Diabetes General Flashcards
1
Q
Overall, well-controlled diabetes is the leading cause of…..
A
NOTHING
2
Q
Define Diabetes Mellitus
A
A metabolic disorder characterized by the presence of hyperglycemia due to defective insulin secretion, insulin action, or both
3
Q
What are some of the complications associated with diabetes? What is the major cause of death?
A
CVD, kidney dx, blindness, neuropathy, amputation……
~80% will die from heart disease or stroke
CVD is a major way people with diabetes die
4
Q
Un-controlled diabetes life expectancy
A
If not properly managed, diabetes may shorten life expectancy by 5-15 years
Poorly controlled diabetes decreases a persons lifespan
5
Q
The pancreas is composed of…..
A
Acini (exocrine) and Islets of Langerhans (endocrine)
6
Q
The islet cells of Langerhans types and functions
A
a) Delta –> Somatostatin –> 10%
b) Beta –> Insulin –> 60%
c) Alpha –> Glucagon –> 30%
7
Q
What is euglycemia? How is it maintained?
A
Euglycemia (sugar at correct levels) is maintained by these 3 hormones (somatostatin, insulin, glucagon) working together
8
Q
One of somatostatins function is…
A
Inhibition of glucagon and insulin secretion
9
Q
Beta Cells compromise what % of endocrine mass? What do they produce? What is the response?
A
- Comprises about 50% of endocrine mass of the pancreas
- Produces insulin and amylin
- Insulin released in response to elevated blood glucose levels
- Amylin is a hormone that can help with satiety (feeling of fulnness)
10
Q
What hormone is released in response to elevated blood glucose levels?
A
Insulin
11
Q
What hormone helps with the feeling of satiety?
A
Amylin
12
Q
Alpha Cells compromise what % of endocrine mass? What do they produce? What is the response?
A
- Compromise about 35% of endocrine mass
- Produce glucagon
- Glucagon released in response to low blood glucose levels
13
Q
What hormone is released in response to low blood glucose levels?
A
Glucagon
14
Q
What is the normal blood glucose levels for people?
A
4-6 millimoles/L
15
Q
Describe the cycle of glucose homeostasis?
A
1) Ingestion of a meal
2) Blood glucose increases
3) Pancreas secretes insulin
4) Insulin acts on muscle, adipose and the liver
- Muscle and Adipose –> Glucose Uptake
- Liver –> Increased glycogenesis, decreased gluconeogenesis
5) Blood glucose levels decrease to normal
6) Absence of meal/Night-time –> Blood glucose decreases
7) Pancreas secretes glucagon
8) Glucagon acts on the liver to increase glycogenolysis and gluconeogenesis
9) Blood glucose increases to normal levels
16
Q
What are the stimulus for secretion of insulin?
A
Increased serum glucose
Increased serum amino acids
Increased serum free fatty acids
Glucagon
GH (growth hormone)
Cortisol
GIP (Gastric Inhibitory hormone)
17
Q
What are the stimuluses for Glucagon secretion?
A
Decreased serum glucose
Decreased serum amino acids
Epinephrine and Norepi
18
Q
Insulin works at what targets? What occurs as a result?
A
a) Liver
- Increases glycogenesis
- Decreased gluconeogenesis
b) Muscle
- Increases protein synthesis
- Increased glycogenesis
c) Adipose Tissue
- Increased lipogenesis
d) Pancreas
- Decreased glucagon secretion
e) Miscellaneous
- Increased K+ uptake into cells
- Increased cholesterol synthesis
19
Q
Glucagon works at what targets? Function?
A
a) Liver
- Increased glycogenolysis
- Increased gluconeogenesis
b) Adipose Tissue
- Increased lipolysis
c) Pancreas
- Decreased insulin secretion
d) Miscellaneous
- Decreased K+ uptake into cells
- Decreased cholesterol synthesis
20
Q
What are some other important counter-regulatory hormones? What do these hormones do?
A
Epinephrine/Norepi
Growth Hormone
Cortisol
Increase serum sugar
21
Q
Insulin is released in the….
