We are facing an obesity epidemic, and obesity itself and its close companion, type 2 diabetes, are independent risk factors for neurodegeneration. While most medical treatments fail to induce a clinically meaningful improvement in neurodegenerative disorders, lifestyle interventions have emerged in the spotlight. A recently rediscovered approach is intermittent fasting (IF), which, compared to the classic caloric restriction regimens, limits only the time of eating, rather than the number of calories allowed per day. There is already a large amount of evidence from preclinical and clinical studies showing the beneficial effects of IF. In this review, we specifically focus on the effects of IF on brain metabolism. Key molecular players modified during IF and involved in its beneficial central effects (ketone bodies, BDNF, GABA, GH/IGF-1, FGF2, sirtuin-3, mTOR, and gut microbiota) are identified and discussed. Studies suggest that IF induces several molecular and cellular adaptations in neurons, which, overall, enhance cellular stress resistance, synaptic plasticity, and neurogenesis. Still, the absence of guidelines regarding the application of IF to patients hampers its broad utilization in clinical practice, and further studies are needed to improve our knowledge on the different IF protocols and long-term effects of IF on brain metabolism before it can be widely prescribed.

Background: Nesidioblastosis and insulinoma are disorders of the endocrine pancreas causing endogenous hyperinsulinemic hypoglycemia. Their coexistence is very unusual and treatment represents a still unresolved dilemma. Case Description: The patient was a 43-year-old Caucasian woman, with a 2-year history of repeated severe hypoglycemic events. The diagnostic work-up was strongly suggestive of insulinoma and the patient was submitted to surgical treatment carried out laparoscopically under robotic assistance. However, surgical exploration and intraoperative ultrasonography failed to detect a pancreatic tumor. Resection was therefore carried out based on the results of selective intra-arterial calcium stimulation test, following a step-up approach, eventually leading to a pancreatoduodenectomy at the splenic artery. The histopathology examination and the immunohistochemical staining were consistent with adult-onset nesidioblastosis. After surgery, the patient continued to experience hypoglycemia with futile response to medical treatments (octreotide, calcium antagonists, diazoxide, and prednisone). Following multidisciplinary evaluation and critical review of a repeat abdominal computed tomography scan, a small nodular lesion was identified in the tail of the pancreas. The nodule was enucleated laparoscopically and the pathological examination revealed an insulinoma. In spite of the insulinoma resection, glycemic values were only partially restored, with residual nocturnal hypoglycemia. Administration of uncooked cornstarch (1.25 g/kg body weight) at bedtime was associated with significant improvement of interstitial glucose levels (p < 0.0001) and reduction of nocturnal hypoglycemia episodes (p = 0.0002). Conclusions: This report describes a rare coexistence of adult-onset nesidioblastosis and insulinoma, suggesting the existence of a wide and continuous spectrum of proliferative β-cell changes. Moreover, we propose that uncooked cornstarch may offer an additional approach to alleviate the hypoglycemic episodes when surgery is impracticable/unaccepted.

The human brain is the least accessible of all organs and attempts to study it in vivo rely predominantly on neuroimaging. Functional near-infrared spectroscopy (fNIRS) allows for the study of cortical neural activity in a non-invasive manner that may resemble free-living conditions. Moreover, compared to other neuroimaging tools, fNIRS is less expensive, it does not require the use of ionizing radiation, and can be applied to all study populations (patients suffering from claustrophobia, or neonates). In this narrative review, we provide an overview of the available research performed using fNIRS in patients with diabetes and obesity. The few studies conducted to date have presented controversial results regarding patients with diabetes, some reporting a greater hemodynamic response and others reporting a reduced hemodynamic response compared to the controls, with an unclear distinction between types 1 and 2. Subjects with obesity or a binge eating disorder have reduced prefrontal activation in response to inhibitory food or non-food stimuli; however, following an intervention, such as cognitive treatment, prefrontal activation is restored. Moreover, we discuss the potential of future applications of fNIRS for a better understanding of cortical neural activity in the context of metabolic disorders.

Background: The treatment of obesity and type 2 diabetes (T2D) in Prader-Willi syndrome (PWS) is still a challenge. Glucagon-like peptide 1 receptor agonists (GLP-1 RA) are attractive options, since they effectively reduce weight and improve blood glucose, without increasing the risk of hypoglycemia. However, data on their use in PWS are scarce.Case description: In 2019, a 27-year-old male came to our Clinic because of first appearance of severe hyperglycemia (fasting plasma glucose 22.5 mmol/L). Based on clinical presentation, PWS was suspected, and diagnosis was confirmed by genetic tests. The patient was discharged on a basal-bolus insulin therapy managed by his parents due to his cognitive impairment. In spite of COVID-19 pandemic, the patient achieved tight glycemic control (HbA1c 41 mmol/mol) with non-severe hypoglycemic events in the face of significant body weight (BW) increase (+ 13 kg vs baseline). Insulin therapy was then discontinued, and once-weekly semaglutide (up to 0,5 mg weekly) was started. At 12-month follow-up, BW dropped from 79 to 73 kg while maintaining excellent glycemic control (HbA1c 40 mmol/mol). At 24-month follow-up, glycemic control remained optimal (HbA1c 38 mmol/mol) with further BW reduction (71 kg). Neither hypoglycemia nor gastro-intestinal or psychiatric adverse events were reported.Conclusion: This case supports the potential use of semaglutide for the treatment of subjects with PWS, obesity and T2D. Ad hoc trials are needed to evaluate the long-term efficacy and tolerability in these subjects.

Background: Type 2 diabetes (T2D) is a common comorbidity in people living with HIV (PLWH). Anti-hyperglycemic treatment in PLWH is still a challenge, and no randomized controlled studies using new glucose-lowering agents are currently available. Case Description: A 55-year-old-women was admitted to our Diabetes Unit because of hyperosmolar hyperglycemic state (HHS) and sepsis. The medical history included HIV infection and insulin-treated diabetes. On clinical examination, the lady appeared dehydrated with dry buccal mucosa, tachycardia, altered mental status, genital infection, and fever. On admission, plasma glucose was 54.5 mmol/L, HbA1c 155 mmol/mol, osmolarity 389.4 mOsm/kg, bicarbonate 24.6 mmol/L with no detectable serum ketones. The patient was treated with i.v. fluid and insulin, and antibiotic therapy commenced. Upon HHS and sepsis resolution, a basal-bolus insulin therapy was implemented that was followed by significant improvement of daily glucose profiles and progressive reduction of insulin requirement until complete discontinuation. A low dose of metformin plus linagliptin was started. Since a severe atherosclerotic disease was diagnosed, a GLP-1 receptor agonist, dulaglutide, was added to metformin upon linagliptin withdrawal with maintenance of good glycemic control, treatment adherence and amelioration of quality of life and no side effects. Conclusion: This case suggests that GLP-1 receptor agonist therapy may be effective and safe for treatment of T2D with high cardiovascular risk in PLWH, supporting the need of clinical trials directly assessing the safety and the efficacy of GLP-1 receptor agonist in these individuals.

The present article is an opinion piece mainly based on selected articles in the field of sarcopenia, with possible relevance for pregnancy. Sarcopenia has gained increasing interest in recent years, since it has emerged that sarcopenia may determine significant health consequences, with related substantial health care expenditure. In particular, some studies suggested that sarcopenia may cause increased risk for several diseases, such as type 2 diabetes, obesity, and major cardiovascular events. On the other hand, some studies have reported that the association between sarcopenia and these diseases may be bidirectional. In particular, this holds for type 2 diabetes, because sarcopenia and type 2 diabetes share many etiological and pathogenetic factors, such as insulin resistance, oxidative stress, low-grade chronic inflammation, and adiposity. It is also worth noting that some studies have shown a non-negligible sarcopenia prevalence even in people below 40 years of age, and therefore of reproductive age. Taken together, the above considerations support the hypothesis that sarcopenia may be present in women with gestational diabetes (GDM), which shares common traits with type 2 diabetes. Notably, we hypothesize that sarcopenia may exacerbate GDM-related complications and may influence maternal–fetal outcomes, such as preterm birth or cesarean delivery. Additionally, since pregnancy often presents with insulin resistance independently of any comorbidity, it is plausible that sarcopenia may be present during pregnancy even in cases of normal glycemia. However, there is a lack of data about sarcopenia prevalence in pregnancy and its potential impact on outcomes. Therefore, future studies addressing these aspects are advisable.