diabetes

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Lilly’s MounjaroTM (Tirzepatide): A New Sheriff in Town

Gaganpreet Kaur

The prevalence of diabetes is increasing at an alarming rate, with more than 34 million Americans suffering from diabetes1. Patients with type 2 diabetes make up 90% to 95% of total diabetes cases1. Type 2 diabetic patients either do not produce enough insulin or develop insulin resistance, resulting in elevation of their blood glucose levels2. The U.S. Food and Drug Administration (FDA) recently, as an adjunct to diet and exercise, approved Eli Lilly and Company’s MounjaroTM (tirzepatide) injection (under the skin, once a week) for Type 2 diabetic patients to control hyperglycemia.  Mounjaro will be offered in 6 different doses, 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, and 15 mg, in an auto-injected pen with a pre-attached hidden needle. However, Mounjaro has not been designated to use in Type 1 diabetic patients and is not yet tested for patients with pancreatitis or children under 18 years of age3.

Mechanism of Action of MounjaroTM (tirzepatide):

Eli Lilly and Company’s new drug is a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor. GIP and GLP-1 are incretin hormones that are released from intestine upon ingestion of food. GLP-1 stimulates the release of insulin from beta cells of pancreas, increases the number and volume of beta cells, and decreases the levels of glucagon, a hormone also released by pancreas that instructs the liver to release stored glucose in the circulation2. Similarly, GIP also fuels insulin release, promotes beta cell production, and prevents destruction of beta cells2. In Type 2 diabetes, patients do not respond properly to incretin hormones. Mounjaro battles this issue by triggering the activation of GIP and GLP-1 receptor2.

Side Effects of MounjaroTM (tirzepatide):

The most common reported side effects, in at least 5% of patients, are nausea, diarrhea, reduced appetite, vomiting, constipation, indigestion, and abdominal pain. Mounjaro may cause severe side effects including hypoglycemia, pancreatitis, allergic reaction, kidney problems, gallbladder problems, and changes in vision. Further, a warning regarding thyroid cancer is issued; therefore, Mounjaro is not advised to use in patients with personal or family history of Medullary Thyroid carcinoma or Multiple Endocrine Neoplasia Syndrome Type 23.

SURPASS clinical trial program of MounjaroTM (tirzepatide):

The SURPASS trials evaluated the efficacy and safety of Mounjaro for Type 2 diabetes as a monotherapy and as an add-on to other standard care medications. Mounjaro was compared as other injectable medicines like semaglutide (GLP-1 mimic), insulin glargine and insulin degludec. Throughout the five global SURPASS studies, Mounjaro exhibited reduction in A1C among participants having Type 2 diabetes from an average of 5 to 13 years3.

