Serum vaspin concentration in elderly patients with type 2 diabetes mellitus and macrovascular complications

Background

Adipose tissue, an endocrine organ of the body, is involved in some obesity-related disease states such as insulin resistance, diabetes mellitus, and atherosclerosis. Vaspin is a novel adipocyte with insulin sensitizing effects. In this study, we planned to estimate serum vaspin concentrations as related to glycemic status and the presence of macrovascular complications among elderly patients with type-2 diabetes mellitus (T2DM).

Methods

A total of 230 elderly patients with T2DM were evaluated. These patients were divided into two groups: patients without complications (T2DM group, n?=?110), and patients with macrovascular complications (T2DM + MC group, n?=?120). In addition, 60 healthy elderly subjects were enrolled and assigned into the control group (NC group). Relevant parameters were matched for age and gender ratio. Serum vaspin concentrations were measured by Enzyme-linked immunosorbent assay (ELISA). Anthropometric measurements, plasma glucose and HbA_1C levels, insulin concentration, liver and kidney functions, and lipid profile were measured for each participant.

Results

Serum vaspin concentrations were significantly higher in the T2DM group than in the T2DM + MC group (F?=?13.122, P?<?0.01). These concentrations were also significantly higher among females, compared to males (T?=?3.567, P?<?0.05). Logistic regression analysis revealed that serum vaspin concentration, systolic blood pressure, HDL-C and T2DM duration were independent influencing factors for diabetic macrovascular complications.

Conclusion

Serum vaspin may be considered as a potential marker to assess the status of elderly patients with T2DM and the risk of developing serious macrovascular complications. Further prospective studies are warranted.

Trial registration

ChiCTR-OPC-14005698, retrospectively registered on 20 Dec. 2014.

     

Single-dose acarbose decreased glucose-dependent insulinotropic peptide and glucagon levels in Chinese patients with newly diagnosed type 2 diabetes mellitus after a mixed meal

Background

Acarbose slows down the intestinal absorption of carbohydrates, but its effects on the secretion of incretins are still poorly known. This study aimed to examine the effects of single-dose acarbose on the secretion of incretins in patients with newly diagnosed type 2 diabetes mellitus (T2DM).

Methods

In this pilot study, twenty-three patients diagnosed with T2DM were randomly assigned to the oral glucose tolerance test (OGTT) group (n?=?11) and the mixed meal test (MMT) group (n?=?12). Fourteen subjects with normal OGTT were included as controls. Plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) were measured at 0 (fasting), 15, 30, 60, 90, and 120 min after nutrient load. A week later, controls underwent MMT, the OGTT group underwent OGTT receiving 100 mg acarbose, and the MMT group underwent MMT receiving 100 mg acarbose. The same blood markers were measured again.

Results

No significant difference was observed in the OGTT group before and after administering acarbose. In the MMT group, postprandial levels of glucose (P?<?0.01), insulin (P?<?0.01), glucagon at 15 min (P?<?0.05), glucagon area under the curve (AUC) (P?<?0.05), GIP levels at 30 min (P?<?0.05), and GIP AUC (P?<?0.05) were decreased after receiving acarbose with a mixed meal, but GLP-1 levels and GLP-1 AUC did not change.

Conclusions

Single-dose acarbose could reduce the secretion of GIP and glucagon after a mixed meal in patients with newly diagnosed T2DM. The influence of acarbose on incretin levels could be related to the types of carbohydrate being consumed.

Trial registration

This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR-TRC-14004260, Date of Registration: 2014-01-19).

     

Characterization of diabetes following pancreatic surgery in patients with congenital hyperinsulinism

Background

Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycaemia in infancy that leads to unfavourable neurological outcome if not treated adequately. In patients with severe diffuse CHI it remains under discussion whether pancreatic surgery should be performed or intensive medical treatment with the acceptance of recurrent episodes of mild hypoglycaemia is justified. Near-total pancreatectomy is associated with high rates of insulin-dependent diabetes mellitus and exocrine pancreatic insufficiency. Little is known about the management and long-term glycaemic control of CHI patients with diabetes after pancreatic surgery. We searched the German/Austrian DPV database and compared the course of 42 CHI patients with diabetes to that of patients with type 1 diabetes mellitus (T1DM). Study groups were compared at diabetes onset and after a follow-up period of 6.1 [3.3–9.7] (median [interquartile range]) years.

