Diabetes (Welch) Flashcards
(163 cards)
1
Q
Does a diabetic have more or less glucose in saliva than non-diabetic ,and what does this mean for caries risk?
A
- More glucose
2. Increased caries risk
2
Q
What is a concern for a diabetic who has a periodontal infection?
A
Infection can lead to increased blood sugar making diabetes harder to control
3
Q
Diabetics are susceptible to what oral problems beyond caries and decreased healing?
A
- Xerostomia
- Candida infections
- Sores/ulcers
4
Q
Before Insulin was discovered in 1921, what type of disease was Type I diabetes?
A
Wasting, fatal w/in weeks to years of onset
5
Q
The majority of diabetes today is which type: Type I or Type II?
A
90% Type II
10% Type I
6
Q
What percentage of the pancreas is exocrine?
A
98%
7
Q
What percentage of the pancreas is endocrine?
A
2%
8
Q
What is the functional unit of the pancreas?
A
Islet of Langerhans
9
Q
What are 4 cell types in the Islets of Langerhans in Pancreas?
A
- Alpha Cells
- Beta Cells
- Delta Cells
- F or PP Cells
10
Q
Alpha cells in the Islets of Langerhans in the Pancreas secrete what?
A
Glucagon
11
Q
Beta cells in the Islets of Langerhans in the Pancreas secrete what?
A
Insulin
12
Q
Delta cells in the Islets of Langerhans in the Pancreas secrete what?
A
Somatostatin
13
Q
F or PP cells in the Islets of Langerhans in the Pancreas secrete what?
A
Pancreatic Polypeptide
14
Q
What links the chains of Insulin as it matures?
A
Disulfide bonds
15
Q
How many chains are in mature insulin and by what are they connected?
A
2 chains, linked by disulfide bonds
16
Q
What is cleaved off of Proinsulin to make it into Insulin when the body needs it?
A
C-peptide
17
Q
Why is C-peptide tested for in diabetics as a sign of insulin amount?
A
C-peptide is 1:1 for insulin
18
Q
Because the disulfide bonds are far apart in insulin, it makes them easily cleaved by insulinase, resulting in a long or short half-life?
A
Short
19
Q
The first precursor of insulin, Preproinsulin is synthesized where in the Beta Cell?
A
Rough endoplasmic reticulum
20
Q
Loss of what converts Preproinsulin to Proinsulin, the direct precursor to Insulin?
A
Loss of hydrophobic signal sequence
21
Q
The Proinsulin is transported to where and packaged with what?
A
Transport to Golgi
Packaged with PC2 and PC3 endopeptidases
22
Q
What 2 things are created when Proinsulin is cleaved in the Beta cell?
A
- Insulin
2. C-peptide
23
Q
Will Insulin be created if the endopeptidases don’t cleave?
A
No. This is one of the ways you can get Type II diabetes
24
Q
Majority of the Pacreatic Islets are what cell type?
A
Beta
25
Insulin is a hormone used when: times of plenty or fasting?
Times of plenty
26
What are 3 general things Insulin does after a large meal?
1. Increase fats
2. Increase proteins
3. Increase sugar storage
27
Glucagon, secreted by the Alpha cells of the Pancreatic Islets, is a hormone for when: times of plenty or fasting?
Fasting
28
What are 3 things Glucagon increases during fasting?
1. Increase glycogenolysis
2. Increase gluconeogenesis
3. Increase ketogenesis
29
What is a normal glucose level range?
90-110
30
What is the general problem in a diabetic with meals?
Glucose increases but never goes back down to a baseline, so blood sugar remains high
31
How is the liver involved in diabetes?
Due to glucose not being used by cells in a diabetic, the liver goes into constant gluconeogenesis thinking there is a lack of glucose
32
What is gluconeogenesis?
Production of glucose from proteins in the liver
33
For Type II diabetes, what is the pancreatic problem?
Decreased insulin secretion
34
For Type II diabetes, what is the body tissue problem?
Decreased glucose uptake
35
What is a layman's way to describe diabetes?
Starving at a banquet
36
Any glucose not used by a cell for energy is stored as what?
Glycogen
37
What is a byproduct of gluconeogenesis, the breakdown of proteins to make glucose for energy?
