module 15 Flashcards
1
Q
What is Diabetes
A
- chronic disease characterized by elevated blood glucose
2
Q
How is diabetes diagnosed
A
when untreated, blood glucose rises so high that proximal tubule kidney transporters are overwelmed
= large amounts of glucose found in urine
3
Q
Causes of diabetes
A
1) not enough insulin produced in the body
2) body’s cells do not respond to the insulin that is produced
4
Q
Common symptoms of diabetes (4)
A
- polyuria
- polydipsia
- polyphagia
- weight loss
5
Q
Polyuria
A
increased urination
6
Q
Polydipsia
A
Increased Thirst
7
Q
Polyphagia
A
Increased hunger
8
Q
What is insulin?
A
A hormone produced by the pancreas that is involved in tightly regulating blood glucose
9
Q
Where is insulin synthesized
A
Beta cells of islets of Langerhans (pancreas)
10
Q
Body’s (normal) response to insulin
A
- causes glucose uptake into muscle, liver, fat cells
11
Q
Insulin + liver cells
A
insulin causes glucose uptake –> glycogen synthesis (storage form of glucose)
12
Q
Insulin + muscle cells
A
insulin causes glucose uptake –> glucose is used as energy and promotes protein synthesis
13
Q
Insulin + fat cells
A
- insulin causes increased synthesis of fatty acids, which results in increased triglyceride synthesis
14
Q
Role of potassium and insulin
A
- extracellular potassium = helps insulin to drive glucose into the cell
15
Q
Normal Cycle of the pancreas (from food to blood sugar) (5)
A
1) stomach converts food to glucose
2) glucose enters bloodstream
3) Pancreas produces insulin
4) Glucose enters body effectively
5) glucose levels in balance
16
Q
Types of Diabetes
A
1) type 1 diabetes
2) Type II diabetes
3) gestational diabetes
17
Q
Type 1 Diabetes - prevalence
A
10% of diabetics are type I
18
Q
Type 1 Diabetes - onset/diagnosis
A
usually in children or adolescence
symptoms may not appear until early adulthood
19
Q
Type 1 Diabetes - cause
A
autoimmune reaction where the body’s own immune cells attack and destroy the insulin secreting beta cells
20
Q
Type 1 Diabetes - insulin
A
body makes too little or no insulin at all and requires insulin replacement
21
Q
Type 1 Diabetes - preventable?
A
not preventable…not caused by eating too much sugar
22
Q
Type 1 Diabetes - cycle (food intake to blood sugar) = 5
A
1) stomach converts food to glucose
2) glucose enteres blood
3) pancreas produces little or no insulin
4) glucose unable to enter body effectively
5) glucose levels increase
23
Q
Type II Diabetes - prevelance
A
approx 90% of diabetics are type II
24
Q
Type II Diabetes - cause
A
- pancreas produces sufficient insulin, however, insulin produced is resistant to use
- over course of disease, insulin synthesis may also decrease
25
Type II Diabetes - risk factors (7)
- age
- family member with diabetes
- previous gestational diabetes
- lack of excercise
- heart disease
- obesity (80% with type II are overweight)
- ethnicity (african and native descent have greater risk)
26
Type II Diabetes - age of onset
typically later in life, but is trending toward younger people getting the disease
27
Type II Diabetes - cycle from food to blood glucose (5)
1) stomach converts food to glucose
2) glucose enters bloodstream
3) pancreas produces sufficient insulin but it is resistant to effective use
4) glucose unable to enter body effectively
5) glucose levels increase
28
Gestational Diabetes
- diabetes that first starts during pregnancy
29
Gestational Diabetes - onset
usually begins approx halfway through pregnancy
30
Gestational Diabetes - diagnosis
- women shoudl have oral glucose tolerance test between weeks 24 and 28 of pregnancy to test for gestational diabetes
31
Gestational Diabetes - treatment
- usually diet and exercise are sufficient to keep blood glucose levels within normal ranges
32
Gestational Diabetes - impact on fetus
- tent to have larger babies + babies with hypoglycemia in the first days of life
