Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders

Maiorana, Arianna; Tagliaferri, Francesco; Dionisi‐Vici, Carlo

doi:10.3389/fendo.2023.1145111

Cited by 9 publications

(5 citation statements)

References 147 publications

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“…Recently, after Wortmann et al reported the use of empagliflozin for treating neutropenia and neutrophil dysfunction in GSD-Ib patients 18 , more than 230 adult or paediatric patients with GSD-Ib who received empagliflozin have been reported in more than 20 pieces of literature, including two international questionnaire studies 20 , 31 and some case reports 21 , 32 – 36 . The efficacy in these studies was assessed by clinical symptoms and the PCDAI 6 , 28 , empagliflozin has been recommended for the treatment of neutrophil dysfunction in GDS-Ib patients with or without IBD.…”

Section: Discussionmentioning

confidence: 99%

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial

Li,

Zhang,

Chen

et al. 2024

Sci Rep

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Glycogen storage disease type Ib (GSD-Ib) is a rare inborn error of glycogen metabolism caused by mutations in SLC37A4. Patients with GSD-Ib are at high risk of developing inflammatory bowel disease (IBD). We evaluated the efficacy of empagliflozin, a renal sodium‒glucose cotransporter protein 2 (SGLT2) inhibitor, on colonic mucosal healing in patients with GSD-associated IBD. A prospective, single-arm, open-label clinical trial enrolled eight patients with GSD-associated IBD from Guangdong Provincial People's Hospital in China from July 1, 2022 through December 31, 2023. Eight patients were enrolled with a mean age of 10.34 ± 2.61 years. Four male and four female. The endoscopic features included deep and large circular ulcers, inflammatory hyperplasia, obstruction and stenosis. The SES-CD score significantly decreased at week 48 compared with before empagliflozin. Six patients completed 48 weeks of empagliflozin therapy and endoscopy showed significant improvement or healing of mucosal ulcers, inflammatory hyperplasia, stenosis, and obstruction. One patient had severe sweating that required rehydration and developed a urinary tract infection. No serious or life-threatening adverse events. This study suggested that empagliflozin may promote colonic mucosal healing and reduce hyperplasia, stenosis, and obstruction in children with GSD-associated IBD.

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Section: Discussionmentioning

confidence: 99%

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial

Li,

Zhang,

Chen

et al. 2024

Sci Rep

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“…Диетотерапия при БНГ Ia и БНГ Ib идентична, но последним в связи с предрасположенностью к ВЗК необходимы дополнительные ограничения. Отказ от голодания -это первая линия лечения путем частого употребления высокоуглеводной диеты с низким содержанием жира, дополненной сырым кукурузным крахмалом [2,12]. На первом году жизни ночные приемы пищи могут быть заменены непрерывным энтеральным питанием через назогастральный зонд или гастростому.…”

Section: современные методы лечения бнг Ib типа аспекты питанияunclassified

“…Эмпаглифлозин потенциально может быть использован также у пациентов с БНГ Ia с целью улучшения метаболических показателей, профилактики митохондриального стресса, инсулинорезистентности, неалкогольной жировой болезни печени (НАЖБП) и нефропатии [12].…”

Section: эмпаглифлозинunclassified

“…Единственным эффективным методом лечения кардиомиопатии является кетогенная диета, но результат сильно зависит от приверженности пациентов [46]. Использование эмпаглифлозина возможно ввиду его благоприятного воздействия на печень и сердце [12].…”

Section: эмпаглифлозинunclassified

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Glycogen storage disease type Ib: modern understanding of the pathogenesis of neutropenia and prospects for its treatment with empagliflozin

Surkov,

Baranov,

Namazova-Baranova

et al. 2023

Pediatr. farmakol.

