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.
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.
Abstract Objectives There is relatively scarce data regarding the association between primary hyperparathyroidism (PHPT) and incident diabetes in large population‐based longitudinal studies. We aimed ...to evaluate the risk of incident diabetes in individuals with and without PHPT and investigate the association between serum calcium concentrations and the risk of incident diabetes in patients with PHPT. Methods We included 2749 PHPT patients and 13,745 age, sex and index year matched non‐PHPT individuals during 2000–2019. We used Cox regression models to compare the risk of incident diabetes in individuals with and without PHPT, and the risk of incident diabetes in PHPT patients with serum calcium concentration above and below the median value. The association between serum calcium concentrations and the risk of incident diabetes was examined by restricted cubic spline analyses in patients with PHPT. Results During a median follow‐up time of 5.17 years (IQR 2.17, 9.58), 433 patients (15.75%) with PHPT and 2110 individuals (15.35%) without PHPT developed diabetes, respectively. Patients with PHPT had a higher incidence rate of diabetes compared to non‐PHPT individuals (27.60 95% CI 25.00, 30.30 vs. 23.90 95% CI 22.80, 24.90 per 1000 person‐years, log‐rank test p = .007. Crude Cox regression model showed PHPT was associated with a 15% higher risk of incident diabetes (HR 1.15, 95%CI 1.04, 1.28). In patients with PHPT, a 44% higher risk of incident diabetes was found in patients with serum calcium concentrations above the median value (2.63 mmol/L), compared to those below the median value (HR 1.44, 95%CI 1.08, 1.90). Restricted cubic spline analyses confirmed a positive linear association between serum calcium concentrations and the risk of incident diabetes in those with PHPT ( p ‐value for nonlinear = .751) Conclusions Patients with PHPT had a higher risk of incident diabetes compared to non‐PHPT individuals. A positive linear association was found between serum calcium concentrations and the risk of incident diabetes in patients with PHPT.
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.
The clinical utility of personal genomic information in identifying individuals at increased risks for dyslipidemia and cardiovascular diseases remains unclear.
We used data from Biobank Japan (n = ...70,657-128,305) and developed novel East Asian-specific genome-wide polygenic risk scores (PRSs) for four lipid traits. We validated (n = 4271) and subsequently tested associations of these scores with 3-year lipid changes in adolescents (n = 620), carotid intima-media thickness (cIMT) in adult women (n = 781), dyslipidemia (n = 7723), and coronary heart disease (CHD) (n = 2374 cases and 6246 controls) in type 2 diabetes (T2D) patients.
Our PRSs aggregating 84-549 genetic variants (0.251 < correlation coefficients (r) < 0.272) had comparably stronger association with lipid variations than the typical PRSs derived based on the genome-wide significant variants (0.089 < r < 0.240). Our PRSs were robustly associated with their corresponding lipid levels (7.5 × 10
< P < 1.3 × 10
) and 3-year lipid changes (1.4 × 10
< P < 0.0130) which started to emerge in childhood and adolescence. With the adjustments for principal components (PCs), sex, age, and body mass index, there was an elevation of 5.3% in TC (β ± SE = 0.052 ± 0.002), 11.7% in TG (β ± SE = 0.111 ± 0.006), 5.8% in HDL-C (β ± SE = 0.057 ± 0.003), and 8.4% in LDL-C (β ± SE = 0.081 ± 0.004) per one standard deviation increase in the corresponding PRS. However, their predictive power was attenuated in T2D patients (0.183 < r < 0.231). When we included each PRS (for TC, TG, and LDL-C) in addition to the clinical factors and PCs, the AUC for dyslipidemia was significantly increased by 0.032-0.057 in the general population (7.5 × 10
< P < 0.0400) and 0.029-0.069 in T2D patients (2.1 × 10
< P < 0.0428). Moreover, the quintile of TC-related PRS was moderately associated with cIMT in adult women (β ± SE = 0.011 ± 0.005, P
= 0.0182). Independent of conventional risk factors, the quintile of PRSs for TC OR (95% CI) = 1.07 (1.03-1.11), TG OR (95% CI) = 1.05 (1.01-1.09), and LDL-C OR (95% CI) = 1.05 (1.01-1.09) were significantly associated with increased risk of CHD in T2D patients (4.8 × 10
< P < 0.0197). Further adjustment for baseline lipid drug use notably attenuated the CHD association.
The PRSs derived and validated here highlight the potential for early genomic screening and personalized risk assessment for cardiovascular disease.
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.
Background
Patients with type 2 diabetes (T2D) are at high risk of developing multiple complications, affecting their health‐related quality of life (HRQoL). Existing studies only considered impact ...of complication on HRQoL in the year of occurrence but not its residual impacts in subsequent years. We investigated temporal impacts of diabetes‐related complications on HRQoL in a 12‐year prospective cohort of ambulatory Chinese patients with T2D enrolled in the clinic‐based Joint Asia Diabetes Evaluation (JADE) Register.
Methods
HRQoL utility measures were derived from EuroQol five‐dimensional three‐level questionnaire (EQ‐5D‐3L) questionnaires completed by 19 322 patients with T2D in Hong Kong (2007–2018). Temporal EQ‐5D utility decrements associated with subtypes of cardiovascular‐renal events were estimated using generalized linear regression model after stepwise selection of covariates with p < .01 as cutoff.
