Paradigmas en diabetes esteroidea Diabetes esteroidea = Hiperglucemia postprandial y predominio vespertino. Prednisona 10 mg. Challenges in managing steroid-induced diabetes stem from wide fluctuations in post-prandial hyperglycemia and the lack of clearly defined treatment protocols. May 25, desayunoparadiabeticos difference type 1 type 2 diabetes – dieta de en diabetes mellitus diabetes esteroidea alcohol para diabeticos

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Since the advent of glucocorticoid diabets for autoimmune disease in the s, their widespread application has led to the concurrent therapy-limiting discovery of many adverse metabolic side effects. Unanticipated hyperglycemia associated with the initiation of glucocorticoids often leads to preventable hospital admissions, prolonged hospital stays, increased risks for infection and reduced graft function in solid organ transplant recipients.

Challenges in managing steroid-induced diabetes stem from wide fluctuations in post-prandial hyperglycemia and the lack of clearly defined treatment protocols.

The mainstay of treatment is insulin therapy coincident with meals. This article aims to diabetse the pathogenesis, risk factors, diagnosis and treatment principles unique to steroid-induced diabetes.

Glucocorticoids are extensively used in almost every subspecialty of medicine. Indications for short-term acute steroid therapy can be seen in exacerbation of chronic obstructive pulmonary disease, acute gout, chemotherapy protocols, bacterial meningitis and in pregnant women for fetal lung maturation, to name a few. Disease processes benefiting from chronic glucocorticoid use include the following: More recently, chronic glucocorticoid therapy plays an important role in modulating the immune system following solid organ transplantation.

Although widely prescribed for their anti-inflammatory and immunosuppressive properties, glucocorticoids have various common metabolic side effects including hypertension, osteoporosis and diabetes.

Diabetes esteroidea en niños prepúberes: un diagnóstico por confirmar | Medicina Clínica

Steroid-induced diabetes mellitus SIDM siabetes been recognized as a complication of glucocorticoid use for over 50 years [ 1 ].

Steroid-induced diabetes mellitus is defined as an abnormal increase in blood glucose associated with the use of glucocorticoids in a patient with or without a prior history of diabetes mellitus. The length of time on steroids, the relative potency of the glucocorticoid and the absolute dose all play a role in the occurrence of SIDM.

In a retrospective study of 11 patients receiving various doses of glucocorticoids, Gurwitz et al. The dabetes odds ratio for patients receiving the equivalent of 50, and greater than mg of hydrocortisone daily were 3. In order to appreciate the magnitude of SIDM, one needs to consider that steroids cause predominantly post-prandial hyperglycemia and therefore, looking at impaired fasting glucose as diagetes sole criteria, may underestimate the true incidence of SIDM.

New onset diabetes after transplant NODAT is used to describe those patients in whom diabetes occurs for the first time in a post-transplant setting [ 5 ]. The incidence of NODAT is quite variable and likely underestimated because of lack of uniformity in the definition [ 6 ]. Varying immunosuppression protocols have caused discrepant incidence rates, although all agree that the incidence of NODAT is high in renal, liver, heart and lung transplant recipients Table 1 [ 7 — 10 ].

In addition, the presence of NODAT has an adverse outcome on the survival of the transplanted organ as well as the health of the recipient [ 10 ]. The population of patients following solid organ transplant is not the only population treated with glucocorticoids who develop SIDM: In addition, endogenous overproduction of glucocorticoids resulting in Cushing’s syndrome often translates to central obesity, muscle wasting, hepatic steatosis, hypertension and insulin resistance.

The effect of glucocorticoids on glucose metabolism is likely the result of impairment of multiple pathways including beta cell dysfunction sensitivity to glucose and ability to release insulin and insulin essteroidea in other tissue. The role of beta cell function and other tissues’ sensitivity to insulin may be different depending on whether the glucocorticoid effect is acute or chronic.

One study compared an acute single dose of prednisolone 75 mg with 30 mg of prednisolone daily for 15 days. The acute treatment esteoridea several parameters of beta cell function. Conversely, prolonged glucocorticoid exposure showed partial recovery of beta cell function but similarly impaired glucose tolerance, suggesting additional factors esteroidex important in SIDM other than beta cell dysfunction [ 14 ]. Furthermore, normoglycemic men given a bolus of either cortisol or corticotropin releasing hormone which causes an increase in endogenous cortisol resulted in the expected elevation of plasma cortisol but caused an abrupt inhibition of insulin secretion even before there was a change in glucose concentration.


