Aim This study aimed to investigate whether in vivo corneal confocal microscopy (CCM) can detect the improvement of corneal nerve parameters following glycemic control in patients with type 2 diabetes in natural history. Methods Thirty-two patients with diabetes complicated by DPN and 12 age-matched control subjects underwent detailed clinical examination and were assessed per the Toronto Clinical Scoring Scale for DPN, nerve conduction studies, and IVCCM at baseline and after approximately one year from the first visit. Results At follow-up, 16 diabetic patients had improved glycemic control (group A, HbA1c < 7.0%, 7.78 ± 1.62% versus 6.52 ± 0.59%, P = 0.005), while the remainder continued to have elevated HbA1c levels (group B, HbA1c ≥ 7.0%, 8.55 ± 1.57% versus 8.79 ± 1.05%, P = 0.527). For patients in group A, corneal nerve fiber density (CNFD) (18.55 ± 5.25 n/mm2 versus 21.78 ± 6.13 n/mm2, P = 0.005) and corneal nerve fiber length (CNFL) (11.62 ± 2.89 mm/mm2 versus 13.04 ± 2.44 mm/mm2, P = 0.029) increased significantly compared to baseline. For patients in group B, sural sensory nerve conduction velocity (47.93 ± 7.20 m/s versus 44.67 ± 6.43 m/s, P = 0.024), CNFD (17.19 ± 5.31 n/mm2 versus 15.67 ± 4.16 n/mm2, P = 0.001), corneal nerve branch density (19.33 ± 12.82 n/mm2 versus 14.23 ± 6.56 n/mm2, P = 0.033), and CNFL (11.16 ± 2.57 mm/mm2 versus 9.90 ± 1.75 mm/mm2, P = 0.011) decreased significantly. Conclusions The results of this study suggest that morphological repair of corneal nerve fibers can be detected when glycemic control improves. In vivo CCM could be a sensitive method that can be applied in future longitudinal or interventional studies on DPN.

An increased incidence of clinical diabetes has been reported in children with previous COVID-19. 1,2 It is plausible that the virus may trigger autoimmune response to the islets or hasten metabolic decompensation in persons with already established islet autoimmunity. We tested the hypothesis that previous SARS-CoV-2 infection was associated with autoimmunity, which predicts future type 1 diabetes.

Objective: As diabetes is a risk factor for severe symptoms, hospitalization, and death with COVID-19 disease, we aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in children and adults with and without type 1 diabetes in Colorado during 2020. Research Design and Methods: We developed a highly sensitive and specific test for antibodies against SARS-CoV-2 and measured the antibodies in children and adults with new-onset (n = 129) and established type 1 diabetes (n = 94) seen for routine diabetes care at our center between January and October 2020. The antibodies were also measured in 562 children and 102 adults from the general population of Colorado. Results: The prevalence of SARS-CoV-2 antibodies in persons with new-onset type 1 diabetes (0.8%; 95% confidence interval 0.1%-4.2%) or those with established disease (4.3%; 1.7%-10.4%) did not differ from that in the general population children (2.8%; 1.8%-4.6%) or adults (3.9%; 1.5%-9.7%). In a subset of individuals with positive antibodies (n = 31), antibodies remained positive for up to 9 months, although the levels decreased starting 3 months after the infection (P = 0.007). Conclusions: From January to October 2020, the prevalence of SARS-CoV-2 antibodies were not different in children and adults with and without type 1 diabetes in Colorado. We found no evidence for increased prevalence of COVID-19 infections among youth with newly diagnosed type 1 diabetes. (COMIRB Protocol 20-1007

Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder. It is characterized by hyperglycemia, insulin resistance (IR), and relative impairment in insulin secretion. IR plays a major role in the pathogenesis of T2DM. Many previous studies have investigated the relationship between estrogen, androgen, and obesity, but few focused on the relationship between sex hormones, abnormal lipid metabolism, and IR. The goal for the present study was to identify the association of IR with sex hormone, abnormal lipid metabolism in type 2 diabetes, and impaired glucose tolerance (IGT) patients.In total 13,400 participants were analyzed based on the results of the glucose tolerance test. Using a cross-sectional study, we showed the relationship between IR and the level of sex hormones among 3 different glucose tolerance states: normal control people, IGT, and T2DM patients. We also analyzed the relationship between IR and abnormal lipid metabolism.Significantly, luteinizing, progesterone, estradiol, prolactin, and follicle-stimulating hormone levels decreased in T2DM and IGT patients compared with those in normal control people. The association between IR and lipid metabolism disorders in T2DM and IGT patients was also observed.Our clinical findings may offer new insights into understanding the mechanism of metabolic disorders and in new therapeutic methods for the treatment of the prevalence of type 2 diabetes.

