulties with other therapies. For
example, degree of chronic kidney disease and the use of metformin. And injectable therapy, of course, may always be required. If
we take that step to injectable therapy, the next consideration is how we approach injectable therapy.
Both FPG and PPG Contribute to Overall Glycemic Control

This slide shows the percentage contribution of either fasting plasma glucose, in yellow, or postprandial glucose, in orange, at
different levels of hemoglobin A1C. On the left are the highest levels of hemoglobin A1C, and on the right, the lowest levels. It
summarizes one of the slides that Dr. Davidson showed. With a hemoglobin A1C of greater than 10.2%, 70% of the contribution
comes from FPG and only 30% from PPG. But at lower hemoglobin A1Cs, only 30% of that comes relatively from FPG and now
70% comes from PPG. It's a complicated slide, but it's a simple message. It basically says that regardless of the hemoglobin A1C, if
you wish to get to target, you will need to address both fasting plasma glucose and postprandial glucose.

The 1-2-3 Study: Dosing of Biphasic Insulin Aspart

Let's look at the use of biphasic insulin in that situation. Many of you are familiar with the 1-2-3 study, in which 100 subjects were
recruited. Biphasic insulin aspart was given initially once daily before dinner for 16 weeks. If at the end of 16 weeks, A1C was 6.5%
or less, then patients who achieved that goal were designated as having completed the study and they ended the study there. But if
the A1C was not at 6.5%, then the second stage of the study was to add a second injection of biphasic insulin aspart before
breakfast for 16 weeks. Again, if you got to an A1C of 6.5% or less, you completed the study. But those who didn't get to 6.5% or
less went on to 3 injections of biphasic insulin aspart at breakfast, lunch, and the evening meal for the final 16 weeks of the study.
The 1-2-3 Study: Patients Reaching A1C Goals

Here we are looking at patients who achieved the target — on the left you have the A1C target of less than 6.5%, on the right the
A1C target of less than 7%. On once-daily biphasic insulin aspart, 21% of subjects got to less than 6.5% and 41% to less than 7%.
On 2 injections, 52% got to less than 6.5% and 70% got to less than 7%. On 3 injections, 60% and 77%. So on 1, 2, or 3 injections
of biphasic insulin aspart used in this way, you could eventually get 77% of patients to an A1C of less than 7%.

The 1-2-3 Study: Hypoglycemia

Rates of major hypoglycemia were similar in the 3 groups, and rates of minor hypoglycemia were also similar across the 3 groups.
Biphasic Insulin Analog Therapy Improves Glycemic Control

This is an interesting study from Malone, looking at insulin glargine plus metformin, in yellow, compared with biphasic insulin lispro
plus metformin, in red. It's a crossover study. In the first limb of the crossover, mean A1C came down to a much greater extent with
biphasic insulin lispro plus metformin than it did with glargine and metformin. When patients were then crossed over — so they went
from biphasic insulin lispro to glargine or vice versa — those who started on glargine showed a further improvement with biphasic
insulin lispro, and those who were on biphasic insulin lispro showed a deterioration when they were put on the basal insulin analog.

The INITIATE Study Design

The INITIATE study compared glargine with a continuation of oral hypoglycemic agents — metformin, but not secretagogues — with
biphasic insulin aspart given twice daily with a continuation of oral agents. This was a study in insulin-nave patients, so they were
poorly controlled patients going to insulin for the first time.
Insulin Analogs: Safety and Efficacy

This chart shows the baseline A1C and then, under that, the change from baseline A1C. For biphasic insulin aspart 70/30, A1C
came down by an average of 2.9%, whereas on glargine it came down by 2.5%, and that is a significantly better result for insulin
aspart than it is for glargine. There were no major hypoglycemic episodes, but of course there was less hypoglycemia — fewer
patients reporting at least 1 episode — in the glargine group than in the biphasic insulin aspart group, as I think you would expect if
you're using a premix insulin and comparing it with a basal insulin.

PREFER Study: Biphasic Insulin Versus MDI

What we've done so far is look at a couple of studies comparing biphasic insulin analogs with basal insulin analogs added to oral
agents. This is the other side. This is a study comparing biphasic insulin analogs with a multiple-injection regimen of insulin aspart 3
times daily with detemir, done in Germany by Andres Liebl. I'm absolutely convinced that the Germans undertook this study in the
assurance of knowledge that the gold standard of MDIs would prove superior to a twice-daily biphasic analog.
Glycemic Control With Twice-Daily Biphasic Insulin Aspart Versus MDI

When you look at the results, with MDI with detemir and insulin aspart the A1C of 8.52% came down to 6.96%, and with twice-daily
insulin aspart it went from 8.40% down to 7.17%. That is a slightly better improvement in A1C for MDIs, but if you delve deeper into
these data, you find something that is quite interesting.

Similar A1C Reduction in Insulin-Nave But Not in Insulin-Treated Patients

If you break down the patients in the study into those who were insulin nave, on the left, and those who had previously been treated
with basal insulin and oral agents, on the right, you'll see that for insulin-nave patients, biphasic insulin aspart did almost as well —
certainly not significantly worse — than the MDIs. It's in the other group, those previously treated with a basal insulin, that you see
significantly better results from MDIs rather than the twice-daily premix insulin. So, for someone like Mildred, who is an insulin-nave
patient, this slide suggests that you could do almost as well — certainly not statistically significantly worse — with a twice-daily
biphasic insulin analog as opposed to using MDI.

Patient Challenges
More News You Can Use: Challenges for This Patient

Let's think about 1 or 2 other aspects of Mildred's treatment

Audience Response Question

What do you think is the biggest treatment challenge for Mildred?

