Diabetes Mellitus

A Silent Killer

Points to Consider
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What is Diabetes? Types of Diabetes


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Epidemiology
Complications of Diabetes Diagnostics in Diabetes

How Does Glucose Enter Cells?

What is diabetes?

Diabetes mellitus (DM) is a chronic, potentially debilitating and often fatal disease, characterized by hyperglycemia (increased blood glucose levels). It occurs as a result of problems with the production and supply of insulin in the body. Thus, there is reduced breakdown of glucose resulting in raised blood sugar levels that have a detrimental effect on the body. Diabetes mellitus is called „the silent killer‟, because it causes serious complications without symptoms, and can affect many of the major organs in the body by the time it is diagnosed.
Insulin A hormone made by the beta-cells of pancreas Helps the body to utilize glucose for bodily functions

Gestational diabetes Other types o Maturity-Onset Diabetes of Youth (MODY) .Types of Diabetes  Diabetes is a disease in which. - Either the body produces no or insufficient insulin (Type 1 diabetes) or The body cannot use the insulin it produces effectively (Type 2 diabetes).

or environmental.Type 1 Diabetes  Type 1 diabetes was previously called insulin-dependent diabetes mellitus (IDDM) or juvenileonset diabetes.  Body's immune system destroys pancreatic beta cells leading to a total halt in insulin production This form of diabetes usually strikes children and young adults Type 1 diabetes accounts for about 5% all diagnosed cases of diabetes Risk factors for type 1 diabetes may be autoimmune. genetic.    .

Type 2 Diabetes  Type 2 diabetes was previously called non-insulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes. physical inactivity. It usually begins as insulin resistance. obesity. As the need for insulin rises. the pancreas gradually loses its ability to produce it Type 2 diabetes is associated with older age.   Type 2 diabetes accounts for about 94-95% of all diagnosed cases of diabetes in India.   . history of gestational diabetes. family history of diabetes. impaired glucose metabolism. The body does not respond well to the insulin made by the pancreatic beta cells. and race/ethnicity.

 It is also more common among obese women and women with a family history of diabetes.   Women who have had gestational diabetes have a 40% to 60% chance of developing diabetes in the next 5–10 years. .Gestational Diabetes  Gestational diabetes is a form of glucose intolerance diagnosed in some women during pregnancy. Gestational diabetes requires treatment to normalize maternal blood glucose levels to avoid complications in the infant.

surgery. and other illnesses.Other Types  Other types of diabetes result from specific genetic conditions (such as maturity-onset diabetes of youth). Such types of diabetes account for 1% to 5% of all diagnosed cases. infections.  . drugs. malnutrition.

 People with pre-diabetes have blood glucose levels higher than normal but not high enough to be classified as diabetes.Pre-Diabetes  Pre-diabetes is a condition that raises the risk of developing type 2 diabetes. and stroke. heart disease. People with pre-diabetes have impaired fasting glucose (IFG) or impaired glucose tolerance (IGT).  .

  . IGT is a condition in which the blood sugar level is 140 to 199 mg/dL after a 2-hour oral glucose tolerance test. Studies have shown that people with pre-diabetes who lose weight and increase their physical activity can prevent or delay diabetes and even return their blood glucose levels to normal.Impaired Glucose Tolerance (IGT)  IFG is a condition in which the fasting blood sugar level is between 100 and 125 milligrams per deciliter (mg/dL) after an overnight fast.

Epidemiology    Diabetes currently affects 246 million people worldwide and is expected to affect 380 million by 2025. and much disability. Diabetes is the fourth leading cause of global death by disease. third edition. Each year 3. people with type 2 diabetes will die 5-10 years before people without diabetes.9 million (2007) [IDF] Every 10 seconds a person dies from diabetes-related causes.and middle-income countries.      80% of diabetes deaths are now occurring in low. Cardiovascular disease is the major cause of death in diabetes.8 million worldwide deaths are attributable to diabetes. 2007. mostly due to cardiovascular disease.: Diabetes Atlas. The number of people with diabetes in India: 40. 10% to 20% of people with diabetes die of renal failure. On average. about 6% of total global mortality. . accounting for >50% of all diabetes fatalities.   Ref. International Diabetes Federation. At least 50% of all people with diabetes are unaware of their condition.

particularly in cities like Chennai and Hyderabad with about 16 per cent people becoming diabetic. Projected Expenses: $333. the incidence was more in the south. Indians tend to suffer from it 10 years earlier than people in developed countries  .India   “Diabetes Capital of the World” Diabetics: 4 crores (2007)  Expenses: International Dollar 210 billion in India in 2005 for diabetes. heart disease and stroke together 5.6 billion in India    Compared to north India.75 crores diabetic people by the year 2025.

