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Background: The global epidemic of diabetes mellitus continues to grow and affects developed and developing countries alike. Intensive glycemic control is thought to modify the risks for vascular complications, hence the risks for diabetes-related death. We investigated the trend of diabetic vascular complication-related deaths between 2000 and 2016 in the global diabetes landscape. Methods: We collected 17 years of death certificates data from 108 countries in the World Health Organization mortality database between 2000 and 2016, with coding for diabetic complications. Crude and age-standardized proportions and rates were calculated. Trend analysis was done with annual average percentage change (AAPC) of rates computed by joinpoint regression. Results: From 2000 through 2016, 7,108,145 deaths of diabetes were reported in the 108 countries. Among them, 26.8% (1,904,787 cases) were attributed to vascular complications in damaged organs, including the kidneys (1,355,085 cases, 71.1%), peripheral circulatory (515,293 cases, 27.1%), nerves (28,697 cases, 1.5%) and eyes (5751 cases, 0.3%). Overall, the age-standardized proportion of vascular complication-related mortality was 267.8 [95% confidence interval (95% CI), 267.5–268.1] cases per 1000 deaths and the rate was 53.6 (95% CI 53.5–53.7) cases per 100,000 person-years. Throughout the 17-year period, the overall age-standardized proportions of deaths attributable to vascular complications had increased 37.9%, while the overall age-standardized mortality rates related to vascular complications had increased 30.8% (AAPC = 1.9% [1.4–2.4%, p < 0.05]). These increases were predominantly driven by a 159.8% increase in the rate (AAPC = 2.7% [1.2–4.3%, p < 0.05]) from renal complications. Trends in the rates and AAPC of deaths varied by type of diabetes and of complications, as well as by countries, regions and domestic income. Conclusion: Diabetic vascular complication-related deaths had increased substantially during 2000–2016, mainly driven by the increased mortality of renal complications. [ABSTRACT FROM AUTHOR]

See the response from Zhao et al. [ABSTRACT FROM AUTHOR]

Objective: Malignancy following renal transplantation remains inconsistent with the reported safety of kidney donation during the long-term follow-up.Methods: We conducted searches of the published literature which included healthy participants, recipients, living kidney donors (LKDs), and the availability of outcome data for malignancy. Eight from 938 potentially relevant studies were analyzed by means of fixed-effects model or random-effects model, as appropriately.Results: In 48,950 participants, the follow-up range was 18 months to 20 years, and the mean age of the subjects was approximately 41 years. The incidence rate with 95% confidence interval (CI) for malignancy after kidney transplantation was 0.03 (0.01–0.05) in recipients and 0.03 (0.1–0.07) in LKDs, giving a pooled incidence rate of 0.03 (95% CI 0.02–0.04). LKDs contrasted nondonors by the overall odds ratio and 95% CI for total cancer of 2.80 (2.69–2.92).Conclusions: Kidney transplantation was associated with an increased risk of cancer during a long-term follow-up. Long-term risk for cancer in LKDs and kidney recipients should be monitored. [ABSTRACT FROM AUTHOR]

Autoimmune diabetes is a disorder of immune homeostasis that leads to targeted insulin-secreting islet β cell destruction characterized by insulitis. Human amylin (hA) is an important neuroendocrine hormone co-secreted with insulin by pancreatic β cells. Here, we report hA immune-modulatory action through inducing regulatory T cells. We ex vivo-treated human peripheral blood mononuclear cells (hPBMCs) with hA for 24 h and counted CD4+Foxp3+ regulatory T cells (Treg) using flow cytometry. Diabetic status was monitored and splenic Treg were measured in non-obese diabetic (NOD) male mice. NOD mice were intraperitoneally injected once daily with hA (n = 25) or solvent for control (n = 25) for 7 months continuously. Spleen tissues were collected at the end of intervention and processed for flow cytometry and Western blot. We found a 2.9-fold (p < 0.05) increase of CD4+Foxp3+ Treg in hPBMCs treated with 10 nmol/L hA compared with negative control. Incidence of diabetes in hA-treated NOD mice decreased 44% (p = 0.045) in the 6th month and 57% (p = 0.0002) in the 7th month. Meanwhile, the hA treatment induced a 1.5-fold increase of CD4+Foxp3+ Treg from mouse splenocytes (p = 0.0013). Expression of transforming growth factor-β (TGF-β) and toll-like receptor-4 (TLR-4) were upregulated in hA-treated mice. Human amylin might protect against autoimmune diabetes via the induction of CD4+Foxp3+ Treg, which suggests a novel approach to improve autoimmune conditions. [ABSTRACT FROM AUTHOR]

