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Diabetes Mellitus
 The name “diabetes mellitus means sweet urine. It
stems from ancient times when physicians would
taste a patients urine as a part of a diagnosis.
Definition
 Hyperglycemia due to Absolute or relative deficiency
of insulin.
What is Diabetes?
 A condition in which
the body cannot make
or cannot use insulin
properly
Pancreas
 The pancreas functions as both an exocrine and an
endocrine gland
 Exocrine function is associated with the digestive
system .
 Endocrine Function: produces two important
hormones in Islets of Langerhans, insulin and
glucagon
 α –Glucagon
 Β-Insulin
 δ-Somatostatin
 PP-Pancreatic polypeptide
 Γ-Gastrin
Dr Padghan Dilip R
M.D. Medicine
Insulin Secretion
Fig. 47-1
NORMAL
CONDITION
Food consumed
Food gets converted
into glucose
Pancreas make
insulin
BLOOD STREAM
MOUTH
DIABETIC
CONDITION
STOMACH
PANCREAS
Pancreas make
little or no
insulin
Fat Accumulation
BLOOD STREAM
Blockage
Body is able to convert glucose into
energy due to the action of insulin
(carrier of glucose)
Body is unable to utilize glucose because
of impaired action/lack of insulin &
glucose concentration in blood raises.
Demographics
Current Age Distribution
Classification of Diabetes
7.6%
Type 1
90.6%
Type 2
1.9%
Others
50
25
0
<15
15-30
30-45
45-55
55-70
>70
Age Groups
53.4 ± 13.0 (n= 2269)
43.6 ± 12.2 (n= 2251)
10.0 ± 6.9 (n= 2251)
Current Mean Age
Mean Age at Onset of Diabetes
Mean Diabetes Duration
DiabCare Asia India
Types of Diabetes
 Type 1 Diabetes Mellitus
 Type 2 Diabetes Mellitus
 Gestational Diabetes
 Other types:
 LADA
(
 MODY
(maturity-onset diabetes of youth)
 Secondary
Diabetes Mellitus
Type 1 diabetes
 Was previously called insulin-dependent diabetes mellitus
(IDDM) or juvenile-onset diabetes.
 Type 1 diabetes develops when the body’s immune system
destroys pancreatic beta cells, the only cells in the body
that make the hormone insulin that regulates blood
glucose.
 This form of diabetes usually strikes children and young
adults, although disease onset can occur at any age.
 Type 1 diabetes may account for 5% to 10% of all diagnosed
cases of diabetes.
 Risk factors for type 1 diabetes may include autoimmune,
genetic, and environmental factors.
Gary Hall Jr.
Olympic
swimming
medalist
Type 1 diabetes
Pathophysiology
 Genetic susceptibility
 Association with HLA DR3/4, DQ 2/8 alleles
 Environmental triggers
 Viruses: congenital rubella, coxsackievirus,
enterovirus, mumps
 Early exposure to cow’s milk
Pathophysiology
 Autoimmune destruction of pancreatic -cell
 Antibodies:
 Islet cell
 Insulin
 Anti-glutamic acid decarboxylase 65
 T-cell mediated
 Lymphocytic infiltration
Pathophysiology
 Genetic susceptibility
 Association with HLA DR3/4, DQ 2/8 alleles
 Association with HLA DR2 is protective
 Environmental triggers
 Viruses: congenital rubella, coxsackievirus,
enterovirus, mumps
 Early exposure to cow’s milk
Associated Autoimmune Disorders
 Thyroid (Hashimoto’s, Graves’): 5-10%
 Celiac Disease: 6%
 Addison’s disease: <1%
Type 2 diabetes
 Was previously called non-insulin-dependent diabetes mellitus
(NIDDM) or adult-onset diabetes.
 Type 2 diabetes may account for about 90% to 95% of all
diagnosed cases of diabetes.
 It usually begins as insulin resistance, a disorder in which the
cells do not use insulin properly. As the need for insulin rises,
the pancreas gradually loses its ability to produce insulin.
 Type 2 diabetes is associated with older age, obesity, family
history of diabetes, history of gestational diabetes, impaired
glucose metabolism, physical inactivity, and race/ethnicity.
 African Americans, Hispanic/Latino Americans, American
Indians, and some Asian Americans and Native Hawaiians or
Other Pacific Islanders are at particularly high risk for type 2
diabetes.
 Type 2 diabetes is increasingly being diagnosed in children and
adolescents.
Gestational diabetes

A form of glucose intolerance that is diagnosed in some
women during pregnancy.

