Effect of sleep deprivation on insulin sensitivity and cortisol concentration in healthy subjects

The objective of this study was to assess insulin sensitivity and cortisol concentration in healthy subjects with 24-hr sleep deprivation. A randomised, single-blind, controlled clinical trial was performed in 28 healthy subjects. Fourteen individuals were studied before and after 24-hr sleep deprivation and 14 volunteers with normal sleep periods (NSP) as a control group. Serum creatinine, uric acid, total cholesterol, high-density lipoprotein cholesterol, and triglyceride concentrations were measured in both groups. Insulin suppression test modified with octreotide (IST) and cortisol levels were performed before and after 24-hr sleep deprivation or NSP. Clinical and metabolic characteristics of the subjects in both groups are similar. Steady-state glucose (SSG) concentration of the IST was significantly higher after 24-hr sleep deprivation (5.7+/-2.1 vs 6.7+/-2.2 mmol/l; p=0.01). SSG level was similar before and after NSP (5.0+/-2.1 vs 5.0+/-1.8 mmol/l, respectively; p=0.91). There were not significant differences in cortisol levels between initial and final tests in both groups. In conclusion, 24-hr sleep deprivation decreased the insulin sensitivity in healthy subjects without changes in cortisol levels.     

Effect of short-term consumption of a high fat diet on glucose tolerance and insulin sensitivity in the rat

The mechanism by which the consumption of high fat, low carbohydrate diets impair glucose tolerance and decrease insulin sensitivity is poorly understood. In an attempt to clarify this question, intravenous glucose tolerance and insulin action in the liver and skeletal muscle were examined in rats after two weeks feeding of either a high fat (HF: 66% energy as fat) or a low fat (LF: 12% energy as fat) diet. Both diets had a P/S ratio (ratio of polyunsaturated to saturated fat in the diet) of 1.3. The high fat diet resulted in mild impairment of intravenous glucose tolerance. Postprandial glucose levels were elevated in the presence of a sustained insulin response. In vitro insulin-stimulated glucose utilisation was decreased significantly in soleus muscle of HF rats, as indicated by decreased [14C]glucose incorporation into muscle glycogen. In contrast, muscle lipogenesis from glucose was not affected by dietary composition. There was no difference in insulin binding to soleus muscle of HF and LF rats, indicating a dissociation between insulin receptor binding and post-receptor metabolic events. Dietary composition did not influence the incorporation of increasing [14C]glucose loads into muscle glycogen or lipid in vivo. However, the HF diet was associated with reduced incorporation of [14C]glucose into lipids and glycogen in the liver and, to a smaller extent, reduced incorporation into adipose tissue lipids in vivo. These results suggest that the mechanism by which HF diets impaired glucose tolerance was mainly hepatic in origin. Decreased glucose uptake, secondary to reduced glucokinase activity, may result in a reduction in glucose utilisation in the liver.     

Seasonal variation in insulin sensitivity in healthy elderly people

OBJECTIVE: There is a seasonal variation in the incidence of diabetes mellitus and cardiovascular diseases. However, there is very little information about the seasonal variation in insulin sensitivity. We report the seasonal variation in insulin sensitivity in a group of elderly subjects followed for 1 y. METHODS: Healthy elderly (>/=70 y) subjects living independently were included. Fifty percent of subjects received a daily nutritional supplement that provided 400 kcal, 15 g of protein, and 50% of vitamin daily reference values (DRVs). Those receiving and not receiving supplements were randomly assigned to a resistance exercise training program. Every 6 mo (winter, summer, and winter), body composition was measured by dual-energy x-ray absorptiometry and blood samples were used to measure serum lipids, fasting and postprandial glucose, and insulin levels. RESULTS: One hundred eight subjects (31 supplemented and trained, 28 supplemented, 16 trained, and 33 without supplementation or training) completed the follow up. Higher homeostasis assessment of insulin sensitivity, postprandial insulin, and fasting triacylglycerol levels were observed during the summer than during the winter. Body fat increased steadily during the study period, and fat-free mass did not change. Serum low-density lipoprotein cholesterol decreased significantly in the supplemented and trained group and increased in the non-intervention group. CONCLUSIONS: In this group of elderly subjects, insulin resistance and triacylglycerol levels were higher during the summer. Nutritional supplementation and training had a positive effect on serum low-density lipoprotein cholesterol.     

