Both type 1 and type 2 diabetes can lead to diabetic nephropathy (DN), a serious microvascular complication. Bromodomain 4 (BRD4), a member of the BET protein family, has been linked to various diseases, including cancer, inflammation, and fibrosis, and may be involved in the development of diabetes and its complications. In this study, we first explored the role and mechanism of BRD4 in DN. We found that BRD4 expression was upregulated in both diabetic cells and animal models, and that BRD4 knockdown alleviated DN. Therefore, we next investigated the effect of AT1, a small-molecule degrader of BRD4 based on proteolysis targeting chimera (PROTAC) technology, on DN improvement. PROTAC has seldom been applied to non-oncological diseases, and this study represents the first application of AT1 to DN. Finally, we explored the molecular mechanisms underlying DN improvement.

Chrononutrition, which examines the relationship between circadian rhythms and nutrition, has been associated with glycemic outcomes in adults. However, published data on delayed meal timing, increased meal frequency and frequent breakfast skipping have shown inconsistent glycemic outcomes due to variations in methodologies and populations studied. This review presents the scoping review protocol designed to map the evidence on the association between chrononutrition factors and glycemic outcomes in adults. The methodology framework from Arksey and O'Malley will be adapted for this scoping review. Relevant publications will be searched on databases including PubMed, EBSCO Host, ProQuest Central, MEDLINE & Ovid, Scopus and Web of Science. This review focuses on original articles published from January 2014 to 2024, involving participants aged 18 years and older, published in English, and encompassing experimental and observational studies. A comprehensive keyword search strategy will be developed to identify relevant articles. Two reviewers will independently screen the abstracts and titles to determine the eligibility. Subsequently, the full text of potentially eligible articles will be reviewed by additional independent reviewer for final inclusion, with full text screening being verified by two reviewers, and interrater reliability will be conducted. Data from the included articles will be extracted, collated and charted to summarize the relevant methods, outcomes and key findings. This Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist will be used to guide the development of protocol. This scoping review represents a novel approach to summarize the association between chrononutrition factors and glycemic outcomes among adults. We anticipate the findings of the review will provide stakeholder with crucial evidence-based information for development of effective intervention to manage glycemic outcome in adults. This protocol has been prospectively registered in the Open Science Framework (https://doi.org/10.17605/OSF.IO/PA9BU).

Sleep is an essential biological function that is critical for a healthy and fulfilling life. Available sleep quality assessment tools contain long questionnaires covering a long period of time, not taking into account daily physical activity patterns and individual lifestyles.

In this paper we present SmartHypnos, an Android application that supports low-end devices. It enables users to report their sleep quality, monitor their physical activity and exercise intensity and gain personalized recommendations aimed at increasing sleep quality. The application functionalities are implemented through sleep quality evaluation questions, passive step counter, efficient data storage and Personal data are stored locally protecting user privacy. All these are integrated into a single interface that requires a single device, is of low learning difficulty and easy to use. SmartHypnos was evaluated during a pilot study that involved 48 adults (ages 18-50) that used the application for seven days and subsequently submitted their data, possible through the interface directly, and evaluated the application through an appropriate questionnaire.

SmartHypnos was rated positively by users, especially it terms of learnability, ease of use and stability, with a mean score over 8. Task completion time and ease, simplicity, user comfort and recommendation utility were scored with a mean over 7. The correlation between the features extracted were in accordance to prior works.

SmartHypnos has the potential to become a sleep monitoring and intervention tool readily available to the general public, including vulnerable populations of low socio-economic status.

Metformin has become the frontline treatment in addressing the significant global health challenge of type 2 diabetes due to its proven effectiveness in lowering blood glucose levels. However, the reality is that many patients struggle to achieve their glycemic targets with the medication and the cause behind this variability has not been investigated thoroughly. While genetic factors account for only about a third of this response variability, the potential influence of metabolomics and the gut microbiome on drug efficacy opens new avenues for investigation. This review explores the different molecular signatures to uncover how the complex interplay between genetics, metabolic profiles, and gut microbiota can shape individual responses to metformin. By highlighting the insights from recent studies and identifying knowledge gaps regarding metformin-microbiota interplay, we aim to highlight the path toward more personalized and effective diabetes management strategies and moving beyond the one-size-fits-all approach.

Diabetes management remains challenging despite advancements in therapeutics, with many subjects developing complications. Yoga has been shown to aid diabetes management. This study investigates the impact of yoga therapy on diabetes progression, utilizing proteomics and metabolomics analyses to explore underlying molecular mechanisms.

A 3-month longitudinal study involving healthy subjects with prediabetes and diabetes was conducted. Blood glucose, glycated hemoglobin (HbA1c), lipid profile, and malondialdehyde (MDA) levels were measured before and after the yoga intervention.

Healthy subjects showed no significant changes in blood glucose, lipid profile, HbA1c, or MDA levels. However, subjects with prediabetes and diabetes experienced positive changes, with decreases in HbA1c and MDA levels. Proteomics and metabolomics analyses provided insights into the molecular mechanisms by which yoga attenuates diabetes progression in subjects with prediabetes and diabetes. This study is a pioneering effort to understand the molecular basis of yoga's beneficial effects on diabetes management.

Over recent decades, cardiovascular diseases (CVDs) and metabolic disorders have emerged as major global health challenges, exacting a heavy toll on human lives and burdening healthcare systems worldwide [...].

Diabetes is becoming a significant health concern in Asia, where the prevalence has reached alarming levels. An important contributing factor is the consumption of high-carbohydrate foods, including rice, bread, etc. These high-carbohydrate foods pose a major risk to public health due to their impact on postprandial hyperglycemia. This research aimed to formulate a chickpea pulao (cooked Indian-Pakistani rice dish) and to evaluate its effects on postprandial blood glucose levels in type 2 diabetic individuals. Antioxidant potential and total phenolic contents of herbs at different concentrations (1, 3, 5, 7, and 9%) were measured through DPPH and Folin Ciocalteu assays. The antidiabetic potential was tested by α-amylase and α-glucosidase inhibition assays. After sensory evaluation, the best-chosen concentration was used to formulate the chickpea pulao. The study trial was advertised under "DP trial," and 12 participants were recruited. A single-blind randomized cross-over trial was conducted for 3 weeks with a one-week wash-over time in between. Participants' preprandial and postprandial blood glucose levels were recorded for control and intervention recipes. Results indicated that both fenugreek seeds (FS) and Indian rennet (IR) showed good antioxidant and hypoglycemic activity (p = .000) in raw and boiled extracts. For DPPH, the IC50 values of unboiled and boiled combined (FS + IR) extracts were calculated as 7.4% and 8.02%, respectively. Similarly, for α-amylase, the IC50 values of combined IR and FS unboiled and boiled extracts were 6.58% and 6.83%, and for α-glucosidase inhibition assay, the values were measured as 14.98% and 16.24%. The single-blind randomized cross-over trial showed that consuming the intervention recipe significantly reduced postprandial hyperglycemia (p = .000) in type 2 diabetic participants. The intervention recipe decreased hyperglycemia by approximately 15% daily compared to the control recipe. Incorporation of hypoglycemic herbs into dietary patterns can work as an adjunct therapy for diabetes management, especially in populations with a high prevalence of this disease.

