Role of Urinary Matrix Metalloproteinase-7 (MMP-7) as an Early Marker of Renal Dysfunction in Diabetic Individuals: A Cross-Sectional Study.

BACKGROUND AND OBJECTIVES: The matrix metalloproteinase 7 (MMP-7) level gets heightened in the urine samples of diabetic individuals with impaired renal function. Renal biopsy is seldom offered because of its invasive nature. These concerns spurred the investigation of relationships between urine MMP-7 levels and the renal function of diabetic individuals. Studies exploring this aspect are scarce. We aimed to evaluate the glycemic and renal parameters of female and male individuals with or without type 2 diabetes mellitus (T2DM) or kidney disease. We also assessed the correlation of urine MMP-7 with various parameters. METHODS: This prospective, analytical, cross-sectional study was conducted at Kalinga Institute of Medical Sciences (KIMS), Bhubaneswar, India, from February 2020 to January 2023. Female and male individuals 18-85 years of age diagnosed with either T2DM, hypertension, or kidney disease were assessed for their glycemic indices and renal parameters. Those with both renal disease and T2DM were placed in group A. The diabetic individuals without kidney disease constituted group B. People in group C had neither kidney disease nor T2DM. Patients in group D had kidney disease but were not diabetics. The parameters of the male and female participants in each of the four groups were assessed and compared, including: age, body mass index (BMI), fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), serum urea, serum creatinine, estimated glomerular filtration rate (eGFR), urine albumin, urine creatinine, urine albumin-creatinine ratio (ACR), serum sodium, serum potassium, and urine MMP-7 levels. Furthermore, we correlated urine MMP-7 with all these traits. We used R software (version 4.4.0, Vienna, Austria) for data analysis. RESULTS: Two hundred eighty-seven (87.5%) of the 328 individuals we screened were eligible. Of them, group A had the maximum number (94) of participants, followed by B (75), C (65), and D (53). Males comprised 60.3% (n = 173) of the study population. The median age of the participants was 52.0 (44.0-61.1) years. The intergroup variations were statistically significant (p < 0.001) owing to their glycemic status and renal function. The gender-basis comparison of FBS and HbA1c yielded non-significant differences. On the contrary, assessment of the renal parameters revealed significant differences (p < 0.001) between females and males. The study population had a median urine MMP-7 level of 19.9 (1.1-50.5) µg/L. Significant associations with urine MMP-7 were found with serum creatinine (r = 0.91, p < 0.001), urine ACR (r = 0.86, p < 0.001), and eGFR (r = -0.84, p < 0.001). CONCLUSION: Our study portrayed that male diabetics, in comparison to female diabetics, had greater levels of urine ACR, urine MMP-7, eGFR, and serum creatinine. Moreover, urine ACR, eGFR, and serum creatinine strongly correlated with the urine MMP-7 level.

A comprehensive overview on Micro RNA signature in type 2 diabetes Mellitus and its complications.

MicroRNAs (miRNAs) are small endogenous, non-coding RNA molecules that can modulate the expression of their target genes. Since its discovery, an enormous breakthrough has been established regarding its biogenesis and pathophysiological action, which has revolutionized the field of molecular biology. In addition, recent studies have identified the existence of stable extracellular/circulating miRNAs tissues and in biological fluids like blood where they are safeguarded from endogenous ribonuclease activity. Type 2 diabetes mellitus (T2DM) has emerged as a prime health issue worldwide. Incidence has increased considerably over the past decade. There are various tests that have been employed to diagnose T2DM. But for early detection and development, the establishment of biomarkers are of paramount importance. Contemporary evidence also validates the signature of a set of this epigenetic factor miRNA in the development of various diseases, including T2DM. This article reviews the contemporary corroboration associating miRNAs and T2DM and emphasizes the potential role of miRNA as a circulatory biomarker that could alert the growing prevalence of T2DM. Also, it acknowledges the valuable compendium of information regarding biogenesis and functional role of circulating miRNA in insulin resistance which is intimately linked to T2DM. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01069-1.

Effect of night shift on development of metabolic syndrome among health care workers.

Circadian desynchronization, sleep deprivation, changes in eating habit, and lack of physical activity resulting in an increase in pro-inflammatory markers in night shift health care workers is associated with various risk factors for the development of metabolic syndrome. This study aimed to estimate the pro-inflammatory markers in night shift work and find its relationship with different criteria of metabolic syndrome. Materials and Methods: A total of 303 participants were recruited for the study. Demographic data and parameters pertaining to the development of metabolic syndrome were taken. Highly sensitive C-reactive protein (Hs CRP) as proinflammatory marker was analyzed. Fasting blood sugar (FBS), serum triglyceride (TG), and high-density lipoprotein (HDL) were estimated. Criteria for metabolic syndrome were taken according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) guidelines. Results: Night shift workers had higher hs CRP compared to day shift workers. TG and FBS were increased significantly (P < 0.001). A total of 6.5% of the night shift workers had a waist circumference greater than 40 inches. It was observed that night shift workers with higher hsCRP had significantly high waist circumference (P < 0.001) and FBS (P < 0.05). A total of 3.57% of the night shift workers were diagnosed with metabolic syndrome with three criteria positive. Conclusion: Night shift work is associated with an increase in pro-inflammatory markers and the development of risk factors leading to metabolic syndrome. Thus, early screening and management of risk factors among night shift health care workers may improve their health status and prevent the development of MS.

