Search Results (2,549)

Adipokines related to gestational diabetes mellitus (GDM) are an emerging area of interest. The aim of this study was to evaluate the associations between GDM and adipokine levels in human milk. This was an observational cohort study targeting mothers with gestational diabetes, which evaluated the association of maternal hyperglycemia severity, classified as GDM-G1 (diet treatment) and GDM-G2 (insulin treatment), with colostral adipokines involved in pro- and anti-inflammatory processes. Colostrum was collected from hyperglycemic (N = 34) and normoglycemic (N = 26) mothers, and adipokine levels were determined by immunoenzymatic assay. Among anti-inflammatory adipokines, only for irisin and vaspin, but not for obestatin and adropin, were significantly different levels noted between the GDM-G1, GDM-G2 and non-GDM cohorts. Colostrum of the GDM-G2 subgroup contained more vaspin (4.77 ng/mL) than that of normoglycemic mothers (3.12 ng/mL) and more irisin (26.95 μg/mL) than in the GDM-G1 subgroup (17.59 μg/mL). The levels of pro-inflammatory adipokines, namely, dermcidin, chemerin and visfatin, were at similar levels irrespective of maternal glycemia. Moreover, irisin showed a negative correlation with dermcidin in GDM-G2 and non-GDM cohorts. Associations were observed between colostral irisin and maternal preconception BMI, dermcidin and gestational age, and vaspin and maternal age. This study provides evidence that the way of restoring glucose homeostasis in pregnant women has an impact on the anti-inflammatory adipokines irisin and vaspin, but not on obestatin and adropin. GDM, regardless of severity, did not influence the colostral pro-inflammatory adipokines visfatin, chemerin and dermcidin. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is considered a serious risk to public health since its prevalence is rapidly increasing worldwide despite numerous therapeutics. Insulin resistance in T2DM contributes to chronic inflammation and other metabolic abnormalities that generate fat accumulation in the liver, eventually leading to the progression of metabolic dysfunction-associated fatty liver disease (MAFLD). Recently, the possibility that microbial-derived metabolites may alleviate MAFLD through enterohepatic circulation has emerged, but the underlying mechanism remains unclear. In this research, we utilized metabolites obtained from the fermentation of guava leaf extract, which is well-known for its antidiabetic activity, to investigate their effects and mechanisms on MAFLD. Methods: Diabetes was induced by a high-fat diet and streptozotocin injection (80 mg/kg body weight) twice in mice. Subsequently, mice whose fasting blood glucose levels were measured higher than 300 mg/dL were administered with metabolites of Limosilactobacillus fermentum (LF) (50 mg/kg/day) or guava leaf extract fermented by L. fermentum (GFL) (50 mg/kg/day) by gavage for 15 weeks. Results: GFL supplementation mitigated hyperglycemia and hepatic insulin resistance. Moreover, GFL regulated abnormal hepatic histological changes and lipid profiles in diabetic mice. Furthermore, GFL enhanced energy metabolism by activating the sirtuin1 (SIRT1)/proliferator-activated receptor γ coactivator 1α (PGC1α)/peroxisome proliferator-activated receptor (PPAR)-α pathway in diabetic mice. Meanwhile, GFL supplementation suppressed hepatic inflammation in diabetic mice. Conclusions: Taken together, the current study elucidated that GFL could be a potential therapeutic to ameliorate hyperglycemia and hepatic steatosis by improving SIRT1/PGC-1α/ PPAR-α-related energy metabolism in T2DM. Full article

Diabetes mellitus (DM) is a global health concern with a rising incidence, particularly in aging populations and those with a genetic predisposition. Over time, DM contributes to various complications, including nephropathy, retinopathy, peripheral arterial disease (PAD), and neuropathy. Among these, diabetic neuropathy and PAD stand out due to their high prevalence and significant impact on patients’ quality of life. Diabetic distal symmetric polyneuropathy, the most common form of diabetic neuropathy, is driven by neuroinflammation stemming from prolonged hyperglycemia. Simultaneously, hyperglycemia significantly increases the risk of PAD, a condition further exacerbated by factors like smoking, age, and sedentary lifestyles. PAD frequently manifests as claudication, a debilitating symptom marked by pain and cramping during physical activity, which limits mobility and worsens patients’ outcomes. Cilostazol, a phosphodiesterase-3 inhibitor, has proven effective in managing intermittent claudication in PAD by improving walking distances and enhancing blood flow. Recent studies have also explored its potential benefits for diabetic neuropathy. Cilostazol’s mechanisms include vasodilation, platelet inhibition, and increased cyclic adenosine monophosphate (cAMP) levels, which may contribute to improved neurological outcomes. However, variability in the clinical evidence due to inconsistent treatment protocols highlights the need for further investigation. This review explores cilostazol’s mechanisms of action and therapeutic applications for managing neuropathy and PAD in diabetic patients, aiming to provide insights into its potential as a dual-purpose pharmacological agent in this high-risk population. Full article

