Exam 2: Endocrine Flashcards
what are the two hormones pancreas makes for glycemic control?
- insulin
- glucagon
what kind of hormone is insulin? and describe the basic function of it
- it is a anabolic hormone
function: it drives sugar into cells and storage, increasing the production of energy proteins glycogen and fat
- the energy helps the cells carry out their purpose and their functions
what kind of hormone is glucagon? and describe its function
- it is a catabolic hormone
function: it drives the release of energy from storage molecules when blood sugar is lower
what is a decrease in insulin caused by? (3)
- defects in the beta cell of the pancreas
-the insulin molecule itself - the insulin receptors of all of these
what are the two types of T1DM?
- autoimmune
- non-immune
describe T1DM in immune mediated
autoimmune destruction of pancreatic beta cells, insulitis
unknown environmental trigger in genetically predisposed individual triggers pancreatic cell destruction
diagnostic criteria for DM (4)
- HbA1C >6.5%
- FPG >126 mg/dL; fasting is defined as no caloric intake for at least 8 hrs
- 2-h plasma glucose >200 mg/dL during OGTT
- in an individual with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose >200
**if just using 4: need both clinical prsentation paired with elevated BG
** if using criteria 1-3 : we need two of these from one sample or two
why is hgb A1C useful for both diagnosing and monitoring glycemic control
because theres a tendency for glucose to bind to the hgb in RBC
-the RBC last about 120 days–> so this gives us a good idea of the average blood glucose levels over the last 4 month
what are the big influencers for T1DM?
-autoimmune
-genetic
what are the big influencers for T2DM
-genetic
- environmental factors–> races and obesity being the biggest influences
what triggers T1DM?
- need both the genetic susceptibility and then exposure to something in the environment that kind of trigger it
–this is why often times children develop T1DM or get the diagnosis after they had some kind of viral infection
what is the genetic susceptibility of DM 1?
- first degree relative (parent or sibling) with type 1 DM
- strongest association with major histocompatibility complex (MHC)
what are environmental factors of DM 1? (4)
- viral infection
- h. pylori
- exposure to cows milk proteins
- relative lack of vitamin D (also implicated)
what is autoimmunity type 1 DM?
a slowly progressive autoimmune T-cell mediated disease that destroys beta cells of the pancreas and occurs in genetically susceptible individuals
the cell mediate immune process of T1DM
o Destruction of beta cells mediated by cytokines, produced by cells such as lymphocytes
- beta cells will slowly be destroyed and insulin levels will drop while the glucagon levels rise, leading to increase BS
what happens when beta cells are destroyed and insulin levels drop causing BS to rise in T1DM?
this causes a lot of catabolic breakdown, an increase in serum osmolarity and resulting in weight loss, low energy, ketone production and since cells cant use the blood sugar thats how the ketones break down and go into ketosis
-then the three polys happen–>polydipsia, polyuria, polyphagia
what are the classifications and treatments of T1DM?
Can occur at any time in life
10% of the diabetic population are T1DM
Treatment- exercise, diet, insulin
what is the asymptomatic phase of T2DM? (3)
- decreasing insulin sensitivity
- hyperinsulinemia
- mild increased postprandial blood glucose and FPG
describe insulin resistance
insulin binds to cell surface receptors and;
* the binding may be impaired
* there may be less receptors
* there may be post-receptor defects
o what normally should happen is- when insulin binds to cell surface receptors, the glucose follows into cells through facilitated glucose transporters
-> insulin can’t do its job in getting glucose into cell
describe the pathophysiology of T2DM
Overall Summary-
* Initially we see people have peripheral insulin resistance
o Some defect in the binding
* then what happens glucose can’t enter the cell effectively
* in response to the resistance beta cells put out a lot of insulin, to try to overcome that (hyperinsulinemia, high levels of insulin in blood)
* eventually you get impaired glucose tolerance
o You will see after eating your glucose is higher than what it should be OR during fasting glucose is higher
o SOME DEFECT IS OCCURING “defective gluco-recognition”
* you will see “early diabetes”
o Problems with BOTH fasting and after eating, glucose is high
* then causes beta cell failure, “late diabetes”
o beta cells can’t produce enough insulin to overcome the resistance
what happens in decrease insulin sensitivity in T2DM?
at some point the body becomes less sensitive to insulin so the body tries to counter this by increasing insulin secretion and glycemic control begins to be affected as evidenced by changes in postprandial and the fasting BG levels
what are the organs that involved that will have defects in T2DM?
