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Abstract: Retinol binding protein 4 (RBP4) is a protein secreted by adipocytes, and closely associated with insulin resistance. Whereas RBP4 is also mainly expressed in hepatocytes as the principal transport protein for retinol (vitamin A) in the circulation, and its pathophysiological role in liver remain unclear. The aim of this paper was to investigate the association between RBP4 and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Serum RBP4 and adiponectin concentrations were measured by radioimmunoassay in 52 diabetic patients who had NAFLD and 50 sex- and age-matched diabetic patients without any clinical features of liver diseases who had normal liver ultrasonic appearance and normal liver function. Serum RBP4 levels were elevated in diabetic patients with NAFLD (32.0±8.9μg/ml vs. 41.3±9.8μg/ml, p <0.001), while adiponectin decreased (17.4±9.3μg/ml vs. 13.8±7.0μg/ml, p =0.032). Male diabetic patients had higher serum RBP4 concentration and lower serum adiponectin concentration than female diabetic patients (38.5±9.9μg/ml vs. 34.0±10.7μg/ml, p =0.031 and 12.7±5.7μg/ml vs. 20.23±9.8μg/ml, p <0.001, respectively). Multiple logistic regression analysis revealed RBP4 and triglyceride as independent association factors for NAFLD, while the association between serum adiponectin and NAFLD was not significant. Increasing concentrations of RBP4 were independently and significantly associated with NAFLD in diabetic patients. In multiple linear regression analysis, alanine aminotransferase, fasting serum insulin and adiponectin were independent factors for serum RBP4 level. The study demonstrates that retinol binding protein 4 might contribute to the pathogenesis of nonalcoholic fatty liver disease. [Copyright &y& Elsevier]

We investigated the real-world incidence of hypoglycemic events among patients with type 1 or type 2 diabetes (T1DM or T2DM) receiving insulin in routine clinical practice in China. In this observational study, data were collected electronically via the Lilly Connected Care Program (LCCP) electronic system from adults with T1DM or T2DM who had registered on LCCP between 1 February 2019 and 31 January 2022, had used insulin for a full 12-week period following registration. The following outcomes were assessed during the 12 weeks following registration: incidence of level 1 and level 2 hypoglycemia. In total, 22,752 patients were enrolled. Among patients with monitoring data, over the 12-week study period, level 1 and 2 hypoglycemia were experienced by 48.8% and 25.9% of patients with T1DM and 26.5% and 13.9% of patients with T2DM. The proportion of patients treated with oral anti-diabetes drugs (OADs) capable of producing hypoglycemia (sulfonylurea or glinide) was 1.3% in T1DM and 1.6% in T2DM, respectively. Questionnaire data revealed that up to 92.5% of hypoglycemic events occurred outside of hospital and 18.6% were serious. These real-world data collected from Chinese patients with diabetes receiving insulin treatment reveal a relatively high percentage of patients experiencing hypoglycemia, with around one quarter of these events classified as severe and as many as 92.5% occurring outside of a hospital or clinic. [ABSTRACT FROM AUTHOR]

Glucose monitoring has evolved from self-monitoring of blood glucose to glycated hemoglobin, and the latest continuous glucose monitoring (CGM). A key challenge to adoption of CGM for management of diabetes in Asia is the lack of regional CGM recommendations. Hence, thirteen diabetes-specialists from eight Asia-Pacific (APAC) countries/regions convened to formulate evidence-based, APAC-specific CGM recommendations for individuals with diabetes. We defined CGM metrics/targets and developed 13 guiding-statements on use of CGM in: (1) people with diabetes on intensive insulin therapy, and (2) people with type 2 diabetes on basal insulin with/without glucose lowering drugs. Continual use of CGM is recommended in individuals with diabetes on intensive insulin therapy and suboptimal glycemic control, or at high risk of problematic hypoglycemia. Continual/intermittent CGM may also be considered in individuals with type 2 diabetes on basal insulin regimen and with suboptimal glycemic control. In this paper, we provided guidance for optimizing CGM in special populations/situations, including elderly, pregnancy, Ramadan-fasting, newly diagnosed type 1 diabetes, and comorbid renal disease. Statements on remote CGM, and stepwise interpretation of CGM data were also developed. Two Delphi surveys were conducted to rate the agreement on statements. The current APAC-specific CGM recommendations provide useful guidance for optimizing use of CGM in the region. [ABSTRACT FROM AUTHOR]