  • SURPASS-1 (NCT03954834): A 40-week study tested the efficacy and safety of three different doses of Mounjaro (5 mg, 10 mg, and 15 mg) as monotherapy in comparison to placebo in Type 2 diabetic patients (naïve to injectable therapy and utilizing diet and exercise alone). Researchers reported that tirzepatide reduced A1C by 1.8% (with 5 mg) and 1.7% (with 10 mg and 15 mg) as compared to 0.1% with placebo. Further, participants lost weight on an average of 14 lb. (5 mg), 15 lb. (10 mg), and 17 lb. (15 mg) whereas participants in placebo group only lost 2 lb3,4.
  • SURPASS-2 (NCT03987919): In this 40-week study, participants were divided in 1:1:1:1 ratio to receive 5 mg, 10 mg, or 15 mg tirzepatide or 1 mg of semaglutide. Mounjaro reduced A1C by 2.0% (5 mg), 2.2% (10 mg) and 2.3% (15 mg) and semaglutide reduced A1C by 1.9%. In a key secondary endpoint, participants in Mounjaro group lost weight by a mean of 17 lb. (5 mg), 21 lb. (10 mg) and 25 lb. (15 mg) in comparison to 13 lb. reduced by semaglutide3,5.
  • SURPASS-3 (NCT03882970): A 52-week study compared the efficacy of previous doses of Mounjaro to insulin degludec (insulin analogue) as an add on to metformin with and without SGLT2 inhibitors. The trial reported 1.9% (5 mg), 2.0% (10 mg) and 2.1% (15 mg) reduction in A1C in patients receiving tirzepatide as compared to 1.3% reduction in patients receiving insulin degludec. Interestingly, participants on Mounjaro lost 15 lb. to 25 lb. depending on the dose, but participants taking insulin degludec gained an average of 4 lb3,6.
  • SURPASS-4 (NCT03730662): A 104-week study compared the efficacy of Mounjaro (5 mg, 10 mg, 15 mg) to insulin glargine in Type 2 diabetic patients with increased risk of cardiovascular disease. Researchers observed a 2.1% (5 mg), 2.3% (10 mg) and 2.4% (15 mg) reduction in A1C in patients receiving tirzepatide as compared to 1.4% reduction in patients receiving insulin glargine. Participants on Mounjaro lost weight (14 lb. with 5 mg, 20 lb. with 10 mg, and 23 lb with 15 mg), whereas insulin glargine group gained 4 lb3,7.
  • SURPASS-5 (NCT04039503): In this 40-week study, the efficacy and safety of Mounjaro as an add on drug to insulin glargine was compared to placebo. An average of 2.1% (5 mg), 2.4% (10 mg) and 2.3%* (15 mg) reduction was observed in Mounjaro group as compared to 0.9% in placebo group. Further, Mounjaro, as an add on drug, reduced body weight by 12 lb. to 19 lb. as compared to placebo group, where participants experienced 4 lb. weight gain3,8.

REFERENCE

  1. National Diabetes Statistics Report. Accessed January 14, 2022. https://www.cdc.gov/diabetes/data/statistics-report/index.html
  2. FDA approves trizepatide: A potent new drug for type 2 diabetes. Accessed May 20, 2022. https://www.medicalnewstoday.com/articles/fda-approves-tirzepatide-a-potent-new-drug-for-type-2-diabetes
  3. FDA arrpvoves Lilly’s MounjaroTM (tirzepatide) injection, the first and only GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes. Accessed May 20, 2022. http://lilly.mediaroom.com/2022-05-13-FDA-approves-Lillys-Mounjaro-TM-tirzepatide-injection,-the-first-and-only-GIP-and-GLP-1-receptor-agonist-for-the-treatment-of-adults-with-type-2-diabetes
  4. Rosenstock J, Wysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 07 10 2021;398(10295):143-155. doi:10.1016/S0140-6736(21)01324-6
  5. Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 08 05 2021;385(6):503-515. doi:10.1056/NEJMoa2107519
  6. Ludvik B, Giorgino F, Jódar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or without SGLT2 inhibitors in patients with type 2 diabetes (SURPASS-3): a randomised, open-label, parallel-group, phase 3 trial. Lancet. 08 14 2021;398(10300):583-598. doi:10.1016/S0140-6736(21)01443-4
  7. Del Prato S, Kahn SE, Pavo I, et al. Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial. Lancet. 11 13 2021;398(10313):1811-1824. doi:10.1016/S0140-6736(21)02188-7
  8. Dahl D, Onishi Y, Norwood P, et al. Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes: The SURPASS-5 Randomized Clinical Trial. JAMA. 02 08 2022;327(6):534-545. doi:10.1001/jama.2022.0078

“The views, opinions, and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness, and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions, or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your health matters. If you think you are having a heart attack, stroke, or another emergency, please call 911 immediately.”
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A Scientific Statement from the American Heart Association on the Management of Cardiovascular Risk Factors for Adults with Type 2 Diabetes

Gaganpreet Kaur

The prevalence of diabetes is increasing at an alarming rate, with more than 34 million Americans suffering from diabetes1. Patients with type 2 diabetes make up 90% to 95% of total diabetes cases1. Cardiovascular diseases (CVD) are the principal cause of death and disability in type 1 and type 2 diabetes patients2. American Heart Association (AHA) recommends a comprehensive and patient-centered approach involving lifestyle management and pharmacological interventions to manage cardiovascular risk factors, such as smoking, obesity, glycemia, blood pressure (BP), and lipid abnormalities, in type 2 diabetes patients3.

A healthy lifestyle can substantially lower the risk of CVD events in type 2 diabetic patients. Lifestyle management involves physical activity, nutrition, psychological and emotional well-being, and smoking cessation3. The lifestyle interventions using meal replacement products and at least 175 minutes of moderate-intensity physical activity /week, with a calorie goal of 1200 to 1800 kcal per day (with <30% from fat and >15% from protein), resulted in weight loss and hemoglobin A1c. Individuals with either ≥10% reduction in their body weight or >2 metabolic equivalent increase in fitness experienced reductions in cardiovascular outcomes; however, the rate of a major adverse cardiovascular event (MACE) was not reduced4. Mediterranean, vegetarian, low-carbohydrate, and diets rich in protein and nuts can lower blood glucose and body weight in type 2 diabetes patients3. Mediterranean diet over 4.8 years exhibited the highest benefits in blood glucose regulation and 29% of CVD events3,5. Further, increased exercise and physical activity can improve blood glucose, blood pressure, insulin sensitivity, lipid profile, and inflammation in type 2 diabetes3. American Diabetes Association (ADA) has recommended more than recommends ≥150 minutes/week of moderate-to-vigorous intensity aerobic activity with no more than 2 days of inactivity in diabetes patients3,6. Including 2-3 sessions/week each of resistance and balance training is also recommended. Further, vigorous activity for a short duration (>75 minutes/week) or interval training is beneficial3,7. Patients with BMI ≥27 kg/m2 can use US Food and Drug Administration (FDA) approved weight loss medication. Orlistat, lorcaserin, liraglutide, naltrexone/bupropion are some of the weight management drugs approved by FDA have demonstrated ability to lower A1c3. Liraglutide at a lower dose can reduce cardiovascular risk in high-risk patients8. However, medicines should be immediately stopped if weight loss after 3 months is less than 5% or any safety concerns arise. Patients with BMI ≥40 kg/m2 or BMI 35.0 to 39.9 kg/m2 with no benefit with nonsurgical methods can consider metabolic surgery3. The long-term effects of weight-loss drugs and metabolic surgery on reducing cardiovascular events are yet to be studied.

Smoking is linked with abnormal lipid profile, worsening of glycemic measures, and increased pro-inflammatory marker in type 2 diabetes. Therefore, cessation of smoking is recommended3. Interestingly, light to moderate alcohol consumption compared to no drinking, particularly wine, has been associated with fewer heart attacks, whereas heavy alcohol consumption increases CVD risk3. Despite the benefits of moderate alcohol intake, non-drinks should not be advised to drink, and adults with diabetes should be mindful of the risk of hypoglycemia, weight gain, and hypertension. No more than 1 drink/day for women and 2 drinks/day for men are recommended3. In America, 12-ounce beer or 5-ounce wine, or 1.5 ounces of distilled spirits are considered as one drink.

In addition to lifestyle management, intensive glycemic control can be valuable to prevent cardiovascular disease events in diabetes patients. Randomized trials involving intensive glucose control using insulin reported a 17% reduction in myocardial infarction (MI), 15% reduction in coronary heart disease, 16% reduction in nonfatal MI, but no effect on stroke or all-cause mortality3. However, tight glucose control increases the two-fold risk of severe hypoglycemia and 47% risk of heart failure3. The research involving intensive glucose control using new anti-hyperglycemic agents is undergoing. Some newer agents are Dipeptidyl peptidase-4 (DPP4) inhibitors, GLP-1 receptor agonists, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. DPP4 inhibitors inhibit the DPP4 enzyme, thereby prolonging the action of incretin hormone GLP-1 and insulinotropic polypeptide, which ultimately results in increased insulin secretion and lower glucose. DPP4 inhibitors agents successfully lowered A1C but showed no reduction in MACE, and one of the agents was associated with an increased risk of heart failure3. GLP-1 receptor agonist stimulates insulin release and slows down gastric emptying to decrease glucose absorption. The intervention with GLP-1 receptor agonists resulted in a significant reduction in MACE, heart attack, stroke, and cardiovascular death; however, it had no beneficial effect on heart failure. The use of GLP-1 receptor agonists is associated with increased heart rate, pancreatitis, pancreatic cancer, thyroid cancer, and retinopathy. SGLT-2 inhibitors limit glucose reabsorption in the renal tubules3. SGLT-2 inhibitors lower the risk of hypertensive heart failure by 27-35%, MACE BY 11%, heart attacks by 11%, and cardiovascular death by 16%. SGLT-2 inhibitors are associated with genital and urinary infections, polyuria, acute kidney injury (with a higher dose), and reduction in bone mineral density3.

CVD risk increases with low and high blood pressure in patients with type 2 diabetes. When initiated at baseline (BP > 140/90 mmHg), Antihypertensive therapy resulted in CVD risk reduction but did not have a robust effect in type 2 diabetes patients compared to patients without diabetes3. ADA does not recommend a specific BP target but suggests risk classification to avoid overtreatment and polypharmacy3. In addition to BP abnormalities, an altered lipid profile is also a central risk factor for CVD in diabetes. The most common lipid abnormalities encountered in diabetes include:

  • Increased serum triglycerides.
  • Triglyceride-rich, very-low-density lipoprotein.
  • Mild increase in small dense low-density lipoprotein cholesterol (LDL-C).
  • Decreased HDL-C.

The lipid therapies include lowering LDL with statin/ non-statin, lowering triglycerides, and increasing HDL. Statin therapies reduce cardiovascular risk by 25%9, but HDL raising therapies had no effect3.

Lastly, clinical care only accounts for 10-20% of health outcomes; the rest 80-90% is contributed by social determinants, including socioeconomic factors, racism, environment, and individual behavior3. Therefore, we need a multifaced approach to address social determinants to eliminate disparities in CVD health. AHA recommends using a patient-centered approach and considering the patient’s family, community, and society while planning their cardiovascular risk management3. ADA and AHA have initiated a “Know Diabetes by Heart” program to improve CVD and outpatient care of type 2 diabetes patients. The program raises awareness about the link between diabetes and CVD, supports clinicians in patient engagement, and empowers patients3.

 Reference

  1. National Diabetes Statistics Report. Accessed January 14, 2022. https://www.cdc.gov/diabetes/data/statistics-report/index.html
  2. Cheng YJ, Imperatore G, Geiss LS, et al. Trends and Disparities in Cardiovascular Mortality Among U.S. Adults With and Without Self-Reported Diabetes, 1988-2015. Diabetes Care. 11 2018;41(11):2306-2315. doi:10.2337/dc18-0831
  3. Joseph JJ, Deedwania P, Acharya T, et al. Comprehensive Management of Cardiovascular Risk Factors for Adults With Type 2 Diabetes: A Scientific Statement From the American Heart Association. Circulation. Jan 10 2022:CIR0000000000001040. doi:10.1161/CIR.0000000000001040
  4. Fox CS, Golden SH, Anderson C, et al. Update on Prevention of Cardiovascular Disease in Adults With Type 2 Diabetes Mellitus in Light of Recent Evidence: A Scientific Statement From the American Heart Association and the American Diabetes Association. Circulation. Aug 25 2015;132(8):691-718. doi:10.1161/CIR.0000000000000230
  5. Esposito K, Maiorino MI, Bellastella G, Chiodini P, Panagiotakos D, Giugliano D. A journey into a Mediterranean diet and type 2 diabetes: a systematic review with meta-analyses. BMJ Open. Aug 10 2015;5(8):e008222. doi:10.1136/bmjopen-2015-008222
  6. Association AD. 5. Facilitating Behavior Change and Well-being to Improve Health Outcomes:. Diabetes Care. 01 2020;43(Suppl 1):S48-S65. doi:10.2337/dc20-S005
  7. Arnett DK, Blumenthal RS, Albert MA, et al. 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 09 10 2019;140(11):e596-e646. doi:10.1161/CIR.0000000000000678
  8. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes. N Engl J Med. 07 28 2016;375(4):311-22. doi:10.1056/NEJMoa1603827
  9. de Vries FM, Denig P, Pouwels KB, Postma MJ, Hak E. Primary prevention of major cardiovascular and cerebrovascular events with statins in diabetic patients: a meta-analysis. Drugs. Dec 24 2012;72(18):2365-73. doi:10.2165/11638240-000000000-00000

