scholarly journals Analytical and clinical challenges in a patient with concurrent type 1 diabetes, subcutaneous insulin resistance and insulin autoimmune syndrome

2014 ◽  
Vol 2014 ◽  
Author(s):  
N Jassam ◽  
N Amin ◽  
P Holland ◽  
R K Semple ◽  
D J Halsall ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 1 Diabetes ◽  
Insulin Antibodies ◽  
List Type ◽  
Subcutaneous Insulin ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
Free Insulin ◽  
Gradual Disappearance

Summary A lean 15-year-old girl was diagnosed with type 1 diabetes based on symptomatic hyperglycaemia and positive anti-islet cell antibodies. Glycaemia was initially stabilised on twice-daily mixed insulin. After 11 months from the time of diagnosis, she complained of hyperglycaemia and ketosis alternating with hypoglycaemia. This progressively worsened until prolonged hospital admission was required for treatment of refractory hypoglycaemia. A high titre of anti-insulin antibodies was detected associated with a very low recovery of immunoreactive (free) insulin from plasma after precipitation with polyethylene glycol, suggesting the presence of insulin in bound complexes. Insulin autoimmune syndrome was diagnosed and metabolic fluctuations were initially managed supportively. However, due to poor glucose control, immunosuppressive therapy was initiated first with steroids and plasmapheresis and later with anti-CD20 antibody therapy (Rituximab). This treatment was associated with a gradual disappearance of anti-insulin antibodies and her underlying type 1 diabetes has subsequently been successfully managed with an insulin pump. Learning points Anti-insulin antibodies may result in low levels of free insulin. Polyclonal anti-insulin antibodies can interfere with the pharmacological action of administered insulin, resulting in hypoglycaemia and insulin resistance, due to varying affinities and capacities. In this patient, rituximab administration was associated with a gradual disappearance of anti-insulin antibodies. It is hypothesised that this patient had subcutaneous insulin resistance (SIR) caused by insulin capture at the tissue level, either by antibodies or by sequestration. A prolonged tissue resistance protocol may be more appropriate in patients with immune-mediated SIR syndrome.

scholarly journals A Case Report of Subcutaneous Insulin Resistance in Type 1 Diabetes, July 2018, Ardabil, Iran

2019 ◽  
Vol 2 (10) ◽  
pp. 42-43
Author(s):  
Zamanpour Mohammadzaman ◽  
Maskani Reza ◽  
Hosseini Anbaran Sonia
Keyword(s):  
Insulin Resistance ◽  
Type 1 Diabetes ◽  
Case Report ◽  
Subcutaneous Insulin

scholarly journals Impact of insulin antibodies on insulin aspart pharmacokinetics and pharmacodynamics after 12-week treatment with multiple daily injections of biphasic insulin aspart 30 in patients with type 1 diabetes

2005 ◽  
Vol 153 (6) ◽  
pp. 907-913 ◽  
Author(s):  
J-W Chen ◽  
J Frystyk ◽  
T Lauritzen ◽  
J S Christiansen
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Aspart ◽  
Insulin Antibodies ◽  
Multiple Daily Injections ◽  
Biphasic Insulin Aspart ◽  
Biphasic Insulin ◽  
Biphasic Insulin Aspart 30 ◽  
Free Insulin ◽  
Different Levels

Objective: This study aimed to evaluate the impact of insulin antibodies on insulin aspart pharmaco-kinetics and pharmacodynamics after 12-week multiple daily injections of biphasic insulin aspart 30 (30% fast-acting and 70% protamine-crystallised insulin aspart, BIAsp30) in patients with type 1 diabetes. Methods: Twenty-three patients (8 women, 15 men) aged 44.8 (20.6–62.5) years (median and range) with diabetes duration of 19.5 (1.6–44.6) years and haemoglobin (Hb)A1C of 9.2% (8.1–12.3%) participated in the study, which consisted of 12-week treatment with multiple injections of BIAsp30. At the end of the treatment period, all patients attended two 24-h profile days 1 week apart for pharmacokinetic and pharmacodynamic assessments. HbA1C and insulin antibodies were also determined. Results: Patients were stratified into two groups depending on whether the level of insulin binding to insulin antibodies was below or above 75% (moderate vs high (%, median and range): 62 (15–74) vs 80 (75–89)). High levels of insulin antibodies resulted in about threefold increase in AUC(0 – 24 h) (the area under the concentration-time curve during 24 h) for total insulin aspart (analysis of variance, P < 0.05). The differences in free insulin aspart pharmacokinetics, insulin pharmacodynamics and HbA1C were not statistically significant between patients with different levels of insulin antibodies. Total daily insulin dosage was significantly lower in patients with high than moderate levels of insulin antibodies. Conclusions: In type 1 diabetic patients, high levels of circulating insulin antibodies result in elevated total, but not free, insulin aspart profiles. Consistent with the finding of similar insulin pharmacodynamics, the long-term glycaemic control is not significantly different between patients with different levels of insulin antibodies.

