EVIDENCE-BASED

MEDICINE
SUGIARTO

SUB DEVISI ENDOCRINOLOGY AND

METABOLIC OF DEPARTEMENT MEDICINE
OF MEDICINE FACULTY OF UNIVERSITY
SEBELAS MARET SURAKARTA
EVIDENCE-BASED
MEDICINE ?
 CURENT BEST EVIDENCE FROM CLINICAL CARE
RESEARCH INTO CLINICAL PRACTICE

 MANAGING INDIVIDUAL PATIENT.

 THE CARE OF PEOPLE WITH DISEASE.

 CLINICAL EVIDENCE RELATED

 DIABETES
 CARDIVASCULER.
 HIPERTENTION.
 KIDNEY DISEASE
HEALTH CARE RESEARCH
OF DISEASE
 DIAGNOSIS
 PROGNOSIS AND RISK
 PREVENTION
 TREATMENT
 COMPLICATION
RATING EVIDENCE FOR
CLINICAL RECOMMENDATIONS
 LEVEL 1 A :
 SYSTEMATIC OVERVIEWS OR META-ANALYSES
OF MULTIPLE-RANDOMIZED CONTROLLED
TRIAL.
 LARGE RANDOMIZED CONTROLLED TRIAL
WITH ADEQUATE POWER TO ANSWER THE
QUESTION.
 LEVEL 1 B :
 NONRANDOMIZED CLINICAL TRIAL OR COHORT
STUDY WITH INDISPUTABLE RESULTS.
 LEVEL 2 :
 RANDOMIZED CONTROLLED TRIAL OR RCT
OVERVIEWS THAT DO NOT MEET LEVEL 1
CRITERIA.

 LEVEL 3:
 NONRANDOMIZED CLINICAL TRIAL OR COHORT
STUDY.

 LEVEL 4 :
 OTHER STUDY DESIGNS AND EVIDENCE
( CONSENSUS)
1.DIABETES MELLITUS
 METABOLIC DISORDER CHARACTERISTIC :
 FASTING PLASMA GLUCOSE LEVEL≥ 126 mg/dl
OR

 2-HOUR PLASMA GLUCOSE LEVEL ≥ 200 mg/dl.

 HIGHER GLUCOSE LEVEL PREDICT HIGHER

OF MICROVASCULER AND MACROVASCULER
DISEASE

 LEVEL 1
THE CLINICAL PRESENTATION OF
DIABETIC
 AGE < 40 WITH IDEAL BODY WEIGHT(<) HAVE TIPE 1
DIABETES
 AGE > 40 WITH OVER WEIGHT HAVE TIPE 2 DIABETES
 LEVEL 3.

 TIPE 2 DIABETES, ANTI-GAD/ ISLET CELL ANTIBODY 

PREDICTING INSULIN REQUIREREMENT.
 LEVEL 1.

 C-PEPTIDE TO HAVE A GREATER SENSITIVITY AND

SPECIVITY THEN EITHER CLINICAL FEATURE OR
PRESENCE OF AUTOANTIBODIES IN DEFERENTIATING TIPE
1 AND TIPE 2 DIABETES.
 LEVEL 3
QUALITY OF LIFE IN ADULT WITH
DIABETES
 OVERALL QUALITY OF LIFE IS IMPAIRED FOR PATIENTS WITH
DIABETES AND SIMILER WITH OTHER CHRONIC DISEASE
 LEVEL 4.

 THE SHORT TERM, INTESIVE THERAPY DOES NOT IMPROVE QOL

FOR PATIENT WITH TIPE 1 AND TIPE 2 DIABETES , BECAUSE
ADVERSE EFFECT FROM HYPOGLYCEMIA, WEIGHT GAIN AND
SELF-CARE REGIMEN.
 LEVEL1

 THERAPY OF THE CHRONIC COMPLICATION MAY IMPROVE QOL

 LEVEL 1.

 TARGETED BEHAVIORAL PROGRAMS MAY IMPROVE QOL.

 LEVEL 2
DIABETIC KETOACIDOSIS
 PATIENTS TREATED WITH INTENSIVE REGIMENT,CONTINOUS
SUBCUTANEUS INSULIN INFUTION IS ASSOCIATED WITH A GREATER
RISK OF DIABETES KETOACIDOSIS
 LEVEL 1A.

