Lactoferrin In Patients Research Articles

LTF as a Potential Prognostic and Immunological Biomarker in Glioblastoma.

The lactoferrin (LTF) gene behaves like a tumor suppressor gene in diverse tumors, such as renal cancer, nasopharyngeal carcinoma and gastric cancer. However, the prognostic value of LTF expression in patients with glioblastoma remains unclear. In this study, the expression levels of LTF in patients with GBM were investigated in TCGA, GEPIA, CGGA and GEO database, and a survival analysis of LTF based on TCGA and CGGA was performed. Furthermore, the present study demonstrated the LTF gene co-expression, PPI network, KEGG/GO enrichment and immune cell infiltration analysis on TCGA and TIMER2.0 database. We found that LTF expression was significantly upregulated in GBM samples compared with normal samples and other glioma samples, and Kaplan-Meier analysis demonstrated that the overexpression of LTF were significantly associated with worse overall survival (OS) and 5-year OS in GBM patients (P < 0.05). KEGG/GO enrichment analysis demonstrated that functions of LTF concentrated in immune and inflammatory response and peptidase regulation (P < 0.05). Immune cell infiltration analysis presented that high LTF expression exhibited dysregulated immune infiltration (i.e., CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells and cancer associated fibroblast). LTF was upregulated in tumors and correlated with worse OS in GBM patients, and LTF might function as an oncogene via inducing dysregulated immune infiltration in GBM.

Serum Level of Lactoferrin in Patients with Acne Vulgaris and the Efficacy of Lactoferrin Supplementation

Serum Level of Lactoferrin in Patients with Acne Vulgaris and the Efficacy of Lactoferrin Supplementation

Modulation, microbiota and inflammation in the adult CF gut: A prospective study

BackgroundCystic Fibrosis (CF) has prominent gastrointestinal and pancreatic manifestations. The aim of this study was to determine the effect of Cystic fibrosis transmembrane conductance regulator (CFTR) modulation on, gastrointestinal inflammation, pancreatic function and gut microbiota composition in people with cystic fibrosis (CF) and the G551D-CFTR mutation. MethodsFourteen adult patients with the G551D-CFTR mutation were assessed clinically at baseline and for up to 1 year after treatment with ivacaftor. The change in gut inflammatory markers (calprotectin and lactoferrin), exocrine pancreatic status and gut microbiota composition and structure were assessed in stool samples. ResultsThere was no significant change in faecal calprotectin nor lactoferrin in patients with treatment while all patients remained severely pancreatic insufficient. There was no significant change in gut microbiota diversity and richness following treatment. ConclusionThere was no significant change in gut inflammation after partial restoration of CFTR function with ivacaftor, suggesting that excess gut inflammation in CF is multi-factorial in aetiology. In this adult cohort, exocrine pancreatic function was irreversibly lost. Longer term follow-up may reveal more dynamic changes in the gut microbiota and possible restoration of CFTR function.

Salivary Lactoferrin Levels, Disease Severity and Correlates in Patients with Chronic Periodontitis Presenting to a Tertiary Health Facility in Nigeria.

Objective: This study compared the concentration of salivary lactoferrin in patients with and without chronic periodontitis and investigated correlations with clinical variables of the disease.&#x0D; Methods: The study included 102 participants (51 cases and 51 controls) who presented at the Periodontology Clinic of University of Benin Teaching Hospital and met the selection criteria of ‘4mm and above’ periodontal probing depths (PPD) and positive bleeding on probing (BOP) using community periodontal index (CPI) probe. Healthy participants (controls) were patients that had PPD less than or equal to 3mm, absence of BOP and simplified oral hygiene index (OHI-S) not more than 1.2. Baseline OHI-S and CPI scores were recorded. Saliva samples were collected and analyzed using enzyme-linked immunosorbent assay. All data were analyzed with the Statistical Package for Social Sciences (SPSS) version 22.0.&#x0D; Results: There was a statistically significant difference between the mean (SD) lactoferrin concentration of control participants 5.27(0.59) mg/l and case participants 6.74(0.61) mg/l (p&lt;0.001). Participants with probing pocket depths (PPD) of 6mm or more had a significantly higher mean concentration [6.85(0.06) mg/l] than that of those with PPD 4-5mm [6.71(0.67) mg/l] (p &lt; 0.001) Lactoferrin levels were highest in participants with ‘poor’ oral hygiene [6.85(0.60) mg/l] and lowest in those with ‘good’ oral hygiene [6.65(0.83) mg/l].&#x0D; Conclusion: Salivary lactoferrin levels were higher among participants with chronic periodontitis than those without chronic periodontitis and correlates positively with the main clinical characteristics of the disease

Modern view in diagnosis of uremic pseudoperitonitis and peritonitis in patients on renal replacement therapy (programmed hemodialysis)

Objective. Determination of blood serum 2-microglobulin and lactoferrin concentration in patients on renal replacement therapy (programmed hemodialysis) for the diagnosis of uremic pseudoperitonitis and peritonitis. Materials and methods. We examined 56 patients admitted to the Surgical Department of Astrakhan Clinical Hospital RZhD-Medicine and City Clinical Hospital № 3, and studied the concentration of blood serum 2-microglobulin and lactoferrin in patients urgently hospitalized with suspicion of uremic pseudoperitonitis or peritonitis, who receive renal replacement therapy (programmed hemodialysis). The control group included 50 outpatients on renal replacement therapy (programmed hemodialysis). The study did not include patients with suspected peritonitis who did not receive renal replacement therapy (programmed hemodialysis). The period of the study is 20192021. Results. The concentration of serum 2-microglobulin is statistically higher than normal in all patients receiving renal replacement therapy (programmed hemodialysis) in anamnesis. The most statistically high concentration of 2-microglobulin was detected in patients with uremic pseudoperitonitis (n = 39), and was 30000 6680 ng/ml compared with the concentration in the blood serum among patients with peritonitis 6000 519.9 ng/ml. The concentration of lactoferrin is statistically high in peritonitis (n = 17) and was 3480 439 ng/ml compared with uremic pseudoperitonitis 1160 148 ng/ml. In the control group of outpatients (n = 50), who received renal replacement therapy (programmed hemodialysis), no statistically significant concentrations of blood serum 2-microglobulin and lactoferrin were detected. Conclusions. A clear dependence of 2-microglobulin and lactoferrin concentrations on the severity of uremic pseudoperitonitis and peritonitis was established. Statistically high values of 2-microglobulin concentration were obtained in patients with uremic pseudoperitonitis, and the level of lactoferrin was statistically high in peritonitis.

A pilot study on serum lactoferrin in patients with mild versus severe acne in correlation with disease duration

Background Acne vulgaris (AV) is a chronic inflammatory disease of the pilosebaceous units. Lactoferrin (LF) is an iron-binding glycoprotein, which is known to have a role in decreasing inflammation and microbial infection. A few studies have reported that many of the patients with acne had acceptable therapeutic response to LF supplementation. However, no studies have directly assessed serum LF level in patients with acne. Objective To evaluate serum LF level in patients with severe versus mild acne in comparison with healthy controls. Patients and methods Serum LF was assessed using enzyme-linked immunosorbent assay in 40 AV patients comprising two subgroups; 20 mild and 20 severe cases, versus 20 healthy controls. Levels were correlated with disease duration. Results Mean serum LF levels were significantly higher in patients with AV than in healthy controls (P Conclusion Serum LF is directly related to acne severity, being elevated in severe rather than mild cases. Therefore, it could be of prognostic value. Serum LF level is higher in acute stages rather than chronic cases, denoting its possible role as a compensatory acute-phase reactant, to overcome the detrimental effects of acute inflammation.

Lactoferrin, as an indicator of inflammatory process on infectious mononucleosis in children

