According to the recent esteems, more than 800 million adults have type 2 diabetes (T2D), with an increase of about 600 million in the last 30 years. The largest increases are in low-income and middle-income countries. As a matter of fact, a parallel increase has been constantly reported for the prevalence of obesity and overweight. Obesity has increased to fewer than 2 billion in the last 5 years. Obesity was recognized as a disease by WHO about 80 years ago and very recently by the Italian Parliament as a chronic, progressive, and relapsing disease.

A multifactorial etiology (both genetic and environmental factor) has been proposed for T2D with two main pathogenetic mechanisms (the defect of insulin production and insulin resistance). The dysfunction of β-cells is commonly attributed to the loss of β-cell mass (by exhaustion) or apoptosis (by glucotoxicity and lipotoxicity). More complex mechanisms and interactions are involved, such as dedifferentiation of β-cells, oxidative stress, induction of disallowed genes, dedifferentiation, transdifferentiation, endoplasmic reticulum stress, altered prostaglandin signaling, mitochondrial dysfunction and amyloidosis. The insulin resistance (IR) is represented by the reduced response to insulin in the target tissues. Many hormones affect the action of insulin (classically, growth factors and insulin-like growth factor 1, glucagon, glucocorticoids, and catecholamines). Beyond the genetics, obesity, sedentary lifestyle, dietary habits, chronic stress and sleep deprivation can all negatively impact insulin sensitivity, and, recently, gut microbiota has been considered in the pathophysiology of T2D.

The signaling pathway of insulin may disrupted at different levels, from upstream (the insulin receptor) to downstream (for example, the glucose transporter or GLUT1-4).

In the development of T2D, extra-pancreatic factors are essential, such as the IR at the level of the skeletal muscles, the adipose tissue and the liver. The detrimental effects of IR virtually involve every tissue of the body that present the insulin receptor, and growing evidence in the literature support an important damage at the central nervous system.

The well-known complications of T2D are: diabetic kidney disease (DKD), diabetic retinopathy (DR), diabetic neuropathy (DN), metabolic dysfunction-associated steatotic liver disease (MASLD), cardiovascular disease (CVD) (coronary artery disease or CAD, stroke and peripheral artery disease or PAD).

Considering obesity, several districts of the body are affected by this disease, such as the respiratory system (apnoeas/hypopnoeas and hypoventilation during sleep), cardiovascular system (preserved or reduced left ventricular systolic function - heart failure, arrythmias and atrial fibrillation, systemic and pulmonary artery hypertension, aortic valve stenosis), lower limbs lymphedema, deep venous system and/or pulmonary thromboembolic disease, metabolism (hyperglycaemia and T2D, high triglyceride levels, and low HDL cholesterol levels, metabolic syndrome), the liver (MASLD and hepatic fibrosis), the kidney (microalbuminuria, reduced glomerular filtration rate), urinary incontinence, reproduction (anovulation, oligo-menorrhea and polycystic ovary syndrome, male hypogonadism), musculoskeletal system (osteoarthritis).

The recent Delphi Consensus defined obesity an excessive adiposity (based on recent anthropometric measures), with or without abnormal distribution or function of the adipose tissue, caused by multifactorial pathogenetic mechanisms (genetic, environmental, neurobiological, psychological, socioeconomic, nutritional and metabolic factors) and still incompletely understood. Obesity can cause systemic, chronic illness (the so-called clinical obesity), resulting in distinct clinical manifestations with specific signs/symptoms or limitations of activities of daily living. Pre clinical obesity confers an increased risk of developing clinical obesity as well as several other non-communicable diseases (NCDs), including T2D, CVD, certain types of cancer and mental illness. Because remission of clinical obesity does not imply cure, treatment of clinical obesity with resolution of clinical manifestations of organ dysfunction is matter of debate in order to evaluate the timing of the ongoing pharmacologic treatment. Clinical obesity may lead to severe organ dysfunction and end-organ damage, causing life-altering and/or potentially life-threatening complications. Coexisting obesity-related diseases should be considered in decision-making about indications to treatment and type of treatment.

The aim of this Collection is to provide a better understanding of the molecular and integrative mechanisms of the development of obesity and T2D, to ameliorate the clinical aspects and the relationships between both the diseases. A deeper knowledge of the specific profile and their multiple components may give a chance to a more efficient treatment in a personalized manner.

Possible topics include: basic mechanisms and clinal profiles of the patients, oxidative stress, chronic inflammation, hormonal and metabolic dysregulation, as areas involved in the development of obesity and/or T2D. Preventing strategies and newly developed agents to enhance fit behaviors and to contrast the pathogenetic mechanisms. Debate and research on advantages and disadvantages of measures of obesity and T2D and the outcomes after specific treatments.

This collection brings together cutting-edge research and perspectives on the mechanisms, diagnosis, and treatment of pain and headache disorders, bridging basic discoveries with clinical applications. Submissions may include original research, reviews, case reports, and translational studies addressing pathophysiology, biomarkers, novel pharmacological and non-pharmacological interventions, as well as patient-centered and health system approaches. By highlighting interdisciplinary contributions from neuroscience and pharmacology to clinical medicine, public health, and rehabilitation, this collection aims to foster dialogue across specialties and provide readers with a comprehensive overview of current advances in the field.