Diabetes Mellitus

Question 1

Type 1 Diabetes

Answer 1

Insulin dependent-juvenile onset
Peak incidence of less than 20 years of age, but can occur at any age.
Symptoms are caused by absolute insulin deficiency
Patients usually lost >80% of the insulin producing beta cells at diagnosis.
The body has to use alternative fuels when there is no insulin, like ketones, cause acidosis.
Glucose and ketones spill into the urine.
Patients urinate excessively (polyuria) and become dehydrated, making them drink more fluids (polydipsia).
Fat breakdown causes weight loss and patients might be very hungry (polyphagia); coma follows without insulin.
Pathogenesis: Genetics and environment are both important.
95% of people with T1D have HLA alleles DR3, DR4 or both compared with 60% of general population; HLA alleles help lymphocytes recognize and destroy foreign antigens; some HLA alleles could allow lymphocytes to mistakenly attack beta cells i pancreatic islets; DR regions, chromosome 6.
Lymphocytes have been found infiltrating islets in patients, suggesting specific destruction of islets by autoimmune process; T lymphocytes lead the attack.
80% of patients have antibodies to islet cells (ICA); can also have antibodies to insulin (IA2), glutamic acid decarboxylase (GAD), zinc transporter 8.
Environment: Viruses (coxsackie B or retroviruses, congenital rubella, varicella, enteroviruses), something in the air, water or soil.
Molecular mimicry; some viruses look similar to set cell proteins and islets are accidentally damaged when body tries to fight off virus; innocent bystander phenomenon.
Drugs: low vit D levels, vacor, alloxan, streptozotocin, cyclosporine, dioxan toxin; unproven: milk protein, immunization.
Pathology: Insulitis, a lymphocytic infiltrate around islets, containing a few macrophages and neutrophils, gradually disrupting islet architecture; fibrosis.
NEED TO HAVE SUSCEPTIPLE GENETICS, AND THEN A SECOND HIT (ENVIRONMENT).

Question 2

Type 2 Diabetes

Answer 2

Disease of insulin resistance.
Beta cells don’t meet the demands of the body; but insulin levels can still be normal or even high.
Controlled by diet, exercise, weight loss, and oral or injectable medications.
Most common over age 40, but can occur in childhood.
Overweight or obese patients over 10 years old should be screened!!! IF they have at least 2 risk factors: family history, ethnicity, hypertension, hyperlipidemia, acanthosis nigricans (dark thick skin associated with increase insulin levels, increased keratinocytes and melanocytes in response to insulin), polycystic ovarian syndrome.
Screening: fasting glucose > 126mg/dl, HgbA1c > or equal to 6.5, oral glucose tolerance test with 2 hour glucose greater than 200 mg/dl; if abnormal, must confirm with a second test.
Pathogenesis: Genetics important; 60% of patients have an affected parent or sibling; identical twins 90% accordance rate; some families have a defective glucokinase gene; HLA IS NOT INVOLVED AT ALL.
Impaired insulin secretion and decreased insulin uptake by the cells that need it.
Some patients have a deficiency of the glucose transporter Glut-2 in beta cell plasma membranes, disrupting how beta cells sense and respond to glucose; may occur in every generation.
High insulin levels and obesity can actually decrease the number of insulin receptors on cells; can be REVERSED with diet, weight loss, exercise.
Pathology: Amyloid or fibrosis in the islets; no immune cell infiltration; over decades, lose beta cells; normal cells.

Question 3

Gestational Diabetes

Answer 3

Especially seen in women predisposed to T2D, can complicate pregnancies, so all women are screened between 2nd and 3rd trimesters.
Controlled with diet or insulin.
Untreated: leads to very large infants with hypoglycemia, jaundice, respiratory failure, or calcium problems.

Question 4

Steroid induced diabetes (common)

Answer 4

Occurs in patients on high dose glucocorticoids like Prednisone because of organ transplants, sever asthma, lupus, or rheumatoid arthritis.
Treated with insulin until steroid is lowered or discontinued.

Question 5

Chemotherapy

Answer 5

Drugs like vincristine can cause temporary or permanent diabetes.

Question 6

Chronic diseases

Answer 6

Cystic fibrosis, hemachromatosis damage the islets.

Trauma can also cause diabetes.

Question 7

Complications

Answer 7

Caused by severity and chronicity of the hyperglycemia.
Good marker for metabolic control is HgbA1c, which is a measure of RBC glycolsylation (usually live about 3 months); correlates with average blood glucose over 12 weeks; target is

Question 8

Treatments

Answer 8

1. Artificial pancreas
2. islet cell transplants
3. stem cell transplants