Diabetes

Question 1

Differentiate the acute from chronic complications of diabetes

Answer 1

Acute: Hyperglycemia (DKA, HONKS), Infections, hypoglycemia
Chronic: Retinal disease, weight gain, hypertension, neuropathy, nephropathy, macrovascular disease (CHD, cerebrovascular, peripheral vascular)

Question 2

What proportion of Canadians does diabetes mellitus affect? How much does it cost the Canadian healthcare system?

Answer 2

> 7%; >$7 billion

Question 3

What are the diagnostic criteria for diabetes?

Answer 3

Fasting plasma glucose ≥ 7.0 mM; or
Casual plasma glucose ≥ 11.1 mM combined with classic symptoms of diabetes; or
2h PG in a 75g oral glucose tolerance test ≥ 11.1 mM; or
Hb A1C ≥ 6.5%

Question 4

What were the threshold levels of PG established based on?

Answer 4

Retinopathy. Can be divided into nonproliferative retinopathy (early), proliferative retinopathy (late, w/vasculogenesis), macular edema, cataracts, glaucoma.

Question 5

What are the classic signs of diabetes?

Answer 5

Polyuria, polydipsia, unexplained weight loss

Question 6

At what plasma glucose concentration does glucose spill into urine to cause osmotic polyuria?

Answer 6

PG ≥ 10 mM

Question 7

What’s type 1 diabetes?

Answer 7

Caused by autoimmune destruction of beta cells -> leads to inability to produce insulin

Question 8

Understand that there is a remission period during the progression of T1DM

Answer 8

After initial symptoms, but eventually stops, and full-blown T1DM ensues.

Question 9

What happens to fatty acid when there’s a depletion of blood glucose? What about glucose production?

Answer 9

Increase FFA mobilization; increase glucose production

Question 10

How does insulin interact with hormone sensitive lipase? How does diabetes impact the downstream pathway of HSL?

Answer 10

Insulin inhibits. Lack of insulin during diabetes causes increase FFA mobilization from adipocytes. This creates more acetyl CoA, which is used for energy by conversion to ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone)

Question 11

Which ketone bodies does acetyl-coa produce?

Answer 11

Acetoacetate, which becomes beta-hydroxybutyrate and acetone

Question 12

Name consequences of ketoacidosis (metabolic acidosis). Complications?

Answer 12

Weakness, fatigue, lethargy, malaise.
Kussmaul breathing (deep breathing).
Fruity breath.
Nausea, vomiting, abdominal pain.
Increase WBC (from catecholamines).

Complications:
hypotension, depressed sensorium, coma, cerebral edema, electrolyte abnormalities

Question 13

Name the 5 steps of managing diabetic ketoacidosis

Answer 13

Prevent hypokalemia by giving lytes.
Restore ECF with normal saline
Correct metabolic acidosis with IV insulin
Manage hyperosmolality (fluids)
Identify precipitating cause and treat

Question 14

Name risk factors for insulin resistance

Answer 14

Age
Obesity
Sedentary lifestyle
Ethnicity
Family history
PCOS
Gestational diabetes (caused by underlying abnormal production, superimposed with the effects of human placental lactogen)
Hypertension, dyslipidemia, etc.

Question 15

What are other types of diabetes?

Answer 15

Beta-cell function defects
Genetic deficits causing insulin resistance
Diseases of the pancreas
Endocrinopathies
Drug or chemical induced
Infections (congenital rubella, cytomegalovirus, coxsackie)
Uncommon forms of immune-mediated diabetes
Other genetic syndromes
Gestational

Question 16

In diabetic nephropathy, which part of the kidney is damaged?

Answer 16

Glomerular basement membrane.

Question 17

How many DM patients die of macrovascular disease?

Answer 17

80%

Question 18

What are the two main clinical trials that defined the threshold values of diabetes?

Answer 18

DCCT (Diabetes Control and Complications Trial; type I)

UKPDS (UK Prospective Diabetes Study; type II)

Question 19

What were the results of the DCCP trial?