It is well known that metabolic disorders, including type 1 diabetes (T1D), are often associated with reduced male fertility, mainly increasing oxidative stress and impairing the hypothalamus-pituitary-testis (HPT) axis, with consequently altered spermatogenesis and reduced sperm parameters. Herein, using a rat model of T1D obtained by treatment with streptozotocin (STZ), we analyzed several parameters of testicular activity.

A total of 10 adult male Wistar rats were divided into two groups of five: control and T1D, obtained with a single intraperitoneal injection of STZ. After 3 months, the rats were anesthetized and sacrificed; one testis was stored at -80°C for biochemical analysis, and the other was fixed for histological and immunofluorescence analysis.

The data confirmed that T1D induced oxidative stress and, consequently, alterations in both testicular somatic and germ cells. This aspect was highlighted by enhanced apoptosis, altered steroidogenesis and Leydig cell maturity, and impaired spermatogenesis. In addition, the blood-testis barrier integrity was compromised, as shown by the reduced levels of structural proteins (N-cadherin, ZO-1, occludin, connexin 43, and VANGL2) and the phosphorylation status of regulative kinases (Src and FAK). Mechanistically, the dysregulation of the SIRT1/NRF2/MAPKs signaling pathways was proven, particularly the reduced nuclear translocation of NRF2, affecting its ability to induce the transcription of genes encoding for antioxidant enzymes. Finally, the stimulation of testicular inflammation and pyroptosis was also confirmed, as highlighted by the increased levels of some markers, such as NF-κB and NLRP3.

The combined data allowed us to confirm that T1D has detrimental effects on rat testicular activity. Moreover, a better comprehension of the molecular mechanisms underlying the association between metabolic disorders and male fertility could help to identify novel targets to prevent and treat fertility disorders related to T1D.

Maturity-onset diabetes of the young, type 13 (MODY13) is a specific subclass of monogenic diabetes mellitus that does not exhibit the typical clinical manifestations of diabetes, necessitating the use of genetic testing for accurate diagnosis. With the progression of monogenic diabetes and MODY, the number of reported MODY13 cases has reached a minimum of 22. Nevertheless, there remains a dearth of information regarding patients diagnosed with MODY13 presenting synonymous variants.

This study presents a description of the clinical and genetic features of a 9-year-old male patient diagnosed with MODY13. A noteworthy finding in this case was the occurrence of a "separation phenomenon" between C-peptide and insulin during the standard meal test. Whole exome sequencing (WES) identified a KCNJ11 c.843C > T (p.L281=) mutation in exon 1, which contradicted the previously reported phenotype. Following the onset of ketosis, the patient underwent insulin therapy for a duration of one month, during which the insulin dosage was gradually modified based on blood glucose levels. In order to maintain normoglycemia, he adhered to a diabetic dietary regimen and participated in 1-2 h of moderate exercise daily.

The study implies that patient with KCNJ11 variant shows a "separation phenomenon" between C-peptide and insulin in standard meal test. Our report also enriched the genotype and phenotype spectrums of MODY13 and highlighted the importance of genetic testing in patients without characteristic clinical symptoms of diabetes.

Diabetes, also known as diabetes mellitus (DM), is a metabolic disorder characterized by an abnormal rise in blood sugar (glucose) levels brought on by a complete or partial lack of insulin secretion along with corresponding changes in the metabolism of lipids, proteins, and carbohydrates. It has been reported that medicinal plants play a pivotal role in the treatment of various ailments such as diabetes mellitus, dyslipidemia, and hypertension. The current study involved exploring the acute toxicity and in vivo antidiabetic activity of berberine (WA1), palmatine (WA2), and 8-trichloromethyl dihydroberberine (WA3) previously isolated from Berberis glaucocarpa Stapf using a streptozotocin (STZ)-induced diabetic rat model. Body weight and blood glucose level were assessed on a day interval for 4 weeks. Biochemical parameters, antioxidant enzymes, and oxidative stress markers were also determined. In an acute toxicity profile, the WA1, WA2, and WA3 were determined to be nontoxic up to 500 mg/kg (b.w). After the second and third weeks of treatment (14 and 21 days), the blood glucose levels in the WA1-, WA2-, and WA3-treated groups were significantly lower than those in the diabetic control group (476.81 ± 8.65 mg/dL, n = 8, P < 0.001). On the 21st day, there was a decrease in the blood glucose level and the results obtained were 176.33 ± 4.69, 197.21 ± 4.80, and 161.99 ± 4.75 mg/dL (n = 8, P < 0.001) for WA1, WA2, and WA3 at 12 mg/kg, respectively, as opposed to the diabetic control group (482.87 ± 7.11 mg/dL, n = 8, P < 0.001). Upon comparison with the diabetic group at the end of the study (28 days), a substantial drop in the glucose level of WA3 at 12 mg/kg (110.56 ± 4.11 mg/dL, n = 8, P < 0.001) was observed that was almost near the values of the normal control group. The treated groups (WA1, WA2, and WA3) treated with the samples displayed a significant decline in the levels of HbA1c. Treatment of the samples dramatically lowered the lipid level profile. In groups treated with samples, plasma levels of triglycerides, total cholesterol, and LDL were significantly lowered [F (5, 42) = 100.6, n = 8, P < 0.001]; these levels were also significantly decreased [F (5, 42) = 129.6 and 91.17, n = 8, P < 0.001]. In contrast to the diabetes group, all treated groups had significantly higher HDL levels [F (5, 42) = 15.46, n = 8, P < 0.001]. As a result, hypolipidemic activity was anticipated in the samples. In addition to that, the activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) was considerably elevated in the groups treated with the sample compared to the diabetic control group (n = 8, P < 0.001).

Diabetes is an ongoing global problem as it affects health of more than 537 million people around the world. Diabetes leaves many serious complications that affect patients and can cause death if not detected and treated promptly. Some of the complications of diabetes include impaired vascular system, increased risk of stroke, neurological diseases that cause pain and numbness, diseases related to the retina leading to blindness, and other complications affecting kidneys, heart failure, muscle weakness, muscle atrophy. All complications of diabetes seriously affect the health of patients. Recently, gene therapy has emerged as a viable treatment strategy for various diseases. DNA and RNA are among the target molecules that can change the structure and function of proteins and are effective methods of treating diseases, especially genetically inherited diseases. RNA therapeutics has attracted deep interest as it has been approved for application in the treatment of functional system disorders such as spinal muscular atrophy, and muscular dystrophy. In this review, we cover the types of RNA therapies considered for treatment of diabetes. In particular, we delve into the mechanism of action of RNA therapies for diabetes, and studies involving testing of these RNA therapies. Finally, we have highlighted the limitations of the current understanding in the mechanism of action of RNA therapies.

