PHYSIOLOGY OF DIABETES

MELLITUS

PRESENTED BY –
Dr. HIMANSHU SHARMA

UNDER GUIDANCE OF ALL

RESPECTED TEACHERS.
 Discussion points :-
(1) Definition of DIABETES MELLITUS.
(2) Metabolic syndrome.
(3) Types of Diabetes Mellitus.
(4) Physiology of Clinical features &
complications.
(5) Investigations.
(6) Management.
(2)
(3)
 DIABETES MELLITUS
 “ DIABETES MELLITUS (DM) IS A MOST
COMMON PART OF METABOLIC
SYNDROME, OF IMPAIRED
CARBOHYDRATE, FAT AND PROTEIN
METABOLISM CAUSED BY EITHER
LACK OF INSULIN SECRETION OR
DECREASED SENSITIVITY OF THE
TISSUE TO INSULINE.”
 METABOLIC SYNDROME
 IDF (INTERNATIONAL DIABETIC
FEDERATION) WORLDWIDE DEFINITION OF
METABOLIC SYNDROME IS- “THE
METABOLIC SYNDROME IS A CLUSTER OF
MOST DANGEROUSE HEART ATTACK RISK
FACTORS” –
 (A) DIABETES & PRE DIABETES.
 (B) CENTRAL OBESITY.
 (C) HIGH CHOLESTEROL &
 (D) HIGH BLOOD PRESSURE.
 DIABETES MELLITUS
 -DIABETES MELLITUS (DM) IS THE
THIRD LEADING CAUSE OF DEATH,
AFTER HEART DISEASE & CANCER IN
DEVELOPED COUNTRIES.
- Basic etiology of DM is –
 (i) Decreased insulin secretion.
 (ii) Decreased glucose utilization.
 (iii) Increased glucose production.
TYPES OF DIABETES
MELLITUS
 Types of diabetes mellitus
 - Two types of DM :-
 (1) Type 1
 (2) Type 2.
From the HARRISON’S there are previous

classification of DM is
 (a) Insulin-dependent DM (IDDM)
 (b) Non insulin-dependent DM
(NIDDM)
-
 But this classification is obsolete now
because in “severe case of Type 2 DM”,
insulin therapy is require, so it does not follow
the term absolutely “Non insulin dependent”.
 There is one term also –
 GESTATIONAL DIABETES MELLITUS
–
 Insulin resistance related to metabolic
changes of Late pregnancy increased insulin
requirements and may leads to DM in later age
called GESTATIONAL DIABETES
MELLITUS.

COMARISON BETWEEN
TWO TYPES OF DM
Sr . FEATURES TYPE TYPE 2
No . 1 ( Juveline ( Adult onset
onset DM ) DM )

1. Age of onset Before age of After the age

40 years of 40 years

2. Body Mass Low (wasted) to Obese

normal

3. Prevalence 10-20% of 80-90% of

diabetic diabetic
population population
Genetic Mild to Very strong
4. predisposition moderate
Sr . FEATURES TYPE TYPE 2
No . 1 ( Juveline ( Adult onset
onset DM ) DM )
5. Concordance rate 33% 100%

6. Basic defect Insulin Impairment in

deficiency due production of
to destruction insulin by β
of β cells cells and/or
resistance of
target cells to
insulin

7. Auto antibodies Frequently found Rare

8. Plama insulin Low or absent Normal or high

initially
9. Ketosis Very common Rare
Sr . FEATURES TYPE TYPE 2
No . 1 ( Juveline ( Adult onset
onset DM ) DM )
10. Acute Ketoacidosis Hyperosmolar coma
Durations of
complications Weeks Months to years
symptoms
11. Oral Not useful for Suitable for
hypoglycemic treatment treatment
Administration
agents Always required Usallynot
12. of insulin necessary except
in severe or when
OHA not
13. indicated (in
surgery)
 HYPERGLYCEMIA
l When blood sugar/glucose level is more then
normal limits, it is called HYPERGLYCEMIA.
 American Diabetic Association Criteria-(normal
range)
(1) Fasting blood sugar (FBS)-

 70-100 mg/dl ‘or’ 3.9-5.5 mmole/lt.

(2) Post prandial BS (PP)-

 70-146 mg/dl ‘or’ 3.9-8.1 mmole/lt.

(3) Random blood sugar (RBS)-

 70-125 mg/dl ‘or’ 3.9-6.9 mmole/lt.

