Diabetes Flashcards
What term “can” be used interchangeably with diabetes mellitus?
Diabetes
What term literally means “excessive excretion of urine”?
Diabetes
What condition refers to the disorder of carbohydrate, fat and protein metabolism with absolute or relative insulin deficiency?
diabetes mellitus
What 3 metabolism disorders make up diabetes mellitus? What deficiency is included?
Carbohydrates, fat, and protein. Relative insulin deficiency
As of 2009, the estimated prevalence of diabetes in Canada was how many Canadians?
2.4 million (6.8% of the population)
From 1998 to 2009, what was the percentage of increase for the prevalence of diabetes?
230%
Approximately half of the new cases of Diabetes Mellitus diagnosed in 2008/2009 were in individuals aged between what age?
a) 45-64 years old
b) 10-19 years old
c) 30-44 years old
d) 65-74 years old
e) 20-34 years old
A
Estimates from the Public Health Agency of Canada suggest that how many Canadians will be diagnosed with diabetes by 2019?
37 million
According to the Canadian Diabetes association, which type of Diabetes Mellitus accounts for approximately 90% of diabetes cases?
type 2 (diabetes mellitus)
According to the Canadian Diabetes association, what percentage of diabetes cases is known as type 2 Diabetes Mellitus?
(approximately) 90%
According to the Canadian Diabetes association, which type of Diabetes Mellitus accounts for approximately 5-10% of diabetes cases?
type 1 (diabetes mellitus)
According to the Canadian Diabetes association, what percentage of diabetes cases is known as type 1 Diabetes Mellitus?
5-10%
According to the Canadian Diabetes association, other than type 1 and type two, what is the other most common form of diabetes?
Gestational Diabetes Mellitus (GDM)
According to CCDSS 2008-2009 data, the prevalence of diagnosed diabetes is significantly lower in which age groups?
a) in adults than adolescents and children
b) in children and adolescents than adults
c) in older adults than adolescents and children
d) in only adolescents than adults
b
Is there is a slightly higher prevalence of diabetes in males or females?
Males
What is an example of a personal cost of diabetes?
a) Reduced quality of life and increased risk of heart disease/ stroke
b) Kidney Disease
c) Blindness
d) Amputation
e) Erectile Dysfunction
f) All of the Above
F
What percentage of people with diabetes will die as a result of heart disease or stroke?
80%
Which stage of life are Canadians most likely to die prematurely in, Childhood or Adulthood?
Adulthood
Type 1 diabetic’s life expectancy may be shortened by as much as ______ years , while type 2 diabetic’s life expectancy may be shorted by _____-_____ years
15 years and 5-10 years
There is a tremendous financial and societal burden to diabetes.
True or False?
true
What is the personal annual medical cost for one with diabetes?
$1000 - $15,000
Diabetes to cost the Canadian Healthcare System ______ billion per year by 2020.
$ 16.9 (billion)
What type of diabetes mellitus accounts for 90-95% of type 1 diabetes?
Type 1A
Type 1A Diabetes Mellitus is known as an autoimmune mediated specific loss of beta cells in the pancreatic islets Langerhans.
True
Type 1A Diabetes Mellitus is known as an autoimmune mediated specific loss of what type of cells? Where are these cells located?
Beta Cells in the pancreatic islets Langerhans
As a whole, type 1 diabetes includes cases of diabetes that are primarily the result of the beta destruction which leads to what?
absolute insulin deficiency (and is prone to ketoacidosis)
There is very little research underway looking at the genetic susceptibility to type 1A diabetes.
True or False?
False (There is much research underway looking at the genetic susceptibility to type 1A diabetes.)
The strongest association and most studied topic regarding the genetic susceptibility to type 1A diabetes is the inherited major histocompatibility complex (MHC) genes on which chromosome?
Chromosome 6
The strongest association and most studied topic regarding the genetic susceptibility to type 1A diabetes is the inherited ________ _______________ __________________(MHC).
Major Histocompatibility Complex (MHC)
The strongest association and most studied topic regarding the genetic susceptibility to type 1A diabetes is the inherited major histocompatibility complex (MHC) which encodes for what human leukocyte antigen?
HLA-DQ and HLA-DR (Specifically, HLA-DR3 ad HLA-DR4 is associated with an increased risk of type 1A diabetes that is 20 to 40 times higher than that of the general population.)
Some specific human leukocyte antigens are thought to decrease the risk of developing type 1 diabetes including what?
HLA-DR2
An insulin gene regulates beta cell replication and function on which chromosome?
Chromosome 11
In MOST cases, there is likely a polygenic inheritance of type 1 diabetes, meaning that susceptible individuals have more than one genetic polymorphism.
True or False?
true
Between 10% and 13% of individuals with newly diagnosed type 1 diabetes have a _______ degree relative with type 1 diabetes.
first
Identifying genes that predispose individuals to diabetes has many advantages and NO disadvantages.
True and False?
False (It also carries many ethical and legal issues.)
Autoantibodies specific to beta cell destruction includes what three types of autoantibodies?
insulin (autoantibodies), islet cell (autoantibodies), and other antibodies (directed at other autoantigens) (such as glutamic acid decarboxylase-GAD and tyrosine phosphate IA-2)
Environmental Factors - Interaction with Genes
Certain chemicals such as Alloxan, Streptozotocin and Vacor (as well as certain drugs such as Pentamidine) have been associated with what type of diabetes?
bovine milk
type one diabetes
Environmental Factors - Interaction with Genes
Nutritional intake of what type of milk have also been linked to Type 1 diabetes?
bovine milk
Environmental Factors - Interaction with Genes
Nutritional intake of high levels of what have also been linked to Type 1 diabetes.?
nitrosamines
Environmental Factors - Interaction with Genes
Nutritional intake of high levels of what have also been linked to Type 1 diabetes.?
nitrosamines
40% of individuals with what type of infection develop type 1 diabetes later?
congenital rubella
Persistent cytomegalovirus infection appears relevant in some cases of type 1 diabetes.
True or False?
True
Mumps and coxsackievirus seem to have small effects on the development of type 1 diabetes.
True or False?
True
There is a seasonal distribution with more new cases reported in what two seasons, in which hemispheres?
(This supports the idea that there is a gene-environment interaction with causes type 1A diabetes.)
Fall & Winter in
Northern Hemisphere
Latent Autoimmune Disease In Adults or LADA
There is a small number of adults (approximately 10%) classified as having type 2 diabetes who appear to have immune mediated destruction of beta cells who actually fall into the category of what type of diabetes?
Type 1A diabetes
Type 1A diabetes is diagnosed in childhood or adulthood for the most part?
Childhood
Diagnosis of type 1A diabetes peaks at ___ years of age and is rare before ___ months of age.
12 years and 9 months
What is Idiopathic Type 1B Diabetes Mellitus also called?
Non-immune type 1 diabetes (Type 1B Idiopathic Diabetes)
In the case of Idiopathic Type 1B Diabetes, there is no evidence of autoimmunity. The etiology (causes) is unknown.
True or False?
True
Idiopathic type 1B accounts for less than what percentage of those with type 1 diabetes?
10%
There is a strong genetic component to the development of type 1B diabetes.
Most affected individuals are of what two descents?
African or Asian
Affected individuals of Idiopathic type 1B have varying degrees of insulin deficiency that can come and go, which leads to episodic __________________.
ketoacidosis
What type of diabetes is a heterogenous condition, characterized by hyperglycemia, insulin resistance, and relative impairment in insulin secretion?
type 2 diabetes
Type 2 diabetes is characterized by what 3 things?
hyperglycemia, insulin resistance, and relative impairment in insulin secretion
Type 2 diabetes may range from predominant ___________ _______________ with relative insulin deficiency to a predominate ________________ ____________ with insulin resistance.
insulin resistance and secretory defect
Environment-Genetic Interaction for Type 2 Diabetes Mellitus
Etiology of type 2 diabetes is thought to not involve an environmental-genetic interaction.
