Skip to main content
Erschienen in: Diabetologia 9/2018

30.06.2018 | Article

Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study

verfasst von: Alexandra K. Lee, Andreea M. Rawlings, Clare J. Lee, Alden L. Gross, Elbert S. Huang, A. Richey Sharrett, Josef Coresh, Elizabeth Selvin

Erschienen in: Diabetologia | Ausgabe 9/2018

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

We aimed to evaluate the link between severe hypoglycaemia and domain-specific cognitive decline, smaller brain volumes and dementia in adults with type 2 diabetes, which so far has been relatively poorly characterised.

Methods

We included participants with diagnosed diabetes from the community-based Atherosclerosis Risk in Communities (ARIC) study. At the participants’ fifth study visit (2011–2013), we examined the cross-sectional associations of severe hypoglycaemia with cognitive status, brain volumes and prior 15 year cognitive decline. We also conducted a prospective survival analysis of incident dementia from baseline, visit 4 (1996–1998), to 31 December 2013. Severe hypoglycaemia was identified, using ICD-9 codes, from hospitalisations, emergency department visits and ambulance records. Prior cognitive decline was defined as change in neuropsychological test scores from visit 4 (1996–1998) to visit 5 (2011–2013). At visit 5, a subset of participants underwent brain MRIs. Analyses were adjusted for demographics, APOE genotype, use of diabetes medication, duration of diabetes and glycaemic control.

Results

Among 2001 participants with diabetes at visit 5 (mean age 76 years), a history of severe hypoglycaemia (3.1% of participants) was associated with dementia (vs normal cognitive status): OR 2.34 (95% CI 1.04, 5.27). In the subset of participants who had undergone brain MRI (n = 580), hypoglycaemia was associated with smaller total brain volume (−0.308 SD, 95% CI −0.612, −0.004). Hypoglycaemia was nominally associated with a 15 year cognitive change (−0.14 SD, 95% CI −0.34, 0.06). In prospective analysis (n = 1263), hypoglycaemia was strongly associated with incident dementia (HR 2.54, 95% CI 1.78, 3.63).

