Glucose tolerance test & blood glucose regulation

Glucose tolerance test & blood glucose regulation

Objective

At the end of this lecture, student will be able to

• Describe glucose tolerance test

• Explain the blood glucose regulation

Glucose Tolerance Test

• Diagnosis of diabetes can be made on the basis of individuals response to the oral glucose load, commonly referred to as oral glucose tolerance test (OGTT)

Preparation of subject to OGTT

• Person should have been taking carbohydrate rich diet for at least 3 days prior to the test

• Drugs influence carbohydrate metabolism should be avoid for least 2 days before test

• Subject should avoid strenuous exercise on previous day of the test

• Helshe should be in an overnight (at least 10hr) fasting state

• Avoid smoking

Procedure

• GTT should be conducted preferably in the morning

• A fasting blood sample is drawn and urine collected

• The subject is given 75 g glucose orally, dissolved in about 300 ml of water, to be drunk in about 5 minutes

• Blood and urine samples are collected at 30 min intervals for at least 2 hours

• All blood samples are subjected to glucose estimation while urine samples are qualitatively tested for glucose

Interpretation of GTT

• The graphic representation of GTT results is depicted in Figure

• Fasting plasma glucose level is 75-110 mg/dl in normal persons

• On oral glucose load, the conc ↑se & peak value (140 mg/dl) is reached in less than an hour which returns to normal by 2 hours

• Glucose is not detected in any of the urine samples

• In individuals with impaired glucose tolerance, the fasting (110-126 mg/dl) as well as 2 hour (14O-2O0 mg/dl) plasma glucose levels are elevated

• These subjects slowly develop frank diabetes at estimated rate of 2% per year, where dietary restriction and exercise are advocated for the treatment of impaired glucose tolerance

• A person is said to be suffering from diabetes mellitus if his/her fasting plasma glucose exceeds 126 mg/dl and, at 2 hrs. 200 mg/dl

• For conducting GTT in children, oral glucose is given on the basis of weight (1.5 to 1.7 g/kg)

• In case of pregnant women, 100 g oral glucose is recommended

Glyeosuria

• Excretion of glucose in urine

• Normally, glucose does not appear in urine until the plasma glucose conc exceeds renal threshold (180 mg/dl)

Renal glycosuria:

• It is a benign condition due to a reduced renal threshold for glucose

Alimentary glycosuria:

blood glucose level rises rapidly after meals resulting in its spill over into urine

Diabetes mellitus

• Diabetes mellitus is a metabolic disorder characterised by rise in blood gucose level

• Associated with several metabolic alterations (Most important are hyperglycemia, ketoacidosis and hypertriglyceridemia

1. Hyperglycemia: Elevation of blood glucose concentration is the hallmark of uncontrolled diabetes

• Primarily due to reduced glucose uptake by tissues and its increased production via gluconeogenesis and glycogenolysis

• When the blood glucose level goes beyond the renal threshold, glucose is excreted into urine (glycosuria)

2. Ketoacidosis: ↑se mobilization of fatty acids results in overproduction of ketone bodies which often leads to ketoacidosis

3. Hypertriglyceridemia: Conversion of fatty acids to triacylglycerols and the secretion of VLDL and chylomicrons is comparatively higher in diabetics (Hypercholesterolemia)

• Hyperglycemia is directly or indirectly associated with several complications, which include atherosclerosis, retinopathy, nephropathy and neuropathy

Management of Diabetes

• Diet, exercise, drug and finally insulin are the management options in diabetics

• Approximately 50%, of the new cases of diabetes can be adequately controlled by diet alone, 20- 30% need oral hypoglycemic drugs while the remaining 20-30% require insulin

Regulation of Blood glucose level

• Glucose is carbohydrate currency of the body

• An adult human body contains about 18 g free glucose

• Liver has about 100 g stored glycogen

• Besides this, it is capable of producing about 125-150 mg glucose/min or 180-220g/24 hrs

• A healthy individuals capable of maintaining the blood glucose concentration within a narrow range i.e. FBS level 70-100mg/dl

