Serial Transient Elastography Examinations to Monitor Patients With Type 2 Diabetes: A Prospective Cohort Study.

BACKGROUND AND AIMS: Type 2 diabetes is an important risk factor for nonalcoholic fatty liver disease (NAFLD) and advanced fibrosis. Current international guidelines recommend the use of noninvasive tests as initial assessments for NAFLD, but the role of noninvasive tests as monitoring tools has not been established. We aimed to study the role of transient elastography as a monitoring tool in patients with type 2 diabetes. APPROACH AND RESULTS: We recruited patients with type 2 diabetes without viral hepatitis or excessive alcohol intake from a complication screening facility in Hong Kong in 2013-2014 and repeated the assessments in 2016-2018. The primary endpoint was an increase of liver stiffness measurement (LSM) to ≥10 kPa. The secondary endpoint was the change in the controlled attenuation parameter (CAP). A total of 611 patients with type 2 diabetes and a valid LSM (mean age, 57.7 ± 10.9 years; 342 men [56.0%]) were included in this study (568 also had a valid CAP). Overall, there was moderate correlation between the baseline and follow-up LSM (r = 0.689, P < 0.001). Among 487 patients with a baseline LSM <10 kPa, 21 (4.3%) had a follow-up LSM ≥10 kPa. Baseline body mass index, alanine aminotransferase (ALT), and ∆ALT were independent factors associated with LSM increase. Among 124 patients with a baseline LSM ≥10 kPa, 70 (56.5%) had a follow-up LSM <10 kPa. Among 198 patients with a CAP <248 dB/m at baseline, 103 (52.0%) had a CAP increased to ≥248 dB/m. CONCLUSIONS: The prevalence and incidence of NAFLD in patients with type 2 diabetes are high. Although advanced fibrosis is common in this population, few patients progress to advanced fibrosis in 3 years. Future studies should define the optimal surveillance interval in patients with diabetes.

Cadherin-related family member 3 gene impacts childhood asthma in Chinese children.

BACKGROUND: A missense variant (rs6967330) of the gene encoding cadherin-related family member 3 (CDHR3) was associated with recurrent severe exacerbations in pre-schoolers. However, there were limited data on its relationship with pre-school lung function and school-age asthma. This study replicated the association between polymorphic markers at the region of CDHR3 around rs6967330 and wheezing phenotypes in two independent cohorts of Chinese children. METHODS: Ten tagging SNPs located 10 kb around rs6967330 were selected by HaploView 5.0 based on 1000 Genomes database for Southern Han Chinese. Their associations with wheezing and lung function were examined in 1341 Chinese pre-school children, while those for asthma phenotypes were examined in an independent group of 2079 school-age children. Genotypic and haplotypic associations were analyzed by multivariate regression, and generalized multifactor dimensionality reduction was used to examine epistatic interactions for wheezing traits. RESULTS: The mean (SD) age of pre-school cohort was 4.7 (1.0) years. Rs6967330 was associated with current wheeze (odds ratio [OR] 1.63, 95% confidence interval [CI] 1.09-2.43) and its severity (OR 1.64, 95% CI 1.10-2.44) among pre-school children. This SNP was also associated with school-age asthma (OR 1.32, 95% CI 1.04-1.69). The minor allele of rs408223 was associated with lower FEV0.5 (ß = -2.411, P = .004) and FEV0.5 /FVC (ß = -1.292, P = .015). Lower spirometric indices were also associated with minor allele of rs140154310. GAC haplotype from rs4730125, rs6967330, and rs408223 was associated with pre-school current wheeze and school-age asthma. Epistatic interaction was found between unrelated CDHR3 SNPs for FEV0.5 among pre-schoolers. CONCLUSION: CDHR3 is a candidate gene for early-life wheezing, school-age asthma, and lung function in Chinese children.

