| 1. |
- Xu, Hong, et al.
(author)
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Circulating alpha-tocopherol and insulin sensitivity among older men with chronic kidney disease
- 2016
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In: Journal of renal nutrition (Print). - : Elsevier BV. - 1051-2276 .- 1532-8503. ; 26:3, s. 177-182
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Journal article (peer-reviewed)abstract
- Objective: Insulin resistance is common in individuals with chronic kidney disease (CKD) and may be partly explained by modifiable risk factors. In the general population, vitamin E supplementation has been suggested to improve both insulin sensitivity and secretion. We here explore the potential role of vitamin E as a modifiable risk factor for insulin resistance among individuals with CKD.Design: Observational study.Setting: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate < 60 mL/minute/1.73 m2 or urinary albumin excretion rate ≥ 20 mg/minute from the third examination cycle of Uppsala Longitudinal Study of Adult Men.Subjects: A total of 273 nondiabetic men aged 70 to 71 years with CKD defined as either cystatin C estimated glomerular filtration rate < 60 mL/minute/1.73 m2 or urinary albumin excretion rate ≥ 20 μg/minute.Methods: Serum α-, β-, and γ-tocopherol concentrations were measured by high-performance liquid chromatography and expressed as μmol/total serum cholesterol and triglycerides (in mmol). Dietary vitamin E intake was estimated from 7-day food records.Main Outcome Measure: Insulin sensitivity index (M/I ratio) was measured by hyperinsulinemic-euglycemic glucose clamps. Univariate and multivariate regression models were fitted to assess the association between M/I and circulating concentrations of tocopherols.Results: The mean serum concentration of α-, β-, and γ- was 37.4 ± 6.58, 0.89 ± 0.23, and 4.32 ± 1.69 μmol/mmol, respectively. Median dietary vitamin E intake was 6.14 (interquartile range, 5.48-6.82) mg/day. In crude and fully-adjusted multivariate regression analyses, serum α-tocopherol levels were directly and strongly associated with M/I (standard β = 0.17, P = .003). No such association was observed for dietary vitamin E, serum β-, and γ-tocopherol concentrations.Conclusions: Serum α-tocopherol concentration associates with insulin sensitivity in nondiabetic older men with CKD.
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| 2. |
- González-Ortiz, Ailema, et al.
(author)
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Plant-based diets, insulin sensitivity and inflammation in elderly men with chronic kidney disease.
- 2020
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In: JN. Journal of Nephrology (Milano. 1992). - : Springer Science and Business Media LLC. - 1121-8428 .- 1724-6059. ; 33, s. 1091-1101
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Journal article (peer-reviewed)abstract
- BACKGROUND: In persons with CKD, adherence to plant-based diets is associated with lower risk of CKD progression and death, but underlying mechanisms are poorly characterized. We here explore associations between adherence to plant-based diets and measures of insulin sensitivity and inflammation in men with CKD stages 3-5.METHODS: Cross-sectional study including 418 men free from diabetes, aged 70-71 years and with cystatin-C estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 and not receiving kidney-specific dietetic advice. Information from 7-day food records was used to evaluate the adherence to a plant-based diet index (PBDi), which scores positively the intake of plant-foods and negatively animal-foods. Insulin sensitivity and glucose disposal rate were assessed with the gold-standard hyperinsulinemic euglycemic glucose clamp technique. Inflammation was evaluated by serum concentrations of C-reactive protein (CRP) and interleukin (IL)-6. Associations were explored through linear regression and restricted cubic splines.RESULTS: The majority of men had CKD stage 3a. Hypertension and cardiovascular disease were the most common comorbidities. The median PBDi was 38 (range 14-55). Across higher quintiles of PBDi (i.e. higher adherence), participants were less often smokers, consumed less alcohol, had lower BMI and higher eGFR (P for trend <0.05 for all). Across higher PBDi quintiles, patients exhibited higher insulin sensitivity and lower inflammation (P for trend <0.05). After adjustment for eGFR, lifestyle factors, BMI, comorbidities and energy intake, a higher PBDi score remained associated with higher glucose disposal rate and insulin sensitivity as well as with lower levels of IL-6 and CRP.CONCLUSION: In elderly men with non-dialysis CKD stages 3-5, adherence to a plant-based diet was associated with higher insulin sensitivity and lower inflammation, supporting a possible role of plant-based diets in the prevention of metabolic complications of CKD.