Gestational diabetes occurs more frequently among
African Americans, Hispanic/Latino Americans, and
American Indians. It is also more common among obese
women and women with a family history of diabetes.

During pregnancy, gestational diabetes requires
treatment to normalize maternal blood glucose levels to
avoid complications in the infant.

After pregnancy, 5% to 10% of women with gestational
diabetes are found to have type 2 diabetes.

Women who have had gestational diabetes have a 20% to
50% chance of developing diabetes in the next 5-10 years.
Other types of DM
 Other specific types of diabetes result from
specific genetic conditions (such as maturityonset diabetes of youth), surgery, drugs,
malnutrition, infections, and other illnesses.
 Such types of diabetes may account for 1% to 5% of
all diagnosed cases of diabetes.
LADA
 Latent Autoimmune Diabetes in Adults (LADA) is a
form of autoimmune (type 1 diabetes) which is
diagnosed in individuals who are older than the usual
age of onset of type 1 diabetes.
 Alternate terms that have been used for "LADA"
include Late-onset Autoimmune Diabetes of
Adulthood, "Slow Onset Type 1" diabetes, and
sometimes also "Type 1.5
 Often, patients with LADA are mistakenly thought to
have type 2 diabetes, based on their age at the time
of diagnosis.
MODY
 MODY – Maturity Onset Diabetes of the Young
 MODY is a monogenic form of diabetes with an autosomal
dominant mode of inheritance
 Originally, diagnosis of MODY was based on presence of
non-ketotic hyperglycemia in adolescents or young adults
in conjunction with a family history of diabetes.
 However, genetic testing has shown that MODY can occur
at any age and that a family history of diabetes is not
always obvious.
Secondary DM
Secondary causes of Diabetes mellitus include:







Acromegaly,
Cushing syndrome,
Thyrotoxicosis,
Pheochromocytoma
Chronic pancreatitis,
Cancer
Drug induced hyperglycemia:
◦
◦
◦
◦
◦
◦
◦
◦
◦
Atypical Antipsychotics
Beta-blockers - Inhibit insulin secretion.
Calcium Channel Blockers - Inhibits secretion of insulin by interfering with cytosolic
calcium release.
Corticosteroids - Cause peripheral insulin resistance and gluconeogensis.
Fluoroquinolones - Inhibits insulin secretion by blocking ATP sensitive potassium
channels.
Naicin - They cause increased insulin resistance due to increased free fatty acid
mobilization.
Phenothiazines - Inhibit insulin secretion.
Protease Inhibitors - Inhibit the conversion of proinsulin to insulin.
Thiazide Diuretics - Inhibit insulin secretion due to hypokalemia. They also cause
increased insulin resistance due to increased free fatty acid mobilization.
Normal Insulin Metabolism
Promotes glucose transport from 
the bloodstream across the cell
membrane to the cytoplasm of
the cell
Analogous to a “key” that unlocks 
the cell door to allow glucose in
Normal Insulin Metabolism
 Insulin after a meal: 
Stimulates storage of glucose as 
glycogen
Inhibits gluconeogenesis 
Enhances fat deposition in adipose 
tissue
Increases protein synthesis 
Normal Insulin Metabolism
Fasting state 
Counter-regulatory hormones (especially glucagon) 
stimulate glycogen  glucose
When glucose unavailable during fasting state 
Lipolysis (fat breakdown) 
Proteolysis (amino acid breakdown) 
What goes wrong in Diabetes ?
Multitude of mechanisms
Insulin 
Regulation 
Secretion 
Uptake or breakdown 
Beta cells 
damage 
ALTERED CHO METABOLISM
 Insulin

 Glucose Utilization
+
 Glycogenolysis

Hyperglycemia

Glucosuria
(osmotic diuresis) 
Polyuria* 
(and electrolyte imbalance)

Polydipsia*
* Hallmark symptoms of diabetes
ALTERED PROTEIN METABOLISM
 Insulin

 Protein Catabolism

 Gluconeogenesis
(amino acids  glucose)

