DIABETES MELLITUS TA SON TEDAVI YAKLASIMLARI

1. DIABETES MELLITUS�TA SON TEDAVI YAKLASIMLARI Do�.Dr.Fulya AKIN PA�TF Endokrinoloji ve Metabolizma Hastaliklari

2. Diyabet Tedavisinde D�n�m Noktalari Uzun-etkili insulin analoglari � It has been more than 80 years since the discovery of ins�lin, and as this timeline shows, there has been continuing progress. In fact, much of our current understanding of diabet, its devastating consequences, and its effective management has been attained during the latter part of this timeline. As this presentation will discuss, despite the progress of science, there are still many challenges to be overcome Researchers at the University of Toronto discovered ins�lin in 19211 The first sulphonylureas appeared during the early 1940s1 Hans Christian Hagedorn�s delayed-action preparation, �neutral protamine Hagedorn,� appeared in 1946; we know it as NPH1 The Lente series appeared in 19521 Metformin became available (outside the United States) in 19601 Portable ins�lin infusion pumps were introduced during the late 1970s1 The Diabet Control and Complications Trial was published in 19931 Rapid-acting ins�lin analogues became available in 19962 The United Kingdom Prospective Diabet Study was published in 19981 Lantus? (ins�lin glargine; the first long-acting ins�lin analogue) received US Food and Drug Administration approval in 20003� It has been more than 80 years since the discovery of ins�lin, and as this timeline shows, there has been continuing progress. In fact, much of our current understanding of diabet, its devastating consequences, and its effective management has been attained during the latter part of this timeline. As this presentation will discuss, despite the progress of science, there are still many challenges to be overcome Researchers at the University of Toronto discovered ins�lin in 19211 The first sulphonylureas appeared during the early 1940s1 Hans Christian Hagedorn�s delayed-action preparation, �neutral protamine Hagedorn,� appeared in 1946; we know it as NPH1 The Lente series appeared in 19521 Metformin became available (outside the United States) in 19601 Portable ins�lin infusion pumps were introduced during the late 1970s1 The Diabet Control and Complications Trial was published in 19931 Rapid-acting ins�lin analogues became available in 19962 The United Kingdom Prospective Diabet Study was published in 19981 Lantus? (ins�lin glargine; the first long-acting ins�lin analogue) received US Food and Drug Administration approval in 20003

3. Diabetes Mellitus�ta Glisemik Kontrol Hedefleri

4. Tip 2 Diabet nasil tedavi edilmelidir?

5. Tip 2 diyabet tedavisinde kalici ve s�rekli glisemi kontrol� ile komplikasyonlara bagli morbidite ve mortaliteyi azaltmak hedeflenmelidir.1 1Reusch JE, Gadsby R: Thiazolidinedione Therapy: The benefits of agressive and early use in type 2 diabetes.Diabetes Technol Ther. 5. 4(2003): 685-93.

6. Yasam tarzi degisiklikleri Ilk basamak tedavidir1 Belfast Diet Study: 223 yeni tani Tip 2 DM, ~80% taniyi takiben 6 yil sadece diyet tedavisi verilmis.2 Ilk birka� ay, kan sekeri ve agirlikta azalma g�zlenmis.2 Diyet tedavisini s�rd�ren hastalarin ?-h�cre fonksiyonunda azalma ile birlikte progresif kan sekeri y�kseklikleri oldugu g�r�lm�st�r.3

7. Glisemik kontrol diyet veya konvansiyonel monoterapilerle saglanamaz.* Traditional monotherapy generally fails Treatment with diet alone, insulin or sulphonylurea is known to improve glycaemia in patients with Type 2 diabetes, but which treatment most frequently attained HbA1c below 7% was unknown. The UKPDS study aimed to assess how often each therapy can achieve the glycaemic control target levels set by the American Diabetes Association. Newly diagnosed Type 2 diabetes patients were followed up every 3 months for 3, 6 and 9 years after enrollment. After 3 months on a low-fat, high-carbohydrate, high-fibre diet, patients were randomised to therapy with diet alone, insulin or sulphonylurea. The proportion of patients who maintained target glycaemic levels declined markedly over 9 years of follow-up. After 9 years of monotherapy with diet, insulin, or sulphonylurea, 8%, 42% and 24%, respectively, achieved FPG levels of less than 7.8 mmol/L (140 mg/dL) and 9%, 28% and 24% achieved HbA1c levels below 7%. Link to next slide: Is combination therapy the answer? Reference Turner RC et al. JAMA 1999; 281: 2005�2012.Traditional monotherapy generally fails Treatment with diet alone, insulin or sulphonylurea is known to improve glycaemia in patients with Type 2 diabetes, but which treatment most frequently attained HbA1c below 7% was unknown. The UKPDS study aimed to assess how often each therapy can achieve the glycaemic control target levels set by the American Diabetes Association. Newly diagnosed Type 2 diabetes patients were followed up every 3 months for 3, 6 and 9 years after enrollment. After 3 months on a low-fat, high-carbohydrate, high-fibre diet, patients were randomised to therapy with diet alone, insulin or sulphonylurea. The proportion of patients who maintained target glycaemic levels declined markedly over 9 years of follow-up. After 9 years of monotherapy with diet, insulin, or sulphonylurea, 8%, 42% and 24%, respectively, achieved FPG levels of less than 7.8 mmol/L (140 mg/dL) and 9%, 28% and 24% achieved HbA1c levels below 7%. Link to next slide: Is combination therapy the answer? Reference Turner RC et al. JAMA 1999; 281: 2005�2012.