Using a rat model of type 1 diabetes (T1D) obtained by treatment with streptozotocin, an antibiotic that destroys pancreatic β-cells, we evaluated the influence of subsequent hyperglycemia on the morphology and physiology of the Harderian gland (HG). HG is located in the medial corner of the orbit of many terrestrial vertebrates and, in rodents, is characterized by the presence of porphyrins, which being involved in the phototransduction, through photo-oxidation, produce reactive oxygen species activating the autophagy pathway. The study focused on the expression of some morphological markers involved in cell junction formation (occludin, connexin-43, and α-tubulin) and mast cell number (MCN), as well as autophagic and apoptotic pathways. The expression of enzymes involved in steroidogenesis [steroidogenic acute regulatory protein (StAR), and 3β-hydroxysteroid dehydrogenase (3β-HSD)] and the level of lipid peroxidation by thiobarbituric acid reactive species assay were also evaluated. The results strongly indicate, for the first time, that T1D has a negative impact on the pathophysiology of rat HG, as evidenced by increased oxidative stress, morphological and biochemical alterations, hyperproduction and secretion of porphyrins, increased MCN, reduced protein levels of StAR and 3β-HSD, and, finally, induced autophagy and apoptosis. All the combined data support the use of the rat HG as a suitable experimental model to elucidate the molecular damage/survival pathways elicited by stress conditions.

Type 2 diabetes mellitus (T2DM) is a severe metabolic condition which is commonly comorbid with depression. Lifestyle factors are involved in the pathophysiology of both conditions; however, the role of lifestyle interventions remains unclear.

The objective of this study is to systematically review the literature on randomized controlled trials evaluating the effect of lifestyle interventions on depressive scores in patients with T2DM.

A systematic search was conducted in computerized databases before October 2022. A random-effects model was used to investigate the effect of lifestyle interventions on depression scores and meta-regression was conducted to assess the influence of age and disease onset.

Six trials met the eligibility criteria for inclusion. A statistically significant reduction in depression scores was found for groups receiving lifestyle interventions compared to controls (SMD = -0.49 [95%CI -0.89 to -0.08]; p = 0.0269]). Interventions increased in efficacy with the age of the participants but no significant correlation was found with years since disease onset. Participants in a control group receiving a less intense lifestyle intervention demonstrated improved depression scores when compared to those who received standard care or no intervention at all. Trial design and outcome measurement tools were heterogeneous between studies and limited data on antidepressant use was available which may introduce bias into the results.

Lifestyle interventions were effective at improving depressive symptom severity in patients with T2DM.

Cardiovascular diseases and diabetes mellitus are currently among the diseases with the highest morbidity and mortality. The pathogenesis and development of these diseases remain strongly connected, along with inflammation playing a major role. Therefore, the treatment possibilities showing a positive impact on both of these diseases could be especially beneficial for patients. SGLT-2 inhibitors and GLP-1 receptor agonists present this dual effect. Moreover, the hostile composition of the gut microbiota could influence the progression of these conditions. In this review, the authors present the latest knowledge on and innovations in diabetes mellitus and CVD-with the focus on the molecular mechanisms and the role of the microbiota.

Mutation of the gene encoding Hepatocyte Nuclear transcription Factor-1 Beta (HNF1B) causes a rare monogenetic subtype of Maturity-Onset Diabetes of the Young (MODY). HNF1B-related MODY results in the dysfunction of multiple organ systems. However, genetic analysis enables personalized medicine for patients and families.

To understand the clinical characteristics and explore the gene mutations in Croatian patients.

This was a retrospective observational study of individuals (and their relatives) who were, due to the clinical suspicion of MODY, referred to the Department of Laboratory Diagnostics at the University Hospital Centre Zagreb for genetic testing.

A total of 118 participants, 56% females, were screened. Seven patients (three females) from five families were identified to have HNF1B-related MODY. The median age at diagnosis was 31 (11-45) years, the median c-peptide was 0.8 (0.55-1.39) nmol/L, the median HbA1c was 9.1 (5.7-18.4)%, and the median BMI was 22.9 kg/m² (17-24.6). Patients had a variety of clinical manifestations; kidney disease was not as frequent as liver lesions, neuropsychiatric symptoms, hyperlipidemia, hyperuricemia, and hypomagnesemia. We identified two new pathogenic mutations (c.1006C > G protein p.His336Asp on exon 4 and c.1373T > G p protein Val458Gly on exon 7).

In a study involving Croatian patients, new genetic (two previously unknown mutations) and clinical (diverse range of clinical presentations) aspects of HNF1B-related MODY were found.

Hypoglycemia, a common consequence of diabetes treatment, is associated with severe morbidity and mortality and has become a major barrier to intensifying antidiabetic therapy. Severe hypoglycemia, defined as abnormally low blood glucose requiring the assistance of another person, is associated with seizures and comas, but even mild hypoglycemia can cause troubling symptoms such as anxiety, palpitations, and confusion. Dementia generally refers to the loss of memory, language, problem-solving, and other cognitive functions, which can interfere with daily life, and there is growing evidence that diabetes is associated with an increased risk of both vascular and non-vascular dementia. Neuroglycopenia resulting from a hypoglycemic episode in diabetic patients can lead to the degeneration of brain cells, with a resultant cognitive decline, leading to dementia. In light of new evidence, a deeper understating of the relationship between hypoglycemia and dementia can help to inform and guide preventative strategies. In this review, we discuss the epidemiology of dementia among patients with diabetes, and the emerging mechanisms thought to underlie the association between hypoglycemia and dementia. Furthermore, we discuss the risks of various pharmacological therapies, emerging therapies to combat hypoglycemia-induced dementia, as well as risk minimization strategies.

Rapid urbanization has led to an exponential increase in lifestyle-associated metabolic disorders presenting a huge socioeconomic burden. Waya is a digital prevention program that guides overweight and obese individuals to maintain a healthy lifestyle through exercise, diet, and educational videos.

We aimed to study the demographic patterns of the Waya cohort and examine the prevalence of diabetes (the most common lifestyle-associated metabolic disorder) and its risk factors in comparison to the GEDA 2014/2015-European Health Interview Survey population.

Waya participants who registered by 1 October 2020 and who answered at least one health survey question were included in this study. Factors such as obesity, hypertension, and diabetes between the two populations were compared using Chi-square test.

Of the 837 participants, 86.1% were women. The proportion of obese participants was higher in Waya than in the German Health Update (GEDA) cohort (women: 39.4% vs. 18%, P < 0.05; men: 37.1% vs. 18.3%, P < 0.05), whereas the proportion of participants with hypertension (women: 12.1% vs. 30.9% in GEDA, P < 0.05; men: 22.4% vs. 32.8% in GEDA, P < 0.05) was lower. The proportion of women with diabetes was low in our cohort (3.9% vs. 7% in GEDA, P < 0.05); however, the proportion of men with diabetes remained the same between the two groups. We observed significant differences between the GEDA and Waya cohorts due to changes in the prevalence pattern over time or target bias of the digital program.

