Pecori Giraldi F, Leoni O. Environment and diabetes: Is there an association between the COVID-19 pandemic and phenotypic variation in diabetes? World J Diabetes 2026; 17(4): 115328 [DOI: 10.4239/wjd.v17.i4.115328]
Corresponding Author of This Article
Francesca Pecori Giraldi, Associate Professor, Department of Clinical Sciences & Community Health, University of Milan, Via Commenda 19, Milan 20122, Lombardy, Italy. francesca.pecorigiraldi@unimi.it
Research Domain of This Article
Endocrinology & Metabolism
Article-Type of This Article
Retrospective Cohort Study
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This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Apr 15, 2026 (publication date) through Apr 14, 2026
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World Journal of Diabetes
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1948-9358
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Pecori Giraldi F, Leoni O. Environment and diabetes: Is there an association between the COVID-19 pandemic and phenotypic variation in diabetes? World J Diabetes 2026; 17(4): 115328 [DOI: 10.4239/wjd.v17.i4.115328]
Francesca Pecori Giraldi, Department of Clinical Sciences & Community Health, Deparment of Excellence 2023-2027, University of Milan, Milan 20122, Lombardy, Italy
Olivia Leoni, Data Monitoring and Control Unit, Welfare Governance, Regione Lombardia, Milan 20122, Lombardy, Italy
Author contributions: Pecori Giraldi F performed study design, data collection and analysis, and drafted manuscript; Leoni O curated methodology and project administration; Pecori Giraldi F and Leoni O revised and approved the final manuscript.
Institutional review board statement: The study was approved by the Ethical Committee of the University of Milan.
Informed consent statement: Not required (data anonymized by data warehouse software).
Conflict-of-interest statement: Pecori Giraldi F has no conflict of interest to disclose; Leoni O is an employee of Regione Lombardia, the state-funded Health Care Provider.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
Data sharing statement: Data that support the findings of this study were created under license for the current study and are therefore not publicly available. As per the undersigned agreement, data ownership rests with the Regione Lombardia.
Corresponding author: Francesca Pecori Giraldi, Associate Professor, Department of Clinical Sciences & Community Health, University of Milan, Via Commenda 19, Milan 20122, Lombardy, Italy. francesca.pecorigiraldi@unimi.it
Received: October 14, 2025 Revised: December 8, 2025 Accepted: February 4, 2026 Published online: April 15, 2026 Processing time: 182 Days and 15.5 Hours
Abstract
BACKGROUND
The development of diabetes is linked to the environment, and major lifestyle changes are known to affect the incidence of diabetes. The recent coronavirus disease 2019 (COVID-19) pandemic changed many aspects of daily life and represents a major environmental effect.
AIM
To investigate whether the COVID-19 pandemic affected the presentation of diabetes in adults.
METHODS
A retrospective fixed cohort study was performed on the Lombard population, one of the hardest hit by the pandemic in Italy. Records from 57870 adults (40-65 years) with diabetes were extracted from the Lombard healthcare database for pandemic (2020-2021) and control (2018-2019) cohorts. Demographic data and data pertaining to concomitant cardiovascular disorders were analyzed. Cohen’s d and rate ratio with 95% confidence interval (CI) were calculated.
RESULTS
During the pandemic, the incidence of newly diagnosed diabetes was greater among men aged 40-46 years old (rate ratio = 1.07, 95%CI: 1.01-1.14) and less among older men (59-65 years old; rate ratio = 0.94; 95%CI: 0.90-0.96) compared with the control cohort. The rate of incident diabetic men with hypertension, hyperlipidemia, cardiovascular events, or prescriptions for cardiovascular-acting medications during the pandemic was lower compared with individuals in the control cohort (rate ratio for cardiovascular risk factors = 0.893; 95%CI: 0.87-0.92). A similar pattern was observed among women diagnosed with diabetes during the pandemic (rate ratio for cardiovascular risk factors = 0.899; 95%CI: 0.87-0.93).
CONCLUSION
The COVID-19 pandemic was associated with greater incident diabetes in younger individuals with fewer cardiovascular comorbidities and suggest that a potent environmental change such as the pandemic can affect the diabetes phenotype in adults.
Core Tip: The development of diabetes is linked to the environment, and major lifestyle changes are known to affect its incidence . The coronavirus disease 2019 pandemic represented a major environmental disruption; however, its impact on diabetes phenotype has not yet been fully evaluated. In this study, we compared adults diagnosed with diabetes during the pandemic in Lombardy, one of the Italian regions most heavily affected, with individuals diagnosed before 2020. We observed a higher incidence of diabetes among younger individuals without cardiovascular comorbidities in 2020-2021, suggesting that a potent environmental factor, such as the pandemic, may influence the phenotype of incident diabetes.
Citation: Pecori Giraldi F, Leoni O. Environment and diabetes: Is there an association between the COVID-19 pandemic and phenotypic variation in diabetes? World J Diabetes 2026; 17(4): 115328
Diabetes, once traditionally classified as type 1 or type 2, is now recognized as a far more heterogeneous disease. The pathways leading to its development, from impaired islet function to insulin resistance[1], may overlap, resulting in substantial variability in clinical presentation, progression and treatment response. Indeed, individuals with diabetes exhibit varying degrees of impaired insulin secretion, insulin resistance and excess weight across different ages, which in turn influence management strategies and therapeutic outcomes[2]. All three determinants contribute to phenotypic variation through the interaction between genetic background and environmental influences[3,4], with environmental and behavioral risk factors acting upon underlying genetic predisposition. This concept has been exemplified in studies in Pima Indians, a Native American population. The prevalence of diabetes among Pima Indians living in Arizona increased dramatically following exposure to a Western lifestyle[5]. In contrast, Pima Indians residing in Northern Mexico - who maintained a more traditional lifestyle - exhibit a substantially lower prevalence of diabetes[6]. These observations underscore the profound impact of environmentally determined behaviors on the development of diabetes among individuals sharing a similar genetic background.
The coronavirus disease 2019 (COVID-19) pandemic profoundly affected daily life, with physical activity, dietary habits and access to healthcare all disrupted by lockdown measures. We hypothesized that the restrictions imposed during 2020 and 2021 constituted a substantial environmental stressor that may have influenced the development of diabetes. To evaluate this potential impact, exposure must be clearly defined in terms of time and population. In Italy, Lombardy was among the regions most severely affected by the COVID-19 pandemic and therefore represents a particularly suitable setting in which to examine this exposure[7].
The aim of the present study was to investigate whether the COVID-19 pandemic influenced the phenotypic presentation of diabetes. We therefore compared the clinical and demographic characteristics of individuals diagnosed with diabetes during the COVID-19 pandemic with those of individuals diagnosed prior to the pandemic.
MATERIALS AND METHODS
A retrospective fixed cohort study was performed among individuals identified with diabetes by the Lombard regional healthcare system from 2018 to 2021. The regional healthcare system provides publicly funded healthcare to all residents of Lombardy. For certain chronic disorders, such as diabetes, hypertension, hyperlipidemia and cardiovascular diseases, individuals can apply for exemption from costs related to exams, drugs and specialist visits that are otherwise subject to prescription charges. Furthermore, novel drugs, e.g., GLP1ra, bempedoic acid, apixaban are prescribed free of charge only to patients with disease exemptions. Along the same line, equipment for glucose monitoring and insulin administration is provided by the healthcare system only to patients certified with diabetes; thus, essentially all individuals with diabetes will apply for exemption and be identified in regional healthcare records. Individuals aged 40-65 at the time of diagnosis were included in the analysis, and pregnant women with gestational diabetes were excluded.
