Homeostasis of Blood Sugar

(OR)

Regulation of Blood Sugar level

 Importance of blood sugar

• Why blood sugar level must be maintained within

the normal range?
• Brain & RBC are depending on free glucose present
in the blood for their fuel
 Blood Glucose level

• Blood glucose level depends on the balance

between glucose entry & glucose utilisation.
 Blood Glucose

Entry Utilisation
Dietary absorption Metabolism by various tissues for energy
Glycogenolysis requirement
Gluconeogenesis
Hyperglycemic Hormones Glycogenesis
Conversion of Glucose into fat (lipogenesis)
Hypoglycemic hormones
 Blood Glucose level: Terminology

• Fasting Blood sugar ( overnight / 12 hr fasting)

• Post-prandial blood sugar (after food)

• Random blood sugar ( at any time of the day)

 Blood Glucose: Normal range

• Fasting blood sugar: 70 – 110 mg %

• Post -prandial blood sugar: 120 – 140 mg %
• Random blood sugar: < 140 mg %
• Diagnostic value : > 126 mg%

• Plasma blood sugar is about 10% more than the

blood sugar level.
 Blood Glucose:

• Normoglycemia: normal level

• Hyperglycemia : more than normal level
• Hypoglycemia : less than normal level
 Blood sugar level: Hormonal Regulation

Hormone

Hyperglycemic Hypoglycemic
Glucagon Insulin
Epinephrine
Norepinephrine
Glucocorticosteroids
Thyroxine
Growth Hormone
ACTH
 Hypoglycemia
• When Blood sugar level is: < 45 mg %
• Hypoglycemic Symptoms:
• Head ache
• Sweating
• Anxiety
• Confusion
• Slurring of speech
• seizure
• Coma (hypoglycemic coma), if not treated,
• Death
 Hypoglycemia: causes

• Pancreatic ß-cell tumor (insulinoma)

• Hepatocellular damage
• Type 1 (Von Gierke)- Glycogen storage disease
• Post-prandial (reactive) hypoglycemia
• Alcohol induced hypoglycemia
• Insulin overdose
 Homeostasis of blood sugar: Role of Liver

• Glycogenesis
• Glycogenolysis
 Homeostasis of blood sugar: Role of kidney

• Renal threshold for glucose: > 180 mg %

• Tubular maximum for glucose (TmG): 360 mg %
• Glucosuria: excretion of glucose in urine

• Renal Glucosuria :
excretion of glucose in urine when blood sugar level
is < 180 mg %
 Glycosuria
• Glycosuria:
general term, presence of any reducing sugar in urine

• Glucosuria : Glucose in urine

• Fructosuria : Fructose in urine
• Galactosuria : Galactose in urine
• Pentosuria : Pentose (L-xylose) in urine
• Lactosuria : Lactose in urine

• Emotional Glucosuria
• Alimentary Glucosuria(gastrectomy & hyperthyroidism)
Diabetes Mellitus
 Diabetes Mellitus (DM)
• Diabetes mellitus is a syndrome consisting of a group of
metabolic diseases.

• Disorder in carbohydrate metabolism

• Characterised by chronic hyperglycemia.

• Caused by relative or absolute deficiency of Insulin / insulin

resistance

• “Heterogeneous group of metabolic disorders characterised

by chronic hyperglycemia”
 Diabetes Mellitus
(Classification)

Type 1 Type 2
Insulin Dependent Diabetes Mellitus Non Insulin Dependent Diabetes
( IDDM ) Mellitus
5 – 10 % ( NIDDM )
90 - 95%
 Type 1 & 2 DM: Difference
Type 1 Type 2

Age of onset During Usually after 40 years

childhood/puberty
Prevalence 5 - 10% 90 - 95%

Etiology Destruction of ß-cells of Obesity

pancreas due to viral Insulin resistance
infection /
autoantibodies
Genetic predisposition moderate Very strong

symptoms Develops rapidly Develops gradually

without clear symptoms

Treatment Insulin Diet, exercise, oral

hypoglycemic drugs
 DM : Symptoms

• Polyuria
• Polydipsia
• Polyphagia
• Susceptibility to infection
• Fatigue
• General weakness
• Weight loss
 DM: Metabolic changes

Type 1 Type 2

Hyperglycemia Hyperglycemia
Ketoacidosis (DKA) Hypertriglyceridemia
Hypertriglyceridemia Hypercholesterolemia
↑ break down proteins ↑ break down proteins
 Diabetes Mellitus
(Complication)

Chronic
Acute Cataract
Diabetic Retinopathy
Hyperglycemia
Diabetic Nephropathy
Diabetic Ketoacidosis (DKA)
Diabetic Neuropathy
Hyper Osmolar Non ketotic Coma
Angiopathy ( CAD, MI & Stroke )
 Angiopathy
Chronic complication

Microangiopathy Macroangiopathy
Retinopathy Atherosclerosis
Nephropathy (CVD, MI & stroke)
 Chronic complications in DM:
Biochemical mechanism

• High level of blood glucose ↑non enzymatic glycation of

protein molecules in various tissues (advanced glycated end
(AGE)product).