Hyperglycemia refers to an ↑se blood glucose above normal level

Hypoglycemia represents ↓se blood glucose concentration

Glycosuria: Excretion of glucose in urine

• The concentration of blood glucose is dependent on the quantity of glucose that enters the circulation from various sources and the amount that is utilized for different metabolic purposes

Sources of blood glucose

• Dietary carbohydrates are digested and absorbed as monosaccharides, which can readily enter blood

• Gluconeogenesis, Glycogenolysis,

Utilization of blood glucose

• Certain tissues like brain, erythrocytes, renal medulla and bone marrow are exclusively dependent on glucose for their energy needs

• Kidney plays a special role in the homeostasis of blood glucose

• Glucose is continuously filtered by the glomeruli, reabsorbed and returned to the blood

• If the level of glucose in bood is above 160-180 mg/dl, glucose is excreted in urine. This value (160-180 mg/dl) is referred to as renal threshold for glucose

• The maximum ability of the renal tubules to reabsorb glucose per minute is known as tubular maximum for glucose (TmC), value for glucose is TmG 350 mg/min

Role of hormones in blood glucose homeostasis

• Hormones play a significant role in regulation of blood glucose concentration

• Primarily, insulin lowers blood glucose level (hypoglycemic) while rest of the hormones oppose the actions of insuiln (hyperglycemia)

Insulin: lnsulin is produced by β-cells of islets of Langerhans in response to hyperglycemia

• Some  amino  acids,  free  fatty  acids,  ketone  bodies,  drugs  such  as tolbutamide also cause secretion of insulin

• Insulin is basically hypoglycemic hormone that lowers in blood glucose level through various means (anti-diabetogenic hormone)

Glucagon: It is synthesized by α-cells of islets of Langerhans of pancreas

• Hypoglycemia stimulates its production

• It is basically involved in elevating blood glucose concentration

• lt enhances gluconeogenesis and glycogenolysis

Epinephrine: This hormone is secreted by adrenal medulla

• lt acts both on  muscle  and  liver  to bring  about glycogenolysis by increasing phosphorylase activity

• The net outcome is that epinephrine increases blood glucose level

Thyroxine: This hormone is secreted by thyroid gland

• It elevates blood glucose level by stimulating hepatic glycogenolysis and gluconeogenesis

Glucocorticoids: These hormones are produced by adrenal cortex

• It stimulate protein metabolism and increase gluconeogenesis

• Glucose utilization by extra hepatic tissues is inhibited by glucocorticoids. Overall effect of glucocorticoids is to elevate blood glucose concentration

Growth hormone (GH) and adrenocorticotropic hormone (ACTH):

• The anterior pituitary gland secretes GH and ACTH

• The uptake of glucose by certain tissues is decreased by growth hormone

• ACTH decreases glucose utilization

• The net effect of both these hormones is hyperglycemic

Summary

• Diagnosis of diabetes can be made on the basis of individuals response to the oral glucose load referred OGTT

• A person is diabetic, if his/her fasting plasma glucose exceeds 126 mg/dl and at 2 hrs. 200 mg/dl

• Diabetes mellitus is a metabolic disorder characterized by rise in blood glucose level and associated with several metabolic alterations

• Glucose level regulated by dietary source of glucose and its utilization by the body and hormonal regulation of glucose

• GSD Type III is inherited and is marked by a buildup of abnormal glycogen due to a deficiency of the glycogen debranching enzyme.

• GSD Type IV is inherited and is marked by a buildup of abnormal glycogen due to a deficiency of the glycogen branching enzyme.

• GSD Type V is inherited and is marked by an inability to break down glycogen in muscle cells, it is due to a deficiency in the myophosphorylase enzyme (McArdle’s disease).

• GSD type VI is due to a deficiency of the enzyme liver glycogen phosphorylase in the liver, leading to enlargement of the liver as glycogen builds up and disruption in its normal function

• GSD type VII is due to a deficiency of the enzyme phosphofructokinase specific to muscles, leading to an inability to use glycogen during exercise and the breakdown of muscle itself for

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