Diabetes Mellitus

A Silent Killer
 Points to Consider

What is Diabetes?
Types of Diabetes
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.

Insulin
Thus, there is reduced breakdown of glucose resulting in raised blood A hormone made by
sugar levels that have a detrimental effect on the body. the beta-cells of
pancreas

Diabetes mellitus is called ‘the silent killer’, because it causes serious Helps the body to
complications without symptoms, and can affect many of the major utilize glucose for
bodily functions
organs in the body by the time it is diagnosed.
 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).

- Gestational diabetes

- Other types

o Maturity-Onset Diabetes of Youth (MODY)

 Type 1 Diabetes
Type 1 diabetes was previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-
onset 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, or environmental.

 Type 2 Diabetes
Type 2 diabetes was previously called non-insulin-dependent diabetes mellitus (NIDDM) or
adult-onset diabetes.

Type 2 diabetes accounts for about 94-95% of all diagnosed cases of diabetes in India.

It usually begins as insulin resistance. The body does not respond well to the insulin
made by the pancreatic beta cells.

As the need for insulin rises, the pancreas gradually loses its ability to produce it

Type 2 diabetes is associated with older age, obesity, family history of diabetes, history of
gestational diabetes, impaired glucose metabolism, physical inactivity, and
race/ethnicity.
 Gestational Diabetes

Gestational diabetes is a form of glucose intolerance diagnosed in some

women during pregnancy.

It is also more common among obese women and women with a

family history of diabetes.

Gestational diabetes requires treatment to normalize maternal blood

glucose levels to avoid complications in the infant.

Women who have had gestational diabetes have a 40% to 60%

chance of developing diabetes in the next 5–10 years.
 Other Types
Other types of diabetes result from specific genetic conditions (such as maturity-onset
diabetes of youth), surgery, drugs, malnutrition, infections, and other illnesses.

Such types of diabetes account for 1% to 5% of all diagnosed cases.

 Pre-Diabetes s .
r e
c ro
Pre-diabetes is a condition that raises the risk of developing type 2 diabetes, n
4
heart disease, and stroke. tha e
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o but
People with pre-diabetes have blood glucose levels higher than normal
e m
not high enough to be classified as diabetes. o b
d t
People with pre-diabetes have impaired fasting glucose a t e (IFG) or impaired
l
glucose tolerance (IGT). stu
p o
a re
nts
t ie
p a
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D ia
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 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.

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.
 Epidemiology
Diabetes currently affects 246 million people worldwide and is expected to affect 380 million by 2025.
Diabetes is the fourth leading cause of global death by disease.
Each year 3.8 million worldwide deaths are attributable to diabetes, about 6% of total global mortality. 
80% of diabetes deaths are now occurring in low- and middle-income countries.
At least 50% of all people with diabetes are unaware of their condition.
The number of people with diabetes in India: 40.9 million (2007) [IDF]
Every 10 seconds a person dies from diabetes-related causes.
Cardiovascular disease is the major cause of death in diabetes, accounting for >50% of all diabetes fatalities,
and much disability.
On average, people with type 2 diabetes will die 5-10 years before people without diabetes, mostly due to
cardiovascular disease.
10% to 20% of people with diabetes die of renal failure.

Ref.: Diabetes Atlas, third edition,

International Diabetes Federation, 2007.
 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
5.75 crores diabetic people by the year 2025.
Projected Expenses: $333.6 billion in India
Compared to north India, the incidence was more in the south, particularly in cities
like Chennai and Hyderabad with about 16 per cent people becoming diabetic.
Indians tend to suffer from it 10 years earlier than people in developed countries
 A Constellation of Complications
Diabetes accounts for an extraordinary amount of human suffering as it is a major cause of
blindness, kidney failure, amputations, and cardiovascular disease, (responsible for 50-80% of
deaths in diabetic patients).

Renal
Sexual
Disease
Dysfunction Peripheral
Neuropathy
Peripheral
Vascular
Disease
Complications of Retinopathy/
Macular Edema
Diabetes
Gastropathy

Autonomic
Dyslipidemia Neuropathy

Hypertension
Cardiovascular
Disease
 A Constellation of Complications: Diagnosis
Diabetes accounts for an extraordinary amount of human suffering as it is a major cause of
blindness, kidney failure, amputations, and cardiovascular disease, (responsible for 50-80% of
deaths in diabetic patients).

Microalbuminuri
Clinical a/Urea/Creatinin
e/Cystatin C Clinical/Nerve
studies

Clinical/Imaging
Studies

Ophthalmological Tests
Complications
Hb A1c of
Diabetes
Gastropathy
Clinical/Nerve Studies
Lipid Prfiles

Clinical
Haptoglobin
Genotyping/Lipid
Profiles/CRP
Diagnostic Tests in Diabetes
 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.

Usually, a diabetes diagnostic test follows eight hours of fasting, as with a

fasting plasma glucose (FPG) test or an oral glucose tolerance test (OGTT).

