• DIABETES MELLITUS

Definition
Classification.
• INSULIN
Physiology of insulin

• MANAGEMENT OF TYPE 1 DIABETES MELLITUS & COMPLICATIONS

• MANAGEMENT OF TYPE 2 DIABETES MELLITUS

• SUMMARY
• Group of metabolic
disorders characterized
by chronic hyperglycemia
associated with
disturbances of
carbohydrate, fat and
protein metabolism due
to relative deficiency in
insulin secretion and/or
insulin action.
 DIABETES
MELLITUS

TYPE 1 TYPE 2
OTHER GESTATIONAL
DIABETES DIABETES
TYPES DIABETES
MELLITUS MELLITUS

Tissue resistance
1.Drugs/Chemical Any abnormality
to the action of
Selective β cell induced in
insulin combined
destruction & 2. Infection glucose levels
with relative
severe or absolute 3. Immune noted
deficiency in
insulin deficiency. mediated for 1st time during
insulin
4. MODY pregnancy.
secretion.
It is a 2 chain polypeptide
having 51 amino acids.
A chain - 21 amino acids.
B chain - 30 amino acids.
These two chains are linked
by disulfide bridges.
 Exocytosis of
Glucose
insulin

GLUT 2

Detachment of Glucose
Ca2+ Insulin granules
Acts on
Voltage Influx microtubule
sensitive microfilaments
Ca + ATP
Ca2+ I/C Ca2+ 1
channel 2
Ca2+ 3 K+
Na+ K+
cAMP
Wave of ATPase
Depolarization Na+
ATP Release of Ca2+
Dependent K+ from stores
Channel closes.
HORMONAL REGULATION NEURAL REGULATION
• Insulin is a peptide – gets degraded in the GIT if given
orally
• Route of administration – Parenteral
• Basal insulin levels – 5 – 15 μU/ml
Peak Meal insulin levels – 60 – 90 μU/ml
• Metabolism – Primarily in liver, to a smaller extent in
kidneys and muscles
• During biotransformation, the disulfide bonds are
reduced – A and B chains are separated and then are
further broken down into constituent amino acids
• Plasma t1/2 = 5-9 mins
 LIFESTYLE
LIFETIME INSULIN MODIFICATIONS
THERAPY •DIET
•EXERCISE
CONVENTIONAL
Produced from beef and pork pancreas.

NEWER
SINGLE PEAK INSULINS

MONOCOMPONENT INSULINS

HUMAN INSULINS
 REGULAR INSULIN – SHORT ACTING

• Administered 30 – 45 mins before meals.

• Cannot be varied according to the size of meal.
Overcome by Insulin analogues

• Not suitable for providing basal level of insulin.

Overcome by mixing with intermediate and long acting insulin

 INSULIN ANALOGUES
TYPE ONSET OF PEAK DURATION OF
ACTION ACTION

RAPID • LISPRO 5 – 15 MINS 1 HOUR 3- 5 HOURS

ACTING •ASPART 10 – 15 MINS 1 HOUR 3 – 5 HOURS

•GLULISINE 5 – 15 MINS 1 HOUR 5 – 6 HOURS

LONG •GLYCINE 1 – 2 HOURS NO PEAK 24 HOURS

( GLARGINE)
ACTING
•DEGLUDEC 30 – 90 MINS NO PEAK 42 HOURS
INSULIN GLULISINE
 INSULIN
REGIMENS

SPLIT-MIXED BASAL-BOLUS
REGIMEN REGIMEN
 SPLIT-MIXED REGIMEN
• Total daily dose of a 30:70 or 50:50 mixture of
REGULAR and NPH insulin usually split into two
• Injected subcutaneous before breakfast and before
dinner
Advantage:
Only two daily injections
Disadvantage:
Post-lunch glycemia may not
be adequately covered.
 BASAL-BOLUS REGIMEN
Long acting Rapid acting
Insulin preparation
(GLARGINE) ( Insulin LISPRO or
ASPART)

Once daily
either before 2-3 times meal time
breakfast injections
or before bed
time for basal
coverage
Advantage: Completely meets the objective of
achieving round-the-clock euglycaemia
Disadvantage: More demanding and expensive.
HYPOGLYCEMIA

LOCAL REACTIONS – Swelling, erythema, stinging

at the injection site.
o Lipodystrophy.
o Lipoatrophy.

ALLERGY
INSULIN INDUCED EDEMA
Hypokalemia
 HIGH DOSE REGIMEN
25-50 U I/V given as
bolus dose followed by
15 -20 U of insulin per hr
INSULIN I/V
LOW DOSE REGIMEN
10 U I/V stat followed by
10 U/hr till ketosis
subsides down

FLUID REPLACEMENT :
For extracellular fluid replacement saline is given
For intracellular fluid replacement dextrose is given

To counter acidosis sodium bicarbonate is given

Estimation of potassium levels is done . If hypokalemia is present

potassium is given 10-20 mEq/l

Antibiotics given to prevent superadded infections

General objectives of diabetes management
• To relieve symptoms
• To correct associated health problems and to reduce morbidity, mortality
and cost of diabetes
• To prevent and monitor acute and long-term complications
• To improve the quality and productivity of life.
ENSURING PROVIDING
WEIGHT NUTRITIONAL
CONTROL REQUIREMENTS