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| 3. |
- Jia, Ting, et al.
(author)
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Kidney function, β-cell function and glucose tolerance in older men
- 2015
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In: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 100:2, s. 587-593
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Journal article (peer-reviewed)abstract
- Context: Kidney dysfunction induces insulin resistance, but it is unknown if β cell function is affected.Objective: To investigate insulin release (β cell function) and glucose tolerance following a standardized oral glucose tolerance test (OGTT) across kidney function strata.Setting and Design: Community-based cohort study from the Uppsala Longitudinal Study of Adult Men (ULSAM).Participants and Main Outcome Measure: Included were 1015 non-diabetic Swedish men aged 70-71 years. All participants underwent OGTT and euglycaemic hyperinsulinaemic clamp (HEGC) tests, allowing determination of insulin sensitivity, β cell function and glucose tolerance. Kidney function was estimated by cystatin C-algorithms. Mixed models were used to identify determinants of insulin secretion after the hyperglycemic load.Results: As many as 466 (46%) of participants presented moderate-advanced kidney disease. Insulin sensitivity (by HEGC) decreased across decreasing kidney function quartiles. After the OGTT challenge, however, β cell function indices (area under the curve for insulin release, the estimated first phase insulin release and the insulinogenic index) were incrementally higher. Neither the oral disposition index nor ths 2-hour post-load glucose tolerance differed across kidney function strata. Mixed models showed that dynamic insulin release during the OGTT was inversely associated to kidney function despite correction for each individual's insulin sensitivity or its risk factors.Conclusions: In older men, β cell function after a hyperglycemic load appropriately compensated the loss in insulin sensitivity that accompanies kidney dysfunction. As a result, the net balance between insulin sensitivity and β cell function was preserved.
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| 4. |
- Jia, Ting, et al.
(author)
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Validation of insulin sensitivity surrogate indices and prediction of clinical outcomes in individuals with and without impaired renal function
- 2014
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In: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 86:2, s. 383-391
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Journal article (peer-reviewed)abstract
- As chronic kidney disease (CKD) progresses with abnormalities in glucose and insulin metabolism, commonly used insulin sensitivity indices (151s) may not be applicable in individuals with CKD. Here we sought to validate surrogate ISls against the glucose disposal rate by the gold-standard hyperinsulinemic euglycemic glucose clamp (HEGC) technique in 1074 elderly men of similar age (70 years) of whom 495 had and 579 did not have CKD (estimated glomerular filtration rate (eGFR) under 60 ml/min per 1.73 m2 (median eGFR of 46 ml/min per 1.73 m2)). All ISls provided satisfactory (weighted K over 0.6) estimates of the glucose disposal rate in patients with CKD. ISls derived from oral glucose tolerance tests (OGTTs) agreed better with HEGC than those from fasting samples (higher predictive accuracy). Regardless of CKD strata, all ISls allowed satisfactory clinical discrimination between the presence and absence of insulin resistance (glucose disposal rate under 4 mg/kg/min). We also assessed the ability of both HEGC and ISls to predict all-cause and cardiovascular mortality during a 10-year follow-up. Neither HEGC nor ISIs independently predicted mortality. Adjustment for renal function did not materially change these associations. Thus, ISls can be applied in individuals with moderately impaired renal function for diagnostic purposes. For research matters, OGTT-derived ISls may be preferred. Our data do not support the hypothesis of kidney function mediating insulin sensitivity (I5)-associated outcomes nor a role for IS as a predictor of mortality
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| 5. |
- Xiong, Zibo, et al.
