Editor’s Choice Articles

Type 2 diabetes (T2D) has increased worldwide at an alarming rate. Metabolic syndrome (MetS) is a major risk factor for T2D development. One of the main reasons for the abrupt rise in MetS incidence, besides a sedentary lifestyle, is the westernized diet consumption, with high content of industrialized foods, rich in added dietary sugars (DS), mainly sucrose and fructose. It has been suggested that a higher intake of DS could impair metabolic function, inducing MetS, and predisposing to T2D. However, it remains poorly explored how excessive DS intake modulates mitochondrial function, a key player in metabolism. This review explores the relationship between increased consumption of DS and mitochondrial dysfunction associated with T2D development, pointing to a contribution of the diet-induced accumulation of advanced glycation end-products (AGEs), with brief insights on the impact of maternal high-sugar diet and AGEs consumption during gestation on offspring increased risk of developing T2D later in life, contributing to perpetuate T2D propagation. Full article

Diabetes mellitus is a metabolic disorder that is prima facie a cause for numerous macro and micro vascular complications. A common macroscopic complication associated with diabetes is cardiomyopathy. Cardiomyopathy refers to diseases of the heart muscle, where the heart muscle becomes enlarged, thick, or rigid. As cardiomyopathy worsens, the heart becomes weaker and is unable to conduct the right amount of blood through the body and maintain a normal electrical rhythm. This can lead to heart failure or arrhythmias. Chronic diabetes is one of the instigating factors behind the etiology of this cardiac complication. Type-II diabetes is associated with impaired glucose metabolism that increases the dependence of a diabetic heart on fatty acid oxidation to meet its functional demands, resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction that finally gives way to heart failure. The increasing diabetic population with cardiac disorders and the ironically decreasing trend in newer medications to counter this complication leave us at a crossroads for pharmacological management of diabetic cardiomyopathy. Keeping this in view, the present study proclaims a newly developed polyherbal combination (PHC) with three herbs, namely Tinospora cordifolia, Withania somnifera and Boerhavia diffusa based in olive oil and administered in fixed dose (PHC-6 and PHC-10) to screen its cardioprotective potential against a well-established experimental model for diabetic cardiomyopathy. The three herbs mentioned have been known through the traditional literature for their antidiabetic and cardioprotective roles, hence they became the obvious choice. The study follows an experimental model proposed by Reed et al., where the capacity of the β-cell is unobtrusively impeded without totally compromising insulin release, bringing about a moderate disability in glucose resilience. Various sophisticated parameters, namely intraventricular septum thickness of hearts, Western blot of α/β- MHC monoclonal antibody (Ab), cardiac pyruvate dehydrogenase (PDH) activity, medium chain acyl coenzyme A dehydrogenase (MCAD) enzyme, etc. showed promising results where treatment with PHC (PHC-6 and PHC-10) significantly (*** p < 0.001 and **** p < 0.0001) prevented the symptoms of cardiomyopathy in subsequent groups when compared to disease control group. Full article

Excessive sugar consumption is a risk factor for the development of several disorders, including metabolic, cardiovascular, neurological conditions and even some cancers, and has been linked to increased morbidity and mortality. The popularization of the typical Western diet, featured by an excessive intake of saturated fats and added sugars and a low consumption of unprocessed fruits, vegetables and fiber, may directly affect the composition and functionality of the gut microbiota, staggering the balance of the intestinal microbiome that ultimately culminates into gut dysbiosis. Although added sugars in the form of nutritive and non-nutritive sweeteners are generally considered as safe, a growing body of evidence correlate their consumption with adverse effects on gut microbial ecosystem; namely an abnormal synthesis of short-chain fatty acids, altered intestinal barrier integrity and chronic inflammation that often fuel a panoply of metabolic conditions. Accordingly, this work revisited the available preclinical evidence concerning the impact of different types of dietary sugars—nutritive and non-nutritive sweeteners—on gut microbiota and metabolic health. Future research should consider gender and species vulnerability when the impact of such substances on GM community and metabolic health is scrutinized in order to guide their adequate use at doses relevant to human use. Full article

Impaired glucocorticoid signaling in diabetes mellitus and its relation to suppressed immune function and hyperglycemia during acute stroke has been shown to be detrimental. Therefore, the aim of this study was to examine the effect of glucocorticoid receptor (GCR) blockers in a type-2 diabetic mouse model following hypoxia–ischemia (HI). We induced stroke in diabetic db/db and non-diabetic db/+ mice by unilateral common carotid artery ligation followed by 20 min of HI. Mice were pretreated with RU-486, GCRII blocker (40 mg/kg), intraperitoneally, the day before, during stroke and post-HI. Blood and brain samples were collected at 24 h post-HI to measure blood glucose, corticosterone and infarct size. Similarly, another set of mice was pretreated with RU-486 + spironolactone, GCR1 blocker (25 mg/kg) subcutaneously for a week before inducing stroke and during recovery. Samples were collected at 48 h post-HI for various analyses. RU-486 treatment did not lower the blood glucose significantly, but RU-486 + spironolactone decreased the blood glucose in db/db mice post-HI. However, none of the treatment groups decreased the ischemia-induced serum corticosterone level or infarct size. This study suggests that even though GCR blockers improve hyperglycemia, they did not improve the infarct volume. Full article

Non-alcoholic fatty liver disease (NAFLD) is associated with prediabetes and can be treated by using a combination of metformin and dietary modification. However, people often fail to adhere to dietary modifications and become more dependent on pharmaceutical intervention, and this affects the effectiveness of the drug. In this study, we investigated the effects of rhenium (V) compound with uracil-derived ligands on liver health in diet-induced prediabetic rats in both the presence and absence of dietary modification. Prediabetic male Sprague Dawley rats were treated with the rhenium (V) compound for 12 weeks in both the presence and absence of dietary modification while monitoring fasting blood glucose levels. Antioxidant enzyme activity, inflammation markers and liver enzymes were measured together with liver glycogen and plasma triglycerides after sacrificing. The administration of rhenium (V) compound to prediabetic rats in both the presence and absence of dietary modification resulted in reduced concentrations of fasting blood glucose and triglycerides. There was also reduced liver glycogen, oxidative stress and liver enzymes while increasing antioxidant enzymes. Altogether, the rhenium (V) compound ameliorated liver injury and prevented hepatotoxicity. Full article

