Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism

Vezzosi, Delphine; Bennet, A.; Fauvel, Josette; Caron, P.

doi:10.1530/eje-07-0109

Cited by 121 publications

(101 citation statements)

References 22 publications

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“…The 32-33 split proinsulin level was undetectable (!2 pmol/l). These findings, together with an appropriate ratio of proinsulin to insulin (19%) below the O25% ratio seen in insulinoma patients (5,6), are consistent with those observed in non-insulinoma insulin hypersecretion. The sulphonylurea screen was negative.…”

Section: Historysupporting

confidence: 85%

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

Myint

Greenfield²,

Farooqi³

et al. 2012

European Journal of Endocrinology

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Background: Spontaneous hyperinsulinaemic hypoglycaemia following gastric bypass surgery (GBS) is increasingly recognised. However, its pathophysiology remains unclear. Some patients require pancreatectomy. Medical therapy with calcium channel blockers, acarbose and diazoxide has been reported to be beneficial but has variable adherence and response. Method: We demonstrate the role of GLP1, counter-regulatory hormones and the subsequent response of GLP1 to somatostatin analogue therapy in a 42-year-old woman with persistent neuroglycopaenia 6 years after GBS. Plasma GLP1, insulin and glucose were measured for 5 h on three settings: i) a 75 g oral glucose tolerance test (OGTT); ii) a standard liquid test meal (LTM); and iii) an OGTT 30 min after a s.c. injection of 100 mg octreotide. Results: In comparison with obese non-diabetic controls, the patient had an elevated fasting and a markedly enhanced GLP1 response during the OGTT, followed by an exaggerated insulin response and a subsequent low glucose level. The GLP1 response to a LTM was similar but greater. Octreotide given prior to the OGTT attenuated both the GLP1 and insulin responses and abolished hypoglycaemia. Octreotide therapy significantly improved the patient's neuroglycopaenic symptoms. The hormone profile was reassessed after 6 months following the LTM preceded by octreotide injection. Peak GLP1 and insulin responses were less pronounced than pretreatment responses and without hypoglycaemia. The patient was treated with lanreotide and had remained symptom-free and euglycaemic for 4 years. Conclusion: An exaggerated incretin response following altered gastrointestinal anatomy was the likely cause of hypoglycaemia in our GBS patient. Somatostatin successfully suppressed this response acutely and in the long term, thereby avoiding pancreatectomy and its sequelae.

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Section: Historysupporting

confidence: 85%

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

Myint

Greenfield²,

Farooqi³

et al. 2012

European Journal of Endocrinology

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“…Occasionally, a patient with an insulinoma may not fulfill these criteria even during a 72-hour fast, and a few have plasma insulin levels lower than 18 pmol/L (< 3 µU/mL) during hypoglycemia, yet plasma C-peptide levels are usually 0.2 nmol/L (0.6 ng/mL) or higher, and plasma pro-insulin levels are usually 5.0 pmol/L or higher in such patients (3). Once a clinical and biochemical diagnosis is established, the imaging modalities are used for localization of the tumor.…”

Section: Discussionmentioning

confidence: 99%

A Case of Insulinoma With Provoked Seizures for the Past Fourteen Years: A Case Report

Kadkhodazadeh¹,

Kazempour²,

Salevatipour³

2015

Arch Crit Care Med

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Introduction: Insulinoma is one of the most common neuro-endocrine tumors of the pancreas. Some cases with insulinoma present neuropsychiatric symptoms and are often misdiagnosed as psychosis thus patients may remain symptomatic from one week to as long as several decades before diagnosis. Case Presentation: A 68-year-old male patient, who presented episodic seizures and a normal Electroencephalography (EEG) recording for the past fourteen years, had referred for evaluation of hypoglycemia. His biochemical profile revealed blood glucose of 45mg/dL. His C-peptide and insulin levels were elevated. Endoscopic pancreatic ultrasonography (EUS) revealed two mass lesions in pancreatic head. Pathological evaluation revealed well-differentiated endocrine neoplasm and granulomatous reaction in lymph nodes. After resection of the tumor, his symptoms resolved and he became seizure free. Conclusions: Some cases with insulinoma that present neuropsychiatric symptoms might remain symptomatic for several decades before diagnosis. Therefore, it is important for physicians to be aware of presentations of insulinoma to avoid diagnostic delays.

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“…As a result, C-peptide concentration has been used as a semi quantitative measure of β-cell secretory activity instead of insulin itself. C-peptide has a half-life 2.5 times longer than insulin and therefore higher concentrations exist in the peripheral circulation and levels fluctuate less [41].…”

Section: Diagnosismentioning

confidence: 99%

Type 2 Diabetes Mellitus and Glucagon Like Peptide-1 Receptor Signalling

Thompson¹

2013

Clin Exp Pharmacol

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It has been estimated that approximately 8.4% of the world population currently live with diabetes mellitus and type 2 diabetes is the most common form. Type 2 diabetes increases the risk of complications such as heart attacks, blindness, amputations and kidney failure. Glucagon like Peptide-1 (GLP-1) is an effective insulinotropic agent and therefore its effects on insulin secretion have been greatly examined for more than two decades. It is a polypeptide hormone secreted by the intestinal L-cells into the blood in response to food uptake. GLP-1 has a very short half-life in vivo due to the rapid proteolytic degradation by Dipeptidyl Peptidase IV (DPP-IV). Therefore DPP-IV resistant GLP-1 analogues, Exenatide and Liraglutide, have been developed and are currently being used in the treatment of type 2 diabetes. GLP-1 agonist functions by binding to its receptor, GLP1R, on the cell surface.The GLP-1R belongs to the class B peptide receptor family based on its structure and function. The binding of GLP-1 to its receptor results in activation of Gαs coupled adenylyl cyclase and the production of cyclic Adenosine Monophosphate (cAMP), which enhances glucose-induced insulin secretion. Continuous GLP-1R activation also causes insulin secretion and pancreatic islet β-cell proliferation and neogenesis. The GLP-1R is internalised following its activation, which regulates the biological responsiveness of the receptor. Structurally the GLP-1R contains a large N-terminal extracellular domain (TM1-TM7) joined by three intracellular loops (ICL1, ICL2, ICL3) and three extracellular loops (ECL1, ECL2, ECL3), and an intracellular C-terminal domain. These domains play critical roles in GLP-1R trafficking to the cell surface, and also in agonist dependent activation and internalisation of the receptor. This review is focused on type 2 diabetes, its treatment with GLP-1, GLP-1R structure and function, and the physiological affects resulting from GLP-1R activation.

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Insulin, C-peptide and proinsulin for the biochemical diagnosis of hypoglycaemia related to endogenous hyperinsulinism

Cited by 121 publications

References 22 publications

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

Prolonged successful therapy for hyperinsulinaemic hypoglycaemia after gastric bypass: the pathophysiological role of GLP1 and its response to a somatostatin analogue

A Case of Insulinoma With Provoked Seizures for the Past Fourteen Years: A Case Report

Type 2 Diabetes Mellitus and Glucagon Like Peptide-1 Receptor Signalling

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