True or False?
False (etiology of type 2 diabetes is thought to involve an environmental-genetic interaction.)
15-25% of first degree relatives of people with type 2 diabetes will develop either impaired ____________ _____________ or _____________.
glucose tolerance or diabetes
There is a two to fourfold increased risk for type 2 diabetes associated with a positive what?
family history
Variants of genes have been identified that increase the risk for type 2 diabetes. Many of them fall in the categories of genetic defects of __________ __________ function and ___________ ____________ in insulin synthesis, secretion and action.
beta cell function and genetic defects
Genes // Type 2 Diabetes Mellitus
Others include genes that encode proteins for pancreatic development, amyloid deposition in beta cells, cellular insulin resistance and impaired regulation of gluconeogenesis.
True or False?
True
What is included in the top risk factors for type 2 diabetes mellitus?
a) Age
b) Obesity
c) Hypertension
d) Physical Inactivity
e) Family History
f) All of the above
F
There is a high risk of developing type 2 diabetes and associated cardiovascular complications with what type of syndrome?
metabolic syndrome
Type 2 Diabetes Mellitus occurs mostly in adults or children?
Adults
Type 2 Diabetes Mellitus occurs mostly in adults, however there is an increasing prevalence in who?
Children (as childhood obesity rates climb)
Which type of children in Canada are particularly affected by type 2 diabetes?
aboriginal children
Canadian data regarding the prevalence of type 2 diabetes is limited by US data suggests a 10-30 fold increase in type 2 diabetes in children over the past how many years?
10-15 years
What type of diabetes is defined as any degree of glucose intolerance with onset or first recognition during pregnancy?
Gestational Diabetes Mellitus (GDM)
What refers to pregnancy in persons with pre-existing diabetes?
Pregestational Diabetes
The exact etiology of glucose intolerance in gestational diabetes is very well known, as very detailed reports and cases have been studied.
True or False?
False (The exact etiology of glucose intolerance in gestational diabetes is unknown)
Although the exact etiology of glucose intolerance in gestational diabetes is unknown, a combination of what two things are most definitely contributing factors?
Insulin resistance and impaired insulin secretion
Older age, family history, history of glucose intolerance, obesity, membership in certain ethnic or racial groups, history of poor obstetric outcomes and infant weighing greater than 9 pounds.
What type of diabetes are these risk factors for?
Gestational Diabetes Mellitus
Diagnosis of Gestational Diabetes Mellitus is made based on the gestational diabetes screen which is a _____g glucose load, followed by a ________ glucose level, 1 hour later.
50g and plasma
Diagnosis of gestational diabetes is made based on the same lab values than for non-pregnant individuals.
True or False?
False (Diagnosis of gestational diabetes is made based on different lab values than for non-pregnant individuals)
Untreated gestational diabetes leads to increased what?
maternal and perinatal (during embryo development) morbidity (If managed well, it is associated with outcomes similar to control populations)
In the US, Canada, and Europe, type 2 diabetes accounts for over _____% of diabetes.
80%
In the US, Canada, and Europe, type 1 diabetes accounts for over ____-_____% of diabetes.
5-10%
Specific Genetically Defined Forms of Diabetes include genetic defects of ________ ________ function and genetic defects in ___________ __________.
beta cell function and insulin action
One specific grouping of genetically defined forms of diabetes is what?
MODY (Maturity Onset Diabetes of the Young)
Those with MODY (Maturity Onset Diabetes of the Young) present at what age?
A young age
Those with MODY (Maturity Onset Diabetes of the Young) have mild disease due to beta cell dysfunction with some _________ __________________ , and inherit the disease via _______________ _______________ transmission.
insulin production and autosomal dominant
There is normal insulin sensitivity with MODY.
True or False?
True
There have been how many different genetic abnormalities identified that are responsible for beta-cell function impairment? (MODY type 2 and 3 accounts for 15 percent of the cases respectively.)
6
These genetic abnormalities are often now referred to as their specific descriptions of known genetic defects instead of MODY subtypes. (For example, MODY 2 encompasses over a dozen mutations in the glucokinase gene on chromosome 7.)
True or False?
True
Which two Endocrinopathies and Exocrine Pancreas issues results in diabetogenic effects due to excess hormone levels?
Cushing Syndrome and acromegaly
There are also specific genetic syndromes sometime associated with diabetes like __________ __________________ and uncommon forms of immune-mediated diabetes like “________ _________ syndrome”.
Down Syndrome and stiff man
Diabetes Induced By Infections, Drugs, or Chemicals
The etiologies for the disorders identified in the “other” section vary, and may be more type 1 in nature meaning what?
beta cell destruction and absolute insulin deficiency
Diabetes Induced By Infections, Drugs, or Chemicals
The etiologies for the disorders identified in the “other” section vary, and may be more type 2 in nature meaning what?
relative insulin deficiency
When classifying diabetes, it is important to understand the underlying etiology to understand how the disease manifests and the corresponding management.
True or False?
true
Glucose is a ___ carbon molecule that is a very efficient fuel, breaking down into CO2 and H2O when metabolized in the presence of oxygen.
6
Glucose is a 6 -carbon molecule that is a very efficient fuel, breaking down into ________ and ________ when metabolized in the presence of _______________.
CO2 and H2O and oxygen
The brain and nervous system rely almost solely on what as a fuel source?
Glucose
Other tissues and organ systems can use other sources of non-carbohydrate fuel such as what two things?
fatty acids and ketones
The brain is not able to synthesize glucose or store more than a few minutes worth of glucose supply.
True or False?
True
A continuous supply of glucose from the circulation is not typically required to maintain normal cerebral function.
True or False?
False (continuous supply of glucose from the circulation is required to maintain normal cerebral function)
Fasting blood glucose is tightly regulated between ___________mmol/L in non-diabetic persons?
4.4-5.0mmol/L
What is secreted by beta cells in the pancreas in response to rising blood glucose?
Insulin
Insulin secreted by what type of cells in the pancreas in response to rising blood glucose?
beta cells
After a meal is ingested, approximately 2/3 of glucose is stored in the liver as what?
glycogen
The liver releases glucose by breaking down glycogen in a process called _____________________ to maintain ________________________ between meals.
glycogenolysis and normoglycemia
Once the liver and skeletal muscles are saturated with glycogen, additional glucose is converted into __________ ________ by the liver and then stored as ______________________ in adipose tissue.
amino acids, glycerol, lactic acid
fatty acids and triglycerides
The liver also synthesizes glucose from what three non-carbohydrate sources?
amino acids, glycerol, lactic acid
The liver also synthesizes glucose from non-carbohydrate sources such as amino acids, glycerol and lactic acid in a process called what?
gluconeogenesis
What is essential for the formation of all body structures?
Protein
Protein are essential for the formation of all body structures including which of the following?
a) genes
b) enzymes
c) contractile structures in muscle
d) matrix of bone
e) hemoglobin of red blood cells
f) all of the above
F
What are the building blocks of proteins?
Amino acids
There is an unlimited capacity for the storage of amino acids.
True or False?
False (There is a limited capacity for the storage of amino acids)
Most stored amino acids are contained in what?
body proteins
Amino acids that not needed for protein synthesis are converted to what three things? Then, what is it stored or used as?
fatty acids, ketones or glucose and metabolic fuel
Amino acids are broken down from proteins and used as a major substrate for ________________________ when metabolic needs exceed what?
gluconeogenesis and food intake
What is the most efficient form of fuel storage?
fat
Fat is the most efficient form of fuel storage, yielding ___ kcal/g of stored carbohydrates and proteins.
9
Approximately _____-____% of calories are obtained from fat in a normal Canadian Diet.
______% obtained by carbohydrates and about _____% from protein
30-35% and 55% and 15%
Many carbohydrates consumed in diet are converted to ___________________ and stored in _____________ ________________.
triglycerides and adipose tissue
Triglycerides are composed of what components?
