Laboratory Diagnosis of

Diabetes Mellitus

Dr. Manoranjan Shrestha MD (IOM)

Department of Biochemistry
NAIHS- COM
 Objectives-
Diabetes Mellitus and its complication.

 Laboratory diagnosis of Diabetes Mellitus

 Diabetic ketoacidosis
 Hyperosmolar nonketotic hyperglycemic.
 Diabetic polyol pathways.
Clinical case-1
An 18-year-old girl consulted her family doctor because of weight loss in
spite of excessive hunger, on questioning she admitted to feeling thirsty
and has been passing more urine than normal. The physical examination
and family history are not significant. The doctor tested her urine and
found glycosuria.

Biochemical Investigation:
Fasting glucose 130 mg/dl (HbA1C, OGTT) ?
Random glucose 210 mg/dl IGT-Fasting N,
TAG 250 mg/dl elevated postload
VLDL 50 mg/dl IFG->110;<126
Potassium 5.5 mEq/L
Sodium 133 mEq/L
Urinary Microalbumin- 118mg/24h
Biochemical investigation in diabetes mellitus-

1. Fasting blood glucose- n 70- 110: > 125 mg/dl

 IFBG- 110- 125 mg/dl

 OGTT-
 Fasting blood glucose < 110mg/dl
 75 g glucose
 2 hour blood glucose n < 140 mg/dl; > 200 mg/dl
 2 hour blood glucose- 140- 200 mg/dl  ?

2. Post prandial (PP) blood glucose- n <140mg/dl

3. Random blood glucose- n < 140 mg/ dl

 Biochemical investigation in diabetes mellitus-

4. HbA1C- n < 6.5%

 Glycated or glycosylated hemoglobin- ?
 Condensation of glucose with N-terminal valine of each betta chain
of HbA1C.
 Diagnostic importance- used for monitoring of diabetic control.

5. Lipid profile- Hypertriglyceridemia

 Normally insulin inhibit HSL and activate LPL.
 Biochemical investigation in diabetes mellitus-

6. Serum electrolytes- Na+, K+

7. Urinary microalbumin-
 Normal urinary protein excretion < 150 mg/d; < 30mg/d is albumin.
 The value between normal and abnormal (macroalbuminuria
>300mg/d) => 30- 300 mg/d.
 Diagnostic significance- indication of incipient nephropathy which can
progress into establish nephropathy (> 300 mg/dl) this can be
prevented by Tx with ACE inhibitor.

8. Blood/ Urine ketone bodies- beta hydroxybuterate, acetoacetate.

9. Arterial blood gas analysis
 Diagnosis of DM

 Symptoms with
 Random blood glucose >200 mg/dl.
 Fasting blood glucose >126 mg/dl

 Without symptoms >1 occasion.

 Oral glucose tolerance test (used for diagnosing gestational

diabetes).

 HbA1c >6.5%
Clinical case-2
A 28 year old resident is admitted to the internal medicine ward
because of confusion, nausea and vomiting.
He is known type 1 DM. one day before his admission he went out to
celebrate his b’day and drank alcohol until he became intoxicated.
On P/E- PR- 115, BP-90/50, rapid deep breathing, dehydration, peculiar
fruity breath smell.

Investigation- ABGs- marked reduced HCO3, pH- 7.1, increased ketones

in blood, hyperglycemia, hyperkalemia.
U/A- glycosuria, Ketonuria.

Give the biochemical basis for your diagnosis?

 DKA is characteristic of Type I
 No insulin Glucose X cell sense low G ⃰  alternative pathway to
get G by ↑ Glucagon & Epinephrine activate HSL act on adipose
tissue

⃰ BUT actually there is HYPERGLYCEMIA:

o Renal glycosuria (urine Glucose +++)
o Polyuria and polydipsia (osmosis & dehydration)

Effect on Lipid: Ketone bodies

o Acetone breath
o Ketoacidosis
o H+ trigger respiratory center and hyperventilation i.e kusmaul
respiration.
Clinical case-3
A 56 year old man is known type 2 DM who has been receiving oral
hypoglycemic agent is brought to ER.
For approximately 2 weeks he had been treated for UTI with antibiotics.
On P/E- tachycardia, hypotension, severe dehydration with dry oral
mucosa and low urinary volume, patient is semiconscious and confused.

Investigation-
Blood glucose-900, serum osmolality- >350 mOsm/kg ABGs- normal
serum HCO3 U/A- glycosuria with no ketonuria
Hyperosmolar hyperglycemic coma/state (HONK)

Cause: the most common precipitating factors is non

compliance with treatment and or chronic infection.

Dx: blood glucose >600mg/dl

High serum osmolality
No ketone bodies.
 Diabetic polyol (sorbitol) pathway-

 Some of the pathological changes associated with diabetes like

cataract formation, peripheral neuropathy, nephropathy are believe
to be due to the accumulation of sorbitol.

 What is this sorbitol pathway?

 Conversion Glucose to fructose via sorbitol (aldose reductase,
sorbitol DH).
 Absent in liver but highly active in tissue that don not require insulin
for uptake of glucose eg- nerves, lens, retina, kidney.

 Sorbitol can not freely pass through cell membrane and accumulates
in these cells and due to its hydrophilic nature cause strong osmotic
effects leading to swelling of the cells.
 Diabetic polyol (sorbitol) pathway-

 Intracellular hyperglycemia is then metabolized by enzyme aldose

reductase to sorbitol, in this process intracellular NADPH is used as
cofactor.
 NADPH is also required as cofactor by enzyme glutathione reductase
for generation of reduced glutathione.

 Therefore, sustained hyperglycemia with depletion of intracellular

NADPH by aldose reductase leads to increased cellular susceptibility
to oxidative stress.