Associations of non-invasive indices of liver steatosis and fibrosis with progressive kidney impairment in adults with type 2 diabetes.

AIMS: Longitudinal data linking non-alcoholic fatty liver disease to kidney dysfunction in type 2 diabetes (T2D) are limited. This study evaluated the associations of non-invasive indices of liver steatosis and liver fibrosis with kidney impairment, and the mediatory role of the pro-angiogenic factor leucine-rich α-2 glycoprotein 1 (LRG1). METHODS: T2D adults (n = 2057) were followed for a mean period of 6.1 ± 1.6 years. Baseline liver steatosis [(hepatic steatosis index (HSI) and Zhejiang University index (ZJU)] and liver fibrosis [aspartate transaminase/alanine transaminase ratio (AAR) and BARD] indices derived from composite scoring systems were calculated. Plasma LRG1 levels were quantified using immunoassay. The study outcomes were progressive kidney function decline defined as estimated glomerular filtration rate (eGFR) decline of ≥ 40% and albuminuria progression defined as an increase in albuminuria category. RESULTS: Cross-sectionally, liver steatosis and liver fibrosis indices were associated with increased albuminuria (urinary albumin/creatinine ratio ≥ 30 µg/mg) and reduced renal function (eGFR < 60 mL/min/1.73 m2) after covariate adjustment, respectively. Approximately 32% of the participants experienced progressive kidney function decline, while 38% had albuminuria worsening over time. Longitudinal analysis revealed that baseline AAR (hazard ratio: 1.56; 95% CI 1.15-2.11) and BARD (hazard ratio: 1.16, 95% CI 1.04-1.28) predicted progressive kidney function decline, partly mediated by LRG1. In contrast, liver steatosis (HSI and ZJU) but not liver fibrosis (AAR and BARD) indices were independently associated with albuminuria progression. CONCLUSIONS: Increased liver steatosis scores were associated with albuminuria deterioration. Conversely, liver fibrosis indices may be associated with progressive kidney function decline, potentially driven by increased inflammation and angiogenesis.

Association between neutrophil/lymphocyte ratio and kidney impairment in type 2 diabetes mellitus: A role of extracellular water/total body water ratio.

AIMS: We explored the predictive utility of baseline neutrophil/lymphocyte ratio (NLR), which reflects a systemic inflammatory tone, in kidney impairment in type 2 diabetes mellitus (T2DM); and investigated the effect of extracellular water/total body water (ECW/TBW) ratio on the relationship. METHODS: This longitudinal study included 1,224 T2DM adults recruited from a single centre. Cox regression analyses examined the association between NLR and progressive kidney function decline or albuminuria progression. Improvements in risk discrimination were assessed using Harrell's concordance-statistics. The mediatory role of ECW/TBW ratio estimated by bioelectrical impedance was evaluated. RESULTS: Higher baseline NLR levels were observed in cases with kidney function decline or albuminuria progression over a median 2-year follow-up. NLR independently predicted progressive kidney function decline (hazard ratio:1.39, 95% CI:1.21-1.60, P < 0.001) or albuminuria progression (hazard ratio:1.34, 95% CI:1.08-1.68, P = 0.009). Addition of NLR to a base model comprising demographics, T2DM duration, metabolic and renal parameters, and medications significantly improved the risk discrimination of kidney function decline (P = 0.022) but not albuminuria progression. ECW/TBW ratio accounted for 19.7% of the total effect between NLR and kidney function loss. CONCLUSIONS: Increased NLR reflecting systemic inflammation is associated with progressive kidney function decline in T2DM, partially explained by dysregulated body fluid balance.

Association of Baseline Triglyceride-Glucose Index with Poor Glycemic Control and Diabetes Remission After Metabolic Surgery.