8. OAD monoterapisi zaman i�inde A1C hedefini s�rd�rmede yetersiz kalir

9. �alismalar hastalarin �ogunun A1C hedeflerine ulasamadiklarini g�stermistir.1,2 Tip 2 diyabet ilerledik�e3 etkin kontrol saglamak i�in sonunda ins�lin gerekinceye kadar diger OAD�ler eklenir �oklu ila� tedavisi gerekliligi4 Tanidan ~ 3 yil sonra hastalarin ~ %50�sinde Tanidan ~ 9 yil sonra hastalarin ~ %75�inde

10. Tip 2 diyabet tedavisinde g�ncel yaklasim Diyabet komplikasyonlarini belirgin sekilde azaltabilir1,2 Son yillarda tip 2 diyabetli hastalarin tedavisine yaklasim bi�imi b�y�k �l��de degismistir3,4 Glisemik kontrol hedeflerinin asagi �ekilmesi ve geleneksel basamakli tedavinin yerine ins�lin ve kombinasyon tedavilerine daha erken baslanmasi benimsenmistir3,4

11. Tip 2 Diyabette Tedavi Yaklasimi This slide illustrates the current treatment algorithm for type 2 diabetes patients. Initially, there is a pre-diabetes period, where normal glucose tolerance shifts into a state of impaired glucose tolerance (IGT). This initial phase probably starts at the age of 20 to 30 years, but is usual undiagnosed because few, if any, clinical symptoms present. As IGT worsens, symptoms become apparent, and type 2 diabetes is diagnosed. Following modification of lifestyle with diet and exercise, monotherapy with an oral antidiabetic agent is the first pharmaco-therapeutic intervention. As the disease progresses, most patients need a combination of agents to control their glycemia. Treatment with insulin, alongside combination therapy might eventually be needed and, if pancreatic failure occurs, intravenous insulin may be administered. Key studies, such as the United Kingdom Prospective Diabetes Study (UKPDS), show that aggressive pharmacotherapy significantly reduces the risk and incidence of microvascular complications, and might reduce the risk of macrovascular complications. Consequently, a global trend is developing to treat diabetes earlier and more aggressively to manage glycemia, delay disease progression, and minimize the development of complications that increase morbidity and mortality in patients with type 2 diabetes.This slide illustrates the current treatment algorithm for type 2 diabetes patients. Initially, there is a pre-diabetes period, where normal glucose tolerance shifts into a state of impaired glucose tolerance (IGT). This initial phase probably starts at the age of 20 to 30 years, but is usual undiagnosed because few, if any, clinical symptoms present. As IGT worsens, symptoms become apparent, and type 2 diabetes is diagnosed. Following modification of lifestyle with diet and exercise, monotherapy with an oral antidiabetic agent is the first pharmaco-therapeutic intervention. As the disease progresses, most patients need a combination of agents to control their glycemia. Treatment with insulin, alongside combination therapy might eventually be needed and, if pancreatic failure occurs, intravenous insulin may be administered. Key studies, such as the United Kingdom Prospective Diabetes Study (UKPDS), show that aggressive pharmacotherapy significantly reduces the risk and incidence of microvascular complications, and might reduce the risk of macrovascular complications. Consequently, a global trend is developing to treat diabetes earlier and more aggressively to manage glycemia, delay disease progression, and minimize the development of complications that increase morbidity and mortality in patients with type 2 diabetes.