These findings showcase the usability of Waya in collecting real-world insights, which will be beneficial in monitoring the prevalence of chronic metabolic disorders and associated risk factors over time.

Diabetes mellitus (DM) is a chronic metabolic disorder with an increasing global prevalence that leads to significant morbidity and mortality. The liver plays a vital role in glycemic regulation in physiological and pathological conditions such as DM. Free radical formation and inhibition of antioxidant defense systems play a role in the liver damage pathogenesis in diabetic patients The antioxidant, anti-diabetic, anti-inflammatory, and radical scavenging properties of crocin are known. This study was designed to determine the possible protective effects of crocin against liver tissue damage in pinealectomized diabetic rats. Sixty rats were divided into six groups: Control, Sham+streptozotocin (STZ), Pinealectomy (PINX), PINX+STZ, PINX+Crocin, and PINX+STZ+Crocin. PNX procedure was carried out on the first day of the experiment. Intraperitoneal (i.p.) injection of 50 mg/kg STZ was performed on the 30th day of the experiment to induce DM. Crocin (50 mg/kg; i.p.) was applied for 15 days after the pinealectomy procedure and induction of DM. Crocin decreased the markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), interleukin-1β (IL-1β), and malondialdehyde (MDA)) of liver damage and increased antioxidant enzyme levels and tissue total antioxidant status. Histological results showed that the administration of crocin exhibited a protective effect against liver damage caused by STZ. These results indicate that crocin evidence protection against liver injury caused by STZ.

To investigate the efficacy of laser photocoagulation combined with ranibizumab in patients with diabetic retinopathy and their effect on VEGF.

The medical records of 98 patients with diabetic retinopathy treated in the First People's Hospital of Linping District from February 2020 to January 2022 were collected for a retrospective analysis. Among them, 48 patients treated with laser photocoagulation were a control group (CG), and another 50 treated with laser photocoagulation combined with ranibizumab were an observation group (OG). The treatment efficacy, best corrected visual acuity (BCVA), central macular concave thickness (CMT), and change in neovascularization area were compared between the two groups. Also, the changes in serum vascular endothelial growth factor (VEGF), homocysteine (HCY), vitamin B12 and folic acid were compared. The adverse effects that occurred with treatment were assessed. The relationship of pre-treatment BCVA, CMT, neovascularization area and VEGF levels with clinical outcomes were observed, and their predictive values were analyzed by receiver operating characteristic (ROC) curve.

The total response rate of patients in the CG was lower than that in the OG (P<0.05). The BCVA, CMT, and neovascularization area were dramatically lower, while vitamin B12 and folic acid were markedly higher in the OG than in the CG after treatment (P<0.05). There was no statistical difference in adverse reactions between the two groups (P>0.05). In patients with effective response, the BCVA, CMT, VEGF and Hcy before treatment were dramatically lower than in those with ineffective response (P<0.05), while the neovascularization area, vitamin B12, and folic acid did not differ between them before treatment (P>0.05). ROC curve analysis revealed that the areas under the curve of BCVA, CMT, VEGF and Hcy were all greater than 0.7 for predicting patient outcomes, and the area under the curve of the combination of the above indexes was 0.945, with a specificity of 92.30% and sensitivity of 88.23%.

Laser photocoagulation combined with ranibizumab may provide good therapeutic efficacy in diabetic retinopathy, by effectively improving neovascularization and reducing VEGF levels to control further progression of the lesions.

Andrographis paniculata (AP) has long been used as an anti-diabetic agent, but the mechanism of action and active substance responsible for the anti-diabetic effect, particularly by inhibiting phosphodiesterase-9 (PDE9), which is one of the targets of anti-diabetic medications, have not been reported. The aim of the present study was to identify a new anti-diabetes candidate from secondary metabolite compounds of AP through PDE9 inhibition.

In order to prepare the chemical structures of the secondary metabolites of AP and PDE9, docking and molecular dynamics simulations were run using Discovery Studio Visualizer, AutoDockTools, AutoDock, and Gromacs, along with a few other supporting software packages.

Molecular docking simulations showed that two of the 46 secondary metabolites of AP had higher free energies of binding, C00003672 (-11.35 kcal/mol) and C00041378 (-9.27 kcal/mol), than native ligand (-9.23 kcal/mol). The results of molecular dynamics showed that compound C00041378 interacted with TRY484 and PHE516, two active side residues of PDE9. ΔGMMGBSA interactions of PDE9 with C00003672, C00041378, and 49E compounds are 51.69, -56.43, and -48.13 kcal/mol, respectively, as well as ΔGMMPBSA interactions of PDE9 with C00003672, C00041378, and 49E compounds, were -12.26, -16.24, and -11.79 kcal/mol kcal/mol, respectively.

Based on the evaluations of AP secondary metabolites using docking and molecular dynamics simulation, it is suggested that the C00041378 compound has the potential to be an antidiabetic candidate by inhibiting PDE9.

Diabetes mellitus comprises a group of heterogeneous disorders, which are usually subdivided into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Both genetic and environmental factors have been implicated in the onset of diabetes. Type 1 diabetes primarily involves autoimmune insulin deficiency. In comparison, type 2 diabetes is contributed by the pathological state of insulin deficiency and insulin resistance. In recent years, significant differences were found in the abundance of microflora, intestinal barrier, and intestinal metabolites in diabetic subjects when compared to normal subjects. To further understand the relationship between diabetes mellitus and intestinal flora, this paper summarizes the interaction mechanism between diabetes mellitus and intestinal flora. Furthermore, the natural compounds found to treat diabetes through intestinal flora were classified and summarized. This review is expected to provide a valuable resource for the development of new diabetic drugs and the applications of natural compounds.

Diabetes mellitus is one of the four priority non-communicable diseases worldwide. It can lead to serious long-term complications and produces significant costs. Due to the chronicle character of the disease, it requires continuous medical treatment and good therapy adherence of those suffering. Therefore, diabetes self-management education (DSME) (and support DSMES) plays a significant role to increase patient's self-management capacity and improve diabetes therapy. Research indicates that these outcomes might be difficult to maintain. Consequently, effective strategies to preserve the positive effects of DSMES are needed. Preliminary results show that peer support, which means support from a person who has experiential knowledge of a specific behavior or stressor and similar characteristics as the target population, is associated with better outcomes in terms of HbA1c, cardiovascular disease risk factors or self-efficacy at a lower cost compared to standard therapy. Peer-supported instant messaging services (IMS) approaches have significant potential for diabetes management because support can be provided easily and prompt, is inexpensive, and needs less effort to attend compared to standard therapy. The major objective of the study is to analyze the impact of a peer-supported IMS intervention in addition to a standard diabetes therapy on the glycemic control of type 2 diabetic patients.

A total of 205 participants with type 2 diabetes mellitus will be included and randomly assigned to an intervention or control group. Both groups will receive standard therapy, but the intervention group will participate in the peer-supported IMS intervention, additionally. The duration of the intervention will last for 7 months, followed by a follow-up of 7 months. Biochemical, behavioral, and psychosocial parameters will be measured before, in the middle, and after the intervention as well as after the follow-up.