PURPOSE: The utility of insulin resistance (IR) as a predictor of diabetes remission after metabolic surgery is not well-defined. We assessed the association of baseline surrogate IR indices including triglyceride-glucose (TyG) index and homeostatic model assessment for IR (HOMA-IR) with glycemic control and diabetes remission after metabolic surgery. MATERIALS AND METHODS: Patients with type 2 diabetes scheduled for metabolic surgery were recruited at a single-center (n = 149; age: 44 ± 10 years, 47.7% men, body mass index: 41.5 ± 7.5 kg/m2), and followed-up for 12 months postoperatively. The relationships between the IR indices and poor glycemic control (HbA1c ≥ 7%) at baseline or complete diabetes remission (HbA1c < 6% without glucose-lowering medications at 12 months) post-surgery were examined. RESULTS: Elevated TyG index was associated with poor glycemic control cross-sectionally. Compared with non-remitters, lower baseline TyG index levels were observed in individuals with complete diabetes remission after surgery (P = 0.012); whereas HOMA-IR was not significantly different. Consistently, the proportion of diabetes non-remitters (compared to remitters) increased with increasing TyG tertiles from 1 to 3 (P = 0.015). Both TyG index (relative risk = 0.62, 95% CI = 0.42-0.91, P = 0.014) and TyG tertile 1 (relative risk = 1.99, 95% CI = 1.25-3.24, P = 0.003) independently predicted diabetes remission. The TyG index identified diabetes remission with an area under the curve of 0.68. The optimal TyG threshold was 9.41, yielding a sensitivity of 69.6%, specificity of 60.9%, positive predictive value of 64.0%, and negative predictive value of 66.7%. CONCLUSION: TyG index, previously suggested to predominantly reflect muscle IR, outperforms HOMA-IR as an IR indicator associated with glycemic control and diabetes remission after metabolic surgery.

Association between lower phase angle and chronic kidney disease progression in type 2 diabetes patients.

Introduction: Phase angle (PhA), derived from bioelectrical impedance analysis (BIA), is the angle of vector determined by the body's resistance and reactance. It indicates cellular integrity and hydration status. Though extracellular volume excess was associated with chronic kidney disease (CKD) progression, the association between PhA and CKD progression is unknown. Matrix metalloproteinase-2 (MMP-2) is a member of zinc-dependent endopeptidase family and promotes renal interstitial fibrosis. We investigated association between PhA and CKD progression, and whether the association was through MMP-2 in patients with type 2 diabetes mellitus (T2DM). Method: We conducted a prospective study on 1,078 patients with T2DM (mean age 58.9±9.1 years). PhA was measured using BIA. CKD progression was defined as ≥25% decrease in estimated glomerular filtration rate (eGFR) from baseline with deterioration across eGFR categories. Multiplex immunoassay was used to quantitate MMP-2. We examined association between PhA and CKD progression using Cox proportional hazards model, adjusting for demographics, clinical parameters and medications. Results: Over 8.6 years of follow-up, 43.7% of participants had CKD progression. Compared to tertile 3 PhA (higher level), tertiles 1 and 2 PhA were associated with higher hazards of CKD progression, with corresponding unadjusted hazard ratios (HRs) of 2.27 (95% confidence interval [CI] 1.80-2.87, P<0.001) and 1.57 (95% CI 1.24-2.01, P<0.001). The positive association between tertiles 1 and 2 PhA with CKD progression persisted in the fully adjusted model with corresponding HRs of 1.71 (95% CI 1.30-2.26, P<0.001) and 1.46 (95% CI 1.13-1.88, P=0.004). MMP-2 accounted for 14.7% of association between tertile 1 PhA and CKD progression. Conclusion: Our findings revealed a previously unobserved association between BIA-derived lower PhA and CKD progression through MMP-2 in patients with T2DM.

Religion and the Mediating Role of Alexithymia in the Mental Distress of Healthcare Workers During the Coronavirus Disease 2019 Pandemic in a Psychiatric Hospital in China.

The outbreak of the coronavirus disease 2019 (COVID-19) has created unprecedented challenges to the healthcare system, religion, and alexithymic trait that impacts the psychological resilience of healthcare workers during the COVID-19 pandemic. This study aimed to investigate the role religion and alexithymia play in mental distress and the level of happiness of psychiatric hospital healthcare workers in China amidst the COVID-19 pandemic. Furthermore, whether symptom dimensions (anxiety, depression, hostility, inferiority, and insomnia) are associated with the level of happiness, and a 6-month follow-up was also investigated. A total of one-hundred and ninety healthcare workers were recruited from a psychiatric hospital in Jilin, China, and 122 were followed up after 6 months. All participants filled out the 20-item Toronto Alexithymia Scale, five-item Brief-Symptom Rating Scale, and the Chinese Oxford Happiness Questionnaire. The mental distress of healthcare workers decreased from 2.6 to 1.5% in 6-months. Religious belief was not associated with the mental distress or happiness of healthcare workers. Instead, for those whose anxiety decreased over 6 months, their social adaptation status increased. For those whose inferiority level decreased over time, their perceived level of psychological well-being and overall happiness increased. In over half a century of living in different societies, religion stabilizes the mental health of those in Taiwan amidst the stress of the COVID-19 pandemic, but not in China. However, both regions found healthcare workers with alexithymic traits experienced a higher level of mental distress, implying that the collectivist culture of Confucian philosophy continues to influence the emotional expression and alexithymic traits of healthcare workers in China and Taiwan. To ensure a healthy and robust clinical workforce in the treatment and control of the pandemic, the cultural impact on the psychological resilience of medical workers needs to be addressed.

