Diabetes Flashcards
Differentiate the acute from chronic complications of diabetes
Acute: Hyperglycemia (DKA, HONKS), Infections, hypoglycemia
Chronic: Retinal disease, weight gain, hypertension, neuropathy, nephropathy, macrovascular disease (CHD, cerebrovascular, peripheral vascular)
What proportion of Canadians does diabetes mellitus affect? How much does it cost the Canadian healthcare system?
> 7%; >$7 billion
What are the diagnostic criteria for diabetes?
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%
What were the threshold levels of PG established based on?
Retinopathy. Can be divided into nonproliferative retinopathy (early), proliferative retinopathy (late, w/vasculogenesis), macular edema, cataracts, glaucoma.
What are the classic signs of diabetes?
Polyuria, polydipsia, unexplained weight loss
At what plasma glucose concentration does glucose spill into urine to cause osmotic polyuria?
PG ≥ 10 mM
What’s type 1 diabetes?
Caused by autoimmune destruction of beta cells -> leads to inability to produce insulin
Understand that there is a remission period during the progression of T1DM
After initial symptoms, but eventually stops, and full-blown T1DM ensues.
What happens to fatty acid when there’s a depletion of blood glucose? What about glucose production?
Increase FFA mobilization; increase glucose production
How does insulin interact with hormone sensitive lipase? How does diabetes impact the downstream pathway of HSL?
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)
Which ketone bodies does acetyl-coa produce?
Acetoacetate, which becomes beta-hydroxybutyrate and acetone
Name consequences of ketoacidosis (metabolic acidosis). Complications?
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
Name the 5 steps of managing diabetic ketoacidosis
Prevent hypokalemia by giving lytes. Restore ECF with normal saline Correct metabolic acidosis with IV insulin Manage hyperosmolality (fluids) Identify precipitating cause and treat
Name risk factors for insulin resistance
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.
What are other types of diabetes?
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
In diabetic nephropathy, which part of the kidney is damaged?
Glomerular basement membrane.
How many DM patients die of macrovascular disease?
80%
What are the two main clinical trials that defined the threshold values of diabetes?
DCCT (Diabetes Control and Complications Trial; type I)
UKPDS (UK Prospective Diabetes Study; type II)
What were the results of the DCCP trial?
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)
What’s EDIC?
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
What were the results of the UKPDS trial?
After 10 year trial, reduction in:
Diabetes related endpoints, microvascular, MI, cataract, retinopathy, albuminuria
How to treat type 2 diabetes? 3 steps:
1: Improve insulin sensitivity (diet, exercise, metformin)
2: Counter insulin deficiency (secretagogues)
3: Administer insulin therapy.
What do biguanides do?
Decrease glucose production. E.g. metformin.
What do thiazolidinediones do?
Increase glucose uptake by fat and muscle by activating PPARgamma receptors. E.g. Rosiglitazone, pioglitazone
What do sulfonylureas do?
Block potassium channels to increase insulin release from pancreatic beta cells. Secretagogue. E.g. glyburide.
What do meglitinides do?
Increase insulin secretion. Shorter-acting than sulfonylureas, so good for patients with erratic eating habits. Secretagogue. E.g. repaglinide.
What do incretins do?
Boost GLP-1 production, which helps everything. E.g. exenatide.
What do DPP-IV inhibitors do?
DPP-IV breaks down GLP-1, so inhibiting allows more GLP-1 to be around. E.g. sitagliptin.
What do sodium-glucose cotransporter 2 inhibitor class drugs do?
Increase renal clearance of glucose through urine. E.g. -liflozin suffix.
Name primary symptoms of hypoglycemia (adrenergic)
Anxiety, hunger, confusion, sweating, tremor, agitation, tachycardia
Name secondary symptoms of hypoglycemia (neuroglycopenic)
More confusion, coma, somnolence, seizure, death
Name long-acting insulin analogues
Glargine, detemir, degludec
Name rapid-acting insulin analogues
Aspart, lispro, glulysine
Name 6 stimulators of insulin secretion
Glucose, amino acids, free fatty acids, GLP-1, glucagon, acetylcholine
Name 3 inhibitors of insulin
Somatostatin, insulin, norepinephrine
How does insulin affect FA and TAG?
