The relationship between glucose tolerance, plasma insulin and corticosteroid therapy in patients with Rheumatoid Arthritis

McKiddie, M. T.; Jasani, M K; Buchanan, K. D.; Boyle, James A.; Buchanan, W. Watson

doi:10.1016/0026-0495(68)90058-9

Cited by 29 publications

(11 citation statements)

References 23 publications

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“…All corticosteroids with glucocorticoid action may cause overt diabetes. It has been claimed that the chronic effects on glucose tolerance are less pronounced than the acute effects and that the development of frank diabetes mellitus in a previously normal patient is unusual [Olefsky and Kimmerling, 1976;McKiddie et al, 1968]. Severe ketoacidosis is unusual and when hyperglycaemic coma occurs it is of the non-ketotic type [Boyer, 1967], No patients in this study developed ketoacidosis or a hy perosmolar non-ketotic diabetic coma and the incidence of diabetes was in reasonable agreement with the 5.5-14% incidence rate quoted for younger patients [de Lange et al, 1975].…”

Section: Discussionmentioning

confidence: 99%

The Complications of Systemic Corticosteroid Therapy in the Elderly

Thomas¹

1984

Gerontology

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The complications of long-term corticosteroid therapy were reviewed in 100 elderly patients who were treated for chronic obstructive airways disease (n = 76), rheumatoid arthritis (n = 19) and ulcerative colitis (n = 5). The incidence of side effects was high (40%) and appeared to be dose-related. Osteoporosis (16%) and hypertension (12%) were the most common. Hypokalaemia occurred infrequently despite the fact that 69 patients were also prescribed diuretics. A further group of 36 patients receiving corticosteroids for polymyalgia rheumatica and giant cell arteritis also seemed to demonstrate a dose-related effect on the incidence of complications although this could not be confirmed statistically.

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Section: Discussionmentioning

confidence: 99%

The Complications of Systemic Corticosteroid Therapy in the Elderly

Thomas¹

1984

Gerontology

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“…Since the effects of glucocorticoid hormones in these cells are first seen within physiological concentrations, these changes may help explain the derangements in glucose metabolism seen in both hypo-and hyperadrenocortical states. (Endocrinology 109: 1723,1981) G LUCOCORTICOID excess results in insulin resistance as well as glucose intolerance in man and experimental animals (1)(2)(3)(4)(5)(6). This insulin resistance is manifested by hyperglycemia in the face of hyperinsulinemia (2,3) and decreased response to exogenous insulin (4,5).…”

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confidence: 95%

Glucocorticoid-Induced Insulin Resistance in Vitro: Evidence for Both Receptor and Postreceptor Defects*

et al. 1981

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Glucocorticoid excess in vivo has been shown to cause decreases in insulin sensitivity and insulin receptor binding in target tissues. It has not been previously possible to produce all of these changes in vitro because of limitations of the isolated rat adipocyte as an experimental model. We have studied the effects of glucocorticoid hormones on insulin binding and insulin action in differentiated mouse 3T3-L1 fatty fibroblasts, in an attempt to develop a complete in vitro model of the insulin resistance associated with glucocorticoid excess. Exposure of 3T3-L1 cells to dexamethasone, a synthetic glucocorticoid, resulted in decreased binding of insulin to its receptor and decreased insulin stimulation of 2-deoxyglucose uptake. Although some effect of dexamethasone on these parameters was observed after 24 h, more than 3 days were required for maximal inhibition of both binding and biological response. The magnitude of these changes was concentration dependent over a range of 0.1-100 nM dexamethasone. Exposure to hydrocortisone produced similar changes, although higher concentrations were required. Cortexolone and deoxycorticosterone, compounds which weakly interact with the glucocorticoid receptor, caused partial inhibition of insulin action. Estradiol, testosterone, and methyl testosterone were inactive.When analyzed by Scatchard plots, the defect in insulin binding was identical to that seen when rodents were treated in vivo with glucocorticoids, namely a decrease in the affinity of the receptor for insulin, with little change in receptor concentration. A marked decrease in the sensitivity of dexamethasonetreated cells to insulin was seen, as well as a reduction in the ability of insulin to maximally stimulate 2-deoxyglucose uptake. When the binding and biological activity data were compared, the decreased affinity of the insulin receptor appeared to account for much, but not all, of the decrease in insulin sensitivity. Some postreceptor changes must also occur to account for the decrease in both maximal responsiveness and insulin sensitivity. In summary, we have been able to demonstrate in cultured cells each of the components of glucocorticoid-induced insulin resistance seen in vivo. Since the effects of glucocorticoid hormones in these cells are first seen within physiological concentrations, these changes may help explain the derangements in glucose metabolism seen in both hypo-and hyperadrenocortical states. (Endocrinology 109: 1723 , 1981) G LUCOCORTICOID excess results in insulin resistance as well as glucose intolerance in man and experimental animals (1-6). This insulin resistance is manifested by hyperglycemia in the face of hyperinsulinemia (2, 3) and decreased response to exogenous insulin (4, 5). Similarly, insulin sensitivity is increased in adrenal insufficiency (4, 6).