Progression of glucose intolerance and cardiometabolic risk factors over a decade in Chinese women with polycystic ovary syndrome: A case-control study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with increased metabolic risk, though data on long-term follow-up of cardiometabolic traits are limited. We postulated that Chinese women with PCOS would have higher risk of incident diabetes and cardiometabolic abnormalities than those without PCOS during long-term follow-up. METHODS AND FINDINGS: One hundred ninety-nine Chinese women with PCOS diagnosed by the Rotterdam criteria and with a mean age of 41.2 years (SD = 6.4) completed a follow-up evaluation after an average of 10.6 ± 1.3 years. Two hundred twenty-five women without PCOS (mean age: 54.1 ± 6.7 years) who underwent baseline and follow-up evaluation over the same period were used for comparison. Progression of glycaemic status of women both with and without PCOS was assessed by using 75-g oral glucose tolerance test (OGTT) screening with the adoption of 2009 American Diabetes Association diagnostic criteria. The frequency of impaired glucose regulation, hypertension, and hyperlipidaemia of women with PCOS at follow-up has increased from 31.7% (95% CI 25.2%-38.1%) to 47.2% (95% CI 40.3%-54.2%), 16.1% (95% CI 11.0%-21.2%) to 34.7% (95% CI 28.1%-41.3%), and 52.3% (95% CI 45.3%-59.2%) to 64.3% (95% CI 57.7%-71.0%), respectively. The cumulative incidence of diabetes mellitus (DM) in follow-up women with PCOS is 26.1% (95% CI 20.0%-32.2%), almost double that in the cohort of women without PCOS (p < 0.001). Age-standardised incidence of diabetes among women with PCOS was 22.12 per 1,000 person-years (95% CI 10.86-33.37) compared with the local female population incidence rate of 8.76 per 1,000 person-years (95% CI 8.72-8.80) and 10.09 per 1,000 person-years (95% CI 4.92-15.26, p < 0.001) for women without PCOS in our study. Incidence rate for women with PCOS aged 30-39 years was 20.56 per 1,000 person-years (95% CI 12.57-31.87), which is approximately 10-fold higher than that of the age-matched general female population in Hong Kong (1.88 per 1,000 person-years, [95% CI 1.85-1.92]). The incidence rate of type 2 DM (T2DM) of both normal-weight and overweight women with PCOS was around double that of corresponding control groups (normal weight: 8.96 [95% CI 3.92-17.72] versus 4.86 per 1,000 person-years [95% CI 2.13-9.62], p > 0.05; overweight/obese: 28.64 [95% CI 19.55-40.60] versus 14.1 per 1,000 person-years [95% CI 8.20-22.76], p < 0.05). Logistic regression analysis identified that baseline waist-to-hip ratio (odds ratio [OR] = 1.71 [95% CI 1.08-2.69], p < 0.05) and elevated triglyceride (OR = 6.63 [95% CI 1.23-35.69], p < 0.05) are associated with the progression to T2DM in PCOS. Limitations of this study include moderate sample size with limited number of incident diabetes during follow-up period and potential selection bias. CONCLUSIONS: High risk of diabetes and increased cardiovascular disease risk factors among Chinese women with PCOS are highlighted in this long-term follow-up study. Diabetes onset was, on average, 10 years earlier among women with PCOS than in women without PCOS.

Progression of diabetic kidney disease and trajectory of kidney function decline in Chinese patients with Type 2 diabetes.

Diabetes is a major cause of end stage renal disease (ESRD), yet the natural history of diabetic kidney disease is not well understood. We aimed to identify patterns of estimated GFR (eGFR) trajectory and to determine the clinical and genetic factors and their associations of these different patterns with all-cause mortality in patients with type 2 diabetes. Among 6330 patients with baseline eGFR >60 ml/min per 1.73 m2 in the Hong Kong Diabetes Register, a total of 456 patients (7.2%) developed Stage 5 chronic kidney disease or ESRD over a median follow-up of 13 years (incidence rate 5.6 per 1000 person-years). Joint latent class modeling was used to identify different patterns of eGFR trajectory. Four distinct and non-linear trajectories of eGFR were identified: slow decline (84.3% of patients), curvilinear decline (6.5%), progressive decline (6.1%) and accelerated decline (3.1%). Microalbuminuria and retinopathy were associated with accelerated eGFR decline, which was itself associated with all-cause mortality (odds ratio [OR] 6.9; 95% confidence interval [CI]: 5.6-8.4 for comparison with slow eGFR decline). Of 68 candidate genetic loci evaluated, the inclusion of five loci (rs11803049, rs911119, rs1933182, rs11123170, and rs889472) improved the prediction of eGFR trajectories (net reclassification improvement 0.232; 95% CI: 0.057--0.406). Our study highlights substantial heterogeneity in the patterns of eGFR decline among patients with diabetic kidney disease, and identifies associated clinical and genetic factors that may help to identify those who are more likely to experience an accelerated decline in kidney function.

Short-term association between ambient temperature and acute myocardial infarction hospitalizations for diabetes mellitus patients: A time series study.

