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Department

Biochemistry

Preferred Sample Type

Insulin

Suitable Specimen Types

  • EDTA Plasma
1 mL blood

Sample Processing in Laboratory

Please spin and separate plasma. Store plasma frozen. Sample ok if refridgerated for up to 48hrs

Sample Preparation

Blood needs to be collected into EDTA plasma. Please note sample type change as of 21.02.2022. Insulin is more stable in EDTA plasma

Turnaround Time

7 days

Sample Stability

RT on receipt, store at -20C (whole blood stable for 20hrs, sepearted plasma stable for 48hrs)

Insulin

General Information

The primary clinical use of insulin measurement is in the differential diagnosis of documented spontaneous hypoglycaemia. Further tests, such as those for ketones, proinsulin, growth hormone and the insulin-like growth factors may also be required to complete the diagnostic process.

Causes of hypoglycaemia in adults

Ill or medicated individual

  1. Drugs
    • Insulin or insulin secretagogue
    • Alcohol
    • Others (Table 3)
  2.  Critical illnesses
    • Hepatic, renal, or cardiac failure
    • Sepsis (including malaria)
    • Inanition
  3. Hormone deficiency
    • Cortisol
    • Glucagon and epinephrine (in insulin-deficient diabetes mellitus)
  4. Nonislet cell tumou

Seemingly well individual

  1. Endogenous hyperinsulinism
    • Insulinoma
    • Functional -cell disorders (nesidioblastosis)
    • Non-insulinoma pancreatogenous hypoglycemia
    • Post gastric bypass hypoglycemia
    • Insulin autoimmune hypoglycemia
    • Antibody to insulin
    • Antibody to insulin receptor
    • Insulin secretagogue
    • Other
  2. Accidental, surreptitious, or malicious hypoglycemia

 

Drugs other than antihyperglycemic agents and alcohol reported to cause hypoglycemia 

Moderate quality of evidence (+++):

  • Cibenzoline
  • Gatifloxacin
  • Pentamidine
  • Quinine
  • Indomethacin
  • Glucagon (during endoscopy)

Low quality of evidence (++):

  • Chloroquineoxaline sulfonamide
  • Artesunate/artemisin/artemether
  • IGF-1
  • Lithium
  • Propoxyphene/dextropropoxyphene

Very low quality of evidence (+):

  • Drugs with >25 cases of hypoglycemia identified
    • Angiotensin converting enzyme inhibitors
    • Angiotensin receptor antagonists
    • Adrenergic receptor antagonists
    • Levofloxacin
    • Mifepristone
    • Disopyramide
    • Trimethoprim-sulfamethoxazole
    • Heparin
    • 6-Mercaptopurine

Ref: J Clin Endocrinol Metab, March 2009, 94(3):709–728 jcem.endojournals.org 713

Patient Preparation

Blood should be collected when patient is hypoglycaemic.

Please note: Exogenous Insulin preparations have been shown to cross-react with the Architect insulin assay, but to varying degrees. The human sequence insulin preparations (Actrapid, Humulin S, Insulatard, Humulin I and Humulin M3) demonstrated similar levels of recovery (between 81 and 89%), indicating extensive cross-reactivity in the insulin assay. The insulin analogues (NovoRapid, Apidra, Humalog, Levemir and Lantus) demonstrated variable degrees of recovery with Apidra, showing the lowest recovery at 12 and 14%, while Lantus, over-recovered at 127 and 140%, demonstrating significant cross-reactivity with the assay.

Notes

If glucose is above 3.1 mmol/L, insulin analysis is not usually carried out

Haemolysed samples are not suitable for analysis

 

Please note sample type change from 21.02.2022.  EDTA is now the required specimen type

Reference Range

No associated reference range. Should be interpreted alongside with glucose and c-peptide.

Non- diabetic hypoglycaemia
Evaluation of hypoglycaemia should only be undertaken for patients in whom Whipple’s triad has been documented. Firstly, review the history and physical findings to exclude more common hypoglycaemic aetiologies such as; drugs (insulin, insulin secretagogues, alcohol ingestion), critical illness (sepsis, organ failure), cortisol deficiency and non-islet cell tumours.
Once these have been excluded, in the seemingly well individual, the differentials lie between accidental/ surreptitious hypoglycaemia and endogenous hyperinsulinaemia. Further evaluation is warranted and should involve the following concomitant tests in the event of an ongoing episode of hypoglycaemia; plasma glucose (for confirmation of hypoglycaemia), insulin, C-peptide, beta-hydroxybutyrate as well as the measurement of circulating oral hypoglycaemic agents (if there is a degree of suspicion). When spontaneous hypoglycaemia cannot be observed, a prolonged fast or mixed meal test may recreate the environment in which hypoglycaemia is likely to occur.

Table 1: Taken from the Endocrine Society Guideline in 2009

Sxs/Signs

Glucose

(mmol/L)

Insulin (pmol/L) C-peptide (pmol/L) BHB (mmol/L) Circulating OHA Ab to insulin Interpretation
No <3.1 <21 <200 >2.7 No No Normal
Yes <3.1 >>21 <200 ≤2.7 No Neg (Pos) Exogenous insulin
Yes <3.1 ≥21 ≥200 ≤2.7 No Neg Insulinoma, NIPHS, PGBH
Yes <3.1 ≥21 ≥200 ≤2.7 Yes Neg Oral hypoglycaemic agent
Yes <3.1 >>21 >>200 ≤2.7 No Pos Oral hypoglycaemic agent
Yes <3.1 <21 <200 ≤2.7 No Neg IGF mediated
Yes <3.1 <21 <200 >2.7 No Neg Not insulin (or IGF) mediated

 

Specifications

  • EQA Scheme?: Yes
  • EQA Status: UK NEQAS Guildford Peptide Hormones