Diabetes Mellitus Subjects Research Articles

Effects of APOE isoforms in diabetic nephropathy patients of South India.

Diabetic nephropathy (DN) is a grave complication and the most common renal dysfunction of diabetes mellitus. Genetic factors, including Apolipoprotein E (APOE) isoforms, have been implicated in the pathogenesis of DN. A total of 577 type 2 Diabetes mellitus subjects were categorized into diabetes non-nephropathic (Controls: n = 321), diabetes nephropathic (DN: n = 256) groups. Demographic, clinical, and biochemical parameters including age, BMI, lipid profiles (TC, LDL-C, HDL-C, TG), glucose metabolism (plasma glucose, HbA1c, serum insulin), renal function (UACR, PCR), and blood pressure (SBP, DBP) were assessed. APOE variant frequencies were determined using restriction fragment length polymorphism (RFLP) analysis, validated against Hardy-Weinberg equilibrium (HWE), and statistically correlated with each clinical and biochemical parameter. The DN group had an increased prevalence of hypertension, fatty liver, and dyslipidemia compared to the Control group. Biochemical analyses revealed elevated levels of TC (213.41mg/dL vs. 189.32mg/dL), LDL-C (134.46mg/dL vs. 107.56mg/dL), and reduced HDL-C (58.13mg/dL vs. 65.32mg/dL) in DN cases compared to Controls (all p < 0.0001). The APOE variants distribution showed a significant increase in E2 allele frequency (69.1% vs. 15.3%) and corresponding homozygous genotype (E2/2: 42.2% vs. 5.6%) in DN cohorts. The study found a higher frequency of E2 allele in the DN group compared to Controls, though no statistically significant risk of DN was linked to this allele. The results suggest a potential association for APOE polymorphisms, requiring broader studies to clarify the role of APOE polymorphisms in DN susceptibility.

Effectiveness of Cognitive Motor Training on Motor Function in Type 2 Diabetes Mellitus Subjects

Effectiveness of Cognitive Motor Training on Motor Function in Type 2 Diabetes Mellitus Subjects

Relationship between self-reported impairments and clinical examination of upper extremity in subjects with type 2 diabetes mellitus

BackgroundUpper Extremity Impairments (UEIs) in type 2 DM(Diabetes Mellitus) usually occur after other complications of DM have occurred and can lead to disability and severely impact the quality of life. This study aimed to identify the UEIs by self-reported questionnaire and clinical findings and to investigate whether self-reported impairments conform to clinical findings and whether any vital questions about UEIs can be identified to screen the UEIs quickly in type 2 DM comprehensive assessment. Methods91 medically diagnosed type 2 DM subjects were enlisted at a tertiary care hospital per the inclusion and exclusion criteria to participate in the study. Participants were asked to fill out a self-reported questionnaire regarding UEIs, following which a clinical examination of the upper extremity was performed to identify the UEIs. Results85% of the participants self-reported UEIs. Self-reported shoulder pain was reported by n = 34 (37.3%), stiffness by n = 21(23.1%), and hand weakness by n = 24 (26.4%). Clinical examination of shoulder and hand revealed impairments such as hands against the back in n = 30(33%), lift-off sign in 22(24.1%), decreased finger extension in 11(12.1%), and thenar strength in 9(9.9%). Self-reported shoulder pain and hand stiffness were associated with clinically examined decreased shoulder mobility and rotator cuff (RC) tests (p < 0.05). Grip strength, thenar strength, and Phalen's sign decreased significantly with self-reported hand weakness (p < 0.05). ConclusionSelf-reported shoulder pain and stiffness, hand stiffness, and weakness should be used to identify patients with UEIs needing comprehensive assessment and treatment. Significantly self-reported hand impairments can also be an indication to screen shoulder pathologies.

