Diabetes and elevated hemoglobin a1c levels are associated with brain hypometabolism but not amyloid accumulation

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Abstract

Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using 11C-Pittsburgh compound B ( 11C-PiB) and brain hypometabolism measured using 18F-FDG PET. Methods: We studied a sample of nondemented participants from the population-based Mayo Clinic Study of Aging. All subjects underwent MR imaging, amyloid PET, and 18F-FDG PET. Alzheimer disease (AD) signature and region-of-interest (ROI) measures for 11C-PiB retention ratio and 18F-FDG ratio were measured. Diabetes was assessed from the Rochester Epidemiology Project medical records linkage system. Results: Among 749 participants (median age, 79.0 y; 56.5% men, 81.0% cognitively normal; 20.6% diabetic individuals), 18F-FDG hypometabolism (18F-FDG ratio < 1.31) in the AD signature meta-ROI was more common in diabetic individuals (48.1%) than in nondiabetic individuals (28.9%; P < 0.001). The median 18F-FDG ratio was lower in diabetic individuals than in nondiabetic individuals in the AD signature meta-ROI (1.32 vs. 1.40, P , 0.001) and in the angular (1.40 vs. 1.48, P < 0.001) and posterior cingulate gyri ROIs (1.63 vs. 1.72, P < 0.001). The odds ratio (OR) for abnormal AD signature 18F-FDG hypometabolism was elevated (2.28; 95% confidence interval [CI], 1.56-3.33) in diabetic individuals versus nondiabetic individuals after adjustment for age, sex, and education and after additional adjustment for apolipoprotein e4 allele, glycemic level, and cognitive status (OR, 1.69; 95% CI, 1.10-2.60). However, the AD signature 11C-PiB retention ratio was similar in diabetic individuals versus nondiabetic individuals (OR, 1.03; 95% CI, 0.71-1.51; P = 0.87). In post hoc analyses in nondiabetic individuals, a 1% increase in hemoglobin A1c was associated with greater AD signature hypometabolism in cognitively normal subjects (OR, 1.93; 95% CI, 1.03-3.62; P = 0.04) and in the total cohort (OR 1.59; 95% CI, 0.92- 2.75; P = 0.10). Conclusion: Diabetes and poor glycemic control in nondiabetic individuals may enhance glucose hypometabolism in AD signature regions. These factors should be investigated in longitudinal studies for their role in detecting onset of symptoms in AD.

Original languageEnglish (US)
Pages (from-to)759-764
Number of pages6
JournalJournal of Nuclear Medicine
Volume55
Issue number5
DOIs
StatePublished - May 1 2014

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Amyloid
Fluorodeoxyglucose F18
Alzheimer Disease
Hemoglobins
Brain
Odds Ratio
Confidence Intervals
Medical Record Linkage
Apolipoprotein E4
Sex Education
Gyrus Cinguli
Type 2 Diabetes Mellitus
Longitudinal Studies
Epidemiology
Alleles
Insulin
Glucose
Population
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole

Keywords

  • Amyloid accumulation
  • Cerebral glucose metabolism
  • Diabetes
  • Hemoglobin A1c

