Insulin Sensitivity In Older Adults Research Articles

The Association of Measures of Cardiovascular Autonomic Function, Heart Rate, and Orthostatic Hypotension With Incident Glucose Disorders: The Cardiovascular Health Study.

The autonomic nervous system (ANS) innervates pancreatic endocrine cells, muscle, and liver, all of which participate in glucose metabolism. We tested whether measures of cardiovascular ANS function are independently associated with incident diabetes and annual change in fasting glucose (FG) levels as well as with insulin secretion and insulin sensitivity in older adults without diabetes. Heart rate (HR) and measures of HR variability (HRV) were derived from 24-h electrocardiographic monitoring. Blood pressure, seated and standing, was measured. Cox proportional hazards models and linear mixed models were used to analyze the associations between HRV, HR, and orthostatic hypotension (SBP >20 mmHg decline) and incident diabetes or longitudinal FG change. The mean annual unadjusted FG change was 1 mg/dL. Higher detrended fluctuation analyses (DFA) values, averaged over 4-11 (DFA1) or 12-20 beats (DFA2)-reflecting greater versus less organization of beat-to-beat intervals-were associated with less FG increase over time (per 1-SD increment: DFA1: -0.49 mg/dL/year [-0.96, -0.03]; DFA2: -0.55 mg/dL/year [-1.02, -0.09]). In mutually adjusted analyses, higher SD of the N-N interval (SDNN) was associated with less FG increase over time (per 1-SD increment: SDNN: -0.62 mg/dL/year [-1.22, -0.03]). Higher values of DFA1, DFA2, and SDNN were each associated with greater insulin secretion and insulin sensitivity but not with incident diabetes. We observed no association of HR or orthostatic hypotension with diabetes or FG change. Specific measures of cardiac autonomic function are prospectively related to FG level changes and insulin secretion and action.

Phenothiazines to Treat Alzheimer’s Disease

Current treatments of Alzheimer’s Disease (AD) are largely ineffective and do not address underlying pathophysiological processes. The model organism C. elegans has been successfully used to discover compounds to treat human diseases, some now in clinical trials. To develop novel drugs and explore pathways to treat AD, we took on a forward pharmacological approach with a C. elegans model for AD, completed with studies to expand results to lifespan as well as healthspan. We screened 2560 drugs from the Microsource Spectrum library for their ability to delay proteotoxicity (indicated by paralysis) in an Abeta transgenic C. elegans muscle model of AD (CL2006) in liquid medium. Among the most protective drugs were phenothiazines, which are orally active and cross the blood-brain barrier, desirable properties of drugs to treat AD. 80 phenothiazines congeners were further assessed; 60% were protective in CL2006 worms. 9/20 tested phenothiazines increased lifespan in N2 worms and 2/3 phenothiazines tested promoted significantly higher pharyngeal pumping rates compared with control till day 10 of adulthood in N2 worms. 2 of the drugs were protective in the C. elegans neuronal model of AD. This phenotypic screening approach led to the discovery of potential drugs to treat AD. These phenothiazines protect against Abeta toxicity, and assessment of efficacy to protect against other forms of proteotoxicity are ongoing. These studies suggest the utility of C. elegans to discover drugs to treat human diseases. Future studies will assess molecular mechanisms mediating the protective effects of these compounds.

Systemic Bioenergetic Capacity Changes with Cognitive Status and Insulin Sensitivity in Older Adults