BACKGROUND: Acute myocardial infarction (AMI) is the leading cause of death among people with diabetes mellitus (DM) and has been found to occur more frequently with extreme temperatures. With the increasing prevalence of DM and the rising global mean temperature, the number of heat-related AMI cases among DM patients may increase. This study compares excess risk of AMI during periods of extreme temperatures between patients with DM and without DM. METHODS: Distributed lag nonlinear models (DLNMs) were used to estimate the short-term association between daily mean temperature and AMI admissions (International Classification of Diseases 9th revision [ICD-9] code: 410.00-410.99), stratified by DM status (ICD-9: 250.00-250.99), to all public hospitals in Hong Kong from 2002 to 2011, adjusting for other meteorological variables and air pollutants. Analyses were also stratified by season, age group, gender, and admission type (first admissions and readmissions). The admissions data and meteorological data were obtained from the Hong Kong Hospital Authority (HA) and the Hong Kong Observatory (HKO). FINDINGS: A total of 53,769 AMI admissions were included in the study. AMI admissions among DM patients were linearly and negatively associated with temperature in the cold season (cumulative relative risk [cumRR] [95% confidence interval] in lag 0-22 days (12 °C versus 24 °C) = 2.10 [1.62-2.72]), while those among patients without DM only started increasing when temperatures dropped below 22 °C with a weaker association (cumRR = 1.43 [1.21-1.69]). In the hot season, AMI hospitalizations among DM patients started increasing when the temperature dropped below or rose above 28.8 °C (cumRR in lag 0-4 days [30.4 versus 28.8 °C] = 1.14 [1.00-1.31]), while those among patients without DM showed no association with temperature. The differences in sensitivity to temperature between patients with DM and without DM were most apparent in the group <75 years old and among first-admission cases in the cold season. The main limitation of this study was the unavailability of data on individual exposure to ambient temperature. CONCLUSIONS: DM patients had a higher increased risk of AMI admissions than non-DM patients during extreme temperatures. AMI admissions risks among DM patients rise sharply in both high and low temperatures, with a stronger effect in low temperatures, while AMI risk among non-DM patients only increased mildly in low temperatures. Targeted health protection guidelines should be provided to warn DM patients and physicians about the dangers of extreme temperatures. Further studies to project the impacts of AMI risks on DM patients by climate change are warranted.

Advanced liver fibrosis but not steatosis is independently associated with albuminuria in Chinese patients with type 2 diabetes.

BACKGROUND & AIMS: Increasing evidence suggests that non-alcoholic fatty liver disease (NAFLD) may be an independent risk factor for chronic kidney disease (CKD). Given the high prevalence of NAFLD among patients with diabetes who are also at risk of CKD, we aimed to investigate the association between NAFLD and albuminuria, a marker commonly found in diabetic nephropathy. METHODS: This study included a cohort of Chinese patients with type 2 diabetes from the Hong Kong Diabetes Registry recruited between March 2013 and May 2014. Liver stiffness measurement (LSM), with probe-specific cut-offs, was used to detect advanced liver fibrosis. While controlled attenuation parameter (CAP) was used to assess liver steatosis using transient elastography. RESULTS: A total of 1,763 Chinese patients with type 2 diabetes were recruited in this analysis. The mean (standard deviation) age and duration of diabetes were 60.7 (11.5) years and 10.8 (8.5) years, respectively. The prevalence of albuminuria was higher in diabetic patients with liver steatosis and those with advanced fibrosis (no NAFLD vs. liver steatosis vs. advanced fibrosis: 41.4% vs. 46.2% vs. 64.2%, p <0.001). After adjustment for potential confounders including glycated hemoglobin, hypertension and body mass index, advanced fibrosis, but not liver steatosis, was associated with increased risk of albuminuria (odds ratio [OR] 1.52; 95% confidence interval [CI] 1.02-2.28; p = 0.039) in patients with eGFR ≥60 ml/min/1.73 m2. The odds of albuminuria increased with greater severity of liver fibrosis in a dose dependent manner, with the highest odds observed in patients with LSM scores ≥11.5 kPa assessed by M probe or ≥11.0 kPa assessed by XL probe (adjusted OR 1.53; 95% CI 1.07-2.20; p = 0.021). CONCLUSIONS: Advanced liver fibrosis, but not steatosis, is independently associated with albuminuria in Chinese patients with type 2 diabetes. Attention should be paid to liver fibrosis in patients with obesity and type 2 diabetes complicated with albuminuria. LAY SUMMARY: In this study, we assessed the link between non-alcoholic fatty liver disease (NAFLD) and albuminuria in a cohort of 1,763 Chinese patients with type 2 diabetes. This study shows that advanced liver fibrosis, a severe form of NAFLD, was independently associated with increased risk of albuminuria. The risk of albuminuria increased with greater severity of liver fibrosis.

Screening diabetic patients for non-alcoholic fatty liver disease with controlled attenuation parameter and liver stiffness measurements: a prospective cohort study.