The research is based on a clinical observation of the neurological and neuro-cognitive status of 300 patients, belonging to the Partinico Hospital and the Post-Long Covid clinic, which had contracted the SARS-CoV-2 virus in the period between April 2021 and May 2022. In this paper, we present the analysis of the first 100 patients subjected to a neurocognitive screening protocol. The procedure consists of tests that examine the mechanism of different brain domains to check for the presence of cognitive deficits that arose after the negativization of the viral infection. Through a neurocognitive protocol, the research aims to investigate different brain areas and mental functioning. This allowed us to raise the possibility that the presence of cognitive alterations may be related to the evidence of point-like brain alterations (from the cortex to the trunk) visible through neuroimaging techniques. In the article, we highlight the hypothesis that SARS-covid 2, as stated in recently published studies, can produce an alteration of executive functions such as to configure a real dysexecutive syndrome. This research evaluates the symptomatic gender variability within the sample, the presence of important differences in the affective state, and provides a first observation of the impact of SARS-CoV-2 in diabetic pathology as well. Full article

Approximately 40% of patients with type 2 diabetes (T2D) experience an early-morning rise in fasting glucose that is not effectively treated by available oral hypoglycemic agents. This study aimed to determine the acute effect of consuming almond butter as an evening snack on fasting and overnight interstitial glucose, compared to a no-snack control, in people with T2D. Adults with T2D, not taking insulin, were recruited to participate in this two-week randomized, controlled, crossover pilot study. Participants received 2 tbsp of natural almond butter as an evening snack, or a no-snack control, for one week each. Glucose was measured by continuous glucose monitor (CGM). Analyses were performed using linear mixed effect modeling in R. Ten adults (60% female; age: 57 ± 5.6 years) completed the study. The intervention did not significantly influence fasting glucose [4–6 a.m.; β = 5.5, 95% CI = [−0.9, 12.0], p = 0.091; Marginal R2 = 0.001, Conditional R2 = 0.954] or overnight glucose (12–3 a.m.; β = 5.5, 95% CI = [−0.8, 11.8], p = 0.089; Marginal R2 = 0.001, Conditional R2 = 0.958). Significant variability in continuously measured glucose was observed. These findings will inform the design of a larger investigation. Full article

During the COVID-19 pandemic, fewer in-person clinic visits resulted in fewer point-of-care (POC) HbA1c measurements. In this sub-study, we assessed the performance of alternative glycemic measures that can be obtained remotely, such as HbA1c home kits and Glucose Management Indicator (GMI) values from Dexcom Clarity. Home kit HbA1c (n = 99), GMI, (n = 88), and POC HbA1c (n = 32) were collected from youth with T1D (age 9.7 ± 4.6 years). Bland–Altman analyses and Lin’s concordance correlation coefficient (𝜌_c) were used to characterize the agreement between paired HbA1c measures. Both the HbA1c home kit and GMI showed a slight positive bias (mean difference 0.18% and 0.34%, respectively) and strong concordance with POC HbA1c (𝜌_c = 0.982 [0.965, 0.991] and 0.823 [0.686, 0.904], respectively). GMI showed a slight positive bias (mean difference 0.28%) and fair concordance (𝜌_c = 0.750 [0.658, 0.820]) to the HbA1c home kit. In conclusion, the strong concordance of GMI and home kits to POC A1c measures suggest their utility in telehealth visits assessments. Although these are not candidates for replacement, these measures can facilitate telehealth visits, particularly in the context of other POC HbA1c measurements from an individual. Full article

Background: COVID-19 has been associated with a higher risk of death in patients with diabetes mellitus (DM). However, there is a dearth of data regarding the effects of diabetic ketoacidosis (DKA) in these patients. We explored the in-hospital outcomes of patients who presented with COVID-19 and DKA. Methods: A propensity score-matched observational retrospective cohort study was conducted in hospitalized patients with COVID-19 in the public healthcare system of New York City from 1 March 2020 to 31 October 2020. Patients were matched, and a subgroup analysis of patients with DKA and COVID-19 and patients without COVID-19 was conducted. Results: 13,333 (16.0%) patients with COVID-19 and 70,005 (84.0%) without COVID-19 were included in the analysis. The in-hospital mortality rate was seven-fold in patients with DKA and COVID-19 compared to patients with COVID-19 and without DKA (80 (36.5%) vs. 11 (5.4%), p < 0.001). Patients with COVID-19 and DKA had a two-fold higher likelihood for in-hospital death (OR: 1.95; 95% CI: 1.41–2.70; p < 0.001) after adjusting for multiple variables. Conclusions: DKA was associated with significantly higher in-hospital mortality in hospitalized patients with COVID-19. Full article

Type 2 diabetes mellitus is a widespread and a chronic disease associated with micro- and macrovascular complications and is a well-established risk factor for cardiovascular disease, which are among the most important causes of death in diabetic patients. This disease is strongly affected by sex and gender: sex-gender differences have been reported to affect diabetes epidemiology and risk factors, as well as cardiovascular complications associated with diabetes. This suggests the need for different therapeutic approaches for the management of diabetes-associated complications in men and women. In this review, we describe the known sex-gender differences in diabetic men and women and discuss the therapeutic approaches for their management. The data reported in this review show that a sex-gender approach in medicine is mandatory to maximize the scientific rigor and value of the research. Sex-gender studies need interdisciplinarity and intersectionality aimed at offering the most appropriate care to each person. Full article

Obstructive sleep apnoea (OSA) and type 2 DM mellitus (T2DM) share obesity as a major risk factor. Furthermore, these conditions share overlapping mechanisms including inflammation, activation of the autonomic nervous system, and hypoxia-linked endocrinopathy. Hence, the pathogenesis of the two conditions may be more closely related than previously recognised. This raises the question of whether treatment of OSA might assist resolution of obesity and/or T2DM. Here, we present a narrative review of the literature to identify clinical and scientific data on the relationship between obstructive sleep apnoea and T2DM control. We found there is a paucity of adequately powered well-controlled clinical trials to directly test for a causal association. While routine screening of all T2DM patients with polysomnography cannot currently be justified, given the high prevalence of sleep disordered breathing in the overweight/obese population, all T2DM patients should at a minimum have a clinical assessment of potential obstructive sleep apnoea risk as part of their routine clinical care. In particular, screening questionnaires can be used to identify T2DM subjects at higher risk of OSA for consideration of formal polysomnography studies. Due to morbid obesity being a common feature in both T2DM and OSA, polysomnography should be considered as a screening tool in such high-risk individuals. Full article

Insulin signaling plays a key role in glucose uptake, glycogen synthesis, and protein and lipid synthesis. In insulin-resistant states like obesity and type 2 diabetes mellitus, these processes are dysregulated. Regular physical exercise is a potential therapeutic strategy against insulin resistance, as an acute bout of exercise increases glucose disposal during the activity and for hours into recovery. Chronic exercise increases the activation of proteins involved in insulin signaling and increases glucose transport, even in insulin resistant states. Here, we will focus on the effect of acute exercise on insulin signaling and protein kinase B (Akt) pathways. Activation of proximal proteins involved in insulin signaling (insulin receptor, insulin receptor substrate-1 (IRS-1), phosphoinoside-3 kinase (PI3K)) are unchanged in response to acute exercise/contraction, while activation of Akt and of its substrates, TBC1 domain family 1 (TBC1D1), and TBC domain family 4 (TBC1D4) increases in response to such exercise/contraction. A wide array of Akt substrates is also regulated by exercise. Additionally, AMP-activated protein kinase (AMPK) seems to be a main mediator of the benefits of exercise on skeletal muscle. Questions persist on how mTORC1 and AMPK, two opposing regulators, are both upregulated after an acute bout of exercise. Full article

Objective: The main aim of this study was to implement the Chronic Care Model (CCM) for the self-management of type 2 diabetes in primary health care settings of rural areas of Pakistan and identify its effectiveness and develop strategies for overcoming its challenges. The two core elements of the Chronic Care Model: patient Self-Management Support (SMS) and Delivery System Design (DSD), were implemented to improve the quality of life and risk behaviour of type 2 diabetes patients in the middle-aged population of rural Pakistan. Methods: Thirty patients with type 2 diabetes and 20 healthcare professionals were included in this study consisting of 10 general practitioners and 10 nurses recruited from various clinics (medical centres) of Al-Rehman Hospital in Abbottabad, Pakistan. The quantitative content analysis method was used to identify the frequency of the most recurring statements. A t-test was performed to see the mean difference of HbA1c at baseline after 3-months and 6-months follow-up between male and female patients with diabetes. The hypothesis was tested to identify that diabetes self-management has a gendered dimension in rural areas of Pakistan. Results: The quantitative analysis demonstrated that diabetes self-management has a gendered dimension in the rural areas of Pakistan as the mean difference of HbA1c after a 6-month intervention of the two components of the chronic care model between male and female patients of diabetes was 0.83 (p = 0.039) with 95% CI (−0.05; −1.61). The mean difference in BMI after the intervention of 6 months between males and females was significant (p < 0.05). The mean difference was 4.97 kg/m², p = 0.040 with 95% CI (−0.24; −9.69). The results have shown that the two components of CCM were effective and improved clinical outcomes for diabetes patients of the rural areas of Pakistan. Conclusions: The application of the two Chronic Care Model’s components provided a viable structure for diabetes self-management education and assistance. As a result, developing systems that incorporate long-term diabetes self-management education has an effect on the health care system’s outcomes. Full article

Autoimmune pancreatic β-cell loss and destruction play a key role in the pathogenesis and development of type 1 diabetes, with a prospective increased risk for developing micro- and macrovascular complications. In this regard, orally administrated verapamil, a calcium channel antagonist, usually intended for use as an anti-arrhythmic drug, has previously shown potential beneficial effects on β-cell preservation in new-onset type 1 diabetes. Furthermore, observational data suggest a reduced risk of type 2 diabetes development. The underlying pathophysiological mechanisms are not well investigated and remain widely inconclusive. The aim of this narrative review was to detail the role of verapamil in promoting endogenous β-cell function, potentially eligible for early treatment in type 1 diabetes, and to summarize existing evidence on its effect on glycemia in individuals with type 2 diabetes. Full article

Several factors affect the relationship between a diabetic patient and a healthcare worker. Among these, there is the well-being of healthcare workers and how they perceive their work environment, especially in the context of the presence or absence of gender inequality. To show the importance of these aspects, a selected sample of healthcare workers who were exposed daily to people (mainly diabetic patients) within the working environment were interviewed. The different opinions of the interviewees show that in an environment where factors that negatively affected their work and personal well-being were minimized, healthcare workers were able to fully express their potential. They expressed great satisfaction with their work involving daily contact with patients, while achieving the type of patient–healthcare worker relationship model desired for a better management of diabetic patients’ care. Full article

The global prevalence of comorbid diabetes and frailty is increasing due to increasing life expectancy. Frailty appears to be a metabolically heterogeneous condition that may affect the clinical decision making on the most appropriate glycaemic target and the choice of the most suitable hypoglycaemic agent for each individual. The metabolic profile of frailty appears to span across a spectrum that starts at an anorexic malnourished (AM) frail phenotype on one end and a sarcopenic obese (SO) phenotype on the other. The AM phenotype is characterised by significant weight loss and less insulin resistance compared with the SO phenotype, which is characterised by significant obesity and increased insulin resistance. Therefore, due to weight loss, insulin therapy may be considered as an early option in the AM frail phenotype. Insulin-related weight gain and the anabolic properties of insulin may be an advantage to this anorexic phenotype. There is emerging evidence to support the idea that insulin may improve the muscle function of older people with diabetes, although this evidence still needs further confirmation in future large-scale prospective studies. Long acting insulin analogues have a lower risk of hypoglycaemia, comapred to intermediate acting insulins. Additionally their simple once daily regimen makes it more appropriate in frail older patients. Future research on the availability of new once-weekly insulin analogues is appealing. The goals of therapy are to achieve relaxed targets, avoid hypoglycaemia and to focus on the maintenance of quality of life in these vulnerable patients. Full article