Aims: This study aims to investigate the association between renin-angiotensin system gene polymorphism and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes.Methods: We consecutively included 1491 patients for the assessment of ACE I/D and AGT M/T gene polymorphisms in 345 DR cases and 1146 patients without retinopathy (DNR). Albuminuria was defined by urine albumin creatinine ratio and albumin excretion rate.Results: Compared with the NDR patients, the DR cases displayed a higher proportion of diabetic nephropathy (32.68% vs. 6.52%, χ2 = 150.713, p < 0.001). The DR cases and DNR individuals did not differ in the frequency of genotypes and alleles of ACE I/D and AGT M/T (all p > 0.05). Intriguingly, DR patients with obesity showed higher frequency of DD (χ2 = 4.181, p = 0.041), but no significant difference exists in the other stratified BMI and hypertension analyses (all p > 0.05). Binary logistic regression displays that the association of the ACE and AGT gene polymorphisms in DR patients is not significant after adjusting for confounding covariates in all the comparisons.Conclusions: The ACE and AGT gene polymorphisms are not associated with the progress of diabetes developing into retinopathy in Chinese patients with type 2 diabetes. However, more investigations are needed to further prove the association. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was used meta-analysis to investigate changes of serum tumor necrosis factor-alpha (TNF-α) in patients with type 1 diabetes mellitus (T1DM). Methods: Relevant literatures were identified from PubMed, Cochrane Library, CNKI, WanFang and Chinese-Cqvip databases (published from January 1, 1999 to September 30, 2016). Eligible reports were included for pooled analysis of serum TNF-α level and subgroup analysis was performed in relation with age, disease duration and ethnicity. Results: A total of 23 articles (1631 T1DM cases, 1429 healthy controls) were included for this meta-analysis. Compared with the controls, the patients had significantly increased serum TNF-α level (P < 0.001). Similar results were also found among all subgroup analysis of different age, disease duration and ethnicity (with the exception of Asian) (all P < 0.05). Regression analysis indicated that age (P = 0.680), disease duration (P = 0.957), and ethnicity (P = 0.526) of patients were not significant impact factors for the high heterogeneity. The results were stable according to the sensitivity analysis and no publication bias existed in this meta-analysis. Conclusions: Serum TNF-α level in T1DM patients has significantly elevated among all age, disease duration and ethnicity groups. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to investigate the changes of regulatory T cells (Treg), interleukin-6 (IL-6), IL-10, transforming growth factor-β (TGF-β), and tumor necrosis factor-alpha (TNF-α) in patients with type 2 diabetes mellitus (T2DM). Methods. We performed a comprehensive search up to July 2016 for all clinical studies about the changes of Treg, IL-6, IL-10, IL-17, TGF-β, and TNF-α in T2DM patients versus healthy controls. Results. A total of 91 articles (5642 cases and 7378 controls) were included for this meta-analysis. Compared with the controls (all p<0.001), the patients had increased serum levels of IL-6, TGF-β, and TNF-α but decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and serum IL-10 level. Furthermore, the percentage of peripheral CD4+CD25+Foxp3+Treg (p<0.001) and serum IL-10 level (p=0.033) were significantly lower in the patients with complication and in the patients without complication, respectively. No significant changes about the percentage of CD4+CD25+Treg (p=0.360) and serum IL-17 level (p=0.459) were found in T2DM patients. Conclusions. T2DM patients have decreased the percentage of peripheral CD4+CD25+Foxp3+Treg and levels of serum IL-10 but elevated serum levels of IL-6, TGF-β, and TNF-α. Presence of diabetic complications further lowers the peripheral CD4+CD25+Foxp3+Treg number. [ABSTRACT FROM AUTHOR]

