共查询到20条相似文献，搜索用时 31 毫秒
1.
Toshio Nishikimi Hiroyuki Okamoto Masahiro Nakamura Naoko Ogawa Kazukiyo Horii Kiyoshi Nagata Yasuaki Nakagawa Hideyuki Kinoshita Chinatsu Yamada Kazuhiro Nakao Takeya Minami Yoshihiro Kuwabara Koichiro Kuwahara Izuru Masuda Kenji Kangawa Naoto Minamino Kazuwa Nakao 《PloS one》2013,8(1)
Background
Recent studies have shown that in addition to brain (or B-type) natriuretic peptide (BNP) and the N-terminal proBNP fragment, levels of intact proBNP are also increased in heart failure. Moreover, present BNP immunoassays also measure proBNP, as the anti-BNP antibody cross-reacts with proBNP. It is important to know the exact levels of proBNP in heart failure, because elevation of the low-activity proBNP may be associated with the development of heart failure.Methodology/Principal Findings
We therefore established a two-step immunochemiluminescent assay for total BNP (BNP+proBNP) and proBNP using monoclonal antibodies and glycosylated proBNP as a standard. The assay enables measurement of plasma total BNP and proBNP within only 7 h, without prior extraction of the plasma. The detection limit was 0.4 pmol/L for a 50-µl plasma sample. Within-run CVs ranged from 5.2%–8.0% in proBNP assay and from 7.0%–8.4% in total BNP assay, and between-run CVs ranged from 5.3–7.4% in proBNP assay and from 2.9%–9.5% in total BNP assay, respectively. The dilution curves for plasma samples showed good linearity (correlation coefficients = 0.998–1.00), and analytical recovery was 90–101%. The mean total BNP and proBNP in plasma from 116 healthy subjects were 1.4±1.2 pM and 1.0±0.7 pM, respectively, and were 80±129 pM and 42±70 pM in 32 heart failure patients. Plasma proBNP levels significantly correlate with age in normal subjects.Conclusions/Significance
Our immunochemiluminescent assay is sufficiently rapid and precise for routine determination of total BNP and proBNP in human plasma. 相似文献2.
Background
Insulin resistance and type 2 diabetes are more prevalent in people of South Asian ethnicity than in people of Western European origin. To investigate the source of these differences, we compared insulin sensitivity, insulin secretion, glucose and lipid metabolism in South Asian and Nordic subjects with type 2 diabetes.Methods
Forty-three Nordic and 19 South Asian subjects with type 2 diabetes were examined with intra-venous glucose tolerance test, euglycemic clamp including measurement of endogenous glucose production, indirect calorimetry measuring glucose and lipid oxidation, and dual x-ray absorptiometry measuring body composition.Results
Despite younger mean ± SD age (49.7±9.4 vs 58.3±8.3 years, p = 0.001), subjects of South Asian ethnicity had the same diabetes duration (9.3±5.5 vs 9.6±7.0 years, p = 0.86), significantly higher median [inter-quartile range] HbA1c (8.5 [1.6] vs 7.3 [1.6] %, p = 0.024) and lower BMI (28.7±4.0 vs 33.2±4.7 kg/m2, p<0.001). The South Asian group exhibited significantly higher basal endogenous glucose production (19.1 [9.1] vs 14.4 [6.8] µmol/kgFFM⋅min, p = 0.003). There were no significant differences between the groups in total glucose disposal (39.1±20.4 vs 39.2±17.6 µmol/kgFFM⋅min, p = 0.99) or first phase insulin secretion (AUC0–8 min: 220 [302] vs 124 [275] pM, p = 0.35). In South Asian subjects there was a tendency towards positive correlations between endogenous glucose production and resting and clamp energy expenditure.Conclusions
Subjects of South Asian ethnicity with type 2 diabetes, despite being younger and leaner, had higher basal endogenous glucose production, indicating higher hepatic insulin resistance, and a trend towards higher use of carbohydrates as fasting energy substrate compared to Nordic subjects. These findings may contribute to the understanding of the observed differences in prevalence of type 2 diabetes between the ethnic groups. 相似文献3.