OBJECTIVE: Type 2 diabetes is an important risk factor for non-alcoholic fatty liver disease (NAFLD), but current guidelines provide conflicting recommendations on whether diabetic patients should be screened for NAFLD. We therefore studied the strategy of screening diabetic patients by FibroScan. DESIGN: Liver fat and fibrosis were assessed by controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) by FibroScan at a diabetic centre for patients from primary care and hospital clinics. Probe-specific LSM cut-offs were used to detect advanced fibrosis. RESULTS: Of 1918 patients examined, 1799 (93.8%) had valid CAP and 1884 (98.2%) had reliable LSM (1770 with the M probe and 114 with the XL probe). The proportion of patients with increased CAP and LSM was 72.8% (95% CI 70.7% to 74.8%) and 17.7% (95% CI 16.0% to 19.5%), respectively. By multivariable analysis, female gender, higher body mass index, triglycerides, fasting plasma glucose and alanine aminotransferase (ALT) and non-insulin use were associated with increased CAP. Longer duration of diabetes, higher body mass index, increased ALT and spot urine albumin:creatinine ratio and lower high-density lipoprotein-cholesterol were associated with increased LSM. Ninety-four patients (80% had increased LSM) underwent liver biopsy: 56% had steatohepatitis and 50% had F3-4 disease. CONCLUSIONS: Diabetic patients have a high prevalence of NAFLD and advanced fibrosis. Those with obesity and dyslipidaemia are at particularly high risk and may be the target for liver assessment. Our data support screening for NAFLD and/or advanced fibrosis in patients with type 2 diabetes.

Genetic effects of multiple asthma loci identified by genomewide association studies on asthma and spirometric indices.

BACKGROUND: Genomewide association study (GWAS) published by GABRIEL consortium identified 10 asthma-associated loci. However, their relationship with lung functions is unclear. This study investigated the association between asthma traits and single-nucleotide polymorphisms (SNPs) of these GWAS loci. METHODS: Rs3894194 and rs9273349 were not genotyped due to unavailable TaqMan assays. Genetic associations of remaining eight SNPs were investigated in 903 school-age asthmatics and 1205 non-allergic controls. Four significant SNPs were then replicated in 479 adult asthmatics and 746 adult controls, and 1341 Chinese preschool children. Meta-analyses were performed by combining data from school-age children and adults. Generalized multifactor dimensionality reduction (GMDR) was used to analyze their interactions for asthma traits. RESULTS: Childhood asthma was associated with GSDMB_rs2305480 (odds ratio [OR] 0.69, 95% confidence interval [CI] 0.57-0.83). IL13_rs1295686 was associated with all asthma (OR 1.64, 95% CI 1.16-2.32) and early-onset asthma (OR 1.92, 95% CI 1.20-3.06) in adults, whereas GSDMB_rs2305480 was only associated with early-onset asthma (OR 0.69, 95% CI 0.49-0.96). According to meta-analyses, the minor allele of rs2305480 was inversely associated with FEV1 , FVC, and FEV1 /FVC (p < 0.01). GMDR analyses revealed 2-locus models of SLC22A5 with SMAD3 to modulate FEVt /FVC in both preschool children and adults, with IL13 to determine FVC in both school-age children and adults, and with IL2RB to modulate FEV1 /FVC in school-age children. CONCLUSIONS: IL13 and GSDMB are replicated as asthma genes. Rs2305480 of GSDMB is also associated with low FEV1 , FVC, and FEV1 /FVC among asthmatics. Moreover, SLC22A5, IL13, SMAD3, and GSDMB interact to modulate spirometric indices.

Childhood asthma and spirometric indices are associated with polymorphic markers of two vitamin D 25-hydroxylase genes.

BACKGROUND: Polymorphic markers of vitamin D pathway genes have been associated with asthma traits in different White populations. This study investigated the relationship between asthma phenotypes and single nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR), vitamin D binding protein (GC), two 25-hydroxylases (CYP2R1 and CYP27A1), and 1α-hydroxylase (CYP27B1) in Hong Kong Chinese children. METHODS: 23 SNPs of the five vitamin D pathway genes were successfully genotyped in 914 asthmatic children and 1231 non-allergic controls. Genotypic and haplotypic associations with asthma phenotypes (diagnosis, spirometric indices, total IgE, and eosinophil percentage) were analyzed by multivariate regression. Generalized multifactor dimensionality reduction was used to detect epistatic interactions between SNPs for asthma phenotypes. RESULTS: Several SNPs of CYP27A1, CYP27B1, GC, and CYP2R1 were associated with asthma or spirometric indices, although only the association between FEV1 and CYP2R1 rs7935792 passed Bonferroni correction (p = 2.73 × 10(-4) ). Patients with CC genotype of rs7935792 had higher FEV1 than those with the other two genotypes. Asthma was also associated with TT haplotype of CYP27A1 and AGGATA haplotype of CYP2R1 (p = 0.021 and 0.024, respectively). Besides, strong association was found between FEV1 and GATAG of CYP2R1 (ß = 13.37, p = 4.83 × 10(-4) ). GMDR failed to identify any 2-locus to 4-locus interaction that modulated asthma or spirometric indices. CONCLUSIONS: Several SNPs and haplotypes of CYP2R1 are associated with asthma diagnosis and FEV1 in children. Asthma is also modestly associated with a CYP27A1 haplotype. These two 25-hydroxylase genes may be genetic determinants for asthma phenotypes in children.

