diabetes type 1 simple introduction

1. Type 1 Diabetes Mellitus.
DM1
Dr. Amany M. Elshamy
Lecturer of Biochemistry and Molecular
Diagnostics

2. Type 1 diabetes
mellitus (T1DM)
• (T1DM) or insulin-
dependent diabetes,
affects almost 2 in 1000
children in the U.S.;
roughly double the
incidence observed just
20 years ago.
• T1DM accounts for about
5% to 10% of individuals
diagnosed with diabetes.
2

3. Type 1
diabetes
mellitus
(T1DM)
• T1DM is caused by an
autoimmune attack against
insulin-producingcells (beta cells)
scattered throughout the
pancreas, which results in
decreased production of insulin
and consequently increased
levels of blood glucose.
3

4. Pathophysiology
4
• The attack begins with cytotoxic T lymphocyte
(CTL) infiltration and activation of
macrophages, frequently referred to as
insulitis , followed by cytokine release and the
production of autoantibodies.
• Autoantibodies specific for beta cells may
contribute to cell destruction.
• which leads to a cell-mediated DTH response.

5. T1DM
• A) pancreas from a
normal mouse
• B) pancreas from a
mouse with a disease
resembling insulin-
dependent
• diabetes mellitus
5

6. Signs and
symptoms
• Polydipsia (excessive thirst)
• Polyphagia (increased food
intake)
• Polyuria (excessive urine
production)
• Rapid weight loss
• Hyperventilation
• Mental confusion, and
possible loss of
consciousness (due to
increased glucose to brain).

7. Major Signs and
symptoms
• Complications include
microvascular problems such as
nephropathy, neuropathy, and
retinopathy.
• Increased heart disease is also
found in patients with diabetes.

8. Complications
• Genetic susceptibility associated with DR3.
• Evaluation for complications of diabetes should be done routinely in diabetic
patients.
A. Routine eye examination
B. Routine foot examination
C. Screening for microalbuminuria
D. Screening for coronary heart disease
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9. Lab findings
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10. Laboratory Findings
• Increased glucose in plasma and urine
• Increased urine specific gravity
• Increased serum and urine osmolality
• Ketones in serum and urine (ketonemia and ketonuria)
• Decreased blood and urine pH (acidosis)
• Electrolyte imbalance
Laboratory
Findings In
Hyperglycemia:

11. Monitoring of
diabetes
mellitus by:
Blood glucose.
Glycated
haemoglobin
(HbA1c).
Glycosuria. Fructosamine.
Blood ketones
(ICU).
Microalbuminuria.

12. Normal Values
12
Fasting plasma glucose (FPG) adults: 100 mg/dL or 5.6 mmol/L
Fasting
Fasting children (2–18 years): 60–100 mg/dL or 3.3–5.6 mmol/L
Fasting
Fasting young children (0–2 years): 60–110 mg/dL or 3.3–6.1 mmol/L
Fasting
Fasting premature infants: 40–65 mg/dL or 2.2–3.6 mmol/L
Fasting

13. Blood Glucose
Level
• Normally the plasma glucose
concentration remains
between about 4 - 10 mmol/L
(70- 180 mg/ml) even after a
carbohydrate meal.
• Significant glycosuria usually
occurs only if the plasma
glucose concentration exceeds
about 10 mmol/L= 180 mg/ml
(the renal threshold).

14. Diabetes Mellitus (DM)
Diabetes mellitus is caused by an absolute or
relative insulin deficiency.
Fasting venous plasma glucose concentration of
7.0 mmol/L=126mg/ml.
Random or post-prandial venous plasma glucose
concentration of 11.1 mmol/L = 200mg/ml.

15. Lab findings
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hyperglycemia (generally ≥300 mg/dL),
glucosuria, ketonemia.
ketonuria, low bicarbonate, elevated
blood urea nitrogen, elevated creatinine
pH usually <7.3.
Decreased total body potassium and
phosphorus

16. Insulin
• Insulin: ( secreted from Pancreas Beta cells)
• Insulin is composed of 51 amino acid in 2
polypeptide chains designated A (21 AA)
and B (30 AA) linked together by 2 disulfide
bridge.
• The 2 polypeptides are connected by C-
peptide.
• C-peptide is released in equimolar amounts
with mature insulin. 16

17. Insulin
17
• Decreased insulin values are found in
the following conditions:
• a. Type 1 diabetes mellitus, severe
Normal
• Adults: 0–35 IU/mL or 0–243 pmol/L
• Children: 0–10 IU/mL or 0–69 pmol/L

18. C-peptide
• C-peptide is formed during
the conversion of pro-insulin
to insulin.
• Pro-insulin is cleaved (holds
and insulin chains together in
the pro-insulin molecule) into
insulin and biologically inactive
C-peptide.
• C-peptide assay provides
distinction between
exogenous and endogenous
circulating insulin. 18

19. C-peptide
• C-peptide levels provide reliable
indicators for pancreatic and
secretory functions and insulin
secretions.
• Decreased C-peptide in DM1
• Normal
• Fasting: 0.51–2.72 ng/mL or
0.17–0.90 mmol/L
19

20. Blood tests
5- Glycosylated Hemoglobin (HbA1C):
• This reaction is irreversible, so glucose will remain attached to the HB until
RBCs are degraded (120 days).
• Hemoglobin A1c (HbA1c), the most commonly detected glycosylated
hemoglobin, is a glucose molecule attached to one or both N-terminal valines of
the - polypeptide chains of normal adult hemoglobin.
• Hyperglycemia: leads to non- enzymatic irreversible attachment of glucose to
a variety of proteins (Mailard Reaction) such as hemoglobin to form HBA1C.
The rate of formation is directly proportional to the plasma glucose
concentrations.
• HbA1c is a more reliable method of monitoring long-term diabetes control than
random plasma glucose.