Systemic mitochondrial dysfunction is reported with AD progression, suggesting that peripheral blood cells may be used to investigate systemic mitochondrial alterations related to cognitive decline. We aimed to identify bioenergetic signatures associated with AD-related dementia and differences in insulin sensitivity associated with AD risk. We analyzed mitochondrial bioenergetics in peripheral blood cells collected from 365 older adults with varying cognitive status (normal, mild cognitive impairment, and AD) and insulin sensitivity. Normoglycemic individuals exhibited lower maximal bioenergetic capacity with AD (PBMCs: 239.6 pmol·min−1, p = 0.02; Platelets: 151.7 pmol·min−1, p = 0.06) compared to normal cognition (PBMCs: 271.5 pmol·min−1; Platelets: 171.7 pmol·min−1). Individuals with impaired insulin sensitivity exhibited lower maximal bioenergetic capacity in platelets with AD (171.6 pmol·min−1, p = 0.008) compared to normal cognition (210.6 pmol.min−1). Participants with impaired insulin sensitivity also exhibited unique bioenergetic profiles exemplified by overall higher levels of mitochondrial respiration, indicating that comorbidities such as diabetes can significantly influence bioenergetic capacity. We observed strong positive associations between maximal respiration in normoglycemic individuals with cognitive function, as measured by Modified Preclinical Alzheimer’s Cognitive Composite (mPACC5) (p = 0.06), and fatty acid oxidation in individuals with impaired insulin sensitivity with cortical thickness (p = 0.05). This study demonstrates that circulating cells may provide a cost-effective and minimally invasive way to monitor systemic bioenergetic changes associated with AD risk, progression, and insulin sensitivity. These findings also suggest that blood-based bioenergetics are related to key features of AD development and progression and should be further developed as a potential biomarker.

The effect of therapeutic exercise on the treatment of symptoms and the delay of foot degeneration in patients with diabetic peripheral neuropathy: An evidenced-based physiotherapy review

Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes. It presents with a symmetrical peripheral degeneration of peripheral nerves. Pain is a major complaint in about 1/3 of people with DPN and DPN-related sensory loss contributes to impaired balance, gait problems, and increased sensitivity to injury. Recent research has shown that a combination of aerobic exercise and resistance training improves fitness, glycemic control and insulin sensitivity in older adults and people with diabetes. The aim of this review was to investigate the effect of exercise on improving the symptoms of patients with DPN and delaying the onset of foot degeneration. The PubMed and Science Direct databases were searched with the following keywords: Diabetic neuropathy, therapeutic exercise, physiotherapy, rehabilitation. The results of this review suggest that exercise can improve the symptoms of DPN by reducing pain as well as improving gait accuracy, enhancing lower limb strength and improving the quality of daily life of patients. Aerobic exercise seems to be the type of training that provides the most benefits. There is also evidence that exercise in diabetic patients may either prevent or delay the onset of peripheral neuropathy. However, further clinical trials are required.

Effects of weight loss during a very low carbohydrate diet on specific adipose tissue depots and insulin sensitivity in older adults with obesity: a randomized clinical trial

BackgroundInsulin resistance and accumulation of visceral adipose tissue (VAT) and intermuscular adipose tissue (IMAT) place aging adults with obesity at high risk of cardio-metabolic disease. A very low carbohydrate diet (VLCD) may be a means of promoting fat loss from the visceral cavity and skeletal muscle, without compromising lean mass, and improve insulin sensitivity in aging adults with obesity.ObjectiveTo determine if a VLCD promotes a greater loss of fat (total, visceral and intermuscular), preserves lean mass, and improves insulin sensitivity compared to a standard CHO-based/low-fat diet (LFD) in older adults with obesity.DesignThirty-four men and women aged 60–75 years with obesity (body mass index [BMI] 30-40 kg/m2) were randomized to a diet prescription of either a VLCD (< 10:25:> 65% energy from CHO:protein:fat) or LFD diet (55:25:20) for 8 weeks. Body composition by dual-energy X-ray absorptiometry (DXA), fat distribution by magnetic resonance imaging (MRI), insulin sensitivity by euglycemic hyperinsulinemic clamp, and lipids by a fasting blood draw were assessed at baseline and after the intervention.ResultsParticipants lost an average of 9.7 and 2.0% in total fat following the VLCD and LFD, respectively (p < 0.01). The VLCD group experienced ~ 3-fold greater loss in VAT compared to the LFD group (− 22.8% vs − 1.0%, p < 0.001) and a greater decrease in thigh-IMAT (− 24.4% vs − 1.0%, p < 0.01). The VLCD group also had significantly greater thigh skeletal muscle (SM) at 8 weeks following adjustment for change in total fat mass. Finally, the VLCD had greater increases in insulin sensitivity and HDL-C and decreases in fasting insulin and triglycerides compared to the LFD group.ConclusionsWeight loss resulting from consumption of a diet lower in CHO and higher in fat may be beneficial for older adults with obesity by depleting adipose tissue depots most strongly implicated in poor metabolic and functional outcomes and by improving insulin sensitivity and the lipid profile.Trial registrationNCT02760641. Registered 03 May 2016 - Retrospectively registered.