A
Fed State
22
Q
Glucagon is released in…
A
Fasting State
23
Q
Does glucagon have any effect on muscle?
A
NO
24
Q
What is the net effect of insulin? What mechanisms does this occur by?
A
- Decreased serum glucose
- Increased storage of energy by increasing protein synthesis, fat synthesis, and glycogen synthesis
25
What is the net effect of glucagon? What mechanisms does this occur by?
- Increased serum glucose
- Increased energy release by increasing protein and fat catabolism and by gluconeogensis
26
Insulins Role Simple
- Drives sugar out of the blood stream and into cells
- Insulin is key for helping cells uptake glucose from the blood
27
What is the major site of glucose uptake?
Muscle
28
After a meal and excess CHO, insulin functions to....
With the ingestion of a meal and excess CHO, insulin stimulates the uptake of glucose in skeletal muscle
Glucose is stored as glycogen in muscle & used in energy metabolism (glycogenesis)
Further, the presence of insulin stimulates production of proteins from amino acids
29
Does insulin only effect glucose? If not, what does it effect?
Insulin stimulates production of proteins from amino acids
30
What occurs in between meals in regards to protein?
In-between meals: body still has energy demands, so in attempt to produce energy, proteins are converted into AA’s
AA’s --> transported to liver --> converted to glucose via gluconeogenesis (formation of glucose from a non-carbohydrate source)
31
Why can insulin stimulate protein formation from amino acids?
Insulin is an Anabolic Agent
32
In regards to diabetes, what is happening in regards to insulin?
In diabetes there is either lack of, or impairment of insulin action, and glucose is not able to be taken up by the muscle cells
33
The liver is the site of....
Glycogen production, storage and break down
34
After a meal, what hormone has an effect on the liver? Function?
When you eat --> insulin is released it and stimulates the liver to store glucose in the form of glycogen (glycogenesis)
Insulin also suppresses gluconeogenesis (glucose from a non-carb source)
35
When one is not eating, what hormone has an effect on the liver? Function?
When you are not eating --> glucagon is released and the liver provides glucose by:
a) Glycogenolysis (liver glycogen is split back into glucose)
b) Gluconeogensis (formation of glucose from non-CHO sources (i.e. AA’s)
36
What happens if the amount of glucose is greater than the glycogen storage capacity of the liver?
If the amount of glucose entering the liver is greater than the storage capacity for glycogen, insulin promotes its conversion to fatty acids
37
How are excess CHO's stored? When does this occur?
When excess CHOs are consumed that cannot be stored as glycogen they are converted to FFA’s and stored as TG’s in adipose tissue
38
Insulin is a ______ storing hormone
FAT
39
How does insulin act as a fat storing hormone?
It stimulates the conversion of glucose to glycerol phosphate & free fatty acids (FFA’s) and is stored as TG’s in fat cells
40
In starvation or insulin deficiency, _____ occurs. Describe such process?
LIPOLYISIS
TG’s split back to glycerol and FAs --> Metabolism of FFA’s --> β-hydroxybutyrate, acetoacetic acid, and acetone (ketone bodies)
These ketone bodies can be used as an energy source
41
What organ uses glucose constantly? Percentages?
The Brain
Brain accounts for ~2% of body weight but uses ~20% of glucose
42
What is the main energy source for the brain? Why is this concerning/important?
Glucose is its main energy source (does not depend on presence of insulin for its use – no ‘key’ required)
The brain is very sensitive to reduced glucose levels - this can lead to states of confusion to unconsciousness (or worse)
43
What are some types of diabetes?
1) Pre-diabetes
- Impaired glucose tolerance (IGT)
- Impaired fasting glucose (IFG)
2) Type 1
3) Type 2
4) Gestational Diabetes (GDM)
5) Others: LADA (latent autoimmune diabetes in adults), MODY (maturity-onset diabetes in the young), Type 3c
44
Type-1 Diabetes Definition
- Characterized by an absolute lack of insulin secretion
45
Type-1 Diabetes Cause
- Primarily due to autoimmune (AI) beta-cell destruction
46
In Type-1 Diabetes, a clinician would typically see examples of ______. Examples?