Urinary MMP-7: A Predictive, Noninvasive Early Marker for Chronic Kidney Disease Development in Patients with Hypertension.

OBJECTIVE: Upregulation of matrix metalloproteinase-7 (MMP-7) is associated with hypertension and kidney fibrosis, which can progress to chronic kidney disease (CKD). Currently, kidney fibrosis is only detectable by an invasive procedure. Therefore, we set out to determine whether MMP-7 can act as a noninvasive biomarker in patients with hypertension to enable early detection of kidney fibrosis. MATERIALS AND METHODS: Diagnosed patients with hypertension and control patients were sampled. We diagnosed CKD using clinical and laboratory parameters. Serum urea, creatinine, urinary microalbumin, the albumin-to-creatinine ratio, and urinary MMP-7 were analyzed. RESULTS: The 195 patients with hypertension had significantly elevated MMP-7. Of these patients, 166 had MMP-7 >25.8 µg/L, whereas only 29 had MMP-7 <25.8 µg/L. Thirty-two patients with hypertension showed features of CKD, all of whom had urinary MMP-7 >25.8 µg/L. However, the urinary MMP-7 level did not differ with the severity of CKD or with the duration of hypertension. CONCLUSION: Elevated urinary MMP-7 can be a potential noninvasive, early indicator in patients with hypertension progressing to CKD, thus enabling early therapeutic intervention.

Is data mining approach a best fit formula for estimation of low-density lipoprotein cholesterol?

BACKGROUND: With the change in the National Cholesterol Education Program ATP III guidelines, the risk of developing atherosclerosis has been now focused on total cholesterol and low-density lipoprotein (LDL) cholesterol levels. Different treatment modalities are now targeted at lowering LDL cholesterol values. Hence greater emphasis is now led on the accurate and precise measurement of LDL cholesterol. Beta-quantification, though, is the best reference method for LDL cholesterol estimation, it has the disadvantage of being inconvenient in our routine practice. The new generation direct homogenous assay is now the method of choice. But being more expensive, various calculated methods have now been developed. This study is an attempt to compare different calculated formula with direct cholesterol assessment and to find out the best one. MATERIALS AND METHODS: We compared LDL cholesterol measured by direct homogenous assay with the data mining approach (DM) and another calculated formula [Friedewald's Formula (FF) and Anandaraja Formula (AF)] in 266 samples with age greater than 18 years. Enrolled participants were divided into seven groups based upon their TG levels. Mean, percentage difference, and the correlation coefficient was assessed between calculated and direct LDL. Bland-Altman analysis was done to see the agreement between calculated vs direct LDL. All formulas were assessed among various TG levels with direct LDL by the Wilcoxon sign rank test. RESULT: 1% level of significance was found between calculated and direct LDL with TG < 600 mg/dl. Mean and the percentage difference between direct and calculated LDL was lowest with the DM approach. Bland-Altman plot shows the best agreement of the DM approach with direct LDL. CONCLUSION: This study indicates that the DM approach is closer to direct LDL compared to FF & AF.

Comparison of test performance of biochemical parameters in semiautomatic method and fully automatic analyzer method.

BACKGROUND: The primary health-care center (PHC) and community health center (CHC) are not well equipped with laboratory services. Semiauto analyzer-based reporting could be an effective modality, provided that the performance standard is comparable to that of the fully automatic analyzer. So, the objective of this study was to analyze the test results of biochemical parameters in semiauto and fully automatic analyzer and to compare the quality performance. MATERIALS AND METHODS: One hundred forty-nine patients undergoing routine biochemical investigations in the department laboratory were enrolled in this study. Two millimeter of venous blood was collected from all the participants and processed for urea, cholesterol, triglyceride (TG), serum glutamate-oxaloacetate transaminase (SGOT) (aspartate aminotransferase), and serum glutamate-pyruvate transaminase (SGPT) (alanine aminotransferase) by using standard kits (ERBA) in semiauto analyzer (Transasia Erba Chem5X by Calbiotech Inc. USA, semiautomated clinical chemistry analyzer) and the fully automatic analyzer (Cobas Integra 400 Roche, Germany) method. RESULTS: There was high variability in the distribution of urea, TG, SGOT, and SGPT values in both measurement methods, whereas cholesterol data followed a normal distribution (skewness: 1.522, 1.037; kurtosis: 2.373, 0.693 in semiauto and automated methods, respectively). A significant positive correlation between both the methods of assessment was observed in urea, cholesterol, TGs, SGOT, and SGPT. The mean difference for urea was -9.85 ± 23.997 (LOA: 37.189, -56.88), whereas it was highest for TG -24.34 ± 38.513 (LOA: 51.144, -99.829), suggesting that both methods can measure urea with less difference in absolute values, whereas for TG the measurement values are highly variable. CONCLUSION: The test performance of biochemical parameters such as urea, total cholesterol, TGs, SGOT, and SGPT taken by semiauto analyzer and fully automatic analyzer method of assessment were highly related and comparable.

