A 52-year-old woman presented with unconsciousness for 1 hour. She has a 5-year history of type 2 diabetes that was not being treated with medication. On examination, she was severely dehydrated with low blood pressure and an elevated heart rate. Her blood sugar was very high at 21 mmol/L. She was diagnosed with diabetic ketoacidosis and treated with fluid replacement and insulin. Her condition stabilized and she was discharged on oral medications for diabetes.

1. DIABETES
MELLITUS

2. Case Scenario:
Ayesha Begum, 52 years, female, hailing from Keraniganj,
Dhaka, was admitted to Mitford hospital with sudden
unconsciousness for 1 hour.
• According to statement of patient’s attendants, she was
reasonably well 1 hour back. Then she developed confusion,
disorientation and finally became unconscious.
Unconsciousness was preceded by polyuria, polydipsia,
nausea, fatigue and blurring of vision. She is a known
patient of DM for 5 years. She has a family history of
Obesity, Diabetes, Hypertension and coronary artery
disease. Currently she is not taking any medication.
• On examination, she is ill looking with severely dehydrated,
tachypnea (RR 40/min), moderately tachycardia (112/min).
Her Blood pressure 90/50 mmHg.

3. Provisional Diagnosis:

4. Differential diagnoses:

5. Investigations:
 RBS: 21 mmol/L
 Hb: 12.8 gm/dl
 HbA1C: 9.5%
 ESR: 24mm in 1st hour
 WBC: 14000/ mm3
 Serum Creatinine: 0.9 mg/dl
 Serum Electrolytes:
1. Na+ : 135 mmol/L
2. K+ : 5.8 mmol/L
3. Cl- : 99 mmol/L
4. HCO3 : 14 mmol/L
 ECG: Normal Study
 Urine RME:
 Reaction: Acidic
 Albumin: ++
 Sugar: +++
 Lipid profile:
 Triglycerides:310 mg/dl
 Serum cholesterol: 280 mg/dl
 LDL: 180 mg/dl
 HDL: 40 mg/dl

6. Confirmatory Diagnosis:
Type 2 Diabetes mellitus

7. Treatment given:
 Fluid replacement
 Parenteral hypoglycemic drug: Regular
Insulin
 Regular monitoring of vital signs, blood
glucose and urine output.
*After condition was stabilized,
patient was switched to oral anti diabetic drugs:
• Metformin: 850 mg twice daily
• Gliclazide: 80 mg twice daily

8. WHAT IS DIABETES?
Diabetes is a chronic disease that occurs when the pancreas
is no longer able to make insulin or when the body cannot
make good use of the insulin it produces.

9. Epidemiology:

10. Types of diabetes :
There are three main types of diabetes:
Type 1 diabetes used to be called juvenile-onset diabetes. It is usually caused
by an auto-immune reaction where the body’s defense system attacks the cells that produce insulin.
People with this form of diabetes need injections of insulin every day in order to control the levels of
glucose in their blood. If people with type 1 diabetes do not have access to insulin, they will die.
Type 2 diabetes used to be called non-insulin dependent diabetes or adult-
onset diabetes and accounts for at least 90 per cent of all cases of diabetes. It is characterized by
insulin resistance and relative insulin deficiency, either or both of which may be present at the time
diabetes is diagnosed. People with type 2 diabetes can often initially manage their condition through
exercise and diet. However, over time, most people will require oral drugs and/or insulin.
Both type 1 and type 2 diabetes are serious. There is no such thing as mild diabetes.

11. Continued…
Gestational diabetes
(GDM) is a form of diabetes consisting
of high blood glucose levels during
pregnancy. It develops in one in 25
pregnancies worldwide and is associated with
complications to both mother and baby. GDM
usually disappears after pregnancy, but
women with GDM and their children are at an
increased risk of developing type 2 diabetes
later in life.
Maintaining blood glucose levels, blood
pressure and cholesterol at or close to
normal can help delay or prevent diabetes
complications. Therefore, people with
diabetes need regular monitoring.

