Eero Lindholm, Linnea Ekman, Targ Elgzyri, Beata Lindholm, Magnus Löndahl, Lars Dahlin
Background: Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes mellitus (T1DM) is declining, but it is not known if this is true also for diabetic neuropathy.
Aim: To investigate the relationship between large fibre diabetic neuropathy and other diabetic complications.
Materials and methods: Neuropathy, defined here as large fibre neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot, using a standard VibroSense Meter and/or neuropathic symptoms, in 599 individuals with T1DM. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications were registered.
Results: Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control participants without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two individuals out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with the rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35-6.49], p=0.007), nephropathy (OR 6.25 [3.21-12.15]; p=6.7×10-8) and macrovascular disease (OR 2.72 [1.50-4.93], p=0.001).
Conclusions: Despite recent changes in the incidence of diabetic complications, the onset of large fibre neuropathy follows that of retinopathy but precedes the onset of nephropathy in T1DM.
{"title":"Diabetic Neuropathy Assessed with Multifrequency Vibrometry Develops Earlier than Nephropathy but Later than Retinopathy.","authors":"Eero Lindholm, Linnea Ekman, Targ Elgzyri, Beata Lindholm, Magnus Löndahl, Lars Dahlin","doi":"10.1055/a-2010-6987","DOIUrl":"https://doi.org/10.1055/a-2010-6987","url":null,"abstract":"<p><strong>Background: </strong>Diabetes is associated with systemic complications. Prevalence of diabetic nephropathy, and retinopathy, in type 1 diabetes mellitus (T1DM) is declining, but it is not known if this is true also for diabetic neuropathy.</p><p><strong>Aim: </strong>To investigate the relationship between large fibre diabetic neuropathy and other diabetic complications.</p><p><strong>Materials and methods: </strong>Neuropathy, defined here as large fibre neuropathy, was assessed by measuring vibration perception thresholds at four different frequencies on the sole of the foot, using a standard VibroSense Meter and/or neuropathic symptoms, in 599 individuals with T1DM. Retinopathy status was graded using the International Clinical Disease Severity Scale. Grade of albuminuria and previous history of any macrovascular complications were registered.</p><p><strong>Results: </strong>Diabetic individuals without retinopathy had similar vibration thresholds as age- and gender-matched control participants without diabetes, whereas those without microalbuminuria had higher thresholds than controls. Two individuals out of 599 (0.3%) had microalbuminuria, but not retinopathy or neuropathy, and 12/134 (9%) without retinopathy had signs of neuropathy. Totally 119/536 (22%) of the patients without microalbuminuria had neuropathy. Vibration thresholds increased with the rising severity of retinopathy and grade of albuminuria. In a multinomial logistic regression analysis, neuropathy was associated with retinopathy (OR 2.96 [1.35-6.49], p=0.007), nephropathy (OR 6.25 [3.21-12.15]; p=6.7×10-8) and macrovascular disease (OR 2.72 [1.50-4.93], p=0.001).</p><p><strong>Conclusions: </strong>Despite recent changes in the incidence of diabetic complications, the onset of large fibre neuropathy follows that of retinopathy but precedes the onset of nephropathy in T1DM.</p>","PeriodicalId":12241,"journal":{"name":"Experimental and Clinical Endocrinology & Diabetes","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9308038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hwa Young Kim, Young Ah Lee, Choong Ho Shin, Tae-Joon Cho, Jung Min Ko
Background: Hypochondroplasia is a skeletal dysplasia caused by activating pathologic variants of FGFR3. The N540K variant accounts for 60-70% of reported cases and is associated with severe manifestations. Here, we analyze the clinical manifestations and outcomes of Korean patients with hypochondroplasia harboring the FGFR3 N540K variant.
Methods: Medical records of 20 unrelated patients with genetically confirmed N540K-related hypochondroplasia were retrospectively reviewed. All individuals were diagnosed with hypochondroplasia by Sanger sequencing for FGFR3, or target-panel sequencing for skeletal dysplasia. The effectiveness of growth hormone therapy was analyzed in 16 patients treated with growth hormones.
