Country 1995 (millions) Country 2025 (millions)

Rank

1 India 19.4 India 57.2

2 China 16.0 China 37.6

3 U.S. 13.9 U.S. 21.9

4 Russian Fed. 8.9 Pakistan 14.5

5 Japan 6.3 Indonesia 12.4

6 Brazil 4.9 Russian Fed. 12.2

7 Indonesia 4.5 Mexico 11.7

8 Pakistan 4.3 Brazil 11.6

9 Mexico 3.8 Egypt 8.8

10 Ukraine 3.6 Japan 8.5

All other countries 49.7 103.6

Total 135.3 300.0

Top ten countries for estimated number of adults with diabetes, 1995 and 2025

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DIABETES MELLITUSDIABETES MELLITUS

• Cardio metabolic syndrome Cardio metabolic syndrome

• Characterized by persistent Characterized by persistent Hyperglycaemia due to absolute or Hyperglycaemia due to absolute or relative deficiency of insulin/ insulin relative deficiency of insulin/ insulin resistant.resistant.

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CLASSIFICATIONCLASSIFICATION

• Primary Primary

• Type 1 or insulin dependent diabetes Type 1 or insulin dependent diabetes mellitus (IDDM)mellitus (IDDM)

• Type 2 or non-insulin dependent Type 2 or non-insulin dependent diabetes mellitus (NIDDM)diabetes mellitus (NIDDM)

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• Other specific types of diabetesOther specific types of diabetes• Pancreatic Disease Pancreatic Disease e.g. e.g.

Pancreatitis, Haemochromatosis, Pancreatitis, Haemochromatosis, Neoplastic disease, Pancreatectomy, Neoplastic disease, Pancreatectomy, Cystic FibrosisCystic Fibrosis

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• Excess endogenous production of Excess endogenous production of hormonal antagonist to insulin hormonal antagonist to insulin • Growth hormone – AcromagalyGrowth hormone – Acromagaly• Glucocorticoids – Cushing’s Syndrome Glucocorticoids – Cushing’s Syndrome • Thyroid hormones – HyperthyroidismThyroid hormones – Hyperthyroidism

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• Catecholamines – Catecholamines – PhaeochromocytomaPhaeochromocytoma

• Human placental lactogen – Human placental lactogen – PregnancyPregnancy

• Glucagon – GlucagonomaGlucagon – Glucagonoma• Counterregulatory hormones – Severe Counterregulatory hormones – Severe

burns, traumaburns, trauma

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• MedicationMedication

• e.g. corticosteroids, thiazide diuretics, e.g. corticosteroids, thiazide diuretics, phenytoinphenytoin

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• Associated with genetic syndromesAssociated with genetic syndromes

• didmoad-diabetes insipidus, diabetes didmoad-diabetes insipidus, diabetes mellitus, optic atrophy, nerve deafnessmellitus, optic atrophy, nerve deafness

• lipoatrophy, muscular dystrophies, lipoatrophy, muscular dystrophies, down’s syndrome, klinefelter’s syndrome, down’s syndrome, klinefelter’s syndrome, turner’s syndrometurner’s syndrome

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ENVIRONMENTAL FACTORSENVIRONMENTAL FACTORS

• Bovine serum albumin (cows milk)Bovine serum albumin (cows milk)

• VirusesViruses

• StressStress

• Auto immuneAuto immune

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Gestational DiabetesGestational Diabetes

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PATHOPHYSIOLOGY of type 2 PATHOPHYSIOLOGY of type 2 diabetesdiabetes

• Complex mechanism Complex mechanism

• Combination of resistance to action of insulin. Combination of resistance to action of insulin.

• Impaired pancreatic beta cell function.Impaired pancreatic beta cell function.

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Visceral Fat Topography

Visceral Fat

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INSULIN RESISTANCEINSULIN RESISTANCE

• Excessive production of glucose in liver.Excessive production of glucose in liver.• Under utilization of glucose in skeletal muscles.Under utilization of glucose in skeletal muscles.• Due to resistance to action of insulin.Due to resistance to action of insulin.