Answer 19

Intensive treatment was able to reduce Hb A1C to 7%, whereas conventional treatment was stuck at 9%. Relative risk reduction for retinopathy and nephropathy progression/incidence were decreased mightily.
Adverse events: more frequent hypoglycemia. Slight weight gain (10lbs)

Question 20

What’s EDIC?

Answer 20

Epidemiology of Diabetes Interventions and Complications. A continuation of the DCCT trial. It showed that intensive therapy also decreased chances of heart attack/stroke, and kidney disease

Question 21

What were the results of the UKPDS trial?

Answer 21

After 10 year trial, reduction in:

Diabetes related endpoints, microvascular, MI, cataract, retinopathy, albuminuria

Question 22

How to treat type 2 diabetes? 3 steps:

Answer 22

1: Improve insulin sensitivity (diet, exercise, metformin)
2: Counter insulin deficiency (secretagogues)
3: Administer insulin therapy.

Question 23

What do biguanides do?

Answer 23

Decrease glucose production. E.g. metformin.

Question 24

What do thiazolidinediones do?

Answer 24

Increase glucose uptake by fat and muscle by activating PPARgamma receptors. E.g. Rosiglitazone, pioglitazone

Question 25

What do sulfonylureas do?

Answer 25

Block potassium channels to increase insulin release from pancreatic beta cells. Secretagogue. E.g. glyburide.

Question 26

What do meglitinides do?

Answer 26

Increase insulin secretion. Shorter-acting than sulfonylureas, so good for patients with erratic eating habits. Secretagogue. E.g. repaglinide.

Question 27

What do incretins do?

Answer 27

Boost GLP-1 production, which helps everything. E.g. exenatide.

Question 28

What do DPP-IV inhibitors do?

Answer 28

DPP-IV breaks down GLP-1, so inhibiting allows more GLP-1 to be around. E.g. sitagliptin.

Question 29

What do sodium-glucose cotransporter 2 inhibitor class drugs do?

Answer 29

Increase renal clearance of glucose through urine. E.g. -liflozin suffix.

Question 30

Name primary symptoms of hypoglycemia (adrenergic)

Answer 30

Anxiety, hunger, confusion, sweating, tremor, agitation, tachycardia

Question 31

Name secondary symptoms of hypoglycemia (neuroglycopenic)

Answer 31

More confusion, coma, somnolence, seizure, death

Question 32

Name long-acting insulin analogues

Answer 32

Glargine, detemir, degludec

Question 33

Name rapid-acting insulin analogues

Answer 33

Aspart, lispro, glulysine

Question 34

Name 6 stimulators of insulin secretion

Answer 34

Glucose, amino acids, free fatty acids, GLP-1, glucagon, acetylcholine

Question 35

Name 3 inhibitors of insulin

Answer 35

Somatostatin, insulin, norepinephrine

Question 36

How does insulin affect FA and TAG?

Answer 36

Increases FA synthesis and TAG deposition; inhibits their breakdown by inactivating HS-lipase and perilipin

Question 37

How does insulin affect glucokinase?

Answer 37

Upregulates it

Question 38

How does insulin affect amino acid uptake?

Answer 38

Upregulates it. Increases protein synthesis as well

Question 39

Which glucose receptor does insulin affect?

Answer 39

GLUT4 (mostly in muscle and fat)

Question 40

Which receptor mechanism does insulin work on?

Answer 40

Tyrosine kinase -> insulin receptor substrate

Question 41

Which receptor mediates glucose absorption in the liver?

Answer 41

GLUT2

Question 42

Where is GLP-1 secreted?

Answer 42

Endocrine cells of small intestines

Question 43

What does GLP-1 do?

Answer 43

Stimulates insulin release and inhibits glucagon release

Question 44

Where is GLP-2 secreted?

Answer 44

Intestinal endocrine cells

Question 45

What does GLP-2 do?

Answer 45

Inhibits food intake

Question 46

Which proteins can be coded by proglucagon?

Answer 46

Glucagon, GLP-1, GLP-2

Question 47

What does amylin do?