A population-level analysis of the protective effects of androgen deprivation therapy against COVID-19 disease incidence and severity

ImportanceThe incidence and severity of coronavirus disease 19 (COVID-19) is higher in men. Sex hormones potentially offer one explanation for differences by sex. ObjectiveTo determine whether men exposed to androgen deprivation therapy (ADT) have lower incidence and severity of COVID-19. DesignWe conducted an observational study of male Veterans treated in the Veterans Health Administration from February 15th to July 15th, 2020. We developed a propensity score model to predict the likelihood to undergo Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) testing. We performed multivariable logistic regression modeling adjusted with inverse probability weighting to examine the relationship between ADT and COVID-19 incidence. We conducted logistic regression analysis among COVID-19 patients to test the association between ADT and COVID-19 severity. SettingThe U.S. Department of Veterans Affairs ParticipantsThe study sample consisted of 6,250,417 male Veterans who were alive as of February 15, 2020. ExposureExposure to ADT was defined as having any prescription for a luteinizing hormone releasing hormone analogue or an antiandrogen in the six months prior to the index date. Main Outcomes and MeasuresTo assess incidence, we used a binary variable indicating any positive reverse transcriptase polymerase chain reaction SARS-CoV-2 test result through July 15, 2020. To measure severity, we constructed a binary variable indicating whether a patient was admitted to the intensive care unit, placed on mechanical ventilation, or dead in the 60 days following a positive test up to July 15, 2020. ResultsWe identified 246,087 patients who had been tested for SARS-CoV-2, of whom 3,057 were exposed to ADT, and 36,096 patients with cancer and no ADT exposure. Of these, 295 ADT patients and 2,427 other cancer patients had COVID-19 illness. In the primary, propensity-weighted comparison of ADT patients to cancer patients not on ADT, ADT was associated with decreased likelihood of testing positive for SARS-CoV-2 (adjusted OR, 0.88 [95% CI, 0.81-0.95]; p=0.001). ADT was associated with fewer severe COVID-19 outcomes (OR 0.72 [95% CI 0.53-0.96]; p=0.03). Conclusions and RelevanceADT is associated with reduced incidence and severity of COVID-19 amongst male Veterans. Repurposing of drugs that modulate androgen production and/or action may represent viable potential treatments for COVID-19. KEY POINTSO_ST_ABSQuestionC_ST_ABSDoes androgen deprivation therapy (ADT) lower incidence and severity of COVID-19? FindingsIn this observational study of male Veterans treated in the Veterans Healthcare System, ADT was associated with decreased likelihood of testing positive for SARS-CoV-2 (adjusted OR, 0.88 [95% CI, 0.81-0.95]; p=0.001). ADT was also associated with fewer severe COVID-19 outcomes (OR 0.72 [95% CI 0.53-0.96]; p=0.03). MeaningThe use of androgen deprivation therapy may be protective against SARS-CoV-2 infection and modulate severity of COVID-19 outcomes.

The Effect of Religion on Psychological Resilience in Healthcare Workers During the Coronavirus Disease 2019 Pandemic.

