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1 Diabetes and Renal Disease Dr Anne Kleinitz KRSS GP 12/11/2009.

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Presentation on theme: "1 Diabetes and Renal Disease Dr Anne Kleinitz KRSS GP 12/11/2009."— Presentation transcript:

1 1 Diabetes and Renal Disease Dr Anne Kleinitz KRSS GP 12/11/2009

2 2 Learning Objectives Type 1 vs Type 2 DM Diabetes Management Diabetic Complications Diabetic Nephropathy & ESKD

3 3 Type 1 Vs Type 2 DM

4 4 Type 1 Young Thin Insulin deficient (pancr. islet cell loss) Acute presentation Ketoacidosis Insulin initially Type 2 Older **** Overweight Insulin resistant (excess fat cell mass) Delayed diagnosis Diet & pills Insulin later or never

5 5 Type 1Type 2 OnsetAcute (symptomatic) Slow or insidious Clinical featuresWeight loss Polyuria Polydipsia Obese/over wt Strong FHx Ethnicity PCOS KetosisOften presentUsually absent Insulin (endog)Low or absentNormal or  Antibodies+ veve Assoc. autoimmune disorders YesNo

6 6

7 7 Type 1 Immune destruction of insulin producing cells in pancreas  leading to insulin deficiency. Prevalence –General population 12 – 17% –Indigenous 1% Acute onset, usually early in life

8 8 Type 2 Tissue resistance to insulin + defects in insulin secretion Gradual onset. One end of spectrum: –Insulin resistance but normal glucose tolerance  Impaired fasting glucose (IFG)  Impaired glucose tolerance “pre-diabetes” (IGT)  Type 2 DM

9 9 NormalIFGIGTDiabetes Fasting<5.55.5 – 6.9 and < 7 and≥ 7.0 2 hr post 75g glucose <7.8 7.8 – 11≥11.1 Random< 5.5≥ 11.1

10 10 Q. More common in T2 than T1? Age < 20 years Overweight High levels of blood insulin Prone to ketoacidosis Albuminuria at time of diagnosis

11 11 Q. More common in T2 than T1? Age < 20 yearsNO** OverweightYES High levels of blood insulinYES Prone to ketoacidosisNO Albuminuria at time of diagnosisYES

12 12 Prevalance (estimated) –Australia - 7.5% (but ½ unDx!) Indigenous –> 25 yrs 10 – 30% –3 – 4 x higher than general population –Higher in remote communities –Hospital admission for DM more common 12 x higher rates eg. Gestational DM –Contributes to CVD – 67% with DM died of CVD (1997-99) –Renal failure is also a common cause of death

13 13 Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes Obesity (BMI ≥30 kg/m 2 ) Diabetes 1994 2000 2007 No Data 26.0% No Data 9.0% CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics

14 14 1994

15 15 1995

16 16 1996

17 17 1997

18 18 1998

19 19 1999

20 20 2000

21 21 2001

22 22 2002

23 23 2003

24 24 2004

25 25 2005

26 26 2006

27 27 2007

28 28 Childhood Diabetes Rising T2DM, parallel with  obesity 10-14% of new paediatric DM ~ 50% in rural and remote Many likely undiagnosed Indigenous children disproportionately represented –> ½ of children with T2DM are indigenous Mx – Diet, exercise, Metformin and Insulin

29 29 Gestational diabetes Temporary Occurs in pregnancy and usually disappears after delivery Mother has much greater risk of developing diabetes later Morbidity

30 30 Metabolic Syndrome “Syndrome X” Associated with increased risk of CVD, CKD and death. DIAGNOSIS 1. Insulin resistance FBG > 5.6 or T2DM 2. Central Obesity WC > 94cm 3. Abnormal lipid profile: HDL Male < 1.03, Female < 1.29 4. Hypertension Sys > 130, dias >85

31 31

32 32

33 33

34 34 Treatment Options

35 35 ↓Glucose load: ↓ meal size & sugars ↑Insulin release (“secretogogues”) sulphonourea eg Gliclazide Insulin, Pancreas Tx ↓Insulin resistance (“insulin sensitizers”) Exercise & weight loss Metformin or glitazones

36 36 Diabetes management Life-style – physical activity –Weight ↓ –Smoking cessation –Alcohol reduction –Low fat diet Oral Medications –Increase insulin production (sulphonoureas) –Increase insulin sensitivity (metformin) Insulin

37 37 4:0016:0020:0024:004:00 BreakfastLunchDinner 8:00 12:008:00 Time Glargine Short acting Plasma insulin Short-acting & Long-acting Insulin

