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As a sensor, glucokinase (GK) controls glucose homeostasis, which progressively declines in patients with diabetes. GK maintains the equilibrium of glucose levels and regulates the homeostatic system set points. Endocrine and hepatic cells can both respond to glucose cooperatively when GK is activated. GK has been under study as a therapeutic target for decades due to the possibility that cellular GK expression and function can be recovered, hence restoring glucose homeostasis in patients with type 2 diabetes. Five therapeutic compounds targeting GK are being investigated globally at the moment. They all have distinctive molecular structures and have been clinically shown to have strong antihyperglycemia effects. The mechanics, classification, and clinical development of GK activators are illustrated in this review. With the recent approval and marketing of the first GK activator (GKA), dorzagliatin, GKA's critical role in treating glucose homeostasis disorder and its long‐term benefits in diabetes will eventually become clear. [ABSTRACT FROM AUTHOR]

This article presents the findings of a study on the effectiveness of dulaglutide, a medication for type 2 diabetes, in Chinese patients. The study found that dulaglutide improved glycemic control, reduced body weight, and decreased insulin dosage compared to a placebo. The researchers also analyzed how patient characteristics influenced the medication's efficacy. The study was conducted ethically and registered with ClinicalTrials.gov. The results suggest that patients with higher baseline HbA1c levels may experience greater improvements in glycemic control, while those with higher baseline fasting serum glucose levels may experience greater weight loss. However, the study has limitations and further research is needed to fully understand these findings. [Extracted from the article]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aim: To determine the efficacy and safety of once‐weekly dulaglutide added to basal insulin in Chinese patients with type 2 diabetes mellitus (T2DM) with inadequate glycaemic control. Materials and Methods: In the phase III, double‐blind AWARD‐CHN3 study, Chinese patients with T2DM (N = 291) and glycated haemoglobin (HbA1c) ≥7.0% and ≤11.0% receiving stable doses of basal insulin glargine with metformin and/or acarbose were randomized (1:1) to receive add‐on dulaglutide 1.5 mg once weekly or placebo once weekly. The primary endpoint was the superiority of dulaglutide/glargine to placebo/glargine for change from baseline in HbA1c at Week 28. Results: The least squares (LS) mean ± standard error change in HbA1c from baseline to Week 28 was −2.0 ± 0.08% with dulaglutide/glargine and −1.1 ± 0.07% with placebo/glargine (LS mean difference: −1.0%, 95% confidence interval [CI] –1.1 to −0.8; P < 0.001), and more patients receiving dulaglutide/glargine achieved HbA1c levels <7.0% (75.9% vs. 33.8%; P < 0.001 vs. placebo/glargine). Body weight decreased with dulaglutide/glargine and increased with placebo/glargine (LS mean difference: −1.2 kg, 95% CI –1.8 to – 0.6; P < 0.001). Reductions in fasting serum glucose were greater with dulaglutide/glargine than with placebo/glargine (LS mean difference: −0.8 mmol/L, 95% CI –1.1 to – 0.5; P < 0.001). The incidence of hypoglycaemia was similar with dulaglutide/glargine and placebo/glargine (29.2% vs. 31.3%; P = 0.704); no patient in either group had severe hypoglycaemia. The most common treatment‐emergent adverse events with dulaglutide/glargine were decreased appetite (22.2%), diarrhoea (13.2%) and nausea (10.4%). Conclusions: Dulaglutide added to basal insulin was efficacious and well tolerated in Chinese patients with T2DM. [ABSTRACT FROM AUTHOR]

Aims: To assess the prevalence of diabetic peripheral neuropathy (DPN) and its risk factors in the type 2 diabetes mellitus (T2DM) population. Methods: This cross‐sectional study enroled patients with T2DM between July and December 2017 from 24 provinces in China. Diabetic peripheral neuropathy and its severity were assessed by the Toronto clinical scoring system, neuropathy symptoms score (NSS) and neuropathy disability score. The prevalence of DPN and its risk factors were analysed. Results: A total of 14,908 patients with T2DM were enroled. The prevalence of DPN was 67.6%. Among 10,084 patients with DPN, 4808 (47.7%), 3325 (33.0%), and 1951 (19.3%) had mild, moderate, and severe DPN, respectively. The prevalence of DPN in females was higher than in males (69.0% vs. 66.6%, P = 0.002). The prevalence of DPN increased with age and course of diabetes and decreased with body mass index (BMI) and education level (all P for trend <0.05). The comorbidities and complications in patients with DPN were higher than in those without DPN, including hypertension, myocardial infarction, diabetic retinopathy, and diabetic nephropathy (all P < 0.001). Age, hypertension, duration of diabetes, diabetic retinopathy, diabetic nephropathy, glycated haemoglobin, high‐density lipoprotein cholesterol, and lower estimated glomerular filtration rate were positively associated with DPN, while BMI, education level, fasting C‐peptide, and uric acid were negatively associated with DPN. Conclusions: Among patients with T2DM in China, the prevalence of DPN is high, especially in the elderly, low‐income, and undereducated patients. [ABSTRACT FROM AUTHOR]

Introduction: Left ventricular global longitudinal strain (GLS) is considered to be the first marker of diabetes mellitus-related subclinical cardiac dysfunction, but whether it is attributable to fat mass and distribution remains uncertain. In this study, we explored whether fat mass, especially fat mass in the android area, is associated with subclinical systolic dysfunction before the onset of cardiac disease. Methods: We conducted a single-center prospective cross-sectional study between November 2021 and August 2022 on inpatients of the Department of Endocrinology, Nanjing Drum Tower Hospital. We included 150 patients aged 18–70 years with no signs, symptoms, or history of clinical cardiac disease. Patients were evaluated with speckle tracking echocardiography and dual energy X-ray absorptiometry. The cutoff values for subclinical systolic dysfunction were set at a global longitudinal strain (GLS) < 18%. Results: After adjusting for sex and age, patients with GLS < 18% had a higher mean (± standard deviation) fat mass index (8.06 ± 2.39 vs. 7.10 ± 2.09 kg/m2, p = 0.02), higher mean trunk fat mass (14.9 ± 4.9 vs. 12.8 ± 4.3 kg, p = 0.01), and higher android fat mass (2.57 ± 1.02 vs. 2.18 ± 0.86 kg, p = 0.02) than those in the GLS ≥ 18%. Partial correlation analysis showed that the fat mass index, truck fat mass, and android fat mass were negatively correlated with GLS after adjusting for sex and age (all p < 0.05). Adjusted for traditional cardiovascular metabolic factors, fat mass index (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.05–1.55, p = 0.02), trunk fat mass (OR 1.13, 95% CI 1.03–1.24, p = 0.01), and android fat mass (OR 1.77, 95% CI 1.16–2.82, p = 0.01) were independent risk factors for GLS < 18%. Conclusion: Among patients with type 2 diabetes mellitus without established clinical cardiac disease, fat mass, especially android fat mass, was associated with subclinical systolic dysfunction independently of age and sex. [ABSTRACT FROM AUTHOR]