Zoe Lysy Leif E. Lovblom Elise M. Halpern Mylan Ngo Eduardo Ng Andrej Orszag Ari Breiner Vera Bril Bruce A. Perkins 《PloS one》2014,9(9)
Objective
Compared to recently-studied novel morphological measures, conventional small nerve fiber functional tests have not been systematically studied for identification of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine and compare the diagnostic performance of cooling detection thresholds (CDT) in a cross-sectional type 1 diabetes cohort.Research Design and Methods
136 subjects with type 1 diabetes and 52 healthy volunteers underwent clinical and electrophysiological examination for DSP classification concomitantly with the Toronto Clinical Neuropathy Score (TCNS) and three small fiber function tests: CDT, heart rate variability (HRV), and laser doppler imaging of axon-mediated neurogenic flare responses to cutaneous heating (LDIFLARE). Area under the curve (AUC) and optimal thresholds were determined by receiver operating characteristic (ROC) curves in the type 1 diabetes cohort.Results
Type 1 diabetes subjects were 42±17 years of age with mean HbA1c 7.9±1.7%. Fifty-nine (45%) met the case definition for DSP. CDT values were lowest in cases with DSP (18.3±8.4°C) compared to controls without DSP (28.4±3.5°C) and to healthy volunteers (29.6±1.8°C; p-value for both comparisons<0.0001). AUCCDT was 0.863 which was similar to AUCTCNS (0.858, p = 0.24) and AUCHRV (0.788, p = 0.05), but exceeded AUCLDIFLARE (0.750, p = 0.001). The threshold of <25.1°C was equivalent to the lower bound of the healthy volunteer 95% distribution [25.1, 30.8°C] and performed with 83% sensitivity and 82% specificity.Conclusions
Akin to novel small fiber morphological measures, CDT is a functional test that identifies DSP with very good diagnostic performance. These findings support further research that revisits the role of CDT in early DSP detection. 相似文献4.
Franciele R. Figueira Daniel Umpierre Karina R. Casali Pedro S. Tetelbom Nicoli T. Henn Jorge P. Ribeiro Beatriz D. Schaan 《PloS one》2013,8(3)
Purpose
To evaluate the effects of aerobic (AER) or aerobic plus resistance exercise (COMB) sessions on glucose levels and glucose variability in patients with type 2 diabetes. Additionally, we assessed conventional and non-conventional methods to analyze glucose variability derived from multiple measurements performed with continuous glucose monitoring system (CGMS).Methods
Fourteen patients with type 2 diabetes (56±2 years) wore a CGMS during 3 days. Participants randomly performed AER and COMB sessions, both in the morning (24 h after CGMS placement), and at least 7 days apart. Glucose variability was evaluated by glucose standard deviation, glucose variance, mean amplitude of glycemic excursions (MAGE), and glucose coefficient of variation (conventional methods) as well as by spectral and symbolic analysis (non-conventional methods).Results
Baseline fasting glycemia was 139±05 mg/dL and HbA1c 7.9±0.7%. Glucose levels decreased immediately after AER and COMB protocols by ∼16%, which was sustained for approximately 3 hours. Comparing the two exercise modalities, responses over a 24-h period after the sessions were similar for glucose levels, glucose variance and glucose coefficient of variation. In the symbolic analysis, increases in 0 V pattern (COMB, 67.0±7.1 vs. 76.0±6.3, P = 0.003) and decreases in 1 V pattern (COMB, 29.1±5.3 vs. 21.5±5.1, P = 0.004) were observed only after the COMB session.Conclusions
Both AER and COMB exercise modalities reduce glucose levels similarly for a short period of time. The use of non-conventional analysis indicates reduction of glucose variability after a single session of combined exercises.Trial Registration
Aerobic training, aerobic-resistance training and glucose profile (CGMS) in type 2 diabetes (CGMS exercise). ClinicalTrials.gov ID: NCT00887094. 相似文献5.
Background
Patients with type 1 diabetes mellitus (DM) and renal hyperfiltration also exhibit systemic microvascular abnormalities, including endothelial dysfunction. The effect of renal hyperfiltration on systemic blood pressure (BP) is less clear. We therefore measured BP, renal hemodynamic function and circulating renin angiotensin aldosterone system (RAAS) mediators in type 1 DM patients with hyperfiltration (n = 36, DM-H, GFR≥135 ml/min/1.73 m2) or normofiltration (n = 40, DM-N), and 56 healthy controls (HC). Since renal hyperfiltration represents a state of intrarenal RAAS activation, we hypothesized that hyperfiltration would be associated with higher BP and elevated levels of circulating RAAS mediators.Methods
BP, glomerular filtration rate (GFR - inulin), effective renal plasma flow (paraaminohippurate) and circulating RAAS components were measured in DM-H, DM-N and HC during clamped euglycemia (4–6 mmol/L). Studies were repeated in DM-H and DM-N during clamped hyperglycemia (9–11 mmol/L).Results
Baseline GFR was elevated in DM-H vs. DM-N and HC (167±6 vs. 115±2 and 115±2 ml/min/1.73 m2, p<0.0001). Baseline systolic BP (SBP, 117±2 vs. 111±2 vs. 109±1, p = 0.004) and heart rate (76±1 vs. 67±1 vs. 61±1, p<0.0001) were higher in DM-H vs. DM-N and HC. Despite higher SBP in DM-H, plasma aldosterone was lower in DM-H vs. DM-N and HC (42±5 vs. 86±14 vs. 276±41 ng/dl, p = 0.01). GFR (p<0.0001) and SBP (p<0.0001) increased during hyperglycemia in DM-N but not in DM-H.Conclusions
DM-H was associated with higher heart rate and SBP values and an exaggerated suppression of systemic aldosterone. Future work should focus on the mechanisms that explain this paradox in diabetes of renal hyperfiltration coupled with systemic RAAS suppression. 相似文献6.
