Guest Editorial: Diabetes and Obesity: Transatlantic Considerations on a Global Public Health Issue

Definitions

Obesity is defined as the presence of abnormal or excessive fat accumulation, which increases the risk for conditions with negative impact on human health, such as diabetes mellitus and cardiovascular disorders, among others. It is diagnosed when the body mass index (BMI) is at or above 30 kg/m². Obesity is causally related to several metabolic complications, including type 2 diabetes (DM2), where >50% of new cases are believed to be directly related to this condition. Thus, the combination of co-morbidities has been named ‘diabesity’; to address them concurrently. Given their shared etiopathogenic mechanisms and complications, along with the potential for therapies with combined beneficial effects for both conditions, this holistic view, aiming to address DM2 and obesity simultaneously, seems most appropriate. Because of the global nature of the diabesity epidemic, we will address some of the major differences observed in the epidemiological, diagnostic, and therapeutic strategies employed in the United States (US) and Europe, despite the common nature of the condition.

Epidemiology

In recent years, obesity has become a global epidemic, reaching record-high levels in industrialized nations, with the US holding the Western world record¹, with an astonishing 41.9% of the population being obese in 2017, and 21 states having obesity rates >35% in 2021. On the other hand, Europe seems to be doing better in that regard², with the obesity prevalence being 23% in 2016, and 9 European states surpassing 30%. Despite this vast difference in prevalence, the trends are discouraging in Europe as well, since European states observed a 21% rise in obesity prevalence over the past ten years, similar to what has been observed in the US (>10% rise in 5 years in 31/50 states). In both continents, women seem slightly more affected than men, while racial differences have a pronounced effect. African Americans and Native Americans/Pacific Islanders tend to have higher rates, while Asian Americans and Non-Hispanic whites seem to lag in that regard. In Western Europe, rising numbers of immigrants from Africa and Asia have altered the demographics in most countries, yielding similar differences in the rates of obesity, especially in countries where the numbers of immigrants are high, such as the United Kingdom (UK) and Germany. Of course, the cutoffs used for the diagnosis of obesity differ in Asian populations, where a BMI >27 Kg/m² is used, due to the higher amount of visceral fat, which is more strongly associated with cardiometabolic risk. Of note, in some European states, the rise in obesity prevalence seems to have stagnated lately, especially among the highest-educated individuals.³

On the other side of the diabesity complex, DM2 has become a global epidemic as well. However, after a period of >40 years of a rising incidence, it has started to decrease in the US over the past ten years. Of course, DM2 prevalence continues to rise, with the implementation of newer therapies that confer longer survival in the affected individuals. The most recent estimates suggest a DM2 prevalence of approximately 10% for the US population (9 states with prevalence >12%),⁴ as compared to 6.2% in the European Union, where large differences are observed between different states (Germany, Portugal, and Turkey ≥10%, while UK, Ireland, Lithuania, Estonia, France, Greece, and Sweden <4%).² Gender differences are universal, with males affected much more commonly as compared to females, despite the small difference in the rates of obesity between genders. The protective effects of estrogens throughout the reproductive years seem to play a significant role in that regard, independently of the effects of other risk enhancing or protective factors. Ethnic or racial variation also produces large differences in DM2 prevalence rates. For example, African Americans, Pacific Islanders, some ethnic groups of Hispanics, and certain tribes of American-Indians have significantly higher rates of DM2 in the US; similarly, South Asians, North and Sub-Saharan Africans have significantly higher rates in Europe. In these populations, the rates improve substantially when studying second- or third-generation immigrants or people of mixed origins, but they don't tend to equalize to natives' prevalence rates. Socioeconomic and educational status seem to play an important role, with these rates improving at a slower pace in the poorest and least educated individuals.

Cardiovascular Disease

One of the main complications of diabesity is the development of atherosclerotic cardiovascular disease (ASCVD), while heart failure is a common first manifestation of DM2. A 2015 study comparing the prevalence of heart disease among volunteer respondents from the US and 5 European countries⁵, found that the prevalence of heart disease was 75% higher in the US and the gap increased with rising age. Overall, cardiovascular diseases accounted for 36.7% of all deaths in Europe for 2017, and approximately 20% of deaths in the US in 2021. Despite these huge numbers, geographical, ethnic, and racial differences are present in both sides of the Atlantic Ocean. People of black race, residing in the southern States and of Asian descent are affected most and die more frequently of ASCVD in the US. Other populations which are unequally represented include incarcerated and uninsured individuals.⁶ On the other hand, Eastern and Central European states exhibit increased rates of ASCVD and related mortality but lower rates of revascularization procedures or bypass surgeries, as compared to the Western and Southern states. In addition, immigrants from South Asia, the Middle East and Eastern Europe migrating to West European States exhibit higher rates of ASCVD events as well⁷, and these are associated with their respective genetic backgrounds, their pre-migration environment, the post-migration lifestyle, and their post-migration generation. Therefore, it is evident that strategies aiming to enhance primordial and primary ASCVD prevention should be instituted, with a focus in underserved populations in both continents.  

