scholarly journals Glucokinase activating mutation causing hypoglycaemia diagnosed late in adult who fasts for Ramadhan

2021 ◽  
Vol 2021 ◽  
Author(s):  
Wann Jia Loh ◽  
Lily Mae Dacay ◽  
Clara Si Hua Tan ◽  
Su Fen Ang ◽  
Fabian Yap ◽  
...  
Keyword(s):  
Glucose Level ◽  
Serum Insulin ◽  
Insulin Level ◽  
Somatostatin Analogue ◽  
List Type ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Hypoglycaemia Unawareness ◽  
C Peptide ◽  
Genetic Causes ◽  
Activating Mutation

Summary Activating mutation of glucokinase gene (GCK) causes resetting of insulin inhibition at a lower glucose threshold causing hyperinsulinaemic hypoglycaemia (GCK-HH). This is the first reported case who tolerated years of regular fasting during Ramadhan, presenting only with seizure and syncope now. We describe a case with GCK gene variant p.T65I diagnosed in a 51-year-old woman with hypoglycaemia unawareness even at glucose level of 1.6 mmol/L. Insulin and C-peptide levels during hypoglycaemia were suggestive of hyperinsulinism, but at a day after intravenous glucagon, hypoglycaemia occurred with low insulin and C-peptide levels, pointing against insulinoma as the underlying aetiology. Imaging studies of the pancreas and calcium arterial stimulation venous sampling were unremarkable. A review of old medical records revealed asymptomatic hypoglycaemia years ago. Genetic testing confirmed activating mutation of GCK. Hypoglycaemia was successfully controlled with a somatostatin analogue. This case highlights the importance of consideration of genetic causes of hypoglycaemia in adulthood, especially when imaging is uninformative. Learning points Consider genetic causes of endogenous hyperinsulinism hypoglycaemia in adulthood, especially when imaging is uninformative. Late presentation of activating mutation of GCK can occur because of hypoglycaemia unawareness. Long-acting somatostatin analogue may be useful for the treatment of activating mutation of GCK causing hypoglycaemia. Depending on the glucose level when the blood was taken, and the threshold of glucose-stimulated insulin release (GSIR), the serum insulin and C-peptide levels may be raised (hyperinsulinaemic) or low (hypoinsulinaemic) in patients with activating mutation of GCK. Glucagon may be useful to hasten the process of unmasking the low insulin level during hypoglycaemia below the GSIR level of which insulin released is suppressed.

scholarly journals Autoimmune hypoglycaemia caused by alpha-lipoic acid: a rare condition in Caucasian patients

2018 ◽  
Vol 2018 ◽  
Author(s):  
A Veltroni ◽  
G Zambon ◽  
S Cingarlini ◽  
M V Davì
Keyword(s):  
Lipoic Acid ◽  
Serum Insulin ◽  
Strong Association ◽  
High Serum ◽  
List Type ◽  
Alpha Lipoic Acid ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
C Peptide ◽  
Sulphydryl Groups ◽  
Caucasian Patients