Hui Peng Meirong Zhong Wenbo Zhao Cheng Wang Jun Zhang Xun Liu Yuanqing Li Sujay Dutta Paudel Qianqian Wang Tanqi Lou 《PloS one》2013,8(12)
Background
Cell-free microRNAs stably and abundantly exist in body fluids and emerging evidence suggests cell-free microRNAs as novel and non-invasive disease biomarker. Deregulation of miR-29 is involved in the pathogenesis of diabetic nephropathy and insulin resistance thus may be implicated in diabetic vascular complication. Therefore, we investigated the possibility of urinary miR-29 as biomarker for diabetic nephropathy and atherosclerosis in patients with type 2 diabetes.Methods
83 patients with type 2 diabetes were enrolled in this study, miR-29a, miR-29b and miR-29c levels in urine supernatant was determined by TaqMan qRT-PCR, and a synthetic cel-miR-39 was added to the urine as a spike-in control before miRNAs extraction. Urinary albumin excretion rate and urine albumin/creatinine ratio, funduscopy and carotid ultrasound were used for evaluation of diabetic vascular complication. The laboratory parameters indicating blood glucose level, renal function and serum lipids were also collected.Results
Patients with albuminuria (n = 42, age 60.62±12.00yrs) showed significantly higher comorbidity of diabetic retinopathy (p = 0.015) and higher levels of urinary miR-29a (p = 0.035) compared with those with normoalbuminuria (n = 41, age 58.54±14.40yrs). There was no significant difference in urinary miR-29b (p = 0.148) or miR-29c level (p = 0.321) between groups. Urinary albumin excretion rate significantly correlated with urinary miR-29a level (r = 0.286, p = 0.016), while urinary miR-29b significantly correlated with carotid intima-media thickness (cIMT) (r = 0.286, p = 0.046).Conclusion
Urinary miR-29a correlated with albuminuria while urinary miR-29b correlated with carotid intima-media thickness (cIMT) in patients with type 2 diabetes. Therefore, they may have the potential to serve as alternative biomarker for diabetic nephropathy and atherosclerosis in type 2 diabetes. 相似文献7.
Objective
Copeptin, a marker for stress mirroring vasopressin concentrations, has been shown to increase upon insulin-induced hypoglycaemia in patients after transsphenoidal surgery of pituitary adenomas. Patients with type 1 diabetes mellitus are prone to hypoglycaemia, but no data about copeptin levels upon hypoglycaemia are available. Furthermore, the perception of hypoglycaemia can vary from total unawareness to disabling episodes. The aim of this study was to investigate whether copeptin increases upon hypoglycaemia in patients with type 1 diabetes mellitus and is associated with the degree of hypoglycaemia awareness.Materials and Methods
In this prospective observational study, 17 patients with type 1 diabetes underwent a standardized insulin infusion test. Blood sampling for glucose and copeptin was performed at baseline and after 60 minutes (min). To assess hypoglycaemia associated symptoms the Mood and Symptom Questionnaire (MSQ) was conducted at baseline and after 60 min.Results
During insulin infusion, blood glucose decreased from 5.1 (SD±0.2) to 3.0 (±0.5) mmol/L at 60 min (p<0.001). Copeptin concentrations increased from 3.2 (±1.7) to 3.8 (±1.9) pmol/L (p = 0.03). Mood and Symptoms Questionnaire scores increased from 14 (±3.0) to 18 (±5.8), (p = 0.006). Patients with good hypoglycaemia awareness had an increase in copeptin from 3.0 (±1.8) to 4.2 (±2.4) pmol/L (p = 0.03) in contrast to patients more unaware of hypoglycaemia who only showed an increase in copeptin from 3.3 (±1.6) to 3.6 (±1.4) pmol/L (p = 0.4). There was a trend to a larger copeptin increase in patients aware of hypoglycemia compared to patients unaware of hypoglycemia (p = 0.074).Conclusion
Copeptin increases in patients with type 1 diabetes upon insulin induced hypoglycaemia. Interestingly, the copeptin increase seems associated with the degree of hypoglycaemia awareness. This hypothesis warrants further verification.Trial Registration
ClinicalTrials.gov NCT00515801 相似文献8.
