Type 1 Diabetes Flashcards
diabetes
Group of metabolic disorders that are characterized by higher than normal blood sugar (dysglycemia) with disturbances in CHO, PRO, and FAT metabolism due to:
- impaired insulin secreation (beta cell dtysfunctioning)
- impaired insulin action/ glucose utilization (insulin resistance)
- both
- or absolute insulin deficiency
- therefore cannot maintain glucose homeostasis
type 1 diabetes
- results from the pancreas’s failure to produce enough insulin
- cause is unknown
what are the 3 main storage areas in the body for glucose (this may mean they being converted first)
1) liver
2) adipose tissue
3) muscle tissue
glycogenolysis
- biochemical breakdown of glycogen to glucose whereas glycogenesis is the opposite, the formation of glycogen from glucose.
- Glycogenolysis takes place in the cells of muscle and liver tissues in response to hormonal and neural signals
gluconeogenesis
metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates
actions of glucagon and insulin on fats
INSULIN:
-uptake of fat into adipose tissues, uptake of CHO into adipose tissue, promotes chemical reactions that convert fa and glc to TGA, inhibits lipolysis (therefore decrease in blood fa and increase is TGA storage)
GLUCAGON:
-promotes fat breakdown, inhibits TGA synthesis, enhances ketogenesis (fa to ketones)
actions of glucagon and insulin on proteins
INSULIN:
-AT of aa into muscle and tissue, increase rate of incorporation into muscle, inhibit protein degradation (therefore blood aa decrease and increase in protein synthesis)
GLUCAGON:
-inhibits hepatic protein synthesis, promotes degradation of hepatic protein, stimulated gluconeogenesis
metabolism of carbs
-sum of anabolic (building) and catabolic (breakdown) process of starches into smaller units, GLUCOSE, fructose, galactose in the body that are in it’s main sources of immediate energy (fuel)
what CHO form is glucose stored as?
glycogen
which CHO is an exception to the metabolism process?
fibre
what is the easiest form of energy for the body to use for fuel?
glucose»» fatty acids
what are carbs a compound of
carbon, hydrogen, and oxygen- (CH2O)n
Do proteins and fats raise blood sugar level?
no (they can later be converted to glucose)
calorie content of macronutrients
1g CHO- 4 calories
1g PRO- 4 calories
1g FAT- 9 calories
Islets of langerhans
- regions of the pancreas that contain its endocrine (i.e., hormone-producing) cells
- alpha-> glucagon (25%)
- beta-> insulin and amylin (60%)
- delta-> somatostatin (10%)
glucagon
- secreted by alpha cells
- catabolic
- release of glucose
- glycogenolysis, gluconeogenesis, lipolysis
insulin
-secreted by beta cells
anabolic
-glucose uptake into cells
-glycogen synthesis, lipid synthesis, protein synthesis (by increasing aa uptake)
somatostatin
- (-) feedback to slow rate of digestion and nutrients
-In the pancreas, somatostatin is produced by the delta cells of the islets of Langerhans, where it serves to block the secretion of both insulin and glucagon from adjacent cells
(-also released by hypothalamus-> affects growth hormone)
what do glucagon and insulin have in common?
- both produced in pancreas
- boh involved in the regulation of metabolites
- however they end up doing the opposite function
what happens when the pancreas senses high blood sugar?
- secretes insulin (anabolic)
- insulin unlocks “doors” on tissue cells on the 3 storage sites
- glucose then moves from circulation into these storage sites
- blood sugar is thus lowered
what happens when the pancreas senses low blood sugar?
