Conjugating Hemoglobin and Albumin by Strain-Promoted Azide-Alkyne Cycloaddition.

A one-to-one conjugate of cross-linked human hemoglobin and human serum albumin results from a strain-promoted azide-alkyne cycloaddition (SPAAC) of the modified proteins. Additions of a strained alkyne-substituted maleimide to the Cys-34 thiol of human serum albumin and an azide-containing cross-link between the amino groups of each b-unit at Lys-82 of human hemoglobin provide sites for coupling by the SPAAC process. The coupled hemoglobin-albumin conjugate can be readily purified from the unreacted hemoglobin. The oxygen binding properties of this two-protein conjugate demonstrate an oxygen affinity and binding cooperativity suitable as an acellular oxygen carrier.

Association of technologically assisted integrated care with clinical outcomes in type 2 diabetes in Hong Kong using the prospective JADE Program: A retrospective cohort analysis.

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.

Effects of Providing Peer Support on Diabetes Management in People With Type 2 Diabetes.

PURPOSE: We examined the effects of participating in a "train-the-trainer" program and being a peer supporter on metabolic and cognitive/psychological/behavioral parameters in Chinese patients with type 2 diabetes. METHODS: In response to our invitation, 79 patients with fair glycemic control (HbA1c <8%) agreed to participate in a "train-the-trainer" program to become peer supporters. Of the 59 who completed the program successfully, 33 agreed to be peer supporters ("agreed trainees") and were each assigned to support 10 patients for 1 year, with a voluntary extension period of 3 additional years, while 26 trainees declined to be supporters ("refused trainees"). A group of 60 patients with fair glycemic control who did not attend the training program and were under usual care were selected as a comparison group. The primary outcome was the change in average HbA1c levels for the 3 groups from baseline to 6 months. RESULTS: At 6 months, HbA1c was unchanged in the trainees (at baseline, 7.1 ± 0.3%; at 6 months, 7.1 ± 1.1%) but increased in the comparison group (at baseline, 7.1 ± 0.5%; at 6 months, 7.3 ± 1.1%. P = .02 for between-group comparison). Self-reported self-care activities including diet adherence and foot care improved in the trainees but not the comparison group. After 4 years, HbA1c remained stable among the agreed trainees (at baseline, 7.0 ± 0.2%; at 4 years: 7.2 ± 0.6%), compared with increases in the refused trainees (at baseline, 7.1 ± 0.4%; at 4 years, 7.8 ± 0.8%) and comparison group (at baseline, 7.1 ± 0.5%; at 4 years, 8.1 ± 0.6%. P = .001 for between-group comparison). CONCLUSIONS: Patients with diabetes who engaged in providing ongoing peer support to other patients with diabetes improved their self-care while maintaining glycemic control over 4 years.

Risk of development of diabetes mellitus in Chinese women with persistently impaired glucose tolerance after gestational diabetes.

OBJECTIVES: To estimate the cumulative incidence for the development of diabetes mellitus in Chinese women with persistently impaired glucose tolerance after gestational diabetes, and evaluate putative risk factors. DESIGN: Historical cohort study. SETTING: A regional hospital in Hong Kong. PATIENTS: Women with postpartum impaired glucose tolerance (as confirmed by a 75-gram oral glucose tolerance test 6 weeks after delivery) seen between January 2000 and December 2006. RESULTS: After a mean follow-up period of 52 (standard deviation, 22; range, 12-106) months, 47 (20%) of the 238 women converted to diabetes mellitus. Concomitant postpartum impaired fasting plasma glucose levels increased the risk of future diabetes mellitus by 3.5-fold (95% confidence interval, 1.7-7.0; P=0.001) when compared to those with postpartum impaired glucose tolerance only. Based on multivariate analysis, only antepartum and postpartum fasting plasma glucose levels predicted future development of diabetes mellitus. At 1 year after delivery in 95/159 (60%) of the women, glucose tolerance regressed to normal, while in only 9/159 (6%) it progressed to diabetes mellitus. At this stage, 29% of those with impaired glucose regulation (impaired glucose tolerance, impaired fasting glucose or both) compared to 2% of those whose glucose tolerance reverted to normal developed diabetes mellitus upon subsequent follow-up (P<0.001). In all, 24/159 (15%) fulfilled the definition of metabolic syndrome and its presence was associated with 4.7-fold increased risk of future diabetes mellitus (95% confidence interval, 1.7-13.4; P=0.004). CONCLUSIONS: Women with persistent postpartum impaired glucose tolerance after gestational diabetes have a high risk of developing diabetes mellitus. However, a significant proportion of these women regress to normal glucose tolerance 1 year after delivery, and their risk of progression to diabetes mellitus is lower than those with persistent impaired glucose regulation. Therefore, women with a history of gestational diabetes, particularly those with persistent glucose intolerance 6 weeks and 1 year after delivery, should have regular surveillance for the development of diabetes mellitus.

Retinal Information is Independently Associated with Cardiovascular Disease in Patients with Type 2 diabetes.

