Type I Diabetes Mellitus
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Introduction
Type I diabetes mellitus, or insulin-dependent DM (IDDM), is the most common type in childhood. With a prevalence of 1:400 children, it represents 5-10% of people with diabetes, with the majority accounted for by the epidemic levels of type II diabetes affecting the world.
More than two million Canadians have diabetes. This number is expected to rise to three million by 2010.
DMI primarily develops in children and young adults, though it may occur at any age. Bimodal peaks occur at ages 5-7 and at puberty.
The Case of...
a simple case introducing clincial presentation and calling for a differential diagnosis. To get students thinking.
Causes and Risk Factors
Type I Diabetes results from an autoimmune attack on pancreatic beta cells. The islets of Langerhans become infiltrated by activated T lymphocytes (insulitis), leading to a decrease in the beta cell population over years. This destruction appears to require both environmental (ie infection) and genetic effects (beta cells need to be recognized as 'non-self').
Environmental Factors
Viruses
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Dietary Factors
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Genetics
In monozygotic twins, the concordance rates for type I diabetes are 30-50%; for type II diabetes, it is close to 100%.
Predisposition to TIDM is polygenic:
- IDDM 1 HLA Class II (6p21)
- IDDM2 (11p15) 5' region of insulin gene
- IDDM 3 to 20
Other risk factors include cystic fibrosis and long term corticosteroid use.
Pathophysiology
80-90% of new TIDM patients have detectable islet cell antibodies, compared with 1% of the nondiabetes population. These may be against GAD65, IA-2, or insulin. The presence of multiple autoantibodies is strongly predictive of diabetes development, though as there are no prevention strategies screening is not routinely done.
Symptoms become abruptly when 80-90% of cells have been destroyed.
A deficiency of insulin and a relative excess of glucagon profoundly affect metabolism in three tissues -liver, muscle, and adipose tissue. As time goes
on, Type I diabetics also develop a deficiency of glucagon, leaving them with epinephrine to prevent hypoglycemia. As disease progresses, autonomic
neuropathy also impairs epinephrine response to hypoglycemia.
Hyperglycemia is caused by increased hepatic production of glucose, together with decreased peripheral uptake.
Ketosis occurs due to increased FA mobilization from adipose tissue and increased hepatic synthesis of 3-hydroxybutyrate and acetoacetate during gluconeogenensis. Diabetic ketoacidosis (30-40 mmol) is very common in the newly diagnosed and those who do not comply with therapy. It is treated with fluid and electrolyte replacement and low-dose insulin. Ketone production can be used to discriminate between Type I and Type II DM.
As FA concentration increases, the liver cannot dispose of it all through oxidation or ketone synthesis. Hypertriglycerolemia results as FFAs are converted to TAGs, which are then secreted as VLDL. As insulin regulates lipoprotein lipase, plasma chylomicron and VLDL concentrations become elevated.
Signs and Symptoms
- history
- physical exam
History
Patients with Type I diabetes are usually diagnosed following abrupt appearance of polyuria, polydipsia, and polyphagia, often triggered by stress or illness. Symptoms are usually accompanied by abdominal pain, fatigue, weight loss, and weakness.
A quarter of patients present with diabetic ketoacidosis.
As Type I diabetics usually show deficiency in glucagon and epinephrine, they sometimes suffer from 'hypoglycemia unawareness' that puts them at risk of serious complications such as seizures or coma. Hypoglycemia can be provoked by strenuous exercise due to glucose uptake by muscle, requring frequent monitoring before and after exercise.
Physical Exam
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
A urine dip for glucose and ketones is an initial screening step.
Diagnosis is confirmed with:
- fasting glucose greater than 7 mmol/L, or 125 mg/dl (normal = less than 100 mg/dl)
- any value above 11.1 mmol/L
- oral glucose tolerance testing is rarely required to diagnose TIDM
- pre-diabetes = 100-125 mg/dl), usually accompanied by ketoacidosis.
Glucose Tolerance Test: A patient is given 75 g of oral glucose after an 8 hour fast. In normal individuals, levels rise from less than 110 mg/dl to less than 140 mg/dl. In diabetics, rates start at higher than 126 mg/dl and exceed 200 mg/dl following oral glucose. Glucose also appears in the urine.
- As the glucose tolerance test can be stress-inducing, epinephrine can inhibit insulin release and cause a false positive to the glucose tolerance test.
Diagnostic Imaging
Treatments
Target Levels
Children are more susceptible to CNS damage from hypoglycemia, so target glucose range is higher at 6-12 mmol/L (110-220 mg/dL).
As children age, control becomes tighter at 4-8 mmol/L (70-140 mg/dL).
Type I diabetics must rely on exogenous insulin to control hyperglycemia and ketoacidosis. patients can receive either standard (1-2 injections/day) or intensive (more than 3 injections per day) treatment. Intensive therapy is more work and required frequent monitoring, but mean glucose levels of 150 mg/dl can be achieved with intensive therapy, as compared to 225-275 mg/dl with standard therapy. There is a substantial decrease in long term complications such as retinopathy, nephropathy, and neuropathy with intensive therapy, although hypoglycemic events are more frequent.
You need basal insulin to match baseline hepatic glucose production.
Carb counting
Exercise
Exercise causes hypoglycemia (less than 4 in someone with diabetes)
Consequences and Course
Normal insulin release continues until approximately 50% of beta cells have died. Release is progressively impaired until treatment begins. There is a brief increase in function (honeymoon phase) following diagnosis, but this soon passes and beta cells eventually all disappear.
Additional Resources
Topic Development
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