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What is insulin sensitivity?
Insulin sensitivity is a state where a small amount of insulin is able to produce severe
Hypoglycemic effect in a diabetic who has been controlled with OHA or insulin. When developing insulin sensitivity the patient gets recurrent Hypoglycemia and dose has to be reduced to keep him euglycemic.
Mechanism - Insulin sensitivity can develop in a person because of one of the following
reasons:
1. Decrease in the rate of insulin metabolism and exertion.
2. Decrease secretion of counter regulatory hormone.
3. Increased secretion of insulin or insulin like hormone.
4. Co-administration of the drug which affect either insulin secretion or
pharmacokinetics of insulin.
INSULIN SENSITIVITY
| Unrelated to Diabetes |
Related to Diabetes |
A. Decreased Secretion of Counter legulatory Hormone:
i. Hypopitularism
ii. Addisons disease
iii. Mvxoedema
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A. Diabetic Nephropathy
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B. Decreased Metabolism of Insulin
Acute Hepatic Disorders |
B. Diabetic Autonomic Neuropathy |
C. Decreased Excretion of Insulin
End Stage Renal Disease |
C. After Discharge Hypoglycemia in Diabetes Mellitus |
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D. Increased Secretion of insulin or Insulin like substances:-
i Islets Cell Tumour
ii Mesothelial Tumour e.g.
Fibroma, Fibrosarcorna
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D. IDDM in Remission
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E. Miscellaneous
i. Severe Cardiac Failure
ii Pregnancy - 1st Trimester
iii Drugs - B-agonist Saiicylates Quinine
Ace - Inhibitor Sulfonamide Thioctic
Acid Vanadium Salts
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Hypopitutarism: e.g. Sheehan's syndrome
The exact cause of increased insulin sensitivity is not known but presumably it is because
of lack of growth hormone or ACTH, of which growth hormone itself is a insulin antagonistic hormone, and decreased secretion ACTH secretion leads to decreased cortisone secretion which is also an insulin antagonist hormone.
In hypopitutarism and post hypophysectomised patients insulin sensitivity and
amelioration of DM is present and despite full replacement of cortisone amount of insulin required usually fall to less than 1/3 rd of prior requirement.
Hypoadrenalism: A diabetic who has developed Addison's disease may develop insulin
sensitivity leads to decreased insulin requirement and frequent hypoglycemic reactions. This occurs because in Addison's disease the aminoacids are diverted to protein synthesis rather than for glueoneogenesis. This decreased rate of gluconeogenesis is accompanied by decreased hepatic store of carbohydrates which explains increased insulin sensitivity.
Sudden increase in insulin sensitivity has also been observed in few case of meningococcal meningitis because of damage to adrenal glands.
Myxoedema: Untreated Myxoedema may reduce the severity of DM and insulin
requirement. Adequate treatment of Myxoedema will lead to the reappearance of the same severity of metabolic state that was present prior to the onset of myxoedema.
Islet cell tumors: This is a rare cause of increased insulin sensitivity seen only in patients with adult onset diabetes mellitus. These tumors causes increased secretion of insulin from remaining islet cells.
Hepatic disease: In normal condition 50% of insulin that reaches the liver via portal vein
is destroyed by enzyme insulinase (insulin breakdown is completed to a major extent in the liver). In various acute onset hepatic disorders there occurs decrease in levels of insulinase there by decreased inactivation of insulin which leads to prolonged effect of insulin in body.
In contrast to acute disorders of liver, in chronic diseases, there may be hyperglycemia.
Pregnancy: During pregnancy diabetics on insulin can develop frequent attacks of
hypoglycemia in 1st trimester due to poor diet and pregnancy induced vomiting.
Within the first 24-28 hrs. of delivery insulin requiremen1 suddenly reduces because of
the fall in levels of oestrogen progesterone and HPL (which have anti insulin effect)
Non pancreatic tumors: e.g. fibromas, fibrosarcomas.
These tumors cause insulin sensitivity because of :
1. Large size of these tumors cause increased glucose utilisation and concomitant
decrease in circulatory glucose level.