Not only diagnosis but, monitoring of glycemic status is also considered a

cornerstone of diabetes care.
 Diabetes Mellitus Diagnostic Criteria: ADA 2007
Symptoms of diabetes plus casual plasma glucose concentration ≥200 mg/dl. Casual is
defined as any time of day without regard to time since last meal. The classic symptoms of
diabetes include polyuria, polydipsia, and unexplained weight loss.

OR

FPG ≥126 mg/dl. Fasting is defined as no caloric intake for at least 8 h.

OR

2-h postload glucose ≥200 mg/dl during an OGTT. The test should be performed as
described by WHO, using a glucose load containing the equivalent of 75 g anhydrous
glucose dissolved in water.
 Fasting Plasma Glucose (FPG)

The fasting plasma glucose (FPG) test, also known as the fasting blood sugar test,
measures blood sugar levels and is used to diagnose diabetes.

Relatively simple and inexpensive, the test exposes problems with insulin functioning.

The test consists of a noninvasive blood test. Prior to being tested, a person must not to
eat for 12 to 14 hours.
 Understanding the Results

Doctors interpret test results by looking at glucose levels in the blood.

Diagnosis categories include the following, 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.
A reading of 100 mg/dL to 126 mg/dL suggests prediabetes.
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.

If the results are borderline, other tests might be done, 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).

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.

An OGTT is also used as a specific diabetes diagnostic test to help identify gestational
diabetes
 Procedure for OGTT

The patient should have been fasting for the previous 8-14 hours (water is allowed).

The patient is then given a glucose solution to drink. The standard dose since the late
1970s has been 1.75 grams of glucose per kilogram of body weight, to a maximum dose
of 75 g.

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.

 Tests Offered

Test Name Sample Test Code

EDTA WB, Fasting Plasma FL, Fasting

Diabetes Screen 3180DS
Urine, PP Plasma FL, PP Urine
EDTA WB, Serum, Fasting Plasma FL,
Diabetes Mellitus Panel II Fasting Urine, PP Plasma FL, PP DT9201
Urine, Urine 24hr or 12hr OR Random
EDTA WB, Serum, Fasting Plasma FL,
Diabetes Monitor Fasting Urine, PP Plasma FL, PP 1579
Urine, Urine 24hr OR Random
14hr Fasting Serum, EDTA WB,
Fasting Plasma FL, Fasting Urine, PP
Diabetes Monitoring Panel DT9200
Plasma FL, PP Urine, Urine 24hr or
12hr OR Random
 Markers for Classification of Diabetes

Once diagnosed, the classification of diabetes as Type 1 or Type 2 is highly important.

Markers

C-peptide

Autoantibodies to islet cells (ICA)

Antibodies to insulin (IAA)

Glutamic acid decarboxylase autoantibodies (GAD Ab)

 C-Peptide

C-peptide test measures the level of this peptide in the blood.

C-peptide is generally found in amounts equal to insulin.

The level of C-peptide in the blood can show how much insulin is being made by the
pancreas.

A person with type 1 diabetes has a low level of insulin and C-peptide.

A person with type 2 diabetes has a normal or high level of C-peptide.

Prior to being tested, a person must not to eat for 8 to 10 hours.

Test Name Sample Test Code

Serum (Freeze, immediately
C-peptide 3140
after separation)
 Understanding the Results

Normal Values
The level of C-peptide in the blood must be read with the results of a blood glucose test.
Both these tests will be done at the same time.
Fasting: 1.89 (ng/mL) or 0.62 (nmol/L)

High values
High levels of both C-peptide and blood glucose are found in people with type 2 diabetes.
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, a severe
infection.
A low level of C-peptide with a high blood glucose level is found in people with type 1
diabetes.
 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.
 Antibodies Markers
Evidence of cellular destruction includes autoantibodies to islet cells (ICA), antibodies to
insulin (IAA) and glutamic acid decarboxylase autoantibodies (GAD Ab).

ICA are present in 80% of newly diagnosed IDDM patients.

ICA, GAD Ab and IAA are all helpful in screening first-degree relatives of patients with
IDDM.

ICA, GAD Ab and IAA do not appear all at once, but at random, varying rates
depending on the patient.

These antibodies also occur before the onset of IDDM, increasing their potential for early
disease detection.

Specifically, IAA is among the first to appear during the asymptomatic period which
characterizes IDDM (lasting anywhere from years to decades).
 Clinical Utility
Autoantibody detection is useful to screen for those relatives of IDDM patients who may be
at risk of developing Type I diabetes.

60-80% of first-degree relatives with both ICA and IAA will develop IDDM within 10 years.

Measurement of GAD Ab is a useful adjunct to measuring ICA, as 43% of ICA-positive,

first-degree relatives also have elevated GAD Ab.

Children less than 14 years of age can be screened for Type I diabetes using ICA, IAA and
GAD Ab.

