6. Carbohydrate metabolism -4 PBBSc

Diabetes Mellitus
Padmanaban
Associate Professor
Department of Biochemistry
CMC, Vellore
Diabetes mellitus
• Diabetes mellitus is a metabolic condition characterised by

hyperglycaemia (high blood glucose level) due to defective insulin
secretion, or insulin action, or both
• Hyperglycaemia can lead to acute complications. Long standing

hyperglycaemia affects multiple organs leading to chronic
complications
Prevalence
of diabetes in India
74 million people
Collaborators IS-LDBID (2018) The increasing burden of diabetes and variations among the states of India: the Global Burden of Disease Study 1990–2016. The
Lancet Global Health 6:e1352. https://doi.org/10.1016/S2214-109X(18)30387-5
Classification
Diabetes mellitus
Specific types of
Type 1 diabetes Type 2 diabetes Gestational
diabetes mellitus
mellitus mellitus diabetes mellitus
due to other causes
Type 1 diabetes mellitus
• Occurs due to autoimmune destruction of β-cells in pancreas leading

to absolute deficiency of insulin
• Type 1 diabetes accounts for 5-10% of all cases of diabetes mellitus
• Type 1 diabetes usually develops in younger age

Type 2 diabetes mellitus
• Characterised by relative insulin deficiency i.e., insulin is secreted in

lesser amount than what is required by the body
• There is a progressive decrease in insulin secretion from beta-cells
• Action of insulin is impaired in type 2 diabetes (insulin resistance)
• Usually develops at an older age (>35 years)

Gestational diabetes mellitus(GDM)
• GDM is defined as diabetes that is diagnosed for the first time during
the second or third trimester of pregnancy
Clinical features of diabetes mellitus
Following are the classical signs of diabetes mellitus
Polyphagia – Increased hunger

Polydipsia – Increased thirst
Polyuria – Increased urination
Weight loss
Patients can also present with acute or chronic complications of

diabetes mellitus
http://www.sanofidiabetes.in/images/hcp/Comorbid-2.jpg
Laboratory investigations for
diabetes mellitus
Role of laboratory investigations in diabetes mellitus
1. Diagnosis of diabetes mellitus
2. Monitoring blood glucose control in patients diagnosed with

diabetes mellitus
3. Monitoring for complications of diabetes mellitus

Laboratory investigations to diagnose diabetes mellitus
1. Fasting plasma glucose
2. Random plasma glucose
3. Oral glucose tolerance test (OGTT)
4. HbA1c (Glycated haemoglobin)

Oral glucose tolerance test (OGTT)
Procedure:
• Fasting plasma glucose level is measured
• Then a standard amount of glucose (usually 75g of glucose) is dissolved in

water and given to patients for drinking it
• Plasma glucose levels is measured at 1 and 2 hr after administering the

glucose
Use: To diagnose gestation diabetes mellitus

HbA1c (Glycated haemoglobin)
• HbA1c is produced in the body by a non-enzymatic addition of

glucose to haemoglobin
• % of HbA1c in blood reflects the average concentration of

blood glucose present over the life time of RBCs
• HbA1c usually reflects the average blood glucose level for the
past 8 to 12 weeks of the patient
Criteria for diagnosis of diabetes mellitus – By American
Diabetes Association
Fasting plasma glucose ≥126 mg/dL
OR
2-hour plasma glucose ≥200 mg/dL during OGTT
OR
HbA1c ≥6.5%
OR
In a patient with classic symptoms of hyperglycemia a random plasma glucose ≥200
mg/dL
Source: Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020., American Diabetes Association., Diabetes
Care Jan 2020.
https://care.diabetesjournals.org/content/43/Supplement_1/S14
Gestational diabetes mellitus(GDM)
• Occurs in pregnant women
• GDM is defined as diabetes that is diagnosed for the first time during
pregnancy
• GDM can result in complications for the fetus and mother

• Diagnostic criteria for gestational diabetes mellitus is different from
the previously mentioned criteria
• GDM is diagnosed by OGTT
At least one of the following
during a 75 g glucose OGTT
Fasting ≥92 mg/dL

1 hour ≥180 mg/dL
2 hour ≥153 mg/dL
Source: International Association of Diabetes and Pregnancy Groups

Investigations for monitoring blood glucose level (glycemic
control) in patients diagnosed with diabetes mellitus
• Fasting plasma glucose
• Plasma glucose measured 2 hours after eating a meal (post-prandial)
• HbA1c
• Self-monitoring of blood glucose (SMBG)

