Lecture 13 Flashcards
(23 cards)
Explain the specific blood tests used to diagnose diabetes. What specific criteria are used to differentiate between prediabetes and diabetes?
1) Fasting plasma glucose levels: fasted glucose test (fast for 12 hours). These levels, if above 126 mg/dL, is considered diabetic. If 100-125 mg/dL, it’s prediabetic.
2) Glucose tolerance test (drink a glucose drink and they measure glucose levels over a few hours to see how your body reacts to it.) Glucose levels should rise after drinking but will clear out over 3 hours. Diabetic people will begin with higher glucose levels before the drink and will take longer to clear out the glucose. Above 200 mg/dL is diabetic. 140-199 mg/dL is prediabetic.
3) Hemoglobin A1C levels: see if a portion of hemoglobin has been glycolated and is converted to hemoglobin A1C. It occurs when blood sugar levels are high. Since blood cells last around 3 months, this is a good indicator of the past 3 months on average. If above 6.5%, it’s diabetic. If it’s 5.7-6.4%, it’s prediabetic.
4) Random plasma glucose levels can be taken at any random time of the day. Blood glucose levels shouldn’t be over 200 mg/dL. If it is, it means diabetes.
Pregnant women have to take fasting plasma glucose, oral glucose tolerance, and Hb A1C level tests even if they do/did not have diabetes. Why might this be?
A lot of women can develop gestational diabetes during pregnancy. It leads to the production of huge babies because there is so much sugar in the blood, these babies can outgrow the placenta and the amount of nutrients that they need.) It can also be detrimental to have any kind of diabetes and turn into a high risk pregnancy.
When is hemoglobin A1C formed? What do levels of this indicate, and what are appropriate levels of hemoglobin A1C?
It’s formed when glucose in the blood binds irreversibly to hemoglobin in red blood cells and forms a very stable glycated hemoglobin complex which last the entire lifetime of the red blood cell. This is the best measurement of glucose control because it gives you a look at the average blood sugar levels over the last three months. Anything around 6% is good control for those who are diabetic. Above 8% means something is wrong and you need to deal with what is happening.
What kind of diseases can result from high HbA1C levels? Around what percent of A1C does an exponential increase in the risk of disease occur?
Kidney disease, nerve disease, retinal disease. Glucose levels can severely affect your nerves and kidneys as well. Above 8% HbA1C is when there is an exponential increase is the risk of disease. Your glucose levels is not normal. As a result, this can cause damage to specific parts of your body, which is why pregnant women need to have their blood glucose controlled because it can lead to some of these diseases.
Why don’t you want to treat diabetes too severely (decrease their blood sugar levels too low or too quickly?)
Diabetic patients may end up hypoglycemic (extremely low blood sugar) It’s important to have them maintain a good blood sugar level that is between having enough sugar circulating.
What are the characteristics of juvenile-onset diabetes, and when do most cases appear? Is this type 1 or type 2 diabetes? What is the main treatment for this disease, and what does it prevent?
It’s type 1 diabetes. Usually, people who develop type 1 diabetes are children and will develop this autoimmune disease which will prevent them from producing insulin. It’s characterized by a lack of insulin because of the killing off of insulin producing beta cells, not a resistance to insulin. The main treatment is injection of insulin to control high blood sugar (hyperglycemia) and ketoacidosis. Frequent blood sugar tests are used to determine blood glucose.
Why is it that the beta cells are destroyed in cases of juvenile-onset diabetes? What occurs as a result of this that allows doctors to determine if a patient is likely to determine juvenile-onset diabetes?
Something occurs to trigger the beginning of your immune systems lymphocytes to start targeting and attacking your beta cells of your pancreas. This autoimmune response could be due to infection, trauma, stress, or any other challenge to the immune system.
As the attack on the beta cells progresses, antibodies against beta cell antigens begin to appear in circulation. The onset of type 1 diabetes is preceded by the development of antibodies against beta cell antigens.
Explain the stages in development of type 1 diabetes.
It’s a genetic predisposition. (having specific major histocompatibility gene variants.)
Stress/trauma/infection happens which marks the beginning of immunological abnormalities, such that antibodies against beta cells begin to form.
As the individual grows older, there is a progressive loss of insulin released (because the amount of beta cells has continually decreased.) Even with a progressive loss of insulin release, the individual will still be able to control their glucose levels but there will be an impairment in glucose tolerance since insulin will be lower.
As soon as these individuals have super low levels of beta cells, their insulin levels will drop and this is the stage of overt diabetes (most advanced.) Levels of glucose will be higher than normal. The C-peptide is still present so some insulin is still being formed.
When all the beta cells have been killed off, there will be no C-peptide present anymore. This means that their body has ceased making insulin.
Before insulin injections were actually available, children suffering from insulin deficiency (T1D) would often have a skin/bone appearance. However, after insulin was made available, their body weight would begin to go up. Why is this the case?
The glucose present in their blood was not able to reach their cells. These children would eat, but not be able to absorb any of the energy they consumed.
With insulin injections, the children were able to gain weight because they were able to utilize the glucose present in their bodies, allowing them to gain weight.
What specific gene variants may occur in individuals with T1D? About what percent of individuals with variants in this gene actually develop T1D?
MHC (major histocompatibility complex): proteins that recognize “self” vs “foreign” might be affected such that specific cells are not able to recognize beta cells in your body as “self”
However, less than 5% of individuals with variants in this gene actually develop T1D. Other genes are believed to be involved in diabetes susceptibility, which may interact with histocompatibility genes to set off destruction of pancreatic beta cells.
Does the occurrence of T1D have a heritable component?
Yes, families where one person has T1D has a 2-3x more likely to have other cases of T1D
What antibodies appear for individuals who are likely to develop T1D? What order do these antibodies appear?
