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Over the municipalities, its popularity has skyrocketed, with the dehydrated world awakening to itsRead MoreBenefits of Halasana (Cosmetic Pose) and How to Do it By Dr. Himani BishtTable of Contents IntroductionWhat is Halasana. Lees of Halasana:Risks of ExerciseConclusionFrequently Dyed QuestionsReferences: Introduction In this topical sedentary lifestyle, our health has been at the overwhelming end of our hectic schedules.
Study record managers: refer to the Data Element Definitions if submitting registration or results information. Based on various suggestions, social behavior is mediated by a change in steroid hormones. These have diverse effects on the neuro- development during critical stages, whereby especially androgen and insulin metabolism seem to play a key role.
Various lines of evidence indicate that metformin could influence and improve the symptoms of social withdrawal. Therefore, the investigators will analyze urinary samples of patients before and after treatment with metformin to elucidate the changes in steroid hormone profiles and measure changes in social behavior to examine a potential correlation. Steroid hormone analysis including the most prominent androgen, estrogen, progesterone, aldosterone, corticosterone, cortisone and cortisol metabolites analyzed with gas chromatography mass spectrometry and a questionnaire Autism-Spectrum Quotient will be performed prior to and after weeks metformin treatment.
It is likely, that due to different pathophysiological mechanisms such as an effect on respiratory chain in mitochondria or via AMP activated protein kinase a general reduction of total androgens will be detected prior versus post metformin treatment. The encompassing measurement of steroid hormones will allow to detect influences on different metabolites and in consequence enzyme activities. The potential changes prior versus post shall give hints concerning the involvement of specific cascades involved, with potential pharmacological targets for future research.
Samples will be collected before and after 12 weeks of Metformin treatment. Drug: Metformin Treatment with Metformin as prescribed by the treating physician.
All will be measured in urinary samples using GC-MS gas-chromatography mass-spectrometry. Changes in urinary oestrogen metabolite levels of interest see below prior to metformin treatment start and after weeks of treatment.
All wil be measured in urinary samples using GC-MS gas-chromatography mass-spectrometry. Changes in urinary progesterone metabolite levels of interest see below prior to metformin treatment start and after weeks of treatment. Changes in urinary aldosterone metabolite levels of interest see below prior to metformin treatment start and after weeks of treatment.
Hormones of interest include Aldosterone-Metabolites Tetrahydroaldosterone. Changes in urinary corticosterone metabolite levels of interest see below prior to metformin treatment start and after weeks of treatment. Changes in urinary cortisone metabolite levels of interest see below prior to metformin treatment start and after weeks of treatment. Hormones of interest include Cortisone-Metabolites Tetrahydrocortisone, a-Cortolone, b-Cortolone, 20a-Dihydrocortisone, 20b-Dihydrocortisone.
Changes in urinary cortisol metabolite levels of interest see below prior to metformin treatment start and after weeks of treatment. Information from the National Library of Medicine Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
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Save this study. Warning You have reached the maximum number of saved studies Steroid and Behaviour Changes Under Metformin The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Last Update Posted : June 18, See Contacts and Locations. Study Description. Background Based on various suggestions, social behavior is mediated by a change in steroid hormones.
Discussion It is likely, that due to different pathophysiological mechanisms such as an effect on respiratory chain in mitochondria or via AMP activated protein kinase a general reduction of total androgens will be detected prior versus post metformin treatment. Drug Information available for: Metformin Metformin hydrochloride. FDA Resources. Treatment with Metformin as prescribed by the treating physician. Outcome Measures. Changes in social behavior measured by the Autism-Spectrum Quotient AQ prior to metformin treatment start and after weeks of treatment.
Secondary Outcome Measures : Correlation between urinary steroid hormone level changes metabolites of androgen, oestrogen, progesterone, aldosterone, corticosterone, cortisone and cortisol and behavioral changes measured with pearson correlation coefficient. Eligibility Criteria. Patients of the the Lindenhofgruppe and its associated practices with a new indication for Metformin treatment. Inclusion Criteria: Patients with type 2 diabetes mellitus and an indication for metformin according to the American Diabetes Association American Diabetes Association, a starting a new metformin treatment.
