Therapeutic options in a patient with MELAS and diabetes mellitus: follow-up after 6 months of treatment

Claudia, Cosentino; Contento, Margherita; Paganini, Marco; Mannucci, Edoardo; Cresci, Barbara

doi:10.1007/s00592-019-01302-z

Cited by 6 publications

(4 citation statements)

References 5 publications

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“…A disturbance of glucose consumption in peripheral tissues can cause insulin resistance and insufficient insulin secretion (reduction of ATP concentration as a result of mitochondrial disease leads to a decrease in insulin release by ATP – sensitive potassium channels). In addition, the higher concentration of lactates found in MELAS causes an increase in gluconeo-genesis, for which lactic acid is a substrate [ 17 ]. In our patient the cause of diabetes remains unknown.…”

Section: Discussionmentioning

confidence: 99%

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Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome – a case report and literature review

Baszyńska-Wilk¹,

Moszczyńska²,

Szarras‐Czapnik³

et al. 2021

pedm

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MELAS syndrome (mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes) is a genetically determined disease caused by mutations in mitochondrial DNA. We present a girl who was suspected of MELAS syndrome during the diagnostic evaluation of short stature. The patient suffered from symptoms potentially indicating mitochondrial disease, such as muscular weakness, cranial nerve VI palsy, headaches, retinitis pigmentosa, sensory-neural hearing loss, and elevated lactic acid. T2-weighted brain MRI showed hyperintense lesions in the white matter. Muscular biopsy revealed ragged red fibres. Genetic evaluation did not detect the most common mutations in the MT-TL1 gene and MT-ND5 gene. Endocrine tests led to the confirmation of growth hormone deficiency, and so replacement treatment was started. After 1 year of recombinant growth hormone therapy the patient was diagnosed with diabetes. At the age of 14 years the LH-RH test showed prepubertal values. Endocrine disorders may be one of the first manifestations of MELAS syndrome. In differential diagnosis of short stature, less common causes, such as mitochondrial diseases, should be taken into consideration.

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Section: Discussionmentioning

confidence: 99%

“…They increase the secretion of insulin from beta cells and also inhibit the glucagon secretion. They also have antioxidant and anti-inflammatory effects [ 17 ]. Currently, our patient is on a carbohydrate exchange diet, achieving normoglycaemia.…”

Section: Discussionmentioning

confidence: 99%

Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome – a case report and literature review

Baszyńska-Wilk¹,

Moszczyńska²,

Szarras‐Czapnik³

et al. 2021

pedm

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“…Studi condotti su modelli animali suggerirebbero un effetto protettivo di questi farmaci sul metabolismo mitocondriale a livello di miocardio o di sistema nervoso (10)(11). In letteratura sono presenti report relativi all'impiego dei DPP4-i con indicazione di una buona efficacia clinica (12).…”

Section: Discussioneunclassified

Quando la centrale elettrica va in black-out: un caso di diabete mitocondriale

2021

ildia

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Il diabete mitocondriale è una rara forma di diabete spesso non considerata e sicuramente sotto-diagnosticata. Esso è parte di un contesto sindromico più ampio, quello delle malattie mitocondriali, delle quali rappresenta la manifestazione endocrinologica più comune. La precocità della diagnosi di diabete e la sua corretta caratterizzazione sono fondamentali per impostare un adeguato programma di follow-up e una terapia che tenga conto delle peculiarità di questi pazienti che si presentano spesso come fragili, per quanto giovani, con importanti comorbidità, maggiormente propensi all'acidosi lattica e allo sviluppo precoce delle complicanze diabetiche (1). FF è una donna di 41 anni, affetta da una grave forma di Mitochondrial Encephalomyopathy, Lactic Acidosis and Strokelike episode (MELAS), giunta a visita presso gli ambulatori del nostro Servizio di Diabetologia un mese dopo l'esordio acuto di diabete con coma chetoacidosico. Le linee

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“…We manually added an article not identified in the search 45 .There were no controlled trials, and the overall level of evidence was low and the risk of bias high. Tables 4 and 5 show a summary of the data for the 13 articles on HNF1B-diabetes [45][46][47][48][49][50][51][52][53][54][55][56][57] and 10 articles on MD 45,[58][59][60][61][62][63][64][65][66] that reported any treatment response even in single cases, and the prevalent treatment modalities in patient cohorts. The articles represent altogether 293 cases with HNF1B-diabetes and 242 with m.3243A>G MD.…”

Section: What Is the Optimal Glucose Lowering Therapy In The Two Comm...mentioning

confidence: 99%

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

Naylor

Patel

Kettunen

et al. 2023

Preprint

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Background: Beta-cell monogenic forms of diabetes are the area of diabetes care with the strongest support for a precision medicine approach. We systematically reviewed treatment of hyperglycemia in GCK-related hyperglycemia, HNF1A-diabetes, HNF4A-diabetes, HNF1B-diabetes, Mitochondrial diabetes (MD) due to m.3243A>G variant, 6q24-transient neonatal diabetes (TND) and SLC19A2-diabetes (Thiamine-Responsive Megaloblastic Anemia, TRMA). Methods: Systematic review with data sources from PubMed, MEDLINE and Embase were performed answering specific therapeutic questions for the different subtypes. Individual and group level data was extracted for glycemic outcomes in individuals with genetically confirmed monogenic diabetes. Results: 147 studies met inclusion criteria with only six experimental studies (four randomized trials for HNF1A-diabetes) and the rest being single case reports or cohort studies. Most studies were rated as having moderate or serious risk of bias. For GCK-related hyperglycemia, six studies (35 individuals) showed no deterioration in HbA1c on discontinuing glucose lowering therapy. A randomized trial (n=18 per group) showed that sulfonylureas (SU) were more effective in HNF1A-diabetes than in type 2 diabetes, and cohort and case studies supported SU effectiveness in lowering HbA1c. Two crossover trials (n=15 and n=16) suggested glinides and GLP-1 receptor agonists might be used in place of SU. Evidence for HNF4A-diabetes was limited to three studies (16 individuals) showing lower HbA1c with SU therapy. The 13 studies in HNF1B-diabetes (n=301) and 10 in MD with m.3243A>G variant (n=250) showed that while some patients can be treated with oral agents the majority of patients were insulin treated. In HNF1B-diabetes the attempts to transfer from insulin to oral hypoglycemic agents (OHA) were unsuccessful in most cases. In 6q24-TND there were insufficient studies supporting OHA close to diagnosis before remission but more support for their use after relapse. In SLC19A2-diabetes there was some evidence that treatment with thiamine improved glycemic control and reduced insulin requirement while less than half achieved insulin-independency. Conclusion: There is limited evidence to guide the treatment in monogenic diabetes with most studies being non-randomized and small. The combined data does support: no treatment being needed in GCK-related hyperglycemia; SU being used as the first line treatment in HNF1A-diabetes; SU can be tried in HNF4A-diabetes; insulin often needed in HNF1B-diabetes and MD with the m.3243A>G variant; SU can be tried in 6q24-TND relapse; and thiamine may improve glycemic control in SLC19A2-diabetes. Further evidence, particularly randomized comparative studies, are needed to examine the optimum treatment for glycemic response in all monogenic subtypes.

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Therapeutic options in a patient with MELAS and diabetes mellitus: follow-up after 6 months of treatment

Cited by 6 publications

References 5 publications

Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome – a case report and literature review

Endocrine disorders in a patient with a suspicion of a mitochondrial disease, MELAS syndrome – a case report and literature review

Quando la centrale elettrica va in black-out: un caso di diabete mitocondriale

Systematic Review of Treatment of Beta-Cell Monogenic Diabetes

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