- Liver- will have an increase glucose production, in spite that the glucose is already high
- Pancreas- becomes impaired, not making enough insulin
o Pancreas still makes insulin, just not enough to what you need - Muscle/Peripheral tissues- there is insulin resistance, glucose can’t enter the muscle due to receptor defects
stage 1 of T2DM
o Insulin resistance is dictated by; environment and genetics
- muscle fat and liver start to struggle to respond to insulin
-The pancreas works harder to compensate by making more insulin
Food, activity, obesity, family hx of T2DM
o hyperinsulinemia
Making a lot of insulin to overcome glucose
o temporary restoration of normal glucose homeostasis
stage 2 T2DM
-sometimes called impaired glucose tolerance
-Prediabetes is when glucose levels become higher than usual, yet are not considered high enough for a type two diabetes diagnosis
o You are making insulin, but it is not enough to suppress fat lipolysis (breakdown of fat)
o -> decrease suppression of visceral fat lipolysis
o As a result, there is an increase release of fatty acids
o Which also increases insulin resistance
–More increase resistance due to a lot of mobilization of fats now
o there is impairment in glucose uptake in insulin sensitive tissues, primarily the muscles
o hyperinsulinemia continues to rise, but still NOT enough to overcome
o you start to see some issues in genetics that will start -> unmasking beta cell secretory defect causing beta cells to get exhausted
o You will start to see higher glucose levels after eating, than what it should be. There is NORMAL fasting glucose levels
stage 3 of T2DM
o MORE INCREASE in free fatty acids
o MORE INCREASE in insulin resistance
o body continue to increase insulin production, hyperinsulinemia
o there is a decrease suppression of hepatic glucose production (liver makes glucose, in spite high glucose levels)
o You will see high glucose levels BOTH fasting and after eating
o as a result, there is down regulation of insulin receptors and impairment of post receptor events
o HIGH GLUCOSE LEVELS, HYPERGLYECEMIA
o REALLY DECREASE IN INSULIN SECRETION
Because that high glucose level is toxic to the beta cells
o diagnosed with T2DM
classifications of T1DM
-beta cell destruction leading to absolute insulin deficency; immune mediated DM is most common form (90%)
idiopathic (10%)
classification of T2DM
progressive loss of b-cell insulin secretion frequency on the background of insulin resistance
characteristics of T1DM (6)
- cellular mediated autoimmune destruction of pancreatic beta cells
-individual prone to ketoacidosis - little to no insulin secretion
-insulin dependent
-75% of individuals develop before 30 years of age; can occur up to tenth decade
-usually not obese
characteristics of T2DM (5)
- usually not insulin dependent but may be requiring insulin
- individual not ketosis prone (but may form ketones under stress)
- generally occurs in those older than 40 y.o, but frequently is rapidly increasing in children
- strong genetic predisposition
- often associated with HTN and dyslipidemia
clinical manifestation and rationale: polydipsia
because of elevated BG levels, water is osmotically attracted from body cells, resulting in intracellular dehydration and hypothalamic stimulation of thirst
clinical manifestation and rationale: polyuria
hyperglycemia acts as an osmotic diuretic; the amt of glucose filtered by the glomeruli of the kidneys exceeds the amt that can be reabsorbed by the renal tubules; glycosuria results, accompanied by large amt of water lost in the urine
clinical manifestation and rationale: polyphagia
depletion of cellular stores of carbs, fats, and protein results in cellular starvation and a corresponding increase in hunger
clinical manifestation and rationale: weight loss
occurs because of fluid loss in osmotic diuresis and the loss of body tissue as fat and proteins are used for energy as a result of the effects of insulin deficiency
clinical manifestation and rationale: fatigue
metabolic changes result in poor use of food products contributing to lethargy and fatigue; sleep loss from severe nocturia also contributes to fatigue
clinical manifestation and rationale: recurrent infections (e.g. boils and carbuncle; skin infections) and prolonged wound healing (T2DM)
growth of microorganisms is stimulated by increase glucose levels; impaired blood supply hinders healing; decline in immune protection
clinical manifestation and rationale: genital pruritus (T2DM)
hyperglycemia and glycosuria favor fungal growth; candidal infections; resulting in pruritus are common presenting symptoms in women
clinical manifestation and rationale (T2DM): visual changes
blurred vision occurs as water balance in the eye fluctuates because of elevated BG levels; diabetic retinopathy is another cause of visual loss
clinical manifestation and rationale (T2DM): paresthesias
common manifestations of diabetic neuropathies
