Insulin Resistance In Older Adults Research Articles

The serum small non-coding RNA (SncRNA) landscape as a molecular biomarker of age associated muscle dysregulation and insulin resistance in older adults.

Small noncoding RNAs (sncRNAs) are implicated in age-associated pathologies, including sarcopenia and insulin resistance (IR). As potential circulating biomarkers, most studies have focussed on microRNAs (miRNAs), one class of sncRNA. This study characterized the wider circulating sncRNA transcriptome of older individuals and associations with sarcopenia and IR. sncRNA expression including miRNAs, transfer RNAs (tRNAs), tRNA-associated fragments (tRFs), and piwi-interacting RNAs (piRNAs) was measured in serum from 21 healthy and 21 sarcopenic Hertfordshire Sarcopenia Study extension women matched for age (mean 78.9 years) and HOMA2-IR. Associations with age, sarcopenia and HOMA2-IR were examined and predicted gene targets and biological pathways characterized. Of the total sncRNA among healthy controls, piRNAs were most abundant (85.3%), followed by tRNAs (4.1%), miRNAs (2.7%), and tRFs (0.5%). Age was associated (FDR < 0.05) with 2 miRNAs, 58 tRNAs, and 14 tRFs, with chromatin organization, WNT signaling, and response to stress enriched among gene targets. Sarcopenia was nominally associated (p < .05) with 12 tRNAs, 3 tRFs, and 6 piRNAs, with target genes linked to cell proliferation and differentiation such as Notch Receptor 1 (NOTCH1), DISC1 scaffold protein (DISC1), and GLI family zinc finger-2 (GLI2). HOMA2-IR was nominally associated (p<0.05) with 6 miRNAs, 9 tRNAs, 1 tRF, and 19 piRNAs, linked with lysine degradation, circadian rhythm, and fatty acid biosynthesis pathways. These findings identify changes in circulating sncRNA expression in human serum associated with chronological age, sarcopenia, and IR. These may have clinical utility as circulating biomarkers of ageing and age-associated pathologies and provide novel targets for therapeutic intervention.

Impact of Dietary Fiber on Inflammation and Insulin Resistance in Older Patients: A Narrative Review.

The beneficial impact of dietary fiber on the prevention and management of several chronic conditions associated with aging, including diabetes, neurodegenerative, cardiovascular diseases, and cancer, is well-known. High fiber intake has been associated with reduced inflammatory mediators counteracting the low-grade chronic inflammation typical of older age. In addition, dietary fiber improves postprandial glucose response and insulin resistance. In contrast, during acute diseases, its effects on insulin resistance and modulation of immune response are unclear. The aim of this narrative is to summarize the evidence for the potential impact of dietary fiber on inflammation and insulin resistance in older adults, with a particular focus on those acutely ill. Available evidence suggests that dietary fiber has the potential to counteract acute inflammation and to improve metabolic health. In addition, modulation of gut microbiota composition may contribute to improved immune function, particularly in the setting of aging-associated dysbiosis. This phenomenon has relevant implications in those acutely ill, in whom dysbiosis can be exacerbated. Our review leads to the conclusion that dietary interventions based on fiber manipulation could exploit its beneficial effects on inflammation and insulin resistance, if conducted from a precision nutrition perspective. This could also be true for the acutely ill patient, even though strong evidence is lacking.

Effect of Preoperative Oral Carbohydrates on Insulin Resistance in Older Adults Who Underwent Total Hip or Knee Arthroplasty: A Prospective Randomized Trial.

