R.B. is a 67-year-old woman with obesity, hypertension, and coronary artery disease (CAD). Eighteen months ago, she suffered an inferior wall myocardial infarction (MI). Cardiac catheterization revealed an occluded right coronary artery and a 40% stenosis in the proximal left anterior descending artery.
The patient was placed on β-blocker and aspirin therapy and was provided education regarding lifestyle modification. A lipid panel revealed mild hypertriglyceridemia and a slightly depressed HDL cholesterol level. Blood glucose was not measured. The patient initially did well, denying chest pain, shortness of breath, or any symptoms related to her cardiac condition.
Over the past month, R.B. complained of increasing fatigue and episodes of polyuria and polydipsia. A fasting blood glucose level was 168 mg/dl. Physical examination revealed a mildly obese woman with blood pressure of 142/86 mmHg and a pulse of 78. A dilated eye exam revealed mild nonproliferative diabetic retinopathy. Only trace pedal edema bilaterally was found. Additional laboratory examination revealed a hemoglobin A1c (A1C) concentration of 9.4%, blood urea nitrogen 11 mg/dl, creatinine 0.9 mg/dl, and urine microalbumin 1,993 μg/dl on a spot urine sample.
What is the relationship between diabetes and complications in the elderly?
What are the risks of intensive therapy for elderly patients?
What approach might be used for glycemic management?
Diabetes affects nearly 20% of those over 65 years of age in the United States. The Diabetes Control and Complications Trial (DCCT) demonstrated that tight glucose control in patients 13–39 years of age with type 1 diabetes was associated with a marked decrease in microvascular complications. The United Kingdom Prospective Diabetes Study (UKPDS) confirmed the relationship between glycemic control and complications in type 2 diabetes. It is now generally agreed that all patients with diabetes should have as tight glycemic control as possible.
Although specific trials with elderly patients who have type 2 diabetes are ongoing, there is indirect evidence supporting the concept that tight glycemic control may help to decrease or prevent microvascular and macrovascular disease in this population. Tight glycemic control in older diabetic patients after MI has been associated with reduced long-term mortality. Other studies have found that elderly patients with elevated fasting blood glucose levels had a 50% higher cardiovascular and all-cause mortality.
The chief concern about tight control in elderly patients with diabetes is the risk for hypoglycemia. The elderly are, in general, less aware of the signs of hypoglycemia and are particularly at risk for this complication. Intensive glucose control in all patients is a trade-off between benefits and risks. Improved glycemic control may reduce the risk of micro- and macrovascular disease, yet the tighter the control, the greater the risk of treatment-induced hypoglycemia.
Until recently, the preference for loose glycemic control for elderly patients has been supported by the notion that elderly patients are more susceptible to oral agent–induced hypoglycemia and less sensitive to the warning signs of hypoglycemia. However, findings from the UKPDS showed that severe hypoglycemia among patients with type 2 diabetes is a rare event. Now, with the recent increased use of newer agents that are less associated with hypoglycemia, it is timely to consider tighter glycemic control for many elderly diabetic patients.
It is important to take into account co-morbid factors when deciding whether an elderly patient is a candidate for tight glycemic control. Certainly, a patient with significant end-organ disease, malignancy, or dementia may not be a good candidate for tight glycemic control. However, in healthy elderly diabetic patients without significant co-morbid disease, one needs to look at the life expectancy and quality of life of each individual. The life expectancy of the average healthy 65-year-old woman is 19 years, and therefore, attention to glucose control with resultant decrease in vascular damage could significantly affect the quality and quantity of the final years of life.
R.B. is a typical patient entering the last decade or two of her life. She has been otherwise healthy yet has significant risk factors for cardiovascular disease. She clearly manifests signs and symptoms of the insulin resistance syndrome, and her only major co-morbid condition is CAD, which is now being medically managed. Given what we now know about a relationship between glycemic control and mortality from macrovascular disease, it is imperative that R.B. be able to achieve as tight glycemic control as possible. Given the existence of a partially obstructed left anterior descending artery, it will be very important to aggressively treat cardiovascular risk factors and to maintain euglycemia to prevent further progression of this coronary lesion.
