Glycemic control and comprehensive metabolic risk factors control in older adults with type 2 diabetes.

BACKGROUND: Older adults with type 2 diabetes are prone to multiple metabolic abnormalities. However, data from these patients on comprehensive metabolic risk factors control are limited. METHODS: The present study included 2736 older adults aged 60 to 90 years with type 2 diabetes from 114 hospitals across 22 provinces in China. Metabolic abnormalities, including hypertension, dyslipidemia, hyperuricemia, and obesity, were recorded. Comprehensive metabolic risk factors control included the control of hemoglobin A1c (HbA1c) level, blood pressure, serum lipids level, serum uric acid level, and body mass index. The target glycemic control was defined as HbA1c <7%. RESULTS: The proportion of older adults who achieved the HbA1c target was 23.0%. The glycemic control rate increased with the number of metabolic abnormalities increased. The patients who had all four metabolic abnormalities had 4.05 times (95% confidence interval: 2.16, 7.61) the odd to meet glycemic target than those with none of metabolic abnormalities. However, only 4.6% of patients met the targets for all 5 metabolic risk factors. The comprehensive rate of all 5 factors in control decreased from 13.4% to 0% with the number of metabolic abnormalities increased. CONCLUSION: The glycemic control rate and the comprehensive metabolic risk factors control rate were 23.0% and 4.6%, respectively. As the number of metabolic abnormalities increased, the number of risk factor targets achieved decreased. Our findings suggest that a strategy for comprehensive control is urgently needed in older adults with type 2 diabetes, especially in those with co-existing metabolic abnormalities.

Angiotensin Type 2 Receptor Agonist C21 Ameliorates the High-Fat Diet-Induced Pancreatic ß-Cell Dysfunction Partially by Activation of Antiapoptosis and Autophagy.

OBJECTIVE: We aim to investigate whether C21, a selective angiotensin type 2 receptor agonist, can exert protective effects on pancreatic ß-cells through activation of antiapoptosis and autophagy. METHODS: The high-fat diet-induced obese rats (HFDs) were under C21 treatment for 4 weeks. RESULTS: C21 treatment decreased the fasting glucose levels and improved ß-cell insulin secretory function in the HFD group. Hematoxylin and eosin staining and electron microscopy indicated that the islet morphology was improved in the C21-treated obese rats, which was associated with increased levels of the key transcription factor PDX1, glucose sensing, and uptaking protein GCK and GLUT2, respectively. C21 treatment exerted antiapoptotic effects through decreasing the levels of apoptotic marker Caspase-3 while increasing the levels of antiapoptotic markers AKT, p-AKT, and BCL2. C21 treatment also induced autophagosome formation in the mitochondria of the ß-cells in the HFD group accompanied by increased levels of autophagy markers, LC-3B and Beclin-1. CONCLUSIONS: The results suggested C21 treatment decreased the fasting glucose level and protected ß-cell function in the HFD-induced obese rat model, which in part through activation of antiapoptotic and autophagy processes. This study provided preclinical evidence for the utilization of C21 in the treatment of type 2 diabetes.

Subthreshold depression among diabetes patients in Beijing: Cross-sectional associations among sociodemographic, clinical, and behavior factors.

BACKGROUND: This study explores the prevalence of subthreshold depression (SubD) and its association with factors in type 2 diabetes mellitus (T2DM) patients. METHODS: This cross-sectional study involved 808 outpatients with T2DM from ten hospitals in Beijing between September 2015 and January 2016. All participants completed the Patient Health Questionnaire 9-item (PHQ-9) to evaluate depressive status, with scores between 5 and 14 considered SubD. Conditional logistic regression was conducted to investigate the variables associated with SubD in T2DM patients. RESULTS: T2DM patients with SubD comprised 11.6% (n = 94) of the sample. The odd ratios for the variables having significant positive associations with SubD were: being a women (OR = 1.90; 95%CI: 1.09-3.32), divorced/widowed (OR = 3.27; 95%CI: 1.46-7.30), comorbidity of cerebrovascular disease (OR = 2.00; 95%CI: 1.06-3.76), more diabetic complications (OR = 8.04; 95%CI: 2.77-23.31), and higher HbA1c in men (OR = 2.41; 95%CI: 1.25-4.64). Being older (OR = 0.78; 95%CI: 0.62-0.98), exercising more (OR = 0.44; 95%CI: 0.22-0.91) and poverty (OR = 0.36; 95%CI: 0.19-0.69) were negatively related to SubD. LIMITATIONS: The sample was mainly recruited from hospital settings, which limits generalization. The study's cross-sectional design precludes making causal inferences. CONCLUSIONS: The proportion of SubD was estimated to be 11.6% among T2DM patients in Beijing. Having more diabetic complications and being divorced/widowed made the odds of having SubD 8-fold and 3-fold higher than not having it, respectively. The relationship between SubD and diabetes necessitates early screening for milder forms of depression, which can alleviate the social burden and individual impairment from major depression or other chronic diseases.

