Cinnamyl alcohol dehydrogenase (CAD) catalyzes the last step in monolignol biosynthesis and genetic evidence indicates CAD deficiency in grasses both decreases overall lignin, alters lignin structure ...and increases enzymatic recovery of sugars. To ascertain the effect of CAD downregulation in switchgrass, RNA mediated silencing of CAD was induced through Agrobacterium mediated transformation of cv. “Alamo” with an inverted repeat construct containing a fragment derived from the coding sequence of PviCAD2 . The resulting primary transformants accumulated less CAD RNA transcript and protein than control transformants and were demonstrated to be stably transformed with between 1 and 5 copies of the T-DNA. CAD activity against coniferaldehyde, and sinapaldehyde in stems of silenced lines was significantly reduced as was overall lignin and cutin. Glucose release from ground samples pretreated with ammonium hydroxide and digested with cellulases was greater than in control transformants. When stained with the lignin and cutin specific stain phloroglucinol-HCl the staining intensity of one line indicated greater incorporation of hydroxycinnamyl aldehydes in the lignin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The impact of faecal microbiota transplantation (FMT) on microbiota engraftment in patients with metabolic syndrome is uncertain. We aimed to study whether combining FMT with lifestyle modification ...could enhance the engraftment of favourable microbiota in obese patients with type 2 diabetes mellitus (T2DM).
In this double-blind, randomised, placebo-controlled trial, 61 obese subjects with T2DM were randomly assigned to three parallel groups: FMT plus lifestyle intervention (LSI), FMT alone, or sham transplantation plus LSI every 4 weeks for up to week 12. FMT solution was prepared from six healthy lean donors. Faecal metagenomic sequencing was performed at baseline, weeks 4, 16 and 24. The primary outcome was the proportion of subjects acquiring ≥20% of microbiota from lean donors at week 24.
Proportions of subjects acquiring ≥20% of lean-associated microbiota at week 24 were 100%, 88.2% and 22% in the FMT plus LSI, FMT alone, and sham plus LSI groups, respectively (p<0.0001). Repeated FMTs significantly increased the engraftment of lean-associated microbiota (p<0.05). FMT with or without LSI increased butyrate-producing bacteria. Combining LSI and FMT led to increase in
and
compared with FMT alone (p<0.05). FMT plus LSI group had reduced total and low-density lipoprotein cholesterol and liver stiffness at week 24 compared with baseline (p<0.05).
Repeated FMTs enhance the level and duration of microbiota engraftment in obese patients with T2DM. Combining lifestyle intervention with FMT led to more favourable changes in recipients' microbiota and improvement in lipid profile and liver stiffness.
NCT03127696.
Type 2 diabetes (T2D) is a progressive disease whereby there is often deterioration in glucose control despite escalation in treatment. There is significant heterogeneity to this progression of ...glycemia after onset of diabetes, yet the factors that influence glycemic progression are not well understood. Given the tremendous burden of diabetes in the Chinese population, and limited knowledge on factors that influence glycemia, we aim to identify the clinical and genetic predictors for glycemic progression in Chinese patients with T2D. In 1995-2007, 7,091 insulin-naïve Chinese patients (mean age 56.8 ± 13.3 SD years; mean age of T2D onset 51.1 ± 12.7 years; 47% men; 28.4% current or ex-smokers; median duration of diabetes 4 IQR: 1-9 years; mean HbA1c 7.4% ± 1.7%; mean body mass index BMI 25.3 ± 4.0 kg/m.sup.2) were followed prospectively in the Hong Kong Diabetes Register. We examined associations of BMI and other clinical and genetic factors with glycemic progression defined as requirement of continuous insulin treatment, or 2 consecutive HbA1c greater than or equal to8.5% while on greater than or equal to2 oral glucose-lowering drugs (OGLDs), with validation in another multicenter cohort of Hong Kong Diabetes Biobank. During a median follow-up period of 8.8 (IQR: 4.8-13.3) years, incidence of glycemic progression was 48.0 (95% confidence interval CI 46.3-49.8) per 1,000 person-years with 2,519 patients started on insulin. Among the latter, 33.2% had a lag period of 1.3 years before insulin was initiated. Risk of progression was associated with extremes of BMI and high HbA1c. On multivariate Cox analysis, early age at diagnosis, microvascular complications, high triglyceride levels, and tobacco use were additional independent predictors for glycemic progression. A polygenic risk score (PRS) including 123 known risk variants for T2D also predicted rapid progression to insulin therapy (hazard ratio HR: 1.07 95% CI 1.03-1.12 per SD; P = 0.001), with validation in the replication cohort (HR: 1.24 95% CI 1.06-1.46 per SD; P = 0.008). A PRS using 63 BMI-related variants predicted BMI (beta SE = 0.312 0.057 per SD; P = 5.84 x 10.sup.-8) but not glycemic progression (HR: 1.01 95% CI 0.96-1.05 per SD; P = 0.747). Limitations of this study include potential misdiagnosis of T2D and lack of detailed data of drug use during follow-up in the replication cohort. Our results show that approximately 5% of patients with T2D failed OGLDs annually in this clinic-based cohort. The independent associations of modifiable and genetic risk factors allow more precise identification of high-risk patients for early intensive control of multiple risk factors to prevent glycemic progression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Heterozygous familial hypercholesterolemia often went unrecognized in China when population cholesterol levels were low, but rapid economic development has changed the situation. This review will ...discuss the current position of awareness, diagnosis, and management of familial hypercholesterolemia in Chinese populations.
