Could you please explain to me in detail how NPH works? I am especially interested in how the insulin molecule is released into the blood stream detaching itself from its binding to protamine. I have read that protamine may cause the immune system to make antibodies to the insulin. Is this the cause of the unpredictable peaks of NPH? Any references to current research will be greatly appreciated.

PS: I am having difficulties making NPH work for me and it is not so easy to obtain slow acting analogues in Denmark (Detemir and Lantus not available yet).

Protamine attached to insulin creates NPH, Neutral Protamine Hagadoorn, named after Dr. Hagadoorn who first figured out how to delay insulin absorption with the addition of the protamine decades ago. This happens somewhat irregularly and this unpredictability leads to some variation in blood glucose control from patient to patient and also from injection to injection. Using small amounts of NPH in an overlapping fashion severely times each day in a multidose insulin regimen often will be helpful if you are having day to day inconsistencies. Making sure that there are minimal variations in food amounts and timing of meals will also be helpful as much as this is possible.

For many of our patients, we used Humalog or NovoLog with NPH premeals in a four or five shot daily regimen with carbohydrate counting to help adjust doses of the fast acting insulins in a basal-bolus program. This mimics the best effects of an insulin pump quite effectively. Lately we have switched to Lantus using the Lantus (glargine) as a more smooth and therefore more predictable basal insulin once or twice each day. All this is guided by blood glucose profiles. There is not much that you can do if the NPH is acting irregularly except to minimize the effects of food and site of injection and see if this helps. Discuss this with your diabetes team and see what they think.

A short ride into Germany may allow you to purchase some Lantus if Lantus and detemir insulin is not yet available in Denmark.

SB