BY SURAJ ADHIKARI

DIABETES MELLITUS:
 Metabolic disorder characterised by
hyperglycemia, glycosuria, hyperlipemia,
Negative nitrogen balance and some
time ketonemia
 Sign and Symptoms
 Increase in frequency of urination
(Polyuria)
 Excessive thirst (polydipsia)
 Excessive eating (Polyphagia)
 Fatigue
 Unexplained weight loss etc
 Obesity
 Race
 History of CVD
 HTN
 Physical inactivity
 Familial history
 Polycystic Ovary Syndrome
 Gestational Diabetes

? ? ? ? ? ??
Why diabetes should be controlled?
Uncontrolled leads to complications:
ACUTE
 Diabetic Ketoacidosis (DKA)
 Hyperglycemic hyperosmolar state
(HHS)
CHRONIC
 Retinopathy, Neuropathy,
Nephropathy- (microvascular)
 Coronary & peripheral vascular
disease and cerebrovascular
disease- (macrovascular)
TYPES OF DIABETES MELLITUS:
Type 1 / Insulin Dependent
Diabetes Mellitus (IDDM)
Characterized by β-cell (pancreatic
islets) destruction leading to absolute
insulin deficiency

Type 2 / Non Insulin Dependent

Diabetes Mellitus (NIDDM)
Characterized by insulin resistance
and relative insulin deficiency
TYPE 1 DM TYPE 2 DM
Juvenile onset (<30 yrs) Maturity onset
β- cells are destroyed: NOT destroyed: relative
absolute deficiency deficiency
Autoimmune(type 1 a) mild or severe
Idiopathic (type 1 b)
Less common & less Very common & high
genetic predisposition Genetic predisposition
Insulin is must Controlled by diet
change, exercise & oral
drugs: Insulin when
other fails
1. Acute fluminant DM
 Due to viral infection

2. Latent autoimmune DM of adults(LADA)

 Aslo called as adults type-1 DM

3. maturity onset diabetes of young (MODY)

 Also called as type-2 Dmin children

4. Protein energy maliate DM (PEM)

5. latent DM stress
 Due to drugs like prednisolone
 Classic
signs of
HYPERGLYSEMIA with
CPG ≥200mg/dL
 OGTT ≥200mg/dL

 FPG ≥126mg/dL

 HbA1C ≥ 6.5%
 HbA1c is a test that measures the
amount of glycated hemoglobin in your
blood. Glycated hemoglobin is a
substance in red blood cells that is
formed when blood sugar (glucose)
attaches to hemoglobin.
Interventions for Diabetes Mellitus
A.Dietary Management

1. Follow individualized meal plan and snacks as scheduled

 Balanced diabetic diet – 50% CHO, 30% fats, 20%
CHON, vitamins and minerals
 diet based on pts. size, wt., age, occupation and activity
2. Pt. must have adequate CHO intake to correspond to the
time when insulin is most effective
3. Routine blood glucose testing before each meal and at
bedtime is necessary during initial control, during illness
and in unstable pts.
4. Do not skip meals
5. Measure foods accurately, do not estimate
6. Less added fat, fewer fatty foods and low-cholesterol
Interventions for Diabetes Mellitus
A.Dietary Management