Impact of Endurance and Resistance Training on Skeletal Muscle Glucose Metabolism in Older Adults.

Aging is associated with insulin resistance and the development of type 2 diabetes. While this process is multifaceted, age-related changes to skeletal muscle are expected to contribute to impaired glucose metabolism. Some of these changes include sarcopenia, impaired insulin signaling, and imbalances in glucose utilization. Endurance and resistance exercise training have been endorsed as interventions to improve glucose tolerance and whole-body insulin sensitivity in the elderly. While both types of exercise generally increase insulin sensitivity in older adults, the metabolic pathways through which this occurs can differ and can be dependent on preexisting conditions including obesity and type 2 diabetes. In this review, we will first highlight age-related changes to skeletal muscle which can contribute to insulin resistance, followed by a comparison of endurance and resistance training adaptations to insulin-stimulated glucose metabolism in older 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.

Relationships between mitochondrial content and bioenergetics with obesity, body composition and fat distribution in healthy older adults

BackgroundMitochondrial function declines with age; however, the relationship between adiposity and mitochondrial function among older adults is unclear. This study examined relationships between skeletal muscle mitochondrial content and electron transport chain complex 2 driven respiration with whole body and thigh composition, body fat distribution, and insulin sensitivity in older adults.Methods25 healthy, sedentary, weight-stable men (N = 13) and women (N = 12) >65 years of age, with a BMI range of 18-35 kg/m2, participated in this study. Vastus lateralis biopsies were analyzed for citrate synthase (CS) activity and succinate mediated respiration of isolated mitochondria. Whole body and thigh composition were measured by DXA and CT. HOMA-IR was calculated using fasting glucose and insulin as an estimate of insulin sensitivity.ResultsSimilar to reports in middle-aged adults, skeletal muscle CS activity was negatively correlated with BMI (R = −0.43) in our cohort of older adults. Higher total and thigh adiposity were correlated with lower CS activity independent of BMI (R = −0.50 and −0.71 respectively). Maximal complex 2 driven mitochondrial respiration was negatively correlated with lower body adiposity in males (R = −0.66). In this cohort of non-diabetic older adults, both HOMA-IR and insulin were positively correlated with CS activity when controlling for BMI (R = 0.57 and 0.66 respectively).ConclusionsAdiposity and body composition are correlated with skeletal muscle mitochondrial content and electron transport chain function in healthy, sedentary, community dwelling, older adults. Specific relationships of mitochondrial bioenergetics with gender and insulin sensitivity are also apparent.Trial registrationClinicalTrials.gov identifier NCT01049698Electronic supplementary materialThe online version of this article (doi:10.1186/s40608-015-0070-4) contains supplementary material, which is available to authorized users.

Increased Skeletal Muscle Capillarization Independently Enhances Insulin Sensitivity in Older Adults After Exercise Training and Detraining.