Renoprotective effects of emodin against diabetic nephropathy in rat models are mediated via PI3K/Akt/GSK-3ß and Bax/caspase-3 signaling pathways.

Emodin is the main active component of the Chinese medicine rhubarb, which has a variety of pharmacological effects and a high clinical value. Its anti-inflammatory and antitumor effects have been widely studied. The aim of the present study was to determine whether emodin has renoprotective effects, and to identify the potential underlying mechanisms in a rat model of diabetic nephropathy (DN). The changes in mean blood glucose levels, normalized kidney weight, urinary albumin excretion, serum creatinine levels and tubulointerstitial injury index (TII) scores of the rats with DN were significantly attenuated by emodin. Furthermore, treatment with emodin significantly inhibited inflammation-related factors and oxidative stress, suppressed the expression of intercellular adhesion molecule 1 (ICAM-1) and B-cell lymphoma 2-associated X protein (Bax), increased phosphorylated Akt and phosphorylated-glycogen synthase kinase 3 (p-GSK-3ß) expression and inhibited caspase-3 activity in diabetic rats. These data suggest that emodin protects against DN and that the underlying mechanism may involve the suppression of inflammation, ICAM-1 and Bax, and activation of the PI3K/Akt/GSK-3ß pathway.

Telmisartan combined with probucol effectively reduces urinary protein in patients with type 2 diabetes: A randomized double-blind placebo-controlled multicenter clinical study.

BACKGROUND: Persistent proteinuria is an important factor contributing to the progression of diabetic nephropathy. The present randomized double-blind placebo-controlled multicenter clinical study evaluated the efficacy and safety of telmisartan combined with the antioxidant probucol in reducing urinary protein levels in patients with type 2 diabetes (T2D). METHODS: Patients with T2D and 24-h proteinuria 0.5-3 g were enrolled in the study and randomly assigned to one of two groups: a telmisartan or a probucol + telmisartan group. Both groups were given telmisartan 80 mg q.d. for 48 weeks. The probucol + telmisartan group was given probucol 500 mg b.i.d. for the first 24 weeks, with the dosage then reduced to 250 mg b.i.d. for the remaining 24 weeks. The telmisartan group was given probucol placebo. RESULTS: In all, 160 patients were enrolled in the present study. The 24-h proteinuria levels were significantly reduced in the probucol + telmisartan compared with telmisartan group. For patients with baseline 24-h proteinuria levels <1.0 g, both treatments resulted in significant reductions in 24-h proteinuria levels after 48 weeks treatment. However, in patients with baseline 24-h proteinuria levels ≥1.0 g, 24-h proteinuria levels after 48 weeks treatment were only reduced in the probucol + telmisartan group. There was no significant difference between the two groups for either adverse cardiovascular or other events. CONCLUSIONS: In patients with diabetic nephropathy, probucol combined with telmisartan more effectively reduces urinary protein levels than telmisartan alone.

Prevalence and influencing factors of co-morbid depression in patients with type 2 diabetes mellitus: a General Hospital based study.