Hyperinsulinmia Hyperinsulinmia Water and Sodium Water and Sodium retention retention Hypertension Hypertension

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• Associated, obesity, dyslipidaemia (increased LDL Associated, obesity, dyslipidaemia (increased LDL and low HDL) and low HDL) metabolic syndrome metabolic syndrome

• Presence of obesity is amplifier of the insulin Presence of obesity is amplifier of the insulin resistanceresistance

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Natural History of T2DM

0

100

200

300

-10 -5 0 5 10 15 20 25 30

50

150

250

350

At risk for Diabetes

Glucose

Relative Function

Post Meal Glucose

Fasting Glucose

Insulin Resistance

Insulin LevelBeta Cell Failure

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 peptideProinsulinInsulinMW

Ca2+-dependent endopeptidases

A Chain

B Chain

PC2(PC3)

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

Basal

Meal

G

luc

os

e, m

g/d

l 120

100

80

80

60

40

20

Insu

lin,

U/m

l

Minutes 0 30 60 90 120 GHB

Insulin metabolism

• Secreted into portal circulation

50% of degradation in liver50% of degradation in other target tissues

and kidneyEnzymatic degradation follows receptor-

mediated endocytosis

Plasma half-life: 3 - 5 min.– Circulates as free monomer

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WHAT IS NEWWHAT IS NEW

• Intra-abdominal or central adipose tissue is metabolically Intra-abdominal or central adipose tissue is metabolically active. active.

• Release large quantities of FFA.Release large quantities of FFA.

• Compete with glucose as fuel supply for oxidation Compete with glucose as fuel supply for oxidation inhance insulin resistance inhance insulin resistance

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• Central adipose tissue release number of Central adipose tissue release number of hormone (adipokines) hormone (adipokines) act on specific receptor act on specific receptor influence on insulin sensitivity. influence on insulin sensitivity.

• Visceral adipose tissue drain to portal vein Visceral adipose tissue drain to portal vein influence on liver insulin sensitivity influence on liver insulin sensitivity gluconeogenosis and hepetic lipid metabolism. gluconeogenosis and hepetic lipid metabolism.

ROLE OF EXERCISEROLE OF EXERCISE• Inactivity is associated with down regulation of Inactivity is associated with down regulation of

insulin sensitive kinase insulin sensitive kinase increased FFA (in increased FFA (in muscles)muscles)

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Pancreatic Beta Cell FailurePancreatic Beta Cell Failure

• In early stage In early stage Decreased in total mass of Decreased in total mass of pancreatic islet tissue pancreatic islet tissue Pancreatic cell damage. Pancreatic cell damage.

What is newWhat is new

• Deposition of amyloid in beta cell Deposition of amyloid in beta cell beta cell beta cell destructiondestruction. .

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HypothesisHypothesis

• Polypeptide (Amylin) is secreted together with Polypeptide (Amylin) is secreted together with insulin. insulin.

• Form insoluble fibrils of amyloid Form insoluble fibrils of amyloid Destruction Destruction of beta cells. of beta cells.

• Number of beta cell reduced to 20-30% but Number of beta cell reduced to 20-30% but alpha cell mass unchanged alpha cell mass unchanged glucogen glucogen secretion increased secretion increased hyperglycemia. hyperglycemia.