Aim of the work — to investigate the level of lactoferrin in patients with IM at hospitalization and after 14 days and compare the findings with those that are determined in a relatively healthy group of patients. Under supervision were 55 children aged 1 to 17 years old who received a course of in patient treatment at the Vinnytsia Regional Clinical Infectious Diseases Hospital for infectious mononucleosis. Given the difficulty in obtaining intravenous material in children in the state of the disease, the oropharyngeal secret (oral fluid) was selected as the study material, which was received in the morning on the on set in the upright position of the body by free graft on the 1 and 14 days after admission to the in patient department. The study used an enzyme-linked method (ELISA). The index was determined using reagents from VEKTOR-BEST, RF, by the solid-state IFA method, by the Stat Fax 2100 analyzer, USA. In order to compare and analyze the results obtained, 55 relatively healthy children who were registered at the Vinnytsia Social Health Center on the day of the “healthy child” received similar surveys. Infectious mononucleosis is a viral disease with a polymorphic clinical course. Among the etiological factors of IM are herpesviruses, which can affect almost all organs and systems. The most significant changes are undergoing the immune system, the violation of which lead stop a prolonged process of inflammation and chronicity of the process. A comparative study of the concentration of lactoferrin in oropharyngeal fluid in patients with IM and in healthy children indicates a significant increase in the conditions of the infectious process (4919.2±117.9 and 753.2±16.3 ng/ml, respectively, at p&lt;0.01). This is absolutely logical, since in a disease the effect of lactoferrin on the activation of immunocompetent cells to fight an infectious agent. Among the examined children, the majority were with EBV etiology (41.8% — 23 children). Accordingly, the level of lactoferrin in this group of children was highest (6114.1±120.9) ng/ml. This indicates significant inflammatory structural changes in this group of children, which appear because of this virus. The smallest value of lactoferrin was in children who isolated HHV6 — (3768.4±115.8) ng/ml.&#x0D; Having examined the level of lactoferrin in oropharyngeal fluid in children in the dynamics after 14 days, we compared the findings with the previous ones. Consequently, children with IM after the received treatment didn’t have a significant difference between the scores (4919.2±117.9 and 4317.8±113.6 ng/ml, respectively, with p0.05). The obtained data proved about the in complete infectious process at the time of the onset of clinical recovery. Thus, the study of the level of lactoferrin in the oropharyngeal fluid allows to estimate the immunological disorders by non-invasive method. This is very important, since venous access in sick children is limited. The value of lactoferrin can be used as an indicator of the completion of the inflammatory process, or to describe the category of children with chronic inflammation.

One-step Card Tests for Fecal Calprotectin and Lactoferrin in Patients with Inflammatory Bowel Disease

One-step Card Tests for Fecal Calprotectin and Lactoferrin in Patients with Inflammatory Bowel Disease

A pilot study of lactoferrin in patients with self-reported, chemotherapy-induced taste and smell abnormalities.

e21643 Background: Taste and smell abnormalities (TSA) are common in patients receiving chemotherapy and may lead to food avoidance, altered nutritional intake, treatment delay or withdrawal, diminished socialization and impaired overall quality of life. Lipid peroxidation of mucosal cell membranes in the oral cavity is one cause of TSA and lactoferrin (LFN), an iron-binding protein normally present in saliva, is an effective scavenger of lipid byproducts that can decrease metallic flavor in healthy volunteers. Methods: Eligible patients with colorectal or pancreatic adenocarcinoma and self-reported TSA while on an oxaliplatin-containing chemotherapy regimen were treated with LFN 250mg three times daily for 4 weeks and then followed for an additional 4 weeks off study drug. A second identical IRB-approved pilot trial enrolled patients with solid tumors, lymphoma or myeloma with self-reported TSA while receiving chemotherapy. The primary outcome was the change in self-reported TSA following 4 weeks of LFN as measured by a validated taste and smell questionnaire (TSQ) consisting of taste (score 0-10) and smell (score 0-6) subscales, which are combined to yield a total composite score (0-16, 0 = no TSA). The TSQ was assessed at 0, 4 and 8 weeks along with the FAACT (FACT–G + anorexia subscale), salivary protein and metals analyses, and the Brief Smell Identification test (B-SIT). Results: 26 total pts were enrolled (14 Males; mean age 60.5 years; range 32-79), and 19 and 17 pts remained on study with analyzable data at 4 and 8 weeks. Baseline mean taste, smell and composite TSQ scores for the 26 enrolled patients were 6.5, 3.1 and 9.6 units. After 4 weeks of LFN treatment, the mean overall TSQ score improved by 1.7 units (p = .018) while the taste and smell subscales improved by 0.6 (p = .062) and 1.1 units (p = .042) respectively. At 8 weeks, the mean TSQ score improved from baseline by 3.8 units (p &lt; .0001) while the taste and smell subscales improved by 1.9 (p = .001) and 1.8 (p = .003) units. No significant change from baseline was recorded in the FAACT or the B-SIT at 4 or 8 weeks. Conclusions: These pilot data suggest that further evaluation of LFN in patients with self-reported TSA is warranted. A randomized trial is in development. Clinical trial information: NCT01941810, NCT01596634.

