De presentatie wordt gedownload. Even geduld aub

De presentatie wordt gedownload. Even geduld aub

Diabetes type 2 Kortrijk, 6 september 2004. Adapted from Zimmet P et al. Diabet Med. 2003;20:693-702. 25.0 39.7 59% 25.0 39.7 59% 10.4 19.7 88% 10.4 19.7.

Verwante presentaties


Presentatie over: "Diabetes type 2 Kortrijk, 6 september 2004. Adapted from Zimmet P et al. Diabet Med. 2003;20:693-702. 25.0 39.7 59% 25.0 39.7 59% 10.4 19.7 88% 10.4 19.7."— Transcript van de presentatie:

1 Diabetes type 2 Kortrijk, 6 september 2004

2 Adapted from Zimmet P et al. Diabet Med. 2003;20: % % % % % % % % % % % % % % 189 million people in million projected for % increase Diabetes: A Growing Global Crisis

3 Diabetes : pandemie Wereldwijd : patienten meer dan 50% in India, China en VS Europa : patienten Belgie : type 1 : type 2 : gediagnosticeerd geschat. Men verwacht tegen miljoen type 2 patienten In Belgie tegen 2010 bijna type 2 patienten

4 Estimated Lifetime Risk of Developing Diabetes in the United States for Those Born in 2000 Men: 33% Women: 39% Hispanics are at greatest lifetime risk –Men: 45% –Women: 53% When diagnosed at age 40 years: –Men lose 12 life-years and 19 quality-adjusted life-years –Women lose 14 life-years and 22 quality-adjusted life-years Narayan KMV et al. JAMA. 2003;290:

5

6 Diabetes Mellitus in the US: Health Impact of the Disease Diabetes Blindness* Renal failure* Amputation* Life expectancy 5 to 10 yr Cardiovascular disease ­ 2X to 4X *Diabetes is the no. 1 cause of renal failure, new cases of blindness, and nontraumatic amputations Nerve damage in 60% to 70% of patients 6th leading cause of death  Diabetes Statistics. October 1995 (updated 1997). NIDDK publication NIH Harris MI. In: Diabetes in America. 2nd ed. 1995:1-13.

7 Impact of Type 2 Diabetes Lifestyle implications Lifestyle implications –heart disease, kidney failure, blindness and foot ulceration Increased risk of mortality Increased risk of mortality –risk of death more than doubled Heavy burden on healthcare resources Heavy burden on healthcare resources –approximately 8% of total healthcare budgets in the developed world Balkau, 1999; WHO, 1998

8 What about Belgium ? Bron IMS Health CODE 2 in BIGE N°28 maart Euro per patiënt / jaar 3000 Euro per patiënt / jaar totaal : 1 miljard Euro per jaar totaal : 1 miljard Euro per jaar = 6,7% van het totale gezondheidsbudget = 6,7% van het totale gezondheidsbudget

9 Most of the costs of diabetes are related to hospitalization Oral anti-diabetic drugs 2–7% Hospitalizations 55% Other drugs 20–25% Ambulatory 18%

10 Kostprijs ( The Economic Impact of the Diabetic Foot, Van Acker K ) Socio-economische impact

11 Increased HbA 1c and SBP Are Associated With Increased Morbidity and Mortality SBP=systolic blood pressure; PY=person-year. 1.Stratton IM et al. BMJ. 2000;321: Adler AI et al. BMJ. 2000;321: SBP Microvascular end points 1,2 Myocardial infarction 1,2 HbA 1c (%) SBP (mm Hg) Incidence (per 1000 PY) HbA 1c (%) SBP (mm Hg) HbA 1c SBP HbA 1c

12 EVERY 1% reduction in HBA 1C REDUCED RISK* 1% Deaths from diabetes Heart attacks Microvascular complications Peripheral vascular disorders UKPDS 35. BMJ 2000; 321: Lessons from UKPDS: Better control means fewer complications -37% -43% *p< % -21%

13 ADA criteria voor diagnose diabetes mellitus (1997)

14 Casus 1 Man, 45 jaar, roker VG : appendectomie, AHT R/Amlor 5 mg Familiale voorgeschiedenis : moeder : DM2 vader: overleden na AMI Klinisch onderzoek : BMI : 32 Bloeddruk : 145/85 Abd omtrek : 105 cm Nu jaarlijks routine labo Wat doen ???? Therapeutische richtlijnen