- it secretes glucagon (catabolic)
- binds to liver and then converts glycogen to glucose which is released into the blood
physiologic fasting blood sugar
3.9-5.7mmol/L
normal post prandial blood sugar
aka after eating
-7.8mmol
Physiological pattern of insulin secretion
- insulin levels peaks and dips throughout the day depending on your meals through the say
- 3 to 6 minutes after blood sugar is raised, insulin will start to be secreted-> it follows the path of the blood glucose
Which hormone dominates during the “fed state”
insulin
Which hormone dominates during the “fasted state”
glucagon
what occurs with an increase in insulin
-increase in glucose oxidation
-increase in glycogen synthesis-glycogenesis (therefore glucose uptake)
(inhibits glycogenogensis and gluconeogenesis)
-increase in fat synthesis
-increase in protein synthesis
what occurs with an increase in glucagon
-increase in glycogeneolysis
-increase in gluconeogenesis
-increase in ketogenesis
(decreases glycogen synthesis)
what is the only source of energy that the brain can use?
glucose-> why there is a system in place to try to keep blood sugar level at a good level
glucotoxicity
-when blood sugar is consistently (chronically) high - over 7
what can glucotoxicity start to damage?
- endothelium-> inflammation; damage to arteries
- this is why ppl with diabetes are 2-3x more at risk for heart disease
- also starts to kill off beta cells (creating a vicious cycle)
- has affinity for RBCs- blood gets thick
- neuropathy, nephropathy (damage to eyes, nerves, kidneys)
inter-relationship between insulin and glucagon
- exist together, depends upon which is predominate
- it is not that when one exists the other doesn’t (always some of each)
- while a person is fasting, there is more glucagon
- once you eat, insulin rises, it reaches its peak (bolus), and then will slowly decrease; there is a second small jump (incretin effect) once it moves into the small intestine
- basal insulin level is around during fasting
Fed state
- mechanical and chemical breakdown to glucose: CHO= 90-100%, protein= 58%, fat= under 10%
- 2 principle circulating fuels: glucose and fa
- first few hours after CHO meal: glucose from the meal
- after first 4 hours: vital organs use glucose or fa as fuel (brain only glucose)
- insulin is required for transport and storage process of glucose and fa
- uptake and storage of glucose in liver, aspires tissue and muscle tissue
Fasting state
- shift in energy homeostasis
- glucagon is regulator
- hour 8-12: liver and muscle: glyceogenolysis (glycogen to glucose)
- after hour 8 to 12: muscle breakdown releases aa’s
- fat tissue breaks down FFA- major source of fuel and glycerol- glucose
- liver and kidney: glyconeogenesis (lactate, aa, and glycerol to glucose)
what do incretins enhance?
- insulin effect
- decreases blood glucose
- GLP-1; amylin
glucagon like peptide 1
- small intestine hormone
- stimulate beta cells to release insulin (hence incretin effect)
- suppress glucagon secretion= suppress hepatic glucose output and rise in glucose levels
- slow gastric emptying= promotes satiety and slows down rate of glucose absorption
- positive effect on beta cell proliferation
amylin
- co-located and co-secreted with insulin by beta cells
- regulates rate of gastric emptying
- suppress glucagon secretion= suppress hepatic glucose output and rise in glucose level
- stimulate satiety center
- presence in type 1 diabetes mimics insulin
counter regulatory hormones
- aka defense mech
- enhances glucagon effect
- increases blood glucose
- catecholamines; glucocorticosteroids; growth hormone
catecholamines
- epinephrine from adrenal glands mobilizes glucose stores= promotes glucose production
- inhibits insulin secretion and action
glucocorticosteroids
- 95% cortisol from adrenal glands stimulates gluconeogenesis
- suppresses glucose storage
- responsible for DAWN effect
growth hormone
- secreted by pancreatic delta cells-> somatostatin
- antagonizes insulin release and action
- responsible for DAWN effect
reabsorption of glucose in kidney
