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OBJECTIVE We examined the associations of GAD antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses, and severe hypoglycemia in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS In 5,230 Chinese patients (47.6% men) with T2D (mean ± SD age: 56.5 ± 13.9 years; median diabetes duration: 6 [interquartile range 1, 12] years), enrolled consecutively in 1996–2012 and prospectively observed until 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes. RESULTS At baseline, 28.6% (n = 1,494) had low CP ( CONCLUSIONS There is considerable heterogeneity in autoimmunity and β-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation, while GADA+ and low CP, increased the risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.

OBJECTIVE To evaluate the performance of a real-time continuous glucose monitor (CGM) in individuals with diabetes on peritoneal dialysis (PD). RESEARCH DESIGN AND METHODS Thirty participants with type 2 diabetes on continuous ambulatory PD wore a Guardian Sensor 3 on the upper arm paired with Guardian Connect for 14 days. We compared CGM readings against Yellow Springs Instrument (YSI) venous glucose during an 8-h in-clinic session with glucose challenge. RESULTS The mean absolute relative difference (MARD) was 10.4% (95% CI 9.6, 11.7) from 941 CGM-YSI matched pairs; 81.3% of readings were within %15/15 of YSI values in the full glycemic range. Consensus error grid analysis showed 99.9% of sensor values in zones A and B. There were no correlations between pH, uremia, hydration status, and MARD. CONCLUSIONS We showed satisfactory performance of a real-time CGM sensor in PD patients with diabetes, supporting future use to facilitate treatment decisions.

Description: The KDIGO 2022 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease is an update of the 2020 guideline from Kidney Disease: Improving Global Outcomes (KDIGO). Methods: The KDIGO Work Group updated the guideline, which included reviewing and grading new evidence that was identified and summarized. As in the previous guideline, the Work Group used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of recommendations and expert judgment to develop consensus practice points. New evidence led to updating of recommendations in the chapters Comprehensive Care in Patients With Diabetes and CKD (Chapter 1) and Glucose-Lowering Therapies in Patients With T2D and CKD (Chapter 4). New evidence did not change recommendations in the chapters Glycemic Monitoring and Targets in Patients With Diabetes and CKD (Chapter 2), Lifestyle Interventions in Patients With Diabetes and CKD (Chapter 3), and Approaches to Management of Patients With Diabetes and CKD (Chapter 5). Recommendations: The updated guideline includes 13 recommendations and 52 practice points for clinicians caring for patients with diabetes and chronic kidney disease (CKD). A focus on preserving kidney function and maintaining well-being is recommended using a layered approach to care, starting with a foundation of lifestyle interventions, self-management, and first-line pharmacotherapy (such as sodium–glucose cotransporter-2 inhibitors) demonstrated to improve clinical outcomes. To this are added additional drugs with heart and kidney protection, such as glucagon-like peptide-1 receptor agonists and nonsteroidal mineralocorticoid receptor antagonists, and interventions to control risk factors for CKD progression and cardiovascular events, such as blood pressure, glycemia, and lipids.

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Glucokinase-maturity-onset diabetes of the young (GCK-MODY) is caused by heterozygous inactivating mutations in glucokinase (GK, gene symbolGCK) and impaired glucose sensing. We investigated effects of dorzagliatin, a novel allosteric GK activator, on insulin secretion rates (ISR) and beta-cell glucose-sensitivity (βCGS) in GCK-MODY and recent-onset type 2 diabetes. In a double-blind, randomized cross-over study, eight participants with GCK-MODY and 10 with type 2 diabetes underwent 2-hour 12-mmol/L hyperglycemic clamps following a single oral dose of dorzagliatin 75mg or matched placebo. Effects of dorzagliatin on wild-type and mutant GK enzyme activity were investigated using a nicotinamide adenine dinucleotide phosphate (NADP+) coupled assay with glucose-6-phosphate dehydrogenase (G6PD) in vitro. In GCK-MODY, dorzagliatin significantly increased absolute and incremental second-phase ISR versus placebo but not the acute insulin response. Dorzagliatin improved βCGS in GCK-MODY with a upward and leftward shift in ISR-glucose response. Dorzagliatin increased basal ISR in type 2 diabetes with smaller changes in second-phase ISR compared with GCK-MODY. In vitro, dorzagliatin directly reduced the glucose half saturation concentration (S0.5) of wild-type GK and selected GK mutants to varying degrees. Dorzagliatin directly restored enzyme activity of select GK mutants and enhanced wild-type GK activity, thereby correcting the primary defect of glucose sensing in GCK-MODY.