- Typically see markers of immune destruction
--> Islet cell antibodies, insulin antibodies, and GAD (glutamic acid decarboxylase) antibodies
47
Type-1 Diabetes is commonly seen with....
Other auto-immune diseases --> Celiacs being a common one
48
Type-1 Diabetes initial presentation.....
- Usually presents as acute metabolic symptoms of relatively short duration in a child, adolescent, or young adult
49
Can type-1 diabetes occur in older generations?
Yes
50
If a clinician can not tell if Type-1 or type-2, they can.....
Can do tests to see if immune destruction has occurred
51
In type-1 diabetes, hyperglycemia occurs when beta cells....
- 80-90% of beta-cells are destroyed
- Threshold to start feeling symptoms
52
What is the honeymoon phase of type-1 diabetes? What is important in regards to counselling pts?
Upon diagnosis of diabetes and initiation of insulin some patients go through a “honeymoon period”
Correction of hyperglycemia causes insulin secretion to recover temporarily & insulin requirements may be quite low
Occurs in the days to weeks following diagnosis and initiation of insulin – can last for months
This period is transient, hence:
Must continue to receive insulin
Monitor for hypoglycemia
53
Pre-diabetes is....
An intermediate state between normal glucose levels and diabetes
- Not at threshold for type-2 diabetes
54
Pre-diabetes includes.....
Includes IFG (impaired fasting glucose) and IGT (impaired glucose tolerance)
55
Pre-diabetes is a strong predictor of what?
Type-2 Diabetes
Cardiovascular Disease
It’s estimated 30-60% will develop T2DM in the following 8-10 years
56
Can interventions in pre-diabetes prevent type-2 diabetes?
Many trials have shown diabetes can be prevented in those with prediabetes with lifestyle interventions or medications – many will revert to normoglycemia
57
What is a 2 H PG in a 75g OGTT (mmol/L) test?
Testing with a 2 Hour Plasma Glucose in a 75 gram oral glucose tolerance test
Includes collection of fasting plasma glucose after an 8-hour fast, followed by consumption of glucose drink, and blood collected at 1 hour and 2 hours post-drink for plasma glucose
58
Diagnosis of prediabetes (test values) includes:
a) Fasting Plasma Glucose (mmol/L) = 6.1-6.9 --> indicates impaired fasting glucose of prediabetes category
b) 2h PG in a 75 g OGTT (mmol/L) = 7.8-11.0 --> Indicates impaired glucose tolerance of prediabetes category
c) A1C (%) = 6.0-6.4 --> indicates prediabetes
59
What is the relation between A1C and the 5 year incidence of diabetes?
A1C Category - 5-year Incidence of Diabetes
5.0-5.5 - <5 to 9%
5.5-6.0 - 9 to 25%
6.0-6.5 - 25 to 50%
60
Type-2 Diabetes accounts for _____ % of Diabetes Mellitus
90%
61
Type-2 Diabetes results from.....
Impaired insulin secretion
Insulin resistance
62
When does Type-2 Diabetes Manifest in a person?
- Only manifests in those who lose the ability to produce sufficient quantities of insulin to maintain normoglycemia in the face of insulin resistance
63
Type-2 Diabetes involves the interaction of....
Involves the interaction of genetic & environmental factors
Genetics: certain genes have been shown to determine risk for T2DM
Enviro: excessive caloric intake, sedentary lifestyle
Aging
64
What are some risk factors for T2DM?
Age ≥40 years
First-degree relative with type 2 diabetes
Member of high-risk population (e.g., African, Arab, Asian, Hispanic, Indigenous or South Asian descent, low socioeconomic status)
Overweight / obesity
History of prediabetes
History of GDM
History of delivery of a macrosomic infant (big baby, greater than 9 llbs)
Presence of end organ damage associated with diabetes:
Microvascular (retinopathy, neuropathy, nephropathy)
CV (coronary, cerebrovascular, peripheral)
Associated diseases
Vascular Risk Factors
Medications
65
Associated diseases that are a risk fcator for Type-2 Diabetes include....
