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Background The bone mineral density (BMD) did not increase significantly after the normalization of serum thyroid hormone levels. Studies on the effect of muscle mass on BMD in patients with Graves’ disease are scarce. This study aimed to determine the association of decreased muscle mass with reduced bone mineral density in patients with Graves’ disease. Methods A total of 758 patients with Graves’ at diagnosis (mean age 41.2 years) were enrolled for a cross-sectional study; of these, 287 patients were enrolled for a cohort study with a median follow-up of 24 months. Meanwhile, 1164 age- and sex-matched healthy controls participants were recruited. All participants underwent dual-energy x-ray absorptiometry and muscle mass index (ASMI) measurements. The changes in ASMI and BMD were calculated from the measurements made at a gap of 2 years. Results Compared with healthy controls participants, the BMD was still significantly lower after normalizing serum thyroid hormone levels (1.131 ± 0.268 vs. 1.07 ± 0.133, p

Paget's disease of bone (PDB) is a rare metabolic bone disorder, which is extremely rare in Asian population. This study aimed to investigate the phenotypes and the pathogenic mutations of woman with early-onset PDB. The clinical features, bone mineral density, x-ray, radionuclide bone scan, and serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and β-carboxy-terminal cross-linked telopeptide of type 1 collagen (β-CTX) were measured in detail. The pathogenic mutations were identified by whole-exon sequencing and confirmed by Sanger sequencing. We also evaluated the effects of intravenous infusion of zoledronic acid on the bones of the patient and summarized the phenotypic characteristics of reported patients with mutation at position 155 of the valosin-containing protein (VCP). The patient only exhibited bone pain as the initial manifestation with vertebral compression fracture and extremely elevated ALP, P1NP, and β-CTX levels; she had no inclusion body myopathy and frontotemporal dementia. The missense mutation in exon 5 of the VCP gene (p.Arg155His) was identified by whole-exome sequencing and further confirmed by Sanger sequencing. No mutation in candidate genes of PDB, such as SQSTM1, CSF1, TM7SF4, OPTN, PFN1, and TNFRSF11A, were identified in the patient by Sanger sequencing. Rapid relief of bone pain and a marked decline in ALP, P1NP, and β-CTX levels were observed after zoledronic acid treatment. Previously reported patients with VCP missense mutation at position 155 (R155H) always had myopathy, frontotemporal dementia, and PDB, but the patient in this study exhibited only PDB. This was the first report of R155H mutation-induced early-onset in the VCP gene in Asian population. PDB was the only manifestation having a favorable response to zoledronic acid treatment. We broadened the genetic and clinical phenotype spectra of the VCP mutation.

Our aim in this study was to investigate the association between diabetic peripheral neuropathy (DPN) and above-normal blood pressure in nonhypertensive adult patients with type 2 diabetes mellitus (T2DM). We also compared achievement of clinical targets for DPN and non-DPN with T2DM.A retrospective survey was administered to 3,810 patients with T2DM. Cases were grouped according to the Toronto Clinical Scoring System as follows: non-DPN, mild DPN, moderate DPN and severe DPN. A total of 1,835 patients (hypertensive, 1,247; nonhypertensive, 588) also underwent nerve conduction velocity testing, and then was divided into quartile groups.Irrespective of hypertension, systolic blood pressure (SBP) and glycated hemoglobin levels in the DPN group were higher than those in the non-DPN group (p0.001). In hypertensive patients, blood pressure goal achievement was lower in the DPN group compared with the non-DPN group (31.1% vs 40.5%, p0.05). Compared with the nerve conduction velocity Q1 (P25%) group, optimal SBP of the Q2 (P25% to P50%), Q3 (P50% to P75%) and Q4 (P75%) groups decreased by 62.2%, 68.2% and 78.0%, respectively. In the nonhypertensive patients, detection of optimal SBP was lower in the DPN group than in the non-DPN group (p0.05). After adjusting for age, sex and diabetes duration (model 2), a 3-point higher DPN score on the Toronto Clinical Scoring System was associated with an SBP level of 4.2 mmHg higher (95% confidence interval, 0.01 to 0.17; p0.01) in nonhypertensive patients with diabetes.DPN is associated with difficulty in hypertension management in T2DM. It is also associated with elevated systolic blood hypertension, even in nonhypertensive patients with diabetes. Elevated SBP in nonhypertensive T2DM may be also worthy of further attention.