Results

The majority of CHI patients with diabetes were treated with insulin (85.2% [70.9–99.5] at diabetes onset, and 90.5% [81.2–99.7] at follow-up). However, compared to patients with T1DM, significantly more patients in the CHI group with diabetes were treated with conventional insulin therapy (47.8% vs. 24.4%, p?=?0.03 at diabetes onset, and 21.1% vs. 6.4% at follow-up, p?=?0.003), and only a small number of CHI patients were treated with insulin pumps. Daily insulin dose was significantly lower in CHI patients with diabetes than in patients with T1DM, both at diabetes onset (0.3 [0.2–0.5] vs. 0.6?IE/kg/d [0.4–0.8], p?=?0.003) and follow-up (0.8 [0.4–1.0] vs. 0.9 [0.7–1.0] IE/kg/d, p?=?0.02), while daily carbohydrate intake was comparable in both groups. Within the first treatment year, HbA1c levels were significantly lower in CHI patients with diabetes (6.2% [5.5–7.9] vs. 7.2% [6.5–8.2], p?=?0.003), but increased to a level comparable to that of T1DM patients at follow-up. Interestingly, in CHI patients, the risk of severe hypoglycaemia tends to be higher only at diabetes onset (14.8% vs. 5.8%, p?=?0.1).

Conclusions

In surgically treated CHI patients insulin treatment needs to be intensified in order to achieve good glycaemic control. Our data furthermore emphasize the need for improved medical treatment options for patients with diazoxide- and/or octreotide-unresponsive CHI.

     

Screening for celiac disease in poorly controlled type 2 diabetes mellitus: worth it or not?

Background

Recent studies have demonstrated that immune factors might have a role in the pathophysiology of insulin resistance and type 2 diabetes mellitus (T2DM). Inappropriate glycemic control in patients with T2DM is an important risk factor for the occurrence of diabetes complications. The prevalence of celiac disease (CD) is high in type 1 diabetes mellitus however, there are scarce data about its prevalence in T2DM. Our aim was to investigate the prevalence of celiac disease among insulin-using type 2 diabetes patients with inappropriate glycemic control.

Methods

IgA tissue transglutaminase antibodies (tTGA IgA) test was performed as a screening test. A total of 135 patients with T2DM whose control of glycemia is inappropriate (HbAlc value >7%) in spite of using insulin treatment for at least 3-months (only insulin or insulin with oral antidiabetic drugs) and 115 healthy controls were enrolled in the study. Upper gastrointestinal endoscopy with duodenal biopsy was performed to all patients with raised tTGA IgA or selective lgA deficiency.

Results

Gender, age, body mass index (BMI) and tTGA IgA, kreatinin, calcium, LDL-cholesterol (LDL-C), total cholesterol, 25-OH vitamin D₃ levels were similar between groups. Systolic and diastolic blood pressure, waist circumference, fasting plasma glucose, postprandial plasma glucose, urea, sodium, HbA1c, LDL-C, triglyceride, vitamin B12 levels were significantly higher in DM group (p < 0.0001). BMI, high-sensitive CRP, microalbuminuria, and AST, ALT, potassium, phosphorus levels were significantly higher in the T2DM group (p < 0.05). HDL-cholesterol and parathormone levels were significantly lower in the T2DM group (p < 0.05). Two of the 135 patients with T2DM were diagnosed with CD (1.45%).

Conclusions

The prevalence of celiac disease among patients with type 2 diabetes, with poor glycemic control despite insulin therapy, is slightly higher than the actual CD prevalence in general population. Type 2 diabetic patients with inappropriate control of glycemia in spite of insulin treatment might be additionally tested for Celiac disease especially if they have low C-peptide levels.

     

The analysis of association between type 2 diabetes and polymorphic markers in the <Emphasis Type="Italic">CDKAL1</Emphasis> gene and in the <Emphasis Type="Italic">HHEX/IDE</Emphasis> locus

The increase in diabetes was noted at the turn of the 21st century. Patients with type 2 diabetes (T2DM) make up the majority of patients. Diabetes is a multifactorial disease. It arises from adverse effects of environmental factors on the body of genetically susceptible peoples. According to modern concepts, T2DM is a polygenic disease. Each of the involved genes contributes to the risk of developing of this disease. In our study, the association between polymorphic genetic markers rs7756992, rs9465871, rs7754840, and rs10946398 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus and T2DM in the Russian population were studied. Four hundred forty patients with type 2 diabetes and 264 healthy individuals without any signs of the disease were examined. The comparative analysis of distribution of genotypes and allele frequencies points to an association between polymorphic genetic markers rs7756992, rs9465871, and rs10946398 in the CDKAL1 gene and this disease. For the other polymorphic genetic markers (rs7754840 in the CDKAL1 gene and rs1111875 in the HHEX/IDE locus), no statistically significant associations are found. On the basis of these data, we can conclude that the CDKAL1 gene is associated with development of T2DM. For the HHEX/IDE locus, such an association is absent.     

