Post-weight loss changes in fasting appetite- and energy balance-related hormone concentrations and the effect of the macronutrient content of a weight maintenance diet: a randomised controlled trial.

PURPOSE: We investigated the effects of the macronutrient composition of diets with differing satiety values on fasting appetite-related hormone concentrations after weight loss and examined whether the hormone secretion adapted to changes in body fat mass (FM) and fat-free mass (FFM) during the weight maintenance period (WM). METHODS: Eighty-two men and women with obesity underwent a 7-week very-low-energy diet (VLED) and were then randomised to a higher-satiety food (HSF) group or a lower-satiety food (LSF) group during 24-weeks of the WM. The groups consumed isoenergetic foods with different satiety ratings and macronutrient compositions. RESULTS: During the WM, the HSF group consumed more protein and dietary fibre and less fat than the LSF group, but the groups showed similar changes in body weight and fasting appetite-related hormones. In the whole study sample, VLED induced 12 kg (p < 0.001) weight loss. At the end of the WM, weight regain was 1.3 kg (p = 0.004), ghrelin concentration increased, whereas leptin, insulin, and glucose concentrations decreased compared to pre-VLED levels (p < 0.001 for all). Peptide YY did not differ from pre-VLED levels. Changes in ghrelin levels were inversely associated with changes in FFM during weeks 0-12 of the WM (p = 0.002), while changes in leptin and insulin levels were positively associated with changes in FM during weeks 0-12 (p = 0.015 and p = 0.038, respectively) and weeks 12-24 (p < 0.001 and p = 0.022) of the WM. CONCLUSIONS: The macronutrient composition of an isoenergetic WM diet did not affect fasting appetite-related hormone concentrations. Leptin and insulin adjusted to the reduced FM, whereas ghrelin reflected FFM during the first months of the WM. TRIAL REGISTRATION: isrctn.com, ID 67529475.

The effects of a 2-year physical activity and dietary intervention on plasma lipid concentrations in children: the PANIC Study.

PURPOSE: We studied the effects of a physical activity and dietary intervention on plasma lipids in a general population of children. We also investigated how lifestyle changes contributed to the intervention effects. METHODS: We carried out a 2-year controlled, non-randomized lifestyle intervention study among 504 mainly prepubertal children aged 6-9 years at baseline. We assigned 306 children to the intervention group and 198 children to the control group. We assessed plasma concentrations of total, LDL, HDL, and VLDL cholesterol, triglycerides, HDL triglycerides, and VLDL triglycerides. We evaluated the consumption of foods using 4-day food records and physical activity using a movement and heart rate sensor. We analyzed data using linear mixed-effect models adjusted for age at baseline, sex, and pubertal stage at both time points. Furthermore, specific lifestyle variables were entered in these models. RESULTS: Plasma LDL cholesterol decreased in the intervention group but did not change in the control group ( - 0.05 vs. 0.00 mmol/L, regression coefficient (ß) = - 0.0385, p = 0.040 for group*time interaction). This effect was mainly explained by the changes in the consumption of high-fat vegetable oil-based spreads (ß = - 0.0203, + 47% change in ß) and butter-based spreads (ß = - 0.0294, + 30% change in ß), moderate-to-vigorous physical activity (ß = - 0.0268, + 30% change in ß), light physical activity (ß = - 0.0274, + 29% change in ß) and sedentary time (ß = - 0.0270, + 30% change in ß). The intervention had no effect on other plasma lipids. CONCLUSION: Lifestyle intervention resulted a small decrease in plasma LDL cholesterol concentration in children. The effect was explained by changes in quality and quantity of dietary fat and physical activity. CLINICAL TRIAL REGISTRY NUMBER: NCT01803776, ClinicalTrials.gov.

A 2 year physical activity and dietary intervention attenuates the increase in insulin resistance in a general population of children: the PANIC study.