Type 2 diabetes mellitus and other non-communicable diseases put healthcare systems worldwide to the test. Peer-supported IMS interventions in addition to standard therapy might be part of new and cost-effective approaches to support patients independent from time and place.

ClinicalTrials.gov NCT04797429 . Registered on 15 March 2021.

We hypothesized that the vitamin A (VA) status regulates type 2 diabetes (T2D) development in Zucker diabetic fatty (ZDF) rats. Zucker Lean and ZDF rats at weaning were fed a VA deficient with basal fat (VAD-BF, no VA and 22.1% fat energy), VA marginal with BF (VAM-BF, 0.35 mg retinyl palmitate (RP)/kg), VA sufficient with BF (VAS-BF, 4.0 mg RP/kg), VAD with high fat (VAD-HF, 60% fat energy), VAM-HF or VAS-HF diet for 8 weeks, including an oral glucose tolerance test (OGTT) at week 7.5. The hepatic mRNA and proteins levels were determined using real-time PCR and Western blot, respectively. The VAD-BF/HF and VAM-BF/HF diets prevented peripheral hyperglycemia and attenuated obesity in ZDF rats, which occurred in the presence of the VAS-BF/HF diets. This lowered VA status reduced venous blood hyperglycemia, hyperinsulinemia and hyperlipidemia, and improved OGTT and homeostasis model assessment for insulin resistance results in ZDF rats. The expression levels of key hepatic genes for glucose and fat metabolism were regulated by VA status and dietary fat contents. An interaction between VA and HF condition was also observed. We conclude that the reduction in the dietary VA status in both BF and HF conditions prevents T2D and obesity in ZDF rats.

Diabetes mellitus is a worldwide health problem that usually comes with severe complications. There is no cure for diabetes yet and the threat of these complications is what keeps researchers investigating mechanisms and treatments for diabetes mellitus. Due to advancements in genomics, epigenomics, proteomics, and single-cell multiomics research, considerable progress has been made toward understanding the mechanisms of diabetes mellitus. In addition, investigation of the association between diabetes and other physiological systems revealed potentially novel pathways and targets involved in the initiation and progress of diabetes. This review focuses on current advancements in studying the mechanisms of diabetes by using genomic, epigenomic, proteomic, and single-cell multiomic analysis methods. It will also focus on recent findings pertaining to the relationship between diabetes and other biological processes, and new findings on the contribution of diabetes to several pathological conditions.

Diabetes mellitus technology (DMT) is increasingly used for routine management in developed countries, yet its uptake in developing countries is not as consistent. Multiple factors may influence this, including country specific patient perception regarding DMT. We conducted a pilot study in Pakistan to understand this important question which has not been studied yet.

A cross-sectional pilot study was conducted in Pakistan. An anonymous survey exploring perceptions of diabetes technology was circulated on social media platforms, collecting responses over 2 weeks. Target population included adults (≥18 years) living in Pakistan, with DM1 or 2.

A total of 40 responses were received. The majority (36/40) reported using conventional glucometers. Nine used continuous glucose monitoring (CGM). Thirty-two of 40 patients believed DMT improved diabetes care, 22 felt it helped decreased risk of Diabetes-related complications. 15/40 stated that DMT results in increased cost of care. Sixteen reported their diabetes care teams had never discussed wearable DMT options whereas 11 disliked them because they did not want a device on their self.

In our pilot study we have identified broad themes of opportunity and challenges to DMT use in Pakistan. Patients' perceptions regarding DMT were generally positive but significant barriers to its acceptance included high cost, lack of discussion between doctor and patient about available technology and personal hesitation. Limitations of our study include sampling bias (online survey) and small sample size, but this data can help inform larger studies, to look at this important topic in greater detail.

Previous reviews and clinical guidelines have identified 10-20 genetic syndromes associated with diabetes, but no systematic review has been conducted to date. We provide the first comprehensive catalog for syndromes with diabetes mellitus. We conducted a systematic review of MEDLINE, Embase, CENTRAL, PubMed, OMIM, and Orphanet databases for case reports, case series, and observational studies published between 1946 and January 15, 2020, that described diabetes mellitus in adults and children with monogenic or chromosomal syndromes. Our literature search identified 7,122 studies, of which 160 fulfilled inclusion criteria. Our analysis of these studies found 69 distinct diabetes syndromes. Thirty (43.5%) syndromes included diabetes mellitus as a cardinal clinical feature, and 56 (81.2%) were fully genetically elucidated. Sixty-three syndromes (91.3%) were described more than once in independent case reports, of which 59 (93.7%) demonstrated clinical heterogeneity. Syndromes associated with diabetes mellitus are more numerous and diverse than previously anticipated. While knowledge of the syndromes is limited by their low prevalence, future reviews will be needed as more cases are identified. The genetic etiologies of these syndromes are well elucidated and provide potential avenues for future gene identification efforts, aid in diagnosis and management, gene therapy research, and developing personalized medicine treatments.

To investigate the effect of 1-deoxynojirimycin (DNJ) for improving diabetic liver fibrosis and explore the underlying mechanism.

Mouse models of type 2 diabetes were established in 10 Kunming mice by high-fat diet feeding for 8 weeks and intraperitoneal injection of STZ, with 5 mice receiving intraperitoneal injection of citrate buffer solution with normal feeding as the control group. The mouse models were randomized into two groups (n=5) for further highfat feeding (model group) and additional treatment with 10% DNJ in drinking water (200 mg · kg-1 per day; DNJ group) for 8 weeks. The mice were monitored for changes in body weight (BW), blood glucose, serum total cholesterol (TC), triglyceride (TG) and superoxide dismutase (SOD) levels. The pathological changes in the liver tissue were observed using HE and Sirius Red staining, and the solubility of collagens in the liver tissues was determined. The expression levels of MCP-1, TNF-α, IL-1β and TGF-β1 mRNA were detected with real-time PCR, and the protein expressions of α-SMA and collagen2 (ColA2) were determined with Western blotting. In the in vitro experiment, mouse fibroblasts L929 cells were pretreated with DNJ (10 μg/ mL) or PBS for 30 min followed by culture in high-glucose medium for 24 h, and the level of ROS production was measured using dihydroethidium (DHE) staining.

In the mouse model of type 2 diabetes, DNJ treatment significantly lowered serum level of glucose, TC, and TG (P < 0.05) and increased serum SOD activity (P < 0.05). DNJ obviously attenuated liver fibrosis in the diabetic mice, as shown by alleviated cross-linking of collagens and reduced contents of pepsin-solubilized collagen (PSC) and total collagen (P < 0.05). DNJ treatment also significantly reduced the overexpression of the proinflammatory cytokines and fibrosis-related cytokines induced by diabetes (P < 0.05). In L929 cells exposed to high glucose, pretreatment with DNJ significantly lowered the intensity of red fluorescence in DHE staining.