Glycated hemoglobin A1c (HbA1c) has reduced reliability in advanced chronic kidney disease (CKD) owing to factors influencing red cell turnover. Recent guidelines support the use of continuous glucose monitoring (CGM) in glycemic assessment in these patients. We evaluated relationships between HbA1c and CGM metrics of average glycemia and glucose variability (GV) in moderate-to-advanced CKD.There were a total of 90 patients with diabetes in CKD stages G3b (Correlations between glucose management indicator (GMI) and HbA1c attenuated with advancing CKD (G3b [CGM-derived indices might serve as an adjunct to HbA1c monitoring to guide glycemic management, especially in those with eGFR 30 ml/min per 1.73 m

Objective: This study aims to unravel genetic determinants of coronary heart disease (CHD) in type 2 diabetes (T2D) and explore their applications. Research Design and Methods: We performed a two-stage genome-wide association studies for CHD in Chinese patients with T2D (3,596 cases and 8,898 controls), followed by replications in European patients with T2D (764 cases and 4,276 controls) and general populations (n=51,442-547,261). Each identified variant was examined for its association with a wide range of phenotypes, and its interactions with glycaemic, blood pressure (BP) and lipid controls on incident cardiovascular diseases. Results: We identified a novel variant (rs10171703) for CHD (OR [95% CI] = 1.21 [1.13–1.30]; P=2.4×10-8) and BP (β±SE = 0.130±0.017; P = 4.1×10-14) at PDE1A in Chinese T2D patients, but found only a modest association with CHD in general populations. This variant modulated the effects of BP goal attainment (130/80 mmHg) on CHD (Pinteraction = 0.0155) and myocardial infarction (MI) (Pinteraction = 5.1×10-4). Patients with CC-genotype of rs10171703 had >40% reduction in either cardiovascular events in response to BP control (2.9×10-8 < P < 3.6×10-5), those with CT-genotype had no difference (0.0726 < P < 0.2614), and those with TT-genotype had a threefold increase in MI risk (P = 6.7×10-3). Conclusions: We discovered a novel CHD- and BP-related variant at PDE1A which interacted with BP goal attainment with divergent effects on CHD risk in Chinese patients with T2D. Incorporating this information may facilitate individualized treatment strategies for precision care in diabetes only when our findings are validated.

Objective We examined the associations of glutamic acid decarboxylase antibodies (GADA) and C-peptide (CP) with insulin initiation, glycemic responses and severe hypoglycemia in type 2 diabetes (T2D). Research Design and Methods In 5230 Chinese patients with T2D (mean±SD age: 56.5±13.9 years, diabetes duration (median, IQR): 6 (1-12) years, 47.6% men) enrolled consecutively in 1996-2012 and prospectively observed till 2019, we retrospectively measured fasting CP and GADA in stored serum and examined their associations with aforementioned outcomes. Results At baseline, 28.6% had low CP (p=0.002) for insulin initiation versus the GADA- group, while the low-CP group had an aHR of 0.88 (0.77-1.00, p=0.051) versus the high-CP group. Following insulin initiation, the GADA+ plus low-CP group had the largest decrements in HbA1c (-1.9% at month 6; -1.5% at month 12) versus -1% in the other 3 groups. The aHR of severe hypoglycemia was 1.29 [(95% CI 1.10-1.52), p=0.002] in the low-CP and 1.38 [(95% CI 1.04-1.83) p=0.024] in the GADA+ group. Conclusions There is considerable heterogeneity in autoimmunity and beta-cell dysfunction in T2D with GADA+ and high CP associated with early insulin initiation while GADA+ and low CP, increased risk of severe hypoglycemia. Extended phenotyping is warranted to increase the precision of classification and treatment in T2D.