Further evidence for a direct effect of glucocorticoids on beta cell function has been from cultured rat insulinoma insulin-secreting, INS-1E cells [ 17 ]. Measurement of impaired insulin release in response to a glucose challenge was seen in prednisone-treated INS-1E cells.

The inhibition was reversed in the presence of prednisone with the glucocorticoid receptor antagonist, RU [ 17 ]. The authors suggest that the defect may be due to impaired endoplasmic reticulum homeostasis, which in turn may lead to beta cell death. One of the etiologies of SIDM is based on the profound and reciprocal effect glucocorticoids have on glyceroneogenesis in liver and adipose tissue Figure 1.

In adipose tissue, glyceroneogenesis controls the rate of fatty acid release in the blood, while in the liver glyceroneogenesis is responsible for the synthesis of triacylglyerol from fatty acids and glycerol 3-phosphate [ 18 ]. The regulation of this process in both liver and adipose is via the enzyme phosphoenylpyruvate carboxykinase PEPCK.

In the presence of glucocorticoids, PEPCK gene expression in adipose tissue is suppressed, inhibiting glyceroneogenesis. In contrast, PEPCK in liver stimulates glycerol production and fatty acid concentration in the blood increased by the action of lipoprotein lipase [ 19 ].

The net result of glucocorticoids, therefore, is to increase the amount of fatty acids released into the rsteroidea. An increase in fatty acids interferes with glucose utilization and results in insulin resistance, especially in skeletal muscle. Thiazolidinediones promote expression of adipose and skeletal muscle PEPCK and reduce serum levels of fatty acids therefore reducing insulin resistance [ 20 ].

The effect of glucocorticoids on glycerneogenesis in adipose tissue and liver. Phosphoenylpyruvate diabetess PEPCK is reciprocally upregulated in liver and downregulated in adipose by glucocorticoids. This results in a buildup of free fatty acids in the blood, which in turn result in insulin resistance and increase gluconeogenesis. The insulin-mediated pathways of glycogen synthesis and protein degradation and synthesis are directly influenced by glucocorticoids Figure 2.

Skeletal muscle is responsible for the majority of insulin-mediated glucose uptake. Insulin recruits GLUT4 glucose transporters to the cell surface enabling glucose uptake into cell. Glucocorticoids impair insulin-mediated glucose uptake by directly interfering with components of the insulin signalling cascade, such as glycogen synthase kinase-3, glycogen synthase and GLUT4 translocation [ 2122 ]. Proposed risk factors for steroid-induced diabetes beyond cumulative dose and longer duration of steroid course include traditional risk factors for type 2 diabetes: The association with family history of diabetes is not well defined.

Those individuals who developed new onset SIDM had significantly less family history of diabetes when compared with individuals estefoidea type 2 diabetes mellitus and glucocorticoid treatment [ 24 ].

Other immunosuppressive agents can also affect glycemic control through other mechanisms, thus confounding impact of glucocorticoid therapy. In transplant patients, the use of calcineurin inhibitors particularly tacrolimus contributes to glucose intolerance by suppressing insulin production [ 24 ]. In those patients with systemic lupus erythematosis, patients on high-dose steroid therapy, development of diabetes was associated with concurrent use of mycophenalate mofetil, possibly attributed to impaired insulin diaabetes from increased beta cell stress [ 1125 ].

Numerous studies have reported an inverse relationship between glycemic control and serum magnesium levels. Van Laecke et al. Liver disease contributes to impaired glucose tolerance, but there is evidence that chronic hepatitis C virus HCV infection itself is an independent risk factor for the development of diabetes in the general population and in liver transplant recipients [ 2728 ].

A meta-analysis by Fabrizi et al. The esteoridea for patients to develop new hyperglycemia in the setting of initiating glucocorticoid therapy is often not anticipated. In the elderly, without close follow-up or monitoring of blood sugars, there is a risk of precipitating hyperglycemic hyperosmolar states [ 30 ], which would require admission to the hospital for aggressive hydration and insulin therapy.

It is generally thought that glucocorticoids result mainly in an increase in post-prandial blood glucose [ diabbetes32 ]. Use of continuous blood glucose monitor in COPD patients treated with prednisolone demonstrated that hyperglycemia predominately occurs in the afternoon and evening, indicating that this would be the most appropriate time to screen for SIDM as well as the period of time to direct specific treatment [ 33 ].

