Mechanisms Responsible for Cardiac and Skeletal Muscle Energetic Impairment in Diabetes

Mechanisms Responsible for Cardiac and Skeletal Muscle Energetic Impairment in Diabetes

Diabetes increases the risk of heart failure. This is mainly due to a disease of the blood vessels supplying the heart muscle and/or high blood pressure, but abnormal metabolism may also contribute. We plan to study the mechanisms involved in this abnormal metabolism, whilst also assessing the effects of a drug called Perhexiline which improves the abnormal metabolism that is present in diabetic patients before the development of heart failure.

Inclusion Criteria:

• Diabetes Mellitus(WHO definition)
• HbA1C <9
• No history of chest pain
• No evidence of Coronary Artery Disease or peripheral vascular disease
• Left ventricular ejection fraction over 50%
• No evidence of respiratory disease

Exclusion Criteria:

• Patients < 16years or who cannot provide informed consent
• Evidence of significant epicardial coronary artery disease
• Evidence of peripheral vascular disease
• Abnormal liver function tests
• Clinically apparent peripheral neuropathy
• Severe chronic renal failure (creatinine >250) or diabetic nephropathy
• Concomitant use of Amiodarone, Quinidine, Haloperidol or Selective serotonin (5HT) uptake inhibitors such as Fluoxetine and Paroxetine which may inhibit the CYP2D6 enzyme
• Patients on statin therapy for primary dyslipidemia.
• Patients with recurrent hypoglycaemia
• Women of child bearing age who are not using effective contraception (or if pregnancy test positive)