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Cite this

@article{b51a7b2abc0940bf92ac28b04567df61,
title = "Diabetes and elevated hemoglobin a1c levels are associated with brain hypometabolism but not amyloid accumulation",
abstract = "Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using 11C-Pittsburgh compound B ( 11C-PiB) and brain hypometabolism measured using 18F-FDG PET. Methods: We studied a sample of nondemented participants from the population-based Mayo Clinic Study of Aging. All subjects underwent MR imaging, amyloid PET, and 18F-FDG PET. Alzheimer disease (AD) signature and region-of-interest (ROI) measures for 11C-PiB retention ratio and 18F-FDG ratio were measured. Diabetes was assessed from the Rochester Epidemiology Project medical records linkage system. Results: Among 749 participants (median age, 79.0 y; 56.5{\%} men, 81.0{\%} cognitively normal; 20.6{\%} diabetic individuals), 18F-FDG hypometabolism (18F-FDG ratio < 1.31) in the AD signature meta-ROI was more common in diabetic individuals (48.1{\%}) than in nondiabetic individuals (28.9{\%}; P < 0.001). The median 18F-FDG ratio was lower in diabetic individuals than in nondiabetic individuals in the AD signature meta-ROI (1.32 vs. 1.40, P , 0.001) and in the angular (1.40 vs. 1.48, P < 0.001) and posterior cingulate gyri ROIs (1.63 vs. 1.72, P < 0.001). The odds ratio (OR) for abnormal AD signature 18F-FDG hypometabolism was elevated (2.28; 95{\%} confidence interval [CI], 1.56-3.33) in diabetic individuals versus nondiabetic individuals after adjustment for age, sex, and education and after additional adjustment for apolipoprotein e4 allele, glycemic level, and cognitive status (OR, 1.69; 95{\%} CI, 1.10-2.60). However, the AD signature 11C-PiB retention ratio was similar in diabetic individuals versus nondiabetic individuals (OR, 1.03; 95{\%} CI, 0.71-1.51; P = 0.87). In post hoc analyses in nondiabetic individuals, a 1{\%} increase in hemoglobin A1c was associated with greater AD signature hypometabolism in cognitively normal subjects (OR, 1.93; 95{\%} CI, 1.03-3.62; P = 0.04) and in the total cohort (OR 1.59; 95{\%} CI, 0.92- 2.75; P = 0.10). Conclusion: Diabetes and poor glycemic control in nondiabetic individuals may enhance glucose hypometabolism in AD signature regions. These factors should be investigated in longitudinal studies for their role in detecting onset of symptoms in AD.",
keywords = "Amyloid accumulation, Cerebral glucose metabolism, Diabetes, Hemoglobin A1c",
author = "Roberts, {Rosebud O} and Knopman, {David S} and Cha, {Ruth H.} and Mielke, {Michelle M} and Pankratz, {V. Shane} and Boeve, {Bradley F} and Kantarci, {Kejal M} and Geda, {Yonas Endale} and Jack, {Clifford R Jr.} and Petersen, {Ronald Carl} and Val Lowe",
year = "2014",
month = "5",
day = "1",
doi = "10.2967/jnumed.113.132647",
language = "English (US)",
volume = "55",
pages = "759--764",
journal = "Journal of Nuclear Medicine",
issn = "0161-5505",
publisher = "Society of Nuclear Medicine Inc.",
number = "5",

}

TY - JOUR

T1 - Diabetes and elevated hemoglobin a1c levels are associated with brain hypometabolism but not amyloid accumulation

AU - Roberts, Rosebud O

AU - Knopman, David S

AU - Cha, Ruth H.

AU - Mielke, Michelle M

AU - Pankratz, V. Shane

AU - Boeve, Bradley F

AU - Kantarci, Kejal M

AU - Geda, Yonas Endale

AU - Jack, Clifford R Jr.