Diabetes mellitus (DM) and osteoporosis are two common diseases that may develop as a cause-and-effect relationship since the incidence of osteoporotic fractures is significantly increased in DM patients. However, the pathophysiology of diabetic osteoporosis is yet to be clearly understood. Iron overload has been reported to lead to bone loss and closely related to osteoporosis. In this study, we hypothesized that high glucose and high fat (HGHF) may induce osteoblastic ferroptosis for the pathogenesis of diabetic osteoporosis and explored the possible molecular mechanisms behind. Using the diabetic rat model established by HGHF feeding with a subsequent intraperitoneal injection of a single low dose of streptozocin, we found that the serum ferritin level (a biomarker for body iron store) was significantly elevated in HGHF-fed rats and the expression of SLC7A11 and GPX4 (inhibitory marker proteins for ferroptosis) was markedly attenuated in the bone tissue of the rats with diabetic bone loss as compared to the normal rats. In an osteoblast cell model, treatment of pre-osteoblastic MC3T3-E1 cells with high glucose and palmitic acid (HGPA) not only suppressed osteoblast differentiation and mineralization but also triggered ferroptosis-related osteoblastic cell death. m

Objective To identify independent risk factors for diabetic neuropathy (DN) in patients with type 2 diabetes mellitus (T2DM). Methods We retrospectively analyzed 376 patients with T2DM at the First Affiliated Hospital of Fujian Medical University, China between January 2013 and October 2016. Multivariate logistic regression was used to explore potential risk factors for progression of DN in patients with T2DM. Effect sizes were estimated using odds ratios (ORs) and 95% confidence intervals (CIs). Results The prevalence of DN in patients with T2DM was 43.1%. Multivariate logistic regression indicated that retinopathy (OR: 2.755, 95% CI: 1.599–4.746); diabetic nephropathy (OR: 2.196, 95% CI: 1.279–3.772); longer duration of T2DM (OR: 1.081, 95% CI: 1.045–1.120); use of insulin (OR: 1.091, 95% CI: 1.018–1.170); longer history of alcohol consumption (OR: 1.034, 95% CI: 1.010–1.059); and higher blood urea nitrogen (OR: 1.081, 95% CI: 1.009–1.159) were associated with increased risk of DN in patients with T2DM. Conclusions Retinopathy, diabetic nephropathy, longer duration of T2DM, use of insulin, longer history of alcohol consumption, and higher blood urea nitrogen were independent risk factors for DN. These findings should be verified in large-scale prospective studies.

Objective This study aimed to elucidate the mechanism of autophagy in bone metabolism in high-glucose environments and its relationship with Toll-like receptor 4 (TLR4). Methods A TLR4 knockout diabetic rat model and MC3T3-E1 with TLR4 silencing by small interfering RNA were used to observe the protective mechanism of TLR4 knockdown or silencing in hyperglycemia-induced bone injury. Results The inhibition of TLR4 expression improved bone metabolism and bone structure; promoted alkaline phosphatase (ALP) and osteocalcin (OCN) secretion, enhanced bone morphogenic protein (BMP)-2 expression, promoted bone mineralization, and reduced hyperglycemia-induced osteoblast apoptosis. TLR4 knockdown or silencing reduced the levels of inflammatory factors interleukin (IL)-1, IL-6, and tumor necrosis factor-alpha at the animal and cell levels, inhibited the expression of inflammatory pathway proteins, and downregulated the expression of Beclin 1 and LC3II/LC-1 proteins. The inhibition of autophagic activity enhanced the osteoprotective effect of TLR4 knockdown, improved cell viability, reduced the apoptosis rate of osteoblasts, and promoted the BMP-2 protein level and ALP and OCN secretion. Conversely, the activation of autophagy significantly aggravated osteoblast apoptosis, reduced BMP-2 protein levels, and inhibited ALP and OCN secretion. Conclusion Taken together, the experimental results supported the hypothesis that TLR4 deficiency might alleviate hyperglycemia-induced apoptosis and differentiation suppression in osteoblasts and exert osteoprotective effects via autophagic inhibition.

Studies showed that TLR4 knockout (TLR4KO) could mitigate obesity and insulin resistance induced by high-fat diet in rats. In this study, we further investigated the effects of TLR4KO on islet function and pancreatic proteomics in obese rats by high-fat diet. PA-induced lipotoxicity β-cells, SD and TLR4KO rats were used in this study. iTRAQ was used to screen out meaningful differential proteins.The protein expression level was evaluated by Western blotting; the cell apoptosis was detected by TUNEL assay. TLR4KO could reduce inflammatory and regulate body composition in obese rats, and improve β-cells function. The quantitative analysis of protein revealed that TLR4KO rebalanced proteomics disorders in pancreas of obese rats. In addition, the pathways involved in differential proteins were mainly metabolic pathways, arachidonic acid metabolism, ECM–receptor interaction, pancreatic secretion, PI3K-Akt signaling pathway, and FoxO signaling pathway. Further analysis of protein–protein interaction (PPI) revealed that Stk39 and Ass1 interacting through Mapk14-Ywhae were node proteins and participated in inflammatory response, carboxylic acid metabolic process, and small molecule metabolic process. In vitro experiments we confirmed that silencing TLR4 can inhibit PA-induced β-cell apoptosis, insulin secretion disorders, and increase Ass1 expression. While, overexpression of Ass1 in β-cell inhibited PA or LPS-induced β-cell damage. Our study confirmed that TLR4KO could improve dysfunction of β-cell, and the underlying mechanism might be involved in ebalancing proteomics disorders in pancreas, affecting the expression of Ass1.

