DAIBETES MELLITUS

DR. SIDDAGANGA S M
 LEARNING OBJECTIVES

Anatomy and physiology of pancreas

Introduction and Epidemiology of DM
Classification of DM (ADA)
Pathogenesis of DM
Normal homeostasis of blood glucose with
various actions of Insulin
Clinical features
Complications – acute and long standing
Diagnosis
ANATOMY OF PANCREAS
 T H E E N D O C R I N E PA N C R E A S

The endocrine pancreas consists of about

1 million clusters of cells, the islets of
Langerhans, which contain four major and
two minor cell types.
Cell type Hormones
B Insulin
A Glucagon
D Stomatostatin
PP Polypeptides
 INTRODUCTION

Diabetes mellitus is not a single disease

entity but rather a group of metabolic
disorders sharing the common
underlying feature of hyperglycemia.

Hyperglycemia in diabetes results from

defects in insulin secretion, insulin
action, or, most commonly, both .
 EPIDEMIOLOGY

According to the American Diabetes Association,

diabetes affects over 20 million children and adults, or
7% of the population, in the United States, nearly a
third of whom are currently unaware that they have
hyperglycemia.
The total number of people with DM worldwide was
estimated to be between 151 million & 171 million, and
is expected to rise to 366 million by 2030. The
prevalence of diabetes is increasingly sharply in the
developing world as people adopt more sedentary life
styles, with India and China being the largest
contributors to the world's diabetic load .
 CLASSIFICATIONS OF DM

Type 1 diabetes (β-cell destruction, usually

1.   
leading to absolute insulin deficiency)
2. Type 2 diabetes (combination of insulin
resistance and β-cell dysfunction)
3. Genetic defects of β-cell function
4. Genetic defects in insulin action
5. Endocrinopathies
6. Infections
7. Genetic syndromes
8. Gestational diabetes mellitus
 TYPE 1 DM

It constitute about 10% cases of DM. previously

termed as JODM and was called as IDDM.
 subtypes of Type 1 DM are:

A. Subtype 1A (Immune mediated) DM:

autoimmune destruction of b cells.
B. Subtype 1B: tendency to develop ketosis but
negative for autoimmune marker.
 TYPE 2 DM

This type comprises about 80% cases of DM, it

was previously called as MOD and NIDDM.

Predominantly it affects older individual.

Many cases of type 2 DM requires insulin

therapy to control ketosis.
 GESTATIONAL DM

About 4% of pregnant women develop DM due to

metabolic changes during pregnancy.
It is defined as diabetes diagnosed in the second
and third trimester of pregnancy who did not have
DM earlier.
These women revert back to normal glycaemic
level after delivery.
Women who have had gestational diabetes have
a 20% to 50% chance of developing diabetes in
the next 5-10 years.
 PREDIABETES

It is state in which plasma glucose level is high

higher than the normal but not high enough for
diagnosis of DM.
Individual with prediabetes develop type 2 DM
within 10 years.
They do not develop acute complications but at
increased risk CVD (1.5 times than normal
individuals)
Modest amount of weight loss, diet modification
and exercise must in these patients.
 GLUCOSE HOMEOSTASIS

Normal glucose homeostasis is tightly

regulated by three interrelated processes:
1) decreased glucose production in the liver;
2) glucose uptake and utilization by
peripheral tissues, chiefly skeletal muscle;
3)and actions of insulin and counter-
regulatory hormones, including glucagon, on

glucose uptake and metabolism.

 NORMAL INSULIN METABOLISM

major stimulus for synthesis and release of

 The
insulin is –GLUCOSE.

Insulin is formed in b cells of islets.

Initially formed as pre proinsulin- 86 aminoacids

Pro insulin gives rise to A(21AA) &B (30AA)

chains of insulin and c peptide
INSULIN ACTION AND INSULIN
SIGNALING PATHWAYS
PATHOGENESIS OF TYPE I DM
 PATHOGENESIS

 Hyperglycaemia results from following


Reduced Reduced
Increased
insulin glucose
glucose use
secretion production
by body
CLINICAL FEATURES
ACUTE METABOLIC COMPLICATIONS

Ketoacidosis and hypoglycemic episodes are

primary complications of type 1 DM

Hyperosmolar non ketotic coma is chiefly

complication of type 2 DM.

 Hypoglycemia- these episodes may develop in pts

with type1 DM. It may results from excessive
administration of insulin, skipping meal and stress,
they are harmful as they produce permanent brain
damage.
 DIABETIC KETOACIDOSIS(DKA)

It can develop in a pt with severe insulin deficiency.