12. Tip 2 diyabet tedavisinde g�ncel yaklasim Hedef A1C degeri Genel olarak: <%7 Bireysel olarak: Hipoglisemi yasanmamasi kosulu ile <%6 Yasam beklentisi d�s�k ve hipoglisemi riski varsa hedefler g�zden ge�irilmeli A1C �l��m� Hedef degere ulasilana dek: 3 ayda bir Hedefe ulasildiktan sonra: En az 6 ayda bir

13. Tip 2 diyabet tedavisinde g�ncel yaklasim KG hedefi �nce a�lik ve �g�n �ncesi KG hedeflenmeli Hedefi 70-130 mg/dl (kapiler) A�lik ve �g�n �ncesi KG hedefleri s�rd�r�lemiyorsa veya A1C =%7 ise postprandiyal KG Hedef: <180 mg/dl �g�nlerden 90-120 dk sonra

14. Tip 2 diyabet tedavisinde g�ncel yaklasim Tedavi se�iminde glukoz d�s�r�c� etkinin yaninda g�venlik, tolerabilite ve maliyet �nemli Siklikla diyabete eslik eden hipertansiyon ve hiperlipidemi vb. g�ncel kilavuzlara uygun tedavi edilmeli

15. Tip 2 diyabet tedavisinde g�ncel yaklasim Taniyi takiben yasam tarzi d�zenlemeleri ve metformin Beslenme Fiziksel aktivite Kilo kaybi (en az 4 kg veya agirligin %5�i) Evde kan sekeri takibi Metformin 2 X 500 mg baslanmali ve 1-2 ay i�inde etkili dozlara �ikilmali: 2 X 850 mg (maksimum 3.000 mg/g�n)

16. Tip 2 diyabet tedavisinde g�ncel yaklasim Glisemik hedeflere ulasilamazsa veya hedefler s�rd�r�lemiyorsa kisa s�rede yeni ila� ve yeni tedavi rejimi A1C =%7 ise ikinci bir ila� eklenmeli (bazal ins�lin en etkili se�enek) A1C >%8.5 ise ve diyabet semptomlari varsa ins�lin (tercihen bazal ins�lin) baslanmali

17. Tip 2 diyabet tedavisinde g�ncel yaklasim Glisemik hedeflere ulasilamadiginda zaman kaybetmeden ins�lin tedavisine baslanmali veya ins�lin tedavisi yogunlastirilmali A1C <%8 ? ���nc� bir ila� (Tedavi maliyeti!) Hizli/kisa etkili ins�lin ile ? Salgilatici ila�lar kesilmeli (sulfonil�re veya glinidler) Ins�lin tedavisi + ins�lin duyarlilastirici bir ila� (tercihen metformin) Ins�lin + glitazon sivi retansiyonu riskini artirabilir!

20. OAD� lerin Metabolik Etkileri

22. RECORD: yorumlar Metformin ve s�lfonil�re alan hastalarla kiyaslandiginda, rosiglitazon olan hastalarda genel kardiyovask�ler (KV) hospitalizasyon ve KV �l�m oranlarinda bir artis g�zlenmedi1 Genel KV sonu�lar, KKY parametresinin eklendigi durumda bile, metformin ve s�lfonil�reye kiyasla rosiglitazon i�in benzerdi1 Metformin , UKPDS �alismasinda MI ve herhangi bir nedene bagli �l�m� azaltmada bir fayda ortaya koymustu2 Sekonder birlesik sonlanim noktasi olan KV �l�m, MI veya inme, rosiglitazon veya aktif kontrol grubundaki hastalarda benzer bulundu1 Metformin veya s�lfonil�reye eklenen rosiglitazon, 5 yilda hastalarda HbA1c �de s�rekli bir azalma sergiledi1 Metformin ve s�lfonil�re alan hastalarla kiyaslandiginda, rosiglitazon olan hastalarda genel kardiyovask�ler (KV) hospitalizasyon ve KV �l�m oranlarinda bir artis g�zlenmedi.1 Genel KV sonu�lar, KKY parametresinin eklendigi durumda bile, metformin ve s�lfonil�reye kiyasla rosiglitazon i�in benzerdi. UKPDS �alismasinda, asiri kilolu hastalarda olusan metformin grubunda, miyokard infarkt�s�nde (%39, P = 0.01) ve herhangi bir nedene bagli �l�mde (%36, P = 0.01) �nemli risk azalmalari, orijinal �alismada intensif tedavi grubunda g�zlendi. Bu risk azalmalari �alisma sonrasi d�nemde de korundu.2 Sekonder birlesik sonlanim noktasi olan kardiyovask�ler �l�m, miyokard infarkt�s� veya inme, rosiglitazon veya aktif kontrol grubundaki hastalarda benzer bulundu.1 Metformin veya s�lfonil�reye eklenen rosiglitazon, 5 yilda hastalarda HbA1c �de s�rekli bir azalma sergiledi.1 Tiazolidindionlarla �nceden bilinen, konjestif kalp yetmezligi ve kemik kirigi riskindeki artis bu �alismada teyit edildi.1 Home PD, et al. Lancet 2009;373:2125�2135. Holman RR, et al. N Engl J Med 2008;359:1577�1589. Metformin ve s�lfonil�re alan hastalarla kiyaslandiginda, rosiglitazon olan hastalarda genel kardiyovask�ler (KV) hospitalizasyon ve KV �l�m oranlarinda bir artis g�zlenmedi.1 Genel KV sonu�lar, KKY parametresinin eklendigi durumda bile, metformin ve s�lfonil�reye kiyasla rosiglitazon i�in benzerdi. UKPDS �alismasinda, asiri kilolu hastalarda olusan metformin grubunda, miyokard infarkt�s�nde (%39, P = 0.01) ve herhangi bir nedene bagli �l�mde (%36, P = 0.01) �nemli risk azalmalari, orijinal �alismada intensif tedavi grubunda g�zlendi. Bu risk azalmalari �alisma sonrasi d�nemde de korundu.2 Sekonder birlesik sonlanim noktasi olan kardiyovask�ler �l�m, miyokard infarkt�s� veya inme, rosiglitazon veya aktif kontrol grubundaki hastalarda benzer bulundu.1 Metformin veya s�lfonil�reye eklenen rosiglitazon, 5 yilda hastalarda HbA1c �de s�rekli bir azalma sergiledi.1 Tiazolidindionlarla �nceden bilinen, konjestif kalp yetmezligi ve kemik kirigi riskindeki artis bu �alismada teyit edildi.1 Home PD, et al. Lancet 2009;373:2125�2135. Holman RR, et al. N Engl J Med 2008;359:1577�1589.

