Counterpoint: Appreciating Homeostasis Model Assessment

Abstract

The insulin-deficient mechanism for diabetes, discovered around a century ago, was questioned by observations on the human response to intravenous insulin (1). Later, it was more severely challenged by the raised plasma insulin values usually found by radioimmunoassay in type 2 diabetic subjects (2), then and since rapidly increasing in number, and often with accompanying adiposity (3). At this time, the pathogenesis of type 2 diabetes was unknown, and it seemed crucial to determine whether it was essentially based on increased resistance to the hypoglycemic action of insulin or on failing β-cells with secondary gluco- and lipotoxicities. Could this be determined from the glucose and insulin levels of single or duplicate basal blood samples? If so, epidemiological logistics might be transformed, without the need for stimulated tests or tests as sophisticated as measurement of the basal endogenous glucose production rate with tritiated glucose, and the calculation of postabsorptive hepatic insulin resistance to the hypoglycemic effect of insulin as the product of this and the overnight fasting insulin concentration (4). Basal and stimulated tests measure two different phenomena, rather than two different aspects of the same thing. In theory, the two islet cell states do not need to be closer than are muscular activity in movement and in posture. There will always be common features (e.g., muscle bulk), and, indeed, there are consistent positive relationships between basal and poststimulation insulin. However, there are also many different properties with altered membrane potentials (e.g., in the basal state, there is no influence on β-cell activity from recent glucose variation [5], which presumably leaves β-cells aware of changes in glucose). Additionally, the various clamp tests do not measure basal function, for while they involve steady states, clamp tests follow considerable interference. In these tests, insulin action in muscle is the major …