3 fatty acids (linked together by) and a glycerol molecule
What is an enzyme that breaks down triglycerides into its 4 components when what occurs?
Lipase and when fat is required for fuel
What is then used in the glycolytic pathway and can be used with glucose to produce energy or to produce glucose?
Glycerol
What are transported to tissues and can be used interchangeably with glucose for energy in almost all body cells EXCEPT the brain, nervous system, and red blood cells?
Fatty acids
Fatty acids are transported to tissues and can be used interchangeably with glucose for energy in almost all body cells EXCEPT in what three areas?
the brain, nervous system, and red blood cells
The liver converts left over fatty acids into ______________ and releases them into the ________________________.
ketones and bloodstream
What occurs when large amounts of ketones (organic acids) are released into the blood stream?
Ketoacidosis
After a meal is consumed, what does the pancreas release in response to increasing plasma glucose? (This allows glucose to enter cells and be used.)
Insulin
Glucose that is not needed will go to the liver and be stored as what in skeletal muscle?
glycogen
What is largely responsible for the hormonal control of blood glucose?
endocrine pancreas
What is the endocrine pancreas is largely responsible for?
hormonal control of blood glucose
The pancreas is an organ located behind the _______________ and between the ___________ and the __________________.
stomach, spleen, and duodenum
The pancreas is made up of what 2 components?
the endocrine pancreas and the exocrine pancreas
Which pancreas produces digestive juices which are secreted into the duodenum?
Exocrine Pancreas
What type of cells make up the exocrine pancreas?
Acini cells (secreted via pancreas duct)
What duct does the exocrine pancreas secrete digestive juices into the duodenum?
pancreas duct
Which pancreas makes up 1-2% of the pancreas’ volume and secretes hormones that regulate most of the carbohydrate metabolism in the body ?
Endocrine Pancreas
How much of the pancreas volume is made up of the endocrine pancreas?
1-2%
What type of cells make up the endocrine pancreas?
islets of Langerhans
The pancreatic islets (within the endocrine pancreas) are made up of what three cells?
alpha, beta, delta cells
The Beta cells of the pancreatic islets (within the endocrine pancreas) secrete what two things?
insulin and amylin
The Alpha cells of the pancreatic islets (within the endocrine pancreas) secrete what?
Glucagon
The Delta cells of the pancreatic islets (within the endocrine pancreas) secrete what?
Somatostatin
What is the only hormone to have a direct effect on lowering blood glucose levels?
Insulin
It is important to understand the effects of insulin resistance in type 2 diabetes is one of the main pathophysiological features.
True or False?
True
The active form of insulin is composed of what two (2) polypeptide chains?
A chain and B chain
Active insulin is formed from what type of insulin?
pro-insulin
What is pro-insulin composed of?
An active insulin and a (biologically inactive) connecting peptide
The Structure of Pro-insulin
The A and B chain are joined by what?
the connecting peptide
The Structure of Pro-insulin
The cleaving of the connecting peptide results in pro-insulin being converted to what?
insulin
Both active insulin and inactive ___-_____________ _________ are packaged into ______________ ______________ and released from the beta cell at the same time.
C-Peptide Chain and secretory granules
Both active insulin and inactive C-peptide chain are packaged into secretory granules and released from the beta cell at the opposite times.
True or False?
False (Both active insulin and inactive C-peptide chain are packaged into secretory granules and released from the beta cell at the same time)
Clinically, it is impossible to measure serum C-peptide to assess beta cell function and the need for insulin therapy. Other methods must be used.
False (Clinically, it is possible to measure serum C-peptide to assess beta cell function and the need for insulin therapy.)
Blood glucose enters the beta cell by means of what?
the glucose transporter
Blood Glucose it is metabolized to form what through what process?
ATP (adenosine triphosphate) through phosphorylation
Blood glucose enters the beta cell by means of the glucose transporter. It is metabolized to form adenosine triphosphate or ATP through phosphorylation by an enzyme called what?
glucokinase
ATP from glucose is needed for what purpose in the beta cell?
close the K+ channels and depolarize the cell
Once the beta cell is depolarized, which channels can open? What does this cause?
calcium channels and insulin secretion
Is insulin secretion is decreased or increased when blood glucose levels are lower?
Decreased
Is insulin secretion is decreased or increased when blood glucose levels are higher?
Increased
Insulin response is known as what?
biphasic
The first release of insulin peaking ____-_____ minutes post food ingestion and returning to baseline within ____-____ hours.
3-5 minutes and 2-3 hours
What occurs during the first phase of insulin response?
stored performed insulin is secreted
When does the second phase of insulin response occur and how long does it last?
around 2 minutes and continues to increase slowly for at least 60 minutes (or until the stimulus ceases)
What is important about the insulin released during the second phase of insulin response?
insulin released is newly synthesized insulin
Insulin has three main actions. What are they?
Study slide - Long response
- Promotes uptake of glucose (by target cells) and increases glycogen synthesis.
- Prevents fat and glycogen breakdown.
- Inhibits gluconeogenesis and increases protein synthesis
As plasma glucose increases, insulin is secreted by the beta cells of the pancreas and enters the what?
portal circulation (in the liver)
Once the insulin enters the portal circulation in the liver, how much of it is used or degraded?
50%
What is the half-life of insulin, once it is released into circulation?
approximately 15 minutes
To initiate the effect on target tissue insulin binds to what?
a membrane receptor
The membrane receptor on the target tissue is composed of two subunits known as?
Alpha Subunit and Beta Subunit
Which subunit of the membrane receptor on the target tissue extends outside of the cell membrane? What occurs here?
Alpha Subunit and insulin binds
Which subunit of the membrane receptor on the target tissue is predominately inside the cell membrane? What occurs here?
Beta Subunit and contains kinase enzyme (that activates with insulin binding)
The beta subunit is predominately inside the cell membrane. This is smaller than the alpha unit and contains kinase enzyme that activates with insulin binding. What does this kinase enzyme result in?
autophosphorylation of the beta subunit (activates some enzymes and inactivates others)
The beta subunit is predominately inside the cell membrane. This is smaller than the alpha unit and contains kinase enzyme that activates with insulin binding.
This kinase enzyme result in the autophosphorylation of the beta subunit which activates some enzymes and inactivates others. What does this cause?
(the desired intracellular effect of) insulin on glucose, fat and protein metabolism as well as cell growth.
Specifically, what causes glucose transport, fatty acid synthesis, glycogen synthesis, cell growth and survival, and amino acid/electrolyte transport?
Insulin receptor substrates 1-4
Cell membranes are almost completely permeable to glucose and therefore can move from the blood into the cell without a problem.
True or False?
False (Cell membranes are almost impermeable to glucose and therefore require a special carrier called a glucose transporter to move glucose from the blood into the cell. )
What are the 3 types of glucose transporters discussed?
GLUT 4, 2, 1
Which glucose transporter discussed is the insulin-dependent glucose transporter for skeletal muscle and adipose tissue?
GLUT-4
What is GLUT-4 stimulated by? Where does it move from? (What does it do here?)
Stimulated by insulin to move from its inactive site to the cell membrane (where it facilitates glucose entry)
Which glucose transporter discussed is the major transporter for glucose into beta cells and liver cells?
GLUT-2
Which glucose transporter discussed present in all tissues and does not require the action of insulin. (Hint: It is important in the transport of glucose into cells of the nervous system)
GLUT-1
All of these glucose transporters move glucose across the cell membrane at a faster rate than they would with diffusion alone.
True or False?
True
Mitogen activated protein (MAP) kinase signaling cascade promotes what three things?
cell growth, cell differentiation, and gene expression
What is released at the same time as insulin, by beta cells?
Amylin
What is the job of Amylin?
It regulates blood sugar by having antihyperglycemic and satiety effects (by delaying nutrient uptake through inhibition of gastric emptying and suppressing glucagon secretion after meals.)