AIMS/HYPOTHESIS: We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children. METHODS: We carried out a 2 year non-randomised controlled trial in a population sample of 504 children aged 6-9 years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4 day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-IR were analysed using the intention-to-treat principle and linear mixed-effects models after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The measures of physical activity, sedentary time, diet and body composition at baseline and 2 year follow-up were entered one-by-one as covariates into the models to study whether changes in these variables might partly explain the observed intervention effects. RESULTS: Compared with the control group, fasting insulin increased 4.65 pmol/l less (absolute change +8.96 vs +13.61 pmol/l) and HOMA-IR increased 0.18 units less (+0.31 vs +0.49 units) over 2 years in the combined physical activity and dietary intervention group. The intervention effects on fasting insulin (regression coefficient ß for intervention effect -0.33 [95% CI -0.62, -0.04], p = 0.026) and HOMA-IR (ß for intervention effect -0.084 [95% CI -0.156, -0.012], p = 0.023) were statistically significant after adjustment for sex, age at baseline, and pubertal status at baseline and 2 year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR. CONCLUSIONS/INTERPRETATION: The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2 years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition. TRIAL REGISTRATION: ClinicalTrials.gov NCT01803776 Graphical abstract.

Longitudinal associations of physical activity and sedentary time with cardiometabolic risk factors in children.

BACKGROUND: There are few prospective studies on the associations of changes in objectively measured vigorous physical activity (VPA∆ ), moderate-to-vigorous physical activity (MVPA∆ ), light physical activity (LPA∆ ), and sedentary time (ST∆ ) with changes in cardiometabolic risk factors (∆ ) in children. We therefore investigated these relationships among children. METHODS: The participants were a population sample of 258 children aged 6-8 years followed for 2 years. We assessed PA and ST by a combined heart rate and movement sensor; computed continuous age- and sex-adjusted z-scores for waist circumference, blood pressure, and fasting insulin, glucose, triglycerides, and high-density lipoprotein (HDL) cholesterol; and constructed a cardiometabolic risk score (CRS) of these risk factors. Data were analyzed using linear regression models adjusted for age, sex, the explanatory and outcome variables at baseline, and puberty. RESULTS: VPA∆ associated inversely with CRS∆ (ß = -0.209, P = 0.001), body fat percentage (BF%)∆ (ß = -0.244, P = 0.001), insulin∆ (ß = -0.220, P = 0.001), and triglycerides∆ (ß = -0.164, P = 0.012) and directly with HDL cholesterol∆ (ß = 0.159, P = 0.023). MVPA∆ associated inversely with CRS∆ (ß = -0.178, P = 0.012), BF%∆ (ß = -0.298, P = <0.001), and insulin∆ (ß = -0.213, P = 0.006) and directly with HDL cholesterol∆ (ß = 0.184, P = 0.022). LPA∆ only associated negatively with CRS∆ (ß = -0.163, P = 0.032). ST∆ associated directly with CRS∆ (ß = 0.218, P = 0.003), BF%∆ (ß = 0.212, P = 0.016), and insulin∆ (ß = 0.159, P = 0.049). CONCLUSIONS: Increased VPA and MVPA and decreased ST were associated with reduced overall cardiometabolic risk and major individual risk factors. Change in LPA had weaker associations with changes in these cardiometabolic risk factors. Our findings suggest that increasing at least moderate-intensity PA and decreasing ST decrease cardiometabolic risk in children.

Cross-linking of sodium caseinate-structured emulsion with transglutaminase alters postprandial metabolic and appetite responses in healthy young individuals.

