Severe Hypoglycemia and Cognitive Function in Older Adults With Type 1 Diabetes: The Study of Longevity in Diabetes (SOLID)

Abstract

In children with type 1 diabetes (T1D), severe hypoglycemia (SH) is associated with poorer cognition, but the association of SH with cognitive function in late life is unknown. Given the increasing life expectancy in people with T1D, understanding the role of SH in brain health is crucial. RESEARCH DESIGN AND METHODS We examined the association between SH and cognitive function in 718 older adults with T1D from the Study of Longevity in Diabetes (SOLID). Subjects self-reported recent SH (previous 12 months) and lifetime history of SH resulting in inpatient/ emergency department utilization. Global and domain-specific cognition (language, executive function, episodic memory, and simple attention) were assessed. The associations of SH with cognitive function and impaired cognition were evaluated via linear and logistic regression models, respectively. RESULTS Thirty-two percent of participants (mean age 67.2 years) reported recent SH and 50% reported lifetime SH. Compared with those with no SH, subjects with a recent SH history had significantly lower global cognition scores. Domain-specific analyses revealed significantly lower scores on language, executive function, and episodic memory with recent SH exposure and significantly lower executive function with lifetime SH exposure. Recent SH was associated with impaired global cognition (odds ratio [OR] 3.22, 95% CI 1.30, 7.94) and cognitive impairment on the language domain (OR 3.15, 95% CI 1.19, 8.29). CONCLUSIONS Among older adults with T1D, recent SH and lifetime SH were associated with worse cognition. Recent SH was associated with impaired global cognition. These findings suggest a deleterious role of SH on the brain health of older patients with T1D and highlight the importance of SH prevention. Severe hypoglycemia (SH) is a common, yet life-threatening, complication of type 1 diabetes (T1D). SH, defined as an episode of low blood glucose requiring external help to recover, affects ;30-50% of people with T1D annually (1-3). Among older adults with T1D ($65 years of age) and those with long-standing diabetes ($40 years' duration), rates of SH are even higher (4).

Sex, diabetes status and cognition: findings from the study of longevity in diabetes

“…Details of participant eligibility and inclusion have been published previously and briefly presented in online supplemental figure 1. [16][17][18] Potential participants with T1D were identified in electronic medical records using International Classification of Diseases (ICD)-9 and ICD-10 codes for T1D (250.x1, 250.x3 or E10.x) or T2D (250.x0, 250.x2, E11.x). As per previous work using the SOLID dataset, [16][17][18] individuals with diagnostic codes related to both types of diabetes were classified as having T1D if at least 75% of diagnostic codes related to diabetes were for T1D specifically and the member was prescribed insulin to reduce the risk of misclassification.…”

The consequences of hypoglycaemia

“…In adults data remain controversial, with consistently reassuring data coming from long-term follow-up of the DCCT/Epidemiology of Diabetes Interventions and Complications (EDIC) cohort of type 1 diabetes patients and from the Outcome Reduction With Initial Glargine Intervention (ORIGIN) trial in people with type 2 diabetes [ 57 , 58 ]. However, a recent large study in older adults with type 1 diabetes demonstrated an association between patient-reported history of severe hypoglycaemia events (episodes resulting in emergency department or inpatient admission), either recent (any) or life-time exposure, and impaired performance in global cognition, language and executive function and recent episodic memory, with evidence for a dose effect [ 59 ]. An earlier meta-analysis also found a bi-directional relationship between dementia and hypoglycaemia in older adults [ 60 ].…”

How Significant Is Severe Hypoglycemia in Older Adults With Diabetes?

“…In this issue of Diabetes Care , complementary articles provide new insights into the consequences of severe hypoglycemia in older adults. Lacy et al ( 3 ) report that severe hypoglycemia is associated with reduced cognitive function in older adults with type 1 diabetes, and Standl et al ( 4 ) confirm the bidirectional nature of the association between severe hypoglycemia and cardiovascular (CV) events in adults with type 2 diabetes. Both investigations support reducing severe hypoglycemia as a clinical imperative in reducing diabetes-associated morbidity.…”

“…In summary, these studies emphasize the need for glycemic treatment to move beyond glycemic control and include reduction of severe hypoglycemia, particularly in an older population with comorbidities. While Standl et al ( 4 ) clearly demonstrate a bidirectional relationship between severe hypoglycemia and CV events, Lacy et al ( 3 ) could not address the bidirectionality between severe hypoglycemia and impaired cognition because of the study’s cross-sectional design. Regardless, practitioners need to consider comorbidities such as frailty and cognitive dysfunction when making glycemic treatment recommendations for their patients with diabetes.…”

“…Lacy et al ( 3 ) used data collected from the 718 patients with type 1 diabetes (mean age 67.2 years) in the Study of Longevity in Diabetes (SOLID) to perform a cross-sectional analysis between cognitive function, recent severe hypoglycemia (self-reported within the last 12 months), and lifetime severe hypoglycemia (self-reported event requiring emergency room visit or hospitalization). Their key finding was that both recent and lifetime severe hypoglycemia were associated with impaired cognition, with the greatest impairment found in those with recent severe hypoglycemia.…”