Failure to take insulin and stress- precipitating factors
Severe lack of insulin leads to lipolysisin the adipose
tissue release of free fatty acid into plasma

These free fatty acids are taken by liver get oxidized

and form ketone bodies with the help of acetyl co
enzyme A
Once there is imbalance between formation and
degradation of ketone bodies---- ketonemia and
ketonuria
 CLINICAL MANIFESTATION AND
TREATMENT
Patient with ketoacidosis will have fatigue,
nausea, vomiting, severe abdominal pain, fruity
odour of breath and urine, deep, labored
breathing (also known as Kussmaulbreathing).
If it persists leads depression of cerebral
consciousness and come.
 Treatment: Immediate insulin therapy,
correction of metabolic acidosis and treatment
for underlying cause.
 HYPEROSMOLAR HYPERGLYCEMIC
NON KETOTIC COMA(HHN)
It’s a complication of type 2 DM
It is caused by dehydration caused by sustained
hyperglycemic diuresis.
The usual clinical symptoms of ketoacidosis are
absent but prominent CNS signs are present.
Blood sugar is extremely high and plasma
osmolality is high.(600-1200mg/dl)
Thrombotic and bleeding complications are high
due to high viscosity of blood.
 PATHOGENESIS OF CHRONIC
COMPLICATIONS

1. Non-enzymatic protein glycosylation :

2. Polyol pathway mechanism

3. Excessive oxygen free radicals.

PATHOGENESIS OF LONG TERM
COMPLICATIONS
SECONDARY SYSTEMIC
COMPLICATIONS
 DIAGNOSIS OF DIABETES

1. Diagnosis of diabetes mellitus

2. Screening of diabetes mellitus
3. Assessment of glycemic control
4. Assessment of associated long term risks
5. Management of acute metabolic
complications
B L O O D G L U C O S E VA L U E S A R E N O R M A L LY M A I N TA I N E D I N A
V E RY N A R R O W R A N G E , U S U A L LY 7 0 TO 1 2 0 M G / D L . T H E
D I A G N O S I S O F D I A B E T E S I S E S TA B L I S H E D B Y N O T I N G
E L E VAT I O N O F B L O O D G L U C O S E B Y A N Y O N E O F T H R E E
C RI T ERI A :
 PREDIABETES: IMPAIRED GLUCOSE
TOLERANCE AND IMPAIRED FASTING
GLUCOSE
 Prediabetes is a term used to distinguish people who
are at increased risk of developing diabetes. People
with prediabetes have (IFG) or (IGT). Some people
may have both IFG and IGT.

 IFG is a condition in which the fasting blood sugar

level is elevated (100 to 125mg/dL) after an overnight
fast but is not high enough to be classified as diabetes.

 IGT is a condition in which the blood sugar level is

elevated (140 to 199 mg/dL after a 2-hour oral glucose
tolerance test), but is not high enough to be classified
as diabetes.
 ESTIMATION OF BLOOD GLUCOSE:

Choice of sample:
whole blood, plasma or serum.
Timing: fasting/ postprandial/ random.
anticoagulant(potassium oxalate/ EDTA)+
sodium fluoride(2.5mg/ml of blood)
Various methods:
a) Chemical methods:
- oxidation-reduction method
- condensation methods
b) Enzymatic methods: they are specific
- glucose oxidase- peroxidase
- hexokinase
- glucose dehydrogenase
ORAL GLUCOSE TOLERANCE TEST:

ADA and WHO recommend OGTT for diagnosis

of gestational diabetes mellitus &with borderline
FG level (100-125mg/dl)
Preparation of patient
Methodology
75 g of glucose dissolved in 300 mL of water is
given after an overnight fast to a person who has
been receiving at least 150–200 g of
carbohydrate daily for 3 days before the test.
 DATA INTERPRETATION-
DATA INTERPRETATION-

The Diabetes Expert Committee criteria for evaluating

the standard oral glucose tolerance test.
 GTT SHOWING BLOOD GLUCOSE
CURVES AND GLUCOSURIA AFTER 75
GM OF ORAL GLUCOSE
 LABORATORY TESTS FOR SCREENING
OF DIABETES MELLITUS:

Aim of screening is to identify asymptomatic

individuals who are likely to have Diabetes
Mellitus.
ADA recommends screening of all
individuals >45yrs every 3 yrs and at an
earlier age if they are overweight(BMI>25)
and have one additional risk factor.
Tests to detect glucose in urine:
Copper reduction tests:
a) Benedict’s test:
Principle: under alkaline conditions, in presence of
reducing sugars cupric ions are reduced to cuprous
ions which form yellow precipitate of cuprous
hydroxide and later to cuprous oxide.
Composition: Sodium carbonate(100gm), copper
sulphate(17.3gm), sodium citrate(173gm), distilled
water(1000ml)
Procedure: 5ml of benedict’s reagent+ 8 drops of
urine, boil for 2 mins.
Observation:
No change- no sugar
Green without ppt-trace
Green with ppt-1+(0.5%)
Brown- 2+(1%)
Yellow-Orange-3+(1.5%)
Brick red- 4+(2% and more)
sensitivity- 200mg/dl of urine
 LABORATORY TESTS TO ASSESS
GLYCEMIC CONTROL:

There is a direct correlation between the

degree of blood glucose control and the
development of microangiopathic
complicatons i.e, nephropathy, retinopathy
and neuropathy.
There is also an association with increased
cardiovascular mortality.
Methods:
Periodic measurement of glycated hemoglobin
Daily self assessment of blood glucose

Amount of glycated hemoglobin in blood

depends on blood glucose concentration and life
span of red cells.
In DM, it is recommended to maintain the values
to <7%.
Normal value is 5%
Thank you