What is a polypeptide molecule produced by the alpha cells and works opposite to insulin?
Glucagon
Where does the glucagon travel to the liver via?
the portal circulation
Where does glucagon exert its main function?
In the liver
How does glucagon maintain blood sugar levels between meals?
by initiating glycogenolysis (in the liver,) and stimulating gluconeogenesis (increasing transport of amino acids into liver)
When there are high levels of glucagon, glucagon activates what? What does this do?
Adipose cell lipase makes fatty acids available for use as an alternative source of energy
Glucagon can also have an inotropic effect, enhance bile secretion and inhibit gastric acid secretion at high levels.
True or False?
True
What is released by delta cells in the endocrine pancreas?
Somatostatin
What stimulates somatostatin secretion?
Almost all aspects related to food ingestion
What are the main two jobs of somatostatin?
decrease GI activity and inhibit release of insulin and glucagon
What does somatostatin cause an extended time for?
food to be absorbed and will extend the use of absorbed nutrients by tissues
What type of hormones counteract the storage functions of insulin in regulating the blood glucose levels during periods of fasting, exercise, and stress?
Counter-regulatory hormones
There can be situations that can limit glucose intake, but not deplete glucose stores.
True or False?
False (There can be situations that either limit glucose intake or deplete glucose stores.)
What is one of the catecholamines released by the adrenal medulla when stimulated by the sympathetic nervous system. (Hint: It is particularly active in the stress response.)
Epinephrine
Epinephrine can cause ______________ ____________________ by promoting gluconeogenesis and glycogenolysis in the liver
transient hyperglycemia
Epinephrine inhibits _____________ formation as well as increasing the breakdown of muscle __________________ stores
glycogen
Epinephrine inhibits insulin release from beta cells which decreases glucose uptake in muscle and other organs. Why is this done?
This preserve glucose for the brain
Glucose released by muscle glycogen is not released into the blood, however the ___________________ of these stores for muscle use conserves blood glucose for use by other tissues that rely almost solely on glucose for energy for what organ and what system?
mobilization and brain and nervous system
What can stimulate lipolysis by freeing triglycerides and fatty acids from adipose tissue?
Epinephrine
Epinephrine can also catalyze the degradation of circulating cholesterol to bile acids.
True or False?
False (It inhibits the degradation of circulating cholesterol to bile acids.)
Which counter-regulatory hormone increases protein synthesis in all cells of the body, stimulates lipolysis and antagonizes the effects of insulin?
Growth Hormone (GH)
Growth Hormone increases or decreases cellular uptake and use of glucose?
decreases
What disease can result in glucose intolerance or the development of diabetes mellitus?
acromegaly (which is characterized by hypersecretion of growth hormone)
For those with diabetes, an increase in growth hormone (which occurs in periods of stress and growth for children) can lead to the whole spectrum of what?
Metabolic Abnormalities (associated with poor regulation) (even though insulin treatment may be optimized)
Which counter-regulatory hormone refer to steroid hormones that have direct effects on carbohydrate metabolism?
Glucocorticoids (specifically cortisol)
Where are glucocorticoids (specifically cortisol) synthesized?
in the adrenal cortex
One of the main effect of cortisol is to stimulate what?
gluconeogenesis
Glucocorticoids also moderately decrease what?
the use of glucose by tissue.
Outside of the liver, glucocorticoids stimulate what?
protein catabolism
Outside of the liver, glucocorticoids inhibit what two things?
amino acid uptake and protein synthesis
Increased cortisol complicates diabetes.
True or False?
TRUE
Glucagon is not considered a counter-regulatory hormone.
True or False?
FALSE
Counter-regulatory hormones play an essential role in glucose homeostasis especially in times of __________ and ____________________.
stress and hypoglycemia
When there is persistent stress or hypersecretion of these hormones for other reasons, there are consequences which can lead to dysfunction of what?
glucose metabolism
What is a metabolic disorder characterized by the presence of hyperglycemia (due to defective insulin secretion, defective insulin action or both) known as?
Diabetes Mellitus
Diabetes Mellitus must have hyperglycemia due to what defects?
Defective insulin secretion, defective insulin action or both
The chronic hyperglycemia of diabetes is associated with relatively specific longterm microvascular complications affecting the _________ , ___________ , ___________ as well as an increased risk for ___________________ ____________ (CVD)
eyes, kidneys, nerves, heart, and cardiovascular disease (CVD)
Diagnostic criteria for diabetes are based on thresholds of ____________ associated with microvascular disease, especially __________________.
glycemia and retinopathy
What is a qualitative term used to describe blood glucose (BG) that is abnormal without defining a threshold?
Dysglycemia
The adoption of the term “dysglycemia) reflects uncertainty about optimal BG ranges and the current understanding that cardiovascular risk and mortality risk exist in people with even slightly elevated BG levels.
True or False?
True
Type 1 diabetes is a catabolic disorder characterized by what three things?
Absolute lack of insulin, Hyperglycemia and a breakdown of fats and proteins (for energy instead of carbohydrates)
The pathophysiology of type 1 diabetes, particularly the absolute lack of insulin, makes these patients prone to what?
ketoacidosis
Type 1B Idiopathic Diabetes contains beta cell destruction; however no evidence of autoimmunity is present.
True or False?
TRUE
What type of diabetes is an autoimmune disorder where genetics and an environmental triggering even cause a T-lymphocyte mediated hypersensitivity reaction against some beta cell antigen?
Type 1A
Type 1A Autoimmune Diabetes
The destruction of beta cells is two-fold because:
- First, there is __________________ and ___________________ infiltration of the islets which results in _________________ or insulitis and islet beta cell death.
- Secondly, there is production of autoantibodies against islet cells, insulin, glutamic acid decarboxylase (GAD) and other cytoplasmic proteins.
(Glutamic acid decarboxylase is an enzyme in beta cells that is involved in glucagon synthesis.)
lymphocyte and macrophage and inflammation
Type 1A Autoimmune Diabetes
The destruction of beta cells is two-fold because:
- First, there is lymphocyte and macrophage infiltration of the islets which results in inflammation or insulitis and islet beta cell death.
- Secondly, there is production of __________________ against islet cells, insulin, glutamic acid decarboxylase (GAD) and other cytoplasmic proteins.
(Glutamic acid decarboxylase is an ______________ in beta cells that is involved in glucagon synthesis.)
autoantibodies and enzyme
Putting It Together: Type 1 Diabetes Mellitus
What two things cause autoantigens to form on insulin-producing beta cella and circulate in the blood stream and lymphatics?
genetic predisposition and environmental factors
Putting It Together: Type 1 Diabetes Mellitus
What occurs as the autoantigens circulate through the body?
Processing and presentation of autoantigens
Putting It Together: Type 1 Diabetes Mellitus
What are activated when circulating autoantigens are ingested by antigen-presenting cells?
T helper 1 lymphocytes
T helper 1 lymphocytes secrete _______________ which activates _______________ and stimulates the release of inflammatory cytokines like IL-1 and TNF-alpha
interferon and macrophages
T helper 1 lymphocytes secrete interferon which activates macrophages and stimulates the release of inflammatory cytokines like _____-___ and ______-________
IL-1 and TNF-alpha
What do inflammatory cytokines such as IL-1 and TNF-alpha cause?
beta cell destruction and apoptosis
Activated T helper 1 lymphocytes also secrete ________________ ____ which activates beta cell autoantigen-specific T lymphocytes.
interleukin 2
Activated T helper 1 lymphocytes also secrete interleukin 2, which activates beta cell autoantigen-specific T lymphocytes.
This leads to the destruction of beta cells which results in what?
decreased insulin secretion
Activation of T helper 2 lymphocytes causes the secretion of _________________-_____, which stimulates B lymphocytes to proliferate and produce antibodies.
interleukin-4
Activation of T helper 2 lymphocytes causes the secretion of interleukin-4, which stimulates B lymphocytes to do what two things?
proliferate and produce antibodies
Activation of T helper 2 lymphocytes causes the secretion of interleukin-4, which stimulates B lymphocytes to proliferate and produce antibodies.