Access to the regional healthcare database was granted by the regional welfare authority. The regional healthcare data warehouse was used to identify individuals granted an exemption for diabetes between January 1, 2018 and December 31, 2021. Data were available through December 31, 2023, allowing for up to 2 years of follow-up for individuals exempted on the final day of recruitment, but only events occurring within 730 days of exemption were analyzed to ensure comparable follow-up across cohorts. Information on exemptions and prescriptions for hypertension, hyperlipidemia and cardiovascular diseases, as well as mortality, was collected. In addition, data on testing and vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were obtained for individuals in the 2020-2021 cohort. The years 2018-2019 served as the pre-pandemic control cohort and were compared with data from 2020-2021. Overall, 57870 individuals were identified: 29081 in the first cohort (2018-2019) and 28789 in the second cohort (2020-2021). In 2018-2019, 18506 adult men and 10575 adult women were granted an exemption for diabetes, compared with 18357 men and 10432 women in 2020-2021. Approximately 80% of individuals in both cohorts were born in Italy (80.6% and 80.1%, respectively). Among the remainder, individuals were born in Africa (7.8% and 8.2% in 2018-2019 and 2020-2021, respectively), the Middle East and Asia (8.8% and 8.6%, respectively) and Central and South America (2.7% and 3.2%, respectively).
Data pertaining to the general population in Lombardy was obtained from the Lombard registry (https://www.dati.lombardia.it/dataset). Individuals enrolled in the regional healthcare system as of January 1, 2018 and January 1, 2020 were considered at-risk population.
Statistical analysis
Data for men and women were analyzed separately[8,9]. Patients were subdivided into age quartiles: I quartile: 40-46 years old, II quartile: 47-52 years old, III quartile: 53-58 years old, IV quartile: 59-65 years old (Supplementary Table 1) for age-related subanalyses. Individuals with exemption for either hypertension, hyperlipidemia or cardiovascular disease were grouped in the composite variable “cardiovascular risk factors”.
Differences between continuous variables were assessed with ANOVA, Student’s t test or Wilcoxon test, as appropriate, and size effect statistics was estimated with Cohen’s d, i.e., standardized mean difference. Qualitative variables were compared with χ2 statistics and rate ratios with 95%CI calculated. Significance was accepted for P < 0.05. Incidence was calculated over 2 years for both cohorts. Mortality was calculated as person-year within 730 days for both groups; survival was estimated with Kaplan-Meier function. Disability-adjusted life years (DALY) was calculated using 0.2 disability weight for diabetes according to the Dutch Burden of Disease Group[10].
Given the cohorts’ sizes (approximately 18000 for men and 10000 for women), we calculated the standardized mean difference (Cohen’s d) required to achieve significance. A standardized mean difference greater than 0.034 achieved two-tailed probability less than 0.05 with 90% potency in men; in women, given the same error probabilities (α = 0.05, β = 0.10), standardized mean difference greater than 0.045 was required for significance. Corresponding values for quartile analysis are given in the statistical analysis plan (Supplementary material). The smallest significant rate ratio corresponded to > 0.07 or > 0.14 for men and > 0.09 or > 0.19 for women for 40% and 6% prevalence in the control cohort, respectively. Further details are provided in the statistical analysis plan (Supplementary material).
Ethics statement
Access to the regional healthcare database was granted under the agreement between the Welfare Governance (Direzione Generale Welfare) of the Regione Lombardia and the University of Milan, and the study was approved by the University of Milan Ethical Committee. Data from individuals were anonymized by data warehouse software and informed consent was not required.
RESULTS
Men
Presentation: The number of new exemptions for diabetes in men living in Lombardy was somewhat less in the pandemic cohort: 469.1 per 100000 inhabitants (95%CI: 462.3-475.9) vs 485.8 per 100000 inhabitants (95%CI: 478.9-492.8) in the reference cohort; the age-standardized rate ratio = 0.965 (95%CI: 0.946-0.985). The Lombard regional healthcare system is subdivided into eight geographically distinct Health Care Agencies [i.e., Agenzia di Tutela della Salute (ATS)]. The number of new exemptions in each ATS was largely comparable between the two cohorts (Supplementary Table 2), as was the proportion of exemptions across ATS (Supplementary Figure 1).
