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Hongjiang Wu,1,2 Eric SH Lau,3 Alice PS Kong,2,4 Ronald CW Ma,2,4 Risa Ozaki,4 Kitty KT Cheung,4 Elaine Chow,4 Chiu Chi Tsang,5 Kam Piu Lau,6 Eric MT Hui,7 Wing Yee So,8 Danijela Gasevic,1,9 Sarah H Wild,1 Juliana CN Chan,2–4 Andrea Luk2–4 1Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK; 2Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; 3Asia Diabetes Foundation, Prince of Wales Hospital, Hong Kong SAR, China; 4Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; 5Alice Ho Miu Ling Nethersole Hospital, Tai Po, Hong Kong SAR, China; 6Northern District Hospital, Fanling, Hong Kong SAR, China; 7Department of Family Medicine, Prince of Wales Hospital, Hong Kong SAR, China; 8Hospital Authority Head Office, Hong Kong SAR, China; 9School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia Purpose: The aim of this study was to describe the association between educational level and incident cardiovascular disease (CVD) and all-cause mortality in Hong Kong Chinese patients with type 2 diabetes.Patients and methods: We included 12,634 patients with type 2 diabetes who were enrolled into the Joint Asia Diabetes Evaluation Program between June 1, 2007, and June 30, 2017. We classified patients’ educational level into the following three groups: ≤6 years, 6–13 years, and >13 years. Incident CVD events were identified using hospital discharge diagnoses. Death was identified from Hong Kong Death Register. We estimated HRs for incident CVD and all-cause mortality using Cox regression models.Results: Patients with the highest educational level were younger and had shorter diabetes duration and better glycemic control at enrollment than those with the lowest educational level. During the median follow-up of 6.2 years for CVD and 6.4 years for all-cause mortality, 954 CVD events and 833 deaths were recorded. HRs for CVD and all-cause mortality were 0.73 (95% CI: 0.57, 0.94) and 0.71 (95% CI: 0.54, 0.94) for the highest educational level compared to the lowest educational level, after adjustment for age, sex, diabetes duration, and family history of diabetes.Conclusion: Educational level is inversely associated with the risk of CVD and all-cause mortality among Hong Kong Chinese patients with type 2 diabetes. Hong Kong Chinese patients with type 2 diabetes and low educational level should be given special attention for the prevention of key complications of diabetes. Keywords: socioeconomic status, educational level, diabetes, cardiovascular disease, all-cause mortality

Background: Diabetes outcomes are influenced by host factors, settings, and care processes. We examined the association of data-driven integrated care assisted by information and communications technology (ICT) with clinical outcomes in type 2 diabetes in public and private healthcare settings., Methods and Findings: The web-based Joint Asia Diabetes Evaluation (JADE) platform provides a protocol to guide data collection for issuing a personalized JADE report including risk categories (1-4, low-high), 5-year probabilities of cardiovascular-renal events, and trends and targets of 4 risk factors with tailored decision support. The JADE program is a prospective cohort study implemented in a naturalistic environment where patients underwent nurse-led structured evaluation (blood/urine/eye/feet) in public and private outpatient clinics and diabetes centers in Hong Kong. We retrospectively analyzed the data of 16,624 Han Chinese patients with type 2 diabetes who were enrolled in 2007-2015. In the public setting, the non-JADE group (n = 3,587) underwent structured evaluation for risk factors and complications only, while the JADE (n = 9,601) group received a JADE report with group empowerment by nurses. In a community-based, nurse-led, university-affiliated diabetes center (UDC), the JADE-Personalized (JADE-P) group (n = 3,436) received a JADE report, personalized empowerment, and annual telephone reminder for reevaluation and engagement. The primary composite outcome was time to the first occurrence of cardiovascular-renal diseases, all-site cancer, and/or death, based on hospitalization data censored on 30 June 2017. During 94,311 person-years of follow-up in 2007-2017, 7,779 primary events occurred. Compared with the JADE group (136.22 cases per 1,000 patient-years [95% CI 132.35-140.18]), the non-JADE group had higher (145.32 [95% CI 138.68-152.20]; P = 0.020) while the JADE-P group had lower event rates (70.94 [95% CI 67.12-74.91]; P < 0.001). The adjusted hazard ratios (aHRs) for the primary composite outcome were 1.22 (95% CI 1.15-1.30) and 0.70 (95% CI 0.66-0.75), respectively, independent of risk profiles, education levels, drug usage, self-care, and comorbidities at baseline. We reported consistent results in propensity-score-matched analyses and after accounting for loss to follow-up. Potential limitations include its nonrandomized design that precludes causal inference, residual confounding, and participation bias., Conclusions: ICT-assisted integrated care was associated with a reduction in clinical events, including death in type 2 diabetes in public and private healthcare settings., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: JCNC is the Chief Executive Officer (on a pro-bono basis) of ADF, a charitable foundation established under the CUHK Foundation for developing the JADE Technology. JCNC, WYS, and RCWM are co-founders of GemVCare, a biotechnology company, supported by the Hong Kong Government Technology Start-up Support Scheme for Universities, which licenses the JADE Technology to provide diabetes risk evaluation and management program, in collaboration with other healthcare organizations. RCWM is a member of the editorial board for PLOS Medicine. RCWM has received research grants for clinical trials from AstraZeneca, Bayer, MSD, Novo Nordisk, Sanofi, and Tricida and honoraria for consultancy or lectures from AstraZeneca and Boehringer Ingelheim.

