Beneficial Effect of Diabetes on Acute Intermittent Porphyria

Acute Intermittent Porphyria (AIP) is an autosomal hereditary metabolic aberration resulting from a partial defect in the activity of the third-step enzyme (porphobilinogen deaminase [PBGD]) during the course of heme synthesis.  Carbohydrate ingestion blocks the enzyme d-aminolevulinic acid (ALA)- synthase.  The mechanisms by which carbohydrates modulate the components of porphyrins and heme synthesis are highly complex and only partially elucidated to date.

Long-term complications of AIP are polyneuropathy, hepatocellular carcinoma (HCC), and renal insufficiency. Treatment of AIP patients entails treating both the symptoms and the complications, but also requires an endeavor to reverse the fundamental disease by prescribing a carbohydrate-rich diet and by treating the attacks with intravenous infusions of glucose or heme.

In a study conducted in northern Sweden included a total of 16 patients (5 women) with AIP and type 2-diabetes with a mean age of 67 years. Eight of these patients had AIP symptoms, with three patients suffering severe, recurring attacks. After the onset of their diabetes, no patient suffered attacks or any other AIP symptoms.  Recurrent AIP attacks ceased when the patients became diabetic. None of the 16 diabetic patients with AIP had HCC. In another study, of all the 30 AIP patients with HCC registered, none had diabetes, whereas in a population-based group of individuals in southern Sweden (mean age 67 years), diabetes was found in 12.8% of the men and 15.0% of the women. This suggests that diabetes also counteracts HCC in AIP patients, probably by normalization of ALA.

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