Chronic administration of nicotinic acid (NA) has been shown to cause a deterioration in glycemic control in diabetic patients (1,2). Acute use of NA inhibits lipolysis in adipose tissue suppressing circulating nonesterfied fatty acid (NEFA) levels. Once the effect of NA abates, NEFA levels increase above baseline (3). According to the Randle cycle hypothesis, when NEFA availability increases, NEFA oxidation occurs at the expense of glucose oxidation with a resultant reduction in glucose uptake by skeletal muscle and an increase in blood glucose levels (4).

Some patients with type 1 diabetes have frequent and often unpredictable hypoglycemic episodes. We hypothesized that the addition of regular oral NA to deliberately induce insulin resistance and increase blood glucose levels would result in an increase in insulin requirements and reduce the propensity to severe hypoglycemia. We report the cases of two patients with long-standing poorly controlled diabetes in whom NA has been used to decrease the occurrence of hypoglycemic episodes. Both patients understood and agreed to the use of NA in an experimental fashion.

A 49-year-old woman with a 30-year history of type 1 diabetes complicated by a painful peripheral neuropathy and autonomic neuropathy (gastroparesis and chronic constipation) reported a long-standing history of erratic blood glucose control and daily hypoglycemic episodes interspersed with marked hyperglycemia. Her insulin requirments were 30–35 U daily. Following an addition of 1.25 g NA daily, insulin requirments increased to 70–75 U daily. There was a more predictable pattern to her glucose levels; the patient felt better and reported a reduction in hypoglycemic episodes to less than once a week. After several months, the patient withdrew from use of NA because of recurrent nausea and vomiting. Blood glucose control again became erratic with more frequent hypoglycemic episodes. Insulin requirements returned to 30–35 U per day. The patient recommenced NA at 1.25 g daily with subsequent improvement in the rate of hypoglycemic episodes and an increase in her insulin requirements.

A 46-year-old woman with secondary diabetes resulting from chronic pancreatitis also suffered from recurring major hypoglycemic episodes. In addition to having chronic low back pain and coronary artery disease, she had exocrine pancreatic insufficiency that required the use of pancreatic enzymes, and she used methadone for the management of chronic narcotic dependency. The introduction of NA at 1.5 g daily did not change her insulin requirements but did cause a reduction in the reported frequency of major and minor hypoglycemic episodes.

The problems encountered by these two patients occur in a small number of patients with long-standing diabetes. Other potential causes of severe recurrent hypoglycemia were excluded, such as hypothyroidism, adrenal insufficiency, and celiac disease. Attempts to regulate blood glucose control through strict control of diet, physical activity, and changes to insulin regimens (including the use of lispro insulin and a return to bovine insulin) all failed to provide relief from symptoms. Both patients benefited from a reduced rate of hypoglycemia, and in the first patient there was an increase in insulin requirements. The malabsorption syndrome in the second patient may have had an impact on her response to the treatment.

We feel that NA therapy as a preventative treatment of recurrent hypoglycemia warrants further investigation in a larger group of patients with a formal randomized controlled trial.

Molnar GD, Berge KG, Rosevear JW, McGuckin WF, Achor RP: The effect of nicotinic acid in diabetes mellitus.
Garg A, Grundy SM: Nicotinic acid as therapy for dyslipidemia in non-insulin-dependent diabetes mellitus.
Fuccella LM, Goldaniga G, Lovisco P, Maggi E, Musatti L, Mandelli V, Sirtori CR: Inhibition of lipolysis by nicotinic acid and acipimox.
Clin Pharmacol Ther
Randle PJ, Garland PB, Hales CN, Newsholme EA: The glucose fatty acid cycle.

Address correspondence to Dr P. Davoren, Gold Coast Hospital, 108 Nerang St., Southport 4215, Australia. E-mail: