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Flashcards in Cell Signaling II/Diabetes Deck (30)
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1
Q

what are the types of diabetes

A
  1. Type 1: Insulin dependent/juvenile- autoimmune destruction of pancreatic beta cells results in lack of insulin production
  2. Type 2: Non insulin dependent DM or adult onset diabetes- insulin resistance due to insuling signaling defect.
  3. Gestational: happens during pregnancy
2
Q

What are the stats of diabetes

A
  1. 25.8 million americans (8.3%) have it.
    - 18.8 million diagnosed
  2. 0.2 million under 20 yrs old
  3. 5-10% of diabetics are Type 1
  4. 4% of pregnant women develop gestational diabetes.
3
Q

Currently, 1 in ____adults have diabetes

A

10; but if trends continue; 1 in 3 adults could have diabetes

4
Q

What are symptoms of acute onset diabetes

A
  1. Polyuria: excess glucose, urea and ketone bodies getting excreted by kidneys + water goes with them.
  2. Polydypsia: Dehydration leads to excess thirst. This can lead to xerostomia and dental caries.
  3. Polyphagia: lack of insulin action on anorexigenic peptide synthesis leads to excessive hunger.
5
Q

In a normal situation, we’re mobilizing fuel. Insulin activates GLUT 4 transporter to uptake glucose to allow nutrients to be stored. In diabetes we lose affect of insulin. Locked in a ____type of metabolism

A

glucagon.

6
Q

Can bypass insulin by :

A

excercise

7
Q

excess acetyl CoA goes to:

A

ketone bodies

8
Q

what is diabetic ketoacidosis

A

caused by insufficient insulin leading to persistenly high blood glucose (>300mg%)

9
Q

what is DKA associated with

A
  1. infection -40%
  2. missed insulin - 25%
  3. untreated/misdiagnosed diabetes - 15%
  4. Other stressors like heart attack or stroke
10
Q

what are DKA symptoms

A
  1. Acetone breath
  2. high blood glucose
  3. thirst
  4. urination
  5. weakness
  6. confusion
  7. vomiting
  8. abdominal pain
  9. shortness of breath/ inc respiration
11
Q

what are diagnostic tests

A
  1. Fasting plasma glucose test (FPG) - prick your finger. Should be below 100
    - 100-125mg% = pre diabetes
    - >126 mg% diagnostic
  2. Oral glucose tolerance (OGTT) - BG levels monitored over 2-3 hr period
    - 140-199 mg% = pre diabetes
    - >200 mg% diagnostic
  3. Hemoglobin A1c - glycosylated Hb.
    - <7% management goal
  4. C- peptide - verifies if Type 1 or Type 2 diabetic
12
Q

what is the glucose tolerance test

A

measures blood glucose levels. Never should be above 135-140/150. Diabetics usually above 200. Gray area = pre diabetes.

13
Q

How does C peptide test work

A

related to idea that insulin is processed into its two chains held together by disulfide bonds and C peptide. Should have equal amounts of insulin and C peptide. If the only insulin you have is artificial insulin, then it doesnt have any C-peptide associated with it, so c peptide levels will be very low, so True Type 1.

14
Q

What is the treatment goal?

A

lower blood glucose!
you can enhance insulin secretion and enhance blood glucose uptake and bypass insulin signaling by excercise and inc in AMP kinase and adiponectin with some drugs

15
Q

How does AMP kinase get activated and what does it do

A

PPAR gamma - a transcription factor that activates adiponectin which activates AMP kinase which activates GLUT4 transporters which increases muscle FA uptake and decreases liver gluconeogenesis. Ehances insulin sensitivity

16
Q

What are treatment options for diabetics

A
  1. weight loss: target adipose; effect is that it restores insulin
  2. excercise: targets muscle, AMPK activation and enhances glucose uptake
  3. metformin: AMPK activator. Enhances glucose uptake
17
Q

Why are K+ channel blockers being used for insulin secretion

A

K+ channels go out and ATP K+ channel closes whenever ATP levels increase when glucose is available. ATP binds to K+ channel and closes it. WHen it closes you get a depolarization affect and calcium channel opens which is a big signal for excytosis of vesicles. Excytose insulin packed vesicles.

18
Q

what activates PPARgamma

A

Thiazolidinediones which activate adiponectin which activate AMPK

19
Q

What happens if you have long term diabetes

A

increased risk for:

  1. cardiovascular disease & stroke
  2. end stage renal disease
  3. peripheral neuropathy
  4. diabetic retinopathy: major cause of blindness
  5. prolonged wound healing
  6. infection
  7. periodontal disease: loss of attachment, get deep pockets breaking down periodontal ligament and bone around teeth.
20
Q

What causes long term sequalae?

A

glucose spontaneously participates in a schiff reaction with free amino groups within proteins which results in ketoamine linkage of glucose to amino termini and lysine residues of proteins, a process called GLYCATION. The products are called advanced glycation end products (AGEs)

21
Q

What are RAGEs

A

Pattern recognition receptor (like Toll receptor which activate NFkB and AP- 1 which act inflammatory response) RAGE receptors do the same thing! Set up chronic inflammation. Glycated products bind with rage receptors and activate NFkb and the inflammatory response.

22
Q

What does chronic vascular inflammation lead to

A
  1. Impaired vasodilatation (high BP)
  2. impaired flow mediation dilation
  3. impaired response to adenosine
  4. inc stiffness of aorta
  5. renal and carotid artery stenosis (kidney damage and stroke)
23
Q

what is diagnosis of periodontitis

A
  1. appearance of gingivae- redness and swelling
  2. bleeding on probing
  3. pocket probing depth
  4. tooth mobility
  5. alveolar bone loss
24
Q

what happens during periodontal disease

A

toll receptors being activated bc bacteria are in the pockets. You get NFkB and prostanoids and cytokines. CAL increases as well as tooth mobility and loss

25
Q

what can perio disease contribute to

A

insulin resistance. pattern recognition receptors that are act by bacteria products and glycation (rage receptors) activate the same pathway.

26
Q

what are some considerations that a dentist should take when their patient is diabetic

A
  1. degree of metabolic control
  2. duration of disease
  3. presence of other long term complications:
    -retinopathy
    -neuropathy
    -delayed wound healing
  4. concurrent risk factors:
    -plaque
    -smoking
    -stress
    HbA1c > 9% have a 3x greater risk for periodontal disease.
27
Q

Insufficient insulin leads to ____ and DKA, but excess insulin leads to _____

A

hyperglycemia; hypoglycemia

28
Q

Hyperinsulinemic and hypoglycemia can cause:

A

confusion, irritability, sweating, shakiness, and unconsciousness.

29
Q

If blood glucose <70 mg% use the rule of 15:

A

15 g carbs inc blood glucose by 15 mg% in 15 min. :
4 oz juice or soda
6-7 lifesavers
1 Tbsp sugar of honey

30
Q

Brain needs _____

A

glucose! Renal threshold is 180-200 mg% Normal range is 60-90 mg/100 mL