Loss of thymidine phosphorylase activity disrupts adipocyte differentiation and induces insulin-resistant lipoatrophicdiabetes. Thymidine phosphorylase (TP), encoded by the TYMP gene, is a cytosolic enzyme essential for the nucleotide salvage pathway. TP catalyzes the phosphorylation of the deoxyribonucleosides, thymidine and 2'-deoxyuridine, to thymine and uracil. Biallelic TYMP variants phenotyping was performed in three patients from two families carrying homozygous TYMP variants and presenting with lipoatrophicdiabetes. The impact of the loss of TP expression was evaluated using a CRISPR-Cas9-mediated TP knockout (KO) strategy in human adipose stem cells (ASC), which can be differentiated into adipocytes in vitro. Protein expression profiles and cellular characteristics were
EPHX1 mutations cause a lipoatrophicdiabetes syndrome due to impaired epoxide hydrolysis and increased cellular senescence. Epoxide hydrolases (EHs) regulate cellular homeostasis through hydrolysis of epoxides to less-reactive diols. The first discovered EH was EPHX1, also known as mEH. EH functions remain partly unknown, and no pathogenic variants have been reported in humans. We identified two de novo variants located in EPHX1 catalytic site in patients with a lipoatrophicdiabetes characterized by loss of adipose tissue, insulin resistance, and multiple organ dysfunction. Functional analyses revealed that these variants led to the protein aggregation within the endoplasmic reticulum and to a loss of its hydrolysis activity. CRISPR-Cas9-mediated knockout (KO) abolished adipocyte
Case of lipoatrophicdiabetes induced by juvenile dermatomyositis Lipodystrophy is a rare condition that is often accompanied by one or more metabolic diseases. Here, we report a case of lipoatrophicdiabetes induced by juvenile dermatomyositis. Although pioglitazone was not effective for lowering blood glucose levels, our observation suggested that it improved liver function slightly . The effectiveness of metreleptin for lowering blood glucose levels could not be determined, as we administered it in a short period. Liver biopsy showed burned-out non-alcoholic steatohepatitis. The present results show that the successful treatment of lipoatrophicdiabetes induced by juvenile dermatomyositis requires an early diagnosis and therapeutic intervention.
Monocyte chemoattractant protein-1 (MCP-1) deficiency enhances alternatively activated M2 macrophages and ameliorates insulin resistance and fatty liver in lipoatrophicdiabetic A-ZIP transgenic mice. Monocyte chemoattractant protein-1 (MCP-1)/chemokine (C-C motif) ligand (CCL) 2 (CCL2) secreted from white adipose tissue (WAT) in obesity has been reported to contribute to tissue macrophage
A Multicenter, Open-Label, Single-Arm Trial of the Efficacy and Safety of Empagliflozin Treatment for Refractory Diabetes Mellitus with Insulin Resistance (EMPIRE-01). Insulin resistance syndrome and lipoatrophicdiabetes are characterized by severe insulin resistance and are often refractory to treatment. Trials assessing the efficacy of antidiabetes drugs for these rare conditions have been limited, however. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, which lower glycemia independently of insulin action, have shown efficacy for type 2 diabetes with insulin resistance. We here investigated the efficacy and safety of the SGLT2 inhibitor empagliflozin for treatment of insulin resistance syndrome and lipoatrophicdiabetes. The trial was conducted at five academic centers in Japan
approved for the indication of symptomatic therapy for lipoatrophicdiabetes mellitus to regulate blood glucose levels, its therapeutic effects are limited (Ebihara K, et al. Journal of Japan Society for the Study of Obesity. 2011;17:15-20). Clinical studies including the Japanese investigator-initiated trial (Study KUTR-003-1) have demonstrated the efficacy of the product
mass (defined as Z-score>+2.5SD). Patients on insulin had lower sclerostin (37.3±9.2 vs. 52.6±13.4pmol/L, p=0.05). The mean TBS was 1.402±0.106, and it was higher than 1.300 in nine patients. Patients with lipoatrophicdiabetes (BSCL) have high serum concentrations of sclerostin, normal or high BMD, and reasonable trabecular bone mass measured by TBS. This is the first report of high sclerostin