(responsible for 50-80% of deaths in diabetic patients).A Constellation of Complications Diabetes accounts for an extraordinary amount of human suffering as it is a major cause of blindness. amputations. kidney failure. Sexual Dysfunction Peripheral Vascular Disease Renal Disease Peripheral Neuropathy Gastropathy Dyslipidemia Complications of Diabetes Retinopathy/ Macular Edema Autonomic Neuropathy Cardiovascular Disease Hypertension . and cardiovascular disease.

and cardiovascular disease.A Constellation of Complications: Diagnosis Diabetes accounts for an extraordinary amount of human suffering as it is a major cause of blindness. amputations. kidney failure. Clinical Microalbuminuri a/Urea/Creatinin e/Cystatin C Clinical/Nerve studies Clinical/Imaging Studies Ophthalmological Tests Gastropathy Lipid Prfiles Complications of Hb A1c Diabetes Clinical/Nerve Studies Clinical Haptoglobin Genotyping/Lipid Profiles/CRP . (responsible for 50-80% of deaths in diabetic patients).

Diagnostic Tests in Diabetes .

Usually. monitoring of glycemic status is also considered a cornerstone of diabetes care.The Role of Diagnostic testing: A primary preventive measure  Blood and urine tests help to show if a diabetes treatment is working and can alert the doctor to early signs of diabetes complications. as with a fasting plasma glucose (FPG) test or an oral glucose tolerance test (OGTT).   Not only diagnosis but. a diabetes diagnostic test follows eight hours of fasting. .

Casual is defined as any time of day without regard to time since last meal. OR 2-h postload glucose ≥200 mg/dl during an OGTT. Fasting is defined as no caloric intake for at least 8 h.Diabetes Mellitus Diagnostic Criteria: ADA 2007 Symptoms of diabetes plus casual plasma glucose concentration ≥200 mg/dl. OR FPG ≥126 mg/dl. and unexplained weight loss. The classic symptoms of diabetes include polyuria. polydipsia. . using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water. The test should be performed as described by WHO.

measures blood sugar levels and is used to diagnose diabetes. The test consists of a noninvasive blood test. a person must not to eat for 12 to 14 hours.   . the test exposes problems with insulin functioning. also known as the fasting blood sugar test. Prior to being tested. Relatively simple and inexpensive.Fasting Plasma Glucose (FPG)  The fasting plasma glucose (FPG) test.

A reading above 126 mg/dL is the threshold at which diabetes is diagnosed. Blood glucose levels lower than 70 mg/dL imply an episode of hypoglycemia.Understanding the Results  Doctors interpret test results by looking at glucose levels in the blood. A reading of 100 mg/dL to 126 mg/dL suggests prediabetes. measured in milligrams per deciliter (mg/dL):   In the fasting plasma glucose test. 70 mg/dL to 99 mg/dL is considered within the normal range.    If the results are borderline. other tests might be done. Diagnosis categories include the following. . including the oral glucose tolerance test or the postprandial plasma glucose test.

Oral Glucose Tolerance Test (OGTT)  A glucose tolerance test in medical practice is the administration of glucose to determine how quickly it is cleared from the blood. The glucose is most often given orally so the common test is technically an oral glucose tolerance test (OGTT). An OGTT is also used as a specific diabetes diagnostic test to help identify gestational diabetes    . The OGTT is a more sensitive test and therefore often considered a better diabetes diagnostic test to identify the existence of a pre-diabetes condition.

The patient is then given a glucose solution to drink.Procedure for OGTT  The patient should have been fasting for the previous 8-14 hours (water is allowed). Blood sample is then drawn at timed intervals (after 2 hours) for the measurement of glucose (blood sugar). .   Interpretation of OGTT results Two-hour plasma glucose ≥ 200 mg/dL confirms diabetes.75 grams of glucose per kilogram of body weight. The standard dose since the late 1970s has been 1. to a maximum dose of 75 g.

Urine 24hr OR Random 14hr Fasting Serum. Fasting Plasma FL. Fasting Plasma FL. PP Plasma FL. PP Urine. PP Plasma FL. Urine 24hr or 12hr OR Random EDTA WB.Tests Offered Test Name Diabetes Screen Diabetes Mellitus Panel II Sample EDTA WB. PP Urine. Serum. PP Plasma FL. PP Urine. Fasting Urine. Fasting Plasma FL. Urine 24hr or 12hr OR Random Test Code 3180DS DT9201 Diabetes Monitor 1579 Diabetes Monitoring Panel DT9200 . Serum. Fasting Urine. EDTA WB. Fasting Urine. PP Plasma FL. Fasting Plasma FL. PP Urine EDTA WB. Fasting Urine.

