CARBOHYDRATE METABOLISM

CARBOHYDRATE

BLOODGLUCOSA

GLYCOGEN FFA TRIGLYSERIDA

LIVER TISSUE AMINO ACID PYRUVATE - LACTATE

ENERGY ATP + H2O + CO2

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.

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

CLASSIFICATION OF DIABETES MELLITUS

PATHOPHYSIOLOGY D.M

D.M INSULIN DEFICIENT

HYPERGLYCEMIA

GLUCOSURIA

ACUTE CHONIC

D.M + STRESS MICROANGIOPATHY

D. KETO-ACIDOSIS

D. COMA MACROANGIOPATHY

COMPLICATIONS OF DM- MACROANGIOPATHY- MICROANGIOPATHY

- DIABETIC RETINOPATHY- DIABETIC NEPHROPATHY- DIABETIC NEUROPATHY- INFECTION, ABSCESS, GANGRENE- HYPERLIPIDEMIA-DIABETES KETOACIDOSIS - COMA

KETON BODIESACETO ACETIC ACIDB.HIDROXY BUTYRIC ACIDACETON

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)

LABORATORY EXAMINATIONS

DIAGNOSIS

BS mg/dl BSFASTING POSTPR

NORMAL < 110 < 150

GLUCOSE < 126 < 200INTOLERANCE

DIABETES > 126 >200MELLITUS

ORAL GLUCOSE TOLERANCE TEST

(OGTT)

100

200

300

100

200

300

1 2 30 1 2 30Hours Hours

BS mg/dlNORMAL DM

SEVERE

MILD

BLOOD GLUCOSEPRE-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

LABORATORY TESTS

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

BLOOD GLUCOSE

PRE-ANALYTIC STEPS (contd….)

OGTTDiet : must consists of > 159g of carbohydrate

per day, over a period of 3 daysDiscontinue any drugs that can affect glucose

plas-ma level 3 days before the testFasting : 12 hours

BLOOD GLUCOSE

PRE-ANALYTIC STEPS (contd….) OGTTA parallel urine sample must be taken for fasting

glucose and ketone. A positive test strip results is a contraindication for OGTT

BLOOD GLUCOSE

PRE-ANALYTIC STEPS (contd….) OGTT

D-glucose : 75 g (adult) 1.75 g/kgBW (children) max up to 75 g 50 g for pregnant womenPatients should remain seated during the testBlood samples are collected in 0; 60; 120 minutes

BLOOD GLUCOSE

ANALYTICAL STEPSMETHODS : 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)

BLOOD GLUCOSE

GLUCOSE OXIDASE-PAP : glucose

H2O

ß-D-glucose + O2 gluconolactone

oxidase O2

gluconic acid + H2O2 peroxidaseH2O2 + phenylamine-phenazone

color changes + H2O

BLOOD GLUCOSE

Measured by photometer in specific wavelength

HEXOKINASE : hexokinaseGlucose + ATP glucose 6-phosphate +

ADP Mg++

G6PDGlucose 6-phosphate + NADP 6-

phosphoglucono-

lactone + NADPH + H+

More expensive, but better in specificity and precision

BLOOD GLUCOSE

INTERPRETATION :NormoglycemiaHyperglycemiaHypoglycemia

“Amended” insulin-to-glucose ratio : Insulin µU/ml Glucose – 30 (mg/dl)Normal : 50 – 100 µU/mg

POST-ANALYTICAL STEPS

X 100

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

POST-ANALYTICAL STEPS

BENEDICT’S TES

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 : negativeGreen : (+)Yellowish green : (++)Yellow : (+++)Red brick : (++++)

GlycohemoglobinGlycated Hemoglobin

Hb A1C atau A1c

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: HbA1c HbA1-total

Kontrol DM baik 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 normalCRF tanpa/dengan hemodialisaSplenomegaliSerum trigliserida tinggi AlkoholismeKeracunan Pb atau opiat.Fe defisiensi anemia

Peningkatan kadar A1c menunjukkan pasti DM bila tak ada faktor-faktor lain yang menyebabkan A1c meningkat :

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

A1c menurun pada :

2. Sesudah transfusi3. Kehamilan4. Penggunaan dosis tinggi Vit C atau E

A1c normal, tidak menghilangkan kemungkinan IGT

A1c menurun pada :

A1c dapat meningkat bila kadar glukosa meningkat setelah terapi dihentikan dan tetap tinggi 2 – 4 minggu setelah terapi dilanjutkan.

INTERPRETASI

Bila kadar glukosa puasa<110 mg/dl; A1c normal pada > 96% kasusBila kadar glukosa puasa 110–125 mg/dl;

A1c normal pada > 80% kasusBila kadar glukosa puasa > 126 mg/dl; A1c normal pada > 60% kasus

INTERPRETASI

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