1 diabetes and renal disease dr anne kleinitz krss gp 12/11/2009
Post on 02-Apr-2015
218 Views
Preview:
TRANSCRIPT
11
Diabetes and Diabetes and Renal DiseaseRenal Disease
Dr Anne KleinitzDr Anne Kleinitz
KRSS GPKRSS GP
12/11/200912/11/2009
22
Learning ObjectivesLearning Objectives
• Type 1 vs Type 2 DM• Diabetes Management• Diabetic Complications• Diabetic Nephropathy & ESKD
33
Type 1 Vs Type 2 DMType 1 Vs Type 2 DM
44
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
55
Type 1 Type 2
Onset Acute (symptomatic)
Slow or insidious
Clinical features Weight lossPolyuriaPolydipsia
Obese/over wtStrong FHx EthnicityPCOS
Ketosis Often present Usually absent
Insulin (endog) Low or absent Normal or
Antibodies + ve ve
Assoc. autoimmune disorders
Yes No
66
77
Type 1Type 1
• Immune destruction of insulin producing cells in pancreasleading to insulin deficiency.
• Prevalence– General population 12 – 17% – Indigenous 1%
• Acute onset, usually early in life
88
Type 2Type 2
• Tissue resistance to insulin + defects in insulin secretion
• Gradual onset. One end of spectrum:– Insulin resistance but normal glucose
toleranceImpaired fasting glucose (IFG)Impaired glucose tolerance “pre-diabetes”
(IGT)Type 2 DM
99
Normal IFG IGT Diabetes
Fasting <5.5 5.5 – 6.9 and
< 7 and ≥ 7.0
2 hr post 75g glucose
<7.8 <7.8 7.8 – 11 ≥11.1
Random < 5.5 ≥ 11.1
1100
Q. More common in T2 than T1?Q. More common in T2 than T1?
• Age < 20 years• Overweight• High levels of blood insulin• Prone to ketoacidosis• Albuminuria at time of diagnosis
1111
Q. More common in T2 than T1?Q. More common in T2 than T1?
• Age < 20 years NO**• Overweight YES• High levels of blood insulin YES• Prone to ketoacidosis NO• Albuminuria at time of diagnosis YES
1122
• 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
1133
Age-adjusted Percentage of U.S. Adults Who Were Obese or Who Had Diagnosed Diabetes
Obesity (BMI ≥30 kg/m2)
Diabetes
1994
1994
2000
2000
2007
2007
No Data <14.0% 14.0-17.9% 18.0-21.9% 22.0-25.9% >26.0%
No Data <4.5% 4.5-5.9% 6.0-7.4% 7.5-8.9% >9.0%
CDC’s Division of Diabetes Translation. National Diabetes Surveillance System available at http://www.cdc.gov/diabetes/statistics
1144
1994
1155
1995
1166
1996
1177
1997
1188
1998
1199
1999
2200
2000
2211
2001
2222
2002
2233
2003
2244
2004
2255
2005
2266
2006
2277
2007
2288
Childhood DiabetesChildhood 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
2299
Gestational diabetesGestational diabetes
• Temporary• Occurs in pregnancy and usually
disappears after delivery• Mother has much greater risk of
developing diabetes later• Morbidity
3300
Metabolic SyndromeMetabolic Syndrome“Syndrome X”“Syndrome X”
• Associated with increased risk of CVD, CKD and death.
• DIAGNOSIS1. Insulin resistance
• FBG > 5.6 or T2DM
2. Central Obesity • WC > 94cm
3. Abnormal lipid profile: HDL • Male < 1.03, Female < 1.29
– Hypertension• Sys > 130, dias >85
3311
3322
3333
3344
Treatment OptionsTreatment Options
3355
Treatment OptionsTreatment Options
• ↓Glucose load: ↓ meal size & sugars
• ↑Insulin release (“secretogogues”) sulphonourea eg
Gliclazide Insulin, Pancreas Tx
• ↓Insulin resistance (“insulin sensitizers”) Exercise & weight loss
Metformin or glitazones
3366
Diabetes managementDiabetes management
• Life-style– physical activity– Weight ↓– Smoking cessation– Alcohol reduction– Low fat diet
• Oral Medications– Increase insulin production (sulphonoureas)– Increase insulin sensitivity (metformin)
• Insulin
3377
4:00 16:00 20:00 24:00 4:00
Breakfast Lunch Dinner
8:0012:008:00
Time
Glargine
Short acting
Pla
sma insu
linShort-acting & Long-acting InsulinShort-acting & Long-acting Insulin
3388
Aims in Mx Aims in Mx (KAMSC Chronic Disease Protocol)(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
3399
Multidisciplinary Team CareMultidisciplinary Team Care
• Diabetes:– Endocrinology/Dietetics
• Microvascular Disease:– Ophthalmology/Nephrology/Podiatry
• Macrovascular Disease:– Vascular Surgery/Cardiology
4400
Specialised TreatmentsSpecialised Treatments• Insulin Pump
– Tight BSL control for brittle diabetes– Awaiting autofeedback sensors
• Pancreas Transplantation– Insulin independence– Operative mortality
4411
Diabetic ComplicationsDiabetic Complications
4422
