ΠΡΟΔΙΑΒΗΣΗ: ΤΠΑΡΦΕΙ ΑΝΑΓΚΗ ΓΙΑ ΘΕΡΑΠΕΙΑ;

Transcript

1 ΠΡΟΔΙΑΒΗΣΗ: ΤΠΑΡΦΕΙ ΑΝΑΓΚΗ ΓΙΑ ΘΕΡΑΠΕΙΑ; Δρ. Σϊββασ Δ. Ιωϊννου MD, PhD candidate Παθολόγοσ -Διαβητολόγοσ

2 Παράγοντεσ κινδύνου για Δ2 Μη τροποποιόςιμοι Ηλικύα Οικογενειακό ιςτορικό/γενετικό προδιϊθεςη Εθνικότητα Διαβότησ κύηςησ PCOs Σροποποιόςιμοι Παχυςαρκύα Καθιςτικό ζωό Νεογνικό Β, πρόωρα νεογνϊ IFG/IGT Μεταβολικό ςύνδρομο (MetSy) Διαιτητικού παρϊγοντεσ Υϊρμακα Κατϊθλιψη Κοινωνικό περιβϊλλον, εργαςύα Φαμηλό κοινωνικοοικονομικό επύπεδο

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4 Προδιαβήτησ 1.Οριςμόσ 2. Παθοφυςιολογύα 3. Κλινικό ςημαςύα 4. Εξϋλιξη ςε ΣΔ2 5. Screening 6.Θεραπευτικό προςϋγγιςη

5 Οριςμόσ iifg iigt IFG/IGT HbA1c % Metabolic syndrome? AACE, ACE ( mg/dl)

6 iifg Διαταραγμένη γλυκόζη νηςτείασ (1) ϊκχαρο νηςτεύασ (FPG): 100 (110) 125 mg/dl Κύπροσ: 17.3% Άτομα με iifg εμφανύζουν μια μεύωςη περύπου 25% ςτην ευαιςθηςύα τησ ινςουλύνησ. Dagogo-Jack S, Askari H, Tykodi G. Glucoregulatory physiology in subjects with lownormal, high-normal, or impaired fasting glucose. J Clin Endocrinol Metab 2009; 94:

7 Assessment of insulin sensitivity and secretion in subjects with low-nfg, high-nfg, pure IFG, and combined IFG-IGT. Dagogo-Jack S et al. JCEM 2009; 94:

8 iifg Διαταραγμένη γλυκόζη νηςτείασ (2) Με απλό μϋτρηςη του FPG ΔΕΝ διαγιγνώςκεται το 30% περύπου των περιπτώςεων ΣΔ2! DECODE Study Group on behalf of the European Diabetes Epidemiology Study Group. Will new diagnostic criteria for diabetes mellitus change phenotype of patients with diabetes? Reanalysis of European epidemiological data. BMJ 1998; 317: Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1999; 20: WHO/IDF Definition and Diagnosis of Diabetes Mellitus and Intermediate Hyperglycemia: Report of a WHO/IDF consultation.

9 iigt Διαταραγμένη ανοχή γλυκόζησ (1) mg/dl μετϊ 2ωρη καμπύλη ανοχόσ γλυκόζησ (75-g OGTT) % ΠΛΗΘΤΜΟ % ΠΛΗΘΤΜΟ ΠΑΓΚΟΜΙΑ εκατ εκατ. ΕΛΛΑΔΑ ΚΤΠΡΟ

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13 iigt Διαταραγμένη ανοχή γλυκόζησ (2) Συχνότερη ςτισ Πιο ιςχυρό ςυςχϋτιςη με CVD ςυγκριτικϊ με IFG The DECODE Study Group on behalf of the European Diabetes Epidemiology Group. Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001; 161: Unwin N, et al. Impaired glucose tolerance and impaired fasting glycaemia: the current status on definition and intervention. Diabet Med 2002; 19: Η δοκιμαςύα ανοχόσ γλυκόζησ (OGTT) εύναι πιο ευαύςθητη μϋθοδοσ από το FPG για διϊγνωςη του διαβότη.

