Objective: To determine whether cognitive function improves with improved glycemic control in older subjects with non-insulin-dependent diabetes (NIDDM). We hypothesized that with improved glycemic control: 1) learning and memory, 2) attention, and 3) complex perceptual-motor function would improve, but that 4) simple perceptual-motor function would not.
Design: Non-randomized control trial.
Setting: Aging Study Unit, Department of Veterans Affairs Medical Center.
Subjects: Thirty subjects with NIDDM; 17 on oral hypoglycemic agents; 13 untreated at study entry. Thirteen normal controls.
Intervention: Subjects on oral hypoglycemic agents were taken off medications. After 1 month, they and previously untreated subjects began treatment with glipizide. Dose was titrated up weekly until fasting plasma glucose was less than 7.8 mmol/L or maximal dose (40 mg/day). Controls received no medication.
Measurements: Fasting plasma glucose (FPG), glycated hemoglobin, and measures of cognitive function in four general categories: 1) learning and memory, 2) ability to sustain attention, 3) complex perceptual-motor function, and 4) simple perceptual-motor function. All were evaluated in subjects with NIDDM at baseline (T1), after 1-month washout (T2), and after 2 (T3) and 4 months (T4) of optimal glycemic control or maximal dose. Controls were evaluated at the same intervals.
Results: FPG and glycated hemoglobin rose in previously treated subjects from T1 to T2 (9.4 +/- SEM 0.4 to 14.7 +/- 0.7 mmol/L and 10.9 +/- 0.7% to 12.2 +/- 0.6%, respectively) but were unchanged in previously untreated subjects (11.3 +/- 0.6 to 11.8 +/- 0.9 mmol/L and 10.9 +/- 0.7% to 11.7 +/- 0.7%). With glipizide treatment, there was a decrease in FPG level at T3 (9.4 +/- 0.5 mmol/L in previously treated, 6.9 +/- 0.4 mmol/L in previously untreated), which persisted at T4. Glycated hemoglobin fell similarly. FPG and glycated hemoglobin were unchanged in controls. As hypothesized, learning and memory improved over time with treatment in both groups of subjects but was unchanged in controls (P < 0.05). Detailed analysis indicated that the improvement occurred primarily in the learning of verbal material. Contrary to hypothesis, attention and complex perceptual-motor function did not show improvement. As expected, simple perceptual-motor function did not show any improvement with treatment.
Conclusions: The results are consistent with previous findings that poor glycemic control in older subjects with NIDDM is associated with decreased cognitive functioning, and suggest that verbal learning and memory may improve with improved glycemic control.