3. Goal: The student must be able understand the
importance of blood glucose regulation and
metabolic derangements in diabetes mellitus,
rational and interpretation of biochemical tests
done in diagnosing a case of diabetes mellitus.
Expected Competency:
1. Discuss the mechanism and significance of
blood glucose regulation in health and disease.
2. Demonstrate the understanding of metabolic
derangements in diabetes mellitus
3. Explain the basis and rationale of biochemical
tests done in diabetes mellitus.
4. Objectives :
At the end of the ECE module, 1st MBBS student shall be
able to:
1. Describe the regulation of blood glucose
2. Discuss the pathophysiology and metabolic alterations in
Diabetes Mellitus
3. Discuss the Biochemical basis of Polyuria, Polydipsia, Polyphagia
and other clinical manifestations in Diabetes Mellitus.
4. Sate the reference range for RPG, FPG, PPPG, HbA1c
5. Define the terms normoglycemia, hyperglycaemia and
hypoglycaemia
6. Mention the different criteria for diagnosis of Diabetes Mellitus
as per American Diabetic Association (ADA) and World Health
Organization (WHO) criteria
7. Interpret the lab report of patients with diabetes
8. List the guidelines to collect blood sample for glucose estimation.
9. Discuss the role of HbA1c in management of diabetes mellitus
10. Describe the steps of use of glucometer to estimate blood
glucose level.
5. Learning Experience: Total 3 hours
1. Introduction and instruction to students - 20 minutes
2. Relevant Basic science content discussion - 60 minutes
3. Case discussion - 60 minutes
4. Summary & Conclusion - 20 minutes
5. Reflections - 20 minutes
12. 5. Other specific types:
A. Genetic defects of β cell function:
Maturity-Onset Diabetes of Young [MODY]
B. Genetic defects in Insulin action:
a) Type A Insulin Resistance.
b) Lipodystrophy syndrome.
C. Endocrinopathies: Cushing’s disease, thyrotoxicosis,
acromegaly.
D. Diseases of exocrine pancreas: Pancreatitis,
pancreatectomy, neoplasia, cystic fibrosis and
hemochromatosis.
13. E. Drug induced: Pentamidine, nicotinic acid,
glucocorticoids, β-adrenergic agonists, β-blockers,
clozapine.
F. Infections: Congenital rubella, Cytomegalovirus,
Coxsackie’s.
G. Uncommon forms of immune mediated diabetes:
Stiff man syndrome, anti insulin receptor antibodies.
H. Genetic syndromes associated with diabetes
mellitus: Down’s syndrome, Klinefelter’s syndrome,
Turner’s syndrome, Wolfram syndrome.
15. The risk of developing Type 2 diabetes:
➢ Family history of diabetes (in particular parents
or siblings with diabetes)
➢ Obesity (BMI ≥ 25 kg/m²)
➢ Age ≥ 45 years
➢ Previously identified IFG or IGT
16. ➢ Hypertension (≥ 140/90 mmHg in adults)
➢ HDL cholesterol level <35 mg/dl and/or a
Triglyceride level ≥250 mg/dl.
➢ Reduced physical activity
➢ History of gestational diabetes mellitus (GDM) or
delivery of babies >4 kg
17.
18. Gestational Diabetes :
Glucose intolerance.
1% to 14% ------ Abnormal glucose tolerance.
Risk factors
6% to 62% ------ Type 2 Diabetes.
24. Immunological markers
Islet cell antibodies (ICAs) 75 to 85%
Auto-antibodies to insulin
(IAAs)
90% ------ before 5 years
40% ------ after 12 years
Auto-antibodies to glutamic acid
decarboxylase (GAD65)
60%
Auto-antibodies to tyrosine
phosphatases (IA-2 and IA-2ßA)
50%
Zinc transporter ZnT8 60 to 80%
25. Insulin secretion
Fasting : 2 to 25μIU/ml
Glucose challenge : 200μIU/ml
Pulses.
Fasting hypoglycemia
Polycystic ovarian syndrome
Classification and prediction of DM
Optimal therapy for DM
Insulin resistance
Coronary artery diseases.
Assessment of β-cell activity
26. Proinsulin:
Clinical utility:
◦ Diagnosis of β cell tumors
◦ Familial Hyperproinsulinemia
◦ Cross reactivity of insulin assay
Healthy, fasting individual ----- 1.1-6.9 to 2.1-12.6pmol/l
High concentration:
◦ Type 2 DM
◦ GDM
◦ Chronic renal failure
◦ Cirrhosis
◦ Hyperthyroidism
28. Estimation of Blood Glucose:
Sample collection.
FPG: ≥126mg/dl on two occasions
PPPG
RPG: >200mg/dl
Glycosuria
Renal threshold for Glucose: 180 mg/dl
29. Glucose Tolerance Test (GTT):
◦ Oral Glucose tolerance test (OGTT)
◦ Intravenous Glucose tolerance test
◦ Corticosteroid stressed GTT
30. Oral Glucose Tolerance Test
Indications:
◦ Diagnosis of Impaired Glucose Tolerance.
