Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

PHRM 844 > Diabetes > Flashcards

Diabetes Flashcards

1
Q

Cardinal Signs of Diabetes

A

Polydipsia (extreme thirst)
Polyuria (high volumes of urine production)
Polyphagia ( Lack of weight- gain)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Diagnosis of Diabetes

A

Fasting blood glucose >= 126 mg/dl
A1C >= 6.5%
Random glucose >= 200mg/dl
2 hr postprandial glucose >= 200mg/dl during an OGTT

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Type 1 Diabetes

A

Glucose intolerance
- No functional insulin-secretion: near to complete loss of pancreatic cells
- These patients cannot secrete insulin during high levels of blood glucose so they have to take exogenous insulin (medications)
- Early onset (mean = 12)
- Patients at risk of metabolic acidosis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Auto-antigens associated with Type 1 diabetes

A

Insulin, islet antigen 2, Phogin, Zinc transporter, Glutamic acid decarboxylase, Voltage gated Ca, Vesicle associated membrane protein-2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Consequences of lack of insulin

A

Hyperglycemia -
1. Decreased glucose uptake in cells where glucose uptake in insulin dependent patients
2. decreases glycogen synthesis
3. Increased conversion of amino acids to glucose (gluconeogenesis)
Glucosuria -
1. due to high blood pressure
Hyperlipidemia -
1. Increased fatty acid mobilization from fat cells
2. increased fatty acid oxidation - Ketoacidosis
Unhibited glucagon -
1.Increased glucagon levels in the presence of increased blood glucose levels

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Complications due to hyperglycemia

A
  1. Cardiovascular- Hyperglycemia can cause damage to small and large blood vessels which lead to compromised blood flow
  2. Neuropathy - accumulation of glucose in nerves that then gets reduced to aldose reductase through the poyol pathway so the ability of the nerves to prevent oxidative damage is compromized
  3. Nephropathy - Can compromise kidney functions due to renal vascular changes and changes in the glomerular basement membrane
  4. Ocular - Cataracts, retinal microaneurysms and hemorrhage
  5. Increased susceptibility to infections
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Goal of insulin therapy and monitoring

A

Goal : Keeping average blood glucose levels below 150 mg/dL
Goal therapy levels
- Fasting : 70-110 mg/dL
- Pre meal : 80-130 mg/dL
- Post meal : <180 mg/dL
HbA1C: <7%
IDEAL goals of therapy
- Fasting : 70-90 mg/dL
- Pre meal : 70 - 105 mg/dL
- Post meal : <120-160
HbA1C : <6%

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Is tight glycemic control worth the risk of hypoglycemia

A

Yes,
running the risk of hyperglycemia is worth it due to the life threatining factors associated with diabetes and high levels of A1C

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Non-obese type 2 diabetes (non-insulin dependent)

A

Incidence in diabetic population: 10%
Age of Onset: Often under 25 ( also known as MODY)
Family history: Yes
Insulin secretion in response to glucose challenge: Low
- Mutations in specific beta cell proteins

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Obese Type 2 diabetes (non-insulin dependent)

A

Incidence in diabetic population: 80%
Age of Onset: Usually over 35
Family history: yes
Insulin secretion in response to glucose challenge: Due to the high body mass although their body produces regular levels of insulin its not enough for their body mass

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

how does hypergylcemia lead to covalent modification of proteins?

A

Oxidation products of glucose react irreversibly with proteins which form advanced glycation end products which leads to loss of normal protein functions and can cause acceleration of aging (leads to many long term complications of diabetes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Receptor of advanced glycation endproducts (RAGE)

A

peptides bind to CML and CEL to bind to RAGE and cause inflammation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Complications due to hyperglycemia
Neuropathy Mechanism

A

The Polyol Pathway is how nerves process glucose for storage. When high levels of glucose are present this pathway depletes NADPH. With low levels of NADPH the nerves cannot protect neurons from oxidative damage leading to neuropathic problems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Complications due to hyperglycemia
Protein Modification

A
  1. Hexosamine pathway - due to high levels of glucose we also see a high level of Fructose-6-P which is taken into the hexosamine pathway and made into glucosamine-6-P which can become UDP-GlcNAc and can become a side chain to proteins and alter their function
  2. Protein Kinase C pathway - Glyceraldehyde-3-P enters this pathway to bind to DAG which activates protein kinase C
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

The insulin receptor
Role of alpha subunit

A

to repress the catalytic activity of the beta subunit (cross-linked). This repression is relieved when insulin binds

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

The insulin receptor
Role of beta subunit

A

Autophosphorylation
Contains the tyrosine kinase catalytic domains

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Insulin effects on various tissues

