Early glucose metabolism in children at risk for type 1 diabetes based on islet autoantibodies compared to low-risk control groups

BackgroundAnatomic variation or early differences in glucose metabolism have been linked to the development of type 1 diabetes. We aimed to describe early glucose metabolism based on HbA1c, oral glucose tolerance test (OGTT), and random plasma glucose years before the presentation of type 1 diabetes in five risk groups based on autoantibody combinations. For the first time, we were able to include for comparison children with very low risk of progression to type 1 diabetes. MethodsThe Finnish Diabetes Prediction and Prevention birth cohort study screened newborn infants for HLA susceptibility to type 1 diabetes since 1994. Those carrying a risk genotype were prospectively followed up with islet autoantibody testing. Glucose parameters were obtained starting from the time of seroconversion. By 31 August 2014, 1162 children had developed at least one islet autoantibody and were included in the current study. Type 1 diabetes was diagnosed in 335 children (progressors). In the non-progressor groups, 207 developed multiple (>= 2) biochemical islet autoantibodies, 229 a single biochemical autoantibody, 370 ICA only, and 64 transient autoantibodies. Children were divided into five risk groups. Glucose metabolism was evaluated. ResultsWe observed lower HbA1c values in early follow-up 4.5 to 6.0 years before diagnosis in the progressors when compared to the same time in children with a single biochemical autoantibody or low-risk (ICA only and transient) participants, who did not progress to clinical type 1 diabetes. However, no such differences were observed in OGTTs or random plasma glucose. The variation was minimal in glucose values in the low-risk groups. ConclusionWe report the possibility of early alteration in glucose metabolism in future progressors. This could suggest early defects in multiple glucose-regulating hormones.Peer reviewe

Continuous glucose monitoring and HbA1c in the evaluation of glucose metabolism in children at high risk for type 1 diabetes mellitus

Aims: Continuous glucose monitoring (CGM) parameters, self-monitored blood glucose (SMBG), HbA1c and oral glucose tolerance test (OGTT) were studied during preclinical type 1 diabetes mellitus. Methods: Ten asymptomatic children with multiple (>= 2) islet autoantibodies (cases) and 10 age and sex-matched autoantibody-negative controls from the Type 1 Diabetes Prediction and Prevention (DIPP) Study were invited to 7-day CGM with Dexcom G4 Platinum Sensor. HbA1c and two daily SMBG values (morning and evening) were analyzed. Five-point OGTTs were performed and carbohydrate intake was assessed by food records. The matched pairs were compared with the paired sample t-test. Results: The cases showed higher mean values and higher variation in glucose levels during CGM compared to the controls. The time spent >= 7.8 mmol/l was 5.8% in the cases compared to 0.4% in the controls (p = 0.040). Postprandial CGM values were similar except after the dinner (6.6 mmol/l in cases vs. 6.1 mmol/l in controls; p = 0.023). When analyzing the SMBG values higher mean level, higher evening levels, as well as higher variation were observed in the cases when compared to the controls. HbA1c was significantly higher in the cases [5.7% (39 mmol/mol) vs. 5.3% (34 mmol/mol); p = 0.045]. No differences were observed in glucose or C-peptide levels during OGTT. Daily carbohydrate intake was slightly higher in the cases (254.2 g vs. 217.7 g; p = 0.034). Conclusions: Glucose levels measured by CGM and SMBG are useful indicators of dysglycemia during preclinical type 1 diabetes mellitus. Increased evening glucose values seem to be common in children with preclinical type 1 diabetes mellitus. (C) 2016 Elsevier Ireland Ltd. All rights reserved.Peer reviewe

Early glucose metabolism in children at risk for type 1 diabetes based on islet autoantibodies compared to low-risk control groups

Background: Anatomic variation or early differences in glucose metabolism have been linked to the development of type 1 diabetes. We aimed to describe early glucose metabolism based on HbA1c, oral glucose tolerance test (OGTT), and random plasma glucose years before the presentation of type 1 diabetes in five risk groups based on autoantibody combinations. For the first time, we were able to include for comparison children with very low risk of progression to type 1 diabetes.Methods: The Finnish Diabetes Prediction and Prevention birth cohort study screened newborn infants for HLA susceptibility to type 1 diabetes since 1994. Those carrying a risk genotype were prospectively followed up with islet autoantibody testing. Glucose parameters were obtained starting from the time of seroconversion. By 31 August 2014, 1162 children had developed at least one islet autoantibody and were included in the current study. Type 1 diabetes was diagnosed in 335 children (progressors). In the non-progressor groups, 207 developed multiple (≥2) biochemical islet autoantibodies, 229 a single biochemical autoantibody, 370 ICA only, and 64 transient autoantibodies. Children were divided into five risk groups. Glucose metabolism was evaluated.Results: We observed lower HbA1c values in early follow-up 4.5 to 6.0 years before diagnosis in the progressors when compared to the same time in children with a single biochemical autoantibody or low-risk (ICA only and transient) participants, who did not progress to clinical type 1 diabetes. However, no such differences were observed in OGTTs or random plasma glucose. The variation was minimal in glucose values in the low-risk groups.Conclusion: We report the possibility of early alteration in glucose metabolism in future progressors. This could suggest early defects in multiple glucose-regulating hormones.</p

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First-emerging islet autoantibody and glucose metabolism: search for type 1 diabetes subtypes

ObjectiveSubtypes in type 1 diabetes pathogenesis have been implicated based on the first-appearing autoantibody (primary autoantibody). We set out to describe the glucose metabolism in preclinical diabetes in relation to the primary autoantibody in children with HLA-conferred disease susceptibility.Design and methodsDysglycemic markers are defined as a 10% increase in HbA1c in a 3-12 months interval or HbA1c ≥5.9% (41 mmol/mol) in two consecutive samples, impaired fasting glucose or impaired glucose tolerance, or a random plasma glucose value ≥7.8 mmol/L. A primary autoantibody could be detected in 295 children who later developed at least 1 additional biochemical autoantibody. These children were divided into three groups: insulin autoantibody (IAA) multiple (n = 143), GAD antibody (GADA) multiple (n = 126) and islet antigen 2 antibody (IA-2A) multiple (n = 26). Another 229 children seroconverted to positivity only for a single biochemical autoantibody and were grouped as IAA only (n = 87), GADA only (n = 114) and IA-2A only (n = 28).ResultsNo consistent differences were observed in selected autoantibody groups during the preclinical period. At diagnosis, children with IAA only showed the highest HbA1c (P ConclusionsThe phenotype of preclinical diabetes defined by the primary autoantibody is not associated with any discernible differences in glucose metabolism before the clinical disease manifestation.</p

First-emerging islet autoantibody and glucose metabolism : search for type 1 diabetes subtypes

Objective: Subtypes in type 1 diabetes pathogenesis have been implicated based on the first-appearing autoantibody (primary autoantibody). We set out to describe the glucose metabolism in preclinical diabetes in relation to the primary autoantibody in children with HLA-conferred disease susceptibility. Design and methods: Dysglycemic markers are defined as a 10% increase in HbA1c in a 3–12 months interval or HbA1c ≥5.9% (41 mmol/mol) in two consecutive samples, impaired fasting glucose or impaired glucose tolerance, or a random plasma glucose value ≥7.8 mmol/L. A primary autoantibody could be detected in 295 children who later developed at least 1 additional biochemical autoantibody. These children were divided into three groups: insulin autoantibody (IAA) multiple (n = 143), GAD antibody (GADA) multiple (n = 126) and islet antigen 2 antibody (IA-2A) multiple (n = 26). Another 229 children seroconverted to positivity only for a single biochemical autoantibody and were grouped as IAA only (n = 87), GADA only (n = 114) and IA-2A only (n = 28). Results: No consistent differences were observed in selected autoantibody groups during the preclinical period. At diagnosis, children with IAA only showed the highest HbA1c (P < 0.001 between groups) and the highest random plasma glucose (P = 0.005 between groups). Children with IA-2A only progressed to type 1 diabetes as frequently as those with IA-2A multiple (46% vs 54%, P = 0.297) whereas those with IAA only or GADA only progressed less often than children with IAA multiple or GADA multiple (22% vs 62% (P < 0.001) and 7% vs 43% (P < 0.001)), respectively. Conclusions: The phenotype of preclinical diabetes defined by the primary autoantibody is noassociated with any discernible differences in glucose metabolism before the clinical disease manifestation.publishedVersionPeer reviewe

Standard Lymphadenectomy for Esophageal and Lung Cancer : Variability in the Number of Examined Lymph Nodes Among Pathologists and Its Survival Implication

AIM: We compared variability in number of examined lymph nodes between pathologists and analyzed survival implications in lung and esophageal cancer after standardized lymphadenectomy. METHODS: Outcomes of 294 N2 dissected lung cancer patients and 132 2-field dissected esophageal cancer patients were retrospectively examined. The primary outcome was difference in reported lymph node count among pathologists. Secondary outcomes were overall and disease-specific survival related to this count and survival related to the 50% probability cut-off value of detecting metastasis based on the number of examined lymph nodes. RESULTS: The median number of examined lymph nodes in lung cancer was 13 (IQR 9-17) and in esophageal cancer it was 22 (18-29). The pathologist with the highest median number of examined nodes had > 50% higher lymph node yield compared with the pathologist with the lowest median number of nodes in lung (15 vs. 9.5, p = 0.003), and esophageal cancer (28 vs. 17, p = 0.003). Survival in patients stratified by median reported lymph node count in both lung (adjusted RMST ratio < 14 vs. ≥ 14 lymph nodes 0.99, 95% CI 0.88-1.10; p = 0.810) and esophageal cancer (adjusted RMST ratio < 25 vs. ≥ 25 lymph nodes 0.95, 95% CI 0.79-1.15, p = 0.612) was similar. The cut-off value for 50% probability of detecting metastasis by number of examined lymph nodes in lung cancer was 15.7 and in esophageal cancer 21.8. When stratified by this cut-off, no survival differences were seen. CONCLUSION: The quality of lymphadenectomy based on lymph node yield is susceptible to error due to detected variability between pathologists in the number of examined lymph nodes. This variability in yield did not have any survival effect after standardized lymphadenectomy.publishedVersionPeer reviewe

Thoracoscopic segmentectomy with simple routine bronchoscopic inflation for intersegmental plane identification : short and mid-term outcomes compared with lobectomy

Background: The technical concepts of thoracoscopic segmentectomy are still evolving. In this study we present a simple bronchoscopy-based intersegmental demarcation technique with short- and mid-term outcomes compared between thoracoscopic segmentectomy and lobectomy. Methods: All 105 consecutive patients with lung cancer intended to treat with video-assisted thoracoscopic surgery (VATS) segmentectomy were compared to 110 consecutive VATS lobectomies. Short- and mid-term outcome comparison included complications, length of hospital stay, pulmonary functions, and 3-year progression-free and overall survival. Mid-term outcomes were adjusted for age, sex, comorbidities, pulmonary functions, histology, stage and adjuvant treatment. Results: Segmentectomy patients had more comorbidities (P=0.006), worse pulmonary functions (FEV1%, P=0.005; DLCO/va, P=0.011), poor exercise capacity (P=0.043) and were considered high-risk patients more often (41.9% vs. 25.5%, P=0.011). Major complication rates did not differ between the groups (P=0.718). Mean length of hospital stay decreased after segmentectomy (4.7 vs. 5.9 days, P=0.033). Following segmentectomy, FEV1% slightly improved (1.0%). After lobectomy, the mean decline of FEV1% was 8.1% (P<0.001). Respectively, in high-risk patients, 2.1% improvement and 9.9% decline (P=0.027) were observed. Overall mortality hazard after segmentectomy was similar to that for lobectomy (unadjusted HR 0.80, 95% CI: 0.45-1.44, adjusted HR 0.87, 95% CI: 0.43-1.76). When considering only stage I non-small cell lung cancer, 3-year overall survival after segmentectomy and lobectomy were 86.8% vs. 79.8% (P=0.412) and 3-year recurrence-free survival 93.0% vs. 89.7%, P=0.450. Conclusions: Following segmentectomy, regardless of worse surgical candidates, hospital stay was shorter. Furthermore, preservation of lung function also in high-risk patients, was observed without compromising mid-term oncologic outcomes.publishedVersionPeer reviewe