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PHPY 305 > Diabetes Management > Flashcards

Diabetes Management Flashcards

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1
Q

Diabetes Mellitus

A

Glucose Homeostasis: insulin promotes uptake of glucose by cells
- reduces blood glucose
Glucagon promotes conversion of glycogen stores to glucose
- increases blood glucose

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2
Q

Stimulation of insulin release

A
  1. Glucose enters cell through GLUT transporter
  2. Glucose metabolized, increases ATP
  3. ATP inhibits Katp channel
  4. This leads to calcium entry through calcium channels
  5. Calcium entry leads to exocytosis of insulin
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3
Q

Diabetes Mellitus key feature

A

Sustained elevations in blood glucose

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4
Q

High blood glucose leads to these complications (5)

A 
Circulatory disorder 
Neuropathy
Nephropathy 
Retinopathy 
Cardiovascular disease
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5
Q

The two types of diabetes and how they are different

A

Type 1: insulin deficiency (reduced secretion)

Type 2: Insulin resistance and (then) reduced secretion

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6
Q

Type 1 characteristics

A

Low insulin

  • due to destruction of pancreatic beta cells
  • likely autoimmune
  • also genetic component
  • typically earlier onset but not always
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7
Q

Type 2 characteristics

A

Often associated with/or worsened by obesity
Typically later onset but that is changing
About 90% of DM cases are type 2

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8
Q

Treatment overview for type 1 and 2 diabetes

A

Type 1: manage with insulin
Type 2: lifestyle changes - diet, exercise, etc.
Manage initially with oral hypoglycaemic
May need to add insulin later as beta cells fail

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9
Q

Monitoring of glucose (acute)

A
  • self-monitoring of blood glucose (glucometer)
  • target fasting blood glucose (4-7 mmol/L)
  • Post-prandial (2 hours): 5-10 mmol/L
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10
Q

Monitoring of glucose (chronic)

A

Hemoglobin A1c

  • glycated hemoglobin
  • Glucose attached to Hb in blood
  • Considered a more stable measure of Glycemic control over time
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11
Q

Insulin

A
  • a 51 amino acid protein

- consists of two peptide chains (A & B) joined by 2 disulphide bridges

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12
Q

Actions of Insulin

A

Promotes entry of glucose into the cells

  1. Insulin binds to tyrosine kinase receptor
  2. Prompts a cascade of intracellular signalling events (protein synthesis and glycogen synthesis)
  3. Prompts translocation of GLUT-4 transporters to cell membrane
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13
Q

Actions of insulin in the liver

A
  • decreases glucose synthesis (Gbuconeogensis)

- increases conversion of glucose to glycogen (storage)

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14
Q

Actions of insulin in muscle

A
  • Increase in glucose to glycogen

- increase in protein synthesis.

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15
Q

Actions of Insulin in Fat

A
  • Increases in Lipogenesis

- decrease in Lipolysis

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16
Q

Insulins route of administration

A

Injected: Subcutaneous

  • intravenous in emergencies
  • absorption depends on site of injection: more rapid in abdomen, slower in thigh or buttocks and exercise, heat tend to increase absorption
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17
Q

Rapid acting insulins

A

Regular insulin: onset is 1/2 hour, peak around 2 hours, duration 8 hours
Aspart insulin: onset is 1/4 hour, peak in 1-1.5 hours, duration 4 hours

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18
Q

Intermediate/long acting insulins

A

NPH: onset 1-2 hours, peak 6-12, duration 18
- Neutral Protamine Hagedorn
Glargine insulin: onset 3-4 hours, duration 20-24 hours

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19
Q

SIde effects of Insulin

A

Hypoglycemia: symptoms include sweating, tachycardia, confusion
- can progress to coma/death
Treatment: SUGAR

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20
Q

Other side effects of Insulin

A

Weight gain
Immune reactions
Lipodystrophy
- atrophy of subcutaneous fat at injection site

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21
Q

Insulin secretagogues two classes

A

Sulfonylureas

Meglitinides

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22
Q

Sulfonylureas example

A

Glyburide

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23
Q

Sulfonylureas mechanism

A
  • act on pancreatic beta cells

- bind to the sulfonylurea receptor-1 (SUR-1) and stimulate insulin release while inhibiting Katp channel

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24
Q

Risk of Sulfonylureas

A

Stimulates insulin regardless of blood glucose levels

Risk of hypoglycemia

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25
Side effects of Sulfonylureas
``` Weight gain Rash (hypersensitivity to sulpha) Gastrointestinal Concern over cardiovascular effects: - receptors in the cardiovascular system ```
26
Meglitinide example
Repaglinide
27
Repaglinide mechanism
Bind to a different sire of SUR-1 and stimulate insulin release More rapid onset and shorter duration of action - may lower risk of hypoglycemia - more flexibility with regards to food intake - need to be taken more often
28
Biguanides example
Metformin
29
Biguanides mechanism
Increases activity of AMP-dependent protein kinase (AMPK) - AMPK is normally activated when cellular energy stores reduced - may have protective (anti-oxidant) effects on endothelial cells
30
Key effects of AMPK:
Enhanced glucose uptake/cell sensitivity to insulin Reduced Glycogenolysis Reduced Gluconeogenesis
31
Biguanides pharmacokinetics
Eliminated by kidneys | Avoid using in patients with impaired renal function
32
Biguanides Side effects
Gastrointestinal: Nausea, diarrhea Rare - Lactic acidosis Avoid using in patients with decompensated heart failure
33
First line drug for Type 2 Diabetes?
Biguanides: good efficacy - not associated with weight gain - does not stimulate insulin release (hypoglycemia unlikely) - Good safety profile
34
Incretins mediate
Mediate communication between gut and brain | - potential target for weight loss drugs
35
Examples of Incretins
Glucagon-like Peptide-1 (GLP-1) | Glucose dependent insulinotropic peptide (GIP)
36
The two variations of Incretins
GLP-1 agonists | DPP-4 inhibitors
37
GLP-1 agonist example
Liraglutide
38
DPP-4 inhibitors example
Sitagliptin
39
Incretins mechanism of action
1. Increase insulin secretion 2. Inhibit glucagon secretion 3. Delay gastric emptying 4. Reduce appetite
40
Administration of GLP-1 agonists
All administered by subcutaneous injection
41
Administration of DDP-4 inhibitors
All administered Orally
42
Difference in GLP-1 agonists and DPP-4 inhibitors
- GLP-1 agonists have more pronounced effects on the GI tract than DDP-4 inhibitors - May reduce gastric emptying enough to interfere with drugs needing rapid absorption
43
Side effects of Incretins
Hypoglycemia: less common than with insulin or the insulin secretagogues, Incretins response to bodies need for insulin Rare AE: Pancreatic disease, pancreatitis, cancer
44
GLP-1 agonist side effects
Gastrointestinal: Nausea, vomiting, diarrhea (or constipation), gall stones - incretins effect communication between gut and brain - GLP-1 agonists have a greater effect on the GI tract than DPP-4 Inhibitors: more GI side effects but more weight loss, liraglutide approved as a weight loss drug - increases heart rate, arrhythmia, possible link to thyroid cancer
45
DPP-4 inhibitors (dipeptidyl peptidase 4) side effects
- Gastrointestinal: less common than GLP-1 agonists - Increased risk of infection: typically upper respiratory or urinary tract - DPP-4 plays role in the immune system (lymphocytes)
46
Thiazolidinediones example
Pioglitazone
47
TZD facts
- Peroxisome proliferator-activated receptor-gamma (PPAR-y) agonists - PPAR-y receptors regulate genes related to glucose and lipid metabolism - because they work on gene expression, TXD effects tend to be delayed
48
TZD actions
- insulin sensitizer: increases uptake of glucose - Enhances uptake of free fatty acids into adipose tissue - less FFA available to enter other tissues - higher adipose tissue levels tend to reduce sensitivity to insulin
49
TZD actions on blood glucose
Reduce hepatic production of glucose | - reduced gluconeogenesis
50
TZD actions on lipids
Reduce triglycerides, increase HDL
51
Thiazolidinediones problems
Consistent safety issues have limited their use | Hepatotoxicity, myocardial infarction, bladder cancer
52
TZD side effects
Cardiovascular: heart failure Edema Weight gain: reduces leptin levels Fractures (women)
53
Alpha-glucosidase inhibitors
- Glucosidases break down carbohydrates to glucose | - AGIs inhibit breakdown of carbs, preventing absorption
54
AGI example
Acarbose
55
Side effects of AGI
Gastrointestinal: bloating, diarrhea, pain. Bacteria feed on undigested carbs, release gas Low risk of hypoglycemia: if it does occur, need to use glucose because sucrose won't be absorbed
56
SGLT2 inhibitors mechanism
- inhibit renal mechanism for reabsorbing glucose - in non-diabetic individuals, all filtered glucose is reabsorbed - 90% of glucose reabsorption occurs at the proximal tubule
57
SGLT2 inhibitor example
Empagliflozin
58
Empagliflozin mechanism
Acts at the proximal tubule | Inhibits sodium-glucose Co-transporter 2 (SGLT)
59
Inhibition of SGLT2 results in
- reduction in glucose reabsorption: osmotic diuresis, reduces blood glucose - induces weight loss May reduce blood pressure via osmotic diuresis
60
SGLT2 inhibitors adverse effects
- Increased glucose in the nephron increases risk of infections: urinary tract infections, genital infections - Dizziness, hypotension - Nausea - Hyperkalemia - Rare cases of diabetic ketoacidosis
61
Type 2 diabetes combinations
Metformin + anything Benefits: adding drugs that cause weight gain lead to a neutral effect Common examples: Metformin + insulin and Metformin + Sulfonylurea These combinations also decrease the risk of Hypoglycemia
62
Other Drug combinations
Metformin + SGLT2 inhibitor + DPP-4 inhibitor | - addition of drugs with neutral effect on weight or weight loss can enhance the weight loss
63
Future direction of Insulin administration
- inhaled insulin, powdered form through mouth Problems: cost, first device failed to catch on, concerns over bronchospasm - Patches: use micro needle technology, patches contain insulin or beta cells which then secrete insulin - Stem cells: Islet cell transplants

PHPY 305 (14 decks)

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