Raffaele Ivan Cincione

Background/Objectives: Regular physical exercise is strongly recommended for individuals with type 1 diabetes mellitus (T1DM) because of its beneficial effects on cardiovascular fitness, insulin sensitivity, metabolic control, and overall health. Nevertheless, participation in physical activity remains limited, largely due to the fear of exercise-induced hypoglycemia and glycemic instability. Glycemic responses to exercise in T1DM are influenced by the interaction between exercise modality, circulating insulin levels, nutritional status, and diabetes technologies. Continuous aerobic exercise, resistance training, high-intensity interval exercise, and mixed intermittent activities elicit distinct metabolic and hormonal responses, resulting in heterogeneous glycemic trajectories. This narrative review aimed to provide a clinically oriented synthesis of the physiological mechanisms underlying exercise-related glycemic fluctuations in T1DM and to discuss integrated insulin- and carbohydrate-based strategies to support safer participation in physical activity in the context of modern diabetes technologies. Methods: A structured narrative review was conducted using PubMed/MEDLINE, Scopus, and complementary searches in Google Scholar to identify experimental studies, observational studies, systematic reviews, consensus statements, and clinical guidelines focused on exercise-related glycemic responses in individuals with T1DM. Only articles published in English were considered. Evidence was selected and synthesized according to relevance to exercise modality, insulin therapy strategies, carbohydrate management, and diabetes technologies, including continuous glucose monitoring, continuous subcutaneous insulin infusion, and automated insulin delivery systems. The final narrative synthesis was based on 44 selected studies, reviews, consensus statements, and guidance documents considered most relevant to the objectives of this narrative review. Results: Available evidence indicates that continuous moderate-intensity aerobic exercise is most consistently associated with progressive glucose declines and increased risk of hypoglycemia, particularly when performed in the presence of elevated insulin on board. In contrast, resistance exercise and short-duration high-intensity or anaerobic exercise more frequently induce stable glycemia or transient hyperglycemia through adrenergic stimulation and increased hepatic glucose output. Mixed and intermittent exercise modalities often produce more variable responses depending on exercise sequencing, nutritional status, and insulin exposure. Across studies, integrated adjustment of basal and prandial insulin doses together with individualized carbohydrate supplementation emerged as the most effective strategy to reduce exercise-related glycemic instability. Continuous glucose monitoring and insulin pump technologies improved glucose trend awareness and management flexibility; however, physical exercise remains a challenging condition for current automated insulin delivery algorithms and still requires active user-driven decision-making. Conclusions: Exercise management in T1DM should be based on an individualized interpretation of exercise modality, glucose trends, insulin exposure, and nutritional context rather than on fixed glucose thresholds alone. Combining anticipatory insulin adjustments, tailored carbohydrate strategies, and appropriate use of diabetes technologies may substantially reduce glycemic variability and improve confidence toward physical activity participation. Structured education and individualized clinical guidance remain essential to translate physiological knowledge into effective real-world exercise management.

Background and Objectives: Intermittent fasting (IF) has emerged as a nutritional strategy capable of modulating circadian alignment, metabolic efficiency, and neuroendocrine regulation in individuals with obesity. Among the neurobiological mediators potentially involved, Orexin-A—a hypothalamic neuropeptide regulating arousal, appetite, and energy balance—may represent a key link between fasting patterns and metabolic homeostasis. This study aimed to evaluate the long-term metabolic and neuroendocrine effects of two intermittent fasting protocols, time-restricted feeding (16:8) and alternate-day fasting (5:2), compared with a hypocaloric Mediterranean diet used as a reference condition. Materials and Methods: Thirty adults with obesity (aged 20–40 years) were allocated to one of three dietary interventions—low-calorie Mediterranean diet, IF 16:8, or IF 5:2—based on habitual dietary patterns and followed prospectively for 12 months. Anthropometric parameters, metabolic indices, inflammatory markers (CRP, TNF-α, IL-6, IL-10), and circulating Orexin-A concentrations were assessed at baseline and at three-month intervals (T0–T3). Results: Both intermittent fasting protocols induced more rapid improvements in body mass index, adiposity, lipid profile, fasting glucose, and inflammatory markers compared with the Mediterranean diet. Among the IF strategies, the 16:8 regimen showed the most consistent and physiologically coherent pattern of adaptation, characterized by a progressive and sustained increase in Orexin-A levels. This response was strongly associated with enhanced metabolic flexibility, reduced systemic inflammation, and improved energy regulation over time. In contrast, the 5:2 protocol produced more variable metabolic and neuroendocrine responses, likely due to alternating cycles of marked caloric restriction and compensatory intake. Conclusions: Intermittent fasting, particularly the 16:8 time-restricted feeding protocol, appears to be an effective and sustainable chrononutritional strategy for obesity management. By reinforcing circadian organization, improving inflammatory balance, and activating orexinergic pathways, the 16:8 model emerges as a promising intervention to address key metabolic and neuroendocrine dysfunctions associated with obesity.

Introduction: The worldwide prevalence of type 2 diabetes mellitus (T2DM) and obesity has been steadily increasing over the past four decades, with projections indicating a significant rise in the number of affected individuals by 2045. Therapeutic interventions in T2DM aim to control blood glucose levels and reduce the risk of complications. Dietary and lifestyle modifications play a crucial role in the management of T2DM and obesity. While conventional medical nutritional therapy (MNT) often promotes a high-carbohydrate, low-fat Mediterranean diet as an elective treatment, low-carbohydrate diets (LCDs), specifically those restricting carbohydrate intake to less than 130 g/day, have gained popularity due to their multifaceted benefits. Scientific research supports the efficacy of LCDs in improving glycemic control, weight loss, blood pressure, lipid profiles, and overall quality of life. However, sustaining these benefits over the long term remains challenging. This trial aimed to compare the effects of a Mediterranean diet vs. a low-carbohydrate diet (carbohydrate intake < 130 g/day) on overweight/obese patients with T2DM over a 16-week period. The study will evaluate the differential effects of these diets on glycemic regulation, weight reduction, lipid profile, and cardiovascular risk factors. Methods: The study population comprises 100 overweight/obese patients with poorly controlled T2DM. Anthropometric measurements, bioimpedance analysis, and blood chemistry assessments will be conducted at baseline and after the 16-week intervention period. Both dietary interventions were hypocaloric, with a focus on maintaining a 500 kcal/day energy deficit. Results: After 16 weeks, both diets had positive effects on various parameters, including weight loss, blood pressure, glucose control, lipid profile, and renal function. However, the low-carbohydrate diet appears to result in a greater reduction in BMI, blood pressure, waist circumference, glucose levels, lipid profiles, cardiovascular risk, renal markers, and overall metabolic parameters compared to the Mediterranean diet at the 16-week follow up. Conclusions: These findings suggest that a low-carbohydrate diet may be more effective than a Mediterranean diet in promoting weight loss and improving various metabolic and cardiovascular risk factors in overweight/obese patients with T2DM. However, it is important to note that further research is needed to understand the clinical implications and long-term sustainability of these findings.

At diagnosis, more than 80% of patients with pancreatic cancer (PC) suffer from significant weight loss due to malnutrition which is a major concern for patient management, and this may negatively impact treatment outcomes and patient prognosis. We performed an observational, retrospective study on patients with metastatic PC (mPC) undergoing first-line chemotherapy with nab-Paclitaxel containing schedules and receiving or not receiving nutritional support (NS) and pancreatic enzyme replacement therapy (PERT) to investigate their relevance in this setting. We observed that PERT and ancillary dietary interventions are related to longer overall survival (OS; median: 16.5 vs. 7.5 months, P < .001) and have a significant, independent, prognostic impact for better outcomes (P = .013), independently from the therapeutic regimen. Furthermore, PERT and NS prevented weight loss during chemotherapy and obtained an improvement of nutritional parameters such as phase angle and free-fat mass index, after 3 months of anticancer treatment. Consistently, the positive impact on OS correlated also with the prevention of Karnofsky performance status deterioration and a lower incidence of maldigestion-related symptoms. Our data suggest that an early and well-conducted NS in patients with mPC may impact on survival and preserve performance status, thus improving quality of life.

Effective nutrition therapy is a pressing issue in obesity and type 2 diabetes mellitus (T2DM) management. As such, this research aimed to determine the performance of a revised dietary strategy built on the protein-sparing diet in obesity and type 2 diabetes mellitus with regard to obtaining a rapid and stable improvement in glucometabolic control, body weight, body composition, and energy metabolism when applying the strategy in just twenty-one days. The revised protein-sparing diet differs from the traditional protein-sparing modified fast (PSMF) because it does not include foods. The daily calorie intake of this diet is exclusively derived from Isolate whey protein in addition to a formulation of Isolate whey protein enriched with essential amino acids in free form, with the addition of lipids such as extra virgin olive oil and coconut oil as a source of medium chain fatty acids, where the latter is taken for only the first four days of the diet, together with the use, for the same duration, of extended-release metformin, as the only antihyperglycemic allowed. Anthropometric measurements, bioimpedance analysis, indirect calorimetry, and blood chemistry assessments were conducted at the beginning of the study, time 0 (T0), and at the end, time 1 (T1), i.e., on the 21st day. The main outcomes of the revised protein-sparing diet after only twenty-one days were a reduction in body weight with the predominant loss of visceral atherogenic abdominal fat and, therefore, a possible contextual reduction in ectopic fat deposits together with a simultaneous reduction in insulin resistance and normalization of insulin levels, maintenance of free fat mass and basal metabolism, restoration of metabolic flexibility, and improvement of the glucometabolic and lipidic parameters. These results demonstrate the promising potential of the revised protein-sparing diet as an “etiologic tool” in the integrated nutritional treatment of metabolic diseases such as obesity and type 2 diabetes mellitus.

Obesity is a multifactorial disease strongly associated with insulin resistance and/or type 2 diabetes mellitus. Correct nutrition represents a valid strategy to fight these dysmetabolic pathologies responsible for numerous diseases, including inflammatory and cardiovascular ones. Medical nutrition therapy, including a Mediterranean diet (MD) and a very low-calorie ketogenic diet (VLKCD), is the first-line treatment for prediabetes/diabetes and overweight/obesity. Eighty patients (forty women and forty men) affected by overweight/obesity and type 2 diabetes mellitus or impaired glucose tolerance or impaired fasting glucose (51 (ys) ± 1.75; BMI (kg/m²) 33.08 ± 1.93; HA1c (%): 6.8% ± 0.25) were enrolled at the University Service of Diet Therapy, Diabetology and Metabolic Diseases, Policlinico Riuniti Hospital of Foggia, and subjected to a very-low-calorie Mediterranean diet and a very-low-calorie ketogenic Mediterranean diet for thirty days. Both diets result in a marked decrease in body weight (kg) and BMI (kg/m²). At the same time, only the very-low-calories ketogenic Mediterranean diet reduced waist and hip circumferences. Both diets helped reduce fat mass, but a major loss was achieved in a very low-calorie ketogenic Mediterranean diet. Among gluco-metabolic parameters, only the very-low-calorie ketogenic Mediterranean diet group showed a significant decrease in fasting blood glucose and HbA1c, insulin, C-peptide total cholesterol, LDL, and triglycerides. The results of our study seem to show that the very-low-calorie ketogenic Mediterranean diet is a good strategy to improve rapidly metabolic, anthropometric, and body composition parameters in patients with prediabetes or diabetes and overweight/obesity.

Background: Dietary fats, and especially saturated fatty acid (SFA), have been blamed for being the culprit in the dramatic increase in obesity and its associated diseases. However multiple systematic reviews and recent meta-analyses do not support the association between SFA and cardiovascular diseases. Thus, the objective of this study was to test whether specific types and subtypes of dietary fats are associated with metabolic outcomes in a cohort of Italian adults. Methods: Nutritional and demographic data of 1936 adults living in the south of Italy were examined. Food frequency questionnaires (FFQs) were administered to assess the intake of total dietary fat and each specific class of dietary fat, such as SFA, monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA). The intake of fatty acids was also examined according to the carbon-chain length of each individual class. Cases of hypertension, type-2 diabetes and dyslipidemias were collected from previous doctor-confirmed diagnosis records (or direct measurement of blood pressure). Results: After adjustment for potential confounding factors, individuals reporting higher intakes of total and saturated fats were associated with lower likelihood of having hypertension (odds ratio (OR) = 0.57, 95% CI: 0.35, 0.91 and OR = 0.55, 95% CI: 0.34, 0.89, respectively). Moreover, higher intake of short-chain saturated fatty acids (SCSFAs) and medium-chain saturated fatty acids (MCSFAs) was inversely associated with dyslipidemia and diabetes (OR = 0.43, 95% CI: 0.23, 0.82 and OR = 0.25, 95% CI: 0.09, 0.72, respectively). Among MUFAs, C18:1 was inversely associated with hypertension and diabetes (OR = 0.52, 95% CI: 0.30, 0.92 and OR = 0.21, 95% CI: 0.07, 0.67, respectively), while C14:1 intake was inversely associated only with hypertension (OR = 0.57, 95% CI: 0.37, 0.88). In contrast, C20:1 intake was associated with dyslipidemia (OR = 3.35, 95% CI: 1.33, 8.42). Regarding PUFA, C18:2 and 20:5 were inversely associated with hypertension (OR = 0.33, 95% CI: 0.18, 0.60 and OR = 0.30, 95% CI: 0.10, 0.89, respectively). Conclusions: The consumption of SFA does not seem to be harmful to cardio-metabolic health and, on the contrary, SCSFA may exert beneficial effects. Further studies are needed to clearly validate the results of the present study.

A eucaloric very low carbohydrate diet (EVLCD) is a diet with a daily caloric intake equal to the total daily energy expenditure (TDEE) with a carbohydrate content of p < 0.01). The number of patients who reached a glycated hemoglobin value of p < 0.01), and there was a statistically significant decrease (p < 0.01) in the units of daily insulin (from 36.7± 14.9 IU to 28.9 ±9.1 IU) A reduction from 54% to 24% in clinical level 2 hypoglycemia episodes was reported. No cases of severe hypoglycemia or ketoacidosis were observed. The results of the study support that EVLCD in DM 1 seems safe and effective when adopted under tight medical supervision.

Background. The purpose of this study was to evaluate the effect of diet and antihyperglycemic drugs on erectile dysfunction (ED) in a setting of subjects affected by diabetes mellitus (DM) or preDM. Methods. This is a prospective observational study on 163 consecutive subjects with preDM or DM. All patients have undergone a medical evaluation (age, Body Mass Index (BMI), family history of DM, duration of DM, smoking, physical activity, dyslipidemia, cardiovascular comorbidities, and testosterone and HbA1c levels) and the International Index of Erectile Function (IIEF)-5 questionnaire. Results. Overall, the mean age was 62.8 ± 9.3 years, and the mean BMI was 28.4 ± 4.6 kg/m². The IIEF-5 score mean value was 14.4 ± 6.2 (range 4–25). Among all confounders investigated for their association with the IIEF-5 score, only age and the duration of DM among diabetic patients showed a significant trend. The IIEF-5 score was higher in patients using GLP-1a compared to insulin (16.7 ± 4.7 vs. 12.9 ± 6.2; p = 0.02). This association was confirmed after adjustment for age and duration of DM (p = 0.01). All other treatments were similar (14.9 ± 6.2, 14.8 ± 9.2, 15.3 ± 5.4, and 13.6 ± 6.8 for metformin, sulfonylureas (SU), dipeptidyl-peptidase-4 inhibitors (DPP-4i), and sodium-glucose cotransporter-2 inhibitors (SGLT2i) treatment, respectively). Conclusions. This prospective observational study increases attention and focus on the effect of antihyperglycemic drugs and diet on ED, above all about the role of new classes, showing a significant higher IIEF-5 mean value in patients using GLP-1a compared to patients on insulin treatment.