Metformin paradoxically worsens insulin resistance in SHORT syndrome
Abstract Background SHORT syndrome is an autosomal dominant condition associated severe insulin resistance (IR) and lipoatrophy due to post-receptor defect in insulin signaling involving phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), where no clear treatment guidelines are available. Metho...
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doaj-dcd3100fef44401483272794d253e94c2020-11-25T01:19:50ZengBMCDiabetology & Metabolic Syndrome1758-59962019-10-011111410.1186/s13098-019-0477-zMetformin paradoxically worsens insulin resistance in SHORT syndromeKrzysztof C. Lewandowski0Katarzyna Dąbrowska1Maria Brzozowska2Joanna Kawalec3Andrzej Lewiński4Department of Endocrinology and Metabolic Diseases, Medical University of LodzDepartment of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital-Research InstituteDepartment of Endocrinology and Metabolic Diseases, Medical University of LodzDepartment of Endocrinology and Metabolic Diseases, Polish Mother’s Memorial Hospital-Research InstituteDepartment of Endocrinology and Metabolic Diseases, Medical University of LodzAbstract Background SHORT syndrome is an autosomal dominant condition associated severe insulin resistance (IR) and lipoatrophy due to post-receptor defect in insulin signaling involving phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), where no clear treatment guidelines are available. Methods We attempted to test the efficacy metformin in a female patient with SHORT syndrome by measuring glucose and insulin during an extended Oral Glucose Tolerance Test (OGTT) in a 21-year old patient (BMI 17.5 kg/m2), who presented for endocrine assessment with a history of amenorrhoea. Results She had lipid concentrations within the reference range, normal thyroid function tests, prolactin, gonadotropins, estradiol and androgens with Free Androgen Index 4.52. Extended Oral Glucose Tolerance Test was performed and showed severe IR. She was then started on metformin 850 mg twice a day, and had repeated OGTT. This showed dramatic worsening of glucose tolerance (e.g. glucose 96 mg/dl versus 187 mg/dl and 68 mg/dl versus 204 mg/dl at 120 and 150 min of OGTT, respectively). This was accompanied by a massive increase of already high insulin concentrations (e.g. from 488.6 to > 1000 µIU/ml, and from 246.8 to > 1000 µIU/ml at 120 and 150 min of OGTT, respectively). Insulin concentrations remained above upper assay detection limit also at 180 min of OGTT on metformin treatment (> 1000 µIU/ml versus 100.6 µIU/ml without metformin). Conclusions Metformin treatment may paradoxically lead to deterioration of insulin resistance and to development of glucose intolerance in SHORT syndrome. Hence, metformin treatment might be potentially harmful in these patients. Though, the precise cause of such profound and paradoxical worsening of glucose tolerance post metformin remains unknown, SHORT syndrome might prove to be an interesting model to study the mechanism(s) of metformin action.http://link.springer.com/article/10.1186/s13098-019-0477-zSHORT syndromeMetforminInsulin resistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Krzysztof C. Lewandowski Katarzyna Dąbrowska Maria Brzozowska Joanna Kawalec Andrzej Lewiński |
spellingShingle |
Krzysztof C. Lewandowski Katarzyna Dąbrowska Maria Brzozowska Joanna Kawalec Andrzej Lewiński Metformin paradoxically worsens insulin resistance in SHORT syndrome Diabetology & Metabolic Syndrome SHORT syndrome Metformin Insulin resistance |
author_facet |
Krzysztof C. Lewandowski Katarzyna Dąbrowska Maria Brzozowska Joanna Kawalec Andrzej Lewiński |
author_sort |
Krzysztof C. Lewandowski |
title |
Metformin paradoxically worsens insulin resistance in SHORT syndrome |
title_short |
Metformin paradoxically worsens insulin resistance in SHORT syndrome |
title_full |
Metformin paradoxically worsens insulin resistance in SHORT syndrome |
title_fullStr |
Metformin paradoxically worsens insulin resistance in SHORT syndrome |
title_full_unstemmed |
Metformin paradoxically worsens insulin resistance in SHORT syndrome |
title_sort |
metformin paradoxically worsens insulin resistance in short syndrome |
publisher |
BMC |
series |
Diabetology & Metabolic Syndrome |
issn |
1758-5996 |
publishDate |
2019-10-01 |
description |
Abstract Background SHORT syndrome is an autosomal dominant condition associated severe insulin resistance (IR) and lipoatrophy due to post-receptor defect in insulin signaling involving phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1), where no clear treatment guidelines are available. Methods We attempted to test the efficacy metformin in a female patient with SHORT syndrome by measuring glucose and insulin during an extended Oral Glucose Tolerance Test (OGTT) in a 21-year old patient (BMI 17.5 kg/m2), who presented for endocrine assessment with a history of amenorrhoea. Results She had lipid concentrations within the reference range, normal thyroid function tests, prolactin, gonadotropins, estradiol and androgens with Free Androgen Index 4.52. Extended Oral Glucose Tolerance Test was performed and showed severe IR. She was then started on metformin 850 mg twice a day, and had repeated OGTT. This showed dramatic worsening of glucose tolerance (e.g. glucose 96 mg/dl versus 187 mg/dl and 68 mg/dl versus 204 mg/dl at 120 and 150 min of OGTT, respectively). This was accompanied by a massive increase of already high insulin concentrations (e.g. from 488.6 to > 1000 µIU/ml, and from 246.8 to > 1000 µIU/ml at 120 and 150 min of OGTT, respectively). Insulin concentrations remained above upper assay detection limit also at 180 min of OGTT on metformin treatment (> 1000 µIU/ml versus 100.6 µIU/ml without metformin). Conclusions Metformin treatment may paradoxically lead to deterioration of insulin resistance and to development of glucose intolerance in SHORT syndrome. Hence, metformin treatment might be potentially harmful in these patients. Though, the precise cause of such profound and paradoxical worsening of glucose tolerance post metformin remains unknown, SHORT syndrome might prove to be an interesting model to study the mechanism(s) of metformin action. |
topic |
SHORT syndrome Metformin Insulin resistance |
url |
http://link.springer.com/article/10.1186/s13098-019-0477-z |
work_keys_str_mv |
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