7. Advise use of complex carbohydrates to help

stabilize blood sugar. Meal should include more
fiber and starch and fewer simple or refined
sugars.
8. Avoid concentrated sweets, high in sugar (jellies,
jams, cakes, ice cream)
9. If taking insulin, eat extra food before periods of
vigorous exercise
10.Avoid periods of fasting and feasting
11.Keep weight at normal level, obese diabetics
should be on a strict weight control program and
should lose weight.
B. Teach pt. on correct administration of insulin and
other hypoglycemic agents.
1. insulin in current use may be stored at room
temp., all others in ref. or cool area
2. avoid injecting cold insulin  lead to tissue
reaction
3. roll insulin vial to mix, do not shake, remove air
bubbles from syringe
4. press (do not rub) the site after injection (rubbing
may alter the rate of absorption of insulin)
5. avoid smoking for 30 mins. after injection
(cigarette smoking absorption)
Polypeptide hormone secreted by the pancreatic Islets of
Langerhans essential for the metabolism of carbohydrates and is
used in the treatment and control of diabetes mellitus
 Small protein
 Mol. Wt. 5808
 Two chains A and B linked by disulfide bridges
 51 amino acids
INSULIN:
 Discovered in 1921 by Banting
and best
 Banting and Macleod got nobel
prize in 1923
 Leonard Thompson: First
patient to receive insulin
Marjorie
On Jan. 11, 1922, 14-year-old Leonard Thompson was the first
human patient to receive insulin made by Banting and Best.

The initial test failed, causing only slight reductions in blood

glucose levels.

A second series of "purified" insulin injections, produced by J.B.

Collip, achieved the desired results.

Leonard's blood glucose dropped to normal, and he began to gain

weight.
PANCREAS
a) Exocrine Gland
b) Endocrine Gland

Exocrine Gland:
 secretes enzymes
 ENDOCRINE
Islets of Langerhans contains:
 α cells : secrete glucagon.
 β cells : secrete insulin.
 δ cells : secrete gastrin &
somatostatin
 Insulin is polypeptide 51
aminoacid (MW 6000). Contains
two chains; chain-A 21 aa &
Chain-B 30
 These chains are held together
by two inter-disulfide bonds &
one intra disulfide bond
 Pork insulin differ by one aa
where as Beef by two aa differ
 SYNTHESIS
 Synthesized as preproinsulin (110
aa) in rough ER (single chain)
 Preproinsulin → proinsulin (86 aa;
molecule fold )
 Transported to Golgi apparatus

 Converted to insulin & C-peptide

 Stored in the granules of β cells

 Diabetes mellitus contd…….

C peptide
Proinsulin
Insulin

PC2 MW 5808
(PC3)
A Chain

B Chain
PC3
Insulin contd…….

 Insulin is measured in IU

FACTORS CONTROLLING THE

SECRETION OF INSULIN
 Blood glucose concentration

 Hormonal control

 Neural control
 Diabetes mellitus contd…….

Glucose β cell integrates input from

various metabolites, hormones
GLUT2 Na+ and neurotransmitters
K+

Glucokinase Na+ KIR K+

K+
Km= 7-9 mM
- K+
Vm
ATP Ca2+
Pancreatic Ca2+
Ca2+ Voltage-gated
ß cell IP3
Ca2+ channel
cAMP Ca2+

Insulin granules
Glucose stimulated insulin secretion
β cells respond to blood glucose
concentration in 2 ways: Initial rapid phase &
delayed release phase
Neuronal control of insulin secretion
Parasympathetic nervous system:
~stimulates insulin secretion
Sympathetic nervous system:
~inhibits insulin secretion
EFFECTS OF INSULIN
ADIPOSE TISSUE
Increased glucose entry
Inhibits lipolysis & release of ffa
Increased triglyceride deposition
Increased K+ uptake
MUSCLE
Increased glucose entry
Increased glycogen synthesis
↑ed aa uptake & protein synthesis
Increased K+ uptake
LIVER
↑ed glucose uptake & glycogen
synthesis
Inhibits glycogenolysis &
glucose output
Inhibits gluconeogenesis

GENERAL
Increased cell growth
 PHARMACOKINETICS
 NOT given orally, given s.c.