One-hour post-load plasma glucose level predicts future type 2 diabetes in a community-based study of Hong Kong Chinese workforce.

BACKGROUND: We compared performance of high 1-hour PG level, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) in predicting type 2 diabetes in a longitudinal community-based cohort of Hong Kong Chinese. METHODS: Between 2001 and 2003, 472 adults aged 18-55 years without diabetes underwent 75-gram oral glucose tolerance test (OGTT). Between 2012 and 2014, progression to diabetes was ascertained by reviewing medical records or repeating OGTT and HbA1c. We defined high 1-hour PG as PG ≥ 8.6 mmol/L at 1-hour. RESULTS: In this cohort, 23.5% had normal glucose tolerance and high 1-hour PG, 10.0% had isolated IGT, 4.2% had isolated IFG. Over 12-year follow-up, 9.3% developed type 2 diabetes. In logistic regression, high 1-hour PG was associated with progression to type 2 diabetes with adjusted odds ratio (95% CI) of 4.20 (1.60, 12.40), independent of IFG, IGT and other clinical variables. Areas under ROC (95% CI) for type 2 diabetes were similar between 1-hour (0.84 [0.78, 0.89], 2-hour (0.79 [0.72, 0.86]) and fasting PG (0.79 [0.71, 0.86]). CONCLUSION: High 1-hour PG identified young Chinese with 5-fold increased risk of type 2 diabetes independent of other intermediate hyperglycaemia status and clinical factors. 1-hour PG is similar to fasting and 2-hour PG in predicting type 2 diabetes.

Intrarenal arterial resistance is associated with microvascular complications in Chinese type 2 diabetic patients.

BACKGROUND: Increased renal arterial resistance is associated with various types of chronic renal parenchymal diseases. A resistance index (RI) > 0.8 predicts deterioration in renal function in diabetic subjects. However, the association between renal RI and other diabetic complications has not been investigated. In this study, we examined the association between intrarenal arterial RI and diabetic complications in Chinese type 2 diabetic subjects. METHODS: Three hundred and eighty-seven Chinese type 2 diabetic patients were recruited from a structured assessment programme to evaluate their risk factors and complications as a part of the quality improvement programme at the Prince of Wales Hospital. All subjects underwent ultrasound examinations for the assessment of intrarenal arterial RI of both kidneys. Clinical and biochemical parameters, including diabetes-related microvascular complications (nephropathy, retinopathy and sensory neuropathy) and macrovascular diseases, were examined. RESULTS: The mean RI of patients with any microvascular complications (0.70 ± 0.09 versus 0.65 ± 0.06) such as nephropathy (0.71 ± 0.09 versus 0.66 ± 0.06), retinopathy (0.71 ± 0.08 versus 0.67 ± 0.08) and sensory neuropathy (0.75 ± 0.07 versus 0.68 ± 0.08) and with any macrovascular complications (0.71 ± 0.09 versus 0.68 ± 0.08) was higher than those without (P < 0.05). On multivariate analysis, after controlling for confounding variables, an RI ≥0.75 was associated with microvascular complications, nephropathy, retinopathy and sensory neuropathy, with odds ratio of 4.02 [95% confidence interval (CI) 1.72-9.4], 4.99 (2.61-9.56), 2.78 (1.52-5.09) and 5.74 (1.8-18.3), respectively. The association of RI with macrovascular complications was not significant in multivariate analysis. CONCLUSION: Increased intrarenal arterial resistance was independently associated with an increased risk of microvascular complications including diabetic nephropathy, diabetic retinopathy and diabetic sensory neuropathy in Chinese type 2 diabetic patients.

Prediction of women's long-term cardiometabolic risks using glycemic indices during pregnancy.

AIMS: To study the prediction of abnormal glucose tolerance (AGT), diabetes mellitus (DM), hypertension (HT) and metabolic syndrome (MetS) among Chinese women using glycemic indices in the mid-trimester of pregnancy. METHODS: A cohort of Chinese women who had had either normal glucose tolerance or gestational diabetes mellitus (GDM) during a pregnancy were assessed at a median of 8 and 15 years post-delivery. All women underwent a 50-g glucose challenge test (GCT) and a 75-g oral glucose tolerance test in the mid-trimester of the index pregnancy. A receiver operating characteristic curve was used to assess the prediction of AGT, DM, HT and MetS. RESULTS: All glycemic indices were significant predictors of AGT and DM, and the 2-h plasma glucose (PG) and GCT were predictive of HT, at both 8 and 15 years post-delivery. MetS can only be predicted by the fasting plasma glucose (FPG) and was confined to 15 years post-delivery. After adjustment for confounding variables, all glycemic indices were still independent predictors of AGT and DM at both 8 and 15 years post-delivery, except for FPG in predicting DM at 8 years, while only the 2-h PG remains an independent predictor of HT at 15 years. The optimal cut-off values for FPG, 2-h PG and GCT are 4.2 mmol/L, 7.2 mmol/L and 7.7 mmol/L, respectively; all are lower than the current cut-off thresholds for the screening and diagnosis of GDM. CONCLUSIONS: Women who had a glycemic level below the criteria for a positive screening test and below the diagnostic threshold for GDM still have a significant cardiometabolic risk.