Fruits are excellent sources of substrate for various fermented products, including fruit vinegars, which are typically produced by submerged fermentation. Some evidence suggests that fruit vinegar consumption can alleviate certain disorders, including hyperlipidemia, inflammation, and hyperglycemia. Fruit vinegars also have bacteriostatic and antihypertensive actions. Recent studies also suggest that apple vinegar may offer benefits in treating insulin resistance, osteoporosis, and certain neurological diseases such as Alzheimer’s disease; it may also support weight loss. Recent studies in animal and human models have considerably broadened our understanding of the biological properties of not only fruit vinegars but also oxymels, i.e., mixtures of vinegar and honey or sugar. This paper reviews the current state of knowledge regarding vinegars and oxymels, with a special emphasis on their chemical composition and the mechanisms behind their biological activity and pro-health potential. The multidirectional effects of fruit vinegars and oxymels result from the synergy of different chemical compounds, including organic acids (mainly acetic acid), phenolic compounds, vitamins, minerals, and fermentation products. However, more studies are needed to understand the interactions between all the different components, not only the phenolic compounds and organic acids. In addition, more research is needed on their mechanisms of action. Although no serious side effects have been noted to date, further studies with large sample sizes are needed to understand the possible side effects of long-term fruit vinegar and oxymel use. Full article

Background/Objectives: Ethnocultural differences between Jewish and Arab communities in Northern Israel may contribute to disparities in type 2 diabetes prevalence. Widespread screening strategies, including hospital-based initiatives, are crucial for early detection of hyperglycemia. This study aimed to determine the prevalence of postprandial hyperglycemia and identify its associated factors in a diverse population of non-diabetic adults visiting the Galilee Medical Center, a tertiary care hospital in Northern Israel. Methods: Participants were recruited between November 2017 and July 2023 through a voluntary screening program for non-diabetic adult visitors to the hospital. Capillary blood glucose measurements were obtained 1–4 h after a meal using a standardized glucometer. Postprandial hyperglycemia was defined as a blood glucose level ≥147 mg/dL, while postprandial normoglycemia was defined as ≤133 mg/dL. Individuals with glucose levels between 134–146 mg/dL were excluded from the analysis. Additional exclusion criteria included known diabetes, acute illness, corticosteroid use, and pregnancy. Demographic data, lifestyle factors, and health status were recorded. Propensity score matching was employed to ensure comparability between religious groups based on age, gender, and body mass index. Logistic regression analyses were conducted to identify independent predictors of postprandial hyperglycemia. Results: 3457 adult visitors underwent postprandial glucose testing and met eligibility criteria. Following propensity score matching, 1845 participants (615 each from Druze, Jewish, and Muslim religious groups) were included in the final analysis. The prevalence of postprandial hyperglycemia was 9.4% in Druze, 6.0% in Jews, and 8.0% in Muslims (p = 0.08). Age >50 years was significantly associated with postprandial hyperglycemia in all groups. Obesity was associated with postprandial hyperglycemia in Muslims, with a similar non-significant trend in the Jewish cohort. Self-reported poor health was also associated with postprandial hyperglycemia in Muslims. In the Druze cohort, a low daily intake of daily fresh vegetable consumption was significantly associated with postprandial hyperglycemia. Conclusions: This study highlights the feasibility of hospital-based screening for postprandial hyperglycemia among adult visitors and reveals ethnic variations in prevalence and associated risk factors. Full article

