Association of high vibration perception threshold with reduced renal function in patients with type 2 diabetes.

Objective: To investigate the correlation between vibration sensory threshold (VPT) and renal function, including glomerulus and renal tubule, in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 1274 patients with T2DM who were enrolled in the Department of Endocrinology of the First Affiliated Hospital of Fujian Medical University between January 2017 and June 2020 were included. Patients were grouped according to VPT levels and divided into three groups, including the normal VPT group (VPT<15V), the mild-moderate elevated VPT group (VPT15~25V), and the severely elevated VPT group (VPT≥25 V). Linear correlation analysis was used to analyze the correlation between VPT and renal functions, including glomerulus markers urine microalbumin (MA) and urinary immunoglobulin G (U-IgG), and renal tubule marker α1-microglobulin (α1-MG). Chronic kidney disease (CKD) was defined according to Kidney Disease Improving Global Outcomes (KDIGO) criteria. The binary logistic regression of the relation between VPT and CKD, eGFR<60 ml/min, and UACR >30 mg/g were expressed. Results: In the mild-moderate and severely elevated VPT group, injury biomarkers of glomerulus (MA and U-IgG), renal tubule (α1-MG), and the incidence of CKD, eGFR<60 ml/min, and UACR > 30 mg/g were gradually increased compared with the normal VPT group. Furthermore, patients with diabetes and severely elevated VPT had significantly higher levels of MA (ß=197.54, p=0.042) and α1-MG (ß=11.69, p=0.023) compared to those with normal VPT. Also, patients with mild-moderate elevated VPT demonstrate significantly higher levels of MA (ß=229.02, p=0.005). Patients in mild-moderate elevated VPT group (OR=1.463, 95% CI 1.005-2.127; OR=1.816, 95% CI 1.212-2.721) and severely elevated VPT group (OR=1.704, 95% CI 1.113-2.611; OR=2.027, 95% CI 1.248-3.294) are at a higher incidence of CKD and elevated levels of UACR>30mg/g compared to those in the VPT normal group. Moreover, the incidence of positive Upro was notably higher in the severely elevated VPT group (OR=1.738, 95% CI 1.182-2.556). However, this phenomenon was not observed in the incidence of eGFR <60 ml/min. Conclusion: A higher VPT is positively associated with the incidence of CKD in patients with T2DM, particularly with elevated UACR. VPT may serve as a marker for glomerulus and renal tubule injury.

Early onset age increases the risk of musculoskeletal damage in patients with type 2 diabetes.

Introduction: It's not clear whether there are differences in musculoskeletal damage and body composition among different age groups of type 2 diabetes. Therefore, the purpose of this study is to analyze the difference between early-onset type 2 diabetes (EOT2D) and non-early-onset type 2 diabetes (NOT2D) in musculoskeletal damage. Methods: A total of 964 patients with type 2 diabetes mellitus were selected by 1:1 propensity score matching, including 534 males and 430 females, with an average age of 52 ± 7 years and an average course of 10 ± 8.5 years. Bone mineral density and body composition were measured, and combined with biochemical tests, linear regression and binary logic regression were used to analyze the relationship between EOT2D, NOT2D and musculoskeletal damage. In addition, 414 patients with T2DM were selected according to whether they were hospitalized twice or not, and the median follow-up period was 44 months. COX survival analysis further elucidates the relationship between EOT2D, NOT2D and musculoskeletal damage. Results: Compared with patients with non-early-onset type 2 diabetes, A/G was negatively correlated with the age of onset, and had statistical significance. EOT2D has a higher risk of sarcopenia, osteoporosis and even musculoskeletal damage. With the prolongation of the course of the disease, the risk of muscle mass and/or bone mineral density decrease in EOT2D increases. Conclusion: EOT2D brings a greater risk of sarcopenia and/or osteoporosis, as well as a higher risk of reduced ASM and BMD. In addition, fat distribution may be more central.

Precedence of Bone Loss Accompanied with Changes in Body Composition and Body Fat Distribution in Patients with Type 2 Diabetes Mellitus.

