Cognition in Patients With Hypoglycemia, Without Diabetes

Pilot Study - Cognition in Patients With Hypoglycemia, Without Diabetes

The purpose of this study is to determine if there are differences in cognitive function (thinking) in individuals who have recurrent hypoglycemia (low blood sugars) following Roux-en-Y gastric bypass, compared with individuals who have also had a Roux-en-Y gastric bypass but do not have hypoglycemia.

Study Overview

• Status: Completed
• Conditions: Hypoglycemia; Cognition
• Intervention / Treatment: Diagnostic test: ECG; Other: Cognitive Assessment (not diagnostic)

Detailed Description

This study will test the hypothesis that a history of recurrent hypoglycemia following gastric bypass is associated with differences in cognition (thinking), by analyzing results of cognitive testing in post-gastric bypass individuals with a history of hypoglycemia as compared to those without known hypoglycemia.

This pilot study will identify cognitive domains of interest, as well as inform the development of a future battery of assessments, which could be replicated in a larger sample. Cognitive domains which will be assessed include: premorbid intelligence, memory, language, executive function, and psychomotor speed.

• Study Type: Observational
• Enrollment (Actual): 22

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Joslin Diabetes Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Participants will be recruited into 2 groups: (1) patients with hypoglycemia after upper gastrointestinal surgery (PBH), recruited from the Joslin Hypoglycemia Clinic, (2) asymptomatic post-bariatric patients without hypoglycemia, recruited from postoperative surgical clinics at Brigham and Women's Hospital or Beth Israel Hospitals.

Some participants may be recruited from other hypoglycemia studies at Joslin.

Description

Inclusion Criteria:

1. Age 18-70 years of age, inclusive, at screening.
2. Willingness to provide informed consent and attend one study visit.
3. For hypoglycemia after upper GI surgery group: Males or females diagnosed with ongoing post upper GI surgery hypoglycemia, with prior episodes of neuroglycopenia, unresponsive to dietary intervention.
4. For hypoglycemia without a history of upper gastrointestinal surgery group: Males or females diagnosed with ongoing hypoglycemia with prior episodes of neuroglycopenia, and without a history of prediabetes, diabetes, or upper GI surgery.
5. For post-bariatric without hypoglycemia group: Males or females with history of bariatric surgery, and no history of symptomatic hypoglycemia.
6. For non-surgical controls only: Males or females with no history of upper GI surgery and no history of hypoglycemia, prediabetes, or diabetes.

Exclusion Criteria:

1. Active treatment with any diabetes medications, except for acarbose.
2. History of cerebrovascular accident.
3. History of a traumatic brain injury not related to hypoglycemia.
4. Active depression.
5. Active alcohol abuse or substance abuse.
6. Known insulinoma, gastrinoma or other neuroendocrine tumor.
7. Having undergone same / similar cognitive assessments within the last calendar year.

