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DIABETES
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Diabetes Mellitus
Definition

A multisystem disease related to:

Abnormal insulin production, or

Impaired insulin utilization, or
Both of the above
Leading cause of heart disease, stroke, adult blindness, and
non-traumatic lower limb amputations
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Diabetes mellitus
Major lifestyle disease
21st centurys - challenging public health problem

World: 387 million (8.3%) and 592 million by 2035

low- and middle income countries: 77% with diabetes

China: 92.3 million diabetics

India: 61.3 million T2DM in 2011 and 70 & 101.2 million by

2015 & 2030 respectively

Doubled between 1995 and 2005

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WHO-ICMR
Report: Self-reported diabetes of 4.5% with urban (7.3%), rural
areas (3.1%).

Three-fold higher (18.9/1000 person years) mortality in

diabetes compared to non-diabetic (5.3/1000 person-years)

Next 10 years (WHO): Predicted a 50% increase in deaths

2030

Diabetes is projected to be the seventh leading cause of death

Women: 184 million 2013 and 288 million by 2030

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Contributing Factors
Indians: have higher propensity to metabolic
syndrome, diabetes mellitus and coronary artery
disease (peculiar genetic composition)

Increased insulin resistance,

Greater abdominal adiposity (higher waist

circumference despite lower body mass index),

Higher prevalence of impaired glucose tolerance

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Cont..
Epidemiological transition (Population)
Economic boom
Urban migration and change in lifestyle
Physical inactivity
Trendy dietary patterns and
Environmental factors also add to this risk.

Greater risk of developing disease at a

relatively younger age.
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Challenges (India)
Clinical inertia
Inadequate follow-up and
Lack of disease awareness
Non availability of HbA1c test for measuring
glycemic control
An inadequacy in Indian guidelines

Limitations in achieving Blood sugar control

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Preventing or postponing the onset of

diabetes
Early identification
Appropriate lifestyle intervention
Awareness
Balanced diet
Avoidance of alcohol, tobacco
Education and
Empowerment of community
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Transverse across abdominal wall

Head, body and tail
Lobules of secretary cells
Endocrine and exocrine glands

Exocrine
- Ducts are seen (Pancreatic duct, Bile duct)
- Secretes juices to duodenum
- Lipase, Amylase, Trypsin

Endocrine
- No Ducts
- Islets of Langerhans
- cells - Glucagon
- cells - Insulin
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Insulin
- Increase glucose uptake and utilisation by
skeletal muscle
- Glucose breakdown and energy stored in
the fat as adipose tissue
- Prevent glycogen break down
- Increase the formation of glycogen
Glucagon
- Mobilisation of glycogen from liver
- Mobilisation of stored fat
- Release of insulin

Opposite in functions
Negative Feed-Back mechanism
Insulin deficiency Diabetes
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Normal Insulin Metabolism

Insulin

Produced by the cells in the islets of

Langherans of the pancreas

Facilitates normal glucose range of 3.9

6.7 mmol/L
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Insulin Secretion
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Normal Insulin Metabolism

Promotes glucose transport from the
bloodstream across the cell

Analogous to a key that unlocks the cell

door to allow glucose in
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Normal Insulin Activity

Insulin after a meal:
Stimulates storage of glucose as
glycogen
Inhibits gluconeogenesis
Enhances fat deposition in adipose
tissue
Increases protein synthesis
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Normal Insulin Activity

Fasting state
Counter-regulatory hormones (especially glucagon)
stimulate glycogen glucose

When glucose unavailable during fasting state

Lipolysis (fat breakdown)
Proteolysis (amino acid breakdown)
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Why is Insulin so Important?

If the sugar stays in your blood it
doesnt do your cells (body) any good.

The sugar has to get inside the cells

for the body to use it.

