Mitochondrial Dysfunction and Diabetes

Case described in conference. Young man with DM and hearing loss. Has a history of some muscle weakness and seizures. --> Dx is MELAS Syndrome.

The Mitochondrial Myopathy Encephalopathy, Lactic Acidosis with Stroke-Like Episodes (MELAS) Syndrome

Sx:

• weakness that may progress to further deterioration in neuromuscular function.
• Headaches, nausea or vomiting.
• Stroke-like episodes (usually occur before 40 years of age).
  
• Encephalopathy--> seizures, dementia, or both.
• Lactic Acidosis (other members of faculty noted that they have had cases present in the cath-lab with severe lactic acidosis)
  
• Normal Weight (cases noted to have BMI of 17-20)...many felt that due to mitochondrial dysfunction, these patients have a high REE.
• Neurosensory deafness (A young man with diabetes, hearing aid, and a mother with diabetes--> what is the mode of inheritance?).

Pathogenesis: Mitochondrial DNA mutation that leads to dysfunction--> inability to generate ATP in response to glucose in beta-cell--> leads to ineffective insulin secretion.

Tx:

• Diet: primary mode of therapy
• Exercise: not as effective since most have some form of myopathy
• Sulfonylureas: good choice
• Metformin: should be avoided due to high rate of lactic acidosis
• TZD: again most faculty would avoid due to high prevalence of cardiomyopathy and risk of further worsening heart failure.
• Insulin: good choice as well.
  

References:

1. MELAS: a review of treatment options. CNS Drugs; 2006, Vol. 20 Issue 6, p443.
2. Mitochondrial gene defects in NIDDM. Diabetologia 37; 818-825
3. Mitochondrial Cytopathies; J neurol 250:267-277