The phenotype of familial hypercholesterolemia in China and other Chinese populations has become similar to that in Western countries, although it may still be somewhat less severe. The prevalence in Chinese populations is also similar to that in other countries and it has been found in up to 7% of Chinese patients with premature coronary heart disease. Most of the mutations are in the low-density lipoprotein receptor gene but the pattern of mutations differs from that in Whites. Chinese patients may be more responsive to statins than Whites but patients with familial hypercholesterolemia are often undertreated.
Increasing population cholesterol levels have changed the phenotype of familial hypercholesterolemia in China and Chinese patients now resemble those in Western countries. International initiatives are facilitating increased awareness and identification of cases and more effective management of the condition.
To investigate association between skin autofluorescence (SAF) and cardiovascular events (CVE) and assess its predictive value in Chinese adults with type 2 diabetes (T2D).
SAF was measured ...non-invasively in 3806 Chinese adults with T2D between 2016 and 2019 with CVE as primary endpoint and individual components as secondary endpoints. Cox proportional hazard models were used to examine associations between SAF and endpoints with adjustment for conventional risk factors. C-statistic, integrated discrimination improvement (IDI), and net reclassification improvement (NRI) were performed to evaluate SAF's predictive value.
During a median 1.8 (interquartile range, 1.2–3.1) years of follow-up, 172 individuals experienced CVE. Multivariate Cox model showed that SAF was independently associated with CVE (HR 1.18 per SD, 95% CI 1.02, 1.37), coronary heart disease (HR 1.29 per SD, 95% CI 1.02, 1.63), and congestive heart failure (HR 1.53 per SD, 95% CI 1.14, 2.05). SAF yielded additional value on CVE risk stratification with enhanced IDI (95% CI) (0.023 0.001, 0.057) and continuous NRI (0.377 0.002, 0.558) over traditional risk factors.
Higher SAF was independently associated with CVE in Chinese adults with T2D and yielded incremental predictive information for CVE. SAF has potential as a prognostic maker for CVE.
High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ. Diabetes modifies the composition and function of HDL. We ...assessed associations of HDL size-based subclasses with incident cardiovascular disease (CVD) and mortality and their prognostic utility.
HDL subclasses by nuclear magnetic resonance spectroscopy were determined in sera from 1991 fasted adults with type 2 diabetes (T2D) consecutively recruited from March 2014 to February 2015 in Hong Kong. HDL was divided into small, medium, large and very large subclasses. Associations (per SD increment) with outcomes were evaluated using multivariate Cox proportional hazards models. C-statistic, integrated discrimination index (IDI), and categorial and continuous net reclassification improvement (NRI) were used to assess predictive value.
Over median (IQR) 5.2 (5.0-5.4) years, 125 participants developed incident CVD and 90 participants died. Small HDL particles (HDL-P) were inversely associated with incident CVD hazard ratio (HR) 0.65 (95% CI 0.52, 0.81) and all-cause mortality 0.47 (0.38, 0.59) (false discovery rate < 0.05). Very large HDL-P were positively associated with all-cause mortality 1.75 (1.19, 2.58). Small HDL-P improved prediction of mortality C-statistic 0.034 (0.013, 0.055), IDI 0.052 (0.014, 0.103), categorical NRI 0.156 (0.006, 0.252), and continuous NRI 0.571 (0.246, 0.851) and CVD IDI 0.017 (0.003, 0.038) and continuous NRI 0.282 (0.088, 0.486) over the RECODe model.
