Hyperinsulinaemic hypoglycaemia in deoxyguanosine kinase deficiency

2019 ◽  
Vol 91 (6) ◽  
pp. 900-903
Author(s):  
Ved Bhushan Arya ◽  
Anil Dhawan ◽  
Ritika R. Kapoor
Keyword(s):  
Hyperinsulinaemic Hypoglycaemia ◽  
Deoxyguanosine Kinase

scholarly journals Hyperinsulinaemic hypoglycaemia in non-anaesthetized Göttingen minipigs induces a counter-regulatory endocrine response and electrocardiographic changes

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Mille K. Lyhne ◽  
Andreas Vegge ◽  
Gro Klitgaard Povlsen ◽  
Rita Slaaby ◽  
Jonas Kildegaard ◽  
...  
Keyword(s):  
Plasma Glucose ◽  
Fold Increase ◽  
Diabetic Group ◽  
Large Animal ◽  
Qtc Interval ◽  
Interval Prolongation ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Large Animal Models ◽  
Qtc Interval Prolongation ◽  
Electrocardiographic Recordings

AbstractThe potentially fatal cardiovascular effects of hypoglycaemia are not well understood and large animal models of the counter-regulatory responses and cardiovascular consequences of insulin-induced hypoglycaemia are needed to understand the mechanisms in humans. The aim of this study was to develop a human-like minipig model of hypoglycaemia including healthy and diabetic pigs to investigate endocrine, electrocardiographic and platelet effects. Hypoglycaemia was induced using a hyperinsulinaemic, hypoglycaemic clamp and an insulin bolus protocol. Plasma glucose, glucagon, C-peptide, insulin, epinephrine and platelet aggregation responses were measured before, during and after hypoglycaemia. Continuous electrocardiographic recordings were obtained. Hypoglycaemia at a plasma glucose concentration of 0.8–1.0 mM in the clamp induced 25-fold increase in epinephrine and sixfold and threefold increase in glucagon for healthy and diabetic pigs, respectively. The hypoglycaemic clamp induced QTc-interval prolongation and increase in cardiac arrhythmias. In the bolus approach, the non-diabetic group reached plasma glucose target of 1.5 mM and QTc-interval was prolonged after insulin injection, but before glucose nadir. The diabetic group did not reach hypoglycaemic target, but still demonstrated QTc-interval prolongation. These results demonstrate effects of hyperinsulinaemic hypoglycaemia closely resembling human physiology, indicating the minipig as a translational animal model of counter-regulatory endocrine and myocardial effects of hypoglycaemia.

scholarly journals Hyperinsulinaemic hypoglycaemia: genetic mechanisms, diagnosis and management

2012 ◽  
Vol 35 (4) ◽  
pp. 589-601 ◽  
Author(s):  
Senthil Senniappan ◽  
Balasubramaniam Shanti ◽  
Chela James ◽  
Khalid Hussain
Keyword(s):  
Hyperinsulinaemic Hypoglycaemia ◽  
Diagnosis And Management ◽  
Genetic Mechanisms

Phosphorylation of anticancer nucleoside analogs by human mitochondrial deoxyguanosine kinase

1998 ◽  
Vol 56 (8) ◽  
pp. 1035-1040 ◽  
Author(s):  
Chaoyong Zhu ◽  
Magnus Johansson ◽  
Johan Permert ◽  
Anna Karlsson
Keyword(s):  
Nucleoside Analogs ◽  
Deoxyguanosine Kinase

scholarly journals Spontaneously remitting insulin autoimmune syndrome in a patient taking alpha-lipoic acid

2018 ◽  
Vol 2018 ◽  
Author(s):  
D Cappellani ◽  
C Sardella ◽  
M C Campopiano ◽  
A Falorni ◽  
P Marchetti ◽  
...  
Keyword(s):  
Differential Diagnosis ◽  
Lipoic Acid ◽  
University Hospital ◽  
Hypoglycaemic Episode ◽  
List Type ◽  
Alpha Lipoic Acid ◽  
Previous Exposure ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome

Summary Insulin autoimmune syndrome (IAS), or Hirata disease, is a rare hypoglycaemic disorder caused by the presence of high titer of insulin autoantibodies (IAA) in patients without previous exposure to exogenous insulin. Even though its pathogenesis is not fully understood, striking evidences link IAS to previous exposure to sulphydryl-containing medications, like alpha-lipoic acid, a widely used nutritional supplement. Although challenging, a careful differential diagnosis from other causes of hyperinsulinaemic hypoglycaemia (such as insulinoma) is mandatory, since these conditions require different therapeutic approaches. In the present study, we report a 35-year-old woman originally from Sri Lanka who was referred to our University Hospital on suspicion of occult insulinoma. Her medical history was positive for endometriosis, treated with estroprogestins and alpha-lipoic acid. The latter supplement was begun 2 weeks before the first hypoglycaemic episode. Our tests confirmed the presence of hypoglycaemia associated with high insulin and C-peptide concentrations. When insulin concentrations were compared using different assays, the results were significantly different. Moreover, insulin values significantly decreased after precipitation with polyethylene glycol. An assay for IAA proved positive (530 U/mL). A genetic analysis revealed the presence of HLA-DRB1*04,15, an immunogenetic determinant associated with IAS. On the basis of clinical data we avoided a first-line approach with immunosuppressive treatments, and the patient was advised to modify her diet, with the introduction of frequent low-caloric meals. During follow-up evaluations, glucose levels (registered trough a flash glucose monitoring system) resulted progressively more stable. IAA titer progressively decreased, being undetectable by the fifteenth month, thus indicating the remission of the IAS. Learning points: Insulin autoimmune syndrome (IAS) is a rare cause of hyperinsulinaemic hypoglycaemia, whose prevalence is higher in East Asian populations due to the higher prevalence of specific immunogenetic determinants. Nevertheless, an increasing number of IAS cases is being reported worldwide, due to the wide diffusion of medications such as alpha-lipoic acid. Differential diagnosis of IAS from other causes of hyperinsulinemic hypoglycaemia is challenging. Even though many tests can be suggestive of IAS, the gold standard remains the detection of IAAs, despite that dedicated commercial kits are not widely available. The therapeutic approach to IAS is problematic. As a matter of fact IAS is often a self-remitting disease, but sometimes needs aggressive immunosuppression. The benefits and risks of any therapeutic choice should be carefully weighted and tailored on the single patient.

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