1 / 42

Diabetic Nephropathy in T2DM: Blood Pressure and Cholesterol Targets

Diabetic Nephropathy in T2DM: Blood Pressure and Cholesterol Targets . Nemanja Stojanovi ć Consultant Endocrinologist Queen’s Hospital, Romford. We will talk about. Kidney in Diabetes Drug related renal injury in T2DM Preventing DM Nephropathy Cholesterol/ BP/ Glucose Treatment

reegan
Download Presentation

Diabetic Nephropathy in T2DM: Blood Pressure and Cholesterol Targets

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript


  1. Diabetic Nephropathy in T2DM: Blood Pressure and Cholesterol Targets Nemanja Stojanović Consultant Endocrinologist Queen’s Hospital, Romford

  2. We will talk about • Kidney in Diabetes • Drug related renal injury in T2DM • Preventing DM Nephropathy • Cholesterol/ BP/ Glucose Treatment • Guidelines/ Conclusion

  3. Nephropathy • 35-50% with Type 1 after 20 years of disease • 10- ? 20% Type 2 patients on diagnosis

  4. Nephropathy: aetiology • HbA1c >7–8% • Genetic factors • Hypertension • Inflammation • Altered vascular permeability • Hyperlipidaemia • Excessive protein intake

  5. Determinants of Glomerular Proteinuria • Mean transcapillary hydraulic-pressure difference • Glomerular surface area • Size selectivity of the glomerular filter • Charge selectivity

  6. Microalbuminuria • Normoalbuminuria <30 mg/day • Microalbuminuria 30–300 mg/day • Clinical or macroalbuminuria >300 mg/day- POINT OF NO RETURN • ACR

  7. Nephropathy: Patient Should Know… • Optimal glycaemic control will prevent it or delay it • Annual urine test: only way to detect it • Importance of BP monitoring • Hypertension: predisposes and aggravates nephropathy

  8. Microalbuminuria: Type 2 DM • 10% have it at diagnosis • 80% CVS mortality over 10 years • Associated with insulin resistance sy • 2 positive samples required for the diagnosis

  9. STENO-2 Study • 160 patients with T2DM and microalbuminuria • 80 treated according to the national guidelines + 80 active treatment • Active group reviewed 3 monthly • Duration: 7.8 years NEJM 2003; 348: 383- 93

  10. STENO-2 Study • Intensive glycaemic control A1c < 7.5 or 6.5% • Systolic Bp < 140 or 130 mmHg • Diastolic BP < 85 or 80 mm Hg • Cholesterol < 4.9 or 4.6 mmol/l • Triglycerides < 1.7mol/l • Most active treatment patients were on Aspirin NEJM 2003; 348: 383- 93

  11. STENO-2 Endpoints • Composite death from CVS causes • CVG • PTCA • Nonfatal CVA • Amputation • Vascular surgery to correct ischaemia • Microvascular NEJM 2003; 348: 383- 93

  12. STENO-2 • After the end of the study • Prospective follow up for 5.5 years • Both groups now treated to the national targets

  13. Preventing Microalbuminuriaand Progression of Diabetic Nephropathy: Antihypertensives

  14. Preventing Microalbuminuria in T2DM: BENEDICT Study • 1204 Hypertensive Subjects with T2DM • No microalbuminuria • Target BP 120/80 • HbA1c ~ 5.8± 1.5% • Duration of Diabetes< 25 years NEJM 351: 1941-51; 2004

  15. Preventing Microalbuminuria in T2DM NEJM 351: 1941-51; 2004

  16. Irbesartan in T2DM Nephropathy • 1715 pts- duration 2.6 years • Irbesartan 300mg OD vs Amlodipine OD vs Placebo • Proteinuria 900mg/day • Cr ♀ 88- 265 umol/l ♂ 107- 265 umol/l • Target BP 135/85 mmHg • Primary composite outcome: ESRF, doubling of Cr & Death: any cause NEJM 2001; 345: 851-61

  17. Irbesartan in T2DM Nephropathy NEJM 2001; 345: 851-61

  18. Losartan and Diabetic Nephropathy • Secondary outcomes • Composite of morbidity and mortality from cardiovascular causes (p=NS) • Proteinuria Losartan: 35% reduction • Progression of renal disease Losartan: 18% reduction NEJM2008 358: 2433-2446