Prevalence of Urolithiasis in Diabetes Mellitus Patients

Background: Urolithiasis and Diabetic Mellitus are common pathologies in the general population, and the lifetime risk of urolithiasis is 12-15% for a man and 5-15% for a woman with up to 50% of the lifetime recurrence ratio. Recent results of urolithiasis prevalence among the diabetic population are varied from 7-21%. We evaluated the prevalence of urolithiasis in the diabetic population in Hasan Sadikin General Hospital, Bandung. Material and Methods: We performed ultrasound and IVP in diabetic people who have a history of colic or other urinary stone symptoms. The presence of urinary calculi was recorded. Result: From June 2011 to July 2012, 139 diabetic subjects were participated. Mean age was 49,73 years (CI95= 47,79-51,67), and 78,57% were males. We found 14 cases of urolithiasis in diabetes mellitus subjects (10,07%), and 78,57% of them were males. The 4th-decade group diagnosed urolithiasis was 6 subjects (42,86%), which was the largest case found in the diabetic population. Conclusions: The prevalence of urolithiasis in the diabetic population in Hasan Sadikin GH was 10.07% in 2012. Keywords: urolithiasis, diabetic mellitus

Sex-based differences in the associations between abdominal obesity and diabetic retinopathy in diabetic patients with normal weight

PurposeTo investigate sex-specific differences in associations of abdominal obesity indexes, systemic factors, and diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) subjects with normal body mass index (BMI). MethodsThis cross-sectional study comprised 653 T2DM subjects (402 women and 251 men) with normal BMI (18.5 kg/m2<BMI<24.0 kg/m2). All participants completed a standard questionnaire and underwent comprehensive ocular and systemic examinations. Anthropometric parameters were measured and recorded, including weight, height, waist circumference (WC), hip circumference, waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR). Sex-specific associated factors for DR were assessed using logistic regression models. ResultsIn the multivariate logistic regressions, the presence of any DR was associated with a longer duration of T2DM (OR = 1.07, p = 0.007) and higher HbA1c (OR = 1.40, p = 0.001) in women, while any DR was associated with younger age at T2DM diagnosis (OR = 0.94, p = 0.020) and higher HbA1c (OR = 1.29, p = 0.011) in men. For women, we identified a positive association between WC (OR = 1.07, p = 0.011), WHR (OR = 1.67, p = 0.002), and WHtR (OR = 1.57, p = 0.004) with any DR after adjusting for confounders, and the third tertiles of WC (OR = 2.29, p = 0.028), WHR (OR = 3.03, p = 0.003), and WHtR (OR = 2.84, p = 0.007) were at high risk of any DR. For men, there were no associations between abdominal obesity indexes and any DR in either continuous variables or categorical variables (all p > 0.05). Main conclusionsThere were sex differences in the relationships between WC, WHR, WHtR, and DR in this T2DM population with normal BMI. Our findings provide new insight into a sex-specific mechanism of DR and management of the condition.

Glycemic Control in Diabetic Patients Receiving a Diabetes-Specific Nutritional Enteral Formula: A Case Series in Home Care Settings.

In patients with Diabetes Mellitus (DM), Enteral Nutrition (EN) is associated with less hyperglycemia and lower insulin requirements compared to Parenteral Nutrition (PN). The primary aim of this study was to assess changes in glycemic control (GC) in DM patients on EN therapy. The secondary objectives included evaluating the impact of the specialized formula on various clinical parameters and the tolerability of the nutritional formula by monitoring potential gastrointestinal side effects. We report a case series on the effects of a Diabetes-Specific Formula (DSF) on GC, lipid profile (LP), and renal and hepatic function in a DM cohort receiving EN support. Twenty-two DM subjects with total dysphagia (thirteen men, nine women) on continuous EN were observed. The use of a DSF in EN was associated with an improvement in glycemic indices across all patients studied, leading to a reduction in average insulin demand. No hospitalizations were reported during the study period. The study demonstrated that the use of DSFs in a multi-dimensional home care management setting can improve glycemic control, reduce glycemic variability and insulin need, and positively impact the lipid profile of the DM cohort. The metabolic improvements were supported by the clinical outcomes observed.

Nuclear Factor-Kappa-B Mediates the Advanced Glycation End Product-Induced Repression of Slc2a4 Gene Expression in 3T3-L1 Adipocytes.