To evaluate the association between a series of retinal information and cardiovascular disease (CVD) and to evaluate whether this association is independent of traditional CVD risk factors in type 2 diabetes patients, we undertook an age-sex matched case-control study with 79 CVD cases and 150 non-CVD controls. All the participants underwent standardized physical examinations and retinal imaging. Retinal information was extracted from the retinal images using a semi-automatic computer program. Three stepwise logistic regression models were evaluated: model 1 with cardiovascular risk factors only; model 2 with retinal information only and model 3 with both cardiovascular risk factors and retinal information. The areas under the receiver operating characteristic curves (AUCs) were used to compare the performances of different models. Results showed that the AUCs were 0.692 (95%CI: 0.622-0.761) and 0.661 (95%CI: 0.588-0.735) for model 1 and model 2, respectively. In addition, model 3 had an AUC of 0.775 (95%CI: 0.716-0.834). Compared to the previous two models, the AUC of model 3 increased significantly (p < 0.05 in both comparisons). In conclusion, retinal information is independently associated with CVD in type 2 diabetes. Further work is needed to validate the translational value of applying retinal imaging analysis into clinical practice.

Gender, diabetes education, and psychosocial factors are associated with persistent poor glycemic control in patients with type 2 diabetes in the Joint Asia Diabetes Evaluation (JADE) program.

BACKGROUND: Factors associated with persistent poor glycemic control were explored in patients with type 2 diabetes under the Joint Asia Diabetes Evaluation (JADE) program. METHODS: Chinese adults enrolled in JADE with HbA1c ≥8% at initial comprehensive assessment (CA1) and repeat assessment were analyzed. The improved group was defined as those with a ≥1% absolute reduction in HbA1c, and the unimproved group was those with <1% reduction at the repeat CA (CA2). RESULTS: Of 4458 enrolled patients with HbA1c ≥8% at baseline, 1450 underwent repeat CA. After a median interval of 1.7 years (interquartile range[IQR] 1.1-2.2) between CA1 and CA2, the unimproved group (n = 677) had a mean 0.4% (95% confidence interval [CI] 0.3%, 0.5%) increase in HbA1c compared with a mean 2.8% reduction (95% CI -2.9, -2.6%) in the improved group (n = 773). The unimproved group had a female preponderance with lower education level, and was more likely to be insulin treated. Patients in the improved group received more diabetes education between CAs with improved self-care behaviors, whereas the unimproved group had worsening of health-related quality of life at CA2. Apart from female gender, long disease duration, low educational level, obesity, retinopathy, history of hypoglycemia, and insulin use, lack of education from diabetes nurses between CAs had the strongest association for persistent poor glycemic control. CONCLUSIONS: These results highlight the multidimensional nature of glycemic control, and the importance of diabetes education and optimizing diabetes care by considering psychosocial factors.

The Clinical Utility of SUDOSCAN in Chronic Kidney Disease in Chinese Patients with Type 2 Diabetes.

There are gaps between recommendations on regular screening for diabetic kidney disease (DKD) and clinical practice especially in busy and low resource settings. SUDOSCAN (Impeto Medical, Paris, France) is a non-invasive technology for assessing sudomotor function using reverse iontophoresis and chronoamperometry which detects abnormal sweat gland function. Vasculopathy and neuropathy share common risk factors and we hypothesized that SUDOSCAN may be used to detect chronic kidney disease (CKD). Between 2012 and 2013, SUDOSCAN was performed in a consecutive cohort of 2833 Hong Kong Chinese adults with type 2 diabetes. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min/1.73m2. In this cross-sectional cohort (mean age 58.6±9.5 years, 55.7% male, median disease duration 8 [interquartile range 3-14] years), 5.8% had CKD. At a cut-off SUDOSCAN-DKD score of 53, the test had sensitivity of 76.7%, specificity of 63.4% and positive likelihood ratio of 2.1 to detect CKD. The area under receiver operating characteristic curve for CKD was 0.75 (95% confidence interval 0.72-0.79). Patients without CKD but low score had worse risk factors and complications than those with high score. We conclude that SUDOSCAN may be used to detect patients at risk of impaired renal function as part of a screening program in Chinese population, especially in outreach or low resource settings.

Effects of telephone-based peer support in patients with type 2 diabetes mellitus receiving integrated care: a randomized clinical trial.

