Diabetes Mellitus

Question 1

Characterized by disordered metabolism with ____ (hyperglycemia)
due to a deficiency of insulin (relative or absolute) and/or insulin resistance in target cells

Answer 1

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

Question 2

5 main types

Type 1 Diabetes:

Answer 2

• Type 1 Diabetes: Autoimmune disease destroys β-cells.

Question 3

5 main type

Type 2 Diabetes

Answer 3

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.

Question 4

5 main type

Monogenic forms of diabetes

Answer 4

• 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.

Question 5

5 main type

• Gestational Diabetes

Answer 5

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

Question 6

5 main type

secondary diabetes

Answer 6

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

Question 7

Type 1 Diabetes

autoimmune diease…

Answer 7

• Autoimmune disease that destroys β cells

process can extend over months or years

Question 8

Type 1 Diabetes

b and a cells

Answer 8

β cell destruction mediated by T cell lymphocytes infiltrating islets
• α-cells are spared

Question 9

Type 1 Diabetes

Liver, skeletal muscle, white adipose tissue:

Answer 9

• 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)

Question 10

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

Answer 10

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

Question 11

Type 1 Diabetes

-

Answer 11

• 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)

Question 12

Type 2 Diabetes

Answer 12

• 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

Question 13

Insulin resistance
T2D:____
(the majority of people with T2D have excess ____)

Answer 13

• T2D: associated with metabolic health problems such as obesity
(the majority of people with T2D have excess adiposity)

Question 14

Insulin resistance

• ___ adiposity (esp. in visceral/central fat depots) = ____ insulin resistance

Answer 14

• Increasing adiposity (esp. in visceral/central fat depots) = increasing insulin resistance

Question 15

Insulin resistance

• Adipocyte cells: ____

Answer 15

Adipocyte cells: secretes signaling molecules (including hormones that signal to distant
tissues, such as leptin and adiponectin) that inhibit or enhance insulin signaling.

Question 16

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

Answer 16

“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)

Question 17

Insulin resistance

Not all tisues necessarily ….

Answer 17

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)

Question 18

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)

Answer 18

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.

Question 19

Glucose tolerance test

Answer 19

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

Question 20

Type 2 Diabetes
• Most genes identified so far:
___
The prevalence of type 2 diabetes in ___ is dramatically increasing.

Answer 20

• 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.

Question 21

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)

Answer 21

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)

Question 22

Diabetes (T1D or T2D) – complication
• Chronic complications:
Most chronic complications involve ____ (can affect kidneys, retinas, nervous system, cardiovascular system)

Answer 22

Most chronic complications involve hyperglycemia’s impacts on the vascular system
(can affect kidneys, retinas, nervous system, cardiovascular system)

Question 23

Insulin resistance – puberty

Answer 23

Puberty: period of insulin
resistance & increased insulin
secretion (normalizes after)

Question 24

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.

Answer 24

• 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.