Gender difference in all fields of medicine and biology has recently become a topic of great interest. At present, most studies report gender differences in their secondary analysis; however, this information receives scant attention from clinicians, and is often overwhelmed by press trumpeting the overall main positive results. Furthermore, and more importantly, any statistical evaluation of results obtained without specific and careful planning in the study for the topic of research is probably worthless. There are few studies in animals, but these are not typically useful because of the different biology, pharmacodynamics and pharmacokinetics compared to humans. Type 1 diabetes is a disease where gender difference can be easily evaluated. Irrespective of the cause of the loss of pancreatic beta-cell function, the common denominators of all forms of type 1 diabetes are the absence of circulating insulin and a reduction in peripheral insulin sensitivity leading to exogenous injections being required. Consequently, exogenous insulin infusion, with any of the widely used research tools, such as the insulin–glucose clamp, can be easily used to evaluate gender difference. Female patients with type 1 diabetes have many factors that impact glucose level. For example, the hormones that drive the ovulatory/menstrual cycle and the connected change at the time of the menopause have a role on insulin action; thus, one should expect great research emphasis on this. On the contrary, there is a dearth of data available on this topic, and no pump producer has created a gender-specific insulin infusion profile. Patients are usually approached on the basis of their diagnosis. This review is intended to focus on personalized treatment, more specifically on gender, according to the modern way of thinking. Full article

The prevalence of non-alcoholic fatty liver disease (NAFLD) and its progressive form, non-alcoholic steatohepatitis (NASH), is increasing in parallel with the rising rates of obesity and type 2 diabetes. Approximately one in four adults are diagnosed with liver steatosis globally. NAFLD is associated with insulin resistance, hypertension, obesity, visceral adiposity, and dyslipidaemia. These risk factors are often accompanied by inflammation and oxidative stress, which also play a role in extrahepatic diseases, including conditions related to the central nervous system, such as mild cognitive impairment and Alzheimer’s disease. The number of people living with dementia is approximately 55 million and is estimated to increase to approximately 2 billion people by 2050. Recent studies have found that NAFLD is associated with poorer cognition. The aim of this review was to summarise the findings of hitherto studies that have linked NAFLD with cognition and dementia, as well as to discuss the potential liver–brain pathways. Full article

Background: Older people consistently report a desire to remain at home. Beat It is a community-based exercise and lifestyle intervention that uses evidence-based strategies to assist older people with type 2 diabetes mellitus (T2DM) to improve physical and functional fitness, which are crucial to maintain independence. This follow up, real-world study assessed the efficacy of Beat It and whether older adults with T2DM were able to maintain improvements in physical activity, waist circumference and fitness one year post completion. Methods: We have previously reported methods and results of short-term outcomes of Beat It. This paper reports anthropometric measurements and physical fitness outcomes of Beat it at 12-months post program completion and compares them to validated standards of fitness required to retain physical independence. Results: Improvements that were observed post program were maintained at 12 months (n = 43). While the number of participants who met fitness standards increased post program, not all increases were maintained at 12 months. Conclusions: This study provides promising early evidence that an eight-week, twenty-hour community-based clinician-led exercise and lifestyle program can improve health outcomes in older adults with T2DM which were retained for at least a year after program completion. Full article

During the first lockdown of the COVID-19 pandemic, people with type 1 diabetes (T1D) were worried, stressed, and experienced changes in their self-management practices. Studies found that many had difficulties managing their disease, while others showed improvements. Since the first lockdown, the virus and subsequent lockdowns have become a more regular part of everyday life. The present study investigated how the COVID-19 pandemic, one year after its outbreak, has affected self-management in people with T1D. The dataset consisted of seven semi-structured interviews with adults with T1D, which were interpreted using Antonovsky’s theory of Sense of Coherence (SOC). We found that the pandemic and the ensuing lockdowns had contributed to better self-management in people with T1D, as they had developed a strong SOC. Knowledge from healthcare professionals and their own experiences with the COVID-19 pandemic had caused them to experience stronger comprehensibility, which had been crucial to experiencing strong manageability, enabling them to make active choices to maintain good glycemic control. Furthermore, better opportunities and more motivation had allowed them to experience stronger meaningfulness regarding immersing themselves in their treatment. Our findings show that, during health crises, having a strong SOC is important for disease management among people with T1D. Full article

There are about 200 million people on the move in the world, and approximately 50% of them are women. There are no clear migration plans for women leaving as a result of persecution, war, famine, climatic disasters or moving away from contexts of external abuse and even intrafamily violence. Gender-related violence, to which women are exposed in cultural contexts characterized by a patriarchal social organization, is manifested through different ways including, but not limited to, early marriages and genital mutilation, with reproductive health already being seriously impaired at an early age. To this must be added the consideration that low-income countries are not able to deal with chronic degenerative diseases with a multidisciplinary approach such as diabetes. Fragile or non-existent health systems are not prepared for this need, which now affects a third of all deaths from this cause. Compared to Italian mothers, women from high-migration pressure countries had a higher risk of gestational diabetes; in addition, young women of Ethiopian ethnicity are more exposed to increased diabetes risk, in an age- and BMI-dependent way. Gender inequalities are also more evident in migrants for other non-communicable diseases besides diabetes. A major effort is needed in terms of training practitioners and reorganization of basic health services, making them competent in an intercultural sense. Health education of the population as a whole and of women specifically is also needed to contain risk behavior and prevent the early onset of metabolic syndromes in general and of type 2 diabetes in particular. Full article

Introduction: Metabolic Syndrome (MS) is a pathologic condition characterized by Type 2 diabetes mellitus (T2DM), insulin resistance, abdominal obesity, hypertension, and hyperlipidemia. Until now, specific drugs such as metformin (MET) have been used to address its individual components; however, according to the recommendation of WHO, various plant extracts might be used as alternative medicines due to the side effects of pharmacologic agents. Policaptil Gel Retard^® (PGR), a macromolecule complex based on polysaccharides which slows down the absorption rates of carbohydrates and fats, proved effective against glucose abnormalities. Our study aimed to verify the short-term efficacy and safety of PGR under real-life conditions. Methods: We evaluated both the 6-month changes in metabolic parameters in Italian patients with MS and T2DM, and the 10-year CV risk score (10-y-CV-RS) from the CUORE equation, competitively randomized to Policaptil Gel Retard (2172 mg before each main meal); Group A, n = 75, or Metformin (1500–2000 mg/day equally divided between the two main meals), and Group B, n = 75. Results: Fasting plasma glucose and HbA1c decreased significantly and similarly (p < 0.001) in the two groups. A significant decrease in BMI (−20% in the PGR group (p < 0.01), −14.3% in the MET group (p < 0.05)), % visceral fat, and UA levels was also apparent in both groups (p < 0.01). The opposite occurred for lipid profile, which improved significantly in the PGR group but remained unchanged in the MET group. Consequently, only the PGR group experienced a significant decrease in the 10-y-CV-RS (31.4 ± 8.0 vs. 19.7 ± 5.2, p < 0.0001), whereas this remained unchanged in the MET group (32.2 ± 3.3 vs. 30.5 ± 8.7; p n.s.). Conclusions: PGR could represent a suitable alternative to MET as a first-line treatment option, especially now that an ever-increasing number of people prefer natural products based on plant extracts. This is particularly pertinent given that, besides trying to avoid gastrointestinal side-effects as much as possible, patients might be sensitive to ecotoxicology-related problems involving plants and animals caused by the worldwide spread of environmental MET metabolites. Full article