“The views, opinions and positions expressed within this blog are those of the author(s) alone and do not represent those of the American Heart Association. The accuracy, completeness and validity of any statements made within this article are not guaranteed. We accept no liability for any errors, omissions or representations. The copyright of this content belongs to the author and any liability with regards to infringement of intellectual property rights remains with them. The Early Career Voice blog is not intended to provide medical advice or treatment. Only your healthcare provider can provide that. The American Heart Association recommends that you consult your healthcare provider regarding your personal health matters. If you think you are having a heart attack, stroke or another emergency, please call 911 immediately.”
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Diabetes Makes Heart Disease Worse

Keerat Kaur, PhD

Global awareness has made us cognizant that people with diabetes are susceptible to various disorders involving eye, kidney or nervous system and blood circulation affecting the limbs in the long run. Along these lines, type 2 diabetic patients are more likely to develop heart disease and have a greater incidence of heart attack. According to American Heart Association (AHA), diabetes is one of the major contributing factors for cardiovascular disease and accounts for at least 68 percent of diabetic population of age 65 or older to die from some form of heart disease.

Diabetic heart disease (DHD) is a broader term used to explain heart problems in patients who have diabetes. DHD may include conditions like coronary heart disease, where plaque accumulating in your arteries reduces the blood flow to the heart eventually leading to heart failure, a condition where your heart cannot pump enough blood to meet your body’s requirements. Another consequence of diabetes can be diabetic cardiomyopathy where the damage is extended to the structure and function of the heart. Patients with diabetic cardiomyopathy are more predisposed to develop irregular heartbeat disorders called arrhythmias.

Arrhythmias are conditions in which there is a problem with the rate or rhythm of your heartbeat. It is observed when the electrical signals to the heart that coordinate heartbeats do not function properly. This leads to increase in heart rate (basal rate of more than 100bpm), a condition called trachycardia or decrease in heart rate (basal rate less than 60bpm), called bradycardia. The detailed illustration of these conditions can be found at AHA website. While these conditions can have serious complications in patients, the condition becomes far worse in patients with DHD.

Under normal conditions, mitochondrias which are the energy sources of the cell, give rise to dangerous chemicals known as reactive oxygen species (ROS), byproducts of aerobic metabolism. Oxidative stress occurs when there is excessive production of ROS and if these chemicals are not removed, they possess damage to proteins, tissues and genetic material of the heart cells. However, mitochondria have antioxidant defense systems which decrease ROS production. Under pathological conditions such as diabetes, glucose fluctuations far exceed the ROS production than the oxidative defense systems are capable of cleaning and thus the problem becomes far more intense.

At this year’s Scientific Sessions, one of my colleagues presented his work establishing an interesting link between oxidative stress and arrhythmias. His project focused on protein which is a key enabler of ROS- mediated cardiac arrhythmias, known as mitochondrial translator protein (TSPO). TSPO is an outer mitochondrial membrane protein, previously described as peripheral benzodiazepine receptor, a secondary binding site for diazepam. It’s primarily associated with cholesterol transport to inside the cell, while the group explains its potential role in mitochondrial instability during arrhythmias by mechanism, where excess ROS generated in diabetic patient positively up-regulates its own levels – a process called ROS induced ROS-release (RIRR). Thus, TSPO can be a potential therapeutic target against arrhythmias in diabetic patients. Preliminary data by the group confirmed the increased levels of TPSO in hearts of diabetic rats, which might be responsible for increased propensity of diabetic hearts to arrhythmic events. While TPSO is probably upregulated as compensatory mechanism during type 2 diabetes, its global gene silencing may interfere with essential homeostatic function including cholesterol import and mitochondrial biogenesis. In relation to that, the group is further looking into avenues for targeted and specific TSPO inhibition in the areas affected after heart attack.