Conclusions/interpretation

Our results demonstrate a strong link between severe hypoglycaemia and poor cognitive outcomes, suggesting a need for discussion of appropriate diabetes treatments for high-risk older adults.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Seaquist ER, Anderson J, Childs B et al (2013) Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine society. Diabetes Care 36:1384–1395CrossRefPubMedPubMedCentral Seaquist ER, Anderson J, Childs B et al (2013) Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine society. Diabetes Care 36:1384–1395CrossRefPubMedPubMedCentral
2.
Zurück zum Zitat American Diabetes Association (2017) Standards of Medical Care in Diabetes -- 2017. Diabetes Care 40(Supp 1) American Diabetes Association (2017) Standards of Medical Care in Diabetes -- 2017. Diabetes Care 40(Supp 1)
3.
Zurück zum Zitat Warren RE, Frier BM (2005) Hypoglycemia and cognitive function. Diabetes Obes Metab 7:493–503CrossRefPubMed Warren RE, Frier BM (2005) Hypoglycemia and cognitive function. Diabetes Obes Metab 7:493–503CrossRefPubMed
4.
Zurück zum Zitat Kang E, Jeon S, Choi S, Song C, Yu I (2010) Diffusion MR imaging OF hypoglycemic encephalopathy. Am J Neuroradiol 31:559–564CrossRefPubMed Kang E, Jeon S, Choi S, Song C, Yu I (2010) Diffusion MR imaging OF hypoglycemic encephalopathy. Am J Neuroradiol 31:559–564CrossRefPubMed
5.
Zurück zum Zitat Ma JH, Kim YJ, Yoo WJ et al (2009) MR imaging of hypoglycemic encephalopathy: lesion distribution and prognosis prediction by diffusion-weighted imaging. Neuroradiology 51:641–649CrossRefPubMed Ma JH, Kim YJ, Yoo WJ et al (2009) MR imaging of hypoglycemic encephalopathy: lesion distribution and prognosis prediction by diffusion-weighted imaging. Neuroradiology 51:641–649CrossRefPubMed
6.
Zurück zum Zitat Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV (2009) Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301:1565–1572CrossRefPubMedPubMedCentral Whitmer RA, Karter AJ, Yaffe K, Quesenberry CP Jr, Selby JV (2009) Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA 301:1565–1572CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Yaffe K, Falvey CM, Hamilton N et al (2013) Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Intern Med 173:1300–1306CrossRefPubMedPubMedCentral Yaffe K, Falvey CM, Hamilton N et al (2013) Association between hypoglycemia and dementia in a biracial cohort of older adults with diabetes mellitus. JAMA Intern Med 173:1300–1306CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Lin CH, Sheu WHH (2013) Hypoglycaemic episodes and risk of dementia in diabetes mellitus: 7-year follow-up study. J Intern Med 273:102–110CrossRefPubMed Lin CH, Sheu WHH (2013) Hypoglycaemic episodes and risk of dementia in diabetes mellitus: 7-year follow-up study. J Intern Med 273:102–110CrossRefPubMed
9.
Zurück zum Zitat Bruce DG, Davis WA, Casey GP et al (2009) Severe hypoglycaemia and cognitive impairment in older patients with diabetes: the Fremantle Diabetes Study. Diabetologia 52:1808–1815CrossRefPubMed Bruce DG, Davis WA, Casey GP et al (2009) Severe hypoglycaemia and cognitive impairment in older patients with diabetes: the Fremantle Diabetes Study. Diabetologia 52:1808–1815CrossRefPubMed
10.
Zurück zum Zitat Feinkohl I, Aung PP, Keller M et al (2014) Severe hypoglycemia and cognitive decline in older people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care 37:507–515CrossRefPubMed Feinkohl I, Aung PP, Keller M et al (2014) Severe hypoglycemia and cognitive decline in older people with type 2 diabetes: the Edinburgh type 2 diabetes study. Diabetes Care 37:507–515CrossRefPubMed
11.
Zurück zum Zitat Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group (2007) Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med 356:1842–1852CrossRef Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) Study Research Group (2007) Long-term effect of diabetes and its treatment on cognitive function. N Engl J Med 356:1842–1852CrossRef
13.
Zurück zum Zitat Mattishent K, Loke YK (2016) Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis. Diabetes Obes Metab 18:135–141CrossRefPubMed Mattishent K, Loke YK (2016) Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis. Diabetes Obes Metab 18:135–141CrossRefPubMed
14.
Zurück zum Zitat Punthakee Z, Miller ME, Launer LJ et al (2012) Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care 35:787–793CrossRefPubMedPubMedCentral Punthakee Z, Miller ME, Launer LJ et al (2012) Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial. Diabetes Care 35:787–793CrossRefPubMedPubMedCentral