Technological advances in the management and treatment of type 1 diabetes have afforded some patients the resources to better manage their condition and live full, healthy lives. One of these technologies is continuous glucose monitoring which allows patients and medical practitioners alike to receive real-time blood glucose readings, evaluate trends, and tailor insulin dosing to avoid both hyper- and hypoglycemic events. The benefit of such technology during exercise, particularly running or cycling, is invaluable. In this case report, we describe the effect of using a continuous glucose monitoring technology in a 38-year-old, brittle, type 1 diabetic female runner over two years. The combined effect of continuous glucose monitoring and exercise, primarily running, resulted in an almost two-fold reduction in HbA1C, a 21% reduction in total daily insulin usage from diagnosis approximately 20 years ago. The patient recorded an over 100% improvement in running capacity. Full article

Metabolic syndrome (MetS) is a major societal concern due to its increasing prevalence and its high risk of cardiovascular complications. The ketogenic diet (KD), a high fat, low carbohydrate, and non-caloric restrictive diet, is a new popular weight loss intervention but its beneficial effects are controversial. This study aims to gather all of the relevant studies using KD for metabolic disease treatment to determine its beneficial effects and evaluate its safety and efficacy for patients. Following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, we included 20 articles in the final review. Overall, most of the studies showed a significant effect of KD on weight loss (17/19 articles), BMI (7/7), glucose levels (9/13), insulin levels (7/9), HOMA-IR (4/5), HbA1c (7/7), total cholesterol (6/9), TG (13/15), AST (3/4), and ALT (3/5), and no major side effects. The results heterogeneity seems to be explained by a difference of diet composition and duration. In conclusion, KD is a safety diet which seems to be a promising approach for obesity and MetS treatment, even if the optimal carbohydrate proportion and diet duration must be explored to enhance the beneficial effects of KD. Full article

Diabetes mellitus has become a non-infectious pandemic. The incidence of T2D has risen dramatically and recent rates have increased in many countries including Muslim countries. As the number of people who participate in Ramadan increases, health care professionals will need to become familiar with the traditions and help people stay healthy during the holy month of Ramadan. A key part of Ramadan is the practice of one month of fasting from sunrise to sunset. While this is a religious practice, it has significant impacts on the management of people with diabetes. This article will discuss the traditions associated with Ramadan and how to help people safely manage their diabetes while participating in Ramadan. Full article

Objective: Assess in a sample of people with type 1 diabetes mellitus whether mood and stress influence blood glucose levels and variability. Material and Methods: Continuous glucose monitoring was performed on 10 patients with type 1 diabetes mellitus, where interstitial glucose values were recorded every 15 min. A daily survey was conducted through Google Forms, collecting information on mood and stress. The day was divided into six slots of 4-h each, asking the patient to assess each slot in relation to mood (sad, normal or happy) and stress (calm, normal or nervous). Different measures of glycemic control (arithmetic mean and percentage of time below/above the target range) and variability (standard deviation, percentage coefficient of variation, mean amplitude of glycemic excursions and mean of daily differences) were calculated to relate the mood and stress perceived by patients with blood glucose levels and glycemic variability. A hypothesis test was carried out to quantitatively compare the data groups of the different measures using the Student’s t-test. Results: Statistically significant differences (p-value < 0.05) were found between different levels of stress. In general, average glucose and variability decrease when the patient is calm. There are statistically significant differences (p-value < 0.05) between different levels of mood. Variability increases when the mood changes from sad to happy. However, the patient’s average glucose decreases as the mood improves. Conclusions: Variations in mood and stress significantly influence blood glucose levels, and glycemic variability in the patients analyzed with type 1 diabetes mellitus. Therefore, they are factors to consider for improving glycemic control. The mean of daily differences does not seem to be a good indicator for variability. Full article

Background: The aim of this study was to evaluate whether secreted frizzled-related protein 4 (sFRP4), secreted frizzled-related protein 5 (sFRP5), and chemerin serum concentrations in early pregnancy are associated with the development of gestational diabetes mellitus (GDM) in an obese cohort. In previous studies, increased sFRP4 and chemerin, and decreased sFRP5 concentrations were associated with the development of GDM in normal and overweight women. Methods: In this exploratory case control study, sFRP4, sFRP5, and chemerin serum concentrations were determined by ELISA in 50 obese women who developed GDM and 100 uncomplicated control pregnancies. Serum samples were obtained between 15⁺⁰–18⁺⁶ weeks’ gestational age and based on a priori known associations with the development of GDM, body mass index (BMI) and maternal age were selected for adjustment in multivariate analyses. Results: In this obese cohort (median BMI 35.7 kg/m², IQR 33.2–40.3 kg/m²), the biochemical markers showed no association with GDM: sFRP5 odds ratio (OR) 0.44 (95% confidence interval (CI) 0.01–23.18, p = 0.687), sFRP4 OR 0.55 (95% CI 0.09–3.52, p = 0.528), and chemerin OR 3.47 (95% CI 0.05–227.72, p = 0.560). Adjustment for BMI and maternal age did not influence the association. None of the markers were significantly correlated with insulin resistance (HOMA2-IR). Conclusion: No association was found between sFRP4, sFRP5, or chemerin concentration and the development of GDM in a cohort of obese pregnant women. The absence of the association may indicate that these proteins play a lesser biological role in the pathophysiology of GDM in obese women. Full article

