Diabetes 1-Endocrin

Front 1

glucose homeostasis

Back 1

-liver-->homeostat
-in well fed state: liver net user of glucose, and converts it to glycogen for future use
-in post-absorptive state: liver is the net producer of glucose by breaking down stored glycogen, gluconeogenesis

Front 2

absorptive phase

Back 2

-within 3-4h of food ingestion
-source of glucose: exogenous carbs
-insulin high, glucagon low time for E storage

Front 3

post absorptive phase

Back 3

-5-6 h after start of meal
-source of glucose: liver
-initially, glycogen breakdown
-later, gluconeogenesis
-insulin low, glucagon high: time for E release

Front 4

pancreas and blood sugar regulation

Back 4

-islet of langerhans- 2% of pancreas
->80% of pancreas: Exocrine pancreas
Alpha cells: glucagon (inc bl sugar)- CATABOLIC
Beta cells: insulin (dec blood sugar)- ANABOLIC
Delta cells: somatostatin; stops glucagon and growth hormone, dec blood sugar

Front 5

Insulin

Back 5

-ANABOLIC HORMONE
-increased synthesis of protein, glycogen and lipogenesis
-increased peripheral glucose utilization: inc glucose entry into cells, increased glycolysis, inc glycogen synthesis
-decreased hepatic glucose output: dec gluconeogensis, dec glycogen breakdown
-polypeptide: 2 chains connect by disulfide bond
-C peptide: a measure of endogenous insulin production
-half life in circulation: 3-5min
-50% removed by 1st pass in liver

Front 6

insulin effects on liver, muscle, adipose tissue

Back 6

Liver: promotes anabolism; glycogen, protein, triglyceride synthesis; inhibits catabolism
Muscle: promotes glycogen and prot syntehsis; inhibits glycogenolysis
Adipose tissue: promotes triglyceride synthesis and storage and inhibits lipolysis

Front 7

effects of insulin (timing)

Back 7

Rapid: inc transport of glucose, aa, and K into insulin sensitive cells
Intermediate:
-inc prot synthesis
-inc glycogen synthesis
-inc glycolysis
-dec glycogen breakdown
-dec gluconeogenesis
Delayed: inc mRNA for lipgenic emzymes

Front 8

insulin secretion

Back 8

-basal insulin secretion
-stimulated insulin secretion
-GLUCOSE: biphasic response-
Early Phase: Release of pre-formed Insulin by B cells
Late Phase: Synthesis & release of insulin by B cells

Front 9

regulation of insulin release

Back 9

-stimulants of insulin release: glucose, sulfonyureas, vagal stimulation
-amplifiers of glucose dependent insulin release: enteric hormones, B-adrenergic stim
-inhibitors of insulin release: somatostatin, a-adrenergic stim, drugs (diazoxide, phenytoin)

Front 10

insulin receptor

Back 10

-membrane glycoprotein
-a-subunit: extracellular domain: insulin binding
-b-subunit: cytoplasmic domain: tyrosine kinase; autophosphorylates on ligand binding leading to downstream events

Front 11

glucose transporters

Back 11

GLUT 1: All Tissues; Basal Glucose Uptake by tissues (esp Blood brain barrier)
GLUT 2: All Tissues (esp Neurons); High affinity for glucose
GLUT 3: Liver, Intestine, Kidney;? B-cells
GLUT 4: Skeletal muscle & Adipose tissue; sequestered intracellularly; translocates to cell membrane after insulin signalling

Front 12

glucagon

Back 12

-A cells of islets
-catabolic hormone
-G- protein coupled receptr --> inc cAMP
-inc glycogenolysis
-inc gluconeogenesis
-inc lipolysis
-inc ketogenesis

Front 13

counter-regulatory hormones

Back 13

-counter insulin effects on glucose metabolism: prevent hypoglycemia, raise blood glucose
1. glucagon
2. cortisol
3. epinephrine
4. GH

Front 14

hypoglycemia causes

Back 14

1. inc insulin
2. dec counter-reg homrones: adrenal insufficiency, dec glucagon and Epi, hpothyroidism

Front 15

hypoglycemia sx

Back 15

1. palpitations
2. shakiness, jitteriness
3. inc sweating
4. confusion
5. seizures, coma

Front 16

whipples triad

Back 16

1. symptoms consistent with hypoglycemia
2. low blood sugar at time of sx
3. sx relieved on correcting hypoglycemia

Front 17

Fasting hypoglycemia

Back 17

1. insulinoma
2. drugs
3. liver dz
4. kidney dz
5. sepsis
6. lack of coutner-reg hormones
-worrisome!