 HYPERGLYCEMIA
l This hyperglycemia is due to-
– Decreased uptake, utilisation & storage of
glucose in muscles, liver & fat tissues.
 (storage form of glucose in muscle & liver is
glycogen & in fat tissues it stored in a form of
triaglycerides)
- Increased in glucose production by-
 glycogenolysis ( glycogen to glucose)
 gluconeogensis ( formation of glucose from
fat & proteins )

 CINICAL FEATURES &
COMPLICATIONS OF DM
1.
2. POLYURIA
POLYDYPSIA 3P’s
3. POLYPHAGIA
4. ASTHENIA & WEIGHT
5. LOSS
GLYCOSURIA
6. NUMBNESS & TINGLING SENSATION IN
7. LEGS.
8. KETOACIDOSIS
DELAYED HEALING OF WOUND &
RECURRENT INFECTIONS OF SKIN(BOILS)
9. MICROVASCULAR, MACROVASCULAR &
NEUROPATHIC COMPLICATIONS OF DM
10. DIABETIC COMA &
DEATH.
1. POLYURIA - (passage of large volume of urine)
Glucose Increased
Hyperglycemia reaches to osmolarity of
nephrons of urine.
kidney

More lose of Decreased tubular

fluids in urine reabsorbation of fluids

Osmotic Diuresis
-So, in DM large volume of urine is passed with
increased frequency of micturition.
2. (it means excessive drinking of water)
POLYDYPSIA -
Increase osmolarity
(1) Blood glucose of extracellular
increase fluid

Severe cell Intracellular fluid

dehydration comes out

(2) osmotic diuresis / increase loss of fluid from urine.

 - When the body fluid become decreased
the thirst center of lateral hypothalamus in
brain get stimulated & patient develops
intense desire to drink water to maintain
loss of fluids.
- Polyuria, intracellular-extracellular
dehydration and increased thirst are classic
symptoms of diabetes.

3.POLYPHAGIA-
- excessive hunger & increased appetite are medically
termed as Polyphagia.
-in DM glucose uptake & utilisation by cell is not done.

(a)
glucose is not use cells become
for energy starvated
production

signal to feeding
intense desire of center in lateral
eating hypothalamus
(b) another mechanism of polyphagia is that one area of
brain is dependent on insulin for glucose uptake, this
is “ventromedial nucleus of hypothalamus” {VMN}.
- This is area of Satiety center, which inhibit the
feeding center to stop excessive eating.
glucose is not
reached to VMN

Satiety center
not stimulated

feeding center excessive

not inhibited eating
4. ASTHENIA & WEIGHT
LOSS-
(asthenia – lack of energy)
“insulin promotes protein synthesis, storage & depress
the rate of gluconeogensis from protein & fat”.

Glucose not use increased utilisation &

for energy decreased storage of
proteins as well as fat

rapidly lose weight &

become asthenic inspite of
Polyphagia
5.
 GLYCOSURIA-
 appearance of glucose in urine called
glycosuria.
 renal threshold for glucose is “180mg/dl.”
 - when the blood glucose rise above the
180mg/dl, it cannot reabsorb totally from
renal tubules & the excess glucose spills into
the urine.

Swarming of ants at
urine.
6. NUMBNESS & TINGLING SENSATION IN LEGS-
NUMBNESS - decreased sensation
- this is important symptom of chronic poorly control
diabetes.

Chronic high Damage of

blood glucose peripheral nerves

decreased sensation & PERIPHERAL

tingling in extremities NEUROPATHY
specially lower limbs.
 7. KETOACIDOSIS-
 Presence of ketone bodies in blood produces
acidosis called KETOACIDOSIS.
 -disturbance of normal fat metabolism in DM
causes increased ketone bodies formation.
 -manifestation of disordered lipid metabolism are
so prominent, so DM has called “more a disease of
lipid than of carbohydrate metabolism”.
 -acidosis resulting stimulates respiration, producing
rapid & deep breathing called KUSSMAUL
BREATHING.
 Stored fat
(triacylglycerols)

Hydrolysis HORMONE-
SENSITIVE LIPASE

Free Glycerol
fatty
acids
Blood

Liver
 Free fatty
acids
Mitochondria of
β- oxidation
Liver

Acetyl-CoA
Condensed
Acetoacetate
KETONE
BODIES
β- hydroxybutyrate Acetone
 8. DELAYED HEALING OF WOUND
& RECURRENT INFECTIONS OF
SKIN(BOILS)-
8.

In DM some imp. Factors which decreased
are-
1.Growth factor production
3.Macrophages function
4.Angiogenic response
5.Granulation tissue
6.Collagern accumulation.
7.Epidermal barrier function.
So in DM there is delayed wound healing.
 RECURRENT INFECTIONS OF
SKIN(BOILS)-
In DM due to poor immune response &
hormonal imbalance causes recurrent infection.
Boil is a staphylococcal infection of skin.
9. MICROVASCULAR,


MACROVASCULAR & NEUROPATHIC

COMPLICATIONS OF DM-
l Microvascular-
Diabetic retinopathy Diabetic nephropathy
(scaring of retina) leading renal failure.
leading blindness
 MACROVASCULAR- it is due to
accelerated atherosclerosis, increased
incidence of stroke & myocardial infraction.
NEUROPATHIC- involve ANS &

peripheral nerves (peripheral neuropathy).