Insulin is like a key that opens up the door

and allows the sugar to get out of the
blood and inside the cell where the cell
can burn the fuel for energy!
 Types of Diabetes
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Gestational Diabetes
Other types
LADA (Latent / Late-onset Autoimmune Diabetes in Adults)
MODY (Maturity Onset Diabetes of the Young)
Diabetes Insipidus (Excess urine due to vasopressin hormone)
Secondary Diabetes Mellitus
Cushing syndrome (e.g. steroid administration)
Hyperthyroidism
Parenteral nutrition
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Type 1 diabetes
Was previously called insulin-dependent diabetes
mellitus (IDDM) or juvenile-onset diabetes.
Type 1 diabetes develops when the bodys 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.
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Insulin Dependent Diabetes Mellitus

(IDDM) - Juvenile onset
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.
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Non-Insulin Dependent Diabetes Mellitus

(NIDDM) - Maturity onset
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Causes of insulin deficiency

Production of abnormal insulin

Anti-insulin receptor antibodies

Toxic effects of drugs

Destruction of pancreas by viral infection

Auto immune process

Post-steroid (Glucocorticoid) therapy

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. increase risk of congenital abnormalities
sacral agenesis, congenital heart
disease,
neural tube defects
Hba1c level Risk
normal not
increased
<8% 5%
>10% 25 %
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Factors
GESTATIONAL DIABETES
Possibility
Pregnancy in Diabetic Women

Diabetes (1st time) during Pregnancy

PCOS
Pregnancy in diabetic women
- Perinatal / Neonatal mortality
- Intra uterine death (3rd trimester)
- Premature labour
- Low / high birth weight
- Congenital malformation
- Birth trauma (Sudden Shock)

1)HbA 8 9 % Normoglycaemia
2)Blood glucose 4.0-5.5 mmol/L
3)No Ketonuria
 Gestation Basal plasma glucose
period concentration
Upto 20 weeks > 5.5 mmol/L
20-40 weeks > 6.5 mmol/L
36-38 weeks gestation Caesarian or Induction
delivery
I.V. infusion
10% dextrose + 10 units insulin/500 ml (100 ml/h
rate)
Every 1-2 h glucose concentration is checked
5-6 mmol/L concentration level maintained
After delivery I.V. is stopped upto 12 h
Resumed with S.C. insulin therapy
DIABETES
SYMPTOMS AND DIAGNOSIS
Polyuria

Polydipsia

Polyphagia
 Maintain carbohydrate
diet
Cease smoking before
hour of testing
Fasting glucose level
75 g of glucose + 300 ml
water
Every hour till 2 hours
or at end of 2 h

Plasma Normal Diabetic

levels
Fasting < 6.1 mmol/L > 7.8mmol/L
After 2 h < 8.9 mmol/L > 11.1 mmol/L
 Other Tests
Urine test
- Glucose 0.55-1.11 mmol/L
- Ketoneuria (Acetoacetate, acetone)
Ketostix test strip
Nitroprusside reaction test
 HbA1c Glycated Hemoglobin

Average level of blood sugar (glucose) over

the previous 3 months
HbA1 > 9.0%
Gestational Diabetes
Each trimester to be tested

Sub-optimal endocrine pancreas - Hyperglycaemia

Glycosuria in normal pregnancy

Increase in renal activity (renal thershold)

GFR (Glomerular Filtration Rate) Kidney filtration is

more

Normal level 10 mmol/L

OGTT - 75 g load is not sufficient

Gestational Diabetes
(1st time diabetes during pregnancy)

OGTT Testing:
50 g glucose load 1 h testing
100 g glucose load 3 h testing
Fasting + 2 h post meal testing

HbA1 Test unreliable - Too sensitive, changes too

slowly, affected by other factors

Plasma albumin, plasma proteins are also tested

DIABETES
CONTROL AND TREATMENT
Type I
- Insulin
- Carbohydrate food

Type II
- Diet
- Exercise
- Oral hypoglycaemic drugs
- Insulin
 Diabetes - Insulin
Discovered in 1921 by Banting and Best
Consist of A & B chains linked by 2 disulfide
bonds (plus additional disulfide in A)

A = 21 amino acids B = 30 amino acids

~
Insulin Disadvantage
- Pig / Horse / Human - Hypersensitivity rxn
- rDNA product - Hypoglycaemia
- Sub-cutaneous inj. - Insulin resistance
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Overview of Insulin and Action
Diabetes Oral Medications
6 Classes :
Biguanides
Sulfonylureas
Sulfonylureas and biguanide combination
Thiazolidinediones
Alpha-glycosidase inhibitors
Meglitinides
 Oral hypoglycaemic agents

