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

Yale University

Status and phase: Completed; Early Phase 1

Conditions: Hyperglycaemia (Diabetic)

Treatments: Behavioral: exercise; Drug: Insulin; Dietary Supplement: Dietary counseling

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03469492

1602017151

1K23DK109284-01 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 8 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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8 participants in 2 patient groups

type 2 diabetes mellitus

Active Comparator group

Description:

Subjects with type 2 diabetes on insulin.

Treatment:

Behavioral: exercise

Dietary Supplement: Dietary counseling

Drug: Insulin

type 1 diabetes mellitus

Active Comparator group

Description:

Subjects with type 1 diabetes on insulin.

Treatment:

Behavioral: exercise

Dietary Supplement: Dietary counseling

Drug: Insulin