OBJECTIVE Several studies support associations between relative leukocyte telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates the relationship between rLTL and the risk of glycemic progression in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS In this cohort study, consecutive Chinese patients with type 2 diabetes (N = 5,506) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative PCR. Glycemic progression was defined as the new need for exogenous insulin. RESULTS The mean (SD) age of the 5,349 subjects was 57.0 (13.3) years, and mean (SD) follow-up was 8.8 (5.4) years. Baseline rLTL was significantly shorter in the 1,803 subjects who progressed to insulin requirement compared with the remaining subjects (4.43 ± 1.16 vs. 4.69 ± 1.20). Shorter rLTL was associated with a higher risk of glycemic progression (hazard ratio [95% CI] for each unit decrease [to ∼0.2 kilobases]: 1.10 [1.06–1.14]), which remained significant after adjusting for confounders. Baseline rLTL was independently associated with glycemic exposure during follow-up (β = −0.05 [−0.06 to −0.04]). Each 1-kilobase decrease in absolute LTL was on average associated with a 1.69-fold higher risk of diabetes progression (95% CI 1.35–2.11). Two-sample Mendelian randomization analysis showed per 1-unit genetically decreased rLTL was associated with a 1.38-fold higher risk of diabetes progression (95% CI 1.12–1.70). CONCLUSIONS Shorter rLTL was significantly associated with an increased risk of glycemic progression in individuals with type 2 diabetes, independent of established risk factors. Telomere length may be a useful biomarker for glycemic progression in people with type 2 diabetes.

Aims/hypothesis Few large-scale prospective studies have investigated associations between relative leucocyte telomere length (rLTL) and kidney dysfunction in individuals with type 2 diabetes. We examined relationships between rLTL and incident end-stage kidney disease (ESKD) and the slope of eGFR decline in Chinese individuals with type 2 diabetes. Methods We studied 4085 Chinese individuals with type 2 diabetes observed between 1995 and 2007 in the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data. rLTL was measured using quantitative PCR. ESKD was diagnosed based on the ICD-9 code and eGFR. Results In this cohort (mean ± SD age 54.3 ± 12.6 years) followed up for 14.1 ± 5.3 years, 564 individuals developed incident ESKD and had shorter rLTL at baseline (4.2 ± 1.2 vs 4.7 ± 1.2, p n = 3521). On Cox regression analysis, each ∆∆Ct decrease in rLTL was associated with an increased risk of incident ESKD (HR 1.21 [95% CI 1.13, 1.30], p 1c, lipids, renal function and other risk factors (HR 1.11 [95% CI 1.03, 1.19], p = 0.007). Shorter rLTL at baseline was associated with rapid decline in eGFR (>4% per year) during follow-up (unadjusted OR 1.22 [95% CI 1.15, 1.30], p p = 0.024). Conclusions/interpretation rLTL is independently associated with incident ESKD and rapid eGFR loss in individuals with type 2 diabetes. Telomere length may be a useful biomarker for the progression of kidney function and ESKD in type 2 diabetes. Graphical abstract

Women with polycystic ovary syndrome (PCOS) have an increased risk of developing type 2 diabetes. FGF19, FGF21 and lipocalin-2 have emerged as important markers of metabolic risk. This study aims to compare the levels of FGF19, FGF21 and lipocalin-2 between subjects with or without PCOS, and to investigate the relationship between proteins and diabetes progression. In this nested case–control cohort study, 128 Chinese PCOS women and 128 controls were recruited and followed-up. All subjects underwent the oral glucose tolerance test for the evaluation of glycaemic status. Baseline serum protein levels were measured using ELISA. Compared with controls, PCOS subjects had higher levels of FGF19 (P < 0.001) and FGF21 (P = 0.022), but had lower lipocalin-2 (P < 0.001). In total, 20.8% of PCOS and 9.2% of controls developed diabetes over a mean duration of 10.4 ± 1.2 and 11.3 ± 0.5 years, respectively. Logistic regression analyses suggested FGF19 was positively associated with diabetes progression in controls, after adjusting for age, follow-up duration, waist and fasting glucose (P = 0.026, odds ratio (OR) (95% CI): 7.4 (1.3–43.6)), and the positive relationship between FGF21 and diabetes progression in controls was attenuated by adjusting for age and follow-up duration (P = 0.183). Lipocalin-2 was positively correlated with diabetes progression in PCOS group (P = 0.026, OR (95% CI)): 2.5 (1.1–5.6)); however, this became attenuated after adjusting for waist and fasting glucose (P = 0.081). In conclusion, there is differential expression of FGF19, FGF21, and lipocalin-2 in PCOS. The serum level of FGF19, and FGF21 is associated with diabetes progression in women without PCOS, while lipocalin-2 was related to diabetes progression in PCOS women.

