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Erschienen in: Diabetologia 4/2015

01.04.2015 | Article

Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes

verfasst von: Elizabeth Guerrero-Berroa, Ramit Ravona-Springer, Anthony Heymann, James Schmeidler, Andrew Levy, Derek Leroith, Michal S. Beeri

Erschienen in: Diabetologia | Ausgabe 4/2015

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Abstract

Aims/hypothesis

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/interpretation

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.
Literatur
1.
Zurück zum Zitat Ahtiluoto S (2010) Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology 75:1195–1202CrossRefPubMed Ahtiluoto S (2010) Diabetes, Alzheimer disease, and vascular dementia: a population-based neuropathologic study. Neurology 75:1195–1202CrossRefPubMed
2.
Zurück zum Zitat Peila R (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes (New York, NY) 51:1256–1262 Peila R (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study. Diabetes (New York, NY) 51:1256–1262
3.
Zurück zum Zitat Schnaider Beeri M, Goldbourt U, Silverman JM et al (2004) Diabetes mellitus in midlife and the risk of dementia three decades later. Neurology 63:1902–1907CrossRefPubMed Schnaider Beeri M, Goldbourt U, Silverman JM et al (2004) Diabetes mellitus in midlife and the risk of dementia three decades later. Neurology 63:1902–1907CrossRefPubMed
4.
Zurück zum Zitat Ravona-Springer R, Schnaider-Beeri M (2011) The association of diabetes and dementia and possible implications for nondiabetic populations. Expert Rev Neurother 11:1609–1617CrossRefPubMedCentralPubMed Ravona-Springer R, Schnaider-Beeri M (2011) The association of diabetes and dementia and possible implications for nondiabetic populations. Expert Rev Neurother 11:1609–1617CrossRefPubMedCentralPubMed
5.
Zurück zum Zitat Yaffe K (2012) Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Arch Neurol (Chicago) 69:1170–1175CrossRef Yaffe K (2012) Diabetes, glucose control, and 9-year cognitive decline among older adults without dementia. Arch Neurol (Chicago) 69:1170–1175CrossRef
7.
Zurück zum Zitat Rathmann W (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:2568–2569, author reply 2569CrossRefPubMed Rathmann W (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:2568–2569, author reply 2569CrossRefPubMed
8.
Zurück zum Zitat Wild S (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053CrossRefPubMed Wild S (2004) Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care 27:1047–1053CrossRefPubMed
9.
Zurück zum Zitat Gurland BJ, Wilder DE, Lantigua R et al (1999) Rates of dementia in three ethnoracial groups. Int J Geriatr Psychiatr 14:481–493CrossRef Gurland BJ, Wilder DE, Lantigua R et al (1999) Rates of dementia in three ethnoracial groups. Int J Geriatr Psychiatr 14:481–493CrossRef
10.
Zurück zum Zitat Tang MX, Cross P, Andrews H et al (2001) Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan. Neurology 56:49–56CrossRefPubMed Tang MX, Cross P, Andrews H et al (2001) Incidence of AD in African-Americans, Caribbean Hispanics, and Caucasians in northern Manhattan. Neurology 56:49–56CrossRefPubMed
11.
Zurück zum Zitat Tseng CF (2004) Antioxidant role of human haptoglobin. Proteomics (Weinheim) 4:2221–2228CrossRef Tseng CF (2004) Antioxidant role of human haptoglobin. Proteomics (Weinheim) 4:2221–2228CrossRef
12.
Zurück zum Zitat Cocciolo A, Di Domenico F, Coccia R et al (2012) Decreased expression and increased oxidation of plasma haptoglobin in Alzheimer disease: insights from redox proteomics. Free Radic Biol Med 53:1868–1876CrossRefPubMed Cocciolo A, Di Domenico F, Coccia R et al (2012) Decreased expression and increased oxidation of plasma haptoglobin in Alzheimer disease: insights from redox proteomics. Free Radic Biol Med 53:1868–1876CrossRefPubMed
13.
Zurück zum Zitat Abraham J-D (2011) Combined measurement of PEDF, haptoglobin and tau in cerebrospinal fluid improves the diagnostic discrimination between Alzheimer's disease and other dementias. Biomarkers 16:161–171CrossRefPubMed Abraham J-D (2011) Combined measurement of PEDF, haptoglobin and tau in cerebrospinal fluid improves the diagnostic discrimination between Alzheimer's disease and other dementias. Biomarkers 16:161–171CrossRefPubMed
14.
Zurück zum Zitat Langlois MR, Delanghe JR (1996) Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 42:1589–1600PubMed Langlois MR, Delanghe JR (1996) Biological and clinical significance of haptoglobin polymorphism in humans. Clin Chem 42:1589–1600PubMed
15.
Zurück zum Zitat Hochberg I, Roguin A, Nikolsky E, Chanderashekhar PV, Cohen S, Levy AP (2002) Haptoglobin phenotype and coronary artery collaterals in diabetic patients. Atherosclerosis 161:441–446CrossRefPubMed Hochberg I, Roguin A, Nikolsky E, Chanderashekhar PV, Cohen S, Levy AP (2002) Haptoglobin phenotype and coronary artery collaterals in diabetic patients. Atherosclerosis 161:441–446CrossRefPubMed
16.
Zurück zum Zitat Eilaghi A (2013) Normal-appearing white matter permeability distinguishes poor cognitive performance in processing speed and working memory. Am J Neuroradiol AJNR 34:2119–2124CrossRef Eilaghi A (2013) Normal-appearing white matter permeability distinguishes poor cognitive performance in processing speed and working memory. Am J Neuroradiol AJNR 34:2119–2124CrossRef
17.
Zurück zum Zitat Ravona-Springer R (2013) Haptoglobin 1-1 genotype is associated with poorer cognitive functioning in the elderly with type 2 diabetes. Diabetes Care 36:3139–3145CrossRefPubMedCentralPubMed Ravona-Springer R (2013) Haptoglobin 1-1 genotype is associated with poorer cognitive functioning in the elderly with type 2 diabetes. Diabetes Care 36:3139–3145CrossRefPubMedCentralPubMed
18.
Zurück zum Zitat Oh HG (2011) Higher glycated hemoglobin level is associated with increased risk for ischemic stroke in non-diabetic Korean male adults. Diabetes Metab J 35:551–557CrossRefPubMedCentralPubMed Oh HG (2011) Higher glycated hemoglobin level is associated with increased risk for ischemic stroke in non-diabetic Korean male adults. Diabetes Metab J 35:551–557CrossRefPubMedCentralPubMed
19.
Zurück zum Zitat Ravona-Springer R, Moshier E, Schmeidler J et al (2012) Changes in glycemic control are associated with changes in cognition in non-diabetic elderly. J Alzheimers Dis 30:299–309PubMedCentralPubMed Ravona-Springer R, Moshier E, Schmeidler J et al (2012) Changes in glycemic control are associated with changes in cognition in non-diabetic elderly. J Alzheimers Dis 30:299–309PubMedCentralPubMed
20.
Zurück zum Zitat Yaffe K, Blackwell T, Whitmer RA, Krueger K, Barrett-Connor E (2006) Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. J Nutr Health Aging 10:293–295PubMed Yaffe K, Blackwell T, Whitmer RA, Krueger K, Barrett-Connor E (2006) Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. J Nutr Health Aging 10:293–295PubMed
21.
Zurück zum Zitat Meneilly GS (1993) The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes. J Gerontol (Kirkwood) 48:M117–M121CrossRef Meneilly GS (1993) The effect of improved glycemic control on cognitive functions in the elderly patient with diabetes. J Gerontol (Kirkwood) 48:M117–M121CrossRef
22.
Zurück zum Zitat Shorr RI (2006) Glycemia and cognitive function in older adults using glucose-lowering drugs. J Nutr Health Aging 10:297–301PubMed Shorr RI (2006) Glycemia and cognitive function in older adults using glucose-lowering drugs. J Nutr Health Aging 10:297–301PubMed