Answer 47

Slows emptying of stomach and acid secretion, decreases food intake, decreases glucagon secretion. Can also increase serum calcium and renin activity

Question 48

How does the body respond to falling glucose?

Answer 48

ACTH and GH release leads to cortisol+epinephrine

Question 49

How does high blood tonicity affect potassium levels?

Answer 49

Can lead to hypokalemia, due to solvent drag.

Question 50

How does consumption of food affect blood glucose in diabetics?

Answer 50

Inhibition of glucagon release from alpha cells, so no liver gluconeogenesis. No insulin leads to poor glucose absorption.

Question 51

How does adding protamine to an insulin formulation affect its release?

Answer 51

Slows it down - promotes aggregation of insulin

Question 52

what are the adverse reactions to insulin?

Answer 52

hypoglycemia, local lipodystrophy, allergy and resistance, insulin presbyopia, edema

Question 53

How do biguanides work?

Answer 53

Decrease ATP production, so increase glucose uptake and decrease glucose production in liver

Question 54

How do sulfonylureas and meglitinides work?

Answer 54

Block K channel; more calcium influx to cause insulin release. Meglitinides are faster acting and shorter duration

Question 55

How do thiazolidinediones work?

Answer 55

Activate PPARgamma receptors to cause differentiation of adipose stem cells. New fat cells are active in glucose absorption and are insulin-sensitive

Question 56

How do SGLT2 inhibitors work?

Answer 56

Block Na/glucose transporter from the kidneys. Prevent glucose reabsorption, so renal excretion of glucose.

Question 57

How do glucosidase inhibitors work?

Answer 57

Inhibits the starch breakdown at the brush border, so delays glucose uptake

Question 58

Eating 1000 kcal less per day leads to how much weight loss per week?

Answer 58

1000 g loss per week

Question 59

How do vegetable omega-3 fatty acids work?

Answer 59

Decrease VLDL and TG

Question 60

What is linkage disequilibrium?

Answer 60

Measure of whether or not there is a marker for a certain disease

Question 61

What is the transmission disequilibrium test?

Answer 61

Evaluate the linkage between a genetic marker and a trait, within a family

Question 62

How does Turner's syndrome affect growth?

Answer 62

Shorter women

Question 63

Name deformities in patients with SHOX deficiencies

Answer 63

High arch palate, cubitus valgus, Madelung deformity, genu valgum

Question 64

How to treat kids with SHOX deficiency?

Answer 64

Give growth hormone

Question 65

What is testotoxicosis?

Answer 65

Activating mutation of the LH receptor, causing early puberty (growth plates close quickly, leading to short stature)

Question 66

How many calories in 1kg of adipose tissue?

Answer 66

8000 kcal

Question 67

What are recommended dietary measures for metabolic syndrome, overweightness, and obesity?

Answer 67

Follow food guide, reduce energy intake, increase activity, modify lifestyle and behaviour, target 5-10% weightloss over 6-12 months

Question 68

What's the definition of metabolic syndrome?

Answer 68

Waist under 102cm, HDL under 1, TG over 1.7, BP over 130/85, glucose around 6.1-6.9 in men. In women, waist over 88cm and HDL under 1.3.

Question 69

Name a few more factors of metabolic syndrome

Answer 69

hi uric acid, hi clotting, hi growth factors, low adiponectin (hi fat redistribution, decreased PPAR agonist), hi CRP

Question 70

Name the steps in cryptogenic cirrhosis

Answer 70

normal, non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), cryptogenic cirrhosis

Question 71

How does insulin contribute to hypertension?

Answer 71

Increases sodium reabsorption at the distal tubule

Question 72

What do nutritionists look at for their focused physical exams?

Answer 72

Skin, nails, hair, eyes, teeth, tongue

Question 73

What's the nutritional intake goal for someone malnourished?

Answer 73

Ensure po intake is >75% of CFG requirements

Question 74

If a patient needs to be fed for <30 days on a tube, what kind is best?

Answer 74

Nasoenteric

Question 75

If a patient needs to be fed for >30 days on a tube, what kind is best?

Answer 75

Percutaneous or surgical gastrostomy/jejunostomy