Intro to Metabolism Flashcards
Pathophys of DM
what part of the body converts glycogen to glucose?
the liver
insulin is important in regulating uptake of glucose into cells but what type of cells does it not regulate uptake well?
muscle
what does glucagon do?
stimulates glycogenolysis mainly
what are the 4 main target cells important for DM?
fat, muscle, liver, brain
where are the endocrine islet cells located in the pancreas compared to the acini of the exocrine cells?
islet cells float within the exocrine acini
what is the structure of proinsulin? how is this converted to insulin?
“A” peptide chain is connected to a “B” peptide chain by the “C” (or connecting) peptide chain; this is converted to insulin once the C peptide is removed
is the C peptide considered active or inactive?
inactive: it is stable *=(unlike A and B peptides that have a short half life); this is why it can be measured to estimate insulin synthesis
what is a major predisposing factor for type 2 diabetes?
obesity, strongly influenced by underlying family history
what is the fasting plasma glucose range for prediabetes? how is this measured?
between 100 and 126 mg/dl (measured with serum glucose)
what is impaired glucose tolerance? what type of diabetes is this seen in? what test measures this?
its a decreased ability to uptake glucose into cells following food intake (get increased plasma glucose levels); seen in prediabetes; glucose tolerance test measures this
what is the glucose tolerance test?
medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood
what is prediabetes a predecessor for?
type 2 DM
what are some risks associated with developing prediabetes? what can decrease risk?
risks- FH, obesity, metabolic syndrome, GDM history, drugs (seizure and antipsychotics)
risks can decrease with weight loss, exercise, gastric bypass surgery, drugs(ACE-I, metformin)
what kind of problems are fat and gut peptides in type 2 DM?
central problems (not pathophys oddities)
what fat/gut peptides are decreased with excess adipose tissue? how about increased?
decreased- adiponectin
increased- interleukin 6, TNF alpha, PAI-1, leptin
what is adiponectin? what is significant about decreased adiponectin due to excess adipose tissue?
a protein hormone involved in regulating glucose and fatty acid breakdown; decreased production reduces insulin sensitivity and leads to insulin resistance
where is amylin released from? what does it do? what diabetes drug is this associated with?
released by beta cells; decreases gastric emptying and increases fullness; smylin, BID injection for type 1 or 2 patients and has weight loss side effect
what do GLP-1 drugs do? what are two benefits of these drugs?
(exenatide/byetta) incretin hormone potentiates meal-related insulin release, decreases gastric emptying, inhibits glucagon release
benefits: may promote b cell regeneration and improved CVD benefits
what do DPP-IV drugs do? what is the biggest side effect?
(ex: gliptin drugs) prolong action of endogenous incretins (prevents breakdown of GLP-1 so insulin levels inc and glucagon levels dec)
worse side effect: nausea
what two peptides increase food intake? what two decrease food intake?
increase- ghrelin, neuropeptide
decrease- pancreatic polypeptide or peptide YY
where is glucagon released from? what is it in response to?
released from alpha cells of pancreas in response to low serum glucose levels
describe glucagon levels in type 2 DM
elevated
what are the three major acute complications of diabetes?
diabetic ketoacidosis(severe high glucose), hyperglycemic hyperosmolar state (HHNK- severe high glucose), and hypoglycemia (low glucose usually therapy induced)
what are the two forms of transient hyperglycemia?
dawn and somogyi effects
what is the dawn effect?
The dawn effect is an early-morning (usually between 5 a.m. and 9 a.m.) increase in blood sugar WITHOUT preceding hypoglycemia
what is the somogyi effect?
it is a rebound response to insulin-induced low blood sugar where the body overcompensates and ends up with too high blood sugar levels in the morning
what are four symptoms of hyperglycemia?
polydipsia/polyuria, blurred vision, weight loss (more common for type 1), fatigue
what is DKA? what symptoms can the pt get?
lack of insulin (primarily type 1) results in fat metabolism and increased free fatty acids; fat metabolism produces ketones and the keto-acids cause metabolic acidosis
pt can have N/V, confusion, BG levels > 250, and end up in a coma
what is the tx for DKA?