15 Casus 1 Labo : Glucose N 120 mg/dl HbA1c : 6.2 ¨% chol : 220 mg/dl TG: 250 mg/dl LDL chol : 145 mg/dl HDL chol : 42 mg/dl Insuline : 24 mU/L

16 Casus 1 Labo : Glucose N 120 mg/dl HbA1c : 6.2 ¨% chol : 220 mg/dl TG: 250 mg/dl LDL chol : 145 mg/dl HDL chol : 42 mg/dl Insuline : 24 mU/L Diagnose IFG Metabool syndroom abd. Omtrek Ins. Resistentie Dyslipidemia AHT M.O. familiaal +

17 Casus 1 Therapie : 1. Risicofactoren : 1. Risicofactoren :rokengewicht beweging 3 X30’ BD familie ?

18 Casus 1 Therapie : 1. Risicofactoren : 1. Risicofactoren :rokengewicht beweging 3 X30’ BD familie ? Andere vragen ? Diabetes dieet ? Statine ? Aspirine ? Metformine ? Glucometer ? CONTINUUM RISICOFACTOREN

19 Diabetes Slechts de top van een grote ijsberg HOGE GLYCEMIE ?

20 Insulin resistance  -cell dysfunction Type 2 diabetes Adapted from: Beck-Nielson H et al. J Clin Invest 1994;94:1714–1721 and Saltiel AR, Olefsky JM. Diabetes 1996;45:1661–1669 What is Type 2 diabetes? A progressive metabolic disorder characterised by:

21 Insulin Resistance and the development of Type 2 diabetes IGTOvert diabetes Insulin resistance Glucose Insulin production Evolution Time

22 The Insulin Resistance Syndrome Type 2 diabetes or impaired glucose tolerance Type 2 diabetes or impaired glucose tolerance Obesity Obesity Dyslipidaemia Dyslipidaemia  Blood pressure  Blood pressure Insulin resistance Insulin resistance Hyperinsulinaemia (initially) Hyperinsulinaemia (initially) Atherosclerosis Atherosclerosis DeFronzo, Ferrannini. Diabetes Care 1991; 14 (3):

23 Conditions Associated With Insulin Resistance Adapted from DeFronzo. Diabetes Care 1991; 14(3): INSULIN RESISTANCE Atherosclerosis Central obesity Dyslipidemia Hypertension Type 2 diabetes Impaired fibrinolysis Hyperinsulinemia Microalbuminuria

24 NCEP: Clinical Identification of the Metabolic Syndrome* Risk FactorDefining Level Abdominal obesityWaist circumference Men>102 cm (>40 in) Men>102 cm (>40 in) Women>88 cm (>35 in) Women>88 cm (>35 in) TG  150 mg/dL HDL-C Men<40 mg/dL Men<40 mg/dL Women<50 mg/dL Women<50 mg/dL BP  130/  85 mm Hg Fasting glucose  110 mg/dL Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285: *The metabolic syndrome comprises  3 risk factors.

25 Dr. DeFronzo (Berlin 2004) Other definition 1. Fasting plasma insulin > of = 21 or BMI > of = 28.9 kg/m² 2. Fasting plasma insulin > of = Fasting plasma insulin > of = 16 and BMI > 27.5

26 Prevalence of Complications at Time of Diagnosis Complication Any complication Retinopathy Abnormal ECG Absent foot pulses (  2) and/or ischemic feet Impaired reflexes and/or decreased vibration sense Myocardial infarction/angina/claudication Stroke/transient ischemic attack Prevalence (%)* ~2-3 ~1 *Some patients had more than 1 complication at diagnosis Adapted from UKPDS VIII. Diabetologia 1991; 34: United Kingdom Prospective Diabetes Study (UKPDS)

27 Strategie 1.Preventie van diabetes type 2 2.Vroege argwaan en vroege behandeling (ICEBERG theorie) 3.Belang van totale behandeling van de patient dwz. Alle risicofactoren : 1+1 = 2 4.Rationele behandeling 5.Op die manier verbetering van cardiovasculaire prognose en microvasculaire complicaties

28 ‘ Double jeopardy’: type 2 diabetes and hypertension and cardiovascular risk Diabetes No diabetes CVD death rate (per 10,000 person-year) Systolic blood pressure (mmHg) < –139140–159160–179180–199  200

29 Goals HbA1c lager dan 6.5% Bloeddruk lager dan 130/80 mm Hg Lipiden LDL cholesterol onder de 100 mg/dl HDL cholesterol hoger dan 40/50 (vrouwen) mg/dl triglyceriden lager dan 150 mg/dl Aspirine (bij alle patienten ouder dan 40 jaar) BMI < 25 kg/m² ROOKSTOP !!!! LICHAAMSBEWEGING!!!!DIEET!!!!

