scholarly journals Cross-Sectional and Prospective Associations of Rest-Activity Rhythms with Metabolic Markers and Type 2 Diabetes in Older Men

2020 ◽  
Author(s):  
Qian Xiao ◽  
Jingyi Qian ◽  
Daniel S Evans ◽  
Susan Redline ◽  
Nancy E. Lane ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fasting Glucose ◽  
Activity Rhythm ◽  
Older Men ◽  
Cross Sectional ◽  
Activity Rhythms ◽  
The Cross ◽  
Rest Activity

<a><b>OBJECTIVE </b>Disruption of rest-activity rhythms is cross-sectionally associated with metabolic disorders, including type 2 diabetes (T2D), yet it remains unclear whether it predicts impaired glucose metabolism and homeostasis. The aim of this study is to examine the cross-sectional and prospective associations between rest-activity rhythm characteristics and glycemic measures in a cohort of older men.</a> <p><b>RESEARCH DESIGN AND METHODS</b> Baseline rest-activity rhythms were derived from actigraphy using extended cosine model analysis. Fasting glucose, insulin and <a>homeostasis model assessment of insulin resistance </a>(HOMA-IR) were measured from fasting blood at baseline and after ~3.5 years. T2D were defined using self-report, medication use and fasting glucose. </p> <p> <b>RESULTS</b> In the cross-sectional analysis (n=2,450), lower 24-hour amplitude:mesor ratio (i.e., mean-activity-adjusted rhythm amplitude) and reduced overall rhythmicity, were associated with higher fasting insulin and HOMA-IR (all <i>p-trend < 0.0001</i>), indicating increased insulin resistance. The odds of baseline T2D were significantly higher among those in the lowest quintile of amplitude (OR <sub>Q1 vs Q4</sub> (95% CI), 1.63 (1.14, 2.30)) and late acrophase group (OR <sub>late vs normal</sub> (95% CI), 1.46 (1.04, 2.04)). In the prospective analysis (n=861), multiple rest-activity characteristics predicted a 2-3 fold increase in T2D risk, including a lower amplitude (OR <sub>Q1 vs Q4</sub> (95% CI), 3.81 (1.45, 10.00)) and amplitude:mesor ratio (2.79 (1.10, 7.07), reduced overall rhythmicity (3.49 (1.34, 9.10)), and a late acrophase (2.44 (1.09, 5.47)).</p> <p><b>CONCLUSIONS</b> Rest-activity rhythm characteristics are associated with impaired glycemic metabolism and homeostasis and higher risk of incident T2D.<br> </p>

scholarly journals Cross-Sectional and Prospective Associations of Rest-Activity Rhythms with Metabolic Markers and Type 2 Diabetes in Older Men

2020 ◽  
Author(s):  
Qian Xiao ◽  
Jingyi Qian ◽  
Daniel S Evans ◽  
Susan Redline ◽  
Nancy E. Lane ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Fasting Glucose ◽  
Activity Rhythm ◽  
Older Men ◽  
Cross Sectional ◽  
Activity Rhythms ◽  
The Cross ◽  
Rest Activity

<a><b>OBJECTIVE </b>Disruption of rest-activity rhythms is cross-sectionally associated with metabolic disorders, including type 2 diabetes (T2D), yet it remains unclear whether it predicts impaired glucose metabolism and homeostasis. The aim of this study is to examine the cross-sectional and prospective associations between rest-activity rhythm characteristics and glycemic measures in a cohort of older men.</a> <p><b>RESEARCH DESIGN AND METHODS</b> Baseline rest-activity rhythms were derived from actigraphy using extended cosine model analysis. Fasting glucose, insulin and <a>homeostasis model assessment of insulin resistance </a>(HOMA-IR) were measured from fasting blood at baseline and after ~3.5 years. T2D were defined using self-report, medication use and fasting glucose. </p> <p> <b>RESULTS</b> In the cross-sectional analysis (n=2,450), lower 24-hour amplitude:mesor ratio (i.e., mean-activity-adjusted rhythm amplitude) and reduced overall rhythmicity, were associated with higher fasting insulin and HOMA-IR (all <i>p-trend < 0.0001</i>), indicating increased insulin resistance. The odds of baseline T2D were significantly higher among those in the lowest quintile of amplitude (OR <sub>Q1 vs Q4</sub> (95% CI), 1.63 (1.14, 2.30)) and late acrophase group (OR <sub>late vs normal</sub> (95% CI), 1.46 (1.04, 2.04)). In the prospective analysis (n=861), multiple rest-activity characteristics predicted a 2-3 fold increase in T2D risk, including a lower amplitude (OR <sub>Q1 vs Q4</sub> (95% CI), 3.81 (1.45, 10.00)) and amplitude:mesor ratio (2.79 (1.10, 7.07), reduced overall rhythmicity (3.49 (1.34, 9.10)), and a late acrophase (2.44 (1.09, 5.47)).</p> <p><b>CONCLUSIONS</b> Rest-activity rhythm characteristics are associated with impaired glycemic metabolism and homeostasis and higher risk of incident T2D.<br> </p>