Male non-insulin users with type 2 diabetes mellitus are predisposed to gastric corpus-predominant inflammation after <Emphasis Type="Italic">H. pylori</Emphasis> infection

Background

Both H. pylori infection and diabetes increase the risk of gastric cancer. This study investigated whether patients with type 2 diabetes mellitus (T2DM) and H. pylori infection had more severe corpus gastric inflammation and higher prevalence of precancerous lesions than non-diabetic controls.

Methods

A total of 797 patients with type 2 diabetes mellitus were screened for H. pylori, of whom 264 had H. pylori infection. Of these patients, 129 received esophagogastroduodenoscopy to obtain topographic gastric specimens for gastric histology according to the modified Updated Sydney System, corpus-predominant gastritis index (CGI), Operative Link on Gastritis Assessment, and Operative Link on Gastric Intestinal Metaplasia Assessment. Non-diabetic dyspeptic patients who had H. pylori infection confirmed by esophagogastroduodenoscopy were enrolled as controls.

Results

The male as well as total T2DM patients had higher acute/chronic inflammatory and lymphoid follicle scores in the corpus than non-diabetic controls (p < 0.05). In contrast, the female T2DM patients had higher chronic inflammatory scores in the antrum than the controls (p < 0.05). In T2DM patients, the males had significantly higher rates of CGI than the females (p < 0.05). Multivariate logistic regression analysis showed that male patients (odds ratio: 2.28, 95% confidence interval: 1.11–4.69, p = 0.025) and non-insulin users (odds ratio: 0.33, 95% confidence interval: 0.15–0.74, p = 0.007) were independent factors for the presence of CGI in the H. pylori-infected patients with type 2 diabetes mellitus.

Conclusions

Patients with type 2 diabetes mellitus and H. pylori infection had more severe corpus gastric inflammation than non-diabetic controls. Moreover, male gender and non-insulin users of T2DM patients were predisposed to have corpus-predominant gastritis after H. pylori infection.

Trial registration

ClinicalTrial: NCT02466919, retrospectively registered may 17, 2015.

     

Associations of polymorphisms in the candidate genes for Alzheimer’s disease <Emphasis Type="Italic">BIN1, CLU,CR1</Emphasis> and <Emphasis Type="Italic">PICALM</Emphasis> with gestational diabetes and impaired glucose tolerance

Alzheimer’s disease (AD) is the most common type of dementia, with a prevalence that is rising every year. AD is associated with type 2 diabetes mellitus (T2DM) and insulin resistance, and is therefore sometimes called “type 3 diabetes mellitus”. The aim of this study was to examine whether the variants of some candidate genes involved in the development of AD, namely BIN1 (rs744373), CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179), are related to several disorders of glucose metabolism—gestational diabetes (GDM), T2DM and impaired glucose tolerance (IGT). Our study included 550 women with former GDM and 717 control women, 392 patients with T2DM and 180 non-diabetic controls, and 117 patients with IGT and 630 controls with normal glucose tolerance. Genotyping analysis was performed using specially-designed TaqMan assays. No significant associations of the genetic variants rs744373 in BIN1, rs11136000 in CLU, or rs3818361 in CR1 were found with GDM, T2DM or IGT, but rs3851179 in PICALM was associated with an increased risk of GDM. The frequency of the AD risk-associated C allele was significantly higher in the GDM group compared to controls: OR 1.21; 95% CI (1.03–1.44). This finding was not apparent in T2DM and IGT; conversely, the C allele of the PICALM SNP was protective for IGT: OR 0.67; 95% CI (0.51–0.89). This study demonstrates an association between PICALM rs3851179 and GDM as well as IGT. However, elucidation of the possible role of this gene in the pathogenesis of GDM requires further independent studies.     

