Flashcards in Ch 22: Obesity/Diabetes Deck (12):
Organize into anorexigenic and orexigenic categories: Neuropeptide Y (NPY), Proopiomelanocortin (POMC), Agouti-related protein (AgRP), Cocaine and amphetamine-regulated transcription (CART) Insulin, Amylin, Cholecystokinin (CCK), Ghrelin, Glucagon-like peptide, Leptin, Melanocortin, Thyroid Hormone, Endocannabinoids
Which are neuropeptides of the brain?
Where is Leptin produced?
Orexigenic: Endocannabinoids, Ghrelin, NPY, AgRP
Anorexigenic: Glucagon-like peptide, Leptin, Melanocortin, Thyroid Hormone, Insulin, Amylin, CCK, POMC, CART
Also: Circadian rhythm disruption can disturb appetite control
Neuropeptides: POMC, CART, NPY, AgRP
Leptin: adipocytes: more is produced in an obese state but it seems to have a decreased effect in the brain (leptin sensitivity).
Leptin injections don't work as anti-obesity cure all
Does the Apple or Pear shape raise the risk of metabolic complicaitons
Which Diabetes Type (I/II) appears to have the greatest genetic component
What do fat cells do in response to high food intake without expenditure?
BMI= (weight (kg))/(height (m))^2
Type II (kinda blew my mind)
Adipocytes undergo hyperplasia and hypertrophy-->results in greater delivery of fat to the liver and this has been implicated in insulin resistance (Ectopic fat storage hypothesis)
What is the major cause of type II diabetes?
What is the major killer in type II diabetes?
What is the best measure of long term glycemic control?
Atherosclerotic cardiovascular disease-->due to dyslipidemia, dyslipoproteinemia, and non-enzymatic glycosylation.
Hemoglobin glycosylation products: A1C
Name some organ systems damaged by obesity:
Cardiovascular: hypertension, CAD, CHF, thromboembolic disease
Neurologic: ischemic strokes to CNS and peripheral nerve damage due to microvasculature disease
Pulmonary: obstructive sleep apnea, decreased ventilatory drive, increased wall tension (chest compression), inability to meet ventilatory demands in severe form=Pickwickian syndrome
Hepatobilary: Nonalcoholic fatty liver disease
Cancer: raises risk of many types
MSK: hyperuricemia/gout and osteoarthritis
Skin: acanthosis nigricans, hirsutism
Renal: diabetic glomerulosclerosis
Where is insulin secreted from? What is its main action?
T1 diabetes is due to:
T2 diabetes is due to:
What might a child who's mother has diabetes blood sugar be like following birth?
Beta-cells in the Islets of Langerhans in the Pancreas. Allows glucose uptake by most cells in the body, thus lowering blood sugar (nerves don't need insulin to do this)... Action on Na/K+ transporter, inhibits gluconeogenesis, enhances glycogen synthesis, antagonize glucagon secretion
T1 diabetes is due to: Cell-mediated autoimmune destruction of beta-cells (abrupt, usually before age 20)
T2 diabetes is due to: Peripheral insulin resistance in the presence of excess insulin secretion (later can progress to beta cell "burnout" and decreased insulin as well)
There is also gestational diabetes
Child will be hypoglycemic due to mom's high circulating insulin and probably rather large (c-section likely)
What is commonly present in beta cells later in the disease state of TII Diabetes? What is it made of?
Amyloid deposits of amylin are present in more patients older than 60. This can also be present in those without diabetes due to aging, though to a lesser extent
Classify the disease:
1. High insulin and C-peptide in an obese patient
2. High insulin and low C-peptide in an overweight patient
3. Low insulin and C-peptide in a patient rapidly losing weight
4. Episodic hypoglycemia with a high insulin and C-peptide.
1. TII Diabetes
2. Malingering Patient! They are shooting up insulin!
3. TI Diabetes (I would have added that it was a child, but what would have been the fun in that!)
What is the preferential source of energy in TI diabetes? What does this commonly lead to?
There is a high association with which HLA
What type of cells predominate in the islets of Langerhans due to this disease?
What virus may be involved?
What are the 3 common P signs?
Body fat is the primary source, leading to an overproduction of ketone bodies, causing metabolic ketoacidosis. Progressive acidosis and dehydration can lead to coma and death.
DR3 and 4 (many have other autoimmune problems like myasthenia gravis, Graves, Hashimotos, Addisons, or pernicious anemia)
Infiltrate of mononuclear cells termed insulitis that is mainly CD8+ with some CD4. Loss of beta cells leaves "ribbonlike cords"
Coxsackie B may be involved due to its close homology to GAD-65
Polyuria, polydipsia, polyphagia
Microvascular complications are highly dependent on? What are 3 big microvascular complications?
Describe how hyaline arteriolosclerosis occurs
Level of Hyperglycemia**
Retinopathy, nephropathy, neuropathy (chronic ulcers also common due to this and decreased wound healing)
Control of glucose level not as well related to preventing macrovascular atherosclerosis
Arteriolosclerosis: Nonenzymatic glycosylation leads to the formation of advanced glycosylation end-products (AGE). These changes allow the binding of albumin and IgG to collagen which contributes to cellular basement membrane thickening as well as direct glycosylation of the basement membrane. Also, the AGE that are normally excreted by the kidneys can contribute to renal failure
Glucose + NADPH --> Sorbitol + NADP
What is this? What accumulation does it lead to? What is the primary site this can cause a problem in?
Aldose Reductase Pathway. Sorbitol accumulation in the lens of the eye can lead to blindness. This sorbitol accumulation may also contribute to peripheral neuropathy/other nerve damage
What causes glomerulosclerosis due to diabetes?
Does diabetes affect both sensory and autonomic innervation? Describe the sequence of pain perception loss
Increased glomerular pressure (due to arteriolosclerosis) favors protein deposition in the mesangium and forms KIMMELSTIEL-WILSON NODULES-->proteinuria (microalbuminuria) and glucose in urine
Rx: ACE inhibitor
Diabetes affects both! At first there is an increased perception of pain independent of any structural lesions in the nerves, followed by abnormal sensations in the extremities then loss of sensation that causes diabetics to ignore irritation and minor trauma, leading to non-healing ulcers. Errectile dysfunction and retrograde ejaculation are common