Transcript Diabetes Mellitus

Top ten countries for estimated number of
adults with diabetes, 1995 and 2025
Country
1995 (millions)
Rank
1
India
2
China
3
U.S.
4
Russian Fed.
5
Japan
6
Brazil
7
Indonesia
8
Pakistan
9
Mexico
10
Ukraine
All other countries
19.4
16.0
13.9
8.9
6.3
4.9
4.5
4.3
3.8
3.6
49.7
Total
135.3
Country
2025 (millions)
India
China
U.S.
Pakistan
Indonesia
Russian Fed.
Mexico
Brazil
Egypt
Japan
57.2
37.6
21.9
14.5
12.4
12.2
11.7
11.6
8.8
8.5
103.6
300.0
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DIABETES MELLITUS
• Cardio metabolic syndrome
• Characterized by persistent
Hyperglycaemia due to absolute or
relative deficiency of insulin/ insulin
resistant.
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CLASSIFICATION
• Primary
• Type 1 or insulin dependent diabetes
mellitus (IDDM)
• Type 2 or non-insulin dependent
diabetes mellitus (NIDDM)
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• Other specific types of diabetes
• Pancreatic Disease
e.g.
Pancreatitis, Haemochromatosis,
Neoplastic disease, Pancreatectomy,
Cystic Fibrosis
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• Excess endogenous production of
hormonal antagonist to insulin
• Growth hormone – Acromagaly
• Glucocorticoids – Cushing’s Syndrome
• Thyroid hormones – Hyperthyroidism
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• Catecholamines –
Phaeochromocytoma
• Human placental lactogen –
Pregnancy
• Glucagon – Glucagonoma
• Counterregulatory hormones – Severe
burns, trauma
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• Medication
• e.g. corticosteroids, thiazide diuretics,
phenytoin
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• Associated with genetic syndromes
• didmoad-diabetes insipidus, diabetes
mellitus, optic atrophy, nerve deafness
• lipoatrophy, muscular dystrophies,
down’s syndrome, klinefelter’s syndrome,
turner’s syndrome
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ENVIRONMENTAL FACTORS
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•
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Bovine serum albumin (cows milk)
Viruses
Stress
Auto immune
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Gestational Diabetes
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PATHOPHYSIOLOGY of type 2
diabetes
• Complex mechanism
• Combination of resistance to action of insulin.
• Impaired pancreatic beta cell function.
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Visceral Fat Topography
Visceral Fat
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INSULIN RESISTANCE
• Excessive production of glucose in liver.
• Under utilization of glucose in skeletal muscles.
• Due to resistance to action of insulin.
Hyperinsulinmia  Water and Sodium
retention  Hypertension
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• Associated, obesity, dyslipidaemia (increased LDL
and low HDL)  metabolic syndrome
• Presence of obesity is amplifier of the insulin
resistance
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Natural History of T2DM
Post Meal Glucose
350
250
Glucose
Fasting Glucose
150
50
300
Insulin Resistance
Relative 200
Function
100
At risk for
Diabetes
0
-10
-5
Insulin Level
Beta Cell Failure
0
5
10
15
20
25
30
Years of Diabetes
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Major Factors Involved In
Pathogenesis of T2DM
Insulin Resistance
-Acquisition of visceral obesity…leads to
Lipotoxicity, & impaired Insulin signaling
Beta Cell Secretory Defects
-Impaired first phase insulin release
secondary to Lipotoxicity, Glucotoxicity, &
loss of Incretion secretion
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C peptide
Proinsulin
Ca2+-dependent
endopeptidases
Insulin
MW 5808
PC2
(PC3)
A Chain
B Chain
PC3
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Insulin Release: Normal Levels
Units: 1 U = 36 µg, i.e. 28 U/mg
Daily secretion in humans: 40 - 50 U
Basal plasma insulin: 12 µU/ml
Postprandial insulin: up to 90 µU/ml
120
Meal
100
80
60
80
40
Basal
Minutes 0
20
30
60
90
120
Insulin, U/ml
Glucose, mg/dl
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Insulin metabolism
• Secreted into portal circulation
50% of degradation in liver
 50% of degradation in other target
tissues and kidney
 Enzymatic degradation follows receptormediated endocytosis


Plasma half-life: 3 - 5 min.