 TREATMENT :
 NORMAL SALINE 500ml/h FOR 4 HOURS,THEN 250 ml/h
 LEVEL 2.

 CONTINOUS INSULIN INFUTION (0,1 u RI /kg, BOLUS,THEN 0,1 U/kg/h.

 LEVEL 2.

 BICARBONAT THERAPY
 LEVEL 2.

 PHOSPHAT REPLACEMENT.
 LEVEL 2.

 MORTALITY FROM DKA RANGE 0,65-3,3 % WITH HIGHER RATES IN

OLDER PATIENT.
 LEVEL 4
 2. CARDIOVASCULAR
DISEASES
 DIABETES IS AN INDEPENDENT RISK FACTOR FOR FUTURE
CARDIOVASCULAR DISEASE EVENT IN GENERAL
POPULATION
 LEVEL 1.

 PEOPLE WITH DIABETES WHO HAVE HAD A PREVIOUS CV

EVENT OR WHO HAVE EVIDENCE OF CV DISEASE ARE TWO –
THREE TO HAVE CV EVENT THAN ARE DIABETIC PEOPLE NO
PREVIOUS CV EVENT
 LEVEL 1

 PLASMA GLUCOSE LEVEL IS A CONTINOUS RISK FACTOR

FOR CV EVENT IN PEOPLE WITH TIPE 1 AND TIPE 2
DIABETES.
 LEVEL 1.
 ELEVETED BLOOD PRESURE IS A CONTINOUS RISK
FACTOR FOR CV EVENTS IN PEOPLE WITH DIABETES.
 LAVEL 1.

 MICROALBUMINURIA DOUBLES THE RISK FACTOR FOR CV

EVENTS IN PEOPLE WITH DIABETES.
 LEVEL 1.

 CLINICAL PROTEINURIA CONSISTENT WITH DIABETIC

NEPHROPATY INCREASE THE RISK FACTOR OF CV EVENT
AND TOTAL MORTALITY GREATER THAN TWOFOLD
 LEVEL 1.

 PATIENT WITH DIABETES A HISTORY OF CHEST PAIN IS AN

UNRELIABLE TEST FOR PRESENCE OF MYOCADIAL
INFARCTION.
 LEVEL 1.
 INTENSIFIED INSULIN THERAPY MY REDUCE THE RISK OF CV
EVENT WITH TYPE 1 DIABETES.
 LEVEL 2.

 TARGETING INTENSIVE GLYCEMIC CONTROL WITH INSULIN OR

ORAL AGENT MY REDUCE THE RISK OF CV EVENT IN TYPE 2
DIABETES
 LEVEL 2.

 INSULIN INFUSION FOLLOWED BY AMBULATORY INTENSIVE

INSULIN THERAPY AFTER AN MYOCARDIAL INFARCTION
REDUCES MORTALTY BY 30 % IN PEOPLE WITH TYPE E
DIABETES.
 LEVEL 1A.

 IN PEOPLE DIABETES INTERVENTION WITH DIURETIC, BETA-

BLOCKER, CALCIUM-CHANEL BLOCKER AND ANGIOTENSI
CONVERTIG ENZYM (ACE) INHIBITOR THAT DECREASE
SYSTOLIC BLOOD PRESURE BY 5- 10 mg Hg RESULT IN A 20-30 %
RRR IN CV EVENT.
 LEVEL 1A.
3.REDUCTION BLOOD PRESURE
 SOME BUT NOT ALL, LARGE TRIAL SUGGEST THAT ACE
INHIBITOR MAY BE SUPERIOR TO CALCIUM- CHANEL BLOCKER
WHEN USE TO TREAT HYPERTENSION IN PEOPLE WITH
DIABETES.
 LEVEL 1A.

 FIRST-LINE THERAPY TO TREAT HYPERTENSION IN PEPLE WITH

DIABETES, ALPHA-BLOCKER LEAD TO A 20% HIGHER RISK OF CV
EVENT THAN DO DIURETIC.
 LEVEL 1A.

 TRIAL SUGGEST THAT IN PATIENT WITH DIABETES AND

MODESTLY ELEVATED LDL LEVEL, THERAPY WITH THE “STATIN”
CLASS OF AGENT REDUCE THE RISK OF CV EVENT BY 20-30%.
 LEVEL 2.