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Other FactorOther Factor

GENETIC PREDISPOSITION GENETIC PREDISPOSITION • Many genes are involved.Many genes are involved.• More than 200 .. Gene are found.More than 200 .. Gene are found.• Three gene polymorphism Three gene polymorphism • Genefor PPARY (Beta cell K ATP channel. Genefor PPARY (Beta cell K ATP channel. • Onchromosoe 1g, 12g – 20g Onchromosoe 1g, 12g – 20g

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ENVIRONMENTAL FACTORENVIRONMENTAL FACTOR

• Obesity Obesity Risk increased when BMI is > 30 kg m2 Risk increased when BMI is > 30 kg m2• Overeating Overeating total calorie content (sweat foods total calorie content (sweat foods

and carbohydrate)and carbohydrate)• Lack of exercise Lack of exercise

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METABOLIC DISTURBANCEMETABOLIC DISTURBANCE

• Slow onset of relative insulin deficiency Slow onset of relative insulin deficiency • Lipolysis Lipolysis and glucose uptake is maintained so don’t and glucose uptake is maintained so don’t

occur weight loss and keto acidosis. occur weight loss and keto acidosis. • In type-II diabetes hyperglycemia develops slowly over In type-II diabetes hyperglycemia develops slowly over

months or years months or years renal threshold rises renal threshold rises osmatic osmatic symptoms less markedsymptoms less marked

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Clinical Feature

• 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

• 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

NormalNormal ImpairedImpaired DiagnostiDiagnosticc

FastinFastingg

< 110< 110 110 – 125110 – 125

IFGIFG

126126

OGTTOGTT < 140< 140 140 – 199140 – 199

IGTIGT

200200

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Indications For OGTT

1. Patients with Impaired Fasting Glycemia (IFG)

2. 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

1. Normal curve

2. IGT

3. Diabetic curve

4. Lag storage curve

5. Flat curve

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Pre-diabetes

1. Impaired Fasting Glucose (IFG)• FPG 100mg/dl (5.6 mmol/L) to 125 mg/dl (6.9 mmol/L)

2. 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 pre-diabetes

• develop type 2 diabetes within 10 years. GHB

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. Normal blood sugar2. Normal body weight3. Normal metabolic profile

ALL WILL LEAD TO RETARDVASCULAR 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

• 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

• MECHANISMS• INSULIN SECRETOGOGUES• DECREASES HEPATIC RELEASE• INCREASE IN WT AND PRODUCE INSULIN

RESISTANCE• EXAMPLES:1. FIRST GENERATION---TOLBUTAMIDE AND

CHLORPROPAMIDE2. 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 GLUCONEOGENESISPREFERRED IN OBESECONTRAINDICATED 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,GLITAZONES,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 & INSULINMETFORMIN & 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 4R(20%) – R(25%) – R(25%) – N(30%)

How to draw insulin?

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1 vial use

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Humulin-NorHumulin-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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33 Clean the tip of Bottle with alcohol swabClean the tip of Bottle with alcohol swab

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1 vial use 1 vial use for examplefor example

40 units 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 .. GHB

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. GHB

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. GHB

2 vials use

Mixing 2 vials of InsulinMixing 2 vials of Insulin

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Humulin-RandHumulin-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 usefor example

Humulin-N 20 unitsHumulin-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 GHB

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 dryGHB

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 dryGHB

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 dryGHB

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 dryGHB

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.GHB

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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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.

TELL YOUR PATIENTTO

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ACUTE METABOLIC COMPLICATIONS

• HYPOGLYCAEMIA• DIABETIC KETOACIDOSIS• NON-KETOTIC HYPEROSMOLAR COMA• LACTIC ACIDOSIS

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LONG TERM COMPLICATIONS

• 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) Urine for sugar

b) FBS blood sugar more than 126mmd/l

c) HBA1C

d) OGTT

e) RBS More than 200

Q.2 Which of Following are micro vascular complications of diabetes?

a) Retinopathy

b) Nephropathy

c) Diabetic foot

d) Cataract

e) Neuropathy

Q.3, 50 year patient is going for dental surgery his blood sugar is 300 which of following treatment is appropriate?

a) Metformin

b) Glimepride

c) Rapid acting Insulin

d) Ultra Short Acting Insulin

e) Insulin determir

Q.4 Which of the following Drugs are not used in treatment of diabetes with CRF?

a) Metformin

b) Insulin

c) Captopril

d) Glibenclamide

e) Meglitinide