The main marker will be fasting plasma glucose levels of 7. Written informed consent. Exclusion Criteria: Patients under 18 years of age. Clinically significant concomitant disease e. Significant musculoskeletal disease. Active infection during sample collection. Immunosuppressive medical therapy. Psychiatric disease and known social behavior altering medication e.
Known or suspected malcompliance, drug or alcohol abuse. Inability to follow the procedures of the study, e. Poor tolerability to metformin treatment with following treatment discontinuation within duration of follow up. Contacts and Locations. Information from the National Library of Medicine To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials. More Information. Physical properties and subunits of Haemopis grandis erythrocruorin. Biochim Biophys Acta. Prematurity is related to high placental cortisol in preeclampsia. Pediatr Res. Azziz R.
Androgen excess is the key element in polycystic ovary syndrome. Fertil Steril. Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity. J Autism Dev Disord. Metformin treatment in young children with fragile X syndrome.
Mol Genet Genomic Med. Epub Sep Using self-report to identify the broad phenotype in parents of children with autistic spectrum disorders: a study using the Autism-Spectrum Quotient. J Child Psychol Psychiatry. Defective lysosomal enzyme secretion in kidneys of Chediak-Higashi beige mice. J Cell Biol. Correlation of hyperandrogenism with hyperinsulinism in polycystic ovarian disease. J Clin Endocrinol Metab. Life-style and metformin for the prevention of endometrial pathology in postmenopausal women.
Gynecol Endocrinol. Epub Sep 5. Genes related to sex steroids, neural growth, and social-emotional behavior are associated with autistic traits, empathy, and Asperger syndrome. Autism Res. Insulin resistance in nonobese patients with polycystic ovarian disease. Zentralbl Gynakol. Clinical, metabolic and endocrine parameters in response to metformin in obese women with polycystic ovary syndrome: a randomized, double-blind and placebo-controlled trial.
Horm Metab Res. Hum Reprod. Epub Dec 2. Hyperandrogenemia in male autistic children and adolescents: relation to disease severity. Int J Adolesc Med Health. Effect of flutamide and metformin administered alone or in combination in dieting obese women with polycystic ovary syndrome. Clin Endocrinol Oxf.
Methods: In a double-blind, placebo-controlled trial, patients starting glucocorticoid treatment (prednisone, prednisolone or methylprednisolone) for four weeks. The use of steroids, such as prednisone, can reduce the effectiveness of metformin and other diabetes medications, leading to high blood glucose. Steroids can lead to high blood glucose levels, known as hyperglycemia, but how and What should I keep in mind while taking steroids? — Metformin improved metabolic profile in patients with chronic inflammatory disease For people on systemic glucocorticoid therapy for various. Methods: In a double-blind, placebo-controlled trial, patients starting glucocorticoid treatment (prednisone, prednisolone or methylprednisolone) for four weeks. European Journal of Clinical Investigation 39 81 — Hospital admission due to adverse events AEs were also significantly lower among those treated with metformin at one versus nine admissions. Epub May With healthcare providers, academic institutions, non-profits and other companies. Karrie Hawbaker.Patients receiving glucocorticoid treatment are prone to develop metabolic complications. In preclinical studies, metformin prevented the development of the metabolic syndrome during glucocorticoid excess. We herein investigated the metabolic effect of metformin during glucocorticoid treatment in non-diabetic patients.
All patients underwent a standardised oral glucose tolerance test at baseline and after four weeks. The primary endpoint was change in the 2-h area under the curve AUC of glucose during the oral glucose tolerance test between baseline and four weeks. Glucocorticoid equivalent doses were similar in both groups placebo: In this first randomised controlled trial of metformin targeting metabolic complications in patients needing glucocorticoid therapy, we observed a beneficial effect of metformin on glycaemic control.
Metformin thus seems to be a promising drug for preventing metabolic side effects during systemic glucocorticoid treatment.
Up to 2. Diabetes mellitus, dyslipidaemia, central obesity and hypertension are well-known and common side effects of glucocorticoid treatment 2 , 3. Even if used as an antiemetic drug in cancer patients, glucocorticoids clearly increased the risk of diabetes mellitus 8.
In contrast to other well-known side effects of glucocorticoids, such as gastric ulcer disease, no randomised controlled evidence exists that has investigated the potential therapeutics for the treatment of metabolic side effects of glucocorticoids.