A 4-wk high-fructose diet alters lipid metabolism without affecting insulin sensitivity or ectopic lipids in healthy humans

BACKGROUND: High fructose consumption is suspected to be causally linked to the epidemics of obesity and metabolic disorders. In rodents, fructose leads to insulin resistance and ectopic lipid deposition. In humans, the effects of fructose on insulin sensitivity remain debated, whereas its effect on ectopic lipids has never been investigated. OBJECTIVE: We assessed the effect of moderate fructose supplementation on insulin sensitivity (IS) and ectopic lipids in healthy male volunteers (n = 7). DESIGN: IS, intrahepatocellular lipids (IHCL), and intramyocellular lipids (IMCL) were measured before and after 1 and 4 wk of a high-fructose diet containing 1.5 g fructose . kg body wt(-1) . d(-1). Adipose tissue IS was evaluated from nonesterified fatty acid suppression, hepatic IS from suppression of hepatic glucose output (6,6-2H2-glucose), and muscle IS from the whole-body glucose disposal rate during a 2-step hyperinsulinemic euglycemic clamp. IHCL and IMCL were measured by 1H magnetic resonance spectroscopy. RESULTS: Fructose caused significant (P < 0.05) increases in fasting plasma concentrations of triacylglycerol (36%), VLDL-triacylglycerol (72%), lactate (49%), glucose (5.5%), and leptin (48%) without any significant changes in body weight, IHCL, IMCL, or IS. IHCL were negatively correlated with triacylglycerol after 4 wk of the high-fructose diet (r = -0.78, P < 0.05). CONCLUSION: Moderate fructose supplementation over 4 wk increases plasma triacylglycerol and glucose concentrations without causing ectopic lipid deposition or insulin resistance in healthy humans.     

The association between plasma adiponectin and insulin sensitivity in humans depends on obesity

OBJECTIVE: In humans, low plasma adiponectin concentrations precede a decrease in insulin sensitivity and predict type 2 diabetes independently of obesity. However, it is possible that the contribution of adiponectin to insulin sensitivity is not equally strong over the whole range of obesity. RESEARCH METHODS AND PROCEDURES: We investigated the cross-sectional association between plasma adiponectin levels and insulin sensitivity in different ranges of body fat content [expressed as percentage of body fat (PFAT)] in a large cohort of normal glucose-tolerant subjects (n = 900). All individuals underwent an oral glucose tolerance test (OGTT), and 299 subjects additionally a euglycemic hyperinsulinemic clamp. In longitudinal analyses, the association of adiponectin at baseline with change in insulin sensitivity was investigated in a subgroup of 108 subjects. RESULTS: In cross-sectional analyses, the association between plasma adiponectin and insulin sensitivity, adjusted for age, gender, and PFAT, depended on whether subjects were lean or obese [p for interaction adiponectin x PFAT = <0.001 (OGTT) and 0.002 (clamp)]. Stratified by quartiles of PFAT, adiponectin did not correlate significantly with insulin sensitivity in subjects in the lowest PFAT quartile (R2 = 0.10, p = 0.13, OGTT; and R2 = 0.10, p = 0.57, clamp), whereas the association in the upper PFAT quartile was rather strong (R2 = 0.36, p < 0.0001, OGTT; and R2 = 0.48, p = 0.003, clamp). In longitudinal analyses, plasma adiponectin at baseline preceded change in insulin sensitivity in obese (n = 54, p = 0.03) but not in lean (n = 54, p = 0.68) individuals. DISCUSSION: These data suggest that adiponectin is especially critical in sustaining insulin sensitivity in obese subjects. Thus, interventions to reduce insulin resistance by increasing adiponectin concentrations may be effective particularly in obese, insulin-resistant individuals.     

