Lecture 16: Diabetes Flashcards
Polydipsia
thirst
Polyuria
frequent urination
Polyphagia
inc appetite
Diabetes diagnostic criteria
just one of the following:
-A1C > 6.5%
-FPG > 126 mg/dL
-2h PG > 200mg/dL
-random PG > 200 mg/dL w sx
Type I diabetes (IDDM)
-10% of DM
-glucose intolerance
-no insulin secretion
-almost no pancreatic beta cells
-need exogenous insulin
-ketoacidosis tendencies
Type I Diabetes onset
-early (age 12)
-autoimmune response that kills pancreatic B cells
-might be triggered by viruses, chemicals, etc in predisposed individuals
-often no family hx
-aka juvenile onset DM (JODM)
Loss of B-cell mass (BCM) in type I
-gradual loss
-FPG normal until 70% of BCM lost
-C-peptide is a maker for insulin secretion when injected insulin present
C-peptide
-part of insulin processing
-C-peptide present = little bit of BCM left
-once gone there’s no more BCM
Stage 1 type 1 diabetes BCM
-ICA and IAA become positive (autoantibodies)
-normal glucose stimulated insullin release
-BCM declines but FBG stays same*
Stage 2 type 1 diabetes
-gradual loss of insulin release
-abnormal OGTT
-FBG starts to increase* (about 70% of BCM loss)
Stage 3 type 1 diabetes
-BCM depletes
-FBG spikes
-C-peptide present vs absent?
-overt diabetes
-OGTT will detect hyperglycemia
Autoantigens associated w type I 1A-2 (islet antigen)
-57% sensitivity = 57% will develop
-99% selectivity = 99% have Abs
-presence of ANTIBODIES against B cell proteins is a risk factor for type 1
-IA-2, ZnT-8, GAD65, Ca1.3, VAMP-2
Type 2 Diabetes
-non-insulin dependent
-insulin resistance or not enough secretion
-NIDDM
-family history present
-non-obese vs obese
Non-obsese NIDDM
-10%
-onset < 25 (MODY)
-low insulin secretion
-mutations in specific proteins
Obese NIDDM
-80%
-fastest growing type of DM around the world
-onset > 35
-low insulin secretion for body mass
-insulin resistance/decreased BCM
Consequence of lack of insulin
-Hyperglycemia
-Glucosuria
-Hyperlipidemia
-Uninhibited glucagon
Hyperglycemia
-dec glucose uptake in cells where uptake is insulin dependent (skeletal muscle uptakes the most)
-dec glYcogen synthesis (stored glucose in liver)
-inc conversion of aas to glucose (inc gluconeogenesis (inhibited by insulin))
Glucosuria
-glucose in urine
-lose more water = dehydration and polydipsia
Hyperlipidemia
-inc fatty acid mobilization from fat cells
-inc fatty acid oxidation = KETOACIDOSIS
-ketone bodies (acetoacetate, hydroxybutyrate)
-unchecked bc low insulin
Uninhibited Glucagon
-inc levels in the presence of inc blood glucose levels
-opposite of insulin
-stimulates release of glucose from liver
=hyperglycemia
Complications of low insulin
- CV: angiopathies (blood vesels)
- Neuropathy: inc use of polyol pathway (aldose reductase) (uses all NADPH which cant be used for oxidative protection)
-water accumulation in neurons and reduced protection from oxidative damage (neuropathies/nerve pain)
-Nephropathy: changes to renal vasc and glomerular basement membrane (kidneys/nephropathies)
-occular: cataracts, microaneurysms, (disrupted blood flow) hemorrhage (retinopathies)
-inc susceptibility to infections
Past goals of insulin therapy and monitoring
-reduce symptoms: polyuria, dehydration, ketoacidosis
Current goals of insulin therapy
-keep AVERAGE BG levels < 150 mg/dL
-prevent/delay onset of complications
-increased risk of hypoglycemia
-A1C < 6 or 7
why risk hypoglycemia to tx diabetes?
-retinopathy risk increases over A1c
-better to keep it low
-hyperglycemia worse