Paget's disease of bone (PDB) is a rare metabolic bone disorder, which is extremely rare in Asian population. This study aimed to investigate the phenotypes and the pathogenic mutations of woman with early-onset PDB. The clinical features, bone mineral density, x-ray, radionuclide bone scan, and serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and β-carboxy-terminal cross-linked telopeptide of type 1 collagen (β-CTX) were measured in detail. The pathogenic mutations were identified by whole-exon sequencing and confirmed by Sanger sequencing. We also evaluated the effects of intravenous infusion of zoledronic acid on the bones of the patient and summarized the phenotypic characteristics of reported patients with mutation at position 155 of the valosin-containing protein (VCP). The patient only exhibited bone pain as the initial manifestation with vertebral compression fracture and extremely elevated ALP, P1NP, and β-CTX levels; she had no inclusion body myopathy and frontotemporal dementia. The missense mutation in exon 5 of the VCP gene (p.Arg155His) was identified by whole-exome sequencing and further confirmed by Sanger sequencing. No mutation in candidate genes of PDB, such as SQSTM1, CSF1, TM7SF4, OPTN, PFN1, and TNFRSF11A, were identified in the patient by Sanger sequencing. Rapid relief of bone pain and a marked decline in ALP, P1NP, and β-CTX levels were observed after zoledronic acid treatment. Previously reported patients with VCP missense mutation at position 155 (R155H) always had myopathy, frontotemporal dementia, and PDB, but the patient in this study exhibited only PDB. This was the first report of R155H mutation-induced early-onset in the VCP gene in Asian population. PDB was the only manifestation having a favorable response to zoledronic acid treatment. We broadened the genetic and clinical phenotype spectra of the VCP mutation.

Osteocalcin (OCN) has been proved to be closely related with the development of type 2 diabetes mellitus (T2DM). We aimed to study if OCN could improve the disorder of islet cell caused by lipotoxicity.Alizarin red staining was used to investigate the mineralization. Western blotting and ELISA methods were used to measure protein expression. Immunofluorescence staining was used to investigate the protein nuclear transfer.High glucose and high fat inhibited the differentiation of osteoblast precursors. Overexpression of insulin receptor (InsROCN could activate the FOXO1 signaling pathway to regulate GLUT2 expression and improve the insulin secretion disorder caused by lipotoxicity.

Introduction: Albuminuria is a risk factor for macro- and microvascular complications of type 2 diabetes (T2D).With an increasing trend of normoalbuminuria, however, of the 2 predictors – estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) – which one is a better predictor of vascular complications of T2D is not clear. Objective: This study aimed to compare the impacts of albuminuria and eGFR on patients with T2D associated with micro- and macrovascular complications. Methods: This retrospective study recruited 4,715 patients with T2D and grouped them based on the values of UACR (high UACR: ≥30 mg/g, low UACR: 2]) (G1: eGFR ≥ 90; G2: eGFR = 60–89; G3–5: eGFR < 60) from April 2008 to November 2018. Logistic regression analysis was carried out for risk factors in patients with diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), peripheral arterial disease (PAD), left ventricular remodeling, diastolic disorders, and carotid atherosclerotic plaque in 6 different groups: low UACR + G1 (control group), low UACR + G2, low UACR + G3–5, high UACR + G1, high UACR + G2, and high UACR + G3–5. Patients were grouped according to the change in the UACR value (UACR-decreased group: ≤−30%, UACR-stable group: −30 to 30%, and UACR-increased group ≥30%), eGFR value (eGFR-decreased group: >3%, and eGFR-stable group: ≤3%) and followed up. Results: Compared with the control group, patients with higher albuminuria and lower eGFR had higher adjusted odds ratio (OR) trends of complications, especially in the high UACR + G3–5 group. The OR of 2.010, 3.444, 1.633, 2.742, and 3.014 were obtained for DR, DPN, PAD, left ventricular remodeling, and diastolic disorders, respectively. No statistically significant difference was found in the risk of complications within each one of 2 phenotypes, regardless of the change in the eGFR. After grouping by eGFR, the regression analysis of the urinary protein level in each stage revealed that a majority of complications had a statistically significant difference, except for DR and PAD in the high UACR + G3–5 group. DR in the follow-up study had a higher risk in the UACR-stable/increased group than the UACR-decreased group (UACR stable: OR = 2.568; 95% confidence interval (CI): 1.128–5.849; p = 0.025; UACR increased: OR = 2.489; 95% CI: 1.140–5.433; p = 0.022). Conclusion: UACR is a more predictive risk factor for diabetic complications compared with a reduced eGFR.