(author)
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Nonesterified fatty acids and cardiovascular mortality in elderly men with CKD
- 2015
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In: American Society of Nephrology. Clinical Journal. - 1555-9041 .- 1555-905X. ; 10:4, s. 584-591
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Journal article (peer-reviewed)abstract
- Background and objectives Although nonesterified fatty acids (NEFAs) are essential as energy substrate for the myocardium, an excess of circulating NEFAs can be harmful. This study aimed to assess plausible relationships between serum NEFA and mortality due to cardiovascular disease (CVD) in individuals with CKD. Design, setting, participants, & measurements This was a prospective cohort study from the third examination cycle of the Uppsala LongitudinaL Study of Adult Men, a population-based survey of 1221 elderly men aged 70-71 years residing in Uppsala, Sweden. Data collection took place during 1991-1995. All participants had measures of kidney function; this study investigated 623 (51.7%) of these patients with manifest CKD (defined as either eGFR<60 ml/min per 1.73 m(2) or urine albumin excretion rate >= 20 mu g/min). Follow-up for mortality was done from examination date until death or December 31, 2007. After a median follow-up of 14 years (nterquartile range, 8-16.8), associations of NEFAs with mortality (related to all causes, CVD, ischemic heart disease [IHD], or acute myocardial infarction) were ascertained. Results The median serum NEFA was 14.1 mg/dl (interquartile range, 11.3-17.8). No association was found with measures of kidney function. Diabetes and serum triglycerides were the only multivariate correlates of NEFA. During follow-up, 453 participants died, of which 209 deaths were due to CVD, including 88 IHD deaths, with 41 attributed to acute myocardial infarction (AMI). In fully adjusted covariates, serum NEFA was an independent risk factor for all-cause mortality (hazard ratio [HR] per log(2) increase, 1.22; 95% confidence interval [95% CI], 1.00 to 1.48) and CVD-related death (HR, 1.51; 95% CI, 1.15 to 1.99), including both IHD (HR, 1.51; 95% CI, 1.00 to 2.32) and AMI mortality (HR, 2.08; 95% CI, 1.09 to 3.98). Conclusions Elevated serum NEFA associated with CVD mortality, and particularly with mortality due to AMI, in a homogeneous population of older men with moderate CKD.
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| 6. |
- Xu, Hong, et al.
(author)
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A proinflammatory diet is associated with systemic inflammation and reduced kidney function in elderly adults
- 2015
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In: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 145:4, s. 729-735
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Journal article (peer-reviewed)abstract
- Background: Diet can affect kidney health through its effects on inflammation. Objective: We tested whether the Adapted Dietary Inflammatory Index (ADII) is associated with kidney function and whether effects of diet on chronic low-grade inflammation explain this association. Methods: This was an observational analysis in 1942 elderly community-dwelling participants aged 70-71 y from 2 independent cohorts: the Uppsala Longitudinal Study of Adult Men (n = 1097 men) and the Prospective Investigation of Vasculature in Uppsala Seniors (n = 845 men and women). The ADII was calculated from 7-d food records, combining putatively proinflammatory and anti-inflammatory effects of nutrients, vitamins, and trace elements. The ADII was validated against serum C-reactive protein (CRP) concentrations. The estimated glomerular filtration rate (eGFR) was assessed from serum cystatin C (cys) and creatinine (crea). Associations between the ADII and eGFR were investigated, and CRP was considered to be a mediator. Results: In adjusted analysis, a 1-SD higher ADII was associated with higher CRP (beta: 6%, 95% Cl: 1%, 10%; P= 0.01) and lower eGFR [Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)(cys): -2.1%, 95% Cl: -3.2%, -1.1%; CKD-EPi(cys+crea): -1.8%; 95% Cl: -2.7%, -0.9%; both P < 0.001]. CRP was also inversely associated with eGFR. Mediation analyses showed that of the total effect of the ADII on kidney function, 15% and 17% (for CKD-EPIcys+crea and CKD-EPIcys equations, respectively) were explained/mediated by serum CRP. Findings were similar when each cohort was analyzed separately. Conclusions: A proinflammatory diet was associated with systemic inflammation as well as with reduced kidney function in a combined analysis of 2 community-based cohorts of elderly individuals. Our results also suggest systemic inflammation to be one potential pathway through which this dietary pattern is linked to kidney function.
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| 7. |
- Xu, Hong, et al.