Methods: A total of 596 patients with T2DM, including 308 male and 288 female patients, were included in the follow-up study; the median follow-up time was 2.17 years. We calculated the difference between the endpoint and the baseline of each body composition index and the annual rate. The research participants were divided into the increased body mass index (BMI) group, stable BMI group, and decreased BMI group. Some confounding factors were adjusted, such as BMI, fat mass index (FMI), muscle mass index (MMI), muscle/fat mass ratio (M/F), trunk fat mass index (TFMI), appendicular skeletal muscle mass index (ASMI), and appendicular skeletal muscle mass/trunk fat mass ratio (A/T). Results: The linear analysis showed that ΔFMI and ΔTFMI were negatively correlated with the change in femoral neck BMD (ΔFNBMD) and ΔMMI, ΔASMI, ΔM/F, and ΔA/T were positively correlated with ΔFNBMD. The risk of FNBMD reduction in patients with increased BMI was 56.0% lower than that in patients with decreased BMI; also, the risk in patients with stable M/F was 57.7% lower than that in patients with decreased M/F. The risk in the A/T increase group was 62.9% lower than that in the A/T decrease group. Conclusions: A reasonable muscle/fat ratio is still beneficial to maintaining bone mass. Maintaining a certain BMI value is conducive to maintaining FNBMD. Simultaneously, increasing the proportion of muscle mass and reducing fat accumulation can also prevent FNBMD loss.

Identification of a novel mutation in ALMS1 in a Chinese patient with monogenic diabetic syndrome by whole-exome sequencing.

Alstrom syndrome (AS) is one type of monogenic diabetic syndromes caused by mutation in the ALMS1. Due to rare prevalence and overlaps of clinical symptoms, monogenic diabetes is often misdiagnosed. Here, we report a Chinese diabetes patient with poor blood glucose control and insulin resistance. With whole-exome sequencing (WES), this patient was classified into monogenic diabetes and diagnosed as AS with one novel gene mutation identified. This study highlights the clinical application of WES in the diagnosis of monogenic diabetes.

Improvement of Lipotoxicity-Induced Islet ß Cellular Insulin Secretion Disorder by Osteocalcin.

Background: 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. Methods: 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. Results: High glucose and high fat inhibited the differentiation of osteoblast precursors. Overexpression of insulin receptor (InsROE) significantly promoted the Runx2 and OCN expression. The increase of insulin, Gprc6a, and Glut2 by osteoblast culture medium overexpressing insulin receptor was reversed by osteocalcin neutralizing antibody. Undercarboxylated osteocalcin (ucOC) suppressed the lipotoxic islet ß-cell damage caused by palmitic acid. The FOXO1 from intranuclear to extranuclear was also significantly increased after ucOC treatment compared with the group PA. Knockdown of Gprc6a or suppression of PI3K/AKT signal pathway could reverse the upregulation of GPRC6A/PI3K/AKT/FoxO1/Pdx1 caused by ucOC. Conclusion: OCN could activate the FOXO1 signaling pathway to regulate GLUT2 expression and improve the insulin secretion disorder caused by lipotoxicity.

Relationship between onset age of type 2 diabetes mellitus and vascular complications based on propensity score matching analysis.

AIMS/INTRODUCTION: To assess the relationship between type 2 diabetes mellitus onset age and vascular complications in China. MATERIALS AND METHODS: A retrospective review of 3,568 patients with type 2 diabetes mellitus using a propensity score-matched (PSM) cohort analysis was carried out in two different age of onset groups (age 40 and 60 years). These groups were then subdivided into two groups, early-onset diabetes (EOD40 and EOD60; the onset age before 40 and 60 years, respectively) and late-onset diabetes (LOD40 and LOD60: the onset age after 40 and 60 years, respectively). Macrovascular and microvascular complications were analyzed before and after PSM. RESULTS: Patients categorized in both the early-onset disease (EOD) groups had a higher risk of developing macro- and microvascular complications before PSM. After PSM, no differences existed between the EOD and late-onset disease groups in the risk of macrovascular complications. Compared with the late-onset disease group, the odds ratio of having a microvascular complication of diabetic retinopathy, chronic kidney disease and diabetic peripheral neuropathy in the 40-year-old EOD group increased to 2.906, 1.967 and 1.672 (P < 0.05), respectively. The odds ratio of diabetic retinopathy and diabetic peripheral neuropathy in the 60-year-old EOD group was 1.763 and 1.675 (P < 0.05), respectively. CONCLUSIONS: The earlier the onset of type 2 diabetes mellitus, the higher risk of microvascular, but not necessarily macrovascular, complications. It is not too late to prevent diabetes at any age. Pre-emptive microvascular treatment or preventative measures in EOD patients who do not yet show symptoms, might be beneficial.

Additive Effect of Sarcopenia and Anemia on the 10-Year Risk of Cardiovascular Disease in Patients with Type 2 Diabetes.