Personally, I am not only proud of his work but also hopeful that research studies like his help us to identify potential targets for curing serious conditions like DHD.

 

References:

Ilkan Z, Akar FG. The Mitochondrial Translocator Protein and the Emerging Link Between Oxidative Stress and Arrhythmias in the Diabetic Heart.Front Physiol. 2018;26;9:1518

Ilkan Z, Strauss B, Akar FG. Reversal of TSPO Upregulation in the Diabetic Heart by Chronic TSPO Gene Silencing Causes Metabolic Sink via an Increase in ROMK Expression. Circulation. 2018;138:A16826.

 

 
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Joint Hypertension 2018 Scientific Sessions – You Should Have Been There

Anberitha Matthews, PhD

hypertension 2018

Just as promised, the Joint Hypertension 2018 Scientific Sessions (Hypertension18) was indeed among the most impactful meetings one could have attended. Council on Hypertension Scientific Sessions Planning Committee Vice Chair Dr. Karen Griffin, FAHA was accurate in her statement that it would be “the premier scientific meeting.” There were experts from all parts of the world covering more cardiovascular topics that I think my fingers could not keep up with in note taking, and each session was more informative than the next with up-to-date information on hypertension.

During the President’s Welcome Address, Dr. Ivor Benjamin, FAHA foreshadowed what was to be expected during the meeting. He gave general overviews of the hypertension guidelines, what the changes mean to clinicians and researchers, as well as the role AHA will play in helping drive those changes forward. His welcome was a great introduction to the ‘Recent Advances in Hypertension’ Session chaired by Drs. Joey Granger from the University of Mississippi Medical Center and John Bisognano from University of Rochester Medical Center. This session covered the new guidelines, implementation, and basic research advances of clinical hypertension moving forward by Drs Basile, Egan, Oparil, and Ellison. The whirlwind of information was just the icebreaker! During the refreshment break and exhibits, I met a number of “Rockstars” including clinicians and researchers from University of Alabama Birmingham, Drs. David and Jennifer Pollock and AHA Early Career blogger Tanja Dudenbostel. Additionally, this was the only time I spent visiting with vendors. Among them, Hulu explained the importance of calibrating automatic blood pressure machines. Historically blood pressure was taken with a manual sphygmomanometer and a technician listening for ausculatory sounds via a stethoscope, but now it is all automated. Generally one machine is used for all patients. This technology forces us to question the accuracy of the readings of the machines. Are they calibrated? Should the BP be taken radially or at the wrist? Should the machine be changed throughout the day? There was Aegis representatives sharing information about products to assist medical professionals determine patient compliance to therapy and toxicology testing equipment. During these conversations, it was surprising to discover some of the rationales behind why people would opt to not take medicine as prescribed.

With my research being focused on oxidative stress-induced vascular injury and since I have become increasingly more interested in health and wellness, I took particular interest in the session focused on “Lifestyle Modifications and Impact on BP” chaired by the Associate Editor of Hypertension, David Harrison, MD, FACC, FAHA, “Recent Advances Obesity and Cardiovascular Disease” chaired by the consulting Editor of Hypertension Suzann Oparil, MD, FAHA, and “Obesity, Diabetes, and Metabolic Syndrome” chaired by Drs. Kamal Rahmouni and Carmen De Miguel. During these sessions, it was not surprising that regular exercise reduced vascular stiffness, but what was noteworthy was that weight training contributes to atherosclerosis. Additionally, the sympathetic nervous system seems to be important in glomerular filtration. Dr. Elizabeth Lambert delivered an intriguing talk about how diet and exercise can significantly decrease metabolic syndrome in middle aged obese individuals, which is consistent with a recent study (Hypertension18 Meeting Report P388) that suggests lifestyle changes can reduce hypertension in both men and women. Further, the study suggests that following the DASH diet, exercising, and weight management over a course of 16 weeks were contributing factors in reducing BP in test subjects. We all know anti-hypertensives work in reducing BP. Lifestyle changes should be the first line of defense in evading hypertension and getting it under control at the onset, according to the American Heart Association/American College of Cardiology  Hypertension Guidelines. We have all heard that we have to get out there and get moving. Choosing the right exercise is just as important as exercising, according to Dr. Tanaka.

I recently wrote a blog discussing metabolic syndrome and therein indicated there is not a direct correlation between obesity and diet. During this conference, Dr. John Hall lectured on the recent advances in CVD and obesity. He suggested that epigenetic transmission of obesity in humans (and others) is associated with increased adiposity and insulin resistance, depletion of nuclear protein, influence chromatin conformation, and altered germ cell methylation and gamete micro RNA.

The new concurrent session Clinical Practice Clinical Science and Primary Care tracks did not go unnoticed. Although I did not get to attend many of these sessions, I did pass them to see that they were well attended. I did attend some of the lunch meetings and they were very insightful. Please refer to my Twitter to see my detailed notes. As mentioned in my pre-conference blog, with all the sessions that were available one should not have had an issue meeting the goals outlined in the program by coordinators (infra vide). Several sessions that met the interest of all researchers/clinicians, early career, and everyone in between. Not a person that attended Hypertension18 could say they could not find a learning opportunity at the Joint Hypertension 2018 Scientific Sessions! Even if one was merely a passerby, there was a session relevant to them. For example, I was on my way to get coffee when I encountered Drs. Yagna Jarajapu from North Dakota State University and Daniel Batlle from University of Chicago discussing research concerning STZ diabetic Foxn1 mice that were ischemic for several days. Subsequently, Eric Metterhausen shared his mission of services (MOS, for you military people) with me as we conversed about field medicine with the United States Public Health Services (USPHS). I did know our US Armed Forces had research officers and divisions of research, but the amount of detail that Major Metterhausen described was a beast that I had not known. Conversations such as these lead to increased mentoring relationship, as well as potential collaborations in research and grant proposals. We all go to conferences to learn, to purchase new research equipment, and to present our data, but we also should not forget to network and build relationships.

Conference Learning Objectives:

  • Discuss changes to the AHA/ACC guidelines for the management of hypertension and their clinical implications.
  • Describe opportunities to improve blood pressure measurement in the clinical setting to provide more accurate results.
  • Identify immune and inflammatory mechanisms that contribute to the development of hypertension and hypertension-related end-organ damage and discuss the research and clinical implications.
  • Educate participants about medical approaches for the management of comorbid obesity in patients with hypertension.

 

  • Describe participants on the impact of value-based reimbursement on hypertension management and identify opportunities to improve its management.

 

See you all in Chicago at Scientific Sessions 2018!!!

  • Leave a comment and follow me on Twitter @AnberithaT and @AHAMeetings if you have questions or are interested in something else specifically.

 

Anberitha Matthews, PhD is a Postdoctoral Fellow at the University of Tennessee Health Science Center in Memphis TN. She is living a dream by researching vascular injury as it pertains to oxidative stress, volunteers with the Mississippi State University Alumni Association, serves as Chapter President and does consulting work with regard to scientific editing.
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Metformin: A diabetes medication with cardiovascular protective effects

Dalia Gaddis, PhD

What if a diabetes medication can improve cardiovascular events? Since patients with type II diabetes are more prone to cardiac events, the use of diabetes medication to help reduce cardiovascular burden would definitely be beneficial. One of such medications is the drug, Metformin.

Metformin, also know with the trade name of Glucophage, is the first-line of treatment for type II diabetes. It is also often prescribed to patients with metabolic syndrome and patients with polycystic ovarian syndrome to control insulin resistance. Metformin works by increasing insulin sensitivity and decreasing glucose production by the liver. While its molecular mechanism of action is not completely understood, one way metformin exerts its effects is through regulating AMP-activated protein kinase (AMPK), an enzyme that plays an important role in insulin signaling and detecting cellular energy levels. By regulating AMPK, metformin also lowers inflammation and thus there is an emerging body of evidence suggesting that metformin regulates the immune system and reduces inflammation and can potentially protect against diseases such as inflammatory bowel disease and atherosclerosis. 

