Diabetes Mellitus - In Terms of Biochemistry. This presentation explains details about Diabetes Mellitus in simple way.

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Diabetes Mellitus
But..we have
changed from a
primitive hunter-
caveman to a
sophisticated
modern man,
especially in the
urban areas

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Diabetes Mellitus
Gains
• Better living conditions
• Variety of foods
• Better transportation
• Better communication
Losses
• More eating
• Less physical activity
• More stress

4. Obesity
Diabetes
Hypertension &
cardiovascular diseases
Cancer
Leading to….

5. Obesity
Diabetes
Cancer
Leading to….
Oxidative Stress
Hypertension &
cardiovascular diseases

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Diabetes Mellitus
Diabetes mellitus is the third
leading cause of death (after heart
disease & cancer) in many developed
countries.
It affects about 2 to 3% of the
general population.
The complications of diabetes
affect the eye, kidney and nervous
system.
Diabetes is a major cause of
blindness, renal failure,
amputation,heart attacks & stroke.
Diabetes mellitus
Mellitus

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Diabetes

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Diabetes Mellitus
Diabetes Mellitus is a chronic disorder of carbohydrate,
protein, & fat metabolism resulting from insulin deficiency
or abnormality in the use of insulin.
Diabetes is sometimes described as:
“STARVATION IN THE MIDST OF PLENTY”
There is plenty of glucose circulating in the blood but it
cannot get into the cells that need it.
It characterised by increased blood glucose level
(hyperglycemia)
Definition

9. Diabetes: A global emergency

10. Diabetes around the world

11. … and the costs to society are high & escalating
Diabetes is a human and economic burden
4.9 million deaths per year
50% of deaths under 60
years of age
Intersects with all
dimensions of
development
US$612 billion
11% of worldwide healthcare
expenditure

12. Diabetes around the world

14. Diabetes around the world

15. Diabetes around the world

16. Diabetes around the world

18. Diabetes around the world

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Diabetes Mellitus
Top 3 countries number of adults with diabetes, 2009
69.2
109.6
29.3
INDIA CHINA US

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Diabetes Mellitus
Insulin is the principal hormone
in the body
– It plays a key role in all forms of
diabetes mellitus.
– It regulates uptake of glucose
from the bloodstream into every
muscle and fat cell,
– But not into the cells of the
central nervous system.
• Deficiency of insulin or insensitivity
of its receptors Causes Diabetes
Miletus

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Diabetes Mellitus
• food is converted to
glucose before it is used
by the blood and body as
fuel.
• As a result, blood glucose
levels in the body rise.
• In response to this, the
Pancreas release Insulin
into the blood.
When our body functions normally …

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Diabetes Mellitus
When our body functions normally …
• about two-thirds of the
body's cells use Insulin to
• Absorption glucose from the
blood
• To use as fuel
• To convert to other needed
chemicals,
• for storage.

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Diabetes Mellitus
Normal Glucose Absorption
Insulin binds to
receptors on the cell
membrane, much as a
key fits into a lock,
signal glucose
transporters
Glucose transporters
move to the cell
membrane and bind
to glucose.
Glucose enters the
cell.

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Diabetes Mellitus

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Diabetes Mellitus

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Diabetes Mellitus

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Diabetes Mellitus
Classification of DIABETES MELLITUS
Type 1
β-Cell
destruction
Absolute insulin
deficiency
Autoantibodies
Type 2 Other Gestational
Islet cell autoantibodies
Insulin autoantibodies
Glutamic acid decarboxylase autoantibodies
Tyrosine phosphatase IA-2 and IA-2B
b autoantibodies

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Diabetes Mellitus
Classification of DIABETES MELLITUS
Type 1 Type 2
Insulin resistance with an insulin
secretary defect
Relative insulin deficiency
Other Gestational

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Diabetes Mellitus
Classification of DIABETES MELLITUS
Type 1 Type 2 Other Gestational
Associated with secondary conditions
Genetic disease of β-cell function and insulin action
Pancreatic disease
Endocrine disease
Drug or chemical induced
Insulin receptor abnormalities
Other genetic syndromes

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Diabetes Mellitus
Classification of DIABETES MELLITUS
Type 1 Type 2 Other Gestational
Glucose intolerance during pregnancy due to
metabolic and hormonal changes

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Diabetes Mellitus

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Diabetes Mellitus
Prevalence