Background
Synthesis of lipid species, including fatty acids (FA) and cholesterol, can contribute to pathological disease. The purpose of this study was to investigate FA and cholesterol synthesis in individuals with type 1 diabetes, a group at elevated risk for vascular disease, using stable isotope analysis.Methods
Individuals with type 1 diabetes (n = 9) and age-, sex-, and BMI-matched non-diabetic subjects (n = 9) were recruited. On testing day, meals were provided to standardize food intake and elicit typical feeding responses. Blood samples were analyzed at fasting (0 and 24 h) and postprandial (2, 4, 6, and 8 hours after breakfast) time points. FA was isolated from VLDL to estimate hepatic FA synthesis, whereas free cholesterol (FC) and cholesteryl ester (CE) was isolated from plasma and VLDL to estimate whole-body and hepatic cholesterol synthesis, respectively. Lipid synthesis was measured using deuterium incorporation and isotope ratio mass spectrometry.Results
Fasting total hepatic lipogenesis (3.91±0.90% vs. 5.30±1.22%; P = 0.41) was not significantly different between diabetic and control groups, respectively, nor was synthesis of myristic (28.60±4.90% vs. 26.66±4.57%; P = 0.76), palmitic (12.52±2.75% vs. 13.71±2.64%; P = 0.65), palmitoleic (3.86±0.91% vs. 4.80±1.22%; P = 0.65), stearic (5.55±1.04% vs. 6.96±0.97%; P = 0.29), and oleic acid (1.45±0.28% vs. 2.10±0.51%; P = 0.21). Postprandial lipogenesis was also not different between groups (P = 0.38). Similarly, fasting synthesis of whole-body FC (8.2±1.3% vs. 7.3±0.8%/day; P = 0.88) and CE (1.9±0.4% vs. 2.0±0.3%/day; P = 0.96) and hepatic FC (8.2±2.0% vs. 8.1±0.8%/day; P = 0.72) was not significantly different between diabetic and control subjects.Conclusions
Despite long-standing disease, lipogenesis and cholesterol synthesis was not different in individuals with type 1 diabetes compared to healthy non-diabetic humans. 相似文献9.
Giacomo Zoppini Anna Galletti Giovanni Targher Corinna Brangani Isabella Pichiri Carlo Negri Vincenzo Stoico Vittorio Cacciatori Enzo Bonora 《PloS one》2013,8(12)
Objective
A correlation between glucose control and 25(OH)D metabolism has been suggested by previous studies. However, this correlation has not yet been evaluated considering the impact of chronic complications of type 2 diabetes, especially the presence of nephropathy. Thus, the aim of this study was to determine the correlation between A1C and 25(OH)D in a well characterized cohort of type 2 diabetic patients.Research Design and Methods
We cross-sectionally examined the association between A1C and serum 25(OH) D in 715 type 2 diabetic patients attending our clinic during the years 2011–2012. The average age was 68±12 years (range 26–94 years). The relation between A1C and serum 25(OH)D levels was modelled by multiple linear regression analyses.Results
Serum 25(OH)D levels were inversely associated with A1C levels (r = −0.116, p = .003). This relation maintains its independence in the multivariate analysis after adjusting for age, sex, A1C, BMI, treatment and duration of diabetes and nephropathy.Conclusions
In type 2 diabetic patients, high A1C levels are associated with low concentrations of serum 25(OH)D independently of duration of diabetes, diabetic treatment and nephropathy. Future studies are needed to clarify the biological relation between glucose control and vitamin D metabolism in type 2 diabetes. 相似文献10.