An evaluation of salivary levels of lysozyme and lactoferrin in patients in the late period after allogeneic hematopoietic stem cell transplantation (HSCT)

An evaluation of salivary levels of lysozyme and lactoferrin in patients in the late period after allogeneic hematopoietic stem cell transplantation (HSCT)

Corrigendum to “Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy”

Corrigendum to “Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy”

Study on the Therapeutic Benefit on Lactoferrin in Patients with Colorectal Cancer Receiving Chemotherapy.

A double-blinded parallel randomized controlled clinical trial was conducted on two groups of colorectal cancer patients to study the therapeutic benefit of orally administered bovine lactoferrin (bLF) on colorectal cancer patients having age ranges from 20 to 71 years and who received 5-fluorouracil and leucovorin calcium. Test group (15 patients) received oral bLF 250 mg/day beside chemotherapy for three months. Control group (15 patients) received chemotherapy only. Serum lactoferrin (LF), serum glutathione-s-transferase enzyme (GST), interferon gamma (INF-γ), tumor marker carcinoembryonic antigen (CEA), renal function tests, hepatic function tests, and complete blood count were measured for both groups before and at the end of the trial. Although, there was a significant effect of oral bLF (250 mg/day) that indicated a significant improvement in mean percent of change of all parameters 3 months after treatment, there was no significant difference between results of patients in the test group and patients in the control group after treatment. This result suggests that oral bLF has significant therapeutic effect on colorectal cancer patients. Our study suggests that daily administration of bLF showed a clinically beneficial effect to colorectal cancer patients with better disease prognosis but that needs further looking into.

Клиническое значение лактоферрина слюны в индивидуальном прогнозировании осложнений при санации полости рта больных с местно-распространенным раком слизистой полости рта

Purpose of the investigation is to develop and introduce the methods of prognosis complications of oral sanitation at the treatment of the patients with locally common cancer of oral mucosa. Sanitation of oral cavity in patients with locally common cancer of oral mucus membrane is connected with development of various complications among which infections and hemorrhages play a leading part. It determines problem of development of methods of forecasting of these complications as relevant. Material and methods: Based on a comparative analysis of 340 patients with above pathology the authors have traced dependence between the development of complications in oral cavity after chemical and radial therapy and levels of lactoferrin (LF) in saliva. This simple and non-invasive method can be as a marker of pathological states in oral cavity. Among the complex of the parameters the authors have studied risk factors of complications after the use of the cytostatics and radial therapy with resulting index of prognosis (IP) for development of complications. Based on the index of prognosis individual tactics of treatment was determined. Results: Depending on the saliva levels of lactoferrin in patients receiving chemo- and radial therapy a complex of prophylactic and curable measures was developed, which allowed to decreasing the number of inflammatory processes in a zone of dental procedures from 14,1 to 2,8% and the number of bleedings from 8,0 to 5,0%. Conclusions. Level of LF in saliva can be considered as valid prognostic marker of the development of destructive complications while oral sanitation in patients received chemo- and radial therapy. Assessment of the probability of these complications with correction of preventive and therapeutic measures should be implemented depending on the prognostic value of the index. Prevention activities for development of complications in sanitation of oral cavity in cancer patients after combined and complex treatment can reduce the number of hemorrhagic complications to 5.0%, and the local inflammatory processes to 2.8%.

Clinical utility of calprotectin and lactoferrin in patients with inflammatory bowel disease: is there something new from the literature?

The identification of noninvasive biomarkers is still one of the major issue for gastroenterologists dealing with inflammatory bowel disease patients, due to the chronicity of these conditions and the early onset of symptoms in the majority of cases. Research attention has focused mainly on fecal proteins, especially calprotectin and lactoferrin, and most of the published data are reassuring about their applicability in the diagnosis and monitoring of these patients. However, there are still pending questions regarding the reliability of fecal proteins especially in the era of mucosal healing and biologics.

