Preventing Diabetic Foot Re-Ulceration Through an Innovative Pressure and Temperature Monitoring Clinical Device.

This study compared the outcome of an innovative in-shoe pressure and temperature measuring device as an adjunct to standard clinical care for diabetic foot versus standard clinical care alone. It included 88 participants with Type 2 diabetes mellitus with a history of one or more plantar foot ulceration who were already using prescription orthoses. These were randomly divided into the control group (n = 44, standard care only) and the experimental group (n = 44, standard care plus the innovative device). Both groups were monitored for re-ulceration for one year. Overall, the control group exhibited a higher number of re-ulcerations (n = 14) with 2 amputations in comparison with the experimental group (only 2 ulcerations and no amputations) at the end of the study. In conclusion, this innovative in-shoe pressure and temperature measuring device appears to reduce re-ulcerations by offering objective data for clinical decision making in the management of the diabetic high-risk foot.

Drawing lines in the sand: The growing threat of obesity in type 1 diabetes.

In this editorial, we comment on the article by Zeng et al published in the recent issue of the World Journal of Diabetes in 2024. We focus on the epidemiological, pathophysiological, and clinical interplay between obesity and type 1 diabetes mellitus (T1DM). Overweight and obesity represent a growing threat for modern societies and people with T1DM could not be an exception to this rule. Chronic exogenous insulin administration, genetic and epigenetic factors, and psy-chosocial and behavioral parameters, along with the modern way of life that incorporates unhealthy eating patterns and physical inactivity, set the stage for the increasing obesity rates in T1DM. As our knowledge of the underlying mechanisms that lead to the development of obesity and hyperglycemia expands, it becomes clear that there are overlap zones in the pathophysiology of the two main types of diabetes. Stereotypes regarding strict dividing lines between "autoimmune" and "metabolic" phenotypes increase the risk of trapping physicians into ineffective therapeutic approaches, instead of individualized diabetes care. In this context, the use of adjuncts to insulin therapy that have the potential to alleviate cardiorenal risk and decrease body weight can reduce the burden of obesity in patients with T1DM.

Mitochondrial Fraction of Circulating Cell-Free DNA as an Indicator of Human Pathology.

Circulating cell-free DNA (ccfDNA) of mitochondrial origin (ccf-mtDNA) consists of a minor fraction of total ccfDNA in blood or in other biological fluids. Aberrant levels of ccf-mtDNA have been observed in many pathologies. Here, we introduce a simple and effective standardized Taqman probe-based dual-qPCR assay for the simultaneous detection and relative quantification of nuclear and mitochondrial fragments of ccfDNA. Three pathologies of major burden, one malignancy (Breast Cancer, BrCa), one inflammatory (Osteoarthritis, OA) and one metabolic (Type 2 Diabetes, T2D), were studied. Higher levels of ccf-mtDNA were detected both in BrCa and T2D in relation to health, but not in OA. In BrCa, hormonal receptor status was associated with ccf-mtDNA levels. Machine learning analysis of ccf-mtDNA datasets was used to build biosignatures of clinical relevance. (A) a three-feature biosignature discriminating between health and BrCa (AUC: 0.887) and a five-feature biosignature for predicting the overall survival of BrCa patients (Concordance Index: 0.756). (B) a five-feature biosignature stratifying among T2D, prediabetes and health (AUC: 0.772); a five-feature biosignature discriminating between T2D and health (AUC: 0.797); and a four-feature biosignature identifying prediabetes from health (AUC: 0.795). (C) a biosignature including total plasma ccfDNA with very high performance in discriminating OA from health (AUC: 0.934). Aberrant ccf-mtDNA levels could have diagnostic/prognostic potential in BrCa and Diabetes, while the developed multiparameter biosignatures can add value to their clinical management.

Expert Opinion on Current Trends in the Use of Insulin in the Management of People with Type 2 Diabetes from the South-Eastern European Region and Israel.

Despite the availability of various antihyperglycaemic therapies and comprehensive guidelines, glycaemic control in diabetes management has not improved significantly during the last decade in the real-world clinical setting. Treatment inertia arising from a complex interplay among patient-, clinician- and healthcare-system-related factors is the prime reason for this suboptimal glycaemic control. Also, the key factor leading to inadequate glycaemic levels remains limited communication between healthcare professionals (HCPs) and people with type 2 diabetes (PwT2D). Early insulin administration has several advantages including reduced glucotoxicity, high efficacy and preserved ß-cell mass/function, leading to lowering the risk of diabetes complications. The current publication is based on consensus of experts from the South-Eastern European region and Israel who reviewed the existing evidence and guidelines for the treatment of PwT2D. Herein, the experts emphasised the timely use of insulin, preferably second-generation basal insulin (BI) analogues and intensification using basal-plus therapy, as the most-potent glucose-lowering treatment choice in the real-world clinical setting. Despite an increase in the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the experts urged timely insulin initiation for inadequate glycaemic control in PwT2D. Furthermore, the combination of BI and GLP-1 RA addressing both fasting plasma glucose and post-prandial excursions as a free- or fixed-ratio combination was identified to reduce treatment complexity and burden. To minimise discontinuation and improve adherence, the experts reiterated quality, regular interactions and discussions between HCPs and PwT2D/carers for their involvement in the diabetes management decision-making process. Clinicians and HCPs should consider the opinions of the experts in accordance with the most recent recommendations for diabetes management.