Citrus fruits are widely distributed in East Asia, and tea made from citrus peels has demonstrated health benefits, such as a reduction in fever, inflammation, and high blood pressure. However, citrus leaves have not been evaluated extensively for their possible health benefits. In this study, the α-glucosidase-inhibitory activity of Jeju citrus hot-water (CW) and ethyl alcohol (CE) extracts, along with hesperidin (HP) (a bioactive compound in citrus leaf extracts), was investigated, and furthermore, their effect on postprandial blood glucose reduction in an animal model was determined. The hesperidin contents of CW and CE were 15.80 ± 0.18 and 39.17 ± 0.07 mg/g-extract, respectively. Hesperidin inhibited α-glucosidase (IC₅₀, 4.39), sucrase (0.50), and CE (2.62) and demonstrated higher α-glucosidase inhibitory activity when compared to CW (4.99 mg/mL). When using an SD rat model, during sucrose and starch loading tests with CE (p < 0.01) and HP (p < 0.01), a significant postprandial blood glucose reduction effect was observed when compared to the control. The maximum blood glucose levels (Cmax) of the CE administration group decreased by about 15% (from 229.3 ± 14.5 to 194.0 ± 7.4, p < 0.01) and 11% (from 225.1 ± 13.8 to 201.1 ± 7.2 hr·mg/dL, p < 0.05) in the sucrose and starch loading tests, respectively. Our findings suggest that citrus leaf extracts standardized to hesperidin may reduce postprandial blood glucose levels through the observed inhibitory effect against sucrase, which results in delayed carbohydrate absorption. Our findings provide a biochemical rationale for further evaluating the benefits of citrus leaves. Full article

Pullulan is an extracellular polysaccharide produced via the fermentation of Aureobasidium pullulans. However, high sugar concentrations and hyperosmotic stress limit pullulan biosynthesis during the fermentation process. Therefore, we investigated the effects of proline supplementation on A. pullulans growth and pullulan biosynthesis under high sugar and hyperosmotic stress using physiological, biochemical, and transcriptomic analyses. High sugar concentrations significantly inhibited A. pullulans growth and pullulan biosynthesis. High sugar and hyperosmotic stress conditions significantly increased intracellular proline content in A. pullulans. However, treatment with proline (400 mg/L proline) significantly increased biomass and pullulan yield by 10.75% and 30.06% (174.8 g/L), respectively, compared with those in the control group. To further investigate the effect of proline on the fermentation process, we performed scanning electron microscopy and examined the activities of key fermentation enzymes. Proline treatment preserved cell integrity and upregulated the activities of key enzymes involved in pullulan biosynthesis. Transcriptome analysis revealed that most differentially expressed genes in the proline group were associated with metabolic pathways, including glycolysis/gluconeogenesis, pyruvate metabolism, and sulfur metabolism. Conclusively, proline supplementation protects A. pullulans against high sugar and hyperosmotic stress, providing a new theoretical basis and strategy for the efficient industrial production of pullulans. Full article

Background: Emphysematous pyelonephritis (EPN) is an infectious disease of the renal system caused by gas-producing microorganisms harboring the kidneys. Patients with diabetes mellitus (DM), an endocrine disease with hyperglycemia, are particularly susceptible to the EPN as their immune system is compromised in fighting against infections. Case Description: We present a case of a 50-year-old female with a history of chronic diabetes and persistent hypertension. She presented with symptoms of pyrexia and flank pain. Following findings from ultrasound, she was advised to undergo computed tomographic (CT) scans that reveal air-filled hypodense areas at the upper and mid pole of the right kidney and in the renal pelvis of the right ureter, which confirms the class I EPN in the patient. Urine culture identifies Escherica coli as the causative agent for EPN. The patient was managed with third-generation antibiotics over two weeks, leading to full recovery without surgical intervention. Discussion: The availability of CT imaging makes early diagnosis and reduces mortality associated with EPN. Conservative medical management should be the initial treatment strategy for EPN. However, severe cases require immediate therapeutic action. In our case, the patient was treated with antibiotic therapy and recovered. Conclusions: CT scan seems to be the optimal diagnosis in patients with acute emphysematous pyelonephritis. Patients with EPN class I respond well to medical treatment with excellent outcomes. Full article

Frequent blood glucose monitoring is crucial for managing blood glucose levels in critically ill hospitalized patients experiencing hyperglycemia or hypoglycemia. Existing blood glucose monitoring methods are often cumbersome, painful, and impractical for hourly testing. This work provides a solution for frequent glucose monitoring (less than 1 h per test) for hospitalized patients, ensuring accuracy while minimizing discomfort from blood collection. The glucose sensor demonstrated accuracy within 10% across a range of 0–20 mM over 96 testing cycles. This meets the need for hourly monitoring during an average 2-day hospital stay. Full article

Endoplasmic reticulum stress (ERS) is activated in all cells by stressors such as hyperglycemia. However, it remains unclear which specific serum biomarkers of ERS are consistently altered in type 2 diabetes (T2D). We aimed to identify serum ERS biomarkers that are consistently altered in T2D and its complications, and their correlation with metabolic and anthropometric variables. We performed a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Meta-Analyses and Systematic Reviews of Observational Studies (MOOSE). The risk of bias was assessed using the Newcastle–Ottawa scale. Random-effects models weighted by the inverse variance were employed to estimate the standardized mean difference and correlations as effect size measures. Indicators of heterogeneity and meta-regressions were evaluated. Of the 1206 identified studies, 22 were finally included, representing 11,953 subjects (2224 with T2D and 9992 non-diabetic controls). Most studies were of high quality. Compared with controls, subjects with T2D had higher circulating levels of heat shock protein 70 (HSP70; SMD: 2.30, 95% CI 1.13–3.46; p < 0.001) and secretagogin (SMD: 0.60, 95%CI 0.19–1.01; p < 0.001). They also had higher serum levels of peroxiredoxin-1, -2, -4, and -6. Secretagogin inversely correlated with HOMA-IR, yet positively correlated with HOMA-B, HbA1c, and FPG. PRX4 negatively correlated with HbA1c and FPG, while HSP70 positively correlated with HbA1c. In conclusion, six ERS biomarkers are consistently elevated in human T2D and correlate with glycemic control, insulin resistance, and β-cell function. Emerging evidence links serum ERS biomarkers to diabetes complications, but further research should evaluate their prognostic implications. Full article

The increase in the incidence of hyperglycemia and diabetes poses the challenge of finding cost-effective natural inhibitors of starch digestion enzymes. Among natural compounds, phenolics have been considered as promising candidates. The aims of this study were as follows: (a) to investigate the effectiveness of the inhibition of different winemaking byproducts towards intestinal brush border α-glucosidase and pancreatic α-amylase in vitro; (b) to calculate an efficacy index relative to the standard acarbose for the phenolic pool of winemaking byproducts, as well as for isolated phenolic compounds and for the phenolic pools of different plants studied in the literature, in order to rank winemaking byproducts with respect to the reference drug and other natural alternatives. Among winemaking byproducts, red grape skins showed the highest inhibitory activities towards both α-glucosidase and α-amylase, which were, on average, 4.9 and 2.6 µg acarbose equivalents/µg total phenolics (µg Ac eq/µg GAE), respectively. A correlation was observed between the total phenolic contents of red grape skins and their inhibitory effectiveness, which is useful for standardizing the efficacy of phenolic extracts obtained from different winemaking processes. In general, the inhibitory activity of the phenolic pool of grape skins was higher than those of isolated phenolic compounds, namely anthocyanins and monomeric and polymeric flavanols and flavonols, probably due to synergistic effects among compounds. Hence, bioactive phenolic fractions could be produced with the focus on functionality rather than purity, in line with the principles of sustainable processing. Based on the efficacy index developed to compare different phenolic compounds and phenolic-rich plants studied in the literature as starch digestion enzyme inhibitors, red grape skins proved to be cost-effective candidates. Full article

Peritonsillar abscesses and deep neck infection are potentially serious infections among patients with chronic kidney disease (CKD), posing risks for severe complications and drawing significant public health concern. This nationwide, population-based longitudinal study (2002–2019) assessed the extended relationship between chronic kidney disease (CKD) and the likelihood of peritonsillar abscess and deep neck infection in a Korean cohort. Using a 1:4 propensity score overlap-weighted matching, we included 16,879 individuals with CKD and 67,516 comparable controls, accounting for demographic variables and comorbidities to ensure balanced group comparisons. Hazard ratios (HRs) and 95% confidence intervals (CIs) for deep neck infection and peritonsillar abscesses in relation to CKD history were calculated with a propensity score overlap-weighted Cox proportional hazards model. Our results revealed no significant increase in the overall incidence of deep neck infections or peritonsillar abscesses in CKD patients compared to controls. Interestingly, CKD patients demonstrated a 50% reduced likelihood of developing peritonsillar abscesses (HR 0.50; 95% CI = 0.30–0.83; p = 0.007), particularly among subgroups aged 70 years or older, females, non-smokers, rural residents, overweight individuals, and those with lower comorbidity burdens (e.g., absence of hypertension, hyperlipidemia, or hyperglycemia). In summary, the results suggest that lifestyle modifications and the effective management of comorbidities could reduce the risk of peritonsillar abscess in certain CKD subgroups. Our findings may help to alleviate public health concerns regarding peritonsillar abscesses and deep neck infections as CKD-related comorbidities. Full article

Black chokeberry (Aronia melanocarpa <Michx.> Elliot) represents a rich source of dietary polyphenols and other bioactive phytochemicals with pleiotropic beneficial cardiovascular effects. The present study was aimed at evaluating the ex vivo effects of two black chokeberry extracts (BChEs), obtained from either dry (DryAr) or frozen (FrozAr) berries, on oxidative stress and vascular function in mice aortic rings after incubation with angiotensin 2 (Ang 2), lipopolysaccharide (LPS) and glucose (GLUC) in order to mimic renin–angiotensin system activation, inflammation and hyperglycemia. The identification of phenolic compounds was performed by means of liquid chromatography with a diode array detector coupled with mass spectrometry using the electrospray ionization interface. The BChE obtained from the FrozAr was rich in cyanidin glucoside, rutin and caffeic acid, while the one obtained from the dried berries was rich in rutin, caffeic acid and chlorogenic acid. Mice aortas were dissected and acutely incubated (12 h) with Ang2 (100 nM), LPS (1 µg/mL) or GLUC (400 mg/dL) in the presence vs. absence of the two BChEs (1, 10, 50, 75, 100, 500 µg/mL). Subsequently, the tissues were used for the assessment of (i) hydrogen peroxide (H₂O₂) and superoxide production (using two methods, spectrophotometry and immunofluorescence), (ii) H₂O₂ scavenger effect and (iii) vascular reactivity (using the organ bath/myograph system). After exposure to Ang2, LPS or GLUC, both types of extracts decreased the H₂O₂ and superoxide levels in a concentration-dependent manner starting from either 50 µg/mL or 100 µg/mL. Also, in the highest concentrations (100 µg/mL, 150 µg/mL and 500 µg/mL), both extracts elicited a significant scavenger effect on H₂O₂ (similar to catalase, the classic H₂O₂ scavenger). Moreover, at 100 µg/mL, both extracts were able to significantly improve vascular relaxation in all stimulated aortic rings. In conclusion, in mice aortas, black chokeberry extracts in acute application elicited a concentration-dependent vasculo-protective effect through the reduction of oxidative stress and the alleviation of endothelial dysfunction in ex vivo conditions that mimic cardio-metabolic diseases. Full article

Objective: A controversial aspect of pediatric septic shock management is corticosteroid therapy. Current guidelines do not recommend its use in forms responsive to fluids and inotropes but leave the decision to physicians in forms refractory to the first steps of therapy. Data Sources: Review of literature from January 2013 to December 2023 from online libraries Pubmed, Medline, Cochrane Library, and Scopus. Study Selection: The keywords “septic shock”, “steroids” and “children” were used. Data Extraction: Of 399 articles, 63 were selected. Data Synthesis: Regarding mortality, although the 2019 Cochrane review supports reduced mortality, benefits on long-term mortality and in patients with CIRCI (critical illness-related corticosteroid insufficiency) are not clear. Yang’s metanalysis and retrospective studies of Nichols and Atkinson show no difference or even an increase in mortality. Regarding severity, the Cochrane review claims that hydrocortisone seems to reduce the length of intensive care hospitalization but influences the duration of ventilatory and inotropic support, and the degree of multi-organ failure appears limited. Further controversies exist on adrenal function evaluation: according to literature, including the Surviving Sepsis Campaign guidelines, basal or stimulated hormonal dosages do not allow the identification of patients who could benefit from hydrocortisone therapy (poor reproducibility). Regarding side effects, muscle weakness, hypernatremia, and hyperglycemia are the most observed. Conclusions: The literature does not give certainties about the efficacy of corticosteroids in pediatric septic shock, as their influence on primary outcomes (mortality and severity) is controversial. A subgroup of patients suffering from secondary adrenal insufficiency could benefit from it, but it remains to be defined how to identify and what protocol to use to treat them. Full article