23. Tiazolidindionlarla �nceden bilinen bir sinif etkisi olan, konjestif kalp yetmezligi ve kemik kirigi riskindeki artis bu �alismada teyit edildi1

24. Yeni oral tedaviler adacik disfonksiyonunu hedef almaktadirlar The primary metabolic defects of T2DM are pancreatic islet dysfunction (?-cell and ?-cell dysfunction) and impaired insulin action (insulin resistance); another contributing factor is uncompensated glucose influx. Many of these specific problems are addressed by one or another existing class of oral antihyperglycemic drugs, each of which has distinctive mechanisms.1 ?-Glucosidase inhibitors moderate glucose influx by delaying intestinal carbohydrate absorption, thereby mitigating postprandial glucose excursions.1 The utility of these agents depends in part on proper dietary compliance and is more effective in populations whose diet does not consist of highly processed foods. The widespread use of these agents in Japan and Spain is an excellent example of their utility in populations where a rice and fish diet is prevalent. Thiazolidinediones (TZDs) work primarily by enhancing both basal and insulin-mediated suppression of hepatic glucose production and to some extent by augmenting insulin-stimulated muscle glucose utilization.2 Metformin (of the biguanide drug class) lowers glucose levels, chiefly by reducing heptic glucose production.1 Sulfonylureas lower the glucose threshold for triggering ?-cell insulin release.1 Glinides resemble sulfonylureas in enhancing acute ?-cell function. Their short metabolic half-lives enable them to produce brief, episodic stimulation of insulin secretion.1 Of the glinides, nateglinide is rapidly reversible, whereas repaglinide is not. No currently available therapy addresses ?-cell function (glucagon) and chronic ?-cell function. References 1. Inzucchi SE. Oral antihyperglycemic therapy of type 2 diabetes: scientific review. JAMA. 2002;287-360�372. 2. DeFronzo RA. Impaired glucose tolerance: do pharmacological therapies correct the underlying metabolic disturbance? Br J Diabetes Vasc Dis. 2003;3(suppl 1):S24�S40. The primary metabolic defects of T2DM are pancreatic islet dysfunction (?-cell and ?-cell dysfunction) and impaired insulin action (insulin resistance); another contributing factor is uncompensated glucose influx. Many of these specific problems are addressed by one or another existing class of oral antihyperglycemic drugs, each of which has distinctive mechanisms.1 ?-Glucosidase inhibitors moderate glucose influx by delaying intestinal carbohydrate absorption, thereby mitigating postprandial glucose excursions.1 The utility of these agents depends in part on proper dietary compliance and is more effective in populations whose diet does not consist of highly processed foods. The widespread use of these agents in Japan and Spain is an excellent example of their utility in populations where a rice and fish diet is prevalent. Thiazolidinediones (TZDs) work primarily by enhancing both basal and insulin-mediated suppression of hepatic glucose production and to some extent by augmenting insulin-stimulated muscle glucose utilization.2 Metformin (of the biguanide drug class) lowers glucose levels, chiefly by reducing heptic glucose production.1 Sulfonylureas lower the glucose threshold for triggering ?-cell insulin release.1 Glinides resemble sulfonylureas in enhancing acute ?-cell function. Their short metabolic half-lives enable them to produce brief, episodic stimulation of insulin secretion.1 Of the glinides, nateglinide is rapidly reversible, whereas repaglinide is not. No currently available therapy addresses ?-cell function (glucagon) and chronic ?-cell function. References 1. Inzucchi SE. Oral antihyperglycemic therapy of type 2 diabetes: scientific review. JAMA. 2002;287-360�372. 2. DeFronzo RA. Impaired glucose tolerance: do pharmacological therapies correct the underlying metabolic disturbance? Br J Diabetes Vasc Dis. 2003;3(suppl 1):S24�S40.