Many of the changes seen in glucocorticoid excess, such as gluconeogenesis, correspond to metabolic steps regulated by adenosine monophosphate-activated protein kinase AMPK 9. AMPK is a key regulator of energy metabolism and mediator of several hormones affecting appetite and metabolism Metformin, a widely used drug for prevention and treatment of diabetes mellitus type 2, exerts most of its beneficial effects on metabolism through the activation of AMPK 11 , Importantly, metformin reversed the effects of corticosteroids on AMPK in vitro both in primary hypothalamic cell culture as well as in adipocytes, suggesting that metformin and glucocorticoids influence the AMPK signalling pathway in opposite ways and that the metformin effect is able to override the cortisol effect 13 , In vivo studies showed that treatment with an AMPK activator prevented glucocorticoid-induced increase in glucose levels, hepatic glycogen production and hepatic steatosis in rats Furthermore, metformin efficiently prevented the dexamethasone-induced deterioration of glucose metabolism in mice and horses 17 , These data suggest that metformin treatment could be beneficial in preventing metabolic complications in patients receiving long-term corticosteroid treatment.
In the first double-blind, randomised, placebo-controlled trial, we investigated the metabolic effects of metformin during glucocorticoid treatment in non-diabetic patients starting treatment with corticosteroids for at least 4 weeks. In this randomised, placebo-controlled, double-blind study, we included patients starting glucocorticoid treatment for at least 4 weeks.
The study was terminated after four weeks in all patients, also in cases where glucocorticoid treatment was continued. The study was registered at Clinicaltrials. Glucocorticoid tapering was determined by the treating physicians. The study was approved by the ethical committees of the participating hospitals and Swissmedic and was conducted in accordance with the ethical guidelines of the Declaration of Helsinki. Written informed consent was obtained from all participating subjects before randomisation.
After an overnight fast, baseline blood samples for fasting glucose, insulin, HbA1c, a full lipid profile and safety blood measurements were taken directly before ingestion of glucose. Physical examination and urine analysis were performed, and doses of glucocorticoids were assessed at both visits.
After one week, a telephone call took place to assess the compliance, adverse events and dosage of glucocorticoids. Three forms of glucocorticoids were prescribed: prednisone, prednisolone and methylprednisolone Supplementary Table 1 , see section on supplementary data given at the end of this article.
If needed, doses of glucocorticoids, e. Due to glucocorticoid tapering, cumulative glucocorticoid doses were calculated as follows: area under the curve was calculated using glucocorticoid doses at baseline, one and four weeks. The average daily prednisone dose was calculated as the area under the curve of the 28 study days. Plasma glucose and lipids were measured with enzymatic assays cobas modular analyzer, Roche Diagnostics.
Measurements of all blood parameters were taken in the routine central laboratory unit of the University Hospital Basel. A randomisation list based on single sequence of random assignments was created by the Pharmaceutical Unit of the University Hospital Basel. Patients as well as study personnel were blinded to the medication allocation.
According to the protocol, the primary analysis followed the intention-to-treat principle, i. Discrete variables are expressed as counts percentages and continuous variables as median interquartile range IQR. The Wilcoxon signed-rank test was used for comparisons within subjects. To adjust for relevant covariates, linear regression analyses were employed. In the metformin group, two patients withdrew from the study due to gastrointestinal symptoms and vertigo respectively; another patient was lost to follow-up after the baseline visit.
In the placebo group, one patient did not receive glucocorticoids and one patient was lost to follow-up. A total of 17 subjects in the metformin group and 12 subjects in the placebo group completed the trial Fig.
Patients in both treatment groups were well matched for baseline characteristics Table 1. Baseline glucocorticoid doses were similar in both groups metformin: AUC prednisone doses in patients completing the trial remained similar in both groups throughout the study metformin: Indications for glucocorticoid treatment are presented in Table 2. Due to slow study recruitment and time of expiry of study drug, the study had to be prematurely terminated.
This led to fewer study participants than intended and to an unbalanced randomisation. Citation: European Journal of Endocrinology , 3; Baseline characteristics including 5 patients with missing outcome variables ; median values IQR. Change in glucose during oral glucose tolerance test. A Plasma glucose values during oral glucose tolerance test at baseline and after four weeks in placebo-treated patients. B Glucose values during oral glucose tolerance test at baseline and after four weeks in patients treated with metformin.