Background: Healthcare workers in the front line of diagnosis, treatment, and care of patients with coronavirus disease 2019 (COVID-19) are at great risk of both infection and developing mental health symptoms. This study aimed to investigate the following: (1) whether healthcare workers in general hospitals experience higher mental distress than those in psychiatric hospitals; (2) the role played by religion and alexithymic trait in influencing the mental health condition and perceived level of happiness of healthcare workers amidst the stress of the COVID-19 pandemic; and (3) factors that influence the resilience of healthcare workers at 6 weeks' follow-up. Methods: Four-hundred and fifty-eight healthcare workers were recruited from general and psychiatric hospitals, and 419 were followed-up after 6 weeks. All participants filled out the 20-item Toronto Alexithymia Scale, five-item Brief-Symptom Rating Scale, and the Chinese Oxford Happiness Questionnaire. Results: Under the stress of the COVID-19 pandemic, 12.3% of frontline healthcare workers in general hospitals reported having mental distress and perceived lower social adaptation status compared with those working in psychiatric hospitals. Christians/Catholics perceived better psychological well-being, and Buddhists/Taoists were less likely to experience mental distress. The results at 6 weeks of follow-up showed that the perceived lower social adaptation status of general hospital healthcare workers was temporary and improved with time. Christian/Catholic religion and time had independent positive effects on psychological well-being; however, the interaction of Christian/Catholic religion and time had a negative effect. Conclusions: Collectivism and individualism in the cultural context are discussed with regard to alexithymic trait and Buddhist/Taoist and Christian/Catholic religious faiths. Early identification of mental distress and interventions should be implemented to ensure a healthy and robust clinical workforce for the treatment and control of the COVID-19 pandemic.

Diabetes predicts severity of COVID-19 infection in a retrospective cohort: A mediatory role of the inflammatory biomarker C-reactive protein.

Diabetes is a risk factor for developing severe COVID-19, but the pathogenesis remains unclear. We investigated if the association of diabetes and COVID-19 severity may be mediated by inflammation. We also hypothesized that this increased risk may extend to prediabetes. Hospitalized patients in Singapore with COVID-19 were subdivided into three groups in a retrospective cohort: normoglycemia (HbA1c: ≤5.6%), prediabetes (HbA1c: 5.7%-6.4%) and diabetes (HbA1c: ≥6.5%). The primary outcome of severe COVID-19 was defined by respiratory rate ≥30, SpO2 ≤93% or intensive care unit admission. The association between clinical factors on severe COVID-19 outcome was analyzed by cox regression. Adjusted mediation analysis of C-reactive protein (CRP) on the relationship between diabetes and severe COVID-19 was performed. Of 1042 hospitalized patients, mean age 39 ± 11 years, 13% had diabetes, 9% prediabetes and 78% normoglycemia. Severe COVID-19 occurred in 4.9% of subjects. Compared to normoglycemia, diabetes was significantly associated with severe COVID-19 on both univariate (hazard ratio [HR]: 9.94; 95% confidence interval [CI]: 5.54-17.84; p < .001) and multivariate analysis (HR: 3.99; 95% CI: 1.92-8.31; p < .001), while prediabetes was not a risk factor (HR: 0.94; 95% CI: 0.22-4.03; p = .929). CRP, a biomarker of inflammation, mediated 32.7% of the total association between diabetes and severe COVID-19 outcome. In conclusion, CRP is a partial mediator of the association between diabetes and severe COVID-19 infection, confirming that inflammation is important in the pathogenesis of severe COVID-19 in diabetes.

Association between depressive symptoms and pulse wave velocity is mediated by increased adiposity in older adults with type 2 diabetes.

Background: Studies investigating the association between depression and aortic stiffness in older patients with type 2 diabetes are lacking. We postulated an association between depressive symptoms and aortic stiffness, and this relationship may be mediated by increased adiposity. Methods: We analyzed participants with type 2 diabetes aged 55 years or older (n = 958). We measured aortic stiffness using carotid-femoral pulse wave velocity (cut-off ≥ 12 m/s) using the tonometry method. We defined depressive symptoms as a score of greater than 5 on the Geriatric Depression Scale-15 (GDS-15). Adiposity indices we assessed were body mass index, waist circumference, waistto-height ratio, visceral fat area and fat mass. Results: Among the participants, 27.2% had aortic stiffness, of whom 6.5% had depressive symptoms. Score on the GDS-15 was correlated with pulse wave velocity, and both variables were correlated with the adiposity markers we analyzed (all p < 0.05). Depressive symptoms were associated with pulse wave velocity (B = 1.79, 95% confidence interval [CI] 0.83-2.75) or aortic stiffness (risk ratio 1.60, 95% CI 1.10-2.33) in the unadjusted model. The association persisted after controlling for demographics, duration of diabetes, glycated hemoglobin, comorbidities and medications. Further adjustment for visceral fat area and fat mass in separate models reduced the association between depressive symptoms and pulse wave velocity or aortic stiffness. Mediation models revealed that the mediation proportions of fat mass and visceral fat area on the association between depressive symptoms and pulse wave velocity were 11.8% and 9.7%, respectively. A preliminary analysis of longitudinal data (n = 184) showed similar findings. Limitations: Causality cannot be inferred from the associations we observed. Conclusion: Depressive symptoms are associated with elevated pulse wave velocity in older people with type 2 diabetes, and this relationship may be partially mediated by increased adiposity.

