Background: Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD. Methods: We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573). Results: Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria. Conclusion Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.

Background/Aims: Colonic stenting plays a vital role in the management of acute malignant colonic obstruction. The increasing use of self-expandable metal stents (SEMS) and the diverse challenges posed by colonic obstruction at various locations underscore the importance of effective training for colonic stent placement. Methods: All the components of the simulator were manufactured using silicone molding techniques in conjunction with three-dimensional (3D) printing. 3D images sourced from computed tomography scans and colonoscopy images were converted into a stereolithography format. Acrylonitrile butadiene styrene copolymers have been used in fused deposition modeling to produce moldings. Results: The simulator replicated the large intestine from the rectum to the cecum, mimicking the texture and shape of the human colon. It enables training for colonoscopy insertion, cecum intubation, loop reduction, and stenting within stenotic areas. Interchangeable stenotic modules for four sites (rectum, sigmoid colon, descending colon, and ascending colon) were easily assembled for training. These modules integrate tumor contours and blood vessel structures with a translucent center, allowing real-time visualization during stenting. Successful and repeatable demonstrations of stent insertion and expansion using the reusable SEMS were consistently achieved. Conclusions This innovative simulator offers a secure colonic stenting practice across various locations, potentially enhancing clinical outcomes by improving operator proficiency during actual procedures.

Background: Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD. Methods: We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573). Results: Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria. Conclusion Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.

Background/Aims: Colonic stenting plays a vital role in the management of acute malignant colonic obstruction. The increasing use of self-expandable metal stents (SEMS) and the diverse challenges posed by colonic obstruction at various locations underscore the importance of effective training for colonic stent placement. Methods: All the components of the simulator were manufactured using silicone molding techniques in conjunction with three-dimensional (3D) printing. 3D images sourced from computed tomography scans and colonoscopy images were converted into a stereolithography format. Acrylonitrile butadiene styrene copolymers have been used in fused deposition modeling to produce moldings. Results: The simulator replicated the large intestine from the rectum to the cecum, mimicking the texture and shape of the human colon. It enables training for colonoscopy insertion, cecum intubation, loop reduction, and stenting within stenotic areas. Interchangeable stenotic modules for four sites (rectum, sigmoid colon, descending colon, and ascending colon) were easily assembled for training. These modules integrate tumor contours and blood vessel structures with a translucent center, allowing real-time visualization during stenting. Successful and repeatable demonstrations of stent insertion and expansion using the reusable SEMS were consistently achieved. Conclusions This innovative simulator offers a secure colonic stenting practice across various locations, potentially enhancing clinical outcomes by improving operator proficiency during actual procedures.

Background: Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD. Methods: We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573). Results: Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria. Conclusion Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.

Background/Aims: Colonic stenting plays a vital role in the management of acute malignant colonic obstruction. The increasing use of self-expandable metal stents (SEMS) and the diverse challenges posed by colonic obstruction at various locations underscore the importance of effective training for colonic stent placement. Methods: All the components of the simulator were manufactured using silicone molding techniques in conjunction with three-dimensional (3D) printing. 3D images sourced from computed tomography scans and colonoscopy images were converted into a stereolithography format. Acrylonitrile butadiene styrene copolymers have been used in fused deposition modeling to produce moldings. Results: The simulator replicated the large intestine from the rectum to the cecum, mimicking the texture and shape of the human colon. It enables training for colonoscopy insertion, cecum intubation, loop reduction, and stenting within stenotic areas. Interchangeable stenotic modules for four sites (rectum, sigmoid colon, descending colon, and ascending colon) were easily assembled for training. These modules integrate tumor contours and blood vessel structures with a translucent center, allowing real-time visualization during stenting. Successful and repeatable demonstrations of stent insertion and expansion using the reusable SEMS were consistently achieved. Conclusions This innovative simulator offers a secure colonic stenting practice across various locations, potentially enhancing clinical outcomes by improving operator proficiency during actual procedures.

Background: Although the prevalence of diabetic kidney disease (DKD) is increasing, reliable biomarkers for its early detection are scarce. This study aimed to evaluate the association of adenosine and succinate levels and their related pathways, including hyaluronic acid (HA) synthesis, with DKD. Methods: We examined 235 participants and categorized them into three groups: healthy controls; those with diabetes but without DKD; and those with DKD, which was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared the concentrations of urinary adenosine, succinate, and HA and the serum levels of cluster of differentiation 39 (CD39) and CD73, which are involved in adenosine generation, among the groups with DKD or albuminuria. In addition, we performed multiple logistic regression analysis to evaluate the independent association of DKD or albuminuria with the metabolites after adjusting for risk factors. We also showed the association of these metabolites with eGFR measured several years before enrollment. This study was registered with the Clinical Research Information Service (https://cris.nih.go.kr; Registration number: KCT0003573). Results: Urinary succinate and serum CD39 levels were higher in the DKD group than in the control and non-DKD groups. Correlation analysis consistently linked urinary succinate and serum CD39 concentrations with eGFR, albuminuria, and ΔeGFR, which was calculated retrospectively. However, among the various metabolites studied, only urinary succinate was identified as an independent indicator of DKD and albuminuria. Conclusion Among several potential metabolites, only urinary succinate was independently associated with DKD. These findings hold promise for clinical application in the management of DKD.

We observed that treatment with dimethyl α-ketoglutarate (DMK) increased the amount of intracellular α-ketoglutarate significantly more than that of α-ketoglutarate in HaCaT cells. DMK also increased the level of intracellular 4-hydroxyproline and promoted the production of collagen in HaCaT cells. In addition, DMK decreased the production of collagenase and elastase and downregulated the expression of selected matrix metalloproteinases (MMPs), such as MMP-1, MMP-9, MMP-10, and MMP-12, via transcriptional inhibition. The inhibition of MMPs by DMK was mediated by the suppression of the IL-1 signaling cascade, leading to the attenuation of ERK1/2 phosphorylation and AP-1 transactivation. Our study results illustrate that DMK, an alkylated derivative of α-ketoglutarate, increased the level of 4-hydroxyproline, promoted the production of collagen, and inhibited the expression of selected MMPs by affecting the IL-1 cascade and AP-1 transactivation in HaCaT cells. The results suggest that DMK might be useful as an anti-wrinkle ingredient.

Novel strategies are required to reduce the risk of developing diabetes and/or clinical outcomes and complications of diabetes. In this regard, the role of the circadian system may be a potential candidate for the prevention of diabetes. We reviewed evidence from animal, clinical, and epidemiological studies linking the circadian system to various aspects of the pathophysiology and clinical outcomes of diabetes. The circadian clock governs genetic, metabolic, hormonal, and behavioral signals in anticipation of cyclic 24-hour events through interactions between a “central clock” in the suprachiasmatic nucleus and “peripheral clocks” in the whole body. Currently, circadian rhythmicity in humans can be subjectively or objectively assessed by measuring melatonin and glucocorticoid levels, core body temperature, peripheral blood, oral mucosa, hair follicles, rest-activity cycles, sleep diaries, and circadian chronotypes. In this review, we summarized various circadian misalignments, such as altered light-dark, sleep-wake, rest-activity, fasting-feeding, shift work, evening chronotype, and social jetlag, as well as mutations in clock genes that could contribute to the development of diabetes and poor glycemic status in patients with diabetes. Targeting critical components of the circadian system could deliver potential candidates for the treatment and prevention of type 2 diabetes mellitus in the future.

Background: We examined the impact of gout on the end-stage renal disease (ESRD) risk in patients with type 2 diabetes mellitus (T2DM) and determined whether this association differs according to chronic kidney disease (CKD) status. Methods: Using the Korean National Health Insurance Service, this nationwide cohort study enrolled 847,884 patients with T2DM who underwent health checkups in 2009. Based on the presence of CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2) and gout (two outpatient visits or one hospitalization within 5 years), patients were classified into four groups: CKD−Gout−, CKD− Gout+, CKD+Gout−, and CKD+Gout+. Patients with incident ESRD were followed up until December 2018. Results: Among 847,884 patients, 11,825 (1.4%) experienced progression to ESRD. ESRD incidence increased in the following order: 0.77 per 1,000 person-years (PY) in the CKD−Gout− group, 1.34/1,000 PY in the CKD−Gout+ group, 8.20/1,000 PY in the CKD+Gout− group, and 23.06/1,000 PY in the CKD+Gout+ group. The presence of gout modified the ESRD risk in a status-dependent manner. Hazard ratios (HR) were 1.49 (95% confidence interval [CI], 1.32 to 1.69) and 2.24 (95% CI, 2.09 to 2.40) in patients without and with CKD, respectively, indicating a significant interaction (P<0.0001). The CKD+Gout+ group had a markedly higher risk of developing ESRD (HR, 18.9; 95% CI, 17.58 to 20.32) than the reference group (CKD−Gout−). Conclusion Gout substantially enhances the risk of ESRD, even in the absence of CKD. Concurrent CKD and gout synergistically increase the risk of ESRD. Therefore, physicians should carefully screen for hyperuricemia to prevent progression to ESRD.