Diabetes Flashcards
Diabetes Definition
- blood glucose that is inc. to the point that it would cause microvascular disease
- fasting glucose > 126
- 2 hr plasma glucose >200 during 75 g oral glucose tolerance test
- sx of diabetes with random plasma glucose >200
- A1C> 6.5%
A1C in Diabetes
- > 6.5% on 2 occasions is diagnostic
- represents avg blood sugar over last 3 months
- must be in absence of other medical illness
Fasting Glucose in Diabetes
->126 mg/dl
2 Hr Plasma Glucose in Diabetes
->200 mg/dl during 75g OGTT
Random Plasma Glucose in Diabetes
->200mg/dl with sx of diabetes
Impaired Glucose Tolerance/Impaired Fasting Glucose
- prediabetic
- inc. risk for macrovascular disease (CAD, CVD)
- 10% risk per year of progressing to T2DM
- impaired fasting glucose: 100-125
- impaired glucose tolerance: 140-199 during OGTT
- A1C: 5.7-6.4%
Sx of Diabetes
- polyuria
- polydipsia (excessive thirst)
- blurry vision
- weight loss
- sx present at ~90% loss of beta cell function in pancreas
Type 1 DM
- due to autoimmune destruction of beta cells in pancreas
- results in insulin deficiency
- occurs in childhood
- evidence of insulin deficiency: low C peptide
- low genetic contribution
- positive antibody blood tests
- normal weight
- predisposed to DKA
- insulin sensitive
- not related to vaccine exposure
Type 2 Diabetes
- most common form of diabetes
- insulin resistance
- more common in adults
- more common in hispanics, blacks, native americans, and pacific islanders
- overweight
- sedentary lifestyle
- strong genetic component
- DKA unlikely
- no beta cell autoimmunity but beta cells are dysfuctional (dec. insulin secretion)
Gestational Diabetes
- weight gain/pregnancy
- resolves after delivery
- inc. risk of T2DM in future
- risks: big baby, delivery complications, child at risk for T2 also
Pancreatic Diabetes
- insulin deficiency for beta cell destruction
- diarrhea and steatorrhea
- underweight
- lack glucagon in addition to insulin
- may occur in alcoholics
- prone to hypoglycemia
- inc. peripheral neuropathy
Stages of T1DM
- genetic predisposition
- overt immunologic abnormalities
- progressive loss of insulin release
- overt diabetes
- no C-peptide
4 Autoantigens Characteristic of T1DM
- insulin
- glutamic acid decarboylase 65 (GAD65)
- tyrosine phsophatase protein (IA2)
- zinc transporter (ZnT8)
- individuals with 2 or more autoantibodies will progress to T1D
- also genetic risk factors such as HLA DR3/4
Possible Environmental Factors of T1DM
- not vaccines
- viruses
- hygiene hypothesis
- diet (formula)
- obesity
C Peptide
-marker of endogenous insulin
Normal Plasma Glucose Values
-fasting
Diabetic Ketoacidosis
- severe hyperglycemia
- anion gap metabolic acidosis
- inc. ketones
- low insulin/glucagon ratio permits ketogenesis in the liver
- counter regulatory
- hormones are elevated
- most common precipitating cause is infection
- tx: volume replacement, insulin, potassium
Signs of Hypoglycemia
- adrenergic: sweating, tremor, tachycardia
- neuroglycopenic: confusion, convulsions, LOC
- pts can be unaware due to dec. adrenergic warning signs
Maturity Onset Diabetes of Young (MODY)
- autosomal dominant
- linked to mutaitons in glucokinase gene and mitochondrial genes
Macrovascular Disease Associated with DM
- MI
- stroke
- peripheral vascular disease
- lipid lowering significantly dec. mortality and CV events in pts with DM
- legacy effect: early blood sugar control in DM leads to dec. CV events 10-20 yrs later
Vascular Wall Response to Diabetes
- abnormal endothelial cell function
- abnormal vascular smooth muscle cell function
- inflammation and dec. fibrinolysis
Tx to Prevent Complications of DM
- B blockers
- antihypertensives
- lipid lowering agents
- ASA in high risk pts
Microvascular Disease Mechanisms in DM
- polyol pathway-> sorbitol, fructose
- non-enzymatic glycosylation-> AGEs
- elevation of protein kinase C
- oxidative/carbonyl stress
Microvascular Diseases Associated with DM
