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DIABETES MELLITUS:
INVESTAGTION , DIAGNOSIS
& MANAGEMENT
Dr.Vivek Reddy
1st M.D.S
CONTENTS

 Laboratory Diagnosis
Blood Biochemistry
Urine analysis
HbA1C
Insulin
Immunological Assays
C-peptide
Management
Management of Type I DM
Management of Type II DM
DIABETES MELLITUS

 There are different test and devices to test and diagnosis diabetes mellitus and
those may differ according to the type of diabetes mellitus
How to investigate for DM

 If a patient is suspected to have diabetes of any type, several investigation can be

done either to confirm it or rule it out.

 Blood sample is usually used and even though less commonly a urine sample may
be used but it is not diagnostic for diabetes.
Blood Biochemistry

Blood test is the most appropriate and most common method to

diagnose all types of diabetes mellitus

- Blood Glucose ( 4 Types)

- Fasting Blood Sugar Level (FBS)

-Post Prandial Blood Sugar Test (PPBS)
- Random blood sugar (RBS)
- Oral glucose tolerance test (OGGT)
FBS- Fasting Blood Sugar Level

• Measures blood glucose after fasting for at least 8-12 hrs

• It often is the first test done to check for diabetes.
• patient with mild or borderline diabetes may present
with normal FBG values.
• If diabetes is suspected, GTT can confirm the diagnosis.

Normal levels:
70-110mg/dl
 PBS - Post-Prandial Blood Sugar

• After the patient fasts for 12 hours, a meal is given which contains starch and
sugar (approx. 100 gm).
• Then after 2 hours blood is collected to measure glucose level.
• home blood sugar test is the most common way to check 2-hour postprandial
blood sugar levels.
 RBS- Random blood sugar

-Measures blood glucose randomly at any time throughout the day without
patient fasting.
- It is useful because glucose levels in healthy people don’t vary widely
throughout the day.
-Blood glucose levels that vary widely may indicate a problem.
 GTT - Oral glucose tolerance test

• Glucose Tolerance is defined as the capacity of the body to tolerate an extra load of
glucose or it measures the body's ability to use glucose.
• It is series of blood glucose measurements taken after drink glucose liquid
• It is considered as definitive diagnostic test for DM.
• It is ordered to:
- Confirm the diagnosis, in pre-diabetic
-Diagnose gestational diabetes (most commonly)
• Recommended if 100-126 mg/dL (5.5 mmol/L-7.0 mmol/L)
 Indication of Glucose tolerance test

-In asymptomatic persons with sustained or transient glycosuria.

- In persons with symptoms of diabetes but no glycosuria or hyperglycemia.
- Persons with family history but no symptoms or positive blood findings.
- In persons with or without symptoms of diabetes mellitus showing one
abnormal blood findings.
- In patients with neuropathies or retinopathies of unknown origin.
Contraindication of Glucose tolerance
test

There is no indication for doing GTT in a person with confirmed diabetics

mellitus.

-GTT has no role in follow-up of diabetics.

-The test should not be done in ill patients.

Types of glucose tolerance test

-Standard Oral glucose tolerance test

Glucose measured for 4-5 hrs after giving glucose to see how the curve behaves below the
normal fasting glucose limits. Done in some conditions causing hypoglycaemia.

-Intravenous Glucose tolerance test

•This test is undertaken for patients with malabsorption (Celiac disease or enteropathies).
•Under these conditions oral glucose load is not well absorbed and the results of oral glucose
tolerance test become inconclusive.

-Mini Glucose tolerance test

Mini Glucose tolerance test
- As per current WHO recommendations, in the mini or modern glucose tolerance
test, only two samples are collected.
-Fasting (zero hour) and 2 hour post glucose load.
-Urine samples are also collected during the same time.
-The diagnosis is made from the variations observed in these results.

