Seasonal variation in physical activity,sedentary behaviour and sleep in a sample of UK adults

Background: Physical activity (PA), sedentary behaviour (SB), sleep and diet have all been associated with increased risk for chronic disease. Seasonality is often overlooked as a determinant of these behaviours in adults. Currently, no study has simultaneously monitored these behaviours in UK adults to assess seasonal variation.

Aim: The present study investigated whether PA, SB, sleep and diet differed over season in UK adults.

Subjects and methods: Forty-six adults (72% female; age?=?41.7?±?14.4 years, BMI?=?24.9?±?4.4?kg/m²) completed four 7-day monitoring periods; one during each season of the year. The ActiGraph GT1M was used to monitor PA and SB. Daily sleep diaries monitored time spent in bed (TIB) and total sleep time (TST). The European Prospective Investigation of Cancer (EPIC) food frequency questionnaire (FFQ) assessed diet. Repeated measures ANOVAs were used to identify seasonal differences in behaviours.

Results: Light-intensity PA was significantly higher in summer and spring (p?p?p?>?0.05).

Conclusions: Findings support the concept that health promotion campaigns need to encourage year-round participation in light intensity PA, whilst limiting SB, particularly during the winter months.     

Short‐term effects of repetitive arm work and dynamic exercise on glucose metabolism and insulin sensitivity

Aim: To determine whether repetitive arm work, with a large component of static muscle contraction alters glucose metabolism and insulin sensitivity. Method: Euglycemic clamps (2 h) were started in ten healthy individuals 15 min after 37 min periods of: (1) repetitive arm work in a simulated occupational setting; (2) dynamic concentric exercise on a cycle ergometer at 60% of VO_2max and (3) a resting regime as a control. During the experimental periods, blood samples were collected, blood pressure was measured repeatedly and electrocardiogram (ECG) was recorded continuously. During the clamps, euglycemia was maintained at 5 mmol l^?1 and insulin was infused at 56 mU m^?2 min^?1 for 120 min. Results: The insulin‐mediated glucose disposal rate (M‐value) for the steady‐state period (60–120 min) of the clamp, tended to be lower following arm work than for both cycling and resting regimes. When dividing the steady‐state period into 20‐min intervals, the insulin sensitivity index (ISI) was significantly lower for arm work compared with the resting control situation between 60–80 min (P = 0.04) and 80–100 min (P = 0.01), respectively. Catecholamines increased significantly for arm work and cycling compared with resting regime. Data from heart rate variability (HRV) measurements indicated significant sympathetic activation during repetitive arm work. Conclusion: The results indicate that repetitive arm work might acutely promote insulin resistance, whereas no such effect on insulin resistance was produced by dynamic concentric exercise.     

Rosiglitazone and ethinyl estradiol/cyproterone acetate as single and combined treatment of overweight women with polycystic ovary syndrome and insulin resistance

BACKGROUND: Few studies have evaluated insulin sensitizers in comparison/association with oral contraceptives (OC) in women with polycystic ovary syndrome (PCOS) with insulin resistance (IR). This study assessed the effects of a thiazolidinedione versus an anti-androgenic estrogen-progestin followed by their sequential combinations in overweight PCOS women. METHODS AND RESULTS: Twenty-eight candidates in whom elevated insulin was not normalized after 4 months of diet were randomly assigned to 6 months of rosiglitazone 4 mg/day or to ethinyl estradiol 35 mg/cyproterone acetate 2 mg (EE/CPA: 21/28 days cycle). Each group then received both medications for another 6 months. Rosiglitazone reduced insulin, IR indices [homeostasis model assessment (HOMA) and quantitative sensitivity check index (QUICKI)] and the insulin area under the curve in response to an oral glucose tolerance test (OGTT), but had limited effect on lipids, androgens and hirsutism. EE/CPA did not modify insulin and OGTT response but increased high-density lipoprotein cholesterol and triglycerides and decreased androgens and hirsutism. Similar changes occurred during combined treatments. End results were highly significant in combined groups without noticeable side-effects or changes in safety parameters. CONCLUSIONS: In obese PCOS women with high insulin not corrected by diet, the combination of rosiglitazone and EE/CPA may be used to achieve complementary beneficial effects on endocrine-metabolic anomalies and clinical symptoms.     