Aims: We assessed the impact of changes in body mass index (BMI), body fat percentage (BF%), and waist circumference (WC) on prediabetes among Chinese middle-aged and elderly adults.Subjects, Materials and Methods: 2.5-year changes in BMI, BF%, and WC were calculated by subtracting baseline levels from follow-up, based on a cohort of 3,632 participants with prediabetes, and outcomes were defined as remission to normal glucose regulation (NGR), persistence in prediabetes, and progression to newly diagnosed diabetes mellitus (NDM).Results: Among participants with prediabetes, 16.9% returned to NGR and 24.6% progressed to NDM. Changes in BMI, BF%, but not WC were associated with remission and progression of prediabetes (risk ratio per standard deviation increase of BMI: 0.86 [0.79-0.93] and 1.15 [1.08-1.23]; BF%: 0.91 [0.84-0.98] and 1.11 [1.03-1.19]). Among participants with combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), only BF% change was significantly associated with remission of prediabetes.Conclusion: Short-term management of BMI and BF% should be stressed to promote the remission and prevent the progression of prediabetes, regardless of whether someone is obese. Moreover, it is of particular clinical importance to monitor BF% among people with combined IFG and IGT. [ABSTRACT FROM AUTHOR]

Aim: This study explored the possibility of developing an alternative, simple and rapid test for the screening of distal symmetrical polyneuropathy (DSPN), for use in local primary care facilities.Methods: 4023 patients with type 2 diabetes mellitus (T2DM), aged 18-80 years, from 21 hospitals in China were screened for inclusion in a prospective diagnostic assessment of DSPN, between April 2011 and March 2012. Patients underwent nerve conduction study (NCS; as the gold standard) and clinical assessments of ankle reflexes (AR) and thermal (T), vibration (V), pressure (P), and pinprick (PP) sensations.Results: Results from various combinations of these clinical assessments were compared to determine the optimal screening regimens. The Toronto Consensus Panel definition was used to confirm clinical DSPN (symptoms or signs plus abnormal NCS). 3883 of the 4023 patients (M:F, 2162:1721; mean age, 56.79±13.16 years) were included. No significant differences were found between the two most efficient clinical assessment combinations, AR+PP+T+V and AR+T+V (P=0.9612). Compared to the diagnosis made using AR+T+V, the same diagnosis was reached using AR+PP+P+V+T in 100% of patients with probable clinical DSPN, 84.05% with possible clinical DSPN, and 96.84% with no DSPN. The AR+T+V assessment was also ∼40% faster than the AR+PP+P+V+T assessment.Conclusions: Combined AR+T+V assessment is a valuable tool for screening diabetic patients for DSPN, potentially decreasing costs to local primary care facilities and making care more available to underserved populations. [ABSTRACT FROM AUTHOR]

Aim: The association between thyroid stimulating hormone (TSH) and type 2 diabetes mellitus (T2DM) is well known. However, whether TSH is related to diabetic peripheral neuropathy (DPN) has not been studied. The aim of this study was to explore the relationship between TSH and DPN in Chinese patients with T2DM.Methods: In this cross-sectional study, 605 patients with T2DM were enrolled. Subclinical hypothyroidism (SCH) was defined as an elevated TSH level (>4.0mIU/L) and a normal free thyroxine level. DPN was evaluated by neurological symptoms, neurological signs, and electromyogram.Results: Serum TSH levels were significantly higher in DPN and signs of DPN compared with non-DPN T2DM patients (both P<0.01).The prevalence of DPN and signs of DPN in SCH subjects was higher than that in euthyroid subjects (both P<0.01). Spearman's correlation analysis showed that the serum TSH level was positively associated with DPN (r=0.172, P<0.01). A significant independent association between TSH and DPN was found by multiple logistic regression analysis after adjusting for potential confounding variables [odds ratio (OR)=1.365, P<0.01]. The patients were sequentially assigned to quartiles according to TSH level. Compared with quartile 1, patients in quartile 2 (P<0.01), quartile 3 (P=0.01), and quartile 4 (P<0.01) had a higher risk of DPN. Receiver-operating characteristic curve analysis revealed that the optimal cutoff point of TSH to indicate DPN was 3.045mIU/L in men and 2.94mIU/L in women.Conclusion: TSH level is independently associated with DPN in Chinese population with T2DM. A high serum TSH level may be a potential risk factor for DPN. [ABSTRACT FROM AUTHOR]