Treatment and Guidelines

To curb the diabesity epidemic, multiple national and international organizations have made substantial efforts and published guidelines, exhibiting a strong concordance overall and an inclusive view regarding newer, beneficial prescription drug classes. In that regard, GLP-1 agonists are strongly supported as first-line agents in treating patients with diabesity, where their maximal benefit is obtained. Unfortunately, due to their proven weight loss effectiveness, the rise in their off-label use globally led to massive shortages. Despite this situation’s logistic and financial constraints, GLP-1 agonists are accepted as a game-changing class of medications by all scientific societies.^8-10 Their additive benefits regarding renal and CVD protection, support their early and targeted incorporation in clinical practice. Similarly, SGLT-2 inhibitors exhibited impressive survival benefits, reductions in the risk of heart failure or hospitalization for heart failure, renal protection, and strong reductions in adverse renal outcomes.^8,11,12 Therefore, it came as no surprise that both medication classes made it to the top for both the US and European guidelines^.8-12 Unfortunately, their incorporation in the medical regimen of patients who would benefit from their use has been inadequate to date, with substantial national and regional differences. A nationwide study in Sweden, which is one of the top achievers globally in that regard, estimated the penetrance of SGLT-2 inhibitors and GLP-1 agonists at 25.4-33.7% of the population in need, based on recent guidelines.⁸ The addition of these medications in the recent guidelines from the ESC, the KDIGO, and the AHA/ACC is expected to raise awareness and allow more patients to obtain the benefits of these medication classes.^9,10,12

A change observed in US and European medical societies’ guidelines include stricter lipid-lowering goals for patients with DM2, given the excessive risk for ASCVD. Therefore, LDL-C lowering of >50% and an LDL-C <70 mg/dL are simultaneously required for these patients. When obesity is present, but DM2 has not ensued, a 10-year ASCVD risk estimation using validated population-specific calculators is required to select an individualized, risk-factors based ASCVD risk reduction strategy. A major difference in the European guidelines is the establishment in 2019 of a tentative LDL-C goal for patients with multiple CVD events, despite LDL reduction, to <55mg/dL, where a further LDL reduction should be considered to attain LDL-C <40mg/dL.^8,13 In addition, the incorporation of non-statin lipid-lowering medications varies significantly between the US and certain European States due to the differences in the availability of newer medications (e.g., inclisiran, etc.), even though their suggested use appears concordant among different guidelines. Finally, an interesting difference between the two continents resides in the use of coronary artery calcium score (CAC), which is enthusiastically incorporated in routine clinical practice in multiple US regions, while its penetration is limited in several European states, due to the limited mention in the 2019 ESC guidelines and the potential lack of access to appropriate instruments/technique, while the US guidelines have been more supportive of its use in patients at intermediate ASCVD risk.^9,13 CAC is an effective stratifier of ASCVD risk, which among patients with diabetes, coronary heart disease (CHD) event rates vary 10-fold according to extent of CAC, documenting the heterogeneity in risk among those with diabetes (and that many are not CHD risk equivalents).¹⁴

Overall, diabesity is a highly prevalent disorder affecting large numbers of patients in the Western World, producing substantial morbidity and mortality. Despite the epidemiological differences observed between the two continents, evidence suggests that change is needed globally, to enhance our primary preventive services and incorporate rapidly and effectively all the advanced treatment modalities available for the secondary prevention of this condition.

Dr. Bantouna has no financial relationships to disclose. Dr. Paparodis has no financial relationships to disclose. 

References

1. Division of Nutrition, Physical Activity, and Obesity, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention, Adult Obesity Facts, Updated May 17, 2022. Accessed July 12, 2023. https://www.cdc.gov/obesity/data/adult.html
2. World Health Organization Regional Office for Europe, WHO EUROPEAN REGIONAL OBESITY REPORT 2022. Accessed July 12, 2023. https://apps.who.int/iris/bitstream/handle/10665/353747/9789289057738-eng.pdf
3. Kagenaar E, Van Hemelrijck WMJ, Kunst AE et al. Long-Term Trends in Obesity Prevalence by Socio-Economic Group in Five European Countries and the USA: The Relevance of the Diffusion of Innovations Theory. Obesity Facts. 2022 15 (6): 753–761. doi: 10.1159/000527070.
4. Diabetes Data and Statistics, Centers for Disease Control and Prevention, Updated March 9, 2022, Accessed July 13, 2023. https://www.cdc.gov/diabetes/data/index.html
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9. 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. J Am Coll Cardiol. 2019 Sep 10;74(10):e177-e232. doi: 10.1016/j.jacc.2019.03.010.
10. Lim CE, Pasternak B, Eliasson B et al. Use of sodium-glucose co-transporter 2 inhibitors and glucagon-like peptide-1 receptor agonists according to the 2019 ESC guidelines and the 2019 ADA/EASD consensus report in a national population of patients with type 2 diabetes. European Journal of Preventive Cardiology. 2023 Jun 1;30(8):634-643. doi: 10.1093/eurjpc/zwac315.
11. Navaneethan SD, Zoungas S, Caramori et al. Diabetes Management in Chronic Kidney Disease: Synopsis of the KDIGO 2022 Clinical Practice Guideline Update.Ann Intern Med 2023 Mar;176(3):381-387. doi: 10.7326/M22-2904. 
12. Samson SL, Vellanki P, Blonde L et al. American Association of Clinical Endocrinology Consensus Statement: Comprehensive Type 2 Diabetes Management Algorithm - 2023 Update. Endocr Pract 2023 May;29(5):305-340. doi: 10.1016/j.eprac.2023.02.001. 
13. Mach F, Baigent C, Catapano AL et al. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). Eur Heart J. 2020 Jan 1;41(1):111-188. doi: 10.1093/eurheartj/ehz455.
14. Malik S, Budoff MJ, Katz R, Blumenthal RS et al. Impact of subclinical atherosclerosis on cardiovascular disease events in individuals with metabolic syndrome and diabetes: the multi-ethnic study of atherosclerosis. Diabetes Care. 2011 Oct;34(10):2285-90. doi: 10.2337/dc11-0816.