12. Continued…
Type 3 diabetes" has been suggested as a term for
Alzheimer's disease.
The following is a comprehensive list of other causes of diabetes:
Genetic defects of β-cell function:
Maturity onset diabetes of the young, Mitochondrial DNA mutations
Genetic defects in insulin processing or insulin action:
Defects in proinsulin conversion, Insulin gene mutations, Insulin
receptor mutations

13. Continued…
Exocrine pancreatic defects : Chronic pancreatitis,Pancreatectomy,Pancreatic
neoplasia,Cystic fibrosis,Hemochromatosis,Fibrocalculous pancreatopathy
Endocrinopathies: Growth hormone excess (acromegaly),Cushing
syndrome,Hyperthyroidism,Pheochromocytoma,Glucagonoma
Infections: Cytomegalovirus infection,Coxsackievirus B
Drugs: Glucocorticoids,Thyroid hormone,β-adrenergic agonists,Statins

14. Comparison of type 1 and 2 diabetes
Feature Type 1 diabetes Type 2 diabetes
Onset Sudden Gradual
Age at onset Mostly in children Mostly in adults
Body size Thin or normal Often obese
Ketoacidosis Common Rare
Autoantibodies Usually present Absent
Endogenous insulin Low or absent
Normal, decreased
or increased
Concordance
in identical twins
50% 90%
Prevalence ~10% ~90%

15. WHAT IS INSULIN ?
Insulin is a hormone made by the pancreas
that allows your body to use sugar (glucose)
from carbohydrates in the food that you eat
for energy or to store glucose for future use.
Insulin helps keeps your blood sugar level
from getting too high (hyperglycemia) or too
low (hypoglycemia).

16. Release of Insulin:

17. Mechanism of Action of Insulin
 Insulin stimulates glucose transport
across cell membrane by ATP dependent
translocation of glucose transporter
GLUT4 to the plasma membrane.
 The second messenger PIP3 and certain
tyrosine phosphorylated guanine
nucleotide exchange proteins play crucial
roles in the insulin sensitive translocation
of GLUT4 from cytosol to the plasma
membrane, especially in the skeletal
muscles and adipose tissue.
 Over a period of time insulin also
promotes expression of the genes
directing synthesis of GLUT4.
 Genes for a large number of enzymes
and carriers are regulated by insulin
through Ras/Raf and MAP-Kinase as well
as through the phosphorylation cascade.

19. Pathophysiology of Diabetes:
Type-I
o Auto Immune destruction
Pathologically, the pancreatic islets are infiltrated with
lymphocytes (in a process termed insulitis).
o After all beta cells are destroyed, the inflammatory process
abates, the islets become atrophic
oThe autoimmune destruction of pancreatic β-cells leads to a
deficiency of insulin secretion.
oIt is this loss of insulin secretion that leads to the metabolic
derangements associated with IDDM.

20. Continued…
o In addition to the loss of insulin secretion, the function of pancreatic α-cells
is also abnormal.
o There is excessive secretion of glucagon in IDDM patients. Normally,
hyperglycemia leads to reduced glucagon secretion.
o However, in patients with IDDM, glucagon secretion is not suppressed by
hyperglycemia.
o The resultant inappropriately elevated glucagon levels exacerbate the
metabolic defects due to insulin deficiency .

21. Genetic considerations in Type 1 DM
o Children of diabetic parents are at increased lifetime risk for developing type 1
diabetes.
o A child whose mother has type 1 diabetes has a 3% risk of developing the
disease and a 6% risk if the child's father has it.
oThe risk in siblings is related to the number of HLA haplotypes that the sibling
shares with the diabetic parent.
o If one haplotype is shared, the risk is 6% and if two haplotypes are shared, the
risk increases to 12–25%
oThe highest risk is for identical twins, where the concordance rate is 25–50%.

22. Type -II
 Type 2 DM is
characterized by
impaired insulin
secretion, insulin
resistance, excessive
hepatic glucose
production, and
abnormal fat
metabolism.
 In the early stages of the
disorder, glucose
tolerance remains near-
normal, despite insulin
resistance, because the
pancreatic beta cells
compensate by increasing
insulin output .

23. Continued…
 As insulin resistance and compensatory hyperinsulinemia progress, the
pancreatic islets in certain individuals are unable to sustain the
hyperinsulinemia state.
 IGT, characterized by elevations in postprandial glucose, then develops.
 A further decline in insulin secretion and an increase in hepatic glucose
production lead to overt diabetes with fasting hyperglycemia.
 Ultimately, beta cell failure may ensue.

24. Etiology of Type 2 Diabetes Mellitus
Type 2 Diabetes mellitus (formerly called non - insulin -
dependent diabetes mellitus (NIDDM) or adult - onset
diabetes mellitus) is a disorder that is characterized by
high blood glucose in the context of insulin resistance and
relative insulin deficiency.
Circulating endogenous insulin is sufficient to prevent
ketoacidosis but is inadequate to prevent hyperglycemia in
the face of increased needs owing to tissue insensitivity
(insulin resistance).
Genetic and environmental factors combine to cause both
the insulin resistance and the beta cell loss.