  19. Irbesartan • In patients with microalbuminuria • Renoprotective, prevents albuminuria in hypertensive patients with T2DM • Higher dose was more effective • A higher proportion of patients restored normoalbuminuria Irbesartan 300mg OD group than placebo 34% vs 21% Parving H et al. N Engl J Med 2001;345:870-878

  20. Telmisartan vs Enalapril • Patients with early diabetic nephropathy • 250 subject over 5 years • Similar decrements in GFR in both groups: -17.9 ml/min/1.73m2 of body surface area • Cr, AER no difference N Engl J Med 2004; 351:1952-61

  21. Drugs: Frequent Offenders • Iodine based contrast • Metformin & Contrast • NSAIDS & COX-2 Inhibitors • ACE • ARBs • Aminoglycoside antibiotics • Amphotericin B • Immunosuppressants

  22. Lipids ± Diabetes

  23. At least One Complication • Hypertension • Retinopathy/ Maculopathy/ Previous laser • Smoking • Micro or macroalbuminuria • LDL < 4.14 mmol/l • Triglycerides< 6.78mmol/l The Lancet 2004; 364: 685 - 696

  24. CARDS 1% 6% 30% 63% The Lancet 2004; 364: 685 - 696

  25. Primary Endpoints • Acute coronary heart disease event (incl. MI, silent MI, unstable angina, death, CPR) • Coronary revascularisation procedures • Stroke The Lancet 2004; 364: 685 - 696

  26. Primary Endpoints: Results No difference between the sexes or risk factor subgroups • Acute coronary heart disease event 36% • Coronary revascularisation procedures 31% • Stroke 48% The Lancet 2004; 364: 685 - 696

  27. CARDS • LDL < 2.6mmol subgroup • 743 patients • 26% reduction in major cardiovascular events The Lancet 2004; 364: 685 - 696

  28. REVERSAL Trial • Endovascular USS • Pravastatin 40mg vs Atorvastatin 80mg OD • Baseline LDL: 3.89mmol/l • End of Study LDL: Pravastatin 2.85mmol/l Atorvastatin 2.05mmol/l • After 18/12 atheroma progressed in pravastatin group but not in Atorvastatin group JAMA. 2004; 291:1071-1080

  29. Simvastatin Atorvastatin Pravastatin Rosuvastatin Ezetamibe Niacin Fibrates Omacor Diet Drugs on Offer

  30. Equivalent Doses + max dose decreases the LDL by additional 20%

  31. Metabolism

  32. Effect of reduction of LDL by 1mmol/l by any means on coronary death and non-fatal MI: meta-analysis of 58 trials Law MR BMJ 2003, 326: 1423-9

  33. Ahead of the Press

  34. ADVANCE • 11140 patients: 5 years • Intensive glycaemic control (A1c 6.5%) vs Conventional (A1c 7.3%) • Intensive group: gliclazide MR 30 to 120 mg daily and other hypoglycamic agents including insulin N Engl J Med 2008;10.1056/NEJMoa0802987

  35. ADVANCE Primary Endpoints • Composite of macro and microvascular events considered jointly and separately • Macro: CVD death, non fatal CVA & MI • Micro:new or worsening nephropathy ; doubling of the serum creatinine; the need for dialysis; death due to renal causes; worsening of retinopathy N Engl J Med 2008;10.1056/NEJMoa0802987

  36. ADVANCE N Engl J Med 2008;10.1056/NEJMoa0802987

  37. ADVANCE Conclusion • The main contributor to the 10% relative reduction in the primary outcome found with intensive control as compared with standard control was a 21% relative reduction in the risk of new or worsening nephropathy • More modest but significant reduction in microalbuminura N Engl J Med 2008;10.1056/NEJMoa0802987

  38. ACCORD Trial • 10,251 patients • Intensive glycaemic control and CVS outcomes • Primary outcomes : CVD death, Non fatal CVA & MI • Intensive Treatment: HbA1c< 6% • Conventional Treatment HbA1c 7-7.9 • Death rates begin to separate after 1 year….. N Engl J Med 2008;10.1056/NEJMoa0802743

  39. ACCORD N Engl J Med 2008;10.1056/NEJMoa0802743

  40. NICE BP < 130/80 ACE/ ARB Cholesterol<4mmol/l LDL< 2mmol/l Aspirin

  41. Instead of Conclusion • If I had T2DM and microalbuminuria: • BP 129 (114)/ 79 mmHg • LDL < 2mmol/l • ACE or ARB • Aspirin

  42. www.EndoDiabetes.com

More Related