Intramuscular signaling and glucose transport mechanisms contribute to improvements in insulin sensitivity after aerobic exercise training. This study tested the hypothesis that increases in skeletal muscle capillary density (CD) also contribute to exercise-induced improvements in whole-body insulin sensitivity (insulin-stimulated glucose uptake per unit plasma insulin [M/I]) independent of other mechanisms. The study design included a 6-month aerobic exercise training period followed by a 2-week detraining period to eliminate short-term effects of exercise on intramuscular signaling and glucose transport. Before and after exercise training and detraining, 12 previously sedentary older (65 ± 3 years) men and women underwent research tests, including hyperinsulinemic-euglycemic clamps and vastus lateralis biopsies. Exercise training increased Vo2max (2.2 ± 0.2 vs. 2.5 ± 0.2 L/min), CD (313 ± 13 vs. 349 ± 18 capillaries/mm(2)), and M/I (0.041 ± 0.005 vs. 0.051 ± 0.007 μmol/kg fat-free mass/min) (P < 0.05 for all). Exercise training also increased the insulin activation of glycogen synthase by 60%, GLUT4 expression by 16%, and 5' AMPK-α1 expression by 21%, but these reverted to baseline levels after detraining. Conversely, CD and M/I remained 15% and 18% higher after detraining, respectively (P < 0.05), and the changes in M/I (detraining minus baseline) correlated directly with changes in CD in regression analysis (partial r = 0.70; P = 0.02). These results suggest that an increase in CD is one mechanism contributing to sustained improvements in glucose metabolism after aerobic exercise training.

Mediators Of The Exercise-induced Change In Insulin Sensitivity In Older Adults

Mediators Of The Exercise-induced Change In Insulin Sensitivity In Older Adults

Increased Skeletal Muscle Capillarization After Aerobic Exercise Training and Weight Loss Improves Insulin Sensitivity in Adults With IGT

OBJECTIVETranscapillary transport of insulin is one determinant of glucose uptake by skeletal muscle; thus, a reduction in capillary density (CD) may worsen insulin sensitivity. Skeletal muscle CD is lower in older adults with impaired glucose tolerance (IGT) compared with those with normal glucose tolerance and may be modifiable through aerobic exercise training and weight loss (AEX+WL). We tested the hypothesis that 6-month AEX+WL would increase CD to improve insulin sensitivity and glucose tolerance in older adults with IGT.RESEARCH DESIGN AND METHODSSixteen sedentary, overweight-obese (BMI 27–35 kg/m2), older (63 ± 2 years) men and women with IGT underwent hyperinsulinemic-euglycemic clamps to measure insulin sensitivity, oral glucose tolerance tests, exercise and body composition testing, and vastus lateralis muscle biopsies to determine CD before and after 6-month AEX+WL.RESULTSInsulin sensitivity (M) and 120-min postprandial glucose (G120) correlated with CD at baseline (r = 0.58 and r = −0.60, respectively, P < 0.05). AEX+WL increased maximal oxygen consumption (VO2max) 18% (P = 0.02) and reduced weight and fat mass 8% (P < 0.02). CD increased 15% (264 ± 11 vs. 304 ± 14 capillaries/mm2, P = 0.01), M increased 21% (42.4 ± 4.0 vs. 51.4 ± 4.3 µmol/kg FFM/min, P < 0.05), and G120 decreased 16% (9.35 ± 0.5 vs. 7.85 ± 0.5 mmol/L, P = 0.008) after AEX+WL. Regression analyses showed that the AEX+WL-induced increase in CD independently predicted the increase in M (r = 0.74, P < 0.01) as well as the decrease in G120 (r = −0.55, P < 0.05).CONCLUSIONSSix-month AEX+WL increases skeletal muscle CD in older adults with IGT. This represents one mechanism by which AEX+WL improves insulin sensitivity in older adults with IGT.

Aerobic exercise + weight loss decreases skeletal muscle myostatin expression and improves insulin sensitivity in older adults

ObjectiveWe sought to determine whether aerobic exercise training+weight loss (AEX+WL) would affect the expression of myostatin and its relationship with insulin sensitivity in a longitudinal, clinical intervention studyDesign and MethodsThirty-three obese sedentary postmenopausal women and men (n=17 and 16, age:61±1 yrs, BMI:31±1 kg/m2, VO2max:21.9 ± 1.0 ml/kg/min, X ± SEM) completed 6 months of 3d/wk AEX+WL. During an 80 mU·m−2·min−1 hyperinsulinemic-euglycemic clamp, we measured glucose utilization (M), myostatin, myogenin, and MyoD gene expression by real-time RT-PCR in vastus lateralis muscle at baseline and 2 hrs.ResultsBody weight (−8%) and fat mass (−17%) decreased after AEX+WL (P<0.001). FFM and mid-thigh muscle area by CT did not change but muscle attenuation increased (P<0.05). VO2max increased 14% (P<0.001). AEX+WL increased M by 18% (P<0.01). Myostatin gene expression decreased 19% after AEX+WL (P<0.05). Basal mRNA myostatin levels were negatively associated with M prior to the intervention (r=−0.43, P<0.05). Insulin infusion increased myoD and myogenin expression before and after AEX+WL (both P<0.001) but basal levels did not change. The insulin effect on myostatin expression was associated with the change in M after AEX+WL (r=0.56, P<0.005).ConclusionsExercise and weight loss results in a down-regulation of myostatin mRNA and an improvement in insulin sensitivity in obese older men and women.

Plasma 25‐hydroxyvitamin D to parathyroid hormone ratio is associated with glucose tolerance and insulin sensitivity in older adults

Purpose To assess the relationships between plasma 25-hydroxyvitamin D (25OHD), plasma parathyroid hormone (PTH), and oral glucose tolerance (OGT) in older adults before and after a dietary protein and resistance training (RT) regimen. Methods 16 males (BMI 27.2 ± 4.2 kg/m2) and 19 females (BMI 25.5 ± 3.0 kg/m2) aged 50–80 y performed RT 3x/wk for 12 wk while consuming diets with either 0.9 or 1.2 g protein · kg BW−1· d−1. Results RT had no effect on body weight, plasma 25OHD or plasma PTH but reduced fat mass and increased lean body mass and strength independent of protein intake. OGT improved after RT (i.e. decreased area under the glucose curve (AUC) and 2-h plasma glucose) (all changes P<0.05). Using non-parametric statistics, at baseline, 25OHD to PTH ratio was correlated inversely with HOMA (Rho = −0.398, Prob > |Rho| = 0.03) and 2-h glucose (Rho = −0.463, Prob > |Rho| = 0.01) and positively with insulin sensitivity index (Rho = 0.406, Prob > |Rho| = 0.02). Similar results were found post intervention and AUC and 2-h glucose were lower in subjects with 25OHD ≥ 30 ng/mL versus subjects with 25OHD ≤ 20 ng/mL (P<0.05). Mean (average of pre & post) 25OHD, PTH, and 25OHD/PTH ratio were not correlated to the response of OGT-related parameters to RT. Conclusion Vitamin D status and the 25OHD to PTH ratio may impact glucose tolerance in older adults regardless of resistance training. Support: Amer. Egg Board; NIH UL 1 RR025761; Purdue Univ. Grant Funding Source: American Egg Board, NIH UL 1 RR025761, Purdue University

Exercise in aging: its important role in mortality, obesity and insulin resistance

The prevalence of overweight and obesity has increased dramatically over the last several decades. Obesity and physical inactivity increase the risk for cardiovascular disease, Type 2 diabetes mellitus, hypertension, dyslipidemia and certain cancers. Obesity and low levels of physical fitness are also associated with increased risk of all-cause and cardiovascular mortality. Central and total obesity, insulin resistance and inactivity increase with age. Exercise training and increased fitness promote positive changes in body composition and improve insulin sensitivity. This article will describe the effects of exercise training, both aerobic and resistive, on body composition and obesity as well as review studies investigating the effects of exercise training on glucose metabolism and insulin sensitivity in older adults. Adopting a physically active lifestyle should be emphasized in overweight and obese individuals with insulin resistance to reduce the risk for cardiovascular events in the aging population.