Molecular genetics of type 1 diabetes mellitus: Achievements and future trends

Type 1 diabetes mellitus (T1DM) is a widespread severe disease that results from autoimmune destruction of β cells in Langerhans islets of the pancreas. To date, several loci involved in T1DM have been reliably identified using various approaches: the MHC locus, VNTR within the 5′-nontranscibed region of the insulin gene (INS), CTLA4 (T-cell surface receptor), PTPN22, PTPN2 (T-cell tyrosine phosphatases), IL2 (interleukin 2, IL-2), IL2RA (IL-2 receptor α chain), KIAA0350 (unknown function), and IFIH1 (receptor for double-stranded DNA generated in virus infections). Functional analysis of their protein products confirmed the hypothesis that T1DM is underlain by deregulation of the mechanisms of immune tolerance and, on the other hand, a destructive immune response against the body’s own proteins after virus infection or some other immune stress. Thus the protein products of MHC, INS, PTPN22, and PTPN2 are involved in the intrathymic formation of the T-cell repertoire, responsible for immune defense of the body. On the other hand, nonspecific activation of T cells, which starts autoimmune destruction of pancreatic β cells, is most likely associated with the protein products of CTLA4, IL2, IL2RA, and, possibly, PTPN22 and PTPN2. Apart from the genes with unknown functions, the only exception is IFIH1, but its association with T1DM confirms that certain virus infections can activate autoreactive T cells and lead to T1DM.     

Association of Pro12Ala Polymorphism of Peroxisome Proliferator-Activated Receptor gamma 2 (<Emphasis Type="Italic">PPARγ2</Emphasis>) Gene with Type 2 Diabetes Mellitus in Ethnic Kashmiri Population

Type 2 diabetes mellitus (T2DM) is characterized by chronic hyperglycemia associated with insulin resistance and relative insulin deficiency. T2DM is believed to be attributable to the combined effect of genetic and environmental factors. Peroxisome proliferator-activated receptor gamma 2 (PPARγ2) is one of the main candidate genes that are implicated in T2DM. A common proline 12 alanine (Pro12Ala) polymorphism in PPARγ2 has been shown to be associated with T2DM. The aim of this work was to investigate the possible role of PPARγ2 gene polymorphism, as a genetic risk factor for T2DM. The study comprised 200 ethnic unrelated subjects (100 T2DM patients and 100 controls). PCR–RFLP technique was used for genotyping analysis. The frequency of the Pro allele was 79 and 91.5 % for controls and cases, respectively (P < 0.05; OR 3.2; 95 % CI 1.64–6.3). The Pro12Ala polymorphism was in Hardy–Weinberg equilibrium in both patients and controls (χ ² = 0.13, P > 0.05). We found a significant association of Pro12Ala polymorphism of PPARγ2 gene with T2DM, however the genotypes showed statistically significant association only with few clinical parameters including body mass index, total cholesterol, and low-density lipoprotein (P < 0.05). The study signifies that Pro allele in PPARγ2 may be a genotypic risk factor that confers susceptibility to T2DM in ethnic Kashmiri population.     

Association of the <Emphasis Type="Italic">POLG1</Emphasis> T(−365)C, <Emphasis Type="Italic">ANT1</Emphasis> G(−25)A,and <Emphasis Type="Italic">PEO1</Emphasis> G(−605)T polymorphisms with diabetic polyneuropathy in patients with Type 1 diabetes mellitus

This study is dedicated to a search for the association of the polymorphic markers T(?365)C of the POLG1 gene G(?25)A of the ANT1 gene and G(?605)T of the PEO1 gene with diabetic polyneuropathy (DPN) in Type 1 diabetes mellitus (DM1) patients. All patients were ethnic Russian Moscow residents, with DM1 records of no more than 5 years and DPN or DM1 records of more than 10 years but without DPN. We found that the polymorphic marker T(?365)C of POLG1 was associated with DPN in Russian patients with DM1. The carriers of the C allele and the CC genotype had a higher risk of DPN development (OR = 1.62; CI = 1.11–2.38; and OR = 1.76; CI = 0.99–3.13; respectively). In contrast, the T allele carrier status and the TT genotype were associated with a lower DPN risk (OR = 0.62, CI = 0.42–0.90; and OR = 0.61; CI = 0.35–1.07; respectively). We found no association of the polymorphic markers G(?25)A of ANT1 or G(?605)T of PEO1 with DPN in Russian DM1 patients living in Moscow.     

The course of diabetes in children,adolescents and young adults: does the autoimmunity status matter?

Background

Initial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes.The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0–25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies.

Methods

Cross-sectional population-based study was performed covering 100% of pediatric (n?=?860) and 70% of 18–25 years old adult patients (n?=?349) with type 1 diabetes in Lithuania.

Results

No antibodies (GAD65, IA-2, IAA and ICA) were found in 87 (7.5%) cases. Familial history of diabetes was more frequent in those with antibodies-negative diabetes (24.1 vs. 9.4%, p?<?0.001). Gestational age, birth weight and age at diagnosis was similar in both groups. Ketosis at presentation was more frequent in patients with autoimmune diabetes (88.1 vs. 73.5%, p?<?0.05). HbA1c at the moment of investigation was 8.6 (3) vs. 8.7 (2.2)% in antibodies-negative and antibodies-positive diabetes groups, respectively, p?>?0.05. In the whole cohort, neuropathy was found in 8.8% and nephropathy - in 8.1% of cases, not depending on autoimmunity status. Adjusted for age at onset, disease duration and HbA1c, retinopathy was more frequent in antibodies-negative subjects (13.8 vs. 7.8%, p?<?0.05).