Acanthosis nigricans (darkening, velevety thickening of skin)
PCOS (polycystic ovarian syndrome)
obstructive sleep apnea
HIV infection
psychiatric illnesses (schizophrenia, bipolar)
gout
non-alcoholic steatohepatitis
cystic fibrosis
history of pancreatitis
66
Vascular risk factors for T2DM include....
low HDL, high TG, hypertension, overweight/obesity, smoking)
67
What are some medications that may increase blood glucose? Which one is considered okay?
5-fluoruracil
Beta-blockers
Corticosteroids
Immunosupressive Agents
Second-generation anti-psychotic agents --> clozepine, olanzepine, quitipiene, risperidone
HMG-CoA reductase Inhibitors --> Statins --> (Benefit of these medications outweighs the risk)
68
What population is insulin resistance found in?
Obese people --> To some degree
69
_____ can be used as an indicator of T2DM; however ____ is better.
The degree of obesity (BMI) correlates with degree of insulin resistance.
Visceral adipose tissue (VAT):
- Fat cells within the abdominal cavity
- Especially resistant to insulin action
- A stronger predictor of T2DM than BMI
70
In regards to waist circumference, what value leads to a 90% chance of resistance?
Male >102cm
Female >88cm
= 90% chance of resistance
71
What is the relation of T2DM and beta cells?
T2DM patients have a significantly decrease β-cell mass, as well as a β-cell secretory defect….this continues to deteriorate with time
72
In Type-2 diabetes, there is _______ in response to food because......
- Impaired Insulin secretion in response to food
- Impaired β-cell function
- A reduced stimulus from incretin hormones (go and tell pancreas to pump out insulin to bring sugars down)
73
What is the main effect of defective insulin secretion? How does this manifest?
Hyperglycemia!
- First see a reduced early phase of insulin secretion --> elevated PPG (post-prandial glucose)
- Then, late phase secretion diminishes --> elevated FPG
74
How is insulin released?
Insulin is released in phases
75
In type-2 diabetes, where does insulin resistance occur?
There is decreased sensitivity to the actions of insulin by the target tissues (muscle, liver, adipocytes)
76
What is the primary site of insulin resistance? Why? What is the response?
SKELETAL MUSCLE
Primary site of glucose disposal after a meal, and hence the primary site of insulin resistance
Muscle is resistant to insulin actions hence there is decreased glucose uptake by it
77
Insulin resistance at the liver has what effect?
Resistance to insulin action on the liver results in the inability to suppress hepatic glucose production
78
Insulin resistance at the adipose tissue manifestation?
Adipocytes become resistant to antilypolytic effects of insulin which leads to ↑ lipolysis
Leads to elevated FFA’s in the circulation which can stimulate liver glucose production, impair skeletal muscle sensitivity & impair insulin release
79
Insulin resistance net effect
Greater serum glucose concentration
80
What is the ominous octet?
Multiple pathophysiologic abnormalities associated with type-2 diabetes
Hyperglycemia is a result of:
1) Pancreas
- Decreased insulin secretion by beta cells
- Increased glucagon secretion by alpha cells
2) Gut
- Decreased incretin effect
3) Adipocytes
- Increased lipolysis
4) Kidneys
- Increased glucose reabsorption
5) Muscle
- Decreased glucose uptake
6) Inflammation
7) Brain
- Neurotransmitter dysfunction
8) Liver
- Increased hepatic glucose production
People Get Annoyed Knowing Men Imitate Being in Love
81
Why is early detection important for Type-2 diabetes?
- T2DM is progressive
- Macrovascular and microvascular complications are occurring before an actual diagnosis
- Earlier detection and intervention may help to prevent complications earlier
82
What is the clinical presentation of type-1 diabetes?
Usually presents as acute symptoms of SHORT duration:
Polyuria
Polyphagia
Polydipsia
Weight loss (some due to cells starving, pee out a lot of sugar)
Fatigue
Blurred vision
Infections
20-40% present with DKA (diabetic ketoacidosis) after several days of the above symptoms --> Very sick --> Nauseau, vomiting, etc
83
What is the clinical presentation of type-2 diabetes?