 TRIAL SUGGEST THAT IN PATIENT WITH DIABETES, THERAPY

WITH THE “FIBRATE” CLASS OF AGENT MAY REDUCE THE RISK
OF CV EVENT.
 LEVEL 2
 LARGE STUDY TRIAL WITH “FIBRAT” AND CARDIOVASCULAR
DISEASE IN PEOPLE TYPE 2 DIABETES

Study N Meaan F/U Initial level LDL TG HD Drug Outcom RR

(DM) Age (y) (y) L e R
(&)

Helsinki(P) 135 49 5 IDL;5,2 -10 -26 6 Gemfibros CHD 68

(Koskinen men il death,n
etal) on fatal
MI
VA- 627 64 5,1 LDL;2,91 0 -31 6 Gemfibros CHD 24
HIT(Sec) men TG;1,76 il death,
(Rubin etal) stroke,n
HDL;0,83
on fatal
MI
BIP (Sec) 309 60 6,2 IDL;3,85 -6,5 -20 17, Bezafibrat MI or 9
(90% TG:1,64 9 sudden
men) death
HDL;0,90

GERSTEIN & HAYNES ,2001. EVIDENCE-BASED DIABETES CARE

ACE INHIBITOR
 HOPE STUDY :
 RAMDOMISED 9.541 PEOPLE (AGE >55
TH) FOLLOWED 4,5 YEARS.

 RAMIPRIL 3.654 DIABETES AND

PREVIOUS CV DISEASE OR 1 OR
MORE CV RISK FACTOR.

 CONTROL : PLACEBO
 RESULT OF THE HOPE STUDY
IN DIABETES PARTICIPANTS ( RAMIPRIL vs PLACEBO)

OUTCOME PLACEBO RRR(%/95% P VALUE

RATE(%) CI

MI,Stroke or CV 19,8 25(12-36) ,0004

death
MI 12.9 22(6-36) ,01

Stroke 6.1 33(10-50) ,0074

CV death 9,7 37(21-51) ,0001
Total death 14 24(8-37) ,004

GERSTEIN & HAYNES ,2001. EVIDENCE-BASED DIABETES CARE

 ACE INHIBITOR TO OTHER EFFECTIVE THERAPIES
REDUCE THE RISK OF CV EVENTS BY 25% IN
HIGH-RISK PEOPLE WITH DIABETES.
 LEVEL 1A.

 PATIENT WITH DIABETES ASPIRIN THERAPY (75-

325 mg/dl) REDUCE THE RISK OF CV EVENT IN
HIGH-RISK PEOPLE WITH DIABETES.
 LEVEL 1A.

 PATIENT WITH DIABETES STUDY SHOW

MORTALITAS REDUCTION DUE TO BETA-
BLOCKER OF 30-40% IN DIABETES PATIENT WITH
ESTABLISHED CORONARY ARTERY DISEASE.
 LEVEL 2.
LARGE TRIAL AND EPIDEMIOLOGIES STUDIES
(POS-MYOCARDIAL INFARCTION OF THE
EFFFECT OF BETA-BLOCKER ON MROTALITY.
%DM N(DM) Follow Bata- Estimated Risk
up blocker Reduction
(mo)
Acute therapy
Gothenburg 8,6 120 3 Metoprolol 0,41 (0,14-
Metololol 1,18)
MIAMI 7,1 413 0.5 Metoprolol 0,5(0,25-0,98)

ISIS-1 6,0 958 0,25 Atenolol 0,76(0,47-1,24

Chronic therapy
Norwegian Timolol 5,5 99 17 Timolol 0,31(0,12-0,82)
BHAT 12,1 465 25 Propanolol 0,61(0,35-1.08)

GERSTEIN & HAYNES ,2001. EVIDENCE-BASED DIABETES CARE

 4.KIDNEY DISEASE
 PROGNOSIS

 RISK FOR KIDNEY FAILUR DUE TO DIABETES IN RECENT POPULATION –BASE

CASE-CONTROL STUDY FROM THE NORTHEASTERN USA WAS 42% OVERAL
(21% FOR TYPE 2 DIABETES)
 LEVEL 1

 COMULATIVE INCIDENCE OF DIABETIC NEPHROPATY FROM EUROPEAN

REGISTRY DAT APPEARS TO BE STABLE OVER THE LAST 20 YEARS, WITH AN
INCIDENCE OF 20% AT 24 YAERS.
 LEVEL 1.