Results: Among 20 patients (7 men, 13 women), the mean age at first visit was 3.5±1.0 years, and the mean follow-up duration was 6.8±0.6 years. The patients presented with a short stature and/or short limbs. Genu varum, macrocephaly, and developmental delay were observed in 11 (55.0%), 9 (45.0%), and 5 (25.0%) patients, respectively. Of the 12 patients who underwent neuroimaging, five (41.7%) showed abnormal findings (one required operation for obstructive hydrocephalus). Among 16 growth-hormone-treated patients (two were growth-hormone deficient), the increase in height standard deviation scores was significant after a mean 5.4±0.7 years of treatment (+0.6 and+1.8 using growth references for healthy controls and achondroplasia children, respectively). Four patients underwent surgical limb lengthening at a mean age of 8.8±3.3 years.
Conclusions: Neurodevelopmental abnormalities are frequently observed in patients with N540K-related hypochondroplasia. Close monitoring of skeletal manifestations and neurodevelopmental status is necessary for hypochondroplasia.
{"title":"Clinical Manifestations and Outcomes of 20 Korean Hypochondroplasia Patients with the FGFR3 N540K variant.","authors":"Hwa Young Kim, Young Ah Lee, Choong Ho Shin, Tae-Joon Cho, Jung Min Ko","doi":"10.1055/a-1988-9734","DOIUrl":"https://doi.org/10.1055/a-1988-9734","url":null,"abstract":"<p><strong>Background: </strong>Hypochondroplasia is a skeletal dysplasia caused by activating pathologic variants of <i>FGFR3</i>. The N540K variant accounts for 60-70% of reported cases and is associated with severe manifestations. Here, we analyze the clinical manifestations and outcomes of Korean patients with hypochondroplasia harboring the <i>FGFR3</i> N540K variant.</p><p><strong>Methods: </strong>Medical records of 20 unrelated patients with genetically confirmed N540K-related hypochondroplasia were retrospectively reviewed. All individuals were diagnosed with hypochondroplasia by Sanger sequencing for <i>FGFR3</i>, or target-panel sequencing for skeletal dysplasia. The effectiveness of growth hormone therapy was analyzed in 16 patients treated with growth hormones.</p><p><strong>Results: </strong>Among 20 patients (7 men, 13 women), the mean age at first visit was 3.5±1.0 years, and the mean follow-up duration was 6.8±0.6 years. The patients presented with a short stature and/or short limbs. Genu varum, macrocephaly, and developmental delay were observed in 11 (55.0%), 9 (45.0%), and 5 (25.0%) patients, respectively. Of the 12 patients who underwent neuroimaging, five (41.7%) showed abnormal findings (one required operation for obstructive hydrocephalus). Among 16 growth-hormone-treated patients (two were growth-hormone deficient), the increase in height standard deviation scores was significant after a mean 5.4±0.7 years of treatment (+0.6 and+1.8 using growth references for healthy controls and achondroplasia children, respectively). Four patients underwent surgical limb lengthening at a mean age of 8.8±3.3 years.</p><p><strong>Conclusions: </strong>Neurodevelopmental abnormalities are frequently observed in patients with N540K-related hypochondroplasia. Close monitoring of skeletal manifestations and neurodevelopmental status is necessary for hypochondroplasia.</p>","PeriodicalId":12241,"journal":{"name":"Experimental and Clinical Endocrinology & Diabetes","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9142817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sebastian Dietmar Barth, Karel Kostev, Magdalene Krensel, Elke Mathey, Wolfgang Rathmann
Objectives: To analyze whether prescription use of GLP-1RA and SGLT2i in individuals with type 2 diabetes with cardiovascular disease (CVD) has increased after the ADA/EASD consensus guidelines (2018) in a German Real-World setting and which clinical characteristics are associated with prescription use of these drugs.
Methods: The Disease Analyzer database (IQVIA) comprises a representative panel of 1,373 general practitioners, diabetologists, and cardiologists throughout Germany (01/2015-12/2020: 12.6 million patients). Newly diagnosed type 2 diabetes (n=45,531) was identified by ICD-10 codes (E11). Matching (1:1) on practice specialty, sex, age, and year of diabetes diagnosis was performed for CVD. Logistic regression models were fitted to obtain adjusted odds ratios (OR) for characteristics associated with prescription use (median follow-up: 1.9 years).