Zero hour After 2 hours

Normal person <110 mg/dl <140 mg/dl
Increase glucose Tolerance 110-126 mg/dl 140-199 mg/dl
Normal Glucose tolerance curve
Diabetic curve
 Gestational diabetes

-Gestational diabetes is high blood sugar that develops at any time during pregnancy in a woman
who does not have diabetes.
-At least 6 weeks after the pregnancy ends, the woman should receive an oral glucose tolerance test
and be reclassified as having diabetes, normal glucose tolerance, impaired
• <25 yrs age, Normal body weight before pregnancy,
Low risk absence of DM in first degree relative, no h/0 poor
obstetric outcome, no h/o abnormal glucose tolera

Average risk • Tested at 24-28 weeks of gestation.

• Marked obesity, strong family history of DM, glycosuria,

High risk personal history of GDM.
Gestational diabetes is diagnosed if the woman is at or exceeds any two of
the following four plasma glucose levels during 100 gm test

Fasting – 95 mg/dl
1 hr – 180 mg/dl
2 hr – 155 mg/dl
3 hr – 140 mg/dl
 Hb1AC - Glycated hemoglobin

-HbA1c comprises 4–6% of total hemoglobin A1 .

-Since glycohemoglobins circulate within red blood cells whose life span lasts up to 120 days,
they generally reflect the state of glycemia over the preceding 8–12 weeks, thereby providing
an improved method of assessing diabetic control.

-Any condition that shortens erythrocyte survival or decreases mean erythrocyte age (eg,
recovery from acute blood loss, hemolytic anemia) will falsely lower HbA1c irrespective of the
assay method used.
Glycated hemoglobin (hemoglobin A1c)

 What is HbA1c ?
It is a form of hemoglobin that is measured primarily to identify the average
plasma glucose concentration over prolonged periods of time.

HbA1c test gives an average blood glucose levels over the previous 3 months
prior to
the measurement

 Normal reference range 4-5.9%

 Insulin Test

- Insulin is the primary hormone responsible for controlling glucose metabolism, and its secretion is
governed by plasma glucose concentration.
-The insulin molecule is synthesized in the pancreas
- The principal function of insulin is to control the uptake and utilization of glucose in the peripheral
tissues.
-Insulin concentrations are severely reduced in insulindependent diabetes mellitus (IDDM) Other
conditions, non-insulin-dependent diabetes mellitus (NIDDM), obesity, and some endocrine
dysfunctions.

Measurement of insulin level by

-Radioimmunoassay & ELISA.
-Crucial for type I DM.
 IMMUNOLOGICAL ASSAYS

-Antibodies to insulin, islet cells, or Glutamic acid decarboxylase (GAD) can be estimated to
differentiate between the types of diabetes mellitus

-They are absent in type 2 diabetes mellitus.

-Latent autoimmune diabetes of adults, or LADA, is a form of slow-onset type 1 diabetes that occurs in
middle-aged (usually white) adults.

-It can be differentiated from type 2 diabetes by measuring anti-GAD65 antibodies.

 C-PEPTIDE

 What is c-peptide test ?

a test that measure the level of this peptide which is produced in the beta-cells of the
pancreas,
o Absence of c-peptide response to carbohydrates ingestion may indicate total beta cells
failure therefore DM type 2 is diagnosed
o This test is important in differentiating between type 1 and
type 2.
 Normal range 0.51–2.72 (ng/mL)
 Urine test

Detection of urinary glucose (Glucosuria)

-First-line screening test for diabetes mellitus
-Normally glucose does not appear in urine until the plasma glucose rises above 160- 180 mg/dl.
-In certain individuals due to low renal threshold glucose may be present despite normal blood
glucose levels.
-Conversely renal threshold increases with age so many diabetics may not have Glycosuria despite
high blood sugar levels.
 Detection of Glucosuria-