25. Tip 2 diabet ve obezitede yeni tedaviler Inkretinler: 1.GLP-1 mimetikler, 2.DPP inhibit�rleri Inhale/oral insulinler Rimonabant Dual PPAR agonistleri

26. Inkretinler (GLP-1 ve GIP) glukoz homeostazini adacik h�cre fonksiyonlari �zerinden etkilerler Incretins (GLP-1 and GIP) Regulate Glucose Homeostasis Through Effects on Islet Cell Function The presence of nutrients in the gastrointestinal tract rapidly stimulates the release of incretins: GLP-1 from L cells located primarily in the distal gut (ileum and colon) and GIP from K cells in the proximal gut (duodenum).1,2 Collectively, GLP-1 and GIP exert several beneficial actions, including stimulating the insulin response in pancreatic beta cells (GLP-1 and GIP) and inhibiting glucagon secretion from pancreatic alpha cells when glucose levels are elevated.2-4 Increased insulin levels improve glucose uptake by peripheral tissues, while the combination of increased insulin and decreased glucagon reduce hepatic glucose output.5,6Incretins (GLP-1 and GIP) Regulate Glucose Homeostasis Through Effects on Islet Cell Function The presence of nutrients in the gastrointestinal tract rapidly stimulates the release of incretins: GLP-1 from L cells located primarily in the distal gut (ileum and colon) and GIP from K cells in the proximal gut (duodenum).1,2 Collectively, GLP-1 and GIP exert several beneficial actions, including stimulating the insulin response in pancreatic beta cells (GLP-1 and GIP) and inhibiting glucagon secretion from pancreatic alpha cells when glucose levels are elevated.2-4 Increased insulin levels improve glucose uptake by peripheral tissues, while the combination of increased insulin and decreased glucagon reduce hepatic glucose output.5,6

27. Inkretinlerin Karsilastirilmasi

28. Mevcut Stratejiler DPP-4 aktivitesini inhibe etmek (DPP-4 inhibit�rleri; inkretin artiricilar)

29. Artiricilar (DPP-4 inhibit�rleri) Oral aktiftir, g�nde bir kez alinirlar. Orta derecede (fizyolojik dozda) inkretin hormon konsantrasyonlarini artirirlar. Her iki inkretin hormon (GIP and GLP-1) �zerine etkileri vardir. Kilo �zerine etkileri n�trd�r ve GI yan etkileri yoktur.

30. Mimetikler (GLP-1 resept�r aktivat�rleri) Injektabl formdadirlar; farkli doz skalalari (2 x g�nde ? 1 x haftada) vardir. Y�ksek (farmakolojik dozda) of GLP-1-resept�r aktivat�r plazma konsantrasyonlarini artirirlar. B�t�nGLP-1 resept�rleri �zerine g��l� etkileri vardir. (a- ve �-h�creleri, istah, yiyecek alimi, v�cut agirligi) Kilo kaybina sebep olurlar. GI yan etkileri vardir. Bazan antikor olusumuna sebep olabilirler.

31. Tip 2 diyabette glisemik kontrol�n saglanmasi

32. Ins�lin Tedavisi Rejimleri Konvansiyonel ins�lin tedavisi G�nde 1-2 enjeksiyon Intensif ins�lin tedavisi Multipl enjeksiyon (bazal-bol�s ins�lin tedavisi) S�rekli subkutan ins�lin enjeksiyonu (pompa tedavisi)

33. Bazal Ins�lin Destegi(Endojen ins�lin rezervi olmasi gerekir) Tek doz NPH/Glargin/Detemir* + SU/MGT Tek veya iki doz NPH /Glargin/Detemir + MF/TZD Tek doz NPH /Glargin/Detemir + SU/MGT + MF

34. Klasik Ins�linlerin Etki Profili

35. Ins�lin Tedavisi Endikasyonlari Tip 1 Diyabet LADA GDM (diyetle kontrol saglanamazsa) Tip 2 Diyabette OAD�ler ile iyi metabolik kontrol saglanamamasi Asiri kilo kaybi Agir hiperglisemik semptomlar Akut miyokard infarkt�s� Akut atesli, sistemik hastaliklar Hiperozmolar veya ketotik koma (HONK, DKA) Major cerrahi operasyon Gebelik ve laktasyon B�brek veya karaciger yetersizligi OAD�lere allerji veya agir yan etkiler Agir ins�lin rezistansi (?)