Abstract: Aims/hypothesis: The aim of this study was to investigate clinical spectrum of hepatocyte nuclear factor-1β (HNF-1β) mutation in Chinese diabetic patients with renal dysfunction and/or structure abnormalities. Materials and methods: A total of 104 diabetic patients with renal structural abnormalities and/or non-diabetic renal dysfunction were recruited and HNF-1β mutation was screened by direct sequencing. Results: Three heterozygous missense mutations including c.494G>A (p.R165H), c.662A>T (p.D221V) and c.780G>C (p.E260D) were identified. Progression of diabetes and mild decline of renal function were observed in the mutation carriers during the follow-up. The p.R165H mutation carrier had severe β-cell dysfunction and different extrapancreatic phenotypes. Compared with type 2 diabetes and normoglycemics, the p.R165H mutation carrier had a lower basal C-peptide (0.30, 0.61±0.07 and 0.50±0.04nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively) and low values of acute C-peptide response to arginine (0.15, 0.48±0.18 and 0.76±0.08nmol/L for p.R165H, type 2 diabetes and normoglycemics, respectively). Conclusion: Patients with the HNF-1β mutation in our population can have different pancreatic and extrapancreatic phenotypes. The exact contributions of mutations to the phenotypes await functional confirmation. [Copyright &y& Elsevier]

Aims: Advanced glycation end products (AGEs) were reported to be associated with diabetes development and diabetes related complications when accumulated in high levels. This study investigated the association between AGEs and diabetic retinopathy (DR).Methods: A total of 1,471 patients with type 2 diabetes were enrolled. Fundus radiography was used for DR measurement. AGEs were detected through non-invasive skin autofluorescence method.Results: Patients with more advanced DR showed a much higher AGEs, and the prevalence of DR (based on the severity) increase with ascending AGEs quartiles (all P for trend < 0.001). The multivariable-adjusted odds ratios of any DR across AGEs quartiles were 1.00, 1.69 (95% confidence interval [CI] 1.16-2.47), 1.58 (95%CI 1.06-2.37) and 1.60 (95%CI 1.05-2.44) (P for trend = 0.044), respectively. Similar results were found in vision-threatening DR (VTDR) subgroup (P for trend = 0.009). When AGEs was considered as a continuous variable by using restricted cubic splines, a graded positive association of AGEs with the odds of any presence of DR was observed (P for trend < 0.001). Further, we found that AGEs presented the similar predictive value for any DR with glycated hemoglobin A1c (HbA1c). When it comes to VTDR, AGEs showed a significantly higher efficacy in early screening than HbA1c (P = 0.002). With a cut-off point of 77.1, the sensitivity, specificity and area under the curve of AGEs were 90.0% (95%CI 76.3-97.2%), 49.4% (95%CI 46.8-52.0%), and 0.728 (95%CI 0.704-0.750), respectively.Conclusion: Non-invasive measured skin AGEs, associated with the prevalence of all stages of DR, might be a more suitable indicator than HbA1c for mimicking the poor prognosis of hyperglycemia. [ABSTRACT FROM AUTHOR]

Aim: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease and also closely related to cardiometabolic disease. Its prevalence was estimated at over one-fourth in the general population in China. We aimed to develop effective score tools for detecting NAFLD.Methods: A total of 17,212 participants aged 45-70 years old were surveyed in Shanghai between 2013 and 2014, and 13,293 participants were included in this analysis. All participants were randomly classified into the exploratory group or the validation group. Candidate categorical variables were selected using a logistic regression model. The score points were generated according to the β-coefficients.Results: We developed the Shanghai Nicheng NAFLD Score I (SHNC NAFLD Score I), which included body mass index and waist circumference with an area under the receiver-operating characteristic curve (AUC) of 0.802 (95% CI 0.792-0.811) in the exploratory group and 0.802 (95% CI 0.793-0.812) in the validation group. We further developed the SHNC NAFLD Score II by adding fasting plasma glucose, triglyceride, and alanine aminotransferase/aspartate aminotransferase ratio to the SHNC NAFLD Score I, achieving an AUC of 0.852 (95% CI 0.843-0.861) in the exploratory group and 0.843 (95% CI 0.834-0.852) in the validation group. The two score tools also performed well in subjects with normal alanine aminotransferase (ALT) levels.Conclusions: Based on anthropometric and clinical categorical variables, our two scores are effective tools for detecting NAFLD in both this southern Chinese population and their subpopulation with normal ALT levels. [ABSTRACT FROM AUTHOR]