HYDRATION, insulin, correction of electrolytes
what DM type is DKA more likely to be found?
type 1 (common presentation for new onset)
what is HHNK? what kinds of symptoms can the pt have?
type 2 DM, without ketones, but much higher glucose (over 600 mg/dl); patient primarily has neuro symptoms (mimics stroke but can have seizures, aphasia, hemiparesis, vision changes, etc)
what is treatment of HHNK?
primarily fluids, careful monitoring of K+, insulin isn’t essential
what are some symptoms of hypoglycemia?
neurologic and sympathetic (confusion/stupor, HA, seizure, inc HR, trembling, vasoconstriction, sweating)
what type of meds are you concerned about a diabetic patient taking and why?
beta blockers block the symptoms of hypoglycemia (except sweating)
what is the tx for hypoglycemia?
carbs/glucose PO for mild; IV glucose or glucagon for severe
do people usually die from diabetes?
NOPE, they die from complications of it (heart attack-2x risk for CVD, stroke, kidney failure- leading cause, blindness- 8% of all cases, amputation- 1/2 of non traumatic cases)
are diagnosed diabetics usually well controlled? what is the major goal in diabetes prevention?
nope; goal is to diagnose early and tx appropriately
compare the at risk BMIs for diabetes in Caucasians, south Asians, Chinese, and African americans
white: 30 kg/m2 south Asians: 24 Chinese: 25 African americans: 26 (overall point: lower for ethnic groups compared to whites)
does subcutaneous fat vs intra-abdominal fat have a higher correlation with diabetes risk?
intra-abdominal fat has higher deposition than subcutaneous (Caucasians follow subcutaneous pattern)
what are the two general rules of screening for diabetes?
1) . screen for DM2: people under 45 with BMI over 25 AND one of many risk factors (physically inactive, familial diabetes, high risk race, high BO, POS, hx of CVD, A1C over 5.7%)
2) . everyone over 45 yrs old every 3 years check FBG or A1C (if person is also at risk or has prediabetes then test every year)
what skin marking is a sign of insulin resistance?
acanthosis nigricans (darkening of skin, looks dirty and might feel velvety)
basic difference between type 1 and 2 DM?
1- lack of insulin secretion
2- tissue insensitivity to insulin
basic pathophys of DM
increased serum glucose stimulates insulin release from pancreatic islet cells; serum insulin stimulates uptake of glucose into skeletal muscle, fat, and liver cells
during the first phase insulin response (after an IV glucose bolus), how does a DM pts response compare to a non-DM person?
insulin secretion rate is decreased in a diabetic during that bolus
what receptor is a part of the insulin resistance pathway?
PPAR gamma
do insulin and glucose have the same cell receptor?
no
what is insulin resistance? how are insulin levels during resistance?
breakdown in signaling that starts with insulin binding, which activates a 2nd messenger and causes glucose transport into cells; pts have HYPERinsulinemia which is what leads to the resistance
what three things are increased when a patient has impaired fasting glucose?
insulin production, fasting plasma glucose, and insulin resistance
when comparing pts with impaired fasting glucose vs type 2 DM, how do fasting blood glucose, insulin production, and insulin resistance compare?
FPG: sharp increase in type 2 DM compared to slight increase in IFG pts
Insulin production: decreased in type 2 DM vs IFG pts
Insulin resistance- higher in Type 2 DM than IFG pts but levels off/hits a threshold in type 2 pts
according to Hadley, what type of disease is related to insulin resistance?
macrovascular disease (due to supranormal insulin levels)
according to the ADA’s criteria for diabetes, what is the A1C level? fasting BS, random BS w diabetic symptoms, and OGTT?
A1C >6.5%
Fasting BS: > or equal to 126
Random BS: > or equal to 200 w symptoms
OGTT: 75g glucose with BS > or equal to 200 at 2 hrs
what are normal A1C, FPG, and OGTT levels?
A1C < 5.7%
FPG < 100 mg/dl
OGTT <140 mg/dl
what is hemoglobin A1C? what does this percent depend on? how often is it checked?
covalent modification of hemoglobin beta chain (glycosylated Hb); the % depends on overall average blood sugar over the lifespan of the RBC; therefore, its checked every 2-3 months
after what fasting plasma glucose number is when you start seeing diabetes complications?
