Diabetes

What is diabetes?

chronic condition characterized by high blood glucose levels due to the body’s inability to produce or effectively use insulin

How is insulin important for diabetes?

it helps glucose enter the cells to be used for energy and without it, glucose accumulates in the bloodstream

What is diabetes insipidus?

rare, causes the body to lose too much water, leading to extreme thirst and large/frequent amounts of urine

What is diabetes mellitus type I?

body’s immune system mistakenly attacks and destroys insulin-producing cells in the pancreas resulting in no insulin production

What is diabetes mellitus type II?

most common form of diabetes where body doesn’t use insulin properlly

Which diabetes has a fast onset early in life?

type I

Which diabetes has a slow onset later in life?

type II

Which diabetes type is autoimmune?

type I

Which diabetes type is inflammatory?

type II

What are risk factors for type I?

genetic or infection history

What are risk factors for type II?

can be genetic but mostly obesity, age, and sedentary lifestyle

What is the pre-prandial test?

done on a fasted state about 8 hours since last meal

What is the 2 hour post prandial test?

done 2 hours after a meal

What is the random blood glucose test?

done at any random point in the day, not going to be fasted

main goal is to see an average reading

What is the A1c test?

measures blood glucose levels over the past 3 months

can be taken regardless of fasted or fed state

What does the A1c test measure?

measures the percentage of hemoglobin that glucose has attached to 

we want this number to be low because we want oxygen bound to the hemoglobin

For the pre prandial test, what levels indicate diabetes?

^{>126 mg/dL}

For the pre prandial test, what levels indicate prediabetes?

100-125 mg/dL

For the 2 hour post prandial test, what levels indicate diabetes?

> 200 mg/dL

For the 2 hour post prandial test, what levels indicate prediabetes?

140-199 mg/dL

For the random blood glucose test, what levels indicate diabetes?

>200 mg/dL

For the A1c test, what levels indicate diabetes?

>6.5%

For the A1c test, what levels indicate prediabetes?

5.7-6.4%

To make a diagnosis for diabetes, how many measurements are required?

2 out of range measurements 

could be any combination of 2 tests (even 2 of the same test on different visits)

How far apart should A1c measurements be taken to be effective?

3 months

What are some goals of diagnosis?

maintain healthy glucose levels

adjustment to diet and lifestyle

prevent complications of diabetes and associated treatments

avoid hypoglycemia

prevent further development of insulin resistance (type II)

What is the range of values for treatment goals for the pre prandial test?

80-130 mg/dL

What is the range of values for treatment goals for the 2 hour post prandial test?

<180 mg/dL

What is the range of values for treatment goals for the random blood glucose test?

<180 mg/dLW

What is the percentage for treatment goals of A1c test?

<7%

What are the 2 main ways to test blood sugar at home?

fingerstick testing

continuous glucose monitor

How do continuous glucose monitors work?

sensor is implanted right under the skin with a microneedle

provides constant stream of glucose levels to an external device

Once you take a sensor off, can you reuse it?

no because it is no longer sterile and it is meant to stay in one place once inserted

How long do most sensors last?

7-14 days depending on brand and model

What are some cons with fingerstick testing?

painful

less accurate at blood glucose extremes

less convenient

relatively cheap

What is a big con with CGMs?

very expensive

What is the cause of diabetes complications?

glucose can build up in the blood vessels and crystallize, causing irritation and inflammation

What are the 3 classifications of complications?

nonvascular

microvascular

macrovascular

What are nonvascular complications?

issues not directly connected to circulation

include hearing loss, poor wound healing, UTIs

What are macrovascular complications?

associated with major arteries and vessels

includes risk for peripheral artery disease, risk for cardiac events like heart attack or stroke, possible link to Alzheimer’s

What are microvascular complications?

glucose enters the capillaries and causes physical harm

includes retinopathy, kidney damage, peripheral neuropathy

What causes diabetic ketoacidosis?

prolonger hyperglycemia

What happens in diabetic ketoacidosis?

body rapidly dissolves fats and produces ketone bodies which decrease the blood pH

What are some symptoms of diabetic ketoacidosis?

mental fatigue, dehydration, fruity breath

Who is most at risk for diabetic ketoacidosis?

patients with type I diabetes

What is the only treatment for type I diabetes?

insulin 

What do the beta cells of the pancreas secrete?

insulin

What do the alpha cells of the pancreas secrete?

glucagon

Describe glucose-induced insulin secretion?

glucose enters beta cells as blood sugar rises

glucose is broken down into ATP

ATP binds to and closes K+ channels on beta cell membrane

depolarization causes Ca2+ channels to open and Ca2+ rushes into cell

insulin vesicles are released into bloodstream

Describe insulin signaling pathways.

signals through tyrosine kinase receptors leading to phosphorylation of many signaling proteins and lead to a variety of changes in the target cell

signaling cascade leads to translocation of vesicles that have glucose transporters on them to the cell surface which brings in glucose from the bloodstream to be used or stored 

What happens with insulin and adipose tissue after we eat?

insulin works on the adipose to prevent fatty acid breakdown

When is onset typically for type I?

childhood

What are some hyperglycemia complications of type I diabetics?

glucose in urine

dehydration

excessive thirst

What are some complications and symptoms of diabetes?

stroke, eye disease/blurred vision, heart disease, high BP, kidney disease, weight loss, increased urination, impaired blood flow to lower extremities, nerve damage, peripheral neuropathy

What is the goal of insulin therapy for type I diabetes?

imitate a healthy pancreas in order to lower blood glucose levels within normal range

What is the target of insulin therapy for type I diabetes?

insulin receptor (catalytic receptor)

What is the MOA of insulin?

1) insulin binds to its receptor (tyrosine kinase)

2) receptor activation triggers intracellular signaling that signals cell to bring glucose transporters to cell surface

3) glucose uptake into cells

4) blood glucose levels fall within normal range

When should you take short-acting insulin?

right before a meal

Which type of insulin is good for maintaining basal levels?

long-acting

What are the rapid-acting insulins?

Humalog, Novolog, Apidura

What are the intermediate acting insulins?

Humulin N, Novolin N (Human NPH)

Humulin R, Novolin R (Human regular)

What are the long-acting insulins?

Levemir, Lantus, Tresiba

What is the brand name for lispro?

Humalog

What is the brand name for aspart?

Novolog

What is the brand name for Glulisine?

Apidura

What is the brand name for Detemir?

Levemir

What is the brand name for Glargine?

Lantus, Basaglar, Toujeo

What is the brand name for Degludec?

Tresiba

What is the purpose of insulin analogues?

modified forms of human insulin that are designed to work better or longer than natural insulin

What is modified in Insulin lispro?

order of lysine and proline are switched

What is modified in Insulin glulisine?

glutamic acid replaces lysine at B29

What is modified in Insulin aspart?

aspartic acid replaces proline at B28

What is modified in Insulin detemir?

myristic acid is attached to lysine at B29

What is modified in Insulin degludec?

fatty acid chain attached to lysine at B29 via a glutamic acid linker which allows it to slowly release insulin

What is the main big risk with insulin?

hypoglycemia

common because insulin has a narrow therapeutic window

What are some symptoms of hypoglycemia?

confused, sluggish, passing out

What is Baqsimi-Glucagon powder?

glucagon in a nasal powder form 

How is insulin not being used properly in type II diabetes?

insulin receptors have become desensitized so glucose transporters do not end up on the cell