BACKGROUND: Depression and diabetes have been recognized as major public health issues in China, however, no studies to date examined the factors associated with the development of depression in patients with diabetes in China. This study aimed to estimate the prevalence of co-morbid depression among adults with type 2 diabetes mellitus (DM) and to examine the influence factors of co-morbid depression in a group of patients with type 2 DM. METHODS: The study was conducted from March l to May 31, 2012, in the Department of Endocrinology of the First Affiliated Hospital of the General Hospital of the People's Liberation Army (PLA). A systematic random sample of 412 type 2 DM patients aged over 18 years was selected. A structured questionnaire was used for collecting the information about socio-demographic data, lifestyle factors and clinical characteristics. Depression and social support was evaluated by using the Chinese version of Beck Depression Inventory (BDI) and Social Support Rate Scale (SSRS), respectively. Weights and heights were measured. Hemoglobin A1c (HbA1c) was abstracted from each patient directly after the interview. RESULTS: Of the total sample, 142 patients had depression according to the BDI scores (BDI scores ≥14), the prevalence of co-morbid depression in this study population was 5.7 % (142/2500). Of which, 56 had major depression (BDI ≥ 21), and 86 had moderate depression (BDI ≥ 14&BDI < 21). Logistic regression analysis indicated that a high HbA1c level, a high BMI, low quality health insurance, and being single, were significantly associated with the development of depression. However, a family history of diabetes and a high social support level are likely protective factors. CONCLUSIONS: The prevalence of co-morbid depression was 5.7 % among Chinese subjects with type 2 DM in this study. High HbA1c level, high BMI score, being single, low social support level, and low quality health insurance were associated with the presence of depression. These findings support a recommendation for routine screening and management in China for depression in patients with diabetes, especially for those in primary care, to reduce the number of the depressed or the misrecognized depressed diabetic patients.

Overexpression of angiotensin II type 2 receptor promotes apoptosis and impairs insulin secretion in rat insulinoma cells.

Angiotensin II (Ang II), the major effector hormone of renin-angiotensin system, acts as a promoter of insulin resistance and diabetes mellitus type 2 pathogenesis. Activation of Ang II type 2 receptor (AT2R) has been examined as a potential therapeutic strategy. However, there are conflicting findings regarding the role of AT2R. In the current study, we evaluated the effects of overexpressing AT2R by viral vector transduction on the apoptosis and function of pancreatic ß-islet cells. The rat insulinoma cell line, INS-1, was transduced with a recombinant adenoviral vector expressing AT2R (Ad-G-AT2R-EGFP). AT2R overexpression resulted in significantly reduced cell viability and subsequently impaired glucose-stimulated insulin secretion (GSIS) function in INS-1 cells. Down-regulated expressions of GSIS pathway components, insulin, glucose transporter 2, and glucokinase were associated with AT2R overexpression. Further analysis determined that overexpression of AT2R induced G1-phase cell cycle arrest and Ang II-independent apoptotic cell death as indicated by increased Annexin V staining. To understand the apoptosis signaling triggered by AT2R overexpression, levels of caspase proteins were measured. Overexpression of AT2R significantly induced caspase-8, caspase-9, and caspase-3 cleavage, and decreased Bcl-2, pAkt, and pERK expression levels. AT2R-induced cell apoptosis was successfully blocked by the caspase inhibitor Z-VAD-FMK. Our findings suggested that AT2R overexpression triggers the apoptosis of INS-1 cells and dysfunction in insulin secretion. In conclusion, more careful design and consideration are required when applying AT2R-related therapies in treating diabetes.

Insulin therapy and colorectal cancer risk among type 2 diabetes mellitus patients: a systemic review and meta-analysis.

BACKGROUND: Insulin is widely used in patients with type 2 diabetes mellitus (T2DM). More attention was focused on its higher risk of colorectal cancer (CRC). This meta-analysis examined the relationship between levels of insulin use and the risk of CRC. METHODS: A meta-analysis using data from 12 published epidemiologic studies (7 case-control, and 5 cohort studies) published before Jan. 2014 was done to examine the association between insulin use and CRC. Random effects analyses were done to calculate relative risk (RR) and 95% confidence intervals (CI). Heterogeneity among studies was measured by the χ2 and I2 statistic. RESULTS: Overall, the risk of CRC was significantly associated with insulin use to a random-effects model (RR, 1.69; 95% CI, 1.25 -2.27). When subgroup analyses were conducted according to the study types, no associations were detected in cohort group (RR, 1.25; 95% CI, 0.95-1.65; I2, 75.7%); however significant association was detected in case-control group (RR, 2.15; 95% CI, 1.41-3.26; I2, 89.1%). CONCLUSIONS: A significant harmful effect of insulin, observed mainly among case-control studies, may result from study design differences and amount of included studies. Although these results suggest a harmful effect of insulin use for CRC risk, additional large studies are warranted to support these preliminary evidences. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2194715731194123.