33
Gestational Diabetes - after delivery
- blood sugar of mother usuallly returns to normal
| - blood glucose should be continually monitored as many patients develop diabetes 5-10 years later
34
Complications of diabetes mellitus (11)
- cognitive impairment
- depression
- cerebrovascular disease
- visual impairment
- cardiovascular disease
- nephropathy
- weight loss
- urinary incontinence
- peripheral vascular disease
- peripheral neuropathy
- foot ulcer
35
Diabetic retinopathy - what/frequency
- most common cause of blindness in people under age 65
36
Diabetic retinopathy - cause
- hyperglycemia causes damage to retinal capillaries
37
Diabetic retinopathy - prevention
- tightly controlling blood sugar minimizes risk of retinopathy
- Patients with type 1 or 2 diabetes should have eye exam once a year
38
Diabetic nephropathy
- characterized by proteinuria (early sign), decreased glomerular filtration, increased blood pressure
39
Proteinuria
protein in the urine
40
Diabetic retinopathy - impact
- leading cause of morbidity and mortality in patients with type I diabetes
41
Diabetic retinopathy - prevention
- tight control of blood glucose both delays and reduces severity of diabetic nephropathy
- ACE inhibitors and ARBs are useful in preventing diabetic retinopathy = take even if the client has a normal BP
42
Cardiovascular Disease (Diabetes)
- CVD = heart attack + stroke
43
Cardiovascular Disease (Diabetes) - impacts
- leading cause of morbidity and mortality in type II diabetes
- atherosclerosis develops much earlier in diabetic patients than in non-diabetics
44
Cardiovascular Disease (Diabetes) - cause
- combo of
- hyperglycemia
- altered lipid metabolism
45
Cardiovascular Disease (Diabetes) - prevention
Statins reduce cardiovascular events in diabetic patients regardless of LDL cholesterol levels
46
Diabetic Foot Ulcers - impact
- most common cause of hospitalization for diabetic patients
| - diabetes accounts for half of all lower limb amputations every year due to infection
47
Diabetic Foot Ulcers - prevention
all diabetics should have regular foot exams
48
Diabetic Foot Ulcers - impact of diabetes (3)
- Diabetes causes nerve damage --> decrease ability to feel pain, heat, cold in foot
- Poor circulation --> decreased blood flow --> decreased ability to heal and fight infection
- nerves controlling oil and moisture --> impair skins ability to be moist = dry cracking skin
49
Diagnosis of Diabetes (4)
1) Fasting Plasma Glucose Test
2) Casual Plasma Glucose Test
3) Oral Glucose Tolerance Test (OGTT)
4) *** Glycosylated Hemoglobin
50
Fasting Plasma Glucose Test (what, normal values)
- patients fast for at least 8 hours and then have blood drawn to measure blood glucose
- if fasting plasma glucose is > or = to 7.0 mmol/L then diabetes is diagnosed
- prefered test for diagnosing diabetes
51
Casual Plasma Glucose Test (what, normal values)
- blood drawn at any time no matter interval since last meal
- diagnose diabetes - plasma glucose greater than 11.1 mmol/L AND patient displays signs of diabetes (polyuria, polydipsia, weight loss)
- positive plasma glucose test = follow up with fasting plasma glucose test
52
Oral Glucose Tolerance Test (OGTT) (what, normal values)
- Used when other tests are unable to definitively diagnose diabetes
- Patients are given oral 75 gram dose of glucose and plasma clucose is measured 2 hours later
- Plasma glucose > or = to 11.1 mmol/L then the patients will be diagnosed with diabetes
53
Glycosylated Hemoglobin
- when upon prolonged exposure in the blood, glucose interacts with hemoglobin to form glycosylated derivatives (HbA 1C)
- Useful in providing an index of the average blood glucose over previous 2-3 months
- good determinant of how well a patient is responding to therapy
- target level = HbA 1C of <7% of total hemoglobin
54
Treatment Goals of Diabetes