Advanced glycated end products (AGEs) are cytotoxic compounds that are mainly increased in diabetes mellitus (DM), kidney failure, inflammation, and in response to the ingestion of AGE-rich diets. AGEs can also impair glycemic homeostasis by decreasing the expression of the Slc2a4 (solute carrier family 2 member 4) gene and its GLUT4 (solute carrier family 2, facilitated glucose transporter member 4) protein in muscle. However, the mechanisms underlying AGE's effect on adipocytes have not been demonstrated yet. This study investigated the effects of AGEs upon Slc2a4/GLUT4 expression in 3T3-L1 adipocytes, as well as the potential role of NFKB (nuclear factor NF-kappa-B) activity in the effects observed. Adipocytes were cultured in the presence of control albumin (CA) or advanced glycated albumin (GA) at concentrations of 0.4, 3.6, and 5.4 mg/mL for 24 h or 72 h. Slc2a4, Rela, and Nfkb1mRNAs were measured by RT-qPCR, GLUT4, IKKA/B, and p50/p65 NFKB subunits using Western blotting, and p50/p65 binding into the Slc2a4 promoter was analyzed by chromatin immunoprecipitation (ChIP) assay. GA at 0.4 mg/mL increased Slc2a4/GLUT4 expression after 24 h and 72 h (from 50% to 100%), but at 5.4 mg/mL, Slc2a4/GLUT4 expression decreased at 72 h (by 50%). Rela and Nfkb1 expression increased after 24 h at all concentrations, but this effect was not observed at 72 h. Furthermore, 5.4 mg/mL of GA increased the p50/p65 nuclear content and binding into Slc2a4 at 72 h. In summary, this study reveals AGE-induced and NFKB-mediated repression of Slc2a4/GLUT4 expression. This can compromise the adipocyte glucose utilization, contributing not only to the worsening of glycemic control in DM subjects but also the impairment of glycemic homeostasis in non-DM subjects under the high intake of AGE-rich foods.

The Role of Pro-Inflammatory Chemokines CCL-1, 2, 4, and 5 in the Etiopathogenesis of Type 2 Diabetes Mellitus in Subjects from the Asir Region of Saudi Arabia: Correlation with Different Degrees of Obesity.

Type 2 diabetes mellitus (T2DM) is becoming a major global health concern, especially in developing nations. The high prevalence of obesity and related diabetes cases are attributed to rapid economic progress, physical inactivity, the consumption of high-calorie foods, and changing lifestyles. We investigated the roles of pro-inflammatory chemokines CCL1, 2, 4, and 5 in T2DM with varying levels of obesity in the Asir region of Saudi Arabia. In total, 170 confirmed T2DM subjects and a normal control group were enrolled. Demographic data, serum levels of CCL-1, 2, 4, and 5, and biochemical indices were assessed in the subjects and control groups by standard procedures. T2DM subjects were divided into four groups: A (normal body weight), B (overweight), C (obese), and D (highly obese). We observed that male and female control subjects had similar mean serum concentrations of pro-inflammatory chemokines CCL-1, 2, 4, and 5. T2DM subjects in all the four groups showed significantly higher levels of all the four chemokines compared to the controls, regardless of gender. In T2DM subjects with obesity and severe obesity, the rise was most significant. There was a progressive rise in the concentrations of CCL-1, 2, and 4 in T2DM subjects with increasing BMI. Serum CCL5 levels increased significantly in all T2DM subject groups. The increase in CCL5 was more predominant in normal-weight people, compared to overweight and obese T2DM subjects. Male and female control subjects had similar serum levels of pro-inflammatory chemokines CCL-1, 2, 4, and 5. The progressive rise in blood concentrations of three pro-inflammatory chemokines CCL-1, 2, and 4 in T2DM subjects with increasing BMI supports the idea that dyslipidemia and obesity contribute to chronic inflammation and insulin resistance. Serum CCL5 levels increased significantly in all T2DM subject groups. The selective and more pronounced increase in CCL5 in the T2DM group with normal BMI, compared to subjects with varying degrees of obesity, was rather surprising. Further research is needed to determine if CCL5 underexpression in overweight and obese T2DM subjects is due to some unexplained counterbalancing processes.

Pattern of Liver Enzymes in Type -2 Diabetes Mellitus Subjects with and without Dyslipidemia

Pattern of Liver Enzymes in Type -2 Diabetes Mellitus Subjects with and without Dyslipidemia

Development of a Physiologically Based Pharmacokinetic Population Model for Diabetic Patients and its Application to Understand Disease-drug-drug Interactions.