Kavita Venkataraman ChinMeng Khoo Hwee Lin Wee Chuen Seng Tan Stefan Ma Derrick Heng Jeannette Lee E. Shyong Tai Julian Thumboo 《PloS one》2014,9(11)
Background
Health related quality of life (HRQoL) is an important dimension of individuals'' well-being, and especially in chronic diseases like diabetes and hypertension. The objective of this study was to evaluate the contributions of disease process, comorbidities, medication or awareness of the disease to HRQoL in diabetes mellitus, hypertension and dyslipidemia.Methods
This was a cross-sectional study of 3514 respondents from the general community in Singapore, assessed for HRQoL, disease and comorbid conditions through self-report, clinical and laboratory investigations. HRQoL was assessed using SF-36 health survey version 2. For each condition, participants were categorized as having 1) no disease, 2) undiagnosed, 3) diagnosed, not taking medication, and 4) diagnosed, taking medication. Analysis used one-way ANOVA and multiple linear regression.Results
Diagnosed disease was associated with lower physical health component summary (PCS) scores across all three conditions. After adjustment for comorbidities, this association remained significant only for those not on medication in diabetes (−2.7±1.2 points, p = 0.03) and dyslipidemia (−1.3±0.4 points, p = 0.003). Diagnosed hypertension (no medication −2.6±0.9 points, p = 0.002; medication −1.4±0.5 points, p = 0.004) and dyslipidemia (no medication −0.9±0.4 points, p = 0.03; medication −1.9±0.5 points, p<0.001) were associated with lower mental health component summary (MCS) scores. Undiagnosed disease was associated with higher MCS in diabetes (2.4±1.0 points, p = 0.01) and dyslipidemia (0.8±0.4 points, p = 0.045), and PCS in hypertension (1.2±0.4 points, p = 0.004).Conclusions
Disease awareness was associated with lower HRQoL across the diseases studied, with PCS associations partially mediated by comorbidities. Equally importantly, undiagnosed disease was not associated with HRQoL deficits, which may partly explain why these individuals do not seek medical care. 相似文献11.
12.
Wen-Chi Pan Molly L. Kile Wei Jie Seow Xihong Lin Quazi Quamruzzaman Mahmuder Rahman Golam Mahiuddin Golam Mostofa Quan Lu David C. Christiani 《PloS one》2013,8(8)
Background
Chronic exposure to arsenic in drinking water is associated with increased risk of type 2 diabetes mellitus (T2DM) but the underlying molecular mechanism remains unclear.Objectives
This study evaluated the interaction between single nucleotide polymorphisms (SNPs) in genes associated with diabetes and arsenic exposure in drinking water on the risk of developing T2DM.Methods
In 2009–2011, we conducted a follow up study of 957 Bangladeshi adults who participated in a case-control study of arsenic-induced skin lesions in 2001–2003. Logistic regression models were used to evaluate the association between 38 SNPs in 18 genes and risk of T2DM measured at follow up. T2DM was defined as having a blood hemoglobin A1C level greater than or equal to 6.5% at follow-up. Arsenic exposure was characterized by drinking water samples collected from participants'' tubewells. False discovery rates were applied in the analysis to control for multiple comparisons.Results
Median arsenic levels in 2001–2003 were higher among diabetic participants compared with non-diabetic ones (71.6 µg/L vs. 12.5 µg/L, p-value <0.001). Three SNPs in ADAMTS9 were nominally associated with increased risk of T2DM (rs17070905, Odds Ratio (OR) = 2.30, 95% confidence interval (CI) 1.17–4.50; rs17070967, OR = 2.02, 95%CI 1.00–4.06; rs6766801, OR = 2.33, 95%CI 1.18–4.60), but these associations did not reach the statistical significance after adjusting for multiple comparisons. A significant interaction between arsenic and NOTCH2 (rs699780) was observed which significantly increased the risk of T2DM (p for interaction = 0.003; q-value = 0.021). Further restricted analysis among participants exposed to water arsenic of less than 148 µg/L showed consistent results for interaction between the NOTCH2 variant and arsenic exposure on T2DM (p for interaction = 0.048; q-value = 0.004).Conclusions
These findings suggest that genetic variation in NOTCH2 increased susceptibility to T2DM among people exposed to inorganic arsenic. Additionally, genetic variants in ADAMTS9 may increase the risk of T2DM. 相似文献13.
