Patho of DM Flashcards
Diabetes- Overview & basics of pathology
T1 v T2
role of obestiy
Obesity
- state of hyperinsulinemia
- normal glucose and glucagon levels - but these “normals” cant be held forever
Diabetes
- a syndrome of insulinin deficency: relative or absloute
Type 1 DM
- generally juvenile onset
- insulin requiring disease due to autoimmune destruction of the beta cells in the pancrease- inability to secrete ANY insulin
Type 2 DM
- “older” disease’ obese individuals
- a loss of the acute response to insulin
- or the acute response is retained, but other factors deminish it due to obesity & realted issues
Type 1 DM
- characterisitcs of the disease process
Overview
- inability to produce insulin: leads to hyperglycemia
- auto-immune destruction of the beta cells
- hyperglycemia in the absence of insuin: no glucose to the cells = so the cells think they’re starving
- trigger the cells to begin the process of glucose production through other means: leads to ketoacidosis from byproducts of breakdown
Complications
- frequent renal issues
- can result in ocular complications: neovascularization
Type 1 DM
Etiology & pathogenesis
Etiology
- role of genetics: not crazy strong, but plays a role to some extent
- found earlier on: younger age: age of dx. peak at 14 females peak earlier; males later
- viruse and seasonal relation: recent history of viral infection (coxasckie, mumps, measles) & early spring
- inflammation & immunologic relation: at time of dx. the beta cells/islets are inflammed & 80% have antibodies present
- sacndinavia and sardinia = larger prevelence
- lease in ages
Type 1 DM
role of inflammation & immune response
Inflammation
- at time of dx. insulinitis detected: attack on the beta cells
- Insulinitis: when beta cells fail to adequatly adapt to increasing insulin demand
- cytokines, IL-1, amyloid deposits and fiberosis occuring
Presence of Antibodies
- glutamic acid decarboxylase: GAD-65 ab.
- some target Beta cells specifically
- some can occur before the diabetes onset (as early as 10 years prior)
Immunological Factors
- T cells involved in the destruction: of beta cells
- cytokines involved
- oxygen and nitrie breakdown as well
all of these inflammatory and immunologica factors eventaully lead to 90% of teh beta cells destoryed: limiting their ability to release insulin in response to glucose & this creates the exogenous need for insulin in these pts.
Type 1 DM
Course of Disease Process
Complications
Course of Disease
- reduced life expectancy; death usually due to renal failure or CVD
- the amount of complications a pt. has is related to how well they can control: better control = better outcomes
better glycemic control = decrease microvascualt complications
better insulin control = better macrovascualr complications
(probably a combo of both)
Complications
- renal failure
- severe neuropathy
- proliferative retinopathy
- CAD
- CVA
diseases of the medium and small arteries
Type 1 DM
Treament
Continuous Glucose Monitoring
reliance on exogenous insulin
- self monitor of glucose
- injections of insulin & pump
- newer: loooking at beta cell transplant
Hallmark of treatment = insulin injections 3+ daily; or subcut. pump of inuslin = goal is to get as close to physiological release of insulin as possible
Downsides
- cost
- weight gain: becuase increaseing insulin = increase glucose into cells to use
- hypoglycemia: if give too much
- requires a lot of pt. control and effort to control
Basal/Bolus Thearpy
- longer acting insulin (glargine) gives the baseline of insulin needs
- faster acting: lispro, aspart give the bolus dose needed after meals
Basal Insulin
- a continued infusion (approx. 1/2 total need)
Bolous Insulin
- given to cover food and to correct higher glucose reads
Continuous Glucose Monitoring (CGM)
- permits measuring of the glucose in a continuous fashon: but not entirely able to replace the blood glucose checks
- Neagtives: risk of hyperglycmies and nocturl hypoglycemia
Role of Pancreatic Transplants in Type 1 DM
can be coupled with renal transplants
Iselt Cell Transplant: can be problematic as its effective for first 2 years then decreases significantly; still requires life-long immunosup. becuase its a transplant
Type 1 DM
SUmmary of Patho and susequent problems
hyperglycemia patho
ketonemia patho
severe metabolic acididosis patho
no insulin = no ability to mobililze the GLUT4 transporters to the cells = no abiltiy to uptake glucose into cells = cells starve & resort to using other ways to make glucose (using fat, protein metabolism) = increase appetite = increases sugar in the blood = hyperglycemic
Giving inuslin
- promotoes glycogen storage of the glucose
- will stop the process of glucogenesis in the liver
- inhibit glucagone secretion: which is only stimualted with the lack of insulin
In severe hyperglycemia
- the blood is hyperosmolar: too much sugar
- glucosuira: glucose in urine becuase max reabsrb is met.