Antibodies are well-known protein mediators of immunity. IgM is the primordial member and the neglected sibling of the later-evolved and more proficient IgG in regard to their therapeutic and diagnostic use. Serendipitously, however, we found a paradox: While murine IgM antibodies specific for guanosine triphosphate (GTP) were able to recognize native guanylyl antigens found in primate or rat muscle tissues by immunofluorescence assays (which mimicked the auto-antibodies from autoimmune patients to skeletal or smooth muscle), the murine and human IgG counterparts failed. The results were replicated in cell-free direct binding assays using small latex microspheres decorated densely with GTP. The IgG antibodies could bind, however, if GTP was presented more spaciously on larger particles or as a univalent hapten. Accordingly, oligomerization of GTP (30-mer) destroyed the binding of the IgG antibodies but enhanced that of the IgMs in inhibition ELISA. We reason that, contrary to current belief, IgM does not bind in a lock-and-key manner like IgG. We hypothesize that whereas the intact and rigid antigen-binding site of IgG hinders the antibody from docking with antigens that are obstructed, in IgM, the two component polypeptides of the antigen-binding site can dissociate from each other and navigate individually through obstacles like the ancestral single-polypeptide antibodies found in sharks and camelids, both components eventually re-grouping around the antigen. We further speculate that polyreactive IgMs, which enigmatically bind to more than one type of antigen, use the same modus operandi. These findings call for a re-look at the clinical potential of IgM antibodies particularly in specific areas of cancer therapy, tissue pathology and vaccine design, where IgG antibodies have failed due to target inaccessibility.