C 2-h AUC glucose in both study groups at baseline and after 4 weeks. D Differences in 2-h AUC glucose between baseline and four weeks in each study group. A HOMA index at baseline and after four weeks for both study groups. C Fasting glucose at baseline and after four weeks in each study group.
D Differences in fasting glucose between baseline and four weeks in each study group. E Fasting insulin at baseline and after four weeks in each study group. F Differences in fasting insulin at baseline and after four weeks in each study group. G HbA1c at baseline and after four weeks in each study group. H Differences in between baseline and four weeks in each study group. Primary and secondary endpoints; median values IQR ; for each parameter, change from baseline was compared between groups metformin vs placebo using the Mann—Whitney U test and within-groups using the Wilcoxon signed-rank test.
Furthermore, we aimed to differentiate between responders and non-responders to metformin. As the 2-h AUC glucose increase in the placebo group was This resulted in three patients, who were classified as non-responders. Their baseline characteristics are listed in Supplementary Table 4. We identified no change in BMI, waist-to-hip ratio, basal metabolic rate, fat free mass and fat mass during the study period; there was no difference across treatment groups Table 3.
Gastrointestinal symptoms were present in All gastrointestinal symptoms were either mild or moderate. In the metformin group, one subject discontinued the study due to gastrointestinal symptoms, and another patient discontinued due to vertigo.
One subject in the metformin group was hospitalised for further evaluation of the underlying disease vasculitis after study inclusion. The hospitalisation was rated as serious adverse event unrelated to the study drug. In this trial, with non-diabetic patients receiving systemic glucocorticoids, we demonstrate for the first time that preventive metformin treatment is superior to placebo with respect to glycaemic control as indicated by 2-h glucose AUC, HOMA index, fasting glucose and fasting insulin.
This effect was consistent after adjustment for gender, cumulative glucocorticoid dose and HbA1c. Although HDL cholesterol levels increased in both groups during GC treatment, we did not observe a change in triglycerides, LDL, body weight or body composition.
Despite the very frequent use of glucocorticoids and the well-known detrimental impact on glucose metabolism, hardly any randomised controlled trials have investigated the prevention of glucocorticoid-induced diabetes 21 , 22 , 23 , In one of these trials, troglitazone prevented deterioration of glucose metabolism during glucocorticoid treatment, whereas pioglitazone and metformin had no effect Noteworthy, troglitazone can no longer be used as it was withdrawn from the market.
Compared to our study, duration of metformin and steroid treatment was very short and metformin dose was low. Two other randomised controlled trials targeting the GLP-1 pathway produced heterogeneous results 26 , Importantly, all three studies were performed in individuals without inflammatory disease, thus not representing the patients in need of glucocorticoid treatment.
As inflammation is a known mediator of insulin resistance, it is important to investigate the potential benefits of metformin in an appropriate study population Therefore, more convincing strategies to prevent metabolic side effects of glucocorticoid treatment in patients indeed suffering from inflammatory diseases are needed.
From a pathophysiological point of view, metformin is an attractive preventive treatment strategy in patients receiving corticosteroids.
Overall, the activation of AMPK seems to play an important role 11 , 12 , 33 , AMPK is generally considered to be a master regulator of energy metabolism, sensing energy depletion and activating energy-generating pathways Glucocorticoids have been shown to inhibit AMPK activity and, importantly, metformin was able to reverse this inhibitory effect of glucocorticoids on AMPK in vitro and in animal studies 13 , 14 , In accordance with these experimental data, our study showed that metformin favourably influences several side effects of glucocorticoid therapy.
We found that metformin prevented an increase of 2-h glucose AUC indicating preservation of glucose tolerance. The HOMA index, a marker of insulin resistance, clearly improved in the metformin group, whereas deterioration was observed in the placebo group. Fasting glucose levels decreased in the metformin group, whereas increased in the placebo group during the study period.
Moreover, change in fasting insulin was different between groups. Still, we could not identify a difference in HbA1c. However, our study was conducted over four weeks while HbA1c reflects average blood glucose over the previous 8—12 weeks Therefore, we speculate that a longer study duration could show a beneficial effect on HbA1c. Compared to glucose metabolism, the role of glucocorticoids in lipid metabolism is more controversial.
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