OBJECTIVE: To investigate the association between sarcopenia and anemia and the 10-year cardiovascular disease risk in diabetic patients. METHODS: A cross-sectional study was conducted involving 4673 hospitalized patients (2271 men and 2402 women) with type 2 diabetes mellitus, with an average age of 60.66 ± 11.93 years, of whom 542 were followed up for a median follow-up period of 24 months. All participants underwent body composition measurements, and they were grouped by sex and presence of sarcopenia using the Framingham risk model to assess their 10-year cardiovascular risk. According to the changes in the cardiovascular risk during follow-up, the patients were divided into four groups: low-low, low-high, high-low, and high-high. RESULTS: The prevalence of anemia was higher in the sarcopenia group than in the nonsarcopenia group (11.5% vs. 24.1% for men, P < 0.001; 13.9% vs. 19.7% for women, P < 0.05), and the difference remained significant after adjusting for confounders. Patients with sarcopenia and without anemia had a 46.2% increased risk of high 10-year cardiovascular disease (CVD) (odds ratio (OR) = 1.462, 95% confidence interval (CI) 1.085-1.972, P = 0.013), and the risk was twofold higher in patients with sarcopenia and anemia than in those without (OR = 3.283, 95% CI 2.038-5.289, P < 0.001). In follow-up studies, sarcopenia was associated with an increased risk of CVD at 10 years, and a reduction in appendicular skeletal muscle mass index independently predicted the increased risk of CVD. CONCLUSION: Sarcopenia is associated with an increased risk of anemia, and the presence of both has an additive effect on the 10-year CVD risk in patients with type 2 diabetes. Loss of muscle mass can independently predict an increased CVD risk in diabetic patients.

Association of decreased muscle mass with reduced bone mineral density in patients with Graves' disease.

AIM: 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' disease at diagnosis (mean age 41.2 years) were enrolled for a cross-sectional study; of these, 287 were enrolled for a cohort study with a median follow-up of 24 months. Meanwhile, 1164 age- and sex-matched healthy controls were recruited. All participants underwent dual-energy x-ray absorptiometry and muscle mass index (ASMI) measurements. The changes in ASMI and bone mineral density (BMD) were calculated from the measurements made at a gap of 2 years. RESULTS: The BMD of patients with Graves' disease was still significantly lower after normalizing serum thyroid hormone levels compared with that of healthy controls. ASMI positively correlated with BMD in patients with Graves' disease (lumbar BMD, r = 0.210; femoral neck BMD, r = 0.259; hip BMD, r = 0.235; P < 0.001), and this relationship persisted after successful anti-thyroid therapy (lumbar BMD, r = 0.169; femoral neck BMD, r = 0.281; hip BMD, r = 0.394; P < 0.001). Low muscle mass was associated with low BMD (OR, 1.436; 95% CI, 1.026-2.010). Improving the muscle mass led to changes in the bone mass of the femoral neck (OR, 0.420; 95% CI, 0.194-0.911) and hip (OR, 0.217; 95% CI, 0.092-0.511) during the follow-up. However, this phenomenon was not observed in lumbar and bone turnover markers. CONCLUSIONS: The recovery of bone mass might be related to the recovery of the muscle mass. Patients with Graves' disease should be helped to regain their muscle mass and thus accelerate the recovery of bone mass while administering anti-thyroid therapy.

Association of sarcopenia with a higher risk of infection in patients with type 2 diabetes.

AIMS: This study aimed to determine whether patients with type 2 diabetes and sarcopenia had a higher risk of infection. STUDY DESIGNS: A cross-sectional study and a follow-up study were performed. METHOD: A total of 2562 patients were enrolled and assessed for body composition and infection status. They were classified into four groups according to body fat (BF) and muscle mass index (ASMI): obese, sarcopenic, sarcopenic obese, and normal. Among these, 275 patients were followed for a median follow-up period of 1.84 years to evaluate the relationship of changes in skeletal muscle with infection status. RESULTS: The sarcopenic and sarcopenic obese groups showed a higher risk of infection, an increase by 49.6% (OR = 1.496, 95% CI 1.102-2.031) and 42.4% (OR = 1.424, 95% CI 1.031-1.967) compared with the normal group, and also had a higher risk of respiratory infection, an increase by 56.0% (OR = 1.560, 95% CI 1.084-2.246) and 57.4% (OR = 1.574, 95% CI 1.080-2.293), respectively. Patients with the increased ASMI (OR = 0.079, 95% CI 0.021-0.298) represented a lower risk of infection than those with the decreased ASMI. Even a minor change (OR = 0.125, 95% CI 0.041-0.378) against age was beneficial to lowering the risk of infection. However, no association was found in the changes of body mass index and BF with infection status. CONCLUSIONS: Sarcopenia, especially in patients with diabetes who are also obese, increases the risk of infection. Maintaining or improving muscle mass is expected to reduce infections.