Aims: It is acknowledged that aberrant liver immunity contributes to the development of type 2 diabetes mellitus (T2DM). Mucosal‐associated invariant T (MAIT) cells, an innate‐like T‐cell subset, are enriched in the human liver. Nevertheless, the characterisation and potential role of hepatic MAIT cells in T2DM remain unclear. Materials and methods: Fourteen newly diagnosed T2DM subjects and 15 controls received liver biopsy. The frequency and cytokine production of MAIT cells were analysed by flow cytometry. The expression of genes involved in glucose metabolism was determined in HepG2 cells co‐cultured with hepatic MAIT cells. Results: Compared with controls, hepatic MAIT cell frequency was significantly increased in T2DM patients (24.66% vs. 14.61%, p = 0.001). There were more MAIT cells producing interferon‐γ (IFN‐γ, 60.49% vs. 33.33%, p = 0.021) and tumour necrosis factor‐α (TNF‐α, 46.84% vs. 5.91%, p = 0.021) in T2DM than in controls, whereas their production of interleukin 17 (IL‐17) was comparable (15.25% vs. 4.55%, p = 0.054). Notably, an IFN‐γ+TNF‐α+IL‐17+/−producing MAIT cell subset was focussed, which showed an elevated proportion in T2DM (42.66% vs. 5.85%, p = 0.021) and positively correlated with plasma glucose levels. A co‐culture experiment further indicated that hepatic MAIT cells from T2DM upregulated the gene expression of pyruvate carboxylase, a key molecule involved in gluconeogenesis, in HepG2 cells, and this response was blocked with neutralising antibodies against IFN‐γ and TNF‐α. Conclusions: Our data implicate an increased Th1‐like MAIT cell subset in the liver of newly diagnosed T2DM subjects, which induces hyperglycaemia by promoting hepatic gluconeogenesis. It provides novel insights into the immune regulation of metabolic homoeostasis. Clinical trial registration number: NCT03296605 (registered at www.clinicaltrials.gov on 12 October 2018). [ABSTRACT FROM AUTHOR]

Diabetic retinopathy, phase III study, randomized trial, type 2 diabetes Keywords: diabetic retinopathy; phase III study; randomized trial; type 2 diabetes EN diabetic retinopathy phase III study randomized trial type 2 diabetes 894 898 5 02/03/23 20230301 NES 230301 BACKGROUND/CONTEXT Diabetic retinopathy (DR) and chronic kidney disease (CKD) are two major forms of microvascular complications in patients with type 1 diabetes and type 2 diabetes (T2D), with shared risk factors (such as poor glycaemic control, smoking, hypertension and dyslipidaemia) and clinical manifestations (microvascular lesions).[1] The steroid hormone aldosterone, which binds to mineralocorticoid receptors, promotes vascular pathology in the retina relevant to the development of DR[2]; antagonism of the retinal mineralocorticoid receptor-aldosterone system may delay progression.[3] Finerenone, a potent and selective, orally administered, non-steroidal mineralocorticoid receptor antagonist (MRA), slowed progression of CKD and reduced the risk of cardiovascular outcomes versus placebo in patients with CKD and T2D in the FIDELIO-DKD (NCT02540993; n = 5674) and FIGARO-DKD (NCT02545049; n = 7352) randomized phase 3 trials.[[4]] In total, 2657 (46.8%) patients in FIDELIO-DKD and 2265 (30.8%) in FIGARO-DKD had DR at baseline.[[6]] No further details on DR were collected in these studies. Effect of finerenone on the occurrence of vision-threatening complications in patients with non-proliferative diabetic retinopathy: Pooled analysis of two studies using routine ophthalmological examinations from clinical trial participants (ReFineDR/DeFineDR) Diabetic retinopathy is a prognostic factor for progression of chronic kidney disease in the patients with type 2 diabetes mellitus. [Extracted from the article]

Aims/Introduction: To explore whether carotid atherosclerosis is an independent risk factor for small fiber nerve dysfunction in type 2 diabetes mellitus patients. Materials and Methods: A total of 247 type 2 diabetes patients from Nanjing Drum Tower Hospital received carotid ultrasonography and quantitative sensory testing, including cold and warm detection thresholds, and some patients received cold and heat pain detection thresholds, respectively. According to the results of quantitative sensory testing, patients were divided into normal small fiber nerve function (NSF) and small fiber nerve dysfunction (SFD) group. Meanwhile, patients were divided into the non‐carotid atherosclerosis group, carotid intimal thickening, unilateral carotid atherosclerosis and bilateral carotid atherosclerosis group. The correlation between carotid ultrasonography with quantitative sensory testing parameters was analyzed by SPSS 26.0. Results: First, the incidence rate of SFD increased significantly in patients with carotid atherosclerosis (72.2%, P < 0.001) especially in bilateral carotid atherosclerosis (81.7%, P < 0.001). Second, compared with the NS group, the carotid intima‐media thickness in SFD was thicker (P = 0.018) and the size of atherosclerotic plaque was larger (P < 0.001). In addition, the cold detection threshold decreased (P < 0.001), whereas the warm detection threshold (P < 0.001) and heat pain detection threshold (P < 0.001) increased as aggravation of carotid atherosclerosis. In the correlation analysis, the size of atherosclerotic plaque presented a positive correlation with the warm detection threshold (r = 0.476, P < 0.001) and heat pain detection threshold (r = 0.213, P < 0.001), but presented a negative correlation with the cold detection threshold (r = −0.239, P < 0.01). Furthermore, carotid atherosclerosis (odds ratio 2.326, P = 0.017), especially bilateral carotid atherosclerosis (odds ratio 5.042, P = 0.001), was an independent risk factor for SFD (P < 0.05). Conclusions: Carotid atherosclerosis was significantly associated with quantitative sensory testing and found to be an independent risk factor for small fiber nerve dysfunction in type 2 diabetes patients. [ABSTRACT FROM AUTHOR]

Aims: To investigate whether peripheral neuropathy scale scores are associated with myocardial infarction (MI) in patients with type 2 diabetes mellitus (T2DM).Materials and Methods: In this cross-sectional study, 32,463 T2DM patients were enroled from 103 tertiary hospitals in 25 Chinese provinces. Based on a history of MI, participants were divided into the MI group (n = 4170) and the non-MI group (n = 28,293). All patients were assessed using four neuropathy scales, namely, Neurological Symptom Score (NSS), Neurological Disability Score (NDS), Toronto Clinical Scoring System (TCSS), and Michigan Neuropathy Screening Instrument (MNSI), and some of the patients underwent evaluation of nerve conduction velocity (NCV) (n = 20,288). The relationship between these scores and myocardial infraction was analysed.Results: The neuropathy scale scores in the MI group were higher than those in the non-MI group (p < 0.001). After dividing patients into four groups based on the grading criteria, our results showed that, in addition to aggravating the degree of neuropathy signs, the incidence of MI increased (p < 0.001). Logistic regression analysis results showed that neuropathy scale scores and NCV were both independent risk factors for MI (p < 0.001). Furthermore, among the scales used, MNSI presented a higher odds ratio and area under the curve (AUC; 0.625, p < 0.001) than the other three scales (AUCNSS  = 0.575, AUCNDS  = 0.606, and AUCTCSS  = 0.602, p < 0.001) for MI.Conclusions: Increased scores on these neuropathy scales (NSS, NDS, TCSS, and MNSI) and NCV were significantly associated with increased risk of MI and were considered independent risk factors. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the immunogenicity of LY2963016 insulin glargine (LY IGlar) versus originator insulin glargine (IGlar [Lantus®]) in Chinese patients with type 1 (T1DM) or type 2 diabetes mellitus (T2DM). Materials and Methods: ABES and ABET were prospective, randomized, active control, open‐label, phase III studies, which enrolled Chinese patients with T1DM (N = 272) and T2DM (N = 536), respectively. Using data from these trials, immunogenicity of LY IGlar and IGlar was evaluated by comparing the proportion of patients with detectable anti‐insulin glargine antibodies and the median antibody levels (percent binding) between the treatment groups. The incidence of anti‐insulin antibodies and treatment‐emergent antibody response (TEAR) were compared using Fisher's exact test or Pearson's chi‐squared test. Levels of anti‐insulin antibodies were compared using the Wilcoxon rank‐sum test. We also evaluated the relationship between antibody formation or TEAR and clinical outcomes using analysis of covariance, negative binomial regression, or partial correlations. Results: There were no significant treatment differences in the incidence of detectable anti‐insulin antibodies, median antibody levels or TEAR, overall or at Week 24 with last observation carried forward, and median antibody levels were low (<5%) after 24 weeks of treatment, in patients with T1DM or T2DM. Levels of anti‐insulin antibodies and development of TEAR were not associated with efficacy (glycated haemoglobin, insulin dose [U/kg/d] and hypoglycaemia) or safety outcomes. Conclusions: The immunogenicity profiles of LY IGlar and IGlar are similar, with low levels of anti‐insulin antibodies observed for both insulins. No association was observed between antibody levels or TEAR status and clinical outcomes. [ABSTRACT FROM AUTHOR]

