Diabetes and its Effect on Metabolism Flashcards
diabetes mellitus
a group of diseases is which the body does not properly control the amount of sugar (glucose) in the blood
type 1 diabetes
destroys beta cells of the pancreas
type 2 diabetes
causes insulin resistance at receptor and post receptor levels
which type is insulin dependent diabetes?
type 1
type 1 diabetes is usually caused by
an autoimmune destruction of insulin producing beta-cells in the pancreas
type 2 diabetes occurs when cells become
resistant to the effects of insulin and the pancreas cannot make enough insulin to overcome the resistance
type 2 diabetes is not
insulin dependent
risk factors of type 2 diabetes (2)
family history
age (can get type 1 at any age, but more likely to develop at younger ages)
type 1 diabetes is a disease which can strike children and adults suddenly and requires supplemental insulin along with
carefully regimented diet and exercise to manage properly
who is generally diagnosed with type 1 diabetes?
children, teenagers, young adults
what causes type 1 diabetes?
it is unknown, but it is believed that autoimmune, genetic, and environmental factors are involved
since the beta cells are the source of insulin, patients with type 1 diabetes must
receive daily insulin injections via a pump to stay alive
prediabetes and type 2 diabetes risk factors (6)
overweight
>45 years of age
immediate family member with type 2 diabetes
not physically active
has gestational diabetes (given birth to a baby over 9 lbs)
certain ethnic groups
how many Americans have diabetes? how many are type 1?
- 3 million
1. 25 million
the percentage of those >65 with diabetes is
25%
how many people over age 18 have prediabetes?
84.1 million
what is the estimated cost of diabetes in the US in 2017
327 billion
common symptoms of diabetes (8)
urinating often feeling very thirsty feeling very hungry extreme fatigue blurry vision cuts/bruises that are slow to heal weight loss even though you are eating more (type 1) tingling, pain, or numbness in the hands/feet (type 2)
fasting blood glucose levels
normal
prediabetes
diabetes
normal: <100 mg/dl
prediabetes: 100-125 mg/dl
diabetes: >126 mg/dl
oral glucose tolerance test
normal
prediabetes
diabetes
normal: <140 mg/dl
prediabetes: 140/199 mg/dl
diabetes: >200 mg/dl
prolonged high blood glucose levels will lead to the production of
advanced glycation end-products (AGEs)
AGEs result from
a chain of chemical reactions following an initial non-enzymatic glycation reaction (chemical reaction of glucose with a body protein or lipid)
AGEs are believed to play a causative role in
vascular complications airing with long term diabetes as well as a factor in normal aging and worsening of many degenerative diseases
the higher the blood glucose concentration and the longer the hyperglycemia, the
higher AGEs
HbA1c
glycated form of hemoglobin
HbA1c corresponding to
3 month average plasma glucose level
HbA1c is used to measure
the average blood glucose concentration over a longer period of time compared to a fasting glucose or glucose tolerance test
glycation is — and is only removed upon degradation or turnover
non-reversible
HbA1c test
glaciated or glycosylated hemoglobin set
a common test used to further diagnose diabetes and/or how well it is being managed
HbA1c
normal
prediabetes
diabetes
normal: <5.7
prediabetes: 5.7-6.4
diabetes: >6.5
cells sense insulin through
insulin receptors
insulin binding to its receptor results in the activation of the
PI3K/Akt/mTOR signaling pathway
signaling through this pathway may be blunted by high circulating levels of
free fatty acids
consequences of diabetes on organ systems (8)
cardiovascular disease neuropathy (nerve damage) nephropathy (kidney damage) retinopathy poor wound healing (especially lesions on feet) skin conditions hearing impairment Alzheimers disease
which autoinflammatory responses are increased in diabetes? (2)
TNF-alpha
IL-1
why might glycemic control may be important in this response>
since the crevicular fluid IL-1 were almost 2 fold higher in patients with HbA1c levels greater than 8% compared with patients whose HbA1c levels were less than 8%
another factor in enhanced inflammation is the accumulation of AGEs which
bind to receptors on inflammatory cells and further increase production of proinflammatory cytokines like IL-1 and TNF-alpha
how can periodontal disease affect diabetes?
systemic bacterial and viral infections such as the common cold or influenza result in increased systemic inflammation which increases insulin resistance. in the same way, chronic periodontal infections can exacerbate insulin resistance and worsen glycemic control
hormone sensitive lipase triggers the
release of FFA from stored triglycerides
diabetic retinopathy
poor vascular tone leads to micro hemorrhage, obscure the retina, leads to blindness
what type of receptor is the insulin receptor?
tyrosine kinase receptor
when insulin binds to the insulin receptor, the tyrosine kinase autophosphorylates, leading to downstream signaling
glucose monomers are strung together into long polymers linked by
a-1,4 linear bonds
a-1,6 branching bonds
ways in which people are born with genetic risk for type 2 diabetes (2)
- a genetic inability of the tissues to respond to insulin (or insulin resistance)
- a genetic instability of the insulin producing cells to secrete enough insulin to overcome the insulin resistance
can you genetically test for type 2 diabetes?
no, there is no single genetic test to identify type 2 diabetes or individuals at risk for type 2 diabetes
type 1 rapid acting insulin (2)
humalog
novorapid
type 1 short acting insulin (2)
humalin R
novolin R
type 1 long acting insulin (3)
Lantus
Levemir
tresiba
insulin formulations come from (3)
animals
human (bioengineered)
analogs (sub group of human insulins)
how to control type 2 diabetes (4)
diet
exercise
maintaining healthy weight
medications
IRS1
insulin receptor substrate-1, substrate of the insulin receptor tyrosine kinase and a participant in insulin signaling
IRS 2
insulin receptor substrate-2, substrate of the insulin receptor tyrosine kinase and a participant in insulin signaling
PPARG
peroxisome proliferator activated receptor gamma. Act by controlling networks of target genes. Act as lipid sensors (fatty acids ) and regulate energy metabolism and adipocyte differentiation.
PAX4
expressed in beta cells of pancreas and functions to increase survival
AKT2
an isoform of phosphoinositide dependent protein kinase AKT which is implicated in insulin dependent signaling
GCK
glucose kinase. The phosphorylation of glucose at the sixth carbon position is the first step in glycolysis. Glucokinase is expressed only in mammalian liver and pancreatic islet beta cells. Because of its unique functional characteristics, the enzyme plays an important regulatory role in glucose metabolism, e.g., the rate of glucose metabolism in liver and pancreas is a function of the activity of the enzyme.
GCGR
glucagon receptor that mediates signaling by coupling via GTP-binding proteins to adenylate cyclase. Mutation in GCGR leads to reduced glucagon affinity and late-onset non-insulin dependent diabetes mellitus.
RETN
resistin. Linked to obesity and down-regulated in adipocytes treated with thiazolidinediones, antidiabetic drugs that interact with PPARgamma receptor.
GLUT4 (SLC2A4)
Mutation in Glut4 glucose transporter: Non-insulin dependent diabetes
insulin hormone lowers blood glucose by stimulating
cellular uptake and glycogen synthesis. (ex: Humalin R)
metformin works on the liver to
reduce release of glucose in type 2 diabetes
acarbose
by inhibition of intestinal alpha glucosides, it delays carbohydrate digestion prolongs overall carbohydrate digestion, reducing the rate of glucose absorption
sulphonylureas increase
insulin release by pancreas
GLP1 receptor agonists
incretin receptor agonists
-bind to incretin receptor to stimulate insulin release
DPP4 inhibitors
increase incretin levels
thiazolidinediones
reduces fatty acid oxidation and thereby increases use of glucose as a fuel
SGLT2 inhibitors
sodium glucose contrasporter inhibitor, blocks reabsorption of glucose to the kidney