Diabetes can cause bone metabolism disorders and osteoporosis. The occurrence of both diabetes mellitus and osteoporosis increases the disability and mortality of elderly individuals due to pathological fracture. Abnormal metabolism of nutrientsis considered to be one of the important mechanisms of diabetes mellitus-induced osteoporosis. This study preliminarily explored the roles of TLR4 (Toll-like receptor 4) and S100B in osteogenic dysfunction induced by glycolipid toxicity. In this study, a diabetic rat model and TLR4-knockdown diabetic rat model were used in vivo. MC3T3-E1 cells in a high glucose and palmitic acid environment were used as glycolipid toxicity cell models in vitro. We investigated the effects of TLR4 and S100B on osteogenesis by overexpression or inhibition of TLR4 and S100B in vitro. We found that when TLR4 or S100B was inhibited, ALP and OCN were significantly up-regulated and p-ERK was significantly down regulated in the glycolipid model. These results suggest that TLR4/S100B may play a role in reducing glycolipid toxicity by regulating ERK phosphorylation.

Objectives. Recent studies have shown that the slightly elevated circulating levels of ketone bodies (KBs) played a significant role in the treatment of various diseases. This study is aimed at investigating the association between different levels of KBs and kidney function in patients with type 2 diabetes mellitus (T2DM). Methods. A retrospective study of 955 patients with T2DM (426 women and 529 men) admitted to our hospital from December 2017 to September 2019 was conducted. Patients were divided into different groups in line with the levels of KBs (low-normal group: 0.02-0.04 mmol/L, middle-normal group: 0.05-0.08 mmol/L, high-normal group: 0.09-0.27 mmol/L, and slightly elevated group: >0.27 and

Irisin is a proteolytic product of the fibronectin type III domain-containing protein 5. The aim of the present study was to verify whether irisin is involved in the pathogenesis of diabetic mild cognitive impairment and elucidate the associated mechanisms. Diabetic rats were divided into four groups: Control, Model, Irisin (overexpression of irisin) and Irisin-short hairpin (sh)-RNA (irisin interference). The levels of irisin, brain-derived neurotrophic factor (BDNF), glycosylated hemoglobin A1c (GHbA1c) and advanced glycated end products (AGEs) in the serum were determined using ELISA. The expression of BDNF in the hippocampal tissue was evaluated by immunohistochemical analysis. Compared with the Control group, the levels of irisin and BDNF were markedly decreased in the Model and Irisin-shRNA groups, whereas those of GHbA1c and AGEs were markedly increased. However, the levels of irisin and BDNF in the Irisin group were significantly higher than those in the Model group, whereas the levels of GHbA1c and AGEs in the Irisin group were significantly lower. Irisin-shRNA significantly downregulated the expression of irisin and BDNF, and upregulated the levels of GHbA1c and AGEs, compared with those in the Model group. Rat primary hippocampal nerve cells were isolated and identified by microtubule-associated protein-2 labeling. The vitality of primary cells from diabetic rats, evaluated using a methyl thiazolyl tetrazolium assay, was markedly decreased and further reduced following the injection of irisin-shRNA, however, it was markedly improved following irisin treatment. The mRNA and protein levels of BDNF in the primary cells were evaluated by fluorogenic reverse transcription-quantitative polymerase chain reaction and western blot analyses, respectively, following the exposure of cells to different concentrations of glucose: 0 (control), 5.5, 15 and 25 mmol/l for 12, 24 and 48 h. The mRNA and protein expression levels of BDNF in the primary cells following exposure to glucose were significantly lower than those observed in the control. Further exposure to glucose led to a significant decrease in the expression of BDNF. In conclusion, irisin may regulate the expression of BDNF and glycometabolism in diabetic rats.

