Insulin secretory defect in familial partial lipodystrophy Type 2 and successful long-term treatment with a glucagon-like peptide 1 receptor agonist

Banning, Friederike; Rottenkolber, Marietta; Freibothe, Ines; Seißler, Jochen; Lechner, Andreas

doi:10.1111/dme.13527

Cited by 24 publications

(21 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Conventional and intensified antidiabetic treatment failed to normalize glycemic control but the introduction of metreleptin resulted in a drastic improvement of glycemic control and plasma triglycerides. Research data regarding the use of glucagon-like-peptide-1 (GLP-1) agonists in patients with lipodystrophy are scarce and their effect has been described only in case reports (21,22). Contrary to our case, in these previous reports authors pointed out that these regimens resulted in improvement of glycemic control and in reduction of insulin requirements, suggesting the positive effect of GLP-1 analogues in the management of diabetes in lipodystrophy syndromes (21,22).…”

Section: Discussioncontrasting

confidence: 82%

“…Research data regarding the use of glucagon-like-peptide-1(GLP-1) agonists in patients with lipodystrophy are scarce and their effect has been described only in case reports ( 21 , 22 ). Contrary to our case, in these previous reports authors pointed out that these regimens resulted in improvement of glycemic control and in reduction of insulin requirements, suggesting the positive effect of GLP-1 analogues in the management of diabetes in lipodystrophy syndromes ( 21 , 22 ). It is noteworthy to mention that there is a concern regarding the use of GLP-1 analogues in patients with lipodystrophy and high TG levels.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance

et al. 2021

View full text Add to dashboard Cite

BackgroundFamilial partial lipodystrophy type 3 (FPLD3) is a very rare autosomal dominant genetic disorder which is caused by mutations in the peroxisome proliferator activated receptor gamma (PPARG) gene. It is characterized by a partial loss of adipose tissue leading to subnormal leptin secretion and metabolic complications. Metreleptin, a synthetic analogue of human leptin, is an effective treatment for generalized lipodystrophies, but the evidence for efficacy in patients with FPLD3 is scarce.Case PresentationWe present a 61-year-old woman, initially misdiagnosed as type 1 diabetes since the age of 29, with severe insulin resistance, who gradually displayed a more generalized form of lipoatrophy and extreme hypertriglyceridemia, hypertension and multiple manifestations of cardiovascular disease. She was found to carry a novel mutation leading to PPARGGlu157Gly variant. After six months of metreleptin treatment, HbA1c decreased from 10 to 7.9% and fasting plasma triglycerides were dramatically reduced from 2.919 mg/dl to 198 mg/dl.ConclusionsThis case highlights the importance of early recognition of FPLD syndromes otherwise frequently observed as difficult-to-classify and manages diabetes cases, in order to prevent cardiovascular complications. Metreleptin may be an effective treatment for FPLD3.

show abstract

Section: Discussioncontrasting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Metformin is the first-line therapy although some patients may require additional agents including high doses of insulin. In individual patients with FPLD insulin secretion disruption [49] or low dipeptidyl peptidase 4 (DPP4) levels were observed in addition to insulin resistance, suggesting the use of glucagon-like peptide 1 receptor agonists (GLP1) [50] to improve glycemic control and reduce the high insulin demand. However, no studies in the other forms of lipodystrophy have yet been conducted [51].…”

Section: Therapeutic Approaches For Lipodystrophymentioning

confidence: 99%

Lipodystrophies—Disorders of the Fatty Tissue

Knebel

Müller‐Wieland

Kotzka

2020

IJMS

View full text Add to dashboard Cite

Lipodystrophies are a heterogeneous group of physiological changes characterized by a selective loss of fatty tissue. Here, no fat cells are present, either through lack of differentiation, loss of function or premature apoptosis. As a consequence, lipids can only be stored ectopically in non-adipocytes with the major health consequences as fatty liver and insulin resistance. This is a crucial difference to being slim where the fat cells are present and store lipids if needed. A simple clinical classification of lipodystrophies is based on congenital vs. acquired and generalized vs. partial disturbance of fat distribution. Complications in patients with lipodystrophy depend on the clinical manifestations. For example, in diabetes mellitus microangiopathic complications such as nephropathy, retinopathy and neuropathy may develop. In addition, due to ectopic lipid accumulation in the liver, fatty liver hepatitis may also develop, possibly with cirrhosis. The consequences of extreme hypertriglyceridemia are typically acute pancreatitis or eruptive xanthomas. The combination of severe hyperglycemia with dyslipidemia and signs of insulin resistance can lead to premature atherosclerosis with its associated complications of coronary heart disease, peripheral vascular disease and cerebrovascular changes. Overall, lipodystrophy is rare with an estimated incidence for congenital (<1/1.000.000) and acquired (1–9/100.000) forms. Due to the rarity of the syndrome and the phenotypic range of metabolic complications, only studies with limited patient numbers can be considered. Experimental animal models are therefore useful to understand the molecular mechanisms in lipodystrophy and to identify possible therapeutic approaches.