 Metabolised in liver, kidney & muscle

 Enzymatic degradation follows

receptor-mediated endocytosis
 t1/2 3-5 min
TYPES OF INSULIN
ACCORDING TO SOURCE
Conventional Insulin:
a) Bovine (More antigenic)
b) Porcine (Less antigenic)
Highly Purified Insulin Preparation
Human insulin:
Produced by rDNA technology
More lipid soluble & hydrophobic than
conventional insulin
More rapid s.c. absorption & shorter acting than
conventional insulin
Valuable in case of allergy to conventional,
insulin resistance, lipodystrophy, pregnancy
ACCORDING TO ONSET & DURATION
OF ACTION:
Rapid acting:
Insulin lispro, Insulin aspart, Insulin
glulisine
Short acting:
Regular (soluble) Insulin
Intermediate acting:
Insulin Zinc suspension (Lente)
Neutral protamine hagedorn (NPH) or
isophane insulin
Long acting:
Protamine zinc insulin (PZI)
Insulin glargine
Rapid acting: insulin lispro
lysine [B28], proline [B29]
Given immediately before or after meal

Insulin
lispro
Insulin

PRO
LYS
LYS
PRO
 Insulin glargine
 Soluble in acidic pH of vial 4.0
 Precipitate in neutral pH & slowly enter
into circulation
 Delayed but peakless effect is obtained
GLY
ASN

glargine
Insulin

ARG

ARG
 Hypoglycemia
 Frequent & potentially more serious
 Common in DM patient receiving large dose
of insulin, missing meals and vigorous
exercise after insulin
 Symptoms: 1) Sympathetic stimulation
2) Neuroglucopenic symptoms
 Treatment: oral/ iv (severe case) Glucose or
Glucagon or Adrenaline treatment
 Local reactions: swelling, erythema ,
Lipodystropy (Common in conventional insulin)
 Allergy & resistance to insulin (esp. conventional)
 Insulin edema- transient on starting insulin
 Weight gain
 Type 1 DM:
 Dose is individualized: sliding scale
 2/3 of dose in morning & 1/3 in evening
 Special cases of Type 2 DM:
 Failure of oral antidiabetic drugs
 Underweight patient
 During infection, trauma, surgery
 Pregnancy (human insulin)
 During complications of diabetes
mellitus
 Non diabetic use: Glucose + insulin to treat
hyperkalemia
 Ultra short acting
Glulisine, aspart

 Ultra long acting

Glargine, detemir

 Afrezza (inhaled insulin)

 Degludec (given alternate day also)

Alpha-Glucosidase inhibitor is also used in type-1 DM

 Drug Onset (min) Peak (hrs)Duration
 Regular 30 – 60 1–5 6 – 10
 Lispro 15 – 30 0.5 – 2.5 3–5
 Aspart 10 – 20 1–3 3–5
 Lente 60 – 180 6 – 14 16–24
 NPH 60 – 180 6 – 14 16–24
 Ultralente 240 – 360 8 – 20 24–28
 Classification & Examples Mechanism of Action
Sulfonylureas  stimulate beta cells of the pancreas to
-Tolbutamide secrete insulin
- Chlorpropamide  improve binding bet. insulin and
- Glipizide insulin receptors
- Glimepiride   no. of insulin receptors
- Glibenclamide
Biguanides   body tissues’ sensitivity to insulin 
- Metformin  glucose uptake
 inhibit glucose prod. by the liver
Alpha-Glucosidase Inhibitors  delay absorption of glucose in the
- Acarbose intestine
- Miglitol
Thiazolidinediones  enhance insulin action at the receptor
- Rosiglitazone sites
- Pioglitazone
 GIP GLP-1 agonist drug
Exenatide, Liraglutide

 DPP-4 inhibitors
Sitagliptin, vildagliptin

 Amylin agonist drug

Pramlintide

 Newer drug
Bile acid sequestrant –colevelam
Bromocriptin (antiparkinsonism)
Corcaserin (antiobesity)
Resveratole
Canaflozin (renal glucose transport inhibitor)
1. β blocker (nonspecific) are contracted in
Diabetic patient receiving insulin?
 Because β blockers mask the symptoms of
hypoglycemia and also
 Delays recovery-prolong hypoglycemic
attack
2. Thiazide, furosemide, corticosteroids,
Oral contraceptives, Salbutamol – reduce
effectiveness
3. Acute ingestion of alcohol-
hypoglycemia
 “Of course
too much is
bad for
you”