Diabetes mellitus

It is characterized by elevated blood glucose level due to disturbance of insulin.

Types of insulin:
1. Type 1 Diabetes
Absolute deficiency of insulin due to destruction of beta cells of pancreas. Loss of beta cells
results from autoimmune mediated process, without functional beta cell pancreas fails to respond
to glucose as a result of insulin deficiency. It will suppress lipolysis, proteolysis and
glucogenolysis.

2. Type 2 diabetes
It is influenced by resistance in insulin resistance. In type 2 diabetes, the pancreas retain some
beta cell function, but insulin secretion is insufficient to maintain glucose level. Obesity and
genetic defect contributes to insulin resistance.

3. Gestational diabetes
It is diagnosed for the first time during pregnancy due to disturbance in sex and growth hormone.
Normally blood sugar returns to normal soon after delivery. But if you have had gestational
diabetes there is high risk of getting type 2 diabetes.

4. Neonatal diabetes
It is a rare form of diabetes that occurs within first 6 months of life. It is due to the deficiency of
insulin.

5. MODY
“Maturity onset diabetes of young”.

It was found in young people but acted like type 2 diabetes.

Sign and symptoms:

 Glycosuria
 Polyuria
 Dehydration
 Polydipsia
 Fatigue
 Lipolysis
 Ketonuria (present in type 1)
Complications:
Micro vascular complications Macro vascular complication
 Diabetic nephropathy (ACEIS or  Coronary heart disease
ARBS)
 Diabetic retinopathy (Vitamin A)
 Diabetic neuropathy (vitamin B)

Emergency in diabetes:
 Diabetic ketoacidosis
 Increased level of ketone bodies in blood.
 Blood glucose level > 300mg/dl
 Hyperosmolar hyperglycemia
 Persistent increase in blood glucose level >600mg/dl
 PH > 7.3
 dehydration

Diagnosis
1) urine analysis
Glucose present in urine of diabetic patient

2) blood glucose monitoring

Fasting blood glucose Blood glucose random (BSR)
(BSF)
On empty stomach 8 hours after any meal

Normal <110mg/dl <140mg/dl

Diabetes >126mg/dl >200mg/dl

3) ICA test
 Islets cell antibodies test
 Used to detect the blood level of pancreatic autoantibodies.
Normal < 6.0%
Diabetes >6.5%

It gives the idea about the plasma glucose control over 2 -3 months.
Management of Diabetes
Type 1 insulin therapy
Type 2 anti-diabetic drug

A. Oral anti diabetic drugs

Tablets are introduced when metabolic control cannot be obtained by diet and lifestyle changes.

I. Insulin secretagogeus
It increase the release of insulin from pancreatic β- cells.

i. Sulfonylureas
M.A.O
It block ATP sensitive K+ channels

↓
Depolarization, Ca2+ influx

↓
Increase the secretion of insulin

Class Examples Indications

1 generation
st
 Tolbutamide Not used in renally impaired
 Tolzamide patient due to risk of
 Chlorpropamide accumulation and toxicity.
Not used in elderly
2nd generation  Glibenclamide 30 minutes before meal
 Glicazide
 Glipizide
3rd generation  Glimepiride Once daily because have
higher affinity for 140-KDA
SUR, almost 100-200 times
more potent than 1st
generation
Used safely in elder and
renally impaired patient.
Adverse effects:
Weight gain, hypoglycemia
 ii. Glinides
MAO:
Binds to ATP sensitive sensitive K+ channels

↓
Result in the release of insulin
Examples Indications Adverse effects
 Repaglinide Rapid onset and duration of Weight gain,
 Netaglinide action. Contraindication in
Used as postprandial glucose pregnancy.
regulators.(should take prior
to meal).
Should not be used in
combination with
sulfonylureas.
Lipid lowering drug increase
the effect.

II. Insulin sensitizer

It act by decreasing he insulin resistance

i. Bigunides
MAO:
Molecular mechanism is unknown.
It activates AMPK (AMP activated protein kinase)

↓
Examples Indication Adverse effects
 Metformin  Initial drug of choice GIT disturbance,
in obese patient Lactic acidosis.
 Prevention of PCOS
 Management of
antipsychotic

Block glycogenesis
 ii. Thiazolidinediones
MAO:
Binds with proliferator activated receptor- γ

↓
Transcription of insulin responsive genes

↓
Increase insulin sensitivity in adipose tissue

Examples Indications Adverse effects

 Pioglitazone Pioglitazone reduce the risk Water retention.
 Rosiglitazone of IHD. Edema,
Rosiglitazone increase IHD Weight gain.
because it increases LDL
cholesterol and triglyceride.

III. α – glycosidase inhibitors

MAO:
Inhibit the intestinal α glucosidase, which breakdown carbohydrate into glucose.
Examples Indications Adverse effect
 Acarbose It lowers the post prandial Flatulence,
 Miglitode increase of blood glucose. Abdominal pain.

IV. Dipeptidyl peptidase – 4 inhibitors ( GLIPTINS)

MAO:
These drugs inhibit the enzyme DPP-4
↓
Activity of incretin hormone increase
↓
Increases insulin release
 Examples Indications Adverse effects
 Sitagliptin These drugs are weight Nasopharyngeal,
 Sexagliptin neutral. Joint pain,
 Linagliption Decrease appetite. Headache.
 Alopliptin

V. Sodium glucose cotransporter 2- inhibitors

MAO:
SGLT2 is responsible for reabsorption of glucose in the tubular lumen of kidney.
By inhibiting SGLT2

↓
Decrease reabsorption of glucose

↓
Increase urinary glucose excretion and lower blood glucose level.
Examples Indications Adverse effects
 Dapagliflozin It also reduce blood pressure, UTI
 Canagliflozin not indicated for the
 Ipragliflozin treatment of hypertension