Endocrinology - Diabetes Flashcards
Differentiate between macrovascular and microvascular complications with diabetes
Macrovascular - medium and large size blood vessels involved - CAD, MI, stroke, PAD Microvascular - involve small capillaries - retinopathy, nephropathy, neuropathy
Discuss the stages of diabetic retinopathy
Non-proliferative
- asymptomatic but could have impaired vision due to macular edema
- progressive blood vessel change including microaneurysm, hemorrhage, hard exudate
Pre-proliferative
- macular edema
- venous shunts and possible bleeding
- intra-retinal microvascular abnormalities
Proliferative
- neovascularization (abnormal BV growth) and fibrous scarring
- blindness due to vitreous hemorrhage or retinal detachment
Discuss the presentation and management of diabetic retinopathy
Presentation - asymptomatic - blurry vision - darkening or distorted vision due to macular edema - cotton wool spots - exudates Management - follow with ophthalmologist - glycemic control - control HTN and lipids
Discuss the stages of diabetic nephropathy
- nephrotic syndrome Stage 1 - hyperfiltration (increased GFR) where kidney may increase in size Stage 2 - microalbuminuria due to damage of glomeruli - ACR 2-20 male or 3-28 in female Stage 3 - increased albumin excretion (macroalbuminemia), rising creatinine and increased BP - ACR >20 male or >28 female Stage 4 - GFR <75 with proteinuria Stage 5 - end stage renal disease, GFR <10
Discuss the management of diabetic nephropathy
- glycemic control
- blood pressure control
- ACEi or ARB to reduce albuminemia
Discuss the presentation of different types of diabetic neuropathy
Peripheral Sensory Neuropathy
- Neuropathic pain, numbness, paresthesia
- decreased tactile sensation (glove and stocking)
Motor Neuropathy
- muscle weakness
- reversible cranial palsy
Autonomic Neuropathy
- alternating constipation and diarrhea due to gastroperesis
- urinary retention
- erectile dysfunction
Discuss the presentation, investigations and management for diabetic foot ulcer/cellulitis
Presentation
- infected ulcer (erythema, warmth, swelling, pain) or pus
- necrotizing if soft tissue gas, skin discoloration or foul odor
Investigation
- wound swab
- CBC, blood glucose, ESR/CRP
- blood culture
Management
- Surgical
- debridement and cleaning
- revascularization
- osteomyelitis then amputation
- Wound care
- relieve pressure on ulcer
- wound cleaning and dressing
- Glycemic Control
- Antibiotic
- Mild: Keflex
- Moderate: Septra plus Amox-Clav or Clindamycin
- Moderate with deep tissue: IV Pip-Tazo, Meropenem, Moxifloxacin, Flagyl + CeftriaxoneDiscuss classification of infection and risk for osteomyelitis for diabetic foot ulcer
Classification
- Infected if >=2 of purulence, erythema, pain, warmth, swelling
- Mild if erythema extends <=2cm around ulcer
- Moderate: erythema extends >2cm around ulcer or involvement of deep tissue
- Severe: systemic toxicity or instability
Risks for Osteomyelitis
- Large ulcer
- deep ulcer, probing to bone
- visualization of bone
- ESR >70
- MRI to r/o
Discuss the pathophysiology, benefits, risks and dosing of biguanides
Pathophysiology - increase sensitivity of the cell to insulin Benefit - A1c lowering of 1-1.5% - low risk of hypoglycemia - improved cardiovascular risk Risks - contraindicated with eGFR <30 (increase risk of lactic acidosis) - GI side effects
Discuss the pathophysiology, benefits, risks and dosing of incretins
Pathophysiology - secreted in the gut and result in increased insulin secretion from the pancreas - glucagon like peptide-1 - glucose dependent insulinotrophic peptide Benefit - increase satiety and decrease gastric emptying which reduces weight gain - increase insulin secretion Benefits - A1c lowering of 1% - significant weight loss - low risk of hypoglycemia - some cardiovascular benefit Risks - GI side effects - subcutaneous injection required - rare cause of pancreatitis - increase parafollicular hyperplasia
Discuss the pathophysiology, benefits, risks and dosing of DDP-IV inhibitors
Pathophysiology - amplify incretin pathway by inhibiting breakdown of endogenous GLP and GIP Benefits - A1c lowering of 0.7% - low risk of hypoglycemia - improve post-prandial control - GI side effects