Diabetic ComplicationsDiabetic Complications
• Microvascular– Retinopathy– Nephropathy– Neuropathy
• peripheral & autonomic
• Macrovascular– Cerebrovascular– Cardiovascular– Peripheral vascular
4433
4444
Natural History of Type INatural 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
4455
Stage Diabetes Duration
Manifestations
1 0 – 3-5 Renal hypertrophy GFR
2 3-5 + Basement M thickeningMesangial expansion
3 7-15 + MicroalbuminuriaHPT
4 15-20 + ProteinuriaHPT↓ GFR
5 15 – 25+ ESKD
4466
Natural History of Type IINatural 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
4477
Hyperfiltration PhaseHyperfiltration Phase
• Elevated GFR 2o ↑BSL/BP/protein/obesity
• ↑Intra-glomerular pressure
• “Too good to be true” serum creatinine
• Accelerated progression to CKD
4488
Albuminuria then ProteinuriaAlbuminuria 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
4499
Diabetic NephropathyDiabetic 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
5500
• 1st 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
5511
Nephropathy Risk FactorsNephropathy 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
5522
Nephropathy Risk FactorsNephropathy Risk Factors
• Modifiable– HbA1c, BP & total cholesterol (Odds Ratio 43)
– Obesity, smoking
• Non-modifiable– Age, ethnicity, male sex
5533
Delaying ComplicationsDelaying 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
5544
ACE Inhibitors can prevent ACE Inhibitors can prevent progression of renal failureprogression of renal failure
120
160
200
240
280
320
350
400
800 1 2 3 4 5 6
Years
Ann Intern Med 118 577-581.1993
Placebo
Enalapril 85
90
95
100
105
110
800 1 2 3 4 5 6
Years
Placebo
Enalapril
Normotensive Type 2 Diabetics
Proteinuria
(mg/day)
% Initial GFR
5555
ACEI/ARB Proteinuria ACEI/ARB Proteinuria RemissionRemission
H
L
H
L
30
40
50
60
70
80
90
2000Jan 2000
2001 2002
Creatinine - Plasma
umol
/L
H 0
500
1000
2000Jan 2000
2001 2002
Protein/Creat Ratio - Urine
mg/
mm
ol
5566
Use of ACEi/ARBsUse 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
5577
Q. Which features are typical of Q. Which features are typical of diabetic CKD at presentation ?diabetic CKD at presentation ?
• Haematuria• Small scarred kidneys• Progress to ESKD in <2yrs• Associated retinopathy• β-blockers better than ACE-I Rx
5588
Q. Which features are typical of Q. Which features are typical of diabetic CKD at presentation ?diabetic CKD at presentation ?
• Haematuria NO• Small scarred kidneys NO• Progress to ESKD in <2yrs NO• Associated retinopathy YES• β-blockers better than ACE-I Rx NO
5599
Diabetes and ESKDDiabetes 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
6600
How can DM effect Dialysis?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
6611
Strict BSL Control in early Type IStrict BSL Control in early Type I
• Target HbA1c < 7%• For every 1%↓ HbA1c:
– 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)
6622
Strict BSL Control in DM CKDStrict 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 HbA1c by 0.5-1%
6633
Metformin in CKDMetformin 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
6644
Glitazones in DMGlitazones 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+/H20, ↑vasc. permeability)
– Expensive
6655
Strict BP Control at any stageStrict 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)
6666
Use of ACEi/ARBs: actionsUse 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
6677
Laverman Kidney Int 2002
Combination ACEI/ARBs ↓ proteinuria by 90%
6688
ACEI/ARB Proteinuria ACEI/ARB Proteinuria RemissionRemission
H
L
H
L
30
40
50
60
70
80
90
2000Jan 2000
2001 2002
Creatinine - Plasma
umol
/L
H 0
500
1000
2000Jan 2000
2001 2002
Protein/Creat Ratio - Urine
mg/
mm
ol
6699
Use of ACEi/ARBs: risksUse 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)
7700
Use of ACEi/ARBs: guidelinesUse 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
7711
Thank YouThank You
Questions ?Questions ?
7722
ReferencesReferences
• Mark Thomas. Nephrologist. Royal Perth Hospital.
• Kidney Diseases, 5th Edition. National Kidney Foundation. 2009
• Couzos and Murray. Aboriginal Primary Health Care, an evidence based approach. 3rd edition. 2008
• Murtagh. Murtagh’s General Practice. 4th edition. 2007
top related