Diabetes Mellitus Flashcards
Characterized by disordered metabolism with ____ (hyperglycemia)
due to a deficiency of insulin (relative or absolute) and/or insulin resistance in target cells
Characterized by disordered metabolism with inappropriately elevated glucose (hyperglycemia)
due to a deficiency of insulin (relative or absolute) and/or insulin resistance in target cells
5 main types
Type 1 Diabetes:
• Type 1 Diabetes: Autoimmune disease destroys β-cells.
5 main type
Type 2 Diabetes
Type 2 Diabetes: Heterogeneous disorder (large number of different genetic &
environmental contributors); Most commonly, a failure of target cells to adequately
respond to insulin (insulin resistance) causes high insulin secretion in early stages, but in
later stages, there is impaired insulin biosynthesis/secretion by β cells.
5 main type
Monogenic forms of diabetes
• Monogenic forms of diabetes (e.g., neonatal diabetes): Individuals can’t produce enough
insulin, usually due to single-gene mutation(s);
could be one of a number of different genes.
5 main type
• Gestational Diabetes
Gestational Diabetes: elevated glucose levels that develops or is first recognized during
pregnancy (usually during the second or third trimester)
these individuals may have an increased risk for T2D later in life
5 main type
secondary diabetes
Secondary Diabetes: secondary changes due to damage to the pancreas, or excess levels
of other hormones (e.g., GH, glucocorticoids, TH, glucagon, etc.), drugs, etc
Type 1 Diabetes
autoimmune diease…
• Autoimmune disease that destroys β cells
process can extend over months or years
Type 1 Diabetes
b and a cells
β cell destruction mediated by T cell lymphocytes infiltrating islets
• α-cells are spared
Type 1 Diabetes
Liver, skeletal muscle, white adipose tissue:
- Liver, skeletal muscle, white adipose tissue:
- Fail to take up absorbed nutrients from the bloodstream
- Also continue to mobilize/release their energy stores (glucose, amino acids, fatty acids)
Discovery of insulin
For many years scientists believed that some kind of internal secretion of the ___
was the key to preventing diabetes and controlling normal metabolism. No one could
find it, unJl in the summer of 1921 a team at the University of Toronto began trying a
new experimental approach suggested by Dr. Frederick Banting. By the spring of ___,
the Toronto researchers — Banting, Charles Best, J.B. Collip and their supervisor, J.J.R.
Macleod – were able to announce the discovery of insulin
For many years scienJsts believed that some kind of internal secreJon of the pancreas
was the key to prevenJng diabetes and controlling normal metabolism. No one could
find it, unJl in the summer of 1921 a team at the University of Toronto began trying a
new experimental approach suggested by Dr. Frederick BanJng. By the spring of 1922,
the Toronto researchers — BanJng, Charles Best, J.B. Collip and their supervisor, J.J.R.
Macleod – were able to announce the discovery of insulin
Type 1 Diabetes
-
• Genetics & environmental factors both play a role
- One group of risk factor genes = in major histocompatibility (MHC) locus (involved in
the funcJon and regulation of the immune response), particularly genes associated
with presenting peptide antigens to T lymphocytes through the T-cell receptor
• Worldwide incidence of T1D is steadily rising, and T1D has the highest incidence in
countries with the best public health systems (e.g., Scandinavian countries)
Type 2 Diabetes
• Associated with metabolic health problems such as obesity (the majority of people with T2D have excess adiposity)
- Earlier stages marked by insulin resistance – target cells show an impaired ability to respond to some aspects of insulin signaling (with glucose uptake)
• When β cells can no longer compensate for the increased
demand (e.g., could be due to an underlying β cell defect),
someone with insulin resistance will develop full diabetes
mul5ple stages mul5ple physiological
changes that may contribut
Insulin resistance
T2D:____
(the majority of people with T2D have excess ____)
• T2D: associated with metabolic health problems such as obesity
(the majority of people with T2D have excess adiposity)
Insulin resistance
• ___ adiposity (esp. in visceral/central fat depots) = ____ insulin resistance
• Increasing adiposity (esp. in visceral/central fat depots) = increasing insulin resistance
Insulin resistance
• Adipocyte cells: ____
Adipocyte cells: secretes signaling molecules (including hormones that signal to distant
tissues, such as leptin and adiponectin) that inhibit or enhance insulin signaling.