We aimed to investigate the potential association between urinary albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) and diabetic peripheral neuropathy (DPN). We were especially interested in the relationship between normal or mildly abnormal UACR and eGFR with DPN. A retrospective study was performed in 1059 patients with type 2 diabetes patients from Fuzhou, China, who were seen between 2010 and 2015. The DPN population demonstrated higher UACR and lower eGFR than the non-DPN population. Nerve conduction velocities (NCVs) were negatively correlated with UACR and were positively correlated with eGFR. UACR and eGFR were associated with the risk of DPN. Even in the UACR

The aim of the present study was to explore the influence of tea consumption on diabetes mellitus in the Chinese population. This multi-centre, cross-sectional study was conducted in eight sites from south, east, north, west and middle regions in China by enrolling 12 017 subjects aged 20–70 years. Socio-demographic and general information was collected by a standardised questionnaire. A standard procedure was used to measure anthropometric characteristics and to obtain blood samples. The diagnosis of diabetes was determined using a standard 75-g oral glucose tolerance test. In the final analysis, 10 825 participants were included and multiple logistic models and interaction effect analysis were applied for assessing the association between tea drinking with diabetes. Compared with non-tea drinkers, the multivariable-adjusted OR for newly diagnosed diabetes were 0·80 (95 % CI 0·67, 0·97), 0·88 (95 % CI 0·71, 1·09) and 0·86 (95 % CI 0·67, 1·11) for daily tea drinkers, occasional tea drinkers and seldom tea drinkers, respectively. Furthermore, drinking tea daily was related to decreased risk of diabetes in females by 32 %, elderly (>45 years) by 24 % and obese (BMI > 30 kg/m2) by 34 %. Moreover, drinking dark tea was associated with reduced risk of diabetes by 45 % (OR 0·55; 95 % CI 0·42, 0·72; P < 0·01). The results imply that drinking tea daily was negatively related to risk of diabetes in female, elderly and obese people. In addition, drinking dark tea was associated with decreased risk of type 2 diabetes mellitus.

Aim This study aimed to investigate the association of sarcopenia and muscle mass with both peripheral neuropathy and nerve function in type 2 diabetes mellitus. Methods A total of 1794 patients (937 men and 857 women) with type 2 diabetes, with a mean age of 60.22 years, were enrolled for a cross-sectional study; of these, 183 patients were enrolled for a follow-up study with a median follow-up of 2.7 years. All participants underwent nerve conduction studies and muscle mass index (ASM/HT2) measurements. The composite Z scores for the sensory nerve conduction velocity (SCV) and the motor nerve conduction velocity (MCV) were calculated. The changes in ASM/HT2, SCV, and MCV were calculated from the measurements nearly 2 years apart and classified into three groups: a decrease in ASM/HT2 of >3%, a minor change within ±3%, and an increase in ASM/HT2 of >3%. Results The ASM/HT2 of men was positively associated with the composite Z scores of MCV and SCV, and sarcopenia highly correlated with DPN after adjusting for confounding factors. The optimal cutoff point for ASM/HT2 that indicated DPN was 7.09 kg/m2. Furthermore, increases in ASM/HT2 independently predicted a greater benefit of MCV and SCV increment outcomes, whereas a minor change in ASM/HT2 only significantly associated with lower benefit in terms of SCV increment. However, this phenomenon was not observed in women. Conclusions Sarcopenia and DPN exhibited a close association. The increased muscle mass improved the partial MCVs and SCVs. However, a sex-related discrepancy was observed in this phenomenon.

Aims To explore the effects of glucose, insulin, and glycosylated hemoglobin (HbA1c) levels on the outcome of sarcopenia in patients with type 2 diabetes mellitus (T2DM). Methods A total of 482 T2DM patients were enrolled in the follow-up study. The median follow-up time was 36 months. Muscle mass and HbA1c were measured in all participants. And glucose, C-peptide and insulin levels were measured at 0 min, 30 min, and 120 min after glucose load. We subsequently analyzed daily glucose fluctuations and islet function before and after readmission as well as the influence of their changes on sarcopenia outcome. Results After glucose load, incident sarcopenia patients showed greater glucose fluctuations and worse islet function than did non-sarcopenia patients. As HbA1c and standard deviation of blood glucose (SDBG) increased, readmitted non-sarcopenia patients showed a significantly increased odds ratio of incident sarcopenia; however, only patients with higher quartiles were statistically significant. Increased ΔAUC-C-peptide reduced the risk of incident sarcopenia (P Conclusions Patients with incident sarcopenia have poor glucose regulation and insufficient insulin secretion. Furthermore, as HbA1c and SDBG increased, AUC-C-peptide and AUC-insulin decreased in readmitted non-sarcopenia patients, the risk of incident sarcopenia increased.