Preoperative carbohydrate drinks are recommended to reduce fasting time before surgery. Older adults are at risk of pulmonary aspiration and hyperglycemia after consuming carbohydrate drinks because of increased insulin resistance and delayed gastric emptying. We investigated the effects of oral carbohydrate drinks on perioperative insulin resistance, metabolic responses, and gastric volume in older adults. Fifty-six patients (aged more than 65 years) were randomly assigned to the control or carbohydrate (CHO) group. The CHO group received 400 mL of a carbohydrate drink 2 to 3 hours before anesthesia. The control group was allowed clear fluid intake 2 hours before anesthesia. Blood glucose and insulin levels were measured before intake of the carbohydrate drink and 1 hour postoperatively. Gastric volume was measured before spinal anesthesia. Insulin resistance was calculated using the homeostasis model assessment for insulin resistance. Homeostasis model assessment for insulin resistance was not different between the control and CHO groups preoperatively (2.5 versus 3.3, P = 0.156) or postoperatively (2.6 versus 2.4, P = 0.817). Preoperative gastric volume was comparable between the control and CHO groups (35.5 versus 30.8 mL, P = 0.696). Preoperative oral consumption of carbohydrates did not affect insulin resistance or gastric volume in older adults undergoing total knee or hip arthroplasty. Preoperative carbohydrate loading is safe in older adults undergoing total knee or hip arthroplasty. The data that support the findings of this study are available from the corresponding author on reasonable request. ClinicalTrials.gov (No. NCT04206189).

Relative Importance of Physical Activity and Body Composition on Insulin Resistance in Older Adult Population

This secondary data analysis project examined the relative importance of physical activity (PA) and body composition on homeostatic model assessment of insulin resistance (HOMA-IR) in older adults and investigated possible racial and/or ethnic differences in these relationships. The analysis included 717 participants from the 2017-2018 National Health and Nutrition Examination Survey study who were 55 years of age or older without diabetes. Results show that HOMA-IR increased with increasing levels of recreational PA, with 1 exception: HOMA-IR decreased with increasing levels of recreational PA in individuals with lower body mass index levels. Racial/ethnic differences in these relationships were identified.

Changes in objectively-measured physical capability over 4-year, risk of diabetes, and glycemic control in older adults: The China Health and Retirement Longitudinal study

AimsHigh physical capability reduces risk of diabetes, but the association of its changes with risk of diabetes and glycemic control is unclear in older adults. This study aimed to quantify their association. MethodsA total of 1,667 participants without diabetes and aged ≥ 60 years from the China Health and Retirement Longitudinal Study were included and followed over 4 years. Physical capability was objectively measured at baseline and 4-year later. Logistic regression models were used to assess the association of changes in physical capability with risk of diabetes. ResultsDuring follow-up, 160 participants developed diabetes. None of the changes in physical capability expressed in continuous scales or in tertiles was associated with risk of diabetes in unadjusted or adjusted models (all P > 0.05), and no favorable joint effects were observed. Changes in physical capability were not associated with changes in fasting plasma glucose or hemoglobin A1c. Yet increases in walking speed or grip strength were related to reduced metabolic score for insulin resistance (both P ≤ 0.03). ConclusionsIncreases in objectively-measured physical capability were not associated with reduced risk of diabetes but may ameliorate insulin resistance in older adults. Studies with longer follow-up periods are required to confirm these findings.

Impact of Recreational Physical Activity And Body Composition On Insulin Resistance In Older Adult Population

Social support in old age has been linked to psychological wellbeing outcomes, such as depressive symptoms. However, insufficient attention has been paid to implications of social support for different domains of psychological wellbeing. In this study, we explored these associations among 797 older adults (mean age = 78.61 years) living in a retirement community in Florida from the ECRC study. Our findings show that measures of social support and connectedness have varying influences on psychological wellbeing. Loneliness was associated with lower life satisfaction (b=- -1.12, p<0.001) and higher depressive symptoms (b=3.52, p<0.001). Higher self-rated social support was associated with higher life satisfaction (b= 1.66, p<0.001) but did not predict depressive symptoms. Depressive symptoms, however, were significantly higher (b=-1.45) among individuals who reported that they don’t have anyone who they can turn to if they feel lonely and want to talk. Feeling lonely also predicted lower positive affects among these older adults (b=-0.65, p<0.001). Similarly, loneliness also predicted higher negative affects (b=1.28, p<0.001). Negative affects were also significantly higher among women (b=-1.15, p<0.001) but lower among those who were living alone (b=-1.06, p<0.001). Overall, our findings underscore the importance of social support and connectedness for psychological wellbeing in later life. This finding is consistent with prior research demonstrating significance of social support in later life for the overall psychological wellbeing of the older adults.