Urea byproduct is created
38
What is a byproduct of lipid breakdown for energy?
Create free fatty acids and ketone bodies
39
What is a byproduct of lipid breakdown for energy?
Free fatty acids and ketone bodies
40
What is the only way for glucose to get into a cell from the blood?
Insulin must bind a receptor on the cell
41
When insulin binds to a cell and glucose is let in, what is done in the cell?
Gluco-1-phosphatase is used for energy. Glucose not used for energy is stored as Glycogen via glycogen synthetase. Proteins and lipids are stored.
42
What decreases when Insulin binds its receptor and allow glucose into the cell?
1. Gluconeogenesis decreases, decreasing urea excretion
| 2. Lipase decreases, decreasing FFA and Ketone bodies
43
What is the problem at the cell level when Insulin is either not present and doesn’t bind the receptor or is not functional to bind the receptor?
Glucose does not enter the cell so blood stays hyperglycemic. Cell breaks down glycogen stores to use for energy
44
What does the cell move onto when its glycogen stores are depleted in a diabetic with either no insulin, or non-functional insulin?
Gluconeogenesis increases causing increased Urea excretion and decreased amino acid excretion
45
What will a diabetic have in their urine that indicates they are undergoing gluconeogenesis for energy?
Azoturia = high concentration of nitrogen in urine
46
After gluconeogenesis has depleted the proteins in the cell, what is used for energy in the diabetic?
Lipids are broken down via lipase increasing free fatty acid excretion causing hyperlipidemia in the blood and increasing ketone bodies in the liver
47
If a diabetic is acidotic due to high amounts of free fatty acids overwhelming the liver, what physical sign will be seen?
Hyperventilation
48
What molarity is diabetic blood: hyperosmolar or hypoosmolar?
Hyperosmolar
49
What will body try to do to hyperosmolar blood?
Dilute it by sucking fluid out of tissues
50
With inherited insulin resistance common in Type II diabetes, what will occur with Normal Beta Cell function?
Beta cells will hypersecrete causing compensatory hyperinsulinemia making person normoglycemic for a time
51
With inheritied insulin resistance common in Type II diabetes, what will occur once the Beta cells stop their hyperfunctioning to compensate for the insulin resistance?
Beta cells secrete less insulin leading to an insulin deficiency, hyperglycemia, and Type II diabetes
52
What stimulates the Beta cell to secrete insulin and via what transporter?
Glucose enters Beta cells via GLUT 2
53
What phosphorylates glucose to its energy usable glucose-6-phosphate?
Glucokinase
54
Glycolysis and oxidative metabolism of glucose?
ATP
55
What causes the secretion of insulin from the Beta cells?
increase of ATP closes ATP sensitive K channels causing cell depolarization which opens Calcium channels leading to an increase of intracellular calcium that causes insulin granules to fuze with Beta cell membrane and secrete insulin via exocytosis
56
Kinases always do what?
Phosphorylate things
57
To have the excretion of a transmitter, you have to have an influx of what?
Calcium
58
What is the most important stimulus for insulin secretion?
Glucose
59
Is insulin excreted in one or two phases?
Two phases.
First phase: Exocytosis of insulin at the membrane.
Second phase: An hour or so later
60
An increase in plasma glucose does what to Beta cells of the pancreas?
Stimulates beta cells
61
Does an increase in plasma glucose stimulate Pancreatic Alpha Cells?
No
62
What is the negative feedback for Beta cells?
They dump insulin which causes blood glucose to drop. A decrease in blood glucose stops Beta cell stimulation
63
Does a Type II diabetic have the first phase insulin dump that is found in a normal person?
No
64
What subunit of the insulin receptor is transmembrane?
Beta subunit
65
What second messenger is the insulin receptor linked to?
Tyrosine kinase
66
What is the glucose transporter in the cel?
GLUT 4
67
What is a group of diseases characterized by high levels of blood glucose resulting from defects of insulin secretion, insulin action, or both?
Diabetes
68
Diabetes is the leading cause of what in adults?
Blindness
69
What is a normal fasting blood glucose?
<110 mg / dl
70
When should diabetes screening start and if normal, how often should it be repeated?