Aims Studies have suggested that low muscle mass is associated with declining renal function in healthy populations, whether the association is relevant to patients with type 2 diabetes is not well understood. This study investigates the association between sarcopenia and estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratios (UACR) in the patients with type 2 diabetes. Methods Two recruited groups consisted of 793 persons without diabetes (males/females=550/243) and 762 persons with type 2 diabetes (males/females=501/261). Results The non-sarcopenia population demonstrated higher ASM/HT 2 , GFR ( P P ＜0.05) than the sarcopenia population. In studied men, the association between ASM/HT 2 and eGFR was statistically significant in the group without diabetes (OR=0.580, P =0.020), a trend which persisted in women (OR=0.491, P =0.014). The association between ASM/HT 2 and UACR persisted in studied women of two groups (OR=0.269, P =0.005; OR=0.405, P =0.008, respectively). The highest quartile of ASM/HT 2 in the non-sarcopenia population exhibited a 3.753-fold risk of abnormal eGFR within the diabetes group (OR=3.753, P =0.020). The cutoff point of ASM/HT 2 to indicate abnormal renal function for population with non-sarcopenia was 6.32kg/m 2 in the group without diabetes and 6.31kg/m 2 in diabetes group. Conclusions Sarcopenia is associated with declining renal function, which induces lower eGFR and higher UACR. In the non-sarcopenia population, ASM/HT 2 presents as renal function risk factor, which perhaps associated with higher muscle mass to induce a greater underestimation for creatinine and urinary albumin.

Aims Metformin was found to protect against hyperglycemia-induced injury in osteoblasts, but the cellular mechanisms involved remain unclear. Therefore, the aim of this study was to determine the effect of metformin on hyperglycemia-induced apoptosis and differentiation suppression in osteoblasts and to explore its relationships with the TLR4 signaling pathway. Main methods A mouse osteoblast cell line, MC3T3-E1, and a diabetic rat model were used to survey the protective effects of metformin on hyperglycemia-induced injury. TLR4 expression was altered using small interfering (si)RNA and lentivirus-mediated TLR4 overexpression. LPS was used as a specific TLR4 activator, and CLI-095 was used as a TLR4 inhibitor. Key findings Metformin improved osteoblast differentiation, reduced apoptosis in hyperglycemic osteoblasts, and inhibited TLR4, MyD88 and NF-κB expression in a dose-dependent manner. Down-regulating the expression or inhibiting the activity of TLR4 enhanced these protective effects of metformin on osteoblast differentiation, cell viability and cell apoptosis in hyperglycemic conditions, whereas up-regulating the expression or activating the activity of TLR4 had the opposite effects. Activating NF-κB suppressed the protective effects of metformin, while inhibiting NF-κB activity had the opposite effects. Metformin increased ALP and OCN secretion, enhanced BMP-2 expression, improved bone mineral density (BMD), and decreased TLR4, MyD88 and NF-κB levels in the femur tissues of diabetic rats. Significance Taken together our experimentation support the hypothesis that metformin may alleviate hyperglycemia-induced apoptosis and differentiation suppression in osteoblasts by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

Aims/Introduction To investigate the relationship between different body mass index (BMI) levels and vascular complications in type 2 diabetes mellitus patients. Materials and Methods Data were collected from 3,224 individuals with type 2 diabetes mellitus (male/female: 1,635/1,589; age 61.31 ± 11.45 years), using a retrospective case study design. The association of BMI quintiles and diabetes mellitus vascular complications was assessed using multiple logistic regression models adjusting for age, sex, diabetes duration, smoking status, drinking and other confounders, using those with the lowest quintile of BMI as the reference group. Results With increasing BMI, the detection rate of diabetic peripheral neuropathy and peripheral arterial disease initially decreased and then it increased, whereas the detection rate of diabetic kidney disease and carotid atherosclerotic plaques showed an upward trend; however, diabetic retinopathy was irregular. The odds ratios of diabetic peripheral neuropathy decreased as BMI increased from the 21st percentile to the 80th percentile initially, and increased when BMI was in >80th percentile. The same result was shown in peripheral arterial disease. BMI >80th percentile showed a 1.426‐fold risk of diabetic kidney disease and a 1.336 ‐fold risk of carotid atherosclerotic plaque. Conclusions In patients with type 2 diabetes mellitus, the relationship between different BMIs and vascular complications varies. A U‐shaped relationship was observed between BMI and diabetic peripheral neuropathy, as well as BMI and peripheral arterial disease. BMI is positively correlated with diabetic kidney disease and carotid atherosclerotic plaque; however, it is not correlated with diabetic retinopathy.

