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Dr V Gounden Department of Chemical Pathology NHLS IALCH

Diabetes Mellitus
Diabetes is a group of metabolic diseases characterized

by hyperglycemia resulting from defects in insulin secretion, insulin action, or both Abnormality of fat, protein and carbohydrate metabolism

Several pathogenic processes are involved in the

development of diabetes. range from autoimmune destruction of the -cells of the pancreas with consequent insulin deficiency to abnormalities that result in resistance to insulin action. The basis of the abnormalities in carbohydrate, fat, and protein metabolism in diabetes is deficient action of insulin on target tissues. Deficient insulin action results from inadequate insulin secretion and/or diminished tissue responses to insulin at one or more points in the complex pathways of hormone action. Impairment of insulin secretion and defects in insulin action frequently coexist in the same patient, and it is often unclear which abnormality, if either alone, is the primary cause of the hyperglycemia.

The chronic hyperglycemia of diabetes is associated with long-term damage, dysfunction, and failure of differentorgans, especially the eyes, kidneys, nerves, heart, and blood vessels

majority of cases of diabetes fall into two broad

etiopathogenetic categories (discussed in greater detail below).


type 1 diabetes, the cause is an absolute deficiency of insulin

secretion.

Individuals at increased risk of developing this type of diabetes can often be identified by serological evidence of an autoimmune pathologic process occurring in the pancreatic islets and by genetic markers.

much more prevalent category type 2 diabetes the cause is a combination of resistance to insulin action and an inadequate compensatory insulin secretory response. hyperglycemia sufficient to cause pathologic and functional changes in various target tissues, but without clinical symptoms, may be present for a long period of time before diabetes is detected. During this asymptomatic period, it is possible to demonstrate an abnormality in carbohydrate metabolism by measurement of plasma glucose in the fasting state or after a challenge with an oral glucose load.

Ref Diabetes care Jan 2010

Other specific types of diabetes mellitus


Genetic defects of the -cell.
These forms of diabetes are frequently characterized by onset of

hyperglycemia at an early age (generally before age 25 years). They are referred to as maturity-onset diabetes of the young (MODY) and are characterized by impaired insulin secretion with minimal or no defects in insulin action. They are inherited in an autosomal dominant pattern

Diseases of the exocrine pancreas.


Any process that diffusely injures the pancreas can cause diabetes.

Acquired processes include pancreatitis, trauma, infection, pancreatectomy, and pancreatic carcinoma. With the exception of that caused by cancer, damage to the pancreas must be extensive for diabetes to occur

Other specific types of diabetes mellitus


Endocrinopathies
Several hormones (e.g., growth hormone, cortisol, glucagon,

epinephrine) antagonize insulin action. Excess amounts of these hormones (e.g., acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma, respectively) can cause diabetes.

Drug- or chemical-induced diabetes. Many drugs can impair insulin secretion. These drugs may not cause diabetes by themselves, but they may precipitate diabetes in individuals with insulin resistance

Infections.
Certain viruses have been associated with -cell destruction.

Diabetes occurs in patients with congenital rubella,

Centuries ago, people known as "water tasters"

diagnosed diabetes by tasting the urine of people suspected to have it. If urine tasted sweet, diabetes was diagnosed. To acknowledge this feature, in 1675 the word "mellitus," meaning honey, was added to the name "diabetes," meaning siphon. It wasn't until the 1800s that scientists developed chemical tests to detect the presence of sugar in urine

Criteria for the diagnosis of diabetes mellitus 1. A1C 6.5%. The test should be performed in a laboratory using a method that is NGSP certified and standardized to the DCCT assay.* OR 2. FPG 7.0 mmol/l Fasting is defined as no caloric intake for at least 8 h.* OR 3. 2-h plasma glucose 11.1 mmol/l during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.* OR 4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose 11.1 mmol/l *In the absence of unequivocal hyperglycemia, criteria 13 should be confirmed by repeat testing.

Fasting blood glucose


For decades the basis of diagnosis of diabetes has been

the glucose test The studies determining the cut off for glucose results used the presence of retinopathy as the key factor with which to identify threshold glucose level. A fasting blood glucose of 7.0 mmol/l on more than one occasion diagnostic of diabetes ( Normal fasting blood glucose < 5.6 mmol/l) Fasting sample needs to be taken after overnight fast of minimum 8 hrs

Fasting blood glucose


Formal glucose testing must be performed i.e collected

via venopuncture and tested in the laboratory Glucometer values must not be used for diagnosis of diabetes Specimens must be collected in a tube containin fluoride oxalate preservative ( prevent glycolysis from continuing after blood has been drawn which could lead to a falsely low glucose values)

Oral glucose tolerance test


Often performed when fasting > than normal but < 7

mmol/l The oral glucose tolerance test is used to screen pregnant women for gestational diabetes between 24 and 28 weeks of pregnancy. It may also be used in cases where the disease is suspected, despite a normal fasting blood glucose level.

OGTT
Performance of OGTT An initial blood sugar is drawn and then the person is given a 75 grams of anhydrous glucose dissolved in water ( baseline or 0 min sample). The person then has their blood tested again at 120 minutes after drinking the glucose water For the test to give reliable resultspatient must be in stable health (not have any other illnesses, not even a cold). be normally active (for example, not lying down or confined to a bed like a patient in a hospital) should not be taking any medicines that could affect your blood glucose. should not smoke or drink coffee of the tests. No increased exertion before or during the test Normal diet at least 3 days before the test

OGTT

Interpretation of the OGTT Must be performed more than once to confirm the findings

Disadvantages of OGTT
Time and discomfort for the patient
Not physiological

Glycated haemoglobin (HbA1c)


Glycated hemoglobin is a form of haemoglobin which is

measured primarily to identify the average plasma glucose concentration over prolonged periods of time. It is formed in a non-enzymatic attachment of glucose to haemoglobin following exposure to plasma glucose. Normal levels of glucose produce a normal amount of glycated hemoglobin. As the average amount of plasma glucose increases, the fraction of glycated hemoglobin increases in a predictable way. This serves as a marker for average blood glucose levels over the previous (3) months prior to the measurement.

Glycated haemoglobin (HbA1c)


A1C is a widely used marker of chronic glycemia,

reflecting average blood glucose levels over a 2- to 3month period of time. The test plays a critical role in the management of the patient with diabetes, since it correlates well with both microvascular and, to a lesser extent, macrovascular complications and is widely used as the standard biomarker for the adequacy of glycemic management recommended use of the A1C test to diagnose diabetes, with a threshold of 6.5%

Advantages of HbA1c
Fasting specimens not needed, greater convenience Samples are more stable vs glucose Less day to day variation with regards to stress/illness

vs glucose
Disadvantages Affected by conditions such as anaemia, haemolysis More expensive, not available in all labs Currently not recommended for diagnosis of Type I Diabetes Mellitus

Categories of increased risk for diabetes*


Impaired fasting glucose: 5.6 mmol/ to 6.9 mmol/l
Impaired glucose tolerance following OGTT test 2hr

glucose of 7.8 mmol/l to 11.0 mmol/l Hb A1C: 5.76.4%

Urine glucose
Urine glucose measurment by dipstix, formal lab

measurement is not used to diagnose diabetes

Other useful tests


Antibody testing Auto immune mediated diabetes ( Type 1) Used for identifying people at risk for the development of Type 1 diabetes Antibodies measured anti GAD Ab, islet cell Ab, anti insulin Ab Currently not done routinely ( no proven management for these patients once identified to prevent or delay onset of diabetes)

Where secondary causes of diabetes is suspected- tests for

diagnosis of these conditions eg Cushings syndrome etc

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