The physico-chemical and interfacial properties of fat emulsions influence lipid digestion and may affect postprandial responses. The aim of the present study was to determine the effects of the modification of the interfacial layer of a fat emulsion by cross-linking on postprandial metabolic and appetite responses. A total of fifteen healthy individuals (26.5 (sem 6.9) years and BMI 21.9 (sem 2.0) kg/m2) participated in a cross-over design experiment in which they consumed two isoenergetic (1924 kJ (460 kcal)) and isovolumic (250 g) emulsions stabilised with either sodium caseinate (Cas) or transglutaminase-cross-linked sodium caseinate (Cas-TG) in a randomised order. Blood samples were collected from the individuals at baseline and for 6 h postprandially for the determination of serum TAG and plasma NEFA, cholecystokinin (CCK), glucagon-like peptide 1 (GLP-1), glucose and insulin responses. Appetite was assessed using visual analogue scales. Postprandial TAG and NEFA responses and gastric emptying (GE) rates were comparable between the emulsions. CCK increased more after the ingestion of Cas-TG than after the ingestion of Cas (P< 0.05), while GLP-1 responses did not differ between the two test emulsions. Glucose and insulin profiles were lower after consuming Cas-TG than after consuming Cas (P< 0.05). The overall insulin, glucose and CCK responses, expressed as areas above/under the curve, did not differ significantly between the Cas and Cas-TG meal conditions. Satiety ratings were reduced and hunger, desire to eat and thirst ratings increased more after the ingestion of Cas-TG than after the ingestion of Cas (P< 0.05). The present results suggest that even a subtle structural modification of the interfacial layer of a fat emulsion can alter the early postprandial profiles of glucose, insulin, CCK, appetite and satiety through decreased protein digestion without affecting significantly on GE or overall lipid digestion.

Validation of metabolic syndrome score by confirmatory factor analysis in children and adults and prediction of cardiometabolic outcomes in adults.

AIMS/HYPOTHESIS: We validated the metabolic syndrome (MetS) score by confirmatory factor analysis (CFA) in children, middle-aged men, and older women and men and by investigating the relationships of the MetS score to incident type 2 diabetes, myocardial infarction, and cardiovascular and overall death in middle-aged men. METHODS: We assessed the core features of MetS, calculated the MetS score using z scores for waist circumference, insulin, glucose, triacylglycerols, HDL-cholesterol and blood pressure, and carried out CFA to investigate whether MetS represents a single entity in population samples of 491 children, 1,900 middle-aged men, 614 older women and 555 older men from Finland. We also followed-up incident type 2 diabetes for 11 years and other outcomes for 17-18 years in middle-aged men. RESULTS: We carried out second-order CFAs in which the MetS was represented by a second-order latent variable underlying four latent variables characterised by abdominal obesity, insulin resistance, dyslipidaemia and raised blood pressure in different age groups. These second-order factors and factors derived from first-order CFA using previously proposed models were strongly associated with a composite MetS score in all age groups (r = 0.84-0.94) and similarly predicted type 2 diabetes, cardiovascular outcomes and mortality in middle-aged men. The risk of type 2 diabetes, myocardial infarction, cardiovascular death and overall death increased 3.67-, 1.38-, 1.56- and 1.44-fold, respectively, for a 1 SD increase in the MetS score. CONCLUSIONS: The MetS can be described as a single entity in all age groups. The MetS score is a valid tool for research evaluating cardiometabolic risk in different age groups. Further research is needed to define cut-off points for risk estimation in clinical practice.

Physical activity and sedentary behaviour in relation to cardiometabolic risk in children: cross-sectional findings from the Physical Activity and Nutrition in Children (PANIC) Study.

