DIABETUL ZAHARAT TIP2 O chemare la actiune Dr Mirela Culman Institutul national de Diabet,Nutritie si Boli metabolice,,Nicolae Paulescu

Bolile cardiovasculare cauz major de deces deces (%)Geiss LS et al. Diabetes in America.2nd ed.Bethesda, MD:NIH;1995

Years of follow-upCumulative hazard (%)Relative risk 3.55 (1.96, 6.43)DMSNo DMSCHD deathsCardiovascular deathsMortalitate cardiovascular crescut la pacienii cu Sindrom metabolicLakka HM et al. JAMA 2002;288:2709-16

Conglomerat de factori de risc pentru boala cardio vascularObezitatea abdominalStatusul protromboticproinflamatorMicroalbuminuria

Riscul de boal cardiovascular se multiplic n funcie de factorii de risc asociai DIABET X 1,8 HIPERTENSIUNE TAS 15o mmHg X 1,5DISLIPIDEMIEColesterol 260 mg/dl X 2,3X 6,2X 3,8 X 2,6 X 4 KannelWB.Importanceof hypertensionas amajor risk factorin cardiovascular disease ,in Hypertension:Physiopathology and treatament. New York NY:MacGraw-Hill BookCo;1977:888-910Risc bazal 15/1000 (1,5%) n 8 ani

Sindromul metabolic - Quartetul ucigaWHOaInsulin resistance &/or FPGPlus 2 or more of:Blood pressureTG, HDL-CMicroalbuminuria Central obesity

EGIRbInsulin resistance (hyperinsulinaemia)Plus 2 or more of:Blood pressureTG, HDL-Cd

Central obesity

NCEPcFPG Plus 2 or more of:Blood pressureTG HDL-CCentral obesity

aWorld Health Organisation; bEuropean Group for the study of Insulin resistance; cNational Cholesterol Education Program; dand/or treatment for dyslipidaemiaEschwege E. Diabetes Metab 2003;29:6S19-27

Prevalena sindromului metabolic n EuropaBalkau B et al. Diabetes Metab 2002;28:364-76 Eschwege E. Diabetes Metab 2003;29:6S19-27

Prevalena sindromului metabolic n USA National Cholesterol Education Program definitionWorld Health Organisation definitionFord ES, Giles WH. Diabetes Care 2003;26:575-81 Eschwege E. Diabetes Metab 2003;29:6S19-27

Cel mai tipic exemplu de sindrom metabolic Diabetul tip 2La fiecare 21 secunde apare un caz nou de diabet !

72% Epidemie global de diabetNumber of people with diabetes world wide (millions)YearInternational Diabetes Federation

Risc de 3 ori mai mare De infarct de miocardRisc de 25 ori mai mare demoarte de cauz crdiovascularDiabetul determin risc crescut pentru evenimente cardiovasculare 1Haffner SM et al. NEJM 1998;339:229-34; 2Stamler J et al. Diabetes Care 1993;16:434-44Incidence (%)CV deaths/100,000 person-years (age adjusted)No diabetesDiabetesNumber of cardiovascular risk factorsRR: relative risk040801200123RR 5.1RR 4.8RR 4.1RR 2.6

10080604002468% SurvivingHaffner SM et al. NEJM 1998;339:229-34Years of follow-upPacientul cu DZ 2 are prognostic asemntor cu cel nediabetic care a suferit un IM

Toate atingerile de organ date de diabet sunt de natur angiopat Micro/MacroLa fiecare 12 minuteLa fiecare 90 minuteLa fiecare 19 minute La fiecare 90 minuteLa fiecare 19 minuteLiebl A. et al. Dtsch. Med. Wochenschr. 126,585,2001

n Statele Uniten fiecare 24 de ore

Peste 65 orbesc656 dezvolt insuficen renal i ncep dializa renalPeste 500 mor datorit complicaiilor2200 persoane sunt diagnosticate cu diabet153 sufer o amputaie de m inferior

Prevalena complicaiilor dibetuluiData from a UK primary care audit (10,709 diabetic patients)% PatientsCHD: coronary heart disease CVD: cerebrovascular diseaseMorgan CL. Diabet Med 2000;17:146-51

Raportul dintre costul global i costul complicaiilorMean cost/patient (1000)Non - overweight patientsOverweight patientsUKPDS 41. BMJ 2000;329:1375-8; UKPDS 51. Diabetologia 2000;44:298-304Mean cost/patient (1000)

