Exam 2 -- Endocrine -- Diabetes Mellitus Flashcards
It is estimated that diabetes is accountable for what percentage of vascular deaths?
11%
What are some other terms for metabolic syndrome?
Syndrome X, insulin resistance syndrome
True or false: about 40% of US adults have metabolic syndrome
True.
Metabolic syndrome is highly associated with prediabetes. Patients with metabolic syndrome have how much greater risk for developing diabetes?
5X
Patients with metabolic syndrome have how much greater risk for developing cerebrovascular disease?
3X
Patients with metabolic syndrome have how much greater risk for developing liver cancer?
2X
What are key characteristics of metabolic syndrome?
Central body obesity, insulin resistant, lipid abnormalities, elevated BP, FPG (100-125mg/dL), HbA1c (5.7-6.4%)
What would therapy for metabolic syndrome consist of?
Education, diet, and exercise, smoking cessation, control of blood pressure and FPG
Which is more common, T1DM or T2DM?
T2DM
What age group has the highest incidence of T1DM?
10-14 years
T1DM most often is due to an autoimmune-mediated destruction of beta cells in the pancreas. What type of hypersensitivity is this?
Type IV
What type of histocompability antigens are associated with T1DM?
HLA-DR 3,4,7,9
It is believed that the incidence of T1DM is preceded by what sort of event?
Preceding viral infection
Latent Autoimmune Diabetes in Adult (LADA) is a subtype of T1DM. It is slowly progressive (in part) due to HLA-DR2, which brings about the disease but is protective against getting it in childhood. What type of antibodies are found in LADA patients?
Glutamic acid decarboxylase antibodies. Important to note is that these antibodies are found in regular T1DM as well, but more references are made to GAD antibodies as they associate with LADA in literature.
LADA is most often seen in what type of patient?
Nonobese patients over 35
What type of medication is useful in managing LADA?
Sulfonylureas (squeeze a little extra insulin out of the pancreas)
True or false: although T2DM patients may eventually need insulin, usually they can manage with diet, exercise, and oral agents
True.
Obese T2DM makes up what percentage of T2DM?
More than 80%
Tissue insulin resistance could be due to what factors?
Decreased number of insulin receptors, or malfunctioning insulin receptors.
Although insulin resistance can be a factor in T2DM, what are other factors that may be in play?
Possible malfunction of GLUT (protein that transports glucose into the cell) or of PPAR (transporting glucose into the nucleus), impaired insulin secretion (the threshold to release insulin from the pancreas is higher; possible glucose-sensitive cells in hypothalamus are damaged)
Maturity-onset diabetes of the young (MODY) is an autosomal dominant cause of diabetes. Generally, what is the molecular malfunction that occurs?
Insufficient insulin production or insufficient insulin release
Is MODY antibody negative or antibody positive?
Negative (It’s a variant of T2DM)
MODY is most often seen in what type of patient?
Thin young adults (under 25 years)
True or false: as soon as a patient is diagnosed with MODY, they should be placed on insulin
False; it is usually controllable without insulin for at least 2 years
Gestational diabetes is a subtype of ______________
T2DM
True or false: gestational diabetes is more common in overweight women
False.
What are some signs and symptoms of diabetes mellitus?
Glucosuria, polyuria, polydipsia, fatigue, possible weight loss (due to fasting metabolism being activated), hyperglycemia (not only due to lack of insulin action but also glycogenolysis and gluconeogenesis in the liver), ketonemia, ketonuria, ketoacidosis (due to liver metabolizing FFA metabolism)
Glucosuria is when there is glucose in the urine. At what glucose plasma concentration do you start finding glucose in the urine? What glucose plasma concentration is a diagnostic finding for diabetes?
180 mg/dL is the level at which you start finding glucose in the urine, 126 mg/dL is diagnostic of diabetes
Renal failure is secondary only to what other condition as a cause of death in diabetic patients?
Myocardial infarction
Nephropathy can cause capillary and glomerular changes, making the glomerulus leaky. What protein can be found in the urine as the first clinical sign of nephropathy?
Albumin. This is after significant renal damage has occurred.
True or false: more than half of non-traumatic amputations are on diabetic patients
True.
How much more common is peripheral vascular disease in diabetic patients compared to normal patients?
4X
What are some signs of peripheral vascular disease?