Results
In this cohort (mean ± SD age:61.2 ± 11.5 years, 55.3% men, median interquartile range duration of diabetes:10.1 3.0–15.0 years, glycated hemoglobin HbA1C 7.5 ± 1.5%), EQ‐5D utility was 0.860 ± 0.163. The largest HRQoL decrements were observed in year of occurrence of hemorrhagic stroke (−0.230), followed by ischemic stroke (−0.165), peripheral vascular disease (−0.117), lower extremity amputation (−0.093), chronic kidney disease (CKD) G5 without renal replacement therapy (RRT) (−0.079), congestive heart failure (CHF) (−0.061), and CKD G3–G4 without RRT (−0.042). Residual impacts on HRQoL persisted for 2 years after occurrence of CHF or ischemic stroke and 1 year after hemorrhagic stroke or CKD G3–G4 without RRT.
Conclusion
This is the first comprehensive report on temporal associations of HRQoL decrements with subtypes of diabetes‐related complications in ambulatory Asian patients with T2D. These data will improve the accuracy of cost‐effectiveness analysis of diabetes interventions at an individual level in an Asian setting.
Highlights
This is the first report on health‐related quality‐of‐life (HRQoL) decrements associated with subtypes of diabetes‐related cardiovascular‐renal complications in the year of occurrence and their residual impacts in subsequent years amongst 19 322 ambulatory Asian patients with type 2 diabetes (T2D) enrolled in the clinic‐based Joint Asia Diabetes Evaluation (JADE) Register (2007–2018)
The largest HRQoL decrements expressed as EuroQol five‐dimensional questionnaire utility scores were observed in the year of occurrence of hemorrhagic stroke (−0.230), followed by ischemic stroke (−0.165), peripheral vascular disease (−0.117), lower extremity amputation (−0.093), chronic kidney disease (CKD) G5 without renal replacement therapy (RRT) (−0.079), congestive heart failure (−0.061) and CKD G3–G4 without RRT (−0.042)
Residual impacts on HRQoL persisted for 2 years after occurrence of CHF or ischemic stroke, and 1 year after hemorrhagic stroke or CKD G3–G4 without RRT
HRQoL estimates considering residual impacts of diabetes complications would improve accuracy of evaluation of cost‐effectiveness of novel diabetes interventions at an individual level in an Asian setting
Diabetes among working population brings to society concerns on productivity and social welfare cost, in addition to healthcare burden. While lower socio‐economic status has been recognised as a risk ...factor of diabetes; occupation, compared with other socio‐economic status indicators (e.g., education and income), has received less attention. There is some evidence from studies conducted in Europe that occupation is associated with diabetes risk, but less is known in Asia, which has different organisational cultures and management styles from the West. This study examines the association between occupation and diabetes risk in a developed Asian setting, which is experiencing an increasing number of young onset of diabetes and aging working population at the same time. This is a cross‐sectional study of working population aged up to 65 with data from a population‐based survey collecting demographic, socio‐economic, behavioural and metabolic data from Hong Kong residents, through both self‐administered questionnaires and clinical health examinations (1,429 participants). Non‐skilled occupation was found to be an independent risk factor for diabetes, with an odds ratio (OR) of 3.38 (p < 0.001) and adjusted OR of 2.59 (p = 0.022) after adjusting for demographic, behavioural and metabolic risk factors. Older age (adjusted OR = 1.08, p < 0.001), higher body mass index (adjusted OR = 1.23, p < 0.001) and having hypertriglyceridemia (adjusted OR = 1.93, p = 0.033) were also independently associated with diabetes. Non‐skilled workers were disproportionately affected by diabetes with the highest age‐standardized prevalence (6.3%) among all occupation groups (4.9%–5.0%). This study provides evidence that non‐skilled occupation is an independent diabetes risk factor in a developed Asian setting. Health education on improving lifestyle practices and diabetes screening should prioritise non‐skilled workers, in particular through company‐based and sector‐based diabetes screening programmes. Diabetes health service should respond to the special needs of non‐skilled workers, including service at non‐office hour and practical health advice in light of their work setting.
To evaluate the effect of a team-based multi-component intervention care (MIC) program in obese patients with type 2 diabetes (T2D) and poor glycemic control.
Patients with T2D and HbA
≥ 8 % and ...body mass index (BMI) ≥ 27 kg/m
and/or waist circumference ≥ 80 cm in women and ≥90 cm in men were recruited. The intervention in Diabetes Centre included 1) nurse-led, group-based workshops; 2) review by endocrinologists; 3) telephone reminders by healthcare assistants and 4) peer support during visits. The usual care (UC) group received consultations at outpatient clinic without workshops or peer support. The MIC group received UC after 1-year of intervention. The primary outcome was change of HbA
from baseline at 1- and 3-year.
Of 207 eligible patients age (mean ± standard deviation): 56.9 ± 8.8 years, 47.4 % men, disease duration: 13.5 ± 8.2 years, HbA
: 9.6 ± 1.3 %, BMI: 28.8 ± 4.3 kg/m
, waist circumference: 101.5 ± 9.9 cm (men), 95.3 ± 9.8 cm (women), 104 received MIC and 103 received UC. 95 % patients had repeat assessments at 1- and 3-year. After adjustment for confounders, MIC had greater HbA
reduction (β -0.51, 95 % confidence interval CI -1.00 to -0.01; P = 0.045) than UC at 1-year, with sustained improvement at 3-year (β -0.56, CI -1.10 to -0.02; P = 0.044).
Team-based MIC for 1 year improved glycemic control in obese T2D which was sustained at 3-year.
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