Small HDL-P were inversely associated with incident CVD and all-cause mortality and improved risk stratification for adverse outcomes in people with T2D. HDL-P may be used as markers for residual risk in people with T2D.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We aim to assess the long-term impact of acute kidney injury (AKI) on progression of diabetic kidney disease (DKD) and all-cause mortality and investigate determinants of AKI in Chinese patients with ...type 2 diabetes (T2D). A consecutive cohort of 9,096 Chinese patients with T2D from the Hong Kong Diabetes Register was followed for 12 years (mean ± SD age 57 ± 13.2 years; 46.9% men; median duration of diabetes 5 years). AKI was defined based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria using serum creatinine. Estimated glomerular filtration rate measurements were used to identify the first episode with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Polygenic risk score (PRS) composed of 27 single nucleotide polymorphisms (SNPs) known to be associated with serum uric acid (SUA) in European populations was used to examine the role of SUA in pathogenesis of AKI, CKD, and ESRD. Validation was sought in an independent cohort including 6,007 patients (age 61.2 ± 10.9 years; 59.5% men; median duration of diabetes 10 years). Patients with AKI had a higher risk for developing incident CKD (hazard ratio 14.3 95% CI 12.69-16.11), for developing ESRD (12.1 10.74-13.62), and for all-cause death (7.99 7.31-8.74) compared with those without AKI. Incidence rate for ESRD among patients with no episodes of AKI and one, two, and three or more episodes of AKI was 7.1, 24.4, 32.4, and 37.3 per 1,000 person-years, respectively. Baseline SUA was a strong independent predictor for AKI. A PRS composed of 27 SUA-related SNPs was associated with AKI and CKD in both discovery and replication cohorts but not ESRD. Elevated SUA may increase the risk of DKD through increasing AKI. The identification of SUA as a modifiable risk factor and PRS as a nonmodifiable risk factor may facilitate the identification of individuals at high risk to prevent AKI and its long-term impact in T2D.
Introduction
Diabetes and bone health are closely related. We examined the incidence and risk factors of hip fractures in Chinese patients with type 2 diabetes (T2D).
Materials and Methods
In this ...prospective cohort, we consecutively enrolled 22,325 adults with T2D above the age of 40 years in the Hong Kong Diabetes Register between 1994 and 2015 with crude hip fracture incidence rate censored in 2017.
Results
At baseline, the mean age of this cohort was 60.9 ± 10.5 years (mean duration of diabetes 6 years, 52.4% male). During a mean ± standard deviation (SD) follow‐up period of 8.7 ± 5.2 years with 193,553 person‐years, 603 patients were hospitalized due to hip fractures with an incidence (95% confidence interval, CI) of 315.1 (290.4–341.3) per 100,000 person‐years. On multivariable analysis with competing death risk adjusted, the independent hazard ratios (95% CI) for hip fractures in T2D were 2.01 (1.61–2.51) for female sex, 1.08 (1.07–1.09) for age, 0.93 (0.90–0.95) for body mass index, 1.52 (1.25–1.85) for albuminuria and 1.12 (1.02–1.23) for low density lipoprotein‐cholesterol. In men, the 30‐day, 1‐year and 5‐year post‐hip fracture mortality rate (95% CI) were 5.8 (2.4–9.1) %, 29.2 (22.3–35.5) % and 65.9 (57.3–72.8) % respectively. The corresponding rates in women were 3.4 (1.6–5.1) %, 18.6 (14.7–22.4) %, and 46.8 (40.9–52.1) %.
Conclusions
Southern Chinese patients with T2D have a high risk of hip fracture associated with suboptimal cardiometabolic‐renal risk factors and a high post‐fracture mortality rate. The effects of improving modifiable risk factors on bone health warrants further evaluation.
With prospective follow up of nearly 9 years, we identified several risk factors associated with increase hip fracture incidence in Southern Chinese patients with type 2 diabetes in the Hong Kong Diabetes Register. These include female sex, age, body mass index, albuminuria and low density lipoprotein.