Leg pain relieved by rest, cold feet with reduced or absent pulses, nocturnal leg pain relieved by dangling legs over side of bed or walking, loss of hair on foot and toes.
The neuropathy that can accompany diabetes is induced by what kind of molecular changes?
Schwann cell damage that delays nerve conduction, changes to vasa nervonum that decreases blood supply to the nerves.
There are a few varieties of neuropathies that can occur in diabetes. Which one involves loss of vibration, pain, temperature, and proprioception?
Symmetrical mainly sensory polyneuropathy (distal)
There are a few varieties of neuropathies that can occur in diabetes. Which one involves diffuse pain? Does this type of neuropathy ever remit?
Acute painful neuropathy; usually remits after 3-12 months of good control
Mononeuropathies can occur in diabetes. Which cranial nerves are most often affected? Do these mononeuropathies remit?
CN III (pupils spared), CN VI; patients spontaneously recover in 3-6 months
There are a few varieties of neuropathies that can occur in diabetes. Which one is the least common? What symptoms does it involve?
Autonomic neuropathy; tachycardia, postural hypotension, vomiting, loss of blasdder tone, erectile dysfunction
What are some ocular complications that can arise from diabetes?
Cataracts, retinopathy, glaucoma
The amount of advanced glycosylated end products (AGEs) is dependent on what factors?
Amount of elevated blood glucose and how long it has been elevated
What are some consequences of AGEs?
Atherogenesis, capillary BM thickening, inflammatory response
If intracellular glucose levels get high enough that they overwhelm the Krebs cycle, how is the glucose used?
It goes down the polyol pathway, in which it is converted by aldose reductase to sorbitol and fructose
Sorbitol and fructos are products of the polyol pathway. What are important results of this pathway?
Sorbitol and fructose increase the intracellular osmolarity since they are bigger than glucose and cannot move in and out of the cell freely. This pathway also creates free radicals, which increases oxidative stress on the cell.
Along with AGEs and the polyol pathway, activation of protein kinase C is one of the mechanisms of complications due to diabetes. What is the result of activation of protein kinase C?
Increased endothelial proliferation, agniogenesis, and vascular permeability (production of VEFG)
What are some diagnostic features of DM?
Casual plasma glucose test over 200 mg/dL with polyuria, polydipsia, fatigue; fasting plama glucose greater than 126 mg/dL on two or more occasions; HbA1c (how much hemoglobin is glycated) greater than 6.5%; oral glucose tolerance test greater than 200 mg/dL within the two hours
What are some of the non-insulin actions a person can take to help manage diabetes?
Maintain good diet, take baby aspirin to decrease thromboxane activity, exercise, good sleep, treat depresesion, get HbA1c below 7%
Though insulin has good effect on blood glucose and HbA1c, what are some downsides?
You have to inject it, it can cause hypoglycemia and weight gain.
Regular insulin has fast action and can be administered IV. Regular insulin preparations have what in common to their names?
“R” – Humulin R, Iletin Regular, Novolin R
Extremely fast action insulin preparations most closely match normal insulin response and are used in insulin pumps. What are some of the names of these preparations?
Insulin lispro (Humalog), glulisine [these two can be administered IV], and aspartate (NovoLog)
Intermediate-acting insulin preparations utilize zinc to slow absorption from the subcutaneous site, and are often mixed with regular insulin. What are a few examples of these preparations?
Neutral Protamine Hagedorn (NPH, Humulin N, Iletin II NPH, Novolin N); Lente
Long-acting insulin preparations allow for 24 hour control through slow release at the injection site. The injection is painful due to drug acidity. What commonality do these preparations have in their names?
Trade names begin with “L” – Insulin glargina (Lantus), determir (Lavemir)
What is an example of an ultra-long-acting insulin preparation?
Insulin degludec (DegludecPlus)
Comparing syringes and insulin pens, which allows you to mix insulin? Which is more comfortable and why?
Syringe allows for mixing, insulin pen is more comfortable because the needle is sharper
What is an example of a buccally-absorbing insulin preparation? What type of diabetes is it approved for?
Oral-lyn; approved for T1 and T2 DM
Which oral drug for diabetes is used as an amylin analog? What does it do? What type of diabetes should it be used for? When should it be used?