Diabetic Sensorimotor Polyneuropathy: An Overview on Epidemiology, Risk Factors, Classification, Diagnosis, and Treatment.

Diabetic distal symmetric sensorimotor polyneuropathy (DSPN) is a common complication of diabetes with devastating consequences. Hyperglycaemia is the major aetiological factor, while emerging data demonstrate that cardiometabolic risk factors also contribute to its development. Diagnosis of DSPN involves interview of medical and neurological history, foot inspection, and sensory and motor function examination with specific tests such as temperature and pinprick perception for small nerve fibers, and vibration and light touch assessments for large nerve fibers. Management includes optimised glycaemic control, treatment of cardiovascular risk factors, and symptomatic treatment aiming at improving life quality. This article provides an overview on epidemiology, risk factors, classification, diagnosis and current treatment of DSPN.

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.

Menopausal Hormone Therapy in Women with Type 2 Diabetes Mellitus: An Updated Review.

Menopause is accompanied by several metabolic adaptations, which are related to insulin resistance, increased total body fat mass, and central abdominal fat accumulation, predisposing women to type 2 diabetes mellitus (T2DM) development. Metabolic syndrome has a high prevalence in postmenopausal women, indicating the loss of estrogen protection on metabolic and cardiovascular health. Moreover, earlier age at menopause has been related to increased risk of T2DM. Menopausal hormone therapy (MHT) has favorable results in glucose metabolism. Indeed, it reduces the risk of T2DM in women without this condition and improves glycemic control in women with T2DM. Before MHT initiation in women with clinical indications, it is imperative to assess their cardiovascular disease (CVD) risk, using official electronic algorithms for score calculation. The latter will determine regimen, dose, and administration route of MHT. Oral estrogens are preferable in women with low CVD risk, while transdermal administration is indicated in those with moderate and high CVD risk, as the risk of stroke and venous thromboembolism (VTE) is increased with oral administration. Oral 17ß-estradiol is usually preferred in women with T2DM, as this route has more beneficial effects on glucose metabolism. Oral estrogens are also suggested in perimenopausal or recently postmenopausal women with low CVD risk. Although oral estrogens have favorable effects when indicated, the risk of VTE or stroke should always be considered. Micronized progesterone, dydrogesterone, and transdermal norethisterone are the progestogens used in postmenopausal women with T2DM and intact uterus. MHT should not be initiated in women > 60 years or > 10 years in menopause, as there is an increased thromboembolic risk in women with established atherosclerosis and no additional cardiovascular benefit in women without atherosclerosis. In conclusion, MHT administration in postmenopausal women with T2DM can be safe and effective as long as the therapeutic regimen has been properly selected according to their cardiovascular, metabolic, and fracture risk.

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.

Diabetic Foot Screening Guidelines and the Role of Artificial Intelligence: Time to Turn the Tide!

Despite medical and technological advancements, foot amputations continue to rise. Thus, the effort of diabetic foot management should be toward prevention and early diagnosis. Healthcare professionals need to be trained, equipped, and supported with adequate resources to be able to identify and deliver appropriate foot care. Every effort should be made to minimize the impact of complications and to ensure prompt access to care for everyone. Artificial intelligence and smart technology could provide a significant opportunity to improve efficiency in diabetes care, which may reduce diabetic foot complications. The possible potential of the new technologies which are emerging together with their current developing applications for diabetic foot care are suggested. A call for immediate change in diabetes foot screening guidelines is imperative to save limbs and lives.

What is New on Diabetic Neuropathy? Insights from the 2023 ADA and EASD Conferences.

Diabetic neuropathy is a common complication of diabetes; yet its pathophysiology is still incompletely understood and until today, there is no specific treatment against it. In the two 2023 large congresses on diabetes (American Diabetes Association, ADA, European Association for the Study of Diabetes, EASD), several high-level studies have been presented. They have attempted to delineate the pathophysiology of DN, the characteristics of affected patients, and future potential treatments. We herein review the presented studies on diabetic neuropathy at these diabetes congresses and discuss the needs for future research on this topic.