A novel SNP at exon 17 of INSR is associated with decreased insulin sensitivity in Chinese women with PCOS

To investigate the association of single-nucleotide polymorphisms (SNPs) in exon 17 of the insulin receptor (INSR) gene with insulin resistance and INSR beta-subunit expression in polycystic ovary syndrome (PCOS) patients, a case-control study was carried out in an academic endocrinology clinic of China. One hundred and nine Chinese patients with PCOS and 107 healthy Chinese women as control were recruited. Their leukocytes and red blood cells were separated from blood samples, for SNP analysis with single-stranded conformation polymorphism and for the INSR beta-subunit expression detection by western blot analysis, respectively. A novel T/C SNP at codon Cys1008 (position 3128 of NM_000208) of INSR was found in two allele genotypes, i.e. the homozygous CC and the heterozygous TC. A higher frequency of the mutant homozygous CC was observed in the PCOS women with PCOS than that in the controls (21.1 versus 5.6%, P < 0.01). In contrast with the women with wild-type genotype, a significantly lower insulin sensitivity index in the women with each of the two mutant genotypes was revealed (CC: 0.335 +/- 0.026/TC: 0.346 +/- 0.027 versus TT: 0.367 +/- 0.029, P < 0.05). No relationship was found between the novel SNP and the INSR beta-subunit expression. We concluded that the novel T/C SNP at codon Cys1008 of INSR is associated with decreased insulin sensitivity in Chinese women with PCOS and that the association is not by the change of synthesis or secretion of INSR beta-subunit, but most possibly by the effects of this novel SNP on the function of INSR beta-subunit.     

Effects of modifying physical activity and sedentary behavior on psychosocial adjustment in overweight/obese children

OBJECTIVES: To evaluate the relationship between changes in physical activity (PA), sedentary behavior, and physical self-perceptions and global self-worth in 30, 8-12 years old, overweight/obese children (13 boys, 17 girls). METHODS: Secondary analyses from a randomized controlled trial designed to increase PA and reduce sedentary behavior. PA was measured by accelerometers worn by participants every day for 8 weeks. Sedentary behavior, defined as minutes per day spent in television viewing, was assessed by self-report. RESULTS: Increases in PA were associated with increases in perceived physical conditioning (r = .54, p < .01), body satisfaction (r = .55, p < .01), and overall physical self-worth (r = .44, p < .05) independent of changes in body mass index (BMI). Reductions in TV viewing were also related to increased physical and global self-worth. CONCLUSIONS: Increases in PA are associated with improvements in physical self-perceptions but not global self-worth, while reductions in TV viewing are associated with increased physical and global self-worth, and these psychosocial benefits appear to be independent of changes in adiposity.     

Acute exercise reverses TRB3 expression in the skeletal muscle and ameliorates whole body insulin sensitivity in diabetic mice

Aim: TRB3 became of major interest in diabetes research when it was shown to interact with and inhibit the activity of Akt. Conversely, physical exercise has been linked to improved glucose homeostasis. Thus, the current study was designed to investigate the effects of acute exercise on TRB3 expression and whole body insulin sensitivity in obese diabetic mice. Methods: Male leptin-deficient (ob/ob) mice swam for two 3-h-long bouts, separated by a 45-min rest period. After the second bout of exercise, food was withdrawn 6 h before antibody analysis. Eight hours after the exercise protocol, the mice were submitted to an insulin tolerance test (ITT). Gastrocnemius muscle samples were evaluated for insulin receptor (IR) and IRS-1 tyrosine phosphorylation, Akt serine phosphorylation, TRB3/Akt association and membrane GLUT4 expression. Results: Western blot analysis showed that TRB3 expression was reduced in the gastrocnemius of leptin-deficient (ob/ob) mice submitted to exercise when compared with respective ob/ob mice at rest. In parallel, there was an increase in the insulin-signalling pathway in skeletal muscle from leptin-deficient mice after exercise. Furthermore, the GLUT4 membrane expression was increased in the muscle after the exercise protocol. Finally, a single session of exercise improved the glucose disappearance (K_ITT) rate in ob/ob mice. Conclusion: Our results demonstrate that acute exercise reverses TRB3 expression and insulin signalling restoration in muscle. Thus, these results provide new insights into the mechanism by which physical activity ameliorates whole body insulin sensitivity in type 2 diabetes.     

