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 (DM) Meaan Age (y) 49 F/U (y) Initial level LDL TG HD L Drug Outcom e RR R (&) 68

Helsinki(P) (Koskinen etal) VAHIT(Sec) (Rubin etal)

135 men

IDL;5,2

-10

-26

Gemfibros il

CHD death,n on fatal MI

627 men

64

5,1

LDL;2,91 TG;1,76 HDL;0,83

-31

Gemfibros il

CHD 24 death, stroke,n on fatal MI MI or sudden death 9

BIP (Sec)

309 (90% men)

60

6,2

IDL;3,85 TG:1,64 HDL;0,90

-6,5

-20

17, 9

Bezafibrat

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 RATE(%) RRR(%/95% CI P VALUE

MI,Stroke or CV 19,8 death MI 12.9 Stroke CV death Total death 6.1 9,7 14

25(12-36) ,0004 22(6-36) ,01

33(10-50) ,0074 37(21-51) ,0001 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 (75325 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 BETABLOCKER 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 up (mo) 3 Batablocker Estimated Risk Reduction

Acute therapy Gothenburg Metololol

8,6

120

Metoprolol

0,41 (0,141,18)

MIAMI
ISIS-1 Chronic therapy Norwegian Timolol BHAT

7,1
6,0

413
958

0.5
0,25

Metoprolol
Atenolol

0,5(0,25-0,98)
0,76(0,47-1,24

5,5 12,1

99 465

17 25

Timolol Propanolol

0,31(0,12-0,82) 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 CREATININECLEARANCE. LEVEL 1A

STUDY

STAGE OF RENAL INVOLVEMENT Microalbuminuria

OUTCOME

ACTIVE RX

CONTR OL

RRR (CI)

NNT(CI)

Type 1 DM Microalumin uria Captopril study group Captopril study group

Progresion to diabetic nephropaty Doubling serum creatinine Combined ESRD, death, or transplantation Progresion to diabetic nephropaty Progresion to diabetic nephropaty Progresion to diabetic nephropaty

Captopril 50 mg bid -

Placebo

69(16-840

15(3-18)

225

Dabetic nephropaty

Usual HT Rx -

43(16-69) 50(18-70)

11(4-18)

409

Captopril 25mg tid

10(4-14)

Type 2 DM Ahmad et al

Microalbuminuria

Enalapril 10 mg qd Enalapril 10 mg qd Ramipril 10 mg qd

Placebo

67

15,8

103

Ravid et al

Microalbuminuria

Placebo

71

3 (2-7)

94

Micro HOPE

Microalbuminuria

Placebo

24(3-40)

51(31-267)

3,57 7

GERSTEIN & HAYNES ,2001. EVIDENCE-BASED DIABETES CARE