Hypoglycemic Episodes and Risk of Dementia in Older Patients with Type 2 Diabetes Mellitus

By R. Whitmer, A. Karter, Kristine Yaffe, C. Quesenberry, J. Selby. Journal of the American Medical Association (JAMA), 2009

1,091 citations recorded by the source corpus.

Context Although acute hypoglycemia may be associated with cognitive impairment in children with type 1 diabetes, no studies to date have evaluated whether hypoglycemia is a risk factor for dementia in older patients with type 2 diabetes. Objective To determine if hypoglycemic episodes severe enough to require hospitalization are associated with an increased risk of dementia in a population of older patients with type 2 diabetes followed up for 27 years. Design, Setting, and Patients A longitudinal cohort study from 1980-2007 of 16,667 patients with a mean age of 65 years and type 2 diabetes who are members of an integrated health care delivery system in northern California. Main Outcome Measure Hypoglycemic events from 1980-2002 were collected and reviewed using hospital discharge and emergency department diagnoses. Cohort members with no prior diagnoses of dementia, mild cognitive impairment, or general memory complaints as of January 1, 2003, were followed up for a dementia diagnosis through January 15, 2007. Dementia risk was examined using Cox proportional hazard regression models, adjusted for age, sex, race/ethnicity, education, body mass index, duration of diabetes, 7-year mean glycated hemoglobin, diabetes treatment, duration of insulin use, hyperlipidemia, hypertension, cardiovascular disease, stroke, transient cerebral ischemia, and end-stage renal disease. Results At least 1 episode of hypoglycemia was diagnosed in 1465 patients (8.8%) and dementia was diagnosed in 1822 patients (11%) during follow-up; 250 patients had both dementia and at least 1 episode of hypoglycemia (16.95%). Compared with patients with no hypoglycemia, patients with single or multiple episodes had a graded increase in risk with fully adjusted hazard ratios (HRs): for 1 episode (HR, 1.26; 95% confidence interval [CI], 1.10-1.49); 2 episodes (HR, 1.80; 95% CI, 1.37-2.36); and 3 or more episodes (HR, 1.94; 95% CI, 1.42-2.64). The attributable risk of dementia between individuals with and without a history of hypoglycemia was 2.39% per year (95% CI, 1.72%-3.01%). Results were not attenuated when medical utilization rates, length of health plan membership, or time since initial diabetes diagnosis were added to the model. When examining emergency department admissions for hypoglycemia for association with risk of dementia (535 episodes), results were similar (compared with patients with 0 episodes) with fully adjusted HRs: for 1 episode (HR, 1.42; 95% CI, 1.12-1.78) and for 2 or more episodes (HR, 2.36; 95% CI, 1.57-3.55). Conclusions Among older patients with type 2 diabetes, a history of severe hypoglycemic episodes was associated with a greater risk of dementia. Whether minor hypoglycemic episodes increase risk of dementia is unknown.

Subfields: Endocrinology, Diabetes and Metabolism

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Citations in the corpus

Hypoglycemia and Diabetes: A Report of a Workgroup of the American Diabetes Association and The Endocrine Society (2013, background): “In a large population study, hypoglycemic episodes that required hospitalization or a visit to the emergency department between 1980 and 2002 were associated with approximately double the risk of incident dementia after 2003 (6).”
Diabetic Kidney Disease: A Report From an ADA Consensus Conference (2014, neutral): “Older individuals also are at greater risk for hypoglycemia and for adverse consequences from hypoglycemia (79,80).”
Inequalities in dementia incidence between six racial and ethnic groups over 14 years (2016, methodology): “Dementia case identification using ICD-9 codes has been used successfully in other publications in this population [24–27].”
Canadian Diabetes Association Clinical Practice Guidelines Expert Committee (2013, background): “Unlike patients with type 1 diabetes, those with type 2 diabetes and previous severe hypoglycemia requiring presentation to the hospital have increased risk of subsequent dementia (14).”
Standards of Medical Care in Diabetes—2012 (2011, background): “A large cohort study suggested that among older adults with type 2 diabetes, a history of severe hypoglycemia was associated with greater risk of dementia (200).”
6. Glycemic Targets: Standards of Medical Care in Diabetes—2020 (2019, background): “reported in clinical practice (68) Young children with type 1 diabetes and the elderly, including those with type 1 and type 2 diabetes (61,69), are noted as particularly vulnerable to”
6. Glycemic Targets: Standards of Medical Care in Diabetes-2022. (2021, background): “Young children with type 1 diabetes and the elderly, including those with type 1 and type 2 diabetes (86,95), are noted as particularly vulnerable to hypoglycemia because of their reduced ability to recognize hypoglycemic symptoms and effectively communicate their needs.”
Diabetes in Older Adults (2012, background): “Hypoglycemia is linked to cognitive dysfunction in a bidirectional fashion: cognitive impairment increases the subsequent risk of hypoglycemia (60), and a history of severe hypoglycemia is linked to the incidence of dementia (63).”
Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: implications for diagnostic and therapeutic strategies. (2013, background): “Our focus on the impairment of hypoglycemia, especially recurrent hypoglycemic episodes, on cognition is based on the evidence that a history of severe hypoglycemic episodes was associated with a greater risk of dementia among older patients with T2DM (Niswender, 2011; Whitmer et al., 2009).”
6. Glycemic Targets: Standards of Medical Care in Diabetes-2021. (2021, background): “Young children with type 1 diabetes and the elderly, including those with type 1 and type 2 diabetes (73,81), are noted as particularly vulnerable to hypoglycemia because of their reduced ability to recognize hypoglycemic symptoms and effectively communicate their needs.”
6. Glycemic Targets: Standards of Medical Care in Diabetes—2019 (2018, background): “with type 2 diabetes, a history of level 3 hypoglycemia was associated with greater risk of dementia (48).”
Standards of Medical Care in Diabetes—2014 (2013, background): “A large cohort study suggested that among older adults with type 2 diabetes, a history of severe hypoglycemia was associated with greater risk of dementia (290).”
Standards of Medical Care in Diabetes—2013 (2012, background): “A large cohort study suggested that among older adults with type 2 diabetes, a history of severe hypoglycemia was associated with greater risk of dementia (224).”