4 BURDEN OF DIABETES : MORBIDITY DIABETIC RETINOPATHY#1 Cause of blindness in working age adultsDIABETIC NEPHROPATHY#1 Cause of ESRDDIABETIC NEUROPATHY AMPUTATIONS#1 Cause of non-traumatic amputations of lowerExtremity.DIABETIC VASCULAR DISEASE2 to 6 fold higher risk of CVD
5 DEFINITIONDiabetes Mellitus is a group of metabolic diseases characterized by Hyperglycemia resulting from defects in Insulin secretion, Insulin action, or both.
7 3.Other specific types: a. Genetic defects of b-cell function b. Genetic defects in insulin actionc. Disease of exocrine pancreasd. Endocrinopathiese. Drug/chemical inducedf. Infectiong. Uncommon immune mediatedh. Other Genetic Syndromes4. GESTATIONAL DIABETES MELLITUS(GDM)
8 IMPAIRED INSULIN SECRETION & ETIOLOGY OF TYPE 2 DMIMPAIRED INSULIN SECRETION &INSULIN RESISTANCEGENES & ENVIRONMENTGENES AND ENVIRONMENTIMPAIRED INSULINSECRETIONIMPAIRED INSULINSECRETION+INSULIN RESISTANCEINSULIN RESISTANCEIMPAIRED GLUCOSETOLERANCEIMPAIRED GLUCOSETOLERANCETYPE 2 DM
16 ORAL ANTI DIABETIC DRUGS Secretogaugesa) Sulphonyluriasb) Non sulphonyluriasBiguanidesAlpha Glucosidase Inhibitors( A G I )ThiozolidinedionesDPP 4 InhibitorsAmylin AnaloguesExenatide
17 SECRETOGOUGES Sulphonyluria Groups First Generation SU 1.Tolbutamide 2.ChlorpropamideSecond Generation SU1.Glibenclamide(Daonil,Euglucon)2.Glipizide(Glynase,Dibizide)3.Gliclazide(Diamicron,Reclide)4.Glimipride(Amaryl,Glipride,Glimer)
18 SECRETOGOGUESCurrently available secretogogues stimulate Insulin secretion by causing closure of ATP dependent Potassium channel in Islet β cells.
19 NON SU SECRETOGOGUESMeglitinidesRepaglinide(Novonorm)
20 INSULIN SENSITIZERSAgents from this group enhances the effect of endogenous Insulin.A reduction in Insulin resistance at each and every stage of diabetes will improve Glucose metabolism.Biguanide(Metformin),Thiozolidinediones(PIO,ROSI)
21 BIGUANIDES METFORMIN(Glyciphage,Glycomet). Primary site of action:Liver.Reduces hepatic glucose output.Reduce fasting hyperglycemia.
22 THIOZOLIDINEDIONES Troglitazone Rosiglitazone(Rezult,Enselin) Pioglitazone(Pioz,Pioglit)Primary site of action : AdiposeCells, Skeletal muscles.
26 INSULIN First hormone to be Discovered Introduced in clinical practice Structurally characterizedSynthesized – chemicallyBiosynthesized – by rDNA technology
27 Insulin – Definitive Therapy for Diabetes In diabetes there is impaired insulin secretion and impaired insulin actionExogenously administered Insulin can overcome both defectsThus insulin is the definitive therapy for all types of diabetes
28 INSULIN ABSOLUTE INDICATIONS Regular UseType 1 Diabetes PatientsType 2 Diabetes Patients with OHA failure- Primary- SecondaryIntermittent UseType 2 diabetes patients during- major surgery- pregnancy, labour and delivery- myocardial infarction- acute infections- acute metabolic crisis like hyperosmolar nonketotic coma and lactic acidosisGestational diabetesmellitus
29 Type 1 DM Insulin Therapy Initiating insulin therapy in uncomplicated ambulatory Type 1 patientsInitiating insulin therapy in ill patients with altered sensorium
30 Type 1 DM Insulin Therapy : Initiation In uncomplicated ambulatory Type 1 patientsPatients should preferably be admitted to hospitalInitiate with short-acting insulin [0.5 IU/Kg body weight per day] divided over 3 doses/day given pre-meal; subcutaneously
31 Type 1 DM Insulin Therapy : Initiation If hospital admission is not possible, close continuous monitoring of the patient is necessaryAfter adequate control is obtained with the above treatment a minimum of twice daily regimen with a short and intermediate-acting insulin may be given as per individual patient requirement
32 ACTION PROFILE OF INSULIN TypeOnsetPeakDurationRapid-Acting Analogues (Aspart, Lyspro)min1-1.5 h4-5 h