-occurs through active transport-> threshold of 10mmol/L (up until this point it is 100% reabsorbed)
what else is 100% reabsorbed by the kidney
aa’s
absolute insulin deficiency
-inability of body to produce insulin
dysglycemia
generically known as high blood sugar
chronic hyperglycemia
- associated with significant long term sequelae in particular damage, dysfunction, and failure of various organs (eyes, kidneys, heart, and blood vessels)
- aka glucotoxicity
aetiology of type 1 diabetes
- result of beta cell destruction and absolute insulin deficiency
- beta cell destruction can be due to autoimmune process, idiopathic, enviro trigger, or genetic inheritance (father 10%, mother 1-4%, sibling 10% or combo)
- rate of beta cell destruction can vary: rapid in young and slower in older
- at any age, but typically before age 30- many have long “honeymoon” periods and diagnosed after 30 and up to 80y
- DKA (diabetes ketoacidosis) may or may not be present
- caucasian> black
LADA
- latent autoimmune diabetes
- typically lean adults (therefore not a typical diabetes patient)
- often mistaken for T2D (10-15%)
differential diagnoses for LADA
- circulating Islet cell Cytoplasmic Antibodies (ICA)
- islet cell Glutamic Acid Decarboxylase (GAD)
5 clinical symptoms of LADA (that differentiates them from type 2)
- between 30-50
- acute symptoms
- BMI under 25kg/m2
- personal history of autoimmune disease
- family history of autoimmune disease
- no absolute insulin deficiency at time of diagnosis
what is the main feature of T1D
-diabetic ketoacidosis (HUGE DIAGRAM ON SLIDE 17)
main side effects of T1D
- hyperglycemic hyperosmolar state (high blood sugar, high loss of body fluids)
- ketoacidosis
- dehydration
- muscle wasting (this starts to occur as a last resort)
diagnostic criteria of T1D
clinical features (lean, young, polydipsia, polyuria, polyphagia)
- family history
- diagnostic testing (FPG, A1C, ZhPG, random PG)
- genetic markers
- islet cell Glutamic Acid Decarboxylase (GAD)
polydipsia
excessive thirst
polyuria
-excessive urination
polyphagia
-excessive hunger
FPG test
- results equal or over 7 mmol/L
- fasting= no caloric intake for at least 8 hours
A1C test
- results equal or over 6.5% in adults
- using a standardized, validated assay in the absence of factors that affect the accuracy of the A1C and not for suspected T1D
- “how sugared up are you and blood”
- looks at last 3 months (can’t do again for 3 months)
ZhPh in a 75g OGTT test
-results equal or over 11.1mmol/L
random PG test
- results equal or over 11.1mmol/L
- random= any time of day, without regard to the interval since last meal
true or false: optimal blood sugar control reduce risk of complications
true
complications: retinopathy, nephropathy, neuropathy, heart disease
true or false: benefits of the control of blood sugar do not increase the earlier you do them
false- early control matters
goals for glycemic control
- Achieve near-normoglycemia (A1C) = or under or equal to 7
- achieve blood pressure targets under 130/80
- achieve lipid targets (cholesterol) LDL under 2mmol/L
- avoid severe hypo- or hyperglycemia
- maintain qol
what are polyphagia, weight loss, weakness and fatigue a result of
-energy starvation (not enough insulin therefore muscle breaks down)
what are polydipsia, nausea, muscle cramps, blurred vision, and polyuria a result of
-hyperglycemic hyperosmolar state (high in blood, high in urine)
what are abdominal discomfort/pain, breath odour, and SOB a result of
ketoacidosis (the build up of ketone bodies)
why does blurred vision occur because of the hyperglycaemic hyperosmlar state?
-the high blood sugar hands onto the fluid -> goes to the eyes-> higher refraction -> blurred vision
what are some treatments for T1D that are in the works
- islet cell transplant
- bionic pancreas
how do insulin, glucagon, and somatostatin all work together
Insulin, glucagon, and somatostatin act in concert to control the flow of nutrients into and out of the circulation. The relative concentrations of these hormones regulate the rates of absorption, utilization, and storage of glucose, amino acids, and fatty acids
