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Glimepiride treatment in a patient with type A insulin resistance syndrome due to a novel heterozygous missense mutation in the insulin receptor gene.

ABSTRACT: AIMS/INTRODUCTION:Glimepiride is a sulfonylurea known to have unique insulin mimetic and sensitizing effects. We aimed to study the efficacy of glimepiride in a patient with type A insulin resistance syndrome. MATERIALS AND METHODS:A 15-year-old girl with type A insulin resistance syndrome was treated with glimpiride for 6 months. Self-monitoring of blood glucose was recorded, and oral glucose tolerance tests on glucose and insulin were measured during the treatment. Hyperinsulinemic euglycemic clamp was used to evaluate whole-body insulin sensitivity before and after the treatment. RESULTS:A novel heterozygous missense mutation at exon 19 (c.3427A>T) in the tyrosine kinase domain of the INSR gene was identified, causing an amino acid replacement of phenylalanine for isoleucine at codon 1143 (Ile1143Phe). Before the treatment, the patient's glycated hemoglobin was 7.0%, plasma glucose during oral glucose tolerance test was 6.7, 12.8 and 17.3 mmol/L, and simultaneous serum insulin was 80.7, 137.5 and >300 ?U/mL. There were no significant differences between self-monitored blood glucose measured at each time-point among different glimepiride dosages, or during the 14 weeks when glimepiride was used at its maximal dosage (6 mg/day). Oral glucose tolerance test showed little change in plasma glucose and serum insulin. Glycated hemoglobin decreased by 0.8% after the treatment. However, a euglycemic clamp study showed that the M value decreased from 5.25 to 2.90 mg/kg/min, showing increased insulin resistance. CONCLUSIONS:Treatment with glimepiride did not improve insulin sensitivity in a patient with type A insulin resistance syndrome carrying Ile1143Phe heterozygous mutation in the INSR gene. Large-scale long-term studies assembled worldwide are required to optimize treatment algorithms for patients with type A insulin resistance syndrome.

SUBMITTER: Huang Z

PROVIDER: S-EPMC6123050 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Glimepiride treatment in a patient with type A insulin resistance syndrome due to a novel heterozygous missense mutation in the insulin receptor gene.

Huang Zhimin Z Liu Juan J Ng Kaka K Wan Xuesi X Xu Lijuan L He Xiaoying X Liao Zhihong Z Li Yanbing Y Li Yanbing Y

Journal of diabetes investigation 20180324 5

<h4>Aims/introduction</h4>Glimepiride is a sulfonylurea known to have unique insulin mimetic and sensitizing effects. We aimed to study the efficacy of glimepiride in a patient with type A insulin resistance syndrome.<h4>Materials and methods</h4>A 15-year-old girl with type A insulin resistance syndrome was treated with glimpiride for 6 months. Self-monitoring of blood glucose was recorded, and oral glucose tolerance tests on glucose and insulin were measured during the treatment. Hyperinsuline ...[more]

PMID: 29469970

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Project description:Background:Lamin A/C (LMNA) gene mutations cause a heterogeneous group of progeroid disorders, including Hutchinson-Gilford progeria syndrome, mandibuloacral dysplasia, and atypical progeroid syndrome (APS). Five of the 31 previously reported patients with APS harbored a recurrent de novo heterozygous LMNA p.T10I mutation. All five had generalized lipodystrophy, as well as similar metabolic and clinical features, suggesting a distinct progeroid syndrome. Methods:We report nine new patients and follow-up of two previously reported patients with the heterozygous LMNA p.T10I mutation and compare their clinical and metabolic features with other patients with APS. Results:Compared with other patients with APS, those with the heterozygous LMNA p.T10I mutation were younger in age but had increased prevalence of generalized lipodystrophy, diabetes mellitus, acanthosis nigricans, hypertriglyceridemia, and hepatomegaly, together with higher fasting serum insulin and triglyceride levels and lower serum leptin and high-density lipoprotein cholesterol levels. Prominent clinical features included mottled skin pigmentation, joint contractures, and cardiomyopathy resulting in cardiac transplants in three patients at ages 13, 33, and 47 years. Seven patients received metreleptin therapy for 0.5 to 16 years with all, except one noncompliant patient, showing marked improvement in metabolic complications. Conclusions:Patients with the heterozygous LMNA p.T10I mutation have distinct clinical features and significantly worse metabolic complications compared with other patients with APS as well as patients with Hutchinson-Gilford progeria syndrome. We propose that they be recognized as having generalized lipodystrophy-associated progeroid syndrome. Patients with generalized lipodystrophy-associated progeroid syndrome should undergo careful multisystem assessment at onset and yearly metabolic and cardiac evaluation, as hyperglycemia, hypertriglyceridemia, hepatic steatosis, and cardiomyopathy are the major contributors to morbidity and mortality.

Dataset Information

Glimepiride treatment in a patient with type A insulin resistance syndrome due to a novel heterozygous missense mutation in the insulin receptor gene.

Publications

Glimepiride treatment in a patient with type A insulin resistance syndrome due to a novel heterozygous missense mutation in the insulin receptor gene.

Similar Datasets

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