Background: Early detection and risk factor control prevent chronic kidney disease (CKD) progression. Evaluation of peripheral autonomic dysfunction may detect incident cardiovascular-renal events in type 2 diabetes (T2D)., Methods: SUDOSCAN, a non-invasive tool, provides an age-adjusted electrochemical skin conductance (ESC) composite score incorporating hands/feet ESC measurements, with a score ≤53 indicating sudomotor dysfunction. A consecutive cohort of 2833 Chinese adults underwent structured diabetes assessment in 2012-13; 2028 participants without preexisting cardiovascular disease (CVD) and CKD were monitored for incident cardiovascular-renal events until 2015., Results: In this prospective cohort {mean age 57.0 [standard deviation (SD) 10.0] years; median T2D duration 7.0 [interquartile range (IQR) 3.0-13.0] years; 56.1% men; 72.5% never-smokers; baseline ESC composite score 60.7 (SD 14.5)}, 163 (8.0%) and 25 (1.2%) participants developed incident CKD and CVD, respectively, after 2.3 years of follow-up. The adjusted hazard ratios (aHRs) per 1-unit decrease in the ESC composite score for incident CKD, CVD and all-cause death were 1.02 [95% confidence interval (CI) 1.01-1.04], 1.04 (1.00-1.07) and 1.04 (1.00-1.08), respectively. Compared with participants with an ESC composite score >53, those with a score ≤53 had an aHR of 1.56 (95% CI 1.09-2.23) for CKD and 3.11 (95% CI 1.27-7.62) for CVD, independent of common risk markers. When added to clinical variables (sex and duration of diabetes), the ESC composite score improved discrimination of all outcomes with appropriate reclassification of CKD risk., Conclusions: A low ESC composite score independently predicts incident cardiovascular-renal events and death in T2D, which may improve the screening strategy for early intervention., (© The Author(s) 2018. Published by Oxford University Press on behalf of ERA-EDTA.)

The rapid increase in diabetes prevalence globally has contributed to large increases in health care expenditure on diabetic complications, posing a major health burden to countries worldwide. Asians are commonly observed to have poorer β-cell function and greater insulin resistance compared to the Caucasian population, which is attributed by their lower lean body mass and central obesity. This "double phenotype" as well as the rising prevalence of young onset diabetes in Asia has placed Asians with diabetes at high risk of cardiovascular and renal complications, with cancer emerging as an important cause of morbidity and mortality. The experience from Hong Kong had demonstrated that a multifaceted approach, involving team-based integrated care, information technological advances, and patient empowerment programs were able to reduce the incidence of diabetic complications, hospitalizations, and mortality. System change and public policies to enhance implementation of such programs may provide solutions to combat the burgeoning health problem of diabetes at a societal level., Competing Interests: Juliana C.N. Chan is the Chief Executive Officer, on a probono basis, of the Asia Diabetes Foundation which designs and operates the JADE Programme (www.adf.org.hk). Other authors reported no conflict of interest relevant to this article., (Copyright © 2018 Korean Endocrine Society.)

Background: Infection occurs more commonly in diabetic patients compared with the general population and is an under-recognised but important morbidity in patients with diabetes. We examined the impact of glycaemic control on hospitalisation for infection in a large prospective cohort of Chinese adults with type 2 diabetes., Methods: Between July 1994 and June 2014, 22 846 patients with type 2 diabetes underwent detailed assessment of metabolic control and diabetes complications. Patients were followed for occurrence of infection requiring hospitalisation as identified using discharge diagnosis codes., Results: Over a median follow-up of 4.8 years, 20.3% of patients were hospitalised for any infection type, with respiratory tract, genitourinary tract, and skin being the most commonly affected sites. In multivariate Cox regression, time-dependent HbA1c was associated with all-site infection (hazard ratio [HR] 1.07 [95% confidence interval {CI}:1.05-1.09, P < 0.001]), genitourinary tract infection (HR 1.09 [95% CI: 1.04-1.14], P < 0.001), and skin infection (HR 1.16 [95% CI 1.12-1.21]. P < 0.001), but not infection of respiratory tract, and was independent of age, gender, disease duration, smoking, body mass index, glomerular filtration rate, haemoglobin, history of stroke, congestive heart failure, coronary heart disease, peripheral artery disease, diabetic neuropathy and cancer, and baseline drug use. Against an arbitrary HbA1c interval of >7.0-8.0% (53-64 mmol/mol), patients with HbA1c ≤6.0% (42 mmol/mol) and >8.0% (64 mmol/mol) had excess risks of infection-related hospitalisation adjusted for other factors., Conclusions: In patients with type 2 diabetes, burden of serious infection is high. In the diabetic population, a U-shape relationship between glycaemia and infection-related hospitalisation was detected., (Copyright © 2017 John Wiley & Sons, Ltd.)