scholarly journals CROSS-SECTIONAL AND LONGITUDINAL RELATIONSHIPS BETWEEN REST-ACTIVITY RHYTHMS AND INFLAMMATION IN OLDER MEN

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S403-S403
Author(s):  
Xiao Qian ◽  
Qian Xiao ◽  
Daniel S Evans ◽  
Susan Redline ◽  
Nancy Lane ◽  
...  
Keyword(s):  
Sleep Disturbances ◽  
Activity Rhythm ◽  
Fold Increase ◽  
Older Men ◽  
Cross Sectional ◽  
Sleep Study ◽  
Activity Rhythms ◽  
Lower Amplitude ◽  
The Cross ◽  
Rest Activity

Abstract Sleep disturbances and physical inactivity have been associated with chronic inflammation, an important risk factor for cognitive decline in the aging population. However most previous studies focused on the cross-sectional relationships between sleep and physical activity and inflammation. In the Outcomes of Sleep Disorders in Older Men (MrOS Sleep) study, we studied both the cross-sectional and prospective associations between characteristics of 24-hour rest-activity rhythms measured by actigraphy and inflammation index measured by multiple circulating markers. In cross-sectional analysis, a lower amplitude is associated with elevated inflammation (Odds ratio Q4 vs Q1 (95% Confidence interval): 1.65 (1.22, 2.24)). In prospective analysis, an earlier acrophase (&lt;12:30) is associated with a two-fold increase in the risk of developing elevated inflammation over four years of follow up (2.08 (1.02, 4.23)). No individual inflammatory markers are associated with rest-activity rhythms. Our findings suggest that rest-activity rhythm characteristics predicts elevated inflammation.

scholarly journals Cross-sectional and Prospective Associations of Rest-Activity Rhythms With Metabolic Markers and Type 2 Diabetes in Older Men

Diabetes Care ◽  
2020 ◽  
Vol 43 (11) ◽  
pp. 2702-2712
Author(s):  
Qian Xiao ◽  
Jingyi Qian ◽  
Daniel S. Evans ◽  
Susan Redline ◽  
Nancy E. Lane ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Older Men ◽  
Cross Sectional ◽  
Metabolic Markers ◽  
Activity Rhythms ◽  
Rest Activity

scholarly journals Cross-Sectional and Prospective Associations of Rest-Activity Rhythms with Circulating Inflammatory Markers in Older Men

2021 ◽  
Author(s):  
Qian Xiao ◽  
Jingyi Qian ◽  
Daniel S Evans ◽  
Susan Redline ◽  
Nancy E Lane ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Activity Rhythm ◽  
Fold Increase ◽  
Older Men ◽  
Cross Sectional ◽  
Activity Rhythms ◽  
Tnf Α ◽  
Lower Amplitude ◽  
Ifn Γ ◽  
Rest Activity

Abstract Chronic increases in pro-inflammatory cytokines in older adults, known as inflammaging, is an important risk factor for morbidity and mortality in the aging population. It has been suggested that circadian disruption may play a role in chronic inflammation, but there has been limited study that investigated the overall profile of 24-hour rest-activity rhythms in relation to inflammation using longitudinal data. In the Outcomes of Sleep Disorders in Older Men Study, we applied the extended cosine model to derive multiple rest-activity rhythm characteristics using multi-day actigraphy, and examined their associations with six inflammatory markers (i.e., CRP, IL-6, TNF-α, TNF-α-sRII, IL-1 β, IFN-γ) measured from fasting blood. We assessed both the cross-sectional association between rest-activity rhythms and inflammatory markers measured at baseline, and the prospective association between baseline rest-activity rhythms and changes in in inflammatory markers over 3.5 years of follow up. We found that multiple rest-activity characteristics, including lower amplitude and relative amplitude, and decreased overall rhythmicity, were associated with higher levels of CRP, IL-6, TNF-α, and TNF-α-sRII, but not IL-1β and IFN-γ at baseline. Moreover, the lowest quartile of these three rest-activity characteristics was associated with an approximately two-fold increase in the odds of having elevated inflammation (i.e. having three or more markers in the highest quartile) at baseline. However, we found little evidence supporting a relationship between rest-activity rhythm characteristics and changes in inflammatory markers. Future studies should clarify the dynamic relationship between rest-activity rhythms and inflammation in different populations, and evaluate the effects of improving rest-activity profiles on inflammation and related disease outcomes.

