Glycolytic lactate in diabetic kidney disease.

Lactate elevation is a well-characterized biomarker of mitochondrial dysfunction, but its role in diabetic kidney disease (DKD) is not well defined. Urine lactate was measured in patients with type 2 diabetes (T2D) in 3 cohorts (HUNT3, SMART2D, CRIC). Urine and plasma lactate were measured during euglycemic and hyperglycemic clamps in participants with type 1 diabetes (T1D). Patients in the HUNT3 cohort with DKD had elevated urine lactate levels compared with age- and sex-matched controls. In patients in the SMART2D and CRIC cohorts, the third tertile of urine lactate/creatinine was associated with more rapid estimated glomerular filtration rate decline, relative to first tertile. Patients with T1D demonstrated a strong association between glucose and lactate in both plasma and urine. Glucose-stimulated lactate likely derives in part from proximal tubular cells, since lactate production was attenuated with sodium-glucose cotransporter-2 (SGLT2) inhibition in kidney sections and in SGLT2-deficient mice. Several glycolytic genes were elevated in human diabetic proximal tubules. Lactate levels above 2.5 mM potently inhibited mitochondrial oxidative phosphorylation in human proximal tubule (HK2) cells. We conclude that increased lactate production under diabetic conditions can contribute to mitochondrial dysfunction and become a feed-forward component to DKD pathogenesis.

Efficacy of an enhanced recovery nursing plan as a rooming-in practice for women with preeclampsia post-cesarean section.

Our purpose was to develop and evaluate the clinical outcomes of a nursing plan as a rooming-in practice for enhanced recovery of women with preeclampsia following a cesarean section. The authors developed a postoperative enhanced recovery nursing plan as a rooming-in practice for women with preeclampsia based on summarizing evidence-based best practices. The authors used convenience sampling to select women with preeclampsia after a cesarean section from the obstetrics department of a Class A tertiary hospital in Nanjing, China, as the participants in our study. There were 30 women in the experimental group. The postoperative enhanced recovery nursing care plan was formulated for five postoperative time points and incorporated management of blood pressure, temperature, and fluids, as well as monitoring of complications, pain management, activity and rest, diet management, and breastfeeding. The control group consisted of 30 women who received routine nursing care and health education. The authors compared levels of maternal self-efficacy, breastfeeding efficacy, anxiety, pain scores, and deep vein thrombosis (DVT) prevention compliance before and after the intervention. Women in the experimental group had a self-efficacy score of 7.5 ± 0.63, which was higher than that in the control group (5.4 ± 0.85); they had a higher breastfeeding efficacy score of 7.13 ± 0.68 when compared to the control group (4.23 ± 0.86); the anxiety score was 6.7 ± 1.62, which was lower than that in the control group (10.03 ± 1.87); and the pain score was lower at 3.26 ± 0.52 when compared to the control group (3.83 ± 0.83). All the differences were statistically significant (P < 0.05). Postoperative blood pressure was controlled within the target range, and the rate of DVT prevention compliance increased in the experimental group. The implementation of a postoperative enhanced recovery nursing intervention for women with preeclampsia as part of the rooming-in practice was effective in helping manage the blood pressure, pain, and fluids of women with preeclampsia, improved their postoperative self-management ability and breastfeeding efficacy, reduced their anxiety levels, improved their compliance with the prevention of related complications, and ultimately promoted enhanced postoperative recovery, thereby guaranteeing the safety of mothers and newborns.

Urine Leucine-Rich α-2 Glycoprotein 1 (LRG1) Predicts the Risk of Progression to End-Stage Kidney Disease in Patients With Type 2 Diabetes.

