Alterations in Glucose Metabolism in Patients with Alzheimer's Disease

OBJECTIVE: To determine the alterations in glucose metabolism that occur in patients with Alzheimer's Disease (AD). DESIGN: Cross-sectional comparison of AD and healthy controls. SETTING: A University teaching hospital. PATIENTS: Healthy controls (n = 14, BMI: 24.9 +/- 0.5 kg/M2, age 73 +/- 1 years) and patients with AD (n = 12, BMI: 23.9 +/- 1.0 kg/M2, age 72 +/- 1 years). All controls and patients with AD had a normal history and physical examination, a negative family history of diabetes, and took no medications. MEASUREMENTS: All patients and controls underwent an assessment of their dietary intake and physical activity, a 3-hour oral glucose tolerance test (OGTT), and a 2-hour hyperglycemic glucose clamp study. RESULTS: Total caloric intake (AD: 27.1 +/- 1.3 kcal/kg/day; CONTROL: 23.6 +/- 1.6 kcal/kg/day; P = ns) and intake of complex carbohydrates (AD: 5.9 +/- 0.4 kcal/kg/day; CONTROL: 6.5 +/- 0.3 kcal/kg/day; P = ns) were not different between groups. Leisure time physical activity was greater in controls (AD: 2970 +/- 411 kcal/week; CONTROL: 5229 +/- 864 kcal/week; P < 0.05). Patients with AD had higher fasting glucose (AD: 5.9 +/- 0.2 mmol/L; CONTROL: 5.1 +/- 0.1 mmol/L; P < 0.01) and insulin (AD: 144 +/- 20 pmol/L; CONTROL: 100 +/- 6 pmol/L; P < 0.05) values. In response to the OGTT, the area under the curve for glucose and insulin was similar in both groups. During the hyperglycemic clamp, steady-state glucose values were higher in the Alzheimer's patients (AD: 11.5 +/- 0.2 mmol/L; CONTROL: 10.9 +/- 0.1 mmol/L, P < 0.01). First- and second-phase insulin responses were similar in each group. The insulin sensitivity index (units: mL/kg.min per pmol/L x 100), a measure of tissue sensitivity to insulin, was reduced in the patients with AD (AD: 0.59 +/- 0.06; CONTROL: 0.79 +/- 0.07; P < 0.05). CONCLUSIONS: We conclude that early AD is characterized by alterations in peripheral glucose metabolism, which may relate, in part, to alterations in physical activity.