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15 IFG/IGT Όςοι παρουςιϊζουν ςυνδυαςμό των δύο αυτών καταςτϊςεων ϋχουν πιθανότητα εμφϊνιςησ διαβότη > 20% για κϊθε ϋτοσ. Hanley AJ, et al. Insulin resistance, beta cell dysfunction and visceral adiposity as predictors of incident diabetes: the Insulin Resistance Atherosclerosis Study (IRAS) Family study. Diabetologia 2009; 52: Κατϊ τη διϊρκεια μιασ περιόδου 3 5 ετών το 25% περύπου των ατόμων εμφανύζει ΣΔ, το 25% επανϋρχεται ςε νορμογλυκαιμύα ενώ το 50% παραμϋνει ςτο ςτϊδιο του προδιαβότη. Shaw JE, et al. Impaired fasting glucose or impaired glucose tolerance. What best predicts future diabetes in Mauritius? Diabetes Care 1999; 22: Stern MP, Williams K, Haffner SM. Identification of persons at high risk for type 2 diabetes mellitus: do we need the oral glucose tolerance test? Ann Intern Med 2002; 136:

16 Μεταβολικό ςύνδρομο (1) MEASURE CATEGORICAL CUT POINTS 1. WAIST CIRCUMFERENCE 102 cm ( ), 88 cm ( ) 2. TRIGLYCERIDES (drug treatment is an alternate indicator) 3. HDL-c (drug treatment is an alternate indicator) 4. BLOOD PRESSURE (drug treatment is an alternate indicator) 5. FASTING GLUCOSE (drug treatment is an alternate indicator) 150 mg/dl < 40 mg/dl ( ), < 50 mg/dl ( ) 130 ± 85 mmhg 100 mg/dl

17 Μεταβολικό ςύνδρομο (2) Ιςχυρόσ προδιαθετικόσ παρϊγοντασ για ΣΔ2 και CVD Ford ES, Li C, Sattar N. Metabolic syndrome and incident diabetes: current state of the evidence. Diabetes Care 2008; 31: Εξύςου καλόσ προγνωςτικόσ παρϊγοντασ για εμφϊνιςη ΣΔ2 όπωσ και η iifg (OR: 5.03 vs. 7.07). Αν ςυνυπϊρχουν και οι δύο καταςτϊςεισ ςτον ύδιο αςθενό, ο κύνδυνοσ για εμφϊνιςη ΣΔ2 εύναι πολύ μεγαλύτεροσ (OR: 21.0). Lorenzo C, Williams K, Hunt KJ, Haffner SM. The National Cholesterol Education Program Adult Treatment Panel III, International Diabetes Federation, and World Health Organization definitions of the metabolic syndrome as predictors of incident cardiovascular disease and diabetes. Diabetes Care 2007; 30: 8 13.

18 Grundy SM. Pre-diabetes, metabolic syndrome and cardiovascular risk. J Am Coll Cardiol 2012; 59:

19 Προδιαβήτησ 1. Οριςμόσ 2. Παθοφυςιολογύα 3. Κλινικό ςημαςύα 4. Εξϋλιξη ςε ΣΔ2 5. Screening 6. Θεραπευτικό προςϋγγιςη

20 Παθοφυςιολογία iifg Ηπατικό αντύςταςη ςτην ινςουλύνη. Διαταραχό β-κυττϊρου. Μεύωςη ςτην πρώτη φϊςη ϋκκριςησ τησ ινςουλύνησ (πρώτα 30 min). Abdul-Ghani MA, DeFronzo RA. Pathophysiology of prediabetes. Curr Diab Rep 2009; 9:

21 Παθοφυςιολογία iigt Υυςιολογικό ό ελαφρϊ μειωμϋνη ηπατικό ευαιςθηςύα ςτην ινςουλύνη. Μϋτρια ό ςοβαρό μυώκό ινςουλινοαντύςταςη. Διαταραχό β-κυττϊρου. Διαταραχό τόςο ςτο πρώτο όςο και ςτο δεύτερο ςτϊδιο ϋκκριςησ τησ ινςουλύνησ. Abdul-Ghani MA, DeFronzo RA. Pathophysiology of prediabetes. Curr Diab Rep 2009; 9:

22 PATHOPHYSIOLOGY i-ifg i-igt IFG/IGT MUSCLE Insulin sensitivity LIVER Insulin sensitivity Hepatic glucose production PANCREAS First-phase insulin response or Disposition index Glucagon secretion GUT GLP-1 secretion or or? GIP secretion or? ADIPOSE TISSUE Insulin sensitivity? NEFA release? Adipocytokine release??? BRAIN??? KIDNEY???