36. Insan Ins�linlerinin Kisitlamalari Reg�ler ins�lin (�g�nlerle iliskili) Emilimi yavas oldugu i�in yemeklerden yarim saat �nce enjekte edilmeli Erken post-prandiyal hiperglisemi riski Ge� post-prandiyal hipoglisemi riski NPH ins�lin (bazal) Erken hiperglisemi kontrol edilemez Ge� d�nemde hipoglisemi riski artar Hazir karisim insan ins�linleri Reg�ler ve NPH ins�linin kisitlamalarini i�erir

37. G�nde Iki Kez Uygulanan NPH Tedavisinin Sinirli Y�nleri The regimen of twice-daily NPH and regular insulin attempts to mimick physiologic insulin secretion. However, this regimen results in many gaps in insulin coverage, during which the patient is at risk for hyperglycaemia, leading to poor long-term control1,2 As a result, NPH and regular insulin profiles do not come close to matching the normal endogenous secretory pattern1,2 �Dawn phenomenon� refers to the early morning fall in tissue insulin sensitivity counteracted by increased insulin secretion in individuals without diabetes but manifested as rising glycaemia in some patients with diabetes3The regimen of twice-daily NPH and regular insulin attempts to mimick physiologic insulin secretion. However, this regimen results in many gaps in insulin coverage, during which the patient is at risk for hyperglycaemia, leading to poor long-term control1,2 As a result, NPH and regular insulin profiles do not come close to matching the normal endogenous secretory pattern1,2 �Dawn phenomenon� refers to the early morning fall in tissue insulin sensitivity counteracted by increased insulin secretion in individuals without diabetes but manifested as rising glycaemia in some patients with diabetes3

38. Normal Ins�lin Sekresyonu: Bazal-Bolus Ins�lin Kavrami In individuals with normal weight who do not have diabetes, 2 patterns of insulin output are seen: basal insulin, which is secreted at a fairly constant rate between meals and at night to maintain euglycaemia, and during early morning hours; and bolus insulin, which is meal-related1 The therapeutic challenge for patients with diabetes is to provide enough basal insulin to control between-meal hyperglycaemia�which is due to hepatic glucose production�and enough bolus insulin to minimise hyperglycaemia immediately after meals. The provision of adequate levels of basal and bolus insulin may reduce risk for hypoglycaemia in individuals with erratic schedules or in those who have greater insulin requirements1 In individuals with normal weight who do not have diabetes, 2 patterns of insulin output are seen: basal insulin, which is secreted at a fairly constant rate between meals and at night to maintain euglycaemia, and during early morning hours; and bolus insulin, which is meal-related1 The therapeutic challenge for patients with diabetes is to provide enough basal insulin to control between-meal hyperglycaemia�which is due to hepatic glucose production�and enough bolus insulin to minimise hyperglycaemia immediately after meals. The provision of adequate levels of basal and bolus insulin may reduce risk for hypoglycaemia in individuals with erratic schedules or in those who have greater insulin requirements1

39. Bazal/Bolus Ins�lin Tedavisi Anlayisi

40. Ins�lin Analoglari A. Hizli ve kisa etkili Lispro: Humalog Aspart: NovoRapid Glulisin: Apidra B. Uzun etkili ve piksiz Glargin: Lantus Detemir: Levemir

41. Etki S�resine g�re Ins�lin Analoglari

43. Ins�lin Doz Hesabi Bazal %50 (%40-60) Bol�s %50 (%40-60)

44. Bazal Ins�lin Dozu Hedef AKS 100-120 mg/dl Tip 2 diyabette tek doz 10 iu basla Veya 0.1-0.2 iu/kg/g�n tek doz basla Tek doz NPH�tan Glargine ayni dozda ge�, 2 doz NPH�dan ge�iste %20-30 azalt NPH�dan Detemir�e %10-15 artir

46. �ZET Tip 2 diyabet hastalarinda uzun d�nemde glisemik kontrol hedeflerine ulasilamamaktadir. Erken, yogun glisemi kontrol� gereklidir.Insulin direnci ve ?-h�cre disfonksiyonunu hedef alan tedavi, hastaligin �nlenmesi ve klinik sonu�larda iyilesmeyi saglayacaktir. CORE SLIDECORE SLIDE

47. TEMD-2009

49. Global Trend Daha erken ve daha agressif tedavi

50. VAKA 1

51. �.�.27.04.06 56 y , erkek 5 yildir tip 2 DM tanisi olan hasta 1.5 yildir novomix sabah 16� aksam 8� kullaniyor AKS; 120-150 TKS; 150 civari max KS; 300 hiperglisemik koma veya hipoglisemik atak tariflemiyor