At age 45
| Repeat every 3 years if normal
71
What are 2 medicines that will increase blood sugar?
1. Steroids
| 2. Dilantin
72
What is an inheritied defect in the immune system that attacks the beta cells that produce insulin and destroys them (Associated with Ketosis and acidosis. Requires insulin replacement)?
Type I diabetes
73
What has insulin resistance or insulin deficiency, and is by far the largest percentage of diabetes (Treated with insulin and/or oral medications)?
Type II diabetes
74
Which diabetes type shows more genetic connection?
Type II diabetes
75
What are symptoms of hyperglycemia, seen in diabetics?
1. Thirst
2. Frequent urination
3. Dry skin
3. Hunger
4. Blurred vision
5. Drowsiness
6. Nausea
76
What is the treatment of reatment of type I diabetes?
1. Diet
2. Exercise
3. Insulin
77
What is the treatment of Type II diabetes?
1. Diet
2. Exercise
3. Metformin
4. Sulfonylurea
5. Metformin and sulfonylurea
6. Metofrmin and sulphonylurea and thiaxolidinedione
7. Insulin
78
If drugs to treat Type II diabetes do not work, what is given?
Insulin
79
What is the Goal of Insulin Therapy?
Mimic as closely as possible physiological insulin secretion
80
For what Diabetes type is Insulin the front line therapy?
Type I
81
What diabetes type is insulin the last line therapy?
Type II
82
The amount of insulin per unit of time necessary to prevent unchecked gluconeogenesis and ketogenesis and regulate metabolism?
Basal insulin
83
What amount of insulin is required to cover elevations in glucose following a meal?
Basal insulin
84
What amount of insulin required to cover elevations in glucose following a meal?
Bolus Insulin
85
What is the supplemental doses of short acting insulin given to correct hyperglycemia that is outside of the recommended range?
Correctional insulin
86
What is the name of a short-acting insulin?
Regular - Humulin R
87
Short-acting Humulin-R is always used for what?
Sliding scale coverage
88
What is an intermediate-acting insulin name?
NPH - Humulin N or Isophane
89
What is the mixture insulin ratio?
70:30
70 units NPH Humulin N intermediate acting
30 units Regular - Humulin R short-acting
90
What is the name of a long-acting insulin?
Lantus
91
Insulin is only active in which state?
Monomer
92
Long-acting insulins (like Lantus) will be in which state?
Hexamers that slowly dissociate to monomers
93
Intermediate acting insulins (NPH-Humuli N) will be in which state?
Dimers
94
Short-acting insulins (Humulin-R) will be in which state?
Monomer
95
When is long-acting insulin (Lantus) given and is it mixed with other insulin types?
Given at bedtime and not mixed
96
What is the key to insulin therapy?
It must be tailored to the individual
97
What insulin injection type that is required for mealtime insulin coverage?
Regular insulin
98
What are 2 rapid acting insulins that have an onset within 5-15 mins, and peak at 1 hr, with a 2-3 hr duration?
1. Humalog
| 2. Novalog
99
What is the name of a short-acting insulin that has an onset of 1/2 to 1 hour, peaks at 2-3 hours, and has a 2-4 hour duration?
Regular
100
What are the names of 2 intermediate-acting insulins that have an onset of 1-3 hours, peak at 4-8 hours and have a 10-16 hour duration?
1. NPH
| 2. Lente
101
What are the names of 2 long-acting insulins with an onset of 6-10 hours, have no peak, and an 18-24 hour duration?
1. Ultra lente
| 2. Glargine
102
Sulfonylureas targets what for type II diabetes?
Stimulate body to make and release more insulin
103
Metformin targets what for Type II diabetes?
Lowers blood sugar by helping insulin work better and decrease liver release of glucose
104
Thiazolidinediones target what for Type II diabetes?
increases muscle sensitivity to glucose
105
Alpha-glucosidase inhibitors target what for Type II diabetes?
Slow process of carbohydrate digestion
106
What are side effects associated with insulin, sulfonylureas, and rapaglinidine and neteglinide, all of which increase glucose uptake by the cells?
Can induce hypoglycemia
107
What is a risk associated with Metformin?
Can induce lactic acidosis
108
What is important about Incretin mimetics in the treatment of Type II diabetes ?