– Circulates as free monomer
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WHAT IS NEW
• Intra-abdominal or central adipose tissue is metabolically
active.
• Release large quantities of FFA.
• Compete with glucose as fuel supply for oxidation 
inhance insulin resistance
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• Central adipose tissue release number of
hormone (adipokines)  act on specific receptor
 influence on insulin sensitivity.
• Visceral adipose tissue drain to portal vein 
influence on liver insulin sensitivity 
gluconeogenosis and hepetic lipid metabolism.
ROLE OF EXERCISE
• Inactivity is associated with down regulation of
insulin sensitive kinase  increased FFA (in
muscles)
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Pancreatic Beta Cell Failure
• In early stage  Decreased in total mass of
pancreatic islet tissue  Pancreatic cell damage.
What is new
• Deposition of amyloid in beta cell  beta cell
destruction.
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Hypothesis
• Polypeptide (Amylin) is secreted together with
insulin.
• Form insoluble fibrils of amyloid  Destruction
of beta cells.
• Number of beta cell reduced to 20-30% but
alpha cell mass unchanged  glucogen
secretion increased  hyperglycemia.
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Other Factor
GENETIC PREDISPOSITION
• Many genes are involved.
• More than 200 .. Gene are found.
• Three gene polymorphism
• Genefor PPARY (Beta cell K ATP channel.
• Onchromosoe 1g, 12g – 20g
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ENVIRONMENTAL FACTOR
• Obesity  Risk increased when BMI is > 30 kg m2
• Overeating  total calorie content (sweat foods
and carbohydrate)
• Lack of exercise
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METABOLIC DISTURBANCE
• Slow onset of relative insulin deficiency
• Lipolysis  and glucose uptake is maintained so don’t
occur weight loss and keto acidosis.
• In type-II diabetes hyperglycemia develops slowly over
months or years  renal threshold rises  osmatic
symptoms less marked
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Clinical Feature
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Polyuria and thirst
Weakness or fatigue
Polyphagia and weight loss
Blurring of vision
Vulvovaginitis or pruritus
Nocturnal enuresis
Asymptomatic
May presented with acute complication
May presented with late complications
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•
• Clinical history, physical exam, ambient glucose levels and
• degree of ketosis usually suffice appropriate diagnostic
• Classification.
• In equivocal setting.
• a) C-peptide or insulin level (low in type I DM)
• b) Glutamic acid decarboxylase a.b
• c) Pancreatic islet cell a.b (+ in 90% of new onset type 1
•
D.M)
•
• All action Allow correct classification
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Clinical Examination
• Physical Exam. must include height,
weight, blood pressure.
• Vision measurement and exam. of eye
grounds.
• Baseline neurological and cardiovascular
exam. should be obtained.
• The foot exam. should include peripheral
pulses, sensation.
• Skin exam. for diabetic dermopathy.
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• Laboratory Evaluation For Newly Diagnosed Diabetes
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Urinanalysis,
Fasting glucose & Random Blood glucose
OGTT
HbA1C,
Fractusamine Test
• Other Investitagation
• Lipid profile,
• , Creatinine,
• Electrolytes, TSH.
• ECG for patient over 40 years.
• should be measured annually.
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Criteria for Diagnosis
 Fasting plasma glucose > 126 mg/dl, or
 Symptoms plus random plasma glucose >
200 mg/dl, or
 Two-hour plasma glucose > 200 mg/dl on
OGTT of 75 gm glucose
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Criteria for Diagnosis
Normal
Impaired
Diagnostic
Fasting
< 110
110 – 125
IFG
126
OGTT
< 140
140 – 199
IGT
200
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Indications For OGTT
1.
2.
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1.
2.
3.
4.
5.
Patients with Impaired Fasting Glycemia (IFG)
Pregnant women and postpartum (in women with
GDM)
* OGTT is performed using a 75 oral glucose load in
the morning after a noncaloric 8hr fast. Water is
allowed but not coffee or smoking.
Types of Curves when performing OGTT
Normal curve
IGT
Diabetic curve
Lag storage curve
Flat curve
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Pre-diabetes
1.
