Increased Risk of Type 2 Diabetes in Alzheimer Disease

Juliette Janson; Thomas Laedtke; Joseph E. Parisi; Peter O'Brien; Ronald C. Petersen; Peter C. Butler

Disclosures

Diabetes. 2004;53(2) 

In This Article

Results

Protocol 1. There was no difference in age or sex distribution between the Alzheimer disease and non-Alzheimer disease control group ( Table 1 ). BMI was slightly but not significantly higher in control subjects versus Alzheimer disease. The prevalence of both type 2 diabetes (34.6 vs. 18.1%; P < 0.05) and IFG (46.2 vs. 23.8%; P < 0.01) was greater in the Alzheimer disease versus the non-Alzheimer disease control group (Fig. 1); 81% of the Alzheimer disease cases therefore had either type 2 diabetes or IFG.

Protocol 1: the prevalence of diabetes and IFG in the Olmsted County community-based cohort of cases of Alzheimer disease (AD) and control subjects (non-Alzheimer disease [non-AD]; top). Protocol 2: the slope of FPG concentration versus age in the same cohort (bottom). TTDM, type 2 diabetes.

Protocol 2. When the trend of FPG with aging was examined, there was a gradual increase with aging in both groups (P < 0.01 vs. no change). However, the Alzheimer disease group had a greater increase per year compared with non-Alzheimer disease control subjects (0.83 vs. 0.57 mg · dl-1 · y-1; P < 0.01; Fig. 1). This greater rate of increase of blood glucose was preserved in Alzheimer disease when cases with diabetes were excluded from the analysis.

Protocol 3: Islet Amyloid in Alzheimer Disease. Both the frequency and the extent of islet amyloid were higher in the Alzheimer disease group versus the non-Alzheimer disease group (both P < 0.05; Fig. 2) despite a trend toward a lower BMI in Alzheimer disease (24.3 ± 3.4 vs. 27.1 ± 6.7 kg/m2 Alzheimer disease vs. non-Alzheimer disease; P = 0.06). As expected, the frequency and the extent of islet amyloid was greater in type 2 diabetes (group 3) versus non-type 2 diabetes (group 4; P < 0.001; Fig. 2).

Protocol 3: frequency of islet amyloid (top) and extent of islet amyloid (bottom) in patients with Alzheimer disease (AD) and control subjects (non-Alzheimer disease [non-AD]) and in patients with type 2 diabetes (TTDM) and their control group (non-TTDM). Individual values (•) and medians (line).

Inclusion of cases in this autopsy protocol was blinded with respect to the presence or absence of diabetes but with the requirement that FPG be documented. Subsequent analysis of the FPG concentrations revealed that the prevalence of type 2 diabetes (FPG >126 mg/dl) in the Alzheimer disease group was 32% and in non-Alzheimer disease cases was 14% (P = 0.15). The mean FPG in Alzheimer disease was not higher than in control subjects (126 ± 8 vs. 110 ± 6 mg/dl; P = 0.09).

Protocol 4: Brain Amyloid in Type 2 Diabetes. The density of diffuse or neuritic plaques or NFT was not different between patients with type 2 diabetes versus nondiabetic control subjects (P = 0.07, P = 0.3, and P = 0.4, respectively; Table 3 ). As expected, the density of neuritic plaques, diffuse plaques, and NFT was greater (P < 0.05) in Alzheimer disease cases (group 1) versus non-Alzheimer disease (group 2).

In 22 of 28 type 2 diabetes cases, the year of diagnosis of diabetes was documented. Diffuse plaques were detected in 12 and neuritic plaques in 7 of these 22 cases of type 2 diabetes with a documented age of onset of diabetes. There was a positive relationship between duration of known diabetes and the extent of diffuse plaques (r s = 0.8, P < 0.001) or neuritic plaques (r s = 0.9, P < 0.01) in these cases (Fig. 3). In contrast, in neither type 2 diabetes nor non-type 2 diabetes was there a correlation with the density of either of these plaques and the age at death.

Protocol 4: relationship between the density of diffuse plaques (rs = 0.8, P < 0.001; top) or neuritic plaques (rs = 0.9, P < 0.01; bottom) versus the duration of diabetes in patients with type 2 diabetes. Cases were included only when the duration of diabetes was documented and the respective plaque type was detected (y did not equal zero).

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