38 38 Aims in Mx (KAMSC Chronic Disease Protocol) HbA1C < 7% Total cholesterol < 4 mmol/L HDL > 1mmol/L, TG < 2, LDL < 1.8 BP < 125/80 BMI 17-25 WC < 100 cm NO smoking Alcohol – max 2 std drinks/day Exercise > 20 mins > 4 day/wk ACR < 3.5 mg/mmol

39 39 Multidisciplinary Team Care Diabetes: –Endocrinology/Dietetics Microvascular Disease: –Ophthalmology/Nephrology/Podiatry Macrovascular Disease: –Vascular Surgery/Cardiology

40 40 Specialised Treatments Insulin Pump –Tight BSL control for brittle diabetes –Awaiting autofeedback sensors Pancreas Transplantation –Insulin independence –Operative mortality

41 41 Diabetic Complications

42 42 Microvascular –Retinopathy –Nephropathy –Neuropathy peripheral & autonomic Macrovascular –Cerebrovascular –Cardiovascular –Peripheral vascular

43 43

44 44 Natural History of Type I 5 stages 1. Hyperfiltration at diagnosis (low s. creat) 2. Microalbuminuria > 5-10 years (urine ACR) 3. Overt proteinuria with ↑BP & retinopathy for 2-5 years, minimal haematuria (MSU) 4. CKD with normal-sized kidneys (renal U/S) 5. ESKD 18-24 months after CKD

45 45 StageDiabetes Duration Manifestations 10 – 3-5Renal hypertrophy  GFR 23-5 +Basement M thickening Mesangial expansion 37-15 +Microalbuminuria HPT 415-20 +Proteinuria HPT ↓ GFR 515 – 25+ESKD

46 46 Natural History of Type II Far commoner than Type I Long asymptomatic phase HPT, nephropathy & retinopathy often present at time of Dx Degree of proteinuria correlates with general vascular risk and 20x CKD risk

47 47 Hyperfiltration Phase Elevated GFR 2 o ↑BSL/BP/protein/obesity ↑Intra-glomerular pressure “Too good to be true” serum creatinine Accelerated progression to CKD

48 48 Albuminuria then Proteinuria Microalbuminuria first (lower MW) –Raised by ↑GFR (i.e. ↑BSL, ↑protein diet, fever, exercise) Spot urine ACR or PCR –more convenient than 24hr collection –more accurate than urinalysis –adjusts for fluid intake –underestimates the muscular patient

49 49 Diabetic Nephropathy From haemodynamic & metabolic stresses Metabolic stress –deposition of advanced glycosylation end products in connective tissue & sml vessels. May take 10-20 yrs but many T2DM asymptomatic for several yrs, hence nephropathy may already be present at Dx

50 50 1 st clinical sign is microalbuminuria (ACR) Kidney not able to catabolise albumin This can also occur transiently with –Fever –Exercise –Short term hyperglycaemia –High protein meal Hence, repeat at a later date/rule out reversible DM + HPT,  x 20 risk of progressive nephropathy DM + HPT + poor diabetic & lipid control,  x 40 risk

51 51 Nephropathy Risk Factors DM Type & Duration –20% of Type I after 20 years –40% of Type II any duration Poor diabetic control Hypertension Aboriginal > Indian > Caucasian Smokers Family history

52 52 Nephropathy Risk Factors Modifiable –HbA1c, BP & total cholesterol (Odds Ratio 43) –Obesity, smoking Non-modifiable –Age, ethnicity, male sex

53 53 Delaying Complications Tight diabetic control –Prevention of microvascular Cmplx Risk of hypos Tight BP control –Prevention and management of micro & macro Cmplx –Use ACEI, ARB’s or both combined

54 54 ACE Inhibitors can prevent progression of renal failure 120 160 200 240 280 320 350 400 80 0123456 Years Ann Intern Med 118 577-581.1993 Placebo Enalapril 85 90 95 100 105 110 80 0123456 Years Placebo Enalapril Normotensive Type 2 Diabetics Proteinuria (mg/day) % Initial GFR

55 55 ACEI/ARB Proteinuria Remission H L H L 30 40 50 60 70 80 90 2000 Jan 2000 20012002 Creatinine - Plasma umol/L H 0 500 1000 2000 Jan 2000 20012002 Protein/Creat Ratio - Urine mg/mmol