Until recently, there has been associations that metformin may protect against cardiovascular disease, although exactly how was never been directly studied. A recent study by a group of researchers in Columbia University in New York, published recently in the ATVB journal, looked at the role of metformin and how it may affect cardiovascular disease. The authors show that exposure of liver cells to metformin increased the expression of ABCG5 and ABCG8, two cholesterol transporter molecules responsible for the efflux of cholesterol. The authors also saw the same effect when they gave metformin to mice fed a western diet, also know as high cholesterol, high fat diet. This increase in expression of ABCG5 and ABCG8 was accompanied by an increase in cholesterol clearance from the plasma in these treated mice. This study provides first evidence of how metformin could have a direct cardiovascular disease protective effect.

Since metformin, through regulating AMPK, has an anti-inflammatory effect, this study shows that metformin may have a combined protective impact regarding cardiovascular disease; the first through increasing cholesterol clearance and the second through reducing immune mediated inflammation, overall resulting in lower cholesterol levels and less inflammatory mediators responsible for atherosclerosis progression and thus reducing cardiovascular disease risk. It would be interesting to see if patients who are taking metformin for diabetes treatment have a decrease in cardiovascular events in a controlled manner. Finally, this study highlights the potential of a drug like metformin, not only as a diabetes medication but as a cardiovascular protective drug as well.

Dalia Gaddis Headshot

Dalia Gaddis is a postdoctoral fellow at the La Jolla Institute for Allergy and Immunology. She has a Ph.D. in microbiology and immunology. She is currently working on understanding the interactions between the immune system and atherosclerosis development.
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Weight Loss And Exercise: A Remedy For A Better Functioning HDL

Dalia Gaddis, PhD

We all know that weight loss and exercise are essential for a better health. A healthy life style reduces cardiovascular risk, obesity, and Type 2 Diabetes. In a previous post, I briefly touched upon the idea that weight loss and exercise make HDL, or our “good cholesterol,” better at reducing cholesterol circulating the bloodstream. In the latest issue of the ATVB journal, in the translational section, a new study from Baker Heart and Diabetes Institute in Melbourne, Australia looked at this specific idea. They asked how does weight loss and exercise affect HDL in patients. So I thought it would be interesting to share the results from this study.

The study examined 95 patients with metabolic syndrome and compared them to healthy individuals. Metabolic syndrome patients have characteristics that include obesity, high blood glucose levels, hypertension and/or dyslipidemia. These patients tend to have dysfunctional HDL, and its level fail to predict the possibility of future cardiovascular events. In the study, patients were divided into 3 groups. The first group had to reduce their caloric intake by 600 calories a day. The second group also reduced their caloric intake by 600 calories and, in addition, had to exercise for 3-4 sessions of about 30 minutes each. The third group kept their usual dietary and exercise patterns. The patients were monitored for 12 weeks and tested at the beginning and at the end of the study. Both groups resulted in similar weight loss. However, the researchers found evidence that the group of patients that followed both healthier diets and an exercise regimen had the most change in HDL capacity to excrete cholesterol.

Upon looking at the details of the study, the researchers first observed that metabolic syndrome patients had smaller HDL particles with different composition, and lesser ability to get rid of cholesterol easily. With diet and exercise, the size of HDL particles in those patients got bigger and their ability to function in cholesterol efflux assay improved making these particles overall better in excreting blood cholesterol.

Despite the small sample size of the study, these results are promising in providing a better understanding of how life style changes can impact HDL function and overall reduce risk for CVD and Type 2 Diabetes. For me personally, this study make me wonder if exercise alone would effect HDL function, since it has become apparent that while exercise is important, exercise alone without appropriate dietary changes are not sufficient to lead to weight loss. Can exercise alone improve HDL composition and function? While this study does not provide an answer to my question, I am sure more studies will come out to address this question specifically. So until we know more, keep those healthy salads and spinning classes coming.

Dalia Gaddis Headshot

Dalia Gaddis is a postdoctoral fellow at the La Jolla Institute for Allergy and Immunology. She has a Ph.D. in microbiology and immunology. She is currently working on understanding the interactions between the immune system and atherosclerosis development.