These autoantibodies contribute to the destruction of beta cells and decreased insulin secretion.
True
Putting It Together: Type 1 Diabetes Mellitus
There is dysfunction in both ____________ and _________-____________________ immunity.
humoral and cell-mediated immunity
Putting It Together: Type 1 Diabetes Mellitus
Remember that T regulatory cells usually act to inhibit the immune response. There have been mutations affecting these cells noted in a rare form of diabetes called _____________ ________________.
Further research is needed to investigate the role or lack-there-of, of T regulatory cells.
neonatal diabetes
Like type 1 diabetes, there is a genetic predisposition as well as environmental influences that result in the basic pathophysiologic mechanisms of what type of diabetes?
type 2
Like type 1 diabetes, there is a genetic predisposition as well as environmental influences that result in the basic pathophysiologic mechanisms of what type of diabetes?
type 2
Like type 1 diabetes, there is a genetic predisposition as well as environmental influences that result in the basic pathophysiologic mechanisms of diabetes type 2.
These include insulin resistance, abnormal insulin secretion beta cells and increased glucose production by the liver.
True or False?
TRUE
Many genes have been identified as being associated with type 2 diabetes.
Which of the following are coded for by genes?
a) beta cell mass
b) beta cell function
c) proinsulin and insulin molecular structure
d) insulin receptors, hepatic synthesis of glucose
e) glucagon synthesis
f) cellular responsiveness to insulin stimulation
g) All of the above
G
A relative insulin deficiency is required to develop what type of diabetes?
type 2 diabetes
Beta cell dysfunction is always present in some extent with type 2 diabetes.
True or False?
True
Many individuals have risk factors for type 2 diabetes including: obesity, metabolic syndrome and hypertension and are insulin resistant.
However, it is only those who are ________________ ________________ to beta cell dysfunction who will develop type 2 diabetes.
genetically predisposed
What prevents the clinical appearance of diabetes for many years?
Compensatory hyperinsulinemia (caused by insulin resistance)
Eventually beta cell dysfunction leads to a relative insulin deficiency, hyperglycemia, and type 2 diabetes.
True or False?
true
What causes a relative insulin deficiency in type 2 diabetes?
Beta cell dysfunction
Beta cell dysfunction may be a result of what three things?
Decrease in beta cell mass, abnormal function of beta cells, or some combination of these.
With beta cell dysfunction, there is progressive decrease in the ________ and ___________ of beta cells.
weight and number
Beta cells are extremely sensitive to high levels what two substances?
Glucose and free fatty acids
Beta cells are extremely sensitive to high levels of glucose and free fatty acids and undergo apoptotic death in what type of conditions?
glucolipotoxic conditions
Adipokine __________ decreases insulin synthesis in beta cell.
leptin
Inflammatory cytokines like ______-______ and _____-________ which are released from adipocytes, are toxic to beta cells.
TNF-alpha and IL-beta
Beta cell exhaustion from increased demand for insulin biosynthesis which is associated with intracellular oxidative stress and endoplasmic reticulum dysfunction.
True or False?
true
What is the suboptimal response of insulin-sensitive tissues to insulin?
Insulin Resistance
What are three insulin-sensitive tissues?
Liver, muscle and adipose tissue.
The mechanisms of insulin resistance include:
a) an abnormality of the insulin molecule
b) high amounts of insulin receptor
c) decreased or abnormal activation of postreceptor kinases
d) alteration of glucose transporter proteins
e) All of the above
E
What is present in 60-80% of individuals with type 2 diabetes?
obesity
What percentage of those with type 2 diabetes are overweight?
90%
Obesity is a significant contributor to both _________ ________________ and ________ __________ _____________________.
insulin resistance and beta cell dysfunction
Obesity is a significant contributor to both insulin resistance and beta cell dysfunction.
Increased ________________ (hormones produced in adipose tissues) and expression of a receptor called peroxisome proliferator-activated receptor gamma which is highly expressed in adipose tissue and responsible for the changes in ____________________.
adipokines
Obesity is a significant contributor to both insulin resistance and beta cell dysfunction.
This includes Increased levels of serum leptin and resistin and decreased levels of adiponectin; adiponectin increases tissue sensitivity to insulin and appears to have what three types of effects?
antidiabetic, anti-inflammatory and antiatherogenic effects.
Which class of drugs modulate the activity of peroxisome proliferator-activated receptor gamma and are used to treat type 2 diabetes?
TZDs (thiazolidinediones)
Elevated serum FFAs, intracellular deposits of ____________________ and ____________________ interfere with intracellular insulin signaling and decrease tissue response to insulin.
triglycerides and cholesterol
What does Lipotoxcitiy causes within the beta cells?
altered insulin secretion
Elevated FFAs inhibit what two things?
Hint: They cause insulin resistance and glucose underutilization
glucose uptake and glycogen storage (in the peripheral tissues)
Elevated FFAs inhibit glucose uptake and glycogen storage in the peripheral tissues causing what two things?
insulin resistance and glucose underutilization
Elevation of FFAs and triglycerides reduces what?
Hint: This leads to increases hepatic glucose production and hyperglycemia. This is heightened in the fasting state.
hepatic insulin sensitivity
Elevation of FFAs and triglycerides reduces hepatic insulin sensitivity, leading to what two things?
increases hepatic glucose production and hyperglycemia. (This is heightened in the fasting state.)
Inflammatory cytokines (like TNF-alpha and IL-6) are released from adipocytes and contribute to insulin resistance through what?
postreceptor mechanism
Obesity is correlated with what two things?
hyperinsulinemia and decreased receptor density
In a joint statement between the American Diabetes Association and the European Association for the Study of Diabetes, what is described as:
“a clustering of specific cardiovascular disease risk factors whose underlying pathophysiology is thought to be related to insulin resistance”
metabolic syndrome
What seems seems to play a role in not only the pathophysiology of type 2 diabetes, but other metabolic abnormalities as well?
(This includes:
- obesity
- high levels of plasma triglycerides and low levels of high density lipoproteins (HDL)
- hypertension
- systemic inflammation detected by measuring plasma CRP and other inflammatory mediators
- abnormal fibrinolysis
- abnormal function of the vascular endothelium and macrovascular disease such as coronary artery, cerebrovascular and peripheral artery disease.)
insulin resistance
Practitioners are cautioned to treat the patient based on whether they meet criteria for metabolic syndrome and not to evaluate and treat each cardiovascular disease risk factor independently of a metabolic syndrome diagnosis.
True or False?
False (Practitioners are cautioned to not treat the patient based on whether they meet criteria for metabolic syndrome but to evaluate and treat each cardiovascular disease risk factor independently of a metabolic syndrome diagnosis.)
There is a universal consensus on metabolic syndrome criteria. It’s world renowned.
False (There is no universal consensus on metabolic syndrome criteria.)
The World Health Organization and International Diabetes Federation have outlined criteria where what was a requisite?
insulin resistance
The criteria are outlined in the Canadian Diabetes Association Clinical Practice Guidelines provide an operational definition based on _______ _________________ and is intended to be used to ensure consistency in North American clinical practice when diagnosing metabolic syndrome.
risk determinants
Metabolic Syndrome is diagnosed when the patient meets three (3) or more of the following criteria:
- Abdominal Obesity: waist circumference ≥ 88 cm in women or ≥ 102 cm in men
- Triglycerides: ≥ 1.7 mmol/L
- HDL: < 1.3 mmol/L in women or < 1.0 mmol/L in men
- Blood Pressure: ≥ 130 systolic or ≥ 85 mmHg diastolic
- Fasting Plasma Glucose ≥ 5.6 mmol/L
True or False?
