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

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

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.

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.

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