Effects of garlic intake on cancer: a systematic review of randomized clinical trials and cohort studies

BACKGROUND/OBJECTIVES@#Due to the rapid increase of global cancer incidence and mortality and a high level of interest in cancer prevention, a systematic review of garlic intake and cancer risk is needed. @*SUBJECTS/METHODS@#We implemented a systematic review to examine the effects of varying levels of garlic intake on cancer. We conducted comprehensive literature searches in three electronic databases (MEDLINE, Embase, and Web of Science) for studies published between database inception and July or September of 2018. Two investigators independently screened abstracts and full-texts, extracted data, and assessed risk of bias (RoB). A total of one medium-quality randomized controlled trial (RCT) and 13 cohort studies graded as high RoB were included. @*RESULTS@#The 1-year follow-up results from a RCT showed that a significant decrease in the number and size of colorectal adenomas among participants with colorectal adenomas who received high-dose aged garlic extract (AGE) compared with those who received low-dose AGE (P < 0.05). The results of prospective observational studies provided inconsistent associations of colorectal cancer risk with garlic supplements and garlic intake as food. @*CONCLUSIONS@#In summary, the AGE was effective in reducing the number and magnitude of colorectal adenomas in one RCT, but there were inconsistent associations between garlic intake and colorectal cancer in cohort studies. Therefore, we could not draw a firm conclusion regarding the effects of garlic on cancer, because the current strength of evidence is inadequate due to a lack of number of high-quality RCTs.

Correlation of Telomere Length in Adipose Tissue and Leukocytes and its Association with Postsurgical Weight Loss.

OBJECTIVE: The aim of this study was to determine the relationship between telomere length (TL) in subcutaneous adipose tissue (SAT), visceral adipose tissues (VAT), and leukocytes, as well as to examine the associations of TL in these tissues with postsurgical weight loss in Asians with severe obesity. METHODS: Presurgery TL was measured in leukocytes, SAT, and VAT of 91 patients who underwent weight loss surgery. Correlation between TL in multiple tissues was assessed using Pearson correlation. The association of presurgery TL and postsurgical weight loss at 6 or 12 months, expressed as a percentage of weight loss, was determined using linear regression in 70 patients. RESULTS: Telomeres were longer in VAT compared with those in leukocytes and SAT (P < 0.001) but were highly correlated between tissues. The strongest correlation was observed between TL in VAT and leukocytes (r = 0.739, P = 6.22 × 10-17 ). Compared with individuals in the highest tertile, those in the lowest tertile of VAT TL showed greater weight loss (ß = 6.23, SE = 3.10, P = 0.044) independent of age, sex, ethnicity, types of surgery, diabetes condition, preoperative BMI, and follow-up period. CONCLUSIONS: Among patients with severe obesity, TL in leukocytes and adipose tissue was highly correlated. However, there was variability in the association of TL in these tissues with weight loss after surgery.

Long-Term Observation of a Man With Severe Obesity and Undiagnosed Monogenic Diabetes Serendipitously Treated With Metabolic Surgery.

