Haptoglobin 1-1 genotype modulates the association of glycemic control with hippocampal volume in elderly individuals with type 2 diabetes

Abigail Livny*, Ramit Ravona-Springer, Anthony Heymann, Rachel Priess, Tammar Kushnir, Galia Tsarfaty, Leeron Rabinov, Reut Moran, Niv Tik, Erin Moshier, Itzik Cooper, Lior Greenbaum, Jeremy Silverman, Andrew Levy, Mary Sano, Barbara B. Bendlin, Aron S. Buchman, Michal Schnaider-Beeri

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Recent evidence suggests that glycemic control is associated with cognitive function in older patients with type 2 diabetes who are carriers of the haptoglobin (Hp) 1-1 genotype compared with noncarriers. We assessed whether poor glycemic control in Hp 1-1 carriers is more strongly associated with smaller hippocampal volume than in noncarriers. Hippocampal volume was generated from highresolution structural T1 MRI obtained for 224 participants (28 Hp 1-1 carriers [12.5%] and 196 noncarriers [87.5%]) from the Israel Diabetes and Cognitive Decline (IDCD) study, who had a mean (SD) number of years in the Maccabi Healthcare Services (MHS) registry of 8.35 (2.63) and a mean (SD) HbA1c level of 6.66 (0.73)% [49 mmol/mol]. A stronger negative association between right hippocampal volume and HbA1c was found in patients with the Hp 1-1 genotype, with a 0.032-mL decrease in right hippocampal volume per 14% increase in HbA1c (P = 0.0007) versus a 0.009-mL decrease in Hp 1-1 noncarriers (P = 0.047), after adjusting for total intracranial volume, age, sex, follow-up years in the registry, and cardiovascular factor (interaction, P = 0.025). This indicates that 29.66% of the total variance in right hippocampal volume is explained by HbA1c levels among Hp 1-1 carriers and that 3.22% is explained by HbA1c levelsamongHp1-1 noncarriers. Our results suggest that the hippocampus of Hp 1-1 carriers may be more vulnerable to the insults of poor glycemic control.

Original languageEnglish
Pages (from-to)2927-2932
Number of pages6
Issue number11
StatePublished - 1 Nov 2017


FundersFunder number
LeRoy Schecter Foundation
National Institutes of HealthR21-AG-043878, R01-AG-034087
National Institute on AgingP50AG005138
American Federation for Aging Research
Bader Philanthropies


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