Symlin; it decreases glucagon release and slows gastric emptying (so may be useful for weight reduction); can be used for either T1 or T2 DM patients; should be given subcutaneously at mealtime with insulin
What is the mechanism of action for GLP-1 agonists? Which type of diabetes should it be used for? What are some examples of drugs in this class?
Slows gastric emptying, decreases glucagon release, stimulates insulin release; used for T2DM; “tide” drugs (exenatide, liraglutide, albiglutide) as well as Bydureon and Trulicity
Are there any risks to using GLP-1 agonists?
They are associated with acute pancreatitis and acute kidney injury
DPP4 degrades GLP-1, so DPP4 inhibitors potentiate GLP-1. What is the mechanism of action for this class of drugs? What type of diabetes should it be used for? What do the names of these drugs have in common?
Triggers pancreas to release more insulin, decreases liver production of glucose; used for T2DM; names end in “gliptin” – sitagliptin, saxagliptin, linagliptin, alogliptin
Which of the DPP4 inhibitors is used for patients with renal problems?
Linagliptin
Biguanides are the first line drugs for obese patients, as they don’t lead to weight gain. What is the mechanism of action for this class? What is an example of a biguanide?
Decreases gluconeogenesis in liver, and increases glucose uptake by skeletal muscle through GLUT-4 activity. Metformin is a biguanide.
Thiazolidinediones are not used as much as they once were. What is their mechanism of action? What are some drawbacks? What do the names of these drugs have in common?
Improve insulin action in liver and skeletal muscles; they are associated with weight gain, fluid retention, and heart failure; “glitazone” (pioglitazone)
Intestinal alpha-glucosidase inhibitors should be taken right before meals. What is their mechanism of action? Which drugs are in this class?
They slow carbohydrate breakdown, thus decreasing glucose absorption; acarbose, miglitol
Sulfonylureas used to be the #1 treatment for T2DM. What is their mechanism of action? What are examples of these drugs?
Stimulate release of insulin from pancreatic beta cells and enhance beta cell sensitivity to glucose; glipizide, glyburide, glimepiride
What are the SE of sulfonylureas that metformin does not have?
Sulfonylureas can cause hypoglycemia and weight gain; metformin does neither. (Sulfonylureas also tend to lose effect after 1-3 years and have been shown to increase risk for cardiac-related death).
What is the mechanism of action for meglitinides? What benefits do they have as compared to sulfonylureas? When should they be taken? What do the names of the drugs in this class have in common?
They stimulate glucose from beta cells in a glucose-dependent manner; they are less likely than sulfonylureas to cause hypoglycemia (but just as likely to cause weight gain); should be taken 1 to 30 minutes before a meal; “glinides” – repaglinide and nateglinide
What is the mechanism of action for sodium-glucose uptake transporter 2 inhibitor drugs? What are some benefits? Some risks? Contraindications? What do the names of these drugs have in common?
They inhibit glucose reabsorption in proximal renal tubules; this promotes weight loss; it also increases genitourinary trarct infections and urination and risk for fracture, as well as breast and bladder cancer; renal impairment may be a contraindication; “flozin” – canagliflozin, dapagliflozin, empagliflozin, remogliflozin
What are a few surgical treatment options that are either available or may someday be availabe for diabetes?
Artificial pancreas, islet cell transplant into liver, stem cell generation of insulin cells, bariatric surgery for obese T2DM patients
Of the ways to monitor glycemic control – urine testing, FPG, HbA1c, fructosamine, and home blood glucose monitoring – which allows direct assessment of day-to-day activities on glucose levels?
Home blood glucose monitoring
Of the ways to monitor glycemic control – urine testing, FPG, HbA1c, fructosamine, and home blood glucose monitoring – which is performed in office but requires no special patient preparation?
HbA1c
Of the ways to monitor glycemic control – urine testing, FPG, HbA1c, fructosamine, and home blood glucose monitoring – which is least useful?
Urine testing – the level at which glucose shows up in the serum is way higher than safe blood levels
Of the ways to monitor glycemic control – urine testing, FPG, HbA1c, fructosamine, and home blood glucose monitoring – which is useful for determining glucose control when treatment plans have been changed?
Fructosamine – it indicates the levels of blood glucose over two to three weeks, so you don’t have to wait as long to see how the new treatment is working long-term