Acquired immunodeficiency syndrome (AIDS) remains ill-defined by lists of symptoms, infections, tumors, and disorders in metabolism and immunity. Low CD4 cell count, severe loss of body weight, pneumocystis pneumonia, and Kaposi's sarcoma are the major disease indicators. Lines of evidence indicate that patients living with AIDS have both immunodeficiency and autoimmunity. Immunodeficiency is attributed to deficits in the skin- and mucosa-defined innate immunity, CD4 T cells and regulatory T cells, presumably relating human immunodeficiency virus (HIV) infection. The autoimmunity in AIDS is evident by: (1) overproduction of autoantibodies, (2) impaired response of CD4 cells and CD8 cells, (3) failure of clinical trials of HIV vaccines, and (4) therapeutic benefits of immunosuppression following solid organ transplantation and bone marrow transplantation in patients at risk of AIDS. Autoantibodies are generated in response to antigens such as debris and molecules de novo released from dead cells, infectious agents, and catabolic events. Disturbances in metabolic homeostasis occur at the interface of immunodeficiency and autoimmunity in the development of AIDS. Optimal treatments favor therapeutics targeting on the regulation of metabolism to restore immune homeostasis. [ABSTRACT FROM AUTHOR]

Gastroesophageal reflux disease (GERD) and bile reflux gastritis (BRG) are common gastrointestinal (GI) disorders with unmet medical needs. Traditional Chinese medicine has long been used for the treatment of GERD and BRG whereas the ginger-containing formula Wendan decoction (WDD) targets homeostatic disturbances characterized by "reflux" and "gut-juice exposure" problems. Here we used WDD as a therapeutic tool to unravel the common pathogenesis of GI reflux disorders. Control clinical trials reporting the WDD-treated patients with GERD and BRG were included in this systematic review and meta-analysis. Outcome measurements were clinical efficacy defined by symptom relief with normal GI endoscopy, radiology, and pathology. Eventually, 33 studies involved 3253 participants (1351 vs. 1035 of the BRG in 20 publications, 449 vs. 418 of the GERD in 13 studies, and 194 vs. 159 of relapse rate in 6 trials). Pooled data showed a consistent therapeutic efficacy of WDD on BRG (OR = 6.00, 95%C = 4.68-7.69) and GERD (OR = 4.39, 95%CI = 2.72-7.07). The relapse rate was 12.4% for WDD, significantly lower than 44.0% for conventional therapies (OR = 0.14, 95%CI = 0.08-0.26). The consistent therapeutic efficacy of the single TCM formula on GERD and BRD indirectly indicates reflux as a common pathogenesis in reflux-associated GI disorders. [ABSTRACT FROM AUTHOR]

Purpose. The objective of this study is to investigate the effect of dual blockage of renin-angiotensin system (RAS) on renal kallikrein expression and inflammatory response in diabetic nephropathy (DN). Methods. Rats were randomly divided into 5 groups with 10 rats in each group: normal control; DN model induced by high fat and high sucrose diets; and DN treated with either benazepril 10 mg/kg/d, irbesartan 30 mg/kg/d, or both. After 8-week treatment, we examined changes in the kidney histopathology, function and immunohistochemical stain of kallikrein, macrophage marker CD68, and profibrotic markers transforming growth factor- (TGF-) β and α-smooth muscle action (SMA). Results. DN rats showed enlarged kidneys with glomerulosclerosis, interstitial chronic inflammation and fibrosis, and proteinuria. All the pathological damage and functional impairments were improved after the RAS blockades (all P<0.05). Compared with monotherapy, combined treatment further alleviated the kidney impairments in parallel to increased tubular immunoreactivity for kallikrein and decreased immunopositive cells for CD68, TGF-β, and α-SMA. Conclusion. The renoprotective effects of the dual RAS blockade in diabetic nephropathy may be attributed to improved tubular kallikrein expression and interstitial inflammatory response. [ABSTRACT FROM AUTHOR]