Roni Nielsen Helene N?rrelund Ulla Kampmann Hans Erik B?tker Niels M?ller Henrik Wiggers 《PloS one》2013,8(1)
Background
It is unknown whether changes in circulating glucose levels due to short-term insulin discontinuation affect left ventricular contractile function in type 2 diabetic patients with (T2D-HF) and without (T2D-nonHF) heart failure.Materials and Methods
In two randomized cross-over-designed trials, 18 insulin-treated type 2 diabetic patients with (Ejection Fraction (EF) 36±6%, n = 10) (trial 2) and without systolic heart failure (EF 60±3%, n = 8) (trial 1) were subjected to hyper- and normoglycemia for 9–12 hours on two different occasions. Advanced echocardiography, bicycle exercise tests and 6-minute hall walk distance were applied.Results
Plasma glucose levels differed between study arms (6.5±0.8 mM vs 14.1±2.6 mM (T2D-HF), 5.8±0.4 mM vs 9.9±2.1 mM (T2D-nonHF), p<0.001). Hyperglycemia was associated with an increase in several parameters: maximal global systolic tissue velocity (Vmax) (p<0.001), maximal mitral annulus velocity (S''max) (p<0.001), strain rate (p = 0.02) and strain (p = 0.05). Indices of increased myocardial systolic contractile function were significant in both T2D-HF (Vmax: 14%, p = 0.02; S''max: 10%, p = 0.04), T2D-nonHF (Vmax: 12%, p<0.01; S''max: 9%, p<0.001) and in post exercise S''max (7%, p = 0.049) during hyperglycemia as opposed to normoglycemia. LVEF did not differ between normo- and hyperglycemia (p = 0.17), and neither did peak exercise capacity nor catecholamine levels. Type 2 diabetic heart failure patients'' 6-minute hall walk distance improved by 7% (p = 0.02) during hyperglycemia as compared with normoglycemia.Conclusions
Short-term hyperglycemia by insulin discontinuation is associated with an increase in myocardial systolic contractile function in type 2 diabetic patients with and without heart failure and with a slightly prolonged walking distance in type 2 diabetic heart failure patients. (Clinicaltrials.gov identifier NCT00653510) 相似文献14.
Sophia Pathai Stephen D. Lawn Paul G. Shiels Helen A. Weiss Colin Cook Robin Wood Clare E. Gilbert 《PloS one》2013,8(2)
Background
Cellular senescence may be a key factor in HIV-related premature biological aging. We assessed features of the corneal endothelium that are known to be associated with biological aging, and cellular senescence markers in HIV-infected adults.Methods
Case-control study of 242 HIV-infected adults and 249 matched controls. Using specular microscopy, the corneal endothelium was assessed for features of aging (low endothelial cell density [ECD], high variation in cell size, and low hexagonality index). Data were analysed by multivariable regression. CDKN2A expression (a cell senescence mediator) was measured in peripheral blood leukocytes and 8-hydroxy-2′-deoxyguanosine (8-OHDG; an oxidative DNA damage marker) levels were measured in plasma.Results
The median age of both groups was 40 years. Among HIV-infected adults, 88% were receiving antiretroviral therapy (ART); their median CD4 count was 468 cells/µL. HIV infection was associated with increased odds of variation in cell size (OR = 1.67; 95% CI: 1.00–2.78, p = 0.04). Among HIV-infected participants, low ECD was independently associated with current CD4 count <200 cells/µL (OR = 2.77; 95%CI: 1.12–6.81, p = 0.03). In participants on ART with undetectable viral load, CDKN2A expression and 8-OHDG levels were higher in those with accelerated aging, as reflected by lower ECD.Conclusions
The corneal endothelium shows features consistent with HIV-related accelerated senescence, especially among those with poor immune recovery. 相似文献15.
Rasmus Ribel-Madsen Mario F. Fraga Stine Jacobsen Jette Bork-Jensen Ester Lara Vincenzo Calvanese Agustin F. Fernandez Martin Friedrichsen Birgitte F. Vind Kurt H?jlund Henning Beck-Nielsen Manel Esteller Allan Vaag Pernille Poulsen 《PloS one》2012,7(12)
Background
Monozygotic twins discordant for type 2 diabetes constitute an ideal model to study environmental contributions to type 2 diabetic traits. We aimed to examine whether global DNA methylation differences exist in major glucose metabolic tissues from these twins.Methodology/Principal Findings
Skeletal muscle (n = 11 pairs) and subcutaneous adipose tissue (n = 5 pairs) biopsies were collected from 53–80 year-old monozygotic twin pairs discordant for type 2 diabetes. DNA methylation was measured by microarrays at 26,850 cytosine-guanine dinucleotide (CpG) sites in the promoters of 14,279 genes. Bisulfite sequencing was applied to validate array data and to quantify methylation of intergenic repetitive DNA sequences. The overall intra-pair variation in DNA methylation was large in repetitive (LINE1, D4Z4 and NBL2) regions compared to gene promoters (standard deviation of intra-pair differences: 10% points vs. 4% points, P<0.001). Increased variation of LINE1 sequence methylation was associated with more phenotypic dissimilarity measured as body mass index (r = 0.77, P = 0.007) and 2-hour plasma glucose (r = 0.66, P = 0.03) whereas the variation in promoter methylation did not associate with phenotypic differences. Validated methylation changes were identified in the promoters of known type 2 diabetes-related genes, including PPARGC1A in muscle (13.9±6.2% vs. 9.0±4.5%, P = 0.03) and HNF4A in adipose tissue (75.2±3.8% vs. 70.5±3.7%, P<0.001) which had increased methylation in type 2 diabetic individuals. A hypothesis-free genome-wide exploration of differential methylation without correction for multiple testing identified 789 and 1,458 CpG sites in skeletal muscle and adipose tissue, respectively. These methylation changes only reached some percentage points, and few sites passed correction for multiple testing.Conclusions/Significance
Our study suggests that likely acquired DNA methylation changes in skeletal muscle or adipose tissue gene promoters are quantitatively small between type 2 diabetic and non-diabetic twins. The importance of methylation changes in candidate genes such as PPARGC1A and HNF4A should be examined further by replication in larger samples. 相似文献16.
Rachel Lieberman R. Paul Wadwa Nhung Nguyen Franziska K. Bishop Christina Reinick Janet K. Snell-Bergeon David M. Maahs 《PloS one》2013,8(10)
Objective
Vitamin D deficiency is common and associated with increased cardiovascular disease (CVD) risk. Pulse wave velocity (PWV) is a marker of vascular stiffness associated with CVD. We hypothesized that Vitamin D (25 (OH) D) levels would be inversely associated with PWV in youth with and without type 1 diabetes (T1D).Study Design
Comparisons were made between adolescents with T1D (n = 211; age = 17.5±2.3 years; diabetes duration = 10.9±3.2 years; A1c = 9.1±1.7%) and non-DM controls (n = 67; age = 16.9±1.9 years). PWV was measured in the carotid-femoral segment (Sphygmocor Vx, AtCor Medical, Lisle, IL).Results
Vitamin D levels were similar in adolescents with T1D and controls (27.7±0.7 v. 26.0±1.3 ng/ml; p = 0.26). Vitamin D was significantly inversely associated with PWV after adjusting for age, sex, quarter of the year, and race-ethnicity in adolescents with T1D (beta = −0.01±0.004, p = 0.02) but not in the non-DM adolescents (beta = −0.008±0.008, p = 0.32). Vitamin D remained significantly associated with PWV after additionally adjusting for hs-CRP in adolescents with T1D (−0.01±0.004, p = 0.01). After adjusting for BMI z-score, lipids, or blood pressure, the relationship of Vitamin D with PWV was not significant.Conclusions
Vitamin D levels were inversely associated with PWV in adolescents with T1D, but not independently of BMI, lipids, or blood pressure. Our data contrast with other reports and suggest further research is indicated to determine if Vitamin D supplementation would be beneficial to lower CVD risk in adolescents with T1D with vitamin D insufficiency or deficiency. 相似文献17.
John Joseph Valletta Andrew J. Chipperfield Geraldine F. Clough Christopher D. Byrne 《PloS one》2014,9(5)
Objective
Encouraging daily physical activity improves cardiorespiratory fitness and many cardiovascular risk factors. However, increasing physical activity often creates a challenge for people with type 1 diabetes, because of difficulties maintaining euglycemia in the face of altered food intake and adjustments to insulin doses. Our aim was to examine the triangular relationship between glucose control measured by continuous glucose monitoring system (CGMS), objective measures of total daily energy expenditure (TEE) recorded by a multi-sensory monitoring device, and cardiorespiratory fitness (CRF), in free-living subjects with type 1 diabetes.Research Design and Methods
Twenty-three individuals (12 women) with type 1 diabetes who were free from micro- and macrovascular complications were recruited. TEE and glucose control were monitored simultaneously for up to 12 days, using a multi-sensory device and CGMS respectively. CRF was recorded as V02 max from a maximal treadmill test with the Bruce protocol.Results
Subjects (mean±SD) were aged 37±11 years, with BMI = 26.5±5.1 kg.m−2, HbA1c = 7.7±1.3% (61±14 mmol/mol) and V02 max (ml.min−1.kg−1) = 39.9±8.4 (range 22.4 – 58.6). TEE (36.3±5.5 kcal.kg−1.day−1) was strongly associated with CRF(39.9±8.4 ml.min−1.kg−1) independently of sex (r = 0.63, p<0.01). However, neither TEE (r = −0.20, p = 0.36) nor CRF (r = −0.20, p = 0.39; adjusted for sex), were significantly associated with mean glycaemia measured by CGMS.Conclusion
Higher levels of energy expenditure (due to a more active lifestyle) are associated with increased cardiorespiratory fitness, but not necessarily better glycaemic control. Since increased levels of energy expenditure and good glycaemic control are both needed to protect against diabetes-related complications our data suggest they need to be achieved independently. 相似文献18.
Xiaomu Kong Xuelian Zhang Qi Zhao Jiang He Li Chen Zhigang Zhao Qiang Li Jiapu Ge Gang Chen Xiaohui Guo Juming Lu Jianping Weng Weiping Jia Linong Ji Jianzhong Xiao Zhongyan Shan Jie Liu Haoming Tian Qiuhe Ji Dalong Zhu Zhiguang Zhou Guangliang Shan Wenying Yang 《PloS one》2014,9(8)
Background and Aims
Obesity is a well-known risk factor for type 2 diabetes. Genome-wide association studies have identified a number of genetic loci associated with obesity. The aim of this study is to examine the contribution of obesity-related genomic loci to type 2 diabetes in a Chinese population.Methods
We successfully genotyped 18 obesity-related single nucleotide polymorphisms among 5338 type 2 diabetic patients and 4663 controls. Both individual and joint effects of these single nucleotide polymorphisms on type 2 diabetes and quantitative glycemic traits (assessing β-cell function and insulin resistance) were analyzed using logistic and linear regression models, respectively.Results
Two single nucleotide polymorphisms near MC4R and GNPDA2 genes were significantly associated with type 2 diabetes before adjusting for body mass index and waist circumference (OR (95% CI) = 1.14 (1.06, 1.22) for the A allele of rs12970134, P = 4.75×10−4; OR (95% CI) = 1.10 (1.03, 1.17) for the G allele of rs10938397, P = 4.54×10−3). When body mass index and waist circumference were further adjusted, the association of MC4R with type 2 diabetes remained significant (P = 1.81×10−2) and that of GNPDA2 was attenuated (P = 1.26×10−1), suggesting the effect of the locus including GNPDA2 on type 2 diabetes may be mediated through obesity. Single nucleotide polymorphism rs2260000 within BAT2 was significantly associated with type 2 diabetes after adjusting for body mass index and waist circumference (P = 1.04×10−2). In addition, four single nucleotide polymorphisms (near or within SEC16B, BDNF, MAF and PRL genes) showed significant associations with quantitative glycemic traits in controls even after adjusting for body mass index and waist circumference (all P values<0.05).Conclusions
This study indicates that obesity-related genomic loci were associated with type 2 diabetes and glycemic traits in the Han Chinese population. 相似文献19.
Khalid M. Alkharfy Nasser M. Al-Daghri Paul M. Vanhoutte Soundararajan Krishnaswamy Aimin Xu 《PloS one》2012,7(10)
Background
Elevated serum level of retinol-binding protein 4 (RBP4) has been associated with obesity-related co-morbidities including insulin resistance, dyslipidemia and hypertension.Objectives
The present study examined the relationship between serum level of RBP4 and various risk factors related to cardiovascular disease (CVD) in men and women.Methods
284 subjects (139 males, 145 females), grouped into healthy (n = 60), obese diabetes (n = 60), non-obese diabetes (n = 60), obese non-diabetes (n = 60) and patients with CVD (n = 44), were assessed for anthropometric and biochemical parameters related to obesity, diabetes and CVD. In addition, serum levels of several adipokines, including fatty acid binding protein 4 (FABP4) and lipocalin 2 (LCN2) and RBP4 were measured using specific immunoassays.Results
Serum RBP4 level correlated significantly with principal component derived from known risk factors of CVD (β = 0.20±0.06, P = 0.002). Significance of this correlation was limited to women (β = 0.20±0.06, P = 0.002) and it persisted even after adjusting for BMI (β = 0.19±0.06, P = 0.002). Overall (n = 284) serum RBP4 values significantly correlated with FABP4 (R = 0.19, p = 0.001). Serum FABP4 level of CVD subjects was significantly higher than healthy control (P = 0.001) and non-obese diabetes (P = 0.04) groups, but this difference was attributable to differences in BMI. Serum LCN2 level correlated well with RBP4 (R = 0.15, P = 0.008) and FABP4 (R = 0.36, P<0.001), but did not differ significantly between CVD and other groups.Conclusions
Results of this study indicate a significant correlation between serum RBP4 and various established risk factors for CVD and suggest RBP4 may serve as an independent predictor of CVD in women. 相似文献20.
Tsung-Hsien Lin Sheau-Fang Yang Chaw-Chi Chiu Ho-Ming Su Wen-Chol Voon Chee-Yin Chai Wen-Ter Lai Sheng-Hsiung Sheu 《PloS one》2014,9(1)