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

Study Overview
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Brief Summary
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To investigate whether longer-term improvement of glycemic control in poorly controlled diabetes patients with a 12-week intensified insulin treatment regimen will lead to decreased polyol pathway activity.

Detailed Description
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Polyol pathway activity will decrease in diabetic individuals who undergo intensification of their insulin treatment regimens as reflected by lower baseline brain intracellular fructose levels and higher intracellular glutathione levels. Furthermore, following longer-term improved glycemic control, patients may also have down-regulation of the pathway as reflected by decreased production of intracellular fructose in response to hyperglycemic clamp.

Official Title
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Investigating the Role of the Polyol Pathway in the Central Nervous System Production of Fructose: an Intervention Study

Conditions
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Hyperglycaemia (Diabetic)

Intervention / Treatment
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* Drug: Insulin
* Behavioral: exercise
* Dietary Supplement: Dietary counseling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 15 Type 2 DM subjects with HbA1C > 7.5% 15 Type 1 DM subjects with HbA1C > 7.5% Age 18-60 BMI ≥18 kg/m2 Weight ≤ 285 pounds 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, current or recent steroid use in last 3 months, illicit drug use; for women: 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: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: type 2 diabetes mellitus<br>Subjects with type 2 diabetes on insulin. | Drug: Insulin<br>* Insulin regimens will be adjusted on a weekly basis as needed to achieve a target blood glucose level.<br>Behavioral: exercise<br>* Exercise in accordance to the guidelines established by the American Diabetes Association.<br>Dietary Supplement: Dietary counseling<br>* Dietary counseling in accordance to the guidelines established by the American Diabetes Association.<br>|
| Active Comparator: type 1 diabetes mellitus<br>Subjects with type 1 diabetes on insulin. | Drug: Insulin<br>* Insulin regimens will be adjusted on a weekly basis as needed to achieve a target blood glucose level.<br>Behavioral: exercise<br>* Exercise in accordance to the guidelines established by the American Diabetes Association.<br>Dietary Supplement: Dietary counseling<br>* Dietary counseling in accordance to the guidelines established by the American Diabetes Association.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HbA1c Levels | HbA1c levels measured by MRS scanning during a hyperglycaemic clamp. Result reported is the mean decrease in HbA1C. A decrease in HbA1c indicates improvement in brain glucose levels. | Baseline and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gluthathione | baseline MRS scan to measure gluthathione | 0 weeks | 
| Gluthathione | MRS scan to measure gluthathione | 12 weeks | 
| Plasma Glucose | MRS scan to measure plasma glucose | 0 weeks | 
| Plasma Glucose | MRS scan to measure plasma glucose | 12 weeks | 
| Plasma Fructose | MRS scan to measure plasma fructose | 0 weeks | 
| Plasma Fructose | MRS scan to measure plasma fructose | 12 weeks | 
| Plasma Insulin | MRS scan to measure plasma insulin | 0 weeks | 
| Plasma Insulin | MRS scan to measure plasma insulin | 12 weeks |