OBJECTIVE: Leucine-rich α-2 glycoprotein 1 (LRG1) was recently identified as an amplifier of transforming growth factor-ß (TGF-ß)-induced kidney fibrosis in animal models. We aimed to study whether urine LRG1 is associated with risk of progression to end-stage kidney disease (ESKD) in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 1,837 participants with type 2 diabetes and estimated glomerular filtration rate (eGFR) >30 mL/min/1.73 m2 were recruited from a regional hospital and a primary care facility. Association of urine LRG1 with risk of ESKD (progression to sustained eGFR <15 mL/min/1.73 m2, dialysis, or death resulting from renal causes) was assessed by survival analyses. RESULTS: During a median follow-up of 8.6 (interquartile range 5.8-9.6) years, 134 incident ESKD events were identified. Compared with those in the lowest tertile, participants with baseline urine LRG1 in the highest tertile had a 1.91-fold (95% CI 1.04-3.50) increased risk of progression to ESKD, after adjustment for cardiorenal risk factors, including eGFR and albuminuria. As a continuous variable, 1 SD increment in urine LRG1 was associated with a 1.53-fold (95% CI 1.19-1.98) adjusted risk of ESKD. Of note, the association of urine LRG1 with ESKD was independent of plasma LRG1. Moreover, urine LRG1 was associated with rapid kidney function decline and progression to macroalbuminuria, two common pathways leading to ESKD. CONCLUSIONS: Urine LRG1, a TGF-ß signaling modulator, predicts risk of progression to ESKD independently of clinical risk factors in patients with type 2 diabetes, suggesting that it may be a novel factor involved in the pathophysiological pathway leading to kidney disease progression.

Clinical variable-based cluster analysis identifies novel subgroups with a distinct genetic signature, lipidomic pattern and cardio-renal risks in Asian patients with recent-onset type 2 diabetes.

AIMS/HYPOTHESIS: We sought to subtype South East Asian patients with type 2 diabetes by de novo cluster analysis on clinical variables, and to determine whether the novel subgroups carry distinct genetic and lipidomic features as well as differential cardio-renal risks. METHODS: Analysis by k-means algorithm was performed in 687 participants with recent-onset diabetes in Singapore. Genetic risk for beta cell dysfunction was assessed by polygenic risk score. We used a discovery-validation approach for the lipidomics study. Risks for cardio-renal complications were studied by survival analysis. RESULTS: Cluster analysis identified three novel diabetic subgroups, i.e. mild obesity-related diabetes (MOD, 45%), mild age-related diabetes with insulin insufficiency (MARD-II, 36%) and severe insulin-resistant diabetes with relative insulin insufficiency (SIRD-RII, 19%). Compared with the MOD subgroup, MARD-II had a higher polygenic risk score for beta cell dysfunction. The SIRD-RII subgroup had higher levels of sphingolipids (ceramides and sphingomyelins) and glycerophospholipids (phosphatidylethanolamine and phosphatidylcholine), whereas the MARD-II subgroup had lower levels of sphingolipids and glycerophospholipids but higher levels of lysophosphatidylcholines. Over a median of 7.3 years follow-up, the SIRD-RII subgroup had the highest risks for incident heart failure and progressive kidney disease, while the MARD-II subgroup had moderately elevated risk for kidney disease progression. CONCLUSIONS/INTERPRETATION: Cluster analysis on clinical variables identified novel subgroups with distinct genetic, lipidomic signatures and varying cardio-renal risks in South East Asian participants with type 2 diabetes. Our study suggests that this easily actionable approach may be adapted in other ethnic populations to stratify the heterogeneous type 2 diabetes population for precision medicine.

Genetic Risk Score for Plasma Uric Acid Levels Is Associated With Early Rapid Kidney Function Decline in Type 2 Diabetes.