Effects of resistance training combined with antioxidant supplementation on fat-free mass and insulin sensitivity in healthy elderly subjects

The aim of this study was to verify the effect of resistance training and antioxidant supplementation on fat-free mass (FFM) and insulin sensitivity (IS). The results demonstrate that 6 months of resistance training combined with antioxidant supplementation significantly increased FFM without concomitant significant improvement in IS in older adults.

Effects of Tai Chi on glucose homeostasis and insulin sensitivity in older adults with type 2 diabetes: a randomised double-blind sham-exercise-controlled trial

a large proportion of adults with type 2 diabetes remain sedentary despite evidence of benefits from exercise for type 2 diabetes. Simplified Yang Tai Chi has been shown in one study to have no effect on insulin sensitivity in older adults. However, a modified Tai Chi form, Tai Chi for Diabetes (TCD) has recently been composed, claiming to improve diabetes control. subjects were randomised to Tai Chi or sham exercise, twice a week for 16 weeks. Primary outcomes were insulin resistance 72 h post-exercise (HOMA2-IR), and long-term glucose control (HbA(1c)). thirty-eight subjects (65 +/- 7.8 years, 79% women) were enrolled. Baseline BMI was 32.2 +/- 6.3 kg/m(2), 84% had osteoarthritis, 76% hypertension, and 34% cardiac disease. There was one dropout, no adverse events, and median compliance was 100 (0-100)%. There were no effects of time or group assignment on insulin resistance or HbA(1c) ( -0.07 +/- 0.4% Tai Chi versus 0.12 +/- 0.3% Sham; P = 0.13) at 16 weeks. Improvement in HbA(1c) was related to decreased body fat (r = 0.484, P = 0.004) and improvement in insulin resistance was related to decreased body fat (r = 0.37, P = 0.03) and central adiposity (r = 0.38, P = 0.02), as well as increased fat-free mass (r = -0.46, P = 0.005). TCD did not improve glucose homeostasis or insulin sensitivity measured 72 h after the last bout of exercise. More intense forms of Tai Chi may be required to produce the body composition changes associated with metabolic benefits in type 2 diabetes.

Relationship between Ambulatory Activity and Insulin Sensitivity in Older Adults

PURPOSE: To investigate the relationships between accumulated physical activity (PA), estimated insulin sensitivity (IS), total body fat percentage (BF), and waist circumference (WC) in an older adult population. METHODS: Thirty four older adults (9 males, 25 females; 65.6 ± 6.8 y; BF 40.5 ± 8.5 %; WC 95.4 ± 10.3 cm) participated in this cross-sectional study. Height, body mass, and WC were measured. BF was assessed via dual energy x-ray absorptiometry. Fasting venous glucose and insulin were measured. IS was calculated according to the Quantitative Insulin Sensitivity Check Index (QUICKI) method. Participants wore a pedometer (Yamax SW-200) for seven consecutive days during all waking hours. Average steps/d were calculated. Correlation analyses were performed to examine relationships between QUICKI scores, steps/d, BF, and WC. Participants were dichotomized into low or high activity groups based on median steps/d (<4917steps/d, ≥4918 steps/d). Independent samples t-tests were performed to examine differences in IS, BF, and WC across the low and high activity groups. RESULTS: Mean IS for the group was 0.3725 ± 0.0316. Average steps/d were 5251 ± 2000. IS was positively correlated with BF (r= .425, p=.014) and WC (r=.392, p=.022), however, there was no significant relationship between IS and steps/d (r= .031, p=.861). Despite significant differences in step/d between the low and high activity groups (3689 ± 214 vs. 6813 ± 367 steps/d, respectively; p=.042), no significant differences were noted in QUICKI (p=.778), BF (p=.866), or WC (p=.081) between these groups. CONCLUSIONS: The current study indicates that IS is related to estimates of obesity, but not PA, in this older adult population. This suggests that level of adiposity may be more important to IS than accumulated PA in this group of older adults. Future research exploring the relationship between intensity of PA and IS in older adults is warranted.

