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