CARBOHYDRATE METABOLISM
CARBOHYDRATE
BLOOD
GLUCOSA
GLYCOGEN FFA TRIGLYSERIDA
LIVER TISSUE AMINO ACID
PYRUVATE - LACTATE
ENERGY ATP + H
2
O + CO
2

NORMAL BLOOD SUGAR CONTROLE
BY HORMONAL REGULATION
BLOOD SUGAR (CONC.)
1. INSULIN
2. GLUCAGON
3. THYROXINE
4. GROWTH HORMONE
5. A.C.T.H
6. CORTICOSTEROID
7. EPINEPHRINE

NORMAL BLOOD SUGAR CONTROLE
BY INTERMEDIARY REGULATION
1. GLYCOGENESIS
2. GLYCOGENOLYSIS
3. GLUCONEOGENESIS
4. GLUCOLYSIS

BLOOD SUGAR CONCENTRATION
NORMAL DM
1. FASTING 70-110mg/dl > 126 mg./dl
2. POST PRAN < 150 mg/dl > 200 mg/dl
DIAL
3. NON FASTING 100-150 mg/dl > 200 mg/dl

CARBOHYDRATE METABOLISM
DISORDERS
- HYPERGLYCEMIC SYNDROME
- HYPOGLYCEMIC SYNDROME
- INBORN ERROR
- HORMONAL DISORDERS

DISTURBANCE OF CARBOHYDRATE
METABOLISM
- INSULIN DEFICIENCY, INSULIN RESISTENCY
- HORMONAL DISORDERS
CAUSES :
DIABETES MELLITUS

DIABETES MELLITUS
IS CHARACTERIZED BY CHANGES IN THE
METABOLISM OF EACH OF THE MAJOR BODY
FUELS (CARBOHYDRATE - FAT AND PROTEIN)
AND IS ASSOSIATED BY DISTURBANCES OF A
VARIETY OF HORMONES.

CLASSIFICATION OF DIABETES MELLITUS
1. IDDM INSULIN DEPENDENT DM
TYPE I DM
2. NIDDM NONINSULIN DEPENDENT DM
TYPE II DM
3. GESTATIONAL DM
4. MALNUTRITION RELATED DM
A. FCPD (FIBROCALCULOUS PANCREATIC DM)
B. PDPD (PROTEIN DEFICIENT PANCREATIC DM)
5. DM OTHER CAUSES

PATHOPHYSIOLOGY D.M
D.M
INSULIN DEFICIENT
HYPERGLYCEMIA
GLUCOSURIA
ACUTE CHONIC
D.M + STRESS
D. KETO-ACIDOSIS
MICROANGIOPATHY
D. COMA MACROANGIOPATHY

COMPLICATIONS OF DM
- MACROANGIOPATHY
- MICROANGIOPATHY
- DIABETIC RETINOPATHY
- DIABETIC NEPHROPATHY
- DIABETIC NEUROPATHY
- INFECTION, ABSCESS, GANGRENE
- HYPERLIPIDEMIA
-DIABETES KETOACIDOSIS - COMA
KETON BODIES
ACETO ACETIC ACID
B.HIDROXY BUTYRIC ACID
ACETON

LABORATORY EXAMINATIONS
1. URINE GLUCOSE (screening)
2. BLOOD GLUCOSE (diagnostic)
3. ORAL GLUCOSE TOLERANCE TEST (confirmatory test)
4. IV- GLUCOSE TOLERANCE TEST (confirmatory test)
5. HbA1C TEST (follow-up)
6. FRUCTOSAMIN TEST (follow-up)
7. C-PEPTIDE CONC (confirmatory test)
8. URINARY KETON (complication)
9. BLOOD KETON (complication)
10. MICROALBUMIN IN URINE (complication)

NORMAL
GLUCOSE
INTOLERANCE
DIABETES
MELLITUS
DIAGNOSIS
BS mg/dl BS
FASTING POSTPR
< 110
< 126
> 126
< 150
< 200
>200

ORAL GLUCOSE TOLERANCE TEST
(OGTT)
BS mg/dl
NORMAL DM
300
200
100
300
200
100
SEVERE
MILD
0 1 2 3 Hours 0 1 2 3 Hours

PRE-ANALYTIC STEPS
 Specimen of choice : venous blood; in certain condition/instruments : capillary blood


Sample of choice : serum or plasma, others : whole blood (venous or capillary blood)
Fasting : 8-10 hours
 Meal after fasting : food in usual amount

PRE-ANALYTIC STEPS (contd….)