Treatment of acquired immunodeficiency syndrome (AIDS) currently relies on the use of antiretroviral drugs. Little is known about Chinese herbal medicine (CHM) outcomes in patients living with AIDS. We conducted a cohort study to investigate long-term survival among CHM-treated AIDS patients. Patients were poor farmers who contracted HIV-1 infection when selling blood in the 1990s. Symptoms of AIDS included recurring respiratory tract infections with a clinical diagnosis of pneumonia, swollen lymph nodes and weight loss. 385 patients with AIDS were included and 165 of them used a 16-herb formula for 14 days to 9 months. The eight-year survival rate was 87% for the CHM users and 34% for the non-users (increased survival probability for CHM user, 9.6; 95% CI = 6.0-15.4; p < 0.0001). Survival probability further increased 14.6-fold (95% CI = 8.2-26.1), when excluding the users who received CHM for less than three months. Zero deaths were found in patients who used CHM for six to nine months. All the survivors regained their body weight and none of them experienced a relapse of AIDS or any severe adverse events. After the CHM treatment for an average of 3.6 months, the plasma HIV load was 74.7% lower (paired t-test, p = 0.151) and the number of blood CD4+ lymphocytes increased from 253 to 314 (paired t-test, p = 0.021). Without life-long medication, CHM may be beneficial for long-term survival of AIDS patients. [ABSTRACT FROM AUTHOR]

In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.57–3.96, P = 8.4×10−5). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02–1.12, Pmeta = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07–2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19–9.19, P = 0.0214) and 3.27(1.25–11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese. [ABSTRACT FROM AUTHOR]

Aims/Introduction Type 2 diabetes is characterized by dysregulation of immunity, oxidative stress and reduced incretin effects. Experimental studies suggest that glucagon-like peptide ( GLP-1) might have immunomodulating effects. We hypothesize that GLP-1 receptor agonist, exendin-4, might reduce inflammatory response in type 2 diabetes. Materials and Methods Using peripheral blood mononuclear cells ( PBMC) sampled from 10 type 2 diabetes and 10 sex- and age-matched control subjects and supernatants from PBMC culture, the expression of phospho-mitogen activated protein kinase ( MAPK) signaling pathways in CD4+ T helper lymphocytes and monocytes was analyzed using flow cytometry. Cytokines/chemokines and superoxide anion before and after treatment with exendin-4 were measured by cytometric bead array and chemiluminesence assay, respectively. Results Compared with control subjects, PBMC from type 2 diabetes patients showed activated MAPK ( P38, c-Jun NH2-terminal protein kinase and extracellular signal-regulated kinase) signaling pathway, elevated superoxide anion, increased pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) and chemokines ( CCL5/regulated on activation normal T-cell expressed and secreted and CXCL10/interferon-γ-induced protein 10). These changes were attenuated by exendin-4, possibly through the suppression of p38 MAPK. Conclusions These results suggest that exendin-4 might downregulate pro-inflammatory responses and reduce oxidative stress by suppressing MAPK signaling pathways in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Vinegar is a traditional remedy for ailments including diabetes. This study was conducted to investigate the beneficial effects of vinegar in streptozotocin (STZ)-induced diabetic rats. STZ-induced diabetic rats were orally administered with white rice vinegar (WRV, 2 ml/kg body weight per day, n = 6) or with an equal volume of drinking water ( n = 6) for 1 month. Fasting and random blood glucose was measured from tail vein samples. Body weight, 24-h food and water intake were monitored 1 week and 1 month after STZ injection. Fasting serum insulin concentrations were assayed using ELISA. Pancreatic beta- and alpha-cell proportions were measured using immunofluorescence microscopy. Periodic acid Schiff staining was performed to access glycogen contents and histological changes in liver tissues. Compared with control animals, the WRV-treated rats had less weight loss, lower fasting and random blood glucose, higher fasting serum insulin and higher beta-cell proportion. The WRV treatment also improved fatty changes and glycogen storages in the liver of STZ rats. Oral intake of WRV improved fasting hyperglycemia and body weight loss through attenuating insulin deficiency, pancreatic beta-cell deficit, and hepatic glycogen depletion and fatty changes in STZ-induced diabetic rats. [ABSTRACT FROM AUTHOR]