Is commonly discovered incidentally, as patients may be asymptomatic
May have nonspecific symptoms (i.e. fatigue) or:
polyuria
polydipsia
nocturia
May already have established diabetic complications at diagnosis (damage to micro and macrovascular system)
84
Comparison of Type-1 and Type 2?
a) Age of Onset
b) Weight
c) Islet Auto-antibodies
d) C-peptide
e) Onset/Symptoms
f) First Line Tx
g) Microvascular Complications
h) DKA
a) Age of Onset
1 - Most <25 but can occur at any age (but not before the age of 6 months)
2 - Usually >24 but incidence increasing in adolescents due to increasing rate of obesity in children and adolescents
b) Weight
1- Usually thin, but with obesity epidemic, can have overwieght or obesity
2- >90% at least overweight
c) Islet Auto-antibodies
1- Usually present (approx. 90%)
2 - Absent
d) C-peptide
1- undetectable/low
2- Normal/high
e) Onset/Symptoms
1- Abrupt/symptomatic
2- Gradual/asymptomatic
f) First Line Tx
1- Insulin
2- Non-insulin antihyperglycemic agents, gradual dependence on insulin may occur
g) Microvascular Complications
1- Absent at diagnosis
2- Present at diagnosis
h) DKA
1- Common
2- Rare
85
C peptide is a measurement of.....
- A measurement to determine whether one is still producing insulin or not
86
genetic pre-disposition is higher in....
Type 2
87
What is gestational diabetes?
A condition that develops during pregnancy primarily due to insulin resistance
88
Gestational diabetes effects in fetus?
GDM increases the risk of fetal hyperinsulinemia, heavier birth weight (future predicter of type-2), higher rates of cesarian deliveries, and neonatal hypoglycemia
89
Gestational Diabetes is associated with what risk?
↑ risk of developing T2DM in both mother and child
90
Screening for GDM should be conducted when....
Weeks 24-28 of pregnancy
91
Risk Factors for GDM
Previous GDM
Member of high-risk population
Previous delivery of macrosomic infant
Age ≥ 35yo
Obesity
PCOS
Acanthosis nigricans
Corticosteroid use
92
Recommendations for screening of GDM. What type of screening is done?
All women should be screened for GDM between weeks 24-28 weeks of pregnancy; earlier if risk factors are present
Screening may be a 1-step or sequential 2-step process (FPG, A1C, OGTT)
93
Can Type-1 diabetes be prevented?
No
94
Can type-2 diabetes be prevented? Who do we target?
If intervention occurs early, may be preventable
Primarily involves targeting high risk individuals (IGT or obesity to prevent progression)
95
Is screening required for type-1 diabetes?
Screening not recommended due to:
overall low prevalence
no identifiable intervention which will prevent it
96
Is screening required for type-2 diabetes? Which tests?
Important as a large amount of people are undiagnosed (up to 1/3 of all cases)
Use FPG or A1C as initial screening tests
97
Is there any difference in the tests used to screen for type 1 and 2?
No
The same tests are used to screen & diagnose
98
Describe the screening algorithm for type-2 diabetes
Look at Slide 56 in lecture deck
99
Diagnosis of Diabetes Values
FPG ≥7.0 mmol/L
Fasting = no caloric intake for at least 8 hours
or
A1C ≥6.5% (in adults)
Using a standardized, validated assay in the absence of factors that affect the accuracy of the A1C and not for suspected type 1 diabetes
or
2hPG in a 75 g OGTT ≥11.1 mmol/L
or
Random PG ≥11.1 mmol/L
Random = any time of the day, without regard to the interval since the last meal
100
What are the advantages and disadvantages of A1C?
Advantages:
- Convenient
- Better predictor of CVD
- No day-to-day variability
Disadvantages:
- Cost
- Not valid for all medical conditions (e.g. anemia, hemoglobinopathesis)
- Altered by ethinicty and aging
- Not to be used for children, GDM, suspected T1DM