Aim: To investigate the diagnostic utility of corneal confocal microscopy (CCM) for small fiber neuropathy in type 2 diabetes. Materials and Methods: There were 186 participants with type 2 diabetes enrolled in this cross‐sectional research. Pure small fiber neuropathy and mixed fiber neuropathy were defined using clinical examination, electromyography, and quantitative sensory testing. Demographics and clinical data, corneal confocal microscopy parameters, and other neuropathy measures were compared among the groups. The diagnostic utility of corneal confocal microscopy for small fiber neuropathy was assessed by the receiver operating curve. Results: Of the 186 patients, 24.7% had a pure small fiber neuropathy and 17.2% of patients were diagnosed with mixed fiber neuropathy. The corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), and corneal nerve fiber length (CNFL) were significantly lower in subjects with pure small fiber neuropathy compared with those without diabetic peripheral neuropathy (all P < 0.05). The receiver operating curve analysis for corneal confocal microscopy diagnosing small fiber neuropathy demonstrated the area under the curve for CNFD of 0.791, CNFL of 0.778, CNBD of 0.710. Conclusions: Patients with type 2 diabetes with pure small fiber neuropathy showed more corneal nerve loss compared with those without diabetic peripheral neuropathy. It was revealed that corneal confocal microscopy can be a reasonable marker in the diagnosis of small fiber neuropathy in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: Cardiovascular autonomic neuropathy (CAN) is one of the most serious types of diabetic autonomic neuropathy and is a class of small fibre neuropathy. Among many inspection methods, quantitative sensory testing is an effective and convenient method for diagnosing diabetic small fibre neuropathy. This cross-sectional study aimed to identify the correlation between the development of cardiovascular autonomic neuropathy and quantitative sensory testing parameters in patients with type 2 diabetes mellitus. Methods: A total of 266 participants with type 2 diabetes mellitus from Nanjing Drum Tower Hospital were enrolled in this study, and each of them received cardiovascular reflex tests (CARTs) and quantitative sensory testing, including testing of cold, warm, cold pain, and heat pain detection thresholds (CDT, WDT, CPT, and HPT, respectively). The results of CARTs were compared with the thermal detection thresholds in quantitative sensory testing by using SPSS 26.0. Results: A total of 266 participants were divided into the CAN group, early CAN (ECAN) group, and without CAN (NCAN) group. There were significant differences in quantitative sensory testing parameters among three groups, and CARTs presented a positive correlation with the WDT and HPT and a negative correlation with the CDT. Moreover, after adjusting for age, sex, diabetes duration, and other influencing factors, WDT, HPT, and CDT were independent risk factors for cardiovascular autonomic neuropathy. Conclusions: The thermal detection thresholds, including cold, warm, and heat pain detection thresholds, in quantitative sensory testing were found to be significantly related to the results of CARTs. Some thermal detection thresholds were independent risk factors for cardiovascular autonomic neuropathy. Therefore, this study showed that quantitative sensory testing has a reliable predictive ability for the occurrence and development of cardiovascular autonomic neuropathy. [ABSTRACT FROM AUTHOR]

Introduction: The clinical characteristics and outcomes of small fiber neuropathy (SFN) in Chinese patients with type 2 diabetes mellitus (T2DM) have not been thoroughly described. In this study, we investigated the metabolic and neurological indexes and the prognosis of patients with T2DM based on skin biopsy. Methods: A total of 34 healthy Chinese volunteers were recruited for skin biopsy to establish the reference range of intra-epidermal nerve fiber density (IENFD), and 89 patients with T2DM attending the Nanjing Drum Tower Hospital were evaluated at baseline. Of these 89 patients, 17 with pure SFN and nine with mixed diabetic polyneuropathy (DPN) were reassessed at the end of the follow-up. Results: Glycated hemoglobin and postprandial blood glucose levels were lower (P = 0.005 and P = 0.041, respectively) and postprandial C-peptide and insulin levels were higher (P = 0.001 and P = 0.019, respectively) in the pure SFN group than in the mixed DPN group. A partial correlation study showed that there was a negative correlation between IENFD of the distal leg and cardiovascular autonomic reflex test (CART) scores (r = − 0.513, P = 0.001) after adjusting for age and duration of diabetes. Only vitamin B12 level (P = 0.028) and motor nerve conduction velocity (MCV) of the common peroneal nerve (P = 0.045) were increased in the patients with pure SFN at the final visit while MCVs of the common peroneal nerve (P = 0.025) and tibial nerve (P = 0.047) were decreased in the mixed DPN group at the final visit. Conclusion: Better islet function and cardiovascular autonomic function were observed in patients with pure SFN compared with mixed DPN. The metabolic and neurological indexes remained relatively stable in the patients with pure SFN during the follow-up. [ABSTRACT FROM AUTHOR]

Aim: To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) with insulin glargine (Lantus; IGlar) combined with oral antihyperglycaemic medications (OAMs) in insulin‐naive Chinese patients with type 2 diabetes (T2D). Materials and Methods: In this phase III, open‐label trial, adult patients with T2D receiving two or more OAMs at stable doses for 12 weeks or longer, with HbA1c of 7.0% or more and 11.0% or less, were randomized (2:1) to receive once‐daily LY IGlar or IGlar for 24 weeks. The primary outcome was non‐inferiority of LY IGlar to IGlar at a 0.4% margin, and a gated secondary endpoint tested non‐inferiority of IGlar to LY IGlar (−0.4% margin), assessed by least squares (LS) mean change in HbA1c from baseline to 24 weeks. Results: Patients assigned to LY IGlar (n = 359) and IGlar (n = 177) achieved similar and significant reductions (p <.001) in HbA1c from baseline. LY IGlar was non‐inferior to IGlar for change in HbA1c from baseline to week 24 (−1.27% vs. −1.23%; LS mean difference: −0.05% [95% CI, −0.19% to 0.10%]) and IGlar was non‐inferior to LY IGlar. The study therefore showed equivalence of LY IGlar and IGlar for the primary endpoint. At week 24, there were no between‐group differences in the proportion of patients achieving an HbA1c of less than 7.0%, seven‐point self‐measured blood glucose, insulin dose or weight gain. Adverse events, allergic reactions, hypoglycaemia and insulin antibodies were similar in the two groups. Conclusions: Once‐daily LY IGlar and IGlar, combined with OAMs, provide effective and similar glycaemic control with comparable safety profiles in insulin‐naive Chinese patients with T2D. [ABSTRACT FROM AUTHOR]