Discuss the pathophysiology, benefits, risks and dosing of SGL2-inhibitors
Pathophysiology
- block glucose transport in proximal renal tubule leading to urinary exretion
Benefits
- glycosuria:
- negative caloric balance and weight loss
- decrease A1c
- increase uric acid release
- natriuresis
- decrease blood pressure resulting in decrease arteriolar stiffness
- decrease plasma volume resulting in decreased myocardial stretch
- increase tubulo-glomerulo fedback and afferent arteriole constriction
Risks
- increase risk of UTI
- osmotic diuresis leading to hypotension
- ketoacidosis in euglycemic individual
Discuss the pathophysiology, benefits, risks and dosing of sulfonylurea
Pathophsyiology - bind to sulfonylurea receptor inhibiting efflux of K -> depolarization and increase in Ca entry into cell -> increase insulin release Benefits - A1c lowering of 0.8% - rapid glucose lowering Risks - may cause hypoglycemia - weight gain
Discuss the pathophysiology, benefits, risks and dosing of meglitinide
Pathophysiology - same as sulfonylurea as is a secretague Benefit - A1c lowering of 0.7% - rapid glucose lowering with lower risk of hypoglycemia due to shorter half-life - safe with renal impairment Risks - weight gain - hypoglycemia - interaction with plavix
Discuss the pathophysiology, benefits, risks and dosing of acarbose-glucosidase inhibitor
Pathophysiology - inhibit intestinal enzymes alpha-glucosidase and pancreatic alpha-amylase resulting in reduced digestion of carbohydrates Benefits - A1c lowering of 0.6% - rare hypoglycemia - GI side effects
Discuss the pathophysiology, benefits, risks and dosing of thiazolidinediones
Pathophysiology - increase sensitivity of tissues to insulin by activation of ppar-gamma receptor Benefit - longer duration of monotherapy - Mild blood pressure lowering - A1c lowering 0.8% - low risk of hypoglycemia Risks - weight gain - increased peripheral edema and heart failure - increased risk of fractures
Discuss the pathophysiology of insulin therapy
- bind to tyrosine kinase receptor on myocytes, hepatocytes, adipocytes to activate P13K -> PIP3 -> PDK/Akt signalling to ellicit
- increased glycogenesis, lipogenesis and triglyceride synthesis
- decreased lipolysis, glycogenolysis, and ketogenesis
- increase glucose uptake from blood
- liver and muscle increase glycogenesis and protein synthesis
- adipocytes inhibit lipolysis
Discuss the correction scale for insulin
- bolus prescribed by correction scale
- determine correction factor 100/TDI (0.3units/kg or number of total daily units of insulin receiving)
- if BG 4-8 no insulin
- if BG (8 - 8+CF) then one additional unit
- if BG (8+CF) - (8+2CF) then two additional units
Discuss the general principles of managing diabetes in hospital
- Type require insulin even if NPO
- diabetic diet
- BG monitoring at before meals, at night and prn
- Continue with pre-admission treatment and change if
- NPO or decreased PO intake
- HbAIc >8%
- measured BG >10
- frequent episodes of hypoglycemia
Discuss management of type 2 diabetic patients in hospital
Patients newly diagnosed (add in order below)
- Max dose oral agent
- add new oral agent from another class
- Start basal insulin
- 0.2-0.3 units/kg long acting (Glaring, Determir) at night or NPH before breakfast and at night
- Add meal time insulin
- discontinue all oral agents except metformin
- 0.1-0.2 units/kg of fast acting at breakfast, lunch supper if long acting or before breakfast and supper if on NPH
- Use corrective insulin sliding scale
- Adjust insulin based on glucose pattenr
- hypoglycemia: decrease at time before noticed
- adjust insulin to get pre-prandial breakfast into range
- correct insulin to correct for high insulin during the day
Patients on Insulin (add in order)
- start basal insulin (same as above)
- add meal time insulin (same as above)
- use corrective insulin sliding scale
- adjust as needed
Discuss the management of diabetic patients that are NPO or cannot take oral agents due to renal failure
Discontinue all oral agents
NPO/Clear Fluids
- CBG Q6H
