Page 844 - Textbook of Pathology, 6th Edition
P. 844

828 Then 75 gm of glucose dissolved in 300 ml of water is given.  6. Insulin assay. Plasma insulin can be measured by
           Blood and urine specimen are collected at half-hourly  radioimmunoasay and ELISA technique. Plasma insulin
           intervals for at least 2 hours. Blood or plasma glucose content  deficiency is crucial for type 1 DM but is not essential for
           is measured and urine is tested for glucosuria to determine  making the diagnosis of DM.
           the approximate renal threshold for glucose. Venous whole  7. Proinsulin assay. Proinsulin is included in immunoassay
           blood concentrations are 15% lower than plasma glucose  of insulin; normally it is <20% of total insulin.
           values.                                             8. C-peptide assay. C-peptide is released in circulation
              Currently accepted criteria for diagnosis of DM (as per
           American Diabetes Association, 2007) are given in Table 27.8:  during conversion of proinsulin to insulin in equimolar
                                                               quantities to insulin; thus its levels correlate with insulin level
              Normal cut off value for fasting blood glucose level is  in blood except in islet cell tumours and in obesity. This test
           considered as 100 mg/dl.                            is even more sensitive than insulin assay because its levels
              Cases with fasting blood glucose value in range of 100-  are not affected by insulin therapy.
           125 mg/dl are considered as impaired fasting glucose tolerance  9. Islet autoantibodies. Glutamic acid decarboxylase and
           (IGT); these cases are at increased risk of developing diabetes  islet cell cytoplasmic antibodies may be used  as a marker for
           later and therefore kept under observation for repeating the  type 1 DM.
           test. During pregnancy, however, a case of IGT is treated as
           a diabetic.                                         10. Screening for diabetes-associated complications.
             Individuals with fasting value of plasma glucose higher  Besides making the diagnosis of DM based on the defined
           than 126 mg/dl and 2-hour value after 75 gm oral glucose  criteria, screening tests are done for DM-associated
                                                               complications e.g. microalbuniuria, dyslipidaemia, thyroid
           higher than 200 mg/dl are labelled as diabetics (Fig. 27.27,D).  dysfunction etc.
              In symptomatic case, the random blood glucose value
           above 200 mg/dl is diagnosed as diabetes mellitus.  ISLET CELL TUMOURS
           V. OTHER TESTS.  A few other tests are sometimes    Islet cell tumours are rare as compared with tumours of the
           performed in specific conditions in diabetics and for research  exocrine pancreas. Islet cell tumours are generally small and
           purposes:                                           may be hormonally inactive or may produce hyperfunction.
           1. Glycosylated haemoglobin (HbA1C). Measurement of  They may be benign or malignant, single or multiple. They
           blood glucose level in diabetics suffers from variation due  are named according to their histogenesis such as:  β-cell
           to dietary intake of the previous day. Long-term objective  tumour (insulinoma), G-cell tumour (gastrinoma), A-cell
     SECTION III
           assessment of degree of glycaemic control is better  tumour (glucagonoma) D-cell tumour (somatostatinoma),
           monitored by measurement of glycosylated haemoglobin  vipoma (diarrhoeagenic tumour from D  cells which elaborate
                                                                                                1
           (HbA ), a minor haemoglobin component present in normal  VIP), pancreatic polypeptide (PP)-secreting tumour, and
               1C
           persons. This is because the non-enzymatic glycosylation of  carcinoid tumour. However, except insulinoma and
           haemoglobin takes place over 90-120 days, lifespan of red  gastrinoma, all others are extremely rare and require no
           blood cells. HbA  assay, therefore, gives an estimate of  further comments.
                          1C
           diabetic control and compliance for the preceding 3-4
           months. This assay has the advantage over traditional blood  Insulinoma (ββ ββ β-Cell Tumour)
           glucose test that no dietary preparation or fasting is required.  Insulinomas or beta (β)-cell tumours are the most common
           Increased HbA   value almost certainly means DM but  islet cell tumours. The neoplastic β-cells secrete insulin into
                        1C
           normal value does not rule out IGT; thus the test is not used  the blood stream which remains unaffected by normal
     Systemic Pathology
           for making the diagnosis of DM. Moreover, since HbA 1C  regulatory mechanisms. This results in characteristic attacks
           assay has a direct relation between poor control and  of hypolgycaemia with blood glucose level falling to 50 mg/
           development of complications, it is also a good measure of  dl or below, high plasma insulin level (hyperinsulinism) and
           prediction of microvascular complications. Care must be  high insulin-glucose ratio. The central nervous mani-
           taken in iterpretation of the HbA  value because it varies  festations are conspicuous which are promptly relieved by
                                       1C
           with the assay method used and is affected by presence of  intake of glucose. Besides insulinoma, however, there are
           haemoglobinopathies, anaemia, reticulocytosis, transfusions  other causes of hypoglycaemia such as: in starvation, partial
           and uraemia.                                        gastrectomy, diffuse liver disease, hypopituitarism and
                                                               hypofunction of adrenal cortex.
           2. Glycated albumin. This is used to monitor degree of
           hyperglycaemia during previous 1-2 weeks when HbA  can  MORPHOLOGIC FEATURES. Grossly, insulinoma is
                                                        1C
           not be used.                                          usually solitary and well-encapsulated tumour which may
           3. Extended GTT. The oral GTT is extended to 3-4 hours for  vary in size from 0.5 to 10 cm. Rarely, they are multiple.
           appearance of symptoms of hyperglycaemia. It is a useful  Microscopically, the tumour is composed of cords and
           test in cases of reactive hypoglycaemia of early diabetes.  sheets of well-differentiated β-cells which do not differ
           4. Intravenous GTT. This test is performed in persons who  from normal cells. Electron microscopy reveals typical
           have intestinal malabsorption or in postgastrectomy cases.  crystalline rectangular granules in the neoplastic cells. It
                                                                 is extremely difficult to assess the degree of anaplasia to
           5. Cortisone-primed GTT. This provocative test is a useful
           investigative aid in cases of potential diabetics.    distinguish benign from malignant β-cell tumour.
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