Four-year changes in central fatness, risk of diabetes, and metabolic control in older adults: a cohort study with mediation analysis.

Background/AimsOlder adults are vulnerable to central obesity, while the association of changes in central fatness with risk of diabetes and metabolic control has not been investigated among this particular population. This study was aimed to address these issues.MethodsA total of 1,815 adults aged ≥ 60 years without diabetes at baseline were followed for 4 years. Incident diabetes was ascertained based on plasma glucose, hemoglobin A1c, medical history, and/or the use of anti-diabetic drugs. Central fatness was assessed by waist circumference (WC), waist-height ratio (WHtR), and body roundness index (BRI). Logistic regression analyses were used to assess the association of changes in central fatness with risk of diabetes, along with dose-response and mediation analyses.ResultsDuring the 4-year follow-up, 177 participants developed diabetes. The risk of diabetes was increased by 42%, 41%, and 40% per 1 standard deviation increases in WC, WHtR, and BRI, respectively, in multivariable-adjusted models (all p < 0.01). Moreover, these relationships were all linearly-shaped (all pnonlinearity ≥ 0.11). Increases in WC, WHtR, and BRI correlated with increases in hemoglobin A1c, triglycerides-and-glucose index, triglycerides, white blood cell, and C-reactive protein (all p ≤ 0.04). Yet only changes in hemoglobin A1c and triglycerides-and-glucose index were identified as the possible mediators for risk of diabetes, with their mediating effect being about 35% and 21%, respectively.ConclusionsIncreases in central fatness were related to elevated risk of diabetes, and this association might be partly explained by the worsening of glycemic control and insulin resistance in older adults.

Creatine supplementation does not promote additional effects on inflammation and insulin resistance in older adults: A pilot randomized, double-blind, placebo-controlled trial

A chronic, low-grade inflammation is commonly present in older adults and has been associated with the onset of age-related chronic diseases. Resistance training (RT) and creatine (CR) supplementation emerged as promising strategies to reduce circulating pro-inflammatory cytokines. This study aimed to investigate the effects of CR supplementation combined with RT on markers of inflammation and insulin resistance in community-dwelling older adults. In a pilot randomized, double-blind, placebo-controlled trial, participants were allocated to one of the following groups: 1) Creatine supplementation and resistance training (CR + RT, n = 13); 2) Placebo and resistance training (PL + RT, n = 14). While engaged in a 12-week RT program, participants from CR + RT group received 5g/day of CR monohydrate and participants from PL + RT group received the same dose of maltodextrin. At baseline and at week 12, blood samples were collected for glucose, insulin, adiponectin, leptin, interleukin 6, interleukin 10, monocyte chemo-attractant protein-1 and C-reactive protein analysis. After 12 weeks of intervention, there were no differences between groups in any of the variables analyzed. Monocyte chemoattractant protein-1 was reduced in both groups (CR + RT:-55.66 ± 48.93pg/mL, p < 0.01, dz = 1.13; PL + RT:-46.52 ± 55.21pg/mL, p < 0.01, dz = 0.84). Resistance training, regardless of CR supplementation, decreased MCP-1 concentration in older adults.

Altered Plasma Amino Acids and Lipids Associated With Abnormal Glucose Metabolism and Insulin Resistance in Older Adults.