Sonographic Measurement of Mesenteric Fat Thickness Is a Better Predictor of Aortic Stiffness Compared With Conventional Obesity Indexes.

Increased aortic stiffness is closely associated with central obesity whereas mesenteric fat is the key adipose tissue in central obesity. We investigated the associations of mesenteric fat thickness with aortic stiffness, with comparison to conventional obesity measures. We used ultrasound to measure mesenteric, pre-peritoneal and subcutaneous fat thickness, carotid intima-media thickness (CIMT) and carotid-femoral pulse wave velocity (c-f PWV), an index of central aortic stiffness. Anthropometric indexes, blood pressure, fasting plasma glucose and lipid profile were measured. One hundred forty-seven healthy volunteers (age [mean ± standard deviation]: 43.2 ± 13.3 y; 41.5% men) were assessed. On univariate analysis, mesenteric, preperitoneal and subcutaneous fat thickness, body mass index (BMI), waist circumference (WC), waist/hip ratio (WHR) and waist/height ratio (WHtR) were associated with c-f PWV with or without adjustment for age. The mesenteric fat thickness had the highest correlation coefficient (r = 0.48, p < 0.001) with c-f PWV among all the investigated obesity indexes. Using multiple linear regression analysis, only mesenteric fat thickness remained to be an independent determinant of c-f PWV after adjustments for other abdominal fat thickness, anthropometric and metabolic indexes and CIMT. In conclusion, mesenteric fat thickness is an independent risk factor for aortic stiffness and has a stronger association with aortic stiffness compared with conventional obesity indexes.

Deciphering the "obesity paradox" in the elderly: A systematic review and meta-analysis of sarcopenic obesity.

Aging and obesity are two global concerns in public health. Sarcopenic obesity (SO), defined as the combination of age-related sarcopenia and obesity, has become a pressing issue. This systematic review and meta-analysis summarize the current clinical evidence relevant to SO. PubMed, Embase, and Web of Science were searched, and 106 clinical studies with 167,151 elderlies were included. The estimated prevalence of SO was 9% in both men and women. Obesity was associated with 34% reduced risk of sarcopenia (odds ratio [OR] 0.66, 95% CI 0.48-0.91; p < 0.001). The pooled hazard ratio (HR) of all-cause mortality was 1.51 (95% CI 1.14-2.02; p < 0.001) for people with SO compared with healthy individuals. SO was associated with increased risk of cardiovascular disease and related mortality, metabolic disorders, cognitive impairment, arthritis, functional limitation, and lung diseases (all ORs > 1.0, p < 0.05). The attenuated risk of sarcopenia in elderlies with obesity ("obesity paradox") was dependent on higher muscle mass and strength. Apart from unifying the diagnosis of SO, more research is needed to subphenotype people with obesity and sarcopenia for individualized treatment. Meanwhile, the maintenance of proper body composition of muscle and fat may delay or attenuate the adverse outcomes of aging.

Advanced liver fibrosis predicts heart failure and hospitalizations in people with type 2 diabetes: A prospective cohort study from Hong Kong Diabetes Register.

AIMS: We aimed to examine the impact of non-alcoholic fatty liver disease (NAFLD) on the clinical outcomes in patients with type 2 diabetes (T2D). METHODS: Between 2013 and 2014, 1,734 patients with T2D underwent transient elastography (TE) to assess liver status indicated by controlled attenuation parameter (CAP) and liver stiffness measurement (LSM). Liver steatosis was defined by CAP ≥ 248 dB/m and advanced liver fibrosis by LSM ≥ 10 kPa. In 2019, we assessed their clinical outcomes including hospitalizations and mortality. RESULTS: In this prospective cohort [56% men, mean (±standard deviation) age:60.8±11.5 years; glycated hemoglobin (HbA1c)7.8±1.6 %], 798 patients had liver steatosis, 296 patients had advanced liver fibrosis and 640 patients had normal liver at baseline. T2D with advanced liver fibrosis had higher body mass index, waist circumference, waist-hip ratio, fasting plasma glucose, HbA1c, blood pressure and lipid profiles than their counterparts with NAFLD or normal liver (all p < 0.05). After a median follow-up of 6.07 (interquartile range:5.84 to 6.30) years, there were 4,403 incident hospitalizations, 32,119 days of hospital stay, and 171 deaths. Using Cox regression analysis, advanced liver fibrosis was associated with increased risk of heart failure (hazard ratio [95% confidence interval] HR:3.07[1.08-8.68], p=0.035) and hospitalizations (HR:1.39[1.14-1.70], p=0.001) while liver steatosis was associated with reduced mortality (HR:0.60[0.41-0.87], p=0.007) compared to their counterparts with normal liver after adjustment for potential confounders. CONCLUSIONS: T2D comorbid with liver steatosis and advanced liver fibrosis are distinct clinical entities with differences in outcomes. Advanced liver fibrosis is an important predictor for worse outcomes including heart failure and hospitalizations in people with T2D.