25. Clinical Features:
Signs: Symptoms:
 Hyperglycaemia
(increased blood
glucose level)
 Glycosuria
 Dehydration
 Tachycardia
 Confusion
 Coma
Classic Symptoms:
1. Polyuria (increase
urination)
2. Polyphagia (increased
hunger)
3. Polydipsia (increased
thirst)
4. Weight loss
Other symptoms-
-blurry vision
-headache
-fatigue
-slow healing of wounds
-itchy skin

26. Risk factors for type 1 diabetes mellitus:
•Family history
•Genetics: The presence of certain genes indicates an
increased risk of developing type 1 diabetes.
•Geography: The incidence of type 1 diabetes tends to
increase as you travel away from the equator
•Age: Although type 1 diabetes can appear at any age.
The first peak occurs in children between 4 and 7 years
old, and the 2nd is in children between10 &14 years old.
•Exposure to certain viruses, such as the Epstein-Barr
virus, Coxsackie virus, mumps virus and cytomegalovirus
•Early exposure to cow's milk

27. Risk factors for type 2 Diabetes
mellitus
 Family history of diabetes (i.e., parent or sibling with type 2
diabetes)
 Obesity (BMI >25 kg/m2)
 Habitual physical inactivity
 Race/ethnicity (e.g., African American, Latino, Native
American, Asian American, Pacific Islander)
 Previously identified IFG or IGT
 History of GDM or delivery of baby >4 kg (>9 lb.)
 Hypertension (blood pressure >140/90 mmHg)
 HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or a
triglyceride level >250 mg/dL (2.82 mmol/L)
 Polycystic ovary syndrome or acanthosis nigricans
 History of vascular disease

28. Complications in Diabetes Mellitus
(At A Glance)
Acute:
1.Diabetic ketoacidosis
2. Hyperglycemia
hyperosmolar state
3. Hypoglycemia
4. Diabetic coma
5. Respiratory infections
6. Periodontal disease
Chronic: Microvascular:

29. Continued….
Chronic:
# Macrovascular disease leads to
cardiovascular disease, to which
accelerated atherosclerosis is a
contributor:
1.Coronary artery disease, leading to
angina or myocardial infarction
("heart attack").
2.Diabetic myonecrosis ('muscle
wasting').
3.Peripheral vascular disease, which
contributes to intermittent
claudication (exertion-related leg and
foot pain) as well as diabetic foot.
4.Stroke (mainly the ischemic type).

30. Investigations:
1. Random blood sugar (RBS)
2. Oral glucose tolerance test (OGTT)
3. Glycosylated haemoglobin (HbA1C)
4. Urine R/M/E
5. Complete blood count (CBC)
6. Serum urea, creatinine and electrolytes
7. Serum Lipid profile

31. WHO diabetes diagnostic criteria
Condition 2 hour glucose Fasting glucose HbA1c
Unit mmol/l(mg/dl) mmol/l(mg/dl) mmol/mol
DCCT %
(Diabetes Control and
Complications Trial)
Normal <7.8 (<140) <6.1 (<110) <42 <6.0
Impaired fasting
glycaemia
<7.8 (<140)
≥6.1(≥110) &
<7.0(<126)
42-46 6.0–6.4
Impaired glucose
tolerance
≥7.8 (≥140) <7.0 (<126) 42-46 6.0–6.4
Diabetes
mellitus
≥11.1 (≥200) ≥7.0 (≥126) ≥48 ≥6.5

32. Management of Diabetes
Mellitus:
Diabetes mellitus is a chronic disease, for which there is no known
cure except in very specific situations. Management concentrates
on keeping blood sugar levels as close to normal, without causing
low blood sugar. This can usually be accomplished with --
 A healthy diet
 Exercise
 Weight loss and
 Use of appropriate medications (insulin in the case of type
1 diabetes; oral medications, as well as possibly insulin, in type
2 diabetes).

33. Targets:
HbA1c of 6% to 7%
Pre-prandial blood glucose: 3.9 to
7.2 mmol/L (70 to 130 mg/dl)
2-hour postprandial blood glucose:
<10 mmol/L (<180 mg/dl)

34. Medications:
Type 1 Medications
 Type 1 diabetes is normally present from childhood. Lacking
proper insulin the body has problems processing glucose,
medications are needed to compensate for the lack of
insulin. Insulin is the most common type of medication used
in type 1 diabetes treatment.
Type 2 Medications
 Type 2 diabetes happens when the body becomes resistant to
insulin. In type 2, over time, the pancreas may no longer
make insulin, and the body might become resistant to it
altogether. For this reason, insulin injections can play a role
in type 2 treatment as well. However, there are other types
of medications often recommended only for type 2.

37. References:
Wikipedia on Diabetes Mellitus
Slide share @ LinkedIn
WHO journal on Diabetes Mellitus
Katzung Basic Pharmacology