CONTEXT: Observational studies have shown that elevated uric acid (UA) is associated with chronic kidney disease (CKD). However, whether the relationship is causal remains unclear. OBJECTIVE: To determine the association of plasma UA and incident CKD and the causal relationship between plasma UA and rapid decline in kidney function (RDKF) in patients with type 2 diabetes (T2D). METHODS: Multivariable Cox regression was conducted to evaluate the hazard ratio (HR) between plasma UA and incident CKD among 1300 normoalbuminuric patients in 2 T2D study cohorts (DN, n = 402; SMART2D, n = 898). A weighted genetic risk score (wGRS) was calculated based on 10 single nucleotide polymorphism (SNPs) identified in genome-wide association studies of UA in East Asians. Mendelian randomization (MR) analysis was performed among 1146 Chinese T2D patients without CKD (estimated glomerular filtration rate [eGFR] > 60 mL/min/1.73m2) at baseline (DN, 478; SMART2D, 668). The wGRS and individual SNPs were used as genetic instruments and RDKF was defined as eGFR decline of 5 mL/min/1.73m2/year or greater. RESULTS: During mean follow-up of 5.2 and 5.4 years, 81 (9%) and 46 (11%) participants in SMART2D and DN developed CKD, respectively. A 1-SD increment in plasma UA conferred higher risk of incident CKD (DN, adjusted-HR = 1.40 [95% CI, 1.02-1.91], P = 0.036; SMART2D, adjusted-HR = 1.31 [95% CI, 1.04-1.64], P = 0.018). Higher wGRS was associated with increased odds for RDKF (meta-adjusted odds ratio = 1.12 [95% CI, 1.01-1.24], P = 0.030, Phet = 0.606). CONCLUSION: Elevated plasma UA is an independent risk factor for incident CKD. Furthermore, plasma UA potentially has a causal role in early eGFR loss in T2D patients.

Association Between Use of Sodium-Glucose Co-Transporter-2 (SGLT2) Inhibitors and Cognitive Function in a Longitudinal Study of Patients with Type 2 Diabetes.

BACKGROUND: The association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) use and cognitive function in type 2 diabetes remains unclear. OBJECTIVE: Explore the association between SGLT2i and longitudinal changes in cognitive function in adults with type 2 diabetes (T2DM) and assessed the cognitive domains which were impacted by SGLT2i. METHODS: We conducted a prospective cohort study of 476 patients aged 60.6±7.4 years with follow-up period up to 6.4 years. Data on SGLT2i use was derived from questionnaire and verified with clinical database. We used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognition. The association between SGLT2i use and rate of RBANS score change was examined using multiple linear regression. RESULTS: There were 138 patients (29.0%) on SGLT2i, including 84 (17.7%) for < 3 years and 54 (11.3%) for ≥3 years. SGLT2i use was positively associated with RBANS total score increase in language (coefficient 0.60; 95% CI 0.10-1.11; p = 0.019) in unadjusted analysis. This positive association persisted in fully adjusted model (coefficient 0.74; 95% CI 0.12 to 1.36; p = 0.019). SGLT2i use for ≥3 years was positively associated with RBANS score increase globally and in language domain in fully adjusted analysis with coefficients 0.54 (95% CI 0.13 to 0.95; p = 0.010) and 1.12 (95% CI 0.27 to 1.97; p = 0.010) respectively. CONCLUSION: Our findings revealed a previously unobserved association between ≥3 years SGLT2i use and improved cognitive scores globally and in language domain and executive function. Future studies should investigate the role of SGLT2i in ameliorating cognitive decline.

Amino acid profile of skeletal muscle loss in type 2 diabetes: Results from a 7-year longitudinal study in asians.

AIMS: Little is known about pathophysiology of sarcopenia in diabetes. We aimed to study amino acid profile associated with skeletal muscle mass loss longitudinally in Type 2 Diabetes Mellitus (T2DM). METHODS: This is a prospective study of 1140 patients aged 56.6 ± 10.6 years from the SMART2D cohort. Skeletal muscle mass was measured using bio-impedance analysis at baseline and follow-up. Amino acids were measured by mass spectrometry. RESULTS: Over a period of up to 7.9 years, 43.9% experienced skeletal muscle mass loss. Lower baseline valine, leucine and isoleucine levels were associated with decreased skeletal muscle mass index (SMI) with corresponding coefficient 0.251(95 %CI 0.009 to 0.493), 0.298(95 %CI 0.051 to 0.544)) and 0.366(95 %CI 0.131 to 0.600). Higher baseline valine, leucine, isoleucine, alanine and tryptophan levels were associated with reduced odds of muscle mass loss with corresponding odds ratio (OR)0.797 (95 %CI 0.690 to 0.921), 0.825 (95 %CI 0.713 to 0.955), 0.826 (95 %CI 0.718-0.950), 0.847 (95 %CI 0.739-0.969) and 0.835 (95 %CI 0.720-0.979). CONCLUSION: The branched-chain amino acids valine, leucine and isoleucine were positively associated with change in SMI and reduced odds of muscle mass loss longitudinally. Further studies should be conducted to elucidate the pathophysiological mechanisms underlying the relationship between these amino acids and muscle mass loss in T2DM.

