Diabetes Mellitus

1. Diabetes Mellitus Hart, Nieren & Hypertensie

2. Microalbuminurie bij Diabetes

3. Definitions of Microalbuminuria and Macroalbuminuria AER=Albumin excretion rate CR# =creatinine

7. Behandeling van Diabetes moet dus in hoge mate zijn gericht op preventie van cardiovasculaire ziekte . . .

8. Treatment Targets for Diabetic Renal Disease With Hypertension GLUCOSE GLUCOSE BP BP LIPIDS LIPIDS

9. 130 134 138 142 146 150 154 170 180 Meta Analysis: Lower SystolicBPResults in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics SBP (mmHg) 0 -2 r = 0.69; P < .05 -4 -6 Untreated HTN GFR (mL/min/year) -8 -10 -12 -14 Parving HH, et al. Br Med J. 1989. Moschio G, et al. N Engl J Med. 1996. Viberti GC, et al. JAMA. 1993. Bakris GL, et al. Kidney Int. 1996. Klahr S, et al. N Eng J Med. 1994. Bakris GL. Hypertension. 1997. Hebert L, et al. Kidney Int. 1994. The GISEN Group. Lancet. 1997. Lebovitz H, et al. Kidney Int. 1994. Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661.

10. Behandeling Microalbuminurie bij DM~ 2e-doel RR: 120-130/<80 mmHg • ACEi met diureticum (eg. Captopril/HCT of Lisinopril/HCT) • 2e middel op indicatie (eg. BB bij angina pectoris) • 2-3e middel: Spironolacton, (z.n. + kaliumbeperkt dieet of HCT/chloortalidon of sorbisterit) • 3-4e middel: Allopurinol

12. Consultatie van of verwijzing naar detweede lijn is aangewezen bij • twijfel over de diagnose, • problemen bij de glycemische instelling, • problemen bij behandeling van risicofactoren, • het onvoldoende onder controle krijgen van de gevolgen van complicaties • zwangerschap(swens). LTA DM-II, 2012

13. From Dr J Vora

14. DM-II • Losartan verhoogt de incidentie van microalbuminurie • RR-verlaging < 120 mmHg systolisch induceert meer sterfte • Vitamine-D vermindert microalbuminurie • Intensieve behandeling hyperglycemie in de initiële fase van DM-I/II reduceert nefropathie en CVR • Mortaliteit stijgt bij HbA1c > 85 en < 42 mmol/mol • Intermitterende episodes van acute nierinsufficientie verslechteren de lange termijn prognose

15. Results Of 5927 allopurinol initiators and 5927 matched comparators, 654 and 718, respectively, died during the follow-up (mean=2.9 years). The baseline characteristics were well balanced in the two groups, including the prevalence of gout in each group (84%). Allopurinol initiation was associated with a lower risk of all-cause mortality (matched HR 0.89 (95% CI 0.80 to 0.99)). When we limited the analysis to those with gout, the corresponding HR was 0.81 (95% CI 0.70 to 0.92). Allopurinol initiation and all-cause mortality in the general population http://dx.doi.org/10.1136 annrheumdis-2014-205269

16. Urinezuur is een cardiovasculaire risicofactor

17. Allopurinol bij DM • Vermindert insuline resistentie • Verlaagt CRP • Vertraagt Atherosclerose • Vermindert Microalbuminurie • Vermindert Chronische nierschade • Vermindert Linkerventrikelhypertrofie • Vermindert Oxidatieve stress

18. Allopurinol risico’s • Acute allergische reactie 4,7 promille • Gerelateerde mortaliteit 0,4 promille • Heupfractuur Odds Ratio (OR) 1,07 • Lager risico op Hartinfarct: OR 0,73 OR 0,52, dosis en duur afhankelijk • Atriumfibrilleren: OR 0,73 JAMA Intern Med. 2015;175(9):1550. Archives of Osteoporosis 2015, 10:36 annrheumdis-2012-202972 heartjnl-2014-306670 annrheumdis-2012

19. Metformine

20. Metformine risico’s • Bij eGFR<15: Mortaliteit OR 1,35 • Lactaat acidose 1,6 vs 1,3/100jaar (n.s.) • Bij eGFR > 30 ml/min/1,73m2: nuttig en veilig • Bij eGFR 15- 30 ml/min/1,73m2: waarschijnlijk nuttig en veilig.

21. Effectiveness and safety of metformin in 51675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register. BMJ Open. 2012 Jul 13;2(4).