IMPORTANCE: In type 2 diabetes mellitus (T2DM), team management using protocols with regular feedback improves clinical outcomes, although suboptimal self-management and psychological distress remain significant challenges. OBJECTIVE: To investigate if frequent contacts through a telephone-based peer support program (Peer Support, Empowerment, and Remote Communication Linked by Information Technology [PEARL]) would improve cardiometabolic risk and health outcomes by enhancing psychological well-being and self-care in patients receiving integrated care implemented through a web-based multicomponent quality improvement program (JADE [Joint Asia Diabetes Evaluation]). DESIGN, SETTING, AND PARTICIPANTS: Between 2009 and 2010, 628 of 2766 Hong Kong Chinese patients with T2DM from 3 publicly funded hospital-based diabetes centers were randomized to the JADE + PEARL (n = 312) or JADE (n = 316) groups, with comprehensive assessment at 0 and 12 months. INTERVENTIONS: Thirty-three motivated patients with well-controlled T2DM received 32 hours of training (four 8-hour workshops) to become peer supporters, with 10 patients assigned to each. Peer supporters called their peers at least 12 times, guided by a checklist. MAIN OUTCOMES AND MEASURES: Changes in hemoglobin A(1c) (HbA(1c)) level (primary), proportions of patients with attained treatment targets (HbA(1c) <7%; blood pressure <130/80 mm Hg; low-density lipoprotein cholesterol <2.6 mmol/L [to convert to milligrams per deciliter, divide by 0.0256]) (secondary), and other health outcomes at month 12. RESULTS: Both groups had similar baseline characteristics (mean [SD] age, 54.7 [9.3] years; 57% men; disease duration, 9.4 [7.7] years; HbA(1c) level, 8.2% [1.6%]; systolic blood pressure, 136 [19] mm Hg; low-density lipoprotein cholesterol level, 2.89 [0.82] mmol/L; 17.4% cardiovascular-renal complications; and 34.9% insulin treated). After a mean (SD) follow-up period of 414 (55) days, 5 patients had died, 144 had at least 1 hospitalization, and 586 had repeated comprehensive assessments. On intention-to-treat analysis, both groups had similar reductions in HbA(1c) (JADE + PEARL, 0.30% [95% CI, 0.12%-0.47%], vs JADE, 0.29% [95% CI, 0.12%-0.47%] [P = .97]) and improvements in treatment targets and psychological-behavioral measures. In the JADE + PEARL group, 90% of patients maintained contacts with their peer supporters, with a median of 20 calls per patient. Most of the discussion items were related to self-management. CONCLUSIONS AND RELEVANCE: In patients with T2DM receiving integrated care, peer support did not improve cardiometabolic risks or psychological well-being. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00950716.

Healing effect of a two-herb recipe (NF3) on foot ulcers in Chinese patients with diabetes: a randomized double-blind placebo-controlled study.

BACKGROUND: In the present study, we examined the effect of a two-herb traditional Chinese medicine (NF3), comprised of Astragali Radix and Radix Rehmanniae, on the healing of diabetic foot ulcer and the possible molecular mechanisms involved. METHODS: This was a prospective randomized double-blind placebo-controlled study. Sixteen diabetic patients were randomized to receive either placebo or NF3 for 6 months. Ulcer healing and sensory changes were examined. Molecular studies included measurement of serum tumor necrosis factor (TNF)-α and RNA microarray investigation. RESULTS: The daily rate of reduction in ulcer area was 3.55% in the NF3 group and 1.52% in the placebo group (P = 0.062). In the index limb, the number of negative tests for sensory neuropathy using monofilament was reduced from 27% to 7% in the NF3 group and from 37% to 35% in the placebo group (P < 0.001). In addition, NF3 significantly decreased serum TNF-α levels (P = 0.034). Microarray studies revealed concerted changes following NF3 treatment in the expression of genes implicated in fibroblast regeneration, angiogenesis, and anti-inflammation. CONCLUSIONS: In this proof-of-concept study, 6-month treatment with NF3 was associated with improved wound healing and sensation accompanied by concerted changes in gene expression.

Delivery of integrated diabetes care using logistics and information technology--the Joint Asia Diabetes Evaluation (JADE) program.

Diabetes is a global epidemic, and many affected individuals are undiagnosed, untreated, or uncontrolled. The silent and multi-system nature of diabetes and its complications, with complex care protocols, are often associated with omission of periodic assessments, clinical inertia, poor treatment compliance, and care fragmentation. These barriers at the system, patient, and care-provider levels have resulted in poor control of risk factors and under-usage of potentially life-saving medications such as statins and renin-angiotensin system inhibitors. However, in the clinical trial setting, use of nurses and protocol with frequent contact and regular monitoring have resulted in marked differences in event rates compared to epidemiological data collected in the real-world setting. The phenotypic heterogeneity and cognitive-psychological-behavioral needs of people with diabetes call for regular risk stratification to personalize care. Quality improvement initiatives targeted at patient education, task delegation, case management, and self-care promotion had the largest effect size in improving cardio-metabolic risk factors. The Joint Asia Diabetes Evaluation (JADE) program is an innovative care prototype that advocates a change in clinic setting and workflow, coordinated by a doctor-nurse team and augmented by a web-based portal, which incorporates care protocols and a validated risk engine to provide decision support and regular feedback. By using logistics and information technology, supported by a network of health-care professionals to provide integrated, holistic, and evidence-based care, the JADE Program aims to establish a high-quality regional diabetes database to reflect the status of diabetes care in real-world practice, confirm efficacy data, and identify unmet needs. Through collaborative efforts, we shall evaluate the feasibility, acceptability, and cost-effectiveness of this "high tech, soft touch" model to make diabetes and chronic disease care more accessible, affordable, and sustainable.