Transcript Diabetes Mellitus Type II – An Overview

Diabetes Mellitus Types I & II
James Bresnahan, MS1
Robert Gyory, MS1
Introduction
• How does your body make use of glucose from
the food you eat?
• What is the difference in etiology between type 1
and type 2 diabetes? How does this affect
treatment?
• What is the homeostatic balance between insulin,
glucose, glucagon, and stress hormones? How
does this differ between nonaffected individuals
vs. type 1 diabetics vs. type 2 diabetcs?
• Why does high blood glucose cause other
complications?
• What are some psychosocial considerations
regarding diabetes?
Glycogen is a good
form of storage. It’s
condensed, easily
broken down, and its
byproducts are used
efficiently to make
energy.
I thought T1DM is
about insulin?
α-1,6linkage
α-1,4linkage
Without insulin…
How do you get Type 1
“Diabeetus?”
-No!!
-T1DM is AUTOIMMUNE.
-Destruction of
Pancreatic B-islet cells.
-What about T2DM? Ask
Rob..
What are B-Islet cells?
How are they destroyed?
• Genetic predisposition
• Environmental stimuli
– Lead to antibodies that attack
pancreatic Beta cells
-Diagnosis is bimodal with peaks at 4-6 years
and 10-14 years
-3M:2F??
-23.6 per 100,000 per year.
What are the general effect
Clinical Presentation
How do you treat T1DM?
 Future?
How do Endocrinologists monitor their
diabetic patients over long periods of time?
So, high glucose
is bad, what
about low
glucose?
-Low blood glucose is FAR
more detrimental in terms
of short term problems.
-Diabetic coma due to
Neuroglycopenia
- Glucagon is released by acells in RESPONSE to b-cells
not making insulin (a sign
of high BG.) If B-cells are
destroyed, a-cells can’t
release glucagon.
Future ways to monitor T1DM?
http://www.youtube.com/watch?v=w0aalblWfj
U
Take into consideration different ethical issues
ranging from cost of supplies/equipment to
the mental demands of current T1DM
patients.
Diabetes Mellitus Type II
But first, a biochemical interlude:
Downregulation vs. Upregulation
Adapted from the common domain of Cornell University
The mechanism of DM II is a complex
sequence of biochemical processes
1) Diet high in fat and carbohydrates + sedentary
lifestyle  highly elevated plasma [glucose]
2) Chronically ↑ plasma [glucose]  chronic
overstimulation of β cells and chronic
hypersecretion of insulin
3) Chronic hypersecretion of insulin  down
regulation of insulin receptors on adipocytes and
skeletal muscles
Down regulation of insulin receptors exhibits a
number of negative consequences
• ↓ glucose uptake by
cells
– ↓ glucose for cells to use
for energy
– ↑↑ plasma [glucose]
• Can cause relatively
minor symptoms or
serious DM I type
symptoms
Adapted from the University of Arizona
Dept. of Biological Sciences
What are the consequences of
decreased glucose for cellular energy?
• Cells begin to burn fats
for energy.
– Can cause pH problems
(DKA)
– Inefficient fuel source
leads to fatigue, low
energy, etc.
*Important: Glucose uptake is
severely decreased, but not
nonexistent as in DM I
What are the consequences of elevated
plasma [glucose]?
• DM Type I Symptoms
– e.g. polyuria, polydypsia,
glycosuria, etc.
• Hypertrophy of β cells
– Extremely chronic
hyperstimulation can
lead to β cell destruction
– Leads to insulin
dependence
Beta cells stained in green
What are the symptoms of Type II
diabetes mellitus?
• Some patients may be asymptomatic for many years
• Others experience lighter versions of many of the
symptoms of diabetes mellitus I
• Rarely, DKA and other complications can occur such
as hyperosmotic coma
• Why do these symptoms differ from DM I when their
mechanisms of pathogenesis are so similar?
How is DM II diagnosed?
• Chronically high fasting
plasma [glucose]
• Elevated glycated
hemoglobin pattern
(HbA1C)
• In difficult cases, insulin
immunoassay
Treatments for DM II are widely
variable
• For most people, diets lower in fats and
carbohydrates coupled with exercise will correct the
down-regulation of insulin receptors
• Others need medications such as biguanides and
sulfonylureas (e.g. metformin) to decrease
endogenous glucose production
• Severe cases in which beta cells have been destroyed
will need to supplement with insulin
– ‘insulin dependent’ diabetes
Biguanides versus sulfonylureas
• Biguanides
–
–
–
–
Metformin
Phenoformin
Buformin
Proguanil
• Sulfonylureas
–
–
–
–
–
Carbutamide
Tolbutamide
Chlorpropamide
Acetohexamide
And others….
The prognosis and sequelae of DM II
are very similar to DM I
Sequelae
• In well controlled diabetics,
there are very few resulting
problems
• With poor control, however:
– Poor circulation  vascular
disease and cardiovascular
problems
– Neuropathy
– Other metabolic dysfunctions
Prognosis
• If a person controls their
condition well, they can
either live an asymptomatic
life or go into remission
altogether
• With poor control, however:
– Myocardial infarction, stroke,
blindness, amputation,
degenerative brain disorders,
renal failure, death
Diabetes mellitus II is one of the most
preventable disease in our society
• Obesity is the number
one predictor of DM II
– Healthy diet and plenty
of exercise are needed
– Patient education!!!
• Prior patient knowledge
about the various
genetic and medical
factors that can increase
DMII predisposition
Systemic Insulin Regulation
How do hormones and other factors
regulate insulin?
The following hormone pathways work
to help regulate the action of insulin
• Epinephrine and cortisol inhibit insulin and
increase secretion of glucagon in the pancreas
– HPA axis
• Growth hormone directly acts on the pancreas
to cause glucagon secretion
• Glucagon inhibits insulin secretion and causes
biochemical effects that are opposite those of
insulin
Other friends that you’ve met throughout
the year that effect insulin secretion
• ↓ insulin secretion
–
–
–
–
Thyroxine and T3
Norepinephrine
Low ATP
And others
• ↑ insulin secretion
–
–
–
–
High ATP
Somatostatin
Leptin
And others
Learning objectives for this lecture
1.
2.
3.
4.
5.
6.
7.
Review the biochemistry, pathology, and medical treatments of diabetes
mellitus 1 and 2
Provide a general overview of biochemical dysfunction, resulting
metabolic derangement, compare and contrast the risks and sequelae,
and discuss the treatments for both diseases and why treatments are
specific to only one disease and not the other
Discuss the utility of HbA1c measurement as a method of monitoring
treatment efficacy
Discuss patient, doctor, and psychosocial issues surrounding diabetes
mellitus
Discuss the prevalence of diabetes mellitus, long term risks to patients,
and cost of care issues
Discuss quality of life issues
Discuss the importance of primary prevention in diabetes mellitus 2