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Glycogen storage disease type Ib (GSD Ib) — is a disease from the group of hereditary metabolic diseases caused by insufficiency of the glucose-6-phosphate transporter (G6PT, SLC37A4), which leads to a violation of both glycogenolysis and gluconeogenesis and, as a consequence, to excessive accumulation of glycogen and fat in the liver, kidneys and intestinal mucosa. The main clinical manifestations and laboratory data include growth retardation, hepatomegaly, hypoglycemia, lactic acidosis, hyperuricemia and hyperlipidemia. Complications of this disease are hepatocellular adenoma with a possible risk of malignancy, nephropathy and osteoporosis. A specific sign of GSD Ib is neutropenia with impaired neutrophil function, which creates prerequisites for recurrent infections and the development of inflammatory bowel disease. Until the present, enzyme replacement therapy of GSD Ib has not been developed, therefore, the main methods of treatment are a specialized diet with the addition of raw corn starch (for relief of hypoglycemia) and the use of granulocyte colony stimulating factor (for relief of neutropenia). However, the recent establishment of the role of 1,5-anhydroglucitol in the pathogenesis of neutrophil dysfunction in GSD Ib has led to a reprofiling of indications for the use of empagliflozin, a type 2 renal sodium—glucose cotransporter inhibitor (SGLT2). In the modern literature, it is reported about a minor, but very successful experience of its use in patients with GSD Ib (outside the framework of official indications for use) and a beneficial effect on neutrophil dysfunction and its clinical consequences. Oddly enough, this hypoglycemic drug improved not only metabolic, but also glycemic control in patients with GSD Ib, despite the fact that the pathology is based on chronic hypoglycemia. More and more evidence points to the role of empagliflozin in the regulation of cellular homeostasis (for example, fatty acid metabolism, glucose, cholesterol, apoptosis and cell proliferation, in particular in the liver) by influencing the activity of sirtuin 1 (SIRT1), AMP-activated protein kinase (AMPK) and signal molecules such as -serine/threonine protein kinase (Akt) and a mechanical target of rapamycin (mTOR), which leads to an improvement in the structure and function of mitochondria, stimulation of autophagy, reducing oxidative stress and suppressing inflammation. Modulation of these pathways shifts oxidative metabolism from carbohydrates to lipids and leads to a key decrease in insulin levels, resistance to it, glucose and lipotoxicity. This review presents current data on the pathogenesis of neutropenia and the possibility of using empagliflozin for its relief in patients with GSD Ib.

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“…Other drugs that inhibit bone resorption include monoclonal antibodies targeting the receptor activator of nuclear factor-κB ligand (RANKL), calcitonin, and estrogen 9 . Bone formation-promoting drugs, as well as bifunctional drugs such as parathyroid hormone analogs, active vitamin D and its analogs, vitamin K, and romosozumab, have been widely recognized for clinical application 10 . However, systemic therapy has limitations, such as the need for treatment continuation for more than one year and the risk of osteoporotic fractures before and after discontinuation of treatment.…”

Section: Introductionmentioning

confidence: 99%

Osteoporotic osseointegration: therapeutic hallmarks and engineering strategies

Chen,

Hao,

et al. 2024

Theranostics

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Osteoporosis is a systemic skeletal disease caused by an imbalance between bone resorption and formation. Current treatments primarily involve systemic medication and hormone therapy. However, these systemic treatments lack directionality and are often ineffective for locally severe osteoporosis, with the potential for complex adverse reactions. Consequently, treatment strategies using bioactive materials or external interventions have emerged as the most promising approaches. This review proposes twelve microenvironmental treatment targets for osteoporosis-related pathological changes, including local accumulation of inflammatory factors and reactive oxygen species (ROS), imbalance of mitochondrial dynamics, insulin resistance, disruption of bone cell autophagy, imbalance of bone cell apoptosis, changes in neural secretions, aging of bone cells, increased local bone tissue vascular destruction, and decreased regeneration. Additionally, this review examines the current research status of effective or potential biophysical and biochemical stimuli based on these microenvironmental treatment targets and summarizes the advantages and optimal parameters of different bioengineering stimuli to support preclinical and clinical research on osteoporosis treatment and bone regeneration. Finally, the review addresses ongoing challenges and future research prospects.

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Current understanding on pathogenesis and effective treatment of glycogen storage disease type Ib with empagliflozin: new insights coming from diabetes for its potential implications in other metabolic disorders

Cited by 9 publications

References 147 publications

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial

Empagliflozin in children with glycogen storage disease-associated inflammatory bowel disease: a prospective, single-arm, open-label clinical trial

Glycogen storage disease type Ib: modern understanding of the pathogenesis of neutropenia and prospects for its treatment with empagliflozin

Osteoporotic osseointegration: therapeutic hallmarks and engineering strategies

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