Page 255 - TNFlipTest

Toronto Notes 2019 Disorders of Glucose Metabolism Macrovascular Complications
• increasedriskofCAD,ischemicstroke,andperipheralarterialdiseasesecondarytoaccelerated atherosclerosis
• CAD(seeCardiologyandCardiacSurgery,C32)
■ risk of MI is 3-5x higher in those with DM compared to age-matched controls
■ CAD is the leading cause of death in Type 2 DM
■ most patients with DM are considered “high risk” under the risk stratification for CAD (see
Dyslipidemias, E2)
• ischemicstroke(seeNeurology,N50)
■ risk of stroke in those with DM is approximately 2-3x higher for men and 2-5x higher for women
■ level of glycemia is both a risk factor for stroke and a predictor of a poorer outcome in patients who
suffer a stroke
■ HbA1c level is a significant and independent predictor of the risk of stroke
• peripheralarterialdisease(seeVascularSurgery,VS2)
■ manifested by intermittent claudication in lower extremities, intestinal angina, foot ulceration ■ risk of foot gangrene is 30x higher in those with DM compared to age-matched controls
■ risk of lower extremity amputation is 15x higher in those with DM
• treatment
■ tight blood pressure control (<130/80 mmHg); especially for stroke prevention
■ tight glycemic control in early DM without established CVD (refer to ACCORD, VADT,
ADVANCE, DCCT, EDIC, UKPDS extension studies)
■ tight low density lipoprotein (LDL) cholesterol control (LDL ≤2.0 mmol/L)
■ ACEIorangiotensinreceptorblockerinhigh-riskpatients
■ smoking cessation
■ for adults with CVD who do not meet glycemic targets, recommended to add anti-hyperglycemic agent
with demonstrated cardiovascular benefit (empagliflozin or liraglutide) to reduce the risk of major cardiovascular events
Microvascular Complications
DIABETIC RETINOPATHY (see Ophthalmology, OP33 for a more detailed description)
Epidemiology
• DM-inducedkidneydiseaseisthemostcommoncauseofkidneydiseaseinNorthAmerica
• 20-40%ofpersonswithType1DM(after5-10yr)and4-20%withType2DMhaveprogressive
nephropathy
Clinical Features
• nonproliferative • preproliferative • proliferative
Treatment and Prevention
• tightglycemiccontrol(delaysonset,decreasesprogression),tightlipidcontrol,manageHTN,smoking cessation
• ophthalmologicaltreatmentsavailable–seeOphthalmology,OP33formoredetails
• annualfollow-upvisitswithanoptometristorophthalmologistexaminationthroughdilatedpupils
whether symptomatic or not (immediate referral after diagnosis of Type 2 DM; 5 yr after diagnosis of
Type 1 DM)
• intervalforfollow-upshouldbetailoredtoseverityofretinopathy
DIABETIC NEPHROPATHY (see Nephrology, NP31 for a more detailed description)
Epidemiology
• DM-inducedrenalfailureisthemostcommoncauseofrenalfailureinNorthAmerica
• 20-40%ofpersonswithType1DM(after5-10yr)and4-20%withType2DMhaveprogressive
nephropathy
Screening
• serumcreatinineforeGFR,randomurinealbumintocreatineratio(ACR)
• ACRisusedasalbuminuriaisconsideredtheearliestclinicalsignofdiabeticnephropathy
(microalbuminuria); diagnosis requires persistent elevated urinary albumin (2 out of 3 urinary samples
required over 3 mo)
• 24hurinecollectionforprotein/albuministhegoldstandardbutisdifficulttoperform,inconvenient,
and often incorrect; random urine albumin is insufficient as albumin levels vary with urine
concentration
• beginscreeningannuallyatdiagnosisforallType2DM,and>5yrafterdiagnosisofDM1for
Endocrinology E13
Laboratory Testing: Ketones
The nitroprusside test for ketones identifies acetone and acetoacetate but does NOT detect β-hydroxybutyrate (BHB), the ketone most frequently in excess. This has two clinical consequences:
• Be wary of a patient with a clinical picture of DKA but negative serum or urinary ketones. These could be false negatives because of the presence of BHB
• As DKA is treated, BHB is converted to acetone and acetoacetate. Serum or urinary ketones may therefore rise, falsely suggesting that the patient is worsening when in fact they are improving
Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes
NEJM 2015;373:2117-2128
Purpose: To examine whether empagliflozin (an SGLT2 inhibitor) has any effect on cardiovascular risk in patients with Type 2 DM.
Study: Multi-centre RCT comparing empagliflozin to placebo control; 7020 patients (test N=4687, placebo N=2333), median observation 3.1 yr. Outcome: Death from cardiovascular causes, nonfatal MI, or nonfatal stroke.
Results: Both groups concurrently received the standard treatment for T2 DM. The empagliflozin group had significantly lower rates of death from cardiovascular causes than control (3.7%, vs. 5.9%; 38% decreased relative risk). The test group also had lower all-cause mortality (5.7% and 8.3%, respectively; 32% decreased relative risk). Conclusion: Adding empagliflozin to standard treatment for Type 2 DM reduced death from macrovascular complications and all-cause mortality when compared to placebo.
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
NEJM 2016; 375:311-322
Purpose: To investigate whether liraglutide (a GLP-1 analogue) has any effect on cardiovascular risk in patients with Type 2 DM when added to standard care.
Study: Multi-centre, double-blind RCT comparing liraglutide to placebo control; 9340 patients (test N=4668, placebo N=4672), median observation 3.8 yr.
Outcome: Death from cardiovascular causes, nonfatal MI, or nonfatal stroke.
Results: Both groups concurrently received the standard treatment for T2 DM. The liraglutide group had significantly lower rates of death from cardiovascular causes than control (4.7%, vs. 6%; p=0.007). The test group also had lower all-cause mortality (8.2% and 9.6%; p=0.02). Rates of nonfatal MI, nonfatal stroke, and hospitalization for HF were not significantly lower in the liraglutide group.
Conclusion: Adding liraglutide to standard treatment for patients with Type 2 DM reduced death from cardiovascular cause and all-cause mortality when compared to placebo.
postpubertal patients