Evaluating the Effects of a Study Medication on Exercise Function in Type 2 Diabetes

Not Applicable

Completed

Conditions: Type 2 Diabetes

Interventions: Drug: Placebo
Drug: Acipimox

Registration Number: NCT01580813

Lead Sponsor: University of Colorado, Denver

Brief Summary: People who are overweight or who have type 2 diabetes mellitus (T2DM) have higher levels of certain fats in their blood. The blood vessels and heart of most of these individuals do not work normally and people with T2DM also have an impaired ability to perform exercise. The purpose of this study is to use the free fatty acid lowering drug, acipimox, to temporarily decrease the level of fat in the bloodstream of people with T2DM and observe the physiological changes to blood vessel function and exercise capacity and insulin sensitivity. This will help the investigators to understand ways of improving blood vessel function and the ability to exercise effectively in people who are overweight or have T2DM.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Sedentary adults not participating in a regular exercise program (≤ one bout of scheduled exercise per week)
Subjects must have Type 2 Diabetes
Subjects must be otherwise healthy
Ages of 30-60 years
BMI of 25-39 and stable weight for 3 months prior to the start of the study
Diabetes controlled by diet +/- insulin secretagogues (sulfonylureas or glinides), metformin, or glucose absorption blockers (acarbose).
Total glycosylated hemoglobin levels (HbA1C) ≤9% (fair control) on current therapy.

Exclusion Criteria

Any comorbid condition which could limit exercise performance including Chronic Obstructive Pulmonary Disease (COPD) or asthma
Concurrent enrollment in an interventional study.
Any tobacco use either current or within the last year
Clinically evident distal symmetrical neuropathy, determined by evaluation of symptoms (numbness, paresthesia) and signs (elicited by vibration, pinprick, light touch, ankle jerks), will be excluded.
Autonomic dysfunction (>20 mm fall in upright BP without a change in heart rate) will be excluded.
Evidence of ischemic heart disease by history or abnormal resting or exercise electrocardiogram (EKG) (> 1 mm ST segment depression) on screening exercise test.
Angina or any other cardiovascular, pulmonary or musculoskeletal symptoms
Presence of systolic blood pressure >190 at rest or >250 with exercise or diastolic pressure >95 at rest or >105 with exercise
Proteinuria (urine protein >200 mg/dl) or a creatinine > 2 mg/dl, suggestive of severe renal disease
Proliferative retinopathy
Insulin, incretin, or glitazone treatment
Niacin treatment
History of peptic ulcers
A history of hereditary angioedema
C1 esterase deficiency
Women who are pregnant or breastfeeding
Use of fibrate drugs

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Subjects will take a placebo pill 250mg (randomized and double-blinded) by mouth four times a day for six days prior to the visit and one dose the morning of study visit
Acipimox	Acipimox	Subjects will take acipimox 250mg (randomized and double-blinded) by mouth four times a day for six days prior to the visit and one dose the morning of study visi

Primary Outcome Measures

Name	Time	Method
Evaluate the Impact of Acipimox on Exercise Parameters in People With Type 2 Diabetes: VO2 Kinetics	7 to 9 days	Evaluate the impact of these effects of NEFA-lowering VO2 kinetics as measured by tau2, the time required for VO2 to reach 67% of peak during submaximal exercise.
Evaluate the Impact of Acipimox on Exercise Parameters in People With Type 2 Diabetes: Peak VO2	7 to 9 days	Evaluate the impact of these effects of NEFA-lowering on exercise capacity measured as peak VO2.

Secondary Outcome Measures

Name	Time	Method
Triglycerides	7 to 9 days
Evaluate the Impact of Acipimox on Exercise Parameters in People With Type 2 Diabetes: Power Output at Anaerobic Threshold and at Peak Exercise	7 to 9 days	Evaluate the impact of these effects of NEFA-lowering on exercise parameters, including VO2 kinetics, peak VO2, peak heart rate, peak power output.
Evaluating the Effect of Acipimox on Insulin Sensitivity and Cardiovascular Function: Endothelial Function	7 to 9 days	Test the hypothesis that lowering of endogenous non-essential fatty acids (NEFA) in diabetic adults will improve endothelial function measured by flow mediated dilation of the brachial artery.
Evaluating the Effect of Acipimox on Insulin Sensitivity and Cardiovascular Function: Cardiac Function	7 to 9 days	Test the hypothesis that lowering of endogenous non-essential fatty acids (NEFA) in diabetic adults will improve cardiac function: echo measurement of resting ejection fraction
Insulin Sensitivity	7 to 9 days	Test the hypothesis that lowering of endogenous non-essential fatty acids (NEFA) in diabetic adults will improve insulin sensitivity measured as glucose disposal by hyperinsulinemic euglycemic clamp. Unit of measure is mg/kg of lean body mass/min/microIU of insulin/ml. The unit of measure reflects the rate at which glucose needs to be infused to maintain a normal blood sugar in the setting of a given serum insulin level from an insulin infusion. As such, a higher number means more glucose was needed and indicates greater sensitivity to insulin.
Evaluate the Impact of Acipimox on Exercise Parameters in People With Type 2 Diabetes: Peak Heart Rate	7 to 9 days	Evaluate the impact of these effects of NEFA-lowering on exercise parameters, including VO2 kinetics, peak VO2, peak heart rate, peak power output.
Evaluating the Effect of Acipimox on Insulin Sensitivity and Cardiovascular Function: Inflammation	7 to 9 days	effect of lowering of endogenous non-essential fatty acids (NEFA) in diabetic adults on inflammation (hsCRP)