Glucose metabolism becomes progressively impaired with older age. Fasting glucose and insulin resistance are risk factors for premature death and other adverse outcomes. We aimed to identifying plasma metabolites associated with altered glucose metabolism and insulin resistance in older community-dwelling adults. A targeted metabolomics approach was used to identify plasma metabolites associated with impaired fasting plasma glucose, 2-hour plasma glucose on oral glucose tolerance testing, and homeostatic model assessment insulin resistance (HOMA-IR) in 472 participants who participated in the Baltimore Longitudinal Study of Aging, with a mean (SD) age of 70.7 (9.9) years. We measured 143 plasma metabolites. In ordinal logistic regression analyses, using a false discovery rate of 5% and adjusting for potential confounders, we found that alanine, glutamic acid, and proline were significantly associated with increased odds of abnormal fasting plasma glucose. Phosphatidylcholine (diacyl C34:4, alkyl-acyl C32:1, C32:2, C34:2, C34:3, and C36:3) was associated with decreased odds of abnormal fasting plasma glucose. Glutamic and acid phosphatidylcholine alkyl-acyl C34:2 were associated with increased and decreased odds of 2-hour plasma glucose, respectively. Glutamic acid was associated with increased odds of higher tertiles of HOMA-IR. Glycine; phosphatidylcholine (diacyl C32:0, alkyl-acyl C32:1, C32:2, C34:1, C34:2, C34:3, C36:2, C36:3, C40:5, C40:6, C42:3, C42:4, and C42:5); sphingomyelin C16:0, C24:1, and C26:1; and lysophosphatidylcholine C18:1 were associated with decreased odds of abnormal HOMA-IR. Targeted metabolomics identified four plasma amino acids and 16 plasma lipid species, primarily containing polyunsaturated fatty acids, that were associated with abnormal glucose metabolism and insulin resistance in older adults.

Associations of sodium intake with obesity, metabolic disorder, and albuminuria according to age.

Sodium intake is associated with obesity and metabolic disorder in the general population. However, sodium intake is significantly reduced according to the decrease of energy intake in older adults although the prevalence of obesity is higher than younger adults. We evaluate the association of sodium excretion (UNa) with blood pressure, obesity, metabolic disorders, and albuminuria according to age. An observational study using data from the Korean National Health and Nutrition Examination Survey IV-V (2008–2011) was performed (N = 18,146). The 24 hour UNa was estimated from a single fasting urine sample.Participants aged≥75 years showed the highest risk for hypertension (HTN) in the highest quartile of UNa (1.769, 95% CI, 1.174–2.665), and the risks for HTN increased with advancing age. Obesity was not associated with UNa in participants aged≥75 years, and hypertriglyceridemia and body fat were not related to UNa in participants aged≥65 years, although these values were significantly associated with UNa in participants aged<65 years. Impaired fasting glucose (IFG) and insulin resistance (IR) were associated with UNa only in participants aged 20–39 years. The highest quartile of UNa showed a 3.777 fold increased risk for albuminuria in those aged 20–39 years (95% CI, 1.130–12.630), and a 1.885 fold increased risk (95% CI, 1.156–3.075) among participants aged 40–64 years. In participants aged≥65 years, albuminuria was not associated with UNa. In contrast with HTN, UNa was not associated with albuminuria, obesity, hypertriglyceridemia, IFG, and IR in older adults despite a strong association in younger adults.

Abdominal Adiposity, Not Cardiorespiratory Fitness, Mediates the Exercise-Induced Change in Insulin Sensitivity in Older Adults.

Abdominal obesity and low cardiorespiratory fitness (CRF) are associated with insulin resistance in older adults. Exercise is associated with improvement in insulin sensitivity. Whether this association is mediated by change in CRF and/or abdominal obesity is unclear. The current study is a secondary analysis of data from a randomized controlled trial in Kingston, Ontario. Sedentary older adults (60–80 years) (N = 80) who completed the exercise (N = 59) or control (N = 21) conditions for 6 months were included. CRF was measured using a treadmill test, adipose tissue (AT) by magnetic resonance imaging, and insulin sensitivity by hyperinsulinemic-euglycemic clamp. Waist circumference (WC) was measured at the iliac crest. Mediation analyses were used to assess whether abdominal AT and/or CRF mediated the exercise-induced change in insulin sensitivity. By comparison to controls, reduction (mean ± SD) was observed for visceral (-0.4 ± 0.4 kg) and abdominal subcutaneous (-0.4 ± 0.4) AT depots, WC (-4.1 ± 3.2 cm) and BMI (-0.9 ± 0.8 kg/m2) (p < 0.05). Insulin sensitivity (4.2 ± 5.2 M/I) and CRF (0.2 ± 0.3 L/min) improved in the exercise group (p < 0.05). All AT variables, BMI and WC were mediators of the change in insulin sensitivity (p < 0.05). After adjustment for change in total AT, abdominal AT remained a mediator with an effect ratio of 0.79 (p < 0.05), whereas total AT was not significant when adjusted for abdominal AT (p > 0.05). The effect ratio for change in WC and BMI combined (0.63, p<0.05) was greater than either alone. In conclusion, CRF did not mediate the exercise-induced change in insulin sensitivity in older adults. Abdominal adiposity was a strong mediator independent of change in total adiposity.