Conclusion

Antibodies-negative pediatric and young adult patients with type 1 diabetes in this study had higher incidence of family history of diabetes, higher frequency of retinopathy, less frequent ketosis at presentation, but similar age at onset, HbA1c, incidence of nephropathy and neuropathy compared to antibodies-positive patients.

     

QTL mapping of downy and powdery mildew resistances in PI 197088 cucumber with genotyping-by-sequencing in RIL population

Key message

Host resistances in PI 197088 cucumber to downy and powdery mildew pathogens are conferred by 11 (3 with major effect) and 4 (1 major effect) QTL, respectively, and three of which are co-localized.

Abstract

The downy mildew (DM) and powdery mildew (PM) are the two most important foliar diseases of cucurbit crops worldwide. The cucumber accession PI 197088 exhibits high-level resistances to both pathogens. Here, we reported QTL mapping results for DM and PM resistances with 148 recombinant inbred lines from a cross between PI 197088 and the susceptible line ‘Coolgreen’. Phenotypic data on responses to natural DM and PM infection were collected in multi-year and multi-location replicated field trials. A high-density genetic map with 2780 single nucleotide polymorphisms (SNPs) from genotyping-by-sequencing and 55 microsatellite markers was developed, which revealed genomic regions with segregation distortion and mis-assemblies in the ‘9930’ cucumber draft genome. QTL analysis identified 11 and 4 QTL for DM and PM resistances accounting for more than 73.5 and 63.0% total phenotypic variance, respectively. Among the 11 DM resistance QTL, dm5.1, dm5.2, and dm5.3 were major-effect contributing QTL, whereas dm1.1, dm2.1, and dm6.2 conferred susceptibility. Of the 4 QTL for PM resistance, pm5.1 was the major-effect QTL explaining 32.4% phenotypic variance and the minor-effect QTL pm6.1 contributed to disease susceptibility. Three PM QTL, pm2.1, pm5.1, and pm6.1, were co-localized with DM QTL dm2.1, dm5.2, and dm6.1, respectively, which was consistent with the observed linkage of PM and DM resistances in PI 197088. The genetic architecture of DM resistance in PI 197088 and another resistant line WI7120 (PI 330628) was compared, and the potential of using PI 197088 in cucumber breeding for downy and powdery mildew resistances is discussed.

     

Urine metabolites are associated with glomerular lesions in type 2 diabetes

Introduction

Little is known about the association of urine metabolites with structural lesions in persons with diabetes.

Objectives

We examined the relationship between 12 urine metabolites and kidney structure in American Indians with type 2 diabetes.

Methods

Data were from a 6-year clinical trial that assessed renoprotective efficacy of losartan, and included a kidney biopsy at the end of the treatment period. Metabolites were measured in urine samples collected within a median of 6.5 months before the research biopsy. Associations of the creatinine-adjusted urine metabolites with kidney structural variables were examined by Pearson’s correlations and multivariable linear regression after adjustment for age, sex, diabetes duration, hemoglobin A_1c, mean arterial pressure, glomerular filtration rate (iothalamate), and losartan treatment.

Results

Participants (n?=?62, mean age 45?±?10 years) had mean?±?standard deviation glomerular filtration rate of 137?±?50 ml/min and median (interquartile range) urine albumin:creatinine ratio of 34 (14–85) mg/g near the time of the biopsy. Urine aconitic and glycolic acids correlated positively with glomerular filtration surface density (partial r?=?0.29, P?=?0.030 and r?=?0.50, P?<?0.001) and total filtration surface per glomerulus (partial r?=?0.32, P?=?0.019 and r?=?0.43, P?=?0.001). 2-ethyl 3-OH propionate correlated positively with the percentage of fenestrated endothelium (partial r?=?0.32, P?=?0.019). Citric acid correlated negatively with mesangial fractional volume (partial r=-0.36, P?=?0.007), and homovanillic acid correlated negatively with podocyte foot process width (partial r=-0.31, P?=?0.022).

Conclusions

Alterations of urine metabolites may associate with early glomerular lesions in diabetic kidney disease.