show abstract

“…The use of a combined intravenous glucose tolerance-euglycemic clamp in cases of FPLD revealed not only increased insulin resistance but also impaired first-phase insulin secretion. 77 In addition, Valerio et al 78 showed that the increased visceral adiposity characterizing FPLD is directly related to low dipeptidyl peptidase 4 (DPP4) levels. The above observations led researchers to investigate the role of glucagon-like peptide 1 receptor agonists (GLP1 Ras) in the management of overt diabetes in FPLD cases with promising results such as improvement of glycemic control and reduced insulin requirements.…”

Section: Treatmentmentioning

confidence: 99%

“…The above observations led researchers to investigate the role of glucagon-like peptide 1 receptor agonists (GLP1 Ras) in the management of overt diabetes in FPLD cases with promising results such as improvement of glycemic control and reduced insulin requirements. 77,79 The sodium-glucose co-transporter 2 (SGLT2) inhibitors have an insulin-independent effect on glucose control and have been proven to be beneficial in cardiovascular and renal disease in type 2 diabetes mellitus. Evidence from cases of congenital generalized lipodystrophy has showed that use of SGLT2 inhibitors is associated with improvement in all metabolic markers and reduced incidence of cardiomyopathy.…”

Section: Treatmentmentioning

confidence: 99%

<p>Familial Partial Lipodystrophy (FPLD): Recent Insights</p>

Bagias¹,

Xiarchou²,

Bargiota³

et al. 2020

DMSO

View full text Add to dashboard Cite

Lipodystrophies are a heterogeneous group of congenital or acquired disorders, characterized by partial or generalized loss of adipose tissue. Familial partial lipodystrophy (FPLD) presents with genetic and phenotypic variability with insulin resistance, hypertriglyceridemia and hepatic steatosis being the cardinal metabolic features. The severity of the metabolic derangements is in proportion with the degree of lipoatrophy. The underpinning pathogenetic mechanism is the limited capacity of adipose tissue to store lipids leading to lipotoxicity, low-grade inflammation, altered adipokine secretion and ectopic fat tissue accumulation. Advances in molecular genetics have led to the discovery of new genes and improved our knowledge of the regulation of adipose tissue biology. Diagnosis relies predominantly on clinical findings, such as abnormal fat tissue topography and signs of insulin resistance and is confirmed by genetic analysis. In addition to anthropometry and conventional imaging, new techniques such as color-coded imaging of fat depots allow more accurate assessment of the regional fat distribution and differentiation of lipodystrophic syndromes from common metabolic syndrome phenotype. The treatment of patients with lipodystrophy has proven to be challenging. The use of a human leptin analogue, metreleptin, has recently been approved in the management of FPLD with evidence suggesting improved metabolic profile, satiety, reproductive function and self-perception. Preliminary data on the use of glucagon-like peptide 1 receptor agonists (GLP1 Ras) and sodium-glucose cotransporter 2 (SGLT2) inhibitors in cases of FPLD have shown promising results with reduction in total insulin requirements and improvement in glycemic control. Finally, investigational trials for new therapeutic agents in the management of FPLD are underway.

show abstract

Insulin secretory defect in familial partial lipodystrophy Type 2 and successful long-term treatment with a glucagon-like peptide 1 receptor agonist

Cited by 24 publications

References 6 publications

Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance

Case Report: Metreleptin Treatment in a Patient With a Novel Mutation for Familial Partial Lipodystrophy Type 3, Presenting With Uncontrolled Diabetes and Insulin Resistance

Lipodystrophies—Disorders of the Fatty Tissue

<p>Familial Partial Lipodystrophy (FPLD): Recent Insights</p>

Contact Info

Product

Resources

About