It has no adverse effects (e.g. hypoglycemia, lactic acidosis)
109
If Metformin, alpha-glucosidase inhibitors, or glitazones (TZDs) were given to a normal person, would they induce hypoglycemia and why?
No. Because they stop working when normal blood glucose is reached
110
What is a common side effect of most oral agents for Type 2 diabetes?
Weight gain (Metformin does not risk weight gain, but has the lactic acidosis risk)
111
What is a problem with Type II diabetic drug prescriptions?
Patient compliance
112
Do Sulfonylureas for the treatment of Type II diabetes by stimulating production and release of insulin, have effect on microvascular and cardiovascular
only on microvascular
113
Does Alpha-glucosidase inhibitors for the treatment of Type II diabetes have an effect on microvascular and cardiovascular?
Only on cardiovascular
114
What is the positive with respect to microvascular and cardiovascular for incretin mimetics?
Has no effects on either. It decreases stickiness of diabetic blood
115
What is the failure of the beta cells to produce enough insulin in type II diabetes called?
Reduced beta cell response
116
What is the other factor in type II diabetes besides reduced beta cell response?
Peripheral insulin resistance
117
Which type of diabetes includes insulin resistance and reduced beta cell response?
Type 2 diabetes
118
What are 2 things beyond insulin resistance and reduced beta cell response that is associated with Type II diabetes?
1. Inappropriately elevated glucagon
| 2. Impaired secretion of incretin hormones
119
What are 4 causes of Beta Cell dysfunction?
1. Molecular defects(mutation) in beta cells
2. Glucose toxicity
3. Lipotoxicity
4. Islet amyloid polypeptide (IAPP) / amylin
120
What is the term for an elevation in free fatty acid concentrations mediated by insulin-resistance at the adipocyte. High fat diets can adversely affect insulin secretion by Beta Cells. Free fatty acids contribute to Beta Cell defect in Type II diabetes?
Lipid toxicity
121
What is co-secreted with insulin by beta cells in 1:100 ratio and is used to slow the rate of gastric emptying, reduces glucose release from liver, reduces appetite, decreases insulin action and hypoglycemia due to insulin. High concentrations in Type 2 diabetics contributing to decreased insulin efficiency?
Islet amyloid polypeptide deposits
122
Incretin, a new Type II drug, is also called what?
Glucose Like Protein 1 = GLP-1
123
Incretin / GLP-1 functions where?
In the gut , can increase insulin response
124
What turns off Incretin / GLP-1?
DPP-IV
125
What does incretin do in the gut?
Delays emptying and induces satiety
126
What does Incretin / GLP-1 do for the Beta Cell?
Stimulates Beta cell function
127
What are 4 things Incretin / GLP-1 does for glucose homeostasis?
1. Enhances glucose dependent insulin secretion 2. Suppresses inappropriate glucagon secretion
3. Promotes satiety leading to less food intake
4. Regulates rate of gastric emptying, limiting postprandial (after eating) glucose excursion
128
What are 2 ways to make Incretin/GLP-1 work longer, since it is naturally short acting?
1. Modify the GLP-1 so DPP-IV enzyme cannot metabolize it
| 2. Impair the DPP-IV enzyme itself
129
What is a long-acting GLP-1 analogue for Type II diabetes treatment?
Liraglutide
130
What s a synthetic version of a hormone found in Gila monster saliva that has been shown to bind and activate the known human GLP-1 receptor to give natural physiologic self-regulating glycemic control?
Byetta / exanatide
131
What are 5 things Byetta, an incretin mimetic, does?
1. Enhances insulin secretion
2. Restore 1st phase insulin response
3. Suppress glucagon secretion from alpha cells when hyperglycemic which decreases glucose output from liver
4. Reduce food intake
5. Slow gastric emptying to allow more time for nutrient absorption
132
Will Byetta enhance insulin secretion even if the patient is not hyperglycemic?
No
133
What does Byetta do to insulin secretion as blood glucose reaches normal levels?
Decreases insulin secretions
134
What does Byetta mimic and when does it start working?
Mimics the body’s natural physiology
135
What is Januvia's mechanism of action?