30

31 Basic Steps in the Management of Type 2 Diabetes ++ diet & exercise oral monotherapy oral combination oral plus insulin insulin +

32 Treatments for Type 2 Diabetes Glucose (G) Carbohydrate Glucose DIGESTIVEENZYMES Insulin (I) I I I I I I I I G G G G G G G G I G G G Acarbose Reduces absorption - Sulphonylurea Repaglinide Stimulates pancreas + Metformin Reduces hepatic glucose output (??muscle/fat effects) - Thiazolidinediones Reduce Insulin Resistance - + -

33 Reducing insulin resistance may be the key to controlling type 2 diabetes and its cardiovascular complications DeFronzo, Ferrannini. Diabetes Care 1991; 14 (3):

34 Oral Anti-diabetic Drugs Differ by Mode of Action and Results GI=gastrointestinal. Adapted from Nathan DM. N Engl J Med. 2002;347: Class Main Actions Typical HbA 1c Reduction, % Insulin secretagogues (sulphonylureas, glitinides) Potentiate insulin secretion Biguanides (metformin) Inhibit hepatic glucose production Thiazolidinediones Enhance insulin action at liver, fat, and muscle  -Glucosidase inhibitors Delay GI absorption of carbohydrates

35 Insulin-augmenting agents Insulin-assisting agents Sulfonylurea Biguanides (Metformin) “Glinides” Alpha-glucosidase inhibitoren Thiazolidinediones Orale antidiabetica

36

37 Biguaniden Docmetformi (°Docpharma) : mg Glucophage (°Merck) : mg Merck-metformine (°Merck) : mg Metformax (°Menarini) : 850 mg deelbaar !! Metformiphar (°Unicophar) Actiemechanisme : verhogen gevoeligheid lever en perifere weefsels verhogen van GLUT 4 transporters inhibitie gluconeogenese verhoging glycogeen synthese

38 Biguaniden Andere effecten : verlagen LDL, TG en FFA Gewichtsverlies Dosis : zo maximaal mogelijk tot max. 3 maal 850 mg Nevenwerking : 1. GI 2. Lactaaintolerantie 3. CI : lever en nierfalen (creat >1.4 bij vr en bij man > 1.5), % is intolerant M.O.- Bij nevenwerkingen terug naar vorige dosis en na 2 weken opnieuw pogen op te drijven - Bij contraststof onderzoek of operatie pas opnieuw starten als 2 dagen normale nierfunctie

39 Thiazolidinediones: wie en wat? Produkten Troglitazone ( Rezulin ) ° Parke Davis (uit de handel genomen omwille van hepatotoxiciteit ) Pioglitazone ( Actos ) ° Eli Lilly mg Rosiglitazone ( Avandia ) °GSK 4-8 mg werken in op de insulineresistentie PLEIOTROOP effect : insuline sensitizer thv lever, vetcel en spier minder circulerend insuline geen hypo’s bewaren van de pancreatische insulinesecretie

40 Thiazolidinediones = PPAR  agonisten (PPAR) = Peroxisome Proliferator Activator Receptoren zijn Nucleaire Receptoren (proteine) DNA Nucleair receptor ppar  Retinoid X receptor PPre PPAR response elements = gene expression A VANDIA Verbetert expressie & translocatie GLUT4 differentiatie van adipocyten opname FFA’s en lipogenese Vermindert productie TNF ⍺ aanmaak leptine productie resistine