126
for patients with increased FPG or HgA1c, what disease state has been on the rise?
retinopathy
what are common diabetic symptoms? (6)
polydipsia, polyuria, weight loss, fatigue, nonhealing skin ulcers, blurring of vision (acute symptom that can be reversed once sugars are controlled)
what are the 5 main disease states due to diabetic complications?
lipid derangements (LDL could go up or down), macrovascular disease, microvascular disease, neurological disease, integumentary/connective tissue changes
what are the three main types of macrovascular disease?
1) . ATHEROSCLEROSIS (main one)
2) . CAD
3) . PVD
what are two main types of microvascular disease?
1) . retinal proliferation and blindness
2) . glomerular changes leading to nephropathy and renal failure
what lab value ratio is a good measure of nephropathy/renal failure?
protein/creatinine ratio
why is neurological disease a severe diabetic complication?
bc there is impairment of nerve vascular supply (bad for healing and ulcers)
based on tight control studies, how did tight control of blood sugars in DM 1 pts impact diabetic complications? what does this result suggest?
when these pts have good control of their sugars, they had a decreased in all diabetic complications, which suggests that glycemic control should be a primary target of tx
what was the first study to show that glycemic control in type 1 diabetics had a beneficial effect on diabetic complications?
DCCT (DM complications vs glycosylated hemoglobin)
what was the main outcome of the UKPDS (united kingdom prospective diabetes study)?
it was the first study to show that reducing BP (having tighter control) had just as beneficial impact in reducing diabetic complications compared to glycemic control for type 2 DM pts
what were the two results of metformin use in the UKPDS?
CVD improved with intensive metformin, but not sulfonylurea/insulin tx; metformin only impacted Macrovascular things
what type of diabetic complication is more strongly related to supranormal insulin levels?
macrovascular disease- atherosclerosis
how do you best monitor Type 2 DM sugar levels?
hemoglobin A1c- more reliable than FPG
Are there guidelines for monitoring type 2 DM pts with fasting blood glucose?
no recommendations for regular self monitoring, UNLESS on meds that can cause hypoglycemia (don’t need to monitor with metformin)
what are 5 steps to tx approach of type 2 DM?
1) . diet and exercise
2) . oral therapy
3) . other insulin therapies (some non oral)
4) . insulin added to oral therapy
5) . surveillance for complications
* *most drugs are additive (can remove agents as needed too)
nowadays what is metabolic syndrome referred to as?
global cardiovascular risk
what are some risk factors of metabolic syndrome?
glucose intolerance/insulin resistance/high insulin levels, obesity, hypertension, dyslipidemia, endothelial dysfunction
what are the criteria for metabolic syndrome? what is an important thing to remember about this criteria?
any three of the following:
1) . inc waist circumference (men>40 in, women>35 in)
2) . FPG (>100)
3) . elevated BP
4) . serum TG level (>150)
5) . dec HDL (men <40 mg/dl, women< 50mg/dl)
* *important to remember there are ethnic differences: Asians are at a higher risk than other ethnicities
what type 2 DM drug must be taken with food? why?
Meglitinides; this drug stimulates beta cells to produce insulin at meal time
what type 2 DM drug is best used to promote 1st phase insulin secretion?
GLP1 agonist byetta/exenatide
what GLP1 agonist drug has a broad indication for Type 2 DM pts with preexisting CVD?
Liraglutide/Victoza
What is one benefit of SGLT2 inhibitors (Type 2 DM)?
weight loss
What is the purpose of intrinsic factor?
binds to B12 and protects it from breaking down in the gut’s acidic environment; if you don’t have intrinsic factor the you’ll be B12 deficient
Should POS be diagnosed with an ultrasound? why?
no, because not all women present with visible ovary cysts
statistically, how can advice from a provider impact obesity tx?
patients are 2x likely to lose 5% of body weight if they have been told that they are overweight
describe leptin levels of obese patients
obese patients have high leptin levels bc the hypothalamus is insensitive to levels (therefore, hypothalamus cant provide appropriate feedback of decreasing appetite for weight loss)