A 43-year-old man, with severe obesity (43 kg/m2) and diabetes (presumed as type 2 diabetes [T2D]), underwent vertical sleeve gastrectomy in 2009 and Roux-en-Y gastric bypass in 2013. Recently, whole exome sequencing (conducted to search for monogenic obesity) serendipitously revealed that the individual harbored a heterozygous glucokinase (GCK) variant p.(Arg422Leu) that was bioinformatically strongly predicted to be likely pathogenic. Therefore, he is likely to have concomitant maturity-onset diabetes of the young (MODY) type 2 (GCK-MODY). A retrospective evaluation of the clinical data showed that the subject was diagnosed with T2D (given his severe obesity) in 2005 and was treated with oral antidiabetic monotherapy. His hyperglycemia was mostly mild (HbA1c [hemoglobin] < 8.1%), consistent with that of MODY2, despite severe obesity. After vertical sleeve gastrectomy, complete diabetes remission (HbA1c <6.0% and fasting plasma glucose <5.6 mmol/L without use of antidiabetic medication) was achieved. The percentage of maximum body weight loss attained after surgery was 23.6%. Euglycemia was maintained during the subsequent decade, up to the last follow-up in 2019, without any sign of hypoglycemia. In conclusion, we report a decade-long clinical experience of a man with severe obesity and diabetes likely due to the coexistence of GCK-MODY and T2D, serendipitously treated with metabolic surgery. Interestingly, metabolic surgery was effective and safe for him.

Metabolic Surgery Diabetes Remission (MDR) Score: a New Preoperative Scoring System for Predicting Type 2 Diabetes Remission at 1 Year After Metabolic Surgery in the Singapore Multi-ethnic Asian Setting.

PURPOSE: The utility of available scoring systems for type 2 diabetes (T2D) remission prediction after metabolic surgery has not been defined in a multi-ethnic Asian population like Singapore. We sought to assess the predictive performance of the Asia-developed ABCD scoring system for T2D remission after metabolic surgery, and develop a new algorithm to improve prediction. MATERIALS AND METHODS: We conducted a retrospective analysis of adults with T2D who underwent either Roux-en-Y gastric bypass or sleeve gastrectomy between 2007 and 2018, and followed for 1 year postoperatively (n = 114, mean age 46 ± 9 years, 48.2% men, body mass index 40.1 ± 6.6 kg/m2). The primary outcome was complete T2D remission defined as HbA1c < 6% without the use of anti-diabetic medication at 1 year after surgery. RESULTS: Complete T2D remission was observed in 47.4% of subjects at 1 year post-surgery. Stepwise logistic regression identified preoperative age, T2D duration, HbA1c, and ß-cell function (estimated by the homeostasis model) as predictors of complete T2D remission. Based on these four variables, we constructed a new 10-point scoring system named Metabolic surgery Diabetes Remission (MDR) score. Compared with ABCD, MDR produced fewer misclassifications at the mid-high scores, achieving a predictive accuracy of 71-100% at 6 points and above. In addition, MDR achieved a higher area under the receiver operating characteristic curve than ABCD for the primary outcome (0.79 versus 0.67, P = 0.007). CONCLUSION: MDR may serve as a useful clinical scoring system for predicting short-term T2D remission after metabolic surgery in Singapore's multi-ethnic Asian cohort.

Association of traditional and novel measures of central obesity with cognitive performance in older multi-ethnic Asians with type 2 diabetes.

Literature evaluating the relationship between central obesity and cognitive deficits in type 2 diabetes (T2DM) remains scarce. This cross-sectional analysis explored the association of novel and traditional central obesity measures with cognitive performance in older (aged ≥60 years) non-demented multi-ethnic Asians with T2DM, including a stratified analysis by body mass index (BMI). Cognitive function was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status. Central obesity measures including visceral fat area (VFA), waist circumference, waist:hip ratio, waist:height ratio, abdominal volume index, body roundness index and conicity index were measured and/or computed. In our cohort (N = 677; mean age = 67 ± 5 years, 51.7% men), VFA emerged as an associate of overall cognitive performance after covariate adjustment and Bonferroni correction (ß = -.10, 95% CI = -0.18, -0.03), outperforming the other adiposity indices. Specifically, VFA was inversely associated with delayed memory and language scores. Additionally, compared with normal-weight individuals, excess visceral obesity (VFA ≥100 cm2 ) was independently associated with lower cognitive scores to a greater extent in normal BMI (<23 kg/m2 ) adults than in those with high BMI (≥23 kg/m2 ). Assessment and management of visceral adiposity may help to prevent cognitive decline in older people with T2DM, and reduce the global burden of dementia in ageing populations.

Plasma osteoprotegerin as a biomarker of poor glycaemic control that predicts progression of albuminuria in type 2 diabetes mellitus: A 3-year longitudinal cohort study.

