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.

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- But this classification is obsolete now because in “severe case of Type 2 DM”, insulin therapy is require, so it does not follow the term absolutely “Non insulin dependent”.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

FEATURES TYPE 1(Juveline onset DM)

TYPE 2 (Adult onset DM)

Age of onset Before age of 40 years

After the age of 40 years

Body Mass Low (wasted) to normal

Obese

Prevalence 10-20% of diabetic population

80-90% of diabetic population

Genetic predisposition

Mild to moderate

Very strong

Sr.No.

1.

2.

3.

4.

FEATURES TYPE 1(Juveline onset DM)

TYPE 2 (Adult onset DM)

Concordance rate 33% 100%

Basic defect Insulin deficiency due to destruction of β cells

Impairment in production of insulin by β cells and/or resistance of target cells to insulin

Auto antibodies Frequently found Rare

Plama insulin Low or absent Normal or high initially

Ketosis Very common Rare

Sr.No.

5.

6.

7.

8.

9.

Acute complications

Ketoacidosis Hyperosmolar coma

Durations of symptoms

Weeks Months to years

Oral hypoglycemic agents

Not useful for treatment

Suitable for treatment

Administration of insulin

Always required Usally not necessary except in severe or when OHA not indicated (in surgery)

FEATURES TYPE 1(Juveline onset DM)

TYPE 2 (Adult onset DM)

Sr.No.

10.

11.

12.

13.

HYPERGLYCEMIA

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

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. POLYURIA

2. POLYDYPSIA

3. POLYPHAGIA

4. ASTHENIA & WEIGHT LOSS

5. GLYCOSURIA

6. NUMBNESS & TINGLING SENSATION IN LEGS.

7. KETOACIDOSIS8. DELAYED HEALING OF WOUND &

RECURRENT INFECTIONS OF SKIN(BOILS)

9. MICROVASCULAR, MACROVASCULAR & NEUROPATHIC COMPLICATIONS OF DM

10. DIABETIC COMA & DEATH.

3P’s

Hyperglycemia

Glucose reaches to nephrons of kidney

Increased osmolarity of urine.

Decreased tubular reabsorbation of fluids

More lose of fluids in urine

Osmotic Diuresis

-So, in DM large volume of urine is passed with increased frequency of micturition.

1. POLYURIA - (passage of large volume of urine)

Blood glucose increase

Increase osmolarity of extracellular fluid

Intracellular fluid comes out

Severe cell dehydration

osmotic diuresis / increase loss of fluid from urine.

2. POLYDYPSIA - (it means excessive drinking of water)

(1)

(2)

- 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.

glucose is not use for energy production

cells become starvated

signal to feeding center in lateral hypothalamus

intense desire of eating

(a)

another mechanism of polyphagia is that one area of brain is dependent on insulin for glucose uptake, this is “ventromedial nucleus of hypothalamus” {VMN}.

(b)

- 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 not inhibited

excessive 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 for energy

increased utilisation & 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-

Chronic high blood glucose

- this is important symptom of chronic poorly control diabetes.

Damage of peripheral nerves

PERIPHERAL NEUROPATHY

decreased sensation & tingling in extremities specially lower limbs.

NUMBNESS - decreased sensation

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)

Free fatty acids

Glycerol

HORMONE-SENSITIVE LIPASE

Hydrolysis

Blood

Liver

Free fatty acids

Acetyl-CoA

Acetoacetate

β- hydroxybutyrate Acetone

β- oxidationMitochondria of

Liver

Condensed

KETONE BODIES

8. DELAYED HEALING OF WOUND & RECURRENT INFECTIONS OF SKIN(BOILS)-

In DM some imp. Factors which decreased are-1. Growth factor production2. Macrophages function3. Angiogenic response4. Granulation tissue5. Collagern accumulation.6. 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-

Microvascular-Diabetic retinopathy (scaring of retina) leading blindness

Diabetic nephropathyleading renal failure.

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.

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 days prior to test.

Over night fasting

Early morning blood & urine sample.

75 gm glucose in 300 ml water

Samples collected after 0.5, 1, 1.5 & 2 hours.

250(13.8)

200(11.1)

150(8.3)

100(5.5)

50(2.5)

010.5 1.5 2

Plas

ma

gluc

ose

mg/

dl (

mm

ol/l

t.)

Hours

Diabetes

Impaired glucose tolerance

Normal

Interpretation of OGTT

Condition

Plasma glucose concentrationmg / dl (mmol/lt. )

Normal Impaired glucose

tolerance

Diabetes

Fasting <100(5.6)

100 - 126(5.6 – 7.0 )

>126(>7.0)

2 hrs. after glucose

<146(8.1)

146 – 200(8.1 – 11.1)

>200(>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”.

Lipids Normal range (mg/dl)

Diabetes mellitus (mg/dl)

Total cholesterol

200-239 235-300

Triglycerides 150-200 200-350

HDL 45-60 35-65

LDL 100-129 115-190

5. Serum lipid profile -

MANAGEMENT OF DM

(1) Exercise.

(2) Dietic management.

(3) Drug treatment.

(1) EXERCISE -

(a) How exercise can Help ?

Decreased obesity

Numbers of insulin receptors are increased.

Decreased insulin resistance.

Enhance glucose uptake by muscles.

Reduce cardiovascular diseases.

1.

2.

3.

(b) What kind of exercise ?

AEROBIC EXERCISE

YOGA

- Jogging & walking

- Aerobic dancing

- Bicycling

(c) Are there any risks to exercising for people who have diabetes?

1. Hypoglycemia :- { Blood glucose level < 55 mg/dl }

- Nervousness

- Excessive sweating - Intense hunger

- Weakness - Palpitations

- Anxiety

People who have diabetes should carry a fast-acting carbohydrate with them.

- Fruit juice (half cup)

- Milk (one cup)

- Candies (5 pieces)

- Glucose tablets (3 tabs.)

Symptoms :-

2. Foot ulcer

Precautions

Blisters Ulcer

(2) Dietic management -

Use :-

- at least one Bitter vegetable in each meal,like Bitter Melon

- Vitamin C containing diet like orange juice.

- Reduce total fat from meal by roasting, baking, streaming etc insteated of frying food.

Donn’t uses :-

Carbohydrate rich diet -

- rice - potatos

- honey, jams, jellyies.

- Sugar & sweets

Fatty rich dietDonn’t uses :- (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.