M.W. is a 48-year-old woman with a 15-year history of type 2 diabetes that has been treated with insulin for 13 years. She has a history of multiple sclerosis for 8 years, and had been relatively stable for 7 years on interferon (IFN) β-1b injections.

Recently she suffered from at least two exacerbations of the disease, requiring steroid therapy with intravenous methylprednisolone. She subsequently presented to the emergency room with uncontrolled diabetes (without acidosis). She also had a history of primary hypothyroidism (secondary to congenital absence of thyroid), hyperlipidemia, peripheral neuropathy, and nephropathy, but no evidence of hypertension or coronary artery disease.

From the time diabetes was diagnosed, her insulin regimen and dosage were modified several times. She received a thiazolidinedione (TZD) for a brief period, which was later discontinued because of bilateral lower extremity swelling. Her diabetes remained uncontrolled after the above hospitalization despite increases of her insulin dose to 52 units of glargine in the morning with 10–12 units of lispro with each meal. The fasting, premeal, and bedtime blood glucose levels remained at 270–330 mg/dl. Therefore, twice-daily metformin (up to 1,000 mg twice daily) was added.

The dose of glargine was gradually increased based on her blood glucose profile up to 200 units in the morning and 240 units at bedtime, with 130 units of lispro with meals. Her blood glucose levels remained in the 400 mg/dl or higher range. The patient remained relatively asymptomatic except for dry mouth.

She was admitted to the hospital electively for planned intravenous insulin therapy in order to break the glucose toxicity. Her lab results were remarkable for normal carbon dioxide and a normal anion gap. Her blood glucose decreased temporarily to 150–180 mg/dl after up to 10 units/hour of regular insulin infusion. It remained in this range for only 48 hours and then increased again to 500–600 mg/dl.

Her medication list included levothyroxine, 100 μg daily; glargine and lispro insulins; metformin, 1,000 mg twice daily; neurontin, 600 mg three times daily; and daily IFN β-1b injections. Both an angiotensin-coverting enzyme inhibitor and an angiotensin receptor blocker were previously discontinued because of dizziness and low blood pressure (in the range of 90/50–100/60 mmHg).

The Physician Drug Reference lists diabetes as one of the side effects of IFN β-1b treatment. Therefore, M.W.’s neurologist was consulted regarding switching the patient to an alternative, IFN β-1a, which does not list diabetes as a known side effect. IFN β-1b was discontinued, and IFN β-1a was introduced. Her blood glucose profile improved remarkably, with fasting and premeal levels in the 86–138 mg/dl range. Her insulin requirement dropped dramatically to 45 units of glargine at bedtime and 3–4 units of lispro with meals. M.W.’s hemoglobin A1c while on IFN β-1b treatment was 12.7%. After 7 weeks of IFN β-1a treatment, it improved to 7.1%.

  1. Can worsening of glycemic control in type 2 diabetes be associated with IFN β-1b treatment?

  2. Can substituting IFN β-1a for IFN β-1b result in better control of blood glucose?

Type 2 diabetes is the result of insulin resistance in the peripheral tissues, together with relative impairment of α-cell insulin secretion. Type 1 diabetes is an autoimmune disease resulting from destruction of α-cells. Cytokines, such as interleukin 2 and α-interferon (α-IFN), can enhance immune functions and initiate or augment an autoimmune process.1 

Stimulation of immune responses may have deleterious consequences. Cytokine-induced exacerbation of underlying diseases or immune dysregulation are examples. α-IFN may enhance an ongoing autoimmune process directed against pancreatic α-cells and be involved in the development of type 1 diabetes in predisposed patients.2,3 

α-IFN treatment has now been clearly linked to the exacerbation or occurrence of several types of autoimmune diseases (thyroiditis, systemic lupus erythematosis, hemolytic disease, as well as type 1 diabetes) and diseases involving altered cell-mediated immune functions (inflammatory dermatological diseases, nephritis, colitis, pneumonitis).4 In contrast, immunological side effects of IFN β and IFN γ (another IFN) have been seldom reported, although a case of type 1 diabetes induced by administration of IFN β has been reported.5 

Interferon β (both 1a and 1b) is now the most widely prescribed therapy for long-term immunomodulation of multiple sclerosis. The recombinant IFN β requires continued administration to decrease disease activity.

IFN, produced in many viral infections, stimulates counter-regulatory hormone secretion, impairs glucose tolerance and insulin sensitivity, and increases insulin clearance.6 

Flu-like symptoms, transient worsening of multiple sclerosis (especially spasticity), laboratory abnormalities, subcutaneous necrosis, and inflammation at the injection site are common side effects. Delayed occurrence of a severe cutaneous reaction has been reported in a multiple sclerosis patient taking IFN β-1b.7 

The mechanism of the development of worsening glycemic control in this patient with type 2 diabetes is not clear. One may speculate based on the observed effects of IFN β-1b that one of two mechanisms occurred:

  1. Worsening of peripheral insulin resistance

  2. Transient damage to pancreatic β-cells via enhancement of an autoimmune process and temporary insulin deficiency.

Either of these phenomena could have resulted in her metabolic deterioration.

  • IFN β-1b must be used with caution in patients with documented diabetes or known predisposition toward developing the disease.

  • Therefore, in patients with preexisting diabetes, IFN β-1a may be desirable because it is less likely to cause worsening of diabetes control.

Hema Padmanabhan, MD, was an endocrinology associate at Geisinger Health System in Wilkes-Barre, Pa., at the time of submission of this article.

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