A

1.Liver
Inhibits : glycogenolysis, Ketogenesis, gluconeogenesis
Stimulates: glycogen synthesis, triglyceride synthesis
2. Skeletal Muscle
Stimulates: glucose transport, amino acid transport
3. Adipose Tissue
Stimulates: triglyceride storage, glucose transports

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Glucose disposal during fasting state

A

75% is non-insulin dependent: Liver GI, Brain
25% is insulin dependent in skeletal muscle
- glucagon is secreted to prevent hypoglycemia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Glucose Disposal during fed state

A

80-85% is insulin dependent in skeletal muscle
4-5% is insulin dependent in adipose tissue
Glucagon secretion is inhibited
Insulin inhibits release of fatty acids from adipose tissue

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Glucose transporters

A

GLUT 1 (Km 1-2mM)
- constitutive and widely expressed throughout the tissue (also in Beta cells in the liver but small amount)
GLUT 2 (Km 15-20mM)
- constitutive and expressed in beta cells in the liver
GLUT 3 (Km <1mM)
- constitutive and expressed in neurons
GLUT 4 (Km 5mM)
- insulin- induced and found in the skeletal muscle adipocytes

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Site of insulin production and secretion

A

Islets of Langerhans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Actions of pancreatic polypeptide hormones

A
  1. Glucagon
    - this is secreted when blood glucose levels are low and it will stimulate glycogen breakdown to increase the blood glucose
  2. Insulin
    - which is released when glucose levels are hight and it stimulates the uptake and utilization of glucose
  3. Amylin
    - this is co secreted with insulin and it will slow gastric emptying, decrease food intake (make you feel full) and inhibit glucagon secretion
  4. Somatostatin
    - this is a general inhibitor of secretion
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

What are the 4 pancreatic polypeptide hormones

A

Glucagon, insulin, somatostatin, and amylin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Explain the process of producing insulin

A

Insulin is synthesized in the beta cells and is produced when proinsulin is cleaved (in 2 spots) by proconvertase which produces insulin and connecting peptide (c peptide) which get released in a 1:1 ratio

24
Q

what are the two types of insulin sources

A

Recombinant human insulin
Human insulin cDNA in plasmid expressed in either E.coli or transformed yeast
- Advantages : it allows control of amino acid sequences and we are able to produce large batches and purify them

25
Q

Why do we have so many different types of insulin

A

We want to mimic the natural secretion of insulin.
Natural insulin release it broken down into phase 1 and phase 2. By having different chemical properties of modified insulin we can use them in combination
Purpose
- provide convenience with dosing
- basal levels vs preprandial dose

26
Q

Insulin treatments: Ultra rapid onset/ very short action

A

Lispro (Humalog)
Aspart (Novolog)
Glulisine (Apidra)

27
Q

explain how Lente insulins worked

A

They would complex insulin and zinc together and the more complexed insulin was to zinc the more slowly the insulin would be absorbed
THESE ARE NO LONGER USED

28
Q

Insulin Treatment: Rapid onset/ short action

A

Regular (R)

29
Q

Insulin Treatment: Intermediate onset/ action

A

NPH (N)

30
Q

Insulin Treatment: slow onset/ long action

A

Glargine (lantus)
Detemir (levemir)
Degludec (tresiba)

31
Q

Lispro insulin (Humalog)

A

Ultra rapid onset/ very short action
Reversing portions of proline 28 (P28) and lysine 29 (K29) on insulin B chain which results in decreased self association (to be rapidly absorbed it must be in monomeric form)
- Place in therapy: Injected immediately before meals

32
Q

NPH insulin

A

doesn’t have recombinant insulin
Its insulin bound to protamine which when injected the protamine is broken down by tissue proteases in the body and release insulin allowing for a slower absorption (1-1 1/2) and a long duration of action (24hrs)

33
Q

Insulin Aspart (Novolog)

A

Human, except Proline 28 in B chain is switched to aspartate
Rapid onset: 5-15min, short duration
Injected immediately before meals

34
Q

Insulin Glulisine (Apidra)

A

Human except Asn 3 and Lys 29 in B chain are switched to Lys and Glu
Rapid onset: 5-15 min, short duration
Injected immediately before meals

35
Q

Insulin Glargine ( Lantus)

A

Changes:
Asn 21 of a- chain is changed to Gly
2 Arg residues added to the end of the B- chain (30&31)
- Basal Insulin
-Action: Glargine is slowly and steadily released from injection site over 24 hours - once daily injection

36
Q

Insulin Detemir (Levemir)

A

Thr 30 of B chain is deleted and lys 29 is myristylated
Binds to serum albumin which provides a slow release and slow absorption

37
Q

Insulin Degludec (Tresiba)

