diabetes mellitus type I __Tuapak

1. Diabetes Mellitus Type I
TuapaK (BWA)

2. Content:
 Def. & Pathophysiology
 Epidemiology
 Temporal Development of DMT1
 Complications
 Treatment

3. Diabetes Mellitus Type I
 Is the result of interactions of genetic, environmental,
& immunological factors that ultimately lead to the
destruction of pancreatic β-cells & insulin deficiency.
 Is caused by selective T lymphocyte-mediated
autoimmune destruction of the β-cells of the
pancreatic islets.
 Autoimmune destruction of the B cell, a process
thought to be mediated by cytokines, occurs
gradually over several years until sufficient(~80%) β-
cell mass is lost to cause symptoms of insulin
deficiency.

4. (cont’d)
 At least 50% of the genetic susceptibility for type 1
diabetes has been linked to the genes of the major
histocompatibility complex(MHC) that encode class II
human leukocyte antigens (HLA).
 These are molecules expressed on the surface of
specific antigen-presenting cells such as
macrophages.
 Class II molecules complex with foreign Ags or
autoAgs; this activates CD4 T lymphocytes via
interaction with the T-cell receptor.

5. (cont’d)
 It is hypothesized that an immune response to
foreign Ags may incite β-cell destruction if these
foreign Ags have some homology with islet cell Ags
(molecular mimicry).
 For example:
 Coxsackievirus protein shares homology-finding(s).
 Bovine serum albumin-a protein present in cow’s milk.
 Only 10% of individuals newly diagnosed with Type 1
diabetes have a family history of diabetes.

6. (cont’d)
 β-cells seem to be particularly susceptible to the
toxic effect of some cytokines (TNF-α, INF-ϒ, IL-1).
 The precise mechanisms of β-cell death are not known
but may involve formation of nitric oxide metabolites,
apoptosis, & direct CD8+ T cell cytotoxicity.
 The islet destruction is mediated by T lymphocytes rather
than islet autoantibodies.

7. Epidemiology:
 More than 90% of cases of diabetes are regarded as
primary processes.
 Type 1 DM is less common than type 2
 Accounts for fewer than 10% of cases of primary
diabetes.
 In a minority of patients of DMT1, the cause is
unknown.

8. Temporal Development of DMT1
The downward
slope of the β-cell
mass varies among
individuals & may not
be continuous.
The progressive
impairment in
insulin release
results in diabetes
when ~80% of β-cell
mass is destroyed.
A “honeymoon”
phase may be seen
in the first 1 or 2
years after onset &
is associated with
reduced insulin
requirements.

9. Complications:
 Acute Complications:
 Diabetic Ketoacidosis (DKA)
 Hyperglycemic Hyperosmolar State (HHS)
 Chronic Complications:
 Vascular:
 Microvascular (Retinopathy, Neuropathy, Nephropathy)
 Macrovascular
 Nonvascular
Gastroparesis, infections, & skin changes.
 Long-standing diabetes may be associated with hearing
loss.

10. Diabetic Ketoacidosis (DKA):
 Absence of insulin, lipolysis is stimulated providing
fatty acids converted to ketone bodies in the liver
by unopposed glucagon action.
 DKA results from relative or absolute insulin
deficiency combined with counterregulatory hormone
excess (glucagon, catecholamines, cortisol, &
growth hormone)

11. (cont’d)
 Reduced insulin levels, in combination with
elevations in catecholamines & growth hormone,
increase lipolysis & the release of free fatty acids.
 Normally converted to TGs or VLDL in the liver.
 However, in DKA, hyperglucagonemia alters hepatic
metabolism to favor ketone body formation, through
activation of the enzyme carnitine
palmitoyltransferase I.
 This enzymes regulates fatty acid transport into
mitochondria, where beta oxidation & conversion to
ketone bodies occur.

12. Clinical Manifestations-DKA:
Manifestations
Symptoms Physical findings
Nausea/vomiting Tachycardia
Thirst/polyuria Dehydration / hypotension
Abdominal pain Tachypnea / Kussmaul respirations /
respiratory distress
SOB Abdominal tenderness (may resemble
acute pancreatitis or surgical
abdomen)
Precipitating events Lethargy /obtundation/ cerebral edema
/ possibly coma
Inadequate insulin administration
Infection
Infarction
Drugs (cocaine)
Pregnancy

13. Management-DKA
1. Confirm diagnosis ( plasma glucose, (+)ve serum ketones, metabolic
acidosis)
2. Admit to hospital; ICU for frequent monitoring or if pH<7.0 or unconscious
3. Assess:
Serum electrolytes
Acid-base status (ABG)
Renal function
4. Replace fluids; 2–3 L of 0.9% saline over first 1–3 h (10–15 mL/kg per hour);
subsequently, 0.45% saline at 150–300 mL/h; change to 5% glucose and
0.45% saline at 100–200 mL/h when plasma glucose reaches 250 mg/dL (14
mmol/L).
5. Administer short-acting insulin
6. Assess patient: What precipitated the episode?
7. Measure capillary glucose every 1-2h; electrolytes (K+ esp.)
8. Monitor BP, pulse, respirations, mental status, fluid intake & output 1-4h
9. Replace K+
10. Continue above until patient is stable, glucose goal 150-250 mg/dL
11. Administer intermediate or long-acting insulin when patient eats.

14. Hyperglycemic Hyperosmolar State:
 Caused by relative insulin deficiency & inadequate
fluid intake.
 Hyperglycemia induces an osmotic diuresis that
leads to intravascular volume depletion, which is
exacerbated by inadequate fluid replacement.
 Lower levels of counterregulatory hormones & free
fatty acids have been found in HHS than in DKA in
some studies.

15. C/Manifestations-HHS
 Elderly patient with DMT2, with:
 Several week history of polyuria
 Weight loss
 Diminished oral intake
 Mental confusion/ lethargy/ coma.
 Physical examination:
 Dehydration & hyperosmolality
Hypotension, tachycardia & altered mental status.
 Precipitating events:
 Serious, concurrent illness(MI or stroke)
 Sepsis, pneumonia, & other serious infections are
frequent precipitants.

16. Treatment-HHS
 Fluid replacement: 1-3L of 0.9% NS over first 2-3h.
 Too rapid a reversal may worsen neurologic function.
 If serum sodium is >150 mmol/L, 0.45% NS be used.
 In patients taking diuretics, the potassium deficit can be
quite large & may be accompanied by magnesium
deficiency.
 Addressed with K+ repletion.
 Hypophosphatemia may occur during therapy:
 Can be improved by using KPO₄ & beginning nutrition.
 Rehydration & volume expansion lower the plasma glucose
initially, but insulin is also required.

17. Chronic Complications-DM:
Vascular Non-vascular
Microvascular Gastrointestinal (gastroparesis,
diarrhea)
Eye disease Genitourinary
Retinopathy
(nonproliferative/proliferative)
Dermatologic
Macular edema Infectious
Neuropathy Cataracts
Sensory & motor (mono- & poly-) Glaucoma
Autonomic Periodontal disease
Nephropathy
Macrovascular
Coronary artery disease
Peripheral arterial disease
Cerebrovascular disease