Ascitic Fluid Lactoferrin for Diagnosis of Spontaneous Bacterial Peritonitis

The diagnosis of spontaneous bacterial peritonitis (SBP) is based on a manual count of ascitic fluid polymorphonuclear cells (PMNs). This procedure is operator-dependent and lysis of PMNs during transport to the laboratory may lead to false-negative results. Furthermore, ascitic fluid culture is insensitive and leads to delays in diagnosis. The aim of this study was to assess the utility of ascitic fluid lactoferrin (AFLAC) for the diagnosis of SBP and to identify a cut-off level that can be used for future development of a rapid bedside test. A total of 218 consecutive ascites samples from 148 patients (1-8 samples per patient) with cirrhosis at 2 tertiary care medical centers were examined for PMN count, bedside culture, and lactoferrin concentration. AFLAC concentrations were determined using a polyclonal antibody-based enzyme-linked immunosorbent assay. An ascitic fluid PMN count of 250 cells/mL or greater with or without a positive culture was used for diagnosis of SBP. Twenty-two (10.1%) samples fulfilled diagnostic criteria for SBP. Samples with SBP had a significantly higher lactoferrin concentration (median, 3744 ng/mL; 25th-75th percentiles [P25-P75], 788-9617) compared with non-SBP samples (median, 31 ng/mL; P25-P75, 12-67; P < .001). By using a cut-off level of 242 ng/mL, the sensitivity and specificity of the assay for diagnosis of SBP were 95.5% and 97%, respectively. The area under the receiver operating characteristic curve was 0.98. AFLAC can serve as a sensitive and specific test for diagnosis of SBP. Qualitative bedside assays for the measurement of AFLAC can be developed easily and may serve as a rapid and reliable screening tool for SBP in patients with cirrhosis.

The Assessment of a Rapid Noninvasive Immunochromatographic Assay Test for Fecal Lactoferrin in Patients with Suspected Inflammation of the Ileal Pouch

Pouchitis is a common complication after ileal pouch-anal anastomosis. Diagnosis is based on the Pouch Disease Activity Index, which comprises clinical symptoms, endoscopic appearance, and histologic confirmation. A Pouch Disease Activity Index > or = 7 confirms pouchitis. Fecal lactoferrin is a marker of intestinal inflammation, which can aid in the diagnosis of pouchitis. The IBD EZ VUE test is a simple, rapid, noninvasive test for fecal lactoferrin. Our goal was to study the sensitivity and specificity of this test in the diagnosis of pouchitis. Consecutive patients with pouch dysfunction were recruited from October 2005 to July 2006. A fecal sample was collected before calculation of the Pouch Disease Activity Index. An IBD EZ VUE test was performed on each fecal sample and the results correlated with the diagnosis of pouchitis to calculate sensitivity and specificity of the IBD EZ VUE test. There were 32 patients (21 healthy and 11 inflamed pouches). The IBD EZ VUE test was positive in 14 patients. It had a sensitivity of 100 percent and a specificity of 86 percent in diagnosing pouchitis. The positive predictive value was 76 percent. There were three false-positive results. The IBD EZ VUE test is a sensitive method that may remove the need for invasive pouch investigations and lead to greater confidence when antibiotic therapy is commenced. Further investigations may be reserved for those patients who have a positive lactoferrin test and fail to respond to antibiotic treatment.

Nasal Mucosa Expression of Lactoferrin in Patients With Chronic Rhinosinusitis

Antimicrobial peptides, such as lactoferrin, are an important component of the innate immune system. They offer the body a first line defense against a wide range of invading pathogens. The diverse antipathogenic action of lactoferrin has been well characterized; however, the role that this peptide plays in chronic conditions such as rhinosinusitis remains largely unknown. This study aims to examine the level of lactoferrin expression in the nasal mucosa of patients with chronic rhinosinusitis (CRS). Nasal biopsies of 85 chronic rhinosinusitis patients, subclassified into allergic fungal sinusitis (AFS), nonallergic fungal eosinophilic sinusitis (NAFES), nonallergic, nonfungal eosinophilic sinusitis (NANFES), and CRS were studied by quantitative real-time reverse-transcriptase polymerase chain reaction and enzyme-linked immunosorbent assay for their expression of lactoferrin at an mRNA and protein level, respectively. All groups of patients with CRS showed a decrease in lactoferrin mRNA expression relative to controls (median fold-change of CRS relative to controls, 0.1550; AFS, 0.1800; NANFES, 0.1900; and NAFES, 0.2100). All groups also showed a decreased expression of lactoferrin protein (controls, 163.3 ng/mL; CRS, 82.19 ng/mL; AFS, 104.1 ng/mL; NANFES, 118.9 ng/mL; and NAFES, 74.33 ng/mL). The most significant reduction was evident in the CRS subgroup as well as in patients with nasal polyposis at the time of surgery. This is the first study of its kind to objectively examine lactoferrin expression in the nasal mucosa of CRS patients. We report a reduction in the expression of this important antimicrobial peptide at both the mRNA and protein level. Such a defect in the innate immune system may explain the predisposition of certain individuals to develop CRS and nasal polyposis, providing further insight into the pathogenesis of such conditions.