Predictive factors of outcomes in personalized radioactive iodine ((131)I) treatment for Graves' disease.

BACKGROUND: Graves' disease (GD) is the most common cause of hyperthyroidism in iodine-sufficient areas. Radioactive iodine I treatment (RIT), as the 1st therapeutic option, is widely accepted by doctors and patients. The aim of this study was to investigate factors influencing the success rate of calculated RIT in GD. METHODS: Thyroid function outcome (hyperthyroidism or euthyroidism/hypothyroidism) was verified retrospectively at least 1 year after RIT and was compared with presenting clinical characteristics and pre-RIT parameters in 167 patients with GD treated with I-iodide in the authors' institute. RESULTS: After RIT, 83 patients (49.7%) became euthyroid, 64 patients (38.3%) became hypothyroid and 20 (12.0%) remained hyperthyroid. Multiple logistic regression analyses demonstrated that there was no statistically significant association between RIT outcomes and sex, age, history of GD, previous antithyroid drug treatment, thyroid hormone levels, thyroid gland mass or radioactive iodine I dosage. The only variables associated with the success rate were the course of disease over 6 months (odds ratio, 3.70; confidence interval, 1.75-7.17; P = 0.014) and 2-hour radioactive iodine uptake (RAIU) >58.5% (odds ratio, 4.08; confidence interval, 2.03-7.83; P = 0.005). CONCLUSIONS: Our study has shown that a calculated approach for the treatment of GD was effective, but high failure rates were observed in patients presenting higher 2-hour RAIU, particularly those with 2-hour RAIU of more than 58.5%.

Association between interleukin 10 gene polymorphisms and risk of type 2 diabetes mellitus in a Chinese population.

OBJECTIVE: To investigate the relationship between the interleukin 10 (IL10) gene single nucleotide polymorphisms (SNP) -1082 G/A (rs1800896), -819 T/C (rs1800871) and -592 A/C (rs1800872) and risk of type 2 diabetes mellitus in a Chinese population. METHODS: This case-control study recruited patients with type 2 diabetes mellitus and healthy control subjects. Genotyping of the -1082 G/A (rs1800896), -819 T/C (rs1800871) and -592 A/C (rs1800872) SNPs was conducted and genotype frequencies were compared between the two groups. RESULTS: The study recruited 364 patients with type 2 diabetes mellitus and 677 healthy controls. Patients carrying the -1082 GG genotype had a significantly increased risk of type 2 diabetes mellitus (adjusted odds ratio [OR] 1.57, 95% confidence interval [CI] 1.03, 2.68), as did those patients carrying the -592 AA genotype (adjusted OR 1.63, 95% CI 1.06, 2.53). Subjects carrying both the -1082 GA + GG and -592 AC + AA genotypes had a significantly increased risk of type 2 diabetes mellitus (adjusted OR 2.03, 95% CI 1.24, 3.15). CONCLUSIONS: The SNPs -1082G/A and -592 A/C increased the risk for type 2 diabetes mellitus, and could be potential targets for screening for the early detection of the risk of type 2 diabetes mellitus.

Randomized controlled trial of zoledronic acid for treatment of osteoporosis in women.