The effects of testosterone on insulin sensitivity in male rats

In order to examine the effects of testosterone (T) on insulin sensitivity, male rats were castrated or sham-operated, and exposed to low or high doses of T to substitute normal or to produce high serum T concentrations. Insulin sensitivity was followed by euglycaemic, hyperinsulinaemic glucose clamp measurements. An index of insulin-stimulated glucose transport was obtained in the white gastrocnemius (WG), extensor digitorum longus (EDL), red gastrocnemius (RG) and soleus (SOL) muscles after a bolus dose of [2-³H]deoxyglucose (2-DOG) when steady state was obtained in the clamp measurements. Glycogen synthesis was followed similarly with [U-14C]glucose as a labelled precursor after isolation of glycogen in the muscles mentioned, and in the liver. Castration and high T were followed by a marked insulin resistance in the clamp measurements. This was paralleled by a diminished insulin stimulation of glucose incorporation into glycogen down to about 50% of control values, apparently equally pronounced in all muscles but not found in liver glycogen synthesis. 2-DOG uptake was diminished by castration in the WG and RG muscles but was unaffected by high doses of T. Substitution of castrated rats with a low dose of T, restoring their serum T concentrations to the normal range, completely abolished these perturbations of insulin sensitivity. It is concluded that T is an important regulator of muscular insulin sensitivity, which seems to be highest in a ‘window’ of normal serum T concentrations.     

Association of a type 2 diabetes genetic risk score with insulin secretion modulated by insulin sensitivity among Chinese Hans

Type 2 diabetes (T2D) is characterized by insulin resistance and impaired insulin secretion. The present study aimed to identify the influence of insulin sensitivity on the genetic risk of impaired insulin secretion among a Chinese Han population. For 3229 controls and 1994 treatment‐naïve T2D, single nucleotide polymorphisms (SNPs) from 24 T2D‐related genomic loci were genotyped and a genetic risk score (GRS) was constructed. Results showed that GRS was associated with insulin secretion and disposition indices in both controls and treatment‐naïve T2Ds. Upon stratifying the participants into tertiles by the Matsuda index, we observed an inhibitory relationship between the GRS and insulin secretion in low insulin sensitive but not in high insulin sensitive controls and treatment‐naïve T2Ds. Moreover, low insulin sensitive individuals exhibited more severe impairment in insulin secretion and beta cell response to insulin sensitivity with an increase in risk alleles. Our findings identified that the association of GRS with insulin secretion was strongly modulated by insulin sensitivity in both controls and T2Ds of Chinese Han. It indicates that insulin sensitization should be emphasized in prevention and treatment of T2D for beta cell protection.     

Reduced glucose tolerance and insulin sensitivity after prolonged exercise in endurance athletes

Aim

The purpose of this study was to 1. investigate if glucose tolerance is affected after one acute bout of different types of exercise; 2. assess if potential differences between two exercise paradigms are related to changes in mitochondrial function; and 3. determine if endurance athletes differ from nonendurance-trained controls in their metabolic responses to the exercise paradigms.

Methods

Nine endurance athletes (END) and eight healthy nonendurance-trained controls (CON) were studied. Oral glucose tolerance tests (OGTT) and mitochondrial function were assessed on three occasions: in the morning, 14 h after an overnight fast without prior exercise (RE), as well as after 3 h of prolonged continuous exercise at 65% of VO₂max (PE) or 5 × 4 min at ~95% of VO₂max (HIIT) on a cycle ergometer.

Results

Glucose tolerance was markedly reduced in END after PE compared with RE. END also exhibited elevated fasting serum FFA and ketones levels, reduced insulin sensitivity and glucose oxidation, and increased fat oxidation during the OGTT. CON showed insignificant changes in glucose tolerance and the aforementioned measurements compared with RE. HIIT did not alter glucose tolerance in either group. Neither PE nor HIIT affected mitochondrial function in either group. END also exhibited increased activity of 3-hydroxyacyl-CoA dehydrogenase activity in muscle extracts vs. CON.

Conclusion

Prolonged exercise reduces glucose tolerance and increases insulin resistance in endurance athletes the following day. These findings are associated with an increased lipid load, a high capacity to oxidize lipids, and increased fat oxidation.     