Folic Acid and Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) remain a major cause of morbidity. This narrative mini-review aimed to investigate the potential role of folic acid (FA) in DFUs. Individuals with DFUs exhibit lower levels of FA and lower daily intake, compared to those without DFUs. There is preliminary evidence that FA administration may contribute to improved DFUs healing. In this context, regular evaluation of dietary FA intake may prove important towards reduction or even prevention of DFUs. However, data are still limited and further research is required to enable definitive conclusions and any recommendations.

The Effect of Sodium-Glucose Cotransporter Inhibitors on Renal Function as Adjunctive to Insulin in Adults with Type 1 Diabetes: An Updated Multilevel Meta-analysis of Randomized Controlled Trials.

INTRODUCTION: This systematic review aimed to summarize the existing evidence from published randomized controlled trials (RCTs) on the impact of sodium-glucose cotransporter (SGLT) inhibitors on albuminuria levels and renal function in patients with type 1 diabetes mellitus (T1D). METHODS: The literature search was performed through Medline (via PubMed), Cochrane Library, and Scopus until November 11, 2023. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled with three-level mixed-effects meta-analysis. RESULTS: In total, 5221 participants with T1D among 11 RCTs were analyzed. All RCTs had low risk of bias according to the Cochrane Collaboration tool (RoB 2). SGLT inhibitors were associated with a significantly greater reduction in urine albumin-to-creatinine ratio (UACR) compared to controls (MD = - 23.13%; 95% CI = [- 33.69, - 12.57]; P < 0.001; level of evidence high). On the basis of subgroup analysis, this effect was consistent across all available SGLT inhibitors, irrespective of the dosage. Finally, a neutral class effect was observed on the estimated glomerular filtration rate (eGFR, MD = - 1.03 mL/min/1.73 m2; 95% CI = [- 2.26, 0.19]; P = 0.1; level of evidence moderate). Only empagliflozin was associated with a significant reduction in eGFR compared to placebo (MD = - 2.23 mL/min/1.73 m2; 95% CI = [- 3.62, - 0.84]; P = 0.002). CONCLUSION: Our findings suggest that adjunctive therapy with SGLT inhibitors results in a significant reduction in albuminuria, while their use is associated with a neutral effect on creatinine clearance, as a measure of renal function. Future renal outcome trials are needed to assess SGLT inhibitors' role in the pharmacological armamentarium against diabetic nephropathy in T1D.

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.

New-Onset Diabetes Mellitus in COVID-19: A Scoping Review.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic became superimposed on the pre-existing obesity and diabetes mellitus (DM) pandemics. Since COVID-19 infection alters the metabolic equilibrium, it may induce pathophysiologic mechanisms that potentiate new-onset DM, and we evaluated this issue. METHOD: A systematic review of the literature published from the 1 January 2020 until the 20 July 2023 was performed (PROSPERO registration number CRD42022341638). We included only full-text articles of both human clinical and randomized controlled trials published in English and enrolling adults (age > 18 years old) with ongoing or preceding COVID-19 in whom hyperglycemia was detected. The search was based on the following criteria: "(new-onset diabetes mellitus OR new-onset DM) AND (COVID-19) AND adults". RESULTS: Articles on MEDLINE (n = 70) and the Web of Science database (n = 16) were included and analyzed by two researchers who selected 20 relevant articles. We found evidence of a bidirectional relationship between COVID-19 and DM. CONCLUSIONS: This link operates as a pathophysiological mechanism supported by epidemiological data and also by the clinical and biological findings obtained from the affected individuals. The COVID-19 pandemic raised the incidence of DM through different pathophysiological and psychosocial factors.

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.

Metformin in Type 2 Diabetes: Evidence for its Beneficial Effects on Frailty and Sarcopenia.

This narrative review aimed to discuss the potential interplay among frailty syndrome, sarcopenia and metformin in type 2 diabetes mellitus (T2DM). There is emerging evidence on the potential protective role of metformin on both frailty and sarcopenia. However, results are not always consistent. Thus, further research is needed to provide a definitive answer on any role of metformin in improving frailty and/or sarcopenia in T2DM.

Zinc Levels and Diabetic Foot Ulcers: A Mini Review.

The aim of this nonsystematic mini review was to discuss serum levels of zinc in subjects with diabetic foot ulcers (DFUs). Most studies have reported low zinc levels in subjects with DFUs. Furthermore, there is some evidence that oral zinc supplementation may have a positive and beneficial impact on DFUs healing. Nonetheless, findings have so far not provided definitive answers. More studies are needed to clarify the role of zinc and its supplementation in this setting.