Years before diagnosisYears after diagnosisTotal treatment cost (US $ x 1000)Costs before diagnosisCosts after diagnosisCosturile diabetului nainte i dup diagnosticBrown JB et al. Diabetes Care 1999;22:1116-24; Nichols GA et al. Diabetes Care 2000;23:1654-9

Age atdiagnosis

20 - 2930 - 3940 - 4950 - 5960 - 6970 +Marks & Krall1971

12 1410 118 96 74 5Goodkin1975

16111065Panzram &Zabel-Langhennig1981

7 85 63 43Panzram G. Diabetologia 1987;30:123-31Diabetul tip 2 reduce sperana de viaYears of life expectancy lost according to age at diagnosis of diabetes

Dysmetabolic syndrome presentDysmetabolic syndrome absentFr diabetDiabet tip2Prevalence (%)Prevalence (%)RR 1.7 p=0.04RR 1.2 p=0.62RR 1.3 p=0.59RR 2.2 p

CHD deaths/ 1000 patient-yearsSerum cholesterol (mmol/L)SBP (mmHg)BMI (kg/m2)DyslipidaemiaHypertensionObesityAdlerberth AM et al. Diabetes Care 1998;21:539-45; Eschwege E. Diabetes Metab 2003;29:6S19-27Componentele sindromului metabolic amplific riscul cardiovascular la diabetici

Complicaiile cronice ale diabetului apar mai frecvent la pacienii care asociaz sindrom metabolic% patients with complicationsPVD: peripheral vascular disease CAD: coronary artery disease DSN: Distal sensory neuropathyCosta LA et al. Diabet Med 2004;21:252-5

Riscul de complicaii cronice crete proporional cu severitatea sindromului metabolicNo. of risk factors:% with each risk factorCosta LA et al. Diabet Med 2004;21:252-5PVD: peripheral vascular disease CAD: coronary artery disease DSN: Distal sensory neuropathy

Managementul intensiv si multifacorial Control glicemic bunRezistena la insulin, obezitate, hiperinsulinemia, hipertensiune, dislipidemia, ateroscleroz, status procoagulant, proinflamatorSindromul metaboloicComplicaii microvasculare imacrovasculareTratament

* Metformin cardiovascular reference lecture materials (slide * of the complete set)* Metformin cardiovascular reference lecture materials (slide * of the complete set)The dysmetabolic syndrome is associated with increased cardiovascular mortalityThese data are from the Kuopio Ischaemic Heart Disease Risk Factor Study, a population-based, prospective, observational study from Finland. A cohort of 1209 middle-aged men (aged 4260 years) with or without the dysmetabolic syndrome (US or World Health Organisation definitions), but without cardiovascular disease or diabetes at baseline, were followed for an average of 11.6 years. The presence of the dysmetabolic syndrome was associated with a more than 3-fold increase in the unadjusted risk of cardiovascular death. The corresponding unadjusted relative risk for all-cause death (not shown on the slide for clarity) was 2.43 (1.643.61).After adjustment for age and cardiovascular risk factors, subjects with the most pronounced features of the metabolic syndrome (upper quartile of a score for dysmetabolic syndrome derived from the statistical analysis) had relative risks of death of 3.61 (1.657.90) for coronary heart disease, 3.18 (1.735.81) for cardiovascular disease, and 2.25 (1.513.35) for death from any cause.

Lakka HM, Laaksonen DE, Lakka TA, Niskanen LK, Kumpusalo E, Tuomilehto J, Salonen JT. The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men. JAMA 2002;288:2709-16.

* Metformin cardiovascular reference lecture materials (slide * of the complete set)The dysmetabolic syndromeAlmost all type 2 diabetic patients are insulin resistant, and there is much evidence to consider loss of insulin sensitivity as the root cause of cardiovascular complications. Insulin resistance tends to cluster with other cardiovascular risk factors, including hyperglycaemia, hypertension, dyslipidaemia, obesity, nephropathy and a pro-coagulant haemostatic state. Together, these risk factors make up the dysmetabolic syndrome, also referred to as the insulin resistance syndrome, or metabolic syndrome X.There are currently three clinical definitions of the dysmetabolic syndrome, produced by the World Health Organisation, a modified version of this definition produced by the European Group for the study of Insulin resistance, and a further definition proposed by the US National Cholesterol Education Program.While there are differences in detail between the definitions, broad themes emerge. For example, all recognise insulin resistance and/or hyperglycaemia, hypertension, dyslipidaemia and abdominal obesity as important facets of the syndrome. Importantly, the definitions relate to a particular presentation of dyslipidaemia commonly encountered in type 2 diabetic subjects, characterised by elevated triglycerides and low HDL-cholesterol. The next slides will explore the prognostic importance of this diabetic dyslipidaemia.