Effects of two antiandrogen treatments on hirsutism and insulin sensitivity in women with polycystic ovary syndrome

Thirty-two women with polycystic ovary syndrome (PCOS) wereallocated to two antiandrogen treatment regimens; 28 women completedthe trial. Twenty women were treated with ethinyloestradioland cyproterone acetate (EO-CA) cyclically for 6 months andeight women were treated with the gonadotrophin releasing hormone(GnRH) analogue, goserelin for 6 months. Effects on hirsutism,insulin sensitivity (estimated by glucose clamp technique),blood lipids and hormones were measured. Women treated withEO-CA showed a reduction in hirsutism (P <0.05), and decreasedserum androgen concentrations (P <0.001) as well as reducedinsulin sensitivity (P <0.05). In women treated with goserelin,serum androgen concentrations also decreased (P <0.001),but there was no significant reduction of hirsutism. This group,however, showed an improved insulin sensitivity (P <0.05)despite an unchanged body mass index. Bone mineral density wasunaltered in both treatment groups. The reduction in androgenconcentrations caused by EO-CA was not paralleled by increasedinsulin sensitivity, most probably due to the effect of ethinyloestradiolper se. In contrast, the reduction in androgen concentrationsby goserelin was accompanied by an improved insulin sensitivity.     

Time‐course effects of physiological free fatty acid surges on insulin sensitivity in humans

Aim: Physiological elevations of free fatty acids (FFAs) occur in bell‐shaped surges lasting some hours, observed nocturnally, during exercise and inflammation. The time‐course effects of such FFA surges on insulin sensitivity are unknown. We therefore aimed to define the effects of a graded 4‐h FFA elevation intended to mimick physiological excursions. Methods: Eight lean, healthy men were studied on two occasions: (1) control (saline) and (2) 4 h graded infusion of intralipid (20%)/heparin. Insulin sensitivity was continuously assessed by isotope dilution (3H‐glucose) during an 8 h hyperinsulinemic‐euglycaemic clamp (0.5 mU kg^?1 min^?1). Phosphorylation of Akt and ERK1/2 was measured in muscle biopsies taken at 0 and 120 min. Inflammatory cytokines were assessed with a Luminex Suspension Array System. Results: Infusion of intralipid caused a bell‐shaped increase in FFA levels reaching peak levels ～1.9 mmol L^?1 and markedly impairing insulin sensitivity. Impairment of insulin sensitivity was apparent (P > 0.05) 120 min after initiation of FFA infusion, significant after 270 min (P < 0.001) and peaked after 360 min. FFA induced insulin resistance prevailed 210 min after cessation of FFA infusion. No effect was observed on Akt and ERK1/2 phosphorylation. Conclusions: (1) Physiological FFA elevations require at least 120 min to induce insulin resistance, (2) that insulin resistance peaks 360 min after initiation of FFA exposure and (3) ceases 210 min after termination of the FFA infusion. These observations add to our understanding of FFA induced insulin resistance in relation to circadian variations, exercise, generalized inflammation and exposure to stress hormones such as growth hormone.     

Significance of bilayer-forming phospholipids for skeletal muscle insulin sensitivity and mitochondrial function

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE), which make up the bulk of mammalian cell membrane phospholipids, are recognized for their importance in metabolic health. Perturbations in the ratio of PC:PE can affect membrane integrity and function, which thus have serious health consequences. Imbalance in the hepatic PC and PE membrane content can be linked to metabolic disturbances such as ER stress, fatty liver and insulin resistance. Given that impaired insulin sensitivity underlies the pathology of many metabolic disorders and skeletal muscle is a significant regulator of energy metabolism, it is likely that aberrant phospholipid metabolism in skeletal muscle affects whole-body insulin sensitivity. Sarco/endoplasmic reticulum Ca²⁺ ATPase (SERCA) activity and mitochondrial function respond to alterations in PC:PE ratio and are associated with glucose homeostasis. Moreover, PC and PE content within the mitochondrial membrane influence mitochondrial respiration and biogenesis and thus, metabolic function. As skeletal muscle phospholipids respond to stimuli such as diet and exercise, understanding the implications of imbalances in PC:PE ratio is of great importance in the face of the rising epidemic of obesity related diseases. This review will summarize the current state of knowledge signifying the links between skeletal muscle PC:PE ratio and insulin sensitivity with respects to PC and PE metabolism, SERCA activity, mitochondrial function and exercise.     