Biguanides
- Phenformin
- Metformin

Mechanism
1. Decrease glucose absorption from stomach /
intestine
2. Decrease gluconeogenesis
3. Increase peripheral utilization of glucose by cells

Do not lower blood glucose in normal human

Sulphonyl Ureas
- Tolbutamide
- Chlorpropamide
- Glibenclamide
- Glipizide
- Gliclazide

Mechanism
1. Activation of K-ATP Channels in -cells Inhibition
of insulin secretion - Sulphonyl ureas block these
channels
2. Increase sensitivity of cells to insulin upregulation in
its cell receptors
3. Increase insulin secretion
Can reduce blood glucose level in normal persons
Sulfonylurea & Biguanide Combo drugs/
Cocktails
Glucovance (Glyburide & Metformine HCl)

NH

O
NH H
S
O
O N N

H
& N N N
H
O H H
O NH

+ HCl
Cl
1-[[ p-[ 2-( 5-chloro-o-anisamido) ethyl] phenyl] sulfonyl]-3-cyclohexylurea
Thiazolidinediones (TZDs) : make cells more
sensitive to insulin (esp. fatty cells)
O
N O
Pioglitazone S
NH
- Actos, Avandia
O
5-{4-[2-(5-Ethyl-pyridin-2-yl)-ethoxy]-benzyl}-thiazolidine-2,4-dione

- binds to and activates peroxisome proliferator-activated receptor (PPAR).

- PPAR is a member of the steroid hormone and found in adipose tissue,

cardiac and skeletal muscle, liver and placenta

- upon activation PPARligand complex binds to a specific region of DNA and

thereby regulates the genes involved in glucose and fatty acid metabolism.

PPAR -
lpha glycosidase inhibitors :
Block enzymes that help digest starches slowing the rise in
Blood Glucose Level.
AGIs
- Precose (acarbose),

- Glyset (miglitol)
H H
O
O
O
H N

O O
H H
1-(2-Hydroxy-ethyl)-2-hydroxymethyl-
piperidine-3,4,5-triol
Meglitinides : Stimulate more insulin production ;
dependant upon level of glucose present
Meglitinides O

N O OH
- Prandin (repaglinide)
NH O

2-Ethoxy-4-{[3-methyl-1-(2-piperidin-1-yl-phenyl)-butylcarbamoyl]-methyl}-benzoic acid

- Starlix (nateglinide)

NH
O
O OH
2-[(4-Isopropyl-cyclohexanecarbonyl)-amino]-3-phenyl-propionic acid
 Diabetes Oral Medications
Summary

6 Classes :
Sulfonylureas stimulate cells

Biguanides improves insulins ability to move glucose

Sulfonylureas and biguanide combination

drugs BOTH
Thiazolidinediones make the cells more sensitive to insulin
Alpha-glycosidase inhibitors Block enzymes that help
digest starches

Meglitinides stimulate cells (dependant upon glucose conc.)

Factors: Dietary Management
- Age
- Body Weight
- Sex
- Activity
- Occupation

< 40 yrs - Weight maintenance diet +

unmodified depot insulin

> 40 yrs
- Obese Low energy diet + biguanides
- Non-obese Weight maintenance diet
+ sulphonyl ureas + biguanides +
insulin
 Low energy, Weight
weight maintenance diet
reducing diet

Unmeasured
diet
 Diabetic
Obese 1000 to 1600 K.Cal/day
sweeteners
- Sorbitol
Elderly 1400 to 1800 K.Cal/day
- Fructose
- Saccharin
Young Active 1800 to 3000
- Aspartame
K.Cal/day
Carbohydrate 50 to 60 %

Protein 10 to 15 %

Fat 30 to 35 %

Salt Not more than 6 g/day

(Diabetic Hypertensive - < 3 g/day)
Diabetic
Food
Pyramid
Alcohol and Smoke
- Potentiate hypoglycaemic
action of oral drugs & insulin
- Develop lactic acidosis with biguanide drugs
- Increase sensitivity in obese and hypertension
- Causes damage to liver and pancreatic cells
Diet management is essential to
prevent
- Diabetic microangiopathy

- Sustained hyperglycaemia

- Incidence of atherosclerosis

- Maintain ideal body weight and blood lipids

- Avoid hyper-insulinaemia
 Diabetes
Management
Algorithm
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