Intensive lifestyle modification showed variable success in the prevention of major clinical events and mortality among people with prediabetes. We propose that age may partly explain the heterogeneity and that health hazards related to prediabetes are age-specific.We conducted a retrospective analysis of a territory-wide diabetes surveillance dataset from the Hong Kong Hospital Authority between 2000 and 2019. Prediabetes was defined according to the American Diabetes Association criteria. Proportional Cox regression was performed, stratified by baseline age categories (20-39, 40-59, 60-79 and ≥80 years).1,630,942 individuals were included in the analysis. Compared with normoglycaemia, prediabetes was associated with greater hazards for cardiovascular disease (CVD) and all-cause mortality in most age groups but the effect size attenuated with ascending age (Prediabetes is associated with higher risk of major clinical events, even excluding subsequent development of diabetes and adjusting for metabolic factors. The risk relationships are stronger in young than older people.This study did not receive any specific funding.

To examine the association of initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) at lower glycemic threshold with decline in estimated-glomerular filtration rate (eGFR).We analyzed a prospective cohort of Chinese patients with type 2 diabetes from Hong Kong. Patients initiating SGLT2i at HbA1c 7.5 % (lower-HbA1c) versus ≥ 7.5 % (higher-HbA1c) were matched using 1:1 propensity score. We compared annual eGFR changes in the lower-HbA1c and higher-HbA1c groups using linear mixed-effect models. Binary logistic regression was used to explore associations of SGLT2i initiation at lower HbA1c with odds of rapid eGFR decline (4% per year).Among 3384 patients with a median follow-up of 1.9 years, the mean age was 60.2 ± 11.5 years and 62.1 % were male. The lower-HbA1c and higher-HbA1c groups had baseline HbA1c (%) of 6.9 ± 0.5 and 9.0 ± 1.3 respectively, with similar pre-index annual eGFR decline. The lower-HbA1c group had a slower post-index annual eGFR decline than the higher-HbA1c group (-0.99 versus -1.63 mL/min/1.73 mIn this real-world study, SGLT2i initiation at HbA1c 7.5 % was associated with slower eGFR decline especially in high risk patients, supporting the potential renal benefits of SGLT2i initiation at lower glycemic thresholds.

We postulated that the increased lifetime risk of chronic kidney disease (CKD) in young-onset diabetes is attributable to both long disease duration and more aggressive disease. We examined whether age at diabetes diagnosis modifies the effect of diabetes duration on risk of CKD. We included 436,744 people with incident type 2 diabetes in the Hong Kong Diabetes Surveillance Database (HKDSD) and 16,979 people with prevalent type 2 diabetes in the Hong Kong Diabetes Register (HKDR). We used Poisson models to describe joint effects of age at diabetes diagnosis, diabetes duration and attained age on incidence of CKD in HKDSD. We used Cox proportional hazards models to examine interaction effect of age at diabetes diagnosis and diabetes duration on risk of CKD with adjustment for confounders in HKDR. During a median follow-up of 5.3 years, 134,043 cases of CKD were recorded in the HKDSD. The incidence rate ratio for CKD comparing people of the same attained age but diagnosed with diabetes at ages 5 years apart was higher for people with a younger age at diabetes diagnosis, but decreased with increasing age at diabetes diagnosis. During a median follow-up of 6.3 years, 6500 people developed CKD in the HKDR. The increased risk of CKD with longer diabetes duration decreased with older age at diabetes diagnosis. The adjusted HR for CKD associated with 5 year increase in diabetes duration was 1.37 (95% CI 1.13, 1.65) in people with diabetes diagnosed at 20–29 years and 1.01 (95% CI 0.87, 1.18) in those diagnosed at ≥70 years. Young age at diabetes diagnosis amplified the effect of increasing diabetes duration on increased risk of CKD.