AIMS: Poor glycaemic control elevates the risk for vascular complications. Biomarkers for predicting susceptibility to glycaemic worsening are lacking. This 3-year prospective analysis assessed the utility of several circulating diabetes-related biomarkers for predicting loss of glycaemic control, and their contribution to albuminuria progression in type 2 diabetes mellitus (T2DM). METHODS: T2DM subjects with adequately-controlled diabetes (HbA1c < 8%) at initial recruitment were analysed (N = 859). Baseline plasma levels of osteoprotegerin (OPG), C-reactive protein (CRP), adiponectin, intercellular-cell adhesion molecule-1, and vascular-cell adhesion molecule-1 were quantified using immunoassay. Definitions for development of uncontrolled diabetes and albuminuria progression were HbA1c ≥ 8.0% and increase in albuminuria category at follow-up, respectively. RESULTS: At follow-up, 185 subjects developed uncontrolled diabetes. Higher baseline CRP and OPG levels were observed in the high-risk individuals, and predicted increased risk for developing uncontrolled diabetes. OPG, but not CRP, was associated with albuminuria progression after multivariable adjustment. The relationship was attenuated following adjustment for development of uncontrolled diabetes, which emerged as a significant associate. Mediation analysis revealed that loss of glycaemic control explained 64.5% of the relationship between OPG and albuminuria progression. CONCLUSIONS: OPG outperformed other diabetes-related biomarkers to be a potentially useful biomarker for predicting loss of glycaemic control and its associated albuminuria deterioration.

Role of endothelium-independent vasodilation in the relationship between visceral adiposity and reduced cognitive performance in older adults with type 2 diabetes.

OBJECTIVE: In this cross-sectional analysis, we sought to assess the relationship of adiposity and forearm microvascular reactivity with cognitive dysfunction among older Asians with type 2 diabetes (T2D). METHODS: Subjects with T2D aged ≥ 55 years were analyzed (N = 907). Cognitive performance was assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Mini-Mental State Exam (MMSE). Visceral fat area (VFA) was estimated by tetrapolar multi-frequency bioimpedance. Forearm microvascular endothelium-dependent vasodilation (EDV) and endothelium-independent vasodilation (EIV) were assessed by laser Doppler imaging with iontophoresis. RESULTS: RBANS total score was correlated with VFA, EDV, and EIV (all P < .05). However, VFA was correlated with EIV, but not with EDV. Multivariable linear regression showed significant association between VFA and RBANS total score (B = -0.02, 95% CI= -0.03 to -0.01) or memory (immediate and delayed) index scores. These associations were attenuated after adjustment for EIV. Mediation analysis showed that EIV partially mediated the relationship between visceral adiposity and RBANS scores (all Sobel tests P < .05). EIV also mediated the relationship between VFA and MMSE score. CONCLUSIONS: Impaired endothelium-independent vascular smooth muscle reactivity may exert a mediatory effect on the association between increased visceral adiposity and decreased cognitive performance in older adults with T2D.

Association between gain in adiposity and diabetic kidney disease worsening in type 2 diabetes is mediated by deteriorating glycaemic control: A 3-year follow-up analysis.

AIMS: Increased adiposity confers elevated risk for diabetic kidney disease (DKD) progression in type 2 diabetes mellitus (T2DM). This 3-year prospective study examined whether worsening of metabolic control e.g. development of uncontrolled diabetes mediated the relationship between increased adiposity and DKD deterioration. METHODS: T2DM subjects who had adequately controlled diabetes (HbA1c < 8%) at initial recruitment were analysed (N = 853). HbA1c ≥ 8% at follow-up was classified as development of uncontrolled T2DM. Absolute changes in body weight (ΔWeight), body mass index (ΔBMI), and body fat mass (ΔBFM) were calculated by subtracting baseline from follow-up values. DKD deterioration (outcome) was defined as an increase in the composite ranking of relative risk by glomerular filtration rate and albuminuria levels (Kidney Disease: Improving Global Outcomes 2009). RESULTS: Subjects with deteriorated DKD displayed lower reduction in body composition at follow-up than those who remained stable or/improved (all P < 0.05). In separate regression models, ΔWeight (risk ratio (RR):1.04, 95% CI:1.01-1.06), ΔBMI (RR:1.07, 95% CI:1.01-1.13), and ΔBFM (RR:1.03, 95% CI:1.01-1.06) were independently associated with worsened DKD. The associations were attenuated after accounting for the loss of glycaemic control. Binary mediation analysis revealed that the development of uncontrolled diabetes explained 41.7%, 45.4% and 39.7%, respectively, of the effects of ΔWeight, ΔBMI and ΔBFM on the outcome. CONCLUSIONS: Among T2DM individuals who had adequately-controlled T2DM at initial recruitment, the relationship between gain in adiposity and DKD deterioration is mediated by the development of poor glycaemic control over time. Therefore, preventing worsening adiposity and hyperglycaemia is pivotal to impede DKD progression.