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Diabetes Mellitus
% of diabetic pop 5-10% 90%
Previous names
Insulin Dependent DM
(IDDM), Juvenile onset DM
Non insulin dependent DM
(NIDDM), Maturity onset DM
Treatment Insulin is always needed
Diet, exercise, oral
hypoglycemic drugs & insulin in
severe cases
Frequency of
ketosis
Very common Rare
Acute Complications Hypoglycemia & ketoacidosis Hyperosmolar non ketotic coma
Insulin sensitivity Normal Reduced
Plasma insulin Low to absent Normal to High
Body weight Low to normal Obese
Genetic
predisposition
Moderate Very strong
Pattern of onset Symptoms develop rapidly Symptoms appear gradually
Age of onset
early during childhood or
puberty, usually <20yrs
Frequently after the age of
35-40 yrs
Features Type 1 DM Type 2 DM

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Diabetes Mellitus

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Diabetes Mellitus
Cause and Onset
It is caused by lack of Insulin secretion due to
destruction of pancreatic beta cells.
The cause of beta-cell destructions may be due to….
 Viral infection
 Autoimmune disorder or
 There may be inhereditary tendency for beta-cell
degeneration.
Onset
The onset of type- I DM occur early during childhood or
puberty, usually <20yrs

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Diabetes Mellitus

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Diabetes Mellitus
 Polyuria
 Polydipsia
 Polyphagia
 Weight loss
 Weakness
 Dry skin
 Ketoacidosis

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Diabetes Mellitus

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Diabetes Mellitus
Cause and Onset
It is caused by decreased sensitivity of target tissues
to insulin.
This reduced sensitivity of insulin is referred to as
insulin resistance.
Onset
The onset of type- II DM occur after the age of 40 yrs
The disorder develops gradually.
Therefore this syndrome is referred to as adult onset
diabetes.

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Diabetes Mellitus
Risk factor
 Family history of diabetes
 Obesity (BMI >25 kg/m2)
 Habitual physical inactivity
 Race (e.g., African American, Latino,
Native American, Asian American,)
 Previously identified IFG or IGT
 History of GDM or delivery of baby >4 kg
 Hypertension (BP >140/90 mmHg)
 HDL cholesterol level <35 mg/dL and/or
a triglyceride level >250 mg/dL
 Polycystic ovary syndrome

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Diabetes Mellitus
 Patients can be
asymptomatic
 Polyuria
 Polydipsia
 Polyphagia
 Fatigue
 Weight loss

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Diabetes Mellitus

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Diabetes Mellitus

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Diabetes Mellitus
Individuals are at much higher risk for developing
type 2 diabetes than insulin-sensitive persons
also elevated plasma triglycerides, lower (HDLs),
and higher blood pressure
25 % of the general obese nondiabetic population has insulin
resistance of a magnitude similar to that seen in type 2 diabetes.

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Diabetes Mellitus

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Diabetes Mellitus
Occurs during pregnancy as a result of
hormonal influences causing insulin resistance

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Diabetes Mellitus
DIABETES
MELLITUS
Insulin↓ and
glucagon↑
↓Glucose uptake Hyperglycemia Glucosuria
• Osmotic diuresis
• Polyuria
• Dehydration
• Coma
• Death
↑Protein catabolism ↑Plasma amino
acids
↑Nitrogen loss in
urine
↑Gluconeogenesis
↑Lipolysis ↑FFA oxidation
↑Ketogenesis
• Ketosis
• Coma
• Death
Metabolic events occurring in diabetes mellitus

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Acute Metabolic Complications
 Diabetic Keto Acidosis
 Ketosis is more common in type 1 diabetes mellitus.
 Normally the blood level of ketone bodies is less than 1 mg/dl and
only traces are excreted in urine (not detectable by usual tests).
 But when the rate of synthesis exceeds the ability of
extrahepatic tissues to utilize them, there will be accumulation of
ketone bodies in blood.
 This leads to ketonemia, excretion in urine (ketonuria) and smell
of acetone in breath.
 All these three together constitute the condition known as
ketosis.
 Hyperosmolar Hyperglycemic Nonketotic Syndrome
(HHNS)

53. Stroke
Neuropathy
Cardiomyopathy
Retinopathy
Chronic Complications of
Diabetes Mellitus
Nephropathy

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Clinical features of diabetes at diagnosis.
Type 1
Diabetes
Type 2
Diabetes
Polyuria and thirst ++ +
Weakness or fatigue ++ +
Polyphagia with weight loss ++ –
Recurrent blurred vision + ++
Vulvovaginitis or pruritus + ++
Peripheral neuropathy + ++
Nocturnal enuresis ++ –
Often asymptomatic – ++

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Diagnosis of Diabetes Mellitus
The following investigations are helpful in
diagnosis of DM
– Blood glucose estimation
– Urine testing for glucose
– GTT (Glucose tolerance Test)
– HbA1c (Glycated hemoglobin estimation)

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Fasting blood Glucose
Fasting blood glucose is
measured after an overnight
fast of 8 - 10 hrs.
o Fasting blood glucose
estimation is better than
random blood glucose.
o FPG < 100 mg/dL is considered normal;
o FPG = 100–125 mg/dL is defined as IFG; and
o FPG >126 mg/dL warrants the diagnosis of DM.

