EAST 501 Lecture Notes - Lecture 9: Acanthosis Nigricans, Polycystic Ovary Syndrome, Insulin Pump
21 Jun 2018
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Feb 21st – Lec 2 Bernard
Diabetes pt.2
1
CONTINUOUS GLUCOSE
INSULIN SUPPLEMENTS
- normally given in combination
o give short acting insulin around meals and glargine for the long term
- peptides delivered by injection in the abdomen, but there are some nasal forms of insulin as well (other route of
administration)
- 4-7 pin pricks per day (just to keep the levels in check)
o therefore people use insulin pumps that are programmable and give you low level coverage throughout
the day (whether it is short or regular insulin, you can just program it)
ARTIFICIAL PANCREASE AT A GLANCE
- possible to kill someone by giving them too much insulin
1. CGM sensor
- continuous glucose monitoring (CGM) sensor is inserted under the skin (interstitium – fluid filled space
between the cells) to continuously measure glucose concentrations in the patient’s cells à sends signals
2. CGM receiver
- CGM receiver displays the updated readings as graphs and trends minute-by-minute and translates the
readings from USB to Bluetooth
3. Control algorithm device (CAD)
- Readings are sent to a control algorithm device (CAD) – eg. a smartphone, tablet or PC – where an algorithm
analyses them and calculates the correct insulin dose, if required.
4. Insulin pump
- The CAD communicates with a body-worn insulin pump that automatically administers the correct insulin
dose via a cannula inserted under the skin
- even using continuous glucose monitoring it is not perfect, but you still need it
UNWANTED EFFECTS OF INSULIN ADMINISTRATION
- Hypoglycemia: this is the main one
o autonomic NS hyperactivity, both sympathetic (tachycardia, palpitations, sweating) and
parasympathetic (nausea and hunger) that may progress to convulsions and coma/death
o this is the result of too much insulin
Feb 21st – Lec 2 Bernard
Diabetes pt.2
2
o insulin mobilizes the GLUT4 to the membrane in all tissues
§ it this is too efficient à all circulating glucose goes here and you starve your brain of glucose
§ brain uptakes glucose with different transporters (not GLUT4)
o this is the main issue for kids and university students (i.e. impaired and drunk)
o even though in the long run too much glucose is a bad thing, the acute concern is having too much
insulin and this isn’t uncommon
- Immunopathology:
o Allergy
o Immune insulin resistance
§ one of the main Ags is insulin itself so you will have Abs that will bind to the insulin
§ reminder: only way to treat Type I DM is to give insulin
- Lipodystrophy at injection sites
o less concerning side effect
WHAT IS DM?
- Heterogeneous metabolic disorder
o Prolonged hyperglycemia
- Type 1
o Juvenile
o Insulin-dependent (IDDM)
o Insulin-deficiency
- Type II (T2DM)
o Adult onset (not true) à a lot of kids are getting T2DM
o Non insulin-dependent (NIDDM)
o Insulin insensitivity/resistance
§ the initial problem is not with the beta cells but with the cell sensitivity to insulin
o there are different drug classes used to treat
o with full blown T2DM you will be insulin deficient and this means that the beta cell function is
compromised
- Gestational
PREVALENCE OF T2DM
- Worldwide:
o 2013: 381.8million
o 2035: 591.9million
o increase = 55% à epidemic (unless something is changed)
T2DM RISK FACTORS
- Older age
- non-white ancestry
- family history of T2DM
- genetic factors
- components of the metabolic syndrome (increased waist circumference, increased blood pressure,
increased plasma triglyceride levels, and low plasma high-density lipoprotein (HDL) cholesterol levels and
small dense low-density lipoprotein (LDL) cholesterol particles)
- overweight or obese (body mass index (BMI) >= 25 kg per m2
o this is the biggest risk factor
- abdominal or central obesity (independent of BMI)
- polycystic ovary syndrome
- history of atherosclerotic cardiovascular disease
Feb 21st – Lec 2 Bernard
Diabetes pt.2
3
- unhealthy dietary factors (regular consumption of sugary beverages and red meats, and low consumption of
whole grains and other fiber-rich foods)
- cigarette smoking
- sedentary lifestyle
- history of gestational diabetes or delivery or newborns >4kg in weight
- presence of acanthosis nigricans (hyperpigmentation of the skin)
- some medications
- short and long sleep duration and rotating shift work
- psychosocial and economic factors
T2DM OFTEN SEEN IN METABOLIC SYNDROME
- Insulin resistance
- High triglyceride levels
- High blood pressure à while taking drugs for the T2DM, also taking bp meds
- low HDL (good) cholesterol à usually taking a statin
- all of this is driven by the underlying obesity
T2DM
- 90% of DM cases
- insulin resistance/insensitivity
o develops into insulin deficiency (beta cell dysfunction and loss) over time
o usually think of the insulin resistance, but there can also be leptin resistance (leptin = satiety signal)
à there are lots of hormones that come from the fat à tissue sensitivity is impaired
- enhanced hepatic gluconeogenesis
o Hyperglucagonemia = increased sensitivity to glucagon à stimulating liver to make sugar
o even in the fasting state the body is secreting more glucose resulting in insulin resistance
- incretin resistance
o incretins will potentiate the insulin action which is usually a good thing, but in T2DM there is
sensitivity to this (gut derived hormones from the intestine)
- most often associated with obesity (80-90%)
o adults and children
o metabolic syndrome
- genetic component
o polygenic (>100 common variants) à genetic link to the obesity
o this is very complicated
o looking for “diabetes gene” à not one single gene
- clinical presentation is variable
o asymptomatic to ketoacidosis à most people don’t know they are diabetic until a checkup
o some may present with ketoacidosis, a complication of T1DM (therefore it is essentially full blow
diabetes, by T2DM) à evident that something is wrong
- Complications:
o microvascular (retinopathy, nephropathy and neuropathy)
o macrovascular (heart attack, stroke) à this is what kills people
§ 60% die of coronary heart disease
o major cause of death is coronary heart disease (60% of cases)
o diabetic may have to have limbs amputated because they would lose feeling in their feet and when
detected it is too late
Document Summary
Normally given in combination: give short acting insulin around meals and glargine for the long term. Peptides delivered by injection in the abdomen, but there are some nasal forms of insulin as well (other route of administration) Cgm receiver displays the updated readings as graphs and trends minute-by-minute and translates the readings from usb to bluetooth: control algorithm device (cad) Readings are sent to a control algorithm device (cad) eg. a smartphone, tablet or pc where an algorithm analyses them and calculates the correct insulin dose, if required. The cad communicates with a body-worn insulin pump that automatically administers the correct insulin dose via a cannula inserted under the skin even using continuous glucose monitoring it is not perfect, but you still need it. Hypoglycemia: this is the main one: autonomic ns hyperactivity, both sympathetic (tachycardia, palpitations, sweating) and parasympathetic (nausea and hunger) that may progress to convulsions and coma/death this is the result of too much insulin.