Endocrine and metabolic effects of rosiglitazone in overweight women with PCOS: a randomized placebo-controlled study

BACKGROUND: The objective of the study was to assess the therapeutic effects of rosiglitazone in overweight women with polycystic ovary syndrome (PCOS). METHODS: A double-blind, placebo-controlled study was conducted on 30 (BMI > 25 kg/m2, mean age 29.1 +/- 1.2 years) overweight women with PCOS treated with rosiglitazone or placebo for 4 months. Waist-to-hip ratios (WHRs), serum concentrations of sex hormones and binding proteins, blood glucose, serum insulin and serum C-peptide during a 75-g oral glucose tolerance test (OGTT), first-phase insulin secretion as determined by an intravenous glucose tolerance test (IVGTT), M values (expressing insulin sensitivity using a euglycaemic clamp) and calorimetric data were assessed at 0 and 4 months of treatment. RESULTS: Rosiglitazone improved menstrual cyclicity, increased serum sex hormone-binding globulin (SHBG) levels and decreased serum levels of androstenedione, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEA-S). Glucose tolerance [expressed as AUC(glucose) during the OGTT] improved (P = 0.002) and peripheral insulin response (expressed as AUC(insulin)) decreased (P = 0.004) in the rosiglitazone group (ROSI group). M value improved in the ROSI group from 33.4 +/- 3.27 to 40.0 +/- 5.51 micromol/kg min (P = 0.04). CONCLUSION: Rosiglitazone, by improving menstrual cyclicity, hyperandrogenism, insulin resistance and hyperinsulinaemia, represents an alternative treatment for overweight anovulatory women with PCOS and no pregnancy desire.     

Effect of endurance and sprint exercise on the sensitivity of glucose metabolism to insulin in the epitrochlearis muscle of sedentary and trained rats

Summary The effects of two types of acute exercise (1 h treadmill running at 20 m· min^–1, or 6 × 10-s periods at 43 m · min^–1, 0° inclination), as well as two training regimes (endurance and sprint) on the sensitivity of epitrochlearis muscle [fast twitch (FT) fibres] to insulin were measured in vitro in rats. The hormone concentration in the incubation medium producing the half maximal stimulation of lactate (la) production and glycogen synthesis was determined and used as an index of the muscle insulin sensitivity. A single period of moderate endurance as well as the sprint-type exercise increased the sensitivity of la production to insulin although the rate of la production enhanced markedly only after sprint exercise at 10 and 100 U· ml^–1 of insulin. These effects persisted for up to 2 h after the termination of exercise. Both types of exercise significantly decreased the muscle glycogen content, causing a moderate enhancement in the insulin-stimulated rates of glycogen synthesis in vitro for up to 2 h after exercise. However, a significant increase in the sensitivity of this process to insulin was found only in the muscle removed 0.25 h after the sprint effort. Training of the sprint and endurance types increased insulin-stimulated rates of glycolysis 24 h after the last period of exercise. The sensitivity of this process to insulin was also increased at this instant. Both types of training increased the basal and maximal rates of glycogen snythesis, as well as the sensitivity of this process to insulin at the 24^th following the last training session. It was concluded that in the epitrochlearis muscle, containing mainly FT fibres, both moderate and intensive exercise (acute and repeated) were effective in increasing sensitivity of glucose utilization to insulin. Thus, the response in this muscle type to increased physical activity differs from that reported previously in the soleus muscle, representing the slow-twitch, oxidative fibres in which sprint exercise did not produce any changes in the muscle insulin sensitivity.     

Serum leptin levels in gastric cancer patients and the relationship with insulin resistance

Introduction

Serum leptin levels have been examined in various cancers, with conflicting results. However, there is limited information regarding serum leptin levels and insulin resistance in gastric cancer patients. Therefore, we aimed to investigate serum leptin levels, performance status, insulin levels and insulin resistance in patients with gastric cancer. In addition, we examined the relationship between these measurements and leptin levels.

Material and methods

Thirty-nine patients with gastric cancer and 30 control subjects were enrolled in the study. Serum leptin, total protein, albumin, growth hormone, insulin and glucose levels were measured. The homeostasis model assessment (HOMA) was used to assess insulin resistance.

Results

Serum levels of insulin, glucose and growth hormone and insulin resistance were significantly lower in gastric cancer patients than controls (p < 0.05 for all). In the Pearson correlation analysis, insulin resistance was found to be significantly correlated with serum leptin levels in gastric cancer patients (r = 0.320, p = 0.047). We observed a significant negative correlation between performance status and insulin resistance in patients with cachexia (r = –0.512, p = 0.030), while no association was found in non-cachectic patients.

Conclusions

We concluded that serum leptin levels are significantly lower in gastric cancer patients. In addition, gastric cancer patients have decreases in insulin levels, insulin resistance and growth hormone levels. This study found a positive association between serum leptin levels and insulin resistance. Moreover, there is a negative association between serum leptin levels and growth hormone levels. Thus, low insulin and growth hormone levels may suppress the production of leptin in gastric cancer patients.