Brain natriuretic peptide and insulin resistance in older adults.

Higher levels of brain natriuretic peptide (BNP) have been associated with a decreased risk of diabetes in adults, but whether BNP is related to insulin resistance in older adults has not been established. N-terminal of the pro hormone brain natriuretic peptide (NT-pro BNP) was measured among Cardiovascular Health Study participants at the 1989-1990, 1992-1993 and 1996-1997 examinations. We calculated measures of insulin resistance [homeostatic model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), Gutt index, Matsuda index] from fasting and 2-h concentrations of glucose and insulin among 3318 individuals with at least one measure of NT-proBNP and free of heart failure, coronary heart disease and chronic kidney disease, and not taking diabetes medication. We used generalized estimating equations to assess the cross-sectional association of NT-proBNP with measures of insulin resistance. Instrumental variable analysis with an allele score derived from nine genetic variants (single nucleotide polymorphisms) within or near the NPPA and NPPB loci was used to estimate an un-confounded association of NT-proBNP levels on insulin resistance. Lower NT-proBNP levels were associated with higher insulin resistance even after adjustment for BMI, waist circumference and other risk factors (P < 0.001 for all four indices). Although the genetic score was strongly related to measured NT-proBNP levels amongst European Americans (F statistic = 71.08), we observed no association of genetically determined NT-proBNP with insulin resistance (P = 0.38; P = 0.01 for comparison with the association of measured levels of NT-proBNP). In older adults, lower NT-proBNP is associated with higher insulin resistance, even after adjustment for traditional risk factors. Because related genetic variants were not associated with insulin resistance, the causal nature of this association will require future study.

Determining the Development of Insulin Resistance in Older Adults of the NuAge cohort Using Trajectory Modeling of the Homeostatic Model Assessment of Insulin Resistance Score

Determining the Development of Insulin Resistance in Older Adults of the NuAge cohort Using Trajectory Modeling of the Homeostatic Model Assessment of Insulin Resistance Score

Effect of Selective Mineralocorticoid Receptor Blockade on Flow-Mediated Dilation and Insulin Resistance in Older Adults with Metabolic Syndrome.

The prevalence of metabolic syndrome is especially high in older adults. Metabolic syndrome is associated with impaired vascular endothelial function, insulin resistance, and increased risk for cardiovascular disease but the underlying mechanisms are not fully elucidated. Plasma aldosterone is independently associated with metabolic syndrome and is linked to endothelial dysfunction and insulin resistance. Thus, we hypothesized that mineralocorticoid receptor (MR) blockade would improve flow-mediated dilation and insulin resistance in older adults with metabolic syndrome. To test this hypothesis, we conducted a balanced, randomized, double-blind, placebo-controlled, crossover study using selective MR blockade (eplerenone; 100 mg/day) for 1 month with 1 month washout in older adults with metabolic syndrome (62.6 ± 3.2 yrs; mean ± standard error). We evaluated brachial artery flow-mediated dilation (ultrasonography), oxidative stress (oxidized low-density lipoproteins and F2-isoprostanes) and insulin resistance (homeostatic model assessment). In response to MR blockade, flow-mediated dilation (5.37 ± 0.85 vs. 5.98 ± 1.29%; placebo vs. eplerenone; P = 0.4), oxidized low-density lipoproteins (51.6 ± 11.5 vs. 56.1 ± 10.9 U/L; P = 0.6), and F2-isoprostanes (0.07 ± 0.02 vs. 0.06 ± 0.01 pg/mL; P = 0.3) did not improve. Insulin resistance also did not change following MR blockade (1.04 ± 0.26 vs. 1.38 ± 0.50; P = 0.6). However, MR blockade resulted in a large reduction (10 mmHg) in systolic blood pressure (140 ± 6 vs. 130 ± 6 mmHg; P = 0.02), with no significant change in diastolic blood pressure (81 ± 3 vs. 75 ± 2 mmHg; P = 0.2). Our data do not support a contributing role for MRs in endothelial dysfunction and insulin resistance in older adults with metabolic syndrome. However, our findings suggest MR activation is an important contributor to systolic hypertension in this patient group.