- retinopathy- hypoxic stress-> neovascularization
- nephropathy
- neuropathy-> ulceration
Retinopathy Treatment and Prevention Strategies
- annual opthalmologic exams
- tight glycemic control
- photocoagulation
- intravitrial medication
DM Nephropathy Pathogenesis
-hyperfiltration-> intrarenal and peripheral hypertension-> basement membrane thickening-> mesangial proliferation-> glomerular obliteration
Rapid Acting Insulin Analogs
- novalog (aspart)
- apidra (glulisine)
- humalog (lispro)
- onset: 5 ming
- peak: 1.5 hr
- duration: 3-5 hr
- subq or pump
- given just prior to meal
- dissociates into monomers after injection
Rapid Acting Insulin: Inhaled
- afrezza
- onset: 5 min
- peak: 1 hr
- duration: 2 hr
- set dose
- administered just prior to meal
Short Acting Insulin: Regular
- Humulin R; Novolin R
- onset: 30-60 min
- peak: 2 hr
- duration: 6-8 hr
- subq, IV, infusion
- inject 30 min prior to meal
Intermediate Acting Insulin: NPH
- Humulin N, Novolin N
- onset: 1-3 hr
- peak: 6-8 hr
- duration: 12-16 hr
- subq only (2x/day for basal coverage)
- cloudy solution
Long Acting Insulin
- glargine (lantus)
- detemir (levemir)
- onset: 1.5 hr
- no peak
- duration: 24 hr glargine, 12-20 hr detemir
- subq only
- cannot be mixed in same syringe w/ other insulin
Premixed Insulin
- 70/30
- 50/50
- used twice a day just before AM and PM meals
- subq only
When to use insulin in T2DM
- if lifestyle modifications and non-insulin combos don’t achieve target A1C
- contraindications to other meds
- when in hospital
Glucose and A1C Targets in DM
- fasting BG: 70-130
- 2 hr post meal BG:
Diabetes Lifestyle Changes
- less calorie dense/refined carbs
- higher fiber, lean protein
- smaller portions
- inc. physical activity
- weight loss
Sulfonylureas
- glyburide, glipizide, glimerpriride
- close ATP sensitive K channels in B cell
- bypass glucose control
- must have some pancreas for this to work
- pros: cheap, available in combo with other meds
- cons: weight gain, hypoglycemia, loses effectiveness
Biguanide: Metformin
- potentiates supportive effect of insulin on hepatic glucose production
- does NOT stimulate insulin secretion or inc. circulating insulin
- risk lactic acidosis
- pros: no hypoglycemia, cheap, no weight gain, combs
- cons: GI side effects, risk of lactic acidosis
Thiazolidinediones
- pioglitazone (actos)
- rosiglitazone (avandia)
- inc. insulin sensitivity- adiponectin stimulation
- cons: worsening of CHF, expensive, risk of bladder cancer
Incretins
- GLP-1- very effective for lowering glucose in diabetes
- lowers glucose via multiple mechanisms
- secreted by cells in GI tract in response to food intake
- augments insulin secretion only if blood glucose is elevated
- native GLP-1 is rapidly cleaved and inactivated in circulation by DPP-4
GLP-1 Agonists
- exenatide (byetta)
- liraglutide (victoza)
- exenatide Qwk (bydureon)
- albiglutide (tanzeum)
- dulaglutide (trulicity)
- pros: multiple MOAs, effects are glucose dependent, weight loss
- cons: subq injection, side effects, expensive
- don’t combine with DPP-4
DPP-4 Inhibitors
-sitagliptin (januvia)
-saxagliptin (onglyza)
-linagliptin (tradjenta)
-alogliptin (nesina)
-DPP-4 cleaves GLP-1
-pros: multiple MOAs, oral, once daily, weight neutral, combos
-cons: less potent, expensive, side effects
don’t combine with GLP1
SGLT-2 Inhibitor
- canagliflozin (invokana)
- dapagliflozin (farxiga)
- emplagliflozin (jardiance)
- block glucose reuptake in the kidney-> pee out glucose
- pros: novel MOA, weight loss, pill, combo
- cons: inc. risk UTI, inc. risk low K, expensive
Amylin
- second peptide hormone secreted by B cells
- actions: suppresses postprandial glucagon, slows gastric emptying, dec. food intake
- T1DM: absolute deficiency
- T2DM: initially elevated, then decline
Amylin Analog
- pros: multiple MOAs to reduce postprandial glycemia, induces weight loss
- cons: subq up to 7x/day, side effects, expensive