The rate of exemption according to age in the two cohorts is shown in Figure 1; the rate ratio across age quartiles showed that the incidence in the pandemic cohort was higher for younger men (I quartile: 40-46 years of age) and lower for older men (IV quartile: 59-65 years of age, Figure 1 inset and Table 1).
Figure 1 Age-related incidence per 100000 inhabitants of exemption for diabetes in 2018-2019 (reference cohort, white bars) and 2020-2021 (pandemic cohort, black bars) among men and women in Lombardy.
Inset: Rate ratio and 95% confidence interval for pandemic vs control cohort across age quartiles.
Table 1 Data across age quartiles in men and women with diabetes, rate ratio in pandemic vs reference cohort (95% confidence interval).
Prevalence of clinical comorbidities, assessed by exemption for cardiovascular disorders or prescription of medication for cardiovascular disease (i.e., class C in Anatomical Therapeutic Chemical classification), revealed clear differences between the pandemic and prepandemic cohort (Figure 2 and Table 2). Indeed, the proportion of diabetic men with concomitant exemption for hypertension was significantly smaller in the 2020-2021 cohort, as was the proportion of men with exemption for cardiovascular disease or for hyperlipidemia. Furthermore, the proportion of men prescribed medications for cardiovascular disease was significantly lower in 2020-2021 compared to 2018-2019 (Figure 2 and Table 2). Overall, men exempted for diabetes in the 2020-2021 cohort had 10% less likelihood of cardiovascular risk factors, i.e., hypertension, hyperlipidemia, and cardiovascular disease, compared with the prepandemic control cohort. These differences were observed across all age quartiles (Figure 3 and Table 1).
Figure 2 Rate ratio and 95% confidence interval in diabetic men and women diagnosed in 2020-2021 (pandemic cohort) compared with the reference cohort (2018-2019) for concomitant exemption for hypertension, cardiovascular disorders, dyslipidemia, cardiovascular risk factors and for patients on cardiovascular drugs.
Dashed line represents equal rates (= 1). CV: Cardiovascular.
Figure 3 Percentage of diabetic men and women with exemption for cardiovascular risk factors according to age in 2018-2019 (reference cohort, white bars) and 2020-2021 (pandemic cohort, black bars).
Inset: Rate ratio and 95% confidence interval for pandemic vs control cohort across age quartiles. CV: Cardiovascular.
Table 2 Clinical features in men and women with exemption for diabetes, % (95% confidence interval).
Mortality: The number of deaths within 2 years from exemption was 607 men in the 2018-2019 cohort and 572 men in the 2020-2021 cohort, resulting in 16.7/1000 person-year and 15.8/1000 person-year mortality rates, respectively (Supplementary Table 3). The mortality rate ratio (0.9498, 95%CI: 0.846-1.066, P = 0.38) and 2-year survival according to Kaplan-Meier function (96.7% vs 96.9%, log-rank χ2 = 0.80, P = 0.37) were comparable between the two cohorts. Mortality across age quartiles was comparable (Table 1). Calculation of disease burden revealed slightly lower DALYs in the pandemic cohort (Table 2), possibly a consequence of the different incidence in the two cohorts (see above).
There was no significant difference between deceased men in the reference and pandemic cohort in regards to age at diagnosis, age at death and time from diagnosis to death, nor in the proportion with exemption for cardiovascular risk factors (Supplementary Table 3).
SARS-CoV-2 infection: A small proportion (11.8%) of men diagnosed with diabetes during the pandemic had tested positive for SARS-CoV-2 prior to exemption. Positive testing was registered on average 5.1 months (range 0-21.9 months) prior to diabetes exemption. There was no difference in the prevalence of hypertension and cardiovascular risk factors between men exempted during the pandemic with or without positive SARS-CoV-2 testing (Supplementary Table 4). Furthermore, the risk of death within 2 years was superimposable in diabetic men with or without prior positive testing (mortality rate ratio = 1.22, 95%CI: 0.96-1.54; Supplementary Table 4).
