Could intranasal insulin be useful in the treatment of non-insulin-dependent diabetes mellitus?

Abstract

To evaluate whether intranasal insulin might be useful as a meal-adjunct in the treatment of NIDDM we compared plasma glucose and insulin responses to a mixed breakfast (9 kcal/kg, 50% carbohydrate) following either intranasal insulin (INI) or placebo in eleven patients with NIDDM. Five patients treated with subcutaneous insulin and in good to moderate glycemic control and six patients who were ‘failing’ on oral agents and in poor glycemic control were studied. In the patients usually on sc insulin, INI inhibited postprandial hyperglycemia. Lower doses (1 U/kg vs 1.5 U/kg b.w.) were needed to accomplish this in 2 patients with low fasting glucose (≤7.8 mmol/l) than in three patients with higher fasting glucose (10.5 ± 0.5 mmol/l). In the patients on oral agents who had marked fasting hyperglycemia (14.8 ± 0.8 mmol/l) an only transient reduction (for 90 to 120 min) of postprandial hyperglycemia was achieved when INI (1 U/kg) was given in addition to po glyburide (10 mg) prior to the meal. Following placebo in the group previously treated with sc insulin, plasma free insulin levels increased maximally by 23 mU/l, 75 min after the meal. The group on oral agents had a comparable but later peak increment (at 180 min) indicative of an even greater impairment of endogenous insulin secretion in response to hyperglycemia. Following INI, the peak increment in plasma insulin occurred earlier (30 min after the meal) and was greater in all patients (55 ± 18, 139 ± 68, 86 ± 24 mU/l respectively for the prior sc insulin therapy group at doses of 1.0 and 1.5 U/kg and for the oral agent group at 1.0 U/kg). In summary, intranasal insulin can reduce postprandial hyperglycemia in patients with NIDDM by increasing early postprandial insulin levels. It is more effective in those with less severe fasting hyperglycemia. Since elevated insulin levels and glucose lowering effect are transient, nasal insulin would need to be added to a regimen achieving fasting glucose control through diet, oral agents or long-acting subcutaneous insulin.