DNJ can attenuate type 2 diabetes-induced liver fibrosis in mice through its hypoglycemic, anti-inflammatory and anti-oxidative effects.

Metabolomics is rapidly evolving omics technology in personalized medicine, it offers a new avenue for identification of multiple novel metabolic mediators of impaired glucose tolerance and dysglycemia. Liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry and nuclear magnetic resonance spectroscopy are most commonly used analytical methods in the field of metabolomics. Recent evidences showed that metabolomic profiles are link to the incidence of diabetes. In this review, an overview of metabolomics studies in diabetes revealed several diabetes-associated metabolites including 1,5-anhydroglycitol, branch chain amino acids, glucose, α-hydroxybutyric acid, 3-hydroundecanoyl-carnitine and phosphatidylcholine that could be potential biomarkers associated with diabetes. These identified metabolites can be used to develop personalized prognostics and diagnostic, and help in diabetes management.

Peritoneal dialysis (PD) is a frequently used and growing therapy for end-stage renal diseases (ESRD). Survival analysis of PD patients is an ongoing research topic in the field of nephrology. Several biochemical parameters (e.g., serum albumin, creatinine, and blood urea nitrogen) are measured repeatedly in the follow-up period; however, baseline or averaged values are primarily associated with mortality. Although this strategy is not incorrect, it leads to information loss, resulting in erroneous conclusions and biased estimates. This retrospective study used the trajectory of common renal function indexes in PD patients and mainly investigated the association between serum albumin change and mortality. Furthermore, we considered patient-specific variability in serum albumin change and obtained personalized dynamic risk predictions for selected patients at different follow-up thresholds to investigate the effect of serum albumin trajectories on patient-specific mortality. We included 417 patients from the Erciyes University Nephrology Department whose data were retrospectively collected using medical records. A joint modeling approach for longitudinal and survival data was used to investigate the relationship between serum albumin trajectory and mortality of PD patients. Results showed that averaged serum albumin levels were not associated with mortality. However, serum albumin change was significantly and inversely associated with mortality (HR: 2.43, 95% CI: 1.48 to 4.16). Risk of death was positively associated with peritonitis rate, hemodialysis history, and the total number of comorbid and renal diseases with hazard ratios 1.74, 3.21, and 1.41. There was also significant variability between patients. The personalized risk predictions showed that overall survival estimates were not representative for all patients. Using the patient-specific trajectories provided better survival predictions within the follow-up period as more data become available in serum albumin levels. In conclusion, using the trajectory of risk predictors via an appropriate statistical method provided better predictive accuracy and prevented biased findings. We also showed that personalized risk predictions were much informative than overall estimations in the presence of significant patient variability. Furthermore, personalized estimations may play an essential role in monitoring and managing patients during the follow-up period.

Genetic variants could aid in predicting antidiabetic drug response by associating them with markers of glucose control, such as glycated hemoglobin (HbA1c). However, pharmacogenetic implementation for antidiabetics is still under development, as the list of actionable markers is being populated and validated. This study explores potential associations between genetic variants and plasma levels of HbA1c in 100 patients under treatment with metformin.

HbA1c was measured in a clinical chemistry analyzer (Roche), genotyping was performed in an Illumina-GSA array and data were analyzed using PLINK. Association and prediction models were developed using R and a 10-fold cross-validation approach.

We identified genetic variants on SLC47A1, SLC28A1, ABCG2, TBC1D4, and ARID5B that can explain up to 55% of the interindividual variability of HbA1c plasma levels in diabetic patients under treatment. Variants on SLC47A1, SLC28A1, and ABCG2 likely impact the pharmacokinetics (PK) of metformin, while the role of the two latter can be related to insulin resistance and regulation of adipogenesis.

Our results confirm previous genetic associations and point to previously unassociated gene variants for metformin PK and glucose control.

Mitochondrial dysfunction and elevated ROS generation are predominant contributors of neuronal death that is responsible for the diabetes-related cognitive impairments. Emerging evidence has demonstrated that long noncoding RNA-MEG3 can serve as an important regulator in the pathogenesis of diabetes. However, the underlying mechanisms remain to be further clarified. Here, it was observed that MEG3 was significantly down-regulated in STZ (streptozotocin)-induced diabetic rats. MEG3 overexpression noticeably improved diabetes-induced cognitive dysfunctions, accompanied by the abatement of Rac1 activation and ROS production, as well as the inhibition of mitochondria-associated apoptosis. Furthermore, either MEG3 overexpression or Rac1 inhibition promoted FUNDC1 dephosphorylation and suppressed oxidative stress and neuro-inflammation. Similarly, in vitro studies confirmed that hyperglycemia also down-regulated MEG3 expression in PC12 cells. MEG3 reintroduction protected PC12 cells against hyperglycemia-triggered neurotoxicity by improving mitochondrial fitness and repressing mitochondria-mediated apoptosis. Moreover, these neuroprotective effects of MEG3 relied on FUNDC1-related mitophagy, since silencing of FUNDC1 abolished these beneficial outcomes. Additionally, MEG3 rescued HG-induced neurotoxicity was involved in inhibiting Rac1 expression via interaction with Rac1 3'UTR. Conversely, knockdown of MEG3 showed opposite effects. NSC23766, a specific inhibitor of Rac1, fully abolished harmful effects of MEG3 depletion. Consistently, knockdown of Rac1 potentiated FUNDC1-associated mitophagy. Meanwhile, colocalization of Rac1 and FUNDC1 was found in mitochondria under hyperglycemia, which was interrupted by MEG3 overexpression. Furthermore, silencing of Rac1 promoted PGAM5 expression, and FUNDC1 strongly interacted with LC3 in Rac1-deleted cells. Altogether, our findings suggested that the Rac1/ROS axis may be a downstream signaling pathway for MEG3-induced neuroprotection, which was involved in FUNDC1-associated mitophagy.

The practice of medicine depends over a long time on identifying therapies that target an entire population. The increase in scientific knowledge over the years has led to the gradual change towards individualization and personalization of drug therapy. The hope of this change is to achieve a better clinical response to given medications and reduction of their adverse effects. Tailoring of medicine on the road of personalized medicine considers molecular and genetic mapping of the individual. However, many factors still impede the smooth application of personalized medicine and represent challenges or limitations in its achievement. In this article, we put some clinical examples that show dilemmas in the application of personalized medicine such as opioids in pain control, fluoropyrimidines in malignancy, clopidogrel as antiplatelet therapy and oral hypoglycemic drugs in Type2 diabetes in adults. Shaping the future of medicine through the application of personalized medicine for a particular patient needs to put into consideration many factors such as patient's genetic makeup and life style, pathology of the disease and dynamic changes in its course as well as interactions between administered drugs and their effects on metabolizing enzymes. We hope in the coming years, the personalized medicine will foster changes in health care system in the way not only to treat patients but also to prevent diseases.