Background: Diabetes is a complex disease requiring a multidisciplinary approach. However, the dynamics of this collaboration and the involvement of healthcare providers remain unclear. Aim(s): To explore the composition, the division of roles/tasks, and the collaboration in a diabetes team. Methods: A qualitative, explorative study with six focus groups was conducted, of which four focus groups were with healthcare providers (n = 34) and two with informal caregivers and persons with diabetes (n = 13). In addition, two in-depth interviews with doctors were performed. An iterative process of data analysis took place, guided by the Qualitative Analysis Guide of Leuven (QUAGOL). Results: All participants confirm the importance of patient empowerment and the fact that the person with diabetes should have a central role within the team. However, this has not been achieved yet. This research gives a clear insight into the dynamics of a diabetes team. Roles and tasks are allocated according to the specific expertise and knowledge of the different healthcare providers. Interprofessional collaboration is the ultimate goal. However, the diabetes team is often formed ad hoc depending on the needs of the person with diabetes and the preferences for collaboration of the healthcare providers. Furthermore, this study revealed some important bottlenecks with regard to the knowledge of healthcare providers, persons with diabetes and their informal caregivers, the regulation and reimbursement. Discussion: Our study uncovers the dynamics of a diabetes team and its members. Healthcare providers work mainly alone, except in hospitals, where they can consult other healthcare providers briefly if necessary. Although collaboration proves to be difficult, all healthcare providers ask for a more intensive interprofessional collaboration. Conclusion: In order to improve quality of diabetes care, patient-centered care and the satisfaction of patients, informal caregivers, and healthcare providers, efforts have to be made to facilitate interprofessional collaboration. This can be achieved by sharing information via electronic shared patient records, coordination, overview, local task agreements, simplified legal regulations, and an adjusted financing system. Full article

The global burden of diabetes and cardiovascular disease (CVD) is increasing and, while cardiovascular event incidence is falling in some high-income countries (HICs), increasing rates are being observed in many middle-income countries (MICs) and low-income countries (LICs). There have been discrepancies in the availability and affordability of medicines for diabetes and cardiovascular disease among countries, of which LICs and MICs have seen low availability and affordability. The Prospective Urban Rural Epidemiological (PURE) study is a large prospective cohort study of over 200,000 people aged 35–70 years from 27 HICs, MICs, and LICs across six geographical regions (Asia, Africa, Europe, South America, North America, and the Middle East). Analyses from this study have contributed greatly to the understanding of the determinants of cardio–metabolic health in LICs and MICs especially. Here, we discuss information learned from the PURE study regarding the availability and affordability of key medicines for diabetes and cardiovascular disease. Full article

Recent Mucorales-mediated outbreaks of infections and an association of fungal infection with COVID-19 cases, as observed for COVID-19-associated mucormycosis (CAM), have posed new challenges for the management of patients in critical care units. Diabetes and hyperglycemia are integrally linked to the severity of COVID-19, and uncontrolled diabetes mellitus and COVID-19 have recently been (independently or in combination) associated with the emergence of aggressive mucormycosis due to attendant defects in innate immune recognition pathways. Therefore, the identification of novel global cellular stressors upregulated during diabetes to understand the contribution of diabetes-associated metabolic vulnerabilities can help build a Metabolic-Stress-Associated Interactome (MSAI). This interactome can help reshape the metabolic inflammation (meta-inflammation) underlying the clinical manifestations of COVID-19 to facilitate the rational design of effective therapies for COVID-19 and CAM. Accordingly, an important area of research in COVID-19 therapeutics is engaged with identifying diabetes-associated pan-cellular stressors to understand their role in immune deregulation during COVID-19 and CAM, including investigating the distant trans-neuro-vascular–endocrine axis’s role in coordinating cellular-stress recognition, transmission, compensation, and decompensation during inter-organ regulation of metabolic homeostasis in diabetes. We reviewed clinico-pathological and laboratory data to propose potential diabetes-linked novel neo-vulnerabilities that can reshape the olfactory mucosal immune landscape during airway infections such as COVID-19 and CAM. Full article

Growing evidence suggests that healthcare provider advice may reduce alcohol use, increase physical activity, and improve the adoption of other desirable lifestyle behaviors among patients. However, how brief interventions and other provider–patient interactions can shape the cumulative adoption of multiple modifiable behaviors is less well studied for diabetes prevention and control. Using weighted Internet panel survey data from a large socio-demographically diverse urban population in the United States (n = 1003), the present study describes differences in group characteristics among those who ‘had been ever diagnosed’ with prediabetes/diabetes versus those who had not. It also examines the associations between the cumulative adoption of lifestyle behaviors and each of the following: (a) lifetime prediabetes/diabetes diagnosis; (b) brief lifestyle intervention exposure (i.e., ever received provider encouragement to modify lifestyle behaviors); and (c) recent provider–patient communication about diabetes. There were several group differences among those who ‘had been ever diagnosed’ with prediabetes/diabetes versus those who had not, by age, employment status, health status, nutrition knowledge, blood pressure/hypertension diagnosis, and diabetes-related health behaviors (p < 0.05). Each of the three provider–patient interactions of interest were positively associated with a higher cumulative sum of adopted modifiable lifestyle behaviors for diabetes prevention and management. The results suggest that provider advice/provider–patient interactions of any type can have a salutary impact on whether individuals with prediabetes or type 2 diabetes will engage in recommended lifestyle behavior modifications. Full article

Diabetes mellitus is one of the most frequently occurring metabolic disorders (DMs), impairing healthy life around the globe, with mild-to-severe secondary complications. DM is associated with secondary complications, including diabetic retinopathy (DR), which damages the retina and can lead to vision loss. Diabetic patients often suffer from extreme retinal capillary aneurysms, hemorrhage, and edema, which is likely to lead to non-proliferative or proliferative diabetic retinopathy (NPDR or PDR) and diabetic macular edema (DME). Several epidemiological studies have illustrated that the occurrence of DR can vary by age of diabetes onset, diabetes type, and ethnicity. Although DR is very well-known, the complexity of its etiology and diagnosis makes therapeutic intervention difficult and challenging. We have reviewed different pathological aspects of diabetic retinopathy and its underlying mechanism of occurrence. In this review, we aim to provide an in-depth understanding and illustration of the progression of diabetic retinopathy, its pathophysiology, epidemiology, and prospective therapeutic targets. Full article