Insulin resistance
“Full”/enlarged adipocytes ______ and this ectopic fat might affect functioning of those tissues
• White adipose tissue also contains ______; active ____
release signaling molecules that further increase insulin resistance & release of fatty
acids by adipocytes
“Full”/enlarged adipocytes release fatty acids into circulation, where they may collect
in other cell types, and this ectopic fat might affect functioning of those tissues
• White adipose tissue also contains inflammatory/immune cells; active macrophages
release signaling molecules that further increase insulin resistance & release of fatty
acids by adipocytes
(potentially this proinflammatory/insulin resistance perpetuating response also
happens in other tissues)
Insulin resistance
Not all tisues necessarily ….
Not all tisues necessarily develop insulin resistance, and it may affect the pathways of
insulin signaling discordantly (i.e., impacting some biological effects but not others)
Type 2 Diabetes
Metabolic syndrome: a ___ of conditions
that ___ risk of developing heart disease,
stroke and/or type 2 diabetes. These conditions
include: ______ (6-7)
Metabolic syndrome: a cluster of conditions
that increase risk of developing heart disease,
stroke and/or type 2 diabetes. These conditions
include: insulin resistance, high blood insulin
levels, high blood glucose levels, obesity
(especially in the central abdominal area),
increased blood pressure, and abnormal
cholesterol or triglyceride levels.
Glucose tolerance test
Glucose tolerance test: glucose is given and blood samples taken afterward (usually key time point is 2 hrs. after) to determine how quickly the glucose is cleared from the blood
Type 2 Diabetes
• Most genes identified so far:
___
The prevalence of type 2 diabetes in ___ is dramatically increasing.
• Most genes identified so far:
involved in β cell function and turnover
The prevalence of type 2 diabetes in younger
people (<40 yrs) is dramaJcally increasing.
Diabetes (T1D or T2D) – complication
Acute complications:
• Most common are ___ reactions (e.g., in patients treating with insulin).
Stimulates ___ nervous system and can eventually lead to symptoms that
indicate that there is insufficient glucose for CNS
• Other acute complications result from metabolic/biochemical/physiological responses
to severe ____ , which ___ plasma osmolality (leading to increased
urination & depletion of intravascular volume, among other effects)
Acute complications:
• Most common are hypoglycemic reactions (e.g., in patients treating with insulin).
Stimulates autonomic nervous system and can eventually lead to symptoms that
indicate that there is insufficient glucose for CNS
• Other acute complications result from metabolic/biochemical/physiological responses
to severe hyperglycemia, which elevates plasma osmolality (leading to increased
urination & depletion of intravascular volume, among other effects)
Diabetes (T1D or T2D) – complication
• Chronic complications:
Most chronic complications involve ____ (can affect kidneys, retinas, nervous system, cardiovascular system)
Most chronic complications involve hyperglycemia’s impacts on the vascular system
(can affect kidneys, retinas, nervous system, cardiovascular system)
Insulin resistance – puberty
Puberty: period of insulin
resistance & increased insulin
secretion (normalizes after)
Insulin resistance – pregnancy
Entering 3rd trimester:….
This is mediated by many factors, including ____ (the major driver of this
shift,_____ ) & other hormones;
also increased adiposity, elevated levels of some cytokines, etc.
• Entering 3rd trimester: the mother’s insulin sensitivity may decline to ~50% of normal
(accompanied by elevated insulin levels: β cell mass doubles during pregnancy)
This is mediated by many factors, including progesterone (the major driver of this
shit, progesterone suppresses PI3K signaling) & other hormones;
also increased adiposity, elevated levels of some cytokines, etc.
