Langvinnir fylgikvillar sykursýki: Flokkun Augu Nýru Fætur Áhættuþættir CVD Stóræðasjúkdómar IHD PVD Ischaemic stroke Smáæðasjúkdómar Retinopathy Neuropathy Nephropathy 1

Langvinnir fylgikvillar sykursýki: Tíðni augnskemmda any DR proliferative 2

Langvinnir fylgikvillar sykursýki: Meinmyndun Erfðir Endurteknar bráðar breytingar á efnaskiptum frumna Hyperglycaemia Vefjaskemmd Kúmúlatívar langtíma breytingar á makrómólikúlum Sjálfstæðir hraðandi þættir (BÞ, blóðfita...) 3

Langvinnir fylgikvillar sykursýki: Retinopathy Background Microaneurysms Hard exudates Haemorrhages IRMA Soft exudates (cotton wool spots) Proliferative Neovascularisation Haemorrhage Retinal detachment Macular oedema 4

Langvinnir fylgikvillar sykursýki: Nephropathy Eðlilegt albumin:kreatinin hlutfall í morgunþvagi < 3,5 mg/mmol Míkróalbúminúría albumin:kreatinin 3,5 - 25 mg/mmol Nýrnabilun Dauði Albúmínúría albumin:kreatinin > 25 mg/mmol MAU AU ESRD 5

Langvinnir fylgikvillar sykursýki: Neuropathy Vaxandi óafturkræf taugatruflun Symmetrísk peripheral sensorimotor Autonomic Bráð afturkræf taugatruflun Diabetic amyotrophy Mononeuritis Taugatruflun vegna þrýstings Carpal tunnel ulnar lateral popliteal Taugatruflun tengd meðferð Insulin neuritis 6

Langvinnir fylgikvillar sykursýki: Er hægt að koma í veg fyrir einhverja eða alla með góðri blóðsykurstjórn ? Tegund 1 Sykursýki Diabetes Control and Complications Trial (DCCT) NEJM 1993; 329:977 Tegund 2 Sykursýki United Kingdom Prospective Diabetes Study (UKPDS) Aðalniðurstöður Lancet og BMJ 12. september 1998 7

Langvinnir fylgikvillar sykursýki: DCCT Karlar og konur 13 - 39 ára n = 1441 Primary og secondary prevention tegund 1 DM Samanburður Usual care HbA1c 9,2% BS 12,8 ± 3,1 mmol/l Intensive care HbA1c 7,2% BS 8,6 ± 1,7 mmol/l 8

Langvinnir fylgikvillar sykursýki: DCCT 9

Langvinnir fylgikvillar sykursýki: DCCT 10

Langvinnir fylgikvillar sykursýki: Hvað er UKPDS ? Hönnuð uppúr 1970. 23 UK sjúkrahús Nýgreind Type 2 Diabetes Mellitus fastandi plasma glúkósa > 6,0 í tvígang ekki ketosis n = 5102. karlar og konur 25 - 65 ára. FU 10ár Útilokanir MI, s-kreatinin >175, angina, CHF, retinopathy, illkynja háþrýstingur ofl 11

Langvinnir fylgikvillar sykursýki: UKPDS markmið Leiðir góð blóðsykurstjórn af sér færri micro- eða macrovascular fylgikvilla í gerð 2 af sykursýki ? Er meðhöndlun blóðþrýstings gagnleg ? Er einhver ein lyfja-meðferð betri eða verri en önnur ? 12

Langvinnir fylgikvillar sykursýki: UKPDS slembiröðun 5102 newly diagnosed Type 2 diabetic patients Diet Alone 3% fpg < 6 asymptomatic 17% Main Randomisation 82% fpg 6.1 - 15.0 68% Diet Failure 15% fpg > 15 or symptomatic Diet therapy 14% 13

Langvinnir fylgikvillar sykursýki: UKPDS slembiröðun Main Randomisation n=4209 (82%) 3867 342 allocated to metformin Conventional Policy 30% (n=1138) attained HbA1c 7,9% Intensive Policy 70% (n=2729) attained HbA1c 7,0% Sulphonylurea n=1573 Insulin n=1156 14

Langvinnir fylgikvillar sykursýki: UKPDS sykurstjórn The intensive glucose control policy maintained a lower HbA1c by 0.9 % over a median follow up of 10 years from diagnosis of type 2 diabetes with reduction in risk of: 12% for any diabetes related endpoint p = 0.029 25% for microvascular endpoints p = 0.0099 16% for myocardial infarction p = 0.052 24% for cataract extraction p = 0.046 21% for retinopathy at twelee years p = 0.015 33% for albuminuria at twelve years p = 0.000054 15

Langvinnir fylgikvillar sykursýki: UKPDS metformin overweight patients RR (95% CI) M v Int RR p A n y d i abete s r ela t ed end oint Metf o rm Inte ve = 0.0034 0.6 8 0.9 3 0.0 23 0.4 6 D a bete deat h 0.11 0.5 0.8 1 7 0.1 9 l c au e mo ta it y 0.021 4 2 oca d al nfa ct on 0.12 0.7 favours metformin or intensive favours conventional 16

Langvinnir fylgikvillar sykursýki: UKPDS blóðþrýstingur 1148 hypertensive patients on antihypertensive not on antihypertensive therapy n = 727 therapy n = 421 randomisation less tight blood tight blood pressure control pressure control aim : BP < 180/105 mmHg aim : BP < 150 / 85 mmHg avoid ACE inhibitor : Beta blocker ACE inhibitor Beta blocker n = 390 n = 400 n = 358 34% 35% 31% 17

Langvinnir fylgikvillar sykursýki: UKPDS blóðþrýstingur in 1148 Type 2 diabetic patients a tight blood pressure control policy which achieved blood pressure of 144 / 82 mmHg gave reduced risk for any diabetes-related endpoint 24% p=0.0046 diabetes-related deaths 32% p=0.019 stroke 44% p=0.013 microvascular disease 37% p=0.0092 heart failure 56% p=0.0043 retinopathy progression 34% p=0.0038 deterioration of vision 47% p=0.0036 18

Langvinnir fylgikvillar sykursýki: UKPDS Niðurstaða intensive management of blood pressure and blood glucose, using existing therapies, markedly reduces the risk of diabetic complications aim for blood pressure 140/80 mm Hg or less and any therapies can be used (e.g. beta blocker, ACE inhibitor, low dose thiazide or loop diuretic) reduce HbA1c to 7.0% or less and any therapies can be used (e.g. metformin, sulphonylurea, insulin, acarbose) 19