Enhances incretin system by inhibiting DPP-IV that breaks down GLP-1 and only works when hyperglycemic
136
Will Byetta , which is a DPP-IV resistant GLP-1 mimetic, or Januvia, a DPP-IV inhibitor so GLP-1 can function, work in a both Type I and Type II diabetics and why?
Only in Type II diabetics because drug relies on a functioning incretin system
137
Can Januvia be used as a monotherapy for Type II diabetes?
Yes
138
This is the oldest Type II therapy and will induce hypoglycemia regardless of blood glucose level?
Sulfonylureas
139
What are some first generation Sulfonylureas that simtulate beta cells to secrete insulin(work at the ATP gated K- channels in the pancreas). Only one mechanism of action. Have adverse effects of cardiovascular disease, hypoglycemia?
1. Acetohexamide (Dymelor)
2. Chlorpropamide (Diabinese)
3. Tolazamide (Tolinase)
4. Tolbutamide (Orinase)
140
What are some second generation Sulfonylureas that stimulates beta cells to release insulin, as well as stimulating releast of glucagon and somatostatin, inhibiting hepatic gluconeogenesis and enhancing insuling receptor sensitivity. Fewer adverse effects than first generation Sulfonylureas, but can still induce hypoglycemia?
1. Glyburide (diabeta)
2. Micronase and Glipizide (Glucotrol)
3. Glimepride
141
What is important about Second generation Sulfonylureas causing release of glucagon and somatostatin at the same time?
Somatostatin inhibits glucagon
142
Meglitinides act in the same way as what other class of Type II diabetic drugs?
Sulfonylureas
143
What is the difference between Meglitinides and Sulfonylureas since they both act on the ATP-gated K- channels on the Beta cells of the pancreas to increase insulin secretion?
Longer onset of action and more expensive
144
What are 2 types of meglitinides?
1. Repaglanide (Prandin, Gluconorm)
| 2. Nateglinide (Starlix)
145
Biguanides act how?
Inhibit hepatic gluconeogenesis and increase muscle insulin sensitivity, but increases lactic acid
146
Which biguanide is the tenth most-used generic medication used in the US?
Metformin (Glucophage)
147
Will Biguanide (Metformin) increase or decrease LDL, triglycerides and C-reactive protein?
Decrease
148
What is the first line drug for Type II diabetes?
Metformin
149
What is the second line drugs for Type II diabetes?
1. Thiazolidinediones
2. Sulfonylureas and meglitidines
3. Alpha-glucose inhibitors
150
Which second-line Type II diabetes drug decreases absorption of carbohydrates in the small intestine, increases triglycerides, and causes flatulence?
Acrobose (Prandise), an Alpha glucose inhibitor
151
What is the dawn phenomenon?
Early morning rise in blood glucose levels believed to be due to a delayed response in Growth Hormone release
152
What insulin type is in an insulin pump?
Short-acting
153
An HbA1c greater than what indicates action is needed?
Greater than 8
154
What effect does an increased amount of glucose in the blood have on red blood cells?
The red blood cells are more glycosylated for their life (3 months)
155
What is the benefit of HbA1c?
Gives an indication of glucose control for and extended time period
156
What is the ADA target for HbAic?
Below 7%
157
What vasculature problem in diabetics makes them more susceptible to prolonged infection and delayed healing?
Blood vessels thicken decreases perfusion leading to decreased waste removal
158
Why are diabetics more susceptible to infection?
Many bacteria thrive on sugars
159
What is the term for pain that is triggered at a certain point after the same amount of exercise and is relieved by rest (found in Peripheral Vascular Disease and include tightness or squeezing in the calf, thigh, or buttock)?
Intermittent claudication
160
PVD can lead to what as it worsens?
Reduced blood supply to skin, muscles, bones, nerves, of skin, legs and feet causing pain and sores that will not heal
161
What is a common treatment for diabetic retinopathy which is the leading cause of blindness in adults 16-65 yrs old?
Laser photocoagulation
162
Why is gangrene well suited infection for diabetic, especially in the foot ulcer area?
Gangrene is anaerobic and diabetics are poorly oxygenated
163
What is a major cause of death and disability among diabetics and a reason why they are the number one users of dialysis?
End stage renal disease