1. The multiple comorbidities that she has, a bit of heart failure, a bit of chronic kidney disease
2. Polypharmacy
3. The risk of hypoglycemia
4. Having to manage her own insulin injections
Audience Response Question

That's very interesting: almost an even split across the 4 options.

Managing Polypharmacy in the Older Adult With Diabetes

Managing polypharmacy is difficult. You have to somehow know what the patient is taking. There has to be an up-to-date list kept, it
has to be updated frequently, and as Dr. Meneghini said, it has to include over-the-counter medicines and herbal remedies.
Managing Hypoglycemia in the Older Adult With Diabetes

We can perhaps minimize the risk of hypoglycemia with a schedule of blood glucose monitoring, but of course that will depend upon
the patient's functional and cognitive abilities, on goals of care, on target A1C, and on the potential for modifying therapy. There
really is little point in repeatedly self-monitoring blood glucose if no changes are made to therapy. But monitoring is useful in
minimizing the risk of hypoglycemia.

Strategies for Improving Adherence With Insulin Therapy

How can we improve the adherence to insulin therapy? You can try and make sure that the patient actually understands the
message that you're trying to get across. You can constantly clarify the potential treatment benefits. Do they understand why this is
being suggested and recommended and why adherence to a regimen is important?

Treatment Outcomes
Audience Response Question

Let's go back and ask the initial question again: Which of the following treatment regimens would you select for Mildred?

1. Continue sulfonylurea therapy tid, and add a single daily injection of a basal insulin analog
2. Reduce sulfonylurea therapy to bid, and add a single daily injection of a biphasic insulin analog with dinner
3. Discontinue sulfonylurea therapy, and add 2 daily injections of a biphasic insulin analog
4. Discontinue sulfonylurea therapy, and initiate full basal-bolus therapy with multiple daily injections.

Audience Response Question

We can compare this with how you voted before. Now 63% of you are happy with the choice of a biphasic insulin analog,
discontinuing sulfonylurea therapy and using the insulin twice daily. I'm delighted to see that of those of you who only wanted to use
a basal insulin analog added to sulfonylurea therapy, your numbers have decreased.
Outcomes: Addition of Basal Insulin With SU

Another outcome that you might have chosen is the addition of basal insulin to a sulfonylurea. It's an easy regimen, but given that it's
almost certain that in whatever country you're from insulin is started in oral agent failures too late — at hemoglobin A1C levels well
above 8.5% — you are already dealing with patients with significant β-cell failure, making it less likely that you will be able to control
postprandial glucose.

Outcomes: Addition of 1 Injection of Biphasic With SU

You might have opted for 1 injection of a biphasic insulin analog with a sulfonylurea, also an easy regimen. Of course, it may require
the addition of a second injection and the chances of improving hemoglobin A1C to the same extent are probably less.
Outcomes: Basal/Bolus Insulin

You could have gone for a basal-bolus regimen. It is more physiologic — that's certainly in our minds — but of course it is more
difficult to comply with and probably poses an increased risk of hypoglycemia because you can get a bigger improvement in A1C.

Video Case Outcome

Mildred returns for a 3-month follow-up visit after initially being prescribed 6 units of premixed insulin analog bid with breakfast and
dinner. She has also met with a diabetes educator to learn how to self-inject with an insulin pen and how to monitor her blood
glucose levels. She was instructed on identifying and treating hypoglycemia, as well as how to self-adjust her insulin. Her daughter
attended the education session with her so she could help her mother if needed. Mildred has experienced 1 mild hypoglycemic event
that she successfully identified and treated. Since initiating insulin therapy, her dose has been titrated up to 12 units bid. She reports
that she has been feeling less fatigued since initiation of insulin therapy.

DOCTOR: Mildred, you look great. How are you feeling?

MILDRED: Well, I haven't been feeling quite as tired.

MILDRED: Well, it was hard at first. But my daughter has been very helpful. She went with me to see the diabetes educator and we
learned together. That way, if I ever forget what to do, she can help me.

DOCTOR: Have you experienced any problems with insulin?

MILDRED: Well, I did get a low blood sugar once, but I found it and was able to drink some juice right away, and just to be sure, I
make sure I carry candy in my purse with me when I go out with my daughter.

DOCTOR: I think we'll continue with this treatment plan since it seems to be working for you.

Mildred

To summarize, Mildred's A1C improved to 7.3%, her FPG to 107 mg/dL, and her self-monitored PPG, which had been 260 mg/dL,
came down to 170.

Conclusion
Conclusion: Diabetes Care in the Elderly

There's no doubt that there's an increasing prevalence of diabetes with age. The risk is increasing. There are numerous challenges,
particularly in the area of comorbidity, polypharmacy, and decreased likelihood of treatment advancement. Compared with basal
insulin, biphasic insulin analogs provide improved glycemic control, but there may be a slightly increased risk of hypoglycemia
because of that improvement in control. They can be used once, twice, or 3 times daily to help patients get to target. It's clearly
important to monitor medications to increase the likelihood of adherence and reduce the risk of drug interactions, and of course, as
always, it's important that older people be properly educated on identification and treatment of hypoglycemia. Thank you very much.

DR. DAVIDSON: Thank you. The next speaker is going to talk to us about younger people — diabetes care in adolescents. In the
United States we diagnose a lot of people with type 2 diabetes in that particular age group. In my state of Texas, since 2000 we have
diagnosed more children and adolescents with type 2 than with type 1 diabetes. We have Dr. Francine Kaufman, Director of the
Comprehensive Childhood Diabetes Center and Head of the Center for Endocrinology, Diabetes and Metabolism at the Childrens
Hospital Los Angeles. Francine has also been the President of the ADA.