Increases FA synthesis and TAG deposition; inhibits their breakdown by inactivating HS-lipase and perilipin
How does insulin affect glucokinase?
Upregulates it
How does insulin affect amino acid uptake?
Upregulates it. Increases protein synthesis as well
Which glucose receptor does insulin affect?
GLUT4 (mostly in muscle and fat)
Which receptor mechanism does insulin work on?
Tyrosine kinase -> insulin receptor substrate
Which receptor mediates glucose absorption in the liver?
GLUT2
Where is GLP-1 secreted?
Endocrine cells of small intestines
What does GLP-1 do?
Stimulates insulin release and inhibits glucagon release
Where is GLP-2 secreted?
Intestinal endocrine cells
What does GLP-2 do?
Inhibits food intake
Which proteins can be coded by proglucagon?
Glucagon, GLP-1, GLP-2
What does amylin do?
Slows emptying of stomach and acid secretion, decreases food intake, decreases glucagon secretion. Can also increase serum calcium and renin activity
How does the body respond to falling glucose?
ACTH and GH release leads to cortisol+epinephrine
How does high blood tonicity affect potassium levels?
Can lead to hypokalemia, due to solvent drag.
How does consumption of food affect blood glucose in diabetics?
Inhibition of glucagon release from alpha cells, so no liver gluconeogenesis. No insulin leads to poor glucose absorption.
How does adding protamine to an insulin formulation affect its release?
Slows it down - promotes aggregation of insulin
what are the adverse reactions to insulin?
hypoglycemia, local lipodystrophy, allergy and resistance, insulin presbyopia, edema
How do biguanides work?
Decrease ATP production, so increase glucose uptake and decrease glucose production in liver
How do sulfonylureas and meglitinides work?
Block K channel; more calcium influx to cause insulin release. Meglitinides are faster acting and shorter duration
How do thiazolidinediones work?
Activate PPARgamma receptors to cause differentiation of adipose stem cells. New fat cells are active in glucose absorption and are insulin-sensitive
How do SGLT2 inhibitors work?
Block Na/glucose transporter from the kidneys. Prevent glucose reabsorption, so renal excretion of glucose.
How do glucosidase inhibitors work?
Inhibits the starch breakdown at the brush border, so delays glucose uptake
Eating 1000 kcal less per day leads to how much weight loss per week?
1000 g loss per week
How do vegetable omega-3 fatty acids work?
Decrease VLDL and TG
What is linkage disequilibrium?
Measure of whether or not there is a marker for a certain disease
What is the transmission disequilibrium test?
Evaluate the linkage between a genetic marker and a trait, within a family
How does Turner’s syndrome affect growth?
Shorter women
Name deformities in patients with SHOX deficiencies
High arch palate, cubitus valgus, Madelung deformity, genu valgum
How to treat kids with SHOX deficiency?
Give growth hormone
What is testotoxicosis?
Activating mutation of the LH receptor, causing early puberty (growth plates close quickly, leading to short stature)
How many calories in 1kg of adipose tissue?
8000 kcal
What are recommended dietary measures for metabolic syndrome, overweightness, and obesity?
Follow food guide, reduce energy intake, increase activity, modify lifestyle and behaviour, target 5-10% weightloss over 6-12 months
What’s the definition of metabolic syndrome?
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.
Name a few more factors of metabolic syndrome
hi uric acid, hi clotting, hi growth factors, low adiponectin (hi fat redistribution, decreased PPAR agonist), hi CRP
Name the steps in cryptogenic cirrhosis
normal, non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), cryptogenic cirrhosis
How does insulin contribute to hypertension?
Increases sodium reabsorption at the distal tubule
What do nutritionists look at for their focused physical exams?
Skin, nails, hair, eyes, teeth, tongue
What’s the nutritional intake goal for someone malnourished?
Ensure po intake is >75% of CFG requirements
If a patient needs to be fed for <30 days on a tube, what kind is best?
Nasoenteric
If a patient needs to be fed for >30 days on a tube, what kind is best?
Percutaneous or surgical gastrostomy/jejunostomy
