Investigating the causal association of generalized and abdominal obesity with microvascular complications in patients with type 2 diabetes: A community-based prospective study.

AIM: The paradoxical protective association between overweight/obesity and diabetic microvascular complications (DMC), a phenomenon well-known as the obesity paradox, has been considered a non-causal association based on methodological influences. We aimed to investigate the association of generalized and abdominal obesity, as measured by body mass index (BMI) and waist circumference (WC), respectively, with DMC in patients with type 2 diabetes (T2D), using a causal inference approach. MATERIALS AND METHODS: We enrolled 1436 patients with clinically diagnosed T2D but not DMC at baseline in a community-based prospective cohort in China between 2017 and 2019 and followed them annually until 2022 with new-onset DMC recorded. Marginal structural Cox models with inverse probability weighting were constructed to determine the causal association. Subgroup analyses were performed to identify potential effect modifiers. RESULTS: We observed 360 incident DMC cases, including 109 cases of diabetic nephropathy (DN) and 277 cases of diabetic retinopathy (DR) during four follow-up visits. Multivariable-adjusted hazard ratios (95% confidence intervals) for overall DMC, DN and DR were 1.037 (1.005-1.071), 1.117 (1.062-1.175) and 1.018 (0.980-1.059) for 1 kg/m2 increase in BMI, and 1.005 (0.994-1.017), 1.034 (1.018-1.051) and 1.000 (0.987-1.014) for 1 cm increase in WC, respectively. Similar patterns were observed across the BMI and WC categories, while the positive association appeared to be more pronounced in women. CONCLUSIONS: Generalized but not abdominal obesity was associated with an increased risk for the overall DMC, whereas both obesities were causally related to DN, albeit not DR, in T2D. Routine weight management should not be neglected in diabetes care, particularly in women.

Association of Visceral Obesity Indices With Incident Diabetic Retinopathy in Patients With Diabetes: Prospective Cohort Study.

BACKGROUND: Visceral adipose tissue plays an active role in the pathogenesis of type 2 diabetes and vascular dysfunction. The lipid accumulation product (LAP), visceral adiposity index (VAI), and Chinese VAI (CVAI) have been proposed as simple and validated surrogate indices for measuring visceral adipose tissue. However, the evidence from prospective studies on the associations between these novel indices of visceral obesity and diabetic retinopathy (DR) remains scant. OBJECTIVE: This study aimed to investigate the longitudinal associations of LAP, VAI, and CVAI with incident DR in Chinese patients with diabetes. METHODS: This was a prospective cohort study conducted in Guangzhou in southern China. We collected baseline data between November 2017 and July 2020, while on-site follow-up visits were conducted annually until January 2022. The study participants consisted of 1403 patients with a clinical diagnosis of diabetes, referred from primary care, who were free of DR at baseline. The LAP, VAI, and CVAI levels were calculated by sex-specific equations based on anthropometric and biochemical parameters. DR was assessed using 7-field color stereoscopic fundus photographs and graded according to the modified Airlie House Classification scheme. Time-dependent Cox proportional hazard models were constructed to estimate the hazard ratios with 95% CIs. Restricted cubic spline curves were fitted to examine the dose-response relationship between the 3 indices of visceral obesity and new-onset DR. Subgroup analyses were performed to investigate the potential effect modifiers. RESULTS: The mean age of study participants was 64.5 (SD 7.6) years, and over half (816/1403, 58.2%) were female. During a median follow-up of 2.13 years, 406 DR events were observed. A 1-SD increment in LAP, VAI, or CVAI was consistently associated with increased risk for new-onset DR, with a multivariable­adjusted hazard ratio of 1.24 (95% CI 1.09-1.41; P=.001), 1.22 (95% CI 1.09-1.36; P<.001), and 1.48 (95% CI 1.19-1.85; P=.001), respectively. Similar patterns were observed across tertiles in LAP (P for trend=.001), VAI (P for trend<.001), and CVAI (P for trend=.009). Patients in the highest tertile of LAP, VAI, and CVAI had an 84%, 86%, and 82% higher hazard of DR, respectively, compared to those in the lowest tertile. A nonlinear dose-response relationship with incident DR was noted for LAP and VAI (both P for nonlinearity<.05), but not for CVAI (P for nonlinearity=.51). We did not detect the presence of effect modification by age, sex, duration of diabetes, BMI, or comorbidity (all P for interaction>.10). CONCLUSIONS: Visceral obesity, as measured by LAP, VAI, or CVAI, is independently associated with increased risk for new-onset DR in Chinese patients with diabetes. Our findings may suggest the necessity of incorporating regular monitoring of visceral obesity indices into routine clinical practice to enhance population-based prevention for DR.