There is very limited data on the time trend of diabetes incidence in Asia. Using population-level data, we report the secular trend of the incidence of type 1 and type 2 diabetes in Hong Kong ...between 2002 and 2015.
The Hong Kong Diabetes Surveillance Database hosts clinical information on people with diabetes receiving care under the Hong Kong Hospital Authority, a statutory body that governs all public hospitals and clinics. Sex-specific incidence rates were standardised to the age structure of the World Health Organization population. Joinpoint regression analysis was used to describe incidence trends. A total of 562,022 cases of incident diabetes (type 1 diabetes n = 2,426: mean age at diagnosis is 32.5 years, 48.4% men; type 2 diabetes n = 559,596: mean age at diagnosis is 61.8 years, 51.9% men) were included. Among people aged <20 years, incidence of both type 1 and type 2 diabetes increased. For type 1 diabetes, the incidence increased from 3.5 (95% CI 2.2-4.9) to 5.3 (95% CI 3.4-7.1) per 100,000 person-years (average annual percentage change AAPC 3.6% 95% CI 0.2-7.1, p < 0.05) in boys and from 4.3 (95% CI 2.7-5.8) to 6.4 (95% CI 4.3-8.4) per 100,000 person-years (AAPC 4.7% 95% CI 1.7-7.7, p < 0.05 in girls; for type 2 diabetes, the incidence increased from 4.6 (95% CI 3.2-6.0) to 7.5 (95% CI 5.5-9.6) per 100,000 person-years (AAPC 5.9% 95% CI 3.4-8.5, p < 0.05) in boys and from 5.9 (95% CI 4.3-7.6) to 8.5 (95% CI 6.2-10.8) per 100,000 person-years (AAPC 4.8% 95% CI 2.7-7.0, p < 0.05) in girls. In people aged 20 to <40 years, incidence of type 1 diabetes remained stable, but incidence of type 2 diabetes increased over time from 75.4 (95% CI 70.1-80.7) to 110.8 (95% CI 104.1-117.5) per 100,000 person-years (AAPC 4.2% 95% CI 3.1-5.3, p < 0.05) in men and from 45.0 (95% CI 41.4-48.6) to 62.1 (95% CI 57.8-66.3) per 100,000 person-years (AAPC 3.3% 95% CI 2.3-4.2, p < 0.05) in women. In people aged 40 to <60 years, incidence of type 2 diabetes increased until 2011/2012 and then flattened. In people aged ≥60 years, incidence was stable in men and declined in women after 2011. No trend was identified in the incidence of type 1 diabetes in people aged ≥20 years. The present study is limited by its reliance on electronic medical records for identification of people with diabetes, which may result in incomplete capture of diabetes cases. The differentiation of type 1 and type 2 diabetes was based on an algorithm subject to potential misclassification.
There was an increase in incidence of type 2 diabetes in people aged <40 years and stabilisation in people aged ≥40 years. Incidence of type 1 diabetes continued to climb in people aged <20 years but remained constant in other age groups.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
People with type 2 diabetes (T2D) have increased cancer risk. Liver cancer (LC) has a high prevalence in East Asia and is one of the leading causes of cancer death globally. Diagnosis of LC at early ...stage carries good prognosis. We used stored serum from patients of Hong Kong Diabetes Register before cancer diagnosis to extract RNA to screen for microRNA markers for early detection of LC in T2D. After screening with Affymetrix GeneChip microarray with serum RNA from 19 incident T2D LC (T2D-LC), 20 T2D cancer free (T2D-CF) and 20 non-T2D non-cancer patients, top signals were validated in a 3-group comparison including 1888 T2D-CF, 127 T2D-LC, and 487 T2D patients with non-liver cancer patients using qPCR. We detected 2.55-fold increase in miR-122-5p and 9.21-fold increase in miR-455-3p in the T2D-LC group. Using ROC analysis, miR-122-5p and miR-455-3p jointly predicted LC with an area under the curve of 0.770. After adjustment for confounders, each unit increase of miR-455-3p increased the odds ratio for liver cancer by 1.022. Increased serum levels of miR-122-5p and miR-455-3p were independently associated with increased risk of incident LC in T2D and may serve as potential biomarkers for early detection of LC in T2D.
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