Markers     C-peptide Autoantibodies to islet cells (ICA) Antibodies to insulin (IAA) Glutamic acid decarboxylase autoantibodies (GAD Ab) .Markers for Classification of Diabetes  Once diagnosed. the classification of diabetes as Type 1 or Type 2 is highly important.

a person must not to eat for 8 to 10 hours. C-peptide is generally found in amounts equal to insulin. A person with type 2 diabetes has a normal or high level of C-peptide. immediately after separation) Test Code 3140 .    Test Name C-peptide Sample Serum (Freeze. A person with type 1 diabetes has a low level of insulin and C-peptide. Prior to being tested. The level of C-peptide in the blood can show how much insulin is being made by the pancreas.C-Peptide    C-peptide test measures the level of this peptide in the blood.

89 (ng/mL) or 0.Understanding the Results Normal Values   The level of C-peptide in the blood must be read with the results of a blood glucose test. A low level of C-peptide with a high blood glucose level is found in people with type 1 diabetes.62 (nmol/L) High values   High levels of both C-peptide and blood glucose are found in people with type 2 diabetes. Fasting: 1. A high level of C-peptide with a low blood glucose level may mean an insulin-producing tumor of the pancreas (insulinoma) is present Low values   Low levels of both C-peptide and blood glucose are found in liver disease. Both these tests will be done at the same time. . a severe infection.

Antibodies in Type I Diabetes Type I diabetes or insulin-dependent diabetes mellitus (IDDM) is also known as an organ-specific autoimmune disease because it develops as a results of pancreatic islet cell destruction. .

     . ICA are present in 80% of newly diagnosed IDDM patients. but at random. GAD Ab and IAA do not appear all at once. ICA. varying rates depending on the patient.Antibodies Markers  Evidence of cellular destruction includes autoantibodies to islet cells (ICA). increasing their potential for early disease detection. IAA is among the first to appear during the asymptomatic period which characterizes IDDM (lasting anywhere from years to decades). These antibodies also occur before the onset of IDDM. Specifically. GAD Ab and IAA are all helpful in screening first-degree relatives of patients with IDDM. ICA. antibodies to insulin (IAA) and glutamic acid decarboxylase autoantibodies (GAD Ab).

Measurement of GAD Ab is a useful adjunct to measuring ICA. testing AITD patients for diabetes mellitus autoantibodies could be a useful means of predicting progression to Type I diabetes. first-degree relatives also have elevated GAD Ab. 60-80% of first-degree relatives with both ICA and IAA will develop IDDM within 10 years. Children less than 14 years of age can be screened for Type I diabetes using ICA. Because of a strong association of IDDM with autoimmune thyroid disease (AITD). as 43% of ICA-positive. IAA and GAD Ab.Clinical Utility  Autoantibody detection is useful to screen for those relatives of IDDM patients who may be at risk of developing Type I diabetes.     .

Tests Offered Test Name Antiislet cell antibodies Sample Serum Test Code 1166 Antiislet cell antibodies with titre Glutamic acid decarboxylase (GAD) IgG antibodies Insulin Anti insulin antibodies Serum Serum Serum Fasting Serum 1166T 3193 3192 3191 .

• Patients with diabetes are at risk of microalbuminuria if they have any of the following factors: – – – – the urine albumin excretion is in the upper range of normal (20–30 mg/d). or the total cholesterol level is greater than 5. the glycosylated hemoglobin level is greater than 9. the systolic blood pressure is greater than 130 mm Hg.24 mmol/L.Microalbuminuria • Early detection of microalbuminuria through screening allows interventions aimed at preventing diabetic nephropathy. Test Code: 3441 UD RANDOM/12 HRS OR 24 HRS URINE SAMPLE CAN BE ACCEPTED .

Guideline for Screening for Diabetic nephropathy .

 The level of HbA1c at any time is contributed by all circulating erythrocytes.HbA1c: A Gold Standard Marker for Diabetes Monitoring Glycosylated hemoglobin (HbA1c)   Hemoglobin in erythrocytes combines with glucose in the blood to form HbA1c. from the oldest to the youngest. HbA1c reflects the blood glucose level during the preceding two to three months. As a result. .   The amount of HbA1c in the blood is thus a Gold Standard marker to monitor long-term blood glucose control in individuals with diabetes mellitus. The amount of stable HbA1c increases with the average concentration of glucose in the blood.

