Special topics: Diabetes and glycemic control -week 1 and 2

What is diabetes mellitus

when plasma glucose is too high for too long; inappropriately elevated plasma glucose

What percentage of all US adults have diabetes mellitus

14.7%

The majority of type 2 diabetes is associated with

bodyweight control, diet, physical activity, genetics, stressors, systemic/oral health

What are some consequences of glycemic dysregulation and diabetes mellitus

periodontal disease, heart disease death rate, stroke, infections, blindness, renal failure, neuropathy, lower limb amputations, birth defects/miscarriages, pregnancy outcome, depression, overall health

The heart disease death rate is ______-_____ x higher with diabetes mellitus

2-4

the stroke risk is ____ -____ x higher with diabetes mellitus

2-4

Plasma glucose is regulated homeostatically to maintain a concentration of between ________ of plasma

70mg-100mg/100ml

what is hypoglycemia

low blood glucose

what can severe hypoglycemia lead to?

unconsciousness, brain and nerve damage, death

what is hyperglycemia

elevated blood glucose levels

what does hyperglycemia lead to?

formation of advanced glaciated end (AGE) products and disordered polyol metabolism which results in damage to blood vessels and tissues

what is glycemic control

plasma glucose homeostasis

what is insulin

functions to decrease plasma glucose when elevated

what is glucagon

functions to increase plasma glucose when its suppressed

What senses high glucose levels (what is the sensor)

pancreatic beta cells

Insulin is released from where

pancreatic beta cells

What are the effectors when glucose is high? (glucose is taken up by what?)

insulin sensitive cells

What senses low glucose levels (what is the sensor)

pancreatic alpha cells

Glucagon is released from where?

pancreatic alpha cells

what are the effectors when glucose is low?

hepatocytes

when glucagon binds to the hepatocytes (receptors on the liver), the glucagon undergoes _________ and________ before glucose is released into the ECF

glycogenolysis, gluconeogenesis

Plasma glucose is homeostatically controlled which means it is a ______ feedback loop

negative

What occurs following a meal

1. carbs digested and glucose enters bloodstream

2. blood glucose increases and taken up by beta cells

3. insulin released into blood stream

4. insulin binds to receptors

5. insulin signals to take in glucose by bringing GLUT4 to surface

6. Glucose enters cells via GLUT4, blood glucose decreases

Insulin receptors are found on insulin sensitive cells that are primarily ______ and _____ cells

skeletal muscle, fat

When blood glucose is high, insulin also strongly inhibits the release of _____ from the liver and the release of _____

glucose, glucagon

When insulin binds to an insulin receptor, insulin signals GLUT4 to translocate from the _____ to the ______

Golgi, cell membrane

plasma glucose enters cell moving _____ its chemical gradient

down

Glucose is not the only regulator of insulin in healthy people. Food in the GI tract signals the release of _______ hormones

incretin

glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide (GLP-1) stimulate ______ release and inhibit ______ release which is known as the ________ _____

insulin, glucagon, incretin effect

During exercise, insulin release is _______

inhibited

What occurs during a period of hypoglycemia in a healthy person

- insulin secretion decreases due to low glucose, GIP, and GLP-1

- glucagon is released primarily due to low insulin and low glucose

- Glucagon stimulates the release of liver glucose to help restore blood glucose level

Following a meal, there is a normal period of hyperglycemia that is corrected by the

increased release of insulin

following a fast, a drop in blood glucose will be corrected by the

increased release of glucagon

if blood glucose is too high for too long what occurs

gradual but progressive damage to blood vessels and tissues; severity dependent on duration and degree of hyperglycemia

How fast does hyperglycemic damage occur

occurs over years

if blood glucose is too low for too long what happens (70-50 mg/ml)

shakiness, dizziness, nauseated, sweaty, irritable, weakness, nervousness, headache

if blood glucose is too low for too long what happens (

neural dysfunction, loss of consciousness, seizure, coma, death

How fast does hypoglycemic damage occur

within minutes

How are type I and II DM different

differentiated by the mechanism leading to hyperglycemia, treatment and specific concerns

What causes type I diabetes

loss of glucose-sensing and insulin-producing beta-cells (autoimmune attack of beta-cells)

What leads to atrophy in type I diabetes

the diminished glucose uptake in skeletal muscle and fat cells

damage in type I DM is due to

excessive glycation, disordered polyol metabolism and other mechanisms occurs throughout body

Lack of insulin in type 1 DM and leads to release of _____ and increased release of

glucagon, glucose from the liver

elevated glucagon in type 1 DM drives processes to increase risk of

diabetic ketoacidosis (DKA)

What is the treatment for type 1 DM

adequate exogenous insulin

What are the clinical considerations for type 1 DM

- Obtain the most recent HbA1c% for all patients with diabetes

- Double your vigilance in obtaining A1c% results for your patients with type 1 Dm

- a type 1 DM patient with poor glycemic control the previous 90-120 day is at increased risk for: Poor wound healing and infection diabetic ketoacidosis in chair

In type 2 DM, effector cells are

insensitive or resistant to insulin

beta cells are functional early in the course of type 2 DM with plasma insulin often

very high

hyperglycemia is due to

insulin resistance by the insulin sensitive cells

in type 2 DM, the signaling capacity is diminished and therefore there is reduced

movement of the GLUT4 transporter to the surface and less glucose uptake

Persistently elevated glucose results in the pathological

glycation of proteins

pathologically glycated proteins often become structurally or functionally altered and then attacked by the body's immune cells leading to

tissue damage

the higher the average plasma glucose, the greater the rate of

glycation

hemoglobin A1c glycation is an index to estimate

overall protein glycation

What are common signs and symptoms of type 1 DM

sudden weight loss, polyuria, thirst, elevated blood glucose levels

Type 2 diabetes is often associated with

family history, obesity and physical inactivity

What are clinical considerations for diabetes mellitus

-keep glucose tablets available throughout your office, and oral glucose if possible

-acarbose is a fairly common diabetes medication that decreases the digestion of carbohydrates into their adsorbate form

-the sugars in soft drinks, frosting, candy and juices all require digestion, glucose tablets does not