Risk of Incident Heart Failure in Individuals With Early-Onset Type 2 Diabetes.

CONTEXT: Early-onset diabetes has been associated with unfavorable cardiovascular risk but data on heart failure (HF) in this subpopulation are scarce. OBJECTIVE: We aimed to study the risk of, and risk factors for, incident HF in individuals with early-onset type 2 diabetes. METHODS: We studied 606 individuals with type 2 diabetes diagnosed before 40 years of age (early-onset) and 1258 counterparts with diabetes diagnosed from 41 to 65 years of age (usual-onset) with no HF history, at a regional hospital, over a median follow-up period of 7.1 years. Incident HF by European Cardiology Society criteria was determined. RESULTS: A total of 62 and 108 HF events were identified in the early- and usual-onset groups (1.55 and 1.29 per 100 patient-years), respectively. Compared with usual-onset counterparts, individuals with early-onset diabetes had a 1.20-fold unadjusted (95% CI, 0.88-1.63; P = 0.26) and 1.91-fold age-adjusted (95% CI, 1.37-2.66; P < 0.001) hazard ratio (HR) for incident HF. Adjustment for traditional cardiometabolic risk factors only moderately mitigated the hazards (adjusted HR 1.69; 95% CI, 1.19-2.40; P = 0.003). However, additional adjustment for estimated glomerular filtration rate and albuminuria markedly attenuated the association of early-onset age with incident HF (adjusted HR 1.24; 95% CI, 0.87-1.77; P = 0.24). Notably, a long diabetes duration was not significantly associated with HF risk after accounting for kidney measures. CONCLUSION: Individuals with early-onset diabetes have at least the same absolute risk and a 2-fold age-adjusted relative risk for incident HF. Excess cardiorenal risk factors but not a long diabetes duration are main drivers for HF development in this diabetic population.

Association of Plasma Leucine-Rich Alpha-2 Glycoprotein 1 (LRG1) with All-Cause and Cause-Specific Mortality in Individuals with Type 2 Diabetes.

BACKGROUND: Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein in the transforming growth factor-beta superfamily. We sought to study whether LRG1 might predict risk for all-cause and cause-specific mortality in individuals with type 2 diabetes. METHODS: 2012 outpatients with type 2 diabetes were followed for a median of 7.2 years and 188 death events were identified. Association of LRG1 with risk for mortality was assessed by multivariable Cox regression models. RESULTS: Participants with a higher concentration of LRG1 had an increased risk for all-cause mortality [HR (95% CI), 1.76 (1.03-3.01), 1.75 (1.03-2.98), and 4.37 (2.72-7.02) for quartiles 2, 3, and 4, respectively, compared to quartile 1]. The association remained significant after adjustment for known cardio-renal risk factors including estimated glomerular filtration rate and albuminuria [adjusted HR 2.76 (1.66-4.59), quartile 4 versus 1]. As a continuous variable, a 1-SD increment in LRG1 was associated with 1.34 (1.14-1.57)-fold adjusted risk for all-cause mortality. High plasma LRG1 was independently associated with mortality attributable to cardiovascular disease, infection, and renal diseases. Adding LRG1 into a clinical variable-based model improved discrimination (c statistics from 0.828 to 0.842, P = 0.006) and reclassification (net reclassification improvement 0.47, 95% CI 0.28-0.67) for prediction of 5-year all-cause mortality. CONCLUSION: Plasma LRG1 predicts risk for all-cause mortality and mortality attributable to cardiovascular disease, infection, and renal disease independent of known cardio-renal risk factors. It may be a potential novel biomarker to improve risk stratification in individuals with type 2 diabetes.

Association of Genetic Variants for Plasma LRG1 With Rapid Decline in Kidney Function in Patients With Type 2 Diabetes.

