Leader: Paolo Marzullo (UPO); Other collaborator(s):
Policies that consider a disease-directed approach may help dissecting health trajectories during targeted interventions and identifying early risk markers in disease-free cohorts. Type 2 diabetes (T2D) is a condition of cardiovascular risk (CVR) responsive to lifestyle interventions. Study aims: 1) To assess CVR through systemic and metabolomic analysis of T2D outpatients free of CV events (CVE) planned to receive behavioural, nutritional, and lifestyle interventions; 2) to identify and resolve patterns of morbidity markers according to individual CVE during targeted interventions. The pathways thus recognized will be tested in the general population (Task 3.3) to identify early markers of metabolic disruption at the population level.
Brief description of the activities and of the intermediate results
This WP is collecting evidence on aging-related health promotion in the human context of diabetes mellitus type 2 (DM2), where two innovative classes of antidiabetic therapy have become available: incretin-mimetics (GLP-1RAs), a group of peptides mimicking intestinal incretins, and sodium-glucose transport-2 inhibitors (SGLT2i), a group of glycosuric agents. These molecules possess pleiotropic effects beyond glucose control, and are thus proven to be useful for cardiorenal protection and bodyweight management within and out of the diabetes spectrum.
This WP aims to demonstrate bidirectionally the impact of these compounds in DM2 patients on age-related changes in tissue function and comorbidities and, by converse, investigate how physiological and metabolic changes related to aging can affect the response to these medications.
We have collected evidence to date on more than 1,000 subjects with DM2. The hallmarks of aging we are focusing on is the accumulation of visceral fat and the changes in pro-inflammatory setting, which are both known to exacerbate cardiovascular diseases, with special reference to the use of GLP-1RAs and SGLT2is.
Main policy, industrial and scientific implications
Bridging the study progression, future crucial aspect of our research will involve metabolic correlates of white fat browning, a type of adipose tissue known for its ability to burn energy and produce heat, and the role in this whole scenario of the reduction in muscle mass, the phenomenon known as sarcopenia, due to the large number of negative effects it generates, such as reduced mobility or loss of muscle strength. Among other critical aspects, we will focus on long-term safety profile of these drugs, especially if used in a fragile population with polypharmacy, with increasing risk of side effects and unwanted interactions.
Brief description of the activities and of the intermediate results
The role of the task within WP10 is to investigate the relationship between diabetes mellitus and aging, particularly in relation to the use of the antidiabetic classes of agents GLP-1RAs and SGLT2i, which have shown to yield pleiotropic effects.
The protocol for the collection of diabetic subjects is prepared and the collection is ongoing.
Main policy, industrial and scientific implications
Not yet available
Brief description of the activities and of the intermediate results
Data recorded from over 1,000 diabetic subjects progressively assigned to GLP1RAs (oral semaglutide vs subcutaneous semaglutide vs dulaglutide) and 1000 diabetic subjects assigned to SGLT2i (empagliflozin, canagliflozin and dapagliflozin) have included anthropometric and biochemical measures and are under analysis to assess changes in pro-inflammatory markers.
Main policy, industrial and scientific implications
Preliminary data have been presented at an endocrinology congress
Brief description of the activities and of the intermediate results
Data records have expanded to all newly-diagnosed diabetic subjects referred to the clinic after the Covid pandemic and assigned to different therapies. Electronic data files with demographic, anthropometric and biochemical measures will be completed and compared to data obtained before Covid pandemic. Complications will be studied according to early and late treatment criteria.
Main policy, industrial and scientific implications
Drafting individual trajectories of diagnostic experience and therapy achievements across the Covid pandemic to profile changes in disease-consciousness and therapy target alignment of epidemiological relevance for health policy makers and stakeholders.
Preliminary data have been presented at endocrinology congress.
Brief description of the activities and of the intermediate results
Analysis of database of patients with diabetes: There is a large ongoing retrospective analysis on over 1,000 diabetic subjects progressively assigned to GLP1RAs (oral semaglutide vs subcutaneous semaglutide vs dulaglutide) and 1000 diabetic subjects assigned to SGLT2i (empagliflozin, canagliflozin and dapagliflozin). Personal data include anthropometric and biochemical measures. Socio-demographic data have been obtained to assess the determinants of onset, evolution, and therapy response.
Aging-related blood markers of pancreatogenic diabetes (DMT3c): New-onset diabetes, especially in individuals over 50, is strongly associated with an increased risk of pancreatic cancer. The incidence of pancreatic cancer also increases with age, and individuals with long-standing diabetes, especially those with elevated fasting blood glucose levels, are at higher risk. A third aging-related pillar within DMt3c relates to enhanced susceptibility of pancreatic cancer survivors to develop postsurgical diabetes due to aging- dependent pancreatic beta-cell regression. Through a metabolomic approach, the study assesses the relationship between aging, demographic, anthopometric and pathology-related determinants of DMT3c.
Main policy, industrial and scientific implications
Establishment of a joint working group named "Permanent Inter-Society Consultation Table" between Società Italiana di Endocrinologia (SIE) and Società Italiana di Geriatria e Gerontologia (SIGG) to address the specific issues of endocrine diseases in elderly patients, with particular attention to the frail elderly. Main goal of the working group is to promote cultural and scientific exchange between Endocrinologists and Geriatricians. The unique features of clinical phenotypes, the frequent presence of comorbidities requiring polypharmacy, and the different expectations and experiences of elderly patients can create significant challenges for the Endocrinologist, who is often trained using standardized clinical models based on the adult population. At the same time, the presence of multiple chronic diseases in elderly patients, along with the often subtle clinical presentation of endocrine disorders, makes diagnosis and treatment difficult for the Geriatrician who lacks specific expertise in endocrine-metabolic disorders. A priority action for the future activities of the Joint Inter-Society Table is to assess the interest of fellow Geriatricians and Endocrinologists in the various topics related to endocrine diseases in geriatric patients.
Preliminary data have been presented at endocrinology congress. A manuscript is preparation. Organization of the 2 nd national conference of Geriatric Endocrinology in Novara on 15-16/11/2024: this two-day conference has been held on analysis and discussion of endocrine and metabolic determinants of longevity and promoting healthy aging, which represents a growing commitment in the health sector. The rationale stemmed from the crucial physiological involvement of the endocrine-metabolic system in the aging process of the person, as well as on the growing medical needs for endocrine-metabolic diseases due to the progressing aging of the population, which is reflected in the degree of functional autonomy of the person under the pressure of chronic inflammation. This event aimed to bring out and discuss the salient elements of endocrine-metabolic problems in the elderly subject with a focus on prevention aspects, diagnostic-therapeutic procedures and targets, innovative therapies for diabetes, and outcome and follow- up planning in the elderly patient with endocrine-metabolic disease.