Weight Gain, Improvements in Metabolic Profiles and Immunogenicity with Insulin or Sulphonylurea Administration in AIDS

Excerpt

AIDS is one of the most common progressively wasting disorders of our times.[1‐8] Malnutrition responsible for promoting the wasting, weakness and debilitation is multifactorial in origin and may also be responsible for an increased incidence of complications and premature deaths.[9,10] Moreover, a direct correlation is demonstrated between nutritional status and immune function.[3,5,8‐11] Therefore, several other therapeutic options have been implemented in inducing reversal or retardation of the progression of the wasting. These measures have included highly active antiretroviral therapy (HAART), home enteral or parenteral nutrition, administration of human growth hormone, insulin-like growth factor 1 (IGF1), thymus preparations and anabolic steroids, i.e. megestrol, in AIDS subjects of both sexes as well as administration of testosterone in men, with variable success and enormous costs.[3,5,12‐27] Moreover, the progressive wasting seen in this disorder has prompted efforts in development of new safer anabolic steroids.[28,29] However, insulin, probably the most potent anabolic substance known to the medical community, has never been used in slowing the wasting noted in any chronic disease. The most probable reason for the lack of insulin use must be the fear of the frequent occurrences of hypoglycaemic episodes if used in euglycaemic individuals. Moreover, it is likely that insulin secretagogues, such as sulphonylurea drugs, known to increase endogenously circulating insulin levels, also have never been used for the same reason. The fear appears legitimate as evidenced by the increased frequency of severe hypoglycaemic events, which occurred when attempts were made to achieve normalisation of diurnal glycaemia by using intensive insulin therapy in subjects with type 1 diabetes mellitus participating in the Diabetes Control and Complications Trial, as well as type 2 diabetic subjects treated with insulin or sulphonylureas in the UK Prospective Diabetes Study (UKPDS).[30,31] However, recent preliminary studies in an attempt to prevent or delay onset of type 1 diabetes in prediabetic normoglycaemic relatives of known type 1 diabetic probands documented no significant increase in hypoglycaemic events.[32,33] National Institutes of Health in a joint effort with the American Diabetes Association has reported on a nationwide clinical trial with subcutaneous insulin administration for primary prevention of type 1 diabetes in susceptible subjects.[34] Moreover, we noted in a preliminary report marked improvement in well-being, including weight gain and normalisation of several laboratory parameters including raised CD4 counts suggestive of better immunogenicity on subcutaneous insulin administration for 3–6 months on two different separate occasions in a subject with AIDS.[35] Therefore, we assessed the effect of either subcutaneous insulin administration or oral sulphonylurea administration for 6 months in conjunction with antiretroviral drug therapy in subjects with AIDS. …