Specimens handling :
Glycolysis ± 7 mg/dl/h in WB w/o inhibitors
At 4ºC ± 2 mg/dl/h will lost
 Bacterial contamination will decrease glucose level
 Delay time in serum containing blood clot :
< 90 minutes

PRE-ANALYTIC STEPS (contd….)
 OGTT
 Diet : must consists of > 159g of carbohydrate per day, over a period of 3 days
 Discontinue any drugs that can affect glucose plas-ma level 3 days before the test
 Fasting : 12 hours

PRE-ANALYTIC STEPS
(contd….)
OGTT
 A parallel urine sample must be taken for fasting glucose and ketone. A positive test strip results is a contraindication for OGTT

PRE-ANALYTIC STEPS (contd….) OGTT
 D-glucose : 75 g (adult)
1.75 g/kgBW (children) max up to 75 g
50 g for pregnant women
 Patients should remain seated during the test
 Blood samples are collected in 0; 60; 120 minutes

 ANALYTICAL STEPS
 METHODS : chemical & enzymatic
 Chemical methods are no longer used, because of lack of specificity, except ortho-toluidine method
 ENZYMATIC method :
 Glucose oxidase (less specific than hexokinase)
 Hexokinase (generally accepted reference method)

 GLUCOSE OXIDASE-PAP :
ß-D-glucose + O
2 glucose H
2
O gluconolactone oxidase O
2 gluconic acid + H
2
O
2 peroxidase
H
2
O
2
+ phenylamine-phenazone color changes + H
2
O
Measured by photometer in specific wavelength

 HEXOKINASE : hexokinase
Glucose + ATP glucose 6-phosphate + ADP
Mg ++
G6PD
Glucose 6-phosphate + NADP 6phosphogluconolactone + NADPH + H +
More expensive, but better in specificity and precision

 INTERPRETATION :
 Normoglycemia
 Hyperglycemia
 Hypoglycemia
 “Amended” insulin-to-glucose ratio :
Insulin µU/ml
X 100
Glucose – 30 (mg/dl)
Normal : 50 – 100 µU/mg

 INTERFERING FACTORS :
 Falsely high : dextrose iv-infusion, steroids, stress, infection, caffeine, nicotine, ß-blockers, adrenal gland infection, total parenteral nutrition (TPN), diuretics, estrogen, phenytoin
 Falsely low : insulin, alcohol, anabolic steroids, OAD

Principle :
Glucose reduces Cu 2+ to become Cu + and precipitated as Cu2O( red brick color substance)

3 ml benedict sol + 3 drops urine
100 °C

Result ;
Blue : negative
Green : (+)
Yellowish green : (++)
Yellow : (+++)
Red brick : (++++)

1
1

 Glukosa plasma bila kadarnya lebih dari normal, akan bereaksi dengan Hb di dalam eritrosit, menjadi
glycated hemoglobin secara ireversibel sepanjang masa hidup eristrosit (120 hari).

 Glycated hemoglobin yang terbentuk proporsional terhadap rerata kadar glukosa plasma selama 6-12 minggu dengan kadar ± 5% kadar total Hb A
 Normal kadar Hb A1c : 3% kadar Hb A kadar Hb A1a < 1% kadar Hb A1b < 2%
 Bila terjadi hiperglikemia, yang meningkat adalah HbA1C

 Glycated hemoglobin memberikan prediksi risiko progresif dari komplikasi diabetik.
 Pemeriksaan A1c digunakan untuk kontrol DM tentang kepatuhan pengobatan 2-3 bulan yang lalu.
 Tidak direkomendasi untuk diagnosis DM

 Hasil:
Kontrol DM baik
HbA1c HbA1-total
2,5-6,0% < 7,5%
Kontrol DM kurang baik 6,1-8,0% 7,6-
9,0%
Kontrol DM buruk > 8% > 9%

Metode pemeriksaan :
 Ion exchange column chromatography; HPLC.
 Untuk cut off A1c diambil sesuai dengan kadar Hb
A1 total yaitu = 5 % dari Hb dewasa (HbA)
 Bila < 1,1 x batas atas normal; komplikasi renal dan retinal jarang dijumpai.
 Bila > 1,7 x batas atas normal; pada > 70% kasus sudah terjadi komplikasi renal dan retinal.

 HbF lebih dari normal
 CRF tanpa/dengan hemodialisa
 Splenomegali
 Serum trigliserida tinggi
 Alkoholisme
 Keracunan Pb atau opiat.
 Fe defisiensi anemia

1. Masa hidup eritrosit menurun misalnya pada penyakit :
 Hemoglobinopati (HbS, HbC,
HbD)
 Anemia hemolitik
 Perdarahan akut atau kronis

2. Sesudah transfusi
3. Kehamilan
4. Penggunaan dosis tinggi Vit C atau E
A
1 c normal, tidak menghilangkan kemungkinan IGT

 A
1 c dapat meningkat bila kadar glukosa meningkat setelah terapi dihentikan dan tetap tinggi 2 – 4 minggu setelah terapi dilanjutkan.

 Bila kadar glukosa puasa<110 mg/dl;
A
1 c normal pada > 96% kasus
 Bila kadar glukosa puasa 110–125 mg/dl; A
1 c normal pada > 80% kasus
 Bila kadar glukosa puasa > 126 mg/dl;
A
1 c normal pada > 60% kasus