Tanshinone IIA (Tan IIA), a natural product from herb Salvia miltiorrhiza Bunge, has potential anti-tumor activity. The aim of this study was to pinpoint the molecular mechanisms underlying Tan IIA-induced cancer cell apoptosis. Human hepatoma BEL-7402 cells treated with Tan IIA underwent assessment with MTT assay for cell viability, 10-day culture for colony formation, flow cytometry and fluorescence microscopy for apoptosis and cell cycle analysis. Changes in intracellular [Ca] and mitochondrial membrane potential (∆ψ) reflected the calcium-dependent apoptosis pathway. RT-PCR was used to detect gene expression of Bad and metallothionein 1A (MT 1A). Cytotoxicity of Tan IIA was tested in human amniotic mesenchymal stem cells (HAMCs). Tan IIA exhibited dose-dependent and time-dependent anticancer effects on BEL-7402 cells through apoptosis and G/G arrest. Cells treated with Tan IIA increased their intracellular calcium, decreased their mitochondrial membrane potential and induced Bad and MT 1A mRNA expression. No adverse effects of Tan IIA were found in HAMCs. In conclusion, these results indicate that Tan IIA-induced cancer cell apoptosis acts via activation of calcium-dependent apoptosis signaling pathways and upregulation of MT 1A expression. [ABSTRACT FROM AUTHOR]

This longitudinal study addressed the sequential events and metabolic consequences of lipid partitioning following uninephrectomy. Adult male Sprague-Dawley rats were randomized into sham operation ( n = 15) or left uninephrectomy (UNX, n = 18). At 1 and 3 months post nephrectomy, three rats from each group were killed for histopathological examination of adipocyte differentiation and lipid accumulation. Renal protein expression of the lipogenic peroxisome proliferator-activated receptor-γ (PPAR-γ), HMG-CoA reductase (HMGCR), and adiponectin receptor was detected by Western blot and immunofluorescence microscopy. Blood lipids, glucose, insulin, and renal functions were longitudinally measured up to 10 months after operation. The UNX rats progressively developed lipodystrophy of subcutaneous and visceral adipose depots with failure of adipocyte differentiation and lipid storage, followed by blood lipid elevation and ectopic lipid deposition with cellular lipid peroxidation, and renal adipogenesis with chronic inflammatory infiltration. Despite having standard diet, normal food consumption and normal body weight, the uninephrectomized rats with defective lipid partitioning manifested a myriad of homeostatic disturbances including insulin resistance, hyperglycemia, adiponectin resistance, and upregulation of PPAR-γ and HMGCR. Abnormal lipid partitioning from adipose depots to circulation and non-adipose tissues and non-adipocytic cells contributes to homeostatic disturbances and lipogenic activation. [ABSTRACT FROM AUTHOR]