Before the discovery of insulin and the critical role of the pancreas vis-à-vis diabetes mellitus pathophysiology, childhood diabetes or what we now call type 1 or autoimmune diabetes mellitus was almost universally fatal. In limited-resource countries (LRC) around the world, this remains sadly true because of the expense and unavailability of medical care, medical information, and/or medications. In 1889, Minkowski and Mering identified the pancreas as the likely source of the problem in pancreatectomized dog experiments, and Langerhans, working with Virchow, identified the islands of pancreatic tissue now named after Langerhans as the likely source of the problem. Prior to that, Cawley, Boucherdat, Zuelzer, Gley, de Meyer, Schafer, Scott, Kleiner, and Paulescu all worked on this problem with varying results until Banting, Best, MacLeod, and Collip in Toronto in 1921 successfully treated pancreatectomized dogs with an alcohol-based pancreatic extract and then were the first to do the same with children and adults with diabetes, starting with Leonard Thompson in early 1922. Urinary and blood glucose levels were reduced, and clinical symptoms decreased concurrently. The magnificent medical historical work by Professor Michael Bliss, also from Toronto, as well as an excellent US NPR Television documentary, describes the trials and tribulations of this event that culminated in the “fastest Nobel Prize” awarded. Progressive biopharmaceutical advances have modified insulin from pigs and cows and then genetically engineered insulin to work much faster and also much slower to provide more modernized ways of providing insulin. Insulin pens then replaced vial and syringe administration, and then insulin pumps coupled with continuous blood glucose sensors have made delivery more physiologic in addition to more attention paid to nutrition advice, education, and psychosocial support around the world. Programs to assist delivery of expensive insulin to LRC administered by Insulin for Life, Life for a Child (LFAC), Changing Diabetes in Children (CDIC) coupled with support by ISPAD (International Society for Pediatric and Adolescent Diabetes) have continued to make such advances available thorough wonderful philanthropy in insulin manufacturers and manufacturers of blood glucose monitoring equipment and insulin pump/sensor suppliers. Full article

Background: There has been evidence that metabolic syndrome (MetS) may increase the risk of frailty. However, there is limited evidence on this association in Asian populations. Aims: This study aims to identify the association between MetS and frailty in older people in Vietnam. Methods: This is a cross-sectional analysis of a dataset that was obtained from an observational study on frailty and sarcopenia in patients aged ≥60 at a geriatric hospital in Vietnam. Frailty was defined by the frailty phenotype. The participants were defined as having MetS if they had ≥3 out of 5 criteria from the definition of the National Cholesterol Education Program (NCEP) Adults Treatment Panel (ATP) III. Multiple logistic regression models were performed to estimate the risk of having frailty in patients with MetS. Results: Of the 669 participants (mean age 71, 60.2% female), 62.3% had MetS and 39.0% were frail. The prevalence of frailty was 42.2% in participants with MetS and 33.7% in participants without MetS (p = 0.029). On the logistic regression models, MetS was associated with an increased likelihood of being frail (adjusted OR 1.52, 95%CI 1.01–2.28), allowing for age, sex, education, nutritional status, history of hospitalization, and chronic diseases. Conclusion: There was a significant association between MetS and frailty in this population. Further longitudinal studies are required to confirm this association. Full article

Diabetes is a common and complex disease affecting multiple organ systems throughout the body. With a consensus in care guidelines emphasizing the importance of glycemic control in determining the disease progression, people with diabetes worldwide have been placed on medication regimens targeting glucose stability from a variety of pathophysiologic pathways. Each of these medications also possesses its own potential for adverse events. In recent years, there has been increased reports of skin reactions to diabetes medications, adding to the more widely known eruptions such as insulin-induced lipohypertrophy and contact dermatitis of subcutaneous injections. The authors searched PubMed, Google, and Embase for articles including adverse reactions to anti-hyperglycemic medications. Key words and titles searched included, “antidiabetic drugs”, “skin reactions”, “adverse drug reactions”, “allergic reactions”, “diabetes”, “metformin”, “insulin”, “DPP4 inhibitors”, “thiazolindineones”, “sulfonylureas”, “SGLT2 inhibitors”, “GLP-1 agonists”, “diabetic medication”, “injection site reactions”. As a result, a total of 59 papers are included in this review. The great majority were case reports ranging from benign fixed drug eruptions to severe cutaneous reactions that threaten patients’ lives. Increasing physician awareness of both the potential for, and presentation of, such reactions to diabetes medications can reduce hospitalizations and optimize care in an already vulnerable patient population. Full article

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells by their own immune system, resulting in lifelong insulin deficiency. Continuous exogenous insulin replacement therapy is the current standard of care for T1D. Transplantation of primary pancreatic islets or the entire pancreas is a viable remedy for managing patients with autoimmune T1D. However, this strategy is not feasible due to several obstacles, including a scarcity of donors, islet cells, and poor vascular engraftment of islets post-transplantation, as well as the need for prolonged immune suppression. Innovative approaches must be developed to counteract pancreatic β-cell destruction and salvage endogenic insulin production, thereby regulating blood glucose levels. This review includes an overview of autoimmune T1D, immune cells involved in T1D pathophysiology, and immunotherapy-based strategies to treat and prevent autoimmune T1D. Recent immunotherapy progress toward targeting pancreatic islet-specific immune pathways tangled tolerance has fueled the advancement of therapies that may allow for the prevention or reversal of this autoimmune T1D while avoiding other adverse reactions associated with the previous attempt, which was mostly immunosuppressive. As a result, significant efforts are currently underway to improve the efficacy of immunotherapy-based approaches by leveraging the beneficial actions of immune cells, specifically effector CD4⁺, CD8⁺, and regulatory T cells. This review will provide an overview of currently available immune-based therapeutic options for T1D and will examine the growing evidence that supports the use of immune cell-based approaches to improve therapeutic outcomes in the prevention or reversal of autoimmune T1D. Full article

Diabetes is a major public health problem and is emerging as a pandemic. The fundamental cause of obesity and overweight is an energy imbalance between calories consumed and calories burned up. Physical activity is one of the mainstay clinical interventions for preventing metabolic diseases, and dietary habits are the primary factor for the rapidly rising incidence of DM. Reducing weight and maintaining a healthy weight, reducing energy intake, and food intake high in vegetables, fruit, whole grains, legumes, nuts, and dairy products are core parts of management. We performed a narrative literature review, manual-search of reference lists of included articles, and relevant reviews. The main purpose of this review was to discuss the role of psychosocial factors and diet in the control of type II Diabetes. Full article