52. 1 yil �nce DRP: - MA�: 128 mg /g�n ( 25/ 4/ 06) EMG yapilmamis

53. �zge�mis: ? DM tip 2:+ ? HT: 5 Yildir accuzide 1x1 aliyor ; TA takibi yok ? Dislipidemi: var ancak medikal tedavi almiyor ? Lumbal herni op:+ ? sigara:+ Soyge�mis: Anne DM:+

54. Sistemlerin g�zden ge�irilmesi ( + bulgular) ? Nokturi ? Klaudia kasyo intermittant+ FM: BOY: 1.63 KILO: 65 BMI: 23 TA: 140/ 90 BB: Tiroid non �palpable, lap:- SS: Bilat ac sesleri aliniyor ral:- ronkus:- KVS: ritmik s1+ s2+ ek ses: - �f�r�m:- Batin: HSM:- defans:- rebound:- Extr: sol dorsalis pedis ve tibialis post alinmiyor

55. laboratuar

56. 27.4.2006 AKS:159 TKS:308 HbA1C: 7.6

57. Bilat alt ext arterial doppler: bilat alt ekst arterlerinde intimal refleksiyonda artis, monofazik paternede akim

58. Tedavi: 1800 kcallik diyabetik 200 mg / g�n kol i�eren diyabetik diyet 8� Ax3, 12 � lantus ASA 1x1 ACCUZIDE 1X1 FLUVASTATIN 1X1 Trental 1x1 Sigara stop

59. takip 22.06.06 fluvastatin ile ciddi kas agrilarindan dolayi atorvastatin 40 mg a ge�ildi. TA diastolik 50 civari AKS: 125 Tkol: 109 TKS: 180 TG: 102 HbA1c: 6.8 HDL: 40 LDL: 49 DEGISIKLIK; atorvastatin 20 mg 1x1 acuitel 1X1

60. 27.09.06 KILO:70 AKS: 132 TKS: 160 HbA1c: 6.2 metformin 2x1 gr eklendi

61. 28.06.07 AKS: 127 TKS: 280 HbA1c: 6 27.09.07 5 kg 1 ayda verdi AKS: 120 TKS: 143 HbA1c: 5.5

62. VAKA 2

63. V.S.05.10.06 54 y , erkek 3 yildir tip 2 DM tanisi olan hasta Diamicron MR 1X1, glukofen 2X1 kullaniyor AKS; 140-190 TKS; 180 civari max KS; 360 hiperglisemik koma tarifliyor o d�nemde hastaya intensif ins�lin tedavisi �nerildi ancak hasta tedaviyi kabul etmedi,hipoglisemik atak tariflemiyor Diyet ve egzersiz uyumu k�t�

64. 1 yil �nce DRP: - MA�: 14.7 mg /g�n ( 23/ 2/ 06) ancak daha �nce iki kez + tespit edildigi i�in ACE inh aliyor EMG yapilmamis

65. �zge�mis: ? DM tip 2:+ ? HT:- ? Dislipidemi: +, lipidor 1x1 ? ? sigara:+ Soyge�mis: �zellik yok

66. Sistemlerin g�zden ge�irilmesi ( + bulgular) ? Nokturi ? poliuri FM: BOY: 1.65 KILO: 67 BMI: 24.5 TA: 130/ 90 BB: Tiroid non �palpable, lap:- SS: Bilat ac sesleri aliniyor ral:- ronkus:- KVS: ritmik s1+ s2+ ek ses: - �f�r�m:- Batin: HSM:- defans:- rebound:- Extr: nabizlar bilat +, PT�: -

67. laboratuar

68. 5.10.2006 AKS:229 TKS:262 HbA1c:8.3

69. Tedavi: 1800 kcallik diyabetik 200 mg / g�n kol i�eren diyabetik diyet 12 � lantus GLIKLAZIDE MR 1X2 METFORMIN 2X1 ASA 1x1 GOPTEN 1X1 ATORVASTATIN 1X1 Sigara stop

70. takip 16.02.07 AKS: 120 TKS: 92 HbA1c: 6.3 LDL: 69 TEDAVI AYNEN DEVAM

71. 03 .07 hasta MI ge�irdi ve intensif ins�lin tedavisine ge�ildi. diyet uyumu ile de birlikte KS hipoglisemik seyredince oad+ lantus ( 10�) ile devam edildi Tedaviye karvedilol eklendi

72. 17.05.07 AKS: 143 TKS: 162 HbA1c: 6.3 20.09.07 AKS: 117 TKS: 112 HbA1c: 5.3

73. VAKA 3

74. A.G.5.4.07 46 Y , erkek 7 yildir tip 2 DM mevcut daha �ncesinde diamicron MR 1X1 kullanan hasta 3 aydir ilacini kesmis , evde AKS nin 160-230 mg /dl civarinda oldugunu ifade ediyor. Max KS : 414 mg/dl imis. Daha �nce komplikasyon arastirisi yapilmamis