In skeletal muscle cells, insulin stimulates cytoskeleton actin remodeling to facilitate the translocation of glucose transporter GLUT4 to plasma membrane. Defect of insulin-induced GLUT4 translocation and actin remodeling may cause insulin resistance. Free fatty acids cause insulin resistance in skeletal muscle. The aim of this study was to investigate the effects of fatty acids on glucose transport and actin remodeling. Differentiated L6 muscle cells expressing c-myc epitope-tagged GLUT4 were treated with palmitic acid, linoleic acid and oleic acid. Surface GLUT4 and 2-deoxyglucose uptake were measured in parallel with the morphological imaging of actin remodeling and GLUT4 immunoreactivity with fluorescence, confocal and transmission electron microscopy. Differentiated L6 cells showed concentration responses of insulin-induced actin remodeling and glucose uptake. The ultrastructure of insulin-induced actin remodeling was cell projections clustered with actin and GLUT4. Acute and chronic treatment with the 3 fatty acids had no effect on insulin-induced actin remodeling and GLUT4 immunoreactivity. However, insulin-mediated glucose uptake significantly decreased by palmitic acid (25, 50, 75, 100 μmol/L), oleic acid (180, 300 μmol/L) and linoleic acid (120, 180, 300 μmol/L). Oleic acid (120, 300 μmol/L) and linoleic acid (300 μmol/L), but not palmitic acid, significantly decreased insulin-mediated GLUT4 translocation. These data suggest that fatty acids inhibit insulin-induced glucose transport associated with actin remodeling in L6 muscle cells. [ABSTRACT FROM AUTHOR]

The expression of nephropathy in type 2 diabetes has several levels of abnormalities. To define the primary abnormalities of diabetic nephropathy, we conducted an autopsy study of 186 consecutive patients with type 2 diabetes to determine correlations among the aldose reductase gene, renal histopathologies, extracellular matrix, glomerular function, and clinical characteristics. Compared with cases of near-normal renal structure (n = 51) and atypical diabetic glomerulopathy (n = 75), patients with classic diabetic glomerulopathy (n = 60) had advanced glomerular disease, as reflected by elevated plasma creatinine levels (133.2 +/- 59.8 vs. 166.0 +/- 65.7 vs. 243.8 +/- 82.6 micromol/l; P < 0.001), glomerular matrix fractions (20.8 +/- 6.7 vs. 33.5 +/- 16.8 vs. 39.2 +/- 14.3%; P < 0.001), and risk of renal failure (odds ratio [OR] 1 vs. 3.5 vs. 21.4; P < 0.001). Compared with noncarriers of the aldose reductase z-2 allele (n = 92) and z-2 heterozygotes (n = 77), z-2 homozygotes (n = 17) had elevated plasma creatinine (164.1 +/- 73.7 vs. 190.6 +/- 60.9 vs. 241.1 +/- 86.2 micromol/l; P < 0.001) and an increased risk of classic diabetic glomerulopathy (OR 1 vs. 0.9 vs. 3.3; P = 0.026). Overexpression of transforming growth factor-beta1, mesangial cell transdifferentiation by expression of alpha-smooth muscle actin, and aberrant deposition of collagen type IV, fibronectin, and laminin were found in classic diabetic glomerulopathy. These data suggest genetic, biochemical, pathophysiological, and clinical correlations among the aldose reductase gene, extracellular matrix, classic diabetic glomerulopathy, and renal insufficiency. Gene mutation, cellular transdifferentiation, growth factor upregulation, extracellular matrix expansion, and glomerular filtration impairment are the primary abnormalities in type 2 diabetic patients with nephropathy. [ABSTRACT FROM AUTHOR]

Islet amyloid has been suggested to be an important link between insulin resistance and β-cell dysfunction in type 2 diabetes. To investigate the prevalence and clinicopathological characteristics of islet amyloid, we examined consecutive autopsies of 235 Chinese patients with type 2 diabetes and 533 nondiabetic subjects. Islet ainyloid deposits were identified using Congo red staining and quantitated by image analysis. We found that 3.0% of the nondiabetic subjects versus 39.6% of the diabetic patients displayed islet amyloid (P < 0.001). In diabetic patients, the amyloid deposits occupied a mean islet area of 36.2%, which was positively associated with BMI, blood pressure, and glycemic control. Pancreatic fibrosis and fat infiltration were more frequently found in diabetic patients with islet amyloid than those without islet amyloid, whereas pancreatic arteriosclerosis was identified in all diabetic patients. These findings suggest that islet amyloid deposits reflect greater insulin resistance and islet failure in a subgroup of type 2 diabetic patients. Islet failure may also have been exacerbated by fat infiltration, fibrosis, and arteriosclerosis. Optimal blood pressure and metabolic control may reduce these pathological changes and help preserve islet cell mass. [ABSTRACT FROM AUTHOR]