Evaluation of osimertinib for advanced non-small cell lung cancer with leptomeningeal metastases: a cost-effectiveness and budget impact analysis.

Background Few regimens for non-small cell lung cancer (NSCLC) with leptomeningeal metastases (LM) patients exist up to date, most with low efficacy. A retrospective analysis showed that osimertinib significantly improved the overall survival of LM patients by 11.5 months (17.0 vs. 5.5) as compared to no osimertinib treatment. Until now, no pharmacoeconomic evaluation of osimertinib has been performed to determine its feasibility for widespread use in LM patients. Aim This study analyzed the cost-effectiveness of osimertinib in LM of NSCLC from the perspective of the Chinese health care system. Methods Based on a retrospective analysis from the Samsung Medical Center, a Markov model was constructed to estimate the lifetime benefits and costs for LM patients who were treated with osimertinib. The main outcomes were cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). Sensitivity analyses were performed to verify the robustness of model. A budget impact analysis was conducted to estimate the annual incremental cost of osimertinib treatment. Results Compared with patients who were not treated with osimertinib, the survival time of patients treated with osimertinib was higher by 0.69 (1.24 vs. 0.55) QALYs. The incremental cost was $11,877 ($29,232 vs. $17,355) and the ICER was $17,214/QALY, which was below the willingness-to-pay threshold of $30,867/QALY. Osimertinib treatment will increase national cancer spending by $220 million in the first year and increase to $474 million in the fifth year. Conclusions Osimertinib treatment is deemed to be cost-effective for NSCLC with LM patients, however, its use would significantly increase annual cancer spending.

Identification of independent risk factors for diabetic neuropathy progression in patients with type 2 diabetes mellitus.

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.

Effect of multimodal preemptive analgesia on postoperative gastrointestinal function and clinical outcome in patients undergoing laparoscopic colorectal surgery.

OBJECTIVE: This study aimed to investigate the effects of multimodal preemptive analgesia on postoperative gastrointestinal function and clinical outcomes in patients undergoing laparoscopic colorectal surgery. METHODS: This prospective study included a total of 108 patients undergoing elective laparoscopic colorectal surgery from June 2019 to June 2020. The patients were divided into the control group and the study group according to the random number table method. Patients in the study group were given flurbiprofen axetil and oxycodone before skin incision combined with bilateral transverse abdominis plane block (TAPB) before anaesthesia induction. In the control group, patients were given sufentanil and flurbiprofen axetil combined with bilateral TAPB in postanaesthesia care unit (PACU). The incidence of postoperative gastrointestinal dysfunction (POGD), I-FEED score, inflammatory factor levels, rehabilitation indicators, postoperative pain assessment and other organ complications were observed and compared between the two groups. RESULTS: The incidence of POGD in the study group was lower compared to the control group, and the difference was statistically significant (P < .05). The study group had lower total and mean scores of I-FEED at 24, 48, 72 and 96 hours after surgery; however, the differences were not statistically significant (P > .05). On the first and third day after operation, Lipopolysaccharide (LPS), C-reactive protein (CRP), Tumour necrosis factor (TNF-α) and Interleukins6 (IL-6) levels of the study group decreased significantly (P < .05). The reduction in inflammation factor levels from 1d to 3d was significantly greater than that of the control group (P < .05). CONCLUSION: The strategy of multimodal preemptive analgesia can effectively prevent the onset of POGD and may accelerate rehabilitation. In short, multimodal preemptive analgesia provides a novel prevention strategy for patients undergoing laparoscopic colorectal surgery.

Relationship between Hyponatremia and Peripheral Neuropathy in Patients with Diabetes.