• Increased production of sorbitol from high glucose,

especially in lens, retina & peripheral nerve - insulin is not
required for transportation of glucose in these tissues.
 DM: Lab investigations

• Blood glucose
• Oral Glucose Tolerance Test (OGTT)
• Glycated Hemoglobin ( HbA1C )
• Fructosamine
• Lipid profile
• Microalbuminuria
• Renal function tests
 Glucose Tolerance Test

• The ability of an individual to metabolise the loading-

dose of glucose is know as glucose tolerance.

• Glucose tolerance is tested by the

oral administration of 75gm of glucose –
Oral Glucose Tolerance test (OGTT)
 Indication for OGTT

• Symptoms suggestive of diabetes but blood sugar value is

inconclusive ( 100 -126 mg%).
• To confirm or rule out DM
• To confirm or rule out renal glucosuria

• During pregnancy:
• Excessive weight gain
• Past history of Macrosemia ( > 4kg Wt)
• Past history of miscarriage
 Contraindications for OGTT

• Confirmed Diabetes
• Acute illness
• Should not be used for follow-up of DM
 Preparation of the patient for OGTT

• 1. Good carbohydrate diet for 3 days prior to the test

• 2. Diet containing about 50g of carbohydrate must be taken

previous night of the test

• 3. should not eat after 8 PM of previous night &

break fast also should not be taken ( 12hr fasting)

• 4. should avoid drugs influence blood sugar 2 days prior to the test

• 5. should avoid strenuous exercise / physical activity on the

previous day of the test.
 OGTT: Procedure
• After overnight (12 hr) fasting, blood & urine samples must be collected
next day morning by 8 AM - Fasting (0 hr).

• 75g glucose dissolved in 250-300ml of water must be administered orally

(1.75g/kg BW incase of children).

• Blood & urine sample must be collected at 30min interval for 2 - 21/2
hours.

• Estimation of glucose in blood samples & detection of glucose in urine

samples must be done.

• The results must be plotted in the graph - GTT curve

 OGTT: Curve

240

215
Plasma Glucose mg %

180
170
170
160

140 135

115
105
90
80

Time ( hr)
 OGTT: Diagnostic value for Diabetes Mellitus:

Normal Diabetes Impaired Glucose Tolerance

(IGT)
Fasting < 110 mg % > 126 mg% 110 -126 mg%

1 hr after glucose < 160 mg % Not prescribed Not prescribed

2 hr after glucose < 140 mg % > 200 mg% 140 – 199 mg%

IGT: Not diabetic but (2% ) likely to develop diabetes.

IGT does not require treatment.

Diet restriction & Exercise are recommended to prevent diabetes.

 Gestational Diabetes

• Glucose intolerance recognised first during pregnancy is

known as Gestational Diabetes Mellitus (GDM).
• The most important clinical risk is: macrosemia (excessive
foetal growth, > 4kg)
• Foetal hyperinsulinemia due to increased maternal blood
glucose may be one of the factors for excessive foetal growth.
• Complications of labor & delivery
• Jaundice
• Hypocalcemia
• Respiratory distress syndrome
• polycythemia
 Gestational Diabetes Mellitus (GDM)

• Diagnosis:

• Screening test must be performed between 24 & 28

gestational weeks by the oral administration of 50 gm of
glucose challenge.
• It can be performed at any time, irrespective of food intake.

• If the plasma glucose level is > 140 mg % then it is positive.

• Then OGTT must be performed by the oral administration of
100gm of glucose
 Diagnostic value for GDM

Plasma 50 g - Screening test 100g - Diagnostic test

Glucose (OGTT)
Fasting - 95mg %
1-h 140mg% 180mg %

2-h - 155mg %

3-h - 140mg %

Screening for GDM is not necessary if the pregnant woman is < 25 y, normal body weight.

If the screening test is positive then only diagnostic test must be performed

Diagnosis of GDM requires any two of the four plasma glucose values obtained during
diagnostic test