This is a response to the article by Eric McDade [ABSTRACT FROM AUTHOR]

A letter to the editor is presented concerning research into the lifestyle characteristics and dietary intake of centenarians living in the Bama Yao Autonomous County in Guangxi Province, China which speculates healthy eating habits and balanced nutrition is behind their longevity.

Introduction: The renal renin-angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown.Methods: Ninety-six rats were stratified into four groups: sham, uninephrectomised, uninephrectomised rats treated with the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin receptor blocker losartan. Histopathological examination at 9 months post-operation and biochemical measurements at 3, 6 and 9 months were performed for changes in renal structure and function. The expression of AMPK and angiotensin II at 9 months was detected by immunofluorescence microscopy and western blot.Results: Compared with sham rats, uninephrectomised rats demonstrated progressive glomerulosclerosis, tubular atrophy with cast formation and chronic inflammatory infiltration, in parallel to elevated serum urea, creatinine, urine total protein to creatinine ratio and reduced serum albumin. Overexpression of angiotensin II coexisted with a 85.6% reduction of phosphorylated to total AMPK ratio in the remnant kidney of uninephrectomised rats. RAS blockade by the angiotensin-converting enzyme inhibitor or angiotensin receptor blocker substantially normalised AMPK expression, morphological and functional changes of the remnant kidney.Conclusions: Uninephrectomy-induced RAS activation and AMPK inhibition in the remnant kidney could be substantially corrected by RAS blockade, suggesting a cross-talk between AMPK and RAS components in uninephrectomised rats. [ABSTRACT FROM AUTHOR]

Introduction: The renal renin–angiotensin system (RAS) and the ultrasensitive energy sensor AMP-activated protein kinase (AMPK) have been implicated in normal and aberrant states of the kidney, but interaction between the RAS and AMPK remains unknown. Methods: Ninety-six rats were stratified into four groups: sham, uninephrectomised, uninephrectomised rats treated with the angiotensin-converting enzyme inhibitor lisinopril or the angiotensin receptor blocker losartan. Histopathological examination at 9 months post-operation and biochemical measurements at 3, 6 and 9 months were performed for changes in renal structure and function. The expression of AMPK and angiotensin II at 9 months was detected by immunofluorescence microscopy and western blot. Results: Compared with sham rats, uninephrectomised rats demonstrated progressive glomerulosclerosis, tubular atrophy with cast formation and chronic inflammatory infiltration, in parallel to elevated serum urea, creatinine, urine total protein to creatinine ratio and reduced serum albumin. Overexpression of angiotensin II coexisted with a 85.6% reduction of phosphorylated to total AMPK ratio in the remnant kidney of uninephrectomised rats. RAS blockade by the angiotensin-converting enzyme inhibitor or angiotensin receptor blocker substantially normalised AMPK expression, morphological and functional changes of the remnant kidney. Conclusions: Uninephrectomy-induced RAS activation and AMPK inhibition in the remnant kidney could be substantially corrected by RAS blockade, suggesting a cross-talk between AMPK and RAS components in uninephrectomised rats. [ABSTRACT FROM AUTHOR]