IntroductionAlthough poor adherence to insulin is widely recognised, periodic discontinuation of insulin may cause more severe hyperglycaemia than poor adherence. We assessed persistence with insulin therapy in patients with type 1 (T1D) or type 2 diabetes (T2D) in developing countries and the reasons for insulin discontinuation.MethodsThe International Diabetes Management Practices Study collected real-world data from developing countries in seven waves between 2005 and 2017. In Wave 7 (2016-2017), we asked adult patients with T1D and insulin-treated T2D to report whether they had ever discontinued insulin, the estimated duration of discontinuation and underlying reasons.ResultsAmong 8303 patients recruited from 24 countries by 620 physicians, 4596 were insulin-treated (T1D: 2000; T2D: 2596). In patients with T1D, 14.0% (95% CI: 12.5-15.6) reported having self-discontinued insulin for a median duration of 1.0 month (IQR: 0.5, 3.5). The respective figures in patients with T2D were 13.7% (12.4-15.1) and 2.0 months (IQR: 1.0, 6.0). The main reasons for discontinuation were impact on social life (T1D: 41.0%; T2D: 30.5%), cost of medications and test strips (T1D: 34.4%; T2D: 24.5%), fear of hypoglycaemia (T1D: 26.7%; T2D: 28.0%) and lack of support (T1D: 26.4%; T2D: 25.9%). Other factors included age < 40 years, non-university education and short disease duration (T1D: 1- 75 mmol/mol (> 9%) and > 50% of physicians recommended diabetes education programmes to improve treatment persistence.ConclusionIn developing countries, poor persistence with insulin is common among insulin-treated patients, supporting calls for urgent actions to ensure easy access to insulin, tools for SMBG and education. Sanofi (Paris, France); Sanofi This study was funded by Sanofi (Paris, France). The sponsor was supported by the steering committee regarding study design, registry structure, protocol amendments, research questions, analyses and publications. Publication fees (including the journal's Rapid Service and Open Access fees) were also funded by Sanofi.

The augmented velocity index (Avi) is a new Doppler index associated with arterial stiffness. We examined associations of renal Avi with blood pressure (BP), aortic stiffness and carotid intima-media thickness (IMT), and compared its performance with that of resistive index (RI). One hundred forty-seven volunteers were recruited. Renal Avi had significant positive correlations with systolic BP (r = 0.37, p0.001), diastolic BP (r = 0.2, p = 0.016), mean arterial pressure (r = 0.29, p0.001), pulse pressure (r = 0.31, p0.001), carotid-femoral pulse wave velocity (r = 0.49, p0.001) and carotid IMT (r = 0.23, p = 0.005). RI correlated positively with pulse pressure (r = 0.3, p0.001) only. After adjustments for co-variables, the associations remained similar. Patients with abnormal BP values (≥130/80 mm Hg), IMT and aortic stiffness (≥1 standard deviation of mean value) had higher Avi than those with normal values, but not RI. In conclusion, renal Avi had stronger associations with BP, arterial stiffness and carotid IMT than RI in apparently healthy volunteers, and was significantly increased in abnormal patients.

The long-term effects of metformin in individuals with type 2 diabetes who are at increased risk of severe respiratory infections are unknown. This study aimed to evaluate the effects of metformin use on the risk of first pneumonia hospitalisation and pneumonia-related death in a cohort of Chinese individuals with type 2 diabetes. We performed a retrospective analysis of a consecutive cohort of 22,638 individuals with type 2 diabetes in the Hong Kong Diabetes Register enrolled between 2001 and 2018, with follow-up until 31 December 2019. Overlap propensity-score weighting was performed to balance baseline characteristics. Of 22,638 individuals with type 2 diabetes, after excluding those who had not been prescribed any glucose-lowering drugs (GLDs) and/or with eGFR ≤30 ml min−1 [1.73 m]−2 or treated by dialysis and/or treated with insulin at baseline, we identified 15,784 either prevalent or incident metformin users and 917 users of other GLDs during a mean follow-up period of 7.5 years. Overlap-weighted analysis showed an HR of 0.63 (95% CI 0.52, 0.77) for first pneumonia hospitalisation and 0.49 (95% CI 0.33, 0.73) for pneumonia-related death in metformin users vs users of other GLDs; similar observations resulted following stratification by sex and kidney function. There was also a negative association between metformin exposure over time (proportion of duration of metformin prescriptions during the total follow-up time) and pneumonia events using the penalised spline analysis. Metformin users had a lower neutrophil/lymphocyte ratio at first pneumonia hospitalisation vs non-metformin users (mean [95% CI]: 12.8 [12.1, 13.5] vs 14.8 [12.3, 17.3], p = 0.032). The rate of metformin-associated lactic acidosis was 2.5 per 100,000 person-years. The lower risk of pneumonia events was also observed among incident metformin users vs other GLD users. Long-term use of metformin was associated with reduced risk of pneumonia and pneumonia-related death among Chinese individuals with diabetes. The relevance of these results to other respiratory infections merits further investigation.

