title: Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes.
abstract: OBJECTIVE
  The purpose of this study was to investigate whether the association of glycaemic control with cognitive function is modulated by the haptoglobin 1-1 (Hp 1-1) genotype in cognitively normal elderly individuals with type 2 diabetes.
  
  
  METHODS
  In this cross-sectional study, we examined 793 participants who were genotyped for Hp (80 Hp 1-1 carriers and 713 Hp 1-1 non-carriers) enrolled in the Israel Diabetes and Cognitive Decline (IDCD) study. Glycaemic control was operationally defined by HbA1c level. The outcome measures were performance in four cognitive domains (episodic memory, attention/working memory, language/semantic categorisation, executive function) and overall cognition, a composite of the domains. Effect sizes were obtained from hierarchical linear regression analyses for each outcome measure, controlling for demographics, type 2 diabetes-related characteristics, cardiovascular risk factors, and their interactions with Hp genotype.
  
  
  RESULTS
  Interaction analyses showed significantly stronger associations of HbA1c with poorer cognitive function among Hp 1-1 carriers than non-carriers; attention/working memory (p < 0.001) and overall cognition (p = 0.003). For these two cognitive domains, associations were significant for Hp 1-1 carriers despite the small sample size (p < 0.00001 and p = 0.001, respectively), but not for non-carriers.
  
  
  CONCLUSIONS
  Our findings suggest that patients with type 2 diabetes and poor glycaemic control carrying the Hp 1-1 genotype may be at increased risk of cognitive impairment, particularly in the attention/working memory domain. The association of glycaemic control with this domain may indicate cerebrovascular mechanisms.
authors: Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA, elizabeth.guerrero-berroa@mssm.edu.
authors: Elizabeth
authors: E
authors: Guerrero-Berroa
authors: Ramit
authors: R
authors: Ravona-Springer
authors: Anthony
authors: A
authors: Heymann
authors: James
authors: J
authors: Schmeidler
authors: Andrew
authors: A
authors: Levy
authors: Derek
authors: D
authors: Leroith
authors: Michal S
authors: MS
authors: Beeri
mesh_terms: D000367:Age Factors; D000368:Aged; D001288:Attention; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003071:Cognition; D003072:Cognition Disorders / Q000175:diagnosis / Q000235:genetics* / Q000523:psychology; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D056344:Executive Function; D005260:Female; D020022:Genetic Predisposition to Disease; D006442:Glycated Hemoglobin / Q000032:analysis*; D006242:Haptoglobins / Q000235:genetics*; D006801:Humans; D007557:Israel; D016014:Linear Models; D008297:Male; D061212:Memory, Episodic; D010641:Phenotype; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D006442:Glycated Hemoglobin; D006242:Haptoglobins; C485359:HP protein, human; C517652:hemoglobin A1c protein, human
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