Summary Insulin autoimmune syndrome (IAS), a rare cause of autoimmune hyperinsulinaemic hypoglycaemia, is relatively well known in Japan. The incidence in Caucasians is less than one-fifth of that reported in Japanese people, but it is becoming increasingly recognised worldwide in non-Asians as well. Drugs containing sulphydryl groups are known to be associated with the disease in genetically predisposed individuals. Moreover, several recent reports showed a direct association between the onset of IAS and the consumption of dietary supplements containing alpha-lipoic acid (LA). Insulinoma remains the most prevalent cause of hypersulinaemic hypoglycaemia in Caucasians. Consequently, primary investigation in these patients is generally focused on localisation of the pancreatic tumour, often with invasive procedures followed by surgery. We described a case of an Italian woman presenting to us with severe recurrent hypoglycaemia associated with high insulin and C-peptide levels and no evidence of pancreatic lesions at imaging diagnostic procedures. She had taken LA until 2 weeks before hospitalisation. After an evaluation of her drug history, an autoimmune form of hypoglycaemia was suspected and the titre of insulin autoantibodies was found to be markedly elevated. This allowed us to diagnose LA-related IAS, thus preventing any unnecessary surgery and avoiding invasive diagnostic interventions. Learning points: IAS is a rare cause of hyperinsulinaemic hypoglycaemia that typically affects Asian population, but it has been increasingly recognised in Caucasian patients. It should be considered among the differential diagnosis of hyperinsulinaemic hypoglycaemia to avoid unnecessary diagnostic investigations and surgery. It should be suspected in the presence of very high serum insulin levels (100–10  000  μU/mL) associated with high C-peptide levels. There is a strong association with administration of drugs containing sulphydryl groups included LA, a dietary supplement commonly used in Western countries to treat peripheral neuropathy.

scholarly journals A case of low serum insulin levels in a patient with insulinoma

2016 ◽  
Vol 2016 ◽  
Author(s):  
Chun-Han Lo ◽  
Ding-Ping Sun
Keyword(s):  
Ct Scan ◽  
Serum Insulin ◽  
Laboratory Data ◽  
Insulin Level ◽  
Laparoscopic Distal Pancreatectomy ◽  
List Type ◽  
Previous Night ◽  
C Peptide ◽  
Insulin Levels ◽  
Glucose Levels

Summary Insulinomas are the most common cause of hypoglycemia resulting from endogenous hyperinsulinism. Traditionally, inappropriately elevated levels of insulin in the face of hypoglycemia are the key to diagnosis. However, contradictory levels of insulin and C-peptide do not necessarily exclude the diagnosis. A 50-year-old female was brought to our emergency department because of conscious disturbance on the previous night. She had no history of diabetes mellitus, and was not using any medications or alcohol. Laboratory data showed low sugar, a significantly low insulin level, and elevated C-peptide. After admission, she had multiple episodes of spontaneous hypoglycemia after overnight fasts without discomfort. It was considered that a neuroendocrine tumor was the source of her hypoglycemia. CT scan of the abdomen revealed a 1.1cm hypervascular nodule in the pancreatic tail. Elective laparoscopic distal pancreatectomy was incorporated into her treatment course. A 1.2×1.0cm homogenous well-encapsulated tumor was resected. We monitored her glucose levels in the outpatient clinic every month for a period of six months. She did not have another episode of spontaneous hypoglycemia. Learning points Insulinoma causes endogenous hypoglycemia – it cannot be ruled out in patients presenting with hypoglycemia and low insulin levels; history and imaging studies should be done for further assessment A 24-h fast test has the same clinical significance as that of 72-h fast test C-peptide is a useful biochemical marker in addition to serum insulin, which can be used to diagnose insulinomas CT scan is used to measure the tumor size and localize the tumor. However, definitive diagnosis is only achieved through histopathologic evaluation of diseased tissue

Palliative Treatment of Hyperinsulinism With Cyproheptadine and Diazoxide

PEDIATRICS ◽  
1992 ◽  
Vol 90 (2) ◽  
pp. 212-215
Author(s):  
Deborah Rotenstein ◽  
Scott Serbin ◽  
Terra Welsh
Keyword(s):  
Glucose Level ◽  
Combination Treatment ◽  
Palliative Treatment ◽  
Neonatal Period ◽  
Insulin Level ◽  
Treatment Modalities ◽  
Normal Range ◽  
C Peptide ◽  
Level Of Consciousness ◽  
In Infants And Children