41 PPAR  : Primary Downstream Tissue-Specific EffectsFat - Adipocyte differentiation - Glucose uptake by muscle - Expression of TNFα Pancreatic β-Cells - Cell morphology and structure Vascular - VSMC size, type, migration - Endothelial function - Atherogenicity of lipids Muscle - Glucose uptake and utilization Liver - Glucose and VLDL synthesis - Hepatic insulin resistance - Glomerular function and structure Desvergne B, Wahli W. Endocrine Reviews 1999;20(5): Rosen ED, Spiegelman BM. J Biol Chem 2001;276(41): Kelly D. Circ Res 2001;89: Benson S, et al. AJH 2000;13: Guan YF, Breyer MD. Kidney Intl 2001;60: Buchan KW, Hassal DG. PPAR agonists as direct modulators of the vessel wall in cardiovascular disease. Wiley&Sons, 2000, pp Kidneys

42 Nevenwerkingen : Klasse effect 1. Oedeem –dubbel blind tr(mono, comb metf.) bij patienten onder Avandia »4 tot 5 % oedeem »metformine 2,2 %, placebo 1,3 % –dubbel blind bij patienten onder Actos »4,8 % ( mono) vs 1,2 % placebo »comb met Insuline (15,3 % vs 7 % ) –mild oedeem, goed beantwoordend aan diuretica –bij ernstig oedeem stop TZD

43 Nevenwerkingen : Klasse effect 2. Hemoglobine troglitazone : 5 % lager dan normale waarde Rosiglitazone : - 1 g/dl pioglitazone : - 1 g/dl 3. Gewichtstoename door vocht retentie en meer subcut vet hoge dosis : gewichtstoename tot 3 kg/jaar 4. Lipiden

44 Nevenwerkingen : Unieke effecten 1. Hepatotoxiciteit troglitazone : 48 leverfalen : 28 doden en 15 levertransplantatie achteraf gezien bleek dat ook in vitro troglitazone hepatotoxisch was voor levercellen achteraf gezien bleek dat ook in vitro troglitazone hepatotoxisch was voor levercellen conc troglit 15 tot 20 X hoger in lever dan in plasma rosiglitazone 100 X potenter dan Trog en 10 X meer dan pio kort T1/2 ( 4 h ) ( trog : h) accumuleert niet in de lever Advies monitoren ALT na 2 maanden R

45 Nevenwerkingen : Unieke effecten 2. Myalgie pioglitazones (33/606) : 5,4 %-2,7 % placebo 3. Rosiglitazone minder potentie tot drug interactie minder potentie tot drug interactie

46 Insulin augmenting agents : SU Short acting (administration before meals): Diamicron-Glurenorm Long acting (once daily): Amarylle, Uni-Diamicron Reason for choice short/long: compliance of patient When When: failing of insulin secretion- high glucose +++, adding to metformin, intolerance of metformin

47 Characteristics of commonly used sulfonylurea Generic name Brand name Posology Duration of action Excretion (h) (Tolbutamide) Rastinon (Tolazamide)Tolinase (Chlorpropamide)Diabinese mg/d60Renal GlibenclamideDaonil mg/d60Renal Euglucon 5/Bevoren 5 GlipizideGlibenese mg/d< 24Renal 80% Minidiab 5 GliquidoneGlurenorm mg/d7Hepatic 95% GliclazideDiamicron 80 Merck Gliclazide40-160mg/d< 24Renal 70% GlimepirideAmarylle 2/3/41-8mg/d24Renal 60%

48 Long acting SU’s Amarylle (Aventis) glimepiride 1-8 mg/dag werkt 24 uur 60 % renale excretie Uni Diamicron (Servier) 30 mg dagelijks 1 tot 4 co in 1 orale inname duur 12 uur switch 1 tablet 80 mg DM = 1 co UniDiamicron

49 Casus 2 Zelfde man Nu klacht van droge mond Labo : glycemie N : 240 mg/dl hbA1c : 8 % chol : 220 mg/dl LDL : 140 mg/dl HDL chol : 42 mg/dl Trig : 480 mg/dl Insuline : 34 mU/L Wat ?

50 Casus 2 Diagnosediabetes Type ? D/C peptide, GAD as Therapie : Diabetes dieet BewegingGewichtRookstopAspirine TG ? SUR/Met/TZD/ins ? Hoeveel ? Glucometer ? Dagprofielen !!!! Wanneer controle ? Verder : AS ? urine oftalmologie

51 Casus 3 Man 54 jaar Familiale VG : CABG vader DM 2 moeder Med Vg : DM 2 R/ 2 co Diamicron HP : AMI HbA1c 7.8 % Insuline ?