Hyperglycemia

Weight Loss and Fatigue
ALTERED FAT METABOLISM
 Insulin

 Lipolysis

 Free fatty acids + ketones

Acidosis + Weight Loss
Type 1 Diabetes Mellitus
Formerly known as “juvenile onset” or “insulin 
dependent” diabetes
Most often occurs in people under 30 years of 
age, but may occur at any age.
Peak onset between ages 11 and 13 
Type 1 Diabetes Mellitus
Etiology and Pathophysiology
Progressive destruction of pancreatic  cells 
Autoantibodies cause a reduction of 80% to 
90% of normal  cell function before
manifestations occur
Type 1 Diabetes Mellitus
Etiology and Pathophysiology
Causes:
Genetic predisposition 
Enviromental 
Type 1 Diabetes Mellitus
Onset of Disease
Weight loss 
Polydipsia (excessive thirst) 
Polyuria (frequent urination) 
Polyphagia (excessive hunger) 
Weakness and fatigue 
Ketoacidosis 
Classification of Diabete
Type I DM
Type II DM
Aetiology
Autoimmune
(- cell destruction)
Insulin resistance and -cell
dysfunction
Peak age
12 years
60 years
Prevalence
0.3%
6% (>10% above 60 years)
Presentation
Osmotic symptoms, weight
loss (days to weeks), DKA
Patient usually slim
Osmotic symptoms, diabetic
complications (months to years).
Patient usually obese
Treatment
Diet and insulin
Diet, exercise (weight loss), oral
hypoglycemics, Insulin later
Criteria for the Diagnosis of Diabetes
A1C ≥6.5%
OR
Fasting plasma glucose (FPG)
≥126 mg/dl
OR
Two-hour plasma glucose ≥200 mg/dl during an
OGTT
OR
A random plasma glucose ≥200 mg/dl
ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.
Prediabetes: IFG, IGT, Increased A1C
Categories of increased risk for diabetes
(Prediabetes)*
FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFG
or
2-h plasma glucose in the 75-g OGTT
140-199 mg/dl (7.8-11.0 mmol/l): IGT
or
A1C 5.7-6.4%
*For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater
at higher ends of the range.
ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 3.
Impaired Fasting Glucose•
Impaired Glucose Tolerance•
Revised Diagnostic Criteria
FPG
mg/dl
Normal
<100
OGTT
2 hr
mg/dl
<140
Prediabetes
>100 and
< 126
>140 and
<200
Diabetes
>126
>200
Casual PG
mg/dl
>200 +
symptoms
Standards of Medical Care in Diabetes--2007. Diabetes Care 30:S4-S41, 2007
Is pre-diabetes dangerous?
Yes. Around 40-50 % of pre-diabetics eventually
progress to develop DM at the end of 5 yrs. Hence
it is recommended to act at this stage itself in
order to prevent DM.
Pre-diabetes may also be associated with ongoing
vascular damage and hence increased risk of
micro/macro-vascular complications of DM even
before the setting in of high blood sugars.
Monitoring of Blood Sugar
 Check when and how often to monitor suggested times include



Fasting, before lunch and dinner
2 hrs after breakfast, lunch and dinner
3 AM
 Test more often




When not well
Suspect hypoglycemia
During pregnancy
When changing treatment or not in control
Plasma insulin or C-peptide
measurement
 These estimations are not required in routine
clinical practice
 However they are useful in research in clinical
situations such as recurrent hypoglycemia and
when clinical classification is difficult
 Can be done only in specialized laboratories
Burden of Diabetes
 The development of diabetes is projected to reach
pandemic proportions over the next10-20 years.
 International Diabetes Federation (IDF) data indicate that
by the year 2025, the number of people affected will reach
333 million –90% of these people will have Type 2 diabetes.
 In most Western societies, the overall prevalence has
reached 4-6%, and is as high as 10-12% among 60-70-yearold people.
 The annual health costs caused by diabetes and its
complications account for around 6-12% of all health-care
expenditure.
The Miracle of Insulin
Patient J.L., December 15, 1922
February 15, 1923
Management of
Diabetes Mellitus
Banting and
Best
1923 Nobel Prize for
discovery and use of
insulin in the
treatment of IDDM
The Miracle of Insulin
Patient J.L., December 15, 1922
February 15, 1923
Overview of Insulin and Action
The major components
treatment of diabetes 
Management
ofof the
DM
are:
A
• Diet and Exercise
B
• Oral hypoglycaemic
therapy
C
• Insulin Therapy