23. Verschillen tussen ACE-remmers

24. CV Mortality in General Population (GP) & Dialysis Patients, By Race Sarnak MJ, Levey AS. Semin Dial. 1999;12:69-76.

25. Tot slot, praktisch: . . .

26. Mijn behandelingsstrategie bij: diabetes + chronische nierziekte(≥ microalbuminurie) ± hypertensie • ≥3x1uur bewegen/week; roken -; gewicht ; voeding. • Bloeddruk ≤125/75 mmHg • Start met een ACE-remmer, liefst een combinatiepil met een lage dosis diureticum ! • +/-Zoutarm dieet (<6 g NaCl/d) • Doseren totdat proteinuria ≤ 0,5 g/dag is • Behandel dislipidemie (LDL <2,5 mmol/L, Trigl ≤ 2,0) • HbA1C < 60 mm/mP C Chang, RZZ

27. 5 1 p<0.0001 17% decrease per 10 mmHg decrement in BP 0 . 5 1 1 0 1 2 0 1 3 0 1 4 0 1 5 0 1 6 0 1 7 0 UKPDS: Relationship Between BP Control And Diabetes-Related Deaths Hazard ratio Mean systolic blood pressure (mmHg) Adler AI, et al. BMJ. 2000;321:412-419. Reprinted by permission, BMJ Publishing Group.

28. Risk of Ischemic Heart Disease Related to SBP and Microalbuminuria N=2,085; 10 year follow-up Borch-Johnsen K, et al. Arterioscler Thromb Vasc Biol. 1999;19(8):1992-1997.

29. Relative Importance of CV Risk Factors in Diabetes 12 10.0 10 8 6.5 Odds Ratio 6 3.2 4 2.3 2 0 Microalbuminuria Smoking Diastolic BP Cholesterol Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.

30. Diabetes and Chronic Renal Disease as CV Risk

31. Behandeling van Diabetes moet dus in hoge mate zijn gericht op preventie van cardiovasculaire ziekte . . .

32. Cardiovasculaire Preventie in Diabetes

33. Vascular Protection: Glycaemic Control

34. Glycaemic Control for Vascular Protection: after all Patients are on ACE Inhibitor, ASA and Lipid Control (statin) - 5 Fatal and Non Fatal Myocardial Infarction 14% decrease per 1% decrement in HbA1c p<0.0001 CDA 2003 Glycaemic Targets A1c  7% for most patients A1c  6% when safely achievable Hazard ratio 1 0 . 5 0 5 6 7 8 9 1 0 1 1 Updated mean HbA1c UKPDS 35. BMJ 2000; 321: 405-12.

35. Vascular Protection:Diabetes and Control of Hypertension

36. Treatment Targets for Diabetic Renal Disease With Hypertension GLUCOSE GLUCOSE BP BP LIPIDS LIPIDS

37. 8 7 6 5 CVmortalityrisk 4 3 2 1 0 115/75 135/85 155/95 175/105 SBP/DBP (mm Hg) CV Mortality Risk Doubles withEach 20/10 mm Hg BP Increment* *Individuals aged 40-69 years, starting at BP 115/75 mm Hg. CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure Lewington S, et al. Lancet. 2002; 60:1903-1913. JNC VII. JAMA. 2003.

38. Goal BP Recommendations for Patients with DM or Renal Disease Renal Disease & Proteinuria >1g (JNC VI)

39. From Dr J Vora

40. Management of Chronic Renal Disease: Initial Diet Therapy • For patients with modest renal insufficiency, reduce intake of high biological quality protein* intake of 1 gm/kg body weight/day • For patients with marked renal insufficiency, reduce dietary protein intake to 0.8 gm/kg body weight/day • Restrict dietary sodium intake to 4-6 gm/day • Avoid foods rich in potassium *high biological quality proteins are those rich in essential amino acids

41. Impact of Blood Pressure Reduction on Mortality in Diabetes Mortality endpoints are: UK Prospective Diabetes Study (UKPDS) – “diabetes related deaths” Hypertension Optimal Treatment (HOT) Study – “cardiovascular deaths” in diabetics Turner RC, et al. BMJ. 1998;317:703-713. Hansson L, et al. Lancet. 1998;351:1755–1762.

42. Diabetes and Hypertension 3.0% No DM 2.0% DM Annual Mortality 1.0% 0.0% <120 120- 140- 160- 180- >200 139 159 179 199 Systolic BP Stamler J, et al, Diabetes Care, 1993;16(2):434-444.

43. Treatment Targets for Diabetic Renal Disease With Hypertension GLUCOSE GLUCOSE BP BP LIPIDS LIPIDS