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2.
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Impaired Fasting Glucose (IFG)
FPG 100mg/dl (5.6 mmol/L) to 125 mg/dl (6.9 mmol/L)
Impaired Glucose Tolerance (IGT)
2 hr plasma glucose 140mg/dl (7.8 mmol/L) to 199 mg/dl
(11.0 mmol/L)
Both IFG and IGT are risk factors for future diabetes and for
cardiovascular disease and associated with insulin resistance
and
metabolic syndrome.
Unless lifestyle modifications are made most people with prediabetes
develop type 2 diabetes within 10 years.
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HbA1c
• Glycosylated haemoglobin
• Average blood glucose over last 8-12 weeks
• Is not diagnostic
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MANAGEMENT OF DM
• 50% ----DIET
• 25% ----OHD
• 25%-----INSULIN
Type of treatment is determined by serum insulin level or by
age and weight (<40 or >40, over wt or normal wt)
LIFESTYLE MODIFICATIONS SHOULD BE STRESSED TO
ACHIEVE GOAL
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• Eat less walk more
• Reduce calories
• Burn calories
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THERAPEUTIC GOAL
NEAR NORMAL METABOLISM
1.
2.
3.
Normal blood sugar
Normal body weight
Normal metabolic profile
ALL WILL LEAD TO RETARD
VASCULAR AND SPECIFIC DIABETIC
COMPLICATIONS
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DIABETIC DIET
2 TYPES
1. LOW ENERGY, WT-REDUCING DIETS FOR
HIGH BMI
2. WT MAINTENANCE DIETS FOR NORMAL
BMI
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AIMS OF DIETRY MANAGEMENT
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ABOLISHES HYPERGLYCEMIC SYMPTOMS
REDUCE BLOOD SUGAR
ACHIEVE WT REDUCTION IN OBESE
AVOID HYPOGLYCEMIA
AVOID WT GAIN
AVOID ATHEROGENIC DIET
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ORAL HYPOGLYCAEMIC DRUGS
• MOST DEPENDS UPON SUPPLY OF
ENDOGENOUS INSULIN
• SUPHONYNUREAS
• BIGUNIDES
• ALPHA-GLUCOSIDASE INHIBITORS
• THIAZOLIDINEDIONES
• MEGLITINIDES
• INCRETINS
• DPP 4 IN HIBITORS
• AMYLIN ANALOGUE
• SGT INHIBITORS
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SULPHONYLEUREAS
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MECHANISMS
INSULIN SECRETOGOGUES
DECREASES HEPATIC RELEASE
INCREASE IN WT AND PRODUCE INSULIN
RESISTANCE
• EXAMPLES:
1. FIRST GENERATION---TOLBUTAMIDE AND
CHLORPROPAMIDE
2. SECOND GENERATION---GLICLAZIDE ,
GLIPIZIDE,GLIBENCLAMIDE, GLIMEPRIDE
Primary treatment failure and secondary
treatment failure
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BIGUANIDES
• MECHANISMS
• INCREASE INSULIN SENSITIVITY NAD
HENCE INCREASE PERIPHERAL UPTAKE
OF GLUCOSE BY TISSUE
• IMPAIRS GLUCOSE ABSORPTION FROM
GUT
• INHIBITS HEPATIC GLUCONEOGENESIS
PREFERRED IN OBESE
CONTRAINDICATED IN
RENAL, HEPATIC FAILURE AND
ALCOHOLICS
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ALPHA-GLUCOSIDASE INHIBITORS
• INHIBITS DISACCHARIDASE OF GUT MUCOSA
AND HENCE DELAY CHO ABSORPTION
• CAUSES FLATULENCE,DIARRHOEA AND
ABDOMINAL BLOATING
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THIAZOLIDINEDIONES(TZD,GLITAZ
ONES,PPAR gamma AGONIST)
• BINDS AND ACTIVATES PEROXISOME
PROLIFERATOR-ACTIVATED
RECEPTOR GAMMA , THUS
ENHANCING ACTION OF
ENDOGENOUS INSULIN—GOOD IN
INSULIN RESISTANCE SYNDROM—
ROSIGLITAZONE AND PIOGLITAZONE
• SHOULD BE COMBINED WITH SU OR
METFORMIN
• CAUSES FLUID RETENTION (C/I IN
CCF) AND OBESITY
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MEGLITINIDES(ORAL PRANDIAL OR
FIRST PHASE INSULIN SECRETOR)
• REPAGLINIDE AND NATEGLINIDE
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DPP4 inhibitors
• Sita glipition
• Vilda gliption
SGT inhibitors
• KANA , gliflozin
COMBINED ORAL AND INSULIN
• IN SECONDARY TREATMENT FAILURE ORAL
AND ISOPHANE INSULIN SHOT AT NIGHT CAN
BE VERY EFFECTIVE TO PREVENT RESIDUAL
BETA CELL FAILURE.