(author)
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Albuminuria, renal dysfunction and circadian blood pressure rhythm in older men : a population-based longitudinal cohort study
- 2015
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In: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 8:5, s. 560-6
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Journal article (peer-reviewed)abstract
- BACKGROUND: Both albuminuria and kidney dysfunction may affect circadian blood pressure (BP) rhythm, while exacerbating each other's effects. We investigated associations and interactions of these two risk factors with circadian BP rhythm variation and non-dipper pattern progression in community-dwelling older men.METHODS: This was a cross-sectional and longitudinal analyses in the third and fourth cycles of the Uppsala Longitudinal Study of Adult Men, including 1051 men (age 71 years) with assessments on urinary albumin excretion rate (UAER), 24-h ambulatory BP monitoring (ABPM) and cystatin-C-estimated glomerular filtration rate (eGFR). Of these, 574 men attended re-examination after 6 years. Study outcomes were ABMP changes and non-dipping BP pattern (prevalence and progression).RESULTS: UAER associated with circadian BP rhythm both cross-sectionally and longitudinally. Longitudinally, significant interactions were observed between UAER and kidney dysfunction (eGFR < 60 mL/min/1.73 m(2)) in its association with the changes of both night-time systolic BP (SBP) and night-day SBP ratio. After stratification, UAER strongly predicted night-day SBP ratio change only in those with concurrent kidney dysfunction. At re-examination, 221 new cases of non-dipper were identified. In multivariable logistic models, high UAER associated with increased likelihood of non-dipper progression, but more strongly so among individuals with concurrent kidney dysfunction. These associations were evident also in the subpopulation of non-diabetics and in participants with normal range UAER.CONCLUSIONS: UAER associates with circadian BP rhythm variation and non-dipper progression in elderly men. Concurrent renal dysfunction modifies and exacerbates these associations.
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| 8. |
- Xu, Hong, et al.
(author)
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Clinical correlates of insulin sensitivity and its association with mortality among men with CKD stages 3 and 4
- 2014
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In: American Society of Nephrology. Clinical Journal. - : American Society of Nephrology. - 1555-9041 .- 1555-905X. ; 9:4, s. 690-697
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: Insulin resistance participates in the pathogenesis of multiple metabolic and cardiovascular diseases. CKD patients have impaired insulin sensitivity, but the clinical correlates and outcome associations of impaired insulin sensitivity in this vulnerable population are not well defined.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The prospective cohort study was from the third examination cycle of the Uppsala Longitudinal Study of Adult Men, a population-based survey of elderly men ages 70-71 years; insulin sensitivity was assessed by glucose disposal rate as measured with euglycemic clamps. Inclusion criterion was eGFR<60 ml/min per 1.73 m(2) (n=543). Exclusion criteria were incomplete data on euglycemic clamp and diabetes (n=97), leaving 446 men with CKD stages 3 and 4 (eGFR median=51.9 ml/min per 1.73 m(2); range=20.2-59.5 ml/min per 1.73 m(2)).RESULTS: The mean of glucose disposal rate was 5.4 ± 1.9 mg/kg per minute. In multivariable analysis, the independent clinical correlates of glucose disposal rate were eGFR (slope, 0.02; 95% confidence interval, 0.01 to 0.04), hypertension (-0.48; 95% confidence interval, -0.86 to -0.11), hyperlipidemia (-0.51; 95% confidence interval, -0.84 to -0.18), and body mass index (-0.32; 95% confidence interval, -0.37 to -0.27). During follow-up (median=10.0 years; interquartile range=8.7-11.0 years), 149 participants died. In Cox regression models, glucose disposal rate was not associated with all-cause or cardiovascular mortality. Multiplicative interactions (P<0.05) were observed between glucose disposal rate and physical activity or smoking in total mortality association. After subsequent stratification, glucose disposal rate was an independent correlate of all-cause mortality in smokers (adjusted hazard ratio, 0.72; 95% confidence interval, 0.54 to 0.96 per 1 mg/kg per minute glucose disposal rate increase) and physically inactive individuals (hazard ratio, 0.77; 95% confidence interval, 0.61 to 0.97) but not their counterparts.CONCLUSION: eGFR, together with various components of the metabolic syndrome, contributed to explain the variance of insulin sensitivity in men with CKD stages 3 and 4. Insulin sensitivity was associated with a lower mortality risk in individuals who smoked and individuals who were physically inactive.