- maintain tight control of plasma glucose levels
- Tight Control = normal range for entiere day
- pre meal, peak post meal glucose goals
55
Pre-meal plasma glucose goal
4.0 - 7.0 mmol/L
56
Peak post-meal glucose (#)
is 5.0 - 10 mmol/L
57
HbA 1C goal
<7%
58
Other treatment goals of Diabetes - cardiovascular
- BP <130 systolic, <80 diastolic
| - lipids = LDL <2.6 mmol/L, triglycerides <1.7 mmol/L, HDL (men) >1.0 mmol/L, HDL (women) >1.3 mmol/L
59
Other treatment goals of Diabetes - kidney
Urine albumin to creatinine ration <30 mg/g (albumin/creatinine)
60
Lifestyle Modifications - Type 1 Diabetes - Diet
- type 1 diabetes patients = thin, GOAL = maintain weight
| - split total caloric intake throughout the day with meals 4-5 hours apart
61
Lifestyle Modifications - Type 1 Diabetes - Exercise
- exercise increases cellular response to insulin + increases glucose tolerance
- encourage patients to exercise
- strenuous exercise may cause hypoglycaemia = close patient oversight
62
Lifestyle Modifications - Type 1 Diabetes - Insulin
- insulin required for survival
| - monitor blood glucose 3 or more times per day
63
Lifestyle Modifications - Type II Diabetes - Diet
- dietary modification alone (caloric restriction) often normalizes insulin release and decreases insulin resistance
- patients with type II dibetes are often obese so losing weight is a treatment goal
64
Lifestyle Modifications - Type II Diabetes - Excercise
Exercise stimulates glucose uptake and should be encouraged
65
Insulin - metabolic actions (general)
- is anabolic (building up or conservative)
| - promote energy storage and conservation
66
Insulin's anabolic actions (5)
- cellular uptake of glucose into liver, muscle, fat
- glucose uptake results from formation of glycogen (liver + muscle) and
triglycerides (adipose tissue)
- Decreased hepatic gluconeogenesis (glucose synthesis)
- cellular uptake of amino acids (mostly muscle)
- amino acid uptake results in increased protein synthesis
67
Insulin deficiency
- puts the body into a catabolic ("breaking down" state)
- body favours breakdown of complex molecules into simpler substances
- these effects contribute to diabetes
68
Insulin Deficiency - catabolic effects (3)
- glycogenolysis
- gluconeogenesis
- decreased glucose utilization
69
Glycogenolysis
conversion of glycogen to glucose
70
gluconeogensis
new glucose synthesis
71
Insulin Therapy - categories (4)
- short duration-rapid acting
- short duration-slower acting
- intermediate duration
- long duration
72
Short Duration Rapid Acting Insulin - types (3)
- Insulin lispro
- Insulin aspart
- insulin glulisine
73
Short Duration Rapid Acting Insulin - when used
- in association with meals to control postprandial (after eating) rise in glucose
74
Postprandial
after eating
75
Short Duration Rapid Acting Insulin - route of administration
subcutaneous (may be used IV if required)
76
Short Duration Rapid Acting Insulin - appearance
clear solution
77
Short Duration Slower Acting Insulin - type(s)
- unmodified human insulin
78
Short Duration Slower Acting Insulin - when used
- injected before meals to control postprandial rises in glucose
79
Short Duration Slower Acting Insulin - route of administration
- subcutaneously
| - IM (rare)
80
Short Duration Slower Acting Insulin - pathophysiology
- after injection, insulin molecules form small aggregates (dimers) which slows absorption
81
Short Duration Slower Acting Insulin - formulation
- clear solution
82
Intermediate Duration Insulin - types
- Neutral Protamine Hormone (NPH) insulin
| - Insulin Detemir
83
Intermediate Duration Insulin - uses
- delayed onset = can't be used at mealtime to control postprandial rises in blood glucose
- injected once or twice daily to control blood glucose between meals and in the evening
84
Intermediate Duration Insulin - why is action delayed for NPH insulin?
