Dataset Information

Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

ABSTRACT: Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27(-)CD45RA(+/-); or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCTLs. This study explored associations between glucose dysregulation and markers of immunosenescence in CMV(+) and CMV(-) individuals.A cross-sectional sample of participants from an occupational cohort study (n?=?1,103, mean age 40 years, 88% male) were assessed for HbA(1c) and fasting glucose levels, diabetes, cardiovascular risk factors (e.g. lipids), numbers of circulating effector memory (EM; CD27(-)CD45RA(-)) and CD45RA re-expressing effector memory (EMRA; CD27(-)CD45RA(+)) T cells, and CMV infection status. Self-report and physical examination assessed anthropometric, sociodemographic and lifestyle factors.Among CMV(+) individuals (n?=?400), elevated HbA(1c) was associated with increased numbers of EM (B?=?2.75, p?

SUBMITTER: Rector JL

PROVIDER: S-EPMC4589544 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

Rector Jerrald L JL Thomas G Neil GN Burns Victoria E VE Dowd Jennifer B JB Herr Raphael M RM Moss Paul A PA Jarczok Marc N MN Hoffman Kristina K Fischer Joachim E JE Bosch Jos A JA

Diabetologia 20150820 11

<h4>Aims/hypothesis</h4>Biological ageing of the immune system, or immunosenescence, predicts poor health and increased mortality. A hallmark of immunosenescence is the accumulation of differentiated cytotoxic T cells (CD27(-)CD45RA(+/-); or dCTLs), partially driven by infection with the cytomegalovirus (CMV). Immune impairments reminiscent of immunosenescence are also observed in hyperglycaemia, and in vitro studies have illustrated mechanisms by which elevated glucose can lead to increased dCT ...[more]

PMID: 26290049

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Project description:BACKGROUND/OBJECTIVE:There is substantial interest in dietary approaches to reducing postprandial glucose (PPG) responses, but the quantitative contribution of PPG to longer-term glycemic control (reflected in glycated hemoglobin, HbA1c) in the general population is not known. This study quantified the associations of preprandial glucose exposure, PPG exposure, and glycemic variability with HbA1c and estimated the explained variance in HbA1c in individuals with and without type 2 diabetes (T2D). SUBJECTS/METHODS:Participants in the A1c-Derived Average Glucose (ADAG) study without T2D (n = 77) or with non-insulin-treated T2D and HbA1c<6.5% (T2DHbA1c?<?6.5%, n = 63) or HbA1c???6.5% (T2DHbA1c???6.5%, n = 34) were included in this analysis. Indices of preprandial glucose, PPG, and glycemic variability were calculated from continuous glucose monitoring during four periods over 12 weeks prior to HbA1c measurement. In linear regression models, we estimated the associations of the glycemic exposures with HbA1c and calculated the proportion of variance in HbA1c explained by glycemic and non-glycemic factors (age, sex, body mass index, and ethnicity). RESULTS:The factors in the analysis explained 35% of the variance in HbA1c in non-diabetic individuals, 49% in T2DHbA1c?<?6.5%, and 78% in T2DHbA1c???6.5%. In non-diabetic individuals PPG exposure was associated with HbA1c in confounder-adjusted analyses (P?<?0.05). In the T2DHbA1c?<?6.5% group, all glycemic measures were associated with HbA1c (P?<?0.05); preprandial glucose and PPG accounted for 14 and 18%, respectively, of the explained variation. In T2DHbA1c???6.5%, these glycemic exposures accounted for more than 50% of the variation in HbA1c and with equal relative contributions. CONCLUSIONS:Among the glycemic exposures, PPG exposure was most strongly predictive of HbA1c in non-diabetic individuals, suggesting that interventions targeting lowering of the PPG response may be beneficial for long-term glycemic maintenance. In T2D, preprandial glucose and PPG exposure contributed equally to HbA1c.

Project description:Aims/hypothesisThe aim of the study was to evaluate longitudinal associations between HbA1c levels, diabetes status and subsequent cognitive decline over a 10 year follow-up period.MethodsData from wave 2 (2004-2005) to wave 7 (2014-2015) of the English Longitudinal Study of Ageing (ELSA) were analysed. Cognitive function was assessed at baseline (wave 2) and reassessed every 2 years at waves 3-7. Linear mixed models were used to evaluate longitudinal associations.ResultsThe study comprised 5189 participants (55.1% women, mean age 65.6 ± 9.4 years) with baseline HbA1c levels ranging from 15.9 to 126.3 mmol/mol (3.6-13.7%). The mean follow-up duration was 8.1 ± 2.8 years and the mean number of cognitive assessments was 4.9 ± 1.5. A 1 mmol/mol increment in HbA1c was significantly associated with an increased rate of decline in global cognitive z scores (-0.0009 SD/year, 95% CI -0.0014, -0.0003), memory z scores (-0.0005 SD/year, 95% CI -0.0009, -0.0001) and executive function z scores (-0.0008 SD/year, 95% CI -0.0013, -0.0004) after adjustment for baseline age, sex, total cholesterol, HDL-cholesterol, triacylglycerol, high-sensitivity C-reactive protein, BMI, education, marital status, depressive symptoms, current smoking, alcohol consumption, hypertension, CHD, stroke, chronic lung disease and cancer. Compared with participants with normoglycaemia, the multivariable-adjusted rate of global cognitive decline associated with prediabetes and diabetes was increased by -0.012 SD/year (95% CI -0.022, -0.002) and -0.031 SD/year (95% CI -0.046, -0.015), respectively (p for trend <0.001). Similarly, memory, executive function and orientation z scores showed an increased rate of cognitive decline with diabetes.Conclusions/interpretationSignificant longitudinal associations between HbA1c levels, diabetes status and long-term cognitive decline were observed in this study. Future studies are required to determine the effects of maintaining optimal glucose control on the rate of cognitive decline in people with diabetes.

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Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

Publications

Elevated HbA(1c) levels and the accumulation of differentiated T cells in CMV(+) individuals.

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