] OR "type 2 diabetes"[Title/Abstract] OR "diabetes mellitus type 2"[Title/Abstract] OR "diabetes mellitus type II"[Title/Abstract] OR "type II diabetes mellitus"[Title/Abstract] OR "DM2"[Title/Abstract] OR "diabetes mellitus adult onset"[Title/Abstract] OR "Adult-Onset Diabetes Mellitus"[Title/Abstract] OR "diabetes mellitus adult onset"[Title/Abstract] OR "lipoatrophicdiabetes*"[Title/Abstract
Pancreatic cancer Lawrence-Moon-Bardet syndrome Pheochromocytoma Lawrence-Seip syndrome Prostate cancer Lipoatrophicdiabetes mellitus Rectal cancer Lupoid hepatitis Pancreatic cancer Lawrence-Moon-Bardet syndrome Pheochromocytoma Lawrence-Seip syndrome Prostate cancer Lipoatrophicdiabetes mellitus Rectal cancer Lupoid hepatitis
Defects in insulin action include the following: * * Structure and function of insulin receptor: postreceptor signal transduction pathways * * Type A insulin resistance * * Leprechaunism * * Rabson-Mendenhall syndrome * * Lipoatrophicdiabetes Diseases of the exocrine pancreas include the following: * * Pancreatitis * * Trauma * * Infection
Lipodystrophy, Generalized (Diagnosis) Generalized Lipodystrophy: Practice Essentials, Overview, Lipodystrophy, Lipoatrophy, and LipoatrophicDiabetes For YouNews & PerspectiveDrugs & DiseasesCME & EducationAcademyVideoDecision PointEdition:EnglishMedscapeEnglishDeutschEspañolFrançaisPortuguêsUKNewUnivadisLog In Sign Up It's Free!English EditionMedscape * English * Deutsch * Español * Français Lipodystrophy * * * Practice Essentials * Overview * Lipodystrophy, Lipoatrophy, and LipoatrophicDiabetes * Mechanisms of Disease * Classification of Lipoatrophy Syndromes * Clinical Abnormalities Observed in Lipoatrophy/Lipodystrophy Syndromes * Treatment of Lipoatrophy/Lipodystrophy * * Show All * Media Gallery * Tables * ReferencesOverview Practice EssentialsLipodystrophy, the abnormal distribution
Pancreatic cancer Lawrence-Moon-Bardet syndrome Pheochromocytoma Lawrence-Seip syndrome Prostate cancer Lipoatrophicdiabetes mellitus Rectal cancer Lupoid hepatitis Pancreatic cancer Lawrence-Moon-Bardet syndrome Pheochromocytoma Lawrence-Seip syndrome Prostate cancer Lipoatrophicdiabetes mellitus Rectal cancer Lupoid hepatitis
Defects in insulin action include the following: * * Structure and function of insulin receptor: postreceptor signal transduction pathways * * Type A insulin resistance * * Leprechaunism * * Rabson-Mendenhall syndrome * * Lipoatrophicdiabetes Diseases of the exocrine pancreas include the following: * * Pancreatitis * * Trauma * * Infection
Lipodystrophy, Generalized (Overview) Generalized Lipodystrophy: Practice Essentials, Overview, Lipodystrophy, Lipoatrophy, and LipoatrophicDiabetes News & PerspectiveDrugs & DiseasesCME & EducationAcademyVideoDecision PointEdition:EnglishMedscapeEnglishDeutschEspañolFrançaisPortuguêsUKNewUnivadisLog In Sign Up It's Free!English EditionMedscape * English * Deutsch * Español * Français Lipodystrophy * * * Practice Essentials * Overview * Lipodystrophy, Lipoatrophy, and LipoatrophicDiabetes * Mechanisms of Disease * Classification of Lipoatrophy Syndromes * Clinical Abnormalities Observed in Lipoatrophy/Lipodystrophy Syndromes * Treatment of Lipoatrophy/Lipodystrophy * * Show All * Media Gallery * Tables * ReferencesOverview Practice EssentialsLipodystrophy, the abnormal distribution
Lipodystrophy, Generalized (Follow-up) Generalized Lipodystrophy: Practice Essentials, Overview, Lipodystrophy, Lipoatrophy, and LipoatrophicDiabetes For YouNews & PerspectiveDrugs & DiseasesCME & EducationAcademyVideoDecision PointEdition:EnglishMedscapeEnglishDeutschEspañolFrançaisPortuguêsUKNewUnivadisLog In Sign Up It's Free!English EditionMedscape * English * Deutsch * Español * Français Lipodystrophy * * * Practice Essentials * Overview * Lipodystrophy, Lipoatrophy, and LipoatrophicDiabetes * Mechanisms of Disease * Classification of Lipoatrophy Syndromes * Clinical Abnormalities Observed in Lipoatrophy/Lipodystrophy Syndromes * Treatment of Lipoatrophy/Lipodystrophy * * Show All * Media Gallery * Tables * ReferencesOverview Practice EssentialsLipodystrophy, the abnormal distribution