Treatment for hyperinsulinism in infants and children can be difficult and has included numerous treatment modalities. This paper reports 16 months of palliative treatment with cyproheptadine and diazoxide in a child with hyperinsulinism initially diagnosed at 6 months of age (her insulin level was 80 µU/mL while her glucose level was 38 mg/dL). She continued to have episodes of staring and alteration in level of consciousness while receiving her usual doses of diazoxide (12 mg/kg) alone. Mean nocturnal glucose values, which were quite low during treatment with diazoxide alone, improved significantly with the addition of cyproheptadine to her therapeutic regimen. Fasted C-peptide values, elevated during diazoxide alone, returned to the normal range with combination treatment for 16 months. Cyproheptadine and diazoxide in combination may be useful for treatment of hyperinsulinism that presents after the neonatal period.

scholarly journals Biochemical and molecular biological aspects of glucose intolerance in elderly persons

2004 ◽  
Vol 23 (2) ◽  
pp. 161-164
Author(s):  
Snezana Djurica ◽  
Goran Koricanac ◽  
Nevena Ribarac-Stepic ◽  
Mladen Davidovic ◽  
Dragoslav Milosevic ◽  
...  
Keyword(s):  
Serum Insulin ◽  
Insulin Receptors ◽  
Insulin Level ◽  
Normal Serum ◽  
Membrane Receptors ◽  
Control Group ◽  
Elderly Persons ◽  
Middle Aged ◽  
C Peptide ◽  
High Affinity

Changes in carbohydrate metabolism in elderly persons have drawn considerable attention but the findings from different studies are in contrast and are even controversial. The insulin receptors in erythrocytes were studied in elderly euglycaemic patients and in a middle-aged control group. The examined persons were also subjected to measurements of blood glucose, insulin and C-peptide concentrations, before and 3 hours after a dietetic meal. In the present study it was found that in spite of the maintained insulin level and C-peptide secretion, some structural and corresponding changes in membrane insulin receptors and the binding site caused differences in postreceptor responses in elderly persons. The examined groups, consisted of 29 males, average age of 66 years (65-70), with normal serum glucose level and 19 middle-aged males, average age of 42 years (32-48), with normal glycoregulation. In basal condition, elderly persons have both normal morning serum insulin (19.68 ? 4.00 mU/L) and C-peptide (2.04 ? 0.78 nmol/L) level. In elderly persons, the number of high affinity insulin receptors in erythrocytes membrane is 22.80 ? 6.18 but the formed insulin-high affinity receptors were not stable. Dissociation constant (Kd1) indicates its elevated dissociation (0.11 ? 0.04). At the same time the number of insulin low affinity binding sites is increased (13 273 ? 5 572) with a fast dissociation of the hormone (13.99 ? 3.37). Food intake raised the number of high affinity receptors compared to the basal value. Alteration in insulin binding affinity suggests the structural and corresponding changes in membrane receptors that may cause differences in postreceptors responses in elderly persons.

scholarly journals Correlation of Estrogen with Serum Insulin and Blood Glucose Levels in Post-menopausal Women

2017 ◽  
Vol 46 (1) ◽  
pp. 32-37
Author(s):  
Nahid Yeasmin ◽  
Qazi Shamima Akhter ◽  
Sayeeda Mahmuda ◽  
Mahmudul Hasan ◽  
Rukhshana Rabbani ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Blood Glucose Level ◽  
Postmenopausal Women ◽  
Glucose Level ◽  
Serum Insulin ◽  
Fasting Blood Glucose ◽  
Insulin Level ◽  
Fasting Insulin ◽  
Glucose Levels ◽  
Estrogen Level