六黄合剂对胰岛素抵抗大鼠胰岛素敏感性影响

目的 探讨中药复方六黄合剂对胰岛素抵抗大鼠胰岛素敏感性的影响。方法 应用地塞米松致大鼠胰岛素抵抗模型,观察六黄合剂对大鼠血糖、血清胰岛素水平和胰岛素敏感指数的影响。结果 六黄合剂能够降低胰岛素抵抗大鼠口服葡萄糖耐量试验后2 h血糖浓度(2 hBG)和空腹血清胰岛素水平(FINS),提高胰岛素敏感指数(ISI)(P<0.01)。结论 中药复方六黄合剂能够增强胰岛素抵抗大鼠胰岛素敏感性。     

Conjugated linoleic acid in humans: regulation of adiposity and insulin sensitivity

Conjugated linoleic acid (CLA) isomers, a group of positional and geometric isomers of linoleic acid [18:2(n-6)], have been studied extensively due to their ability to modulate cancer, atherosclerosis, obesity, immune function and diabetes in a variety of experimental models. The purpose of this review was to examine CLA's isomer-specific regulation of adiposity and insulin sensitivity in humans and in cultures of human adipocytes. It has been clearly demonstrated that specific CLA isomers or a crude mixture of CLA isomers prevent the development of obesity in certain rodent and pig models. This has been attributed mainly to trans-10, cis-12 CLA, both in vivo and in vitro. However, CLA's ability to modulate human obesity remains controversial because data from clinical trials using mixed isomers are conflicting. In support of some studies in humans, our group demonstrated that trans-10, cis-12 CLA prevents triglyceride (TG) accumulation in primary cultures of differentiating human preadipocytes. In contrast, cis-9, trans-11 CLA increases TG content. Closer examination has revealed that CLA's antiadipogenic actions are due, at least in part, to regulation of glucose and fatty acid uptake and metabolism. This review presents our current understanding of potential isomer-specific mechanisms by which CLA reduces human adiposity and insulin sensitivity.     

Effects of short-term moderate alcohol administration on oxidative stress and nutritional status in healthy males

The effects of moderate amounts of different alcoholic beverages on oxidative stress and nutritional parameters were investigated in 40 healthy subjects. Ethanol 40 g/day was administered at the two main meals for 30 days by beer (group A), wine (group B) or spirit (group C); controls (group D) maintaned abstinence. Malondyaldeide (MDA), adenosine-triphosphate (ATP), reduced-glutathione (GSH), E-vitamin and nutritional status were evaluated at the start (T0) and the end (T1) of the study. At T1 controls did not present significant changes in the assessed parameters, while a significant increase of malondyaldeide (MDA) and a significant decrease of reduced-glutathione and E-vitamin in group A, B and C and of ATP in group C were observed. Fat mass (FM) increased slightly in group A and B and decreased in group C. Ethanol decreased antioxidant parameters and increased lipoperoxidation parameters. However some of these changes appeared attenuated when ethanol was consumed in beer or wine. Finally, short-term moderate ethanol intake appeared to influence the FM, although it was not able to significantly affect nutritional or body composition.     

High-fiber rye bread and insulin secretion and sensitivity in healthy postmenopausal women

BACKGROUND: Fiber and whole-cereal intakes may protect against hyperinsulinemia and the risk of type 2 diabetes. OBJECTIVE: The aim was to study whether the long-term use of high-fiber rye bread and white-wheat bread modifies glucose and insulin metabolism in healthy postmenopausal women. DESIGN: The study was a randomized crossover trial consisting of 8-wk test and 8-wk washout periods. The subjects were 20 postmenopausal women [macro x +/- SD age: 59 +/- 6.0 y; body mass index (in kg/m(2)): 27.5 +/- 2.9; baseline fasting serum cholesterol: 6.5 +/- 0.8 mmol/L], of whom 3 had impaired glucose tolerance as determined by a 2-h oral-glucose-tolerance test. The test breads were high-fiber rye and white-wheat breads, planned to make up > or =20% of energy. Fasting blood samples were collected for the measurement of plasma glucose and insulin at the beginning and at the end of both bread periods. The frequently sampled intravenous-glucose-tolerance test was performed at the run-in and at the end of both bread periods. The acute insulin response, insulin sensitivity, and glucose effectiveness were calculated. RESULTS: The rye bread made up 23.4 +/- 4.3% and wheat bread 26.7 +/- 8.2% of total energy intake. Compared with that during the run-in period, the acute insulin response increased significantly more during the rye bread period (9.9 +/- 24.2%) than during the wheat bread period (2.8 +/- 36.3%; P = 0.047). Other measured variables did not change significantly during the study. CONCLUSIONS: Modification of carbohydrate intake by high-fiber rye bread did not alter insulin sensitivity in postmenopausal, hypercholesterolemic women. High-fiber rye bread appears to enhance insulin secretion, possibly indicating improvement of b cell function.     

Effect of nicotinamide administration on the tryptophan-nicotinamide pathway in humans

The vitamin nicotinamide is synthesized in the liver from tryptophan, and distributed to non-hepatic tissues. Although it is generally accepted that 60 mg tryptophan is equivalent to 1 mg nicotinamide in humans, the conversion ratio of tryptophan to nicotinamide is changeable. To determine if de novo nicotinamide synthesis from tryptophan is influenced by nicotinamide intake itself, six young women consumed controlled diets containing 30.4 or 24.8 mg niacin-equivalent nicotinamide supplements with 0, 89, 310, or 562 micromol/day (0, 10.9, 37.8, or 68.6 mg/day, respectively), and urinary excretion of intermediates and metabolites of the tryptophan-nicotinamide pathway were measured. Urinary excretion of nicotinamide metabolites increased linearly in a dose-dependent manner. None of the intermediates, including anthranilic acid, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, and quinolinic acid, changed at all, even when up to 562 micromol/day nicotinamide was given. That is, exogenous nicotinamide did not affect de novo nicotinamide synthesis. Therefore, when niacin equivalent is calculated, the intake of nicotinamide itself need not be considered as a factor that changes the tryptophan-nicotinamide conversion ratio.     

Effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans

BACKGROUND: Metabolomics in human nutrition research is faced with the challenge that changes in metabolic profiles resulting from diet may be difficult to differentiate from normal physiologic variation. OBJECTIVE: We assessed the extent of intra- and interindividual variation in normal human metabolic profiles and investigated the effect of standardizing diet on reducing variation. DESIGN: Urine, plasma, and saliva were collected from 30 healthy volunteers (23 females, 7 males) on 4 separate mornings. For visits 1 and 2, free food choice was permitted on the day before biofluid collection. Food choice on the day before visit 3 was intended to mimic that for visit 2, and all foods were standardized on the day before visit 4. Samples were analyzed by using 1H nuclear magnetic resonance spectroscopy followed by multivariate data analysis. RESULTS: Intra- and interindividual variations were considerable for each biofluid. Visual inspection of the principal components analysis scores plots indicated a reduction in interindividual variation in urine, but not in plasma or saliva, after the standard diet. Partial least-squares discriminant analysis indicated time-dependent changes in urinary and salivary samples, mainly resulting from creatinine in urine and acetate in saliva. The predictive power of each model to classify the samples as either night or morning was 85% for urine and 75% for saliva. CONCLUSIONS: Urine represented a sensitive metabolic profile that reflected acute dietary intake, whereas plasma and saliva did not. Future metabolomics studies should consider recent dietary intake and time of sample collection as a means of reducing normal physiologic variation.     

Short-term administration of dark chocolate is followed by a significant increase in insulin sensitivity and a decrease in blood pressure in healthy persons

BACKGROUND: Numerous studies indicate that flavanols may exert significant vascular protection because of their antioxidant properties and increased nitric oxide bioavailability. In turn, nitric oxide bioavailability deeply influences insulin-stimulated glucose uptake and vascular tone. Thus, flavanols may also exert positive metabolic and pressor effects. OBJECTIVE: The objective was to compare the effects of either dark or white chocolate bars on blood pressure and glucose and insulin responses to an oral-glucose-tolerance test in healthy subjects. DESIGN: After a 7-d cocoa-free run-in phase, 15 healthy subjects were randomly assigned to receive for 15 d either 100 g dark chocolate bars, which contained approximately 500 mg polyphenols, or 90 g white chocolate bars, which presumably contained no polyphenols. Successively, subjects entered a further cocoa-free washout phase of 7 d and then were crossed over to the other condition. Oral-glucose-tolerance tests were performed at the end of each period to calculate the homeostasis model assessment of insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI); blood pressure was measured daily. RESULTS: HOMA-IR was significantly lower after dark than after white chocolate ingestion (0.94 +/- 0.42 compared with 1.72 +/- 0.62; P < 0.001), and QUICKI was significantly higher after dark than after white chocolate ingestion (0.398 +/- 0.039 compared with 0356 +/- 0.023; P = 0.001). Although within normal values, systolic blood pressure was lower after dark than after white chocolate ingestion (107.5 +/- 8.6 compared with 113.9 +/- 8.4 mm Hg; P < 0.05). CONCLUSION: Dark, but not white, chocolate decreases blood pressure and improves insulin sensitivity in healthy persons.     

Acute effects of meal fatty acid composition on insulin sensitivity in healthy post-menopausal women

Postprandial plasma insulin concentrations after a single high-fat meal may be modified by the presence of specific fatty acids although the effects of sequential meal ingestion are unknown. The aim of the present study was to examine the effects of altering the fatty acid composition in a single mixed fat-carbohydrate meal on glucose metabolism and insulin sensitivity of a second meal eaten 5 h later. Insulin sensitivity was assessed using a minimal model approach. Ten healthy post-menopausal women underwent four two-meal studies in random order. A high-fat breakfast (40 g fat) where the fatty acid composition was predominantly saturated fatty acids (SFA), n-6 polyunsaturated fatty acids (PUFA), long-chain n-3 PUFA or monounsaturated fatty acids (MUFA) was followed 5 h later by a low-fat, high-carbohydrate lunch (5.7 g fat), which was identical in all four studies. The plasma insulin response was significantly higher following the SFA meal than the other meals after both breakfast and lunch (P<0.006) although there was no effect of breakfast fatty acid composition on plasma glucose concentrations. Postprandial insulin sensitivity (SI(Oral)) was assessed for 180 min after each meal. SI(Oral) was significantly lower after lunch than after breakfast for all four test meals (P=0.019) following the same rank order (SFA < n-6 PUFA < n-3 PUFA < MUFA) for each meal. The present study demonstrates that a single meal rich in SFA reduces postprandial insulin sensitivity with 'carry-over' effects for the next meal.     

Effect of the dietary fat quality on insulin sensitivity

Recent evidence shows that specific fatty acids affect cell metabolism, modifying the balance between fatty acid oxidation and lipogenesis. These effects may have important implications in addressing the present epidemic of nutrition-related chronic disease. Intake of dietary saturated and n-6 PUFA have increased while n-3 fatty acid intake has decreased. Obesity, type 2 diabetes and insulin resistance are highly prevalent, and both are strongly related to disorders of lipid metabolism characterized by an increased plasma and intracellular fatty acid availability. Thus, it has been hypothesized that change in the quality of dietary fat supply is able to modify the degree of insulin sensitivity. Animal studies provide support for this notion. However, there is limited human data either from normal or diabetic subjects. This review aims to analyse human studies that address this question. To this purpose, the experimental design, dietary compliance, insulin-sensitivity method used and confounding variables are discussed in order to identify the role of dietary fat quality as a risk factor for insulin resistance. Most studies (twelve of fifteen) found no effect relating to fat quality on insulin sensitivity. However, multiple study design flaws limit the validity of this conclusion. In contrast, one of the better designed studies found that consumption of a high-saturated-fat diet decreased insulin sensitivity in comparison to a high-monounsaturated-fat diet. We conclude that the role of dietary fat quality on insulin sensitivity in human subjects should be further studied, using experimental designs that address the limitations of existing data sets.     

Deleterious effects of omitting breakfast on insulin sensitivity and fasting lipid profiles in healthy lean women

BACKGROUND: Breakfast consumption is recommended, despite inconclusive evidence of health benefits. OBJECTIVE: The study's aim was to ascertain whether eating breakfast (EB) or omitting breakfast (OB) affects energy intake, energy expenditure, and circulating insulin, glucose, and lipid concentrations in healthy women. DESIGN: In a randomized crossover trial, 10 women [x+/-SD body mass index (BMI; in kg/m2): 23.2+/-1.4] underwent two 14-d EB or OB interventions separated by a 2-wk interval. In the EB period, subjects consumed breakfast cereal with 2%-fat milk before 0800 and a chocolate-covered cookie between 1030 and 1100. In the OB period, subjects consumed the cookie between 1030 and 1100 and the cereal and milk between 1200 and 1330. Subjects then consumed 4 additional meals with content similar to usual at predetermined times later in the day and recorded food intake on 3 d during each period. Fasting and posttest meal glucose, lipid, and insulin concentrations and resting energy expenditure were measured before and after each period. RESULTS: Reported energy intake was significantly lower in the EB period (P=0.001), and resting energy expenditure did not differ significantly between the 2 periods. OB was associated with significantly higher fasting total and LDL cholesterol than was EB (3.14 and 3.43 mmol/L and 1.55 and 1.82 mmol/L, respectively; P=0.001). The area under the curve of insulin response to the test meal was significantly lower after EB than after OB (P<0.01). CONCLUSION: OB impairs fasting lipids and postprandial insulin sensitivity and could lead to weight gain if the observed higher energy intake was sustained.     

The effect of consuming instant black tea on postprandial plasma glucose and insulin concentrations in healthy humans

OBJECTIVE: To determine the effects of black tea on postprandial plasma glucose and insulin concentrations in healthy humans in response to an oral glucose load. METHODS: A four-way randomised, crossover trial was designed in which 16 healthy fasted subjects would consume 75g of glucose in either 250ml of water (control), 250ml of water plus 0.052g of caffeine (positive control) or 250 ml of water plus 1.0g or 3.0g of instant black tea. Blood samples were collected at fasting and at 30min intervals for 150min from commencement of drink ingestion. Glucose and insulin concentrations were measured using standard methodology. The tea was chemically characterised using colorimetric and HPLC methods. RESULTS: Chemical analysis showed that the tea was rich in polyphenolic compounds (total, 350mg/g). Results from only 3 treatment arms are reported because the 3.0g tea drink caused gastrointestinal symptoms. Plasma glucose concentrations <60min in response to the drinks were similar, but were significantly reduced at 120min (P<0.01), following ingestion of the 1.0g tea drink, relative to the control and caffeine drinks. Tea consumption resulted in elevated insulin concentrations compared with the control and caffeine drinks at 90min (P<0.01) and compared with caffeine drink alone at 150min (P<0.01). CONCLUSIONS: The 1.0g tea drink reduced the late phase plasma glucose response in healthy humans with a corresponding increase in insulin. This may indicate that the attenuation in postprandial glycemia was achieved as a result of an elevated insulin response following stimulation of pancreatic beta-cells. This effect may be attributable to the presence of phenolic compounds in the tea.     

Effect of naltrexone administration on short-term memory in chronically ethanol-treated outbred rats

AIMS: The purpose of this study was to evaluate the effect of naltrexone treatment for 21 consecutive days on short-term memory in ethanol-preferring and non-preferring outbred rats. METHODS: Ethanol preferring, non-preferring and control Wistar rats were treated with naltrexone [0.1 mg/kg intraperitoneally (i.p.)] for 21 consecutive days. Short-term memory was assessed by using an olfactory social recognition test. RESULTS: A single administration of naltrexone (0.1 mg/kg i.p.) to non-ethanol-treated animals facilitated social memory, whereas the drug did not affect short-term memory in either group of chronically ethanol-treated rats. Multiple naltrexone treatment also lowered alcohol intake in ethanol-preferring rats. CONCLUSION: Naltrexone-ethanol interaction does not seem to produce any negative effect on the short-term memory in outbred rats.