23 Προδιαβήτησ 1. Οριςμόσ 2. Παθοφυςιολογύα 3. Κλινικό ςημαςύα 4. Εξϋλιξη ςε ΣΔ2 5. Screening 6. Θεραπευτικό προςϋγγιςη

24 Κλινική ςημαςία (1) Άτομα με iigt εμφανύζουν διπλϊςιο κύνδυνο καρδιαγγειακόσ θνηςιμότητασ ςυγκριτικϊ με μη διαβητικούσ, ενώ ϊτομα με iifg δεν παρουςιϊζουν αυξημϋνο κύνδυνο θνηςιμότητασ. The DECODE Study Group on behalf of the European Diabetes Epidemiology Group. Glucose tolerance and CVD mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001; 161: Tominaga M, Eguchi H, Manaka H, et al. Impaired glucose tolerance is a risk factor for CVD disease, but not impaired fasting glucose. The Funagata Diabetes Study. Diabetes Care 1999; 22: Crandall JP, Shamoon H, Cohen HW, et al. Post-challenge hyperglycemia in older adults is associated with increased CVD risk profile. J Clin Endocrinol Metab 2009; 94: Levitan EB, SongY, Ford ES, Liu S. Is nondiabetic hyperglycemia a risk factor for CVD disease? A meta-analysis of prospective studies. Arch Intern Med 2004; 164:

25 Cumulative survival rate of the Funagata cohort population, classified into NGT, IGT, and diabetic groups according to the WHO criteria (1985). A: Cumulative survival rates from all causes of death, determined by the life-table method, of both the IGT ( ) and the diabetic group ( ) were significantly lower when compared with those of the NGT group ( ) B: Cumulative survival rates from CVD of the IGT and diabetic groups were also significantly lower than that of the NGT group. *P, 0.05.

26 Κλινική ςημαςία (2) 7.9 9% των ατόμων με iigt εμφανύζουν διαβητική αμφιβληςτροειδοπάθεια (ΔΑ) % των ατόμων με ΣΔ2 ϋχουν ΔΑ ςτα αρχικϊ ςτϊδια τησ νόςου. Diabetes Prevention Program Research Group. The prevalence of retinopathy in impaired glucose tolerance and recent-onset diabetes in the Diabetes Prevention Program. Diabet Med 2007; 24: Wong TY, et al. Relation between fasting glucose and retinopathy for diagnosis of diabetes: three population-based cross-sectional studies. Lancet 2008; 371: % αύξηςη ςτον επιπολαςμό τησ ΑΥ ςε ϊτομα με iigt Chiasson JL, et al. Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 2002; 359:

27 Κλινική ςημαςία (3) 25 62% αςθενών με ιδιοπαθό περιφερική νευροπάθεια πϊςχουν από προδιαβότη Σε ϊτομα με προδιαβότη, 11 25% πϊςχουν από περιφερικό νευροπϊθεια ενώ 13 21% εμφανύζουν νευροπαθητικό πόνο. Ηπιότερη νευροπϊθεια με προςβολό μικρών αιςθητικών ινών Papanas N, Vinik AI, Ziegler D. Neuropathy in prediabetes: does the clock start ticking early? Nat Rev Endocrinol 2011; 7: Papanas N, Ziegler D. Prediabetic neuropathy: does it exist? Curr Diab Rep 2012; 12:

28 Εξέλιξη του ΣΔ τύπου 2 Impaired Glucose Tolerance Type 2 Diabetes 30 CV Mortality in IGT and Diabetes Microvascular disease 5 0 NHANES 2, USA Normals IGT undiagn. Diabetes Typ II Macrovascular disease Janka HU. Metabolic syndrome and type 2 diabetes. Relations to macroangiopathy. Fortschr Med 1992; 110:

29 Προδιαβήτησ 1. Οριςμόσ 2. Παθοφυςιολογύα 3. Κλινικό ςημαςύα 4.Εξϋλιξη ςε Δ2 5. Screening 6.Θεραπευτικό προςϋγγιςη