BackgroundIslet autoantibodies (IAbs) are the most reliable biomarkers to assess risk of progression to clinical type 1 diabetes (T1D). There are four major biochemically defined IAbs currently used in clinical trials that are equally important for disease prediction. The current screening methods use a radio-binding assay (RBA) for single IAb measurement, which are laborious and inefficient for large-scale screening. More importantly, up to 40% of patients with T1D have other autoimmune conditions that can be identified through relevant autoantibody testing. Thus, there is a need to screen for T1D and other autoimmune diseases simultaneously.MethodsBased on our well-established electrochemiluminescence (ECL) assay platform, we developed a multiplexed ECL assay that combines 7 individual autoantibody assays together in one single well to simultaneously screen T1D, and three other autoimmune diseases including celiac disease, autoimmune thyroid disease and autoimmune poly-glandular syndrome-1 (APS-1). The 7-Plex ECL assay was extensively validated against single antibody measurements including a standard RBA and single ECL assay.FindingsThe 7-Plex ECL assay was well correlated to each single ECL autoantibody assay and each RBA.InterpretationThe multiplexed ECL assay provides high sensitivity and disease specificity, along with high throughput and a low cost for large-scale screenings of T1D and other relevant autoimmune diseases in the general population.Fund grants 2-SRA-2015-51-Q-R, 2-SRA-2018-533-S-B, grants DK32083 and DK32493. grants 81770777.

Aims/hypothesis It is important to differentiate the two major phenotypes of adult-onset diabetes, autoimmune type 1 diabetes and non-autoimmune type 2 diabetes, especially as type 1 diabetes presents in adulthood. Serum GAD65 autoantibodies (GADA) are the most sensitive biomarker for adult-onset autoimmune type 1 diabetes, but the clinical value of GADA by current standard radiobinding assays (RBA) remains questionable. The present study focused on the clinical utility of GADA differentiated by a new electrochemiluminescence (ECL) assay in patients with adult-onset diabetes. Methods Two cohorts were analysed including 771 diabetic participants, 30–70 years old, from the Action LADA study (n = 6156), and 2063 diabetic participants, 20–45 years old, from the Diabetes in Young Adults (DiYA) study. Clinical characteristics of participants, including requirement of early insulin treatment, BMI and development of multiple islet autoantibodies, were analysed according to the status of RBA-GADA and ECL-GADA, respectively, and compared between these two assays. Results GADA was the most prevalent and predominant autoantibody, >90% in both cohorts. GADA positivity by either RBA or ECL assay significantly discriminated clinical type 1 from type 2 diabetes. However, in both cohorts, participants with ECL-GADA positivity were more likely to require early insulin treatment, have multiple islet autoantibodies, and be less overweight (for all p < 0.0001). However, clinical phenotype, age at diagnosis and BMI independently improved positive predictive value (PPV) for the requirement of insulin treatment, even augmenting ECL-GADA. Participants with GADA detectable by RBA, but not confirmed by ECL, had a phenotype more similar to type 2 diabetes. These RBA-GADA positive individuals had lower affinity GADA compared with participants in which GADA was confirmed by ECL assay. Conclusions/interpretation Detection of GADA by ECL assay, given technical advantages over RBA-GADA, identified adult-onset diabetes patients at higher risk of requiring early insulin treatment, as did clinical phenotype, together allowing for more accurate clinical diagnosis and management. Graphical abstract

Background The risk of progression to type 1 diabetes (T1D) in subjects positive only for ZnT8 autoantibody (ZnT8A) is currently not known. Methods We developed an electrochemiluminescence (ECL) assay to detect high-affinity ZnT8A and validated it in three populations: 302 patients newly diagnosed with T1D, 135 non-diabetic children positive for ZnT8A by standard radio-binding assay (RBA) among 23400 children screened by the Autoimmunity Screening for Kids (ASK), and 123 non-diabetic children multiple autoantibody positive or single ZnT8A positive by RBA participating in the Diabetes Autoimmunity Study in the Young (DAISY). Results In 302 patients with T1D at diagnosis, the positivity for ZnT8A was 62% in both RBA and ECL. Among ASK 135 participants positive for RBA-ZnT8A, 64 were detected ZnT8A as the only islet autoantibody. Of these 64, only 9 were confirmed by ECL-ZnT8A, found to be of high affinity with increased T1D risk. Overall positive predictive value of ECL-ZnT8A for T1D risk was 87.1%, significantly higher than that of RBA-ZnT8A (53.5%, P&lt;0.0001). In DAISY, 11/2547 children who had no positivity previously detected for other islet autoantibodies were identified as single ZnT8A by RBA; of these, three were confirmed positive by ECL-ZnT8A and all three progressed to clinical T1D. Conclusions Large proportion of ZnT8A by RBA are single ZnT8A with low T1D risk while ZnT8A by ECL were of high-affinity and high prediction for T1D development.

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