Overt Proteinuria Research Articles

DPDCD: The Intelligent Prediction Strategy for the Course Development of Diabetic Kidney Disease

Diabetic nephropathy (DKD) is a severe diabetes complication and a leading cause of mortality. While urine microalbuminuria and eGFR are common markers, some advanced cases may exhibit normal values. The progression from microalbuminuria to overt proteinuria in DKD is gradual and requires comprehensive physiological tests for diagnosis. This study employs deep reinforcement learning to predict DKD progression based on patients’ physiological data, aiming to assist clinical diagnosis and treatment. A multivariate logistic regression algorithm is used to describe the DKD prediction probability. An optimized DKD progression prediction algorithm (DPDCD) based on deep reinforcement learning determines the best model coefficients, enabling accurate prediction of DKD progression using routine clinical data. Experimental results demonstrate that DPDCD outperforms other algorithms in predicting DKD progression, providing valuable support for clinicians.

Empagliflozin protects the kidney by reducing toxic ALB (albumin) exposure and preventing autophagic stagnation in proximal tubules

ABSTRACT The renoprotective effects of SLC5A2/SGLT2 (solute carrier 5 (sodium/glucose cotransporter), member 2) inhibitors have recently been demonstrated in non-diabetic chronic kidney disease (CKD), even without overt albuminuria. However, the mechanism underlying this renoprotection is largely unclear. We investigated the renoprotective mechanisms of the SLC5A2 inhibitor empagliflozin with a focus on ALB (albumin) reabsorption and macroautophagy/autophagy in proximal tubules using wild-type or drug-inducible lrp2/Megalin or atg5 knockout mice with high-fat diet (HFD)-induced obesity or 5/6 nephrectomy that elevated intraglomerular pressure without overt albuminuria. Empagliflozin treatment of HFD-fed mice reduced several hallmarks of lipotoxicity in the proximal tubules, such as phospholipid accumulation in the lysosome, inflammation and fibrosis. Empagliflozin, which decreases intraglomerular pressure, not only reduced the HFD-induced increase in ALB reabsorption via LRP2 in the proximal tubules (i.e. total nephron ALB filtration), as assessed by urinary ALB excretion caused by genetic ablation of Lrp2, but also ameliorated the HFD-induced imbalance in circulating ALB-bound fatty acids. Empagliflozin alleviated the HFD-induced increase in autophagic demand and successfully prevented autophagic stagnation in the proximal tubules. Similarly, empagliflozin decreased ALB exposure and autophagic demand in 5/6 nephrectomized mice. Finally, empagliflozin reduced HFD-induced vulnerability to ischemia–reperfusion injury, whereas LRP2 blockade and atg5 ablation separately diminished this effect. Our findings indicate that empagliflozin reduces ALB exposure and prevents autophagic stagnation in the proximal tubules even without overt albuminuria. Autophagy improvement may be critical for the renoprotection mediated by SLC5A2 inhibition.

Morphometric Analysis of Different Nephron Segments in Patients with Diabetic Nephropathy and Overt Proteinuria

Morphometric Analysis of Different Nephron Segments in Patients with Diabetic Nephropathy and Overt Proteinuria

Excreted albumin of diabetic microalbuminuria cases exhibits pseudo esterase activity: A new way to explore microalbuminuria, perhaps with more information

BackgroundMicroalbuminuria is associated with several clinical conditions of public health concern. Particularly in diabetic patients, there is routine microalbuminuria screening to understand whether the renal complication has progressed to the microalbuminuria stage or not. Therefore, microalbuminuria detection is a matter of considerable interest. For such detection, the clinical labs rely on immunochemical methods. Nevertheless, the immunochemical methods are believed to be less sensitive for the purpose. So, the need arises for continuous research in the field. We believe that pseudoesterase activity of the excreted albumin in microalbuminuria cases is a potential target. This aspect is investigated here and it is shown that the excreted albumin in diabetic microalbuminuria cases retains its pseudoesterase activity, unlike the overt albuminuria cases. MethodsThe cases of diabetic nephropathy and healthy controls were included in the study. The patients were divided into diabetic controls microalbuminuria, and overt albuminuria group considering the albumin to creatinine ratio (ACR). The urinary proteins of the cases were isolated by centrifugation. The obtained protein pellet was then checked for pseudoesterase activity by electrophoretic and fluorescence-based methods. The CD spectroscopy and LC-MS study was carried out to show the suitability of the substrate for the detection of albumin pseudoesterase activity. To further, understand the structure–function relation, molecular docking studies were carried out. ResultsFrom the CD and LC-MS study the suitability of the used substrate was confirmed. The electrophoretic and fluorescence study showed that the protein of the microalbuminuria group retained the pseudoesterase activity whereas the same is lost in the overt albuminuria group. The molecular docking studies indicated that a change in albumin structure may result in a change in its pseudoesterase activity. ConclusionThe urinary protein of diabetic microalbuminuria cases exhibits pseudoesterase activity. It distinguishes the excreted protein in the diabetic albuminuria group and the overt albuminuria group. This is the first study that showed the retention of pseudoesterase property in excreted albumin. Further, in this study a simple test is developed that distinguishes the excreted albumin in the microalbuminuria group and overt albuminuria group.

Fabry nephropathy: a treatable cause of chronic kidney disease

Fabry disease is a rare X-linked inborn error of metabolism that has a high prevalence of chronic kidney disease (CKD) and renal failure. It is due to the deficiency of the α-galactosidase A (α-Gal) lysosomal enzyme with subsequent accumulation of globotriaosylceramide (Gb3) in lysosomes. In the kidney, the podocyte is the main target of this disease, although all cell types are involved. The podocyte, being terminally differentiated, does not replicate and thus accumulates Gb3 throughout life. Podocytes are injured by Gb3, leading to their detachment from the glomerular basement membrane and subsequent loss in the urine. Albuminuria starts in childhood and progresses to overt proteinuria in the teens and 20 s. CKD ensues with adults starting dialysis at an average age of 42 years. Patients have a high prevalence of stroke and cardiomyopathy with hypertrophic change, heart failure, and dysrhythmias. Patient survival is limited in both genders. Diagnosis is based on the demonstration of a low α-Gal activity and a pathogenic GLA mutation. Clinical features are highly variable, which makes recognition of this condition difficult. Treatment with intravenous recombinant human enzyme replacement therapy (ERT) and oral pharmacologic chaperone are available. Control of proteinuria to 0.5 g/day or less is of critical importance to limit progression to end-stage renal disease. Early initiation of treatment gives the best results, but the optimal age to start is uncertain. Fabry nephropathy remains a challenge due to its multisystem nature, difficult diagnosis, and complicated management. It is important as a treatable cause of CKD.

Evaluation of serum MicroRNA 21, MicroRNA 192 and serum TGFβ1 in type 2 diabetes mellitus patients and their relation to diabetic nephropathy

BackgroundDiabetic nephropathy (DN) is a frequent and long-lasting microvascular consequence that has an established connection with diabetes. It serves as the primary etiological agent of end-stage renal disease, a critical renal disorder that develops on a worldwide level. The molecular pathophysiology of DN is multifactorial, such as transforming growth factor-beta [TGF-β] which affects the expression of miRNAs such as miRNA-21 and miRNA-192 during renal fibrosis. However, to date, the clinical application is inadequate due to discrepancies observed in the published data. This cross-sectional investigation aimed to assess the correlation between serum TGF-β1, miRNA-21 and 192, and glycemic control, metabolic abnormalities, and renal function in patients with type II diabetes.MethodsBased on the albumin/creatinine ratio (ACR), fifty subjects with type II diabetes were divided into three categories: Group I consisted of individuals with normoalbuminuria (n = 16), Group II of microalbuminuria (n = 16), and Group III of overt proteinuria (n = 18). All participants were subjected to the estimation of mature miRNA-21 and miRNA-192 by TaqMan two-step stem loop qRT-PCR and serum TGFβ1 level by ELISA.ResultsThere was an upregulation in miRNA-21 expression in the 3 different groups of patients (p value = 0.043). The serum fold change (FC) of miRNA-21 showed significantly greater median values in patients with overt proteinuria compared to those with normoalbuminuria (5.57 FC versus 1.11 FC, p = 0.017). A positive correlation (r = 0.343) (p = 0.013) was observed between the ACR and the median levels of miRNA-21, which was statistically significant. No statistically significant distinctions were detected in the concentrations of serum TGF-β1 or miRNA-192 among the three patient groups (p values of 0.234 and 0.225, respectively).ConclusionThe findings of the present research implied that miRNA-21 might function as an early indicator of renal pathology associated with diabetes mellitus (DM).

Oral alkalinizing supplementation suppressed intrarenal reactive oxidative stress in mild-stage chronic kidney disease: a randomized cohort study.

The beneficial effects of oral supplements with alkalinizing agents in patients with chronic kidney disease (CKD) have been limited to the severe stages. We investigated whether two types of supplements, sodium bicarbonate (SB) and potassium citrate/sodium citrate (PCSC), could maintain renal function in patients with mild-stage CKD. This was a single-center, open-labeled, randomized cohort trial. Study participants with CKD stages G2, G3a, and G3b were enrolled between March 2013 and January 2019 and randomly assigned by stratification according to age, sex, estimated glomerular filtration rate (eGFR), and diabetes. They were followed up for 6months (short-term study) for the primary endpoints and extended to 2years (long-term study) for the secondary endpoints. Supplementary doses were adjusted to achieve an early morning urinary pH of 6.8-7.2. We observed renal dysfunction or new-onset cerebrovascular disease and evaluated urinary surrogate markers for renal injury. Overall, 101 participants were registered and allocated to three groups: standard (n = 32), SB (n = 34), and PCSC (n = 35). Two patients in the standard group attained the primary endpoints (renal stones and overt proteinuria) but were not statistically significant. There was one patient in the standard reduced eGFR during the long-term study (p = 0.042 by ANOVA). SB increased proteinuria (p = 0.0139, baseline vs. 6months), whereas PCSC significantly reduced proteinuria (p = 0.0061, baseline vs. 1year, or p = 0.0186, vs. 2years) and urinary excretion of 8-hydroxy-2'-deoxyguanosine (p = 0.0481, baseline vs. 6months). This study is the first to report supplementation of PCSC reduced intrarenal oxidative stress in patients with mild-stage CKD.

Association of podocyte ultrastructural changes with proteinuria and pathological classification in type 2 diabetic nephropathy

AimsPodocyte injury plays an essential role in the progression of diabetic nephropathy (DN). The associations between the ultrastructural changes of podocyte with proteinuria and the pathological classification of DN proposed by Renal Pathology Society (RPS) have not been clarified in patients with type 2 diabetic nephropathy (T2DN). MethodsWe collected 110 patients with kidney biopsy-confirmed T2DN at Peking University First Hospital from 2017 to 2022. The morphometric analysis on the podocyte foot process width (FPW) and podocyte detachment (PD) as markers of podocyte injury was performed, and the correlations between the ultrastructural changes of podocytes with severity of proteinuria and the RPS pathological classification of DN were analyzed. ResultsMean FPW was significantly broader in the group of T2DN patients with nephrotic proteinuria (565.1 nm) than those with microalbuminuria (437.4 nm) or overt proteinuria (494.6 nm). The cut-off value of FPW (> 506 nm) could differentiate nephrotic proteinuria from non-nephrotic proteinuria with a sensitivity of 75.3% and a specificity of 75.8%. Percentage of PD was significantly higher in group of nephrotic proteinuria (3.2%) than that in microalbuminuria (0%) or overt proteinuria (0.2%). FPW and PD significantly correlated with proteinuria in T2DN (r = 0.473, p < 0.001 and r = 0.656, P < 0.001). FPW and PD correlated with RPS pathological classification of T2DN (r = 0.179, P = 0.014 and r = 0.250, P = 0.001). FPW value was increased significantly with more severe DN classification (P for trend =0.007). The percentage of PD tended to increase with more severe DN classification (P for trend = 0.017). ConclusionsPodocyte injury, characterized by FPW broadening and PD, was associated with the severity of proteinuria and the pathological classification of DN.

#2199 Kidney involvement aspects in women with Fabry disease from the Romanian cohort

Abstract Background and Aims Fabry disease (FD) is an X-linked rare lysosomal storage disease causing progressive nervous system, kidney and heart disorders. Progressive kidney impairment is common, and an important cause of morbidity and mortality. In FD females, treatment guidelines recommend therapy initiation when there is evidence of organ involvement, but determining the proper moment to start FD specific treatment could be a real challenge in the cases. The aim of our retrospective study is to investigate clinical and histological aspects of kidney involvement in female patients with genetically confirmed FD evaluated in our Expert Center for Rare Diseases of the Reno-Urinary System between 2015–2023, with focus on the clinical phenotype and initiation of FD specific treatment. Method All patients had comprehensive assessment for target organ manifestations of Fabry disease. Renal function was assessed using serum creatinine, albumin creatinine ratio and proteinuria. Also, 14 (40%) FD females underwent kidney biopsy (KB) in order to reveal the FD specific lesions and/or to establish the indication for FD pathogenic therapy. Kidney biopsy specimens were analyzed by light and electron microscopy. Results Our study included 35 heterozygous adult females with FD from 25 unrelated families. Most females (91.4%) were diagnosed through family screening, while 3 females (8.6%) were index cases. The mean age at diagnosis was 43.8 ± 15.3 years (range 17-73 years), although mean age of symptoms onset was 34.3 ± 13.5 years (range 14-61 years). Six women from our cohort were considered healthy carriers, three females presented only neurological manifestations, nine patients had combined renal and neurological involvement, one patient had cardiac and renal involvement and the others presented multiple organ involvement. Significant co-morbidities were: arterial hypertension in 13 patients, diabetes mellitus in 2 patients, and obesity in 9 patients. Overall baseline mean eGFR was 79.9 ± 28.2 (range 25-135) ml/min/1.73 m2. Eleven patients had no obvious kidney involvement, 10 patients presented chronic kidney disease (CKD) stage 2, 11 patients CKD stage 3, one CKD stage 4 and 1 was hemodialyzed. Seventeen patients presented normal UACR, thirteen patients showed microalbuminuria, and four patients presented macroalbuminuria. Overt proteinuria (&amp;gt; 0.3 g/24 h) was noticed in 8 patients. Thirteen females performed KB before the initiation of FD specific treatment, and one patient was already treated. At the moment of KB, five patients had normal biologic kidney assessment, three patients presented CKD stage 2 (microalbuminuria in 2 cases and proteinuria in 1 case), and five patients presented CKD stage 3 (normoalbuminuria in 1 case, microalbuminuria in 1 case and overt proteinuria in 3 cases). All KBs showed lysosomal accumulation in the podocytes, 92.8% showed inclusions in the parietal cells of the Bowman capsule, 85.7% in the tubules, while vascular inclusions were found in 78.5% of cases. Also, we observed segmental glomerular sclerosis in 5 cases, interstitial fibrosis and tubular atrophy in 3 cases, each. Only 2 patients were treated with pathogenic therapy before the first evaluation in our center. After multidisciplinary evaluation, 22 patients (62.8%) from our cohort received recommendation to initiate FD specific treatment, and 11 patients entered in our follow-up program. Evidence of specific FD lesions in KB was a strong reason to support the recommendation to initiate FD specific treatment. Conclusion Our results showed that kidney involvement in FD females can vary from asymptomatic or mildly symptomatic, to severely symptomatic, with end stage kidney disease. Thus, females should be carefully evaluated and monitored in a multidisciplinary team, in order to diagnosed FD affected organs. Also, we underline that a normal standard assessment of the kidney cannot rule out kidney involvement in female patients with FD, and strengthen the importance of KB for detection of early kidney involvement and for additional support for early initiation of FD specific therapy.

Urgency or Emergency – A Report on Hypertensive Crisis with Severe Retinopathy

Hypertensive crisis is a common condition encountered in primary care clinics. It may result from uncontrolled hypertension or a known cardiovascular risk disease but may also be the first occurrence of undiagnosed secondary hypertension. However, there is confusion on the classification of whether certain atypical presentations, particularly in young patients without acute symptoms and exact duration of symptoms, are to be considered as hypertensive urgency or emergency. Some abnormal signs, such as proteinuria or retinopathy, could be signs of an existing progression of underlying chronic disease rather than a manifestation of acute hypertensive crisis. Nonetheless, in any situation where the findings have occurred recently without prior follow-up, they should be treated as if they are signs of an acute hypertensive crisis. Bedside clues, such as concomitant anaemia and proteinuria, are valid evidence for the presence of end-stage renal disease (ESRD) causing the hypertensive crisis, even without the features of fluid overload or failure symptoms. We report the case of a young man presented with an acute hypertensive crisis with an isolated one-month history of blurred vision. Despite the initial dilemma, the case was treated as a hypertensive emergency due to the presence of retinopathy and overt proteinuria. The renal profile later confirmed that the patient had ESRD. This case proves that ESRD is still possible even in a young patient without a long medical history or other supporting signs. Making the right decision on the first visit saved the patient’s life.

Interactive exploration of adverse events and multimorbidity in CKD.

Persons with chronic kidney disease (CKD) are at increased risk of adverse events, early mortality, and multimorbidity. A detailed overview of adverse event types and rates from a large CKD cohort under regular nephrological care is missing. We generated an interactive tool to enable exploration of adverse events and their combinations in the prospective, observational German CKD (GCKD) study. The GCKD study enrolled 5217 participants under regular nephrological care with an estimated glomerular filtration rate of 30-60 or >60mL/min/1.73m2 and an overt proteinuria. Cardio-, cerebro- and peripheral vascular, kidney, infection, and cancer events, as well as deaths were adjudicated following a standard operation procedure. We summarized these time-to-event data points for exploration in interactive graphs within an R shiny app. Multivariable adjusted Cox models for time to first event were fitted. Cumulative incidence functions, Kaplan-Meier curves and intersection plots were used to display main adverse events and their combinations by sex and CKD etiology. Over a median of 6.5 years, 10271 events occurred in total and 680 participants (13.0%) died while 2947 participants (56.5%) experienced any event. The new publicly available interactive platform enables readers to scrutinize adverse events and their combinations as well as mortality trends as a gateway to better understand multimorbidity in CKD: incident rates per 1000 patient-years varied by event type, CKD etiology, and baseline characteristics. Incidence rates for the most frequent events and their recurrence were 113.6 (cardiovascular), 75.0 (kidney), and 66.0 (infection). Participants with diabetic kidney disease and men were more prone to experiencing events. This comprehensive explorative tool to visualize adverse events (https://gckd.diz.uk-erlangen.de/), their combination, mortality, and multimorbidity among persons with CKD may manifest as a valuable resource for patient care, identification of high-risk groups, health services, and public health policy planning.

Urinary Angiotensinogen Displays Sexual Dimorphism in Non-Diabetic Humans and Mice with Overweight.

Increased body weight (BW) induces inappropriate renin-angiotensin system (RAS) activation. The activation of the intrarenal RAS is associated with increased urinary angiotensinogen (uAGT), blood pressure (BP), and kidney damage. Here, we examined uAGT excretion levels in young non-diabetic human subjects with overweight (OW) and non-diabetic mice with high-fat diet (HFD)-induced OW. Human subjects (women and men; 20-28 years old) included two groups: (a) overweight (OW, n = 17, BMI ≥ 25); and (b) controls (normal weight (NW; n = 26, BMI ≤ 25). In these subjects, we measured BP, albuminuria, and protein levels of uAGT by ELISA adjusted by urinary creatinine (expressed by uAGT/uCrea). Mice (female and male C57BL/6J mice, 8 ± 2 weeks of age) also included two groups: HFD or normal fat diet (NFD) fed for 8 weeks. We measured BW, fasting blood glucose (FBG), BP by telemetry, albuminuria, and uAGT by ELISA. In humans: (i) no significant changes were observed in BP, albuminuria, and FBG when comparing NW and OW subjects; (ii) multivariate logistic regression analysis of independent predictors related to uAGT/uCrea levels demonstrated a strong association between uAGT and overweight; (iii) urinary reactive oxygen species (ROS) were augmented in men and women with OW; (iv) the uAGT/uCrea ratio was higher in men with OW. However, the uAGT/uCrea values were lower in women even with OW. In mice: (i) males fed an HFD for 8 weeks became OW while females did not; (ii) no changes were observed either in FBG, BP, or albuminuria; (iii) kidney ROS were augmented in OW male mice after 28 weeks but not in females; (iv) OW male mice showed augmented excretion of uAGT but this was undetectable in females fed either NFD or HFD. In humans and mice who are OW, the urinary excretion of AGT differs between males and females and overcomes overt albuminuria.

Angiotensin II type 1 receptor-associated protein deletion combined with angiotensin II stimulation accelerates the development of diabetic kidney disease in mice on a C57BL/6 strain.

The progress in the research field of diabetic kidney disease (DKD) has been disturbed by the lack of reliable animal models. Angiotensin II (Ang II) type 1 receptor (AT1R)-associated protein (ATRAP) promotes internalization of AT1R and selectively inhibits pathological AT1R signaling. In this study, we investigated whether overactivation of the renin-angiotensin system (RAS) through a combination of ATRAP deletion with Ang II stimulation developed a progressive DKD model in C57BL/6 mice, which are resistant to the development of kidney injury. Eight-week-old male systemic ATRAP-knockout mice on the C57BL/6 strain (KO) and their littermate wild-type mice (Ctrl) were divided into five groups: 1) Ctrl, 2) Ctrl-streptozotocin (STZ), 3) KO-STZ, 4) Ctrl-STZ-Ang II, and 5) KO-STZ-Ang II. Ang II was administered for 6 weeks from 4 weeks after STZ administration. At 10 weeks after STZ administration, mice were euthanized to evaluate kidney injuries. Neither ATRAP deletion alone nor Ang II stimulation alone developed a progressive DKD model in STZ-induced diabetic C57BL/6 mice. However, a combination of ATRAP deletion with Ang II stimulation accelerated the development of DKD as manifested by overt albuminuria, glomerular hypertrophy, podocyte loss, mesangial expansion, kidney interstitial fibrosis and functional insufficiency, concomitant with increased angiotensinogen and AT1R expression in the kidneys. In STZ-induced diabetic C57BL/6 mice that are resistant to the development of kidney injury, the combination of ATRAP deletion and Ang II stimulation accelerates the development of DKD, which may be associated with intrarenal RAS overactivation.

Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort

Mineral and bone disorder (MBD) in chronic kidney disease (CKD) is tightly linked to cardiovascular disease (CVD). In this study, we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular (CV) outcomes and mortality. In 5 217 participants of the German CKD (GCKD) study enrolled with an estimated glomerular filtration rate (eGFR) between 30–60 mL·min−1 per 1.73 m2 or overt proteinuria, serum osteoprotegerin (OPG), C-terminal fibroblast growth factor-23 (FGF23), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), cross-linked C-telopeptide of type 1 collagen (CTX1), procollagen 1 intact N-terminal propeptide (P1NP), phosphate, calcium, and 25-OH vitamin D were measured at baseline. Participants with missing values among these parameters (n = 971) were excluded, leaving a total of 4 246 participants for analysis. During a median follow-up of 6.5 years, 387 non-CV deaths, 173 CV deaths, 645 nonfatal major adverse CV events (MACEs) and 368 hospitalizations for congestive heart failure (CHF) were observed. OPG and FGF23 were associated with all outcomes, with the highest hazard ratios (HRs) for OPG. In the final Cox regression model, adjusted for CV risk factors, including kidney function and all other investigated biomarkers, each standard deviation increase in OPG was associated with non-CV death (HR 1.76, 95% CI: 1.35–2.30), CV death (HR 2.18, 95% CI: 1.50–3.16), MACE (HR 1.38, 95% CI: 1.12–1.71) and hospitalization for CHF (HR 2.05, 95% CI: 1.56–2.69). Out of the nine biomarkers examined, stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.

Characteristics of glucose change in diabetes mellitus generalized through continuous wavelet transform processing: A preliminary study.

The continuous glucose monitoring (CGM) system has become a popular evaluation tool for glucose fluctuation, providing a detailed description of glucose change patterns. We hypothesized that glucose fluctuations may contain specific information on differences in glucose change between type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), despite similarities in change patterns, because of different etiologies. Unlike Fourier transform, continuous wavelet transform (CWT) is able to simultaneously analyze the time and fre-quency domains of oscillating data. To investigate whether CWT can detect glucose fluctuations in T1DM. The 60-d and 296-d glucose fluctuation data of patients with T1DM (n = 5) and T2DM (n = 25) were evaluated respectively. Glucose data obtained every 15 min for 356 d were analyzed. Data were assessed by CWT with Morlet form (n = 7) as the mother wavelet. This methodology was employed to search for limited frequency glucose fluctuation in the daily glucose change. The frequency and enclosed area (0.02625 scalogram value) of 18 emerged signals were compared. The specificity for T1DM was evaluated through multiple regression analysis using items that demonstrated significant differences between them as explanatory variables. The high frequency at midnight (median: 75 Hz, cycle time: 19 min) and middle frequency at noon (median: 45.5 Hz, cycle time: 32 min) were higher in T1DM vs T2DM (median: 73 and 44 Hz; P = 0.006 and 0.005, respectively). The area of the > 100 Hz zone at midnight to forenoon was more frequent and larger in T1DM vs T2DM. In a day, the lower frequency zone (15-35 Hz) was more frequent and the area was larger in T2DM than in T1DM. The three-dimensional scatter diagrams, which consist of the time of day, frequency, and area of each signal after CWT, revealed that high frequency signals belonging to T1DM at midnight had a loose distribution of wave cycles that were 17-24 min. Multivariate analysis revealed that the high frequency signal at midnight could characterize T1DM (odds ratio: 1.33, 95% confidence interval: 1.08-1.62; P = 0.006). CWT might be a novel tool for differentiate glucose fluctuation of each type of diabetes mellitus using CGM data.

Analysis of influencing factors and interaction of body weight and disease outcome in patients with prediabetes.

The trend of prediabetes progressing to type 2 diabetes mellitus (T2DM) is prominent, and effective intervention can lead to a return to prediabetes. Exploring the factors influencing the outcome of prediabetes is helpful to guide clinical intervention. The weight change in patients with prediabetes has not attracted much attention. To explore the interaction between body weight and the factors affecting the progression of prediabetes to T2DM. We performed a retrospective analysis of 236 patients with prediabetes and 50 with normal glucose tolerance (NGT), and collected clinical data and follow-up results of all patients. Based on natural blood glucose outcomes, we classified 66 patients with progression to T2DM into the disease progression (DP) group, and 170 patients without progression to T2DM into the disease outcome (DO) group. We analyzed the factors that influenced prediabetes outcome and the influence of body weight on prediabetes blood glucose outcome by unconditional logistic regression. A general linear model (univariate) was used to analyze the inter-action between body weight and independent influencing factors. There were 98 cases of impaired fasting glucose (IFG), 90 cases of impaired glucose tolerance (IGT), and 48 cases of coexistent IFG and IGT. The body weight, waist circumference, body mass index, fasting blood glucose, and 2 h plasma glucose of patients with IFG, IGT, and coexistent IFG and IGT were higher than those in patients with NGT (P < 0.05). Logistic regression analysis showed that body weight, glycosylated hemoglobin, uric acid, fasting insulin, and homeostatic model assessment for insulin resistance were independent factors affecting progression of prediabetes to T2DM (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve predicted by the above indicators combined was 0.905 [95% confidence interval (CI): 0.863-0.948], which was greater than that predicted by each indicator alone. Logistic regression analysis with baseline body weight as an independent variable showed that compared with body weight 1, the odds ratio (95%CI) of body weight 3 was 1.399 (1.142-2.126) (P = 0.033). There was a multiplicative interaction between body weight and uric acid (β = 1.953, P = 0.005). High body weight in patients with prediabetes is an independent risk factor for progression to T2DM, and the risk of progression is increased when coexisting with high uric acid level.

Accessibility and utilization of healthcare services among diabetic patients: Is diabetes a poor man's ailment?

Diabetes is a non-communicable ailment that has adverse effects on the individual's overall well-being and productivity in society. The main objective of this study was to examine the empirical literature concerning the association between diabetes and poverty and the accessibility and utilization of medical care services among diabetic patients. The diabetes literature was explored using a literature review approach. This review revealed that diabetes is an ailment that affects all individuals irrespective of socioeconomic status; however, its pre-valence is high in low-income countries. Hence, despite the higher prevalence of diabetes in developing countries compared with developed countries, diabetes is not a poor man's ailment because it affects individuals of all incomes. While the number of diabetic patients that access and utilize diabetes medical care services has increased over the years, some personal and institutional factors still limit patients' access to the use of diabetes care. Also, there is a lacuna in the diabetes literature concerning the extent of utilization of available healthcare services by diabetic patients.

Effect of individualized nutrition interventions on clinical outcomes of pregnant women with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) can lead to excessive pregnancy weight gain (PWG), abnormal glucolipid metabolism, and delayed lactation. Therefore, it is necessary to provide appropriate and effective interventions for pregnant women with GDM. To clarify the effects of individualized nutrition interventions on PWG, glucolipid metabolism, and lactation in pregnant women with GDM. The study population consisted of 410 pregnant women with GDM who received treatment at the Northern Jiangsu People's Hospital of Jiangsu Province and Yangzhou Maternal and Child Health Hospital between December 2020 and December 2022, including 200 who received routine in-terventions [control (Con) group] and 210 who received individualized nutrition interventions [research (Res) group]. Data on PWG, glucolipid metabolism [total cholesterol, (TC); triglycerides (TGs); fasting blood glucose (FPG); glycosylated hemoglobin (HbA1c)], lactation time, perinatal complications (cesarean section, premature rupture of membranes, postpartum hemorrhage, and pregnancy-induced hypertension), and neonatal adverse events (premature infants, fetal macrosomia, hypo-glycemia, and respiratory distress syndrome) were collected for comparative analysis. The data revealed markedly lower PWG in the Res group vs the Con group, as well as markedly reduced TG, TC, FPG and HbA1c levels after the intervention that were lower than those in the Con group. In addition, obviously earlier lactation and statistically lower incidences of perinatal complications and neonatal adverse events were observed in the Res group. Individualized nutrition interventions can reduce PWG in pregnant women with GDM, improve their glucolipid metabolism, and promote early lactation, which deserves clinical promotion.

Effects of insulin aspart and metformin on gestational diabetes mellitus and inflammatory markers

Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic opportunities offered by novel drugs.

Multifaceted relationship between diabetes and kidney diseases: Beyond diabetes.

Diabetes mellitus is one of the most common causes of chronic kidney disease. Kidney involvement in patients with diabetes has a wide spectrum of clinical presentations ranging from asymptomatic to overt proteinuria and kidney failure. The development of kidney disease in diabetes is associated with structural changes in multiple kidney compartments, such as the vascular system and glomeruli. Glomerular alterations include thickening of the glomerular basement membrane, loss of podocytes, and segmental mesangiolysis, which may lead to microaneurysms and the development of pathognomonic Kimmelstiel-Wilson nodules. Beyond lesions directly related to diabetes, awareness of the possible coexistence of nondiabetic kidney disease in patients with diabetes is increasing. These nondiabetic lesions include focal segmental glomerulosclerosis, IgA nephropathy, and other primary or secondary renal disorders. Differential diagnosis of these conditions is crucial in guiding clinical management and therapeutic approaches. However, the relationship between diabetes and the kidney is bidirectional; thus, new-onset diabetes may also occur as a complication of the treatment in patients with renal diseases. Here, we review the complex and multifaceted correlation between diabetes and kidney diseases and discuss clinical presentation and course, differential diagnosis, and therapeutic oppor-tunities offered by novel drugs.