The long-term effect of bariatric/metabolic surgery versus pharmacologic therapy in type 2 diabetes mellitus patients: A systematic review and meta-analysis.

Metabolic/bariatric surgery as a treatment for obesity and related diseases, such as type 2 diabetes mellitus (T2DM), has been increasingly recognised in recent years. However, compared with conventional pharmacologic therapy, the long-term effect (≥ 5 years) of metabolic surgery in T2DM patients is still unclear. This study aimed to evaluate the diabetes remission rate, incidence of diabetic microvascular complications, incidence of macrovascular complications, and mortality in T2DM patients who received metabolic surgery versus pharmacologic therapy more than 5 years after the surgery. Searching the database, including PubMed, Embase, Web of Science, and Cochrane Library from the inception to recent (2024), for randomised clinical trials (RCTs) or cohort studies comparing T2DM patients treated with metabolic surgery versus pharmacologic therapy reporting on the outcomes of the diabetes remission rate, diabetic microvascular complications, macrovascular complications, or mortality over 5 years or more. A total of 15 articles with a total of 85,473 patients with T2DM were eligible for review and meta-analysis in this study. There is a significant long-term increase in diabetes remission for metabolic surgery compared with conventional medical therapy in the overall pooled estimation and RCT studies or cohort studies separately (overall: OR = 4.58, 95% CI: 1.89-11.07, P < 0.001). Significant long-term decreases were found in the pooled results of microvascular complications incidence (HR = 0.57, 95% CI: 0.41-0.78, P < 0.001), macrovascular complications incidence (HR = 0.59, 95% CI: 0.50-0.70, P < 0.001) and mortality (HR = 0.53, 95% CI: 0.53-0.79, P = 0.0018). Metabolic surgery showed more significant long-term effects than pharmacologic therapy on diabetes remission, macrovascular complications, microvascular complications incidence, and all-cause mortality in patients with T2DM using currently available evidence. More high-quality evidence is needed to validate the long-term effects of metabolic surgery versus conventional treatment in diabetes management.

Independent and interactive associations of heart rate and obesity with type 2 diabetes mellites: A population-based study.

BACKGROUND: Although obesity and heart rate (HR) were closely related to the prevalence and development of type 2 diabetes mllitus (T2DM), few studies have shown a co-association effect of them on T2DM. We aimed at assessing the interactive effects of HR and obesity with prevalence of T2DM in Chinese population, providing the exact cutpoint of the risk threshold for blood glucose with high HR. MATERIALS AND METHODS: In the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal study (REACTION) cohorts (N = 8398), the relationship between HR and T2DM was explored by linear regression, logistic regression, and restricted cubic spline, and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Interaction terms between HR and body mass index (BMI) and HR and waist circumference (WC) were introduced into the logistic regression model. RESULTS: In those with HR > 88.0 beats/min, fasting plasma glucose and oral glucose tolerance tests were significantly correlated with HR, and the prevalence of T2DM was highly correlated with HR (all p < .05). There were interactive associations of HR and obesity in patients with T2DM with HR < 74 beats/min. CONCLUSION: High HR was in interaction with obesity, associating with prevalence of T2DM. The newly subdivided risk threshold for HR with T2DM might be HR > 88 beats/minute.

The Effect of Glycemic Status on P Wave Dispersion.

Background and aim The growing number of people with diabetes mellitus (DM) across the world is a public health concern. The diabetes epidemic involves enormous health costs to the patients, their careers, and society at large. Cardiovascular diseases such as atrial fibrillation (AF) often develop in the diabetic population. An increase in the P wave dispersion (PWD) has been established as an independent risk factor for the occurrence of AF, hence the present study was conducted to establish a possible relationship between PWD and the glycemic status of the individual to predict the occurrence of AF ahead of clinical symptomology. Methodology A comparative cross-sectional study was conducted at a tertiary care hospital after obtaining approval from the institutional ethics committee and written consent of each study subject. The main steps included the selection and categorization of the study population based on their glycemic status, collection of demographic data, performing ECGs calculating PWD using digital calipers, and recording the data systematically for evaluation. Results In this study, 234 patients with a mean age of 53.3 ± 13.1 years were studied, of which 121 (51.7%) were male and 113 (48.29%) were female. The 234 patients were divided into four groups based on their glycemic status - 74 uncontrolled DM patients (31.62%), 51 type 2 DM (T2DM) patients (21.78%), 56 prediabetes patients (23.93%), and 53 patients in the control group (22.64%; not a known case of diabetes with normal HbA1c and fasting blood sugar (FBS) levels). Minimal correlation was observed between FBS with PWD (r value 0.175) and age with PWD (r value 0.161), but statistical significance was observed only between age and PWD (p-value 0.014). The difference in means between the four different study groups was found to be not statistically significant (p-value- 0.104); hence, no intergroup variation was noted. Conclusion Advancing age and higher fasting blood sugars have shown minimal correlation with widening P-wave dispersion. With further studies involving larger populations, this can be a promising aid in identifying PWD as a probable early predictor of atrial arrhythmias among diabetic patients.

Recent Patterns and Assessment of Long-term Complications followi ngSARS-CoV-2 Infection and Vaccination in the Context of Diabet esPrevalence among Blood Donors.

BACKGROUND: Much increasing evidence has suggested that long-term complications post vaccination of SARS-CoV-2 experience a wide range of complication including diabetes. The risk and burden of type 1 diabetes is extensively reported, but type 2 diabetes mellitus (T2D) has yet to be characterized. To address this gap, we aimed to examine trends of long-term complications post SARS-CoV-2 infection and vaccination in diabetes incidence among the Saudi population. METHODS: In this cross-sectional hospital-based study, we analyzed the blood profile of first-time blood donors from the University Hospital of King Abdulaziz University, Jeddah. Saudi Arabia. Various blood parameters, HbA1c was measured in the month of May 2023. All the donors were non-diabetic and were never diagnosed with T2D before the current blood donation. 203 healthy subjects donated their blood, out of which 104 had abnormally high HbA1c tending towards diagnosis of T2D and 99 had with blood profiles. The study followed the STROBE reporting guidelines. RESULTS: Out of 203 donors 104 (male 50(48.1%), female 54(51.9%)) were diagnosed with increased HbA1c (8.24 in males) compared to 7.61 of HbA1c in females. 35.6% were above ˃65 years, with 52.9% with O+ from the ABO blood group. Liver functions indicated significant p˂0.05, 0.04, increased amount of GGT (46.47 U/L), Alkaline phosphatase (99.93 ±64.26 uL) respectively in HbA1c elevated donors KFT represented significant p˂0.05, 0.02 elevated levels of urea (6.73 ±5.51 mmol/L), creatinine (129.97 ±195.17 umol/L) respectively along with elevated values of Lactate dehydrogenase (LDH) (263.72± 196.70 uL) and triglycerides (1.66 ±0.74mmol/L) when compared to normal value of HbA1c donors. DISCUSSION: In the present cross-sectional study, significant increase in HbA1c, trending towards increased cases of T2D post SARS-CoV-2 infection and vaccination. Males are much affected compared to females. Further maximum number of cases were from donors above the age of 65 years with altered partial LFT (GGT, Alkaline phosphatase), KFT (urea, creatinine), lipid profile (TG) and LDH in post SARS-CoV-2 and vaccination blood donors. CONCLUSION: Increase in HbA1c in 50% of donors, irrespective of gender, is an alarming figure for health authorities, with altered LFT, KFT and LDH tests and, in the near future, may increase the incidence of T2D. Large-scale population-based studies are required to prevent future incidences of T2D in young children who will be vaccinated.

Correlation of Platelet Indices in Patients With Type 2 Diabetes Mellitus and Associated Microvascular Complications: A Hospital-Based, Prospective, Case-Control Study.

Background Diabetic patients exhibit increased platelet activity. Insulin inhibits the activation of platelets. Therefore, a relative or absolute deficiency of insulin would increase platelet reactivity. The younger (larger) platelets are also more metabolically and enzymatically active. If detected early, microvascular complications could alert us regarding the possible macrovascular complications. Thus, the aims and objectives of the present study were to determine platelet indices in patients with type 2 diabetes mellitus with controls (non-diabetics) and to find an association of platelet indices with microvascular complications.  Material & methods In this prospective case-control study conducted from 2021 to 2022 (2 years), a total number of 200 subjects were taken and were divided into two groups of 100 each, cases (I) and controls (II). The cases included patients of diabetes mellitus (DM) of a duration of more than 5 years, which were further divided into two groups of 50 each, IA and IB. Group IA consisted of patients with diabetes mellitus of a duration of more than five years with at least one microvascular complication and group IB was diabetics of more than five years duration without any microvascular complications, which includes diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy. An automated cell counter (Thermo Fisher Scientific, Waltham, MA, US) provided hemoglobin values along with the platelet count and platelet indices, i.e. mean platelet volume (MPV), platelet large cell ratio (P-LCR), and platelet distribution width (PDW). Results The present study consisted of 200 subjects divided into 2 groups of 100 each, cases (I) and controls (II). The average MPV (9.4-12.3 femtolitre) in diabetics was 12.089±1.450 fL as compared to the controls where it was 9.464±1.424 fL with a statistically significant p-value of 0.001. PDW among the cases was 16.868±2.352 fL while in controls, it was 12.753±10.559 fL (p=0.001). The mean P-LCR was 34.975±8.056% among the cases, in comparison to the mean P-LCR among the controls, which was 26.031±7.004 (p=0.001). In this study, the MPV, PDW, and P-LCR were significantly raised in individuals having diabetes with microvascular complications when compared with patients without complications. The mean MPV in diabetics with complications was 12.5960±0.95660 fL and in those without complications was 11.5820±1.67609 fL (with a p-value of P = 2×10-3)which is statistically significant. Similar results were obtained in cases of PDW and P-LCR. The mean PDW in diabetics with complications was 17.1140±2.58228 fL and without complications was 15.6220±2.10532 fL ((with a p-value of P = 2×10-3)). The mean P-LCR in diabetics with microvascular complications was 35.408±3.5490% and without complications was 33.542±4.8694% (with a p-value of P = 3.1×10-3). Conclusion Based on the findings of the present study, there is a statistical correlation between type 2 diabetes and variations in platelet indices, resulting in the associated microvascular complications. Higher MPV, PDW, and P-LCR values suggest that these parameters are more reliable predictors of early vascular complications in individuals with type 2 diabetes mellitus and can be utilized as an easy-to-use, low-cost method. They are a readily available, economical, practical, noninvasive, and simple-to-understand approach for assessing platelet dysfunction, which in turn helps anticipate the existence of microvascular complications.

Triple Infectious Syndrome: Pulmonary Tuberculosis and HIV in a Case of Pure Neuritic Leprosy With Underlying Diabetes Mellitus.

Pulmonary tuberculosis (PTB), human immunodeficiency virus (HIV), and leprosy are of public health importance, as all three diseases are communicable and contribute to disease burden in society. Co-infection with these three entities is extremely rare but leads to significant mortality and morbidity. We report a case that highlights the diagnostic challenges and therapeutic management of a patient who was diagnosed with pure neuritic leprosy on multibacillary-multidrug therapy (MB-MDT) and subsequently co-diagnosed with PTB and HIV. The patient was started on anti-tubercular therapy and anti-retroviral therapy for treatment under India's national health programs, which play a major role in treating those of low socioeconomic status. The optimization of these therapeutic drugs is quite challenging during treatment due to potential drug interactions and toxicities. High clinical suspicion is required to rule out PTB before initiating rifampicin-containing MB-MDT, which can lead to rifampicin-resistant TB and screening for HIV. As there is a social stigma associated with these patients, they require good psychological support during and after treatment.

Effects of Non-surgical Periodontal Therapy on Saliva and Gingival Crevicular Fluid Levels of Chemerin in Periodontitis Subjects With and Without Type 2 Diabetes Mellitus.

Background Evidence had shown a bi-directional link between diabetes mellitus and periodontitis. Chemerin, an adipose tissue-specific adipokine plays a significant role in adipocyte initiation and differentiation that directly influences glucose metabolism, lipid metabolism, and inflammatory mediators. Non-surgical periodontal therapy (NSPT) for patients with periodontitis and diabetes mellitus improves the periodontal condition and regulates glycemic level. Aims and objectives To assess the impact of chemerin on periodontal disease and diabetes mellitus pathogenesis and to analyze the impact of NSPT on saliva and gingival crevicular fluid (GCF) chemerin levels in patients with periodontitis with and without type 2 diabetes mellitus (T2DM). Materials and methods A total of 60 patients were divided into four groups: Group I: Systemically and periodontally healthy subjects (n=15), Group II: Systemically healthy subjects with periodontitis (n=15), Group III: Subjects with periodontitis and T2DM (n=15), Group IV: Periodontally healthy subjects with T2DM (n=15). Indices and parameters like plaque index (PI), gingival index (GI), periodontal probing depth (PPD), and clinical attachment level (CAL) were assessed at baseline in all four groups and six weeks after NSPT in Group II and Group III. A glycated hemoglobin (HbA1c) test was taken to assess the patient's blood glucose level. Fasting blood sugar (FBS) level was taken at baseline in all the groups and six weeks after NSPT in Group II and Group III subjects. Saliva and GCF chemerin levels were assessed at baseline in all four groups and six weeks after NSPT in Group II and Group III subjects. Results A statistically significant difference was observed in comparing chemerin levels at baseline with all four groups (p < 0.001). After NSPT, there was a reduction in clinical parameters, FBS, and chemerin levels in Group II and Group III. A positive correlation was observed between salivary chemerin and FBS in Group II, GCF chemerin, PI, and FBS in Group II, and PPD and FBS in Group III. A negative correlation was observed between salivary chemerin and all parameters in Group II and between salivary chemerin and GCF chemerin in Group III. Conclusion Based on the observed relationship between chemerin and the parameters, their utility as a dual biomarker for diagnosis and prognosis in periodontal disease seems promising. However, further studies with a larger sample size on the role of chemerin in health and various states of diseases are required to substantiate the result of the study.

Device-measured physical activity and type 2 diabetes mellitus risk.

Objectives: We investigated how device-measured physical activity (PA) volume (PA energy expenditure [PAEE]) and intensity (fraction of PAEE from moderate-to-vigorous PA [FMVPAEE]) were associated with the incidence of type 2 diabetes mellites (T2DM). Methods: This population-based prospective cohort study included 90,044 participants. The primary exposures were PAEE and FMVPAEE. The secondary exposures were energy expenditure exerted during light, moderate, and vigorous PA and their fraction of PAEE. Results: Each 1-SD increase in PAEE was associated with a 17% lower risk of T2DM (hazard ratio [HR]: 0.83, 95% confidence interval [CI]: 0.78-0.98). Each 1-SD increase in FMVPAEE was associated with a 21% lower incidence of T2DM (HR: 0.79, 95% CI: 0.74-0.83). Achieving the same PA volume (KJ/kg/day) through vigorous PA (HR: 0.88, 95% CI: 0.85-0.91) was more effective in preventing T2DM than moderate PA (HR: 0.97, 95% CI: 0.96-0.98) and light PA (HR: 0.99, 95% CI: 0.98-1.00). Conclusion: A higher PA volume is associated with a lower incidence of T2DM. Achieving the same PA volumes through higher-intensity PA is more effective than low-intensity PA in reducing T2DM incidence.

Fecal microbiota transplantation reverses insulin resistance in type 2 diabetes: A randomized, controlled, prospective study.

Objectives: Recent studies have shown that fecal microbiota transplantation (FMT) improved the metabolic profiles of patients with type 2 diabetes mellitus (T2DM), yet the effectiveness in reversing insulin resistance and increasing metformin sensitivity in T2DM patients have not been reported. In this study, we evaluated the improvements of T2DM patients and their gut microbiota by FMT alone and FMT plus metformin. Methods: A total of 31 patients with newly diagnosed T2DM were randomized to intervention by metformin, FMT, or FMT plus metformin in the study. Patients were followed up at baseline and week 4 after treatment. Blood and stool samples were collected and subject to analyze clinical parameters and microbial communities by metagenomic sequencing, respectively. Results: FMT alone and FMT plus metformin significantly improved the clinical indicators HOMA-IR and BMI in T2DM, besides fasting blood glucose, postprandial blood glucose, and hemoglobin A1c that were also controlled by metformin. Donor microbiota effectively colonized in T2DM with slightly higher colonization ration in FMT than FMT plus metformin within 4 weeks, resulting in increased microbial diversity and community changes from baseline after treatment. A total of 227 species and 441 species were significantly alerted after FMT and FMT plus metformin, respectively. FMT were significantly associated with the clinical parameters. Among them, Chlorobium phaeovibrioides, Bifidibacterium adolescentis and Synechococcus sp.WH8103 were potential due to their significantly negative correlations with HOMA-IR. Conclusions: FMT with or without metformin significantly improve insulin resistance and body mass index and gut microbial communities of T2DM patients by colonization of donor-derived microbiota.

First-in-Class Oral Semaglutide: Overcoming Barriers of Incretinisation in the Indian Context.

Despite the availability of multiple therapeutic options and strategies, patients with type 2 diabetes mellitus (T2DM) the world over have inadequate glycaemic control and India is no exception. Patients with T2DM in India have benefitted from glucagon-like peptide-1 analogues similar to that of patients from other parts of the world. However, subcutaneous treatment with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) is limited by their injectable mode of administration. The present review highlights barriers to incretinisation with GLP-1RAs and the role of first-in-class oral semaglutide in the Indian context and provides guidance to physicians on its initiation and uses.

A Step Toward the Exploration of Better Spirometric Parameters for Early Diagnosis of Pulmonary Dysfunction in Persons With Type 2 Diabetes Mellitus.

OBJECTIVES: This study aims to determine the forced vital capacity (FVC) and slow vital capacity (SVC) along with other pulmonary functions in Indian diabetic patients for early diagnosis of pulmonary function reduction and to compare the ratios of forced expiratory volume in one second (FEV1) with FVC and SVC (FEV1/FVC and FEV1/SVC) in diabetic patients. MATERIALS AND METHODS:  A prospective observational study was carried out in the physiology department for two years after the approval of the institutional ethics committee. The study included 90 type 2 diabetes mellitus patients previously diagnosed by the physician and 90 age and sex-matched controls for spirometric tests. Medspiror having Helios 401 software (Recorders & Medicare Systems Pvt. Ltd., Panchkula, India) was used to assess the pulmonary function in all subjects. A comparison of dynamic pulmonary function parameters among non-diabetic and diabetic groups and non-obese vs. overweight/obese individuals of the diabetic group has been done. FEV1/FVC ratio vs. FEV1/SVC ratio comparison was conducted between the non-obese vs. the overweight/obese group in diabetic patients. RESULTS: A significant variation in FEV1 and FVC was observed in the type 2 diabetic group as compared to the non-diabetic group. However, in the case of type 2 diabetic subjects, FEV1/FVC ratio was almost constant in both BMI groups, whereas the FEV1/SVC ratio increased in the overweight/obese group. CONCLUSION: Type 2 diabetes mellitus accounts for a predictive factor for worsening pulmonary function. SVC, particularly the FEV1/SVC ratio, can be an earlier diagnostic marker for pulmonary dysfunction in diabetic subjects as this ratio changes even with a constant FEV1/FVC ratio.

Nonalcoholic steatohepatitis and mechanisms by which it is ameliorated by activation of the CNC-bZIP transcription factor Nrf2.

Non-alcoholic steatohepatitis (NASH) represents a global health concern. It is characterised by fatty liver, hepatocyte cell death and inflammation, which are associated with lipotoxicity, endoplasmic reticulum (ER) stress, mitochondrial dysfunction, iron overload and oxidative stress. NF-E2 p45-related factor 2 (Nrf2) is a transcription factor that combats oxidative stress. Remarkably, Nrf2 is downregulated during the development of NASH, which probably accelerates disease, whereas in pre-clinical studies the upregulation of Nrf2 inhibits NASH. We now review the scientific literature that proposes Nrf2 downregulation during NASH involves its increased ubiquitylation and proteasomal degradation, mediated by Kelch-like ECH-associated protein 1 (Keap1) and/or ß-transducin repeat-containing protein (ß-TrCP) and/or HMG-CoA reductase degradation protein 1 (Hrd1, also called synoviolin (SYVN1)). Additionally, downregulation of Nrf2-mediated transcription during NASH may involve diminished recruitment of coactivators by Nrf2, due to increased levels of activating transcription factor 3 (ATF3) and nuclear factor-kappaB (NF-κB) p65, or competition for promoter binding due to upregulation of BTB and CNC homology 1 (Bach1). Many processes that downregulate Nrf2 are triggered by transforming growth factor-beta (TGF-ß), with oxidative stress amplifying its signalling. Oxidative stress may also increase suppression of Nrf2 by ß-TrCP through facilitating formation of the DSGIS-containing phosphodegron in Nrf2 by glycogen synthase kinase-3. In animal models, knockout of Nrf2 increases susceptibility to NASH, while pharmacological activation of Nrf2 by inducing agents that target Keap1 inhibits development of NASH. These inducing agents probably counter Nrf2 downregulation affected by ß-TrCP, Hrd1/SYVN1, ATF3, NF-κB p65 and Bach1, by suppressing oxidative stress. Activation of Nrf2 is also likely to inhibit NASH by ameliorating lipotoxicity, inflammation, ER stress and iron overload. Crucially, pharmacological activation of Nrf2 in mice in which NASH has already been established supresses liver steatosis and inflammation. There is therefore compelling evidence that pharmacological activation of Nrf2 provides a comprehensive multipronged strategy to treat NASH.

Reactive Oxygen Species Downregulate Transient Receptor Potential Melastatin 6 Expression Mediated by the Elevation of miR-24-3p in Renal Tubular Epithelial Cells.

BACKGROUND: A low level of serum magnesium ion (Mg2+) is associated with type 2 diabetes mellitus (T2D). However, the molecular mechanism of Mg2+ deficiency has not been fully clarified. The current study sought to assesses the effect of reactive oxygen species on the expression of Mg2+ channels and miRNA. METHODS: The expression of Mg2+ channels and miRNA were examined by real-time polymerase chain reaction. Intracellular Mg2+ concentration was measured by Magnesium Green fluorescence measurement. RESULTS: The mRNA level of transient receptor potential melastatin 6 (TRPM6), which functions as Mg2+ influx channel in the distal convoluted tubule (DCT) of the kidney, was decreased by glycated albumin (GA), but not by insulin in rat renal tubule-derived NRK-52E cells. The mRNA levels of TRPM7, a homologue of TRPM6, and CNNM2, a Mg2+ efflux transporter located at the basolateral membrane of DCT, were changed by neither GA nor insulin. The generation of reactive oxygen species (ROS) was increased by GA. Hydrogen peroxide (H2O2) dose-dependently decreased TRPM6 mRNA, but it inversely increased the reporter activity of TRPM6. H2O2 accelerated the degradation of TRPM6 mRNA in actinomycin D assay without affecting TRPM7 and CNNM2 mRNA expressions. Nine miRNAs were considered as candidates for the regulator of stability of TRPM6 mRNA. Among them, miR-24-3p expression was increased by H2O2. The H2O2-induced reduction of TRPM6 mRNA was rescued by miR-24-3p siRNA. Magnesium Green fluorescence measurement showed that Mg2+ influx is suppressed by H2O2, which was rescued by an antioxidant and miR-24-3p siRNA. CONCLUSIONS: We suggest that GA decreases TRPM6 expression mediated by the elevation of ROS and miR-24-3p in renal tubular epithelial cells of T2D.

Determining the correlation between olive oil consumption, BMI, and waist circumference in the adult Saudi population.

OBJECTIVE: This study aimed to explore the correlation between dietary intake of olive oil, body mass index (BMI), and waist circumference (WC). METHODS: In this cross-sectional study, we recruited 200 participants aged 20-30 years using pre-determined inclusion and exclusion criteria. Demographic data was collected via a questionnaire, while dietary data was collected for two days using a 24-hour dietary recall. Anthropometric data such as BMI and WC were collected, and all the information was entered into the Diet Organizer software and statistical package for social sciences (SPSS) software for statistical analysis. The test results were assessed on the basis of a significance level of 95% (p < 0.05). RESULTS: We did not find a significant difference in BMI and WC between high and low olive oil consumers. Carbohydrate intake was significantly higher among low olive oil consumers. Although high olive oil consumers had a significantly higher caloric intake, they had a similar BMI compared to low olive oil consumers. CONCLUSION: This study provides baseline data on the intake of olive oil in a Saudi cohort aged 20-30 years. This study suggests that high olive oil intake may have a role in maintaining body weight.

Comprehensive analysis of vitreous humor chemokines in type 2 diabetic patients with and without diabetic retinopathy.

AIMS: To compare the vitreous levels of chemokines in diabetic patients with and without retinopathy. To find the relationship between stages of diabetic retinopathy (DR) and levels of vitreous chemokines. METHODS: The study involved 20 non-diabetic and 20 diabetic patients without clinical signs of DR (NDR) and 40 diabetic patients with proliferative diabetic retinopathy (PDR). The vitreous humor was collected and the levels of 40 chemokines were measured using magnetic color-bead-based multiplex assay. RESULTS: The control group, NDR group, PDR with vitreous hemorrhage (VH) group, and PDR with tractional retinal detachment group comprised 20, 20, 21, and 19 eyes, respectively. Only the concentration of CCL3 was significantly higher in the NDR group compared with the controls (p = 0.038). Twenty-five types of chemokines were statistically higher in the PDR with VH group in comparison to NDR group (all p < 0.05). All chemokines were statistically higher in the PDR with TRD group in comparison to NDR group (all p < 0.05) apart from 3 chemokines: GM-CSF, MIF, and CCL3(p = 0.086, p = 0.109, p = 0.094, respectively). The concentration of CCL21, CCL15 in PDR with TRD group was significantly higher compared with PDR with VH group, while other 36 chemokines were not significantly different between PDR with VH group and PDR with TRD group. CONCLUSIONS: The inflammation gradually worsen with the progression of DR. CCL3 may be associated with the onset of early diabetic retinal damage, and CCL15 and CCL21 may be closely related to the formation of fibrovascular membrane and the progression of the end stage of DR.

Disturbed neurovascular coupling in type 2 diabetes mellitus patients: Evidence from a comprehensive fMRI analysis.

BACKGROUND: Previous studies presumed that the disturbed neurovascular coupling to be a critical risk factor of cognitive impairments in type 2 diabetes mellitus (T2DM), but distinct clinical manifestations were lacked. Consequently, we decided to investigate the neurovascular coupling in T2DM patients by exploring the MRI relationship between neuronal activity and the corresponding cerebral blood perfusion. METHODS: Degree centrality (DC) map and amplitude of low-frequency fluctuation (ALFF) map were used to represent neuronal activity. Cerebral blood flow (CBF) map was used to represent cerebral blood perfusion. Correlation coefficients were calculated to reflect the relationship between neuronal activity and cerebral blood perfusion. RESULTS: At the whole gray matter level, the manifestation of neurovascular coupling was investigated by using 4 neurovascular biomarkers. We compared these biomarkers and found no significant changes. However, at the brain region level, neurovascular biomarkers in T2DM patients were significantly decreased in 10 brain regions. ALFF-CBF in left hippocampus and fractional ALFF-CBF in left amygdala were positively associated with the executive function, while ALFF-CBF in right fusiform gyrus was negatively related to the executive function. The disease severity was negatively related to the memory and executive function. The longer duration of T2DM was related to the milder depression, which suggests T2DM-related depression may not be a physiological condition but be a psychological condition. CONCLUSION: Correlations between neuronal activity and cerebral perfusion maps may be a method for detecting neurovascular coupling abnormalities, which could be used for diagnosis in the future. Trial registry number: This study has been registered in ClinicalTrials.gov (NCT02420470) on April 2, 2015 and published on July 29, 2015.

A fMRI observation on the changes of striatum-dorsolateral prefrontal cortex(ST-dlPFC)pathway in T2DM patients with cognitive flexibility decline / 神经解剖学杂志

Objectve:To observe the change of functional connectivity(FC)characteristic and its correlation with cognitive flexibility in type 2 diabetes mellites(T2DM)patients with cognitive flexibility decreased.Methods:A retro-spective analysis was performed in 24 T2DM patients with cognitive flexibility decreased(T2DM+CD),34 T2DM pa-tients without cognitive flexibility decreased(T2DM-CD)and 31 healthy controls(HC).Wisconsin Card Sorting Test(WCST)and the Stroop Color Word Test(Stroop)were respectively used in three groups of subjects to assess cognitive flexibility and functional magnetic resonance imaging(fMRI)scans was used to assess the FC.The differences of cogni-tive flexibility were found between three groups of subjects.The differences of FC between the bilateral(Left and Right,L.and R.)striatum(ST)and the dorsolateral prefrontal cortex(dlPFC)were found between three groups of subjects.Further analysis was focused on the interactive effect of T2DM and cognitive flexibility on FC changes.Results:Com-pared with T2DM-CD and HC,the number of response administered,errors responses,perseverative response,and time in WCST of T2DM+CD were significantly increased,while the number of correct responses was decreased.In Stroop,the number of correct,word-color contradiction and correct word-color indifference in T2DM+CD were lower than HC.In T2DM+CD,FC between L.ST-L.dlPFC,R.ST-L.dlPFC and R.ST-R.dlPFC were decreased,and decreased FC between R.ST-R.dlPFC was associated with cognitive flexibility scale scores.There existed an interactive effect between T2DM and cognitive flexibility on FC changes.Conclusion:Decreased FC between ST and dlPFC is the neural mechanism of cognitive flexibility impairment in T2DM.