DIETARY
TREATMENT AND
EXERCISE SHOULD
AIM AT

CORRECTING ANY
MAINTENANCE OF ASOOCIATED
BLOOD GLUCOSE BLOOD LIPID
LEVELS ABNORMALITIES
 ANTI HYPERGLYCAEMICS

PARENTERAL
(INSULIN) ORAL

BIGUANIDES: MEGLITINIDE MISCELLANEOU NEWER

SULFONYL FENFORMIN INSULIN S
UREAS METFORMIN SENSITIZERS- REPAGLINID
BUFORMIN THIAZOLIDINEDIO ACARBOSE INCRETINS
E VOGLIBOSE
NES NATEGLINID EXENATIDE
MIGLITOL
FIRST GENERATION: ROSIGLITAZONE E FENFLURAMINE LIRAGLUTIDE
PIOGLITAZONE
TOLBUTAMIDE
CHLORPROPAMIDE DIPEPTIDYL
ACETOHEXAMIDE PEPTIDASE 4
INHIBITORS:
SITAGLIPTIN
VILDAGLIPTIN
SECOND
GENERATION: SODIUM
GLIBENCLAMIDE GLUCOSE
GLIPIZIDE COTRANSPORT 2
GLIQUIDONE INHIBITOR:
GLICLAZIDE DAPAGLIFLOZIN
GLIMEPIRIDE CANAGLIFLOZIN
EMPAGLIFLOZIN
 SULFONYL UREAS

FIRST GENERATION-
TOLBUTAMIDE, SECOND GENERATION-
CHLORPROPAMIDE, GLIBENCLAMIDE, GLIPIZIDE,
ACETOHEXAMIDE GLIQUIDONE, GLICLAZIDE,
GLIMEPIRIDE
SIDE EFFECTS
• HYPOGLYCAEMIA
• NAUSEA
• VOMITING
• FLATULENCE
• DIARROHEA
• HEADACHE
• PARAESTHESIAS
• HEMOLYTIC ANAEMIA
• CHOLESTATIC JAUNDICE
• AGRANULOCYTOSIS
• HYPONATREMIA(CHLORPROPAMIDE)
• HYPOTHYROIDISM(TOLBUTAMIDE)
• DISULFIRAM LIKE REACTION
• COMA
 MEGLINITIDE ANALOGUES
1) Repaglinide
2) Nateglinide
is same as Sulfonylureas

Have Rapid Onset and Duration of ADVERSE EFFECTS :

Action as compared to Sulfonylureas.
HYPOGLYCEMIA
They are categorised as Post prandial
Glucose Regulators. WEIGHT GAIN

Should not be used in combination CAUTIOUS USE IN HEPATIC

with sulfonylureas due to action IMPAIREMENT
overlap
• Metformin Pharmacokinetics:
• Fenformin • Well Absorbed when taken orally.
• Buformin • Bound to Plasma proteins
• T1/2= 1.5 to 3 hours
• Not metabolized
• Excreted through kidneys.

Adverse effect : Abdominal pain ,

Anorexia , bloating , Nausea ,Metallic
taste, Mild Diarrhoea ,Tiredness
Increases risk of Lactic acidosis ,
vitamin B12 deficiency

Contraindications : alcoholism , renal

and hepatic diseases , hypotensive state
, heart failure , respiratory diseases .
Pharmacokinetics:
-Absorbed within 2-3 hours
-Metabolized by hepatic CYPs

Adverse Effects:
-Headache
-Myalgia
-Mild Anemia
-Plasma volume expansion
-Edema
-Weight Gain

Rosiglitazone: Cardiotoxic. Increases the risk of MI, CHF,

Stroke and Death.
 MISCELLANEOUS ANTIDIABETIC DRUGS

ALPHA DOAMINE D2
AMYLIN
GLUCOSIDASE RECEPTOR GUARGUM
ANALOGUE
INHIBITOR AGONIST

Acarbose
Pramlintide Bromocriptine
Miglitol
Voglibose
 ALPHA GLUCOSIDASE INHIBITOR
ACARBOSE
MECHANISM OF ACTION:
MIGLITOL
-Inhibits alpha glucosidasesand alpha amylase
VOGLIBOSE which is responsible for the digestion of
carbohydrates
-GLP 1 release is promoted

ADR:
Flatulence
Abdominal discomfort
Loose stools
Transaminases may rise
 DOPAMINE D2 AGONIST

BROMOCRIPTINE

MECHANISM OF ACTION – Affects the circadian rhythm of hormone release.

AMYLIN ANALOGUE

PRAMLINTIDE

MECHANISM OF ACTION – Centrally mediated anorectic action.

 Mechanism of action

Forms a thick viscous coating over G.I. tract

Providing a mechanical barrier

Absorption of carbohydrates doesn’t take place

Adverse effects :

Symptoms of malabsorption(further chances

of inadequate absorption of main drug )
 GLP-1 receptor
agonists (Injectable DPP-4 inhibitors SGLT-2 inhibitors
drugs)

Sitagliptin Canagliflozin
Vildagliptin Empagliflozin
Exenatide,
Saxagliptin Ipragliflozin
Liraglutide
Alogliptin Dapagliflozin
Linagliptin Ertugliflozin
• Exenatide
• Liraglutide
GLP-1 is an important
incretin.

• Adverse Effects:
1. Nausea
2. Vomitting
3. Diarrhoea
4. Risk of Pancreatitis
5. Medullary thyroid cancer
6. Acute renal damage.
• MECHANISM OF ACTION – Prevents rapid degradation of GLP-1
PHARMACOKINETICS :
• Drugs: Sitagliptin Well absorbed orally
Food does not interfere with
Vildagliptin
absorption
Saxagliptin Excretion is unchanged in urine
Alogliptin Cautious use in Renal Impairment

Linagliptin ADVERSE EFFECTS :

Headache
Nasopharyngitis
 1st drug to be discovered was
Phlorizin/Phloridzin a flavanoid obtained
from the bark of an apple tree.
• Newer drugs:
Canagliflozin(Prototype)
Empagliflozin ADVERSE EFFECTS –
Ipragliflozin 1. UTI Infections
Dapagliflozin 2. Co-administration with insulin –
Ertugliflozin Hypoglycemia