56 56 Use of ACEi/ARBs BUT: ARF risk if underperfused Hyperkalaemia risk with many types of pills (spironolactone) SO: Check BP & electrolytes at 1/12 and 6/12 Check all new pills

57 57 Q. Which features are typical of diabetic CKD at presentation ? Haematuria Small scarred kidneys Progress to ESKD in <2yrs Associated retinopathy  -blockers better than ACE-I Rx

58 58 Q. Which features are typical of diabetic CKD at presentation ? HaematuriaNO Small scarred kidneysNO Progress to ESKD in <2yrs NO Associated retinopathyYES  -blockers better than ACE-I RxNO

59 59 Diabetes and ESKD Reducing insulin requirements Difficult vascular access Accelerated macrovascular disease Advanced microvascular disease Frequent sepsis Silent ischaemia 2-3 x death rate vs non-DM patients

60 60 How can DM effect Dialysis? Autonomic neuropathy – may suffer hypotension increased by large fluid shift in HD Uncontrolled BSLs – may absorb some glucose in PD fluid Severe PVD – difficult to get vascular access for HD PVD may also affect peritoneum and reduce PD success Increased risk of infections – problem in both Transplants – new kidneys develop nephropathy, hence good glycaemic control important

61 61 Strict BSL Control in early Type I Target HbA 1 c < 7% For every 1%↓ HbA 1 c: –10% ↓CVD –40% ↓Microvascular Cmplx BUT: Doubles risk of hypoglycaemia Loss of control with DM duration: –50% at 3yr –30% at 6yr –15-25% at 9yr (= % patients with HbA1c < 7% on Met or OHA alone)

62 62 Strict BSL Control in DM CKD AND: Minimal benefit if overt proteinuria Diabetes “cured” by advancing CKD –reduced appetite and CHO intake –prolonged insulin half-life –false elevation of HbA 1 c by 0.5-1%

63 63 Metformin in CKD No hypos or weight gain Inexpensive BUT: –Renally-excreted –Excess doses → anorexia, diarrhoea –Dose adjust to GFR: 2g to 250mg/day –Protocol says eGFR 30 – 59 max 1gm/day cease when eGFR <30 but… –Risk of fatal lactic acidosis if unwell

64 64 Glitazones in DM Av.1% fall in HbA1c as monoRx or add-on Preserves beta-cell fn - use early Durable effect >3yrs BUT: –1-2/12 delayed onset –Average 4kg SC fat gain, visceral fat loss –Oedema (Na + /H 2 0, ↑vasc. permeability) –Expensive

65 65 Strict BP Control at any stage ½’s (or even stops) rate of fall in GFR Greater benefit than tight BSL control Falling BP Target = 120/70 currently Preferential use of ACEi/ARBs Complete regression of proteinuria possible Helps all micro- & macrovascular disease (Parving, UKPDS, Captopril Trial, MicroHOPE, IRMA/IDNT, JNC VI)

66 66 Use of ACEi/ARBs: actions Antihypertensive –↓ by salt excess, ↑by thiazides –need mean of 3 agents in mild CKD Antiproteinuric –30-50%↓ alone, 40-70%↓ together Renoprotective –corrects ↑GFR, expected 30% ↑creatinine

67 67 Laverman Kidney Int 2002 Combination ACEI/ARBs ↓ proteinuria by 90%

68 68 ACEI/ARB Proteinuria Remission H L H L 30 40 50 60 70 80 90 2000 Jan 2000 20012002 Creatinine - Plasma umol/L H 0 500 1000 2000 Jan 2000 20012002 Protein/Creat Ratio - Urine mg/mmol

69 69 Use of ACEi/ARBs: risks BUT: ON-TARGET –  CVD & death if no proteinuria Risk of ARF –Esp. if dry, in CCF, bilateral RAS, on NSAIDs Risk of hyperkalaemia in diabetic CKD –Esp. if high fruit/nut/choc diet, acidotic –Esp. if other K + -sparing Rx (NSAIDs, spironolactone, trimethoprim)

70 70 Use of ACEi/ARBs: guidelines SO: Always check BP & electrolytes 1 month after starting or adding thiazide Check after 1 week in high-risk patients Stop temporarily if unwell

71 71 Thank You Questions ? Questions ?

72 72References Mark Thomas. Nephrologist. Royal Perth Hospital. Kidney Diseases, 5 th Edition. National Kidney Foundation. 2009 Couzos and Murray. Aboriginal Primary Health Care, an evidence based approach. 3 rd edition. 2008 Murtagh. Murtagh’s General Practice. 4 th edition. 2007


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