Circulating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion, and impact on glucose control

Abstract

The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence, but not completely suppressed, the development of anti-insulin antibodies (IAs). Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), continuous peritoneal insulin infusion (CPII) and more recently inhaled insulin administration, appear to significantly increase circulating levels of immunoglobulin G (IgG) anti-IAs in diabetic patients. However, the increase is usually moderate and mostly transient as compared to previous observations with poorly purified animal insulin preparations. The clinical impact of these circulating anti-IAs remains unclear. Nevertheless, several studies have suggested that antibodies could retard insulin action, leading to a worsening of postprandial hyperglycaemia and/or serve as a carrier, thus leading to unexpected hypoglycaemia. CPII may be associated with more marked and sustained increase in IAs levels, possibly related to the use of an unstable insulin and the formation of immunogenic aggregates of insulin. The possible clinical consequences of these high levels of IAs remain to be evaluated because a low-glucose morning syndrome or severe insulin resistance with ketone bodies production have been reported in some cases. In conclusion, even if CSII and CPII may promote the development of circulating IAs, this increase does not lead to immunological insulin resistance, compared to that previously described with animal non-purified insulin preparations, and seems to have only marginal influence on blood glucose control or complications in most diabetic patients.

The Role of “Mixed” Orexigenic and Anorexigenic Signals and Autoantibodies Reacting with Appetite-Regulating Neuropeptides and Peptides of the Adipose Tissue-Gut-Brain Axis: Relevance to Food Intake and Nutritional Status in Patients with Anorexia Nervosa and Bulimia Nervosa

“…Intriguingly, this is a potentially analogous situation in which autoantibodies against insulin may play a role in the shifts of bioavailable levels of insulin with possible effects on hypoglycemia. Involvement of insulin autoantibodies in insulin resistance has been extensively studied as a mechanism underlying insulin resistance after insulin administration [49] and autoantibodies against insulin have been studied as a marker of type 1 diabetes [50]. Using homeostasis model assessment of insulin resistance (HOMA-IR), we found significantly lower values of HOMA-IR in malnourished and underweight AN patients when compared with the controls [28, 29].…”

Impact of Gemini Surfactants on the Stability of Insulin using Computational Tools

“…Formation of aggregates may cause the altered release profile of insulin in the body and further it may cause the normoglycemia [33][34][35][36][37][38][39][40]. Interaction between insulin and the Gemini surfactants was studied and total energy was calculated.…”

Is insulin pro-atherogenic at the cellular level?

“…They were characterized by rather low level of antibodies to insulin (less than 50 nU/mL), therefore, the possibility of insulin resistance attributable to antibodies was excluded [18] . The type of diabetes was verified according to recommendations from the American Diabetes Association [19] .…”