Hyperglycemia is a major risk factor for cardiovascular diseases in postmenopausal women. Increased incidence of cardiovascular diseases in postmenopausal women may be due to hyperglycemia caused by lower level of estrogen hormone. This cross sectional study was conducted in the Department of Physiology, Dhaka Medical College, Dhaka, Bangladesh during the period of January to December 2011 to observe the correlation of estrogen with fasting serum insulin (FSI) and fasting blood glucose (FBG) levels in postmenopausal women. A total of 90 women were selected from different areas of Dhaka city, among them, 60 postmenopausal women of age group 50 to 60 years were taken as study group and 30 apparently healthy premenopausal women of age group 20 to 30 years were included as comparison group. The study parameters fasting blood glucose level was estimated by enzymatic method in both groups. Serum insulin level was estimated by Enzyme Linked Immunosorbent Assay (ELISA) and serum estrogen level by RIA method in order to assess the hormonal level of both groups. Data was analyzed by Unpaired Student’s‘t’ test and Pearson's correlation co-effcient (r) test as applicable. Mean serum fasting insulin level and mean blood glucose level was higher in postmenopausal women than premenopausal and result was statistically significant. In postmenopausal women serum estrogen level was lower than premenopausal and serum estrogen level showed negative correlation with serum fasting insulin level. Blood glucose level also showed negative correlation with serum estrogen level. All these correlation were statistically non-significant. It may be concluded that the serum fasting insulin and blood glucose levels are significantly higher in postmenopausal women that may be due to low level of estrogen.Bangladesh Med J. 2017 Jan; 46 (1): 32-37

scholarly journals Emerging role of C-peptide as an early biomarker of metabolic syndrome

2021 ◽  
Vol 9 (8) ◽  
pp. 2376
Author(s):  
Rana Usmani ◽  
Tariq Masood ◽  
Kanika Kakkar ◽  
Gunjan Mishra ◽  
Adarsh Uniyal ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Serum Insulin ◽  
Insulin Level ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
C Peptide ◽  
Insulin Levels ◽  
General Physical Examination ◽  
Early Biomarker ◽  
General Physical

Background: Metabolic syndrome is a health issue of rising concern as it has a correlation with the occurrence of cardiovascular events. Early identification of this syndrome by evaluating levels of biomarkers such as C peptide can help medical professionals prevent the occurrence of life-threatening cardiovascular diseases.Methods: This cross-sectional study was carried out in 89 subjects who were diagnosed to have metabolic syndrome. General Physical examination was done and fasting C peptide and insulin levels were quantified, followed by statistical analysis and their correlation. The prevalence of defining parameters of Metabolic Syndrome as per IDF 2005 was studied.Results: Out of 89 (100%) subjects, 80 (89.8%) subjects (Mean±SD=6.14±3.47) had C- peptide level >1.89 ng/ml which was statistically highly significant (p<0.001). Also, out of 89 (100%) subjects, 67 (24.71%) subjects had insulin level <25 mIU/L which was statistically significant (p<0.001).Conclusions: It was thereby concluded that serum C peptide levels were raised in patients of Metabolic syndrome and it is superior to serum Insulin levels as an early biomarker of the same.

scholarly journals Partial diazoxide responsiveness in a neonate with hyperinsulinism due to homozygous ABCC8 mutation

2019 ◽  
Vol 2019 ◽  
Author(s):  
Sarah Kiff ◽  
Carolyn Babb ◽  
Maria Guemes ◽  
Antonia Dastamani ◽  
Clare Gilbert ◽  
...  
Keyword(s):  
Total Pancreatectomy ◽  
Significant Risk ◽  
Somatostatin Analogue ◽  
List Type ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Elevated Glucose ◽  
Diffuse Form ◽  
Term Baby ◽  
Learning Points ◽  
Analogue Octreotide