Front 18

postprandial hypoglycemia

Back 18

-post gastric surgery
-reactive hypoglycemia

Front 19

evaluation of hypoglycemia

Back 19

-check serum glucose and insulin at time of sx
-If Insulin elevated in face of hypoglycemia, insulin-induced hypoglycemia --> C peptide high: insulinoma, exogenous use of sulfonylurea; Low: exogenous insulin use

Front 20

Insulinoma

Back 20

-islet cell tumors
-rare
-87% single benign tumor
-7% multiple benign tumor, 6% malignant tumor, 8% MEN 1 syndrome
-can be lethal
-FASTING hypoglycemia
-secrete large amts of insuline, pro-insuline, C-peptide
-Dx: 48h or 72 h Supervised Fast : ↑ Pro-insulin, C peptide, Insulin, in setting of LOW blood Glucose, AND Negative Sulfonylurea screen
-Rx: surgical

Front 21

drug induced hypoglycemia

Back 21

-insulin (c-peptide LOW)
-Sulfonylurea (C peptide elevated; blood or urine sulfonylurea screen positive)
-Pentamidine
-Ethanol
-Insulin or Sulfonylurea use may be surreptitious (Factitious Hypoglycemia)
-elderly pts, poor PO intake, chronic liver or kidney dz or hear failure
-Insulin level would be HIGH or inappropriately in the normal range in setting of hypoglycemia.
-Duration of hypoglycemia depends on the duration of action of the drug
You can confirm the diagnosis by measuring serum or urine for sulfonylureas

Front 22

hypoglycemia- history

Back 22

1. duration: each episode, prior episodes
2. seizure
3. coma
4. accidents due to hypoglycemia
5. fasting or postprandial
6. ? acess to insulin or DM meds

Front 23

reactive hypoglycemia

Back 23

1. gastric resection: Rapid absorption of carbs--->Insulin release delayed, and somewhat exuberant--->hypoglycemia
2. defect in 1st phase insulin response: delayed, and exuberant
-postprandial sx, esp after high carb mean
-in predisposed individuals, inc risk of DM in longterm
-often NO HYPOGLYCEMIA demonstatable
-often hx of anxiety, depression
-Rx: dietary modification; nibble rather than gobble, mixed carbs and protein, eliminated simple/refined carbs from diet

Front 24

Most common caue of hypoglycemia in diabetis is..

Back 24

1. insuline to carb mismatch
-too much insulin, too little carbs in the food
-gastroparesis
OR
2. increased exercise (ie dec insulin requirement)
-postpartum also
3. dec counter-reg homones
-addrenal insufficiency (schmidts syndrome)

Front 25

Facticious hypoglycemia

Back 25

-healthcare workers
-72 hr (or 48 hr fast)
-simultaneous C-peptide & pro-insulin along with the serum glucose and insulin
-surreptitious insuline intake: inc insulin, LOW c-peptide, LOW pro-insulin
-surreptitious sulfonlyurea ingestion

Front 26

hypoglycemia- sick appearing pt (with co-existing diseasE)

Back 26

1. starvation
2. anorexia nervosa
3. severe liver dz
4. chronic renal failure
5. isolated growth hormone deficiency
6. isolated corticotropin def
7. primary adrenal insuff
8. hypopituitarism
9. sepsis
10. drugs
11. glycogen storage dz
12. defects in aa and fatty acid metab
13. lage mesenchymal tumors

Front 27

hypoglycemia-healthy appearing pt (with co-exisiting dz)

Back 27

1. DM
2. drugs
3. dispensing error
4. ackee-fruit poisoning and undernutrition
5. alcohol
6. insulinoma
7. factitious hypoglycemia
8. intense exercise

Front 28

Classification of DM

Back 28

1. Type 1 DM: B cell destruction --> absolute lack of insulin
2. Type 2 DM: dual defect, insulin resistance and impaired insulin secretion
-gestational
-specific types: genetic defects of B cell function, genetic defect in insulin action, disease of exocrine pancreas, drug induced, rare syndromes

Front 29

Diabetes presentations

Back 29

-Asymptomatic: detected onroutine labs
-Acute hyperglycemic crisis: DKA, NKHS
-Classic sx: polyuria, nocturia, polydipsia, polyphagia, wt loss

Front 30

Making the diagnosis of DM

Back 30

1. symptoms of DX plus random plasma glucose >/= 200 mg/dL
or
2. FPG >/= 126 mg/dL
or 3. 2 hr PG during a 75-g OGTT >/= 200 mg/dL

