Diabetes Mellitus Group Research Articles

What is the influence of maternal weight gain in different gestational clinical conditions on the prole weight in pre-school age?

The aim of the current study was to assess the influence of maternal weight gain in different clinical gestational conditions on the child's weight at pre-school age. This was a longitudinal observational study of a prospective and controlled multiple cohort of 372 mother-child pairs withfour causal groups of different adverse intrauterine environments (smoking, diabetic, hypertensiveand intrauterine growth-restricted pregnant women) and a control group, in the period of,from 2011 to 2016 in three hospitals in Porto Alegre (Brazil). Sociodemographic, prenatal and perinatal data were analysed. Gestational weight gain (GWG) was categorised as 'insufficient', 'adequate' and 'excessive'. The generalised estimation equations (GEE) model was used to assess changes in the z-score of the child's body mass index from birth to pre-school age according to the GWG and gestational group. The child's GWG and weight gain were adjusted for maternal age and education, marital status, family income, pregnancy planning, number of children, prepregnancy BMI, prenatal consultations and type of delivery. A triple interaction effect was observed involving the gestational group, weight gain and study time (p = 0.020) through an adjusted model. Maternal weight gain above the recommended is associated with a significant increase in the child's z - BMI score over time, except for children from pregnant smokers. Children from diabetic mothers, hypertensive mothersand the control group who had a weight gain above that recommended during pregnancy changed their nutritional status from eutrophic to overweight, becoming obese in the DM and hypertension groups and overweight in control. Monitoring of the GWG, especially in the presence of hypertensive diseases and DM, should be effective to prevent children from developing overweight or obesity in pre-school age with an important impact on health conditions in the future.

Drug resistance in drug-resistant tuberculosis patients with and without diabetes mellitus: a comparative analysis

BackgroundThis dual burden of tuberculosis (TB) and diabetes mellitus (DM) has become a global public health concern. This study aims to compare drug resistance in drug-resistant tuberculosis (DR-TB) patients with and without DM and analyse the risk factors of multidrug-resistant tuberculosis (MDR-TB).MethodsA total of 893 DR-TB patients were admitted to Wenzhou Central Hospital between January 2018 and December 2022. After excluding 178 cases with incomplete clinical and laboratory data, 715 patients were included in the study. These patients were then categorized into two groups based on the presence of type 2 DM: the DM group (160 cases) and the non-DM group (555 cases). Demographic information, baseline clinical characteristics, laboratory and imaging test results, clinical diagnoses, and other relevant data were collected for analysis. Statistical analysis was conducted on demographic information, clinical parameters, drug resistance spectrum, and risk factors for multidrug resistance.ResultsIn both the DM and non-DM groups, the order of resistance to first-line anti-tuberculosis drugs is isoniazid, streptomycin, rifampicin, and ethambutol. There is no significant difference in the proportion of mono-resistant tuberculosis, polydrug-resistant tuberculosis, and multidrug-resistant tuberculosis between the two groups (P > 0.05). The prevalence of MDR-TB in both groups shows a downward trend between 2018 and 2022, but the trend is not statistically significant (P > 0.05). Among patients without DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and uric acid ≥ 346 µmol/L are identified as independent risk factors for MDR-TB. Among patients with DM, residence in rural areas, retreatment of tuberculosis, pulmonary cavity, and HbA1c ≥ 9.8% were identified as independent risk factors for MDR-TB.ConclusionIsoniazid is the most resistant drug among DR-TB patients with and without DM. There is no statistically significant difference in drug resistance patterns between the two groups. Some progress has been made in the prevention and control of DR-TB in this area, but the effect is not very significant. There are differences in the risk factors of MDR-TB between patients with and without DM.

Effect of diabetes mellitus on 3-year outcomes in patients with acute myocardial infarction with nonobstructive coronary arteries.

Diabetes mellitus (DM) is a significant factor in increased mortality rates among patients with acute myocardial infarction (AMI), but research on its impact on the long-term outcomes in patients with MI with nonobstructive coronary arteries (MINOCA) is limited. Thus, a comparison of the 3-year clinical outcomes between the DM and non-DM groups among patients with MINOCA was undertaken. From the Korea AMI Registry-National Institute of Health dataset, 10,774 AMI patients were enrolled. After applying the exclusion criteria, 379 patients with MINOCA were included. The primary clinical outcomes were major adverse cardiac and cerebrovascular events (MACCE), defined as all-cause death, recurrent myocardial infarction (MI), repeat coronary revascularization, and stroke. The secondary outcomes were the individual components of MACCE. The adjusted hazard ratios for 3-year MACCE (2.287, p = 0.010), all-cause death (2.845, p = 0.004), and non-cardiac death (non-CD, 3.914, p = 0.008) were higher in the DM group than in the non-DM group. It is speculated that the higher non-CD rate in the MINOCA group is attributable to a higher proportion of patients with non-ST-segment elevation MI in the total study population. The CD, recurrent MI, revascularization, and stroke rates were similar between the DM and non-DM groups. DM, advanced age, cardiopulmonary resuscitation on admission, and non-use of statin medications were significant predictors of MACCE. In this study involving patients with MINOCA, the DM group exhibited a higher 3-year mortality rate than the non-DM group. Thus, DM demonstrated a hazardous effect even in patients with MINOCA.

Adverse complications of cervical spinal fusion in patients with different types of diabetes mellitus: A retrospective nationwide inpatient sample database cross-sectional study.

Diabetes mellitus (DM) is a prevalent chronic condition that influences spine surgery outcomes. The impact of type Ⅰ and type Ⅱ DM on adverse postoperative outcomes, mortality, prolonged length of stay (LOS), and increased in-hospital costs following cervical fusion surgery remains unclear in the past decade. This study aims to determine the specific effect of different classifications of DM on postoperative complications in patients experiencing cervical fusion surgery. Data from the Nationwide Inpatient Sample database was acquired between 2010 and 2019. Patients experiencing cervical fusion were included and classified as having type I DM, type II DM, or neither. Patient demographics, hospital characteristics, operative variables, comorbidities, complications, and other postoperative outcomes were assessed. Propensity score matching analysis was used to balance baseline differences. Univariate and multivariate logistic regression were employed to determine the risk of postoperative outcomes in patients with different classifications of DM. A total of 267,174 cervical spinal fusions were identified (224,255 were patients without DM, 670 patients had type I DM, and 42,249 patients had type II DM). After propensity score matching, the multivariate analysis of non-DM and type I DM patients shows significant difference in pneumonia (P=0.020). However, type Ⅱ DM served as an independent predictor of an increased risk of acute cerebrovascular disease (P=0.001), acute myocardial infarction (P=0.014), pneumonia (P=0.045), continuous trauma ventilation (P=0.016), chest pain (P<0.001), urinary tract infection (P<0.001), transfusion (P=0.005) and dysphagia (P=0.013), prolonged LOS (P<0.001) and increased costs (P=0.008). Using non-DM patients as a reference, type II DM group demonstrated a higher risk of postoperative complications than type I DM group among patients receiving cervical fusion surgery. This vital distinction could enhance risk stratification and guidance for patients diagnosed with DM before cervical fusion surgery.

Docosahexaenoic acid eliminates endoplasmic reticulum stress and inflammatory pathways in diabetic rat keratopathy

Diabetic keratopathy, characterized by corneal structural changes, is a common complication of diabetes mellitus (DM). Docosahexaenoic acid (DHA), an omega-3 fatty acid, has shown potential therapeutic benefits in various diabetic complications. This study aimed to investigate the protective effect of DHA on corneal tissue in streptozotocin (STZ)-induced type 2 DM in rats. Forty male Sprague–Dawley rats were randomly assigned to four groups (n = 10 per group): Control, DHA, DM, and DM + DHA. The DHA group received DHA by oral gavage at a dose of 100 mg/kg daily for 10 days. In the DM group, diabetes was induced by a single intraperitoneal injection of STZ at 50 mg/kg. Confirmation of diabetes induction was based on monitoring fasting blood glucose levels on the third day post-injection. The DM + DHA group underwent the same diabetes induction protocol with STZ and received DHA at 100 mg/kg daily via oral gavage for 10 consecutive days. Corneal tissue samples were collected at the end of the study period for histopathological, immunohistochemical, qRT-PCR, and ELISA analyses. Histopathological analysis showed significant edema, angiogenesis, and degeneration in the DM group compared to the control (p < 0.001). DHA treatment significantly mitigated these changes, approaching control levels (p < 0.01). Immunohistochemistry showed increased VEGFR2 and iNOS expression in the DM group, which was significantly reduced in the DM + DHA group (p < 0.01). qRT-PCR results indicated a significant decrease in Bcl-2 expression (p < 0.001) and an increase in ATF-6, IRE1, NF-κB, TNF-α, IL-1β, NLRP3, Bax, and Caspase-3 expressions in the DM group (p < 0.001). ELISA analyses revealed significantly elevated levels of inflammatory markers NF-κB, TNF-α, IL-1β, and IL-6 in the DM group compared to the control (p < 0.001). DHA treatment significantly upregulated Bcl-2 and downregulated apoptotic and inflammatory markers (p < 0.01). DHA demonstrated significant protective effects against STZ-induced corneal damage in diabetic rats by modulating apoptotic and inflammatory pathways. These findings suggest that DHA may be a promising therapeutic agent for preventing diabetic keratopathy.

Increased Thyroid Hormone Action Alleviates Hippocampal Damage by Downregulating Neuronal Type I Interferon Signaling/Necroptosis in Diabetes-Associated Cognitive Dysfunction.

Background: Thyroid dysfunction plays an important role in the pathology of diabetes-associated cognitive dysfunction (DACD). However, thyroid hormone (TH) signaling and action changes in DACD brains remain unknown. This study evaluated the alternations in TH signaling and action in the brains of DACD mice and explored the beneficial effects of levothyroxine (L-T4) treatment. Methods: KK-Ay mice, serving as a spontaneous type 2 diabetes mellitus model, underwent intragastric administration of 10 ng/g and 20 ng/g of L-T4 solution or normal saline for 8 weeks. Age-matched C57BL/6J mice were used as normal controls. Cognitive and memory functions were examined through the open field and Morris water maze tests. Hippocampal TH signaling and pathogenic status were evaluated. The potential signaling pathways involved in the neuroprotective action of L-T4 were investigated through RNA sequencing and further verified through quantitative real-time PCR (qPCR), Western blotting (WB), immunofluorescence (IF), and fluorescent multiplex immunohistochemistry (mIHC) invivo and vitro. Results: The expressions of hippocampal TH transporters (Mct8 and Oatp1c1), Dio2, and TH receptor were upregulated, whereas Dio3 as well as the TH-positive regulated genes MBP, Enpp2, and Klf9 were downregulated in DACD mice. Exogenous L-T4 partially alleviated cognitive and memory dysfunction and restored hippocampal neuronal activity by optimizing TH signaling. RNA sequencing provided insights into the role of type I interferon (IFN-I) signaling and necroptosis on the amelioration of hippocampal damage after L-T4 treatment. WB and qPCR further confirmed that the levels of key proteins for IFN-I signaling and necroptosis (p-STAT1, p-STAT2, IRF9, ZBP1, p-RIP3, and p-MLKL) were increased, but largely returned after L-T4 administration invivo and T3 treatment in vitro. IF and mIHC revealed that IRF9 and p-MLKL colocalized in neurons, but not in astrocytes or microglia, of the hippocampus in DACD mice. The diabetes mellitus group had an increased number of IRF9+ p-MLKL+ NeuN+ cells, which decreased after L-T4 treatment. The elevated IFN-I signaling-mediated necroptosis in HT22 cells was also decreased by T3. Conclusion: We demonstrated abnormal hippocampal TH signaling and action in DACD. Promoting TH action with exogenous L-T4 ameliorated hippocampal impairment through inhibiting IFN-I signaling-induced necroptosis.

Retinochoroidal Vascular Changes in Long-Term Type 1 Diabetic Patients Assessed by Optic Coherence Tomography Angiography.

To study retinal and choriocapillaris (CC) alterations using optical coherence tomography angiography (OCTA) in long-term type 1 diabetic (DM1) patients without diabetic retinopathy (DR). Seventy-eight eyes from 78 well-controlled DM1 patients diagnosed at least 15 years prior and 130 eyes of 130 healthy subjects were included in a cross-sectional descriptive study. Six eyes were excluded from the DM1 group. OCTA with Deep Range Imaging (DRI)-Triton swept source (SS)-OCT was performed. Statistically significant differences were found in all areas of the superficial capillary plexus (SCP), with lower values in DM1 patients. Differences were noted in all quadrants of the deep capillary plexus (DCP) except for the central area. Significant changes in CC blood flow were only found in the center. The foveal avascular zone (FAZ) area and diameters in the SCP were significantly different, while the DCP FAZ area was similar in both groups. Disease duration and microalbuminuria correlated negatively with some SCP areas and positively with FAZ values. Anatomical evaluation revealed microaneurysms in both plexuses, FAZ modifications, and areas lacking blood perfusion. Long-term type 1 diabetic patients without DR display microvascular abnormalities affecting retinal and CC blood perfusion, along with anatomical changes in retinal blood vessels.

N-acetylcysteine combined with insulin therapy can reduce myocardial injury induced by type 1 diabetes through the endoplasmic reticulum pathway

With the development of Type 1 diabetes mellitus (T1DM), various complications can be caused. Hyperglycemia affects the microenvironment of cardiomyocytes, changes endoplasmic reticulum homeostasis, triggers unfolding protein response and eventually promotes myocardial apoptosis. However, insulin therapy alone cannot effectively combat the complications caused by T1DM. Forty adult beagles were randomly divided into five groups: control group, diabetes mellitus group, insulin group, insulin combined with NAC group, and NAC group. 24-hour blood glucose, 120-day blood glucose, 120-day body weight, and serum FMN content were observed, furthermore, hematoxylin-eosin staining, Periodic acid Schiff reagent staining, and Sirius red staining of the myocardium were evaluated. The protein expressions of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase 3, Bcl2, and Bax were detected. Results of the pathological section of myocardial tissue indicated that insulin combined with NAC therapy could improve myocardial pathological injury and glycogen deposition. Additionally, insulin combined with NAC therapy down-regulates the expression of GRP78, ATF6, IRE1, PERK, JNK, CHOP, caspase3, and Bax. These findings suggest that NAC has a phylactic effect on myocardial injury in beagles with T1DM, and the mechanism may be related to the improvement of endoplasmic reticulum stress-induced apoptosis.

Association between Hemoglobin A1c and Renal Arteriolar Sclerosis in Subjects Presenting without any Apparent Kidney Dysfunction.

Diabetic kidney disease is a major vascular complication in patients with diabetes mellitus (DM). However, the association between the hemoglobin (Hb)A1c levels, notably the prediabetic levels, and renal pathological changes remains unclear. We investigated the association between the HbA1c levels and renal arteriolar lesions in subjects without any apparent kidney dysfunction using a living kidney donor cohort. Between January 2006 and May 2016, 393 living kidney donors underwent a "zero-time" biopsy at Kyushu University Hospital. The patients were divided into four groups (HbA1c levels ＜5.6%, 5.6%-5.7%, 5.8%-6.4%, and ≥ 6.5%, or diagnosed with DM [DM group]). Renal arteriolar hyalinization and wall thickening were assessed using semi-quantitative grading. We then investigated the association between the HbA1c levels and renal pathological changes. 158 (40.2%) patients had arteriolar hyalinization and 148 (37.6%) showed wall thickening. A significant correlation was observed between the HbA1c levels and wall thickening (p for trend ＜0.001). An elevated HbA1c level was significantly associated with wall thickening according to a multivariable logistic analysis in subjects with HbA1c levels of 5.6%-5.7% and 5.8%-6.4%, and the DM group, compared with those with HbA1c levels of ＜5.6% (odds ratio [OR], 1.91; 95% confidence interval [CI]: [1.03-3.54] for 5.6%-5.7%, OR, 1.96; 95% CI: [1.09-3.53] for 5.8%-6.4%, and OR, 2.86; 95% CI: [0.91-9.01] for the DM group), whereas arteriolar hyalinization did not increase within the nondiabetic HbA1c levels. Elevated high-normal HbA1c levels are considered to be independent risk factors for arteriolar wall thickening. Subclinical renal arteriolar sclerosis may develop in patients with prediabetic HbA1c levels.

Neuroprotective Effects of Bexarotene and Icariin in a Diabetic Rat Model.

Objective Type 2 diabetes mellitus (T2DM), a chronic metabolic disorder affecting over 400 million people globally, is increasingly recognized for its detrimental impact on the central nervous system. T2DM is linked to neurodegenerative diseases like Alzheimer's and vascular dementia. This study investigates the neuroprotective effects of bexarotene and icariin in a T2DM rat model, focusing on brain-derived neurotrophic factor (BDNF), glial fibrillary acidic protein (GFAP), and neurofilament-light chain (NfL) levels. Methods Before the study, rats underwent fasting blood glucose tests, lipid profile assessments, and general health evaluations, followed by a high-fat diet for two weeks and a single streptozotocin dose (35 mg/kg). Rats with fasting blood glucose levels ≥250 mg/dl were classified as diabetes mellitus (DM) and continued on the high-fat diet throughout the experiment. Forty-seven male Wistar Albino rats were divided into six groups: a healthy control group, a DM control group, a DM group treated with bexarotene, a DM group treated with icariin, and two DM groups treated with combinations of low and high doses of bexarotene and icariin. After the 45-day treatment, blood samples were collected under thiopental sodium anesthesia, with HbA1c (glycosylated hemoglobin) and hematological parameters analyzed within eight hours, and serum stored at -80°C for further analysis. The animals were then euthanized, and brain tissues were harvested, frozen, and stored at -80°C until further examination. Brain tissues were analyzed for BDNF, GFAP, and NfL levels using ELISA (enzyme-linked immunosorbent assay). For comparing multiple groups, the Kruskal-Wallis test was applied to nonparametric data, and one-way ANOVA was used for parametric data, followed by Bonferroni's post hoc test for pairwise comparisons. Statistical significance was determined with two-tailed tests at p < 0.05. Results Significant changes in GFAP levels were observed across groups (p < 0.001). The DM control group showed the highest GFAP levels, while treatment groups exhibited reductions. The DM control group also showed the highest BDNF levels, while treatment groups exhibited reductions. The DM control group showed the lowest NfL levels, while treatment groups exhibited increments. Conclusion This study highlights the neuroprotective potential of bexarotene and icariin in a diabetic rat model, evidenced by significant changes in GFAP levels. The lack of significant changes in BDNF and NfL suggests that longer study durations may be necessary to observe these effects. Future research should include extended study periods, larger sample sizes, varied dosages, and comprehensive behavioral assessments to better understand the therapeutic potential of these agents.

Association between ACE (rs4343 and rs1799752), AGTR1 (rs5186), and PAI-1 (rs2227631) polymorphisms in the host and the severity of Covid-19 infection

Objective It is necessary to identify appropriate clinical, biochemical, epidemiological and genetic biomarkers to elucidate the underlying mechanisms of the coronavirus disease-2019 (COVID-19) disease. The study focused on not only the link between disease severity (non-intense unit care (non-ICU) versus intensive unit care (ICU) and genetic susceptibility in COVID-19 patients but also the connection between comorbidity and genetic susceptibility affecting the severity of COVID-19. Subject and methods One hundred and sixty-two COVID-19 patients treated in the non-ICU and ICU in Kayseri City Hospital were included. All volunteers underwent a physical examination and biochemical evaluation. Angiotensin-converting enzyme (ACE p.T776T G > A(rs4343) and g.16471_16472delinsALU (also referred to as I/D polymorphism; rs1799752), angiotensin II receptor type-1 (AGTR1) c.*86A > C (also referred to as A1166C; rs5186), and plasminogen activator inhibitor-1 (PAI-1-844 G > A (rs2227631) polymorphisms were analysed as well. Results To have ACE “ID” genotype did not change the severity of the disease (OR: 0.92, 95% CI: 0.41–2.1, p = 0.84), but decreased the mortality risk 2.9-fold (OR: 2.9, 95% CI: 1.1–7.0, p = 0.03). In PAI-1-844 G > A, having the “AA” genotype in the “A” recessive model increased the risk of the diabetes mellitus (DM) 2.3-fold (OR: 2.3 95%, CI: 1.16–4.66, p = 0.018). In the “G” recessive model, to have the GG genotype increased the risk of chronic kidney disease (CKD) 4.8-fold (OR:4.8, 95% CI: 1.5–15.5, p = 0.008). “GG” genotype in the DM group had a higher fibrinogen level compared to those with the “AG” genotype (AG:4847.2 mg/L (1704.3) versus GG:6444.67 mg/L (1861.62) p = 0.019) and “AA” genotype in the CKD group had lower platelet levels and those with “GG” had higher platelet levels (AA:149 µL (18–159) versus GG: 228 µL (146–357) p = 0.022). Conclusion This study was shown that genetic predispositions that causes comorbidities were also likely to affect the prognosis of COVID-19.

Impaired glycemic control as a risk factor for reduced lung function in the Indian diabetic population

Diabetes mellitus (DM) is a metabolic syndrome associated with chronic hyperglycemia, which results in various acute and chronic complications. DM leads to a state of chronic low-grade inflammation, which can have adverse effects on pulmonary functions. There have been contradictory studies related to the relationship between defects in lung functions in diabetic individuals and their correlation with glycemic control and systemic inflammatory markers. The present study aims to compare pulmonary function in controlled and uncontrolled diabetes in the Indian population while exploring the link between inflammatory markers and lung functions in diabetic patients. This observational, case-control study was conducted in the Department of Biochemistry at Sri Guru Ram Das Institute of Medical Sciences and Research in Amritsar, Punjab, on 116 subjects suffering from DM in the age group of 30-65 years. 58 diabetic patients with poor glycemic control [glycated hemoglobin (HbA1c)&gt;7%] and 58 diabetic patients with good glycemic control served as controls (HbA1c≤7%). The duration of the study was two years. Blood samples of each patient were investigated for glycemic control, high-sensitivity C-reactive protein (hsCRP), and serum fibrinogen. Spirometry as a pulmonary function test was undertaken for all participants. The statistical analysis of good and poor glycemic control diabetics showed that the average duration of disease (in years) was 8±5 and 10.2±5.4, respectively. A significant positive correlation was found between inflammatory markers (hsCRP and fibrinogen) and HbA1c and fasting blood glucose. A substantial decline in forced vital capacity and normal values of forced expiratory volume in the first second was observed in poor glycemic control diabetics, depicting a restrictive pattern of lung disease. Lung damage is seen to be more prevalent in patients with a longer duration of disease and increased levels of inflammatory markers. Chronic inflammation due to DM can lead to fibrosis and destruction of lung tissue, resulting in the development of diabetic lung disease, which includes a decline in lung function, an increased risk of infection, and an increased risk of respiratory failure. Therefore, it is essential for individuals with DM to have regular pulmonary function tests and to manage their diabetes to minimize the impact on their lung health.

Outcomes of Transcatheter Aortic Valve Implantation in Patients with and without Diabetes Mellitus.

Diabetes mellitus (DM) in patients undergoing cardiac transcatheter or surgical interventions usually is correlated with poor outcomes. Transcatheter aortic valve implantation (TAVI) has been developed as a therapy choice for inoperable, high-, or intermediate-risk surgical patients with severe aortic stenosis (AS). To evaluate the impact of DM and hemoglobin A1c (HbA1c) on outcomes and survival after TAVI. Five hundred and fifty-two symptomatic severe AS patients who underwent TAVI, of whom 164 (29.7%) had DM, were included in this retrospective study. Follow-up was performed after 30 days, six months, and annually. The device success and risks of procedural-related complications were similar between patients with and without DM, except for acute kidney injury, which was more frequent in the DM group (2.4% vs. 0%, P=0.021). In-hospital and first-year mortality were similar between the groups (4.9% vs. 3.6%, P=0.490 and 15.0% vs. 11.2%, P=0.282, respectively). There was a statistical difference between HbA1c ≥ 6.5 and HbA1c ≤ 6.49 groups in total mortality (34.4% vs. 15.8%, P<0.001, respectively). The only independent predictors were Society of Thoracic Surgeons score (hazard ratio [HR] 1.28, 95% confidence interval [CI] 1.09-1.51; P=0.003) and HbA1c level ≥ 6.5 (HR 10.78, 95% CI 2.58-21.50; P=0.003) in multivariable logistic regression analysis. In this study, we conclude that DM was not correlated with an increased mortality risk or complication rates after TAVI. Also, it was shown that mortality was higher in patients with HbA1c ≥ 6.5, and it was an independent predictor for long-term mortality.

Heparin-binding epidermal growth factor-like growth factor improves erectile function in streptozotocin-induced diabetic mice.

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) serves as a pro-angiogenic factor; however, there is to our knowledge currently no reported research on the relationship between HB-EGF and diabetic erectile dysfunction (ED). In this study we aimed to determine whether HB-EGF can improve the erectile function of streptozotocin-induced diabetic mice and to explore the related mechanisms. Eight-week-old male C57BL/6 mice were used for diabetes induction. Diabetes mellitus (DM) was induced by low-dose injections of streptozotocin (50mg/kg) for 5 consecutive days. Eight weeks after streptozotocin injections, DM was determined by measuring blood glucose and body weight. Diabetic mice were treated with two intracavernous administrations of phosphate-buffered saline (20μL) or various doses of HB-EGF (days -3 and 0; 1, 5, and 10μg in 20μL of phosphate-buffered saline). The angiogenesis effect of HB-EGF was confirmed by tube formation and migration assays in mouse cavernous endothelial cells and mouse cavernous pericytes under high-glucose conditions. Erectile function was measured by electrical stimulation of the cavernous nerve, as well as histological examination and Western blot analysis for mechanism assessment. In vitro angiogenesis, cell proliferation, in vivo intracavernous pressure, neurovascular regeneration, cavernous permeability, and survival signaling were the outcomes measured. Expression of HB-EGF was reduced under diabetic conditions. Exogenous HB-EGF induced angiogenesis in mouse cavernous endothelial cells and mouse cavernous pericytes under high-glucose conditions. Erectile function was decreased in the DM group, whereas administration of HB-EGF resulted in a significant improvement of erectile function (91% of the age-matched control group) in association with increased neurovascular content, including cavernous endothelial cells, pericytes, and neuronal cells. Histological and Western blot analyses revealed a significant increase in the permeability of the corpus cavernosum in DM mice, which was attenuated by HB-EGF treatment. The protein expression of phospho-Akt Ser473 and phosphorylated endothelial nitric oxide synthase Ser1177 increased after HB-EGF treatment. The use of HB-EGF may be an effective strategy to treat ED associated with DM or other neurovascular diseases. Similarly to other pro-angiogenic factors, HB-EGF has dual roles in vascular and neuronal development. Our study focused on broadly evaluating the role of HB-EGF in diabetic ED. In view of the properties of HB-EGF as an angiogenic factor, its dose concentration should be strictly controlled to avoid potential side effects. In the diabetic ED mouse model in this study erectile function was improved by HB-EGF, which may provide new treatment strategies for patients with ED who do not respond to phosphodiesterase 5 Inhibitors.

&lt;i&gt;IGF1R&lt;/i&gt; rs907806 and &lt;i&gt;GHSR&lt;/i&gt; rs572169 genetic variants in fetal macrosomia

BACKGROUND: Being strongly affected by maternal and fetal genetic factors, intrauterine environment plays a critical role in fetal growth. Intrauterine conditions, in turn, are largely determined by the genetic factors. AIM: The aim of this study was to evaluate the effect of the IGF1R rs907806 and GHSR rs572169 genetic variants on the weight of newborns. MATERIALS AND METHODS: This prospective study included 221 mother-newborn pairs. The inclusion criteria were singleton pregnancy and informed consent to participate in the study. The exclusion criteria were severe somatic, oncological and acute illnesses three months prior or during pregnancy, gestational diabetes mellitus, refusal to participate in the study at any stage, and insufficient data. The study groups included patients with type 1 diabetes mellitus (group I), type 2 diabetes mellitus (group II), and no carbohydrate metabolism disorders (group III). Cord blood samples were obtained after delivery. The IGF1R rs907806 and GHSR rs572169 genotypes were determined by polymerase chain reaction with restriction fragment length polymorphism analysis. The main outcomes were delivery of a large for gestational age fetus (weight of more than the 90th percentile INTERGROWTH-21st). The secondary outcomes were diabetic fetopathy, diabetic cardiomyopathy, and neonatal hypoglycemia. RESULTS: In group III, the minor G allele of the IGF1R rs907806 variant was more frequent in large-for-gestational-age newborns (p = 0.017; odds ratio 3.039; 95% confidence interval 1.244–7.424) than in those with a weight of less than 90th percentile. For the GHSR rs572169 variant, no similar trend was observed. This pattern was pronounced in the male newborns only (rs907806 AA vs. AG+GG; p = 0.046; odds ratio 4.229, 95% confidence interval 1.181–15.139). In newborns with hypoglycemia, a higher frequency of the GG genotype of the GHSR rs572169 (GA) variant was observed in the total sample (p = 0.004) and the type 1 diabetes mellitus group (p = 0.0496). CONCLUSIONS: The IGF1R rs907806 variant may affect birthweight in the male newborns of mothers without carbohydrate metabolism disorders. The observed association of neonatal hypoglycemia with the GG genotype of the GHSR rs572169 variant requires further investigation. Genetic factors can contribute to prognostic models of perinatal complications, while improving their early diagnosis opportunities.

The role of umbilical-portal venous hemodynamics in fetal macrosomia pathogenesis in pregnancy complicated by diabetes mellitus

BACKGROUND: During pregnancy complicated by diabetes mellitus, the risks of developing fetal macrosomia and other perinatal complications increase. Redistribution of blood flow in the fetal umbilical-portal venous system may be an important but poorly understood compensatory mechanism that affects macrosomic fetal growth. AIM: The aim of this study was to determine the features of the fetal umbilical-portal venous hemodynamics in pregnant women with various types of diabetes mellitus and the absence of carbohydrate metabolism disorders, taking into account the gestational age and the macrosomic fetal growth. MATERIALS AND METHODS: In this prospective cohort study, 86 pregnant women with pregestational diabetes mellitus, 44 pregnant women with gestational diabetes mellitus and 58 patients without carbohydrate metabolism disorders underwent ultrasound examinations from 30+0 to 41+3 weeks of gestation. During ultrasound, we performed Doppler assessment of venous hemodynamic parameters in the vessels of the umbilical-portal venous system, with volumetric blood flow calculated for each vessel. Additionally, the total liver volumetric blood flow and ductus venosus shunt fraction were calculated. RESULTS: The presence of fetal macrosomia in patients from the pregestational diabetes mellitus group is associated with an increase in the volumetric blood flow of the umbilical vein by 89.5 ml/min (p = 0.003) and the left portal vein by 33.3 ml/min (p = 0.008), as well as the total volumetric blood flow of the fetal liver by 95.7 ml/min (p = 0.001) compared with normal-weight fetuses. At the same time, the ductus venosus shunt fraction decreased in macrosomic fetuses by 3.83% (p = 0.001). In the gestational diabetes mellitus and control groups, despite the tendency for these parameters to increase in fetuses with macrosomia, the differences did not reach statistical significance. With a left portal vein volume flow threshold of 94.51 ml/min, the sensitivity and specificity for predicting large births were 84.46 and 72.09%, respectively. CONCLUSIONS: Pregestational diabetes mellitus in the mother is associated with a priority redistribution of blood flow to the fetal liver and is accompanied by a decrease in the ductus venosus shunt fraction. The severity of these hemodynamic changes increases in the presence of fetal macrosomia, which confirms the role of liver perfusion in the regulation of fetal growth in uncomplicated pregnancy and maternal diabetes mellitus.

The burden and care cascade in young and middle-aged patients with diabetes hypertension comorbidity with abdominal obesity in India: A nationally representative cross-sectional survey.

We ascertained the burden, determinants, and care cascade in the young and middle-aged patients having co-existing hypertension (HTN), Diabetes Mellitus (DM), and abdominal obesity in India from a secondary data analysis of nationally representative data. The study examined cross-sectional data from the National Family Health Survey (NFHS-5) conducted in India from 2019 to 2021 in 788974 individuals aged 15-49 years including 695707 women and 93267 men. The weighted prevalence of DM-HTN comorbidity with high waist circumference in the sample was 0.75% (95% CI: 0.71 to 0.79) including 46.33% (95% CI: 44.06 to 48.62) newly diagnosed cases detected for HTN and high blood sugars. The weighted prevalence of Metabolic syndrome as per NCEP ATPIII criteria was found to be 1.13% (95% CI: 1.08 to 1.17). Only 46.16% existing cases were treated with both anti-diabetes and antihypertensive medication (full treatment), while 34.71% cases were untreated. On adjusted analysis, increasing age, females, higher wealth index, high fat diet, obesity and comorbidities were significantly associated with having DM-HTN comorbidity along with high-waist circumference. More than half of young and middle aged-population in India with DM-HTN-abdominal obesity triad are not initiated on treatment for DM and HTN comorbidities, while a majority of the previously diagnosed cases have uncontrolled blood pressure and poor glycemic control. The poor cascade of care for DM and HTN in these high-risk group of patients may substantially increase their risk for early progression and severity of microvascular and macrovascular complications especially cardiovascular disease.

Metformin administration in prevention of colorectal polyps in type 2 diabetes mellitus patients.

Colorectal polyps are frequently observed in patients with type 2 diabetes mellitus (DM), posing a significant risk for colorectal cancer. Metformin, a widely prescribed biguanidine drug for type 2 DM, has been suggested to have potential chemoprophylactic effects against various cancers. To explore the correlation between colorectal polyps and metformin use in type 2 DM patients. Type 2 DM patients were categorized into polyp and non-polyp groups. Following this, all patients were categorized into the type 2 DM-metformin, type 2 DM-non-metformin, and non-type 2 DM groups. Based on the baseline colonoscopy results, we performed pairwise comparisons of the incidence of colorectal polyps among the three groups. Additionally, we analyzed the relationship between colorectal polyps and the duration of metformin use and between the size and number of polyps and metformin use. Simultaneously, we focused on the specific pathological types of polyps and analyzed their relationship with metformin use. Finally, we compared the incidence of polyps between metformin and non-metformin groups according to the interval colonoscopy results. The rate of metformin use in patients with colorectal polyps was 0.502 times that of patients without colorectal polyps [odds ratio (OR) = 0.502, 95% confidence interval (CI): 0.365-0.689; P < 0.001]. The incidence of colorectal polyps did not differ significantly between the type 2 DM-metformin and non-type 2 DM groups (P > 0.05). Furthermore, the correlations between the duration of metformin use and the incidence of colorectal polyps and between the size and number of polyps and metformin use were not statistically significant (P > 0.05). Metformin use did not affect the incidence of colorectal polyps during interval colonoscopy (P > 0.05). Metformin use and colorectal polyp incidence in type 2 DM patients showed a negative correlation, independent of the hypoglycemic effect of metformin.

Effect of NLRP3 gene knockdown on pyroptosis and ferroptosis in diabetic cardiomyopathy injury

Diabetic cardiomyopathy (DCM) is a chronic disease caused by diabetes mellitus, which is recognized as a worldwide challenging disease. This study aimed to investigate the role and the potential mechanism of knocking down the NACHT-, LRR- and PYD domains-containing protein 3 (NLRP3), an inflammasome associated with onset and progression of various diseases, on high glucose or diabetes -induced cardiac cells pyroptosis and ferroptosis, two regulated non-necrosis cell death modalities discovered recent years. In the present study, both in vivo and in vitro studies were conducted simultaneously. Diabetic rats were induced by 55 mg/kg intraperitoneal injection of streptozotocin (STZ). Following the intraperitoneal injection of MCC950 (10 mg/kg), On the other hand, the DCM model in H9C2 cardiac cells was simulated with 35 mmol/L glucose and a short hairpin RNA vector of NLRP3 were transfected to cells. The results showed that in vivo study, myocardial fibers were loosely arranged and showed inflammatory cell infiltration, mitochondrial cristae were broken and the GSDMD-NT expression was found notably increased in the DM group, while the protein expressions of xCT and GPX4 was significantly decreased, both of which were reversed by MCC950. High glucose reduced the cell viability and ATP level in vitro, accompanied by an increase in LDH release. All of the above indicators were reversed after NLRP3 knockdown compared with the HG treated alone. Moreover, the protein expressions of pyroptosis- and ferroptosis-related fators were significantly decreased or increased, consistent with the results shown by immunofluorescence. Furthermore, the protective effects of NLRP3 knockdown against HG were reversed following the mtROS agonist rotenone (ROT) treatment. In conclusion, inhibition of NLRP3 suppressed DM-induced myocardial injury. Promotion of mitochondrial ROS abolished the protective effect of knockdown NLRP3, and induced the happening of pyroptosis and ferroptosis. These findings may present a novel therapeutic underlying mechanism for clinical diabetes-induced myocardial injury treatment.

Linalool exerts antioxidant activity in a rat model of diabetes by increasing catalase activity without antihyperglycemic effect.

Diabetes mellitus (DM) is a prevalent metabolic disorder often accompanied by oxidative stress, which contributes to various diabetic complications. Investigating the antioxidant activity of linalool (LIN) is crucial as it may offer a natural therapeutic approach to mitigate oxidative damage in DM. The aim of the present study was to investigate the antioxidant activity of LIN in a DM rat model. A total of 40 male Wistar albino rats (age, 8 weeks; weight, 250-300 g) were used. CONTROL and DM groups were administered physiological saline solution by oral gavage for 21 days. In rats in the DM + LIN and LIN groups, 100 mg/kg LIN was administered intragastrically after streptozotocin injection (n=10 per group). In the first (48 h after STZ injection), second (1 week later), third (2 weeks later), and fourth (3 weeks later) blood glucose measurements, a statistically significant increase was found in the blood glucose values of the DM and DM + LIN groups compared with those of the CONTROL group. During the 21-day experimental period, there was no reduction in blood glucose levels of the DM + LIN group. Consequently, no discernible anti-hyperglycemic effect of LIN was observed. Catalase enzyme activity, superoxide dismutase (SOD) enzyme activity, malondialdehyde (MDA) levels and glutathione (GSH) levels were measured spectrophotometrically. All assays were conducted according to the protocols provided in the respective kits. The results were analyzed to assess the oxidative status and antioxidant capacity in the experimental groups. Catalase (CAT) activity was decreased in the DM group compared with that in the CONTROL group in both the serum and liver. However, LIN administration restored CAT activity in the DM + LIN group to the level of the CONTROL group. In the liver, the DM + LIN-treated group showed a notable reduction in malondialdehyde (MDA) levels compared with those in the DM group. In conclusion, the present results suggest that the antioxidant properties of LIN may have a regulatory effect on the oxidative status in diabetes-affected systems, potentially offering therapeutic benefits in managing oxidative stress associated with diabetes.