• INEFFECTIVE IN C-PEPTIDES NEGATIVE
PATIENTS
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INSULINS(100u/ml)
• FAST-ACTING---LISPRO
• SHORT-ACTING –
SOLUBLE,REGULAR,UNMODIFIED
• INTERMEDIATE-ACTING,ISOPHANE ,LANTE,NPH
• LONG-ACTING, BOVINE ULTRALENTE
• LONG-ACTING,INSULIN ANALOGUE GLARGIN
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Diabetes Mellitus
• Medications
• Injectable
• Humulin
• Glucagon
Diabetes Mellitus
• Insulin Pumps
• Device a little bit larger than a pager that delivers insulin
via a small plastic infusion set usually located in abdomen
• Infusion set is usually moved every 2-3 days
INSULIN THERAPY IN DM TYPE - 2
COMBINATION OF OAA & INSULIN
METFORMIN & OR SU AND BEDTIME NPH
IF TARGET NOT REACHED IN 4-8 WKS
INSULIN STAGE 2
(2/3)R/N(1/2) – 0 –(1/3) R/N (1/1) - 0
INSULIN STAGE 3
(2/3)R/N(1/2) – 0 – R(1/6) – N(1/6)
INSULIN STAGE 4
R(20%) – R(25%) – R(25%) – N(30%)
How to draw insulin?
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1 vial use
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Humulin-N
or
Humulin-70/30
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3 Roll the bottle of insulin gently between the palms of your
hands .This will mix the insulin well. Do not shake,
Shaking leaves air bubbles that can get into the syringe
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3 Clean the tip of Bottle with alcohol swab
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1 vial use
for example
40 units
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Take the needle cap off the syringe.
Hold the syringe with needle pointing toward the ceiling .
Keep syringe at eye level , so you can easily see the
markings on the barrel.
You must put air into the insulin bottle before you can get the insulin out
of the bottle .First ,pull the syringe plunger down until the top of the
black tip crosses the mark of the dose to be taken .This draws air
into the syringe. For example : If you take 40 units of insulin , draw
about 40 units of air into syringe .
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Now turn the syringe tip down . Put the needle through
the rubber stopper of the insulin bottle .Push down all the
way on the plunger, and hold the plunger in. This puts air
into the bottle
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Make sure the tip of needle is in the insulin .Pull down slowly
on the plunger . This brings insulin into the syringe .
Pull down slowly on the plunger to the exact line of your insulin
dose . The right amount of insulin now be in your syringe
Look in the syringe for air bubbles .If you see air bubbles , push
the insulin back into the bottle . Then pull the plunger back
to the exact line of your insulin dose .If the bubbles are still
in the syringe, repeat the process until they are gone.
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When all the bubbles are out and you have the right dose
,pull the bottle straight up and off the needle .Put the
needle cap back on the syringe over the needle . You
will know that it’s right if the top of the plunger crosses
the right mark on the syringe and there are no air
bubbles.
Now you are ready to give yourself your shot .Take a deep
breath and let it out slowly to help u relax.
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2 vials use
Mixing 2 vials of Insulin
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Humulin-R
and
Humulin-N
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1 Gather all of your equipment :
Syringe
Alcohol swab
Insulin
2 Wash your hands.
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3 Roll the bottle of insulin gently between the palms of your
hands .This will mix the insulin well. Do not shake,
Shaking leaves air bubbles that can get into the syringe
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3 Clean the tip of Bottle with alcohol swab
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2 vials use
for example
Humulin-N 20 units
Humulin-R 10 units
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Pull 20 units of air into the empty syringe . Put the
needle through the rubber stopper of the bottle of
cloudy insulin( Humulin N) while its placed on table.