True
Insulin resistance and metabolic syndrome are associated and the associated cardiovascular risks must each be evaluated and treated either within the treated either within the context of a type 2 diabetes diagnosis or not.
True or False?
True
What three things leads to obesity?
Diet, inactivity, and genetic predisposition
Obesity causes derangement of ______________, increased ____________ ___________ _________ and release of ____________________ ______________ from adipocytes.
adipokines, increased free fatty acids and release of inflammatory cytokines
When there is resistance to insulin, the demand for insulin synthesis increases leading to what?
hyperinsulinemia
When there is resistance to insulin, the demand for insulin synthesis increases, leading to hyperinsulinemia.
- The clinical appearance of diabetes is avoided for many years due to compensatory hyperinsulinemia.
-The result is damaging tissue effects without hyperglycemia or insulin resistance without diabetes.
Remember, that these
Individuals often meet criteria for ________________ _______________ and should be treated accordingly.
metabolic syndrome
Genetic predisposition to beta cell dysfunction leads to what?
hypoinsulinemia
Insulin resistance causes an increased demand for what?
insulin synthesis
Beta cell exhaustion is associated with what two things? What does this lead to?
Intracellular oxidative stress and endoplasmic reticulum dysfunction, leading to beta cell apoptosis.
What two things have a direct toxic effect to beta cells?
Lipotoxic conditions and inflammatory cytokines
Normally, glucagon release is inhibited by what?
hyperglycemia
Pancreatic alpha cells are less responsive to glucose inhibition in type 2 diabetes causing what?
increased glucagon secretion (and contributing to hyperglycemia)
Decreased amylin activity parallels the reduction in insulin secretion.
True or False?
True
Amyloid deposition in the pancreas, does not contribute to islet cell dysfunction.
False (Amyloid deposition in the pancreas which contributes to islet cell dysfunction. )
Amylin normally inhibits what?
glucagon secretion
What are peptides released in the GI tract when food is ingested?
Incretin
What is the job of incretin after it binds to receptors on beta cells?
increase the synthesis and secretion of insulin (in response to glucose levels)
In type 2 diabetes, is incretin activity increased or decreased?
Decreased (which impairs beta cell function)
There are drugs approved in the US aimed at augmenting one of the incretin peptides and inhibiting an enzyme that inactivates them.
True or False?
True
What is the peptide produced in the stomach and pancreatic islets that stimulates growth hormone secretion and is involved in homeostasis regulation of energy, glucose, GI motility and secretion?
(HINT: this is often termed the ‘hunger hormone’ because it stimulates appetite, increases food intake and promotes fat storage.)
Ghrelin
What 3 things is ghrelin involved in homeostasis regulation of?
energy, glucose, GI motility and secretion.
Ghrelin has an effect on insulin however the effect is unclear.
True or False?
True
Although the effect ghrelin has on insulin, is unclear. Decreased levels of circulating ghrelin have been associated with what two things?
insulin resistance and increased fasting insulin levels
Counter Regulatory Mechanisms in Diabetes Mellitus
What Effect or Phenomenon is characterized by insulin by insulin induced hypoglycemia followed by rebound hyperglycemia?
Somogyi Effect
Counter Regulatory Mechanisms in Diabetes Mellitus - Somogyi Effect
The cycle occurs when hyperglycemia and insulin resistance is treated with larger insulin doses.
The hypoglycemia state stimulates which 4 glucose counter-regulatory hormones?
redistributing dietary carbohydrates and altering insulin dose (or time of administration.)
cathecholamines, glucagon, cortisol and growth hormone
Counter Regulatory Mechanisms in Diabetes Mellitus - Somogyi Effect
Management to prevent hypoglycemia and subsequent counter-regulatory mechanisms activation includes what two things?
redistributing dietary carbohydrates and altering insulin dose (or time of administration.)
Somogyi effect usually occurs in which type of diabetes?
Type 1
Somogyi effect usually cannot occur at all in type 2 diabetes.
True or False?
False (Somogyi effect usually occurs in type 1 diabetes however it can occur in type 2 diabetes if insulin is prescribed.)
Counter Regulatory Mechanisms in Diabetes Mellitus
What Effect or Phenomenon is characterized by hyperglycemia between 0500-0900 without preceding hypoglycemia?
Dawn Phenomenon
Counter Regulatory Mechanisms in Diabetes Mellitus - Dawn Phenomenon
One possible cause is that there is a change in the normal _____________ ________________ for glucose tolerance in diabetes.
circadian rhythm
Counter Regulatory Mechanisms in Diabetes Mellitus - Dawn Phenomenon
Which of the following Statement(s) are/is correct?
A) Glucose is normally higher during the later part of the morning.
B) It also appears to be related to daytime elevations of growth hormone.
C) Management includes altering the time and dose of glucagon.
A
Are the following acute or chronic complications of diabetes?
- Hypoglycemia
- diabetic ketoacidosis
- hyperosmolar hyperglycemic nonketotic syndrome
Acute Complications
Can acute or chronic complications can be classified either microvascular or macrovascular disease?
chronic complications
Chronic Complications can be classified microvascular or macrovascular disease.
Which type includes retinopathy, neuropathy, and nephropathy?
Microvascular disease
Chronic Complications can be classified microvascular or macrovascular disease.
Which type includes coronary artery disease, cerebrovascular disease and peripheral vascular disease?
Macrovascular disease
Both type 1 and 2 diabetes evolve over time eventually to a point where there is either a relative or absolute deficiency of insulin which results in some common clinical manifestations.
True or False?
True
What term means excessive urination?
polyuria
Why does polyuria occur?
the amount of glucose (filtered by the glomeruli of the kidneys) exceeds that which can be reabsorbed by the renal tubules (and glucose acts as an osmotic diuretic.)
What term means excessive thirst?
Polydipsia
Why does Polydipsia occur?
hyperglycemia pulls water out of body cells (intracellular dehydration, occurs) (Furthermore, polyuria contributes to a state of dehydration.)
What term means excessive hunger?
polyphagia
Polyphagia: which means excessive hunger, usually does NOT occur in type 1 diabetics.
True or False?
False (Occurs in type 1 diabetes, not type 2)
Why does Polydipsia occur?
(In type 1 diabetes, it is the result of cellular starvation) The depletion of cellular stores of carbohydrates, fats, and proteins. (This depletion corresponds with increased hunger.)
Despite normal or increased appetite, weight loss is common in uncontrolled type 1 or 2 diabetes?
Type 1
Why does weight loss occur in Type 1 Diabetes Mellitus?
The loss of fluid through osmotic diuresis and vomiting during periods of ketoacidosis (this may exaggerate the weight loss due to fluid loss)
The absolute insulin deficiency leads to the loss of body tissue as fat and proteins are used for energy as a result of insulin deficiency
True or False?
True
Which type of diabetes is seen with obesity?
Type 2
Genetics may have a role in obesity; however lifestyle and nutrition contribute significantly.
True or False?
True
What can occur as with exposure of the lens and retina to hyperosmolar fluids?
Blurred Vision
What is the result of lowered plasma volume, poor use of food products due to metabolic changes and possibly sleep loss from severe nocturia?
Fatigue
What can occur due to dysfunction of the peripheral sensory nerves called peripheral vascular disease?
Paresthesias
What can occur due to injury in person with peripheral vascular disease that was not attended to?
(Candida or yeast infections are common causes of vulvovaginitis and balanitis.)
Infections
Signs and symptoms related to diabetes will be heightened in individuals whose blood sugar is not managed well.
True or False?
True
What is the preferred diagnostic test for diabetes?
fasting blood glucose (FBG)
The fasting blood glucose (FBG) requires that the individual fast for at least ___ hours?
8
Diagnosis of diabetes is made when the FBG be ≥ 7.0 mmol/L on 2 occasions *if asymptomatic.
True or False?
True
Which Diabetes Diagnostic Test can be done without regard to time or last meal?