15.
Zurück zum Zitat De Galan BE, Zoungas S, Chalmers J et al (2009) Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the action in diabetes and vascular disease: preterax and diamicron modified release controlled evaluation (ADVANCE) trial. Diabetologia 52:2328–2336CrossRefPubMed De Galan BE, Zoungas S, Chalmers J et al (2009) Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the action in diabetes and vascular disease: preterax and diamicron modified release controlled evaluation (ADVANCE) trial. Diabetologia 52:2328–2336CrossRefPubMed
16.
Zurück zum Zitat Lee AK, Lee CJ, Huang ES, Sharrett AR (2017) Risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 40:1661–1667CrossRefPubMed Lee AK, Lee CJ, Huang ES, Sharrett AR (2017) Risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities (ARIC) Study. Diabetes Care 40:1661–1667CrossRefPubMed
17.
Zurück zum Zitat Prinz N, Stingl J, Dapp A et al (2015) High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: a multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry. Diabetes Res Clin Pract 112:73–81CrossRefPubMed Prinz N, Stingl J, Dapp A et al (2015) High rate of hypoglycemia in 6770 type 2 diabetes patients with comorbid dementia: a multicenter cohort study on 215,932 patients from the German/Austrian diabetes registry. Diabetes Res Clin Pract 112:73–81CrossRefPubMed
18.
Zurück zum Zitat Rawlings AM, Sharrett AR, Schneider ALC et al (2014) Diabetes in midlife and cognitive change over 20 years: a cohort study. Ann Intern Med 161:785–793CrossRefPubMedPubMedCentral Rawlings AM, Sharrett AR, Schneider ALC et al (2014) Diabetes in midlife and cognitive change over 20 years: a cohort study. Ann Intern Med 161:785–793CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat ARIC Investigators (1989) The Atherosclerosis Risk In Communities (ARIC) Study: design and objectives. Am J Epidemiol 129:687–702CrossRef ARIC Investigators (1989) The Atherosclerosis Risk In Communities (ARIC) Study: design and objectives. Am J Epidemiol 129:687–702CrossRef
20.
Zurück zum Zitat Ginde AA, Blanc PG, Lieberman RM, Camargo CA (2008) Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits. BMC Endocr Disord 8:4CrossRefPubMedPubMedCentral Ginde AA, Blanc PG, Lieberman RM, Camargo CA (2008) Validation of ICD-9-CM coding algorithm for improved identification of hypoglycemia visits. BMC Endocr Disord 8:4CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Knopman DS, Gottesman RF, Sharrett AR et al (2016) Mild cognitive impairment and dementia prevalence: the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Alzheimers Dement 2:1–11 Knopman DS, Gottesman RF, Sharrett AR et al (2016) Mild cognitive impairment and dementia prevalence: the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Alzheimers Dement 2:1–11
22.
Zurück zum Zitat Gottesman RF, Albert MS, Alonso A et al (2017) Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol 74:1246–1254CrossRefPubMed Gottesman RF, Albert MS, Alonso A et al (2017) Associations between midlife vascular risk factors and 25-year incident dementia in the Atherosclerosis Risk in Communities (ARIC) Cohort. JAMA Neurol 74:1246–1254CrossRefPubMed
23.
Zurück zum Zitat Knopman DS, Griswold ME, Lirette ST et al (2015) Vascular imaging abnormalities and cognition: mediation by cortical volume in nondemented individuals: Atherosclerosis risk in Communities-Neurocognitive Study. Stroke 46:433–440CrossRefPubMedPubMedCentral Knopman DS, Griswold ME, Lirette ST et al (2015) Vascular imaging abnormalities and cognition: mediation by cortical volume in nondemented individuals: Atherosclerosis risk in Communities-Neurocognitive Study. Stroke 46:433–440CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Gross AL, Power MC, Albert MS et al (2015) Application of latent variable methods to the study of cognitive decline when tests change over time. Epidemiology 26:878–887CrossRefPubMedPubMedCentral Gross AL, Power MC, Albert MS et al (2015) Application of latent variable methods to the study of cognitive decline when tests change over time. Epidemiology 26:878–887CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Georgakis MK, Dimitriou NG, Karalexi MA (2017) Albuminuria in association with cognitive function and dementia: a systematic review and meta-analysis. J Am Geriatr Soc 65:1190–1198CrossRefPubMed Georgakis MK, Dimitriou NG, Karalexi MA (2017) Albuminuria in association with cognitive function and dementia: a systematic review and meta-analysis. J Am Geriatr Soc 65:1190–1198CrossRefPubMed
27.
Zurück zum Zitat Helmer C, Stengel B, Metzger M et al (2011) Chronic kidney disease, cognitive decline, and incident dementia: the 3C Study. Neurology 77:2043–2051CrossRefPubMed Helmer C, Stengel B, Metzger M et al (2011) Chronic kidney disease, cognitive decline, and incident dementia: the 3C Study. Neurology 77:2043–2051CrossRefPubMed
28.
Zurück zum Zitat Zhang Z, Lovato J, Battapady H et al (2014) Effect of hypoglycemia on brain structure in people with type 2 diabetes: epidemiological analysis of the ACCORD-MIND MRI Trial. Diabetes Care 37:3279–3285CrossRefPubMedPubMedCentral Zhang Z, Lovato J, Battapady H et al (2014) Effect of hypoglycemia on brain structure in people with type 2 diabetes: epidemiological analysis of the ACCORD-MIND MRI Trial. Diabetes Care 37:3279–3285CrossRefPubMedPubMedCentral
29.
Zurück zum Zitat Auer RN, Siesjo BK (1993) Hypoglycaemia: brain neurochemistry and neuropathology. Bailliere Clin Endocrinol Metab 7:611–625CrossRef Auer RN, Siesjo BK (1993) Hypoglycaemia: brain neurochemistry and neuropathology. Bailliere Clin Endocrinol Metab 7:611–625CrossRef
30.
Zurück zum Zitat Schneider ALC, Selvin E, Sharrett AR et al (2017) Diabetes, prediabetes, and brain volumes and subclinical cerebrovascular disease on MRI: the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Diabetes Care 40:1514–1521CrossRefPubMed Schneider ALC, Selvin E, Sharrett AR et al (2017) Diabetes, prediabetes, and brain volumes and subclinical cerebrovascular disease on MRI: the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS). Diabetes Care 40:1514–1521CrossRefPubMed
31.
Zurück zum Zitat Biessels GJ, Strachan MWJ, Visseren FLJ, Kappelle LJ, Whitmer RA (2014) Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions. Lancet Diabetes Endocrinol 2:246–255CrossRefPubMed Biessels GJ, Strachan MWJ, Visseren FLJ, Kappelle LJ, Whitmer RA (2014) Dementia and cognitive decline in type 2 diabetes and prediabetic stages: towards targeted interventions. Lancet Diabetes Endocrinol 2:246–255CrossRefPubMed
32.
Zurück zum Zitat Wilson RS, Schneider JA, Barnes LL et al (2002) The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period. Arch Neurol 59:1154–1160CrossRefPubMed Wilson RS, Schneider JA, Barnes LL et al (2002) The apolipoprotein E epsilon 4 allele and decline in different cognitive systems during a 6-year period. Arch Neurol 59:1154–1160CrossRefPubMed
34.
Zurück zum Zitat Karter AJ, Warton EM, Lipska KJ et al (2017) Development and validation of a tool to identify patients with type 2 diabetes at high risk of hypoglycemia-related emergency department or hospital use. JAMA Intern Med 36:3535–3542 Karter AJ, Warton EM, Lipska KJ et al (2017) Development and validation of a tool to identify patients with type 2 diabetes at high risk of hypoglycemia-related emergency department or hospital use. JAMA Intern Med 36:3535–3542
35.
Zurück zum Zitat Munshi MN, Slyne C, Segal AR, Saul N, Lyons C, Weinger K (2016) Simplification of insulin regimen in older adults and risk of hypoglycemia. JAMA Intern Med 176:1023–1025CrossRefPubMed Munshi MN, Slyne C, Segal AR, Saul N, Lyons C, Weinger K (2016) Simplification of insulin regimen in older adults and risk of hypoglycemia. JAMA Intern Med 176:1023–1025CrossRefPubMed
36.
Zurück zum Zitat Vimalananda VG, DeSotto K, Chen T et al (2017) A quality improvement program to reduce potential overtreatment of diabetes among veterans at high risk of hypoglycemia. Diabetes Spectr 30:211–216CrossRefPubMedPubMedCentral Vimalananda VG, DeSotto K, Chen T et al (2017) A quality improvement program to reduce potential overtreatment of diabetes among veterans at high risk of hypoglycemia. Diabetes Spectr 30:211–216CrossRefPubMedPubMedCentral
Metadaten
Titel
Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study
verfasst von
Alexandra K. Lee
Andreea M. Rawlings
Clare J. Lee
Alden L. Gross
Elbert S. Huang
A. Richey Sharrett
Josef Coresh
Elizabeth Selvin
Publikationsdatum
30.06.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 9/2018
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-018-4668-1

Weitere Artikel der Ausgabe 9/2018

Diabetologia 9/2018 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.