Women
Presentation: The number of new exemptions for diabetes across the female population in Lombardy was slightly lower in the pandemic cohort (266.1 per 100000 inhabitants, 95%CI: 261.1-271.3) compared with the control cohort (276.8 per 100000 inhabitants, 95%CI: 271.5-281.1), and the rate ratio for age-standardized incidence only just reached significance (0.962, 95%CI: 0.94-0.99). The number of new exemptions at local Health Care Agencies was largely comparable between the two cohorts (Supplementary Table 2), as was the proportion of new exemptions across ATS (Supplementary Figure 1).
Exemptions according to age are shown in Figure 1. Quartile analysis revealed that the incidence of exemptions in older women (IV quartile: 59-65 years old) was lower in the pandemic cohort compared with the reference cohort (Figure 1 inset and Table 1).
Analysis of comorbidities revealed clear differences between women diagnosed during the COVID-19 pandemic and the control cohort (Figure 2 and Table 2). In fact, the proportion of diabetic women with an exemption for hypertension was significantly smaller in the 2020-2021 cohort across all age quartiles (Table 1). In addition, the proportion of women with concomitant medication for cardiovascular diseases (i.e., class C in Anatomical Therapeutic Chemical classification) was significantly lower in 2020-2021 compared with 2018-2019; women exempted for diabetes in the 2020-2021 cohort had 10% less likelihood of being exempted for cardiovascular risk factors compared with the prepandemic, control cohort. Analysis across age quartiles confirmed this finding (Figure 3 and Table 1).
Mortality: Over the course of 2 years since exemption, 322 deaths were registered in women from the 2018-2019 cohort and 329 deaths from the 2020-2021 cohort, resulting in 15.6/1000 person-year and 16.1/1000 person-year mortality rates, respectively (Supplementary Table 3). Mortality was comparable among women with diabetes diagnosed before or during the pandemic (mortality rate ratio = 1.033, 95%CI: 0.88-1.219). Likewise, 2-year survival was comparable between the two groups (96.9% vs 96.8%, log-rank χ2 = 0.21, P = 0.65). Analysis of mortality across age quartile yielded comparable results (Table 1). Differences in DALYs were borderline significant (Table 2).
There were no significant differences between deceased patients in the two cohorts in regards to age at diagnosis, age at death and time from diagnosis to death, nor in the proportion of women with exemption for cardiovascular risk factors (Supplementary Table 3).
SARS-CoV-2 infection: Among women diagnosed with diabetes during the pandemic, 11.8% tested positive for SARS-CoV-2 prior to being exempted. In these individuals, positive testing was registered an average of 6 months (range 2 days to 22.2 months) prior to diabetes exemption. There were no differences in the prevalence of hypertension, cardiovascular risk factors or medication for cardiovascular disease between diabetic women exempted during the pandemic with or without positive SARS-CoV-2 testing (Supplementary Table 4). Furthermore, the risk of death within 2 years was similar in women with or without prior positive testing (mortality rate ratio = 1.09, 95%CI: 0.77-1.51; Supplementary Table 4).
DISCUSSION
Phenotypic variation underlies different clinical trajectories in individuals diagnosed with diabetes and has led to the current emphasis on precision medicine[1,11]. Both cluster analysis[11] and models with continuous variables[12,13] have been used to stratify diabetic individuals based upon their clinical presentation in order to forecast disease progression and response to treatment[14]. The underlying heterogeneity is thought to result from gene-environment interaction[3,4], with environmentally-determined circumstances and individual lifestyle choices acting upon the background of inherited risk gene variants to determine phenotypic variability. Some of the best-known environmental factors include eating habits and sedentary behavior, which have contributed heavily to the current diabetes epidemic among populations previously spared from the disease. Indeed, “Westernization” led to major increases in diabetes among Native American populations, most notably Pima Indians[5,6]. In addition to lifestyle changes, a variety of environmental factors have been linked to the development of diabetes from pesticides[15] and ambient air fine particulate matter[16] to heat and artificial light exposure[17,18]. In addition, individually determined circumstances, such as sleep loss[19] or diet-induced changes in gut microbiome[20], have been associated with increased risk of diabetes.