Rapid, direct, visualized and antibody-free bacterial detection with extra species identification and susceptibility evaluation capabilities.

Bacterial antimicrobial resistance (AMR) driven by the abuse of antibiotics is a global highlight challenge, calling for a rapid, economical and generalizable bacterial detection technology. Here, in case of urinary tract infections (UTIs), a naked-eye, antibody-free and multi-functional bacterial assessment platform was designed, which consisted of concanavalin A modified gold nanoparticles (ConA-AuNPs), vancomycin modified gold nanoparticles (Van-AuNPs), and polymyxin B modified Prussian blue nanoparticles (PMB-PBNPs). Based on the fast agglutination of bacterial cells induced by concanavalin A, ConA-AuNPs could aggregate on bacterial cells of Escherichia coli and Staphylococcus aureus, resulting in a visible color change due to alteration of surface plasmon resonance properties within 30 min. Besides, due to the different affinity of vancomycin and polymyxin B to bacteria, Van-AuNPs preferred to bind to Gram-positive bacteria, generating colorimetric response within 2-3 h; while PMB-PBNPs could be reduced colourless Prussian white (PW) by the prior Gram-negative bacterial metabolization in contrast to Gram-positive bacterial metabolization within 4-6 h. Combining our platform with antibiotics, the minimum inhibitory concentration of bacteria could be determined within 4-8 h, which was proved by incubating Escherichia coli and Staphylococcus aureus with various antibiotics. The feasibility was verified by clinical samples, which was consistent with the classical clinical test within only 1/48 of the process timing. Therefore, this colorimetric nanoplatform orderly realized the rapid detection, species identification (Gram-positive and Gram-negative), and susceptibility evaluation of bacteria, satisfying multiple needs from timely clinical diagnosis to accurate medication guidance.

Taxonomic notes on the Chinese endemic genus Straneostichus Sciaky, 1994 (Coleoptera: Carabidae: Pterostichini), with descriptions of three new species.

A total of eleven species and two subspecies are recognized within the Chinese endemic genus Straneostichus Sciaky, 1994 (Carabidae: Pterostichini), including three new species described in the present paper: Straneostichus politus sp. nov. (Sichuan: Wolong), Straneostichus liupanensis sp. nov. (Ningxia: Liupanshan) and Straneostichus ganqingensis sp. nov. (Qinghai: Mengda and Gansu: Dangchang). Taxonomical notes and new distribution records for all the known species are provided, along with an updated key to the species of Straneostichus.

Healthcare needs, experiences and treatment burden in primary care patients with multimorbidity: An evaluation of process of care from patients' perspectives.