◦ Gestational DM
◦ Unexplained complications of DM with RPG <140mg/dl
◦ Population studies.
Preparation of the patient
Procedure
31. Factors influencing OGTT
◦ Patient preparation.
◦ Administration of glucose.
◦ During the test.
Contraindications
32. Intravenous Glucose Tolerance Test
Indication: Malabsorbtion
DOSAGE: 25gm/dl over 3min ± 15 sec.
Blood samples for 1 hr at 10 min interval.
K=70/ t1/2
Normal : 1.5%
Diabetes:< 1.0%
33. Corticosteroid Stressed GTT
Cortisol ----100mg (8hr and 2hr) then Glucose
given orally
Normal:
◦ <180mg/dl at 1 hr
◦ <160mg/dl at 2hr.
High in pre-diabetics.
38. Glycated Hemoglobin:
Glycated hemoglobin A: “HbA1”
◦ HbA1a: Fructose-1,6-diphosphate (HbA1a1) or glucose-6-
phosphate (HbA1a2) at N-terminus of β chain
◦ HbA1b: Pyruvate at N-terminus of β chain
◦ HbA1c: Glucose at N-terminus of β chain (>80% of
HbA1)
Schiff base
Amadori rearrangement.
39. Specimen and storage
◦ Venous blood----- EDTA, oxalate and fluoride
◦ Stable at 4º C ----- 1 week
◦ -70º C ---- 18 months.
Reference intervals:
◦ 4 to 6%
◦ 5.7 to 6.4% ----- high risk
◦ ≥6.5% ----- decision point
◦ Goal of treatment : <7% (<6.5%)
Advantages
40.
41. Mean plasma glucose
A1C (%) mg/dL mmol/L
6 126 7.0
7 154 8.6
8 183 10.2
9 212 11.8
10 240 13.4
11 269 14.9
12 298 16.5
Correlation of HbA1c with Average Glucose
42. Fructosamine
Glycated albumin
Advantage
Conditions not useful
Reference interval
◦ 205 to 285 μmol/l
◦ Corrected albumin --- 191 to 265 μmol/l
◦ Glycated albumin --- 11- 16%
43. Ketone bodies
Monitoring:
◦ Type 1 DM
◦ Pregnancy with preexisting DM
◦ GDM
Reference interval:
◦ Normal : 0.21 to 2.81 mg/dl
◦ DM : >20mg/dl
44. UrinaryAlbumin Excretion(UAE)
Persistent proteinuria ---- ≥200μg/min
Microalbuminuria ---- 20- 200μg/min(30-300mg/24h)
Albumin to creatinine ratio
μg/min mg/24h Correctedurine
creatinine(mg/g)
Normal <20 <30 <30
Increased UAE 20-200 30-300 30-300
Clinical
albuminuria
>200 >300 >300
45. Other Laboratory tests
Renal profile: Blood urea and serum creatinine
Lipid profile
Acid base status
Serum electrolytes : Abnormalities related to
dehydration and therapy.
50. 1.A patient arrived at the ED with a blood sugar
of 578,serum osmolarity of 300,pH of 7.3,
severe thirst, dehydration and confusion.The
patient is breathing rapidly and has a fruity
breath smell.This patient has symptoms of
a) Diabetic ketoacidosis
b) Hyperosmolar hyperglycemic non ketotic
coma
c) Hypoglycemia
d) Diabetic neuropathy
51. 2.The nurse enters a patient’s room and sees the patient
breathing rapidly with a fruity breath smell.This is known
as
a) Trousseau’s
b) Cullen’s
c) Kussmaul’s
d) Bitot’s
52. 3.The diabetic patient’s lab work comes back
with a pH of 7.4, serum blood sugar of 950,
serum osmolarity of 460,pCO2 of 35, HCO3 of
25.The patient is confused and dehydrated.This
patient is showing signs and symptoms of
a) Diabetic ketoacidosis
b) Hyperosmolar hyperglycemic non ketotic
coma
c) Hypoglycemia
d) Diabetic neuropathy
53. 4.Ben comes into the ED with blurred vision. He
has polyuria and complains of pain in his legs.
Labs show that he has elevated insulin levels and
high triglyceride levels. Ben also complains of
always being thirsty.What type of diabetes does
ben have?
a) Diabetes I
b) Diabetes II
55. 7.The hormone that is secreted by the
alpha cells of the pancreas that raises blood
glucose when levels are low is:
a) Glucagon
b) Epiniphrine
c) Insulin
d) Cortisol
56. 8.Type 2 diabetes is characterized by:
a) . Insulin resistance.
b) Insulin lack
c) Beta cell destruction
d) None of the above
57. 9.A 35 year old patient comes to your
clinic with newly diagnosed diabetes. Lab
tests reveal no C-peptide in her blood.