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“…Insulin resistance, as manifested by glucose intolerance in the face of hyperinsulinemia, is a known sequela of in vivo corticosteroid administration (1,2). It is well established in vitro that corticosteroids decrease the ability of isolated adipocytes (3)(4)(5) and muscle tissue (6) to oxidize glucose, and the potential relationship between these in vitro observations and in vivo insulin resistance is obvious.…”

Section: Introductionmentioning

confidence: 99%

Effect of dexamethasone on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes.

Olefsky¹

1975

J. Clin. Invest.

273

128

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A B S T R A C T We have studied the in vitro effects of dexamethasone on isolated rat adipocytes at concentrations of dexamethasone therapeutically achieved in man. Glucose oxidation, glucose transport, and insulin binding were assessed. In dexamethasone-treated cells, glucose oxidation was decreased by 30-40% both in the absence of insulin (basal state) and at low insulin levels (less than 25 AsU/ml). At maximally effective insulin levels (over 100 F'U/ml) no differences existed between control and treated cells. If glucose transport were the ratelimiting step for glucose oxidation in the basal state and at low (submaximal) insulin levels, but not at maximally effective insulin concentrations, then these data could be explained by postulating that dexamethasone has a direct affect on glucose transport and does not affect intracellular oxidative pathways. We tested this hypothesis by directly assessing glucose transport in dexamethasone-treated cells. Glucose transport was assessed by measuring the uptake of [14C]2-deoxy glucose. These studies demonstrated a 30-40% decrease in 2-deoxy glucose uptake by treated cells both in the basal state and at all insulin concentrations. Thus, a direct glucocorticoid effect on the glucose transport system seems to account for the decreased ability of dexamethasone-treated cells to oxidize glucose. Since dexamethasone treatment leads to decreased insulin binding to adipocytes in vivo, we examined the possibility that the in vitro decreases in insulin-mediated glucose transport could be due to decreased insulin receptors. Insulin binding to control and treated adipocytes was measured, and no differences were found. Therefore, in contrast to previously reported in vivo studies, adipocytes treated in vitro with Dr. Olefsky is a Restarch Associate with the Veterans Administration (MRIS #6488).

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The relationship between glucose tolerance, plasma insulin and corticosteroid therapy in patients with Rheumatoid Arthritis

Cited by 29 publications

References 23 publications

The Complications of Systemic Corticosteroid Therapy in the Elderly

The Complications of Systemic Corticosteroid Therapy in the Elderly

Glucocorticoid-Induced Insulin Resistance in Vitro: Evidence for Both Receptor and Postreceptor Defects*

Effect of dexamethasone on insulin binding, glucose transport, and glucose oxidation of isolated rat adipocytes.

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