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| 9. |
- Xu, Hong, et al.
(author)
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Dietary acid load, insulin sensitivity and risk of type 2 diabetes in community-dwelling older men
- 2014
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In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 57:8, s. 1561-1568
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Journal article (peer-reviewed)abstract
- Aims/hypothesis We tested the hypothesis that dietary acid load may increase the risk of type 2 diabetes, and studied the association between acid load and insulin sensitivity as a possible mechanism involved. Methods An observational survey with prospective follow-up including 911 non-diabetic Swedish men aged 70-71 years was carried out. The gold standard euglycaemic-hyperinsulinaemic clamp technique and the OGTT were used to determine insulin sensitivity and beta cell function, respectively. Diabetes incidence was assessed during 18 years of follow-up. Renal function was estimated from serum cystatin C concentrations. Dietary acid load was calculated as potential renal acid load (PRAL) and net endogenous acid production (NEAP) algorithms from 7 day food records. Adequate dietary reporters were identified by Goldberg cut-offs. Results PRAL and NEAP were not associated with insulin sensitivity or beta cell function. Underlying kidney function or consideration of dietary adequate reporters did not modify these null findings. During follow-up, 115 new cases of diabetes were validated. Neither PRAL nor NEAP was associated with diabetes incidence. Conclusios/interpretation Our results do not support the hypothesis that dietary acid load influences insulin sensitivity, beta cell function or diabetes risk. Interventional studies modifying acid-base dietary intake are needed to further elucidate a possible role of acid load in the development of type 2 diabetes.
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| 10. |
- Xu, Hong, et al.
(author)
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Dietary fiber, kidney function, inflammation, and mortality risk
- 2014
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In: American Society of Nephrology. Clinical Journal. - : American Society of Nephrology. - 1555-9041 .- 1555-905X. ; 9:12, s. 2104-2110
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Journal article (peer-reviewed)abstract
- BACKGROUND AND OBJECTIVES: In the United States population, high dietary fiber intake has been associated with a lower risk of inflammation and mortality in individuals with kidney dysfunction. This study aimed to expand such findings to a Northern European population.DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Dietary fiber intake was calculated from 7-day dietary records in 1110 participants aged 70-71 years from the Uppsala Longitudinal Study of Adult Men (examinations performed during 1991-1995). Dietary fiber was adjusted for total energy intake by the residual method. Renal function was estimated from the concentration of serum cystatin C, and deaths were registered prospectively during a median follow-up of 10.0 years.RESULTS: Dietary fiber independently and directly associated with eGFR (adjusted difference, 2.6 ml/min per 1.73 m(2) per 10 g/d higher; 95% confidence interval [95% CI], 0.3 to 4.9). The odds of C-reactive protein >3 mg/L were lower (linear trend, P=0.002) with higher fiber quartiles. During follow-up, 300 participants died (incidence rate of 2.87 per 100 person-years at risk). Multiplicative interactions were observed between dietary fiber intake and kidney dysfunction in the prediction of mortality. Higher dietary fiber was associated with lower mortality in unadjusted analysis. These associations were stronger in participants with kidney dysfunction (eGFR<60 ml/min per 1.73 m(2)) (hazard ratio [HR], 0.58; 95% CI, 0.35 to 0.98) than in those without (HR, 1.30; 95% CI, 0.76 to 2.22; P value for interaction, P=0.04), and were mainly explained by a lower incidence of cancer-related deaths (0.25; 95% CI, 0.10 to 0.65) in individuals with kidney dysfunction versus individuals with an eGFR≥60 ml/min per 1.73 m(2) (1.61; 95% CI, 0.69 to 3.74; P value for interaction, P=0.01).CONCLUSIONS: High dietary fiber was associated with better kidney function and lower inflammation in community-dwelling elderly men from Sweden. High dietary fiber was also associated with lower (cancer) mortality risk, especially in individuals with kidney dysfunction.
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