Type 2 diabetes mellitus (T2DM) is a complex and progressive chronic disease characterised by elevating hyperglycaemia and associated need to gradually intensify therapy in order to achieve and maintain glycaemic control. Treating hyperglycaemia with sequential therapy is proposed to allow holistic assessment of the efficacy and risk-to-benefit ratio of each added component. However, there is an array of evidence supporting the scientific rationale for using synergistic, earlier, modern drug combinations to achieve glycaemic goals, delay the deterioration of glycaemic control, and, therefore, potentially preserve or slow down the declining β-cell function. Additionally, implementation of early combination(s) may lead to opportunities to combat clinical inertia and other hurdles to optimised disease management outcomes. This review aims to discuss the latest empirical evidence for long-term clinical benefits of this novel strategy of early combination in people with newly diagnosed T2DM versus the current widely-implemented treatment paradigm, which focuses on control of hyperglycaemia using lifestyle interventions followed by sequentially intensified (mostly metformin-based) monotherapy. The recent reported Vildagliptin Efficacy in combination with metfoRmin For earlY treatment of T2DM (VERIFY) study results have provided significant new evidence confirming long-term glycaemic durability and tolerability of a specific early combination in the management of newly diagnosed, treatment-naïve patients worldwide. These results have also contributed to changes in clinical treatment guidelines and standards of care while clinical implementation and individualised treatment decisions based on VERIFY results might face barriers beyond the existing scientific evidence.

Metal-organic complexes bearing physiological substrates have been the target of several investigations, probing into the potential of well-defined atoxic metalloforms to influence fundamental cellular processes overcoming insulin resistance in Diabetes mellitus 2. Outstanding cases of such metals include zinc and vanadium, both being the target of intense synthetic and biological studies toward insulin mimesis. Owing to the close proximity in the periodic table, an early transition metal, titanium, emerges as another potential candidate of biologically relevant complexation, reflecting species capable of promoting insulin mimetic activity. Driven by the so far explored aqueous synthetic chemistry of Ti(IV)-hydroxycaboxylato systems, a well-defined Ti(IV)-citrate compound was synthesized under physiological conditions, isolated, and characterized, followed by its introduction in biological assays, targeting adipogenic events linked to glucose uptake and catabolism. The mononuclear Ti(IV)-citrate complex was introduced to 3T3-L1 cells, thereby probing into its biological activity (toxicity, morphology, migration, and adipogenic capacity). The results project an atoxic profile for the Ti(IV)-citrate species, thus justifying further incorporation in cellular differentiation processes, leading to mature adipocytes in a time- and concentration-dependent fashion. The experiments suggest that Ti(IV)-citrate is a competent agent promoting fibroblast differentiation, as evidenced by key adipogenic biomarkers, while concurrently exhibiting synergistic/enhancing action with insulin. The collective results show, for the first time, that an appropriately configured soluble-bioavailable complex Ti(IV) form exhibits a distinctly unique bioprofile, thereby lending credence to the notion that titanium metallopharmaceuticals hold merit as competent agents in adipogenesis and insulin mimesis in Diabetes mellitus.

Personalized, stratified, or precision medicine (PM) introduces a new era in healthcare that tries to identify and predict optimum treatment outcomes for a patient or a cohort. It also introduces new scientific terminologies regarding therapeutic approaches and the need of their adoption from healthcare providers. Till today, evidence-based practice (EBP) was focusing on population averages and their variances among cohorts for clinical values that are essential for optimizing healthcare outcome. It can be stated that EBP and PM are complementary approaches for a modern healthcare system. Healthcare providers through EBP often see the forest (population averages) but miss the trees (individual patients), whereas utilization of PM may not see the forest for the trees. Nursing personnel (NP) play an important role in modern healthcare since they are consulting, educating, and providing care to patients whose needs often needs to be individualized (personalized nursing care, PNC). Based on the clinical issues earlier addressed from clinical pharmacology, EBP, and now encompassed in PM, this review tries to describe the challenges that NP have to face in order to meet the requisites of the new era in healthcare. It presents the demands that should be met for upgrading the provided education and expertise of NP toward an updated role in a modern healthcare system.

Diabetes mellitus, also known simply as diabetes, has been described as a chronic and complex endocrine metabolic disorder that is a leading cause of death across the globe. It is considered a key public health problem worldwide and one of four important non-communicable diseases prioritized for intervention through world health campaigns by various international foundations. Among its four categories, Type 2 diabetes (T2D) is the commonest form of diabetes accounting for over 90% of worldwide cases. Unlike monogenic inherited disorders that are passed on in a simple pattern, T2D is a multifactorial disease with a complex etiology, where a mixture of genetic and environmental factors are strong candidates for the development of the clinical condition and pathology. The genetic factors are believed to be key predisposing determinants in individual susceptibility to T2D. Therefore, identifying the predisposing genetic variants could be a crucial step in T2D management as it may ameliorate the clinical condition and preclude complications. Through an understanding the unique genetic and environmental factors that influence the development of this chronic disease individuals can benefit from personalized approaches to treatment. We searched the literature published in three electronic databases: PubMed, Scopus and ISI Web of Science for the current status of T2D and its associated genetic risk variants and discus promising approaches toward a personalized management of this chronic, non-communicable disorder.

Exercise is considered as an important intervention for treatment and prevention of several diseases, such as osteoarthritis, obesity, hypertension, and Alzheimer's disease. This review summarizes decadal exercise intervention studies with various rat models across 6 major systems to provide a better understanding of the mechanisms behind the effects that exercise brought.

PubMed was utilized as the data source. To collect research articles, we used the following terms to create the search: (exercise [Title] OR physical activity [Title] OR training [Title]) AND (rats [Title/Abstract] OR rat [Title/Abstract] OR rattus [Title/Abstract]). To best cover targeted studies, publication dates were limited to "within 11 years." The exercise intervention methods used for different diseases were sorted according to the mode, frequency, and intensity of exercise.

The collected articles were categorized into studies related to 6 systems or disease types: motor system (17 articles), metabolic system (110 articles), cardiocerebral vascular system (171 articles), nervous system (71 articles), urinary system (2 articles), and cancer (21 articles). Our review found that, for different diseases, exercise intervention mostly had a positive effect. However, the most powerful effect was achieved by using a specific mode of exercise that addressed the characteristics of the disease.

As a model animal, rats not only provide a convenient resource for studying human diseases but also provide the possibility for exploring the molecular mechanisms of exercise intervention on diseases. This review also aims to provide exercise intervention frameworks and optimal exercise dose recommendations for further human exercise intervention research.

For more than 3500 years, metabolic disorders were recognized by symptoms similar to those indicating diabetes mellitus today. Over centuries, explanations remained elusive and shed sparse light on the origin of the disease and any treatments. The poor prognosis triggered myths and misconceptions, some even lasting until today. Two hundred years ago, major advances were made in the understanding of the pathophysiology, which has led to more successful treatments. Presently, useful preventive, diagnostic, and therapeutic procedures exist. However, old myths and misconceptions still influence the treatments. This article reviews ongoing myths dealing with the genesis and treatment of diabetes and the growing evidence for improved therapies.Increasingly more studies focus on cardiovascular endpoints while considering more realistic therapeutic goals. This paves the way to polyvalent treatment concepts reaching beyond the classic glucocentric treatment concept of type 2 diabetes. The introduction of molecular medicine, the current opportunities and future prospects of new drugs, personalized medicine, and technical innovations prompt hopes and expectations for a change of paradigms in therapeutic concepts. It is quite possible that traditional and newly generated myths will accompany this development. This has to be kept in mind when developing new concepts for treatment.