- insulin is conjugated to protamine (large protein) which makes the molecule less soluble and decreases the absorption
85
Intermediate Duration Insulin - why is the action delayed Insulin Determir
Insulin detemir molecules bind strongly to each other which delays absorption
86
Intermediate Duration Insulin - route of administration
subcutaneous injection
87
Intermediate Duration Insulin - appearance - NPH insulin
- cloudy suspension
88
Intermediate Duration Insulin - appearance - insulin detemir
clear solution
89
Long Acting Insulin - type(s)
- Insulin glargine
90
Long Acting Insulin - use
- long duration of action - administered once daily at bedtime
91
Long Acting Insulin - route of administration
subcutaneous injection
92
Long Acting Insulin - why is it a long duration of action
- low solubility at physiological pH (injected it forms microprecipitates that slowly dissolve and slowly release insulin glargine in small amounts over an extended time)
93
Long Acting Insulin - formulation
clear solution
94
Glucagon
- hormone produced by pancreas
| - causes conversion of glycogen to glucose, reverses hypoglycemia
95
Glucagon - uses (3)
- when a hypoglycaemic patient is unconscious (once patient regains consciousness you should use oral sugar solution)
- IV glucose is prefered to glucagon but is impractical outside medical supervision
- ineffective in starving/malnourished patients (as they do not have any glycogen stores)
96
Oral Antidiabetic Drugs - target disease
- type 2 diabetes
97
Oral Antidiabetic Drugs - classes (6)
- biguanides
- sulfonylureas
- meglitinides
- thiazolidinediones (glitazones)
- alpha-glucosidase inhibitors
- gliptins
98
Biguanides
- drug of choice for type II diabetes
99
Biguanides - mechanism of action (3)
1) increase sensitivity and number of insulin rceptors
2) decrease hepatic gluconeogenesis
3) decrease intestinal glucose absorption
100
Biguanides - advantage
does not increase insulin levels = no risk of hypoglycemia
101
Biguanides - adverse effects (5)
- nausea
- decreased apetite
- diarrhea
- decreased absorption of vitamin B12 and folic acid
- lactic acidosis (rare, but mortality of 50% in those who get it)
102
Sulfonylureas - mechanism of action
- act by stimulating release of insulin from pancreas
| - inhibit glycogenolysis (breakdown of glycogen to glucose
103
Sulfonylureas - Classes, and differences between classes
1st generation and 2nd generation
| - difference =2nd generation are much more potent and cause fewer drug interactions
104
Sulfonylureas - adverse effects (2)
- hypoglycemia
| - prolonged use --> pancreatic burnout (pancreas has reduced capacity to synthesize insulin)
105
Meglitinides - mechanism of action
- stimulate insulin release form the pancreas
- short half life (treat postprandial rises in glucose
- less likely to cause hypoglycemia
- less likely to cause pancreatic burnout
106
Meglitinides - adverse effects
- less likely to cause hypoglycemia than sulfonylureas
| - less likely to cause pancreatic burnout
107
Thiazolidinediones (Glitazones) - mechanism of action (4)
- increasing insulin sensitivity in target tissues and decreasing hepatic gluconeogenesis
- activate the PPAR(gamma) receptor (intracellular) --> turns on genes that regulate carb metabolism --> increases sensitivity of insulin by increasing number of glucose transporters
- also increase HDL and decrease triglyceride level via activation of PPAR(alpha)
108
Alpha-glucosidase inhibitors - mechanism of action
- act in intestine to delay carbohydrate absorption
- blocks alpha glucosidase (enzyme in intestine that breaks down carbs
to monosaccharides) --> decrease in carbohydrate metabolism
109
Gliptin - mechanism of action
- inhibit an enzyme called dipeptidyl peptidase 4 (DPP-4)
- DPP-4 breaks down incretin hormones GLP-1 and GIP
- Incretin hormones are released from GI tract after a meal and cause
increased release of insulin and decreased release of glucagon
- inhibit DPP-4 --> more GLP-1 adn GIP reach pancreas = increased insulin release and suppression of glucagon release
110
Gliptin - adverse effects
no known major adverse effects
111
Incretin Mimetics - mechanism of action
- synthetic incretin analogs that mimic actions of incretin hormones
- increase in insulin release, decrease in glucagon relase
112
Incretin mimetics - route of administration
subcutaneous injection
113
incretin mimetics - use
in combination with biguanides or sulfonylureas
