Investigating the Role of the Polyol Pathway in the Central Nervous System

Study Overview
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Brief Summary
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Patients will undergo magnetic resonance spectroscopy (MRS) scanning to noninvasively measure intracerebral and plasma metabolite levels at baseline and following 2 and 4 hours of hyperglycemia. Subjects will also undergo a lumbar puncture at a separate occasion to assess cerebrospinal fluid levels of metabolites.

Official Title
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Investigating the Role of Polyol Pathway in the Central Nervous System

Conditions
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Hyperglycemia

Intervention / Treatment
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* Other: Brain MRS during hyperglycemic clamp
* Other: Analysis of Metabolites in cerebrospinal fluid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 DM with HbA1C treated with metformin, sulfonylurea, insulin, or combination OR age-matched, non-diabetic obese (BMI > 30 kg/m^2) OR age-matched lean, healthy control subjects (BMI < 25 kg/m^2) Age 18-55 BMI 18-45 kg/m^2 Exclusion Criteria: Creatinine > 1.5 mg/dL Hgb < 10 mg/dL ALT > 2.5 x ULN Untreated thyroid disease Uncontrolled Hypertension Known Neurological Disorders Untreated Psychiatric Disorders Malignancy Bleeding Disorders Smoking Current or recent steroid use in last 3 months Illicit drug use Pregnancy, actively seeking pregnancy, or breastfeeding Inability to enter MRI/MRS

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 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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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Subjects with Type 2 Diabetes<br>Type 2 DM subjects with HbA1C > 7.5% treated with metformin, sulfonylurea, insulin or combination | Other: Brain MRS during hyperglycemic clamp<br>* All patients will undergo brain MRS at baseline and following 2 and 4 hours of hyperglycemia using the clamp technique<br>Other: Analysis of Metabolites in cerebrospinal fluid<br>* All patients will have the option to undergo a lumbar puncture for analysis of metabolites in cerebrospinal fluid<br>|
| Active Comparator: Non-Diabetic Obese<br>Age-matched, non-diabetic obese (BMI > 30 kg/m^3) individuals | Other: Brain MRS during hyperglycemic clamp<br>* All patients will undergo brain MRS at baseline and following 2 and 4 hours of hyperglycemia using the clamp technique<br>Other: Analysis of Metabolites in cerebrospinal fluid<br>* All patients will have the option to undergo a lumbar puncture for analysis of metabolites in cerebrospinal fluid<br>|
| Active Comparator: Lean, healthy control subjects<br>Age-matched, lean, healthy control subjects (BMI < 25 kkg/m^3) | Other: Brain MRS during hyperglycemic clamp<br>* All patients will undergo brain MRS at baseline and following 2 and 4 hours of hyperglycemia using the clamp technique<br>Other: Analysis of Metabolites in cerebrospinal fluid<br>* All patients will have the option to undergo a lumbar puncture for analysis of metabolites in cerebrospinal fluid<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metabolite Measurements by MRS | metabolite levels will be measured by MRS | 4 hours post hyperglycemia | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hunger Ratings | Hunger will be measured using a visual analog scale | 4 hours post hyperglycemia | 
| Satiety Ratings | Satiety will be measured using a visual analog scale | 4 hours post hyperglycemia | 
| Cognitive State | Participants will be asked to complete basic cognitive testing using the mini-mental status exam and the Montreal cognitive assessment | 4 hours post hyperglycemia |