Because of a strong association of IDDM with autoimmune thyroid disease (AITD), testing
AITD patients for diabetes mellitus autoantibodies could be a useful means of predicting
progression to Type I diabetes.
 Tests Offered

Test Name Sample Test Code

Antiislet cell antibodies Serum 1166

Antiislet cell antibodies with titre Serum 1166T

Glutamic acid decarboxylase (GAD)

Serum 3193
IgG antibodies

Insulin Serum Fasting 3192

Anti insulin antibodies Serum 3191

 Microalbuminuria

• Early detection of microalbuminuria through screening allows

interventions aimed at preventing diabetic nephropathy.

• 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);
– the systolic blood pressure is greater than 130 mm Hg;
– the glycosylated hemoglobin level is greater than 9; or
– the total cholesterol level is greater than 5.24 mmol/L.

Test Code: 3441 UD

RANDOM/12 HRS OR 24 HRS URINE SAMPLE CAN BE ACCEPTED
Guideline for Screening
for Diabetic
nephropathy
 HbA1c: A Gold Standard Marker for Diabetes
Monitoring
Glycosylated hemoglobin (HbA1c)

Hemoglobin in erythrocytes combines with glucose in the blood to form HbA1c.

The amount of stable HbA1c increases with the average concentration of glucose in the blood.

The level of HbA1c at any time is contributed by all circulating

erythrocytes, from the oldest to the youngest.

As a result, HbA1c reflects the blood glucose level during the

preceding two to three months.

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.
 Normal HbA1c Levels
The normal range of HbA1c is 4 to 5.9% of the total hemoglobin.

In diabetics the higher the average blood glucose levels over a two to three month period, the
higher the percentage of HbA1c.

Each 1% increase in HbA1c corresponds to an increase in mean plasma glucose level of

approximately 35 mg/dL (2 mmol/L).

Increased HbA1c is closely linked to risk of long-term microvascular diabetic complications.

Whereas, decreased HbA1c levels may sometime lead to hypoglycemia.

 Factors affecting HbA1c test results

A number of factors may confound the interpretation of the test result:

Any condition that shortens the erythrocyte lifespan, such as hereditary spherocytosis,
hemolysis, sickle cell anemia, thalassemias, etc. would lead to falsely low and inaccurate
HbA1c level.

Conversely, any condition which lengthens the erythrocyte lifespan, such as iron
deficiency anemia, vitamin B12 deficiency anemia, or folate deficiency anemia, would lead
to falsely high and inaccurate HbA1c level.
 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.

HbA1c is used as a measure of risk for the development of diabetes complications.

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, a 25-44% risk
reduction for nephropathy and a 30% risk reduction for neuropathy.

Note: With HbA1c as a guideline, the physician can monitor glucose control and can continue or modify the
therapy as per the requirement.

Test Name Sample Test Code

Glycosylated Hemoglobin EDTA Whole Blood 3179
 Haptoglobin Genotyping

Cardiovascular disease (CVD) is the most frequent, severe, and costly

complication of diabetes.
Patients with diabetes have a three- to fivefold increase in risk of
atherosclerotic CVD compared with nondiabetic individuals.
Studies have also suggested that, among diabetic patients, genetic
factors could contribute to differences in susceptibility to CVD.
One such factor is a functional allelic polymorphism in the
Haptoglobin gene.
 Haptoglobin
Haptoglobin - a serum protein
- functions as an antioxidant
- prevents the oxidative tissue damage

Two classes of alleles - class 1 and class 2,

And, three potential genotypes denoted Hp 1-1, Hp 2-
1, and Hp 2-2.

All three types of haptoglobin proteins bind free hemoglobin equally well with high affinity.

The haptoglobin-hemoglobin complex binds with high affinity to the CD163 scavenger.

This results in rapid clearance of Hp-Hb complex from blood as well as release of anti-
inflammatory cytokines like IL-10 and IL-6.
Haptoglobin in Diabetic Cardiovascular Complications
Free Hb enters into the subendothelial space.

Intravascular free Hb will be rapidly bound by Hp, preventing Hb-induced oxidation.

This ability of Hp is lost when hemoglobin becomes heavily glycosylated.
Diabetic individuals with Hp 1-1 are exposed to less hemoglobin-driven oxidative stress than
diabetic Hp 2-2 individuals.
 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.
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.
Diabetic patients with the Hp 2-2 genotype have up to 5 fold increased risk of
cardiovascular disease and therefore, should be more aggressively managed.
 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.

There is almost 50% decrease in cardiovascular events in patients with Hp 2-2 taking
Vitamin E. Arteriosclerosis, Thrombosis and Vascular Biology March 2008

Test Name Sample Test Code

Haptoglobin Genotyping EDTA- Whole Blood 7375

Note: Hp genotyping is not currently recommended in the assessment of cardiovascular

risk for Non-diabetics, as there is no proven correlation between the genotype and
cardiovascular risk.
Thank You