2/8 Diabetes Clinical Pathophys - Schneider Flashcards
diabetes mellitus
definition
syndrome characterised by hyperglycemia and other metabolic abnormalities resulting in associated neurologic, small, and large blood vessel complications
- fasting glucose > 126 on 2 occasions (not under stress, 8 hr fast)
- casual glucose > 200 w classic sx
- HbA1c > 6.5%
types of DM
Type 1
- idiopathic
- autoimmune (target: beta cells of islets of Langerhans)
Type 2
- dual defect (dont make enough insulin AND dont respond to insulin)
- gestational
- type “3”
pancreatic destruction
- pancreatitis
- rubella; CMV
- cystic fibrosis
- hemochromatosis
type 1 DM
- absolute insulin def
- antibodies against
- insulin
- islet cells
- glutamic acid decarboxylase
- prevalence in younger pop
- relatively weak genetic predisp
- more common in N Euro groups
- envi stimuli: virus, cow’s milk
- acute onset of sx
- ketosis-prone
why does DM1 present with acute onset of sx?
- we have 10x the number of beta cells we need
- when antibodies start to form and take out beta cells, insulen levels slowly drop, but not at a rate or magnitude that leads to sx quickly
- instead, do fine until the hit critical insulin level, at which point glucose shoots up → acute onset of sx
“honeymoon phenomenon”
DM1 phenomenon where kids whose beta cells and insulin levels have been dropping and are around the critical level are asymptomatic UNTIL…
get sick → epi secretion → insulin decreased → dx of diabetes
later on, get well → diabetes disappears, seems “cured”
until later on in life when it reappears and now kid has lifelong DM1
reason? were hovering on that critical insulin point
type 2 DM
dual defect
- impaired insulin synthesis (but still have SOME capability - unlike type 1)
- insulin resistance
- tends to become evident in older pt
- strong genetic component (prob polygenic)
- more common in non-Caucasian ethnic groups
strong prevalence?
- Pima Native Americans
- Indians
devpt of DM2
- pts prob born with abnormal insulin sensitivity
- early on? no prob → pancreas compensates by putting out more insulin → hyperinsulinemia
- over time, weight gain/central obesity (often in adolescence)
- pts have abnormal aerobic exercise capacity
- might be mito dysfx
types of obesity
1. benign obesity
- gynoid
- normal abd fat stores (ex. hip)
- often childhood onset
- few assoc metabolic abnormalities
2. metabolic obesity = android obesity
- android
- increased abd fat stores
- adult weight gain
- multiple assoc metabolic abnormalities
fat repartitioning
in diabetics, excess calories → fat in places where it doesnt belong (ex. belly fat)
fat accumulates and gets redistributed INTRACELLULARY into liver and skeletal muscle
- intracellular fat causes insulin resistance
metabolic syndrome
cluster of CV risk factors related to insulin resistance/hyperinsulinemia prior to onset of overt diabetes
- HTN
- dyslipidemia (low HDL)
- PCO
- impaired fibrinolysis
- CVD
all related to insulin resistance and obesity
link between hyperglycemia and glucose tox
hyperglycemia can partially paralyze the beta cells → causes it to lose ability to make insulin in short term
hyperglycemia hit skeletal muscle cells as well → causes insulin resistance to become worse
hyperglycemia sets off vicious cycle
causes of hyperglycemia in diabetes
symptoms of hyperglycemia
incr glucose
- incr hepatic glucose production
- impaired glucose disposal
impaired insulin secretion
insulin resistance
3Ps - POLYURIA, POLYDIPSIA, POLYPHAGIA
weight loss, blurred vision, muscle fatigue and cramps, paresthesia
acute metabolic decompensation
2 conds
- DKA: younger, DM1, not very high glucose
- NKHC: _non ketotic hyperglycemic com_a: elderly pateints, super high glucose
both:
- decr insulin conc or action
- incr glucagon
- incr catecholamines
DKA vs hyperosmolar state
severity of insulin deficiency
- need to have almost no insulin to develop DKA
- fat metab doesnt require a lot of insulin to regulate it → if youre in DKA and youve got ketones, youve lost what little you needed to handle your fat metab too
dehydration
- dehydration → hyperosmolality → blocks ketone body production
therefore. ..elderly patients are “protected” from DKA by minimal insulin stores (that are still capable of handling fat metab) and tendency towards dehydration
relative resopnsiveness to metabolic pathways to insulin
- potassium
- lipolysis
- hepatic glucose output
- peripheral glucose disposal
severe diabetic complications
MICROVASCULAR
- retinopathy
- nephropathy
- neuropathy
*what do they all have in common? dont require insulin!
MACROVASCULAR
- stroke
- heart disease
- periph vascular disease
early changes in diabetes
(vasc)
- endothelial dysfx
- incr bloodflow
- thickening of basement membrane
- incr permeability of bm (so protein leaks out)
mononeuropathy multiplex
microinfarction of small vessels to nerve
hits cranial nerves, can cause radiculopathy
autonomic neuropathy
impacts survival
etiology
- sorbitol and fructose accumulation
- endothelial dysfx
- glycerol 3P
- FFA
- non-enzymatic glycosylation
non enzymatic glycosylation
virtually any protein with an ammonia group can be glycosylated by glucose nonenzymatically → Amadori pdt
- alters structure and fx
- measured in HbA1C
diets for DM
type 2: WEIGHT REDUCTION
exercise and DM2
in mild DM2, exercise restores insulin sensitivity
helps prevent CVD
oral pharma tx
- insulin secretagogues
- stimulate insulin secretion
- negs: hypoglycemia, weight gain
- GLP1
- gut hormone: inhibits appetite, stimulates insulin secretion, inhibits glucagon secretion
- biguanides
- not sure how it works…maybe inhibits hepatic glucose prod?
- blocks AMP kinase
- alpha glucosidase inhibitors
- block sucrase in gut so dont absorb glucose when you eat
- negs: gas!!!
- insulin sensitizers
- repartition fat: from liver/muscle → butt
- SGT2 blockers
- causes leakage of glucose in urine
effect of drugs on CV events