Random Blood Glucose Test
Random Blood Glucose Test
A finding of greater than 11.1 mmol/L and classical clinical manifestations of diabetes like polyuria, polydipsia and unexplained weight loss, meets the criteria for the diagnosis of what?
Diabetes
Which Diabetes Diagnostic Test measures plasma glucose response to 75 g concentrated glucose solution at 2 hours post glucose load?
(A diagnosis of diabetes mellitus is made for a finding of ≥ 11.1 mmol/L.)
Oral Glucose Tolerance Test (OGTT)
What test measures the proportion of glycated hemoglobin in circulation?
Glycated Hemoglobin or A1C Test
What does Glycated Hemoglobin or A1C Test measure?
average plasma glucose concentration over the past 2 to 3 months.
When can the Glycated Hemoglobin or A1C Test be taken?
Diagnosis of diabetes mellitus is made for a finding of ≥ 6.5% glycated hemoglobin
at any time of the day (and avoids the problem of day-to-day variations in plasma glucose levels)
What is the gold standard for monitoring diabetes at home?
Capillary Blood Glucose Monitoring
What uses capillary blood from pricking the finger or forearm, then the blood is placed on the reagent strip and the strip is entered into the glucometer to determine capillary blood glucose?
Capillary Blood Glucose Monitoring
Capillary Blood Glucose Monitoring
What type of blood is used?
(Which gives results that are 10-15% lower than when plasma is used in laboratory tests)
Whole Blood
Newer glucometers can be calibrated to give plasma values?
True or False?
True
Hemoglobin A1C has become part of the standard of care in the management of diabetes. What is the goal % that is outlined in the Canadian Diabetes Association clinical practice guidelines.
less than 7%
Hemoglobin A1C
Hemoglobin requires insulin for glucose entry into red blood cells.
True or False?
False (Hemoglobin A1C)
Hemoglobin A1C
The rate at which glucose becomes attached to hemoglobin is dependent on what?
blood glucose levels
Hemoglobin A1C
During RBCs _______ day life span, they become glycated to form A1a and A1b and A1C.
120
Hemoglobin A1C
Glycosylation of hemoglobin is essentially irreversible/reversible?
Irreversible (and individuals with hyperglycemia will have a higher percentage of glycosylated hemoglobin.)
Hgb A1C is found to be useful in screening for what two things?
chronic hyperglycemia and assessing the effectiveness of therapy
What can be used to measure glucose or ketones?
Urine Tests
In uncontrolled diabetes, hyperglycemia will persist and when the renal threshold for glucose reabsorption is reached, what ensues?
glycosuria ensues
What are the metabolic end-products of fat metabolism?
Ketones
Normally, ketones are completely metabolized but when fat metabolism is the predominant source of energy, excessive amounts of ketones are formed and excreted through the urine. This occurs when?
In diabetic ketoacidosis.
Genetic Studies and testing for plasma Antibodies specific to diabetes can be done in certain circumstances.
True or False?
True
Insulin therapy is required in the management of type 1 diabetes and many people with type 2 diabetes will eventually require some sort of insulin therapy.
True or False?
True
Insulin can be administered by what two methdods?
injection or inhalation
Which injection routes are used for Insulin Therapy?
subcutaneous and intravenous
Where is intravenous insulin therapy used?
in the hospital setting (only regular insulin can be given intravenously)
Regular insulin can bind to plastic IV tubing and therefore the insulin solution is often run through the tubing for a period of time before attaching to patient.
True
Inhaled Insulin is NOT approved and used in Canada.
True or False?
False (It is; but not commercially available yet)
Inhaled Insulin was used as a rapid-acting insulin in combination with 1 or 2 SC injections of ________-______________ insulin doses.
The study results are promising, finding that in adults’ equivalent glycemic control was achieved with reduced fasting plasma glucose levels and increased patient satisfaction.
long-acting
Inhaled Insulin
The short-term safety data suggest no significant pulmonary dysfunction; however, it is recommended that it not be used in patients with what?
abnormal baseline spirometry
Insulin is destroyed in the GI tract and therefore cannot be given by what route?
orally
Insulin preparations are primarily produced by what? What is the preparations called?
recombinant DNA technology (to be identical to human insulin or modified to alter pharmacokinetics) and insulin analogues.
The Diabetes Control and Complications Trial (DCCT) concluded that intensive treatment of type 1 diabetes through the following, significantly delayed the onset and slowed the progression of microvascular and macrovascular complications.
- Basal/Bolus insulin regimens or continuous subcutaneous insulin infusion
- CBG Checks
- Meal Planning
True or False?
True
An intermediate acting or long-acting insulin analogue given once or twice daily provides what type of insulin?
basal insulin
A short-acting or rapid-acting insulin analogue given at each meal provides what type of insulin?
bolus (or prandial) insulin
For continuous subcutaneous insulin infusion insulin aspart and lispro, both rapid-acting insulin analogues, were shown to be superior to regular insulin by improving post-prandial glycemic control and reducing hypoglycemia.
True or False?
True
What is a major obstacle for achieving glycemic targets?
Hypoglycemia
Hypoglycemia can only have negative physical consequences such as confusion, coma, or seizure. No social consequences.
True or False?
False (It can have negative social and emotional impacts as well as significant physical consequences such as confusion, coma, or seizure.)
The health care team will work diligently with the diabetic to provide the safest insulin therapy to achieve the safest insulin therapy to achieve the best glycemic target.
True or False?
TRUE
Any individual prescribed insulin therapy should be taught how to care and use of insulin; the prevention, recognition and treatment of hypoglycemia; what to do when they are sick; how to make adjustments for food intake and physical activity; and how to perform CBG monitoring.
True or False?
TRUE
What are the two types of rapid-acting insulin called?
lispro (Humalog) and aspart (Novolog)
What is the onset of lispro (Humalog) and aspart (Novolog)?
5-15 minutes
What is the onset of regular insulin?
0.5-1 hour
Pharmacologic Therapy - Oral Antidiabetic Agents
What are the two types of Insulin Secretagogues?
sulfonylurea and nonsulfonylurea agents
Pharmacologic Therapy - Oral Antidiabetic Agents
Which part of an Insulin Secretagogue acts by binding to sulfonylurea receptor on the beta cell, which is linked to ATP sensitive K+ channel. (This causes the K+ channel to close and depolarization to occur.)
Sulfonylureas
Pharmacologic Therapy - Oral Antidiabetic Agents
Which part of an Insulin Secretagogue acts by requiring glucose to close ATP-dependent K+ channel and subsequent insulin release through the same mechanisms as the sulfonylurea agents?
Nonsulfonylurea
What can Insulin secretagogues cause if uneducated?
hypoglycemia (to avoid, recognize and manage hypoglycemic episodes)
Pharmacologic Therapy - Oral Antidiabetic Agents
Which medication inhibits hepatic glucose production and increase the insulin sensitivity peripheral tissues?
What is the only one on the market in Canada?
Biguanides and Metformin
Pharmacologic Therapy - Oral Antidiabetic Agents
Which medications are used when insulin secretagogues or Metformin is not effective in decreasing postprandial hyperglycemia?
Alpha-Glucosidase Inhibitors
Pharmacologic Therapy - Oral Antidiabetic Agents
Alpha-Glucosidase Inhibitors
Alpha-Glucosidase is an enzyme that breaks down what in the small intestine?
Complex Carbohydrates
Pharmacologic Therapy - Oral Antidiabetic Agents
Alpha-Glucosidase Inhibitors
By inhibiting this enzyme, the breakdown of complex carbohydrates is delayed thus blunting what?
the postprandial increase in plasma glucose and insulin levels
Pharmacologic Therapy - Oral Antidiabetic Agents
Alpha-Glucosidase Inhibitors
Hypoglycemia can occur when alpha-glucosidase inhibitors are used in conjunction with sulfonylurea agent. If it does occur, glucose (which is dextrose, not sucrose or table sugar) should be used as sucrose breakdown may be blocked by the action of alpha-glucosidase inhibitors.