Therapeutic plasma exchange normalizes insulin-mediated response in a child with type 1 diabetes and insulin autoimmune syndrome

2017 ◽  
Vol 19 (1) ◽  
pp. 171-179 ◽  
Author(s):  
Erin F Sharwood ◽  
Ian P Hughes ◽  
Carel J Pretorius ◽  
Peter Trnka ◽  
Jane Peake ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Plasma Exchange ◽  
Therapeutic Plasma Exchange ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome

scholarly journals Insulin autoimmune syndrome

2020 ◽  
Vol 2020 ◽  
Author(s):  
Marina Yukina ◽  
Nurana Nuralieva ◽  
Maksim Solovyev ◽  
Ekaterina Troshina ◽  
Evgeny Vasilyev
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Insulin Antibodies ◽  
List Type ◽  
Surgical Interventions ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome ◽  
Low Prevalence ◽  
Learning Points ◽  
Undetermined Significance

Summary Insulin autoimmune syndrome (Hirata’s disease) is a disorder caused by development of autoantibodies to insulin and manifested by hypoglycaemic syndrome. The overwhelming majority of physicians do not include it in the differential diagnosis of hypoglycaemic states because of a misconception of an extremely low prevalence of this condition. This results in unnecessary drug therapy and unjustified surgical interventions in patients that otherwise would be successfully treated conservatively. This disease is strongly associated with certain alleles of the HLA gene. In most cases, this condition develops in predisposed individuals taking drugs containing sulfhydryl groups. Formation of autoantibodies to insulin may be observed in patients with other autoimmune disorders, as well as in those with multiple myeloma or monoclonal gammopathy of undetermined significance. This paper presents the first Russian case report of insulin autoimmune syndrome in an adult patient. Learning points: Insulin autoimmune syndrome, Hirata’s disease, anti-insulin antibodies, and hypoglycaemia.

scholarly journals Hyperinsulinemic hypoglycemia associated with insulin antibodies caused by exogenous insulin analog

2016 ◽  
Vol 2016 ◽  
Author(s):  
Chih-Ting Su ◽  
Yi-Chun Lin
Keyword(s):  
High Serum ◽  
Insulin Antibodies ◽  
Insulin Analog ◽  
Hyperinsulinemic Hypoglycemia ◽  
Oral Glucose ◽  
List Type ◽  
Exogenous Insulin ◽  
C Peptide ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome

Summary Insulin antibodies (IA) associated with exogenous insulin administration seldom caused hypoglycemia and had different characteristics from insulin autoantibodies (IAA) found in insulin autoimmune syndrome (IAS), which was first described by Dr Hirata in 1970. The characteristic of IAS is the presence of insulin-binding autoantibodies and related fasting or late postprandial hypoglycemia. Here, we report a patient with type 1 diabetes mellitus under insulin glargine and insulin aspart treatment who developed recurrent spontaneous post-absorptive hyperinsulinemic hypoglycemia with the cause probably being insulin antibodies induced by exogenous injected insulin. Examinations of serial sera disclosed a high titre of insulin antibodies (33%, normal <5%), high insulin concentration (111.9 IU/mL) and undetectable C-peptide when hypoglycemia occurred. An oral glucose tolerance test revealed persistent high serum levels of total insulin and undetectable C-peptide. Image studies of the pancreas were unremarkable, which excluded the diagnosis of insulinoma. The patient does not take any of the medications containing sulfhydryl compounds, which had been reported to cause IAS. After administering oral prednisolone for 3 weeks, hypoglycemic episodes markedly improved, and he was discharged smoothly. Learning points: Insulin autoimmune syndrome (IAS) or IAS-like situation should be one of the differential diagnosis in patients with hyperinsulinemic hypoglycemia. Although less reported, insulin antibodies (IA) caused by exogenous insulin analog should be considered as the cause of hypoglycemia. Patients with suspected insulin autoimmune syndrome (IAS) should be screened for drugs related to autoimmunity to endogenous insulin.

A Novel Type of Extreme Insulin Resistance: Nonhypoglycemic Insulin Autoimmune Syndrome

2020 ◽  
Author(s):  
He Liu ◽  
Siyu Liang ◽  
Yu Li ◽  
Junling Fu ◽  
Shi Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Current Knowledge ◽  
Immunoreactive Insulin ◽  
Therapeutic Effects ◽  
Good Glycemic Control ◽  
Insulin Autoimmune Syndrome ◽  
Intravenous Insulin ◽  
Autoimmune Syndrome ◽  
Free Insulin ◽  
Extreme Insulin Resistance

Abstract Context Extreme insulin resistance is caused by genetic defects intersecting with the insulin action pathway or by the insulin receptor antibodies. Insulin autoimmune syndrome (IAS) is not considered one of the causes of extreme insulin resistance. Objective This work aimed to expand the current knowledge of extreme insulin resistance and to propose the diagnostic criteria and management strategy of a novel type of extreme insulin resistance. Methods A patient with IAS never experienced hypoglycemia but had persistent hyperglycemia and extreme insulin resistance with treatment with 200 U of intravenous insulin per day. Immunoreactive insulin (IRI), free insulin, and total insulin were measured. The ratio of free insulin to total insulin (insulin-free ratio, IFR) was calculated. Results Extreme insulin resistance has not been reported to be caused by IAS. At admission, IRI and free insulin were undetectable in our patient; total insulin was more than 20 160 pmol/L; and the IFR was lower than 0.03% (control, 90.9%). After adding 500 U porcine insulin to the precipitate containing insulin antibodies, the IRI was still undetectable. Since the patient started glucocorticoid therapy, the free insulin has gradually increased to 11.16 pmol/L, his total insulin has decreased to 5040 pmol/L, and the IFR has increased to 18.26%. Intravenous insulin was stopped, with good glycemic control. Conclusion High-affinity insulin autoantibodies with a large capacity can induce a novel type of extreme insulin resistance characterized by extremely high total insulin and very low free insulin levels. The IFR can be used to evaluate therapeutic effects.

Insulin autoimmune syndrome in a child with type 1 diabetes: Clinical, immunological, and biochemical correlations

Pathology ◽  
2016 ◽  
Vol 48 ◽  
pp. S89
Author(s):  
Erin Sharwood ◽  
Rehna Gous ◽  
John Cardinal ◽  
Ian Hughes ◽  
Tony Huynh
Keyword(s):  
Type 1 Diabetes ◽  
Insulin Autoimmune Syndrome ◽  
Autoimmune Syndrome
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