23.
Zurück zum Zitat Heymann AD, Chodick G, Halkin H et al (2006) The implementation of managed care for diabetes using medical informatics in a large Preferred Provider Organization. Diabetes Res Clin Pract 71:290–298CrossRefPubMed Heymann AD, Chodick G, Halkin H et al (2006) The implementation of managed care for diabetes using medical informatics in a large Preferred Provider Organization. Diabetes Res Clin Pract 71:290–298CrossRefPubMed
24.
Zurück zum Zitat Hughes CP (1982) A new clinical scale for the staging of dementia. Br J Psychiatry 140:566–572CrossRefPubMed Hughes CP (1982) A new clinical scale for the staging of dementia. Br J Psychiatry 140:566–572CrossRefPubMed
25.
Zurück zum Zitat Fillenbaum GG (1996) Estimating the validity of the clinical Dementia Rating Scale: the CERAD experience. Consortium to Establish a Registry for Alzheimer's Disease. Aging (Milan, Italy) 8:379–385 Fillenbaum GG (1996) Estimating the validity of the clinical Dementia Rating Scale: the CERAD experience. Consortium to Establish a Registry for Alzheimer's Disease. Aging (Milan, Italy) 8:379–385
26.
Zurück zum Zitat Folstein MF (1975) "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefPubMed Folstein MF (1975) "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12:189–198CrossRefPubMed
27.
Zurück zum Zitat Beeri MS, Schmeidler J, Sano M et al (2006) Age, gender, and education norms on the CERAD neuropsychological battery in the oldest old. Neurology 67:1006–1010CrossRefPubMedCentralPubMed Beeri MS, Schmeidler J, Sano M et al (2006) Age, gender, and education norms on the CERAD neuropsychological battery in the oldest old. Neurology 67:1006–1010CrossRefPubMedCentralPubMed
28.
Zurück zum Zitat Welsh KA, Butters N, Mohs RC et al (1994) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part V. A normative study of the neuropsychological battery. Neurology 44:609–614CrossRefPubMed Welsh KA, Butters N, Mohs RC et al (1994) The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part V. A normative study of the neuropsychological battery. Neurology 44:609–614CrossRefPubMed
29.
Zurück zum Zitat Wechsler D (1987) Wechsler Memory Scale—revised manual. Psychological Corporation, San Antonio Wechsler D (1987) Wechsler Memory Scale—revised manual. Psychological Corporation, San Antonio
30.
Zurück zum Zitat Godeau P, Frances-Michel C, Wechsler J et al (1981) [Immunofluorescence study of skin biopsies of healthy skin in bacterial endocarditis]. La Revue de medecine interne / fondee par la Societe nationale francaise de medecine interne 2:29–32 [article in French]CrossRefPubMed Godeau P, Frances-Michel C, Wechsler J et al (1981) [Immunofluorescence study of skin biopsies of healthy skin in bacterial endocarditis]. La Revue de medecine interne / fondee par la Societe nationale francaise de medecine interne 2:29–32 [article in French]CrossRefPubMed
31.
Zurück zum Zitat Spreen O, Benton AL (1977) Neurosensory center comprehensive examination for aphasia (NCCEA), 1977 revision : manual of instructions. Neuropsychology Laboratory, University of Victoria, [Victoria, B.C.] Spreen O, Benton AL (1977) Neurosensory center comprehensive examination for aphasia (NCCEA), 1977 revision : manual of instructions. Neuropsychology Laboratory, University of Victoria, [Victoria, B.C.]
32.
Zurück zum Zitat Newcombe F (1969) Missile wounds of the brain: a study of psychological deficits. Oxford University Press, Oxford Newcombe F (1969) Missile wounds of the brain: a study of psychological deficits. Oxford University Press, Oxford
33.