- polyuria: excess peeing because as glcose spills it daraws water with it
- excessive thirst from this as a result
Ketonemia
- increase lipolysis creates ketone bodies as byproducts & decreases the amoutn of fat and triglycerides
- FFAs= –> acetyl coA = eventaully acetoacetate, beta hydroxybuteric acid
Severe metabolic acidosis
- H+ from teh acids is neutralzied by bicarbs until its overwhelemd in teh system
- then = H+ increased in the serum
- bodily response is to respiration pick up (Kussmaul breathing)
- water loss, lose of Na + and K+ due to osmotic diuresis
- dehydration due to lack of electrolytes
Type 1 DM
DKA
treatment
acidosis due to ketone production within the body resulting in a metabolic acidosis
- hypovolemic
- hypotensive
- hyperosmolar urine
Treatment
- FLUIDS
- insulin
- alkali to reduce the acidosis
- parenteral water, Na+ and K+ repletion
Type 2 DM
etiology: physiological
secretory patterns of insulin
lipid role
insulin resistance
Etiology
- complex pathophys.
- variabel hyperglycemia
- beta cell probelms
- significant abnormal response to insulin secretion at the target cells
Changes in the Secretory Patterns
- phase 1: the immediate release of stored insulin from the Beta cells is lost
- phase 2: production and subsequent release is decreased
Changes in Lipid amoutn impact secretion
- long term expsoure to lipids seems to decrease the insulin release response and release
Insulin Resistance
- the inability of insulin target cells to respond to the insulin produced within the body = triggers an over production of insulin to “get the signal across” but ends up leading to a downregulation of the insulin receptors on these cells becuase theyre overwhemled by the amoutn of insulin
Type 2 DM
Role of metabolic syndrome
role of HTn
a variety of conditions which are associated with insulin resistance = leading to diabetes
- obestiy
- hypertension
- hyperlipidemia
- hyperureicemia
- sedintary lifestyle
Metabolic Syndrome
- major player in the insulin resistance pattern
- a compensatroy insulinemid (increase) occurs
- high serum triglycerides
- low HDL
- increase uricemia
- increase coag. factors
Role of Hypertension & T2DM
- insulin stimulates endothelian 1 production on the vascualr wall = this is a potent vasoconstrictor = increase blood pressure
- with continued insulin = this continues
- targeting endothelin receptors has shown to decreased insulin resistance in studies
Type 2 Dm
Etiology
inheritance
obesity
hyperglycemia
Inheritance
- a stronger genetic relation than first thought
- autosomal pattern of inheritance
- native and pacific islanders with higer level s
obesity
- upper body segment: apple pattern most associated with risk
- lower body segmenet: pear pattern less assocaited
Etiolgoy of all factors
- genetic predisposition results in increased risk of obesity, insulin resistance patterns and deranged insulin release from the pancreas over time
- these patterns increase insulin in the blood, but a decreased ability to uptake glucose and respond to the insulin
- this leads to hyperglycemia
- lack of insulin leads to increased hepatic glucose (beacuse it thinks cells arent getting any food) = adds to the high glucose
Stages of T2Dm
early
middle
late
early (prediabetic)
- hyperinsulinemia
- reversible stagge with WEIGHT LOSS!!!
- lab test will appear normal at this time: body is able to compenstate
- (exercise directly upregulates insulin receptors)
middle
- insulin secretion decreases
- gradual failure of the pancreas with inability to secrete
- blood glucose tests abnormal
late
- beta cells become exhusted: insulin deficent continues
- lab tests abnormal
- generlaly: this is the point at which exogenous insulin is needed
Risk Factors for T2DM
course progression of the disease
- insulin resistances (30 mins postpradial)
- increased age
- obestiy
- fat distribution (apple shape)
- physical inactivity
- hyperinsulinemia
Course progression
- diagnosed later in life
- juvinile obesity= increased early age of dx.
- progression of disease related to their ability to contrl
Management of T2DM
- reduce weight: 5-10% is critical
- oral agents: help to decrease insulin resistance & increase insulin release
- use of exogenous insulin in later stages
- exercise can reduce insulin resistance