 DEGREE OF GLYCEMIC AS MEASURE BYTHE GLYCATE HAEMOGLOBIN, IS

STRONG INDEPENDENT RISK FACTOR FOR ALBUMINURIA AND RENAL
INSUFISINCY.
 LEVEL 1.

 HIGHER SYSTOLIC AND DIASTOLIC BLOOD PRESURE, MALE SEX,LONGER

DURATION OF DIABETES, AND HIGHER TOTAL CHOLESTEROL,ARE
INDEPENDENT RISK FACTOR FOR RENAL INSUFFICIENCY.
 LEVEL 1

 SMOKING INCREASE THE RISK OF PROGRESSION OF NEPROPATHY.

 LEVEL 1.
 DIAGNOSIS

 DIABETIC NEPHROPATY IS DIAGNOSED CLINICALLY AND NOT BY

RENAL BIOPSY; A URINARY ALBUMIN EXCRETION (UAE) > 300 mg/dl
AND APPROPIATE TIME COURSE IN THE ABSENCE OF OTHER
OBIVIOUS SECONDARY CAUSE OF RENAL DISEASE IN DIABETERS
DEFINES DIABETIC NEPHROPATY IN TYPE 1 DIABETES WITH NEAR
100%.(LEVEL 3). I TYPE 2 DIABETES THE SPECIFITY IS REDUCE TO
88% (LEVEL4).

 THE A/C RATIO IS HE BEST SCREENING TEST FOR

MICROALBUMINURIA, WITH HIGH SENSITIVITY AND SPECIFICITY
FOR CUTOFF OF 2 TO 3 mg/mmol.
 Level 1.

 MICROALBUMINURIA IS AN IMPORTANT RISK FACTOR FOR

DIABETIC NEPHROPATY IS APPROXIMATELY 4% PER YEARS FOR
TYPE 1 AND 4,7 % FOR TIPE 2 DIABETES.
 LEVEL 1.
 MANAGEMENT

 PEOPLE WITH TYPE 1 DIABETES, GLUCOSE LOWERING USING INTENSIVE INSULIN

THERAPY REDUCES THE RISK OF MICROALBUMINURIA AND THE PROGRESSION OF
ALBUMINURIA.
 LEVEL 1 A.

 PEOPLE WITH TYPE 2 DIABETES, GLUCOSE LOWERING REDUCES THE RISK OF

MICROALBUMINURIA AND RENAL INSUFFICIENCY.
 LEVEL 1 A.

 BLOOD PRESURELOWERING REDUCES THE DECLINE IN GFR AND ALBUMIURIA’

 LEVEL 1A.

 ANGIOTENSIN COVERTING ENZYME INHIBITOR REDUCE THE RATE OF DIABETIC

NEPHROPATY IN PATIENT WITH MICROALBUMINURIA.
 LEVEL 1A.

 ANGIOTENSIN COVERTING ENZYME INHIBITOR REDUCE THE RATE OF DEATH,

DIALYSIS, OR TRANSPLANTATION IN PATIENT WITH TYPE 1 DIABETES, OVERT
NEPHROPATY AND IMPARED RENAL FUNCTION.
 LEVEL 1A.

 PROTEIN RETRICTION REDUCES THE DECLINE IN THE GFR AND CREATININE-

CLEARANCE.
 LEVEL 1A
STUDY STAGE OF OUTCOME ACTIVE CONTR RRR (CI) NNT(CI) N
RENAL RX OL
INVOLVEMENT
Type 1 DM
Microalumin Microalbuminuria Progresion to Captopril Placebo 69(16- 15(3-18) 225
uria diabetic 50 mg 840
Captopril nephropaty bid
study group
Captopril Dabetic Doubling - Usual 43(16-69) 11(4-18) 409
study group nephropaty serum HT Rx
creatinine 50(18-70)
Combined Captopril - 10(4-14) -
ESRD, death, 25mg tid
or
transplantation
Type 2 DM
Ahmad et al Microalbuminuria Progresion to Enalapril Placebo 67 15,8 103
diabetic 10 mg
nephropaty qd
Ravid et al Microalbuminuria Progresion to Enalapril Placebo 71 3 (2-7) 94
diabetic 10 mg
nephropaty qd
Micro HOPE Microalbuminuria Progresion to Ramipril Placebo 24(3-40) 51(31-267) 3,57
diabetic 10 mg 7
nephropaty qd

GERSTEIN & HAYNES ,2001. EVIDENCE-BASED DIABETES CARE