Background and objective: Clinical characteristics of obesity are heterogenous, but current classification for diagnosis is simply based on BMI or metabolic healthiness. The purpose of this study was to use machine learning to explore a more precise classification of obesity subgroups towards informing individualized therapy. Subjects and Methods: In a multi-center study (n=2495), we used unsupervised machine learning to cluster patients with obesity from Shanghai Tenth People's hospital (n=882, main cohort) based on three clinical variables (AUCs of glucose and of insulin during OGTT, and uric acid). Verification of the clustering was performed in three independent cohorts from external hospitals in China (n = 130, 137, and 289, respectively). Statistics of a healthy normal-weight cohort (n=1057) were measured as controls. Results: Machine learning revealed four stable metabolic different obese clusters on each cohort. Metabolic healthy obesity (MHO, 44% patients) was characterized by a relatively healthy-metabolic status with lowest incidents of comorbidities. Hypermetabolic obesity-hyperuricemia (HMO-U, 33% patients) was characterized by extremely high uric acid and a large increased incidence of hyperuricemia (adjusted odds ratio [AOR] 73.67 to MHO, 95%CI 35.46-153.06). Hypermetabolic obesity-hyperinsulinemia (HMO-I, 8% patients) was distinguished by overcompensated insulin secretion and a large increased incidence of polycystic ovary syndrome (AOR 14.44 to MHO, 95%CI 1.75-118.99). Hypometabolic obesity (LMO, 15% patients) was characterized by extremely high glucose, decompensated insulin secretion, and the worst glucolipid metabolism (diabetes: AOR 105.85 to MHO, 95%CI 42.00-266.74; metabolic syndrome: AOR 13.50 to MHO, 95%CI 7.34-24.83). The assignment of patients in the verification cohorts to the main model showed a mean accuracy of 0.941 in all clusters. Conclusion: Machine learning automatically identified four subtypes of obesity in terms of clinical characteristics on four independent patient cohorts. This proof-of-concept study provided evidence that precise diagnosis of obesity is feasible to potentially guide therapeutic planning and decisions for different subtypes of obesity. Clinical Trial Registration: www.ClinicalTrials.gov , NCT04282837. [ABSTRACT FROM AUTHOR]

Aim: Few studies have investigated the associations between diabetic peripheral neuropathy (DPN) and cognitive decline. Olfactory impairment is related to neurodegenerative diseases and type 2 diabetes mellitus (T2DM); however, the cognitive alterations of patients with DPN and the role of olfactory function in DPN are not known. We explored alterations in cognition with DPN and the associations of neuropathy parameters with cognition and olfaction. Methods: Healthy controls (HCs) and patients with T2DM underwent nerve-conduction tests, detailed cognitive assessment, olfactory-behavior tests, and odor-induced functional magnetic resonance imaging (fMRI). T2DM patients were divided into two groups (non-DPN [NDPN] and DPN). Olfactory brain regions showing different activation between the two groups were selected for functional connectivity (FC) analyses. A structural equation model (SEM) was also generated to demonstrate the association among cognition, olfactory, and neuropathy parameters. Results: One hundred individuals (36 HCs, 36 NDPN, and 28 DPN) were matched for age, sex, and educational level. Compared with the NDPN group, the DPN group had significantly lower scores for memory and processing speed, as well as lower olfactory identification and memory scores, decreased activation of the left frontal lobe, and reduced seed-based functional connectivity in the right insula. The nerve conduction velocity in patients with T2DM was associated with cognitive functions. The association between nerve conduction and executive function was mediated by olfactory behavior. Conclusion: Patients with DPN had worse cognition than the NDPN patients in the domains of memory and processing speed. Cognitive dysfunction could be predicted by olfactory-behavior tests and electrophysiological examination. [ABSTRACT FROM AUTHOR]

Objective: Morphological alterations including adipocyte hypertrophy and fibrosis deposition are important surrogate markers of visceral adipose tissue function, but the relationships between these morphological changes and type 2 diabetes mellitus (T2DM) and impaired insulin sensitivity are poorly defined.Methods: Omental adipose tissue was obtained from 66 individuals with obesity but without T2DM (OB group), 93 individuals with both obesity and T2DM (T2DM group), and 15 individuals with normal BMI and normal glucose tolerance (NGT group). Adipocyte diameter and volume were measured through pathological section analysis. Pericellular and perilobular fibrosis was determined through picrosirius red staining and immunochemistry, while fibrosis-related genes were tested through gene expression and hydroxyproline content.Results: Compared with the NGT and OB groups, individuals from the T2DM group displayed increased adipocyte diameter and volume levels. Increased adipocyte size (diameter and volume) was positively associated with hyperglycemia and insulin resistance and inversely correlated with insulin sensitivity (using the Matsuda whole-body insulin sensitivity index assessment of insulin sensitivity) and β-cell function (disposition index 30 and disposition index 120). The fibrosis levels of the OB group were the highest out of the three groups, whereas the fibrosis levels of T2DM individuals were lower than the OB group but higher than the NGT group. Although fibrosis was negatively correlated with T2DM, fibrosis deposition was not remarkably associated with impaired systemic insulin sensitivity and glucose metabolism.Conclusions: Compared with fibrosis deposition, adipocyte hypertrophy is more closely associated with T2DM and impaired systemic insulin sensitivity. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes mellitus (T2DM) are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD), which are important causes of disabling and death in patients with T2DM. For the prevention and management of ASCVD or CKD, cardiovascular risk factors should be systematically evaluated, and ASCVD and CKD should be screened in patients with T2DM. In this consensus, we recommended that metformin should be used as the first‐line therapy for patients with T2DM and ASCVD or very high cardiovascular risk, heart failure (HF) or CKD, and should be retained in the treatment regimen unless contraindicated or not tolerated. In patients with T2DM and established ASCVD or very high cardiovascular risk, addition of a glucagon‐like peptide 1 receptor agonist (GLP‐1RA) or sodium–glucose cotransporter type 2 (SGLT2) inhibitor with proven cardiovascular benefits should be considered independent of individualised glycated haemoglobin (HbA1C) targets. In patients with T2DM and HF, an SGLT2 inhibitor should be preferably added regardless of HbA1C levels. In patients with T2DM and CKD, SGLT2 inhibitors should be preferred for the combination therapy independent of individualised HbA1C targets, and GLP‐1RAs with proven renal benefits would be alternative if SGLT2 inhibitors are contraindicated. Moreover, the prevention of hypoglycaemia and management of multiple risk factors by comprehensive regimen, including lifestyle intervention, antihypertensive therapies, lipid‐lowering treatment and antiplatelet therapies, should be kept in mind in treating patients with T2DM and ASCVD, HF or CKD. [ABSTRACT FROM AUTHOR]

Aims. Epidemiological data on diabetic retinopathy (DR) in Chinese population is still rather scarce, and risk factors for diabetic retinopathy are inconsistent because of study designs, grading standards, and population samples. Materials and Methods. This hospital-based retrospective study included 1052 type 2 diabetes patients. Diabetic retinopathy was diagnosed by nonmydriatic fundus photography and/or fundus examination apparatus. Logistic regression analysis was performed to evaluate the risk of diabetic retinopathy. Results. A total of 352 (33.5% prevalence) subjects were diagnosed with diabetic retinopathy based on our population. The patients in the DR group not only had significantly higher hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), urinary microalbumin-creatinine ratio (ACR), and systolic blood pressure but also had higher follicle-stimulating hormone (FSH), luteinizing hormone (LH), and sex hormone-binding globulin (SHBG) levels compared to those in the non-DR group. Moreover, we confirmed that diabetes duration and HbA1c are strongly associated with DR risk. We also found that serum LH was an independent risk factor in male diabetic retinopathy patients (OR = 1.086 , 95% CI 1.024–1.152), and the levels of LH were significantly associated with diabetic retinopathy prevalence (P = 0.018). Conclusions. Our study strengthens the argument that diabetes duration and HbA1c are risk factors for patients with DR. Additionally; we firstly confirmed that serum LH was an independent risk factor in male diabetic retinopathy patients. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In this post hoc analysis of the randomized controlled LixiLan‐O trial in insulin‐naive patients with type 2 diabetes mellitus (T2DM) not controlled with metformin, with or without a second oral antihyperglycaemic drug (OAD), the efficacy and safety of the fixed‐ratio combination, iGlarLixi (insulin glargine 100 U [iGlar] and lixisenatide [Lixi]), compared to its individual components was assessed in two patient subgroups: group 1) baseline HbA1c ≥9% (n = 134); group 2) inadequate control (HbA1c ≥7.0% and ≤9.0%) despite administration of two OADs at screening (n = 725). Treatment with iGlarLixi resulted in significantly greater reduction in least squares mean HbA1c compared to treatment with iGlar or Lixi alone in both subgroups (group 1: 2.9%, 2.5%, 1.7% and group 2: 1.5%, 1.2%, 0.7%, respectively). Target HbA1c less than 7% was achieved in more than 70% of patients using iGlarLixi in both subgroups, while mitigating the weight gain observed with use of iGlar alone. Rates of hypoglycaemic events were low overall. These results suggest that treatment with iGlarLixi achieves superior glycaemic control compared to treatment with iGlar or Lixi alone in T2DM patients with HbA1c ≥9% or in those inadequately controlled with two OADs. [ABSTRACT FROM AUTHOR]