45 INSULIN REGIMENS – Type 1 Diabetes Insulin secretion totally absentInsulin administration tailored to match demand(food intake)Need for multiple injectionsPopular Regimens* Basal Bolus: Ideal but difficult to implement* Split mix therapy: Popular regimen; Patients find mixing insulins difficultPremixed Insulins: Most popular regimen world- wide and in IndiaRight mix of compliance and controlInsulin requiredi.u/kg body weight/day- Regimen depends on blood glucose profiles
46 BASAL BOLUS THERAPY At least four injections/day Intermediate injection at bedtimesoluble insulin before breakfast, lunch and dinnerRegular blood monitoring mustRequires highly motivated patient
48 SPLIT MIX REGIMENS Two injections (intermediate + soluble) per day before breakfast and before bedtimeProportion/dosage of insulin titrated based on blood glucose profileMixing insulin is tedious and problematic
51 A. COMPLIANCE Defective insulin regimen Incorrect technique of mixing and measuringInconsistent eating and exercise habitsOmission of insulin during inter current illnessLack of awareness about diabetes at the beginning and during the course of illnessEmotional and psychological disturbance
52 B. CHANGE IN INSULIN REQUIREMENTS InactivityWeight gain / LossPregnancy and Post delivery phaseChange in the exercise patternChange in the food habitsStress period
53 PREMIXED REGIMENS – Human Mixtard Very Popular regimenMost popular World-wide & in IndiaRight balance of convenience and controlImproves compliancePopular schedule is2/3rd daily dose half an hour before breakfast1/3rd daily dose half an hour before dinner
54 Insulin Therapy for Type 2 DM Basal Insulin Supplementation: Bedtime NPHSuppresses basal hepatic productionReduces fasting plasma glucoseGenerally used in combination with OHAHelps initiate the patient on insulin therapy with Insulatard NovoLet
56 Guidelines for Initiating Insulin Alone or in combination with an OHA0.2 units/kg body wt./day of intermediate acting insulin e.g. Insulatard NovoLetIncrease dose by 2-4 u every 3-4 days if necessary. If requirement exceeds u, split the dose into two daily : 2/3 before breakfast, 1/3 before dinnerIf postprandial glucose levels are high introduce short acting insulin in 30:70 or 50:50 ratio
57 Early Insulin Initiation Is therefore beneficial in:Providing better control of hyperglycemiaReversing other metabolic defectsControlling inflammation which may initiate and aggravate development and progression of diabetes and diabetes-induced tissue damagePreserving beta cell function and thus helping maintain better glycemic control in the long-termShould be done when it can be useful to the patient
59 Injection Site The absorption varies with change of area Rotation of site within the same areaShort Acting - ABDOMEN - If rapid action desiredSuspensions - THIGH - for longer actionRandom rotation of the site should be avoided
60 Rotation of Site in a given area Blood flowTemperatureHeavy massage in the injected area
61 ExerciseExercise following insulin injection increases the amount of insulin absorbed as well as the rate at which it is absorbedExercise increases the peripheral glucose utilisation by increasing the insulin sensitivity
62 Depth of injection IM Vs SC inj Absorbed faster with IM injectionsIM injections are not recommended for routine useUseful only in patients with subcutaneous insulin degradation or resistanceIM injections are more painfulSC is therefore idealSoluble [ Human Actrapid ] can be given IV during surgery and diabetic emergencies
63 Source of insulin Human Insulin is absorbed quicker Bovine Insulin is the slowestPorcine is absorbed little slower than HumanAuxiliary SubstancesPreservative - phenol, metacresolRetarding Agent – protamine, zincWater as solvent
64 Insulin AntibodiesCirculating antibodies and exogenous insulin bind to form insulin antibody complexThe antibody bound insulin may produce a delayed effect at an unexpected timeResulting from Reduced absorption , Delayed clearance