Diabetes Mellitus & Diabetic Ketoacidosis

Question 1

glucose utilization to generate ATP

Answer 1

• anaerobic glycolysi (Embden-Meyerhof cycle)
  glucose = pyruvate + lactate
• aerobic glycolysis (Krebs or TCA cycle)
  glucose - CO2 + H2O

Question 2

gluconeogenesis

Answer 2

non-sugar sources => glucose-6-phosphate

pyruvate, lactate, AAs, fatty acids => KETOSIS

Question 3

hormonal control of glucose

Answer 3

insulin reduces blood glucose

• preproinsulin => proinsulin => insulin + (inactive) C peptide
• synthesis and cleavage within pancreatic B cells of islets of Langerhans

Question 4

insulin antagonists …

Answer 4

increase blood glucose

- epinephrine, growth hormone, cortisol, thyroxine, intestinal hormones (ghrelin stimulates GH release)

Question 5

stimulates insulin secretion after a meal

Answer 5

gastric inhibitory protein (GIP)

Question 6

these cells on the islets of Langerhans produce insulin

Answer 6

pancreatic beta cells

Question 7

destruction of beta cells result in:

Answer 7

• decrease/no insulin production
• no secretion into blood
• type I diabetes

Question 8

a metabolic disorder characterized by presence of hyperglycemia due to defective insulin secretion, insulin or both

Answer 8

diabetes mellitus (DM0; 4 types based on cause)
type I, II, gestational, specific ...

Question 9

type I diabetes

Answer 9

• 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)

Question 10

type II diabetes

Answer 10

• 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

Question 11

T or F. type I diabetes is 5-10% of incidences and all are insulin-dependent

Answer 11

T

Question 12

gestational diabetes

Answer 12

• 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)

Question 13

specific types of diabetes due to other causes …

Answer 13

• underlying genetic defects: beta cell function, pancreatic diseases (CF)
• endocrine diseases (Cushing’s syndrome, acromegaly)
• other genetic conditions: Down’s syndrome, Klinefelter’s syndrome

Question 14

consequences of gestational diabetes to baby

Answer 14

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

Question 15

why use HbA1c to diagnose diabetes mellitus?

Answer 15

• patient preparation (not fasting)
• HbA1c methods standardized
• HbA1c better for long-term hyperglycemia
• correlates better with compilation
• minimal influence from Hb variants

Question 16

glycated form of HbA0

Answer 16

HbA1

Question 17

quantitaation of HbA1c

Answer 17

• 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)

Question 17

quantitaation of HbA1c

Answer 17

• 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

Question 18

this monitors glycemic control

Answer 18

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

Question 19

why is glycated Hb the major test used to monitor glycemic control?

Answer 19

• reinforce self-glucose monitoring
• reassure patient program is working
• evaluate newly diagnosed diabetocs
• question patient or glucometer reliability

Question 20

T or F. hyperglycemia happens with just diabetes

Answer 20

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

Question 21

hypoglycemia

Answer 21

• pancreative islet cell tumor (too much insulin produced)
• insulin overdose
• inefficiency in antagonist to insulin hormones
• prolonged carb deprivation
• certain non-insulin producing tumors

Question 22

diagnosing hypoglycemia

Answer 22

• 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

Question 23

idiopathic hypoglycemia of infancy

Answer 23

occurs within 72h of birth: tremors, twitching

Question 24

leucine sensitivity

Answer 24

- usualy within first 2 y of life and resolved by 5 y/o | - leucine-roch food => overproduction of insulin

Question 25

nesidioblastosis

Answer 25

pancreatic islet cell hyperplasia

Question 26

galactosemia

Answer 26

inborn error: galactose does NOT get made into glucose

Question 27

ketosis

Answer 27

- 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

Question 28

neonatal and early childhood hypoglycemia (5)

Answer 28

- idiopathic hypoglycemia of infancy - leucine sensitivity - nesidioblastosis - galactosemia - ketosis

Question 29

diabetic ketoacidosis (DKA)

Answer 29

- 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

Question 30

clinical features of ketoacidosis

Answer 30

- polyuria - polydipsia - weakness - nausea, vomitting - dry skin - fruity sweet odour on breath (acetone)

Question 31

factors contributing to development of ketoacidosis

Answer 31

- 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

Question 32

most important test or indication of diabetic ketoacidosis

Answer 32

elevated beta hydroxybutyrate = replaced other tests

Question 33

test choice for diagnosis of DKA

Answer 33

beta hydroxybutyrate > specifity and sensitivity supeiror to other methods > test availability on instments has improved > point of care instrument available

Question 34

for a comatose patient with possible diabetes. perform serum beta-hydroxybutyrate test =

Answer 34

- positive = diabetic ketoacidosis | - negative = consider other causes