- IV D5W 100cc/hr
- discontinue meal time insulin
- NPO >2days or peri-operative then IV protocol
- previously on oral agents/diet and not on insulin
- use corrective scale
- if >8 units after 2 days then start basal
- previously on insulin
- switch basal to 1/2 to 2/3 basal insulin dose
- use corrective
Discuss insulin use for patients on steroids
- cause hyperglycemia 5-12 hrs after steroid intake
Morning Steroid Only - NPH 0.2-0.4units/kg before breakfast
Steroid BID-QID - NPH 0.2-0.4 units/kg before breakfast and dinner
Discuss the presentation and management of hypoglycemia
Presentation
- autonomic/adrenergic symptoms
- hunger
- diaphoresis
- tremulousness, tingling
- palpitation
- anxiety
- Neuroglycopenic symptoms
- dizziness
- unusual behaviour
- seizure
- visual changes
- late type 1 and type 2 there is hypoglcyemia unawareness so less symptoms
Diagnosis
- Whipple's triad: blood glucose <2.8 with symptoms that is corrected with food or glucose
Management
- conscious eat food or drink with carbohydrate or 15-20g glucose tablet
- should improve in 5-10 and complete in <20
- Unconscious glucagon 1mg SC/IM or 50mL D50W
- thiamine 100mg IMList the 5 I’s of diabetic ketoacidosis
Insulin Deficiency - inadequate dose - omission of insulin - new diagnosis Infection - most common Ischemia - MI - stroke Intra-abdominal process - pregnancy - pancreatitis Intoxication - drugs or alcohol
Discuss the pathophysiology of diabetic ketoacidosis
Severe Insulin Deficiency
- stress increase insulin demand that is not matched by pancreas
- decrease peripheral glucose utilization and uptake, leading to hyperglycemia
- K shift out of cell leading to hyperkalemia with low body store of K
Severe Cell Starvation
- liver produce and release glucose -> hyperglycemia
- adipose tissue release free fatty acids which are converted to ketones by liver
- peripheral muscle decrease glucose utilization leading to weakness
Ketone Bodies
- cause metabolic acidosis, which can be compensated by breathing
Hyperglycemia and Ketone Bodies
- cause osmotic diuresis
- dehydration
- electrolyte depletion
- hyperosmolality (hyponatremia and cerebral dehydration)
Discuss the presentation, investigation and diagnosis of DKA
Presentation - sleepiness, LOC - blurry vision - N/V - polyuria, polydipsia - Kaussmaul breathing - hypovolemic - fruity ketone breath Investigation - CBC, electrolytes, creatinine BUN - blood glucose - serum osmolality - serum ketone - VBG - urine analysis - ECG Diagnosis (all of the following) - metabolic acidosis with increased anion gap - serum and urine ketone bodies - hyperglycemia
Discuss the management of DKA
Q2-4H electrolytes, anion gap, glucose, creatinine, plasma osmolality, LOC
IV Fluids for decreased Effective Circulating Volume
- Severe shock give NS 1-2L/h until hypotension correction and then switch to NS 500mL/hr for 4hr then 250mL/hr for 4 hr
- mild to moderate start at 500mL
- Once euvolemic
- Na is normal/high or rate of plasma osmolality fall is <3 switch to 0.45NS
- Na is low or rate of plasma osmolality fall >=3 then continue with 0.9%NS
- Once plasma glucose reaches 14 add D5W to IV fluids to maintain glucose 12-14
Serum K
- <3.3 then give 40mmol/L KCl and no insulin until K >=3.3
- >=3.3 and less 5-5.5 then 10-40KCl
Acisosi
- if K <3.3 correct hypokalemia before insulin
- if K >=3.3 administer IV short acting insulin 0.1unit/kg/h
- adjust rate of insulin based on anion gap resolution
- if pH <7.0 then NaHCO3 1 amp/h until pH >=7
Discuss the screening for Diabetes
- screen every 3 years for those over 40
- If screen positive for diabetes must do confirmatory test unless symptomatic (polydipsia, polyphagia, polyuria, weight loss, blurry vision)
FPG <5.6 or A1c <5.5% - normal rescreen in 3 years
FPG 5.6-6.6 and/or AIc 5.5-5.9% - no risk factors then rescreen more often
- risk factors then go to 75g OGTT
FPG 6.1-6.9 and/or A1c 6.0-6.4% - go to 75g OGTT
- fasting <6.1 and 2h <7.8
- if A1c <6% then rescreen more often
- if A1c 6-6.4% then prediabetes
- fasting <6.1 and 2h 7.8-11 then impaired glucose tolerance and prediabetes
- fasting 6.1-6.9 and 2h <7.8 then impaired fasting glucose and prediabetes