scholarly journals The cross-sectional association of renal dysfunction with tests of cognition in middle-aged adults with early type 2 diabetes

2020 ◽  
pp. 107805
Author(s):  
Joshua I. Barzilay ◽  
Naji Younes ◽  
Rodica Pop-Busui ◽  
Hermes Florez ◽  
Elizabeth Seaquist ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Renal Dysfunction ◽  
Early Type ◽  
Middle Aged ◽  
Cross Sectional ◽  
The Cross ◽  
Middle Aged Adults

Increasing endogenous PPARγ ligands improves insulin sensitivity and protects against diet-induced obesity without side effects of thiazolidinediones

2021 ◽  
Author(s):  
Yu-Hua Tseng ◽  
Lee-Ming Chuang ◽  
Yi-Cheng Chang ◽  
Meng-Lun Hsieh ◽  
Lun Tsou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Insulin Sensitivity ◽  
Side Effects ◽  
Knockout Mice ◽  
Fasting Glucose ◽  
Binding Mode ◽  
Fluid Retention ◽  
Diet Induced Obesity

Abstract Insulin resistance and obesity are pivotal features of type 2 diabetes mellitus. Peroxisome proliferator-activated receptor γ (PPARγ) is a master transcriptional regulator of systemic insulin sensitivity and energy balance. The anti-diabetic drug thiazolidinediones are potent synthetic PPARγ ligands and insulin sensitizers with undesirable side effects including increased adiposity, fluid retention, and osteoporosis, which limit their clinical use. We and others have proved that 15-keto-PGE2 is an endogenous natural PPARγ ligand. 15-keto-PGE2 is catalyzed by prostaglandin reductase 2 (PTGR2) to become inactive metabolites. We found that 15-keto-PGE2 level is increased in Ptgr2 knockout mice. Ptgr2 knockout mice were protected from diet-induced obesity, insulin resistance, and hepatic steatosis without fluid retention nor reduced bone mineral density. Diet-induced obese mice have drastically reduced 15-keto-PGE2 levels compared to lean mice. Administration of 15-keto-PGE2 markedly improved insulin sensitivity and prevented diet-induced obesity in mice. We demonstrated that 15-keto-PGE2 activates PPARγ through covalent binding to its cysteine 285 residue at helix 3, which restrained its binding pocket between helix 3 and β-sheets of the PPARγ ligand binding domain. This binding mode differs from the helix12-dependent binding mode of thiazolidinediones. We further identified a small-molecule PTGR2 inhibitor BPRPT245, which interferes the interaction between the substrate-binding sites of PTGR2 and 15-keto-PGE2. BPRPT245 increased 15-keto-PGE2 concentration, activated PPARγ, and promoted glucose uptake in adipocytes. BPRPT245 also prevented diet-induced obesity, improved insulin sensitivity and glucose tolerance, lowers fasting glucose without fluid retention and osteoporosis. In humans, reduced serum 15-keto-PGE2 levels were observed in patients with type 2 diabetes compared with controls. Furthermore, serum 15-keto-PGE2 levels correlate inversely with insulin resistance and fasting glucose in non-diabetic humans. In conclusion, we identified a new therapeutic approach to improve insulin sensitivity and protect diet-induced obesity through increasing endogenous natural PPARγ ligands without side effects of thiazolidinediones.

scholarly journals Effect of folate supplementation on insulin sensitivity and type 2 diabetes: a meta-analysis of randomized controlled trials

2019 ◽  
Vol 109 (1) ◽  
pp. 29-42 ◽  
Author(s):  
Mads Vendelbo Lind ◽  
Lotte Lauritzen ◽  
Mette Kristensen ◽  
Alastair B Ross ◽  
Jane Nygaard Eriksen
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Randomized Controlled Trials ◽  
Fasting Glucose ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Folate Supplementation ◽  
Randomized Controlled ◽  
Meta Analyses