Summary Background Diabetes prevalence is increasing in most places in the world, but prevalence is affected by both risk of developing diabetes and survival of those with diabetes. Diabetes incidence is a better metric to understand the trends in population risk of diabetes. Using a multicountry analysis, we aimed to ascertain whether the incidence of clinically diagnosed diabetes has changed over time. Methods In this multicountry data analysis, we assembled aggregated data describing trends in diagnosed total or type 2 diabetes incidence from 24 population-based data sources in 21 countries or jurisdictions. Data were from administrative sources, health insurance records, registries, and a health survey. We modelled incidence rates with Poisson regression, using age and calendar time (1995–2018) as variables, describing the effects with restricted cubic splines with six knots for age and calendar time. Findings Our data included about 22 million diabetes diagnoses from 5 billion person-years of follow-up. Data were from 19 high-income and two middle-income countries or jurisdictions. 23 data sources had data from 2010 onwards, among which 19 had a downward or stable trend, with an annual estimated change in incidence ranging from −1·1% to −10·8%. Among the four data sources with an increasing trend from 2010 onwards, the annual estimated change ranged from 0·9% to 5·6%. The findings were robust to sensitivity analyses excluding data sources in which the data quality was lower and were consistent in analyses stratified by different diabetes definitions. Interpretation The incidence of diagnosed diabetes is stabilising or declining in many high-income countries. The reasons for the declines in the incidence of diagnosed diabetes warrant further investigation with appropriate data sources. Funding US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.

Introduction To compare glycemic variability (GV) and time in range (TIR) in Chinese patients with type 2 diabetes (T2D) initiated on once-daily bedtime insulin glargine 300U/ml (Gla-300) versus neutral protamine Hagedorn (NPH) insulin using continuous glucose monitoring (CGM). Methods This was a 24-week, open-label exploratory study with 1:1 randomization comparing patient-adjusted titration of Gla-300 (n = 23) versus NPH (n = 23) at bedtime in insulin-naïve T2D patients on maximum oral glucose-lowering drugs. The starting dose was 0.2 U/kg/day and with self-titration of one unit per week to achieve a target fasting glucose of 4.4–6 mmol/l, without hypoglycemia. Participants had masked CGM at baseline, weeks 11 and 24. The primary outcome was between-treatment differences in CGM glucose standard deviation (SD) at week 24. Results HbA1c at week 24 were similar, with 21% of Gla-300 versus 4% of NPH-treated patients achieving HbA1c

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.

Aims/Introduction β‐Cell dysfunction is a hallmark of type 2 diabetes. In a previous pilot study, we identified an association between genetic variants within the human DACH1 gene and young‐onset type 2 diabetes. Here, we characterized the function of dachb, the only dach homologue to be expressed in the pancreas, in developing zebrafish embryos. Materials and Methods We injected one‐cell stage embryos with a dachb‐morpholino (MO) or with the dachb‐MO and dachb messenger ribonucleic acid, and determined the effect on the development of the pancreatic islet. We also carried out quantitative polymerase chain reaction and ribonucleic acid sequencing on the dachb‐MO group to determine the effect of dachb knockdown on gene expression. Results MO‐mediated dachb knockdown resulted in impaired islet cell development, with a significant decrease in both the β‐cell and islet cell numbers. This islet developmental defect was rescued when embryos were co‐injected with dachb‐MO and dachb messenger ribonucleic acid. Knockdown of dachb was associated with a significant downregulation of the β‐cell specific marker gene, insa, and the somatostatin cell marker, sst2, as well as regulators of pancreas development, ptf1a, neuroD, pax6a and nkx6.1, and the cell cycle gene, insm1a. Furthermore, ribonucleic sequencing analysis showed an upregulation of genes enriched in the forkhead box O and mitogen‐activated protein kinase signaling pathways in the dachb‐MO group, when compared with the control groups. Conclusions Together, our results suggest the possible role of dachb in islet development in zebrafish., Morpholino (MO)‐mediated knock‐down of dachb resulted in impaired islet cell development, with a significant decrease in both the β‐cell and islet cell numbers in zebrafish. Embryos co‐injected with dachb mRNA and dachb‐MO expressed a similar phenotype as the uninjected control groups, indicating rescue of the islet developmental defect. The studies highlight the role of dachb in islet development in zebrafish.