75. �zge�mis: ? DM tip 2:+ ? HT: - ? Dislipidemi: var ancak medikal tedavi almiyor ? ses tellerinden op:+ ( etyo?) ? sigara:+ Soyge�mis: �zellik yok

76. Sistemlerin g�zden ge�irilmesi ( + bulgular) ? Nokturi ? Poli�ri FM: BOY: 1.71 KILO: 65 BMI: 22.5 TA: 160/ 90 BB: Tiroid non �palpable, lap:- SS: Bilat ac sesleri aliniyor ral:- ronkus:- KVS: ritmik s1+ s2+ ek ses: - �f�r�m:- Batin: HSM:- defans:- rebound:-

77. laboratuar

78. 5.4.2007 AKS:266 TKS:333 HbA1c:11

79. Tedavi: 1800 kcallik diyabetik diyet 8� Ax3, 10 � lantus ASA 1x1 Metformin 2X1 GR Sigara stop

80. takip 04.07.07 AKS: 146 TKS: 63 HbA1c: 5.6 DEGISIKLIK; analog ins�linler kesilip lantus 16� ve metformin 2x1 gr ile devam

81. 18 .09.07 AKS: 135 Hba1C: 5.5 Metformin 2x1 , lantus 14� gr ile devam 14.11.07 KS hioglisemik seyretmeye basladigi i�in lantus dozu azaltiliyor, takipte kesilip oad kombinasyonu d�s�n�lebilir

82. Tip2 DM vaka �alismalari IDF Diyabet egitim mod�lleri

83. Vaka 1 58 y,erkek 10 yildir Tip 2DM. KS�ine daha �nce hi� bakilmamis ve ila� kullanimi yok. Random KS:576mg/dl Keton�ri yok HbA1c:8.5 BMI:32 Agirlik:113.6

84. Hasta doktorun acil hastaneye gitmesi teklifini reddediyor,ama diyabet klinigine gelebilecegini belirtiyor. Daha �nce hi� DM egitimi almamis. Kendini iyi hissettigini s�yl�yor.Esi ise �ok ajite oldugunu ifade ediyor. Son 6 haftadir yurtdisindan ziyaret�ileri oldugunu ve aksam yemeklerini disarida yedigini belirtiyor.

85. Hastanin durumu nedir?Hangi ek bilgileri bilmek istersiniz?

86. Sizce bu kisinin tedaviye ihtiyaci var mi? Hangi tip tedavi verirsiniz?

87. Bu kisiye nasil bir diyet tavsiye edersiniz?

88. Vaka 2 53 y bayan,evli, 2 �ocugu var. Agirlik:91.5 kg, Boy:165cm TA:140/95-160/110 mm Hg Bazen kahvaltilarini ka�irabiliyor. 30dk herg�n y�r�yor.Y�r�y�s�n� artirma fikrini kabul etmiyor.

89. KS Profili 1.g�n AKS:260mg/dl �gle KS: 230 mg/dl Aksam yemegi �ncesi KS:245mg/dl 2.G�n AKS:232mg/dl �gle KS:240mg/dl Aksam yemegi �ncesi KS:225mg/dl 3.G�n AKS:226mg/dl �gle KS:230mg/dl Aksam yemegi �ncesi KS:234 mg/dl

90. Tedavi: Metformin 1000mg 2*1+Gliburid 10 mg 2*1 HbA1c:9.5

91. Tedavisi yeterli seviyede mi?

92. DM tedavisinde ne gibi degisiklikler yapmak istersiniz? Ni�in?

93. Hastayi bazi degisiklikler yapmaya nasil ikna edersiniz?

94. Hedef kan glikoz seviyesi ne olmali? Hangi siklikta takibe alirsiniz ve ne zaman degisiklik yapmayi planlarsiniz?

95. Vaka 3 50 y erkek hasta, is�i. 10 yildir diyabetik. Agirlik:81.8 kg, Boy:178 cm. TA:155/94 mmHg. Son HbA1c:8.5

96. Tedavi: Metformin 1000mg 2*1, Gliburid 10 mg 2*1 ve gece yatarken 30� NPH ins�lin aliyor. KS profili 1.G�n AKS:180, �gle KS:287 aksam KS:40 2. G�n AKS:153, �gle KS:257, aksam KS:270 3.G�n AKS:162, �gle KS:268, aksam KS:290

97. �g�nlerini d�zenli yapiyor. Isinde �ok aktif.

98. Tedavisi yeterli mi? Ne gibi degisiklikler yapmayi planlarsiniz ? Neden?

99. Hastayi bazi degisiklikler yapmaya nasil ikna edersiniz?

100. Hedef kan glikoz seviyesi ne olmali? Hangi siklikta takibe alirsiniz ve ne zaman degisiklik yapmayi planlarsiniz?

101. TESEKK�RLER