Insulin Resistance Caused by Massive Degradation of Subcutaneous Insulin

Paulsen, Elsa P.; Courtney, J. W.; Duckworth, William C.

doi:10.2337/diab.28.7.640

Cited by 98 publications

(37 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the majority of cases, other known factors (insulin antagonists, insulin antibodies, etc.) 15 We now report increased insulin degrading activity in both muscle and fat obtained from human subjects with insulin resistance. 13 Although accelerated insulin degradation has been recognized for many years as a theoretical cause of an altered response to insulin, 14 only recently has a patient been described with diabetes mellitus and extreme resistance to subcutaneous insulin (but a normal response to intravenous insulin), with markedly elevated adipose tissue insulin degrading activity.…”

Section: Methodsmentioning

confidence: 74%

Accelerated Insulin Degradation: An Alternate Mechanism for Insulin Resistance

et al. 1979

Self Cite

View full text Add to dashboard Cite

We have examined insulin and glucagon degrading activities of muscle and fat tissues in 11 subjects (4 lean controls, 3 insulin-resistant obese subjects, 2 non-insulin-dependent diabetic subjects, and 2 insulin-treated diabetic subjects) and correlated degrading activity with (1) basal insulin level and (2) state of insulin resistance. We found hyperinsulinemia and insulin resistance to be significantly correlated with accelerated insulin and glucagon degrading activity. Weight reduction in an insulin-resistant obese patients results in parallel reduction in both basal insulin level and insulin-glucagon degrading activity. These data are consistent with the hypothesis that an alternative mechanism for insulin resistance may be an accelerated insulin degradation at the level of target tissues.

show abstract

Section: Methodsmentioning

confidence: 74%

Accelerated Insulin Degradation: An Alternate Mechanism for Insulin Resistance

et al. 1979

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, it is obvious from this case that a short tissue resistant test as proposed by Pualsen et al . (16) is not sufficient to exclude SIR. A prolonged tissue resistance protocol may be more appropriate in patients with immune-mediated SIR.…”

Section: Discussionmentioning

confidence: 95%

“…insulin;lack of increase in the circulatory insulin after subcutaneous insulin andincreased insulin degrading activity in the subcutaneous tissue (16). …”

Section: Discussionmentioning

confidence: 99%

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

Jassam

Amin

Holland

et al. 2014

Endocrinology, Diabetes &Amp; Metabolism Case Reports

View full text Add to dashboard Cite

SummaryA 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.

show abstract

“…Extreme subcutaneous insulin resistance is characterized by severe resistance to subcutaneous insulin with normal or near normal intravenous insulin sensitivity [5]. Though mechanism unknown, insulin degradation in subcutaneous adipose tissue and muscle has been reported [6,7]. Established mechanisms of insulin resistance include genetic defects in insulin receptors, insulin receptor antibodies and interference with intracellular insulin action due to the excess of counter-regulatory hormones of inflammatory cytokines and increased insulin clearance [3].…”

Section: Discussionmentioning

confidence: 99%

A Male with Extreme Subcutaneous Insulin Resistance: A Case Report

Ahmed

Prasad

Rahman

et al. 2016

Romanian Journal of Diabetes Nutrition and Metabolic Diseases

View full text Add to dashboard Cite

Introduction Though insulin has no upper limit in dosage, we do not encounter very high dose requirements too often. The reported case is the first in Bangladesh to require more than 1000 international units (IU) of subcutaneous insulin per day. Case presentation A 44-year old male diabetic patient from Bangladesh presented with unusually uncontrolled diabetes mellitus due to extreme insulin resistance. Despite dramatic increase in insulin step by step up to 1110 IU of concomitant short and intermediate acting insulin per day by subcutaneous route, his blood glucose remained over 12 mmol/L persistently, in all the fasting, pre-prandial, postprandial and random samples. He was also treated with several oral hypoglycemic agents including metformin, vildagliptin, glimepiride, pioglitazone and miglitol along with insulin but blood glucose levels remained almost unchanged. However, intravenous infusion of insulin over 4 hours caused a plummet in the glucose level. His blood test for insulin autoantibody was negative. Conclusion This paper provides a scope to review literatures on extreme subcutaneous insulin resistance and its management. It also reveals the limitations of management due to lack of facilities in an underdeveloped country, which hinders proper exploration to many medical issues.

show abstract

Insulin Resistance Caused by Massive Degradation of Subcutaneous Insulin

Cited by 98 publications

References 6 publications

Accelerated Insulin Degradation: An Alternate Mechanism for Insulin Resistance

Accelerated Insulin Degradation: An Alternate Mechanism for Insulin Resistance

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

A Male with Extreme Subcutaneous Insulin Resistance: A Case Report

Contact Info

Product

Resources

About