Summary We report a case of partial diazoxide responsiveness in a child with severe congenital hyperinsulinaemic hypoglycaemia (CHI) due to a homozygous ABCC8 mutation. A term baby, with birth weight 3.8 kg, born to consanguineous parents presented on day 1 of life with hypoglycaemia. Hypoglycaemia screen confirmed CHI. Diazoxide was commenced on day 7 due to ongoing elevated glucose requirements (15 mg/kg/min), but despite escalation to a maximum dose (15 mg/kg/day), intravenous (i.v.) glucose requirement remained high (13 mg/kg/min). Genetic testing demonstrated a homozygous ABCC8 splicing mutation (c.2041-1G>C), consistent with a diffuse form of CHI. Diazoxide treatment was therefore stopped and subcutaneous (s.c.) octreotide infusion commenced. Despite this, s.c. glucagon and i.v. glucose were required to prevent hypoglycaemia. A trial of sirolimus and near-total pancreatectomy were considered, however due to the significant morbidity potentially associated with these, a further trial of diazoxide was commenced at 1.5 months of age. At a dose of 10 mg/kg/day of diazoxide and 40 µg/kg/day of octreotide, both i.v. glucose and s.c. glucagon were stopped as normoglycaemia was achieved. CHI due to homozygous ABCC8 mutation poses management difficulties if the somatostatin analogue octreotide is insufficient to prevent hypoglycaemia. Diazoxide unresponsiveness is often thought to be a hallmark of recessively inherited ABCC8 mutations. This patient was initially thought to be non-responsive, but this case highlights that a further trial of diazoxide is warranted, where other available treatments are associated with significant risk of morbidity. Learning points: Homozygous ABCC8 mutations are commonly thought to cause diazoxide non-responsive hyperinsulinaemic hypoglycaemia. This case highlights that partial diazoxide responsiveness in homozygous ABCC8 mutations may be present. Trial of diazoxide treatment in combination with octreotide is warranted prior to considering alternative treatments, such as sirolimus or near-total pancreatectomy, which are associated with more significant side effects.

scholarly journals Heterogeneity of glucagonomas due to differential processing of proglucagon-derived peptides

2015 ◽  
Vol 2015 ◽  
Author(s):  
Benjamin G Challis ◽  
Nicolai J Wewer Albrechtsen ◽  
Vishakha Bansiya ◽  
Keith Burling ◽  
Peter Barker ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Biological Activities ◽  
Clinical Manifestations ◽  
Somatostatin Analogue ◽  
List Type ◽  
Diverse Range ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Differential Processing ◽  
Clinical Phenotypes ◽  
Necrolytic Migratory Erythema

Summary Pancreatic neuroendocrine tumours (pNETs) secreting proglucagon are associated with phenotypic heterogeneity. Here, we describe two patients with pNETs and varied clinical phenotypes due to differential processing and secretion of proglucagon-derived peptides (PGDPs). Case 1, a 57-year-old woman presented with necrolytic migratory erythema, anorexia, constipation and hyperinsulinaemic hypoglycaemia. She was found to have a grade 1 pNET, small bowel mucosal thickening and hyperglucagonaemia. Somatostatin analogue (SSA) therapy improved appetite, abolished hypoglycaemia and improved the rash. Case 2, a 48-year-old male presented with diabetes mellitus, diarrhoea, weight loss, nausea, vomiting and perineal rash due to a grade 1 metastatic pNET and hyperglucagonaemia. In both cases, plasma levels of all measured PGDPs were elevated and attenuated following SSA therapy. In case 1, there was increased production of intact glucagon-like peptide 1 (GLP-1) and GLP-2, similar to that of the enteroendocrine L cell. In case 2, pancreatic glucagon was elevated due to a pancreatic α-cell-like proglucagon processing profile. In summary, we describe two patients with pNETs and heterogeneous clinical phenotypes due to differential processing and secretion of PGDPs. This is the first description of a patient with symptomatic hyperinsulinaemic hypoglycaemia and marked gastrointestinal dysfunction due to, in part, a proglucagon-expressing pNET. Learning points PGDPs exhibit a diverse range of biological activities including critical roles in glucose and amino acid metabolism, energy homeostasis and gastrointestinal physiology. The clinical manifestations of proglucagon-expressing tumours may exhibit marked phenotypic variation due to the biochemical heterogeneity of their secreted peptide repertoire. Specific and precise biochemical assessment of individuals with proglucagon-expressing tumours may provide opportunities for improved diagnosis and clinical management.

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