There will be no involvement of special vulnerable populations such as fetuses, neonates, pregnant women, children, prisoners, institutionalized or incarcerated individuals, or others who may be considered vulnerable populations.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hypoglycemia after gastric bypass surgery - post-bariatric hypoglycemia (PBH); Participants with PBH, recruited from the Joslin Hypoglycemia Clinic and from other hypoglycemia studies at Joslin.	Diagnostic test: ECG; ECG will take place during screening visit.; Other Names: Electrocardiogram (ECG); Other: Cognitive Assessment (not diagnostic); Cognitive testing will assess premorbid intelligence, working memory and attention, verbal memory and delayed memory, executive function, and psychomotor speed.
Post-gastric bypass participants without a history of hypoglycemia; Participants with a history of Roux-en-Y gastric bypass, but without a diagnosis of hypoglycemia, or symptoms of hypoglycemia, recruited by advertisement flyers at postoperative surgical clinics at local hospitals (such as Brigham and Women's and Beth Israel Deaconess Hospitals), research match, and from other hypoglycemia studies at Joslin.	Diagnostic test: ECG; ECG will take place during screening visit.; Other Names: Electrocardiogram (ECG); Other: Cognitive Assessment (not diagnostic); Cognitive testing will assess premorbid intelligence, working memory and attention, verbal memory and delayed memory, executive function, and psychomotor speed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Immediate Verbal Memory	Rey Auditory Verbal Learning Test (RAVLT) immediate recall accuracy scores was used to measure immediate verbal memory. Scores for this assessment were compared between groups. Scores for this assessment range 0 to 69, with a higher score indicating a superior immediate verbal memory. Wilcoxon rank-sum tests was used to examine differences between groups.	During the one day of cognitive assessment administration.
Assessment of Delayed Verbal Memory	RAVLT 20 minute recall accuracy scores, was used to measure delayed memory and was compared between groups. Scores for this assessment range 0 to 15, with a higher score indicating less delays in memory. Wilcoxon rank-sum tests was used to examine differences between groups.	During the one day of cognitive assessment administration.
Working Memory Assessed by the Letter Number Sequencing Scaled Score	Letter-Number Sequencing subtest from the Wechsler Memory Scale III scaled scores were used to measure working memory and were compared between groups. Wilcoxon rank-sum test was used to examine differences between groups. Scores for this assessment range 1 to 19, with a higher score indicating a superior working memory.	During the one day of cognitive assessment administration.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of Cognitive Flexibility Using Trails Scaled Score	Delis-Kaplan Executive Function System (DKEFS),Trail Making Task score was used to assess the cognitive flexibility component of executive function. Scores are derived from time to complete the task plus errors. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive flexibility.	During the one day of cognitive assessment administration.
Assessment of Cognitive Flexibility Using Color-word Inference Test	DKEFS Color-Word Interference Test (CWIT) Inhibition Switching scores was used to measure the cognitive flexibility component of executive function. The CWIT is scored by time to complete plus errors. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive flexibility.	During the one day of cognitive assessment administration.
Assessment of Inhibition Using Color-word Inference Test	DKEFS CWIT scores was used to measure the inhibition component of executive function. The CWIT is scored by time to complete plus errors. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior inhibition.	During the one day of cognitive assessment administration.
Verbal Ability Cognitive Control Assessed by Letter Fluency	DKEFS Letter Fluency Task will be used to assess the verbal functioning cognitive control ability component of executive function. Scores are derived from the number of unique, correct words. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior verbal functioning cognitive control ability.	During the one day of cognitive assessment administration.
Assessment of Psychomotor Speed	The grooved pegboard test is a manipulative dexterity task that assesses psychomotor speed, fine motor control, and rapid-visual motor coordination. Participants were asked to insert 25 grooved pegs into holes within the given time limit up to 300 seconds (the score upper limit is thus 300). Time taken to complete the test has been found to be inversely correlated with cognitive ability; therefore, a higher score represents an inferior score. Wilcoxon rank-sum test was used to examine differences between groups.	During the one day of cognitive assessment administration.
Verbal Ability Cognitive Control Assessed by Category Fluency	DKEFS Category Fluency scores were used to measure cognitive control of verbal ability, specifically measuring an individuals ability to access and retrieve semantic information (memory) as a component of executive function. Category fluency is scored by number of correct words plus errors in a 60 second trial in each of 3 categories. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of verbal ability.	During the one day of cognitive assessment administration.
Verbal Ability Cognitive Flexibility, Assessed by Category Switching Scaled Score	DKEFS Category Switching scores will be used to measure cognitive control of verbal ability, specifically measuring an individuals ability to access and retrieve semantic information (memory), switching back and forth between 2 different semantic categories, a component of executive function. Category switching is scored by number of correct words plus errors. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of verbal ability.	During the one day of cognitive assessment administration.
Verbal Ability Cognitive Control of Inhibition, Assessed by Category Switching Accuracy Scaled Score	DKEFS Category Switching Accuracy scores will be used to measure cognitive control of verbal ability, specifically measuring an individuals ability to inhibit incorrect or repetitive semantic information (memory), while switching back and forth between 2 different semantic categories, a component of executive function. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of verbal ability.	During the one day of cognitive assessment administration.
Lexical Processing Assessed by Letter Fluency, First Interval.	DKEFS Letter Fluency, first interval scores will be used to measure cognitive control of lexical processing, specifically measuring an individuals ability to retrieve phonemic information, a component of executive function. Participants are asked to name as many words a they are able starting with a specific letter, without repetition. Wilcoxon rank-sum test was used to examine differences between groups. There are four intervals of this task the first assessing initiation of retrieval while the following trials measuring the ability to sustain retrieval. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of lexical processing.	During one day of cognitive assessement administration.
Lexical Processing as Assessed by Letter Fluency, Second Interval	DKEFS Letter Fluency, second interval scores will be used to measure cognitive control of lexical processing, specifically measuring an individuals ability to retrieve phonemic information, a component of executive function. There are four intervals of this task the second through fourth trial assess ability to sustain retrieval. Participants are asked to name as many words a they are able starting with a specific letter, without repetition. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior cognitive control of lexical processing.	During one day of cognitive assessement administration.
Lexical Processing Assessed by Letter Fluency, Third Interval	DKEFS Letter Fluency, third interval scores will be used to measure sustainment of cognitive control of lexical processing, specifically measuring an individuals ability to continue to retrieve phonemic information after multiple trials, a component of executive function. There are four intervals of this task the second through fourth trial assess ability to maintain retrieval. Participants are asked to name as many words a they are able starting with a specific letter, without repetition. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior sustainment of cognitive control of lexical processing.	During one day of cognitive assessment administration.
Lexical Processing Assessed by Letter Fluency, Fourth Interval	DKEFS Letter Fluency, fourth interval scores will be used to measure sustainment of cognitive control of lexical processing, specifically measuring an individuals ability to continue to retrieve phonemic information after multiple trials, a component of executive function. There are four intervals of this task the second through fourth trial assess ability to maintain retrieval. Participants are asked to name as many words a they are able starting with a specific letter, without repetition. Wilcoxon rank-sum test was used to examine differences between groups. Normative scores for this assessment range 1-19 (mean of 10, and standard deviation of 3), and a higher score indicates superior sustainment of cognitive control of lexical processing.	During one day of cognitive assessment administration.

Collaborators and Investigators

• Sponsor: Joslin Diabetes Center
• Investigators: Principal Investigator: Mary Elizabeth Patti, MD, Joslin Diabetes Center

Publications and helpful links

General Publications

• Puleio A, Sheehan A, Musen G, Patti ME. Cognition in patients with post-bariatric hypoglycemia. Obesity (Silver Spring). 2024 Mar;32(3):466-471. doi: 10.1002/oby.23862. Epub 2023 Sep 5.

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2020
• Primary Completion (Actual): August 4, 2021
• Study Completion (Actual): August 4, 2021

Study Registration Dates

• First Submitted: June 10, 2020
• First Submitted That Met QC Criteria: June 10, 2020
• First Posted (Actual): June 12, 2020

Study Record Updates

• Last Update Posted (Estimated): November 4, 2024
• Last Update Submitted That Met QC Criteria: October 30, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Memory; Executive Function; Post-Bariatric Hypoglycemia
• Additional Relevant MeSH Terms: Metabolic Diseases; Glucose Metabolism Disorders; Hypoglycemia
• Other Study ID Numbers: 00000098

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No