Investigations for monitoring complications of diabetes mellitus
• Lipid profile
• Serum creatinine
• Urine protein
Principles of treatment of diabetes mellitus
• Aim of the treatment is to maintain the blood glucose level within

target levels to prevent complications
• This involves regular monitoring of glycaemic control

Components in treatment
Lifestyle modifications Drugs
➢Diet must be low in ➢Oral hypoglycaemic agents

carbohydrate and lipids which act by multiple
but rich in proteins and mechanisms e.g.,
fibre Sulfonylurea class of drugs
increase insulin secretion
➢Exercise
➢For type 1 diabetes and
uncontrolled type 2
diabetes, insulin injections
are necessary
Hypoglycemia
Dr. Padmanaban
Associate Professor
Department of Biochemistry
CMC, Vellore
Hypoglycemia
• Hypoglycemia is decrease in blood glucose level
• It can lead to impaired function of the brain since glucose is the only
source of energy for the brain
• If severe, hypoglycemia can cause coma and death and so it is a

medical emergency
Hypoglycemia
Hypoglycemia is clinically diagnosed when all three are present:
1. Symptoms of hypoglycemia
2. Decrease in blood glucose level
3. Relief of symptoms after blood glucose level is increased by

treatment
Causes of hypoglycemia
1. Treatment of diabetes mellitus (Insulin and oral hypoglycemic drugs)
2. Alcohol intake (Decreased NAD+ due to alcohol inhibits gluconeogenesis)
3. Critical illness (Sepsis, hepatic failure)
4. Endocrine disorders (Insulinoma, deficiency of glucagon/epinephrine/cortisol)
5. Metabolic defects affecting gluconeogenesis (E.g. Von Gierke’s disease)
6. Exercise, Starvation
Autonomic nervous system symptoms
http://satisfactorycomics.blogspot.com/2009/12/unsung-cartoonists-little-symptom-guy.html
Brain symptoms
More severe symptoms include seizures, coma and ultimately death if untreated
http://satisfactorycomics.blogspot.com/2009/12/unsung-cartoonists-little-symptom-guy.html

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Diabetes Mellitus

• Diabetes mellitus is a metabolic condition characterised by

• Hyperglycaemia can lead to acute complications. Long standing

• Occurs due to autoimmune destruction of β-cells in pancreas leading

• Type 1 diabetes accounts for 5-10% of all cases of diabetes mellitus

• Type 1 diabetes usually develops in younger age

• Characterised by relative insulin deficiency i.e., insulin is secreted in

• There is a progressive decrease in insulin secretion from beta-cells

• Action of insulin is impaired in type 2 diabetes (insulin resistance)

• Usually develops at an older age (>35 years)

Following are the classical signs of diabetes mellitus

Polyphagia – Increased hunger

Patients can also present with acute or chronic complications of

1. Diagnosis of diabetes mellitus

2. Monitoring blood glucose control in patients diagnosed with

3. Monitoring for complications of diabetes mellitus

1. Fasting plasma glucose

2. Random plasma glucose

3. Oral glucose tolerance test (OGTT)

4. HbA1c (Glycated haemoglobin)

• Then a standard amount of glucose (usually 75g of glucose) is dissolved in

• Plasma glucose levels is measured at 1 and 2 hr after administering the

Use: To diagnose gestation diabetes mellitus

• HbA1c is produced in the body by a non-enzymatic addition of

• % of HbA1c in blood reflects the average concentration of

• Occurs in pregnant women

• GDM can result in complications for the fetus and mother

Fasting ≥92 mg/dL

Source: International Association of Diabetes and Pregnancy Groups

• Fasting plasma glucose

• Plasma glucose measured 2 hours after eating a meal (post-prandial)

• Self-monitoring of blood glucose (SMBG)

• Aim of the treatment is to maintain the blood glucose level within

• This involves regular monitoring of glycaemic control

➢Diet must be low in ➢Oral hypoglycaemic agents

• Hypoglycemia is decrease in blood glucose level

• If severe, hypoglycemia can cause coma and death and so it is a

2. Decrease in blood glucose level

3. Relief of symptoms after blood glucose level is increased by

2. Alcohol intake (Decreased NAD+ due to alcohol inhibits gluconeogenesis)

3. Critical illness (Sepsis, hepatic failure)

4. Endocrine disorders (Insulinoma, deficiency of glucagon/epinephrine/cortisol)

5. Metabolic defects affecting gluconeogenesis (E.g. Von Gierke’s disease)

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