Push air into the bottle .Remove the needle.
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Pull 10 units of air into the same empty syringe .Put
the needle into the Humulin Regular (R) insulin bottle .
This insulin is clear .Push air into the bottle.
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With the needle still in the Regular insulin bottle ,turn the
bottle upside down . Pull plunger halfway down the syringe .
This brings insulin into the syringe .Push the insulin back into
the bottle to get rid of the air bubbles . Now pull your dose of
insulin into the syringe .Carefully measure 10 units of clear
insulin (Humulin R). Pull the syringe out of the bottle
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Turn the cloudy Humulin N insulin bottle upside down .Put
the plunger back slowly to total 30 units .Pull the bottle
off the needle.
Clear the total dosage . The dose should be :
Humulin N (cloudy) 20 units .
Humulin R (clear) 10 units .
Total of 30 units now in the syringe
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Sites of Injection
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Pick a spot from the chart and then find this spot on
yourself .Pick a spot at least 1 inch from the place you
gave your last shot.
If desired .clean the spot with alcohol .Let dry
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Pick a spot from the chart and then find this spot on
yourself .Pick a spot at least 1 inch from the place you
gave your last shot.
If desired .clean the spot with alcohol .Let dry
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Pick a spot from the chart and then find this spot on
yourself .Pick a spot at least 1 inch from the place you
gave your last shot.
If desired .clean the spot with alcohol .Let dry
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Pick a spot from the chart and then find this spot on
yourself .Pick a spot at least 1 inch from the place you
gave your last shot.
If desired .clean the spot with alcohol .Let dry
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How to inject Humulin?
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If desired .clean the spot with alcohol .Let dry
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Remove the top from the needle .Hold the
syringe in one hand as you would hold a
pencil.
With your other hand ,pinch up a couple of
inches of skin .
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Stick the needle straight into the pinched skin .Put the
needle all the way in through the skin with one smooth
motion
Relax the pinch ,and slowly push the plunger all the way
down.
Be sure the insulin is in ,then remove the needle.
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Lightly press down on the side BUT don’t RUB. Don’t worry if a
drop of blood
appears where the needle was.
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When you are ready to discard your used needles and
syringes , break the needle and put them into a hard plastic
or metal container with a screw-on lid .Label and discard
according to local regulations.
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TELL YOUR PATIENT
TO
Record the insulin dose you just gave yourself in your
diabetes diary.
It may be hard to give yourself a shot for the
first time ,but with practice it will become much
easier.
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ACUTE METABOLIC
COMPLICATIONS
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HYPOGLYCAEMIA
DIABETIC KETOACIDOSIS
NON-KETOTIC HYPEROSMOLAR COMA
LACTIC ACIDOSIS
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LONG TERM COMPLICATIONS
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DYSLIPIDAEMIA
CARDIOVASCULAR DISEASES
DIABETIC RETINOPATHY
DIABETIC NEPHROPATHY
DIABETIC NEUROPATHY
DIABETIC FOOT
DIABETES AND PREGNANCY
DIABETES AND SURGERY
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Q.1 For diagnosis of diabetes
mellitus which of following are
true?
a)
b)
c)
d)
e)
Urine for sugar
FBS blood sugar more than 126mmd/l
HBA1C
OGTT
RBS More than 200
Q.2 Which of Following are micro vascular
complications of diabetes?
a)
b)
c)
d)
e)
Retinopathy
Nephropathy
Diabetic foot
Cataract
Neuropathy
Q.3, 50 year patient is going for dental
surgery his blood sugar is 300 which of
following treatment is appropriate?
a)
b)
c)
d)
e)
Metformin
Glimepride
Rapid acting Insulin
Ultra Short Acting Insulin
Insulin determir
Q.4 Which of the following Drugs are not
used in treatment of diabetes with CRF?
a)
b)
c)
d)
e)
Metformin
Insulin
Captopril
Glibenclamide
Meglitinide