The activity changes of cytochrome P450 (CYP450) enzymes, along with the complicated medication scenarios in diabetes mellitus (DM) patients, result in the unanticipated pharmacokinetics (PK), pharmacodynamics (PD), and drug-drug interactions (DDIs). Physiologically based pharmacokinetic (PBPK) modeling has been a useful tool for assessing the influence of disease status on CYP enzymes and the resulting DDIs. This work aims to develop a novel diabetic PBPK population model to facilitate the prediction of PK and DDI in DM patients. First, mathematical functions were constructed to describe the demographic and non-CYP physiological characteristics specific to DM, which were then incorporated into the PBPK model to quantify the net changes in CYP enzyme activities by comparing the PK of CYP probe drugs in DM versus non-DM subjects. The results show that the enzyme activity is reduced by 32.3% for CYP3A4/5, 39.1% for CYP2C19, and 27% for CYP2B6, while CYP2C9 activity is enhanced by 38% under DM condition. Finally, the diabetic PBPK model was developed through integrating the DM-specific CYP activities and other parameters and was further used to perform PK simulations under 12 drug combination scenarios, among which 3 combinations were predicted to result in significant PK changes in DM, which may cause DDI risks in DM patients. The PBPK modeling applied herein provides a quantitative tool to assess the impact of disease factors on relevant enzyme pathways and potential disease-drug-drug-interactions (DDDIs), which may be useful for dosing regimen optimization and minimizing the DDI risks associated with the treatment of DM.

Association Between Corneal Changes and Retinal Oximetry in Diabetes Mellitus.

Diabetes mellitus (DM) causes different corneal changes that are associated with the severity of diabetic retinopathy. To identify the pathophysiological reasons for this, corneal tomography and optical densitometry (COD) were combined with retinal oximetry. Patients with DM and healthy subjects were included in this pilot study. Spatially resolved corneal thickness and COD were assessed using the Pentacam HR (Oculus). The pachymetry difference (PACDiff) was calculated as an indicator of an increase in the peripheral corneal thickness. Oxygen saturation (SO2) of the retinal vessels was measured using the Retinal Vessel Analyzer (Imedos Systems UG). Subsequently, the associations between corneal and retinal parameters were analyzed. Data from 30 patients with DM were compared with those from 30 age-matched healthy subjects. In DM, arterial (P = 0.048) and venous (P < 0.001) SO2 levels were increased, and arteriovenous SO2 difference was decreased (P < 0.001). In patients, PACDiff was higher than that in healthy subjects (P < 0.05), indicating a stronger increase in peripheral corneal thickness. The COD was reduced in DM (P = 0.004). The PACDiff of concentric rings with a diameter of 4 mm (r = -0.404; P = 0.033) to 8 mm (r = -0.522; P = 0.004) was inversely correlated with the arteriovenous SO2 difference. Furthermore, PACDiff 4 mm was negatively associated with arterial SO2 (r = -0.389; P = 0.041), and the COD of the peripheral corneal areas correlated positive with arterial SO2 (COD total 10-12 mm: r = 0.408; P = 0.025). These associations might indicate a common pathogenesis of corneal and retinal changes in DM, which could be caused by reduced oxygen supply, mitochondrial dysfunction, oxidative stress, and cytokine effects.

Impaired Sensitivity to Thyroid Hormones Is Associated With the Change of Abdominal Fat in Euthyroid Type 2 Diabetes Patients: A Retrospective Cohort Study.

Background and Aims: This study is aimed at investigating the potential correlation of thyroid hormone sensitivity with visceral fat area (VFA), subcutaneous fat area (SFA), and body mass index (BMI) among euthyroid type 2 diabetes mellitus (T2DM) subjects. Methods: Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free thyroxine (fT4)/free triiodothyronine (fT3) ratio. These indices were then categorized into quartiles for analysis. The outcomes were the change rates in VFA, SFA, and BMI among the participants. Result: The present study included 921 patients, with a median follow-up of 2.2 years. In multivariate linear regression, when compared to the first quartile, SFA demonstrated a notable decline in the fourth quartile of TFQI, TSHI, and TT4RI (β coefficient = -5.78, -7.83, and - 6.84 cm2 per year), while it significantly increased in the fourth quartile of fT4/fT3 ratio (β coefficient = 6.13 cm2 per year). Similarly, in the fourth quartile of TFQI, TSHI, and TT4RI, VFA decreased significantly, evidenced by β coefficients of -5.14, -4.80, and -4.08 cm2 per year. Yet, among the quartiles of the fT4/fT3 ratio, no discernible trend in VFA was observed. There was no significant association between indices of thyroid hormone sensitivity and change in BMI. Conclusion: Impaired central sensitivity to thyroid hormones was significantly associated with the reduction of VFA and SFA, while impaired peripheral sensitivity was associated with an increase of SFA in euthyroid individuals with T2DM.