CONTEXT: Elevated levels of plasma leucine-rich α-2-glycoprotein 1 (LRG1), a component of transforming growth factor beta signaling, are associated with development and progression of chronic kidney disease in patients with type 2 diabetes (T2D). However, whether this relationship is causal is uncertain. OBJECTIVES: To identify genetic variants associated with plasma LRG1 levels and determine whether genetically predicted plasma LRG1 contributes to a rapid decline in kidney function (RDKF) in patients with T2D. DESIGN AND PARTICIPANTS: We performed a genome-wide association study of plasma LRG1 among 3694 T2D individuals [1881 (983 Chinese, 420 Malay, and 478 Indian) discovery from Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes cohort and 1813 (Chinese) validation from Diabetic Nephropathy cohort]. One- sample Mendelian randomization analysis was performed among 1337 T2D Chinese participants with preserved glomerular filtration function [baseline estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2)]. RDKF was defined as an eGFR decline of 3 mL/min/1.73 m2/year or greater. RESULTS: We identified rs4806985 variant near LRG1 locus robustly associated with plasma LRG1 levels (meta P = 6.66 × 10-16). Among 1337 participants, 344 (26%) developed RDKF, and the rs4806985 variant was associated with higher odds of RDKF (meta odds ratio = 1.23, P = 0.030 adjusted for age and sex). Mendelian randomization analysis provided evidence for a potential causal effect of plasma LRG1 on kidney function decline in T2D (P < 0.05). CONCLUSION: We demonstrate that genetically influenced plasma LRG1 increases the risk of RDKF in T2D patients, suggesting plasma LRG1 as a potential treatment target. However, further studies are warranted to elucidate underlying pathways to provide insight into diabetic kidney disease prevention.

Low muscle mass is associated with progression of chronic kidney disease and albuminuria - An 8-year longitudinal study in Asians with Type 2 Diabetes.

AIMS: We examined the longitudinal relationship between baseline skeletal muscle mass and its change over time with eGFR decline and albuminuria progression among Asians with type 2 diabetes(T2D). METHODS: This was a prospective cohort study of 1272 T2D patients. Skeletal muscle mass was estimated using tetra-polar multi-frequency bio-impedance analysis and Skeletal Muscle Mass Index(SMI) was defined as skeletal muscle mass/weight * 100. RESULTS: After up to 8 years of follow-up, 33.3% of participants had CKD progression and 28.3% albuminuria progression. Every 1-SD above baseline SMI was associated with 18% lower risk of CKD progression[Hazards Ratio(HR)0.82; 95%CI 0.70-0.97; p = 0.018] and 17% lower risk of albuminuria progression [HR 0.83 (95%CI 0.71-0.97; p = 0.017)]. The largest decrease in SMI over time was associated with 67% higher risk of CKD progression, compared to those with the smallest change from baseline SMI tertile 2[HR 1.67 (95%CI 1.10-2.55); p = 0.016]. Pigment epithelium-derived factor(PEDF) and plasma leucine-rich α-2-glycoprotein (LRG1) accounted for 40.1% of the association between SMI and CKD progression. CONCLUSIONS: Low baseline skeletal muscle mass and its reduction over time is associated with increased risk of progression of CKD among Asians with T2D. PEDF and LRG1 mediated the inverse relationship between SMI and CKD progression.

The role of pulse pressure in navigating the paradigm of chronic kidney disease progression in type 2 diabetes mellitus.