Self-monitoring of blood glucose forms an important part of the management of diabetes and the prevention of hyperglycaemia and hypoglycaemia. Current glucose monitoring methods either use needle-prick enzymatic glucose-meters or subcutaneous continuous glucose sensors (CGM) and thus, non-invasive glucose measurements could greatly improve the self-management of diabetes. A wide range of non-invasive sensing techniques have been reported, though achieving a level of precision comparable to invasive meters remains a challenge. Optical sensors, which utilise the interactions between glucose and light, offer the potential for non-invasive continuous sensing, allowing real-time monitoring of glucose levels, and a range of different optical sensing technologies have been proposed. These are primarily based upon optical absorption and scattering effects and include infrared spectroscopy, Raman spectroscopy and optical coherence tomography (OCT), with other optical techniques such as photoacoustic spectroscopy (PAS) and polarimetry also reported. This review aims to discuss the current progress behind the most reported optical glucose sensing methods, theory and current limitations of optical sensing methods and the future technology development required to achieve an accurate optical-based glucose monitoring device. Full article

Insulin-dependent diabetes mellitus (IDDM) is a metabolic condition that induces blood glucose levels to rise due to insulin deficiency and the formation of reactive oxygen species (ROS). The purpose of this study is to assess how efficient the antioxidant extracts Tribulus terrestris (TT) and metformin (MET) are in reducing oxidative stress and histopathology produced by streptozotocin in rat hepatocytes. The 36 male rats weighing 170–190 g of this study were randomly sorted into 6 groups. The first group was considered a normal control group, and the second and third groups were normal and remedy with MET and TT extract, respectively. The fourth group was positive diabetic, and the fifth and sixth groups were diabetic rats that were treated with MET and TT extract, respectively. Lipid peroxidation (LPO), catalase (CAT), glutathione-S-transferase (GST), and glutathione (GSH) were detected, and the histopathology of the liver was evaluated after 8 weeks of treatment. Compared to regulation, morphological changes in the liver were found in diabetic animals, with a rise in LPO and a change in GSH levels as well as CAT and GST activities. The oxidative stress and histological architecture of the hepatocytes caused by hyperglycemia were improved as a result of therapy in the rats with MET and TT extract. Because of its antioxidant activities, diabetic rats with TT extract are more effective than MET in normoglycemia and hepatocyte reconditioning. Beneficial intervention tends to benefit primarily from direct ROS scavenging and CAT, GST, and GSH regeneration. Full article

The focus in diabetes care has traditionally been around the optimisation of the glycaemic control and prevention of complications. However, the prevention of frailty and improvement in physical function have now emerged as new targets of diabetes management. This is mainly driven by the significant adverse impact that early onset frailty and decline in physical function have on health outcomes, functional independence, and quality of life in people with type 2 diabetes (T2D). There is an increasing emphasis in the expert consensus and management algorithms to improve physical function in people with T2D, predominantly through lifestyle interventions, including exercise and the control of modifiable risk factors. Trials of novel glucose-lowering therapies (GLTs) also now regularly assess the impact of these novel agents on measures of physical function within their secondary outcomes to understand the impact that these agents have on physical function. However, challenges remain as there is no consensus on the best method of assessing physical function in clinical practice, and the recognition of impaired physical function remains low. In this review, we present the burden of a reduced physical function in people with T2D, outline methods of assessment used in healthcare and research settings, and discuss strategies for improvement in physical function in people with T2D. Full article

Objectives: The middle-aged population from rural areas of Pakistan is disproportionately at risk of developing and mismanaging their diabetes. The purpose of this study was to explore the self-management experiences of two focus groups in the middle-aged population with type 2 diabetes mellitus living in rural Pakistan. Methods: The study design is based on the exploratory research using a qualitative approach. Purposive sampling was used to recruit patients with diabetes from the metabolic outpatient clinics of medical centers in rural areas of Pakistan. The data were collected for two focus groups consisting of 20 persons (10 men and 10 women) with type 2 diabetes mellitus, ranging in age from 40 to 65 years, who were receiving diabetic care at a local health facility. Focus group discussions with a sample size of 10 participants each were all recorded, transcribed, and analyzed. The data were evaluated thematically. Results: Participants described diabetes management as emotionally, physically, and socially taxing. The analysis of the data indicated three major themes: (1) diabetes as a challenging disease; (2) understanding diabetes and its challenges; (3) following diabetes self-management practices. Throughout the session, participants discussed the impact of diabetes on their daily life. This study provided new insights into the experiences of the middle-aged population of Pakistan regarding their self-management of diabetes. Conclusions: Healthcare professionals should become involved in diabetes self-management education as soon as feasible to alleviate patient worry and establish better patient-centered, culturally sensitive professional abilities. Along with monitoring patients’ self-management, healthcare professionals should place a greater emphasis on patients’ understanding of the disease and its challenges and associated complications. It is recommended to establish diabetes support groups to encourage patients to share their experiences of diabetes self-management. Full article

Screening diabetic retinopathy, a major cause of blindness, is time-consuming for ophthalmologists and has some constrains in achieving full coverage and attendance. The handheld fundus camera EyeFundusScope was recently developed to expand the scale of screening, drawing on images acquired in primary care and telescreening made by ophthalmologists or a computer-aided diagnosis (CADx) system. This study aims to assess the diagnostic accuracy of the interpretation of images captured using EyeFundusScope and perform its technical evaluation, including image quality, functionality, usability, and acceptance in a real-world clinical setting. Physicians and nurses without training in ophthalmology will use EyeFundusScope to take pictures of the retinas of patients with diabetes and the images will be classified for the presence or absence of diabetic retinopathy and image quality by a panel of ophthalmologists. A subgroup of patients will also be examined with the reference standard tabletop fundus camera. Screening results provided by the CADx system on images taken with EyeFundusScope will be compared against the ophthalmologists’ analysis of images taken with the tabletop fundus camera. Diagnostic accuracy measures with 95% confidence intervals (CIs) will be calculated for positive and negative test results. Proportion of each category of image quality will be presented. Usability and acceptance results will be presented qualitatively. Full article