- fasting 6.1-6.9 and 2h 7.8-11 then prediabetes
- fasting >7 or 2h >11.1 then diabetes
FPG >7.0 and/pr A1c >6.5% then diabetes
- fasting <6.1 and 2h <7.8
Discuss the monitoring for diabetes
Fasting Blood Glucose - 4-7 2hr Post Prandial - 5-10 or 5-8 if not achieving A1c target - HbA1c <7.0% done every 3 months Blood Pressure - <130/80 Lipids - LDL <=2 or >=50% reduction - apoB <0.8 or non-HDL <=2.6 - done yearly Chronic Kidney Disease - Normal ACR <2.0 - normal eGFR >60 - type 1 screen at 5 year and then yearly - type 2 at diagnosis then yearly Retinopathy - type 1 5 years after diagnosis then yearly - type 2 at diagnosis then 1-2 years Neuropathy - screen with 10g monofilament (until bends) at 1st, 3rd, and 5th metarsal head and base of great toe - type 1 at 5 years then yearly - type 2 yearly Waist Circumference/BMI - Maintain WC <102cm in males and <88cm in females - BMI between 18.5-24.9 Lifestyle Modification - 150minutes/week of aerobic exercises
Discuss screening following adding antihyperglycemic agent
- make timely increase in dose or add drug from different class in order to reach A1C target in 3-6 months
- if A1c is <1.5 above target of 7% then begin with lifestyle for three months before switching to metformin
- if A1c is >1.5 above target of 7 begin metformin right away and possibly other drug
Discuss when to initiate insulin therapy
Suboptimal control with oral agents Marked Hyperglycemia at Presentation - A1c >9% - require basal-bolus regimen Stress on Body - infection - pregnancy
List risk factors for diabetes
- First degree relative with type 2 diabetes
- history of prediabetes
- history of gestational diabetes
- metabolic syndrome
- PCOS
- aconthosis nigricans
- OSA
- glucorticoids
- atypical antipsychotics
- retroviral therapy
List factors that can alter A1c
Increase A1c - B12 or iron deficiency - chronic renal failure - hyperbilirubinemia - EtOH or opioids Decrease A1c - use of EPO, iron or B12 - reticulocystosis - ASA - Vitamin C or E - hemoglobinopathies - Splenomegaly - rheumatoid
Discuss the algorithm for starting insulin
- can be combined with oral agent
Basal (glargine or detemir) - start at 10 units or 0.2units/kg at bedtime
- check fasting glucose daily and increase by 2 units every 3 days until in in fasting range
- if FBG >10 then can increase by 4 units every 3 days
Second Injection - If A1c >=7% after 2-3 months then add bolus (lispart or aspart) at pre-lunch, -dinner, -bed
- if pre-lunch high then do at breakfast, etc - if after 2 months A1c still out of range then check 2h post-prandial
Discuss when to add additional therapy to diabetes
ACEI or ARB - clincal macrovascular disease - age >55 - age <55 and microvascular disease Statin - clinical macrovascular disease - age >=40 - age <40 and diabetes duration >15yr, microvascular complication or cardiovascular risk factor Low Dose ASA - for those with cardiovascular disease
Discuss causes and pathophysiology hyperosmolar hyperglycemic state
Causes
- Sepsis
- Stroke
- Mi, CHF
- Renal failure
Pathophysiology
- partial or relative insulin deficiency decrease glucose utilization in muscle, fat, liver leading to hyperglycemia and liver glucose production
- small amount of insulin prevents ketosis
- Have more severe dehydration to DA due to gradual onset and increased duration of metabolic decompensation
Discuss the presentation, investigations, and manageemtn of HHS
- hyperglycemia (44-133), hyperosmolality, dehydration without ketosis
- More common in T2DM
Presentation - Polyuria, polydipsia leading to weakness
- decreased fluid intake
- decreased LOC
Investigation - Increase BG
- Hyponatremia in mild dehydration (every 10 increase in BG have 3 decrease in Na)
- Hypernatremic in severe - Increase osmolality
Management - Rehydration
- 500mL/h x4h then 250mL/h for 4h then 0.45% NS when euvolemic unless corrected Na is low or rate of osmolality fall is >=3
- Switch to D5W when BG at 14 - K replacement
- K <3.3mmol then give 40mEq/L and hold insulin until K>3.3
- K 3.3-5 then start insulin with 10-40 of K
- K >5 then recheck in 2hrs - Insulin
- Monitor plasma osmolality