Association of insomnia with incident chronic cognitive impairment in older adults with type 2 diabetes mellitus: A prospective study of the Hong Kong Diabetes Register.

AIMS: To examine the risk association of insomnia with incident chronic cognitive impairment in older adults with type 2 diabetes mellitus (T2D). METHODS: Between July 2010 and June 2015, patients with T2D aged ≥60 years enrolled in the Hong Kong Diabetes Register completed the Insomnia Severity Index (ISI) questionnaire. Patients were considered having insomnia if they had ISI score > 14. We prospectively followed up the cohort and censored outcome through reviewing diagnoses and clinical notes entered by attending physicians in electronic medical record to identify incident cases of mild cognitive impairment and dementia. RESULTS: After excluding shift workers and those with established chronic cognitive impairment at baseline, we included 986 patients with T2D in this study (58.3 % men, mean age ± standard deviation: 62.5 ± 2.6 years, disease duration of diabetes: 10.7 ± 8.2 years, HbA1c: 7.4 ± 1.3 %, insulin users: 28.7 %, insomnia: 9.1 %). After a median follow-up of 7.6 (interquartile range = 2.0) years, 41 (4.2 %) developed chronic cognitive impairment. Using Cox regression analysis, insomnia (hazard ratio, HR 2.909, p = 0.012) and HbA1c ≥ 7 % (HR 2.300, p = 0.038) were positively associated with incident chronic cognitive impairment while insulin use (HR 0.309, p = 0.028) showed negative association. CONCLUSIONS: Insomnia, suboptimal glycemic control and non-insulin use are independent risk factors for incident chronic cognitive impairment in older adults with T2D.

US assessment of medial arterial calcification: a sensitive marker of diabetes-related microvascular and macrovascular complications.

PURPOSE: To examine the sensitivity of ultrasonography (US) compared with conventional radiography in detection of lower limb (thigh) medial arterial calcification (MAC) in type 2 diabetic patients and evaluate its association with diabetes-related complications. MATERIALS AND METHODS: The study was approved by the local research ethics committee, and informed written consent was obtained. US was performed in 289 patients with type 2 diabetes mellitus, and MAC severity was assigned a score from 0 to 8. Among the patients, 263 underwent radiographic examinations. All subjects underwent clinical evaluation to detect the presence of diabetes-related complications. RESULTS: US helped detect MAC in more subjects compared with radiography (65.8% vs 12.2%). US helped detect MAC from mild (scores 1-4) to severe (scores 5-8) degrees, while mild degree of MAC was poorly demonstrated with radiography. The incidence of nephropathy, retinopathy, sensory neuropathy, and macrovascular complications increased with the severity of MAC (based on US scoring). With univariate analysis, the presence of MAC was associated with nephropathy (P<.001), retinopathy (P<.001), sensory neuropathy (P=.004), and macrovascular complications (P<.001). After adjustment for potential confounders, the presence of severe MAC was associated with nephropathy, retinopathy, and macrovascular complications, with the odds ratios of 3.4 (95% confidence interval [CI]: 1.53, 7.43; P=.003), 2.6 (95% CI: 1.22, 5.32; P=.013), and 3.8 (95% CI: 1.37, 10.6; P=.01), respectively. CONCLUSION: In type 2 diabetic Chinese patients, US was more sensitive than conventional radiography in the detection of MAC, particularly when the MAC was mild. The presence of severe MAC was associated with diabetic nephropathy, retinopathy, and macrovascular complications. US detection of MAC was a potential early marker to identify diabetes-related complications.

Cardiometabolic risk in Chinese women with prior gestational diabetes: a 15-year follow-up study.

AIMS: The progression to type 2 diabetes mellitus (DM) and other long-term cardiometabolic risks in Chinese women with prior history of gestational diabetes (GD) was studied at 15 years postpartum. METHODS: 139 Chinese women (45 with GD and 94 with normal glucose tolerance (NGT) at the index pregnancy) who had their insulin sensitivity and ß-cell functions examined at 8 years postpartum were again followed up at 15 years for the investigation of the rate of type 2 DM, hypertension and metabolic syndrome. RESULTS: Women with prior history of GD had a significantly higher rate of hypertension (35.6% vs. 16.0%, p = 0.01), type 2 DM (24.4% vs. 5.3%, p < 0.001) and impaired glucose regulation (26.6% vs. 14.9%, p < 0.001) than women with NGT during the index pregnancy. The Matsuda insulin sensitivity index and the quantitative insulin sensitivity check index at 8 years postpartum were independent predictors of both DM and metabolic syndrome at 15 years postpartum. CONCLUSIONS: The conversion rate of type 2 DM increased at an average rate of 1.6% per year after a pregnancy affected by GD. Insulin resistance at 8 years postpartum could refine a future diabetic risk in women with prior history of GD.