A

Thr 30 of B chain is replaced by gamma-Glu/C16 fatty acid
which binds to serum albumin allowing for slow release and absorption

38
Q

Multi-dose insulin regimens

A

Fast onset, short acting taken before meals
Long, or intermediate acting taken at bedtime or at bet time and after breakfast
Mixing provides a transient preprandial bolus and a prolonged basal level in a single injection

39
Q

Inhaled Insulin

A

Afrezza (Approved by FDA June 2014)
Regular Human insulin in dry powder form
Rapid onset, shorter duration of action than SC injection - used as pre-prandial insulin
CONTRAINDICATION - Patients with asthma and COPD, may reduce lung function

40
Q

Routes of administration

A

Subcutaneous - all preparations
Insulin infusion pump - Buffer Regular, also rapid acting, (i.e. Lispro, Aspart, Glulisine)
IV- Regular (for severe hyperglycemia or ketoacidosis
Inhalation - Afrezza (not commonly used)

41
Q

Types of patients using insulin

A
  • Type 1 Diabetics
    -Patients with ketosis and hyperosmolar coma
  • some type II diabetics
42
Q

Mode of action of insulin in diabetic patients

A

Decrease liver glucose output
Increase fat storage
Increase glucose uptake

43
Q

Adverse reactions to insulin
inside the body

A

Hypoglycemia - blood glucose <60 mg/dL
Signs and symptoms include:
weakness, sweating, hunger, tachycardia, increased irritability, tremor, blurred vision, seizures, coma, increased sympathetic output
TX
- treat with glucose or glucagon

44
Q

Adverse reaction to insulin
skin

A

Lipodystrophy - changes in fat at over use of injection site
Lipoatrophy - Loss of fat in subcutaneous tissue
Lipohypertrophy - Accumulation of fat in subcutaneous tissue

45
Q

Agents that increase blood glucose levels

A

Thyroid hormone, contraceptives, morphine, catecholamines, Calcitonin

46
Q

Agents that decrease blood glucose

A

Ethanol, ACE inhibitors, Somatostatin, fluoxetine, anabolic steroids, beta adrenergic blockers

47
Q

How does insulin secretion in type 2 diabetics differ from normal insulin release

A

In type two diabetics we do not see that peak of insulin that follows after a meal. We also refer to this peak as phase 1

48
Q

Pathophysiology of type 2 diabetes

A

Insulin resistance and reduced insulin secretion

49
Q

Pathophysiology of type 2 diabetes - Liver

A

After a meal usually in a normal patient you would see a peak in insulin secretion by the beta cells in the liver. In diabetes there is a blunting of this peak in response to a meal

50
Q

Pathophysiology of type 2 diabetes - Skeletal muscles

A

Normal:
With an increase of plasma insulin levels you would see an increase in the utilization of glucose in the skeletal muscles

Type 2 diabetes:
The skeletal muscle is not taking up as much glucose like it usually would which also effects the excretion of glucose which has a huge effect on blood glucose levels

51
Q

Pathophysiology of type 2 diabetes - Pancreatic islet

A

Normal
insulin normal inhibits glucagon secretion
Type 2 diabetics
glucagon secretion is not inhibited

52
Q

Pathophysiology of type 2 diabetes - Adipose tissue (fat)

A

Normal
insulin will stimulate the storage of fat
Type 2 diabetics
Not stimulated

53
Q

Agents that enhance insulin secretion

A

Sulfonylureas
and
Meglitinides

54
Q

Sulfonylureas and Type 2 diabetes

A

Must have functioning beta cells
- These work to restore the first phase insulin release and increase beta cell sensitivity to glucose and increase glucose stimulated insulin release

55
Q

Sulfonylureas MOA

A

These when taken will bind to the sulfonyurea receptors which closes the K+ channel. This closure will lead to decreased cell polarization of the membrane potential. This depolarization will lead to the opening of voltage sensitive Ca+ channels. With high levels of calcium now in the cell it will promote insulin release and increase the release of insulin.

56
Q

First generation sulfonylureas

A

Tolbutamide (Orinase)
Duration - 6-12hrs
Tolazamide (Tolinase)
Duration - 12-14hrs
Chlorpropamide (Diabinese)
Duration - 24-72hrs

57
Q

Second generation sulfonylureas

A

Glipizide (Glucotrol)
Duration - 12-24
Glyburide (Diabeta glynase)
Duration - 24
Glimepiride (amaryl)
24

58
Q

Nateglinide (starlix)

A

Non sulfonylurea Katp channel blocker
- very specifi for Katp channels in pancrease vs CV tissue
Shorter t1/2 than prandin (less risk of hypoglycemia

PHRM 844 (23 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions