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• The blood pH is 7.1 which indicates Acidosis. This is due the presence of
excess ketone bodies in plasma which starts to appear in the urine.
Acetoacetate and 3-Hydroxybutyrate (ketone bodies) are fairly strong acids, the
hydrogen ions from these are buffered, but the buffering capacity is soon
exceeded when the production is high. This leads to an accumulation of protons
and a fall in pH.
• The blood glucose levels are above normal, this is due to either decreased
production of Insulin (as in case of Diabetes type 1) or due to insulin resistance
in the tissues (as in case of Diabetes type 2). Insulin is a hypoglycaemic
hormone, absence of insulin leads to an increase in blood glucose and it also
decreases the peripheral glucose utilisation by tissues.
• Insulin promotes incorporation of amino acids into proteins and combats the
catabolism of fats that produces beta kept acids. Thus Arginine, Leucine and
other amino acids stimulate insulin secretion, as do beta kept acids such as
acetoacetate. (Compounds that generate ATP when metabolised and closes
ATP-sensitive Potassium channels in B cells)
• L-Arginine is a precursor of NO which stimulates Insulin secretion.
• Tolbutamide and other sulphonyl urea derivates such as acetohexamide,
tolazamide, glipizide and glyburide increase the secretion of insulin and act as
hypoglycaemic agents. (Bind to ATP-sensitive potassium channels and inhibit
channel activity.
• Stimuli that increase cAMP levels in B cells increase insulin secretion, including
Beta adrenergic agonists, glucagon and phosphodisesterase inhibitors such as
theophylline.
• Catecholamines have a dual effect on insulin secretion ; they inhibit secretion via
Alpha 2 adrenergic receptors and stimulate insulin secretion via beta adrenergic
receptors. The net effect is usually inhibition.
d) Explain how the diagnosis of diabetes mellitus is generally made.
Give the utility of C peptide and HbA1c measurements in diabetic
patients.
• C peptide -
The peptide segment connecting A and B chains of insulin (connecting peptide /
C-peptide) is detached in the granule before secretion from B cells of Pancreas.
Thus insulin is released along with equimolar concentration of C peptide.
C peptide can be measured by radiommunoassay, and it’s level in blood provides
an index of B cell function in patients receiving exogenous insulin.
• HbA1c -
When plasma glucose is episodically elevated over time, small amounts of
Hemoglobin A are non enzymatically glycated to form HbA1c.
Normal HbA1c lies between 4% - 5.6%. Levels above 6.5% is indicative of
Diabetes.
HbA1c concentration is measured clinically as an integrated index of diabetic
control for the 4- to 6- weeks period before measurement. Careful control of the
diabetes with insulin reduces the amount of HbA1c formed.