Strategies are needed to detect those at risk for developing steroid-induced diabetes before starting chronic therapy. The updated international consensus guidelines for NODAT suggest that pre-transplant evaluation include fasting plasma glucose, esyeroidea when this is normal, an OGTT [ 22 ].

When OGTTs were performed in a cohort of renal transplant patients 1 week before and approximately 1 year after transplant, Additionally, the ratio of proinsulin to insulin was higher at baseline in the patients that developed NODAT group [ 34 ]. Oral glucose tolerance testing should be performed as early as possible in post-transplant patients to detect diabetes in those deemed to be at risk [ 35 ].


In a cohort of renal transplant recipients 3 months post-transplant, Valderhaug et al. New onset diabetes after transplant is a strong predictor of graft failure in the transplant population.

Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment

Graft failure in the renal transplant population who develop NODAT is attributed to ongoing hyperglycemia leading to recurrent diabetic nephropathy [ 36 ]. One of the largest barriers to tapering glucocorticoids or switching to steroid-sparing immunosuppression to improve glucose control is the risk of allograft rejection [ 36 ], which itself is associated with increased risk for NODAT.

Diabetes is also associated with increased risk of cardiovascular events and a myriad of microvascular complications. The literature suggests that kidney transplant recipients who develop NODAT are at a twofold—threefold increased risk of fatal and non-fatal cardiovascular disease events as compared with non-diabetic patients [ 37 ]. Optimal treatment of SIDM warrants a different management strategy than non-steroid-induced diabetes.

As noted previously in the discussion about glyceroneogenesis, the role of thiazolidinediones is yet to be fully explored. As with all types of diabetes, initial steps to improve glycemic control include lifestyle modification which includes exercise and dietary counselling to provide options that can perhaps lessen post-prandial hyperglycemia. Because initiation of glucocorticoids can cause post-prandial hyperglycemia and the tapering of glucocorticoids can lead to normalization of glycemic control, current guidelines may insufficiently address this.

Basal bolus insulin therapy remains the most flexible option for patients and includes three components: Conventional use of long-acting basal insulin with traditional weight-based dosing may cause nocturnal hypoglycemia [ 33 ]. More studies exploring dose titration of insulin in patients on glucocorticoids possibly utilizing technology like continuous glucose monitoring system are needed.

In general, however, timing of glucocorticoids, to a midday or an evening meal with concomitant administration of intermediate acting insulin, is judicious. Oral secretagogues such as sulfonylurea therapy do not specifically target post-prandial hyperglycemia and thus long-acting agents may be associated with hypoglycemia if the patient does not eat meals regularly.

For patients with mild hyperglycemia who are unable or unwilling to give injections of insulin, a trial of short-acting secretagogues such as nateglinide or repaglinide taken before meals could be considered [ 38 ].

Incretin-based therapy with GLP-1 receptor agonists and DPP-4 inhibitors control glucose levels by stimulating insulin and inhibiting glucagon secretion in the fasting and post-prandial setting.

Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment

A single dose of exenatide was able to improve glucose intolerance and insulin resistance in mice [ 39 ]. In humans, a randomized, double-blind, placebo-controlled trial was performed in which subjects on prednisone therapy received either the GLP-1 receptor agonist exenatide or saline [ 40 ].

Exenatide prevented prednisone-induced glucose intolerance and islet cell dysfunction primarily by decreasing glucagon and decreasing gastric emptying Table 2 [ 40 ]. In the post-transplant setting, as more studies will be conducted with these and other agents, attention to drug—drug interactions is essential. As the therapeutic benefits of glucocorticoids continue to expand across medical specialties, the incidence of steroid-induced or steroid-exacerbated diabetes will continue to rise. Similar to non-steroid-related diabetes, the principles of early detection and risk factor modification apply.

Diagnosing impaired fasting glucose or impaired glucose tolerance prior to the initiation of chronic glucocorticoids will diabbetes identify those who would benefit from esteroideaa treatment, or if this is not an option, blood glucose monitoring while starting therapy. Further investigation into the precise mechanism of steroid-induced insulin resistance will provide insight into future diabetes prevention efforts and targeted therapies.

The authors have no conflicts of interest. National Center for Biotechnology InformationU. Diabetes Metab Res Rev. Author manuscript; available in PMC Jul Hwang 1 and Roy E.

Author information Copyright and License information Disclaimer. The publisher’s final edited version of this article is available at Diabetes Metab Res Rev. See other articles in PMC that cite the published article.