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CardioNerds (Amit Goyal and Daniel Ambinder) discuss diabetes mellitus with Dr. Dennis Bruemmer. This is a must-listen for anyone engaged in the case of the cardiovascular patient. Given the alarming obesity epidemic, we anticipate a rising worldwide tide of diabetes mellitus and ensuing cardiovascular disease. Here we discuss the epidemiology and approach to diabetes management, with emphasis on what CardioNerds need to know. Dr. Bruemmer is board-certified in both cardiology and endocrinology, and is the director of the Center for Cardiometabolic Health in the section of Preventive Cardiology and Rehabilitation at the Cleveland Clinic.
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Show notes
- Why should CardioNerds pay attention to diabetes mellitus (DM)?
- As a cardiovascular risk equivalent, DM is a key CVD risk factor, associated with a 2-4 fold increased risk. 70% of ACS patients have DM.
- Cardiologists will see more patient with DM given the rising prevalence of obesity, subsequent diabetes and ensuing CVD.
- Only 6% of patients with DM and cardiovascular disease (CVD) get appropriate care for DM and CVD.
- Historically, hypoglycemic agents improved microvascular outcomes (retinopathy, nephropathy, neuropathy), but not macrovascular outcomes (MI, CVA, PAD). However, this has changed with the advent of mandatory cardiovascular safety trials with positive data for GLP1 agonists and SGLT2 inhibitors!
- There aren’t enough endocrinologists! They only see ~5% of DM patients. In 2012 the US generated 280 endocrinologists versus 100 million patient with DM or pre-DM. Primary care physicians are key allies in the care of these patients.
- So as CardioNerds, let’s get over this therapeutic inertia and take ownership of our patients’ DM as we already do for their HTN and HLD; in collaboration with a multidisciplinary team including the PCP, dietician, pharmacist, DM educators, +/- behavioral therapist, +/- endocrinologist, +/- metabolic surgeon.
- What is your global approach to the patient with DM?
- Optimize the non-DM CVD risk factors with lifestyle intervention and medical management: CVD risk factors are very common in patients with DM (sedentary lifestyle, unhealthy weight, HTN, HLD). The Steno-2 Study (Gaede et al., NEJM 2008) showed that in patients with T2DM & microalbuminuria, intensive intervention with multiple drug combinations and behavioral modification was better with regards to: vascular complications, death from any cause, and death from CV causes.
- Emphasize a healthy lifestyle – use a patient-centered approach with motivational interviewing and shared decision making, provide education, set realistic goals, identify barriers (socioeconomic, etc), engage family and a multidisciplinary team (nutritionist, exercise physiologist), utilize behavioral interventions.
- Pharmacologic intervention – medical weight loss for BMI > 27 and DM (enjoy upcoming Ndumele episode), anti-HTN (enjoy upcoming Laffin episode), and anti-HLD (enjoy the Navar-Shah episode). NOTE that statins have been shown to have a small effect on increasing incident or worsening DM, but the effect size is small and overcome by the benefit in whom statins are indicated.
- Treat the Hyperglycemia itself! Let’s discuss this deeper…
- Optimize the non-DM CVD risk factors with lifestyle intervention and medical management: CVD risk factors are very common in patients with DM (sedentary lifestyle, unhealthy weight, HTN, HLD). The Steno-2 Study (Gaede et al., NEJM 2008) showed that in patients with T2DM & microalbuminuria, intensive intervention with multiple drug combinations and behavioral modification was better with regards to: vascular complications, death from any cause, and death from CV causes.
- What is your approach to non-insulin DM management?
- First-line agents: US guidelines: in addition to lifestyle intervention, start with metformin as the first line agent.
- European guidelines: now give preference to GLP1 agonists and SGLT2 inhibitors in patients with or at risk for cardiovascular disease.
- Sulfonylureas: increase pancreatic insulin secretion. Dr. Bruemmer feels they obsolete for the preventive cardiologist from the standpoints of safety, efficacy, and cardiovascular disease. There is no efficacy data past 4 years and no cardiovascular benefit. In contrast data suggests increase all-cause mortality and possibly MACE events. Low cost may make these more affordable for some patients.
- Thiazolidinediones (aka: “glitazones”): increase insulin sensitivity, the primary defect in T2DM. Rosiglitazone is discouraged due to adverse cardiovascular outcomes. Pioglitazone has better data, especially in those who’ve had a stroke or TIA (IRIS Trial, NEJM 2016). They may have a role in those for whom other classes are contraindicated or cost-prohibitive.
- DPP4 Inhibitors: increase incretin levels (GLP-1 and GIP) which inhibit glucagon release, increase insulin secretion, and delay gastric emptying. They do not cause hypoglycemia or weight gain. These have a very modest glycemic effect and have no CV benefit. There was a signal for increased heart failure hospitalizations with saxagliptin and alogliptin, but not with sitagliptin. These should have very little, if any, role in your management.
- See Figures for the “Overall Approach” from the 2019 EASD-ADA update.
- Which anti-glycemic drugs have a proven cardiovascular outcomes benefit?
- GLP1 Agonists: bind to GLP1 receptor and promote glucose dependent insulin release, inhibit glucagon secretion, and delay gastric emptying. Note that patients should be counseled that these are injectables (oral semaglutide has not yet proven CV benefit). Liraglutide (LEADER trial) and injectable semaglutide (SUSTAIN-6) showed significant MACE reduction, but CV benefit does not appear to be a class effect. They likely have an anti-atherothrombotic effect as well as benefits on blood pressure, weight, and glycemic control without hypoglycemia. There is no apparent impact on heart failure hospitalizations. Warn of primarily GI side effects and infrequent risk of acute pancreatitis. Start low and slowly up-titrate as tolerated as GI symptoms typically abate with time. There is a black box warning for medullary thyroid cancer so AVOID if there is a family or personal history of this.
- SGLT2 Inhibitors: bind to and block the SGLT2 co-transporter in the renal proximal renal tubules, thereby inhibiting glucose reabsorption and increasing glucose loss via urine (glycosuria) along with osmotic diuresis as well as weight and blood pressure reduction. They have both cardiovascular and renal outcomes benefits. Importantly they reduce HF and cardiovascular death in those with HFrEF independent of hypoglycemic action and are now a key component for HFrEF optimal medical therapy (enjoy Ep #36 with Dr. Robert Mentz). Risks include: dehydration due to osmotic diuresis (consider reducing concurrent diuretic doses), genitourinary fungal infections (not UTIs including pyelonephritis; caution in those with urinary incontinence and poor perineal hygiene), euglycemic DKA (caution in T1DM and those with ketosis-prone T2DM), and a questionable risk of amputations and fractures associated with canagliflozin but not others in the class.
- NOTE: many patients with CVD remain on outdated hypoglycemic agents rather than on these newer agents with proven CV benefit. Much of this is related to cost and access. Whenever you see a patient with DM, review their med list and help them bring it up to speed with the latest data!
- What is the role of metabolic surgery in patients with DM?
- The prevalence of obesity is rising at an alarming rate and portrays an equally grim epidemiology for rising rates of diabetes and cardiovascular disease. By 2025, 1/5 of the world may be obese. Already, >1/3 of US adults are obese with stark differences based on race and socioeconomic status. The worldwide prevalence of diabetes is similarly expected to rise: >50% in the next decade! Rates of CV disease and mortality will follow suit.
- Preventing obesity via education, lifestyle, and policy is of the utmost importance.
- Managing obesity requires a multipronged approach with shared decision making including: promoting a healthy lifestyle with diet and exercise, +/- pharmacologic weight loss, +/- metabolic (bariatric) surgery.
- Behavioral intervention promoting a healthy lifestyle is the cornerstone for all overweight and obese patients as part of primary, secondary, and tertiary prevention. However the results are typically modest and inconsistently sustained over longer periods.
- Pharmacologic intervention for weight loss may provide added benefit over lifestyle alone and is indicated for individuals with BMI ≥30 kg/m2 or BMI ≥27 kg/m2 with at least 1 obesity-associated comorbidity who are motivated, but have failed to lose weight or maintain weight loss by using high-intensity lifestyle intervention alone. Obesity-associated comorbidities include: T2DM, HTN, HLD, ASCVD (CAD, CVA, PAD), CHF, Afib, VTE, OSA, and CKD. There are 5 antiobesity drugs approved by the US FDA: orlistat, lorcaserin, naltrexone-bupropion, phentermine-topiramate, and liraglutide. Of these, only liraglutide has proven CV benefit.
- Metabolic (bariatric) surgery is most effective for clinically significant and sustained weight loss and for diabetes remission in obese individuals. Surgical options include: Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), adjustable gastric banding (AGB), and biliopancreatic diversion with duodenal switch (BPDDS). Metabolic surgery is recommended for patients with a BMI ≥40 kg/m2 without concomitant medical problems and in patients with a BMI ≥35 kg/m2 who have at least 1 severe obesity-associated comorbidity (e.g. T2DM). Interestingly, some of the cardiometabolic benefits of metabolic surgery are independent of weight loss and include mechanisms related to incretin levels, insulin secretion/sensitivity, inflammatory mediator profile, bile acid circulation, and gut microbiota. The peri-operative risk is low and has declined with improved technique. Nutritional deficiencies are the most common long-term complications and can be prevented with follow-up and supplementation.
Show notes updated as of 12.13.2020
The Cardionerds CV prevention series includes in-depth deep dives on so many prevention topics including the ABCs of prevention, approach to obesity, hypertension, diabetes mellitus and anti-diabetes agents, personalized risk and genetic risk assessments, hyperlipidemia, women’s cardiovascular prevention, coronary calcium scoring and so much more!
We are truly honored to be producing the Cardionerds CVD Prevention Series in collaboration with the American Society for Preventive Cardiology! The ASPC is an incredible resource for learning, networking, and promoting the ideals of cardiovascular prevention! This series is kicked off by a message from Dr. Amit Khera, President of the American Society for Preventive Cardiology and President of the SouthWest Affiliate of the American Heart Association.
Guest Profiles
Dr. Dennis Bruemmer is the Director of the Center for Cardiometabolic Health in the Section of Preventive Cardiology and Rehabilitation at the Cleveland Clinic. Dr. Bruemmer earned his MD/PhD degrees from the University of Hamburg in Germany. Following residency training in internal medicine and cardiology in Berlin, Dr. Bruemmer completed a two-year research fellowship as the Diabetes Center Fellow in the Department of Endocrinology at UCLA. He is board-certified in Internal Medicine, Endocrinology, Cardiovascular Disease, and Echocardiography, quite a unique combination! Dr. Bruemmer’s research is focused on mechanisms of atherosclerosis and risk factor intervention for the prevention of coronary artery disease.
References and Links – (bold indicates review or guideline)
Dennis Bruemmer, MD, PhD 
Amit Goyal, MD 
Daniel Ambinder, MD
