Clinical approach to the patient with diabetes mellitus and very high insulin requirements

Abstract 

A number of patients with diabetes require very high (>2Ukg⁻¹day⁻¹), or extremely high (>3Ukg⁻¹day⁻¹), insulin doses for the management of their hyperglycemia. Unfortunately, many of the physicians who treat these patients limit themselves to prescribing ever higher doses of insulin, without questioning why. Furthermore, when the insulin requirements get to be extreme, demanding an explanation, clinicians are frequently lost in a sea of literature where there is not a single paper dealing with this problem systematically.

A systematic approach to the evaluation of these patients is necessary to facilitate an appropriate diagnosis, select the most reasonable therapy, and hopefully improve the long-term outcome of these patients. This manuscript intends to provide the clinician with a review of the literature pertinent for the differential diagnosis, work-up, and management of these patients.

We will review the definitions of insulin sensitivity during normality, the various degrees or categories of insulin resistance, and the expected insulin requirements during each of these states. Subsequently, we propose a simple alphabetic mnemonic approach to help remember the differential diagnosis, and a clinical algorithm to help guide the work-up of these patients. Lastly, we briefly discuss general management considerations in these conditions.

Abbreviations: ANA, anti-nuclear antibodies, CFTDM, congenital fiber type disproportion myopathy, EIR, euglycemic insulin requirement, FSIVGTT, frequently sampled intravenous glucose tolerance test, GH, growth hormone, GnRH, gonadotropin releasing hormone, HAIRAN, hyperandrogenism, insulin resistance, acanthosis nigricans, HIV, human immunodeficiency virus, IGF-1, insulin like growth factor, IGFBP-1, insulin like growth factor binding protein-1, IR, insulin receptor, ITT, insulin tolerance test, LDHIV, lipodystrophy in HIV-infected patients, MyD, myotonic dystrophy, PI, protease inhibitors, SHBG, sex hormone binding globulin, SIR, subcutaneous insulin resistance, SSIR, syndrome of sever insulin resistance, TDID, total daily insulin dose, TSH, thyroid stimulating hormone

Keywords: Diabetes, Insulin, Algorithm, High insulin requirement, Severe insulin resistance, Extreme insulin resistance