Results: Overall, 35% of patients (n=16,006) were treated with glucose-lowering drugs during the first year after type 2 diabetes diagnosis (HbA1c≥7.0%: 80%). GLP-1RA (2.4%) and SGLT2i (8.5%) were rarely prescribed. After the consensus, use of GLP-1RA and SGLT2i increased, however, almost independently of pre-existing CVD (12/2019-11/2020 vs. 12/2017-11/2018: yes, no): GLP-1RA: from 5.7 to 9.2%, 5.2 to 7.6%; SGLT2i: from 13.9 to 20.4%, 12.1 to 16.6%. Among cardiovascular risk factors, the largest OR for GLP-1RA was for obesity (4.5; 95%CI: 3.2-6.3). CVD was moderately related with SGLT2i (1.45; 1.32-1.60) and GLP-1RA (1.35; 1.08-1.69) prescriptions. A weak association was observed between SGLT2i and heart failure (1.18; 95%CI: 1.05-1.32).
Conclusion: National prescription use of GLP-1RA and SGLT2i did not come close to the recommendation in subjects with CVD issued by the 2018 ADA/EASD consensus.
{"title":"Do Glucagonlike Peptide-1 Receptor Agonist and Sodium-glucose Co-transporter 2 Inhibitor Prescriptions in Germany Reflect Recommendations for Type 2 Diabetes with Cardiovascular Disease of the ADA/EASD Consensus Report?","authors":"Sebastian Dietmar Barth, Karel Kostev, Magdalene Krensel, Elke Mathey, Wolfgang Rathmann","doi":"10.1055/a-1927-4454","DOIUrl":"https://doi.org/10.1055/a-1927-4454","url":null,"abstract":"<p><strong>Objectives: </strong>To analyze whether prescription use of GLP-1RA and SGLT2i in individuals with type 2 diabetes with cardiovascular disease (CVD) has increased after the ADA/EASD consensus guidelines (2018) in a German Real-World setting and which clinical characteristics are associated with prescription use of these drugs.</p><p><strong>Methods: </strong>The Disease Analyzer database (IQVIA) comprises a representative panel of 1,373 general practitioners, diabetologists, and cardiologists throughout Germany (01/2015-12/2020: 12.6 million patients). Newly diagnosed type 2 diabetes (n=45,531) was identified by ICD-10 codes (E11). Matching (1:1) on practice specialty, sex, age, and year of diabetes diagnosis was performed for CVD. Logistic regression models were fitted to obtain adjusted odds ratios (OR) for characteristics associated with prescription use (median follow-up: 1.9 years).</p><p><strong>Results: </strong>Overall, 35% of patients (n=16,006) were treated with glucose-lowering drugs during the first year after type 2 diabetes diagnosis (HbA1c≥7.0%: 80%). GLP-1RA (2.4%) and SGLT2i (8.5%) were rarely prescribed. After the consensus, use of GLP-1RA and SGLT2i increased, however, almost independently of pre-existing CVD (12/2019-11/2020 vs. 12/2017-11/2018: yes, no): GLP-1RA: from 5.7 to 9.2%, 5.2 to 7.6%; SGLT2i: from 13.9 to 20.4%, 12.1 to 16.6%. Among cardiovascular risk factors, the largest OR for GLP-1RA was for obesity (4.5; 95%CI: 3.2-6.3). CVD was moderately related with SGLT2i (1.45; 1.32-1.60) and GLP-1RA (1.35; 1.08-1.69) prescriptions. A weak association was observed between SGLT2i and heart failure (1.18; 95%CI: 1.05-1.32).</p><p><strong>Conclusion: </strong>National prescription use of GLP-1RA and SGLT2i did not come close to the recommendation in subjects with CVD issued by the 2018 ADA/EASD consensus.</p>","PeriodicalId":12241,"journal":{"name":"Experimental and Clinical Endocrinology & Diabetes","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9089528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Judith Charlotte Witzel, Anna Giessel, Christina Heppner, Annette Lamersdorf, Andreas Leha, Claus Glueer, Heide Siggelkow
Introduction: Established scores estimate 10-year fracture risk in osteoporosis to assist with treatment recommendations. This study compared the risk probabilities of major osteoporotic and hip fractures calculated by the FRAX tool with those of the DVO score, established in German-speaking countries.
Material and methods: This seven-year retrospective study analyzed data of 125 male patients (mean age: 59.2±10.7 years) evaluated for osteoporosis. For the DVO score, the therapy threshold of>30% for vertebral and hip fractures suggested by DVO guidelines was implemented. We calculated fracture risks based on FRAX scores with aBMD and applied a common therapy threshold of≥3% for hip fracture and subsequently determined the "DVO-equivalent risk level" for FRAX-based assessment that would identify as many male patients as identified by the DVO score.
Results: Based on DVO score, 60.0% of patients had a 10-year risk of hip and vertebral fractures>30%. The recommendations for individuals based on FRAX scores for hip fracture with aBMD with risk≥3% overlapped with those based on DVO score in 36% of patients. Patients identified for treatment only by DVO score presented a higher percentage of spine fractures (65 vs. 41%). The thresholds for this "DVO-equivalent risk level" for 'FRAX with aBMD' was estimated to be≥6.7% for major osteoporotic fracture and≥2.1% for hip fracture.This study demonstrates that the DVO score was more sensitive than the FRAX score for patients with prevalent spinal fractures. We suggest considering the appropriate score and therapy threshold carefully in the daily care of male patients.
{"title":"Discrepancies Between Osteoporotic Fracture Evaluations in Men Based on German (DVO) Osteoporosis Guidelines or the FRAX Score.","authors":"Judith Charlotte Witzel, Anna Giessel, Christina Heppner, Annette Lamersdorf, Andreas Leha, Claus Glueer, Heide Siggelkow","doi":"10.1055/a-1977-4413","DOIUrl":"https://doi.org/10.1055/a-1977-4413","url":null,"abstract":"<p><strong>Introduction: </strong>Established scores estimate 10-year fracture risk in osteoporosis to assist with treatment recommendations. This study compared the risk probabilities of major osteoporotic and hip fractures calculated by the FRAX tool with those of the DVO score, established in German-speaking countries.</p><p><strong>Material and methods: </strong>This seven-year retrospective study analyzed data of 125 male patients (mean age: 59.2±10.7 years) evaluated for osteoporosis. For the DVO score, the therapy threshold of>30% for vertebral and hip fractures suggested by DVO guidelines was implemented. We calculated fracture risks based on FRAX scores with aBMD and applied a common therapy threshold of≥3% for hip fracture and subsequently determined the \"DVO-equivalent risk level\" for FRAX-based assessment that would identify as many male patients as identified by the DVO score.</p><p><strong>Results: </strong>Based on DVO score, 60.0% of patients had a 10-year risk of hip and vertebral fractures>30%. The recommendations for individuals based on FRAX scores for hip fracture with aBMD with risk≥3% overlapped with those based on DVO score in 36% of patients. Patients identified for treatment only by DVO score presented a higher percentage of spine fractures (65 vs. 41%). The thresholds for this \"DVO-equivalent risk level\" for 'FRAX with aBMD' was estimated to be≥6.7% for major osteoporotic fracture and≥2.1% for hip fracture.This study demonstrates that the DVO score was more sensitive than the FRAX score for patients with prevalent spinal fractures. We suggest considering the appropriate score and therapy threshold carefully in the daily care of male patients.</p>","PeriodicalId":12241,"journal":{"name":"Experimental and Clinical Endocrinology & Diabetes","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9090016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ralf Schiel, Mathias Block, Günter Stein, Antje Steveling, Sarah Lücking, Jürgen Scherberich
Introduction: Uromodulin is a kidney-specific tubular protein, and its assessment in serum (sUMOD) reveals the potential as a novel marker for function and the integrity of renal parenchymal cells and does not directly depend on the glomerular filtration rate. Early diabetic nephropathy parallels glomerular hyperfiltration, often leading to diagnostic misinterpretation. Moreover, traditional kidney function markers are not able to diagnose structural lesions. Recent data show that sUMOD is linked to glucose intolerance in adults. Thus, we launched to assess the hypothesis that sUMOD is also associated with kidney function, biometric data, and quality of metabolic control in children/adolescents with type 1 diabetes.
Patients and methods: Patients with type 1 diabetes (n=135) and healthy controls (n=69) were recruited to participate in the trial. Clinical, biometrical data, sUMOD, and other laboratory parameters were assessed.