Elderly patients with type 2 diabetes are at a greater risk for cognitive decline. The purpose of this study was to assess the relationship between the degree of hyperglycemia and cognitive status in nondemented, elderly diabetics. Between Jan 2013 and Dec 2014, 1174 geriatric patients with type 2 diabetes were enrolled in the study (579 males; age ≥ 60 years; from Fuzhou, Fujian, China). Cognitive function was measured with the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). A statistically significant, age-adjusted association was observed between the A1C levels and the scores on two cognitive tests (MMSE and MoCA). Specifically, a 1% higher A1C value was associated with a 0.21-point lower MMSE score (95% CI; compare -0.11 to -0.28; P < 0.0001), as well as a 0.11-point lower MoCA score (95% CI; compare -0.10 to -0.38; P < 0.0001). Higher A1C levels were not significantly associated with lower MMSE and MoCA test scores after adjusting for all variables. No significant correlation was found between the two variables in patients older than 80 years of age (n = 215; OR = 1.019; 95% CI = 0.968 - 1.099; p = 0.251). Evidence strongly suggests that chronic hyperglycemia is associated with a decline in cognitive function in nondemented elderly patients with type 2 diabetes. When cognitive assessments are made, comprehensive factors such as advanced age, education level, duration of diabetes, hypertension and other vascular risks should be taken into account. For older geriatric patients (age ≥ 80 years), there is no significant correlation between A1c levels and cognitive function.

The aim of this study are to analyze the value of the body mass index (BMI) to diagnose obesity in the population of Fuzhou, China, and to determine the BMI optimal cut-off and percentage body fat (BF%) values for obesity. A retrospective analysis was performed on 2,317 volunteers, ages 20–87 years, from Fuzhou, China. In this study, the World Health Organization (WHO) BF% criteria to diagnose obesity were set as the reference standard. Receiver operating characteristic curve, Venn diagram, and evaluation indicators of diagnostic tests were plotted to determine the performance of BMI as defined by the 1999 WHO criteria, the 2002 Asian criteria, and the 2002 Chinese criteria. The obesity detection rates were 3.02, 32.54, and 9.37 % for the WHO, Asian, and Chinese criteria, respectively. In all cases, the values were lower than the one determined by the BF% criteria (39.15 %). Of the obese subjects defined by BF% criteria, false-negative rates yielded by using the three BMI criteria described above were 35.87, 12.13, 28.35 % for male subjects and 36.56, 17.71, 32.46 % for female subjects. For the population of Fuzhou, China, the optimal BMI cut-off points to diagnose obesity were 24.45 kg/m2 for male subjects and 23.16 kg/m2 for female subjects. Current BMI criteria have high false-negative rates and underestimate the prevalence of obesity. The optimal BMI cut-off point for the population of Fuzhou, China, needs further characterization.

Background Cardiovascular disease is prevalent in type 2 diabetics, and microalbuminuria is associated with cardiovascular disease morbidity. We aimed to investigate the potential association between low-grade albuminuria and arterial stiffness in patients with type 2 diabetes. Methods Between 2009 and 2013, a retrospective study was performed in 578 patients with type 2 diabetes (339 male patients and 239 female patients) with normal urinary albumin-to-creatinine ratios (ACRs

SummaryObjective To analyse the effectiveness of age on HbA1c as a criterion for the diagnosis of diabetes in Chinese different age subjects. Methods This retrospective study enrolled a total of 1147 outpatients with untreated newly diagnosed diabetes (aged 18–80 years, 42·55% women) from the Fujian Province, China, and 427 age and gender-matched (control) subjects without diabetes. Receiver operating characteristic curve (ROC) was plotted to determine the performance of HbA1c against results of oral glucose tolerance test (OGTT) performed at the same time according to specific age groups. The ORs and 95%CIs between diabetes and other metabolic disorders were analysed. Results (i) HbA1c provided an age-specific diagnosis for diabetes: there was a high diagnostic titter of HbA1c in the 18- to 39-year age group; conversely, there was a low diagnostic titter of HbA1c in the ≥70-year-old age groups. (ii) After adjusted for age, individuals with diabetes by OGTT criteria but not by WHO HbA1c criteria had an increased chance of having abnormal weight, hypertriglyceridaemia, HDL hypocholesterolaemia and insulin resistance. (iii) The diagnostic cut-off points of HbA1c for diabetes in different age groups (18–39, 40–49, 50–59, 60–69 and ≥70 years) were 6·1, 6·3, 6·4, 6·5 and 6·4, respectively. The age-specific HbA1c criteria exhibited the higher positive rate, sensitivity and lower false-negative rate when compared with WHO HbA1c criteria. Conclusions This provided evidence indicating that there may be drawbacks in the use of HbA1c in the diagnosis of diabetes. Thus, we proposed that the impact of introducing HbA1c for diabetes diagnosis should be considered in terms of age. Cohort studies are needed to further confirm the suitability of age-specific HbA1c criteria for the diagnosis of diabetes.

