Insulin level 

Sample for Insulin level

1. This test is done on the serum of the patient.
2. A fasting sample is preferred.
   1. Freeze the sample.
3. With OGTT, draw a fasting sample and then at 30, 60. and 120 minutes.
4. Avoid hemolysis.

Purpose of the test (Indications) of Insulin level

1. It helps in the management of glucose metabolism.
2. Insulin level helps in the diagnosis of insulinoma.
3. Insulin levels can be advised in starting the initial therapy for patients with type 2 Diabetes Mellitus.
   1. In case of lower insulin levels, the most adequate is insulin or an insulin secretagogue as the treatment of choice.
4. Insulin level is advised in case of fasting hypoglycemia.
   1. It helps patients with diabetes requiring insulin as treatment and patients who can control it with diet only.
5. Advised in the case of abnormal carbohydrate and lipid metabolism.
6. Insulin was recently advised in case of polycystic ovary syndrome.
   1. Ladies with this disease have insulin resistance and abnormal carbohydrate metabolism that may respond to oral hypoglycemic agents.
7. Insulin is not clinically advised for the diagnosis of diabetes mellitus.
   1. People were estimating insulin levels in OGTT to help early diagnose diabetes mellitus.

Precautions for insulin level

1. Keep in mind that insulin antibodies can interfere with radioimmunoassay.
2. The patients treated with insulin develops antibodies.
3. Obesity and food may increase insulin levels.
4. Radioisotopes if given in before the test, will affect the result.
5. Drugs like corticosteroids, oral contraceptives, and levodopa increase insulin levels.

Pathophysiology of Insulin level

Definition of Insulin level:

1. It is an islet cell, an anabolic hormone that controls glucose uptake, fat, and protein synthesis.
2. It is a protein hormone produced by the beta cells of islets of Langerhans in the pancreas.
3. Its molecular weight is 6000 D and consists of 51 amino acids.
4. It has two amino acid chains A and B joined by the disulfide bridge.
5. Insulin in humans is similar to insulin in animals.
6. Now mostly the patients are treated with human recombinant insulin.

Insulin formation:

1. Insulin forms from the preproinsulin which consists of 100 amino acids and is inactive. It is not found in the blood.
   1. Preproinsulin converts into proinsulin which cleaves by the proteolytic enzymes.
   2. There is the formation of insulin and C-peptide.
      1. C-peptide has no insulin-like action, but it can be measured to assess the β-cell function.
   3. Insulin is stored in secretory granules, when plasma glucose is increased, insulin is released by an exostosis.
   4. insulin half-life is 10 to 25 minutes (another reference is 4 to 9 minutes).

Insulin regulates carbohydrate metabolism (Insulin functions):

1. Insulin maintains blood glucose at a constant level within the defined normal range.
2. Insulin facilitates the movement of glucose from the bloodstream into the cell.
3. Insulin is the anabolic hormone that stimulates the uptake of glucose into the fat and muscles.
4. Insulin promotes the conversion of glucose into glycogen or fat storage.
5. Insulin inhibits glucose production from the liver.
6. Insulin stimulates protein synthesis and inhibits protein breakdown.

7. The insulin level secretion is dependent upon the level of glucose.

Insulin secretion is reduced during fasting and starvation.

1. Glucose decreases in the first three days of the fast at around 18 mg/dL.
2. Glucagon secretion is doubled to maintain the glucose level.
3. Lipolysis and liver ketogenesis is stimulated.
4. Ketone bodies, fatty acids, and glycerol levels in the blood are increased.
5. Initially triglyceride increases and later decreases.
6. Cholesterol also decreases.
7. Due to catabolism in starvation, the concentration of the protein in the blood increases.
8. There are chances to develop metabolic acidosis.
   1. Reduced blood pH.
   2. Reduced pCO2.

Insulin levels can be evaluated with OGTT or fasting glucose:

1. There are suggestions that insulin level on the same sample with OGTT level is more reliable than a single insulin level.
2. Patient with Juvenile diabetes has a typical picture in OGTT:
   1. Low fasting insulin level and display flat GT insulin curve.
   2. This shows that there is no increase in the insulin level.

3. Patients with mild diabetes mellitus show:
   1. Normal fasting insulin level.
   2. GT curve with a delayed rise in insulin.
4. Patients with diabetes mellitus type 2 show:
   1. Fasting insulin level is normal and there is a delayed response of the insulin to glucose.

5. Insulinoma has a characteristic picture of the fasting glucose level and insulin level.
   1. There is increased insulin with low fasting glucose.
   2. Persistent hypoglycemia with an increased insulin level.
   3. The insulin/glucose ratio should be less than 0.3.
   4. The insulin/fasting glucose ratio is more than 0.3 in Insulinoma.

Turner amended the ratio calculated by his formula:

1. When the glucose level increases, the insulin level also increases. When the glucose level decreases then, insulin secretion stops.
2. Insulin levels will be low in Insulin-dependent diabetes mellitus.
3. While insulin level is high in non-insulin-dependent diabetes mellitus but due to resistance to insulin patient needs more insulin.

Insulinoma:

1. This is the tumor of beta cells in the islets cells of  Langerhans of the pancreas.
2. There is persistent hypoglycemia which may be below 30 mg/dL.
3. There is raised the level of insulin.
4. There is a persistently high level of C-peptide.
5. The Turner (modified)  insulin/glucose ratio is above 50.

Insulinoma

Normal insulin level

Source 1

Insulin free

• Infants and  prepubertal child = <13 µU/mL
• Prepubertal child and adult = <17 µU/mL
  • To convert into SI units x 6.945 = pmol/L
• Insulin immunoreactive 
  • 2 to 12 year = <10 µU/mL
  • Adult = <35 µU/mL
• Insulin with oral glucose tolerance test
  • 0 minute = 3 to 28 µU/mL
  • 30 minutes = 20 to 112 µU/mL
  • 60 minutes = 29 to 88 µU/mL
  • 120 minutes = 22 to 79 µU/mL
  • 180 minutes = 4 to 62 µU/mL

Source 2

• Adult = 6 to 26  µU/mL (43 to 186 pmol/L)
• Newborn = 3 to 20 µU /mL
  • Possible critical value = >30 µU/mL

Increased Insulin level is seen in the following:

1. Insulinoma.
   1. Fasting insulin level is >50 µU/mL in the presence of normal or low blood glucose.
2. Insulin autoimmune syndrome.
3. Acromegaly.
   1. There are raised glucose levels.
   2. The overproduction of growth hormone in these patients gives rise to constant stimuli for insulin production.
4. Cushing’s syndrome.
   1. There is a raised level of glucose by the overproduction of cortisol.
   2. There is constant stimulation for the production of insulin.
5. Pancreatic islet cell hyperplasia.
6. Obesity. There is a constantly raised level of insulin.
7. Fructose or galactose intolerance.
8. Cirrhosis is where insufficient clearance from the blood circulation.

Decreased or absent Insulin level is seen in:

1. Diabetes mellitus type 1 (maybe total lake or very low).
2. In diabetes mellitus type 2, there is a low level of resistance to insulin.
   1. In the case of severe diabetes mellitus with ketosis and weight loss.
   2. In less severe cases of diabetes, insulin is present but at a lower glucose level.
3. Hypopituitarism.

• Critical Value of Insulin = >30 mU/mL

Questions and answers: