Diabetes

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What does Diabetes Mellitus mean?
Passing though/honey (because of freq urination and "sweet urine" containing sugar)
Total: ___ ________ children and adults in the United States have DM
25.8 million
Total: ______ % of population has DM
8.3%
Diagnosed population with DM in US
18.8 million
undiagnosed population with DM in US
7.0 million
amount of people in US with prediabetes
79 million
How many new cases of DM dx in people 20 and older in 2010
1.9 million
if current rates continue, ______ in ______ babies born in 2000 will eventually develop DM
one in three
DM is ______ leading cause of death in US
5th
Both _________ (heart disease and stroke) and ___________ (retinopathy, nephropathy, neuropathy) are typically seen in patients.
macrovascular, microvascular
Heart disease and stroke account for about ___% of deaths in people with Diabetes.
68 %
Adults with Diabetes have heart disease death rates about ____ to ____ times higher than adults without Diabetes.
2 to 4
The risk for stroke is _____ to ____ times higher among people with Diabetes
2 to 4
About __% of adults with Diabetes have blood pressure greater than or equal to 130/80 mm Hg, or use prescription medications for hypertension
73 %
Diabetes is the leading cause of kidney failure, accounting for __% of new cases in 2008
44%
In 2008, _____ people with diabetes began treatment for end-stage kidney disease in the United States.
48,374
In 2008, a total of ______ people with end-stage kidney disease due to diabetes were living on chronic dialysis or with a kidney transplant in the United States
202,290
Diabetes is the leading cause of ____ _______ of blindness among adults aged 20 to 74 years.
new cases
In 2005-2008, ____ ______ (28.5%) people with diabetes aged 40 years or older had diabetic retinopathy, and of these, almost ________ (4.4% of those with diabetes) had advanced diabetic retinopathy that could lead to severe vision loss.
4.2 million, 0.7 million
About ____ to ____ %of people with Diabetes have mild to severe forms of nervous system damage.
60 to 70 %
What do results of nervous system damage in DM include?
impaired sensation or pain in the feet or hands, slowed digestion of food in the stomach, carpal tunnel syndrome, and other nerve problems.
Almost ___% of people with Diabetes aged 40 years or older have impaired sensation in the feet (i.e., at least one area that lacks feeling).
30 %
Severe forms of diabetic nerve disease are a major contributing cause of________-_____ ________
lower-extremity amputations.
More than ____% of nontraumatic lower-limb amputations occur among people with
Diabetes.
60 %
In 2006, about ______ nontraumatic lower-limb amputations were performed in people with Diabetes.
65,700
DM is a heterogeneous group of syndromes characterized by an ______ in fasting blood glucose caused by a _______ or ________ deficiency of insulin.
elevation, relative or absolute
Type 1 DM is characterized by
Insulin deficiency due to autoimmunity (formerly called insulin dependent).
Type 2 DM is characterized by
Insulin resistance progressing to pancreatic B cell failure and insulin deficiency
(formerly called insulin independent).
Gestational DM is characterized by
A temporary form of hyperglycemia that develops between the 24th and 28th week of pregnancy.
DM can come from genetic defects T or F
T
What are the drugs that can cause drug induced DM?
Steroids, Dilantin, Thiazides, a-Interferon.
what incidents can cause acquired DM?
trauma, infection, pancreatitis, pancreatic cancer, cystic fibrosis, hemochromatosis.
What endocrinopathies can cause DM?
acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma, somatostatinoma, and aldosteronoma.
Type 1 Diabetes accounts for ___to ___% of patients with Diabetes.
5-10%
Type 1 DM is caused by cellular-mediated autoimmune destruction of the ___-______ ______ _____ ________ (islets of Langerhans) and results in an absolute deficiency of insulin.
B- cells of the pancreas
Over a period of years, there is a gradual loss of the B-cells however symptoms appear abruptly when _____ to _____% of the cells have been destroyed.
80-90%
________ are detected in 85-90% of individuals when hyperglycemia is initially detected.
Autoantibodies
A small proportion of people with type 1 Diabetes carry a mutated gene that causes _______ ________ _______ ___ ___ ________
maturity onset Diabetes of the young (MODY)
Type 1 DM onset is typically during _________ or _______ and symptoms develop rapidly.
childhood or puberty
Patients are usually recognized by the sudden appearance of __________, _________, and _________ often triggered by stress or illness.
polyuria (frequent urination), polydipsia (excessive thirst), polyphagia (excessive hunger)
What other symptoms are diagnostic of DM type 1?
fatigue, weight loss, and weakness
How can DM type 1 Dx be confirmed?
by a fasting blood glucose greater than 126mg/dl.
Metabolic changes in DM type 1 rseult from lack of _____ and relative excess of ________
insulin, glucagon
Where are the abnormalities in metabolism most profound for DM type 1?
liver, muscle, and adipose tissue.
What are the hallmarks of untreated DM type 1?
Elevated levels of blood glucose and ketones
In DM type 1, ________ results from increased hepatic production of glucose and the inability of muscle and adipose tissue to take it up.
Hyperglycemia
In DM type 1, _____ results from increased mobilization of fatty acids from adipose tissue combined with an increased hepatic rate of hydroxybutarate and acetoacetate synthesis (ketone bodies)
Ketosis
How is ketoacidosis treated?
by fluid replacement therapy followed by administration of low dose insulin.
Since not all FAs flooding liver can be disposed of through oxidation or ketone body syn, FAs are converted to TAGs and packaged into _____ which are exported to blood from liver
VLDLs
Along with a VLDL increase in blood, there is also an increase in __________
chylomicrons (dietary lipids)
Why do both VLDLs and Chylomicrons accumulate?
lipoprotein degradation is decreased
as lipoprotein lipase (synthesis is sensitive to insulin) levels in adipose tissue drop
T or F, Hypertriacylglycerolemia is present in DM type 1
true
Ketoacidotic coma is more common in people with ______ ___ diabetes.
Type 1
Ketoacidotic coma is triggered by...
the accumulation of ketone bodies (ketones)
What are the common causes of ketoacidosis?
a missed dose of insulin or an acute infection.
Symptoms of ketoacidotic coma
extreme thirst, lethargy, frequent urination, nausea, vomiting, abdominal pain, progressive drowsiness, deep rapid breathing, a fruity or acetone smell on the breath
Tx of ketoacidotic coma
Intravenous fluids, insulin, and administration of potassium and sodium.
Patients with type 1 Diabetes require _________ _________ which is administered via a
subcutaneous injection.
exogenous insulin
Goal of standard therapy for type 1 DM
the clinical well being of the individual and consists of one or two daily injections of insulin.
In standard therapy for type 1 DM, Mean blood glucose levels obtained are typically ___________mg/dL with an HbA1C of _____% of total hemoglobin
225-275 mg/dL, 8-9 %
HbA1C is a glycosylated (with glucose) form of hemoglobin and the rate of its formation is proportional to ...
the average blood glucose concentration for the several prior months.
The HbA1C measurement gives an indication of...
how effective treatment has been over a period of time (2-3 months)
Goal of intensive therapy for type 1 DM
to normalize blood glucose levels and
requires more frequent monitoring and injections.
with intensive therapy for type 1 DM, A mean blood glucose levels of ______ mg/dL and HbA1C of ___% can be achieved.
150 mg/dl, 7 %
what is the risk of intensive therapy for type 1 DM pts?
hypoglycemia
Patients that receive intensive therapy have shown a ___% reduction in the long term complications of Diabetes such as; retinopathy, nephropathy and neuropathy.
60%
However, patients with type 1 Diabetes also develop a deficiency of ________ secretion.
glucagon
Type 1 DM pts must rely on ________ to counteract hypoglycemia, and as the disease progresses, they develop autonomic neuropathy which impairs the ability to secrete epinephrine.
epinephrine
Cause of hypoglycemic coma: Too much ______ (type I) or ______ ______ (type II).
insulin, diabetes medication
Exercises strenuously without eating extra food or reducing their insulin intake could cause a ___________ coma
hypoglycemic
Too much alcohol consumption or drinks alcohol without eating food could cause a ___________ coma
hypoglycemic
cause of hypoglycemic coma: Inadequate food intake and insulin injection during ...
pregnancy for diabetic women
symptoms of hypoglycemic coma:
Trembling, Palpitations, Weakness, Sweating, Intense hunger, Confusion, Altered behavior, Drowsiness
Tx for hypoglycemic coma
Administration of the hormone glucagon to reverse the effects of insulin, or glucose given intravenously.
______ _____ Diabetes is the most common form of Diabetes afflicting 90 % of the diabetic population in the United States.
Type 2
Type 2 DM occurs primarily in the ______ and is very common in adults, becoming more common in children.
obese
Type 2 DM has a _____ onset without obvious symptoms and is generally detected through routine check-ups, however, some may exhibit, polyuria and polydipsia of several weeks duration
gradual
T or F, There is a strong genetic predisposition component to DM type 2 development
True
Patients with type 2 Diabetes have a combination of _______ ______ and __-_______ ________.
insulin resistance, B-cell dysfunction
The decline in B-cell function begins an estimated ____ ______ before type 2 Diabetes is diagnosed
and B-cell function is typically about ___% of the normal level at the time of diagnosis
10 years, 30%
Do type 2 diabetics require insulin to sustain life?
No, but might require it to control hyperglycemia
In type 2 DM The metabolic alterations are _____ severe in part because insulin secretion, although not adequate, does restrain ketogenesis and blunts the development of diabetic ketoacidosis
less
Insulin resistance is the _______ ______ of target tissues to respond
to normal circulating levels of insulin.
decreased ability
Is obesity correlative with insulin resistance?
Yes
Most people with obesity and insulin resistance do/do not become diabetic as they do not have a B cell defect.
DO NOT
people with insulin resistance compensate for the resistance by producing _____ insulin
more (on average 3 fold higher).
Type 2 Diabetes, does/does not develop in individuals who have insulin resistance which is accompanied by impairment of B cell function.
DOES
Insulin resistance and type 2 DM is most commonly observed in ...
the elderly, the obese, the physically inactive, or temporarily in women who are pregnant.
There is a strong correlation of Diabetes type 2 incidence and _____ BMIs
higher
There is an inverse relationship between type 2 DM and _________
exercise
In type 2 DM Hyperglycemia results from the _________ hepatic production of glucose and the ________ ability of muscle and adipose tissue to take it up
increased, decreased
in type 2 DM, Ketosis is usually ________ or ________ due to the presence of insulin
minimal or absent
T or F, in type 2 DM As in type 1 Diabetes, both VLDLS and chylomicrons accumulate
True
The current pandemic of type 2 Diabetes is closely associated with ...
obesity and insulin resistance
What age is a risk factor for DM type 2?
45 or older
what BMI is a risk factor for DM type 2?
25 kg/m2 or higher (obesity)
having a ________ degree relative with DM is a risk factor for DM type 2
first
Habitual ________ ________ is a risk factor for DM type 2
physical inactivity
What are the high risk ethnic groups for DM type 2?
African-American, Latino, Native American, Asian- American, Pacific Islander
History of ______ _______ or delivery of a baby weighing > 9 lbs is a risk factor for DM type 2
gestational Diabetes
what blood pressure is a risk factor for DM type 2?
140/90 mm Hg or above (hypertensive)
What HDL level is a risk factor for type 2 DM?
35 mg/dL or below (low HDL)
What triglyceride level is risk factor for DM type 2?
250 mg/dl or higher (high triglycerides)
What ovarian disease is a risk factor for DM type 2?
polycystic ovarian disease
History of _______ disease is a risk factor for DM type 2
vascular
The risk of type 2 Diabetes greatly ________ with increasing waist circumference.
increases
Risk of retinopathy, nephropathy and neuropath ________ with increasing HbA1C levels
increase
As HbA1C goes up, risk of _____ from cardiovascular disease and ischemic heart disease goes up. The same trend is seen with macrovascular complications
death
The goal in treating type 2 diabetes is to _______ _______ ________ ________ within normal limits and to prevent the development of long term complications.
maintain blood glucose concentrations
Weight reduction, exercise and dietary modifications are usually sufficient to correct the __________.
hyperglycemia
If weight reduction, exercise and diet are not enough, _______ _______ or _______ may be required to achieve satisfactory plasma glucose levels.
other agents or insulin
1 % reduction in mean HbA1C is accompanied by a ___% reduction in risk of death related to Diabetes.
21 % (3)
1 % reduction in mean HbA1C is accompanied by a ____% reduction in risk of any Diabetes related endpoint.
14% (4)
1 % reduction in mean HbA1C is accompanied by a ___ % reduction in risk of microvascular complications.
37 % (2)
1 % reduction in mean HbA1C is accompanied by a ___% reduction in fatal and non myocardial infarction.
14 % (4)
1 % reduction in mean HbA1C is accompanied by a ___%reduction in risk of amputation or death from peripheral vascular disease.
43 % (1st mst significant)
Hyperosmolar coma Is a complication of type 2 diabetes caused by severe _______ and very ____ blood glucose levels (hyperglycaemia) without the presence of ketones.
dehydration, high
In hyperosmolar coma, The blood is concentrated with sodium, glucose, and other molecules that...
normally attract water into the bloodstream.
Causes that may lead to hyperosmolar coma are improperly managed their _____ and ____. Or an infection or illness.
medications and diet
symptoms of hyperosmolar coma
lethargy, extreme thirst, nausea, confusion, convulsions, speech impairment, loss of feeling or function of muscles, dysfunctional movement
Tx of hyperosmolar coma
plenty of intravenous fluids, insulin, potassium and sodium given as soon as possible.
High glucose ultimately results in an ______ flux through the electron transport chain.
increased
Increased flux through ETC causes a significant increase in the voltage gradient which in turn causes...
a blockage of electrons transfer at complex 3
Blockage of electrons at complex III then results in a back-up at ____ and transfer to O2 yielding _______
CoQ, superoxide
Through a series of events, including DNA damage by the ROS, _______ activity is reduced.
glyceraldehyde 3 phosphate dehydrogenase (GAPDH)
This now causes a backup of the glycolytic pathway and increased flow through the ...
polyol, hexosamine, PKC, AGE pathways
the cells of the retina, kidney and nervous tissues are _______ _________, so glucose moves freely across the cell membrane.
insulin independent
insulin independent cells do not have the ______ ________ enzyme that can oxidize sorbitol to produce fructose and therefore an accumulation of sorbitol occurs
sorbitol dehydrogenase
what is the result of the insulin independent cells not having sorbitol dehydrogenase?
This will cause water to move into the cells and causes them to swell.
activation of the polyol pathway results in a decrease of _____ _______ therefore causing a decrease in the ability to handle ROS.
reduced NADPH
Excess glucose shunted into the hexosamine pathway generates _____________ which when bound to the transcription factor Sp 1 stimulates the synthesis of TGF B which stimulates _____ ________
N-acetyl-glucosamine, cell proliferation
Hyperglycemia leads to increased _____ and this increases PKC
DAG
PKC increase can cause...
blood flow abnormalities, vascular permeability, angiogenesis, capillary occlusion, decreased fibrinolysis, vascular occlsion, pro-inflammatory gene expression, increase in ROS
________ _________ ________ ______ are the result of a chain of chemical reactions after an initial glycation reaction
Advanced Glycation End products (AGEs)
What are the names of the intermediate AGE products?
Amadori, Schiff base and Maillard products
T or F, AGEs may be less, or more, reactive than the initial sugars they were formed from.
True
Many cells in the body from tissue such as lung, liver, kidney or peripheral blood bear the _______ ___ ________ _________ ________ ______ that, when binding AGEs induces the formation of more reactive oxygen species.
Receptor for Advanced Glycation End products (RAGE)
AGEs cause _______ turnover and _______ of basement membranes and other events that cause vascular pathology.
less, thickening
Insulin exerts important functions in non-classical insulin target tissues such as ...
the brain, pancreas, and the vascular endothelium
Insulin acts as a vasodilator in the vascular endothelium by increasing _____ ______ production.
nitric oxide (NO)
The insulin-mediated signaling pathway that triggers production of NO in vascular endothelium involves the same signaling proteins (PI3K, PKD, and Akt/PKB) that are components of ....
metabolic regulatory pathways induced by insulin
In addition to modulating vascular tone by activating signaling events in the underlying vascular smooth muscle cells, endothelial cell-derived NO ...
reduces the production of pro- inflammatory cytokines, reduces leukocyte and monocyte recruitment and adhesion to the endothelium, inhibits the proliferation of vascular smooth muscle cells, inhibits apoptosis, and attenuates platelet aggregation
Inactivation of endothelial cell NO production, as occurs due to insulin resistance results in _________ __________ and promotes the development of _________ through the increased expression of cell adhesion molecules and the inflammatory response
endothelial dysfunction, atherosclerosis
Insulin acts as a _____ ______ and reduces hunger through binding receptors in the hypothalamus.
satiety signal
Metabolic syndrome is a combination of medical disorders that increase one's risk for ...
cardiovascular disease and Diabetes.
other names for metabolic syndrome
syndrome X, the insulin resistance syndrome, the deadly quartet
What is the deadly quartet?
diabetes, coronary heart disease, stroke, and peripheral vascular disease
Most patients with metabolic syndrome are...
older, obese, sedentary, and have a degree of insulin resistance
What is the most important factor in metabolic syndrome?
againg
what is the second most important factor in metabolic syndrome?
lifestyle (i.e., decreased physical activity and excess caloric intake)
what is the third most important factor in metabolic syndrome?
genetics
Diagnosis of metabolic syndrome established when 3/5 of the risk factors are present. They are...
Abdominal obesity: waist circumference, hypertension, hypertriglyceridemia, LOW HDL cholesterol, abnormal fasting glucose
Mature ______ synthesize and secrete numerous enzymes, growth factors, cytokines and hormones that are involved in overall energy homeostasis
adipocytes
There are currently over ____ _______ ________ recognized as being secreted from adipose tissue.
50 different adipokines