Diabetic Ketoacidosis: Brain Morphology and Cognition

Study Overview
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Brief Summary
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The purpose of this study is to assess brain and memory changes in patients with uncontrolled diabetes (a condition called diabetic ketoacidosis (DKA))

Detailed Description
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Diabetic ketoacidosis (DKA) is a common and serious medical problem. Most cases occur when patients forget or stop insulin injections. Some patients require frequent admissions to the hospital with DKA after stopping insulin. Many patients do not know why they stop insulin therapy. The investigators will test if patients with one or more episodes of DKA have poor memory and brain changes that may lead to poor management. In this study, the investigators will perform memory testing and brain images in subjects with initial DKA episode and subjects with more than 3 episodes of DKA. The results will be compared to subjects with diabetes and no history of DKA and healthy (non-diabetic) subjects. Each subject with DKA will have an MRI and cognitive testing done shortly after hospital discharge, 1 month, and 3 months after hospital discharge. Diabetic subjects without DKA and healthy controls will only come in for a single baseline visit and have a MRI and cognitive testing done.

Official Title
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Acute and Long-term Neuroanatomical and Cognitive Evaluation of Adult Patients With First and Recurrent Episodes of Diabetic Ketoacidosis

Conditions
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Diabetic Ketoacidosis

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 or type 2 diabetes with diabetic ketoacidosis (DKA) Age 18-50 years Newly diagnosed or history of noncompliance with insulin therapy as precipitating cause of DKA No significant medical or surgical illness as precipitating cause of DKA Exclusion Criteria: Significant medical/surgical illness as precipitating cause of DKA (i.e. myocardial infarction, major surgery) Associated significant medical or surgical condition within 6 months history History of hypoglycemia unawareness History of seizures, ischemic stroke or hemorrhage, and severe head trauma History of symptomatic stenosis of major intracranial vessels Dementia (mini-mental state examination (MMSE) score (r ≤ 24) or inability to cooperate) Liver or renal failure or transplant Severe hypertension (systolic blood pressure (BP) >160 mm Hg and/or diastolic BP >100 mm Hg or subjects taking ≥ 2 antihypertensive medications) Malignancy Current recreational drug or alcohol abuse Magnetic resonance imaging (MRI) exclusions: any metal and bio-implants not compatible with 3 Tesla MRI, claustrophobia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Healthy Controls<br>Non-diabetic subjects | |
| Diabetics without DKA<br>Diabetic subjects (recent(< 1 year) diagnosis of diabetes) without a history of diabetic ketoacidosis (DKA) | |
| First episode of DKA<br>Diabetic subjects that just had their primary event of diabetic ketoacidosis (DKA) | |
| Three or more DKA episodes<br>Diabetic subjects who have had three or more diabetic ketoacidosis (DKA) episodes | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute change in brain morphology | Changes in brain morphology will include quantitative measurements of regional cortical volume as well as of hippocampal and thalamic volumes. Change is the difference from baseline MRI and 1 month MRI. | Baseline, 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term change in brain morphology | Changes in brain morphology will include quantitative measurements of regional cortical volume as well as of hippocampal and thalamic volumes. Change is the difference from baseline MRI and 4 month MRI. | Baseline, 4 months | 
| Change in neurocognitive assessment | Assessment will focus in composite domains: verbal memory, visual memory, working memory, prospective memory, executive function processing speed, and reaction time. Change is the difference from baseline assessment and 3 month assessment. | Baseline (72 hours after DKA), 3 months | 
| Change in neurocognitive assessment | Assessment will focus in composite domains: verbal memory, visual memory, working memory, prospective memory, executive function processing speed, and reaction time. Change is the difference from baseline assessment and 6 month assessment. | Baseline (72 hours after DKA), 6 months |