     

Metabolomics reveals alterations of serotonin pathway in carriers of <Emphasis Type="Italic">NOS1AP</Emphasis> variant rs12742393

Introduction and objectives

NOS1AP variant rs12742393 is a functional single nucleotide polymorphism (SNP) and has been reported to be associated with schizophrenia and type 2 diabetes (T2DM) susceptibility in different populations. However, the molecular mechanisms are not clear. The main focus of the present study was to identify metabolic differences among different genotypes of the variant and to identify potential physiological and pathological mechanisms for the diseases.

Methods

In this study, we conducted a comprehensive serum metabolomic analysis in healthy subjects with different genotypes of rs12742393 (n?=?49 for AA, AC, and CC, respectively) using gas chromatography–time of flight mass spectrometry and ultra-performance liquid chromatography–quadruple time of flight mass spectrometry. Serotonin was also measured by enzyme-linked immunosorbent assay.

Results

Our data showed that there were significant metabolic differences among the different genotypes of rs12742393: compared with AA carriers, serum serotonin and N-acetyl-5-hydroxytryptamine were significantly higher; while tryptophan and kynurenine were significantly lower in CC allele carriers (variable importance in the projection (VIP) >1 and P?<?0.05). In addition, CC allele carriers showed low levels of aromatic amino acids (phenylalanine and tyrosine) and fatty acids (lauric acid, 2-methyl-4-pentenoic acid, and adrenic acid), but a high level of isolithocholic acid (VIP >1 and P?<?0.05).

Conclusion

The influence of rs12742393 variant is involved in a set of complex metabolic alterations, including amino acids, fatty acids and cholic acids, especially those in the serotonin and kynurenine pathway, probably associates with the early development of schizophrenia and T2DM.

     

HCV monoinfection and HIV/HCV coinfection enhance T-cell immune senescence in injecting drug users early during infection

Background

Injecting drug users (IDU) are at premature risk of developing multimorbidity and mortality from causes commonly observed in the elderly. Ageing of the immune system (immune-senescence) can lead to premature morbidity and mortality and can be accelerated by chronic viral infections. Here we investigated the impact of HCV monoinfection and HIV/HCV coinfection on immune parameters in (ex-) IDU. We analyzed telomere length and expression of activation, differentiation and exhaustion markers on T cells at baseline (t?=?1) and at follow-up (t?=?2) (median interval 16.9 years) in IDU who were: HCV mono-infected (n?=?21); HIV/HCV coinfected (n?=?23) or multiple exposed but uninfected (MEU) (n?=?8).

Results

The median time interval between t?=?1 and t?=?2 was 16.9 years. Telomere length within CD4⁺ and CD8⁺ T cells decreased significantly over time in all IDU groups (p?≤?0.012). CD4⁺ T-cell telomere length in HCV mono-infected IDU was significantly reduced compared to healthy donors at t?=?1 (p?<?0.008). HIV/HCV coinfected IDU had reduced CD4⁺ and CD8⁺ T-cell telomere lengths (p?≤?0.002) to healthy donors i at t?=?1. This was related to persistent levels of immune activation but not due to increased differentiation of T cells over time. Telomere length decrease was observed within all T-cell subsets, but mainly found in immature T cells (CD27⁺CD57⁺) (p?≤?0.015).

Conclusions

HCV mono-infection and HIV/HCV coinfection enhance T-cell immune-senescence. Our data suggest that this occurred early during infection, which warrants early treatment for both HCV and HIV to reduce immune senescence in later life.

     

Interleukin-6 and C-reactive protein,successful aging,and mortality: the PolSenior study

Background

In the elderly, chronic low-grade inflammation (inflammaging) is a risk factor for the development of aging-related diseases and frailty. Using data from several thousand Eastern Europeans aged 65 years and older, we investigated whether the serum levels of two proinflammatory factors, interleukin-6 (IL-6) and C-reactive protein (CRP), were associated with physical and cognitive performance, and could predict mortality in successfully aging elderly.