Eschwege E. The dysmetabolic syndrome, insulin resistance and increased cardiovascular (CV) morbidity and mortality in type 2 diabetes: aetiological factors in the development of CV complications. Diabetes Metab 2003;29:6S19-27.* Metformin cardiovascular reference lecture materials (slide * of the complete set)Prevalence of the dysmetabolic syndrome in EuropeThe World Health Organisation definition provides somewhat higher estimates of prevalence, compared with the European Group for the Study of Insulin Resistance definition, in European subjects. Nevertheless, the prevalence of the dysmetabolic syndrome increases steeply with increasing age in both men and women. Overall, about a quarter of the population above the age of 55 years may have the dysmetabolic syndrome. This has important implications for public health, given the strong association between the dysmetabolic syndrome and adverse cardiovascular outcomes, which is discussed later in this presentation.

Balkau B, Charles MA, Drivsholm T, et al. Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome. Diabetes Metab 2002;28:364-76. Eschwege E. The dysmetabolic syndrome, insulin resistance and increased cardiovascular (CV) morbidity and mortality in type 2 diabetes: aetiological factors in the development of CV complications. Diabetes Metab 2003;29:6S19-27.

* Metformin cardiovascular reference lecture materials (slide * of the complete set)Prevalence of the dysmetabolic syndrome in the USAThis slide compares the prevalence of the dysmetabolic syndrome according the US definition, with that of the World Health Organisation. The age-adjusted prevalence of dysmetabolic syndrome among the 20,050 people studied within the third National Health and Nutrition Examination Survey (NHANES III) according to the National Cholesterol Education Program (24%) was almost identical to that according to the World Health Organisation definition (25%). However, the prevalence of the dysmetabolic syndrome appears to be especially high in Mexican-Americans and in African-American women.

Ford ES, Giles WH. A comparison of the prevalence of the metabolic syndrome using two proposed definitions. Diabetes Care 2003;26:575-81. Eschwege E. The dysmetabolic syndrome, insulin resistance and increased cardiovascular (CV) morbidity and mortality in type 2 diabetes: aetiological factors in the development of CV complications. Diabetes Metab 2003;29:6S19-27.

* Metformin cardiovascular reference lecture materials (slide * of the complete set)Global diabetes epidemicWe face a global epidemic of type 2 diabetes in the coming decades. The latest data from the International Diabetes Federation (IDF) were presented at the 18th Meeting of the IDF, held in Paris, France, 2429 August 2003, by Sir George Alberti.The number of people world wide who have diabetes will increase from 194 million to 333 million by 2025. Ninety percent of cases of diabetes will be the type 2 form of the disease, with an even higher percentage in developing countries.

International Diabetes Federation. http://www.idf.org * Metformin cardiovascular reference lecture materials (slide * of the complete set)High risk of adverse cardiovascular outcomes in diabetesMost type 2 diabetic patients will ultimately die from a cardiovascular cause.In the left-hand panel, the 7-year incidence of myocardial infarction among 1373 non-diabetic subjects was compared with the corresponding incidence among 1059 diabetic subjects in a population-based study conducted in Finland. The risk of myocardial infarction was about 3-fold higher in the diabetic population.The right-hand panel shows age-adjusted death rates among 347,978 men screened for the Multiple Risk Factor Intervention Trial (MRFIT, followed up for 12 years). Subjects were stratified for the presence of a number of cardiovascular risk factors: Serum cholesterol >200 mg/dL (5 mmol/L) Systolic blood pressure >120 mmHg SmokingThe risk of cardiovascular death increased more steeply with increasing numbers of risk factors in the diabetic group, compared with the non-diabetic group. Thus, the diabetic individuals with cardiovascular risk factors were at markedly greater cardiovascular risk then their non-diabetic counterparts with the same risk factors. These data underline the urgent clinical need to protect the cardiovascular system in type 2 diabetes.

1. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339: 229-34. 2. Stamler J, Vaccaro O, Neaton JD, Wentworth D. Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care 1993;16:434-44. * Metformin cardiovascular reference lecture materials (slide * of the complete set)Type 2 diabetes confers the same adverse prognosis as a prior myocardial infarctionData from a population-based study in Finland, involving 1373 type 2 diabetic patients and 1059 non-diabetic control subjects were used to establish the influence of type 2 diabetes on prognosis. The follow-up period was 7 years.The mortality rate in non-diabetic subjects without a history of myocardial infarction was lowest, and the mortality rate among diabetic subjects with a previous myocardial infarction was highest, as would be expected. However, these data show that developing diabetes, or having previously had a myocardial infarction, confers the same risk of a subsequent myocardial infarction.

Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med 1998;339:229-34.

* Metformin cardiovascular reference lecture materials (slide * of the complete set)* Metformin cardiovascular reference lecture materials (slide * of the complete set)Type 2 diabetes reduces life expectancyThis slide shows the expected reduction in future life expectancy in adult patients given a diagnosis of diabetes at different ages.A survey of three observational studies in this area shows that a diagnosis of type 2 diabetes is associated with significant loss of life expectancy. Patients diagnosed in middle age (highlighted on the slide) lose a substantial portion f their remaining life expectancy, with a potential loss of 58 years of life consistently found across three studies. There is no doubt that type 2 diabetes causes loss of a significant proportion of patients lives.

Panzram G. Mortality and survival in type 2 (non-insulin-dependent) diabetes. Diabetologia 1987;30:123-31.

* Metformin cardiovascular reference lecture materials (slide * of the complete set)Type 2 diabetes amplifies the adverse effects of the dysmetabolic syndromeThe classic cardiovascular risk factors within the dysmetabolic syndrome exert a greater effect on prognosis in diabetic individuals, compared with their normoglycaemic peers.Data from the Botnia study, shown on this slide, illustrate this point. A total of 4483 subjects, aged 35-70, were surveyed in Finland and Sweden, with the dysmetabolic syndrome identified using definition given by the World Health Organisation. The presence of the dysmetabolic syndrome was associated with an increased prevalence of previous coronary heart disease (CHD), myocardial infarction (MI) and stroke in both diabetic and non-diabetic populations. However, both the absolute prevalence of these conditions, and the increase in relative risk associated with the dysmetabolic syndrome, were higher in the type 2 diabetic population.

Isomaa B, Almgren P, Tuomi T et al. Cardiovascular morbidity and mortality associated with the metabolic syndrome. Diabetes Care 2001;24:683-9. * Metformin cardiovascular reference lecture materials (slide * of the complete set)Individual components of the dysmetabolic syndrome and cardiovascular risk Elevated plasma cholesterol contributes to cardiovascular risk on type 2 diabetic, and non-diabetic subjects. Indeed, the effect of cardiovascular risk factors associated with the dysmetabolic syndrome, including hyperlipidaemia, on clinical outcomes is magnified in type 2 diabetic subjects, compared with non-diabetic subjects.These data are from a population of 6,851 diabetic and 249 non-diabetic middle-aged (5059 years) men in Sweden. Their clinical outcomes were stratified on the basis of their glycaemic status and cardiovascular risk factor profile at baseline.

Adlerberth AM, Rosengren A, Wilhelmsen L. Diabetes and long-term risk of mortality from coronary and other causes in middle-aged Swedish men. Diabetes Care 1998;21:539-45.Eschwege E. The dysmetabolic syndrome, insulin resistance and increased cardiovascular (CV) morbidity and mortality in type 2 diabetes: aetiological factors in the development of CV complications. Diabetes Metab 2003;29:6S19-27.

* Metformin cardiovascular reference lecture materials (slide * of the complete set)Patients with the dysmetabolic syndrome are at increased risk of diabetic complicationsA cross-sectional study in 548 type 2 diabetic patients evaluated the association between the presence of the dysmetabolic syndrome (here defined as the presence of two of hypertension, dyslipidaemia, obesity or microalbuminuria) and the risk of a range of chronic diabetic complications.The presence of cardiovascular risk factors associated with the dysmetabolic syndrome was clearly associated with an increased risk of both macrovascular complications (peripheral vascular disease, coronary artery disease) and microvascular complications (retinopathy, neuropathy and microalbuminuria).

Costa LA, Canani LH, Lisboa HR, Tres GS, Gross JL. Aggregation of features of the metabolic syndrome is associated with increased prevalence of chronic complications in Type 2 diabetes. Diabet Med 2004 Mar;21:252-5.

* Metformin cardiovascular reference lecture materials (slide * of the complete set)The risk of complications increases with the severity of the dysmetabolic syndromeThese data are from the study described in the previous slide. Patients were stratified according to the number of cardiovascular risk factors they had for this analysis, which can be considered to be an index of the severity of the dysmetabolic syndrome.The incidence of microvascular and macrovascular diabetic complications increased in line with the number of cardiovascular risk factors.

Costa LA, Canani LH, Lisboa HR, Tres GS, Gross JL. Aggregation of features of the metabolic syndrome is associated with increased prevalence of chronic complications in Type 2 diabetes. Diabet Med 2004 Mar;21:252-5.