SUGIARTO

SUB DEVISI ENDOCRINOLOGY AND

METABOLIC OF DEPARTEMENT MEDICINE
OF MEDICINE FACULTY OF UNIVERSITY
SEBELAS MARET SURAKARTA
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
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)

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)
F/U
(y)
Initial level LDL TG HD
L
Drug Outcom
e
RR
R
(&)
Helsinki(P)
(Koskinen
etal)
135
men
49 5 IDL;5,2 -10 -26 6 Gemfibros
il
CHD
death,n
on fatal
MI
68
VA-
HIT(Sec)
(Rubin etal)
627
men
64 5,1 LDL;2,91
TG;1,76
HDL;0,83
0 -31 6 Gemfibros
il
CHD
death,
stroke,n
on fatal
MI
24
BIP (Sec) 309
(90%
men)
60 6,2 IDL;3,85
TG:1,64
HDL;0,90
-6,5 -20 17,
9
Bezafibrat MI or
sudden
death
9
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
OUTCOME PLACEBO
RATE(%)
RRR(%/95%
CI
P VALUE
MI,Stroke or CV
death
19,8 25(12-36) ,0004
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
RESULT OF THE HOPE STUDY
IN DIABETES PARTICIPANTS ( RAMIPRIL vs PLACEBO)
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
up
(mo)
Bata-
blocker
Estimated Risk
Reduction
Acute therapy
Gothenburg
Metololol

8,6

120

3

Metoprolol

0,41 (0,14-
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
RENAL
INVOLVEMENT
OUTCOME ACTIVE
RX
CONTR
OL
RRR (CI) NNT(CI) N
Type 1 DM
Microalumin
uria
Captopril
study group

Microalbuminuria

Progresion to
diabetic
nephropaty

Captopril
50 mg
bid

Placebo

69(16-840

15(3-18)

225
Captopril
study group
Dabetic
nephropaty
Doubling
serum
creatinine
Combined
ESRD, death,
or
transplantation
-


Captopril
25mg tid
Usual
HT Rx

-

43(16-69)

50(18-70)
11(4-18)


10(4-14)
409


-
Type 2 DM
Ahmad et al

Microalbuminuria


Progresion to
diabetic
nephropaty

Enalapril
10 mg
qd

Placebo


67

15,8

103
Ravid et al Microalbuminuria

Progresion to
diabetic
nephropaty
Enalapril
10 mg
qd
Placebo

71 3 (2-7) 94
Micro HOPE Microalbuminuria

Progresion to
diabetic
nephropaty
Ramipril
10 mg
qd
Placebo

24(3-40) 51(31-267) 3,57
7
GERSTEIN & HAYNES ,2001. EVIDENCE-BASED DIABETES CARE