ABSTRACT Background Various mechanisms link higher total homocysteine to higher insulin resistance (IR) and risk of type 2 diabetes (T2D). Folate supplementation is recognized as a way to lower homocysteine. However, randomized controlled trials (RCTs) show inconsistent results on IR and T2D outcomes. Objective The aim of this study was to examine the effect of folate supplementation on IR and T2D outcomes. Design We conducted a systematic literature search in PubMed, Web of Science, and EMBASE and prior systematic reviews and meta-analyses and identified 29 RCTs (22,250 participants) that assessed the effect of placebo-controlled folate supplementation alone or in combination with other B vitamins on fasting glucose, insulin, homeostasis model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), or risk of T2D. The meta-analysis was conducted using both random- and fixed-effects models to calculate weighted mean differences (WMDs) or risk ratios with 95% CIs. Subgroup analyses were conducted based on intervention type (folate alone or in combination with other B vitamins), as well as analysis based on population characteristics, duration, dose, and change in homocysteine. Results When compared with placebo, folate supplementation lowered fasting insulin (WMD: −13.47 pmol/L; 95% CI: −21.41, −5.53 pmol/L; P &lt; 0.001) and HOMA-IR (WMD: −0.57 units; 95% CI: −0.76, −0.37 units; P &lt; 0.0001), but no overall effects were observed for fasting glucose or HbA1c. Heterogeneity was low in all meta-analyses, and subgroup analysis showed no signs of effect modification except for change in homocysteine, with the most pronounced effects in trials with a change of &gt;2.5 µmol/L. Changes in homocysteine after folate supplementation correlated with changes in fasting glucose (β = 0.07; 95% CI: 0.01, 0.14; P = 0.025) and HbA1c (β = 0.46; 95% CI: 0.06, 0.85; P = 0.02). Only 2 studies examined folate supplementation on risk of T2D, and they found no change in RR (pooled RR: 0.91; 95% CI: 0.80, 1.04; P = 0.16). Conclusion Folate supplementation might be beneficial for glucose homeostasis and lowering IR, but at present there are insufficient data to conclusively determine the effect on development of T2D. This trial was registered on the Prospero database as CRD42016048254.

scholarly journals Legume consumption and its association with fasting glucose, insulin resistance and type 2 diabetes in the Indian Migration Study

2016 ◽  
Vol 19 (16) ◽  
pp. 3017-3026 ◽  
Author(s):  
Preet K Dhillon ◽  
Liza Bowen ◽  
Sanjay Kinra ◽  
Ankalmadugu Venkatsubbareddy Bharathi ◽  
Sutapa Agrawal ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Large Scale ◽  
Fasting Glucose ◽  
Epidemiological Studies ◽  
Model Assessment ◽  
Dietary Intakes ◽  
Migration Status

AbstractObjectiveLegume consumption is associated with lower fasting glucose (FG) and insulin levels in nutrition trials and lower CVD mortality in large-scale epidemiological studies. In India, legumes are widely consumed in various preparations, yet no epidemiological study has evaluated the association of legumes with FG levels, insulin resistance and diabetes risk. The present study aimed to fill this gap.DesignFasting blood samples, in-person interviews to obtain information on demographic/socio-economic factors, physical activity, alcohol and tobacco use, and anthropometric measurements were collected. Dietary intakes were assessed by an interviewer-administered, validated, semi-quantitative FFQ.SettingLucknow, Nagpur, Hyderabad and Bangalore, India.SubjectsMen and women (n 6367) aged 15–76 years – urban residents, urban migrants and their rural siblings.ResultsIn multivariate random-effects models adjusted for age, BMI, total energy intake, macronutrients, physical activity and rural/migration status, daily legume consumption was not associated with FG (P-for-trend=0·78), insulin resistance (homeostasis model assessment score; P-for-trend=0·73) or the prevalence of type 2 diabetes mellitus (P-for-trend=0·41). Stratified analyses by vegetarian diet and migration status did not change the findings. Inverse associations between legumes and FG emerged for participants with lower BMI and higher carbohydrate, protein, fat and sugar intakes.ConclusionsAlthough legumes are essential in traditional Indian diets, as well as in prudent and Mediterranean diets in the West, we did not find an association between legumes and markers of glycaemic control, insulin resistance or diabetes, except for subgroups based on BMI and macronutrient intake. The ubiquitous presence and complexity of legume preparations in Indian diets may contribute to these findings.

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