30 ΠΑΡΑΓΟΝΣΕ IFG RR IGT RR Υύλο ( vs. ) Ηλικύα (για κϊθε 5 ϋτη) ΒΜΙ (για κϊθε kg/m2) * 1.02 ΑΤ * Οικογενειακό ιςτορικό Δ HbA1c (για κϊθε 0.5%) Γλυκόζη πλϊςματοσ νηςτεύασ (για κϊθε 10 mg/dl) Γλυκόζη πλϊςματοσ 2 ώρεσ μετϊ ΟGΣΣ * 1.23* 3.19* 1.65* 1.10* 1.26* Rasmussen SS, et al. Determinants of progression from impaired fasting glucose and impaired glucose tolerance to diabetes in a high-risk screened population: 3 year follow-up in the ADDITION study, Denmark. Diabetologia 2008;51:

31 AETIOLOGY iifg iigt IFG/IGT Environmental factors Physical inactivity? Low dietary quantity Smoking or Heritability Family Hx of diabetes TCF7L2? MTNR1B? GCK? GCKR? G6PC2? FTO? PPARG? Sex and anthropometry Male sex Low birthweight? Short adult stature?

32 Annualized relative risk (RR) for progression to diabetes iifg iigt IGT+IFG Gerstein HC, Santaguida P, Raina P, Morrison KM, Balion C, Hunt D, Yazdi H, Booker L. Annual incidence and relative risk of diabetes in people with various categories of dysglycemia: a systematic overview and meta-analysis of prospective studies. Diabetes Res Clin Pract 2007; 78:

33 Annualized relative risk (RR) for progression to diabetes iifg iigt IFG+IGT Santaguida PL, Bailon C, Hunt D, Morrison K, Gerstein H, Raina P, Booker L, Yazdi H. Diagnosis, prognosis, and treatment of impaired glucose tolerance and impaired fasting glucose. AHRQ Evidence Reports and Summaries (2006).

34 Εξέλιξη ςε Δ2 iifg 33% των ατόμων μετϊ παρακολούθηςη ετών. De Vegt F, et al. Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population: The Hoorn Study. JAMA 2001; 285: % των ατόμων μετϊ παρακολούθηςη 30 μηνών. Eschwège E, et al. Reproducibility of the diagnosis of diabetes over a 30-month follow-up: the Paris Prospective Study. Diabetes Care 2001; 24: % των ατόμων μετϊ παρακολούθηςη 11.5 ετών. Vaccaro O, et al. Risk of diabetes in the new diagnostic category of impaired fasting glucose: a prospective analysis. Diabetes Care 1999; 22:

35 Εξέλιξη ςε Δ2 iigt 40 50% των ατόμων μϋςα ςε 10 ϋτη και 30% περύπου μϋςα ςε 5 ϋτη. Rasmussen SS, Glumer C, Sandbaek A, Lauritzen T, Borch-Johnsen K. Determinants of progression from impaired fasting glucose and impaired glucose tolerance to diabetes in a high-risk screened population: 3 year follow-up in the ADDITION study, Denmark. Diabetologia 2008; 51: Εμφϊνιςη ΣΔ ςτο 25% των ατόμων μετϊ παρακολούθηςη τησ εξϋλιξησ από νορμογλυκαιμύα ςε IFG ό IGT για 10 ϋτη. Meigs JB, Muller DC, Nathan DM, et al. The natural history of progression from normal glucose tolerance to type 2 diabetes in the Baltimore Longitudinal Study of Aging. Diabetes 2003; 52:

36 Εξέλιξη ςε Δ2 ΙFG/IGT 64.5% των ατόμων μετϊ παρακολούθηςη ετών. De Vegt F, et al. Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population: The Hoorn Study. JAMA 2001;285: % των ατόμων μετϊ παρακολούθηςη 30 μηνών. Eschwège E, et al. Reproducibility of the diagnosis of diabetes over a 30-month follow-up: the Paris Prospective Study. Diabetes Care 2001; 24: % των ατόμων μετϊ παρακολούθηςη 11.5 ετών. Vaccaro O, et al. Risk of diabetes in the new diagnostic category of impaired fasting glucose: a prospective analysis. Diabetes Care 1999; 22:

37 Εξέλιξη ςε Δ2 ΙFG/IGT 10% των ατόμων εμφανύζουν ΣΔ2 ςε ετόςια βϊςη Vendrame F, Gottlieb PA. Prediabetes: prediction and prevention trials. Endocrinol Metab Clin North Am 2004; 33: Knowler WC, et al. Diabetes Prevention Program Research Group.Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication). Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet 2006; 368:

38 STUDY Ν F/U iifg iigt IFG/IGT Hoorn Study (2001) Paris Prospective Study (2001) ITALIAN Study (1999) ϋτη μόνεσ ϋτη 33% 64.5% 2.7% 14.9% 9.1% 44.4% ADDITION Study (2008) DPP (2002), DREAM (2006) MAURITIUS (1999) ϋτη 3234, ϋτη, 3 ϋτη ϋτη 21.6% 30% 10% PIMA INDIANS 5 ϋτη 41.2%

39 Προδιαβήτησ 1. Οριςμόσ 2. Παθοφυςιολογύα 3. Κλινικό ςημαςύα 4. Εξϋλιξη ςε ΣΔ2 5. Screening 6. Θεραπευτικό προςϋγγιςη

40 STUDY DA QUING (1997) STOP NIDDM (2002) FINNISH DPS (2001) DPP (2002) XENDOS (2004) DREAM (2010) No. OF PARTICI PANTS STUDY POPULATION 577 Chinese, IGT, mean age 45 yrs, BMI 26 kg/m IGT, mean age 55 yrs, BMI 31 kg/m2 522 IGT, mean age 55 yrs, BMI 31 kg/m USA, IGT, mean age 51 yrs, BMI 34 kg/m Swedish, BMI > 30 kg/m2, mean age 43 yrs, 21% IGT (694) 5269 IGT ± IFG, mean age 54 yrs, BMI 30.9% INTERVENTION Diet and/or exercise DIABETES RISK REDUCTION DURATION 36 47% 6 yrs Acarbose 25% 3.3 yrs Diet and exercise Diet and exercise, OR Metformin Orlistat + diet + exercise 58% 3.2 yrs Lifestyle 58%, Metformin 31%, Entire group 37%, IGT 45% 2.8 yrs 4 yrs Rosiglitazone 62% 3 yrs

41 STUDY IDPP (2006) No. OF PARTICI PANTS STUDY POPULATION 531 Indian, IGT INTERVENTION Lifestyle modification, metformin, and combined lifestyle modification/ metformin DIABETES RISK REDUCTION Lifestyle 29%, Metformin 26%, Lifestyle modification/ metformin 28% DURATION 30 months JAPANESE REVENTION TRIAL (2005) 458, IGT Intensive lifestyle intervention OR standard management Lifestyle 67.4% 4 years GLP NALOGUES (2008) 564 ΒΜΙ kg/m² Placebo vs. acarboze vs. liraglutide Liraglutide mg 84 96% 20 weeks ORIGIN (2012) 1456 CV risk factors, IFG, IGT, mean age 63.5 yrs Glargine vs. standard care Glargine 28% 6.2 years

42 Lifestyle modifications STUDY No. OF PARTICI PANTS STUDY POPULATION INTERVENTION DIABETES RISK REDUCTION DURATION DA QUING (1997) 577 Chinese, IGT, mean age 45 yrs, BMI 26 kg/m2 Diet only vs. exercise only vs. diet and exercise vs. no intervention Diet only 36%, diet + exercise 39%, exercise only 47% 6 yrs FINNISH DPS (2001) 522 IGT, mean age 55 yrs, BMI 31 kg/m2 Diet and exercise vs. control 58% 3.2 yrs DPP (2002) 3234 USA, IGT, mean age 51 yrs, BMI 34 kg/m2 Diet + exercise vs. metformin vs. troglitazone vs. placebo 58% (older pts, BMI), [33% in HTN, HDL, TG] 2.8 yrs JAPANESE PREVENTION TRIAL (2005) 356 (control) 102 Males, IGT Intensive diet and exercise (BMI < 22 kg/m²) vs. control 67.4% 4 yrs

43 STUDY No. OF PARTICI PANTS STUDY POPULATION Metformin INTERVENTION DIABETES RISK REDUCTION DURATION DPP (2002) 3234 USA, IGT, mean age 51 yrs, mean BMI 34 kg/m² Diet + exercise vs. metformin 850 mg bid vs. troglitazone vs. placebo Metformin 31% (younger pts, BMI > 35 kg/m²) Lifestyle 58% 2.8 years IDPP (2006) 531 Indian, IGT, slightly younger, less overweight Lifestyle modification vs. metformin 250 mg bid vs. Combined arm vs. control Lifestyle 29% Metformin 26% Combined lifestyle modification + metformin 28% 30 months