Zurück zum Zitat Reitan RM (1958) Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 8:271–276CrossRef Reitan RM (1958) Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills 8:271–276CrossRef
34.
Zurück zum Zitat West RK, Ravona-Springer R, Schmeidler J et al (2014) The association of duration of type 2 diabetes with cognitive performance is modulated by long-term glycemic control. Am J Geriatr Psychiatry 22:1055–1059 West RK, Ravona-Springer R, Schmeidler J et al (2014) The association of duration of type 2 diabetes with cognitive performance is modulated by long-term glycemic control. Am J Geriatr Psychiatry 22:1055–1059
35.
Zurück zum Zitat Sheikh JI, Yesavage JA (1986) Geriatric Depression Scale (GDS): recent evidence and development of a shorter version. Clin Gerontol 5:165–172CrossRef Sheikh JI, Yesavage JA (1986) Geriatric Depression Scale (GDS): recent evidence and development of a shorter version. Clin Gerontol 5:165–172CrossRef
36.
Zurück zum Zitat Wilson RS, Barnes LL, Mendes de Leon CF et al (2002) Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology 59:364–370CrossRefPubMed Wilson RS, Barnes LL, Mendes de Leon CF et al (2002) Depressive symptoms, cognitive decline, and risk of AD in older persons. Neurology 59:364–370CrossRefPubMed
37.
Zurück zum Zitat Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Stat 6:65–70 Holm S (1979) A simple sequentially rejective multiple test procedure. Scand J Stat 6:65–70
38.
Zurück zum Zitat Luk AO (2013) Risk association of HbA1c variability with chronic kidney disease and cardiovascular disease in type 2 diabetes: prospective analysis of the Hong Kong Diabetes Registry. Diabetes Metab Res Rev 29:384–390CrossRefPubMed Luk AO (2013) Risk association of HbA1c variability with chronic kidney disease and cardiovascular disease in type 2 diabetes: prospective analysis of the Hong Kong Diabetes Registry. Diabetes Metab Res Rev 29:384–390CrossRefPubMed
39.
Zurück zum Zitat Penno G, Solini A, Bonora E et al (2013) HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the renal insufficiency and cardiovascular events (RIACE) Italian Multicenter Study. Diabetes Care 36:2301–2310CrossRefPubMedCentralPubMed Penno G, Solini A, Bonora E et al (2013) HbA1c variability as an independent correlate of nephropathy, but not retinopathy, in patients with type 2 diabetes: the renal insufficiency and cardiovascular events (RIACE) Italian Multicenter Study. Diabetes Care 36:2301–2310CrossRefPubMedCentralPubMed
40.
Zurück zum Zitat Ravona-Springer R (2014) Trajectories in glycemic control over time are associated with cognitive performance in elderly subjects with type 2 diabetes. PLoS One 9:e97384CrossRefPubMedCentralPubMed Ravona-Springer R (2014) Trajectories in glycemic control over time are associated with cognitive performance in elderly subjects with type 2 diabetes. PLoS One 9:e97384CrossRefPubMedCentralPubMed
41.
Zurück zum Zitat Nelson PT, Smith CD, Abner EA et al (2009) Human cerebral neuropathology of type 2 diabetes mellitus. Biochim Biophys Acta (BBA) – Mol Basis Dis 1792:454–469 Nelson PT, Smith CD, Abner EA et al (2009) Human cerebral neuropathology of type 2 diabetes mellitus. Biochim Biophys Acta (BBA) – Mol Basis Dis 1792:454–469
42.
Zurück zum Zitat van Harten B (2006) Brain imaging in patients with diabetes: a systematic review. Diabetes Care 29:2539–2548CrossRefPubMed van Harten B (2006) Brain imaging in patients with diabetes: a systematic review. Diabetes Care 29:2539–2548CrossRefPubMed
43.
Zurück zum Zitat Viana-Baptista M (2008) Cognitive function correlates with frontal white matter apparent diffusion coefficients in patients with leukoaraiosis. J Neurol 255:360–366CrossRefPubMed Viana-Baptista M (2008) Cognitive function correlates with frontal white matter apparent diffusion coefficients in patients with leukoaraiosis. J Neurol 255:360–366CrossRefPubMed