OBJECTIVE: To assess the effect of zoledronic acid (ZOL) on bone mineral density (BMD) and fracture risk at the L1-L4 vertebrae, femoral neck, hip and trochanter in Chinese women with osteoporosis. METHODS: A randomized controlled trial was conducted in female patients with osteoporosis, randomized to receive one 5-mg ZOL intravenous infusion per year or placebo equivalent. Facture risk and BMD were measured over a 2-year follow-up period. RESULTS: A statistically significant reduction in the risk of fracture was observed at the trochanter in the ZOL group (n = 242) compared with the placebo group (n = 241); (odds ratio 0.54 [95% confidence interval 0.29, 0.98]): BMD was 0.24, 0.28, 0.31 and 0.22 greater at the L1-L4 vertebrae, total hip, femoral neck and trochanter, respectively, in the ZOL group. The incidence of adverse events was comparable between treatment groups. CONCLUSIONS: This study indicated that ZOL could increase BMD and reduce fracture risk in women with osteoporosis over a 2-year follow-up period, and was not associated with any serious drug-related adverse effects.

[The safety and effectiveness of once daily detemir in patients with type 2 diabetes previously failing oral agents: the Chinese cohort from SOLVE(TM) observational study].

OBJECTIVE: Study of Once-daily LeVEmir(®) (SOLVE(TM)) was a 24-week international observational study to evaluate the safety and effectiveness of initiating once-daily insulin detemir (Levemir) as add-on therapy in patients with type 2 diabetes mellitus (T2DM) who failed treatment of oral anti-diabetic drugs (OAD). METHODS: The present study was derived from the data of Chinese cohort. A total of 3272 patients with T2DM failing OAD were enrolled in the study. Determir were prescribed to the patients by the decision of the physician. Clinical data were collected at baseline, week 12 and week 24 to evaluate the safety and effectiveness of detemir. RESULTS: The age of the patients was (56.2 ± 10.8) years with a diabetes duration of (7.1 ± 5.2) years. Their BMI was (25.3 ± 3.3) kg/m(2). No patient experienced any major or nocturnal hypoglycaemic event during the study. After 24 weeks of treatment, the glycosylated hemoglobin A1c (HbA1c) decreased from (8.33 ± 1.69)% to (7.16 ± 1.18)% with a mean change of -1.17%, the fasting plasma glucose decreased from (9.52 ± 2.59) mmol/L to (6.84 ± 1.42) mmol/L with a mean change of -2.7 mmol/L, and the 7-point blood glucose profile improved overall. Totally 49.1% of patients achieved HbA1c < 7%. The mean body weight decreased by 0.15 kg. CONCLUSIONS: Insulin detemir administered once daily as add-on therapy in patients with T2DM failing OAD regimen significantly reduces the risk of major hypoglycemia, improves glycemic control, increases the percentage of patients achieving treatment target with neutral effect on body weight.

Pharmacokinetics, tissue distribution and excretion of recombinant human parathyroid hormone 1-84 in animals.

To study the plasma pharmacokinetics and accumulation of the recombinant human parathyroid hormone (rhPTH) (1-84) in rhesus monkeys, and the tissue distribution and excretion profiles of (125)I-rhPTH (1-84) in rats. The concentration of rhPTH (1-84) in plasma samples were determined by an enzyme immunoassay (EIA) method after subcutaneous and intravenous bolus injection. The tissue distribution and urinary, fecal and biliary excretion patterns of (125)I-rhPTH (1-84) were investigated by trichloroacetic acid (TCA) precipitation method. Following subcutaneous (sc) administration rhPTH (1-84) in rhesus monkeys, rhPTH (1-84) exhibited rapid absorption and elimination and had no accumulated tendency after successive sc administration. Following sc administration (125)I-rhPTH (1-84) in rats, the TCA-precipitated radioactivity was widely distributed and rapidly diminished in most tissues. Approximately 83.9 and 6.8 % of the total radioactivity was recovered in urine and feces by 72 h postdosing, respectively; whereas 4.1 % excreted into bile up to 24 h postdosing. The pharmacokinetics of rhPTH (1-84) complied with linear kinetics within the examined dose range following a single sc administration had no accumulated tendency following multiple sc administration in rhesus monkeys. The accumulation of (125)I-rhPTH (1-84) in tissues/organs examined, appeared to be low in rats. The major elimination route was by urinary excretion.

[The baseline characteristics of patients with type 2 diabetes initiating insulin detemir : the Chinese cohort from the SOLVE(TM) study].