Objective: Large numbers of people with type 2 diabetes are obese. However, changes in cognition and related brain function in obese people with diabetes have not been characterized. Here, we investigated cognition, olfactory function, and odor-induced brain alterations in these patients and therapeutic effects of glucagon-like peptide 1 receptor agonists (GLP-1Ras) on their psychological behavior and olfactory networks.Research Design and Methods: Cognitive, olfactory, and odor-induced brain activation assessments were administered to 35 obese and 35 nonobese people with type 2 diabetes and 35 control subjects matched for age, sex, and education. Among them, 20 obese individuals with diabetes with inadequate glycemic control and metformin monotherapy received GLP-1Ra treatment for 3 months and were reassessed for metabolic, cognitive, olfactory, and neuroimaging changes.Results: Obese subjects with diabetes demonstrated lower general cognition and olfactory threshold scores, decreased left hippocampal activation, and disrupted seed-based functional connectivity with right insula compared with nonobese subjects with diabetes. Negative associations were found between adiposity and episodic memory and between fasting insulin and processing speed test time in diabetes. Mediation analyses showed that olfactory function and left hippocampus activation mediated these correlations. With 3-month GLP-1Ra treatment, obese subjects with diabetes exhibited improved Montreal Cognitive Assessment (MoCA) score, olfactory test total score, and enhanced odor-induced right parahippocampus activation.Conclusions: Obese subjects with type 2 diabetes showed impaired cognition and dysfunctional olfaction and brain networks, the latter of which mediated adiposity in cognitive impairment of diabetes. GLP-1Ras ameliorated cognitive and olfactory abnormalities in obese subjects with diabetes, providing new perspectives for early diagnosis and therapeutic approaches for cognitive decrements in these patients. [ABSTRACT FROM AUTHOR]

Aims: To compare the efficacy and safety of saxagliptin and glimepiride in type 2 diabetes (T2D) patients who are inadequately controlled with metformin monotherapy. Materials and methods: In this 48‐week, multi‐centre, open‐label, randomized, parallel trial (NCT02280486, clinicaltrials.gov), a total of 388 T2D patients were randomized 1:1 to saxagliptin or glimepiride groups. The primary endpoint was achievement of HbA1c <7.0%, without hypoglycaemia, defined as blood glucose <3.9 mmol/L and weight gain <3.0% after 48 weeks of treatment. Results: Over 48 weeks, a greater proportion of patients achieved the primary endpoint with saxagliptin compared with glimepiride (43.3% vs 31.3%; odds ratio, 1.38, 95% CI, 1.05‐1.82; P = 0.019), especially among patients with baseline HbA1c <8.0%, duration <5 years or baseline BMI ≥25 kg/m2. Mean reduction in HbA1c was similar in the two treatment groups at Week 48 (−0.94% with saxagliptin vs −0.98% with glimepiride; P = 0.439). Bodyweight decreased with saxagliptin, but increased with glimepiride over the treatment period, and the treatment difference was −1.6 kg (P < 0.001) at Week 48. The proportion of patients experiencing hypoglycaemia was much lower with saxagliptin vs glimepiride (3.1% vs 12.8%; P < 0.001). Conclusions: This study provides evidence that, compared to glimepiride, saxagliptin more effectively achieves a composite endpoint of adequate glycaemic control without hypoglycaemia and without weight gain in T2D patients who are inadequately controlled with metformin monotherapy, especially in overweight patients with moderate hyperglycaemia and a relatively short duration of diabetes. [ABSTRACT FROM AUTHOR]

Aims: To investigate the prevalence of adult‐onset autoimmune diabetes (ADM) and predisposition to autoimmune diseases by quantifying serum organ‐specific autoantibodies in people with phenotype of type 2 diabetes (T2D). Materials and methods: We included a nationally representative sample of 46 239 adults aged ≥20 years from 14 provinces, of whom 4671 had diabetes, plus 1000 control subjects with normal glucose tolerance (NGT). Participants were screened centrally for autoantibodies to glutamic acid decarboxylase (GAD), islet antigen 2 (IA2) and zinc transporter isoform‐8 (Znt8) and were defined as having ADM where positive for these antibodies. We then assayed thyroid peroxidase (TPO), tissue transglutaminase (tTG) and 21‐hydroxylase (21‐OH) autoantibodies in randomly selected participants with ADM and in age‐matched, sex‐matched and non‐ADM controls with T2D plus controls with NGT. Results: Post‐normalization, the standardized prevalence rate of ADM was 6.0% (95% confidence interval [CI] 5.3‐6.8) in initially non‐insulin‐requiring participants with ADM, corresponding to six million adults in China, in whom adjusted antibody positivity was: TPO autoantibodies 16.3% (95% CI 10.8‐21.8), tTG autoantibodies 2.1% (95% CI 0.0‐4.2), and 21‐OH autoantibodies 1.8% (95% CI ‐0.2 to 3.8). Those participants with ADM who were GAD autoantibody‐positive had high risk of TPO autoantibody positivity (odds ratio [OR] 2.39, P = 0.0031) and tTG autoantibody positivity (OR 6.98, P = 0.027), while those positive for IA2 autoantibodies had a high risk of tTG autoantibody positivity (OR 19.05, P = 0.001). Conclusions: A proportion of people with phenotype of T2D in China have ADM, with diabetes‐associated autoantibodies, and may be at risk of developing other organ‐specific autoimmune diseases; therefore, it may be clinically relevant to consider screening such Chinese populations. [ABSTRACT FROM AUTHOR]