OBJECTIVES: Hyponatremia is a common complication of diabetes. However, the relationship between serum sodium level and diabetic peripheral neuropathy (DPN) is unknown. This study was aimed at investigating the relationship between low serum sodium level and DPN in Chinese patients with type 2 diabetes mellitus. METHODS: A retrospective study was performed on 1928 patients with type 2 diabetes between 2010 and 2018. The multivariate test was used to analyze the relationship between the serum sodium level and the nerve conduction function. A restricted cubic spline was used to flexibly model and visualize the relationship between the serum sodium level and DPN, followed by logistic regression with adjustment. RESULTS: As the serum sodium level increased, the prevalence of DPN had a reverse J-curve distribution with the serum sodium levels (69.6%, 53.7%, 49.6%, 43.9%, and 49.7%; P = 0.001). Significant differences existed between the serum sodium level and the motor nerve conduction velocity, sensory nerve conduction velocity, part of compound muscle action potential, and sensory nerve action potential of the participants. Compared with hyponatremia, the higher serum sodium level was a relative lower risk factor for DPN after adjusting for several potential confounders (OR = 0.430, 95%CI = 0.220-0.841; OR = 0.386, 95%CI = 0.198-0.755; OR = 0.297, 95%CI = 0.152-0.580; OR = 0.376, 95%CI = 0.190-0.743; all P < 0.05). Compared with low-normal serum sodium groups, the high-normal serum sodium level was also a risk factor for DPN (OR = 0.690, 95%CI = 0.526-0.905, P = 0.007). This relationship was particularly apparent in male participants, those aged <65 years, those with a duration of diabetes of <10 years, and those with a urinary albumin - to - creatinine ratio (UACR) < 30 mg/g. CONCLUSIONS: Low serum sodium levels were independently associated with DPN, even within the normal range of the serum sodium. We should pay more attention to avoid the low serum sodium level in patients with type 2 diabetes mellitus.

Stronger Association of Albuminuria with the Risk of Vascular Complications than Estimated Glomerular Filtration Rate in Type 2 Diabetes.

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: <30 mg/g) and eGFR (mL/[min × 1.73 m2]) (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.

Influence of glucose, insulin fluctuation, and glycosylated hemoglobin on the outcome of sarcopenia in patients with type 2 diabetes mellitus.

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 < 0.05). 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.

Diabetic Peripheral Neuropathy Is Associated With Higher Systolic Blood Pressure in Adults With Type 2 Diabetes With and Without Hypertension in the Chinese Han Population.

OBJECTIVES: 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. METHODS: 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. RESULTS: Irrespective of hypertension, systolic blood pressure (SBP) and glycated hemoglobin levels in the DPN group were higher than those in the non-DPN group (p<0.001). In hypertensive patients, blood pressure goal achievement was lower in the DPN group compared with the non-DPN group (31.1% vs 40.5%, p<0.05). Compared with the nerve conduction velocity Q1 (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 (p<0.05). 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; p<0.01) in nonhypertensive patients with diabetes. CONCLUSIONS: 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.

Irisin regulates the expression of BDNF and glycometabolism in diabetic rats.

Irisin is a proteolytic product of the fibronectin type III domain­containing 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 Irisin­short hairpin (sh)­RNA (irisin interference). The levels of irisin, brain­derived 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 Irisin­shRNA 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. Irisin­shRNA 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 microtubule­associated protein­2 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 irisin­shRNA, however, it was markedly improved following irisin treatment. The mRNA and protein levels of BDNF in the primary cells were evaluated by fluorogenic reverse transcription­quantitative 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.

Low-grade albuminuria is associated with poor memory performance in the nondemented Chinese elderly with type 2 diabetes.

Recent studies have correlated cognitive function with albuminuria. We investigated the association between low-grade albuminuria and cognitive performance in nondemented elderly with type 2 diabetes in Fuzhou, China. Between January, 2013 and December, 2014, a retrospective study was performed in 815 patients with type 2 diabetes (398 female and 417 male patients), ages ≥60 years, with normal urinary albumin to creatinine ratios (UACR <30 mg/g). Patients were stratified into tertiles based on UACR levels (lowest tertile, UACR <5.8 mg/g; highest tertile, UACR ≥18.1 mg/g). Cognitive function was measured using the Mini Mental State Examination. UACR tertiles correlated directly (p < 0.05) with age, duration of diabetes, systolic blood pressure (SBP), and pulse wave velocity (PWV). Patients in the second and highest tertiles performed significantly worse on memory and language than those in the lowest UACR tertile (p < 0.05). The association between UACR and memory loss was stronger in patients younger than 70 years of age and in those with a history of diabetes for less than 10 years. Low-grade albuminuria is associated with poor memory performance, especially in the youngest old (60-69 years) and in those with shorter duration of diabetes (< 10 years). Type 2 diabetics with urinary albumin excretion in the upper normal range were also at risk for declining memory performance.

Osteocalcin Improves Metabolic Profiles, Body Composition and Arterial Stiffening in an Induced Diabetic Rat Model.

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.