True or False?
True
Pharmacologic Therapy - Oral Antidiabetic Agents
Which medications promote the activity of incretins by inhibiting dipeptidyl pepitidase-4 enzyme, which degrades the main incretins GLP-1 and glucose-dependent insulinotropic polypeptide?
(Remember that these incretins are released following a meal and stimulate insulin secretion from the beta cell.)
DPP (Dipeptidyl Peptidase)-4 Inhibitor
Pharmacologic Therapy - Oral Antidiabetic Agents
Which medications • modulate the activity of peroxisome proliferator-activated receptor gamma specifically increasing adipocyte production of adiponectin and are the only class of drugs that target insulin resistance?
TZDs (thiazolidinediones)
Pharmacologic Therapy - Oral Antidiabetic Agents
TZDs
They target insulin resistance by binding to the nuclear peroxisome proliferator-activated receptor gamma that is highly expressed in adipose tissue and seems to be responsible for the changes in adipokines in type 2 diabetes.
True or False?
TRUE
Pharmacologic Therapy - Oral Antidiabetic Agents
TZDs
Changes include increased levels of serum leptin and resistin and more importantly decreased levels of what?
adiponectin
Pharmacologic Therapy - Oral Antidiabetic Agents
TZDs
What increases tissue sensitivity to insulin and appears to have antidiabetic, anti-inflammatory and antiatherogenic effects?
adiponectin
The mechanism of Thiazolidinedione is complex and not entirely understood however other beneficial effects include a decrease in FFA and triglycerides, blood pressure, inflammatory mediators like fibrinogen and CRP and procoagulation factors.
True or False?
TRUE
Which medications can be used as an adjunct pharmacology therapy to lose weight in the management of type 2 diabetes mellitus?
Orlistat (or sibutramine) (Weight loss agents)
Incretins and Amylin analogs are not available in Canada and were not discussed.
True or False?
True
What are the 5 main components in patient teaching for diabetes?
Lifestyle (physical activity, smoking cessation, self-monitoring of blood glucose should be promoted)
Nutrition and diet (adjusting the components of carbohydrates, fat, and protein as required),
Education Regarding Medications (insulin and oral antidiabetic agents)
Avoiding/Recognizing Complications (including both acute and chronic complications will decrease mortality and morbidity and hopefully increase quality of life.)
Equipment (including the use and cost of can be a significant part of teaching. This includes but is not limited to teaching for subcutaneous injections, self-monitoring of blood glucose using capillary poke and glucometer an insulin pumps.)
Multi-disciplinary or Inter-Professional Team
What are the 5 main components in patient teaching for diabetes?
Diabetes carriers no significant personal or societal burden.
True or False?
False (Diabetes carriers a significant personal and societal burden)
Heterogenous and diverse groups require individualized treatments plans.
True or False?
True
As obesity rates continue to climb, type 2 diabetes rates will decrease.
True or False?
False (As obesity rates continue to climb, type 2 diabetes rates will also increase.)
Multiple co-morbidities in diabetes
True or False?
TRUE
Decrease in complications IF glucose levels remain near normal levels of Hgb A1C, which are?
Less than 7%
FROM TUTORIAL:
Definition of metabolic syndrome Includes:
- Elevated waist circumference
- Elevated Trigycerides
- Reduced HDL
- Elevated Blood Pressure
- Elevated Fasting blood glucose
- Elevated Visceral Fat
True or False?
False (Visceral fat is more related to diabetes (stomach versus more pear shaped))
FROM TUTORIAL:
Diabetes is defined as:
A) A disorder characterized by excessive blood glucose levels
B) A disorder of carbohydrate, protein and fat metabolism
C) A disorder characterized by excessive urination
D) A disorder of dysfunctional counter regulatory hormones
C
FROM TUTORIAL:
Which of the following complications accounts for most deaths in those with DM?
A) Coronary artery disease and stroke
B) Renal disease (nephropathy)
C) Erectile dysfunction
D) Non-traumatic amputation
A
FROM TUTORIAL:
Which of the following is NOT an environmental factor contributing to an increased risk for Type I DM?
A) Use of pentamidine - an antimicrobial
B) Dietary intake of bovine milk
C) Congenital rubella infection
D) Infection with human papillomavirus
D
FROM TUTORIAL:
Adult patients that develop DM as a result of latent autoimmune disease are best classified as:
A) Type 1A diabetics
B) Type 1B diabetics
C) Type 2 diabetics
D) Adult onset diabetics
A
FROM TUTORIAL:
Which of the following is an endocrinopathy that may contribute to Type 2 DM?
A) Adrenal insufficiency
B) Overproduction of hGH
C) ADH insufficiency
D) Aldosteronism
B
FROM TUTORIAL:
Which of the following clinical manifestations is predominantly observed in Type 1 DM but not Type 2 DM?
A) Polyuria (excessive urination)
B) Polydipsia (excessive thirst)
C) Polyphagia (excessive hunger)
D) Paresthesia (abnormal dermal sensation (e.g., a tingling, pricking, chilling, burning, or numb sensation on the skin) damage to peripheral nerves)
c
FROM TUTORIAL:
What is the preferred test for diagnosing DM?
A) Fasting blood glucose
B) Random blood glucose
C) Oral glucose tolerance test (T2)
D) Insulin tolerance test
A
FROM TUTORIAL:
What is the mechanism of action of the class of oral anti-diabetics known as thiazolidinediones (TZDs)?
A) They stimulate the secretion of insulin from pancreatic beta-cells
B) They inhibit hepatic glucose production
C) They delay the breakdown of complex carbs in the gut, thereby regulating glucose absorption
D) They modulate PPAR-gamma signalling in adipocytes, resulting in increased production of adiponectin
E) They inhibit dipeptyidyl peptidase, thereby preventing the breakdown of incretins
D
FROM TUTORIAL:
Why is acquiring insulin paramount to ensuring Carl’s (A Type 1 Diabetic) survival?
A) Without insulin Carl may suffer the complications of severe hypoglycemia
B) Carl may experience beta-cell exhaustion and pancreatic destruction if exogenous insulin is not provided immediately
C) Carl’s pancreas may fail and he will be unable to secrete the enzymes necessary to break down the food stuffs in his gut
D) Carl may suffer severe weight loss due to protein catabolism, diuresis and emesis, and will not be able to defend himself from zombies
d
FROM TUTORIAL:
Which of the following fuel sources packs the most energy per gram?
A) Triglycerides (fats)
B) Glucose
C) Proteins
D) Amino acids
a
FROM TUTORIAL:
Which of the following events is thought to contribute to the development of Type 1A DM?
A) Secretion of IL-1 and TNF-α by macrophages, creating a pro-inflammatory environment
B) Secretion of IL-2 by TH1 cells, which activates autoreactive CD8+ T-cells
C) Secretion of IL-4 by TH2 cells, which activates B-cells that produce autoantibodies
D) Relative inactivity of regulatory T-cells that normally inhibit autoimmune responses
E) All of the above can contribute to Type 1A DM
e
FROM TUTORIAL:
Symptoms of Hypoglycemia - usually seen in type 1.
Overshooting the insulin
(glucose <4 mmol/L)
Headache Blurred vision Hunger Irritability Anxiety Diaphoresis Dizziness Tachycardia Shaking (tremor) Weakness Fatigue Feeling tired
True or False?
true
FROM TUTORIAL:
What is the normal value for blood glucose 2-hr post prandial?
(5.0-8.0 mmol/L)
Random Blood Glucose levels should be
no greater than 11.1
- without regard to last meal or time
Oral glucose tolerance test levels
- no greater than 11.1 for diagnosis
Glycated hemoglobin or A1C test levels
no greater than 6.5
Impaired fasting blood glucose ranges from
6.1-6.9
Normal plasma glucose is
less than 6