Results

IL-6 and CRP levels systematically increased in an age-dependent manner in the entire study group (IL-6: n?=?3496 individuals, p?<?0.001 and CRP: n?=?3632, p?=?0.003), and in the subgroup of successfully aging individuals who had never been diagnosed with cardiovascular disease, myocardial infarction, stroke, type 2 diabetes, or cancer, and had a Mini Mental State Examination (MMSE) score ≥24 and a Katz Activities of Daily Living (ADL) score ≥5 (IL-6: n?=?1258, p?<?0.001 and CRP: n?=?1312, p?<?0.001). In the subgroup of individuals suffering from aging-related diseases/disability, only IL-6 increased with age (IL-6: n?=?2238, p?<?0.001 and CRP: n?=?2320, p?=?0.249). IL-6 and CRP levels were lower in successfully aging individuals than in the remaining study participants (both p?<?0.001). Higher IL-6 and CRP levels were associated with poorer physical performance (lower ADL score) and poorer cognitive performance (lower MMSE score) (both p?<?0.001). This association remained significant after adjusting for age, gender, BMI, lipids, estimated glomerular filtration rate, and smoking status. Longer survival was associated with lower concentrations of IL-6 and CRP not only in individuals with aging-related diseases/disability (HR?=?1.063 per each pg/mL, 95 % CI: 1.052-1.074, p?<?0.001 and HR?=?1.020 per each mg/L, 95 % CI: 1.015-1.025, p?<?0.001, respectively) but also in the successfully aging subgroup (HR?=?1.163 per each pg/mL, 95 % CI: 1.128-1.199, p?<?0.001 and HR?=?1.074 per each mg/L, 95 % CI: 1.047-1.100, p?<?0.001, respectively). These associations remained significant after adjusting for age, gender, BMI, lipids and smoking status. The Kaplan-Meier survival curves showed similar results (all p?<?0.001).

Conclusions

Both IL-6 and CRP levels were good predictors of physical and cognitive performance and the risk of mortality in both the entire elderly population and in successfully aging individuals.

     

Hydrogen production by the hyperthermophilic bacterium <Emphasis Type="Italic">Thermotoga maritima</Emphasis> part I: effects of sulfured nutriments,with thiosulfate as model,on hydrogen production and growth

Background

Thermotoga maritima and T. neapolitana are hyperthermophile bacteria chosen by many research teams to produce bio-hydrogen because of their potential to ferment a wide variety of sugars with the highest theoretical H₂/glucose yields. However, to develop economically sustainable bio-processes, the culture medium formulation remained to be optimized. The main aim of this study was to quantify accurately and specifically the effect of thiosulfate, used as sulfured nutriment model, on T. maritima growth, yields and productivities of hydrogen. The results were obtained from batch cultures, performed into a bioreactor, carefully controlled, and specifically designed to prevent the back-inhibition by hydrogen.

Results

Among sulfured nutriments tested, thiosulfate, cysteine, and sulfide were found to be the most efficient to stimulate T. maritima growth and hydrogen production. In particular, under our experimental conditions (glucose 60 mmol L^?1 and yeast extract 1 g L^?1), the cellular growth was limited by thiosulfate concentrations lower than 0.06 mmol L^?1. Under these conditions, the cellular yield on thiosulfate (Y X/Thio) could be determined at 3617 mg mmol^?1. In addition, it has been shown that the limitations of T. maritima growth by thiosulfate lead to metabolic stress marked by a significant metabolic shift of glucose towards the production of extracellular polysaccharides (EPS). Finally, it has been estimated that the presence of thiosulfate in the T. maritima culture medium significantly increased the cellular and hydrogen productivities by a factor 6 without detectable sulfide production.

Conclusions

The stimulant effects of thiosulfate at very low concentrations on T. maritima growth have forced us to reconsider its role in this species and more probably also in all thiosulfato-reducer hyperthermophiles. Henceforth, thiosulfate should be considered in T. maritima as (1) an essential sulfur source for cellular materials when it is present at low concentrations (about 0.3 mmol g^?1 of cells), and (2) as both sulfur source and detoxifying agent for H₂ when thiosulfate is present at higher concentrations and, when, simultaneously, the pH₂ is high. Finally, to improve the hydrogen production in bio-processes using Thermotoga species, it should be recommended to incorporate thiosulfate in the culture medium.

     

Genetic and environmental influences on root development in cuttings of selected <Emphasis Type="Italic">Salix</Emphasis> and <Emphasis Type="Italic">Populus</Emphasis> clones – a greenhouse experiment

Aims

This study investigated how genetic determination of adventitious root development compared in experimental hybrid and parental Salix and Populus clones, and how soil bulk density influenced root development.

Methods

Cuttings of 11 Salix clones and 10 Populus clones were grown in pots with water, a low bulk density soil and a high bulk density soil for 4 (water) or 10 weeks (soils). Parameters relating to root development were measured.

Results

Root initiation, total root length (RL), and dry mass (DM), as well as root: shoot relationships in Salix clones exceeded that of Populus clones in all media. For Salix clones RL and DM were highest in S. matsudana?×?pentandra and for Populus clones RL and DM were generally higher in hybrid clones having P. trichocarpa parentage. Mean RL and DM for all clones were generally greater in the low bulk density soil than in the high bulk density soil. There were a greater proportion of thinner roots in the low bulk density soil than in the high bulk density soil.