Abdominal Adiposity Assessed by Dual Energy X-Ray Absorptiometry Provides a Sex-Independent Predictor of Insulin Sensitivity in Older Adults

An increase in total adiposity and in particular an abdominal distribution of adiposity may contribute to the decline in metabolic insulin sensitivity observed in older men and women. The objective of this cross-sectional study was to determine which measure of abdominal adiposity would provide the best sex-independent predictor of metabolic insulin sensitivity in older men and women. Insulin sensitivity and abdominal adiposity were measured in healthy, nondiabetic older (64 +/- 6 years; mean +/- standard deviation) men (n = 23) and women (n = 31). Metabolic Insulin Sensitivity Index (S(I)) was determined from a frequently sampled insulin-assisted intravenous glucose tolerance test. Body fat mass and abdominal fat mass were determined from dual energy X-ray absorptiometry (DXA) scans. Anthropometric measures included waist and hip circumferences, height, and body weight. Although waist circumference, waist index (waist circumference divided by height), and waist-hip ratio (WHR) were all lower in women than in men, there was no sex difference in DXA L1-L4 fat mass. In univariate analyses, S(I) was significantly inversely related with body weight, body mass index, waist circumference, waist index, percentage of total body and abdominal fat, and DXA L1-L4 fat mass but not with WHR. The DXA L1-L4 fat mass was identified as the best independent predictor of S(I), accounting for 41.2% of the variance (p <.0001) in a stepwise multiple regression model that controlled for sex. WHR is not associated with S(I) in either men or women. Abdominal adiposity measured by DXA L1-L4 fat mass provides a sex-independent predictor of S(I) in older men and women.

Insulin Pathway Takes a Jog: Workouts might benefit young and old by employing different molecular messengers (Insulin signaling)

Athletes of all ages can handle a sugar-laced Hershey bar better than their couch potato counterparts can. That's because workouts boost muscle cells' ability to respond to insulin, the hormone that instructs such cells to bring glucose aboard. Hitting the gym provides protection from the root cause of type II diabetes: insulin resistance, a condition in which muscle cells lose the ability to take up glucose efficiently even when insulin is present. But a new study suggests that hours spent riding a stationary bike might trigger different molecular tripwires in young and old people. The work highlights the importance of studying insulin resistance in older subjects. When insulin binds to a receptor attached to the exterior of a muscle cell, it sets off a sequence of events within. First it recruits several insulin receptor substrates (IRSs). IRS-1 then docks with and activates many other molecules, including phosphatidylinositol (PI) 3-kinase, which incites poorly defined cellular pathways that relay insulin's signal. As a result of this signaling cascade, the insulin-sensitive glucose transporter GLUT-4 moves to the muscle cell membrane, where it helps sugar flow into the cell. Scientists know little about how exercise affects the many molecular couriers that handle insulin's message before it reaches GLUT-4. Understanding the influence of exercise on these envoys might help pinpoint targets for drugs that can reverse or prevent insulin resistance, as workouts do. Finding such drug targets matters most to older people: After age 30, sedentary humans' resistance to insulin increases, rendering them vulnerable to high cholesterol levels, arterial damage, cardiac problems, hyperglycemia, obesity, and type II diabetes. To identify molecular messengers whose activity might change in response to exercise, Tanner and colleagues first examined the muscle tissue of otherwise sedentary young (19- to 28-year-old) men before and after a weeklong endurance exercise regimen. In that study, published a year ago, the subjects exhibited not only an enhanced response to insulin but also increased PI 3-kinase activity. Expecting the same result, the researchers placed nine inactive 50- to 70-year-old men on the same regimen and followed the same experimental protocol. Like in the young men, sugar in the older subjects' blood moved into cells more efficiently after the week's exercise than it had before the workouts. But, unlike the muscle cells of young men, those of older men showed little change in PI 3-kinase activity after the exercise program. Older men still experience the increased insulin sensitivity that comes with short-term exercise, but the new results suggest that they don't achieve it by boosting PI 3-kinase activity as young men do. Exercise might benefit the older men either by altering a molecular messenger in the murky realm downstream of PI 3-kinase or by exploiting a signaling pathway that doesn't involve PI 3-kinase. Further study of more people at more time points and over a longer course of exercise is required to confirm the findings. But the results introduce a new possibility for how exercise impacts insulin signaling with age. Understanding the disparity between young and old people's responses to exercise might help scientists develop additional ways to maintain insulin sensitivity in older adults. --Katharine Miller; suggested by James M. Harper C. J. Tanner, T. R. Koves, R. L. Cortright, W. J. Pories, Y.-B. Kim, B. B. Kahn, G. L. Dohm, J. A. Houmard, Effect of short-term exercise training on insulin-stimulated PI 3-kinase activity in middle-aged men. Am. J. Physiol. Endocrinol. Metab. 282 , E147-E153 (2002). [Abstract] [Full Text]

