Potential New Therapeutic Implications of Semaglutide: New Colours of the Rainbow?

Semaglutide is a potent glucagon-like peptide 1 receptor agonist for the management of type 2 diabetes mellitus. In addition to this, it has emerging potential clinical implications. First, there is accumulating preliminary data on its potential role in type 1 diabetes mellitus. In this setting, we need to know which patient subgroups may benefit more. Furthermore, its role in non-alcoholic fatty liver and in non-alcoholic steatohepatitis is emerging. Other potential therapeutic implications of semaglutide include kidney disease, Alzheimer disease and pulmonary diseases. Nonetheless, we still need much more information on its long-term efficacy, safety and utility in these new implications before any definitive conclusions may be drawn for everyday practice.

Diabetic Foot and Work Outcomes: A Review.

The aim of this review article was to discuss impact of diabetic foot ulcers (DFUs) on employment status and work productivity. We performed a literature search from 2000 to 2023 in PubMed, Scopus, Google Scholar and in national repositories. The major work outcomes studied were presenteeism and absenteeism. Many DFUs patients had a poor social and educational background. Overall, DFUs patients experienced increased loss of productivity in their workplaces: either they had to be absent more working hours than average or they faced increased difficulty in meeting their daily requirements. The total loss in productivity is estimated to exceed almost one-third of anticipated working time, while 15 to 34.3% of DFUs patients expressed concerns about severe changes in their working environment, attributed directly to their condition. More than 1 out of 5 DFUs patients (ranging from 20 to 31.7%) were even confronted with overall job loss and unemployment. Amputations had an even more marked negative effect. In conclusion, DFUs negatively affect employment status and work productivity. Therefore, we need more studies with large participant numbers to increase our experience and to explore potential measures to mitigate these adverse effects.

Unraveling the Link between Ιnsulin Resistance and Bronchial Asthma.

Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has proven to be a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.

Effect of sodium-glucose cotransporter-2 inhibitors on continuous glucose monitoring metrics, as adjunctive to insulin in adults with type 1 diabetes mellitus: a meta-analysis of randomized controlled trials.

AIMS: This meta-analysis of randomized controlled trials (RCTs) aimed to evaluate the effect of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on continuous glucose monitoring metrics as adjunctive to insulin in adults with type 1 diabetes mellitus (T1D). METHODS: A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until October 25, 2023. Dual-independent study selection, data extraction and quality assessment were conducted. Results were summarized with random effects meta-analysis. RESULTS: Eight RCTs were identified, involving a total of 2310 T1D patients. The use of SGLT2is on top of standard insulin therapy was associated with a significantly higher time in range (TIR) compared to placebo (mean difference (MD) 9.7 %; 95 % confidence interval (CI) [8.3, 1.11]; P < 0.001). The time above range was significantly lower in patients receiving SGLT2is (MD -8.71 %; 95 % CI [-11.62, -5.79]; P < 0.001), whereas no difference was observed regarding the time below range (TBR) (MD 0.34 %; 95 % CI [-0.17, 0.85]; P = 0.19). A significantly lower sensor-recorded mean daily glucose was noted in the group receiving SGLT2is (MD -16.55 mg/dL; 95 % CI [-19.82, -13.29]; P < 0.001). When considering the metrics of glucose variability, SGLT2is demonstrated a significant favorable effect on the mean amplitude of glucose excursions (MD -16.92 mg/dL; 95 % CI [-25.31, -8.13]; P < 0.001) and the mean standard deviation of weekly glucose levels (MD -7.67 mg/dL; 95 % CI [-11, -4.35]; P < 0.001). No significant effect was observed concerning the coefficient of variation (MD -1 %; 95 % CI [-2.39, 0.4]; P = 0.16). Regarding safety outcomes, SGLT2is were significantly linked to higher odds of diabetic ketoacidosis compared to insulin alone (OR 3.18; 95 % CI [1.79, 5.66]; P < 0.001), with no significant impact on severe hypoglycemia events (OR 1; 95 % CI [0.54, 1.85]; P = 0.1). CONCLUSION: Our findings suggest that in individuals with T1D, adjunct therapy with SGLT2is provides a significant benefit in terms of TIR and reduced glucose variability, without an increase in TBR.

The prevalence of long COVID-19 syndrome in hospitalized patients with COVID-19 pneumonia.

Introduction: Long COVID affects millions of individuals worldwide with a wide range of persistent symptoms. Pathogenesis, prevalence and clinical approach of this syndrome remain not well characterized.The aim of the study is the estimation of prevalence of long-COVID and identification of possible risk factors. Patients and Methods: This is an observational prospective study including COVID-19 patients hospitalized at the Department of Infectious Diseases of the University General Hospital of Alexandroupolis (Greece). Eligible COVID-19 patients were interviewed and examined 6, 12 and 18 months after COVID-19 symptoms onset and hospital discharge in order to evaluate the prevalence and consequences of long-COVID symptoms. Results: A total number of 995 patients were included. The median age at discharge was 55 years and 53% of patients were retired. The majority was males (57%). Vaccination against SARS-CoV-2 was completed in 52% (n=517) COVID-19 patients. More than 40% of COVID-19 patients had at least one symptom at 18 months after hospitalization. Intravenous antiviral 0treatment with remdesivir and complete vaccination status were found to lead to lower rates of Long-COVID. Conclusions: More studies in larger patient cohorts are needed in order to identify the underlying biological mechanisms of long-COVID and create effective interventions for prevention and treatment.

Τhe Endless Beauty of Metformin: Does It Also Protect from Skin Aging? A Narrative Review.

Metformin has shown multiple effects beyond its widely known antidiabetic effect. Impressively, it has already been proposed as an anti-aging factor. However, the potentially protective role of metformin in skin aging, the most common manifestation of aging, is not well examined. Existing evidence based on experimental studies suggests a potential anti-aging effect on skin. Proposed molecular skin anti-aging mechanisms of metformin include mainly reduction of nuclear factor kappa B (NF-κB) (p65) activity. Moreover, metformin appears to inhibit ultraviolet B (UVB)-induced secretion of pro-inflammatory cytokines. Nonetheless, data is still limited, and so more studies are needed. Importantly, we need more studies conducted in humans to further examine this interesting potential. Until then, whether oral administration of metformin or local use of the agent could be used to delay skin aging remains to be answered.

A Smartphone-Based Application to Assist Insulin Titration in Patients Undergoing Basal Insulin-Supported Oral Antidiabetic Treatment.

INTRODUCTION: INSULIA is an insulin-titration app developed for patients with type 2 diabetes treated with basal insulin as part of a basal insulin-supported oral therapy (BOT). The app uses patient-logged fasting blood glucose (FBG) values and a titration plan defined by the treating physician to provide basal insulin dosing recommendations. Physicians use the web portal to monitor their patients' therapy progress and, if necessary, adjust therapy. The aim of this study was to assess the app, specifically its features, handling and impact on diabetes treatment and self-management in Germany. METHODS: This German retrospective pilot study included physicians (diabetologists, general practitioners, and internists) and patients with type 2 diabetes who either receive or start BOT using the app. Both groups completed group-specific questionnaires between December 2018 and June 2019. RESULTS: Overall, 10 physicians and 34 patients with type 2 diabetes completed their respective questionnaires. Physicians perceived their app-using patients to be more involved and more confident in managing their insulin therapy than patients not using the app. The majority of patients considered the app as a tool that assists with safer insulin treatment. The physicians perceived that due to the app use, FBG and HbA1c target values were achieved more often than patients not using the app and the number and severity of hypoglycemic episodes was reduced. CONCLUSION: The titration app seems to have a positive impact on BOT patients' FBG and HbA1c target achievement and was highly appreciated by both physicians and patients alike.

From an Empty, to an Almost Full, and Eventually to a Never Full Glass: The Evolving Challenges of Medical Education.

It has traditionally been considered that the larger the amount of knowledge, the greater the competency of a physician. However, the vertiginously fast accumulation of novel knowledge in modern medicine raises the risk that students and residents get lost in the chaos of information to which they are exposed. Thus, it becomes evident that redefining the model of medical education (and possibly rethinking what a "good" doctor means) becomes inevitable. Current challenges in medical training include early engagement of medical students in research activities and evidence-based medicine procedures, as well as adoption of new technologies, such as artificial intelligence. Gradually, the paradigm of the competent physician will transform from the "one who knows well" to "one who knows well where to search for knowledge." Given that person-centeredness remains an essential goal of medical education, supervision and assistance by academic staff are needed to ensure that the new training model has a positive impact on person-centered and doctor-patient relationships.

The Emerging Role of Continuous Glucose Monitoring in the Management of Diabetic Peripheral Neuropathy: A Narrative Review.

The aim of this narrative review is to present data on the role of continuous glucose monitoring (CGM) in the management of peripheral diabetic neuropathy (DPN) among individuals with type 1 and type 2 diabetes mellitus. Adequate glycaemic control is crucial to prevent the development or progression of DPN. CGM systems are valuable tools for improving glycaemic control and reducing glycaemic variability (GV). Chronic hyperglycaemia is known to be a risk factor for the development of diabetic microvascular complications, including DPN. In addition, there is now evidence that GV, evaluated by mean amplitude of glycaemic excursions, may be a novel factor in the pathogenesis of diabetic complications. Increased GV appears to be an independent risk factor for DPN and correlates with painful neuropathy. Similarly, time-in-range correlates positively with peripheral nerve function and negatively with sudomotor dysfunction. However, relevant studies are rather limited in scope, and the vast majority are cross-sectional and use different methodologies for the assessment of DPN. Therefore, the causal relationship between CGM-derived data and the development of DPN cannot be firmly established at the present time. It also remains to be elucidated whether CGM measures can be considered the new therapeutic targets for DPN management.

Does Obstructive Sleep Apnoea Syndrome Influence the Development and Treatment of Diabetic Foot? A Brief Narrative Review.

Both obstructive sleep apnoea syndrome (OSAS) and diabetes mellitus (DM) are common conditions that often coexist and share many similar risk factors. Diabetic foot is a common complication of DM, which may lead to lower-limb amputation. OSAS is considered a risk factor for type 2 DM (T2DM). There is also evidence that OSAS may be linked with the development, as well as the healing of diabetic foot. Multiple mechanisms triggered by sleep fragmentation and intermittent hypoxaemia in OSAS could contribute to the development of diabetic foot ulcers (DFUs). More interestingly, emerging evidence implies a favourable impact of continuous positive airway pressure (CPAP) treatment on DFU healing. Healing DFUs and minimising recurrence rates remains a challenge for health care professionals. In this context, management of OSAS might prove a useful therapeutic adjunct for DFUS. However, data is still limited and randomised controlled trials are needed to further explore this interesting potential.

Olfactory Dysfunction: A Complication of Diabetes or a Factor That Complicates Glucose Metabolism? A Narrative Review.

The present narrative review presents emerging data regarding the association between diabetes mellitus and olfactory dysfunction and discusses the role of olfactory dysfunction in glucose metabolism. We searched relevant published articles in PubMed and Google Scholar until October 2021. Main key words included "olfactory dysfunction", "diabetes mellitus", and "glucose metabolism". Olfactory dysfunction has been associated with diabetes mellitus. Furthermore, it has been proposed to be a diabetic complication, given that it has been linked with microvascular complications, such as diabetic peripheral neuropathy. Interestingly, it has been suggested that olfactory dysfunction is a manifestation of central neuropathy in diabetes, a hypothesis based on the observation that diabetes, olfactory dysfunction, and cognitive decline often coexist. However, evidence is limited and inconsistent. More importantly, olfactory and endocrine systems are closely linked, and olfactory dysfunction plays a significant role in glucose metabolism and obesity. Indeed, food behaviour and energy balance are influenced by olfaction status.

Significance of Neutrophil to Lymphocyte Ratio (NLR) and Platelet Lymphocyte Ratio (PLR) in Diabetic Foot Ulcer and Potential New Therapeutic Targets.

Diabetic foot ulcer (DFU) is a well-known complication of diabetes and a significant burden on the national health systems. The neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio are inexpensive and easily accessible biomarkers that have proved to be useful in several inflammatory, infectious and cardiovascular diseases. We carried out a comprehensive review examining the association of NLR and PLR with the onset and progression of DFU. PLR and NLR were significantly increased in patients with DFU, compared with a control group of T2DM patients without DFU, and correlate well with DFU severity, evaluated by Wagner and IWGDF grading scales. In patients with diabetic foot infections (DFI), elevated NLR and PLR were correlated with osteomyelitis, increased risk of amputation, and septic complications. The significance of the elevated value of these biomarkers in DFU is related to chronic hyperglycemia and low-grade systemic inflammation, atherosclerotic and vascular complications, and also the associated septic factor. Serial, dynamic follow-up can provide useful information in planning and monitoring DFU treatment, as well as in risk stratification of these vulnerable patients. Further randomized studies are needed to set the cut-off values with clinical significance.

Charcot osteoarthropathy in diabetes: A brief review with an emphasis on clinical practice.

Charcot osteoarthropathy (COA) is a potentially limbthreatening condition that mainly affects diabetic patients with neuropathy. In everyday practice, it presents as a red, hot, swollen foot, usually painless, and is frequently triggered by trivial injury. Its etiology is traditionally attributed to impairment of either the autonomic nervous system, leading to increased blood flow and bone resorption, or of the peripheral nervous system, whereby loss of pain and protective sensation render the foot susceptible to repeated injury. More recently, excessive local inflammation is thought to play a decisive role. Diagnosis is based on clinical manifestation and imaging studies (plain X-rays, bone scan, Magnetic Resonance Imaging). The mainstay of management is immediate off-loading, while surgery is usually reserved for chronic cases with irreversible deformities and/or joint instability. The aim of this review is to provide an overview of COA in terms of pathogenesis, classification and clinical presentation, diagnosis and treatment, with an emphasis on the high suspicion required by clinicians for timely recognition to avoid further complications.

The female breast and diabetes.

The present review outlines the various issues of breast pathology in diabetes. Diabetic mastopathy is an uncommon proliferation of fibrous tissue in the breast that mimics tumour. Breast arterial calcifications represent calcium deposits in the media of arterioles and are more frequently detected on mammograms of diabetic subjects. Importantly, type 2 diabetes mellitus (T2DM) has been associated with breast cancer, but the mechanism underlying this association is complex, since the two entities frequently co-exist and seem to share common aetiological factors and pathways. Furthermore, diabetes has been suggested to negatively affect breast cancer outcomes, but it is unclear whether better glycaemic control would ameliorate prognosis. Preliminary data suggest that antidiabetic treatment may also influence both the incidence and prognosis of breast cancer. However, available evidence is inconclusive and further research is needed. Therefore, treatment of diabetes should not be determined by its potential effect on breast cancer.

Mediterranean diet and metabolic syndrome in an urban population: the Athens Study.

BACKGROUND: Previous studies demonstrated the beneficial impact of the Mediterranean diet (MedDiet) on metabolic syndrome (MetS). The aim of this study was to retrospectively investigate the association between MedDiet and MetS in a representative sample of the Athenian population in the early 1980s, when MetS had not been established as an entity yet. METHODS: In a cross-sectional epidemiologic survey of cardiovascular disease (CVD), 2,074 randomly selected adults were examined: 900 men and 1,174 women (age, 46.9 ± 14.9 years). MetS was defined according to criteria of the National Cholesterol Education Program-Adult Treatment Panel III. A validated questionnaire concerning nutrition habits was administered, and MedDiet was assessed according to guidelines of the Division of Nutrition/Epidemiology, Athens University Medical School. RESULTS: Overall, 1,023 participants (49.3%) followed MedDiet (47.3% men, 52.0% women, P = .033) with similar rates across age groups (P = .337). MetS was diagnosed in 24.0% of those following MedDiet, compared with 27.9% of those not following it (P = .041). Participants with CVD or diabetes mellitus were less likely to follow MedDiet (43% vs 50%, P = .009). Multivariate analysis revealed that MedDiet is associated with a 20% reduction in MetS (odds ratio = 0.80, 95% confidence interval = 0.65-0.98), after adjustment for age, gender, smoking, light physical activity, serum levels of low-density lipoprotein cholesterol and γ-glutamyl transferase, diabetes mellitus, CVD, family history of hypertension, and/or hyperlipidemia. CONCLUSIONS: Results indicate that adherence to MedDiet may attenuate the prevalence of MetS and, consequently, the increasing burden of diabetes mellitus and CVD, especially in urban populations.