OBJECTIVE: To characterize the baseline status of Chinese diabetic patients based on data derived from Chinese cohort from SOLVE(TM) study. METHODS: Patients with type 2 diabetes initiating basal insulin detemir at the decision of the physician were eligible for the study. Data on demographics, medical history, glycemic profile and treatment regimen at baseline were collected by physicians. RESULTS: A total of 3272 patients [female 42%, male 58%, mean age (56.2 ± 10.8) years] were included in the study. Their BMI was (25.3 ± 3.3) kg/m(2). The duration of diabetes was 4.0 (0.1 - 27.0) years, and the duration of treatment with oral antidiabetic drugs (OADs) was 3.0 (0.0 - 20.2) years. The proportions of subjects with diabetic macro- and micro-vascular complications were 15.8% (515 cases) and 27.1% (866 cases), respectively. The hemoglobin A1c (HbA1c) at baseline was (8.33 ± 1.70)%, and the fasting blood glucose (FPG) was (9.5 ± 2.6) mmol/L. CONCLUSIONS: A large proportion of patients with type 2 diabetes remain in poor glycemic control, and the prevalence of diabetic complications is high, which requires optimal therapeutic strategy for the patients with suboptimal glycemic control.

Interaction between the polyol pathway and non-enzymatic glycation on mesangial cell gene expression.

BACKGROUND/AIMS: Both activation of the polyol pathway and enhanced non-enzymatic glycation have been implicated in the pathogenesis of diabetic glomerulopathy. We investigated the interaction between these two pathways using normal mesangial cells (MCs) and transgenic (TG) MCs with elevated aldose reductase (AR) activity. METHODS: TG mice with expression of the human AR (hAR) gene in kidney MCs were established. Mouse glomeruli and primary cultures of MCs from hAR TG and wild-type (WT) mice were studied regarding the changes in AR activity, transforming growth factor-beta1 (TGF-beta1) and type IV collagen mRNA and protein levels, in response to BSA modified by advanced glycation end-products (AGE-BSA). RESULTS: Ex vivo addition of AGE-BSA increased AR activity, TGF-beta1 and type IV collagen mRNA levels in both WT and TG glomeruli, with greater rise in TG glomeruli. These increments were attenuated by zopolrestat, an AR inhibitor. In cultured MCs, AGE-BSA enhanced AR activity, TGF-beta(1) and type IV collagen mRNA and protein levels both in WT and TG MCs, again with greater increases in TG MCs. The AGE-induced enhancement in TGF-beta1 and type IV collagen expression were suppressed by either zopolrestat or transfection with an AR antisense oligonucleotide. CONCLUSION: These data suggest that the activation of the polyol pathway by AGEs, more marked in genetic conditions with increased AR activity, may contribute to the pathogenesis of diabetic glomerulopathy, through enhancing mesangial cell expression of TGF-beta1 and type IV collagen.

Adiponectin ameliorates dyslipidemia induced by the human immunodeficiency virus protease inhibitor ritonavir in mice.

Although the clinical application of HIV protease inhibitors (PIs) has markedly reduced HIV-related morbidity and mortality, it is now recognized that PI-based therapy often causes serious metabolic disorders, including hyperlipidemia and premature atherosclerosis. The etiology of these adverse effects remains obscure. Here, we demonstrate that deficiency of the fat-derived hormone adiponectin might play a role. The steady-state mRNA levels of the adiponectin gene and secretion of this protein from 3T3-L1 adipocytes are significantly decreased after treatment with several PIs (indinavir, nelfinavir, and ritonavir), with ritonavir having the greatest effect. Intragastric administration of ritonavir into mice decreases plasma concentrations of adiponectin and concurrently increases the plasma levels of triglyceride, free fatty acids, and cholesterol. Adiponectin replacement therapy markedly ameliorates ritonavir-induced elevations of triglyceride and free fatty acids. These beneficial effects of adiponectin are partly due to its ability to decrease ritonavir-induced synthesis of fatty acids and triglyceride, and to increase fatty acid combustion in the liver tissue. In contrast, adiponectin has little effect on ritonavir-induced hypercholesterolemia and hepatic cholesterol synthesis. These results suggest that hypoadiponectinemia is partly responsible for the metabolic disorders induced by HIV PIs, and adiponectin or its agonists might be useful for the treatment of these disorders.