Blood glucose response to stress hormone exposure in healthy man and insulin dependent diabetic patients: prediction by computer modeling

Abstract

To establish a qualitative and quantitative model of blood glucose response to stress hormone exposure, healthy subjects (HS) on and off somatostatin (250 micrograms/h) as well as insulin dependent diabetic patients were infused with either epinephrine (E), glucagon (G), cortisol (F), growth hormone (GH) or with a cocktail of these hormones raising plasma stress hormones to values seen in severe diabetic ketoacidosis. The developed input/output model consists of two submodels interconnected in series plus two additional submodels for correction of gains describing both sensitivity of tissue response and utilisation as well as provision of glucose. It was shown and confirmed experimentally that blood glucose response to stress hormones was essentially nonlinear. Furthermore, the mathematical models for healthy subjects and for insulin dependent diabetic patients proved to be of the same structure and differed only in the values of some typical parameters. The model raises the possibility to describe and in part to predict blood glucose response to stress hormone exposure in healthy man and insulin dependent diabetic patients.

Both acute and chronic near-normoglycaemia are required to improve insulin resistance in Type 1 (insulin-dependent) diabetes mellitus

“…insulin (groups A and C), causes peripheral insulin resistance but rather short-term hyperglycaemia, i. e. an acute increase in the glucose/insulin ratio. Thus, fasting glycaemia but not HbAlc values was related inversely to Mvalues (p < 0.001) and directly to HGP (p < 0.0001) for groups A, B, C and D. These findings are in line with the observation that fasting hyperglycaemia decreases glucose uptake in Type 1 diabetes [26] and determines blood glucose response to subsequent stress hormone exposure [27]. Similarly, correction of hyperglycaemia by 7 days of phlorizin administration has been shown to normalize peripheral insulin action in streptozotocin-diabetic rats, while low-dose insulin treatment at persistent hyperglycaemia was of no avail [28].…”

“…Some data suggest that glucose "toxicity" [29] operates even in the presence of normal or elevated basal serum insulin concentration and prevents insulin action from returning to normal. From this a decisive role has to be attributed to "acute glucose toxicity" [27,29,30] in the development of insulin resistance, which most likely results from any hyperglycaemic state, i.e. both in Type 1 and Type 2 diabetes.…”

Quantitation of basal endogenous glucose production in Type II diabetes: importance of the volume of distribution

“…In fact, it seems that cortisol [139] contributes to the dawn phenomenon in patients with Type II diabetes since deletion of cortisol secretion during the night with metyrapone, also decreased the early morning glucose excursion [140]. The correlation between EGP and cortisol [137] is also consistent with a 4 to 6 h delay in its action on glucose metabolism [141,142,143]. Other studies have shown an influence of sleep on subsequent glucose metabolism [144,145].…”

Acute mental stress impairs insulin sensitivity in IDDM patients

“…This was, however, not unexpected, since it has been considered that the relationship between stress and blood glucose response is essentially non-linear [17] and, furthermore, that the interrelationship between the different stress hormones is a complex one. Thus, previous studies on post-hypoglycaemic insulin resistance are not conclusive whether cortisol alone causes an impairment of the insulin sensitivity, whereas it clearly elicits an amplification of the GH effect in this situation [7,18].…”