In addition, R.B. is manifesting early signs of microvascular disease from diabetes. In all likelihood, her diagnosis of diabetes lagged the clinical development of hyperglycemia. She has had enough time to manifest microvascular changes in her retina, as well as in her glomeruli. By starting R.B. on an aggressive regimen to achieve near-normal glycemic control, we may be able to limit further progression of her microvascular disease. R.B.’s care will need to take into account her current medical condition, drug regimen, and ability to detect hypoglycemic reactions.
R.B.’s treatment plan will include aggressive hypertension control, lipid management, use of angiotensin-converting enzyme inhibitors or angiotensin receptor therapy for renal disease, and a stepwise management plan to achieve euglycemia. Goals for hypertension control will be established to minimize cardiovascular disease while avoiding hypotension. In general, the target will be to keep blood pressure below 130/80 mmHg. In addition, the target for LDL cholesterol will be <100 mg/dl. It is very important that we establish a target blood glucose as well as a target A1C concentration for her.
R.B. will need to be aware of the complications and risks associated with tight control. It will also be important to explain the perceived benefits of tight glycemic control on slowing the progression of her CAD and microvascular disease. She should be referred to a certified diabetes educator to learn more about diabetes and to outline a self-management plan. A nutritional assessment needs to be performed, and a food plan needs to be initiated.
Blood glucose awareness training may be of special utility for R.B. She will continue to take a β-blocker because she is status-post an acute MI, and this may further impair her ability to detect hypoglycemia.
Additionally, R.B. should be referred to social services or counseling for financial case management, if necessary. Many Medicare risk plans may pay for medication and monitoring supplies when Medicare itself will not.
If R.B. does not achieve her target glucose levels and A1C concentration, she should be started on an oral hypoglycemic agent and followed closely to see if she is achieving her target glycemic control. The use of metformin (Glucophage) or a thiazolidinedione (Actos or Avandia) may be the best first choice in this elderly patient with obesity and insulin resistance. Neither produces hypoglycemia in the absence of insulin or a sulfonylurea agent.
If glycemic targets are not achieved within a short time frame after starting an oral agent, the patient should have her medications increased to the maximum dose and then should be considered as a candidate for combination therapy with other oral hypoglycemic agents. Finally, there should be no hesitation to initiate R.B. on a regimen that includes insulin. Although there is a relationship between endogenous insulin levels and atherosclerosis, it is clear that hyperglycemia is far worse than the use of exogenous insulin for patients who will no doubt benefit from tighter glycemic control.
Our current understanding of the relationship between glycemic control and microvascular disease suggests that tight glycemic control should be considered for select elderly patients with diabetes. With proper education, medication choices, and consideration of co-morbid diseases, elderly patients with diabetes can improve their quality and quantity of life with improved glycemic control.
The elderly comprise an increasingly larger proportion of diagnosed cases of diabetes in the United States.
All complications of diabetes can occur in elderly patients.
Reduction in risk for microvascular and macrovascular disease should be the goal for all patients with diabetes. Elderly diabetic patients should be considered candidates for intensive blood glucose control.
The risk of hypoglycemia in type 2 diabetes, while rare, may be higher among the oldest patients and those who are cognitively impaired.
Certain patients with significant co-morbid disease may not be appropriate candidates for tight control.
Careful selection of elderly patients for aggressive glycemic control will result in lower rates of diabetic complications and hypoglycemia.
Evan M. Benjamin, MD, FACP, is director of the Division of Healthcare Quality at Baystate Medical Center and an assistant professor of medicine at Tufts University School of Medicine in Springfield, Mass.
Note of disclosure: Dr. Benjamin has received honoraria for speaking engagements from GlaxoSmithKline and research support from Eli Lilly and Co. Both companies market thiazolidinediones for the treatment of diabetes.