Diabetes as a risk factor for pneumococcal disease and severe related outcomes and efficacy/effectiveness of vaccination in diabetic population. Results from meta-analysis of observational studies

AimsTo collect all available evidence on the effect of diabetes mellitus (DM) as a risk factor for pneumococcal disease incidence and related complications, and on the efficacy/effectiveness of vaccines in patients with DM.MethodsTwo distinct systematic searches on MEDLINE, Cochrane, ClinicalTrials.gov and EMBASE databases were performed, one for each meta-analysis, collecting all observational (cohort and case–control) studies and randomized clinical trials performed on humans up to June 1st, 2023.ResultsWe retrieved 36 observational studies comparing risk for pneumococcal disease and related complications in people with or without DM, and 11 studies (1 randomized clinical trial and 10 observational studies) assessing conjugated and polysaccaridic vaccines efficacy/effectiveness on preventing such outcomes. People with DM were at higher risk for Invasive Pneumococcal Disease (unadjusted OR 2.42 [2.00; 2.92]); Case-Fatality Rate (unadjusted OR 1.61 [1.25; 2.07], Pneumococcal pneumonia (unadjusted OR 2.98 [2.76; 3.22), and Intensive care unit admission for pneumococcal disease (unadjusted OR 2.09 [1.20; 3.66]). In diabetic individuals vaccinated with conjugated vaccine, incidence of pneumonia specific for vaccine type in a clinical trial (OR 0.237 [0.008; 0.704]), and hospitalization for overall pneumonia during the year following the polysaccharide vaccination in observational studies (unadjusted OR 0.63 [0.45–0.89]) were significantly lower in comparison with unvaccinated DM subjects, with no significant differences for other outcomes.ConclusionsPeople with diabetes mellitus are at higher risk for less favourable course of pneumococcal disease and should be therefore targeted in vaccination campaigns; more evidence needs to be collected on vaccination outcomes in people with diabetes.

Determination and Correlation of Finger Print Pattern and Blood Grouping in Diabetes Mellitus: An Analytical Study

BACKGROUND: To Determine and correlate between fingerprint patterns and blood group in type II diabetes mellitus. RESULTS: One hundred individuals with type II diabetes mellitus and One hundred normal individuals as controls were selected for study. Fingerprints were obtained by dactyloscopy. Various fingerprint patterns like arches, whorls, loops were studied and correlated with the respective blood group based on ABO system among the volunteer controls and diabetics. After obtaining results, the analysis was made using Chi square test and One way ANOVA which showed, the most predominant fingerprint pattern among the 100 diabetic volunteers is “Arch pattern” and the most predominant blood group was “O” positive among the diabetic volunteers. Also correlating both finger print and blood group “Whorl pattern” with “B” blood group showed higher predominance among the healthy volunteers. CONCLUSIONS: This is the first study correlating finger print pattern with blood grouping in subjects of Diabetes mellitus. Our study findings showed that O positive blood group with arch pattern type of finger print was the most common findings among diabetes. Thus correlating fingerprint pattern and blood grouping act as a early predictor tool for diagnosing Type II Diabetes mellitus.

GLYCOSYLATED HAEMOGLOBIN: A SURROGATE MARKER FOR DYSLIPIDEMIA AND GLYCEMIC INDEX IN TYPE 2 DIABETES MELLITUS SUBJECTS

Glycosylated haemoglobin is the substance formed when glucose chemically combine with haemoglobin molecule. This study examined glycosylated haemoglobin as a possible surrogate marker for dyslipidemia and glycemic index in type 2 diabetes mellitus subjects. A cross- sectional study was carried out in Warri, Delta State with a total of four hundred (400) volunteers recruited comprising of three hundred and twenty (320) diabetes mellitus subjects and eighty (80) apparently healthy subjects. Standard methods were used for anthropometric measurement and biochemical assays. Data were analyzed using statistical package for social sciences (SPSS). Parameters including Blood pressure, body mass index, fasting blood glucose, glycosylated haemoglobin, total cholesterol, triglycerides, LDL-C were significantly higher in diabetic subjects than non- diabetics while HDL-C was significantly lower in diabetics. Glycosylated haemoglobin is positively correlated with blood glucose, cholesterol, triglycerides, and LDL-C but inversely associated with HDL-C. Based on this study, glycosylated haemoglobin has the potential to serve as surrogate marker of dyslipidemia.