BACKGROUND: Lower levels of physical activity (PA) and sedentary behaviour (SB) have been associated with increased cardiometabolic risk among children. However, little is known about the independent and combined associations of PA and SB as well as different types of these behaviours with cardiometabolic risk in children. We therefore investigated these relationships among children. METHODS: The subjects were a population sample of 468 children 6-8 years of age. PA and SB were assessed by a questionnaire administered by parents and validated by a monitor combining heart rate and accelerometry measurements. We assessed body fat percentage, waist circumference, blood glucose, serum insulin, plasma lipids and lipoproteins and blood pressure and calculated a cardiometabolic risk score using population-specific Z-scores and a formula waist circumference + insulin + glucose + triglycerides - HDL cholesterol + mean of systolic and diastolic blood pressure. We analysed data using multivariate linear regression models. RESULTS: Total PA was inversely associated with the cardiometabolic risk score (ß = -0.135, p = 0.004), body fat percentage (ß = -0.155, p < 0.001), insulin (ß = -0.099, p = 0.034), triglycerides (ß = -0.166, p < 0.001), VLDL triglycerides (ß = -0.230, p < 0.001), VLDL cholesterol (ß = -0.168, p = 0.001), LDL cholesterol (ß = -0.094, p = 0.046) and HDL triglycerides (ß = -0.149, p = 0.004) and directly related to HDL cholesterol (ß = 0.144, p = 0.002) adjusted for age and gender. Unstructured PA was inversely associated with the cardiometabolic risk score (ß = -0.123, p = 0.010), body fat percentage (ß = -0.099, p = 0.027), insulin (ß = -0.108, p = 0.021), triglycerides (ß = -0.144, p = 0.002), VLDL triglycerides (ß = -0.233, p < 0.001) and VLDL cholesterol (ß = -0.199, p < 0.001) and directly related to HDL cholesterol (ß = 0.126, p = 0.008). Watching TV and videos was directly related to the cardiometabolic risk score (ß = 0.135, p = 0.003), body fat percentage (ß = 0.090, p = 0.039), waist circumference (ß = 0.097, p = 0.033) and systolic blood pressure (ß = 0.096, p = 0.039). Resting was directly associated with the cardiometabolic risk score (ß = 0.092, p = 0.049), triglycerides (ß = 0.131, p = 0.005), VLDL triglycerides (ß = 0.134, p = 0.009), VLDL cholesterol (ß = 0.147, p = 0.004) and LDL cholesterol (ß = 0.105, p = 0.023). Other types of PA and SB had less consistent associations with cardiometabolic risk factors. CONCLUSIONS: The results of our study emphasise increasing total and unstructured PA and decreasing watching TV and videos and other sedentary behaviours to reduce cardiometabolic risk among children. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01803776.

Metabolic risk factors are associated with stiffness index, reflection index and finger skin temperature in children--Physical Activity and Nutrition in Children (PANIC) study.

BACKGROUND: Childhood metabolic syndrome (MetS) has been found to predict adulthood MetS, type 2 diabetes and cardiovascular disease, emphasizing the early identification of children at increased risk of these diseases. Children with clustering of metabolic risk factors have been reported to have a mild arterial stiffness and endothelial dysfunction, but limited evidence is available from population-based samples of children. METHODS AND RESULTS: The associations of metabolic risk factors with arterial stiffness, tone and endothelial function were studied in 173 prepubertal children (90 girls) 6-8 years of age. MetS was assessed both by continuous MetScore and dichotomously. Stiffness index (SI), reflection index (RI) and finger skin temperature (FST) were measured before and after maximum exercise test, and percent change was calculated for RI (RI%Δ) and FST (FST%Δ). MetScore (r=0.26, P=0.001), fasting insulin (r=0.24, P=0.002), fasting triglycerides (r=0.20, P=0.009), systolic (SBP; r=0.24, P=0.002) and diastolic blood pressure (DBP; r=0.19, P=0.013) correlated with SI. MetScore (r=-0.17, P=0.024, r=0.21, P=0.006), waist circumference (r=-0.19, P=0.012, r=0.23, P=0.003) and SBP (r=-0.16, P=0.035, r=0.21, P=0.005) correlated with RI and FST. High-density lipoprotein cholesterol correlated with FST (r=-0.22, P=0.004) and FST%Δ (r=-0.24, P=0.002). RI decreased and FST increased with exercise (P<0.001). Waist circumference correlated inversely with RI%Δ in boys (r=-0.22, P=0.046) and directly with RI%Δ in girls (r=0.27, P=0.011). CONCLUSIONS: Metabolic risk factors are associated with arterial stiffness, tone and endothelial function in prepubertal children.

Effect of intensive counselling on the quality of dietary fats in pregnant women at high risk of gestational diabetes mellitus.

As part of a feasibility study to prevent gestational diabetes mellitus (GDM), we evaluated the effect of an intensive dietary therapy on quality of diet, weight gain and birth weight in women at high risk of GDM. Women with risk factors for GDM (n 54) were randomly assigned from April 2005 to May 2006 to a lifestyle intervention group (n 27) including dietary advice six times during pregnancy or to a close follow-up group (n 27) in a community-based setting in Finland. Dietary intake was recorded three times during pregnancy using 4 d food records. The main outcome was the incidence of GDM. The secondary outcomes were the changes in nutrient intake, weight gain and birth weight. Overall, seventeen (65 %) women in the intervention group and eighteen (69 %) women in the close follow-up group returned all three food records. PUFA intake increased (P = 0·008) during pregnancy in the intervention as compared to the close follow-up group. There were no clear differences in the changes of saturated fat or fibre intake between the groups. Intensive dietary education resulted in a somewhat lower weight gain during pregnancy (P = 0·062) and higher birth weights of the infants (P = 0·047) without an effect on macrosomia as compared to the close follow-up group. Individualised counselling by a clinical nutritionist as part of a lifestyle intervention improved the quality of dietary fat intake in pregnant women at high risk of GDM.

Crosslinking with transglutaminase does not change metabolic effects of sodium caseinate in model beverage in healthy young individuals.

BACKGROUND: Postprandial metabolic and appetitive responses of proteins are dependent on protein source and processing technique prior to ingestion. Studies on the postprandial effects of enzymatic crosslinking of milk proteins are sparse. Our aim was to study the effect of transglutaminase (TG)-induced crosslinking of sodium caseinate on postprandial metabolic and appetite responses. Whey protein was included as reference protein. METHODS: Thirteen healthy individuals (23.3 ± 1.1 y, BMI 21.7 ± 0.4 kg/m2) participated in a single-blind crossover design experiment in which the subjects consumed three different isovolumic (500 g) pourable beverages containing either sodium caseinate (Cas, 29 g), TG-treated sodium caseinate (Cas-TG, 29 g) or whey protein (Wh, 30 g) in a randomized order. Blood samples were collected at baseline and for 4 h postprandially for the determination of plasma glucose, insulin and amino acid (AA) concentrations. Gastric emptying (GE) was measured using the 13 C-breath test method. Appetite was assessed using visual analogue scales. RESULTS: All examined postprandial responses were comparable with Cas and Cas-TG. The protein type used in the beverages was reflected as differences in plasma AA concentrations between Wh and Cas, but there were no differences in plasma glucose or insulin responses. A tendency for faster GE rate after Wh was detected. Appetite ratings or subsequent energy intake did not differ among the protein beverages. CONCLUSIONS: Our results indicate that the metabolic responses of enzymatically crosslinked and native sodium caseinate in a liquid matrix are comparable, suggesting similar digestion and absorption rates and first pass metabolism despite the structural modification of Cas-TG.

Low-grade inflammation and depressive symptoms as predictors of abdominal obesity.

AIM: Abundant evidence suggests that depression is a risk factor for cardiovascular disease and metabolic syndrome. Systemic low-grade inflammation and evolving abdominal obesity are hypothesised to be underlying mechanisms explaining the relationship. To test this hypothesis we examined the association of depressive symptoms and inflammation in developing abdominal obesity. METHODS: The subjects were 726 non-diabetic men, 42-60 of age at baseline, participating in the Kuopio Ischemic Heart Disease Risk Factor Study. The follow-up data was collected 11 years after the baseline. Low-grade inflammation was defined as serum C-reactive protein ≥2 mg/l and depressive symptoms were assessed by the Human Population Laboratory Depression Scale. Incident abdominal obesity was defined as waist girth >102 cm. RESULTS: Men with low-grade inflammation and depressive symptoms were more likely (OR 4.28, 95% CI 1.93-12.01) to develop abdominal obesity during the 11-year follow-up than in men not having either of these conditions, adjusting for age, smoking, alcohol consumption, prevalent cardiovascular disease, physical activity and socioeconomic status. These men were also more likely (OR 3.94, 95% CI 1.38-11.26) to develop metabolic syndrome. CONCLUSIONS: The presence of systemic low-grade inflammation together with depressive symptoms seems to detect men at a particularly high risk of developing abdominal obesity over a long period of time.

Structure modification of a milk protein-based model food affects postprandial intestinal peptide release and fullness in healthy young men.