Appendicular skeletal muscle mass and insulin resistance in an elderly korean population: the korean social life, health and aging project-health examination cohort.

BackgroundIncreasing evidence supports an association between age-related loss of muscle mass and insulin resistance. However, the association has not been fully investigated in the general population. Thus, we investigated the association between appendicular skeletal muscle mass (ASM) and insulin resistance in an elderly Korean population.MethodsThis cross-sectional study included 158 men (mean age, 71.8) and 241 women (mean age, 70.6) from the Korean Social Life, Health and Aging Project, which started in 2011. In this study, ASM was measured by bioelectrical impedance analysis and was analyzed in three forms: ASM (kg), ASM/height2 (kg/m2), and ASM/weight (%). The homeostasis model assessment of insulin resistance (HOMA-IR) was used as a measure of insulin resistance. The relationships between the ASM values and the HOMA-IR were investigated by multiple linear regression models.ResultsThe HOMA-IR was positively associated with ASM (β=0.43, P<0.0001) and ASM/height2 (β=0.36, P<0.0001) when adjusted for sex and age. However, after additional adjustment for body weight, HOMA-IR was inversely associated with ASM (β=-0.43, P<0.001) and ASM/height2 (β=-0.30, P=0.001). Adjustment for other potential confounders did not change these associations. Conversely, HOMA-IR was consistently and inversely associated with ASM/weight before and after adjustment for other potential confounders.ConclusionOur results support the idea that lower skeletal muscle mass is independently associated with insulin resistance in older adults. When evaluating sarcopenia or muscle-related conditions in older adults, their whole body sizes also need to be considered.

Urinary benzene metabolite and insulin resistance in elderly adults

BackgroundBenzene is a volatile organic compound present in traffic-related and indoor air pollution. It is of particular concern since it is known to induce oxidative stress, which can affect insulin resistance (IR). We therefore examined the association between exposure to environmental benzene and IR in the elderly. Study DesignBetween 2008 and 2010, benzene metabolite levels (urinary trans,trans-muconic acid (t,t-MA)) and homeostatic model assessment index (HOMA-IR) were repeatedly measured in 505 adults aged ≥60years. Linear mixed-effect models and marginal logistic models were used to evaluate associations of t,t-MA concentration with HOMA-IR score and elevated IR, defined as HOMA-IR ≥2.6. ResultsAfter adjustment for sociodemographic and behavioral factors, environmental co-exposures, and metabolic conditions, quartile levels of urinary t,t-MA demonstrated a dose-dependent association with elevated IR (p-trend<0.001) and the level of oxidative stress estimated by urinary malondialdehyde (p-trend<0.001). As compared to the lowest quartile, the upper quartiles of t,t-MA (t,t-MA concentration >0.017mg/g CR) were associated with elevated IR [odds ratio=Q2: 2.00 (95% confidence interval (CI): 1.16–3.46); Q3: 3.33 (95% CI: 1.90–5.84); Q4: 2.07 (95% CI: 1.02–4.22)]. ConclusionUrinary benzene at levels currently observed in the urban elderly population is associated with IR, independent of traditional risk factors. Reduction of community-level exposure to benzene is therefore important for the effective prevention of IR in older adults.

Muscle Mass and Respiratory Quotient as Predictors of Insulin Resistance in Older Adults: A Cross-Sectional Study

Muscle Mass and Respiratory Quotient as Predictors of Insulin Resistance in Older Adults: A Cross-Sectional Study