BACKGROUND AND AIMS: Arterial stiffness is a risk factor for chronic kidney disease progression (CKD). Pulse pressure is a surrogate marker of arterial stiffness. It is unclear if pulse pressure predicts CKD progression in type 2 diabetes mellitus. METHODS: This was prospective study involving 1494 patients with estimated glomerular filtration rate (eGFR) ≥ 15 ml/min/1.73 m2. Carotid-femoral pulse wave velocity was measured using applanation tonometry. Pulse pressure was calculated as difference between systolic and diastolic blood pressures. CKD progression was defined as worsening of eGFR categories (stage 1, ≥ 90 ml/min/1.73 m2; stage 2, 60-89 ml/min/1.73 m2; stage 3a, 45-59 ml/min/1.73 m2; stage 3b, 30-44 ml/min/1.73 m2; stage 4; 15-29 ml/min/1.73 m2; and stage 5, < 15 ml/min/1.73 m2) with ≥ 25% decrease in eGFR from baseline. RESULTS: After follow-up of up to 6 years, CKD progression occurred in 33.5% of subjects. Subjects in 2nd, 3rd and 4th quartiles of peripheral pulse pressure experienced higher risk of CKD progression with unadjusted hazard ratios (HRs) 1.55 [95% confidence interval (CI) 1.13-2.11; p = 0.006], 2.58 (1.93-3.45; p < 0.001) and 3.41 (2.58-4.52; p < 0.001). In the fully adjusted model, the association for 2nd, 3rd and 4th quartiles remained with HRs 1.40 (1.02-1.93; p = 0.038), 1.87 (1.37-2.56; p < 0.001) and 1.75 (1.25-2.44; p = 0.001) respectively. Similarly, 2nd, 3rd and 4th quartiles of aortic pulse pressure were associated with higher hazards of CKD progression with HRs 1.73 (1.25-2.40; p = 0.001), 1.65 (1.18-2.29; p = 0.003) and 1.81 (1.26-2.60; p = 0.001). Increasing urinary albumin-to-creatinine ratio accounted for 44.0% of the association between peripheral pulse pressure and CKD progression. CONCLUSIONS: Individuals with high pulse pressure were more susceptible to deterioration of renal function. Pulse pressure could potentially be incorporated in clinical practice as an inexpensive and readily available biomarker of renal decline in type 2 diabetes mellitus. Graphic abstract.

Higher ratio of extracellular water to total body water was associated with reduced cognitive function in type 2 diabetes.

BACKGROUND: Fluid imbalance is associated with various clinical conditions, but the association between elevated extracellular-water to total-body-water (ECW/TBW) ratio, an indicator of fluid balance, and cognitive impairment is unknown. We aimed to investigate relationship between ECW/TBW ratio and cognitive function in type 2 diabetes mellitus. METHODS: This study was a cross-sectional design, comparing 1233 patients aged 61.4 ± 8.0 years from the Singapore Study of Macro-angiopathy and Micro-vascular Reactivity in Type 2 Diabetes (SMART2D) cohort. ECW/TBW was measured using bioelectrical impedance method. Cognitive function was assessed with Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multiple linear regression was used to examine association between ECW/TBW and RBANS scores, adjusting for demographics, education, clinical covariates, and apolipoprotein E allele. RESULTS: In unadjusted analyses, there was an inverse dose-dependent association between ECW/TBW and RBANS total score. The associations persisted in fully adjusted model with ß = -1.18 (95% confidence interval [CI] -2.19 to -0.17; P = 0.022) for slight edema and -2.33 (-3.99 to -0.67; P = 0.006) for edema. Slight edema and edema were significantly associated with reduced cognitive function in delayed memory and attention. There was significant association between edema but not slight edema, with reduced cognitive function in language. Pulse pressure accounted for 16.8% of association between ECW/TBW and RBANS total score. CONCLUSIONS: Our novel finding of an independent association between higher ECW/TBW and poorer cognitive function highlights the potential importance of maintaining body fluid balance in the management of cognitive impairment.

Association of Plasma Leucine-Rich α-2 Glycoprotein 1, a Modulator of Transforming Growth Factor-ß Signaling Pathway, With Incident Heart Failure in Individuals With Type 2 Diabetes.