DIABETIC FOOT:-

In DM poor imune response,

peripheral neuropathy &
atherosclerotic circulatory
insufficeny causes chronic
ulceration & gangrene
particularly in medial side of
foot.
 10. COMA & DEATH-
 In DM coma is due to Diabetic
Ketoacidosis & dehydration.
 In severe case it may leads to Death.
 Mortality rate is about 10%.
INVESTIGATIONS OF DM
 Routine investigation for
control of DM
1. Blood sugar examintion.
2. Oral glucose tolerance test (OGTT)
3. Glycated hemoglobin (HbA1C)
4. Fructosamine.
5. Serum lipid profile.
6. Urine examination for sugar, protein &
ketone bodies.
2.
 1. Blood sugar examintion
 Diagnostic criteria by WHO & National diabetic data
group:-
Symptoms of Diabetes present with-

 (1) RBS > 200 mg/dl (11.1 mmol/lt.) ‘or’

 (2) FBS > 126 mg/dl (7.0 mmol/lt.) ‘or’
 (3) 2 hr. plasma glucose > 200 mg/dl (11.1
mmol/lt.) during an oral GTT.
If, FBS < 100 mg/dl (5.6mmol/lt.) = Normal.

If, FBS between 100-126 mg/dl = Impaired FG.

If, FBS > 126 mg/dl = DIABETES MELLITUS


So, The common and best indicator for estimating diabetes

prevalence and incidence is fasting blood sugar (FPS)

2. Oral glucose tolerance test
(OGTT) -
Carbohydrate rich
diet for at least 3 Over night fasting
days prior to test.

Early morning
blood & urine
sample.

Samples collected after 75 gm glucose in

0.5, 1, 1.5 & 2 hours. 300 ml water
 250
(13.8)
Diabetes
200
Plasma glucose mg/dl (mmol/lt.)

(11.1)

150
(8.3)
Impaired glucose
tolerance
100
(5.5)
Normal
50
(2.5)

0
0.5 1 1.5 2
Interpretation of
OGTT Hours
 Plasma glucose concentration
mg / dl (mmol/lt. )
Condition Normal Impaired Diabetes
glucose
tolerance

Fasting <100 100 - 126 >126

(5.6) (5.6 – 7.0 ) (>7.0)
2 hrs. after <146 146 – 200 >200
glucose (8.1) (8.1 – 11.1) (>11.1)

Mini OGTT Fasting & 2 hrs sample are collected ( half

hours interval samples are not collected)
 3. Glycated Haemoglobin (HbA1C) –
 glucose + N terminal valine of each β chain of
HbA
 Normal HbA1C = 3-5% of total Hb.
 - if it is more than 7% = poor control of Diabetes.
 - HbA1C is used for monitoring the diabetic
control, not as a routine test of DM because it is
costly.
 - HbA1C reflect mean blood level over 2 months
periode prior to its measurment.
 4. Fructosamine –
 it is a glycated serum protein, which
mostly measure glycated serum albumin.
 - as we know half life of albumin 14
days so this test indicate mean blood
glucose level over “past 2-3 weeks”.
5. Serum lipid profile -

Lipids Normal range Diabetes mellitus

(mg/dl) (mg/dl)
Total cholesterol 200-239 235-300

Triglycerides 150-200 200-350

HDL 45-60 35-65
LDL 100-129 115-190
 MANAGEMENT OF DM

(1) Exercise.
(2) Dietic management.
(3) Drug treatment.
(1) EXERCISE -
(a) How exercise can Help ?

Numbers of insulin Decreased

1. Decreased receptors are insulin
obesity increased. resistance.

2. Enhance glucose uptake by muscles.

3. Reduce cardiovascular diseases.
(b) What kind of exercise ?

AEROBIC EXERCISE
- Jogging & walking - Bicycling
- Aerobic dancing

YOGA
(c) Are there any risks to exercising for people
who have diabetes?
1. Hypoglycemia :- { Blood glucose level < 55 mg/dl }
Symptoms :-
- Nervousness - Anxiety
- Excessive sweating - Intense hunger
- Weakness - Palpitations
People who have diabetes should carry a fast-acting
carbohydrate with them.

- Fruit juice (half cup) - Candies (5 pieces)

- Milk (one cup) - Glucose tablets (3 tabs.)
 2. Foot ulcer
Blisters Ulcer

Precautions
 (2) Dietic management -

Use :-
- at least one Bitter - Vitamin C
vegetable in each containing diet like
meal,like Bitter Melon orange juice.

- Reduce total fat from meal by roasting, baking,

streaming etc insteated of frying food.
Donn’t uses :-
Carbohydrate rich diet -
- Sugar & sweets - honey, jams,
jellyies.

- rice - potatos
Donn’t uses :- Fatty rich diet (Saturated fat products)
Butter Cheese

Ice creams Coconut oils

Example diet for DM patient :-
(1) Breakfast – 2 slice of bread + juice of
citrus fruits / half glass of milk, tea or
coffee without sugar.
(2) Lunch – any green vegetables including

one bitter vegetables+ wheat chapaties +

green salad.
(3) Dinner – same as lunch.

(4) Bed time – glass of milk without sugar.

- If exercise & dietic management are fail to
control DM then we switch over Drug
treatment like Oral Hypoglycemic Agents
(OHA).
In severe or not responding cases we can use

Insuline Therapy.