Introduction: Previous analysis showed that passive smoking and overweight were associated with an increased risk of gestational diabetes mellitus (GDM) in a synergistic manner, while GDM increased the risk of macrosomia/large for gestational age (LGA). This study aimed to examine any interactive effects between passive smoking and overweight/obesity on risk of macrosomia/LGA. Methods: From 2010 to 2012, 22,302 pregnant women registered for pregnancy at a primary hospital in Tianjin, China. Data were collected longitudinally; that is, from their first antenatal care visit, at the glucose challenge test (GCT) time (24–28 weeks of gestation) and at delivery. Passive smoking was self-reported. Macrosomia was defined as birth weight ≥4,000 g. Binary logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was used to test the synergistic effect. Results: Passive smokers accounted for 57.4% of women (n = 8,230). Using nonpassive smoking and prepregnancy body mass index (BMI) 2 as the reference, the adjusted ORs of overweight alone and passive smoking alone for macrosomia were 2.39 (95% CI: 2.11–2.71) and 1.17 (95% CI: 1.04–1.32). Copresence of passive smoking and prepregnancy BMI ≥24.0 kg/m2 increased the OR to 2.70 (95% CI: 2.28–3.20), with a significant additive interaction. After further adjustment for GDM or GCT, the OR of copresence of both risk factors was slightly attenuated to 2.52 (2.13–3.00) and 2.51 (2.11–2.98), with significant additive interaction. However, the additive interaction between prepregnancy overweight/obesity and passive smoking for LGA was nonsignificant. Conclusions: Prepregnancy overweight/obesity was associated with an increased risk of macrosomia in Chinese women synergistically with passive smoking during pregnancy, and most of the association was not modified by hyperglycemia during pregnancy.

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 HbAOf 207 eligible patients [age (mean ± standard deviation): 56.9 ± 8.8 years, 47.4 % men, disease duration: 13.5 ± 8.2 years, HbATeam-based MIC for 1 year improved glycemic control in obese T2D which was sustained at 3-year.

Early onset of type 2 diabetes and a high prevalence of co‐morbidities predispose the Asian population to a high risk for, and rapid progression of, diabetic kidney disease (DKD). Apart from renin‐angiotensin system inhibitors, sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors have been shown to delay renal disease progression in patients with DKD. In this review article, we consolidate the existing literature on SGLT‐2 inhibitor use in Asian patients with DKD to establish contemporary guidance for clinicians. We extensively reviewed recommendations from international and regional guidelines, data from studies on Asian patients with DKD, global trials (DAPA‐CKD, CREDENCE and DELIGHT) and cardiovascular outcomes trials. In patients with DKD, SGLT‐2 inhibitor therapy significantly reduced albuminuria and the risk of hard renal outcomes (defined as the onset of end‐stage kidney disease, substantial decline in renal function from baseline and renal death), cardiovascular outcomes and hospitalization for heart failure. In all the cardiovascular and renal outcomes trials, there was an initial decline in the estimated glomerular filtration rate (eGFR), which was followed by a slowing in the decline of renal function compared with that seen with placebo. Despite an attenuation in glucose‐lowering efficacy in patients with low eGFR, there were sustained reductions in body weight and blood pressure, and an increase in haematocrit. Based on the available evidence, we conclude that SGLT‐2 inhibitors represent an evidence‐based therapeutic option for delaying the progression of renal disease in Asian patients with DKD and preserving renal function in patients at high risk of kidney disease.

