Effects of Acipimox on Insulin Action, Vascular Function, and Muscle Function in Type 1 Diabetes

Role of Lipotoxicity in Insulin Resistance, Vascular, and Mitochondrial Dysfunction in Type 1 Diabetes

Insulin resistance (IR) is an important contributor to increased cardiovascular disease risk in type 1 diabetes (T1D). Non-esterified fatty acid elevation is a significant contributor to IR in T1D and may be a target of intervention. The hypothesis of the study is that isolated fatty acid lowering with acipimox will improve insulin action and blood vessel function and have the benefit of reducing mitochondrial oxidant generation and improving mitochondrial function in T1D. Targeting IR through fatty acid lowering is a novel approach to T1D treatment that may significantly improve current management of TID and of cardiovascular disease (CVD) risk in this high risk population.

Inclusion Criteria:

1. Men and women, with and without type 1 diabetes between 25-59 years of age,

2. HbA1c 6.0-9.5 (T1D only),

3. Subjects who are willing to commit to:

   • 14 days of prescribed diet,
   • two 44 hour inpatient stays, and
   • two muscle biopsies.

Exclusion Criteria:

1. Any comorbid condition associated with inflammation, insulin resistance, or dyslipidemia,
2. Tobacco use,
3. Pregnancy,
4. Steroid use,
5. Scheduled physical activity >3 days a week,
6. Angina or any other cardiovascular or pulmonary disease,
7. History of chronic obstructive pulmonary disease or asthma,
8. Systolic blood pressure >190 at rest or >250 with exercise, or
9. Diastolic pressure >95 at rest, or >105 with exercise,
10. Proteinuria (urine protein >200 mg/dl), or
11. Creatinine > 2 mg/dl, suggestive of severe renal disease,
12. Severe Proliferative retinopathy,
13. Niacin treatment,
14. History of peptic ulcers,
15. History of hereditary angioedema, and
16. C1 esterase deficiency.