44.
Zurück zum Zitat O'Brien JT (2002) Cognitive associations of subcortical white matter lesions in older people. Ann N Y Acad Sci 977:436–444CrossRefPubMed O'Brien JT (2002) Cognitive associations of subcortical white matter lesions in older people. Ann N Y Acad Sci 977:436–444CrossRefPubMed
45.
Zurück zum Zitat Rouhl RPW, van Oostenbrugge RJ, Damoiseaux JGMC et al (2009) Haptoglobin phenotype may alter endothelial progenitor cell cluster formation in cerebral small vessel disease. Curr Neurovasc Res 6:32–41CrossRefPubMed Rouhl RPW, van Oostenbrugge RJ, Damoiseaux JGMC et al (2009) Haptoglobin phenotype may alter endothelial progenitor cell cluster formation in cerebral small vessel disease. Curr Neurovasc Res 6:32–41CrossRefPubMed
46.
Zurück zum Zitat Rouhl RPW, Mertens AECS, van Oostenbrugge RJ et al (2012) Angiogenic T cells and putative endothelial progenitor cells in hypertension-related cerebral small vessel disease. Stroke 43:256–258CrossRefPubMed Rouhl RPW, Mertens AECS, van Oostenbrugge RJ et al (2012) Angiogenic T cells and putative endothelial progenitor cells in hypertension-related cerebral small vessel disease. Stroke 43:256–258CrossRefPubMed
47.
48.
Zurück zum Zitat Mattila KM (1994) Altered blood–brain-barrier function in Alzheimer's disease? Acta Neurol Scand 89:192–198 Mattila KM (1994) Altered blood–brain-barrier function in Alzheimer's disease? Acta Neurol Scand 89:192–198
49.
Zurück zum Zitat Johnson G (1992) Cerebrospinal fluid protein variations in common to Alzheimer's disease and schizophrenia. Appl Theor Electrophor 3:47–53PubMed Johnson G (1992) Cerebrospinal fluid protein variations in common to Alzheimer's disease and schizophrenia. Appl Theor Electrophor 3:47–53PubMed
50.
Zurück zum Zitat Levy AP (2004) Haptoglobin: a major susceptibility gene for diabetic cardiovascular disease. Isr Med Assoc J 6:308–310PubMed Levy AP (2004) Haptoglobin: a major susceptibility gene for diabetic cardiovascular disease. Isr Med Assoc J 6:308–310PubMed
51.
Zurück zum Zitat Levy AP (2002) Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Cardiol 40:1984–1990CrossRefPubMed Levy AP (2002) Haptoglobin phenotype is an independent risk factor for cardiovascular disease in individuals with diabetes: The Strong Heart Study. J Am Coll Cardiol 40:1984–1990CrossRefPubMed
52.
Zurück zum Zitat Mascie-Taylor CG (1985) Associations between some polymorphic markers and variation in IQ and its components in Otmoor villagers. Behav Genet 15:371–383CrossRefPubMed Mascie-Taylor CG (1985) Associations between some polymorphic markers and variation in IQ and its components in Otmoor villagers. Behav Genet 15:371–383CrossRefPubMed
53.
Zurück zum Zitat Ritchie SJ (2013) Education is associated with higher later life IQ scores, but not with faster cognitive processing speed. Psychol Aging 28:515–521CrossRefPubMed Ritchie SJ (2013) Education is associated with higher later life IQ scores, but not with faster cognitive processing speed. Psychol Aging 28:515–521CrossRefPubMed
Metadaten
Titel
Haptoglobin genotype modulates the relationships of glycaemic control with cognitive function in elderly individuals with type 2 diabetes
verfasst von
Elizabeth Guerrero-Berroa
Ramit Ravona-Springer
Anthony Heymann
James Schmeidler
Andrew Levy
Derek Leroith
Michal S. Beeri
Publikationsdatum
01.04.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 4/2015
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-014-3487-2

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