Type 2 diabetes mellitus (T2DM) in East Asian population is characterized by phenotypes such as low body mass index, an index of β-cell dysfunction, and higher percentage of body fat, an index of insulin resistance. These phenotypes/pathologies may predispose people to early onset of diabetes with increased risk of stroke and renal disease. Less than 50% of patients with T2DM in East Asia achieve glycemic targets recommended by national or regional guidelines, which may be due to knowledge and/or implementation gaps. Herein, we review the latest evidence with special reference to East Asian patients with T2DM and present arguments for the need to use early combination therapy to intensify glycemic control. This strategy is supported by the 5-year worldwide VERIFY study, which has reported better glycemic durability in newly diagnosed patients with T2DM with a mean HbA1c of 6.9% treated with early combination therapy of vildagliptin plus metformin versus those treated with initial metformin monotherapy followed by addition of vildagliptin only with worsening glycemic control. This paradigm shift of early intensified treatment is now recommended by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). In order to translate these evidence to practice, increased awareness and strengthening of the healthcare system are needed to diagnose and manage patients with T2DM early for combination therapy. This article is protected by copyright. All rights reserved.

Sirtuin 3 (SIRT3) is a protein deacetylase regulating beta cell function through inhibiting oxidative stress in obese and diabetic mice, but the detailed mechanism and potential effect of beta cell specific SIRT3 on metabolic homeostasis, and its potential effect on other metabolic organs are unknown. We found glucose tolerance and glucose stimulated insulin secretion (GSIS) were impaired in high fat diet (HFD)-fed beta cell selective Sirt3 knockout (Sirt3f/f;Cre/+) mice. In addition, Sirt3f/f;Cre/+ mice had more severe hepatic steatosis than Sirt3f/f mice upon HFD feeding. RNA sequencing (RNA-Seq) of islets suggested that Sirt3 deficiency over-activated 5-hydroxytryptamine (5-HT) synthesis as evidenced by up-regulation of tryptophan hydroxylase 1 (TPH1). 5-HT concentration was increased in both islets and serum of Sirt3f/f;Cre/+ mice. 5-HT also facilitated the effect of palmitate to increase lipid deposition. Treatment with TPH1 inhibitor ameliorated hepatic steatosis and reduced weight gain in HFD-fed Sirt3f/f;Cre/+ mice. These data suggested that under HFD feeding, SIRT3 deficiency in beta cells not only regulates insulin secretion but also modulates hepatic lipid metabolism via the release of 5-HT.

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

The Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease represents the first KDIGO guideline on this subject. The guideline comes at a time when advances in diabetes technology and therapeutics offer new options to manage the large population of patients with diabetes and chronic kidney disease (CKD) at high risk of poor health outcomes. An enlarging base of high-quality evidence from randomized clinical trials is available to evaluate important new treatments offering organ protection, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists. The goal of the new guideline is to provide evidence-based recommendations to optimize the clinical care of people with diabetes and CKD by integrating new options with existing management strategies. In addition, the guideline contains practice points to facilitate implementation when insufficient data are available to make well-justified recommendations or when additional guidance may be useful for clinical application. The guideline covers comprehensive care of patients with diabetes and CKD, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and self-management and health systems approaches to management of patients with diabetes and CKD.

This study aimed to examine impacts of gestational diabetes mellitus (GDM) on quality of life (QoL) domains in Chinese pregnant women.We recruited 13,358 pregnant women in Tianjin, China. GDM was diagnosed using the criteria of International Association of Diabetes and Pregnancy Study Group. QoL was measured using the 36-Item Short-Form Health Survey. General linear model was used to obtain β-coefficient and 95% confidence intervals (CI) of GDM for QoL domain and summary scores.7.25% of the pregnant women developed GDM. Among the QoL domain and summary scores, only general health (GH) score was lower in the GDM group than in the non-GDM group. GDM and advanced maternal age (i.e., ≥ versus30 years) were negatively associated with GH in multivariable analyses (β-coefficient: -1.17, 95%CI: -2.17 to -0.17-0.79, -1.40 to -0.18, respectively). In subgroup analyses, the β-coefficient of GDM for GH among women with maternal age ≥30 years was enhanced to -2.17 (-3.94 to -0.40) in multivariable analysis while the β-coefficient of GDM for GH among women aged30 years was attenuated to non-significance.GDM and advanced maternal age were associated with reducing GH, and presence of advanced maternal age markedly increased the effect of GDM on GH.