Front 31

measures of hyperglycemia

Back 31

Random plasma glucose (RPG)—without regard to time of last meal
Fasting plasma glucose (FPG)—before breakfast
Oral glucose tolerance test (OGTT)—2 hours after a 75-g oral glucose drink
Postprandial plasma glucose (PPG)—2 hours after a meal
Hemoglobin A1c (A1C)—reflects mean glucose over 2–3 months
Fructosamine—reflects mean glucose over 1–2 weeks

Front 32

type 1 DM

Back 32

-beta cell destruction
-immune mediated
-idiopathic
-only 10% of all DM in N. America
-higher in whites
-absolute lack of insulin
-at least 80% of B cells destroyed before DM 1

Front 33

natural history of type 1 DM

Back 33

-genetic predisposision
-putative trigger
-insulinitis B-cell injury
-"pre" diabetes
-diabetes (clinical onset- only 10% of B-cell remain)

Front 34

clinical features of DM 1

Back 34

1. lean
2. juvenile onset (<40, often <20)
3. often NO FH
4. positive auto-AB
5. often acute onset: DKA, sometimes after acute viral illness
6. Ketosis prone: insulin dependent DM, need insuline to live, absolute def of insulin (low C-peptide)

Front 35

DM 1 tx

Back 35

-Insulin
-basal insulin: NEED BASAL INSULIN EVEN IF NPO; else, DKA----> Death
-prandial insulin
-best to replace insulin physiologically with basal-bolus insulin replacement with designer insulin analogs

Front 36

Basal insulin

Back 36

-control glucose production b/t meals and overnight
-nearly constant levels
-50% of daily needs
-insuline Glargine
-insuline Detemir

Front 37

Bolus insulin

Back 37

-limits hyperglycemia after meals
-immediate rise and sharp peak at 1 hr postmeal
-50% of total daily insulin requirement

Front 38

rapid acting insulin analogs

Back 38

-ideal for mealtime admin: prandial insulin
-quick in, quick out
-decreased risk of hypoglycemia later
-insulin Lispro,
-insulin Aspart
-insuline Glulisine

Front 39

insulin transport and storage

Back 39

-insulin is a small polypeptide
-very sensitive to temp
-must be refrigerated in storage, and preferable for transport
-a vial or pen of insulin in use may be left on 'room temp' for up to 4 wks
-vial: 1000 units (in 10 mL)
-insulin pen: 300 units (in 3 mL)

Front 40

insulin pumps

Back 40

-external insulin pumps
-CSII (continuous subcutaneous insulin infusion)
-program basal rates
-pt takes a bolus at meal times based on pts carb intake!!!
-Insulin Pump Management Requires an INTELLIGENT & MOTIVATED patient capable of FULLY PARTICIPATING in the overall plan of care

Front 41

insulin pump cont

Back 41

Pt has to:
1. check sugars 6-8 times daily
2. insert the infusion set every 3 days
3. take prandial insulin at EACH mel and DECIDE how much insulin to take at EACH MEAL
4. take correction dose insulin if sugars are elevated
-80 yr old pt with dementia: NOT A GOOD IDEA
-30 yr old schizophrenic pt: BAD IDEA!

Front 42

insulin pump in hospitals

Back 42

-IF intelligent motivated patient, alert, awake, and co-operative, and aware of their Insulin:Carb ratios, and correction factors: CONTINUE the insulin Pump
-let pt manage the pump
-Tell the staff to check sugars qac/qhs (If Eating) or q4-6h (as clinically appropriate), and LET the pt give CORRECTION dose insulin via the pump.

Front 43

insulin pump in hospitals cont.

Back 43

IF patient
Comatose
Sleepy/drowsy/intoxicated
Unable to or unwilling to fully co-operate with you
Then best to Discontinue the pump Temporarily AFTER giving the patient a dose of BASAL insulin (Glargine or NPH) AFTER close consultation with an Endocrinologist
-Do NOT STOP the pump before speaking with an endocrinologist
IF type 1 diabetic does not get their basal insulin even for a few hours, they will go into a DKA, and could potentially die

Front 44

inhaled insulin

Back 44

Safety issues:
Longterm inhalation of growth factor in the lungs: Need to monitor pulmonary function
Absorption: ? Consistent in those with pre-existing lung disease
NOT to be used in SMOKERS or those with pre-existing lung disease
Prandial Insulin
DISCONTINUED by Pfizer in 2008
Novo-Nordisk & Eli Lilly also stopped development of their inhaled insulin products

Front 45

pancreas replacement tranplantation

Back 45

-pancreas transplant: PK, PTA
-islet cell transpltan
-stem cell transplant