Diabetes Mellitus & Diabetic Ketoacidosis Flashcards
glucose utilization to generate ATP
- anaerobic glycolysi (Embden-Meyerhof cycle)
glucose = pyruvate + lactate - aerobic glycolysis (Krebs or TCA cycle)
glucose - CO2 + H2O
gluconeogenesis
non-sugar sources => glucose-6-phosphate
pyruvate, lactate, AAs, fatty acids => KETOSIS
hormonal control of glucose
insulin reduces blood glucose
- preproinsulin => proinsulin => insulin + (inactive) C peptide
- synthesis and cleavage within pancreatic B cells of islets of Langerhans
insulin antagonists …
increase blood glucose
- epinephrine, growth hormone, cortisol, thyroxine, intestinal hormones (ghrelin stimulates GH release)
stimulates insulin secretion after a meal
gastric inhibitory protein (GIP)
these cells on the islets of Langerhans produce insulin
pancreatic beta cells
destruction of beta cells result in:
- decrease/no insulin production
- no secretion into blood
- type I diabetes
a metabolic disorder characterized by presence of hyperglycemia due to defective insulin secretion, insulin or both
diabetes mellitus (DM0; 4 types based on cause) type I, II, gestational, specific ...
type I diabetes
- B cell destruction (insulin def)
- prone to ketosis
- autoimmune: Abs present in most or idiopathic
- onset at any age: 75% before 18 y/o
- ABRUPT onset of symptoms:
> polyuria
> polydipsia
> rapid weight loss (high [glucose] but can’t enter cells; gluconeogenesis so ketosis)
type II diabetes
- impaid insulin action
- [insulin] may be N, decreased, increased; not prone to ketosis
- predominant insulin resistance; relative insulin def
- OR predominant secretory defect with insulin resistance
- onset at any age; commonly after 40 y/o; emerging in teens and children
- onset of symptoms: obesity (poor diet, inactive lifestyle)
- 90%; more common; not insulin-dependent mostly
T or F. type I diabetes is 5-10% of incidences and all are insulin-dependent
T
gestational diabetes
- glucose intolerance with onset or first recognition of pregnancy (excludes diabetic women who become pregnant)
- unable to produce insulin required = hyperglycemia (placental hormones block action of insulin in mother)
- usually c lears after delivery
- increases risk of type teoo diabetes of mom later in life (esp. with marked hyperglycemia, obesity, or diagnosis prior to 24 wks)
specific types of diabetes due to other causes …
- underlying genetic defects: beta cell function, pancreatic diseases (CF)
- endocrine diseases (Cushing’s syndrome, acromegaly)
- other genetic conditions: Down’s syndrome, Klinefelter’s syndrome
consequences of gestational diabetes to baby
mother’s insulin does not cross body but glucose does so baby pancreas just make more insulin = extra E stored as fat = macrosomia (larger baby)
- complications in delivery
- higher risk of breathing probs
- neonatal hypoglycemia
- increased risk of obesity in childhood and type II DM in adulthood
why use HbA1c to diagnose diabetes mellitus?
- patient preparation (not fasting)
- HbA1c methods standardized
- HbA1c better for long-term hyperglycemia
- correlates better with compilation
- minimal influence from Hb variants
glycated form of HbA0
HbA1
quantitaation of HbA1c
- ion exchange HPLC: detects different Hbs, HbF slower glycation rate; measure total glycated Hb/non-glycated Hb
- HPLC STD: calibration std, chromatographic peak (IFCC: glucose adduct to the valine of the beta chain of Hb)
quantitaation of HbA1c
- ion exchange HPLC: detects different Hbs, HbF slower glycation rate; measure total glycated Hb/non-glycated Hb
- HPLC STD: calibration std, chromatographic peak (IFCC: glucose adduct to the valine of the beta chain of Hb)
HbA1c-specific immunoassays: MOST COMMON, Abs to 4-1o AA on N-terminal valine; some methods affected by mutation in HbS or HbC wwhoch may be close to N-terminus
this monitors glycemic control
glycated hemoglobin
- every three months (treatment goal <7.0%)
- reflects blood glucose over previous 90 days; rBC lifespan 120 days
- mean values predict progression of complications = retinopathy, nephropathy, neuropathy
- major test used to monitor glycemic control
why is glycated Hb the major test used to monitor glycemic control?
- reinforce self-glucose monitoring
- reassure patient program is working
- evaluate newly diagnosed diabetocs
- question patient or glucometer reliability
T or F. hyperglycemia happens with just diabetes
F!
- Cushings syndrome
- Phepochromocytomas of the adrenal medulla
- primaaary aldosteronism
- hyper or hypothyroidism
- acromegaly (GH antagonist)
- acute pancreatitis
- cerebral lesipoons
- CO poisoning
- lipoproteinemia
- liver disease
hypoglycemia
- pancreative islet cell tumor (too much insulin produced)
- insulin overdose
- inefficiency in antagonist to insulin hormones
- prolonged carb deprivation
- certain non-insulin producing tumors
diagnosing hypoglycemia
- fasting hypoglycemia: stress testing: prolonged fast (72 h, done in hospital); random glucose measurement
- postprandial hypoglycemia: measures blood glucose wen symptoms occur and relief of symptoms when glucose values return to normal > alimentary - dumping syndrome > sub-clinical diabetes mellitus > alcoholism > functional hypoglycemia
idiopathic hypoglycemia of infancy
occurs within 72h of birth: tremors, twitching
leucine sensitivity
- usualy within first 2 y of life and resolved by 5 y/o
- leucine-roch food => overproduction of insulin
nesidioblastosis
pancreatic islet cell hyperplasia
galactosemia
inborn error: galactose does NOT get made into glucose
ketosis
- onset age 1.5-5y, disappears by age 10
- prolonged lack of food, or low CHO diet
- more common in males of lower birth weight and kids in low socioeconomic groups
neonatal and early childhood hypoglycemia (5)
- idiopathic hypoglycemia of infancy
- leucine sensitivity
- nesidioblastosis
- galactosemia
- ketosis
diabetic ketoacidosis (DKA)
- acute life-threatening medical emergency due to an absolute or relative deficiency in insulin arising from:
> failure of endogenous insulin secretion (new onset)
> inadequate administration of insulin
> increased requirement for insulin
major threat: osmotic diuresis, dehydration
no glucose enters cells = increase in blood glucose
clinical features of ketoacidosis
- polyuria
- polydipsia
- weakness
- nausea, vomitting
- dry skin
- fruity sweet odour on breath (acetone)
factors contributing to development of ketoacidosis
- 40% infection
- 25% missed insulin dose
- 15% previously unknown, new onset DM
- 20% other causes:
> insulin resistance
> emotional/physical trauma
> insufficient fluid intake in hot weather
> heart attack or store
> alcohol or drug abuse
> pancreatitis
> thyroid crisis
most important test or indication of diabetic ketoacidosis
elevated beta hydroxybutyrate = replaced other tests
test choice for diagnosis of DKA
beta hydroxybutyrate
> specifity and sensitivity supeiror to other methods
> test availability on instments has improved
> point of care instrument available
for a comatose patient with possible diabetes. perform serum beta-hydroxybutyrate test =
- positive = diabetic ketoacidosis
- negative = consider other causes