Aims: To investigate the frequency of dawn phenomenon (DP) and its relationship with time in range (TIR) and glycemic variability (GV) using continuous glucose monitoring (CGM).Methods: 781 subjects of a multicenter CGM study in China were included: those with normal glucose tolerance (NGT n = 360); impaired glucose regulation (IGR n = 173); newly diagnosed type 2 diabetes mellitus (T2D n = 248). Analysis of the magnitude of DP (ΔG) was conducted with the primary definition of 1.11 mmol/L and a secondary definition of 0.56 mmol/L.Results: The frequency of DP was 8.9%, 30.1% and 52.4% in NGT, IGR and T2D group, respectively, using the primary definition. In all three groups, TIR was lower (all P < 0.05), coefficient of variation (CV) was higher in DP subgroup (all P < 0.05). In DP subgroup of T2D, TIR was 7.0% (1.68 h) lower and CV was 3.0% higher, and HbA1c was 0.6% (7 mmol/mol) higher using the primary definition (all P < 0.05).Conclusions: DP was present in a high percent of subjects with NGT and IGR. In newly diagnosed T2D group, the presence of DP was associated with poorer overall glycemic control. [ABSTRACT FROM AUTHOR]

Aims: Continuous glucose monitoring (CGM)-derived time-in-range (TIR) of 3.9-10 mmol/L is associated with diabetic retinopathy in type 2 diabetes (T2DM), but its relationship to peripheral nerve function has not been previously investigated. To explore the association between the TIR and nerve conduction study parameters in patients with T2DM, we performed a cross-sectional analysis.Methods: A total of 740 patients with T2DM were enrolled in this study. All of the participants were divided into tertiles according to the TIR (TIR low: ≤53%; TIR medium: 54-76%; TIR high: ≥77%). Composite Z-scores of nerve conduction velocity (CV), latency, and amplitude were calculated. The linear correlation between the TIR and composite nerve function Z-score was evaluated and risk assessment was analysed using binary logistic regression.Results: The composite Z-score of the CV and amplitude increased with higher TIR and the composite Z-score of latency significantly decreased as the TIR tertiles increased (all P trend < 0.05). After adjusting for age, diabetes duration, height, weight and other confounding factors, higher TIR was associated with a higher composite Z-score of CV (β = 0.230, P < 0.001), amplitude (β = 0.099, P = 0.010), and lower composite Z-score of latency (β = -0.172, P < 0.001). The risk of TIR tertiles and low composite Z-score of CV remained significant even after adjustment of HbA1c (TIR medium: OR = 0.48, P = 0.001; TIR high: OR = 0.41, P < 0.001).Conclusions: Higher TIR tertiles were independently associated with better peripheral nerve function. CGM-derived TIR may be a promising approach to screen patients for further assessment of possible diabetic peripheral neuropathy. [ABSTRACT FROM AUTHOR]

Background: Alterations in gut microbiota have been associated with improvements in blood glucose due to bariatric surgery.Objectives: Our aim is to identify specific gut microbiota that contribute to the remission of T2D after RYGB and SG.Methods: Rats fed a high-fat diet (HFD) were administered a low dose of streptozotocin as T2D models; next, their caecum content was collected 8 weeks after RYGB and SG. We also used case-control of gut microbial profiles of T2D patients and healthy people by collecting the mucosal-luminal interface from the ascending colon. Samples were profiled by 16S rRNA gene sequencing.Results: RYGB and SG reduced weight and improved glucose and insulin tolerance. Principal coordinate analysis showed that SG and, especially, RYGB cause changes in the composition of gut microbiota. We found that family Alcaligenaceae (genus Sutterella) was significantly decreased in the ascending colon of patients with T2D and increased after RYGB surgery in the caecum of T2D rats as shown by a linear discriminant analysis effect size (LEfSe) analysis, with no significant changes after SG. This result might benefit the improvement of glycometabolism.Conclusions: RYGB can significantly reduce weight, improve glycometabolism and change the composition of the gut microbiota. Sutterella may have beneficial effects on glycometabolism in T2D patients after RYGB. [ABSTRACT FROM AUTHOR]

Aims: Although there is a linear relationship between time in range (TIR) and hemoglobin A1c (HbA1c), a great variability of calculated TIR values for a given HbA1c, and vice versa, has been reported. Whether glycemic variability accounts for part of this variability remains to be investigated.Methods: The data of continuous glucose monitoring (CGM) from 2559 patients with type 2 diabetes was analyzed. Glycemic variability was assessed by glucose coefficient of variation (CV), and estimated HbA1C (eHbA1c) was calculated from mean sensor glucose.Results: A strong correlation between TIR and eHbA1c (r = -0.908) was observed. The slopes of regression lines fitted to TIR values as a function of eHbA1c differed significantly for individuals with varying degrees of CV, especially when patients were stratified as stable (CV < 36%) or unstable (CV ≥ 36%) glucose levels. For patients in the high- or low-range of eHbA1c, there was a high variability of TIR values according to CV.Conclusions: Glycemic variability significantly mediates the relationship between TIR and eHbA1c, and should be taken into consideration when setting an individualized target of TIR. [ABSTRACT FROM AUTHOR]