-A specific and convenient method to detect glucosuria is the paper strip impregnated with glucose
oxidase and a chromogen system (Clinistix, Diastix), which is sensitive to as little as 0.1% glucose
in urine.
-Diastix can be directly applied to the urinary stream, and differing color responses of the indicator
strip reflect glucose concentration.
-Benedict’s and Fehling’s test can also detect glucosuria.
Ketonuria

 Ketone test is preformed n the urine sample of the patient

 This test detects the presence of ketones, which are byproducts of metabolism
that form in the presence of severe hyperglycemia (elevated blood sugar). Ketones
are formed from fat that is burned by the body when there is insufficient insulin to
allow glucose to be used for fuel.
 Increasing ketones level indicates insufficient insulin
 Ketones occur most commonly in people with type 1diabetes, but uncommonly,
people with type 2 diabetes may test positive for ketones.
 Microalbuminuria

-May be defined as an albumin excretion rate intermediate between normality (2.5-25 mg/day) and
macroalbuminuria (250mg/day).
- The importance of microalbuminuria in the diabetic patient is that it is a signal of early reversible
renal damage. o Performing an albumin-tocreatinine ratio is probably easiest. o Microalbuminuria is
a common finding (even at diagnosis) in type 2 diabetes mellitus and is a risk factor for macro
vascular (especially coronary heart) disease.
How to differentiate between type 1 and
type 2

 C-peptide test gives a very negative result in patient with

type 1, while it gives a normal result with type 2
 Urine ketone test gives a higher result in type 1
 autoantibodies or anti-insulin antibodies may give a positive
result in early stages of diabetes mellitus type 1.
 Management of Diabetes Mellitus

The goals of therapy for type 1 or type 2 DM are to:

(1)Eliminate symptoms related to hyperglycemia,
(2)Reduce or eliminate the long-term micro vascular and macro vascular complications of DM,
and
(3)Allow the patient to achieve as normal a lifestyle as possible.
 Management of Type I Diabetes Mellitus

-Because individuals with type 1 DM partially or completely lack endogenous insulin production,
administration of basal, exogenous insulin is essential for regulating glycogen breakdown,
gluconeogenesis, lipolysis, and ketogenesis.

-Likewise, insulin replacement for meals should be appropriate for the carbohydrate intake and promote
normal glucose utilization and storage.
 Management of Type I Diabetes Mellitus

-Islet
cell transplantation is a minimally invasive procedure, wide application of this
procedure for the treatment of type 1 diabetes is limited by the dependence on multiple
donors and the requirement for potent longterm immunotherapy.
 Management of Type I Diabetes Mellitus

-Stem cell therapyStem cell therapy is one of the most promising treatments for the near future. It is
expected that this kind of therapy can ameliorate or even reverse some diseases.
 Management of Type II Diabetes Mellitus

-The goals of therapy for type 2 DM are similar to those in type 1.

-The care of individuals with type 2 DM must also include attention to the treatment of conditions
associated with type 2 DM (obesity, hypertension, dyslipidemia, cardiovascular disease) and

- Detection/management of DM-related complications.

 Management of Type II Diabetes Mellitus

Weight reduction

-Treatment is directed toward achieving weight reduction, and prescribing a diet is only one means to
this end.
-Behavior modification to achieve adherence to the diet
- Increased physical activity to expend energy—is also required.
 Management of Type II Diabetes Mellitus

Hypoglycemic agents

• If the patient is not able to achieve target glycemic control with weight management and exercise, then
pharmacologic therapy is indicated.
• Based on their mechanisms of action, glucoselowering agents are subdivided into agents that increase
insulin secretion, reduce glucose production and increase insulin sensitivity
 Management of Diabetes Mellitus

a) Sulfonylurea—first generation
Chlorpropamide
Tolazamide
Tolbutamide
b) Sulfonylurea— second generation
Glimepiride
Glipizide
Glyburide
c) Nonsulfonylureas
Repaglinide
Nateglinide
Management of Diabetes Mellitus