In diabetics the higher the average blood glucose levels over a two to three month period. .    Whereas. Each 1% increase in HbA1c corresponds to an increase in mean plasma glucose level of approximately 35 mg/dL (2 mmol/L).9% of the total hemoglobin. the higher the percentage of HbA1c. Increased HbA1c is closely linked to risk of long-term microvascular diabetic complications.Normal HbA1c Levels   The normal range of HbA1c is 4 to 5. decreased HbA1c levels may sometime lead to hypoglycemia.

would lead to falsely high and inaccurate HbA1c level. or folate deficiency anemia. such as hereditary spherocytosis. any condition which lengthens the erythrocyte lifespan. . vitamin B12 deficiency anemia.Factors affecting HbA1c test results A number of factors may confound the interpretation of the test result:  Any condition that shortens the erythrocyte lifespan. thalassemias.  Conversely. sickle cell anemia. etc. would lead to falsely low and inaccurate HbA1c level. hemolysis. such as iron deficiency anemia.

Test Name Glycosylated Hemoglobin Sample EDTA Whole Blood Test Code 3179 . HbA1c is used as a measure of risk for the development of diabetes complications.   Note: With HbA1c as a guideline. a 25-44% risk reduction for nephropathy and a 30% risk reduction for neuropathy.Clinical Significance of HbA1c in management of diabetes  Concentration of HbA1c is an indicator of average blood glucose concentration over the preceding 2-3 months. A study by Diabetes Control and Complications Trial (DCCT) has demonstrated that the 10% stable reduction in HbA1c determines a 35% risk reduction for retinopathy. the physician can monitor glucose control and can continue or modify the therapy as per the requirement.

to fivefold increase in risk of atherosclerotic CVD compared with nondiabetic individuals. Studies have also suggested that.Haptoglobin Genotyping  Cardiovascular disease (CVD) is the most frequent. severe.    . genetic factors could contribute to differences in susceptibility to CVD. and costly complication of diabetes. among diabetic patients. Patients with diabetes have a three. One such factor is a functional allelic polymorphism in the Haptoglobin gene.

Haptoglobin  Haptoglobin . The haptoglobin-hemoglobin complex binds with high affinity to the CD163 scavenger. three potential genotypes denoted Hp 1-1. This results in rapid clearance of Hp-Hb complex from blood as well as release of antiinflammatory cytokines like IL-10 and IL-6.    All three types of haptoglobin proteins bind free hemoglobin equally well with high affinity.a serum protein . .class 1 and class 2. Hp 2-1. And. and Hp 2-2.prevents the oxidative tissue damage   Two classes of alleles .functions as an antioxidant .

This ability of Hp is lost when hemoglobin becomes heavily glycosylated. Intravascular free Hb will be rapidly bound by Hp. Diabetic individuals with Hp 1-1 are exposed to less hemoglobin-driven oxidative stress than diabetic Hp 2-2 individuals. . preventing Hb-induced oxidation.Haptoglobin in Diabetic Cardiovascular Complications     Free Hb enters into the subendothelial space.

Haptoglobin Genotyping Haptoglobin genotyping is performed by polymerase chain reaction and three genotypes of Haptoglobin (Hp 1-1. 2-1 & 2-2) are identified. .

Clinical Significance of Haptoglobin Genotyping  Haptoglobin genotyping is indicated in diabetic patients to predict higher risk for cardiovascular disease. Diabetic patients with the Hp 2-2 genotype have up to 5 fold increased risk of cardiovascular disease and therefore. Patients who are homozygous for the Hp 1 allele (Hp 1-1) are at a lower risk of developing both microvascular and macrovascular complications associated with diabetes. should be more aggressively managed.   .

.Whole Blood Test Code 7375  Note: Hp genotyping is not currently recommended in the assessment of cardiovascular risk for Non-diabetics. There is almost 50% decrease in cardiovascular events in patients with Hp 2-2 taking Vitamin E.How Haptoglobin genotyping will benefit the patient?  Haptoglobin testing may help physicians tailor optimal therapy for patients with diabetes who are at high risk for cardiovascular events. Thrombosis and Vascular Biology March 2008 Test Name Haptoglobin Genotyping Sample EDTA. as there is no proven correlation between the genotype and cardiovascular risk. Arteriosclerosis.

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