Aims/Introduction: To investigate the direct medical costs for patients with type 2 diabetes in China and to examine the influencing factors. Materials and Methods: In the present multicenter study, 1,070 patients with type 2 diabetes from 16 tertiary hospitals in 14 major cities of China were enrolled. Patient data and direct medical costs were collected during a follow‐up period of 6 months at intervals of 1 month. The log‐transformed direct medical costs were fitted by a generalized estimation equation to indicator variables for demographics, metabolic control, treatments, complications and comorbidities. Results: Data of 871 participants were included in the analysis. The mean annual total direct medical costs and outpatient medical costs were $1,990.20 and $1,687.20 respectively. The average costs per inpatient per admission were $2,127.10. The share of out‐of‐pocket for total medical costs, outpatient costs and cost per inpatient per admission were 45.4, 46.3 and 26.0% respectively. Independent determinants of total medical costs were diabetes duration, dyslipidemia and diabetic complications, such as neuropathy and nephropathy, as well as diabetes treatment, such as the use of glucagon‐like peptide‐1 receptor agonists. Costs showed prominent variation across centers. Conclusions: Diabetes is imposing a growing economic burden in patients with type 2 diabetes in China. Diabetes‐related complications and comorbidities have a great impact on the medical costs. As different health policies, economic development and regional health inequalities also have an important influence on the direct medical cost, healthcare reform needs to optimize resource allocation in health service delivery systems, and provide more equitable and affordable healthcare. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Type 2 diabetes mellitus is frequently accompanied by fatty liver disease. Lipid accumulation within the liver is considered as one of the risk factors for insulin resistance. Hepatocyte growth factor (HGF) is used to treat liver dysfunction; however, the effect and mechanism of HGF on hepatic lipid metabolism are still not fully understood. Materials and Methods: Male C57BL/6 mice were induced with a high‐fat diet for 12 weeks, followed by a 4‐week treatment of HGF or vehicle saline. The levels of fasting blood glucose, fasting insulin and homeostatic model assessment of insulin resistance were calculated for insulin sensitivity. Biochemical plasma parameters were also measured to assess the effect of HGF on lipid accumulation. Additionally, genes in the lipid metabolism pathway were evaluated in palmitic acid‐treated HepG2 cells and high‐fat diet mice. Results: HGF treatment significantly decreased the levels of fasting blood glucose, hepatic triglyceride and cholesterol contents. Additionally, HGF‐regulated expression levels of sterol regulatory element‐binding protein‐1c/fatty acid synthase, peroxidase proliferator‐activated receptor‐α, and upstream nuclear receptors, such as farnesoid X receptor and small heterodimer partner. Furthermore, c‐Met inhibitor could partially reverse the effects of HGF. Conclusions: HGF treatment can ameliorate hepatic insulin resistance and steatosis through regulation of lipid metabolism. These effects might occur through farnesoid X receptor–small heterodimer partner axis‐dependent transcriptional activity. HGF reduced the levels of fasting blood glucose, blood lipid level, and improved the HFD‐fed mice. HGF significantly regulated lipogenesis‐related genes SREBP‐1c/FAS as well as PPARα, and nuclear receptors such as FXR, SHP. HGF ameliorates hyperglycemia and by improving hepatic insulin resistance and steatosis in HFD‐fed C57BL/6 mice. [ABSTRACT FROM AUTHOR]

Type 2 diabetes is reported to be associated with olfactory dysfunction and cognitive decline. However, whether and how olfactory neural circuit abnormalities involve cognitive impairment in diabetes remains uncovered. This study thus aimed to investigate olfactory network alterations and the associations of odor-induced brain activity with cognitive and metabolic parameters in type 2 diabetes. Participants with normal cognition, including 51 patients with type 2 diabetes and 41 control subjects without diabetes, underwent detailed cognitive assessment, olfactory behavior tests, and odor-induced functional MRI measurements. Olfactory brain regions showing significantly different activation between the two groups were selected for functional connectivity analysis. Compared with the control subjects, patients with diabetes demonstrated significantly lower olfactory threshold score, decreased brain activation, and disrupted functional connectivity in the olfactory network. Positive associations of the disrupted functional connectivity with decreased neuropsychology test scores and reduced pancreatic function were observed in patients with diabetes. Notably, the association between pancreatic function and executive function was mediated by olfactory behavior and olfactory functional connectivity. Our results suggested the alteration of olfactory network is present before clinically measurable cognitive decrements in type 2 diabetes, bridging the gap between the central olfactory system and cognitive decline in diabetes. [ABSTRACT FROM AUTHOR]

Summary Objective To investigate exenatide, a GLP-1 analogue, compared with acarbose, for intra-abdominal fat reduction in patients with obesity and type-2 diabetes. Methods This randomized controlled trial included 36 patients with obesity and type-2 diabetes, who were metformin-unresponsive, receiving metformin/exenatide (GLP-1 group) or metformin/acarbose (control group) for 3 months. Primary end-point: intra-abdominal fat content from baseline to 3 months; Secondary end-points: changes in fasting blood glucose, glycated haemoglobin (HbAlc), fasting insulin, blood lipids, weight, body mass index, and inflammatory cytokines from baseline to 3 months. Results Intra-abdominal fat content decreased in the GLP-1 group from baseline to 3 months (17,947 ± 5804; 13,717 ± 3628 mm 2 , P = 0.001, respectively), but was not significantly reduced in the control group (P = 0.197) and at 3 months post-treatment, it was significantly lower in the GLP-1 group than control group (P = 0.043). Glucose control, measured by HbA1c (GLP-1: 9.72 ± 1.38; 7.09 ± 0.60%, P < 0.001, 9.46 ± 1.25; 7.42 ± 0.84%, P < 0.001, respectively) and insulin resistance index LN(HOMA-IR) (GLP-1: 1.58 ± 0.40; 1.01 ± 0.33, P < 0.001, Control: 1.53 ± 0.57; 1.10 ± 0.33, P = 0.003, respectively) significantly improved in both groups with no significant difference between them. TNF-α, IL-6, and leptin were lower and adiponectin levels higher in the GLP-1 group at 3 months compared with baseline (all P < 0.05), but not significantly changed in the control group. TNF-α, IL-6 and leptin levels were similar between groups. Adiponectin level was higher in the GLP-1 group than the control group at 3 months (P = 0.025). Conclusion Combined exenatide/metformin reduced intra-abdominal fat content, and enhanced insulin resistance and inflammatory status in patients with obesity and type-2 diabetes, representing a novel treatment regimen. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Correction to: Diabetes Ther https://doi.org/10.1007/s13300-021-01185-w In the original publication, there is an error in discussion section "The "CD14 SP + sp KDR SP + sp CD133 SP + sp EPCs" will be corrected as "CD34 SP + sp KDR SP + sp CD133 SP + sp EPCs"". The original article can be found online at https://doi.org/10.1007/s13300-021-01185-w. [Extracted from the article]

Background and Aims: Obesity is a well-known risk factor for type 2 diabetes. Genome-wide association studies have identified a number of genetic loci associated with obesity. The aim of this study is to examine the contribution of obesity-related genomic loci to type 2 diabetes in a Chinese population. Methods: We successfully genotyped 18 obesity-related single nucleotide polymorphisms among 5338 type 2 diabetic patients and 4663 controls. Both individual and joint effects of these single nucleotide polymorphisms on type 2 diabetes and quantitative glycemic traits (assessing β-cell function and insulin resistance) were analyzed using logistic and linear regression models, respectively. Results: Two single nucleotide polymorphisms near MC4R and GNPDA2 genes were significantly associated with type 2 diabetes before adjusting for body mass index and waist circumference (OR (95% CI) = 1.14 (1.06, 1.22) for the A allele of rs12970134, P = 4.75×10−4; OR (95% CI) = 1.10 (1.03, 1.17) for the G allele of rs10938397, P = 4.54×10−3). When body mass index and waist circumference were further adjusted, the association of MC4R with type 2 diabetes remained significant (P = 1.81×10−2) and that of GNPDA2 was attenuated (P = 1.26×10−1), suggesting the effect of the locus including GNPDA2 on type 2 diabetes may be mediated through obesity. Single nucleotide polymorphism rs2260000 within BAT2 was significantly associated with type 2 diabetes after adjusting for body mass index and waist circumference (P = 1.04×10−2). In addition, four single nucleotide polymorphisms (near or within SEC16B, BDNF, MAF and PRL genes) showed significant associations with quantitative glycemic traits in controls even after adjusting for body mass index and waist circumference (all P values<0.05). Conclusions: This study indicates that obesity-related genomic loci were associated with type 2 diabetes and glycemic traits in the Han Chinese population. [ABSTRACT FROM AUTHOR]

