Page 580 - Concise Pathology for Exam Preparation ( PDFDrive )

20 Endocrinology 565

Glycylated Haemoglobin
During the 120-day lifespan of a red cell, haemoglobin A and other forms become glycated
due to nonenzymatic, largely irreversible, post-translational attachment of glucose to the
a- and b-chains. Degree of glycation is directly proportional to the level of glucose in the
blood, and it has been shown that amount of glycated haemoglobin present in blood is a
reflection of average blood glucose level over the lifespan of a red cell. Thus, quantitative
determination of glycated haemoglobin has become a useful adjunct in assessment of ef-
ficacy of long-term therapeutic control of diabetic patients. Glycated haemoglobin can be
measured in several ways. The two most common methods are ion exchange and affinity
chromatography. When measured by ion exchange, the results are reported as HbA 1c
Reference Range: 3.8–6.3%; target for therapy is ,7%.

Fructosamine Test
As albumin also contains free amino groups, nonenzymatic reaction with glucose in
plasma occurs. Therefore, glycated albumin can serve as a marker to monitor blood glu-
cose. Glycated albumin provides a retrospective measure of average blood glucose concen-
tration over a period of 1–3 weeks. Under alkaline conditions, glycated proteins (ke-
toamine) reduce nitroblue tetrazolium (NBT) to formazan. In the fructosamine test,
absorption of formazan at 530 nm is photometrically measured and compared with ap-
propriate standards to determine the concentration of glycated proteins in plasma, the
major part being contributed by albumin.

Determination of Insulin and C-peptide
Insulin is synthesized first as a precursor molecule, proinsulin. The A and B chains in
proinsulin are held together by a connecting peptide called C-peptide. Proinsulin is then
converted in the b cells to insulin, which is secreted together with C-peptide. Measure-
ments of serum insulin and C-peptide are mostly used to verify classification and for
various investigational purposes. Measurements are performed by radioimmunoassay.
C-peptide assays are more sensitive than insulin assays because C-peptide levels are not
affected by insulin therapy.

Islet Autoantibodies

Markers of cell-mediated autoimmune destruction of islet b cells that can be demonstrated
in Type 1 DM are
1. Islet cell antibodies (ICAs)
2. Autoantibodies to insulin (IAAs)
3. Autoantibodies to glutamic acid decarboxylase (GAD65)
4. Autoantibodies to tyrosine phosphatases IA-2a and IA-2b

Population Screening for Type 2 DM
American Diabetes Association (ADA), now recommends this for those at risk of developing
DM. The ADA proposes that all asymptomatic people aged 45 years or more, particularly
2
those with BMI 25 kg/m , should be screened in a healthcare setting. Either FPG, 2-h
OGTT or both are appropriate for screening. The FPG is more convenient, more reproduc-
ible, less costly and easier to administer than the 2-h OGTT. The FPG is, therefore, the
recommended initial screening test. If FPG is ,5.6 mmol/L (100 mg/dL) and/or 2-h plasma
glucose is ,7.8 mmol/L (140 mg/dL), testing should be repeated at 3-year intervals.
Major Risk Factors for Type 2 DM (ADA 2010)
1. Family history of Type 2 DM
2. Obesity
3. Physical inactivity
4. Previously identified impaired fasting glucose or OGTT
5. History of gestational diabetes
6. Hypertension
7. Dyslipidaemia
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