Effects of RAS inhibitors on all-site cancers and mortality in the Hong Kong diabetes surveillance database (2002-2019).

BACKGROUND: Cancer is replacing cardiovascular-disease as a leading cause of death in type 2 diabetes (T2D). The association of RAS-inhibitors (RASi) and cancer, including differences between angiotensin-converting-enzyme-inhibitor (ACEi) and angiotensin-receptor-blocker (ARBs) as well as their associations independent of blood pressure lowering, remains inconclusive in T2D. METHODS: We conducted a cohort study with new-user design in 253,491 patients in the Hong-Kong-Diabetes-Surveillance-Database (HKDSD) in 2002-2019. We evaluated the associations of time-varying RASi use (ACEi and ARBs) with all-site cancer, diabetes-related cancers, and cancer-specific mortality including comparison with new-users of calcium-channel-blockers (CCBs) as an active-comparator group. FINDINGS: Of 253,491, 133,730 (52.8%) were new-RASi and 119,761 (47.2%) were non-RASi users with a median follow-up period of 6.3 (interquartile ragne: 3.4-9.2) years (1,678,719 patient-years). After propensity-score weighting and adjustment for time-varying covariables, RASi use was associated with lower risk of all-site cancer (HR=0.76, 95%CI: 0.74-0.79), diabetes-related cancer (HR=0.79, 95%CI: 0.75-0.84), cancer-specific mortality (HR=0.50, 95%CI: 0.47-0.53), and diabetes-related cancer mortality (HR=0.49, 95%CI: 0.45-0.54) versus non-RASi. Amongst RASi users, ARBs use was associated with lower risk of cancer-specific mortality versus ACEi (HR=0.77, 95%CI: 0.66-0.91). Use of RASi was associated with an estimated-prevention of 2.6 (95%CI: 2.3-3.0) all-site cancer per-1000-person-years and 2.2 (95%CI: 2.0-2.5) cancer-related mortality per-1000-person-years. Lower risk of cancer-specific mortality was similarly observed in new-RASi compared with new-CCBs users. INTERPRETATION: RASi use was independently associated with lower cancer risk in T2D with stronger associations in users of ARBs than ACEi. The benefits of RASi in patients with diabetes might go beyond cardiovascular-renal protection if confirmed by other real-world studies and trials. FUNDING: Dr. Aimin Yang was supported by a CUHK Impact-Research-Fellowship Scheme.

A randomized clinical trial of genetic testing and personalized risk counselling in patients with type 2 diabetes receiving integrated care -The genetic testing and patient empowerment (GEM) trial.

AIMS: We evaluated the effect of personalized risk counseling incorporating clinical and genetic risk factors on patient empowerment and risk factor control in diabetes. METHODS: Patients with type 2 diabetes (T2D) with suboptimal glycaemic control (HbA1c ≥ 7.5%) were randomized to a genetic counselling (GC) or control group. All patients underwent genetic testing for alleles at three loci associated with diabetic complications. The GC group received additional explanation of the joint associations of genetic and modifiable risk factors on risk of complications. All patients were reassessed at 12 months including validated questionnaires for patient reported outcomes. The primary outcome was proportion of patients reaching ≥ 3 of 5 predefined treatment targets (HbA1c < 7%, BP < 130/80 mmHg, LDL-C < 2.6 mmol/L, Triglyceride < 2.0 mmol/L, use of renin-angiotensin system inhibitors). Secondary outcomes included new-onset chronic kidney disease or microalbuminuria and patient reported outcome measures. RESULTS: A total of 435 patients were randomized and 420 patients were included in the modified intention-to-treat analysis. At 12 months, the proportion of patients who attained ≥ 3 targets increased from 41.6% to 52.3% in the GC group (p = 0.007) versus 49.5% to 62.6% in the control group (p = 0.003), without between-group difference. Both groups had similar reduction in HbA1c, LDL-C and increased use of medications. In per protocol analysis, the GC group had higher diabetes empowerment, with reduced diabetes distress. In the GC group, the greatest improvement in positive attitude and self-care activities was observed in the intermediate to high genetic risk score (GRS) groups. CONCLUSIONS: In patients with T2D receiving integrated care, additional counselling on genetic risk of complications did not further improve risk factor control, although the improvement in self-efficacy warrants long-term evaluation.