Background: Though multiple single nucleotide polymorphisms (SNPs) associated with type 2 diabetes have been identified, the genetic bases of isolated fasting hyperglycaemia (IFH) and isolated postprandial hyperglycaemia (IPH) were still unclear. In present study, we aimed to investigate the association of genome-wide association study-validated genetic variants and IFH or IPH in Han Chinese. Methods/Principal Findings: We genotyped 27 validated SNPs in 6,663 unrelated individuals comprising 341 IFH, 865 IPH, 1,203 combined fasting hyperglycaemia and postprandial hyperglycaemia, and 4,254 normal glycaemic subjects of Han ancestry. The distributions of genotype frequencies of FTO, CDKAL1 and GCKR were significant different between individuals with IFH and those with IPH (SNP(ptrend): rs8050136(0.0024), rs9939609(0.0049), rs7756992(0.0122), rs780094(0.0037)). Risk allele of FTO specifically increased the risk of IFH (rs8050136: OR 1.403 [95% CI 1.125–1.750], p = 0.0027; rs9939609: 1.398 [1.120–1.744], p = 0.0030). G allele of CDKAL1 specifically increased the risk of IPH (1.217 [1.092–1.355], p = 0.0004). G allele of GCKR increased the risk of IFH (1.167 [0.999–1.362], p = 0.0513), but decreased the risk of IPH (0.891 [0.801–0.991], p = 0.0331). In addition, TCF7L2 and KCNQ1 increased the risk of both IFH and IPH. When combined, each additional risk allele associated with IFH increased the risk for IFH by 1.246-fold (p<0.0001), while each additional risk allele associated with IPH increased the risk for IPH by 1.190-fold (p<0.0001). Conclusion/Significance: Our results indicate that genotype distributions of variants from FTO, GCKR, CDKAL1 were different between IPH and IFH in Han Chinese. Variants of genes modulating insulin sensitivity (FTO, GCKR) contributed to the risk of IFH, while variants of genes related to beta cell function (CDKAL1) increase the risk of IPH. [ABSTRACT FROM AUTHOR]

To evaluate the role of insulin resistance and beta cell function to increasing fasting plasma glucose (FPG), 1,272 Chinese subjects (18-80 years of age) were divided into normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT), combined glucose intolerance (CGI), and type 2 diabetes mellitus (T2DM) according to oral glucose tolerance test. Insulin sensitivity was measured by Matsuda index (ISI) and homeostasis model assessment of insulin resistance (1/HOMA-IR); β-cell function adjusted by insulin sensitivity was assessed from disposition index (DI) at basal DI (homeostasis model assessment of β-cell function (HOMA-B) × [1/HOMA-IR]), early-phase DI (the ratio of total insulin AUC and total glucose AUC during 0-30 min of the OGTT (InsAUC/GluAUC) × ISI) and total DI (the ratio of total insulin AUC and total glucose AUC during 0-120 min of the OGTT (InsAUC/GluAUC) × ISI). Compared with NGT, in IFG, ISI (−23%), DI (−38%), DI (−30%), and DI (−31%) were decreased significantly. As the FPG increased across categories classified by FPG levels from NGT → IFG → T2DM with 2 h PG < 7.8 mmol/l, ISI, DI, DI and DI showed decline beginning from normal range of FPG, compared with the reference category of FPG < 4.0 mmol/l. Correlation analysis showed that ISI and DI were correlated inversely with FPG concentration ( r = −0.242 for ISI, r = −0.933 for DI, r = −0.806 for DI, r = −0.817 for DI; P < 0.001). Both the impairment of beta cell function and insulin sensitivity started at the low point of FPG within the normoglycemic range and contributed to the deterioration of fasting glucose. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hyperglycemia could accelerate monocyte chemoattractant protein 1 (MCP-1) production in monocytes and vascular endothelial cells. Recently, a genetic polymorphism (–2518 A/G) located in MCP-1 gene promoter has been found that could influence the expression of MCP-1. A large cohort study of Caucasians reported that MCP-1 G–2518 gene variant was negatively correlated with the prevalence of insulin resistance and type 2 diabetes. However, it is unclear whether this polymorphism is associated with type 2 diabetes in Han Chinese. Methods: We conducted a population-based case–control study of 416 type 2 diabetes cases and 416 controls. Results: Compared with the wild genotype AA, MCP-1 G–2518 gene variant could significantly decrease the prevalence of type 2 diabetes in Han Chinese (adjusted OR=0.49, 95% CI 0.32–0.77, P <0.0001). The results of stratified analyses indicated that a decreased risk of type 2 diabetes related with variant genotypes was evident in younger participants (age ≤50) (adjusted OR=0.35, 95% CI 0.20–0.61, P <0.0001), and similar results were observed in males (adjusted OR=0.37, 95% CI 0.21–0.66, P =0.001) and urban participants (adjusted OR=0.35, 95% CI 0.21–0.58, P <0.0001). In addition, a statistically significant difference was observed between MCP-1–2518 A/G polymorphism and waist to hip ratio. Conclusions: Our present pilot study indicated that MCP-1 G–2518 gene variant could significantly decrease the risk of type 2 diabetes in a Chinese population. [ABSTRACT FROM AUTHOR]

Objectives: The aims of the study were to determine the following: the status of glycemic control in patients with type 2 diabetes mellitus (DM) at primary, secondary, and tertiary hospitals in the Jiangsu province of China; and the factors associated with achieving glyce-mic targets. Methods: This study, in which patients were enrolled from July 20 to 31, 2009, at 56 diabetes centers, used a multiple-stage, stratified sampling method to select a representative sample of the population with DM in Jiangsu. The sampling process was stratified by geographic and demographic regions, and by the outpatient numbers in the hospitals. A primary hospital was defined as a community medical institution that provided primary health services; a secondary hospital was a local medical institution that provided comprehensive health services; and a tertiary hospital was a regional medical institution that provided comprehensive and specialist health services. In primary hospitals, patients with DM were treated by general physicians; at secondary and tertiary hospitals, they were seen by specialists. Also, primary and tertiary hospitals treated patients in cities, whereas secondary hospitals treated patients from towns or rural areas. Patients with a medical history of type 2 DM for >6 months and registration at each diabetes center for ≥6 months, and who were residents of Jiangsu province, were recruited. During the patient enrollment visit, information about DM complications and comor-bidities, as well as DM management, was obtained by retrospectively reviewing medical records; basic patient data (eg, date of birth, sex, weight, height) were obtained by patient interview. Blood samples were collected for assessment of glycosylated hemoglobin (HbA1c) at a central laboratory. Results: Of 3046 sampled subjects, the analysis was performed in 2966 subjects with complete data. The mean (SD) HbA1c value for analyzed patients was 7.2% (1.6%). The proportion of patients with tight glycemic control was 40.2% (1193/2966) when a threshold of HbA1c <6.5% was used, and 56.1% (1665/2966) when a threshold of HbA1c <7.0% was used. Compared with patients who had inadequate glycemic control, those with tight control were younger (P < 0.001), had shorter duration of DM (P < 0.001), had lower body mass index (BMI) (P = 0.005 for HbA1c <6.5% and P = 0.01 for HbA1c <7.0%), had more education (P < 0.001) and income (P = 0.003 for HbA1c <6.5% and P = 0.008 for HbA1c <7.0%), were more likely to monitor their glucose (P = NS for HbA1c <6.5% and P = 0.043 for HbA1c <7.0%) and attend DM education (P = 0.027 for HbA1c <6.5% and P = 0.002 for HbA1c <7.0%) at least once a month, and were more likely to receive oral antidiabetic drugs (OADs) (P < 0.001). Age, BMI, and DM duration did not differ significantly between hospital types. Compared with primary (36.2%) and secondary hospitals (36.5%), tertiary hospitals (42.2%) had more patients with HbA1c <6.5% (P = 0.043); tertiary hospitals also had more patients with once-monthly glucose self-monitoring (P = 0.001), patients with higher income (P < 0.001) and education (P < 0.001), and those who were more likely to use ≥2 OADs or insulin with OADs (P < 0.001). Conclusion: The overall status of glycemic control was unsatisfactory during the study period, although patients at tertiary hospitals appeared to have better control than those at primary or secondary hospitals. [Copyright &y& Elsevier]