OBJECTIVE: Leucine-rich α-2 glycoprotein 1 (LRG1) is a circulating protein potentially involved in several pathways related to pathogenesis of heart failure (HF). We aimed to study whether plasma LRG1 is associated with risks of incident HF and hospitalization attributable to HF (HHF) in individuals with type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 1,978 individuals with type 2 diabetes were followed for a median of 7.1 years (interquartile range 6.1-7.6). Association of LRG1 with HF was studied using cause-specific Cox regression models. RESULTS: In follow-up, 191 incident HF and 119 HHF events were identified. As compared with quartile 1, participants with LRG1 in quartiles 3 and 4 had 3.60-fold (95% CI 1.63-7.99) and 5.99-fold (95% CI 2.21-16.20) increased risk of incident HF and 5.88-fold (95% CI 1.83-18.85) and 10.44-fold (95% CI 2.37-45.98) increased risk of HHF, respectively, after adjustment for multiple known cardiorenal risk factors. As a continuous variable, 1 SD increment in natural log-transformed LRG1 was associated with 1.78-fold (95% CI 1.33-2.38) adjusted risk of incident HF and 1.92-fold (95% CI 1.27-2.92) adjusted risk of HHF. Adding LRG1 to the clinical variable-based model improved risk discrimination for incident HF (area under the curve [AUC] 0.79-0.81; P = 0.02) and HHF (AUC 0.81-0.84; P = 0.02). CONCLUSIONS: Plasma LRG1 is associated with risks of incident HF and HHF, suggesting that it may potentially be involved in pathogenesis of HF in individuals with type 2 diabetes. Additional studies are warranted to determine whether LRG1 is a novel biomarker for HF risk stratification.

Association between vascular measures and cognitive function in type 2 diabetes.

AIM: To examine correlation between vascular measures and cognitive performance in type 2 diabetes (T2D). METHODS: This was a cross-sectional study on patients (N = 1167) aged ≥45 years attending Diabetes Centre in a tertiary hospital and primary care polyclinic. The following vascular measures were measured: systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), pulse wave velocity (PWV) and augmentation index (AI). Cognition was assessed by Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multiple linear regression was used to examine relationships between vascular measures and cognition, adjusting for demographics, education, depression, clinical covariates and presence of APOE Ɛ4 allele. RESULTS: In unadjusted analyses, all the vascular measures, except for MAP, were associated with RBANS total score. In fully adjusted analyses, the association with RBANS total score persisted for peripheral PP, aortic PP and aortic DBP with ßs -0.05 (95%CI -0.07 to -0.02; p = 0.001), -0.04 (95%CI -0.06 to -0.01; p = 0.002) and 0.05 (95%CI 0.00 to 0.09; p = 0.033). Association between peripheral and aortic PP and RBANS total score was unaffected by age-stratification (age <60 and ≥60 years). In contrast, significant association between aortic DBP and RBANS total score was only observed for those ≥60 years. Peripheral and aortic PP (which estimate pulsatility) are negatively associated with attention, visuospatial/constructional and language ability. CONCLUSIONS: Peripheral and aortic PP, and aortic DBP were independently correlated with cognitive performance globally and in multiple domains. Further research should be conducted to establish the clinical relevance and importance.

The neglected perioperative population of undiagnosed diabetics - a retrospective cohort study.

BACKGROUND: Diabetes is known to increase morbidity and 30-day mortality in adults undergoing non-cardiac surgery, but longer term outcomes are less studied. This study was done to explore how undiagnosed and known diabetes affect 30-day and one-year morbidity and mortality outcomes. The secondary aim was to study the prevalence of undiagnosed diabetics in our perioperative Asian surgical population. METHODS: A retrospective cohort study of 2106 patients aged > 45 years undergoing non-cardiac surgery in a single tertiary hospital was performed. Undiagnosed diabetics were identified (HbA1c ≥6.5% or fasting blood glucose ≥126 mg/dL) and relevant demographic, clinical and surgical data were analyzed to elicit the relationship to adverse outcomes. Univariate analysis was first performed to identify significant variables with p-values ≤0.1, which were then analyzed using multiple logistic regression to calculate the adjusted odds ratio. RESULTS: The prevalence of undiagnosed diabetes was 7.4%. The mean and median HbA1c of known diabetics were 7.9 and 7.5%, while the mean and median HbA1c for undiagnosed diabetics were 7.2 and 6.8% respectively. 36.4% of known diabetics and 20.5% of undiagnosed diabetics respectively had a random blood glucose > 200 mg/dL. Undiagnosed diabetics had a three-fold increase in 1-year mortality compared to non-diabetics (adjusted OR 3.46(1.80-6.49) p < 0.001) but this relationship was not significant between known and non-diabetics. Compared to non-diabetics, known diabetics were at increased risks of new-onset atrial fibrillation (aOR 2.48(1.01-6.25) p = 0.047), infection (aOR 1.49(1.07-2.07) p = 0.017), 30-day readmission (aOR 1.62(1.17-2.25) p = 0.004) and 30-day mortality (aOR 3.11(1.16-8.56) p = 0.025). CONCLUSIONS: Although undiagnosed diabetics have biochemically less severe disease compared to known diabetics at the point of testing, they are at a one-year mortality disadvantage which is not seen among known diabetics. This worrying trend highlights the importance of identifying and treating diabetes. Congruent to previous studies, known diabetics have higher morbidity and 30-day mortality compared to non-diabetics.