Results: The mean concentrations of sUMOD in diabetic patients and controls were comparable (201.19±103.22 vs. 198.32±84.27 ng/mL, p=0.832). However, in contrast to healthy controls, sUMOD levels in patients with diabetes were associated with serum-creatinine (r=-0.368, p<0.0001), age (r=-0.350, p<0.0001), height (r=-0.379, p<0.0001), body weight (r=-0.394, p<0.0001), Body mass index (r=-0.292, p=0.001), daily insulin dosage (r=-0.300, p<0.0001), HbA1c (%) (r=-0.190, p=0.027), standardized HbA1c/IFCC (mmol/mol) (r=-0.189, p=0.028), and systolic (r=-0.299, p<0.0001) and diastolic (r=-0.235, p=0.006) arterial blood pressure.
Conclusions: Our study shows that children/adolescents with type 1 diabetes disclose similar sUMOD concentrations as healthy controls. Serum UMOD appears to indicate higher risks for kidney tissue remodeling and possibly subsequent cardiovascular alterations. However, further studies are mandatory to settle these findings.
{"title":"Serum Uromodulin in Children and Adolescents with Type 1 Diabetes Mellitus and Controls: Its Potential Role in Kidney Health.","authors":"Ralf Schiel, Mathias Block, Günter Stein, Antje Steveling, Sarah Lücking, Jürgen Scherberich","doi":"10.1055/a-1944-2686","DOIUrl":"https://doi.org/10.1055/a-1944-2686","url":null,"abstract":"<p><strong>Introduction: </strong>Uromodulin is a kidney-specific tubular protein, and its assessment in serum (sUMOD) reveals the potential as a novel marker for function and the integrity of renal parenchymal cells and does not directly depend on the glomerular filtration rate. Early diabetic nephropathy parallels glomerular hyperfiltration, often leading to diagnostic misinterpretation. Moreover, traditional kidney function markers are not able to diagnose structural lesions. Recent data show that sUMOD is linked to glucose intolerance in adults. Thus, we launched to assess the hypothesis that sUMOD is also associated with kidney function, biometric data, and quality of metabolic control in children/adolescents with type 1 diabetes.</p><p><strong>Patients and methods: </strong>Patients with type 1 diabetes (n=135) and healthy controls (n=69) were recruited to participate in the trial. Clinical, biometrical data, sUMOD, and other laboratory parameters were assessed.</p><p><strong>Results: </strong>The mean concentrations of sUMOD in diabetic patients and controls were comparable (201.19±103.22 vs. 198.32±84.27 ng/mL, p=0.832). However, in contrast to healthy controls, sUMOD levels in patients with diabetes were associated with serum-creatinine (r=-0.368, p<0.0001), age (r=-0.350, p<0.0001), height (r=-0.379, p<0.0001), body weight (r=-0.394, p<0.0001), Body mass index (r=-0.292, p=0.001), daily insulin dosage (r=-0.300, p<0.0001), HbA1c (%) (r=-0.190, p=0.027), standardized HbA1c/IFCC (mmol/mol) (r=-0.189, p=0.028), and systolic (r=-0.299, p<0.0001) and diastolic (r=-0.235, p=0.006) arterial blood pressure.</p><p><strong>Conclusions: </strong>Our study shows that children/adolescents with type 1 diabetes disclose similar sUMOD concentrations as healthy controls. Serum UMOD appears to indicate higher risks for kidney tissue remodeling and possibly subsequent cardiovascular alterations. However, further studies are mandatory to settle these findings.</p>","PeriodicalId":12241,"journal":{"name":"Experimental and Clinical Endocrinology & Diabetes","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9089549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sebastian Hörber, Matthias Orth, Andreas Fritsche, Andreas Peter
C-peptide is an increasingly used and established marker for beta cell function by assessing endogenous insulin secretion. Accurate and comparable C-peptide measurements are needed in clinical practice and research studies. For example, to calculate HOMA-indices, the C-peptide/glucose ratio, and the classification of recently published novel subgroups of diabetes and prediabetes have used C-peptide measurements. Although the process for standardization of C-peptide measurements is advanced, its full implementation is still missing; therefore, the current status of the comparability of C-peptide measurements using different immunoassays is unclear. Here we compared five widely used C-peptide immunoassays on different analyzers (Abbott ALINITY i, DiaSorin Liaison XL, Roche Cobas e411, Siemens Healthineers ADVIA Centaur XPT, and Immulite 2000 XPi) using serum samples covering the clinically relevant C-peptide concentration range. Although all investigated immunoassays are traceable to the international reference reagent for C-peptide (NIBSC code: 84/510), results of C-peptide measurements showed significant differences between analyzers in the entire concentration range, especially with increasing C-peptide concentrations. The mean bias was largest (36.6%) between results of the immunoassays by Roche and Siemens Healthineers (ADVIA Centaur XPT), and both assays revealed large discrepancies compared to immunoassays by Abbott, DiaSorin, and Siemens Healthineers (Immulite 2000 XPi). In contrast, the three latter assays showed similar C-peptide results (mean bias: 2.3% to 4.2%). Consequently, C-peptide discrepancies might affect clinical diagnosis and the interpretation of study results. Therefore, there is an urgent need to implement and finalize the standardization process of C-peptide measurements to improve patient care and the comparability of research studies.