52 Insulinetherapie ????? --.- % is the mean HbA1c of patients with type 2 being started on insulin -- % of patients with type 2 diabetes treated with SU need insulin by 6 years of follow up -- % of patients with type 2 diabetes treated with SU need insulin by 9 years of follow up

53 Insulinetherapie ???? 10.4 % is the mean HbA1c of patients with type 2 being started on insulin -- % of patients with type 2 diabetes treated with SU need insulin by 6 years of follow up -- % of patients with type 2 diabetes treated with SU need insulin by 9 years of follow up

54 Insulinetherapie ????? 10.4 % is the mean HbA1c of patients with type 2 being started on insulin 53 % of patients with type 2 diabetes treated with SU need insulin by 6 years of follow up -- % of patients with type 2 diabetes treated with SU need insulin by 9 years of follow up

55 Insulinetherapie ???? 10.4 % is the mean HbA1c of patients with type 2 being started on insulin 53 % of patients with type 2 diabetes treated with SU need insulin by 6 years of follow up 80 % of patients with type 2 diabetes treated with SU need insulin by 9 years of follow up

56 BARRIERS TO INSULIN THERAPY Reassurance About Theoretical Concerns Insulin therapy in Type 2 DM Improves Insulin Sensitivity by Reducing Glucotoxicity Probably Reduces Cardiovascular Risk Causes Modest Weight Gain Rarely Causes Severe Hypoglycemia

57 Hoe insuline starten ? Verder orale aan dezelfde dosis Start 1 injectie insuline 10 U (bedtime) –NPH (bedtime) –Glargine (bedtime or with evening meal) in case of hypo Titreer de dosis wekelijks op basis van de nuchtere glycemie Increase 8 U if FPG > 180 mg/dL Increase 6 U if FPG Increase 4 U if FPG Treat to target (use FPG <120mg/dl) Verminder de dosis van de orale als hypo’s overdag Easiest way to start insulin

58 Initiating Basal Insulin Therapy: Treat-to-Target Trial Tactics Continue oral agent(s) at same dosage Continue oral agent(s) at same dosage Add single daily insulin dose (10 IU) Add single daily insulin dose (10 IU) –Glargine (morning, with evening meal, or at bedtime)* –NPH (bedtime) † Titrate dose weekly according to fasting SMPG Titrate dose weekly according to fasting SMPG –Increase by 8 IU if FPG >180 mg/dL (>10 mmol/L) –Increase by 6 IU if FPG mg/dL ( mmol/L) –Increase by 4 IU if FPG mg/dL ( mmol/L) –Increase by 2 IU if FPG  120 mg/dL (  6.7 mmol/L) Treat-to-target: usually FPG  100 mg/dL (  5.6 mmol/L), unless hypoglycaemia prevents further titration Treat-to-target: usually FPG  100 mg/dL (  5.6 mmol/L), unless hypoglycaemia prevents further titration Reduce insulin dosage (2-4 IU/d per adjustment) if serious hypoglycaemia occurs Reduce insulin dosage (2-4 IU/d per adjustment) if serious hypoglycaemia occurs *Please see full prescribing information for insulin glargine (rDNA origin) injection. † Please see full prescribing information for NPH human insulin (rDNA origin) isophane suspension. NPH=neutral protamine Hagedorn; SMPG=self-monitored plasma glucose; FPG=fasting plasma glucose. Riddle MC et al. Diabetes Care. 2003;26:

59 En verder ??? Op basis van de streefwaarden : naar 2 of 4 injecties ….. als HbA1c 7 (6.5 %) niet wordt behaald……. Op moment van 2 injecties best stop SUR

60 Heel hoge HbA1c met onmiddellijk complicaties (micro en macrovasculair bij diagnose) : best onmiddellijk insuline (potentieel) Zwangere vrouwen Operaties gepland Patient wil zelf insuline Heel ernstig risicoprofiel Insulinetherapie onmiddellijk superieur in volgende gevallen