Objective We sought to determine whether free fatty acid receptor 1 (FFAR1), a receptor for free fatty acids on the β-cell membrane, can mediate the pioglitazone (PIO)-attenuating effect on lipoapoptosis in β cells and its relationship to oxidative stress. Methods The glucose-sensitive mouse beta pancreatic cell line βTC6 was used to investigate the effect of FFAR1 on PIO-attenuating palmitic acid (PA)-induced oxidative stress and apoptosis. Results (1) PIO reduced PA-induced lipoapoptosis in β cells and upregulated the expression of FFAR1 at the mRNA and protein levels in a dose- and time-dependent manner. Silencing of FFAR1 expression was shown to weaken the protective effect of PIO on PA-induced lipoapoptosis in βTC6 cells; while lentiviral-mediated overexpression of FFAR1 was shown to enhance the protective effect of PIO against lipoapoptosis in β cells. (2) Downregulation of FFAR1 expression reduced the attenuating effect of PIO on the expression of NAPDH oxidase subunit p47 phox , Bax, cleaved caspase 3, and the production of reactive oxygen specific (ROS) induced by lipotoxicity, thereby preventing the upregulation of the expression of bcl-2. Inducing the overexpression of FFAR1 enhanced the anti-oxidative stress effect of PIO. Similarly, these effects of FFAR1 on PIO were reproduced under conditions of oxidative stress and apoptosis in βTC6 cells that were induced by H 2 O 2 . (3) PIO was found to increase the expression of PLCγ, ERK1/2, and PPARγ in lipotoxic β cells. Silencing FFAR1 expression reduced the PIO-mediated increases in the expression of above proteins; while inducing FFAR1 overexpression showed the opposite effect. Use of an inhibitor of PLCγ, ERK1/2, PPARγ was shown to restrict the protective effect of PIO on oxidative stress and lipoapoptosis of β cells. Conclusions FFAR1 can mediate PIO suppression of β-cell lipoapoptosis through anti-oxidative stress, which may be related to the activation of the PLCγ-ERK1/2-PPARγ pathway.

Recent studies have demonstrated the benefits of osteocalcin (OCN) on glucose homeostasis and metabolic dysregulation. However, its role in body composition and vascular function remains unknown. This study was designed to examine changes in metabolic parameters and body composition as well as arterial stiffness after OCN treatment in type 2 diabetic rats. Adult male Sprague Dawley (SD) rats were fed chow or high fat diet (HFD) for 8 weeks, and then diabetes was induced with an injection of low-dose streptozotocin (STZ) and treated daily with intraperitoneal injections of OCN for 12 weeks. Our data showed that OCN treatment improved glucose homeostasis and lipid metabolism. Further analysis revealed that OCN treatment resulted in increased insulin sensitivity. In addition, untreated diabetic rats experienced significant weight loss, whereas OCN-treated rats better maintained body weight (300.75±38.14 g vs. 335.50±23.70, p=0.005). OCN also changed body composition, as evidenced by reduced body fat mass, specifically abdominal fat mass. OCN-treated diabetic rats also demonstrated decreased pulse-wave velocity, indicating of improved arterial stiffness. Taken together, our findings in the current study revealed that OCN therapy prevents arteriosclerosis in an induced diabetic rat model by exerting beneficial effects on glucose levels, insulin sensitivity, lipid metabolites, and body composition changes.

A cross-sectional analysis was performed to explore the relationship between regional body fat distribution and blood pressure in non-obese subjects with different status of blood pressure. Dual-energy X-ray absorptiometry was performed to measure fat mass. Obesity was defined as present body fat ≥25% in males and ≥35% in females. The ratio of leg fat mass to total fat mass (L/T) decreased gradually while the ratio of trunk fat mass to total fat mass (Tr/T) increased gradually with the increasing blood pressure for both genders in non-obese subjects (P .01), which was consistent with the change in obese ones; and the blood pressure status in the low Tr/T + high L/T group was better than that in the high Tr/T + low L/T group, obviously. After adjustment for confounding factors, blood pressure was still positively related with Tr/T but negatively associated with L/T in non-obese groups. A multiple linear regression analysis showed that L/T was the major negative factors of blood pressure in the non-obese population. Abnormal fat distribution also exists in non-obese subjects with high blood pressure; compared to trunk fat, leg fat may be a more important factor against blood pressure.