Most recently, the COVID-19 pandemic represented a major, worldwide environmental impactor and its long-term consequences are slowly coming to light, well beyond the initial devastating morbidity and mortality[21]. In Italy, lockdown was imposed from February 2020 to June 2020, with some restrictions lifted during the summer but reimposed during the second pandemic wave up to mid-2021. Similar restrictions were imposed globally with lockdown or social distancing maintained until 2022 in some countries. Restrictions inevitably impacted individual behavior and had detrimental consequences on diseases linked to lifestyle and environment, such as obesity[22] and mental health[23].
Studies published to date on the impact of COVID-19 on diabetes have focused on increased diagnoses during and after the pandemic. Case reports on individuals with insulin-dependent diabetes mellitus after SARS-CoV-2 infection were published shortly after the first pandemic wave[24,25], followed by larger studies reporting an increased incidence of diabetes type 1 in individuals positive for SARS-CoV-2[26-29]. The role of viral infections on type 1 diabetes[30] and the detection of SARS-CoV-2 antigens at postmortem examination in islets of Langerhans and pancreatic vascular endothelial cells[31,32] suggested a possible pathophysiological link. Evidence for increased incident diabetes type 2[33,34] or all-cause diabetes[35] after SARS-CoV-2 infection is less straightforward[36-39].
Our study was distinct from previous studies, as we investigated whether a major environmental stressor-such as the pandemic- affected the phenotype of incident diabetes, in order to further our understanding of gene-environment interaction on diabetes heterogeneity[1]. Specifically, the aim of the present study was to establish whether adult individuals newly diagnosed with diabetes during the COVID-19 pandemic presented different demographic and cardiovascular profiles compared with individuals diagnosed prior to the pandemic. Lombardy was one of the most heavily affected regions in Italy[7] and was deemed the most representative; thus, we retrieved data from the Lombard regional healthcare and compared entries from the 2 years preceding the pandemic to the same collected during the pandemic.
Interestingly, we observed that incident diabetes during the pandemic biennial was greater among younger men, i.e., 40-46 years of age, and less among older adults, i.e., 59-65 years of age. Further, concomitant exemption for cardiovascular comorbidities, e.g., hypertension, cardiovascular disease, hyperlipidemia, as well as the use of cardiovascular drugs, was less common among diabetic men diagnosed during the pandemic, and this held true across all ages. Overall, the likelihood of concomitant cardiovascular risk factors was 10% less in adult men exempted for diabetes in 2020-2021 compared to prepandemic newly diagnosed diabetic men. To a lesser extent, the same findings were also observed in adult women diagnosed with diabetes in 2020-2021: Lower incidence in the older (i.e., 59-65 years) age group, lower prevalence of hypertension and use of cardiovascular drugs. Again, adult women diagnosed with diabetes during the pandemic had 10% less likelihood of presenting cardiovascular risk factors compared with prepandemic years.
Our findings suggest that the pandemic may have acted as an environmental driver and affected the diabetes phenotype. Of note, in our series, most patients diagnosed with diabetes during the pandemic did not present a positive SARS-CoV-2 test, thus the change in presentation was not associated with full-blown infection or steroid treatment[40]. Milder, asymptomatic infection could have taken place and gone undetected; indeed, positive tests are known to be a gross underestimation of the real extension of SARS-CoV-2 infection[41]. However, the likelihood of long-term consequences in asymptomatic COVID appears low[42]; overall, viral infection per se is unlikely to play a major role in the phenotypic change in incident diabetes. In this context, it is worth noting that SARS-CoV-2 infection did not appear to play a role in the increased severity of newly diagnosed type 1 diabetes reported during the COVID-19 pandemic[27,43]. In fact, the higher proportion of children requiring treatment for ketoacidosis compared with a prepandemic series was not restricted to children infected with SARS-CoV-2[44,45]; reticence to access health care during the pandemic may underlie the greater number of patients presenting with incident diabetic ketoacidosis. In fact, a recent study on the severity of diabetes in youths diagnosed after the pandemic revealed lower rates of diabetic ketoacidosis and hyperglycemia[46].