Introduction: The effects of renin-angiotensin system blockade with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs) on cancer remain inconsistent.Methods: We searched existing databases from 1960 to August 2015, for randomised controlled trials and observational studies (case-control studies and cohort studies) of ARB/ACEI therapy with a minimal one year of follow-up. Outcomes were incidence and mortality of cancer.Results: We included 14 randomised controlled trials and 17 observational studies of 3,957,725 participants (350,329 ARB/ACEI users). The users had a lower incidence of cancer in the observational studies (RR 0.82, 95% CI 0.73-0.93) but not in the randomised controlled trials (RR 1.00, 95% CI 0.92-1.08). The protection persisted for lung cancer (RR 0.85, 95% CI 0.75-0.97) but not for other sites of cancer. The relative risk of cancer associated with renin-angiotensin system blockade was reduced along with time of follow-up. Mortality reduction with ARB/ACEI was marginally significant in the observational studies (RR 0.71, 95% CI 0.55-0.93) but not in the randomised controlled trials (RR 0.99, 95% CI 0.89-1.09).Conclusions: The significant benefits of renin-angiotensin system blockade observed in case-control studies and cohort studies might diminish in randomised controlled trials. Clinical design, site of cancer and duration of follow-up may affect the clinical outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) are widely used to block the renin-angiotensin system (RAS). Yet it remains uncertain whether these drugs are equally effective and safe.Methods: Systematic reviews and meta-analyses of ACEis/ARBs in diabetes and kidney disease published in PubMed, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases were searched for clinical outcomes including all-cause mortality, end-stage renal disease (ESRD), hyperkalemia and cough.Results: Eight meta-analyses included 2177-61,264 patients with follow-up of 6-108 months. RAS blockers reduced mortality (relative risk ratio (RR), 0.90, 95% confidence interval (CI), 0.86-0.95) without heterogeneity. The death protection was significant specifically with ACEis (RR, 0.85, 95% CI, 0.79-0.91), but not with ARBs. Protection against ESRD was homogenously evident by ARBs (RR, 0.79, 95% CI, 0.73-0.87), ACEis (RR, 0.79, 95% , 0.64-0.94), and both (RR, 0.79, 95% CI, 0.73-0.87). Significant side effects were hyperkalemia by ARBs (RR, 2.44, 95% CI, 1.13-5.26), and cough by ACEis (RR, 2.38, 95% CI, 1.75-3.22) CONCLUSIONS: In patients with diabetes and kidney disease, ACEis and ARBs are consistently protective for the development of ESRD. Use of ACEis alone additionally reduces deaths and increases the risk for cough. Use of ARBs alone increases the risk for hyperkalemia without additional benefit of death protection. [ABSTRACT FROM AUTHOR]

Background. Diabetic nephropathy represents a heterogeneous group of renal pathologies that may be associated with genetic susceptibility. There have been clinical reports on the risk association of diabetic nephropathy with an apolipoprotein E (ApoE) exon 4 polymorphism although its correlations with renal histopathological changes have not been explored. Methods. A total of 213 adult autopsies with type 2 diabetes and 111 non-diabetic control cases were analysed. Genomic DNA samples were obtained from spleen tissues. The ApoE genotype was determined by PCR-LDR analysis. Histopathological examination of kidney sections was performed in a subset of 51 diabetic and 111 control cases. ApoE protein expression in diabetic carriers with similar clinical status was examined by immunohistochemical staining. Results. In type 2 diabetes, ε2 carriers (P = 0.04; odds ratio = 5.42; 95% CI: 1.10–26.8) and ε3/ε4 (P = 0.04; odds ratio = 22.5; 95% CI: 1.11–454.90) genotype carriers were more likely to have glomerular hypertrophy than were ε3/ε3 carriers. The ε2 carriers showed an increase in glomerular ApoE protein expression. A correlation between ApoE genotype and nodular glomerulosclerosis was not found. Conclusions. Our findings confirm the risk association of the ApoE polymorphism with diabetic nephropathy in clinical studies and is the first study demonstrating the correlations between ApoE genotypes, protein expression and structural changes in diabetic nephropathy. [ABSTRACT FROM AUTHOR]