Most monogenic diabetes is misdiagnosed as either type 1 or type 2 diabetes (T1D/T2D). Few studies have examined the diagnostic challenges from the patients' perspective. This qualitative study aimed to investigate patients' journeys to obtaining a diagnosis of maturity-onset diabetes of the young (MODY) by elucidating the range of factors that can act as barriers and facilitators throughout this process. We recruited participants from the Personalized Diabetes Medicine Program (PDMP) at University of Maryland and used respondent-driven sampling to recruit additional patients. We conducted qualitative phone interviews between October 2016 and June 2017 with nine patients with diagnoses of monogenic diabetes (one HNF4A-MODY, seven GCK-MODY, and one HNF1A-MODY) and one parent of a patient with INS-MODY. Interview data were audio recorded, transcribed, and analyzed both inductively and deductively using thematic content analysis. All patients were female, with a mean age of 35 (range: 7-67 years). The amount of time these patients were misdiagnosed ranged from a few months to 41 years. We identified barriers and facilitators in three broad themes: (a) patient-related (nature of MODY symptoms, perceived test utility, individual personality); (b) provider-related (provider awareness and knowledge, provider communication); and (c) healthcare system-related (cost of testing, access to knowledgeable providers, patient education, and support resources). The diverse range of barriers and facilitators reiterates the complexity of the MODY diagnostic process. Limited awareness and knowledge of MODY from healthcare professionals and patients themselves account for most diagnostic delays described in this study. Efforts to promote awareness of MODY and expand access to screening and testing may result in quicker diagnosis and ensure the downstream benefits of proper treatment.

Aim: We aimed to understand the individual and shared features of Type 1 diabetes (T1D) and Type 2 diabetes (T2D) by analyzing the gene expression profile. Materials & methods: An integrated analysis was performed with microarray datasets for T1D and T2D. Compared with normal control, shared and specific differentially expressed genes (DEGs) in T1D and T2D were obtained. Functional annotation, further validation and receiver operating characteristic curve analysis were performed. Results: Five and three datasets for T1D and T2D were downloaded, respectively. In total, 141 (85 T1D vs 56 normal controls) and 70 (29 T2D vs 41 normal controls) peripheral blood samples were included in T1D and T2D group, respectively. Compared with normal controls, 119 and 146 DEGs were found in T1D and T2D, respectively. PNP and CCR1 have great diagnostic value for both T1D and T2D. MGAM and NAMPT had great diagnostic value for T2D. Conclusion: Our finding provided clues for developing biomarkers for diabetes.

The organic cation transporters OCT1 and OCT2 and the multidrug and toxin extrusion transporter MATE1, encoded by the SLC22A1, SLC22A2, and SLC47A1 genes, respectively, are responsible for the absorption of metformin in enterocytes, hepatocytes, and kidney cells. The aim of this study was to evaluate whether genetic variations in the SLC22A1, SLC22A2, and SLC47A1 genes could be associated with an altered response to metformin in patients with type 2 diabetes mellitus. A cohort study was conducted in 308 individuals with a diagnosis of type 2 diabetes mellitus of less than 3 years and who had metformin monotherapy. Three measurements of blood glycated hemoglobin (HbA_1c ) were obtained at the beginning of the study and after 6 and 12 months. Five polymorphisms were analyzed in the SLC22A1 (rs622342, rs628031, rs594709), SLC22A2 (rs316019), and SLC47A1 (rs2289669) genes by real-time polymerase chain reaction. The results showed a significant association among genotypes CC-rs622342 (β = 1.36; P < .001), AA-rs628031 (β = 0.98; P = .032), and GG-rs594709 (β = 1.21; P = .016) in the SLC22A1 gene with an increase in HbA_1c levels during the follow-up period. Additionally, a significant association was found in the CGA and CAG haplotypes with an increase in HbA_1c levels compared to the highest-frequency haplotype (AGA). In conclusion, the genetic variation in the SLC22A1 gene was significantly related to the variation of the HbA_1c levels, an important indicator of glycemic control in diabetic patients. This information may contribute to identifying patients with an altered response to metformin before starting their therapy.

Epigenetics modulated tissue-specific gene expression during the onset of type 1 and type 2 diabetes and their complications.

We searched the PubMed recent studies about the main epigenetic tags involved in type 1 and type 2 diabetes onset and their clinical complications. PubMed studies about the epigenetic tags involved in type 1 and 2 diabetes onset was searched.

The epigenetic methylation maps of cord blood samples highlighted differences in the methylation status of CpG sites within the MHC genes between carriers of diabetes type 1 DR3-DQ2 and DR4-DQ8 risk haplotypes. β cell-derived unmethylated INS DNA showed the decline of β-cell mass preserving insulin secretion. Differentially methylated regions in pancreatic islets from type 2 diabetes covered PDX1, TCF7L2, and ADCY5 promoters during islet dysfunction. The recruitment of SET7 and SUV39H1 histone methyltransferases and LSD-1 lysine-specific demethylase-1 at NF-kβ-p65 promoter in vascular cells was involved in coronary heart disease. Neutrophil extracellular trap, activated by protein arginine deiminase-4, impaired wound healing from diabetic foot ulcers. MiR-199a-3p over-expression induced coagulative cascade, swelling and pain by a down-regulation of SERPIN-E2 in diabetic peripheral neuropathy. A DNA hypo-methylation and histone hyper-acetylation at MIOX promoter led an overexpression of ROS, fibronectin, HIF-1α, and NOX-4 associated with diabetic tubulopathy. A hypo-methylation of H3K4 at SOD2 promoter by LSD-1 increased ROS causing diabetic retinopathy.

Epigenetics played a relevant role in prevention, diagnosis, and treatment of diabetes.

We provide a review of monogenic diabetes in young children and adolescents with a focus on recognition, management, and pharmacological treatment.

Monogenic forms of diabetes account for approximately 1-2% of diabetes in children and adolescents, and its incidence has increased in recent years due to greater awareness and wider availability of genetic testing. Monogenic diabetes is due to single gene defects that primarily affect beta cell function with more than 30 different genes reported. Children with antibody-negative, C-peptide-positive diabetes should be evaluated and genetically tested for monogenic diabetes. Accurate genetic diagnosis impacts treatment in the most common types of monogenic diabetes, including the use of sulfonylureas in place of insulin or other glucose-lowering agents or discontinuing pharmacologic treatment altogether. Diagnosis of monogenic diabetes can significantly improve patient care by enabling prediction of the disease course and guiding appropriate management and treatment.