Serum Uric Acid in Chronic Obstructive Pulmonary Disease: A Hospital Based Case Control Study.

INTRODUCTION: Airway inflammation and imbalance between oxidant/anti-oxidant mechanisms are postulated to play a major role in the pathogenesis and exacerbation of Chronic Obstructive Pulmonary Disease (COPD). Previous studies on the role of serum Uric Acid (UA) in COPD subjects have been both confounding and inconclusive. AIM: To measure the serum UA levels among COPD subjects and to correlate with different stages of the disease. MATERIALS AND METHODS: The study included 39 stable COPD subjects (21 males, 18 females; 13 smokers, 26 nonsmokers; age group; 40 to 60 years) and compared with 46 control subjects from the general population. Serum UA levels were measured by enzymatic colorimetric assay in fully automated analyser (Cobas Integra 400+, Roche, Germany) using commercially available kits from Roche. This was further correlated with duration and severity of COPD {determined as per Global Initiative for Obstructive Lung Disease (GOLD) criteria}. RESULTS: The mean age of COPD and control subjects was 62.97±11.30 and 48.76±12.71 years, respectively (p<0.001). COPD cases had significantly higher level of UA compared to control subjects (4.85±1.67 vs. 2.32±0.93 mg/dl, respectively, p<0.001). Female subjects with COPD had higher levels of UA compared to their male counterparts (5.15±1.89 vs. 4.59±1.45 mg/dl, respectively, p=0.3). Similar insignificant (p=0.56) trend was also observed among control subjects. Hyperuricaemia correlated significantly (p< 0.05) with advance duration (≥ 10 years) of COPD; whereas, statistically insignificant trend was observed for GOLD stage 3/4 versus stage 1/2 disease. Nonsmokers were having higher uric acid level than smokers. Alcohol intake did not affect the level of uric acid in COPD cases (p=0.79). CONCLUSION: Serum uric acid is a simple, cost effective biochemical test which may be useful in risk stratification of subjects with newly diagnosed chronic obstructive pulmonary disease. Hyperuricaemia is associated with advance duration and stage of COPD.

Ischemia Modified Albumin as a Marker of Oxidative Stress in Normal Pregnancy.

INTRODUCTION: Normal pregnancy is always associated with immense stress in order to accommodate the increasing demands of the developing fetus. Various metabolic changes along with vascular remodeling occur in maternal system. Due to this, pregnancy is always associated with oxidative stress and generation of Reactive Oxygen Species (ROS). Ischemia Modified Albumin (IMA) generated by ROS is found to be sensitive and early biochemical marker of ischemic heart disease and now used as an important marker to distinguish between ischemic and non-ischemic pathologies. Pregnancy being a hypoxic ischemic condition may lead to increase in serum IMA. AIM: The present study was aimed at evaluating maternal serum Ischemia Modified Albumin (IMA) in normal pregnancy and correlate it with serum Malondialdehyde (MDA), a known lipid peroxidation marker. Similarly IMA/Albumin was evaluated for correction of decrease in serum albumin in pregnancy and correlated with serum MDA. MATERIALS AND METHODS: Serum IMA, IMA/Albumin and MDA was analysed in 40 healthy normal pregnant women and 41 non-pregnant healthy controls. Serum IMA was estimated by albumin cobalt binding test. Student t-test and Pearson's correlation coefficient was used for statistical analysis. RESULTS: Serum IMA and IMA/Albumin was significantly higher (p < 0.001) in normal pregnant women (72.54±9.89 U/L, 20.16±3.94) compared to non-pregnant healthy control (48.47±8.30 U/L, 10.51±1.76). Serum MDA was also significantly higher in normal pregnant women. A statistical significant positive correlation was found between serum IMA, IMA/Albumin with MDA in normal pregnant women. CONCLUSION: Maternal serum IMA is also increased in normal pregnancy and its correlation with MDA shows maternal serum IMA, can be considered as the marker of oxidative stress and can be used to monitor the progress of pregnancy, which may be remarkably increased in various complications related to pregnancy.