BACKGROUND: Patients with multimorbidity often experience treatment burden as a result of fragmented, specialist-driven healthcare. The 'family doctor team' is an emerging service model in China to address the increasing need for high-quality routine primary care. OBJECTIVE: This study aimed to explore the extent to which treatment burden was associated with healthcare needs and patients' experiences. METHODS: Multisite surveys were conducted in primary care facilities in Guangdong province, southern China. Interviewer-administered questionnaires were used to collect data from patients (N = 2160) who had ≥2 clinically diagnosed long-term conditions (multimorbidity) and had ≥1 clinical encounter in the past 12 months since enrolment registration with the family doctor team. Patients' experiences and treatment burden were measured using a previously validated Chinese version of the Primary Care Assessment Tool (PCAT) and the Treatment Burden Questionnaire, respectively. RESULTS: The mean age of the patients was 61.4 years, and slightly over half were females. Patients who had a family doctor team as the primary source of care reported significantly higher PCAT scores (mean difference 7.2 points, p < .001) and lower treatment burden scores (mean difference -6.4 points, p < .001) when compared to those who often bypassed primary care. Greater healthcare needs were significantly correlated with increased treatment burden (ß-coefficient 1.965, p < .001), whilst better patients' experiences were associated with lower treatment burden (ß-coefficient -0.252, p < .001) after adjusting for confounders. CONCLUSION: The inverse association between patients' experiences and treatment burden supports the importance of primary care in managing patients with multimorbidity. PATIENT CONTRIBUTION: Primary care service users were involved in the instrument development and data collection.

Association between Systolic Blood Pressure and Diabetic Retinopathy in Both Hypertensive and Normotensive Patients with Type 2 Diabetes: Risk Factors and Healthcare Implications.

A common diabetes-related microvascular complication is diabetic retinopathy (DR), yet associations between blood pressure (BP) and risks for DR in diabetic patients with normal BP received inadequate attention. This may lead to 'clinical inertia' in early DR prevention. We aimed to assess whether the extent to which systolic BP levels were associated with DR in patients with type 2 diabetes (T2DM) and normal BP were similar to that in those with concurrent hypertension. Data were collected from patients with T2DM attending ophthalmic check-up with primary care referral (n = 2510). BP measurements, clinical laboratory tests, and dilated fundus examination were conducted according to gold standard of diagnosis and routine clinical procedure. Of all subjects, over 40% were normotensive and one fifth were clinically diagnosed with DR. Systolic BP levels increased across DR categories of escalated severity irrespective of the coexistence of hypertension. Ordinal logistic regression analysis showed that an increased systolic BP was independently and significantly associated with DR (adjusted odds ratio [aOR] = 1.020, p < 0.001 for hypertensives; aOR = 1.019, p = 0.018 for normotensives), after adjusting for diabetes duration, sex, lifestyles, and haemoglobin A1c levels. Regular monitoring of systolic BP should not be neglected in routine diabetes management even when BP falls within the normal range. (200 words).

The ERK1/2-ATG13-FIP200 signaling cascade is required for autophagy induction to protect renal cells from hypoglycemia-induced cell death.

Autophagy, an evolutionarily conserved lysosomal degradation pathway, is known to regulate a variety of physiological and pathological processes. At present, the function and the precise mechanism of autophagy regulation in kidney and renal cells remain elusive. Here, we explored the role of ERK1 and ERK2 (referred as ERK1/2 hereafter) in autophagy regulation in renal cells in response to hypoglycemia. Glucose starvation potently and transiently activated ERK1/2 in renal cells, and this was concomitant with an increase in autophagic flux. Perturbing ERK1/2 activation by treatment with inhibitors of RAF or MEK1/2, via the expression of a dominant-negative mutant form of MEK1/2 or RAS, blocked hypoglycemia-mediated ERK1/2 activation and autophagy induction in renal cells. Glucose starvation also induced the accumulation of reactive oxygen species in renal cells, which was involved in the activation of the ERK1/2 cascade and the induction of autophagy in renal cells. Interestingly, ATG13 and FIP200, the members of the ULK1 complex, contain the ERK consensus phosphorylation sites, and glucose starvation induced an association between ATG13 or FIP200 and ERK1/2. Moreover, the expression of the phospho-defective mutants of ATG13 and FIP200 in renal cells blocked glucose starvation-induced autophagy and rendered cells more susceptible to hypoglycemia-induced cell death. However, the expression of the phospho-mimic mutants of ATG13 and FIP200 induced autophagy and protected renal cells from hypoglycemia-induced cell death. Taken together, our results demonstrate that hypoglycemia activates the ERK1/2 signaling to regulate ATG13 and FIP200, thereby stimulating autophagy to protect the renal cells from hypoglycemia-induced cell death.