Effect of lactoferrin in patients with chronic hepatitis C: Combination therapy with interferon and ribavirin

Lactoferrin has been reported to inhibit hepatitis C virus (HCV) infection in cultured human hepatocytes and HCV viremia in patients with chronic hepatitis C (CHC). The aim of this study was to evaluate the effect of combined triple therapy of lactoferrin, interferon and ribavirin in patients with CHC. A total of 111 Japanese patients with CHC were randomly assigned to a lactoferrin group (n = 50) and a control group (n = 61). The lactoferrin group was treated with lactoferrin for 8 weeks and then with lactoferrin, interferon and ribavirin for 24 weeks; the control group was treated with interferon and ribavirin for 24 weeks. Serum anti-lactoferrin antibody, clinical and laboratory measurement were determined. The mean HCV RNA titer significantly decreased at the end of lactoferrin monotherapy. Sustained virological response to therapy was significantly higher (P < 0.05) in the lactoferrin responder group (55%) than in the control group (18%). The results show that the decrease in HCV RNA titer by lactoferrin monotherapy contributes to the effectiveness of the combined therapy of interferon and ribavirin in patients with CHC. Lactoferrin is a potential useful adjunct treatment for patients with CHC.

Randomized, double‐blind, placebo‐controlled trial of bovine lactoferrin in patients with chronic hepatitis C

Several studies have suggested that lactoferrin administration may decrease the serum level of hepatitis C virus (HCV) RNA in patients with chronic hepatitis C. The aim of the present study was to confirm the efficacy of orally administered bovine lactoferrin (bLF) in patients with chronic hepatitis C. The patients with chronic hepatitis C randomly received either oral bLF at a dose of 1.8 g daily for 12 weeks, or an oral placebo. The primary endpoint was the virologic response, defined as a 50% or greater decrease in serum HCV RNA level at 12 weeks compared with the baseline. The secondary endpoint was the biochemical response, which was defined as a 50% or greater decrease in the serum alanine aminotransferase (ALT) level at 12 weeks compared with the baseline. One hundred and ninety-eight of 199 patients were evaluable for efficacy and safety. bLF treatment was well tolerated and no serious toxicities were observed. A virologic response was achieved in 14 of 97 patients (14.4%) in the bLF group, and 19 of 101 (18.8%) in the placebo group. There was no significant difference in virologic response rates between the two groups (-4.4%, 95% confidence interval -14.8, 6.1). In addition, bLF intake did not have any favorable effect on the serum ALT level. The virologic responses were not different between two groups in any subgroup analysis. In conclusion, orally administered bLF does not demonstrate any significant efficacy in patients with chronic hepatitis C.

Prevalence of Autoantibodies to Carbonic Anhydrase II and Lactoferrin in Patients with Type 1 Diabetes

Recently, the high prevalence of autoantibodies against antigens expressed in exocrine pancreatic cells such as carbonic anhydrase II (ACA) and lactoferrin (ALF) was found in sera from adult Japanese patients with type 1 diabetes. Hence, we determined by ELISA the presence of ACA and ALF both in children (n = 27) and adult (n = 15) Caucasian patients with type 1 diabetes at diagnosis. Among children, ACA were found in one patient (3.7%) and ALF in three (11.1%). Among adults, CAA and ALF were detected in three patients (20%) and in one patient (6.7%), respectively. The prevalence of ACA and ALF observed in our Caucasian patients with type 1 diabetes at diagnosis did not reach the high value previously reported in adult Japanese patients.