Prevalence

Diabetes mellitus is common, occurring in 18.7% of persons between 65 to 74.(1) It is even more common in African Americans and Native Americans. Nearly half the persons with Type 2 diabetes are over 60 years. Physicians are "sugar blind". Half the older persons with diabetes do not have the diagnosis made.

Older persons with diabetes mellitus have both insulin resistance and impaired insulin secretion. Age, visceral adiposity and lack of physical activity all play a role in its pathogenesis. Elevated amylin levels inhibit the return of glucose to normal levels following a meal in older persons.(2)

Clinical Features

Diabetes is associated with increased mortality in persons over 65 years of age.(3) Poor glycemic control in persons over 60 years of age is associated with progression of retinopathy(4) and increased coronary artery disease events and mortality.(5)

Reasons for Maintenance of Normoglycemia in Older Persons

1. Prevention of hyperosmolar, ketoacidotic or lactic acidotic hyperglycemia coma
2. Prevention of long-term diabetic complications
   1. Retinopathy
   2. Nephropathy
   3. Neuropathy
   4. Atherosclerotic disease (myocardial infarction and stroke)
3. Prevention of the effects of glucotoxicity
   1. Pain
   2. Incontinence
   3. Nocturia (excessive)
   4. Dehydration
   5. Infection
   6. Trace mineral deficiency (e.g., zinc, magnesium)
   7. Accelerated aging

Diabetes and Pain

Persons with diabetes complain of pain more often than non-diabetics (Figure 1). Glucose infusion lowers the pain threshold (Figure 2).(6) Older diabetics have a decreased pain threshold. This is due to glucose inhibiting the ability of beta-endorphin to bind to its receptors.

Figure 1. Comparison of Stimulus Detection, Pain Perception, and Pain Threshold in Diabetics and Controls.

Figure 2.

Diabetes and Memory

• Hyperglycemic diabetics perform poorly on cognitive tasks
• In diabetic mice, insulin restores memory function
• In humans, improved diabetic control improves cognitive performance
• Diabetics remember medication alterations less well than non-diabetics

Diabetes and Amputations

"In the 30th year of his reign, King Azo became affected with gangrene of the feet; he did not seek the guidance of the Lord, but resorted to physicians. He rested with his forefathers in the 41st year of his reign."

II Chronicles XVI:12-14

Two-thirds of all amputations occur in persons over 65 years of age. Two-thirds of these occur in diabetics. Careful preventive maintenance of feet is an essential component of good diabetic care. In addition, persons with diabetes mellitus have an increase in pressure ulcers.

Depression in older diabetics causes poor compliance, increased hospital admission and increased mortality.(7)

Age Related Factors Modulate the Management of Diabetes

• Altered vision
• Tremor/arthritis
• Anorexia
• ↓Thirst
• ↓Renal function
• ↓Exercise
• Multiple drugs
• Psychological
• Social

Management of Diabetes

Diabetes treatment in the elderly requires an interdisciplinary team approach. The UKPDS study showed that both treatment of hypertension and diabetes improved outcomes in middle-age and older diabetics.

Goals for Treatment of the Elderly

1. A fasting glucose < 140 mg/dl (7.7 mmol/L)
2. No glucose > 200 mg/dl (11 mmol/L)

Therapeutic Options

1. Diet
2. Exercise
3. Sulfonylureas
4. Meglitinides
5. Thiazolidinediones
6. Alpha glucosidase inhibitors
7. Insulin

Exercise

Exercise is a cornerstone of therapy. The exercise prescription should include endurance, balance, strengthening, posture and flexibility.

Dietary Therapy

There is little evidence to support the use of dietary therapy in older diabetics.(8) Special diets in the nursing home are associated with protein energy malnutrition.(9)

Hyperglycemia can result in zinc loss in the urine and zinc deficiency.(10) This is associated with poor healing of vascular and pressure ulcers.

Ingestion of high levels of vitamin C can interfere with the ability to measure glucose in the serum. Limit diabetics to one gram of vitamin C daily.

Oral Sulfonylureas

Chlorpropamide

• Long half-life
• Prolonged hypoglycemia
• Hyponatremia
• Never use in the elderly

Glipizide vs. Glyburide Effectiveness

Repaglinide and Nateglinide

These are new non sulfonylurea agents (meglitinides and Dphenylalanine derivaties(12) that produce insulin release. It needs to be given before meals. It has been well tolerated in older patients.

Biguanides

Metformin is a safe oral agent that reduces insulin resistance.

Metformin Metabolism

• Six hour half-life
• Slowed clearance in older persons
• Not protein bound
• Excreted in urine
• Plasma levels are higher in older persons

Metformin-Associated Lactic Acidosis is Reduced When:

• Decreased usage in very old
• Reduced dosage
• Not used
• Renal disease
• Cardiovascular
• Liver disease
• Chronic acidosis
• Hypoxia

Symptoms of Lactic Acidosis

• Malaise
• Muscle pains
• Hyperventilation
• Feeling cold
• Dizziness
• Excessive sleepiness
• Bradycardia
• Arrhythmias

Metformin Prescribing

• Not used if serum creatinine greater than 1.4 mg/dl
• If older person has lost weight or is 10% below average body weight, reduce acceptable creatinine level
• Don't prescribe if creatinine clearance < 60 ml/min
• Only prescribe over 80 years if creatinine clearance has been measured
• Never give to persons with cardiac failure, liver disease, chronic acidosis
• Diarrhea and anorexia occur in up to 30% (5% long term); monitor weight loss
• Monitor creatinine 4 monthly and liver functions 6 monthly
• Stop metformin if acute hypotension, overwhelming infection or iodinated contrast material.

Thiazolodinedione

Troglitazone is a thiazolidinedione coupled with vitamin E. It can be used as monotherapy in combination with other oral agents and in combination with glucose to decrease glucose swings. It was withdrawn from the market because of liver toxicity. Rosiglitazone and pioglitazone are now available. They have low potential for producing hepatotoxicity. They can be used as monotherapy or in combination with other drugs(13) Liver function should be measured every two months.

Alpha-1 Glucosidase Inhibitors

Acarbose delays the breakdown of carbohydrates. It has a high rate of gastrointestinal disturbances. Miglitol also delays breakdown of carbohydrates. It causes abdominal pain in some individuals. Both agents also increase glucagon-like peptide which is a peptide hormone that increases insulin secretion. Both need to be taken at the start of a meal.

Orlistat®

This agent inhibits metabolism by lipases. Besides reducing weight it improves glucose tolerance. It is not yet approved by the FDA.

Insulin

Insulin should not be avoided in older persons. It can be safely used in the elderly as demonstrated by the VA cooperative trial.(11) Lis-Pro insulin has a very rapid onset. Insulin glargine provides basal control of glycemia for about 24 hours. There appears to be little advantage of these new insulins over the older insulins in the elderly.(14),(15)

Conclusion

Diabetes control in older persons decreases complications and improves quality of life. An approach to the management of diabetes in older persons is: