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The entero-endocrine response following a mixed-meal tolerance test with a non-nutritive pre-load in participants with pre-diabetes and type 2 diabetes: A crossover randomized controlled trial proof of concept study.
Muilwijk, M, Beulens, JWJ, Groeneveld, L, Rutters, F, Blom, MT, Agamennone, V, van den Broek, T, Keijser, BJF, Hoevenaars, F
PloS one. 2023;18(8):e0290261
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There is a process within the mouth and gut that is responsible for sensing nutrients and releasing hormones, which is called the entero-endocrine response. This response is responsible for ensuring that we do not overeat and maintain normal metabolism. The use of stevia, which is a sweetener, instead of sugar in food has been reported to have blood sugar lowering effects, which may be of benefit to individuals with type 2 diabetes (T2D). However, it is not fully understood how stevia can affect the entero-endocrine response, especially in individuals with T2D and prediabetes. This cross-over randomised control trial aimed to determine the entero-endocrine response in 20 individuals with either T2D or prediabetes following the consumption of stevia before a meal. The results showed that there was an enhanced entero-endocrine response to stevia in individuals with T2D compared to those with prediabetes. Blood sugar and the hormones responsible for lowering blood sugar and appetite suppression were all higher in individuals with T2D. There were no associations between the composition of the oral or gut microbiota and the entero-endocrine response. It was concluded that the consumption of stevia before a meal differentially effects the entero-endocrine response in individuals with T2D and prediabetes. This study could be used by healthcare professionals to understand that the consumption of stevia before a meal elicits an individual response. However, as this was a small study, further understanding of the mechanisms involved would be of benefit.
Abstract
INTRODUCTION This crossover randomized controlled trial (RCT) investigated differences in short-term entero-endocrine response to a mixed-meal tolerance test preceded by nutrient sensing between participants with pre-diabetes (pre-T2D) and type 2 diabetes (T2D). Additionally, differences in gut and oral microbiome composition between participants with a high and low entero-endocrine response were investigated. RESEARCH DESIGN AND METHODS Ten participants with pre-T2D and ten with T2D underwent three test days with pre-loads consisting of either swallowing water (control), or rinsing with a non-nutritive sweetener solution, or swallowing the sweetener solution before a mixed-meal tolerance test. Blood glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-1 (GLP-1), glucagon, glucose, insulin and peptide YY (PYY) were determined at t = -20, 0, 15, 30, 60, 120 and 240 minutes. The composition of the oral and gut microbiome at baseline were also determined. RESULTS The entero-endocrine response differed by pre-loads, e.g. a lower PYY response after swallowing the non-nutritive sweetener (-3585.2pg/mL [95% CI: -6440.6; -729.8]; p = 0.01). But it also differed by T2D status, e.g. a higher glucose, glucagon and PYY response was found in participants with T2D, compared to those with pre-T2D. Evidence for associations between the oral and gut microbiome composition and the entero-endocrine response was limited. Still, the level of entero-endocrine response was associated with several oral microbiome measures. Higher oral anterior α-diversity was associated with a lower PYY response (e.g. Inverse Simpson index -1357pg/mL [95% CI -2378; -336; 1.24]), and higher oral posterior α-diversitywith a higher GIP response (e.g. Inverse Simpson index 6773pg/mL [95% CI 132; 13414]) in models adjusted for sex, age and T2D status. CONCLUSIONS Non-nutritive pre-loads influence the entero-endocrine response to a mixed-meal, and this effect varies based on (pre-)T2D status. The entero-endocrine response is likely not associated with the gut microbiome, and there is limited evidence for association with the α-diversity of the oral microbiome composition. TRIAL REGISTRATION Trial register: Netherlands Trial Register NTR7212, accessible through International Clinical Trials Registry Platform: ICTRP Search Portal (who.int).
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A combination of green tea, rhodiola, magnesium and B vitamins modulates brain activity and protects against the effects of induced social stress in healthy volunteers.
Boyle, NB, Billington, J, Lawton, C, Quadt, F, Dye, L
Nutritional neuroscience. 2022;25(9):1845-1859
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Stress is a leading cause of work-related time off. Low magnesium intake has been shown to be associated with anxiety and supplementation has been shown to relieve anxiety-related-symptoms, especially when combined with B vitamins. Green tea and rhodiola have also been used to alleviate stress, anxiety, and fatigue, the latter after just 3 days of intake. This randomised control trial of 100 moderately stressed adults aimed to determine the effects of combining magnesium, B vitamins, green tea, and rhodiola after induced social stress. The results showed that supplementation with a combination of magnesium, B vitamins, green tea, and rhodiola induced a relaxed, alert state and lowered stress, anxiety, and mood disturbances. However, it did not affect stress hormones, heart rate or blood pressure in response to stress. It was concluded that combination treatment is a promising therapy for stress. This study could be used by healthcare professionals to recommend the combination of magnesium, B vitamins, green tea, and rhodiola to individuals with social anxiety before they enter a socially stressful situation.
Abstract
BACKGROUND Magnesium (Mg), green tea and rhodiola extracts have, in isolation, been shown to possess stress and anxiety relieving effects. Green tea and rhodiola have been shown to modulate EEG oscillatory brain activity associated with relaxation and stress perception. The combined capacity of these ingredients to confer protective effects under conditions of acute stress has yet to be examined. We tested the hypothesis that a combination of Mg (with B vitamins) + green tea + rhodiola would acutely moderate the effects of stress exposure. METHODS A double blind, randomised, placebo controlled, parallel group design was employed (Clinicaltrials.gov:NCT03262376; 25/0817). One hundred moderately stressed adults received oral supplementation of either (i) Mg + B vitamins + green tea + rhodiola; (ii) Mg + B vitamins + rhodiola; (iii) Mg + B vitamins + green tea; or (iv) placebo. After supplementation participants were exposed to the Trier Social Stress Test. The effects of the study treatments on electroencephalogram (EEG) resting state alpha and theta, subjective state/mood, blood pressure, heart rate variability and salivary cortisol responses after acute stress exposure were assessed. RESULTS The combined treatment significantly increased EEG resting state theta (p < .02) - considered indicative of a relaxed, alert state, attenuated subjective stress, anxiety and mood disturbance, and heightened subjective and autonomic arousal (p < .05). CONCLUSIONS Mg, B vitamins, rhodiola and green tea extracts are a promising combination of ingredients that may enhance coping capacity and offer protection from the negative effects of stress exposure.Trial registration: ClinicalTrials.gov identifier: NCT03262376.
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Impact of Experimentally Induced Cognitive Dietary Restraint on Eating Behavior Traits, Appetite Sensations, and Markers of Stress during Energy Restriction in Overweight/Obese Women.
Morin, I, Bégin, C, Maltais-Giguère, J, Bédard, A, Tchernof, A, Lemieux, S
Journal of obesity. 2018;2018:4259389
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The treatment of obesity has become a public health priority given the negative impact of this condition on physical and mental health. The aim of this study was to compare the effects of energy restriction alone or in combination with induced cognitive dietary restraint (CDR) on eating behaviour traits, appetite sensations, and markers of stress in overweight and obese premenopausal women. The study is a single-blinded randomised clinical study which recruited premenopausal women aged between 26 and 50 years. The participants were randomised to either an energy-restriction-plus-induced CDR condition (CDR+group) or an energy-restriction-without induced CDR condition (CDR−group). Results indicate that inducing CDR in a context of energy restriction had no further effects on eating behaviour traits, appetite sensations, and markers of stress in the short term as well as in the longer term than energy restriction alone. Authors conclude that increasing CDR has no negative impact on factors regulating energy balance in the context of energy restriction.
Abstract
Weight loss has been associated with changes in eating behaviors and appetite sensations that favor a regain in body weight. Since traditional weight loss approaches emphasize the importance of increasing cognitive dietary restraint (CDR) to achieve negative energy imbalance, it is difficult to untangle the respective contributions of energy restriction and increases in CDR on factors that can eventually lead to body weight regain. The present study aimed at comparing the effects of energy restriction alone or in combination with experimentally induced CDR on eating behavior traits, appetite sensations, and markers of stress in overweight and obese women. We hypothesized that the combination of energy restriction and induced CDR would lead to more prevalent food cravings, increased appetite sensations, and higher cortisol concentrations than when energy restriction is not coupled with induced CDR. A total of 60 premenopausal women (mean BMI: 32.0 kg/m2; mean age: 39.4 y) were provided with a low energy density diet corresponding to 85% of their energy needs during a 4-week fully controlled period. At the same time, women were randomized to either a condition inducing an increase in CDR (CDR+ group) or a condition in which CDR was not induced (CRD- group). Eating behavior traits (Three-Factor Eating Questionnaire and Food Craving Questionnaire), appetite sensations (after standardized breakfast), and markers of stress (Perceived Stress Scale; postawakening salivary cortisol) were measured before (T = 0 week) and after (T = 4 weeks) the 4-week energy restriction, as well as 3 months later. There was an increase in CDR in the CDR+ group while no such change was observed in the CDR- group (p=0.0037). No between-group differences were observed for disinhibition, hunger, cravings, appetite sensations, perceived stress, and cortisol concentrations. These results suggest that a slight increase in CDR has no negative impact on factors regulating energy balance in the context of energy restriction.
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A lecithin phosphatidylserine and phosphatidic acid complex (PAS) reduces symptoms of the premenstrual syndrome (PMS): Results of a randomized, placebo-controlled, double-blind clinical trial.
Schmidt, K, Weber, N, Steiner, M, Meyer, N, Dubberke, A, Rutenberg, D, Hellhammer, J
Clinical nutrition ESPEN. 2018;24:22-30
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PMS is characterized by a cluster of somatic and psychological symptoms of varying severity. These symptoms occur only during the luteal phase of the menstrual cycle and resolve during the first days of menses. Recent observational data suggest that supplementation with Lipogen's phosphatidylserine and phosphatidic acid complex (PAS) alleviates these PMS symptoms. The aim of this study was to observe the effects of PAS on PMS symptom severity. This study is a prospective, randomised, placebo-controlled, double-blind single centre study with two arms (PAS or placebo). Participants were randomly assigned to one of the two groups. Results show beneficial effects of a daily intake of PAS over 3 cycles on symptom levels as assessed by several well-recognized instruments for PMS evaluation. The PAS complex alleviated the PMS symptoms, providing a safe alternative to standard pharmacological treatment. Authors conclude that their findings merit consideration of developing the PAS complex as a botanical drug for treatment of PMS symptoms.
Abstract
BACKGROUND & AIMS Many women experience emotional and physical symptoms around the time of ovulation and more so before menstruation interfering with their daily normal life also known as premenstrual syndrome (PMS). Recent observational data suggest that supplementation with Lipogen's phosphatidylserine (PS) and phosphatidic acid (PA) complex (PAS) alleviates these PMS symptoms. The aim of this study was to confirm these observations on the effects of PAS on PMS symptom severity within a controlled clinical trial setting. METHODS Forty women aged 18-45 years with a diagnosis of PMS were assigned to either take PAS (containing 400 mg PS & 400 mg PA per day) or a matching placebo. The study comprised 5 on-site visits including 1 baseline menstrual cycle followed by 3 treatment cycles. Treatment intake was controlled for by using an electronic device, the Medication Event Monitoring System (MEMS®). Primary outcome of the study was the PMS symptoms severity as assessed by using the Daily Record of Severity of Problems (DRSP). Further, SIPS questionnaire (a German version of the Premenstrual Symptoms Screening Tool (PSST)), salivary hormone levels (cortisol awakening response (CAR) and evening cortisol levels) as well as serum levels (cortisol, estradiol, progesterone and corticosteroid binding globulin (CBG)) were assessed. RESULTS PMS symptoms as assessed by the DRSP Total score showed a significantly better improvement (p = 0.001) over a 3 cycles PAS intake as compared to placebo. In addition, PAS treated women reported a greater improvement in physical (p = 0.002) and depressive symptoms (p = 0.068). They also reported a lower reduction of productivity (p = 0.052) and a stronger decrease in interference with relationships with others (p = 0.099) compared to the placebo group. No other DRSP scale or item showed significant results. Likewise, the reduction in the number of subjects fulfilling PMS or premenstrual dysphoric disorder (PMDD) criteria as classified by the SIPS did not differ between the PAS and the placebo group. For the biomarkers, the salivary cortisol percentage increase of the CAR was significantly less pronounced in the follicular phase of cycle 4 than in the follicular phase of cycle 1 for subjects taking PAS when compared to subjects taking placebo (p = 0.018). Furthermore, the change of serum cortisol levels between visit 1 and visit 5 differed significantly between groups (p = 0.043). While serum cortisol levels of PAS treated females slightly decreased between visit 1 and visit 5, cortisol levels of females treated with placebo increased. For all other biomarkers, no treatment effects were observed over the 4 cycles study period. Overall, this study confirms that a daily intake of PAS, containing 400 mg PS and 400 mg PA, can be considered as safe. CONCLUSIONS Results substantiate the efficacy of PAS in reducing symptoms of PMS. In view of the recent inclusion of severe PMS symptoms (PMDD) in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), the positive results of this clinical study merits consideration of developing the PAS complex as a botanical drug for treatment of PMDD. CLINICAL TRIAL REGISTRATION The study is registered at Deutsches Register Klinischer Studien with the registration number DRKS00009005.
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Placebo-controlled dietary intervention of stress-induced neurovegetative disorders with a specific amino acid composition: a pilot-study.
Chaborski, K, Bitterlich, N, Alteheld, B, Parsi, E, Metzner, C
Nutrition journal. 2015;14:43
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Psychosocial stress leads to altered neuroendocrine functions resulting in imbalances between various neurotransmitters and hormones. Supplementation of amino acids as precursors of neurotransmitters is an important therapeutic approach that may reduce sensitivity to stress. The aim of this study was to investigate whether daily administration of an amino acid and micronutrient mixture could reduce neurovegetative disorders in 32 psychologically stressed patients. Psychological status, serotonin level, cortisol level and dietary intake were recorded at baseline and 12 weeks after amino acid supplementation. This study showed that both treatment and placebo group resulted in a significant decrease of neurovegetative symptoms, indicating that daily supplementation of the amino acid composition used in this study resulted in no improvement of neurovegetative disorders compared with placebo.
Abstract
BACKGROUND Psychosocial stress leads to altered neuroendocrine functions, such as serotonergic dysfunction, as well as alterations of the autonomic nervous system and the hypothalamic-pituitary-adrenal (HPA)-axis activity resulting in an imbalance between inhibitory and excitatory neurotransmitters. Poor dietary intake of L-tryptophan as a precursor of serotonin increases sensitivity to stress. METHODS This randomized, double-blind, placebo-controlled study investigated the effect of a specific amino acid composition with micronutrients on neurovegetative disorders and the cardiometabolic risk profile in psychosocially stressed patients. 32 patients (18-65 years) were eligible for protocol analysis. Points in the Psychological Neurological Questionnaire (PNF), clinical and blood parameter, in particular the serotonin level, salivary cortisol levels, and dietary intake were evaluated at baseline and 12 weeks after supplementation. RESULTS The intervention in the form of either verum or placebo resulted in both groups in a significant decrease of neurovegetative symptoms. However, patients of the placebo group achieved significantly less points in the PNF compared to the verum group. But the rate of responders (≥10 points loss in PNF) was not significantly different between the groups. The macronutrient intake did not differ between verum and placebo group. On average, the HPA-axis was not disturbed in both groups. Blood serotonin indicated in both groups no significant correlation with dietary tryptophan intake or PNF. CONCLUSIONS Daily supplementation of a specific amino acid composition with micronutrients in psychologically stressed patients resulted in no improvement of neurovegetative disorders as measured by the PNF when compared to the placebo group. TRIAL REGISTRATION Clinical Trials.gov ( NCT01425983 ).
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Excessive Sugar Consumption May Be a Difficult Habit to Break: A View From the Brain and Body.
Tryon, MS, Stanhope, KL, Epel, ES, Mason, AE, Brown, R, Medici, V, Havel, PJ, Laugero, KD
The Journal of clinical endocrinology and metabolism. 2015;100(6):2239-47
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It is widely known that people eat to relieve stress. Rodent studies have shown that sugar consumption switches off activity in the networks that mediate the stress induced hypothalamic-pituitary-adrenal (HPA) autonomic nervous system. This study aimed to compare the effects of consuming drinks, sweetened with either sucrose or aspartame, on cortisol responses induced by stress. The researchers found that sucrose consumption was associated reduced stress induced cortisol, and a trend towards lower cortisol. Aspartame did not have the same effect. The Montreal Imaging Stress Task (MIST) was used to map areas of the brain associated with stress. It was found that sugar consumption caused a diminished response to MIST after two weeks of sucrose consumption, and cortisol was elevated after two weeks of aspartame. The study concluded that brain negative feedback pathways are affected by sugar, and consequently may make stressed individuals more reliant or addicted to sugar. In turn, this increases the likelihood of obesity and its associated chronic diseases.
Abstract
CONTEXT Sugar overconsumption and chronic stress are growing health concerns because they both may increase the risk for obesity and its related diseases. Rodent studies suggest that sugar consumption may activate a glucocorticoid-metabolic-brain-negative feedback pathway, which may turn off the stress response and thereby reinforce habitual sugar overconsumption. OBJECTIVE The objective of the study was to test our hypothesized glucocorticoid-metabolic-brain model in women consuming beverages sweetened with either aspartame of sucrose. DESIGN This was a parallel-arm, double-masked diet intervention study. SETTING The study was conducted at the University of California, Davis, Clinical and Translational Science Center's Clinical Research Center and the University of California, Davis, Medical Center Imaging Research Center. PARTICIPANTS Nineteen women (age range 18-40 y) with a body mass index (range 20-34 kg/m(2)) who were a subgroup from a National Institutes of Health-funded investigation of 188 participants assigned to eight experimental groups. INTERVENTION The intervention consisted of sucrose- or aspartame-sweetened beverage consumption three times per day for 2 weeks. MAIN OUTCOME MEASURES Salivary cortisol and regional brain responses to the Montreal Imaging Stress Task were measured. RESULTS Compared with aspartame, sucrose consumption was associated with significantly higher activity in the left hippocampus (P = .001). Sucrose, but not aspartame, consumption associated with reduced (P = .024) stress-induced cortisol. The sucrose group also had a lower reactivity to naltrexone, significantly (P = .041) lower nausea, and a trend (P = .080) toward lower cortisol. CONCLUSION These experimental findings support a metabolic-brain-negative feedback pathway that is affected by sugar and may make some people under stress more hooked on sugar and possibly more vulnerable to obesity and its related conditions.
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Favourable effects of consuming a Palaeolithic-type diet on characteristics of the metabolic syndrome: a randomized controlled pilot-study.
Boers, I, Muskiet, FA, Berkelaar, E, Schut, E, Penders, R, Hoenderdos, K, Wichers, HJ, Jong, MC
Lipids in health and disease. 2014;13:160
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The prevalence of metabolic syndrome (MetS) is increasing rapidly worldwide and is a major risk factor for type 2 diabetes (DM2) and cardiovascular disease (CVD). Modern lifestyle-induced insulin resistance and chronic systemic low grade inflammation are considered at the root of the MetS. Therefore, dietary patterns of our Palaeolithic ancestors may be ideal for prevention and treatment of metabolic disorders since they are thought to be in line with the evolution of human physiology and metabolism. The aim of this randomized controlled pilot study was to assess the efficacy of a Palaeolithic-type diet in improving the characteristics of MetS, compared to a diet based on healthy eating guidelines. The study included 34 participants with MetS who consumed their allocated diets for two weeks. Efforts were made to prevent weight loss so that any favourable effects could be explained by the dietary intervention and not by the positive health effects of weight loss. The findings of this study showed that the Palaeolithic-type diet significantly lowered blood pressure, total cholesterol and triglycerides, as well as improved HDL-cholesterol, compared to the reference diet. The participants in the Palaeolithic diet intervention also had fewer characteristics of MetS and a tendency to higher insulin sensitivity at the end of the study. Despite efforts to keep body-weight stable, more weight was lost by the participants in the Palaeolithic group. No changes were observed in the secondary outcomes of inflammation, intestinal permeability and salivary cortisol, which the authors explain by the short duration of the intervention and the attempt to prevent weight loss. The authors conclude that future studies should take full additional advantage of the greater weight loss with the Palaeolithic diet, which may be more satiating than other diets, hence allowing weight loss to happen.
Abstract
BACKGROUND The main goal of this randomized controlled single-blinded pilot study was to study whether, independent of weight loss, a Palaeolithic-type diet alters characteristics of the metabolic syndrome. Next we searched for outcome variables that might become favourably influenced by a Paleolithic-type diet and may provide new insights in the pathophysiological mechanisms underlying the metabolic syndrome. In addition, more information on feasibility and designing an innovative dietary research program on the basis of a Palaeolithic-type diet was obtained. METHODS Thirty-four subjects, with at least two characteristics of the metabolic syndrome, were randomized to a two weeks Palaeolithic-type diet (n = 18) or an isoenergetic healthy reference diet, based on the guidelines of the Dutch Health Council (n = 14). Thirty-two subjects completed the study. Measures were taken to keep bodyweight stable. As primary outcomes oral glucose tolerance and characteristics of the metabolic syndrome (abdominal circumference, blood pressure, glucose, lipids) were measured. Secondary outcomes were intestinal permeability, inflammation and salivary cortisol. Data were collected at baseline and after the intervention. RESULTS Subjects were 53.5 (SD9.7) year old men (n = 9) and women (n = 25) with mean BMI of 31.8 (SD5.7) kg/m2. The Palaeolithic-type diet resulted in lower systolic blood pressure (-9.1 mmHg; P = 0.015), diastolic blood pressure (-5.2 mmHg; P = 0.038), total cholesterol (-0.52 mmol/l; P = 0.037), triglycerides (-0.89 mmol/l; P = 0.001) and higher HDL-cholesterol (+0.15 mmol/l; P = 0.013), compared to reference. The number of characteristics of the metabolic syndrome decreased with 1.07 (P = 0.010) upon the Palaeolithic-type diet, compared to reference. Despite efforts to keep bodyweight stable, it decreased in the Palaeolithic group compared to reference (-1.32 kg; P = 0.012). However, favourable effects remained after post-hoc adjustments for this unintended weight loss. No changes were observed for intestinal permeability, inflammation and salivary cortisol. CONCLUSIONS We conclude that consuming a Palaeolithic-type diet for two weeks improved several cardiovascular risk factors compared to a healthy reference diet in subjects with the metabolic syndrome. TRIAL REGISTRATION Nederlands Trial Register NTR3002.
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No effect of caloric restriction on salivary cortisol levels in overweight men and women.
Tam, CS, Frost, EA, Xie, W, Rood, J, Ravussin, E, Redman, LM
Metabolism: clinical and experimental. 2014;63(2):194-8
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Alterations in normal cortisol patterns have been observed in people who are obese. The effect of weight loss on cortisol levels, a measure of hypothalamic pituitary adrenal (HPA) activity, in overweight individuals is not known. The aim of this study was to test the hypothesis that 6 months of moderate caloric restriction would alter morning and diurnal salivary cortisol levels. Thirty-five overweight adults (average BMI 27.8 kg/m2) took part in this randomised control trial. Participants were assigned to either calorie restriction (CR: 25% reduction in energy intake), calorie restriction+exercise (CR+EX: 12.5% reduction in energy intake+12.5% increase in exercise energy expenditure) or control (healthy weight-maintenance diet) for 6 months. Salivary cortisol was measured at 8:00, 8:30, 11:00, 11:30, 12:30, 13:00, 16:00 and 16:30. Morning cortisol was defined as the mean cortisol concentration at 08:00 and 08:30. Diurnal cortisol was calculated as the mean of the 8 cortisol measures across the day. Across all groups, higher morning and diurnal cortisol levels were associated with impaired insulin sensitivity. There was no significant effect of group, time or sex on morning or diurnal cortisol levels. The authors concluded that a 10% weight loss with a 25% CR diet alone or with exercise did not impact morning or diurnal salivary cortisol levels in overweight individuals. Their findings suggest that prolonged restriction of energy intake is not perceived by the body as a stressor, and therefore CR may present a viable intervention.
Abstract
OBJECTIVE The effect of weight loss by diet or diet and exercise on salivary cortisol levels, a measure of hypothalamic pituitary adrenal activity, in overweight individuals is not known. The objective was to test the hypothesis that 24 weeks of moderate caloric restriction (CR) (25%) by diet or diet and aerobic exercise would alter morning and diurnal salivary cortisol levels. DESIGN AND SETTING Randomized control trial in an institutional research center. PARTICIPANTS Thirty-five overweight (BMI: 27.8±0.7 kg/m(2)) but otherwise healthy participants (16 M/19 F). INTERVENTION Participants were randomized to either calorie restriction (CR: 25% reduction in energy intake, n=12), calorie restriction+exercise (CR+EX: 12.5% reduction in energy intake+12.5% increase in exercise energy expenditure, n=12) or control (healthy weight-maintenance diet, n=11) for 6 months. MAIN OUTCOME MEASURE Salivary cortisol measured at 8:00, 8:30, 11:00, 11:30, 12:30, 13:00, 16:00 and 16:30. Morning cortisol was defined as the mean cortisol concentration at 08:00 and 08:30. Diurnal cortisol was calculated as the mean of the 8 cortisol measures across the day. RESULTS In the whole cohort, higher morning and diurnal cortisol levels were associated with impaired insulin sensitivity (morning: P=0.004, r(2)=0.24; diurnal: P=0.02, r(2)=0.15). Using mixed model analysis, there was no significant effect of group, time or sex on morning or diurnal cortisol levels. CONCLUSION A 10% weight loss with a 25% CR diet alone or with exercise did not impact morning or diurnal salivary cortisol levels.
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Sleep restriction for 1 week reduces insulin sensitivity in healthy men.
Buxton, OM, Pavlova, M, Reid, EW, Wang, W, Simonson, DC, Adler, GK
Diabetes. 2010;59(9):2126-33
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Short sleep duration is associated with an increased risk of many chronic diseases including diabetes, however the effects of sleep restriction on insulin sensitivity have not yet been established. The aim of study was to assess the effects of decreased sleep duration on insulin sensitivity in a controlled environment. This 12-day inpatient study included 20 healthy men who were randmoised to receive a wakefulness-promoting drug, modafinil, or placebo during the sleep restriction phase. This study showed that sleep restriction for one week significantly reduces insulin sensitivity. These findings raise concerns about chronic insufficient sleep on the development of metabolic diseases and promote further research into these effects.
Abstract
OBJECTIVE Short sleep duration is associated with impaired glucose tolerance and an increased risk of diabetes. The effects of sleep restriction on insulin sensitivity have not been established. This study tests the hypothesis that decreasing nighttime sleep duration reduces insulin sensitivity and assesses the effects of a drug, modafinil, that increases alertness during wakefulness. RESEARCH DESIGN AND METHODS This 12-day inpatient General Clinical Research Center study included 20 healthy men (age 20-35 years and BMI 20-30 kg/m(2)). Subjects spent 10 h/night in bed for >or=8 nights including three inpatient nights (sleep-replete condition), followed by 5 h/night in bed for 7 nights (sleep-restricted condition). Subjects received 300 mg/day modafinil or placebo during sleep restriction. Diet and activity were controlled. On the last 2 days of each condition, we assessed glucose metabolism by intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp. Salivary cortisol, 24-h urinary catecholamines, and neurobehavioral performance were measured. RESULTS IVGTT-derived insulin sensitivity was reduced by (means +/- SD) 20 +/- 24% after sleep restriction (P = 0.001), without significant alterations in the insulin secretory response. Similarly, insulin sensitivity assessed by clamp was reduced by 11 +/- 5.5% (P < 0.04) after sleep restriction. Glucose tolerance and the disposition index were reduced by sleep restriction. These outcomes were not affected by modafinil treatment. Changes in insulin sensitivity did not correlate with changes in salivary cortisol (increase of 51 +/- 8% with sleep restriction, P < 0.02), urinary catecholamines, or slow wave sleep. CONCLUSIONS Sleep restriction (5 h/night) for 1 week significantly reduces insulin sensitivity, raising concerns about effects of chronic insufficient sleep on disease processes associated with insulin resistance.