Physico-chemical and textural properties of foods in addition to their chemical composition modify postprandial metabolism and signals from the gastrointestinal tract. Enzymatic cross-linking of protein is a tool to modify food texture and structure without changing nutritional composition. We investigated the effects of structure modification of a milk protein-based model food and the type of milk protein used on postprandial hormonal, metabolic and appetitive responses. Healthy males (n 8) consumed an isoenergetic and isovolumic test product containing either whey protein (Wh, low-viscous liquid), casein (Cas, high-viscous liquid) or Cas protein cross-linked with transglutaminase (Cas-TG, rigid gel) in a randomised order. Blood samples were drawn for plasma glucose, insulin, cholecystokinin (CCK), glucagon-like peptide 1 and peptide YY analysis for 4 h. Appetite was assessed at concomitant time points. Cas and Wh were more potent in lowering postprandial glucose than Cas-TG during the first hour. Insulin concentrations peaked at 30 min, but the peaks were more pronounced for Cas and Wh than for Cas-TG. The increase in CCK was similar for Cas and Wh in the first 15 min, whereas for Cas-TG, the CCK release was significantly lower, but more sustained. The feeling of fullness was stronger after the consumption of Cas-TG than after the consumption of Cas and Wh. The present results suggest that food structure is more effective in modulating the postprandial responses than the type of dairy protein used. Modification of protein-based food structure could thus offer a possible tool for lowering postprandial glucose and insulin concentrations and enhancing postprandial fullness.

Feasibility of a lifestyle intervention in early pregnancy to prevent deterioration of glucose tolerance.

BACKGROUND: In conjunction with the growing prevalence of obesity and the older age of pregnant women gestational diabetes (GDM) is a major health problem.The aim of the study was to evaluate if a lifestyle intervention since early pregnancy is feasible in improving the glucose tolerance of women at a high-risk for GDM in Finland. METHODS: A 75-g oral glucose tolerance test (OGTT) was performed in early pregnancy (n = 102). Women at high risk for GDM (n = 54) were randomized at weeks 8-12 from Apr 2005 to May 2006 to a lifestyle intervention group (n = 27) or to a close follow-up group (n = 27). An OGTT was performed again at weeks 26-28 for the lifestyle intervention and close follow-up groups. RESULTS: The values of the OGTT during the second trimester did not differ between the lifestyle intervention and close follow-up groups. In the lifestyle intervention group three women had GDM in the second trimester and respectively one woman in the close follow up group. Insulin therapy was not required in both groups. The intervention resulted in somewhat lower weight gain 11.4 ± 6.0 kg vs. 13.9 ± 5.1 kg, p = 0.062, adjusted by the prepregnancy weight. CONCLUSIONS: Early intervention with an OGTT and simple lifestyle advice is feasible. A more intensive lifestyle intervention did not offer additional benefits with respect to glucose tolerance, although it tended to ameliorate the weight gain. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01130012.

Long-term morbidity and mortality in patients diagnosed with an insulinoma.

OBJECTIVE: Insulinomas are rare functional pancreatic neuroendocrine tumours. As previous data on the long-term prognosis of insulinoma patients are scarce, we studied the morbidity and mortality in the Finnish insulinoma cohort. DESIGN: Retrospective cohort study. METHODS: Incidence of endocrine, cardiovascular, gastrointestinal and psychiatric disorders, and cancers was compared in all the patients diagnosed with an insulinoma in Finland during 1980-2010 (n = 79, including two patients with multiple endocrine neoplasia type 1 syndrome), vs 316 matched controls, using the Mantel-Haenszel method. Overall survival was analysed with Kaplan-Meier and Cox regression analyses. RESULTS: The median length of follow-up was 10.7 years for the patients and 12.2 years for the controls. The long-term incidence of atrial fibrillation (rate ratio (RR): 2.07 (95% CI: 1.02-4.22)), intestinal obstruction (18.65 (2.09-166.86)), and possibly breast (4.46 (1.29-15.39) and kidney cancers (RR not applicable) was increased among insulinoma patients vs controls, P < 0.05 for all comparisons. Endocrine disorders and pancreatic diseases were more frequent in the patients during the first year after insulinoma diagnosis, but not later on. The survival of patients with a non-metastatic insulinoma (n = 70) was similar to that of controls, but for patients with distant metastases (n = 9), the survival was significantly impaired (median 3.4 years). CONCLUSIONS: The long-term prognosis of patients with a non-metastatic insulinoma is similar to the general population, except for an increased incidence of atrial fibrillation, intestinal obstruction, and possibly breast and kidney cancers. These results need to be confirmed in future studies. Metastatic insulinomas entail a markedly decreased survival.