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Detection of urinary glucose (Glucosuria)
First-line screening test for diabetes
mellitus
o Normally glucose does not appear in urine
until the plasma glucose rises above 160-
180 mg/dl.
o In certain individuals due to low renal
threshold glucose may be present despite
normal blood glucose levels.
o Conversely renal threshold increases with
age so many diabetics may not have
Glycosuria despite high blood sugar levels. Positive
Benedict’s test

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Paper strip
impregnated with
glucose oxidase and a
chromogen system
Sensitive to as little as
0.1% glucose in urine.
Urinalysis

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By nitroprusside
tests (Acetest or
Ketostix).
Do not detect β-
hydroxybutyric
acid
Urinalysis

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c) Microalbuminuria
o May be defined as an albumin
excretion rate intermediate
between (2.5-25 mg/day).
o It is a predictor of progressive
renal damage.
o Albumin more than 300 mg/day
indicates overt diabetic
nephropathy.
o Microalbuminuria is to be checked
at least once in an year.
Gradation of turbidity is linked to
protein concentration

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Blood testing procedures
Normal
carbohydrate diet
for 3 days
Overnight fast on
the day of the test
FPG is drawn
Give 75gm of
anhydrous glucose
in about 300ml of
water
Blood & urine
specimens are
collected at half
hourly for 2hours
A curve is plotted
for time against
blood glucose

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The Diabetes Expert Committee criteria for evaluating the
standard oral glucose tolerance test.1
Normal Glucose
Tolerance
Impaired Glucose
Tolerance
Diabetes Mellitus
Fasting plasma
glucose (mg/dL)
< 110 110–125 ≥126
Two hours after
glucose load
(mg/dL)
< 140 ≥140–199 ≥200
Criteria for laboratory confirmation of diabetes mellitus

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 Estimation of Glycated hemoglobin (HbA1c) levels in blood is
used as a guide to the degree of control over a long period.
 Glucose in the blood reacts with the Hemoglobin A to form
Glycated Hb.
 The RBCs of all the people contain a small proportion of HbA1c.
 The rate of formation is proportional to the glucose levels.
 So, persons with diabetes have higher proportion of HbA1c
than the normal individual.
 Once formed, glycated Hb, stays within the RBC for its lifetime
(120 days).
 An elevated HbA1c indicates poor control of bl glucose level in
the previous 2-3 months,
Glycated hemoglobin (HbA1c)

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(HbA1c)

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WHO Criteria for Diagnosing
DM • A1C ≥ 6.5%
OR
• FBG ≥126mg/dL
OR
• 2 hr plasma glucose ≥200mg/dL during
OGTT
OR
• Classic signs of HYPERGLYCEMIA
with RBG ≥200mg/dL

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Management of Diabetes
Mellitus
 Promote healthy eating
 Promote regular physical activity
 Having regular check ups

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Healthy eating plan
 Stop eating excessive amounts of
fats, oils, sugars, salt and limit
alcohol intake
 Eat some but not to much of starchy
vegetables, breads, cereals, rice,
pasta, dairy products and protein
 Eat lots of non starchy vegetables
and fruit, drinks (Diet soft drinks,
water, trim milk)

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Regular physical activity plan
 Encourage any kind of physical
activity that elevates heart rate
e.g. walking, swimming,
running, sporting activities for
20-30 minutes per day at least 3
times per week.
 Taking children to the park or bike
riding around the neighbourhood
can be a cost free activity.

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Regular check ups
 Consistent check ups with health professionals
 Self-monitoring of blood glucose
Capillary blood
glucose
measurements
performed by
patients themselves,
as outpatients, are
extremely useful

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DexCom system MiniMed system Glucowatch system

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Diabetes Mellitus
How to prevent/control diabetes
 Prevention all starts with a better lifestyle
 eating healthier
 being active
 taking medicine as directed
 control blood pressure
 no smoking!
 check in with your doctor at least once a month
 have your blood sugar checked along with weight,
blood pressure, and feelings
 Check blood sugar levels daily by using home
monitoring device

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Contact no. – 07418831766
E mail – ashokkt@gmail.com
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Dept. of Biochemistry,
Dhanalakshmi Srinivasan Medical College,
Perambalur
Thankyou