Diabetes Mellitus Type I

“Insulin Dependent Diabetes”:

Distinguished from Type II by a C-peptide assay
(measures endogenous insulin production)

Classic symptoms (of hyperglycemia):

-polyuria (frequent urination)
-polydipsia (↑ thirst)
-polyphagia (↑ hunger)
-weight loss

Other symptoms: fatigue, blurry vision,

tingling/numbness in feet
 DM Type I

Problems 2' DM that often lead to DM Dx:

-MI
-CVA
-neuropathy
-poor wound healing/foot ulcers
-eye problems
-fungal infx
-delivering LGA baby (>4000g)
 DM Type I: Ketoacidosis

Symptoms of very high blood sugar:

-Deep, rapid breathing (Kussmaul pattern)
-Dry skin/mouth
-Flushed face
-Breath smells fruity (acetone)
-N/V
-Stomach pain
DM Type I – Genes vs Environment
Strongly influenced by environmental factors
(possibly virus-related) as evidenced by studies
of twins: only 50% chance of DM type 1 if
identical twin has it, vs 75% chance w/ DM type
2

There is a genetic component: main gene is

IDDM1 (MHC Class II region of Chr. 6, @ 6p21)
→ beta cells display improper antigens to T cells

Increased genetic risk: HLA types DR3 & DR4

 DM Type I - Dx

-Fasting glucose >= 126 mg/dL (100-125)

-Plasma glucose >= 200 mg/dL (140-199) two hr
after 75g glucose load (GTT)
-Glycated Hb (HbA1c) >= 6.5% (5.7-6.4)

If positive, repeat on a 2nd day to establish Dx

Approx 25% w/ new onset DM Type I develop

diabetic ketoacidosis before they are diagnosed
 DM Type I
“Impaired Fasting Glucose”: fasting glucose
between 100-125 mg/dL

“Impaired Glucose tolerance”: plasma glucose

after GTT between 140-199 mg/dL
→ major risk factor for:
(1) progression to DM
(2) cardiovascular disease

HbA1c between 5.7% and 6.4% is considered

“pre-diabetes”
 DM Type I - Treatment

Total daily insulin (TDI) = weight (in lb) / 4

(50:50 or 40:60 basal/bolus)

1 unit bolus = 12-15g carbs (can use 500/TDI)

= drops blood sugar by 30-100 mg/dL,
avg 50mg/dL (can use 1800/TDI)

**Adjust dose for: exercise, travel, sickness, or

changes in caloric intake
DM Type I – Types of Insulin
 DM Type I – Blood Sugar Levels

 American Diabetes Association recommends

these blood sugar levels (in mg/dL):
Before meal At bedtime
Adults 70-130 <180
Teens 13- 90-130 90-150
19yo
Kids 6-12yo 90-180 100-180
Kids <6yo 100-180 110-200
 DM Type I - Complications:
-Hypoglycemia: irritability, shaking/trembling,
weakness, sweating, impaired coordination,
drowsiness, confusion, headache, dizziness,
diplopia, palpitations, seizures,
unconsciousness

*Children w/ DM are more at risk of hypoglycemia

than adults & should maintain higher blood
sugars

Other complications: cardiovascular disease,

diabetic neuropathy, diabetic retinopathy
 DM Type I – Preventative

-HbA1c every 3-6 mo

-Check skin & bones on feet & legs
-Keep BP <= 130/80 mmHg
-Annual BUN/creatinine & cholesterol/triglyceride
tests
-Visit opthalmologist at least once/year
-Dentist appt every 6 mo
-Regular exercise
-Consistent meals
 DM Type I - Prevention
-DiaPep277 (phase 3 trials): peptide fragment of
HSP60, given subQ, induces Th1-Th2 shift
(change from pro- to anti-inflammatory
cytokines): clinical success in newly diagnosed
DM Type I Pts (prolongs honeymoon period,
when beta cells can be saved by insulin Tx)

-Bacillus Calmette-Guerin (BCG): inexpensive

generic drug for TB immunization, stimulates
TNF-alpha production (helps immune system
differentiate self from non-self), human trials
began 2008 → permanent cure in 1/3 of test
mice
 DM Type I – Prevention (cont'd)

-Diamyd vaccine: started phase 3 trials in USA in

2008, involves injection of GAD65 (autoantigen),
delays destruction of beta cells for >= 30mo,
recipients have higher lvls of regulatory
cytokines (protective effect)
 Practice Question
A 32-year-old woman with type 1 diabetes mellitus has had progressive renal failure
over the past 2 years. She has not yet started dialysis. Examination shows no
abnormalities. Her hemoglobin concentration is 9 g/dL, hematocrit is 28%, and mean
corpuscular volume is 94 μm3. A blood smear shows normochromic, normocytic
cells. Which of the following is the most likely cause?

(A) Acute blood loss

(B) Chronic lymphocytic leukemia
(C) Erythrocyte enzyme deficiency
(D) Erythropoietin deficiency
(E) Immunohemolysis
(F) Microangiopathic hemolysis
(G) Polycythemia vera
(H) Sickle cell disease
(I) Sideroblastic anemia
(J) β-Thalassemia trait