Low plasma insulin-like growth factor-1 concentrations predict worsening of insulin-mediated glucose uptake in older people.

The relationship among insulin action, advancing age, and insulin like growth factor-1 (IGF-1) is poorly understood. To gain further insight, the predictive role that low plasma IGF-1 concentration may have on insulin- mediated glucose uptake in older persons was investigated. The study was designed as a longitudinal, observational trial. Fifty-eight healthy aged (73.1+/-9.4 years) subjects (31 males/27 females) were followed up for 12 months. At baseline and at the end of the follow-up, insulin-mediated glucose uptake was assessed by euglycemic glucose clamp and plasma total IGF-1 and IGF-binding protein 3 (IGF-BP-3) in each subject, and concentrations were determined. At baseline, plasma IGF-1 concentrations correlated with whole body glucose uptake (WBGD) (r = 0.39, P < .003), insulin-stimulated glucose oxidation (GOX) (r = 0.35, P < .009), and non-oxidative glucose metabolism (r = 0.37, P < .007). Such correlations were also independent of age, sex, body fat, and waist/hip ratio. Fasting plasma total IGF-1 concentrations (84+/-56 vs 63+/-44 microg/L, P < .040), plasma IGF-1/IGF-BP3 molar ratio (0.13+/-0.05 vs 0.10+/-0.03 P < .050), and WBGD (34.8+/-5.0 vs 23.1+/-4.6 micromol/kg x min, P < .010) were more elevated at baseline than at the end of the follow-up. Low baseline fasting plasma IGF-1 concentration (RR = 1.5, 95%CI = 1.3-1.7) and plasma IGF-1/IGFBP-3 molar ratio (RR = 1.4, 95% CI = 1.3-1.8) predicted a decline in WBGD. The predictive role of plasma IGF-1 on age-related decline in WBGD was independent of age, sex, body fat, waist/hip ratio, and degree of physical activity (model 1), or of fasting plasma free fatty acid and triglyceride concentrations, LDL/HDL ratio, and basal adjusted respiratory quotient (model 2). Finally, low plasma IGF-1 concentration predicts a decline in WBGD independent of body fat, free fatty acids, waist/hip ratio, and basal adjusted respiratory quotient (model 3). Our study demonstrates that fasting plasma IGF-1 concentration may have a modulatory role on insulin action in older people. This finding might prompt an evaluation of the direct effect of IGF-1 administration on insulin sensitivity in older adults.