61 Insulin glargine 2000 Treatment Milestones in Diabetes Biguanides 1960 Insulin therapy 1922 Sulphonylurea therapy 1950s Insulin pump Late 1970s NPH=neutral protamine Hagedorn; DCCT=Diabetes Control and Complications Trial; UKPDS=United Kingdom Prospective Diabetes Study. Data from Tattersall RB. In: Pickup JC, Williams G, eds. Textbook of Diabetes. 3rd ed. Boston, Mass: Blackwell Science; US FDA Center for Drug Evaluation and Research. Available at: Accessed 18 March Lantus Consumer Information. Available at: Accessed 18 March NPH insulin 1946 Lente insulin therapy 1952 HbA 1c testing 1975 DCCT 1993 Rapid-acting insulin analogues 1996 UKPDS 1998 Blood glucose self-monitoring

62 Insulin excursions in a non-diabetic Insulin (mU/l) Normal free insulin levels (Mean) Meals Adapted from Polonsky et al Time of day DinnerBreakfastLunch

63 Insuline excursies bij vier injecties Insulin (mU/l) Normal free insulin levels (Mean) Meals Adapted from Polonsky et al Time of day DinnerBreakfastLunch

64 Limitations of today’s soluble human insulin Inability of s.c. injected soluble insulin to mimic the physiological pattern of endogenous insulin secretion observed in non-diabetic subjects after meals Delayed onset of action (30-60 min after injection) i.e. should be injected min prior to a meal Prolonged duration of action (6-8 hrs after injection) The higher the dose - the longer the duration of action Absorption and duration of action dependent on injection site

65 Insulin Analogues Human Insulin Dimers and hexamers in solution A-chain B-chain Lys Pro Gly Arg Asp Lispro 2 Limited self-aggregation Monomers in solution Aspart 1 Limited self-aggregation Monomers in solution Glargine 3 Soluble at low pH Forms microprecipitates at neutral (subcutaneous) pH, slow glargine release 1.Novolog [package insert]. Bagsvaerd, Denmark: Novo Nordisk Pharmaceuticals, Inc; Humalog [package insert]. Indianapolis, Ind: Eli Lilly and Company; Lantus [package insert]. Frankfurt, Germany: Aventis Pharma Deutschland GmbH; 2003.

66 Action Profiles of Insulin Analogues Plasma insulin level Regular, 6-8 h NPH, h Ultralente, h Time (h) Glargine, 24 h Aspart, lispro, glulisine, 2-5 h NPH=neutral protamine Hagedorn.

67 NPH insulin shows high within- subject variability Data from study1450 (T. Heise et al. Diabetes 2003; 52 ( Suppl.1) A121) (GIR profiles in 3 patients with type 1 diabetes) Dose at each injection: NPH insulin 0.4U/kg, tigh

68 Current insulin preparations and their pharmacokinetics following s.c. injection Adapted from Burge and Schade Onset of action minutes 5-15 minutes 1-2 hours 1-3 hours 2-4 hours Peak of action 2-4 hours 1-2 hours 5-7 hours 4-8 hours 8-10 hours Duration of action 6-8 hours 4-5 hours hours hours hours Insulin Soluble Lispro/Aspart NPH Lente Ultralente Glargine1-2 hourspeakless>24 hours

69 Structure of insulin detemir

70 Terugbetalingscriteria Lantus TERUGBETALING VOOR 1 JAAR 1. Patient behoort tot groep 1 of 2 van diabetes conventie 2. Patient met type 2 onder combinatie met orale OAD en 1 injectie Insuline EN 1 van de 2 volgende voorwaarden. HbA1c > 7.5 % onder combinatie van OAD en 1 injectie NPH, ULtratard, Humuline Long of Menginsulines. Ernstig hypoglycemie (nood aan hulp van derden) onder combinatie van OAD met 1 maal per dag NPH, Ultratard HM, Humuline long, Menginsulines VERLENGING VOOR 12 MAANDEN 1. conventiepatient groep 1 of injectie Lantus en OAD en HbA1c < 7 % op een test die de laatste 3 maanden is uitgevoerd (Bewijzen)

71


Download ppt "Diabetes type 2 Kortrijk, 6 september 2004. Adapted from Zimmet P et al. Diabet Med. 2003;20:693-702. 25.0 39.7 59% 25.0 39.7 59% 10.4 19.7 88% 10.4 19.7."

Verwante presentaties


Ads door Google