The appearance of 1 or 2 of these antibodies has a predictive value of ____% for appearance of type I diabetes within ___ years.
The appearance of 3 or 4 of these antibodies has a predictive value of ____% for appearance of type I diabetes within ___ years.
1) Islet Cell Antibodies (ICA) - cells specific to kill beta cells in the pancreatic islet, which usually appear first
2) Antibodies against Protein Tyrosine Phosphatase (IA2) - insulin activates certain pathways and leads to the activation of certain phosphatases. These antibodies are targeting downstream targets of the insulin response
3) Antibodies against Glutamic Acid Decarboxylases (GAD) - glutamic acid decarboxylases are involved in the production of GABA from the pancreatic beta cells. These antibodies will target GAD (which is produced from the beta cells of the pancreas
The appearance of 1 or 2 of these antibodies has a predictive value of 50% for appearance of type I diabetes within 10 years.
The appearance of 3 or 4 of these antibodies has a predictive value of 90% for appearance of type I diabetes within 10 years.
What treatments are paired together for individuals who suffer from type 1 diabetes? What are the different types of insulin that type 1 diabetics can take for treatment? Do individuals only take one type of insulin?
Usually insulin injections and drugs used for T2D to promote insulin sensitivity and promote natural insulin secretion are paired.
- rapid acting insulin: shoots insulin way up when you inject it, acts super fast but lasts for a short period of time
- short acting
- intermediate acting
- long acting (slow release): lower levels after injection but last longer
What is “maturity-onset diabetes” characterized by? What diabetes type is this?
It’s T2D, characterized by insulin resistance in the target tissue. Insulin is still produced, but they don’t respond to it.
What are risk factors for development of type II diabetes?
- being overweight or severely obese
- not physically active
- first degree relative with diabetes mellitus
- being a specific ethnicity
- women with history of gestational diabetes mellitus or if you deliver a 9+ lbs baby
- women with PCOS
- history of high blood pressure
- diagnosed with pre-diabetes
Is T2D heritable?
Yes, but we don’t know what genes.
1/3 of siblings and offspring of a T2D parents are likely to develop T2D.
In cases of individuals with T2D, glucagon levels do not drop after eating. Why? Because
Their body believes that glucose levels are still low (because they are not able to access glucose present.) Since the body thinks glucose levels are low, glucagon gets secreted from the pancreas to increase blood glucose levels. However, no response occurs, so glucagon secretion remains high.
Insulin receptors are also not being activated, thus the crosstalk between insulin receptors and glucagon receptors will not occur. Because inhibition of the glucagon receptor will not occur, the body will keep producing glucagon.
What stage appears for individuals prior to diagnosis of T2D? What levels are measured by doctors which usually tell them that these individuals are now past pre-diabetes?
Pre-diabetes metabolic syndrome: stage of undetected insulin insensitivity. This gradually merges into impaired glucose tolerance. Some glucose tolerance issues will show up in pre-diabetes. When these individuals end up reaching fasted glucose levels > 125 mg/dL and HbA1C > 7.0, this will usually indicate to doctors that they now have T2D
Why is it that individuals suffering from type 2 diabetes might need to take insulin injections later on in life? Isn’t T2D characterized by insulin resistance, not insulin production issues?
Initially, their body doesn’t respond well to insulin. It tries to compensate and increase the amount of insulin that is produced. As a result of overproduction of insulin, this can cause damage to their beta cells. Over time, these beta cells can become dysfunctional, leading to lower levels of insulin or no insulin production. As a result, insulin injections will be needed.
What is metabolic syndrome (pre-diabetes?)
Clinical manifestations of metabolic syndrome: obesity, glucose intolerance, high blood sugar levels (hyperglycemia), high blood pressure (hypertension), atherosclerosis (buildup of plaque in arteries), impaired kidney function
Biochemical Abnormalities: Insulin resistance, high insulin levels and not being able to respond to this insulin, high triglycerides (formation of ketone bodies), low HDLs and high LDLs (low good cholesterol, high bad cholesterol), as well as issues with clotting as well (insulin important for wound healing).
What puts people at risk for developing T2D?
Abdominal and visceral fat (fat under the muscles, surrounding the organs.) This has bene associated with the development of T2D. Deposits here have been associated with the increase in insulin resistance.
When individuals develop T2D, does their beta cell function decrease immediately? Explain
Their beta cell function decreases over time. The reason that beta cells decrease in function over time is because of the insulin resistance that is characteristic of T2D, since their body is desperate to lower blood sugar levels, insulin levels end up remaining much higher than normal.
Since the beta cells begin working overtime to produce the insulin, this ends up impacting their function, which causes it to decrease over time. As a result, not only does beta cell function end up decreasing, but they will still not be able to respond to insulin. Therefore insulin and T2D medication will need to be administered.
What is the ominous octet? Explain how these 8 things lead to hyperglycemia (high blood sugar)
1) increase in lipolysis: breakdown of fats leads to ketone body production because your body thinks it’s in starvation mode
2) increased glucose reabsorption by the kidneys: more glucose goes back into the blood
3) a decrease in glucose uptake by the muscles: no signal to take up glucose, so can’t decrease blood sugar
4) neurotransmitter dysfunction
5) increased liver (hepatic) glucose production: gluconeogenesis occurs to increase blood sugar
6) increased glucagon secretion from alpha cells of the pancrease: pushes more glucose into the blood by glycogen breakdown/gluconeogenesis
7) impaired insulin secretion from beta cells of the pancreas (can’t take glucose from the blood)
8) decreased incretin effect: intestine involved in the absorption efficiently and to help excrete some of it. Decreasing this increases blood glucose