Conclusions

There were significant differences in root initiation, RL, and DM among clones within each genus. Increasing soil bulk density significantly reduced root development in both Salix and Populus clones. Evaluating cutting root development in pot trials could be a useful clone selection tool in willow and poplar breeding.

     

Development and psychometric testing of a theory-based tool to measure self-care in diabetes patients: the Self-Care of Diabetes Inventory

Background

Self-care is essential for patients with diabetes mellitus. Both clinicians and researchers must be able to assess the quality of that self-care. Available tools have various limitations and none are theoretically based. The aims of this study were to develop and to test the psychometric properties of a new instrument based on the middle range-theory of self-care of chronic illness: the Self-Care of Diabetes Inventory (SCODI).

Methods

Forty SCODI items (5 point Likert type scale) were developed based on clinical recommendations and grouped into 4 dimensions: self-care maintenance, self-care monitoring, self-care management and self-care confidence based on the theory. Content validity was assessed by a multidisciplinary panel of experts. A multi-centre cross-sectional study was conducted in a consecutive sample of 200 type 1 and type 2 diabetes patients. Dimensionality was evaluated by exploratory factor analyses. Multidimensional model based reliability was estimated for each scale. Multiple regression models estimating associations between SCODI scores and glycated haemoglobin (HbA1c), body mass index, and diabetes complications, were used for construct validity.

Results

Content validity ratio was 100%. A multidimensional structure emerged for the 4 scales. Multidimensional model-based reliabilities were between 0.81 (maintenance) and 0.89 (confidence). Significant associations were found between self-care maintenance and HbA1c (p?=?0.02) and between self-care monitoring and diabetes complications (p?=?0.04). Self-care management was associated with BMI (p?=?0.004) and diabetes complications (p?=?0.03). Self-care confidence was a significant predictor of self-care maintenance, monitoring and management (all p?<?0.0001).

Conclusion

The SCODI is a valid and reliable theoretically-grounded tool to measure self-care in type 1 and type 2 DM patients.

     

Male-specific Y-linked transgene markers to enhance biologically-based control of the Mexican fruit fly, <Emphasis Type="Italic">Anastrepha ludens</Emphasis>(Diptera: Tephritidae)

Background

Reliable marking systems are critical to the prospective field release of transgenic insect strains. This is to unambiguously distinguish released insects from wild insects in the field that are collected in field traps, and tissue-specific markers, such as those that are sperm-specific, have particular uses such as identifying wild females that have mated with released males. For tephritid fruit flies such as the Mexican fruit fly, Anastrepha ludens, polyubiquitin-regulated fluorescent protein body markers allow transgenic fly identification, and fluorescent protein genes regulated by the spermatocyte-specific β2-tubulin promoter effectively mark sperm. For sterile male release programs, both marking systems can be made male-specific by linkage to the Y chromosome.

Results

An A. ludens wild type strain was genetically transformed with a piggyBac vector, pBXL{PUbnlsEGFP, Asβ2tub-DsRed.T3}, having the polyubiquitin-regulated EGFP body marker, and the β2-tubulin-regulated DsRed.T3 sperm-specific marker. Autosomal insertion lines effectively expressed both markers, but a single Y-linked insertion (Y^EGFP strain) expressed only PUbnlsEGFP. This insertion was remobilized by transposase helper injection, which resulted in three new autosomal insertion lines that expressed both markers. This indicated that the original Y-linked Asβ2tub-DsRed.T3 marker was functional, but specifically suppressed on the Y chromosome. The PUbnlsEGFP marker remained effective however, and the Y^EGFP strain was used to create a sexing strain by translocating the wild type allele of the black pupae (bp⁺) gene onto the Y, which was then introduced into the bp^- mutant strain. This allows the mechanical separation of mutant female black pupae from male brown pupae, that can be identified as adults by EGFP fluorescence.

Conclusions

A Y-linked insertion of the pBXL{PUbnlsEGFP, Asβ2tub-DsRed.T3} transformation vector in A. ludens resulted in male-specific expression of the EGFP fluorescent protein marker, and was integrated into a black pupae translocation sexing strain (T(Y^EGFP/bp⁺), allowing the identification of male adults when used in sterile male release programs for population control. A unique observation was that expression of the Asβ2tub-DsRed.T3 sperm-specific marker, which was functional in autosomal insertions, was specifically suppressed in the Y-linked insertion. This may relate to the Y chromosomal regulation of male-specific germ-line genes in Drosophila.