Sustained Release of Salicylic Acid for Halting Peri-Implantitis Progression in Healthy and Hyperglycemic Systemic Conditions: A Gottingen Minipig Model.

To develop a peri-implantitis model in a Gottingen minipig and evaluate the effect of local application of salicylic acid poly(anhydride-ester) (SAPAE) on peri-implantitis progression in healthy, metabolic syndrome (MS), and type-2 diabetes mellitus (T2DM) subjects. Eighteen animals were allocated to three groups: (i) control, (ii) MS (diet for obesity induction), and (iii) T2DM (diet plus streptozotocin for T2DM induction). Maxillary and mandible premolars and first molar were extracted. After 3 months of healing, four implants per side were placed in both jaws of each animal. After 2 months, peri-implantitis was induced by plaque formation using silk ligatures. SAPAE polymer was mixed with mineral oil (3.75 mg/μL) and topically applied biweekly for up to 60 days to halt peri-implantitis progression. Periodontal probing was used to assess pocket depth over time, followed by histomorphologic analysis of harvested samples. The adopted protocol resulted in the onset of peri-implantitis, with healthy minipigs taking twice as long to reach the same level of probing depth relative to MS and T2DM subjects (∼3.0 mm), irrespective of jaw. In a qualitative analysis, SAPAE therapy revealed decreased levels of inflammation in the normoglycemic, MS, and T2DM groups. SAPAE application around implants significantly reduced the progression of peri-implantitis after ∼15 days of therapy, with ∼30% lower probing depth for all systemic conditions and similar rates of probing depth increase per week between the control and SAPAE groups. MS and T2DM conditions presented a faster progression of the peri-implant pocket depth. SAPAE treatment reduced peri-implantitis progression in healthy, MS, and T2DM groups.

Effect of Regulated Type-2 Diabetes Mellitus on the Ocular Surface

The aim of this study was to see whether well-regulated Type-2 diabetes mellitus (DM) under than 10 years impacted meibography and tear film break-up time. DM (n=45) and normal subjects (n=45) were recruited. Two years’ mean glycated hemoglobin data were calculated as the regulation indicator. Eye examination followed by noninvasive tear break‑up time (NTBUT) measurement and then meibography were conducted. Regression analyses corrected for age and gender were used for comparisons between groups. Pearson correlation analysis was used to examine the linear relationship between NTBUT and meibomian gland loss to mean glycated hemoglobin. A value of p&lt;0.05 was considered statistically significant. The meiboscale comparisons within groups did not show any statistical difference. The mean meibomian gland loss comparisons between groups for the right lower eyelid (r=0.017, p=0.69), right upper eyelid (r=0.04 p=0.24), left lower eyelid (r=0.009, p=0.68) and left upper eyelid (r=0.027, p=0.13) were all similar. NTBUT for right and left eye were similar between groups (p=0.69 and p=0.36 respectively). Pearson’s correlation did not show any significant correlation between glycated hemoglobin, NTBUT and gland loss. In conclusion, it was found that patients with less than 10-year disease duration under DM regulation had similar ocular surfaces to normal subjects.

Low CD4+ T Cell count among HIV-seronegative Type 2 Diabetes Mellitus patients in Ilorin metropolis

Background and aims: Diabetes Mellitus (DM) is a metabolic disorder that manifests as chronic hyperglycemia accompanied by a dysfunctional metabolism of carbohydrates, lipids, and proteins. Several studies have earlier pointed out several complications associated with the disease and in particular, the sufferer’s susceptibility to various infectious diseases. We therefore sought to investigate the adaptive immune status of the condition, as represented by the assessment of CD4+ T cell count among DM patients. Method: Seventy-six type 2 DM patients were recruited for the study. Thirty (30) age and sex-matched, non-diabetic individuals were enrolled as negative controls. Their fasting blood sugar (FBS), HbA1c, and CD4 count were assayed using standardized procedures. The demographic and clinical data of the studied group and controls were compared with respect to age, sex, BMI, FBS, HbA1c, and CD4+ T cell counts. Result: The mean concentration of glucose (7.82 ± 2.58) and the percentage concentration of HBA1c (8.21 ± 2.31) were significantly higher in DM individuals as against the control (3.67 ± 0.66) (p = 0.0001) and (5.20 ± 0.48) (p = 0.0001) respectively. The CD4+ cell count was also significantly lower in DM subjects (843.58 ± 297.6) when compared with the control (1067.9 ±195.4) (p = 0.035). Conclusion: A significant reduction in CD4+ T cell level was noted among diabetic patients in our study, which could be a contributing factor for aggravating some of the associated complications in DM, especially those that involve susceptibility to infectious diseases. We found out that having Hb-AA is associated with normal or elevated CD4+ T cells in DM patients; whereas having the Hb-AS variant increases the chance of a low CD4+ T cell count. Assessment of CD4+ T cell count should be included as part of periodic investigations in DM patients, especially for those with unresolved complications, in spite of treatment.

High-Throughput Microfluidic Extraction of Platelet-free Plasma for MicroRNA and Extracellular Vesicle Analysis.

Cell-free RNAs and extracellular vesicles (EVs) are valuable biomarkers in liquid biopsies, but they are prone to preanalytical variabilities such as nonstandardized centrifugation or ex vivo blood degradation. Herein, we report a high-throughput and label-free inertial microfluidic device (ExoArc) for isolation of platelet-free plasma from blood for RNA and EV analysis. Unlike conventional inertial microfluidic devices widely used for cell sorting, a submicrometer size cutoff (500 nm) was achieved which completely removed all leukocytes, RBCs, platelets, and cellular debris based on differential lateral migration induced by Dean vortices. The single-step operation also reduced platelet-associated miRNAs (∼2-fold) compared to centrifugation. We clinically validated ExoArc for plasma miRNA profiling (39 samples) and identified a 7-miRNA panel that detects non-small cell lung cancer with ∼90% sensitivity. ExoArc was also coupled with size exclusion chromatography (SEC) to isolate EVs within 50 min with ∼10-fold higher yield than ultracentrifugation. As a proof-of-concept for EV-based transcriptomics analysis, we performed miRNA analysis in healthy and type 2 diabetes mellitus (T2DM) subjects (n = 3 per group) by coupling ExoArc and ExoArc+SEC with quantitative polymerase chain reaction (RT-qPCR) assay. Among 293 miRNAs detected, plasmas and EVs showed distinct differentially expressed miRNAs in T2DM subjects. We further demonstrated automated in-line EV sorting from low volume culture media for continuous EV monitoring. Overall, the developed ExoArc offers a convenient centrifugation-free workflow to automate plasma and EV isolation for point-of-care diagnostics and quality control in EV manufacturing.

7-year follow-up atherosclerotic plaque progression in patients with antiphospholipid syndrome versus diabetes mellitus and healthy controls.

Patients with antiphospholipid syndrome (APS) carry a substantial burden of cardiovascular disease and subclinical atherosclerosis. We aimed to assess a 7-year follow-up atherosclerotic plaque progression in APS patients vs diabetes mellitus (DM) and healthy controls (HC). Eighty-six patients with thrombotic APS, 86 with DM and 86 HC (all age- and sex-matched) who underwent a baseline ultrasound of carotid and femoral arteries were invited for a 7-year follow-up ultrasonography examination. We compared atherosclerosis progression among the three groups and examined determinants of plaque progression in APS patients. Sixty-four APS patients (75% females, 43.8% with primary APS), 58 patients with DM and 66 HC were included in the 7-year ultrasound re-evaluation. New plaque was detected in 51.6%, 36.2% and 25.8% of APS, DM and HC subjects, respectively. After adjusting for traditional cardiovascular risk factors (CVRFs) and baseline plaque presence, APS patients showed a 3-fold (OR = 3.07, p= 0.007) higher risk for atherosclerosis progression vs HC and 2-fold (OR = 2.25, p= 0.047) higher risk than DM patients. In multivariate analysis in the APS group, plaque progression was independently associated with systemic lupus erythematosus (SLE) co-existence (OR = 7.78, p= 0.005) and number of CVRFs (OR = 3.02, p= 0.002), after adjusting for disease-related parameters and CVRF-related medications. Sustained low-density lipoprotein target attainment reduced plaque progression risk (OR = 0.34, p= 0.021). Half of APS patients develop new atherosclerotic plaques over a 7-year follow-up, having a three-times higher risk vs HC. Concomitant SLE and number of traditional CVRFs are associated with plaque progression, supporting the need for thorough CVRF assessment and control.