Diabetes Mellitus Flashcards
What are the most common end complications of chronic diabetes
ESRD
Adult onset blindness
Non traumatic lower extremity amputations due to atherosclerotic peripheral arteries
Stats about diabetes mellitus
Affect 9.3% of the US population
1.4 million new cases of diabetes are diagnosed each year
86 million adults in the US have prediabeties
Normal glucose = 70-120 mg/dL
American diabetes association diagnostic criteria for diabetes
Any of the following**
1) a fasting plasma glucose greater than 126 mg/dL
2) a random plasma glucose non fasting of > or equal to 200 mg/dL
3) a 2hr plasma glucose test during a OGTT of 75 mg that shows a > or equal to 200 mg/dL
4) a glycated HbA1C level greater than or equal to 6.5%
ADA definition of prediabetes
Any of the following
1) fasting plasma glucose between 100-125 mg/dL
2) a 2hr plasma glucose between 140-199 mg/dL after a OGTT of 75mg
3) a HbA1C between 5.7-6.4%
roughly 25% of these patients will develop actual diabetes within 5 years
Type 1 vs type 2 DM
Type 1 = autoimmune disease that results in pancreatic B-cell destruction and absolute deficency in insulin
- 5-10% of total cases and more common in younger than 20 yrs
Type 2 = peripheral resistance and insulin insufficiency
- 90-95% of total cases and more common in patients > 20yrs
What are three interrelated process that induce glucose homeostasis
1) glucose production in the liver
2) glucose uptake and utilization by peripheral tissues
3) actions of insulin and counter regulatory hormones
Insulin in muscle and adiopcytes and liver
Muscle
- increases glucose uptake and breaks down glucose to ATP
Adipose tissues
- increases glucose uptake and promotes glucose -> lipids
- also inhibits lipid degradation
Liver
- reduces Gluconeogenesis in liver
Type 1 diabetes information
Is an autoimmune disease in which pancreatic islets are destroyed
Most common form in diabetes
After 90% of beta cells are destroyed = diabetic ketoacidosis will present
Genetic association = Class 2 MHC (HLA-DR3/4) genes
- presence of CTLA4 and PTPN22
It is believed that certain viruses (mumps/rubella/coxsackie B) can initiate the autoimmune pathogenesis in type 1 DM
What is the fundamental immune abnormality in DM type 1
Failure of self-tolerance in T cells specific to B-cell antigens
Produces autoantibodies to pancreatic B-cells
- these are seen in roughly 80% of patients
Type 2 diabetes information
Is a heterogenous and multifactorial disease
- there is no evidence of an autoimmune basis for this disorder
Very heavily genetic based (even more than type 1)**
Characterized by two defects
1) decreased ability of peripheral tissues to insulin
2) beta cell dysfunction due to chronic hyperinsulinemia from #1
How does free fatty acids and LDL particles increase in type 2 diabetes
Low glucose uptake and insulin resistance prevents inhibition of hormone-sensative lipase release in adipose Tissues which results in excess FAs in blood
How does obesity impact insulin sensitivity
1) excess FFAs increases insulin sensitivity
2) adipokine activity
- cytokines form adipocytes that are released from adipocytes under chronic lipolysis which induces inflammation
3) overall inflammation results in peripheral insulin and B-cell dysfunction
What is the classic triad of diabetes symptoms
Polydipsia
Polyphagia w/ weight loss
- increased catabolism of proteins and fats due to lack of insulin leads to polyphagia and weight loss
Polyuria
note these 3 are more likely to be seen in combo in type 1 than type 2, but is often seen in both
Diabetic ketoacidosis
Increased lipolysis from fat cells leads to increased FFAs in blood and results in increased ketone body production from the liver
- normally the body can get rid of ketone bodies well enough, but in times of extreme ketone body accumulation can decreased blood pH significantly
Causes of increased ketone bodies
- in times of stress, increased physical activity or infection = ketone body levels can get so high that it produced ketoacidosis
- osmotic diuresis also increases ketoacidosis since the concentration goes up (osmalority)_
Hyperosmolarity nonketotic coma
Caused by severe dehydration due to sustained osmotic diuresis from chronic hyperglycemia
- is harder to notice early unless ketoacidosis is present