A psyllium fiber-enriched meal strongly attenuates postprandial gastrointestinal peptide release in healthy young adults.

Dietary fiber (DF) and protein are essential constituents of a healthy diet and are well known for their high satiety impact. However, little is known about their influence on postprandial gastrointestinal (GI) peptide release. Our aim in this single-blind, randomized, cross-over study was to investigate the effects of DF and/or protein enrichments on satiety-related metabolic and hormonal responses. Sixteen healthy, nonobese volunteers participated in the study and ingested 1 of 5 isoenergetic test meals in a randomized order on separate days. The test meals were as follows: 1) low in protein (2.8 g) and fiber (7.6 g); 2) low in protein (2.6 g) and high in soluble fiber (psyllium, 23.0 g); 3) high in protein (soy, 19.7 g) and low in fiber (6.2 g); 4) high in protein (18.4 g) and fiber (23.0 g); and 5) white wheat bread. Serum insulin and plasma glucose, ghrelin, glucagon-like peptide 1 (GLP-1), and peptide YY (PYY) concentrations were determined for 2 h following the meals. In addition, hunger and satiety ratings were collected. Postprandial glucose, insulin, ghrelin, GLP-1, and PYY responses all differed among the meals (P

Sedentary lifestyle and emergence of hopelessness in middle-aged men.

BACKGROUND: A sedentary lifestyle and psychosocial factors such as hopelessness and depression increase cardiovascular risk. Cross-sectional evidence suggests positive effects of physical exercise on psychological well being, but the time order of the relationship between physical activity and hopelessness has not been addressed. DESIGN: Population-based prospective cohort study with 630 middle-aged men participating in the 4-year follow-up and 509 men in the 11-year follow-up. METHODS: We investigated the association of leisure-time physical activity (LTPA) with the development of hopelessness during the follow-up. LTPA and hopelessness were quantified with questionnaires. RESULTS: In cross-sectional analyses, LTPA was inversely associated with hopelessness, independently of depression. Among men who did not have feelings of hopelessness at baseline, those who reported engaging in at least 2.5 h/week of moderate-to-vigorous physical activity had a lower risk (odds ratio 0.65, 95% confidence interval: 0.39-1.09, P for the trend=0.047) to feel hopeless than sedentary men 4 years later after adjustment for age, smoking, alcohol consumption, cardiovascular disease and socioeconomic status. Furthermore, this relationship was not explained by body mass index or maximal oxygen uptake. Adjustment for depressive symptoms slightly weakened the association (odds ratio 0.66, 95% confidence interval: 0.39-1.11, P for the trend=0.060). After 11 years, men who reported being physically active at baseline were still less likely to feel hopeless, after adjusting for age. However, after further adjustment for other confounding factors the association was no longer significant. CONCLUSION: Moderate-to-vigorous physical activity seems to prevent development of hopelessness in middle-aged men. This protective effect may diminish over time.

Alpha-lipoic acid does not alter stress protein response to acute exercise in diabetic brain.

Heat shock proteins (HSPs) are molecular chaperones which may act protective in cerebrovascular insults and peripheral diabetic neuropathy. We hypothesized that alpha-lipoic acid (LA), a natural thiol antioxidant, may enhance brain HSP response in diabetes. Rats with or without streptozotocin-induced diabetes were treated with LA or saline for 8 weeks. Half of the rats were subjected to exhaustive exercise to investigate HSP induction, and the brain tissue was analyzed. Diabetes increased constitutive HSC70 mRNA, and decreased HSP90 and glucose-regulated protein 75 (GRP75) mRNA without affecting protein levels. Exercise increased HSP90 protein and mRNA, and also GRP75 and heme oxygenase-1 (HO-1) mRNA only in non-diabetic animals. LA had no significant effect on brain HSPs, although LA increased HSC70 and HO-1 mRNA in diabetic animals and decreased HSC70 mRNA in non-diabetic animals. Eukaryotic translation elongation factor-2, essential for protein synthesis, was decreased by diabetes and suggesting a mechanism for the impaired HSP response related to translocation of the nascent chain during protein synthesis. LA supplementation does not offset the adverse effects of diabetes on brain HSP mRNA expression. Diabetes may impair HSP translation through elongation factors related to nascent chain translocation and subsequent responses to acute stress.

Dietary fatty acids and cardiovascular disease: an epidemiological approach.

The quality of dietary fat in relation to cardiovascular disease forms the basis of the diet-heart hypothesis. Current recommendations on dietary fat now emphasise quality rather than quantity. The focus of this review is to summarise the results from prospective cohort studies on dietary fat and cardiovascular disease outcomes. Relatively few prospective cohort studies have found an association between dietary fat quality and cardiovascular disease, partly because of limitations in estimating dietary intake. Saturated and trans fatty acids have increased cardiovascular risk in several studies. Both n-6 and n-3 polyunsaturated fatty acids have been associated with lower cardiovascular risk. Within the n-6 series, linoleic acid seems to decrease cardiovascular risk. Within the n-3 series the long-chain fatty acids (eicosapentaenoic and docosahexaenoic acids) are associated with decreased risk for especially fatal coronary outcomes, whereas the role of alpha-linolenic acid is less clear. Dietary fat quality also influences the activity of enzymes involved in the desaturation of fatty acids in the body. Serum desaturase indices have been consistently associated with adverse cardiovascular outcomes. Data from metabolic and clinical studies reinforce findings from observational studies supporting recommendations to replace saturated and trans fat with unsaturated fat in the prevention of cardiovascular disease.

Intake of Camelina Sativa Oil and Fatty Fish Alter the Plasma Lipid Mediator Profile in Subjects with Impaired Glucose Metabolism - A Randomized Controlled Trial.

n-3 and n-6 polyunsaturated fatty acids (PUFAs) and their lipid mediator metabolites are associated with inflammation. We investigated the effect of dietary intake of plant- and animal-derived n-3 PUFAs and fish protein on the circulatory concentrations of lipid mediators. Seventy-nine subjects with impaired fasting glucose who completed the controlled dietary intervention after randomization to the fatty fish (FF, n=20), lean fish (LF, n=21), Camelina sativa oil (CSO, n=18) or control group (n=20) for 12 weeks were studied. Lipid mediator profiling from fasting plasma samples before and after the intervention was performed by liquid chromatography-mass spectrometry (LC-MS/MS). The FF diet increased concentrations of 18-hydroxyeicosapentaenoic acid (18-HEPE) and 4- and 17-hydroxydocosahexaenoic acid (4-, 17-HDoHE) derived from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), respectively. Concentrations of lipid mediators derived from α-linolenic acid (ALA) increased and arachidonic acid (AA) derived 5-iso prostaglandin F2α-VI decreased in the CSO group. There were no significant changes in lipid mediators in the LF group. The dietary intake of both plant and animal-based n-3 PUFAs increased circulatory concentrations of lipid mediators with potential anti-inflammatory properties.

Heat shock proteins in diabetes and wound healing.

The heat shock proteins (HSPs), originally identified as heat-inducible gene products, are a highly conserved family of proteins that respond to a wide variety of stress. Although HSPs are among the most abundant intracellular proteins, they are expressed at low levels under normal physiological conditions, and show marked induction in response to various stressors. HSPs function primarily as molecular chaperones, facilitating the folding of other cellular proteins, preventing protein aggregation, or targeting improperly folded proteins to specific pathways for degradation. By modulating inflammation, wound debris clearance, cell proliferation, migration and collagen synthesis, HSPs are essential for normal wound healing of the skin. In this review, our goal is to discuss the role and clinical implications of HSP with respect to skin wound healing and diabetes. The numerous defects in the function of HSPs associated with diabetes could contribute to the commonly observed complications and delayed wound healing in diabetics. Several physical, pharmacological and genetic approaches may be considered to address HSP-directed therapies both in the laboratory and in the clinics.