Aside from SARS-CoV-2 itself, the pandemic was associated with significant restrictions, leading to changes in eating behavior, alcohol consumption, physical activity and weight gain[47,48], with evidence for further increases even after restrictions were lifted[49]. The prevalence of obesity increased with the pandemic[22], and an increase in individuals with metabolic syndrome and greater risk of cardiovascular disorders would be expected. Surprisingly, however, in the 2 years that followed the start of the pandemic, most individuals with newly diagnosed diabetes presented fewer cardiovascular risk factors. Of note, we analyzed 40-65-year-old individuals, an age group where hypertension, hyperlipidemia and cardiovascular disease account for a considerable risk of diabetes onset[50,51]. Evaluation of body weight or waist circumference was outside the scope of this study but is certainly of interest in follow-up studies.
Therefore, the increase in diabetes in younger adults with less cardiovascular risk factors was not linked to either SARS-CoV-2 or adverse metabolic profiles. Obviously, some lifestyle changes imposed by the pandemic, e.g., increased consumption of processed food and alcohol intake[52,53] may have accelerated diabetes development and diagnosis in these subjects. In this context, it is worth noting that diabetes is likely widely underdiagnosed[54] and, in fact, the widespread media coverage of the link between diabetes and COVID-19 mortality may have led to heightened awareness and increased testing in individuals without known risk factors, at least in Italy.
As this is the first report on distinctive diabetes phenotype during the pandemic, the causes underlying our observation are unknown, and further studies on diabetes heterogeneity after COVID-19 will hopefully shed light on its determinants. Obviously, any study on diabetes from 2020 onward will have to consider the phenotypic variability associated with the pandemic. From a clinical viewpoint, an increase in diabetes among younger adults translates into longer exposure to the disease and mandates stricter surveillance for target organ damage, be it cardiovascular, kidney or eye disease.
Major strengths of our study are the large sample size and near-to-complete coverage of the regional population. Our study also has some limitations. First, failure to submit the request for exemption in the midst of the upheaval brought by the pandemic may have led to the selection of younger patients, who may have been less afraid to reach out for healthcare. However, the difference we observed occurred between 40-45- and 60-65-year-old individuals, age groups that were not likely to be at risk for COVID-19-determined age discrimination[45]. Indeed, studies that evaluated access to healthcare during the pandemic observed a marked disruption in individuals aged over 65 years of age[55-57].
Furthermore, as with any study conducted on electronic healthcare records, missing or incorrectly imputed data may lead to biased findings. The variables analyzed in the present study, i.e., age, sex, and exemption for chronic diseases, represent basic patient data with little chance for gross errors. Lastly, no data on ethnicity is available in healthcare records; immigrants from Asia, Africa or Central-South America account for 20% of residents in both cohorts but the proportion of individuals born in Italy to immigrant parents is unknown. Therefore, the impact of ethnic background cannot be assessed.
CONCLUSION
In conclusion, our study has shown that a major environmental factor, the COVID-19 pandemic, was associated with a change in clinical presentation of incident diabetes in the adult population. We observed a greater incidence of diabetes in younger individuals without cardiovascular comorbidities during the pandemic, a presentation which is at odds with the current trend for diabetes[58]. This finding adds an additional layer of complexity to the heterogeneity of diabetes, linking a potent environmental factor to the emergence of distinctive clinical presentation.
ACKNOWLEDGEMENTS
The Authors wish to thank Dr. Marco Forlani, Azienda Regionale per l’Innovazione e gli Acquisti (ARIA SpA), Milan, for invaluable support.
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