Ethnic disparities in relationships of obesity indices with telomere length in Asians with type 2 diabetes.

BACKGROUND: Obesity and shorter telomeres increase the risk for diabetes complications and mortality. However, the relationship between obesity and telomere length in diverse Asian populations with type 2 diabetes (T2D) is not well understood. This study examined the association of baseline and changes in obesity indices with telomere length in multiethnic Asian populations with T2D. METHODS: Leukocyte telomere length (LTL) was measured by quantitative polymerase chain reaction in the SMART2D cohort (n = 1431 at baseline, n = 1039 after 3.2 years median follow-up). Associations between obesity indices and LTL were assessed by linear regression. RESULTS: Compared with Chinese, LTL was longer in Malays (P < 0.0001) and similar in Indians. Cross-sectionally, body mass index (BMI)-adjusted (residual) visceral fat area (VFA; ß = -0.004, P = 0.006), and waist-to-hip ratio (ß = -1.95, P = 0.030) were significantly associated with LTL in Chinese but not in Malays and Indians. Changes in BMI (r = -0.080; P = 0.053) and VFA (r = -0.126; P = 0.002) were inversely correlated with changes in LTL only in Chinese. Furthermore, in Chinese, 1-SD incremental changes in BMI (ß = -0.070; P = 0.040) and VFA (ß = -0.088, P = 0.028) were significantly associated with larger telomere attrition, independent of age, sex, diabetes condition, baseline LTL, obesity, and inflammation markers. CONCLUSIONS: Three-year changes in BMI and VFA were associated with telomere dynamics in Chinese but not in Malays and Indians with T2D. Reducing obesity may reduce the risk of diabetes complications associated with shorter LTL in the Chinese population.

Gain in adiposity over 3 years is associated with progressive renal decline in multi-ethnic South-east Asians with type 2 diabetes.

BACKGROUND: This study evaluated the association between gain in adiposity and renal decline in a large prospective multiethnic South-east Asian cohort with type 2 diabetes mellitus (T2DM). METHODS: Three years after the baseline visit, 2057 T2DM subjects were recalled for reassessment. The final cohort comprised 1014 subjects and was categorized into tertiles based on changes in body weight (ΔWt), body mass index (ΔBMI), visceral fat area (ΔVFA), and BMI-adjusted VFA (ΔVFABMI ). Outcomes included annual and rapid (≥3 mL/min per 1.73 m2 per year) decline in estimated glomerular filtration rate (eGFR) and progression of albuminuria. RESULTS: Participants (mean [±SD] age 57 ± 11 years, 48.8% women, BMI 27.7 ± 5.4 kg/m2 ) exhibited a median annual decline in eGFR of 1.0 mL/min per 1.73 m2 . Compared with the lower tertiles, Tertile 3 of ΔWt, ΔBMI, ΔVFA, and ΔVFABMI had the highest anthropometric increase, albeit of modest magnitude, and this was accompanied by the worst renal outcomes (all P < 0.05). The relationship between annual eGFR decline and Tertile 3 of ΔWt, ΔBMI, and ΔVFABMI persisted after multivariate adjustment in men but not in women. In addition, Tertile 3 of ΔWt, ΔBMI, ΔVFA, and ΔVFABMI predicted rapid eGFR decline. Anthropometric gains were also associated with progression of albuminuria. CONCLUSIONS: Modest longitudinal gain in adiposity was associated with progressive renal decline in T2DM patients, suggesting that increased adiposity over time adversely affects renal outcomes. Therefore, a carefully designed weight-neutral or -loss antidiabetic treatment regimen is important when managing T2DM in the clinic.