AU - Petersen, Ronald Carl

AU - Lowe, Val

PY - 2014/5/1

Y1 - 2014/5/1

N2 - Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using 11C-Pittsburgh compound B ( 11C-PiB) and brain hypometabolism measured using 18F-FDG PET. Methods: We studied a sample of nondemented participants from the population-based Mayo Clinic Study of Aging. All subjects underwent MR imaging, amyloid PET, and 18F-FDG PET. Alzheimer disease (AD) signature and region-of-interest (ROI) measures for 11C-PiB retention ratio and 18F-FDG ratio were measured. Diabetes was assessed from the Rochester Epidemiology Project medical records linkage system. Results: Among 749 participants (median age, 79.0 y; 56.5% men, 81.0% cognitively normal; 20.6% diabetic individuals), 18F-FDG hypometabolism (18F-FDG ratio < 1.31) in the AD signature meta-ROI was more common in diabetic individuals (48.1%) than in nondiabetic individuals (28.9%; P < 0.001). The median 18F-FDG ratio was lower in diabetic individuals than in nondiabetic individuals in the AD signature meta-ROI (1.32 vs. 1.40, P , 0.001) and in the angular (1.40 vs. 1.48, P < 0.001) and posterior cingulate gyri ROIs (1.63 vs. 1.72, P < 0.001). The odds ratio (OR) for abnormal AD signature 18F-FDG hypometabolism was elevated (2.28; 95% confidence interval [CI], 1.56-3.33) in diabetic individuals versus nondiabetic individuals after adjustment for age, sex, and education and after additional adjustment for apolipoprotein e4 allele, glycemic level, and cognitive status (OR, 1.69; 95% CI, 1.10-2.60). However, the AD signature 11C-PiB retention ratio was similar in diabetic individuals versus nondiabetic individuals (OR, 1.03; 95% CI, 0.71-1.51; P = 0.87). In post hoc analyses in nondiabetic individuals, a 1% increase in hemoglobin A1c was associated with greater AD signature hypometabolism in cognitively normal subjects (OR, 1.93; 95% CI, 1.03-3.62; P = 0.04) and in the total cohort (OR 1.59; 95% CI, 0.92- 2.75; P = 0.10). Conclusion: Diabetes and poor glycemic control in nondiabetic individuals may enhance glucose hypometabolism in AD signature regions. These factors should be investigated in longitudinal studies for their role in detecting onset of symptoms in AD.

AB - Dysfunctional insulin signaling may affect brain metabolism or amyloid deposition. We investigated the associations of type 2 diabetes with amyloid accumulation measured using 11C-Pittsburgh compound B ( 11C-PiB) and brain hypometabolism measured using 18F-FDG PET. Methods: We studied a sample of nondemented participants from the population-based Mayo Clinic Study of Aging. All subjects underwent MR imaging, amyloid PET, and 18F-FDG PET. Alzheimer disease (AD) signature and region-of-interest (ROI) measures for 11C-PiB retention ratio and 18F-FDG ratio were measured. Diabetes was assessed from the Rochester Epidemiology Project medical records linkage system. Results: Among 749 participants (median age, 79.0 y; 56.5% men, 81.0% cognitively normal; 20.6% diabetic individuals), 18F-FDG hypometabolism (18F-FDG ratio < 1.31) in the AD signature meta-ROI was more common in diabetic individuals (48.1%) than in nondiabetic individuals (28.9%; P < 0.001). The median 18F-FDG ratio was lower in diabetic individuals than in nondiabetic individuals in the AD signature meta-ROI (1.32 vs. 1.40, P , 0.001) and in the angular (1.40 vs. 1.48, P < 0.001) and posterior cingulate gyri ROIs (1.63 vs. 1.72, P < 0.001). The odds ratio (OR) for abnormal AD signature 18F-FDG hypometabolism was elevated (2.28; 95% confidence interval [CI], 1.56-3.33) in diabetic individuals versus nondiabetic individuals after adjustment for age, sex, and education and after additional adjustment for apolipoprotein e4 allele, glycemic level, and cognitive status (OR, 1.69; 95% CI, 1.10-2.60). However, the AD signature 11C-PiB retention ratio was similar in diabetic individuals versus nondiabetic individuals (OR, 1.03; 95% CI, 0.71-1.51; P = 0.87). In post hoc analyses in nondiabetic individuals, a 1% increase in hemoglobin A1c was associated with greater AD signature hypometabolism in cognitively normal subjects (OR, 1.93; 95% CI, 1.03-3.62; P = 0.04) and in the total cohort (OR 1.59; 95% CI, 0.92- 2.75; P = 0.10). Conclusion: Diabetes and poor glycemic control in nondiabetic individuals may enhance glucose hypometabolism in AD signature regions. These factors should be investigated in longitudinal studies for their role in detecting onset of symptoms in AD.

KW - Amyloid accumulation

KW - Cerebral glucose metabolism

KW - Diabetes

KW - Hemoglobin A1c

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JO - Journal of Nuclear Medicine

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