She has lost a lot of weight recently,
despite the fact that she has been eating a
lot.This patient has:
a) Adult-onset diabetes
b) GDM
c) Type 2 diabetes
d) Type 1 diabetes
58. 10.Type 2 diabetes typically is diagnosed
at a young age.
a) true
b) false
59. 11.Which of the following tissues requires
insulin for glucose entry into cells:
a) Muscle
b) Liver
c) Kidney tissue
d) Nervous tissue
61. 14.Determination of glycosylated
hemoglobin is used for:
a) Assessing present glucose control
b) Assessing blood glucose control for the past 3
day
c) Assessing long-term( 2 - 4 months) blood
glucose control
d) Adjusting daily insulin doses
62. 15.Insulin promotes all the following
except :
a) lipolysis
b) lipogenesis
c) protein synthesis
d) glucose entry into cells
64. 17.Ketones are a metabolic
by-product of body protein
catabolism.
a) true
b) false
65. 18.Factors that seem to play a role in
the development of type 2 diabetes
include:
a) Weight and heredity
b) liver disease
c) enzyme deficiencies
d) childhood illnesses
66. 19. Which of the following is not a major
risk factor for type 2 diabetes mellitus?
a) Exposure to environmental pollutants
b) Hypertension
c) Family history of type 2 diabetes in a first-
degree relative
d) Age older than 45 years
67. Case 1:
Mr. Venkatesh, a 45 year old businessman was happy
that he had lost 4 kg weight in the last 2 months. He
felt that he was losing weight as he had started
drinking more water than usual though he kept
feeling hungry all the time. He was feeling tiered
throughout the day, he felt as he was getting up 2-3
times a night to urinate that was disturbed his sleep
and made him feel tired all through the day. His lab
investigations revealed following significant findings:
Laboratory Findings:
Fasting Plasma Glucose: 170 mg/dl
Urine Sugar: Absent
Postprandial Plasma Glucose: 240 mg/dl
Urine Sugar: +
Urine ketones: Absent
HbA1c: 7.9 %
68. a. Suggest the probable diagnosis? Why is
urine sugar absent in fasting sample?
b. Discuss the Biochemical basis of
Polyuria, Polydipsia and Polyphagia
c. Discuss the Renal Tubular Reabsorption
of Glucose
69. Case 2:
An 18-year-old male presented to emergency
department with the complaints of vomiting and
abdominal pain since 10 hours. He was diagnosed as
diabetic at 10 years of age. On examination, the
patient had rapid breathing and a fruity odour of
breath. His lab report is as follows,
Random Plasma Glucose:- 500 mg/dl Blood Urea:-
72 mg/dl
Serum Creatinine:- 2.5 mg/dl
Sodium:- 126 mmol/L
Potassium:- 6.3 mmol/L
Chloride:- 86 mmol/L
Bicarbonate: - 12 mmol/L
70. Urine examination:
pH -5
Urine Sugar- ++++
Ketone Bodies- +++
a. Suggest the probable diagnosis? State the
Reference values of the parameters tested
b. Explain the biochemical basis for rapid
breathing and characteristic fruity odour
of breath
c. Blood sample for glucose estimation is
collected in Sodium fluoride tube – Justify
71. Case 3:
Mr. Arun, a 35-year-old male software engineer
sits in-front of computer for more than 10 hours
a day. A month ago when he got checked his
blood glucose level, for his surprise his glucose
levels were in the impaired range. He is obese,
his BMI is 37.2 kg/m2 and he is worried about
developing diabetes.
a. State the diagnostic criteria of ADA for
diagnosis of diabetes mellitus
b. Mention the indications for conduction of
Glucose tolerance test
c. What advice will you give him regarding life
style modification?
72. Case 4:
A 60-year-old female patient with a 8-year history of
T2DM presents with an HbA1c of 9.0% despite
receiving hypoglycaemic drugs for treatment. Her BMI
is 29 kg/m2. Renal function is near normal (estimated
glomerular filtration rate [eGFR] of 89 mL/min/1.73
m2). She has mild dyslipidemia controlled with a statin
and hypertension controlled with an angiotensin II
receptor blocker (blood pressure ≤140/90 mm Hg).
Urine analysis was positive for glucose but negative for
protein
a. What is HbA1c? and state its referenceinterval
b. What is microalbuminuria? Write its diagnostic
significance
c. What is estimated GFR? Grade the chronic kidney
failure based on the GFR
73. Formative assessment:
1. Illustrate the various factors maintaining the
blood glucose level
2. Explain the role of hormones in regulating the
blood glucose level
3. Discuss the metabolic derangement in Diabetes
Mellitus
4. Sate the reference range for RPG, FPG, PPPG,
HbA1c
5. State the Diagnostic Criteria of Diabetes Mellitus
based on American Diabetes Association (ADA)
6. Describe the initial laboratory evaluation of a
case of type 2 Diabetes Mellitus
7. Explain the role of HbA1c in monitoring of
diabetic patients
8. Explain the procedure and interpretation of
Glucose tolerance test with illustrations
74. Reflection:
What happened? (What did you learn
from this experience)
So what? (What are the applications of
this learning)
What next? (What knowledge or skills
do you need to develop so that you can
handle this type of situation?