Objective: Statins are extensively used for lowering LDL-cholesterol and reducing cardiovascular events. Recent studies have shown that statins have beneficial anti-inflammatory effects. We aimed to determine whether and how adipokines are regulated during statin treatment in type 2 diabetic patients.Method: In this study,we investigated the changes of CRP and inflammation-related adipokines (SAA,IL-6,TNFα and adiponectin) in 23 type 2 diabetic patients with atherosclerosis who received statin therapy, and 20 diabetic patients with atherosclerosis and 14 diabetic patients without atherosclerosis who did not receive statin therapy for a period of three months.Results: By the end of the simvastatin treatment (40 mg, daily), LDL-cholesterol was decreased by 16.7% and HDL-cholesterol was increased by 31.9%. SAA, CRP, TNFα and IL-6 levels were decreased by 31.8%, 66.2%, 53.9% and 14%, respectively and adiponectin was increased by 59.6%, compared with the baseline levels. Interestingly, the decrease of SAA was positively correlated with that of LDL-cholesterol but negatively with HDL-cholesterol during statin treatment. Among the adipokines, the decrease of SAA was positively correlated with TNFα (r = 0.50, p = 0.016).Conclusion: The results suggest that adipokines may be differentially regulated and independent of cholesterol changes and that adipokines may be a mediator, and the adipose tissue may be a target of statins’ anti-inflammatory effect. [ABSTRACT FROM PUBLISHER]

Aims: Diminished energy turnover of skeletal muscle is involved in the development of type 2 diabetes. Intensive insulin therapy has been reported to maintain glycaemic control in newly diagnosed type 2 diabetes, while the underlying mechanism remains unclear. Herein, we aimed to characterize the contribution of muscular mitochondrial oxidative phosphorylation (OxPhos) activity to insulin-induced glycaemic control.Materials and Methods: There were 21 drug naïve patients with type 2 diabetes receiving continuous subcutaneous insulin infusion for 7 days. Nine nondiabetics matched for age, body mass index, and physical activity were recruited as controls. We applied 31 P magnetic resonance spectroscopy to record in vivo muscular phosphocreatine (PCr) flux in controls and diabetics before and after insulin therapy. The mitochondrial OxPhos rate was calculated as ΔPCr / Δtime during the first 50 seconds after cessation of exercise.Results: In drug naïve type 2 diabetes, muscular mitochondrial OxPhos rate was restored after insulin therapy. Notably, this alteration was positively associated with the improvements of 1,5-anhydroglucitol, a serum marker for glucose control over the last 1 week, as well as homeostasis model assessment of β cell function and C-peptide/glucose ratio t0 , two indices for basal insulin secretion. Furthermore, patients with diabetes family history and more severe glucotoxicity tend to achieve greater improvement in mitochondrial function by insulin.Conclusions: This study provides evidence that intensive insulin therapy facilitates muscular energy metabolism in drug naïve type 2 diabetes. It correlates to the recovery of β cell function, contributing to insulin-induced glucose control. [ABSTRACT FROM AUTHOR]

The prevalence of diabetes in China has increased rapidly from 0.67% in 1980 to 10.4% in 2013, with the aging of the population and westernization of lifestyle. Since its foundation in 1991, the Chinese Diabetes Society (CDS) has been dedicated to improving academic exchange and the academic level of diabetes research in China. From 2003 to 2014, four versions of Chinese diabetes care guidelines have been published. The guidelines have played an important role in standardizing clinical practice and improving the status quo of diabetes prevention and control in China. Since September 2016, the CDS has invited experts in cardiovascular diseases, psychiatric diseases, nutrition, and traditional Chinese medicine to work with endocrinologists from the CDS to review the new clinical research evidence related to diabetes over the previous 4 years. Over a year of careful revision, this has resulted in the present, new version of guidelines for prevention and care of type 2 diabetes in China. The main contents include epidemiology of type 2 diabetes in China; diagnosis and classification of diabetes; primary, secondary, and tertiary diabetes prevention; diabetes education and management support; blood glucose monitoring; integrated control targets for type 2 diabetes and treatments for hyperglycaemia; medical nutrition therapy; exercise therapy for type 2 diabetes; smoking cessation; pharmacologic therapy for hyperglycaemia; metabolic surgery for type 2 diabetes; prevention and treatment of cardiovascular and cerebrovascular diseases in patients with type 2 diabetes; hypoglycaemia; chronic diabetic complications; special types of diabetes; metabolic syndrome; and diabetes and traditional Chinese medicine. [ABSTRACT FROM AUTHOR]

Aim: To assess metabolic effects and safety of Roux-en-Y gastric bypass (RYGB) versus conventional medication (CM) in obese Chinese patients with type 2 diabetes (T2DM).Methods: This retrospective cohort study included 40 patients who underwent RYGB (mean age 44.1 years, body mass index [BMI] 33.3 kg/m2 ) and 36 patients administered CM (mean age 49.4 years, BMI 32.1 kg/m2 ). The primary endpoint was achievement of the triple endpoint (haemoglobin A1C [HbA1c] < 7.0%, low-density lipoprotein cholesterol < 2.6 mmol/L, and systolic blood pressure < 130 mmHg). Changes in weight, BMI, medication usage, complications, and adverse events were assessed.Results: After 1-year follow-up, 35% of RYGB patients and 8% of CM patients achieved the triple endpoint (P = 0.005). More patients in the RYGB group achieved complete (48% vs 3%, P < 0.001) and partial (23% vs 0%, P = 0.007) remission of diabetes, and complete remission of hypertension (58% vs 24%, P = 0.019). Patients in the RYGB group had greater weight loss and decrease in BMI, waist circumference, fasting and postprandial of blood glucose and insulin levels, HbA1c, blood pressure, triglycerides, and increased high-density cholesterol (P < 0.001- < 0.05). A lower proportion of the RYGB group received antidiabetics, antihypertensives, or antilipemic treatments, and had non-alcoholic fatty liver disease (NAFLD) than the CM group during follow-up. More patients had nutrient deficiency-related diseases in the RYGB group over 1-year follow-up.Conclusions: For obese Chinese patients with T2DM, RYGB resulted in better metabolic control, greater weight loss, and lower medication usage and NAFLD, but more frequently resulted in diseases related to nutrient deficiency. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Although long-acting insulin analogs are recommended in type 2 diabetics failing on oral agents, their efficacy is uncertain. Here we compared the efficacy and safety of regimens based on long-acting insulin analogs with other preparations in insulin-naïve type 2 diabetics failing on oral agents. Materials and Methods: Data from 9548 participants in 22 English studies were included. Most of the studies were of short to medium duration and of low quality. Results: In terms of decreasing hemoglobin A1c, long-acting insulin analogs were not statistically significant to rapid-acting insulin analogs or intermediate neutral protamine Hagedorn (NPH) insulin or glucagon-like peptide-1 (GLP-1) analogs, and the differences between long-acting and biphasic insulin analogs were marginal. Compared with rapid-acting insulin analogs, long-acting insulin analogs were similar in the incidence of total hypoglycemia, and the superiority in less weight gain was inconsistent. Relative to biphasic insulin analogs, long-acting insulin analogs were associated with lower incidence of total hypoglycemia and less weight gain. Compared with NPH insulin, long-acting insulin analogs were associated with lower incidence of total and nocturnal hypoglycemia. Relative to GLP-1 analogs, long-acting insulin analogs were associated with lower incidence of treatment related adverse events but with greater weight gain. Conclusions: For type two diabetics failing on oral agents, initiating long-acting insulin analogues seems to provide glycemic control similar to rapid-acting insulin analogs or NPH insulin or glucagon-like peptide-1 analogs and slightly inferior to biphasic insulin analogs with fewer side-effects. (J Diabetes Invest, doi: 10.1111/j.2040-1124.2011.00187.x, 2011) [ABSTRACT FROM AUTHOR]