Endoscopic treatment modalities and outcomes in nonvariceal upper gastrointestinal bleeding.

BACKGROUND: In nonvariceal upper gastrointestinal bleeding (NVUGIB), the optimal volume of adrenaline, the optimal number of hemoclips, and the application of thermal coagulation in determining patient outcomes have not been well studied. AIM: To demonstrate a dose-response relationship between the commonly used endoscopic modalities for the treatment of non-variceal upper gastrointestinal bleeding and various clinical outcomes. METHODS: Patients presenting with NVUGIB were retrospectively identified and analyzed. These patients were stratified as follows: (1) > 10 mL of adrenaline injected vs ≤ 10 mL; (2) > 1 hemoclip placed vs ≤ 1 hemoclip; (3) Heater probe used or not; and (4) > 2 treatment modalities used vs ≤ 2. The primary outcomes were rebleeding and the need for repeat endoscopy. The secondary outcomes were the need for surgery, required transfusions, length of hospital stay, death during the same admission period and 30 d mortality. Patients with NVUGIB who required endoscopic therapy were included. Those who did not require endoscopic therapy or were initially treated with surgery or embolization were excluded. RESULTS: In all, 501 patients with NVUGIB were treated. One hundred sixty-one (32.1%) patients needed endoscopic therapy. The injection of < 10 mL of adrenaline was associated with less rebleeding (P < 0.0001), the need for repeat endoscopy (P = 0.001) and a decreased length of hospital stay (P = 0.026). The use of > 2 treatment modalities were associated with increased rebleeding (P = 0.009) and the need for repeat endoscopy (P = 0.048). The placement of > 1 hemoclip was associated with a decreased length of hospital stay (P = 0.044). The rates of surgery and death were low, and there were no other significant differences between the patient groups. CONCLUSION: The more restrictive use of adrenaline and number of endoscopic modalities to treat NVUGIB with the more liberal use of hemoclips was associated with better patient outcomes.

Association between Lower Extremity Skeletal Muscle Mass and Impaired Cognitive Function in Type 2 Diabetes.

Lower extremity skeletal muscle mass (LESM) in Type 2 Diabetes (T2D) has been linked to adverse clinical events, but it is not known whether it is associated with cognitive difficulties. We conducted a cross-sectional study on 1,235 people (mean age 61.4 ± 8.0 years) with T2D under primary and secondary care in Singapore. Bioelectrical impedance analyses (BIA) measures of upper extremity skeletal muscle mass (UESM), LESM and appendicular skeletal muscle index (SMI) were related to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measures of cognition, in multiple linear regression. In multivariable models, tertile 1 LESM (b = -2.62 (-3.92 to -1.32)) and tertile 2 LESM (b = -1.73 (-2.73 to -0.73)), referenced to tertile 3) were significantly associated with decreased RBANS total score. Significant associations of LESM with cognitive domain performances were observed for tertile 1 (b = -3.75 (-5.98 to -1.52)) and tertile 2 (b = -1.98 (-3.69 to -0.27)) with immediate memory, and for tertile 1 (b = -3.05 (-4.86 to -1.24)) and tertile 2 (b = -1.87 (-3.25 to -0.48)) with delayed memory, and for tertile 1 (b = -2.99 (-5.30 to -0.68)) with visuospatial/constructional ability. Tertile 1 SMI (b = -1.94 (-3.79 to -0.08) and tertile 2 SMI (b = -1.75 (-3.14 to -0.37)) were also associated with delayed memory. There were no associations between UESM with cognitive performance. Lower LESM may be a useful marker of possible co-occuring cognitive dysfunction.