44 Simulated cumulative incidence of diabetes among adults with IGT (DPP)

45 Αναςτολέασ α-γλυκοςιδάςησ ςουλφονυλουρίεσ STUDY No. OF PARTICI PANTS STUDY POPULATION INTERVENTION DIABETES RISK REDUCTION DURATION STOP NIDDM (2002) 1429 IGT, mean age 55 yrs, BMI 31 kg/m2 Acarbose vs. placebo Acarbose 25%, 36% (ςε 2 η OGTT) (49% in CVD, HTN, and progression of carotid intimamedia thickness) 3.3 years BOTNIA (2006) 34 IGT, 1 st degree relatives of pts with DM2 and Glipizide OR placebo Glipizide 23.5% ( risk of hypoglycemia!) 18 months

46 Θειαζολιδινεδιόνεσ STUDY No. OF PARTICI PANTS STUDY POPULATION INTERVENTION DIABETES RISK REDUCTION DURATION DREAM (2010) 5269 IGT ± IFG, mean age 54 yrs, BMI 30.9% Rosiglitazone vs. placebo OR ramipril vs. placebo Rosiglitazone 62% ( risk of renal disease) 3 years TRIPOD (2002) 235 Hispanic with Hx GDM Troglitazone vs. placebo 56% ( progression of carotid intimamedia thickness) 30 months PIPOD (2006), ΑCT- NOW 89 Hispanic from TRIPOD, IGT Pioglitazone 78%, 81% 36 months, 2.6 years DPP 3234 Troglitazone Liver toxicity (0.9 yrs) 2.8 years

47 GLP-1 ΑΝΑΛΟΓΑ 564 participants (18 65 yrs) with a BMI kg/m² without DM2 20 week trial 1 4 liraglutide doses (1.2, 1.8, 2.4, 3.0) vs. placebo vs. orlistat Lost significantly more weight ( kg) than did those on placebo (2.8 kg) and orlistat (4.1 kg) Liraglutide reduced BP at all doses, and reduced the prevalence of prediabetes (84 96% reduction) with mg per day. Astrup A, et al. Effects of liraglutide in the treatment of obesity: a randomised, double-blind, placebo-controlled study. Lancet 2009; 374:

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49 INSULIN GLARGINE 12,537 participants in 40 countries (mean age, 63.5 yrs) with CV risk factors plus IFG, IGT, or DM2 Follow up: 6.2 years 1456 with prediabetes Insulin glargine (737) OR standard care (719) Insulin glargine had a neutral effect on CV outcomes and cancers 28% RR, but increased hypoglycemia and modestly increased weight ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med 2012; 367:

50 Θεραπεία κατά παχυςαρκίασ: ορλιςτάτη, βαριατρική χειρουργική STUDY No. OF PARTICI PANTS STUDY POPULATION INTERVENTION RISK REDUCTION DURATION SMOMS (2007) 309 Obese with MetSy Orlistat + lifestyle modification vs. placebo + lifestyle intervention Orlistat 58% 3 yrs XENDOS (2004) 3277 Swedish, mean age 43 yrs, BMI > 30 kg/m2, 21% IGT (694) Orlistat + lifestyle modification vs. placebo + lifestyle intervention Entire group 37%, IGT subgroup 45% 4 yrs SOS (2008) 2010, 2037 Swedish, BMI > 35 kg/m2 Surgery for obesity vs. conventional treatment Surgical group greatly risk (OR: 0.16) 8 yrs

51 Υιβράτεσ Ενεργοπούηςη ειδικών ορμονικών πυρηνικών υποδοχϋων PPARs Βεζαφιβρϊτη (αγωνιςτόσ PPAR-a) Μικρότερη αναλογύα κινδύνου (hazard ratio) για εμφϊνιςη ΣΔ, καθώσ και για προςθόκη διςκύων ό ινςουλύνησ ςε προώπϊρχον ΣΔ ςε ςχϋςη με ϊλλεσ φιβρϊτεσ Flory JH, Ellenberg S, Szarapy PO, et al. Antidiabetic action of bezafibrate in a large observational database. Diabetes Care 2009; 32: Tenenbaum A, Motro M, Fisman EZ, et al. Effect of bezafibrate on incidence of type 2 diabetes mellitus in obese patients. Eur Heart J 2005;26: Tenenbaum A, Motro M, Fisman EZ, et al. Peroxisome proliferator-activated receptor ligand bezafibrate for prevention of type 2 diabetes mellitus in patients with coronary artery disease. Circulation 2004; 109:

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53 Who should be screened for prediabetes Method of screening Recommended treatment ADA Consensus Statement Individual with risk factors for DM 1. FPG 2. OGTT if metformin is considered Lifestyle modification for IFG or IGT. Lifestyle modification ± Metformin for IFG or IGT and at least one of the following: age < 60 years, BMI > 35 kg/m², family Hx of DM in 1 st degree relative, TG, HDL-c, HTN, HbA1c > 6% Follow-up Metformin group: HbA1c every 6 months, Lifestyle: annual follow-up Indian Health Services Annual testing for individuals with risk factors for DM 1. FPG 2. Optional OGTT Lifestyle modification. Metformin treatment on an individualized basis Monitor glucose every 6 months Australian Diabetes Society Statement Incidental detection when screening for DM Incidental detection when screening for DM Lifestyle modification for a minimum of 6 months before pharmacotherapy OGTT initially annually, then every 1 3 years

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55 Paulweber B, et al. A European evidence-based guideline for the prevention of type 2 diabetes. Horm Metab Res 2010; 42 Suppl 1: S3 36.

56 1. Intensive lifestyle interventions that encourage people to change their diet and to increase their level of physical activity. [A] 2. Weight reduction by 5 7% is sufficient to substantially lower the risk of T2DM. [A] 3. An increase in physical activity even at a level of 30 min/day of moderate exercise. [B] 4. A diet with high fibre ( 15 g/1000 kcal), moderate fat ( 35% of total energy) reduced saturated and trans fat (< 10% ) and is therefore recommended. [B] 5. Comorbidities, particularly MetSy, should be monitored and taken into account while planning the diet. [C] 6. Currently there is no evidence from long-term prevention studies that reducing total dietary carbohydrate prevents T2DM. Carbohydrate sources should mainly be wholegrain cereal, fruit, vegetables, and legumes. [C]

57 1. In persons with IGT, metformin and acarbose can be used as second line strategies for prevention of T2DM. [A] 2. In obese people with or without IGT, carefully monitored antiobesity treatment with orlistat, in addition to intensive lifestyle modification, can be used as a second line strategy. [A] 3. In severely obese patients, bariatric surgery can induce sustained weight loss for, but longterm safety is less clear so that it cannot be recommended for diabetes prevention at present. [C] 4. Glucose lowering drugs such as glipizide or thiazolidendiones may reduce the risk of T2DM in certain high risk groups, but either long-term efficacy or safety are unclear so that these drugs cannot be recommended for diabetes prevention at present. [C]

58 Κριτήρια ελέγχου (1) 1. Άτομα λευκόσ φυλόσ 40 ετών ό ϊτομα μαύρησ φυλόσ ό αςιατικόσ καταγωγόσ 25 ετών με 1 από τουσ εξόσ παρϊγοντεσ κινδύνου: 1 ου βαθμού ςυγγενή με ΣΔ ± ΒΜΙ 25 kg/m2 ± ΠΜ > 94 cm για λευκήσ ή μαύρησ φυλήσ, > 80 cm για λευκήσ ή μαύρησ φυλήσ ή αςιατικήσ καταγωγήσ, > 90 cm για αςιατικήσ καταγωγήσ ± ΣΑΠ 140 mmhg ή ΔΑΠ 90 mmhg ή αγωγή για υπέρταςη ± HDL 35 mg/dl ή TG 250 mg/dl ή υπολιπιδαιμική αγωγή

59 Κριτήρια ελέγχου (2) 2. με Ηx GDM ό γϋννηςησ νεογνού > 4 kg 3. με Hx PCOs και BMI 30 kg/m² 4. Άτομα με Hx ιςχαιμικόσ καρδιοπϊθειασ, καρδιαγγειακόσ νόςου και ΠΑΝ 5. Άτομα με ςοβαρϊ νοητικϊ προβλόματα ό λόψη αντιψυχωςικών φαρμϊκων 6. Άτομα με IFG ό IGT 7. Άτομα με προςωρινϊ επαγόμενο

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