Diabetes

Question 1

type 1 diabetes

Answer 1

insulin-dependent

insulin is absent or very low (catabolic disorder)…need exogenous insulin

autoimmune disorder - islet cell antibodies (Against glutamic acid decarboxylase) and insulin antibodies

juveniles with rapidly progressing symptoms

generally not obese, may present with diabetic ketoacidosis initially

Question 2

type 2 diabetes

Answer 2

non-insulin dependent

obese (adult onset)

peripheral insulin resistance with an insulin secretory defect (need both to be type 2 diabetes instead of just being obese)

happens when insulin resistance overwhelms the ability to compensate in insulin levels

since retain ability to retain insulin secretion to a certain extend….they normally do NOT develop ketoacidosis if stop insulin treatment….which is not necessary if make lifestyle changes

Question 3

maturity onset diabetes of the young (MODY)

Answer 3

form of type 2

affects many generations of the same family with an onset of individuals younger than 25

generally have impaired beta cell function

can be detected with gene mutation assays

Question 4

gestational diabetes

Answer 4

glucose intolerance of variable degree with an onset or first recognition during pregnancy

easy for pregnant women to develop (interprandial) hypoglycemia between meals and during sleep…since fetus is hoging

rise in placental steroid and peptide hormones –> confer inceasing tissue insulin resistance –> raises demand for insulin

hyperglycemia occurs maternally than fetally if insulin secretion cannot keep up –> very bad for fetus –> HTN cardiac remodeling etc

Question 5

prediabetes

Answer 5

110-125 mg/dL glucose fasting

140-200 oral glucose tolerance test

increased risk for macrovascular disease and eventually developing diabetes

**confused with metabolic syndrome

Question 6

metabolic syndrome (syndrome X)

Answer 6

insulin resistance syndrome

= group of metabolic risk factors in a person

• obesity
• high glucose
• atherogenic dyslipidemia
• HTN
• insulin resistance or glucose intolerance
• prothrombotic state
• proinflammatory state

3+ of these = high risk to get diabetes

Question 7

fasting blood glucose

Answer 7

most common blood test for glucose

normal = 70-110 mg/dL

Question 8

oral glucose tolerance test (OGTT)

Answer 8

measures metabolic response to a carb challenge

impaired glucose tolerance = remain at 140-200

> 200 = diabetes after 2-3 hours

Question 9

Hb1AC test

Answer 9

> 6.5% diabetic

normal = 5.5

between = prediabetic

best for type 2….only use in type 1 if suspected even though other symptoms are not present

Question 10

type 1 diabetes incidence and risk factors

Answer 10

ethnicity = most common in non hispanic whites than blacks

gender = more common in men

age = diagnosed in children 4 years and older, peak at 11-13 years

most common metabolic disease in childhood

Question 11

type 2 diabetes incidence and risk factors

Answer 11

ethnicity = everything besides non hispanic whites are most prevalent

gender = equal

age = older than 45 years

family history of a first degree relative

history of impaired glucose tolerance

polycystic ovarian syndrome (results in insulin resistance)

HTN

history of gestational diabetes or birthing a kid >9 lbs

Question 12

effects of type 1 diabetes on metabolism

Answer 12

(-) insulin secretion….insulin:glucagon ratio remains low even in the presence of glucose in blood

body will always respond as if it was starving

primary issue = glucose is not taken up into cells (GLUT-4 is insulin dependent)

LIVER: Low insulin –>
- no glycolysis
(+) gluconeo and glycogenolysis
leads to secretion of glucose into blood –> hyperglycemia
ALSO
beta-ox builds up acetyl-CoA which is converted to ketone bodies –> ketoacidosis

also increased availability of FAs decreases use of glucose –> adds to high glucose levels
low insulin –> uncontrolled use of hormone sensitive lipase in adipose tissue

Question 13

effects of type 2 diabetes on metabolism

Answer 13

insulin:glucagon ratio is higher than in type 1

glucose is not readily taken up in muscle and adipose tissue due to insulin resistance

liver gluconeo and glycogenlysis are upregulated

–> hyperglycemia occurs

lipid metabolism effects are changed less than in type 1
- insulin production is enough to blunt ketoacidosis

instead FA mobilized in liver are still packaged in VLDLs –> hyperTGemdia

Question 14

consequences of diabetic ketoacidosis

Answer 14

ketone bodies deplete ECF and IC buffers (HCO3-)

hyperglycemia –> induces osmotic diuresis –> dehydration and hypokalemia

glucose is also excreted in urine (so glucose levels drop to abnormal levels for Type 1 diabetics)

hypokalemia can drop more after insulin treatment so great care must be used

symptoms: thirst, polyuria, polydipsia, nocturia, weakness, nausea, decreased sweating, confusion, ketone breath

Question 15

lab results with DKA

Answer 15

glucose = may be as low as 250

Na+ = Na+ rises 1.6 for each 100 of glucose over 100…when glucose starts to fall….it rises in the opposite fashion

K+ = drop rapidly with insulin treatment

HCO3- = used in conjunction with anion gap to assess level of acidosis
- more bicab buffers depleted by ketone and anion depletion by osmotic diuresis –> the more anion gap increases
> 12 anion gap (normal 8-12)

CBC = if elevated (WBC) = infection

Question 16

initial treatments of DKA

Answer 16

IV isotonic saline for 1st hour….replaces electrolyte loses and dilutes glucose level

next hour = give insulin to reverse catabolic state and frequently check K+ levels

Question 17

hyperosmolar hyperglycemia nonketotic coma

Answer 17

HHNC

extreme high glucose (>600), hyperosmolarity and dehydration without significant ketoacidosis

more dangerous than DKA

seen in older people with type 2

usually brought upon by a secondary event –> concurrent reduction in insulin and increase in counter regulatory hormones like catecholamines or glucagon

treatment = similar to DKA

Question 18

alpha-glucosidase inhibitors

Answer 18

acarbose, miglitol,

in SI brush border….they decrease the digestion and absorption of glucose into circulation and allow beta cells to productively regulate insulin secretion

Question 19

sulfonylureas

Answer 19

reduce serum glucose by increasing insulin secretion in patients with beta cell impairment

bind to and inhibit pancreatic ATP K+ channel that is involved in inhibiting insuling secretion

cannot use in type 1

Question 20

meglitinides

Answer 20

short acting insuling secretors

inhibit ATP K+ channel in beta cells

cannot be used in type 1

Question 21

biguanides

Answer 21

insulin sensitizing drug - increase insulin sensitivity in liver mostly by increasing insulin receptor tyrosine kinase activity

improve blood glucose clearance

no effect on insulin secretion

Question 22

TZDs

Answer 22

agonists for PPAR-gamma receptors

regulates insuling responsive gene transcription involved in glucose production transport and uses

so reduces blood glucose conectrations and hyperinsulinen

stimulates glucose u[take and FA ox in muscule

FA ox in liver while inhibit gluconeo enzmyes

Question 23

incretins

Answer 23

glucagon like peptide 1

increases glucose dependent insulin secretion, inhibition of glucagon secretion and gastric acid secretion and gastirc emptyyinh