2. Release of substances that sensitise different tissues to the action of insulin.
3. Possibly secretion of insulin like substances from the tumor,
Diabetic nephropathy and end stage Renal disease of any etiology
a) lower food intake and increase renal threshold for glucose
b) increase half life of insulin because of decrease in excretion of insulin
c) loss of insulin binding antibodies or other antagonist of insulin (synalbumin) along with
proteinuria.
Autonomic neuropathy
In subjects with insulin dependent diabetes mellitus of longer duration, the glucagon
secretory response to hypoglycemia becomes deficient, but effective glucose counter regulation still occurs because epinephrine play a compensatory role. But when this mechanism becomes deficient as in automatic neuropathy, incidence of severe hypoglycemia increases.
After discharge hypoglycemia
Usually when a patient is hospitalized he has restricted physical activity and so the level
of insulin independent glucose uptake is low and thereby requiring high level of insulin to remain euglycemic. But when this patient is discharged and resumes his physical activity, insulin independent glucose uptake is increased there by improving diabetes control. Hence the dose of insulin to keep him, euglycemic in hospital may now leads to hypoglycemia and to prevent this we should reduce the dose of insulin by 2 IU at the time of discharge.
Drugs: Co-administration of B-agonist: It inhibits gluconegenesis and
glycogenolysis.leading to decrease in blood glucose level there by reducing
requirement of insulin.
Salicylates: It enhances the pancreatic B-cell sensitivity to glucose and potentiate
insulin secretion and thus increases insulin sensitivity.
Quinine: It increases the insulin secretion from B-cell.
Ace-inhibitor: It improves insulin sensitivity and in insulin resistant hypertensive, a
change of therapy from B -Blocks to captopril may improve glucose control.
Clinical recognition and management of increased insulin sensitivity
More frequent attacks of Hypoglycemia in a previously euglycemica patient suggest
development of one of the above conditions.
By the help of history, clinical examination and various laboratory parameters we have to
find out the exact cause of insulin sensitivity and manage the patient accordingly.
If the cause is potentially reversible like pregnancy/after discharge hypoglycemia treat the
primary cause and for the time being reduce the dose of insulin.
If the cause is not reversible as in diabetic nephropathy try to prevent by reducing the
dose of insulin according to blood glucose level.
If a patient is on oral hypoglycemic agent, bring him/her on insulin, so that the minor
changes in dose can be managed.
Blood glucose should be monitored regularly and dose adjustment to be made
accordingly.
REFERENCES
1. Stephen N.Davis & Daryl K: Granner: Insulin, oral hypo glycemic agent &
Pharmacology of endocrine pancrease, Goodman & Gilmen - The pharmacological
basis of therapeutics, 9th ed., 4, 1996.pg. 1487-1513.
2. Howard F. Root & Robert F. Bradley: Clinical disorders of the glands of internal
secretion complication diabetes. The treatment of diabetes mellitus, Joslin, 10th ed.,
pg.619-654.
3. Goldfine A.B., Simonson De et al, In vivo & In vitro studies of Vanadak in human
rodent diabetes mellitus, molecular and cellular bio chemistry, 153 (1-2), 217-31,
1995, Dec.6-20.
4. Alexander Marble: Hyperinsulinism & Chronic hypoglycemia. The treatment of
diabetes meliitus, Joslin, 10th ed., pg.328- 349.
5. Jacob S. Henriksen E.J.: Improvement of insulin stimulated glucose disposal in type
2 diabetes after repeated parenteral administration of Thioctic acid, experimental
clinical endocrinology and diabetes. 104 (3): 284-8, 1996.
6. Berntorp K., Lindgrade F., Mattiasson I.: Long term effects on insulin sensitivity in
sodium transport in glucose in tolerant hypertensy subjects when beta blockade is
replaced by captopril treatment. J. human hyper tension. 1992, 6291-298.
7. Daniel W. Foster: Diabetes Mellitus. Harrison's principles of internal medicine. 13th
ed., pg.1979-1999.
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