{"title":"Comparability of C-Peptide Measurements - Current Status and Clinical Relevance.","authors":"Sebastian Hörber, Matthias Orth, Andreas Fritsche, Andreas Peter","doi":"10.1055/a-1998-6889","DOIUrl":"https://doi.org/10.1055/a-1998-6889","url":null,"abstract":"<p><p>C-peptide is an increasingly used and established marker for beta cell function by assessing endogenous insulin secretion. Accurate and comparable C-peptide measurements are needed in clinical practice and research studies. For example, to calculate HOMA-indices, the C-peptide/glucose ratio, and the classification of recently published novel subgroups of diabetes and prediabetes have used C-peptide measurements. Although the process for standardization of C-peptide measurements is advanced, its full implementation is still missing; therefore, the current status of the comparability of C-peptide measurements using different immunoassays is unclear. Here we compared five widely used C-peptide immunoassays on different analyzers (Abbott ALINITY i, DiaSorin Liaison XL, Roche Cobas e411, Siemens Healthineers ADVIA Centaur XPT, and Immulite 2000 XPi) using serum samples covering the clinically relevant C-peptide concentration range. Although all investigated immunoassays are traceable to the international reference reagent for C-peptide (NIBSC code: 84/510), results of C-peptide measurements showed significant differences between analyzers in the entire concentration range, especially with increasing C-peptide concentrations. The mean bias was largest (36.6%) between results of the immunoassays by Roche and Siemens Healthineers (ADVIA Centaur XPT), and both assays revealed large discrepancies compared to immunoassays by Abbott, DiaSorin, and Siemens Healthineers (Immulite 2000 XPi). In contrast, the three latter assays showed similar C-peptide results (mean bias: 2.3% to 4.2%). Consequently, C-peptide discrepancies might affect clinical diagnosis and the interpretation of study results. Therefore, there is an urgent need to implement and finalize the standardization process of C-peptide measurements to improve patient care and the comparability of research studies.</p>","PeriodicalId":12241,"journal":{"name":"Experimental and Clinical Endocrinology & Diabetes","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b3/5d/10-1055-a-1998-6889.PMC9998184.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9447968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Objective: The E2F2 transcription factor can accelerate cell proliferation and wound healing. However, its mechanism of action in a diabetic foot ulcer (DFU) remains unclear. Therefore, this study explores the influence of E2F2 on wound healing in DFU by examining cell division cycle-associated 7-like (CDCA7L) expression.
Methods: CDCA7L and E2F2 expression in DFU tissues were analyzed with databases. CDCA7L and E2F2 expression were altered in human umbilical vein endothelial cells (HUVECs) and spontaneously transformed human keratinocyte cell culture (HaCaT) cells. Cell viability, migration, colony formation, and angiogenesis were evaluated. Binding of E2F2 to the CDCA7L promoter was examined. Subsequently, a diabetes mellitus (DM) mouse model was established and treated with full-thickness excision followed by CDCA7L overexpression. Wound healing in these mice was observed and recorded, and vascular endothelial growth factor receptor 2 (VEGFR2) and hematopoietic progenitor cell antigen CD34 (CD34) expression were determined. E2F2 and CDCA7L expression levels in cells and mice were evaluated. The expression of growth factors was tested.
Results: CDCA7L expression was downregulated in DFU tissues and wound tissues from DM mice. Mechanistically, E2F2 bound to the CDCA7L promoter to upregulate CDCA7L expression. E2F2 overexpression enhanced viability, migration, and growth factor expression in HaCaT cells and HUVECs, and augmented HUVEC angiogenesis and HaCaT cell proliferation, which was nullified by silencing CDCA7L. In DM mice, CDCA7L overexpression facilitated wound healing and elevated the expression level of growth factors.
Conclusions: E2F2 facilitated cell proliferation and migration and fostered wound healing in DFU cells through binding to the CDCA7L promoter.
{"title":"E2F2 Promotes Wound Healing of Diabetic Foot Ulcer by Regulating CDCA7L Transcription.","authors":"Meimei Xiao, Jiusong Wang, Yanming Chen","doi":"10.1055/a-1989-1918","DOIUrl":"https://doi.org/10.1055/a-1989-1918","url":null,"abstract":"<p><strong>Objective: </strong>The E2F2 transcription factor can accelerate cell proliferation and wound healing. However, its mechanism of action in a diabetic foot ulcer (DFU) remains unclear. Therefore, this study explores the influence of E2F2 on wound healing in DFU by examining cell division cycle-associated 7-like (CDCA7L) expression.</p><p><strong>Methods: </strong>CDCA7L and E2F2 expression in DFU tissues were analyzed with databases. CDCA7L and E2F2 expression were altered in human umbilical vein endothelial cells (HUVECs) and spontaneously transformed human keratinocyte cell culture (HaCaT) cells. Cell viability, migration, colony formation, and angiogenesis were evaluated. Binding of E2F2 to the CDCA7L promoter was examined. Subsequently, a diabetes mellitus (DM) mouse model was established and treated with full-thickness excision followed by CDCA7L overexpression. Wound healing in these mice was observed and recorded, and vascular endothelial growth factor receptor 2 (VEGFR2) and hematopoietic progenitor cell antigen CD34 (CD34) expression were determined. E2F2 and CDCA7L expression levels in cells and mice were evaluated. The expression of growth factors was tested.</p><p><strong>Results: </strong>CDCA7L expression was downregulated in DFU tissues and wound tissues from DM mice. Mechanistically, E2F2 bound to the CDCA7L promoter to upregulate CDCA7L expression. E2F2 overexpression enhanced viability, migration, and growth factor expression in HaCaT cells and HUVECs, and augmented HUVEC angiogenesis and HaCaT cell proliferation, which was nullified by silencing CDCA7L. In DM mice, CDCA7L overexpression facilitated wound healing and elevated the expression level of growth factors.</p><p><strong>Conclusions: </strong>E2F2 facilitated cell proliferation and migration and fostered wound healing in DFU cells through binding to the CDCA7L promoter.</p>","PeriodicalId":12241,"journal":{"name":"Experimental and Clinical Endocrinology & Diabetes","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9097571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michèle Weber, Matthias Hannes Diebold, Peter Wiesli, Andreas David Kistler
Aims: Glucose and insulin metabolism are altered in hemodialysis patients, and diabetes management is difficult in these patients. We aimed to validate flash glucose monitoring (FGM) in hemodialysis patients with and without diabetes mellitus as an attractive option for glucose monitoring not requiring regular self-punctures.
Methods: We measured interstitial glucose using a FreeStyle Libre device in eight hemodialysis patients with and seven without diabetes mellitus over 14 days and compared the results to simultaneously performed self-monitoring of capillary blood glucose (SMBG).
Results: In 720 paired measurements, mean flash glucose values were significantly lower than self-measured capillary values (6.17±2.52 vs. 7.15±2.41 mmol/L, p=1.3 E-86). Overall, the mean absolute relative difference was 17.4%, and the mean absolute difference was 1.20 mmol/L. The systematic error was significantly larger in patients without vs. with diabetes (- 1.17 vs. - 0.82 mmol/L) and on dialysis vs. interdialytic days (-1.09 vs. -0.90 mmol/L). Compared to venous blood glucose (72 paired measurements), the systematic error of FGM was even larger (5.89±2.44 mmol/L vs. 7.78±7.25 mmol/L, p=3.74E-22). Several strategies to reduce the systematic error were evaluated, including the addition of +1.0 mmol/L as a correction term to all FGM values, which significantly improved accuracy.
Conclusions: FGM systematically underestimates blood glucose in hemodialysis patients but, taking this systematic error into account, the system may be useful for glucose monitoring in hemodialysis patients with or without diabetes.
目的:血液透析患者的葡萄糖和胰岛素代谢发生改变,这些患者的糖尿病管理困难。我们的目的是验证在有或没有糖尿病的血液透析患者中,快速血糖监测(FGM)是一种有吸引力的血糖监测选择,不需要定期自我穿刺。方法:我们使用FreeStyle Libre装置测量了8例合并糖尿病和7例非糖尿病血液透析患者14天间质血糖,并将结果与同时进行的毛细血管血糖(SMBG)自我监测进行比较。结果:在720组配对测量中,平均瞬时血糖值显著低于自测毛细血管值(6.17±2.52 vs. 7.15±2.41 mmol/L, p=1.3 E-86)。总体而言,平均绝对相对差为17.4%,平均绝对差为1.20 mmol/L。无糖尿病患者的系统误差明显大于糖尿病患者(- 1.17 vs - 0.82 mmol/L),透析患者的系统误差明显大于透析期间的系统误差(-1.09 vs -0.90 mmol/L)。与静脉血血糖(72对测量)相比,FGM的系统误差更大(5.89±2.44 mmol/L vs. 7.78±7.25 mmol/L, p=3.74E-22)。评估了几种减少系统误差的策略,包括在所有女性生殖器切割值中添加+1.0 mmol/L作为校正项,这显着提高了准确性。结论:女性生殖器切割系统地低估了血液透析患者的血糖,但考虑到这一系统误差,该系统可能对伴有或不伴有糖尿病的血液透析患者的血糖监测有用。
{"title":"Accuracy of Flash Glucose Monitoring in Hemodialysis Patients With and Without Diabetes Mellitus.","authors":"Michèle Weber, Matthias Hannes Diebold, Peter Wiesli, Andreas David Kistler","doi":"10.1055/a-1978-0226","DOIUrl":"https://doi.org/10.1055/a-1978-0226","url":null,"abstract":"<p><strong>Aims: </strong>Glucose and insulin metabolism are altered in hemodialysis patients, and diabetes management is difficult in these patients. We aimed to validate flash glucose monitoring (FGM) in hemodialysis patients with and without diabetes mellitus as an attractive option for glucose monitoring not requiring regular self-punctures.</p><p><strong>Methods: </strong>We measured interstitial glucose using a FreeStyle Libre device in eight hemodialysis patients with and seven without diabetes mellitus over 14 days and compared the results to simultaneously performed self-monitoring of capillary blood glucose (SMBG).</p><p><strong>Results: </strong>In 720 paired measurements, mean flash glucose values were significantly lower than self-measured capillary values (6.17±2.52 vs. 7.15±2.41 mmol/L, p=1.3 E-86). Overall, the mean absolute relative difference was 17.4%, and the mean absolute difference was 1.20 mmol/L. The systematic error was significantly larger in patients without vs. with diabetes (- 1.17 vs. - 0.82 mmol/L) and on dialysis vs. interdialytic days (-1.09 vs. -0.90 mmol/L). Compared to venous blood glucose (72 paired measurements), the systematic error of FGM was even larger (5.89±2.44 mmol/L vs. 7.78±7.25 mmol/L, p=3.74E-22). Several strategies to reduce the systematic error were evaluated, including the addition of +1.0 mmol/L as a correction term to all FGM values, which significantly improved accuracy.</p><p><strong>Conclusions: </strong>FGM systematically underestimates blood glucose in hemodialysis patients but, taking this systematic error into account, the system may be useful for glucose monitoring in hemodialysis patients with or without diabetes.</p>","PeriodicalId":12241,"journal":{"name":"Experimental and Clinical Endocrinology & Diabetes","volume":null,"pages":null},"PeriodicalIF":1.8,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f9/d2/10-1055-a-1978-0226.PMC9998185.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9088415","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael Hummel, Martin Füchtenbusch, Wilgard Battefeld, Christoph Bührer, Tanja Groten, Thomas Haak, Franz Kainer, Alexandra Kautzky-Willer, Andreas Lechner, Thomas Meissner, Christine Nagel-Reuper, Ute Schäfer-Graf, Thorsten Siegmund