In Parkinson&... more In Parkinson's disease, striatal dopamine transporter (DAT) binding and cardiac sympathetic function are disturbed. In addition, heart rate (HR)-corrected cardiac repolarisation time (QTc interval), which is partly under autonomic control, is prolonged. Whether there is physiological coupling between striatal DAT binding and QTc time (QTc-DAT relation) is not known. The purpose of this study is to evaluate QTc-DAT relation in healthy young adults. Thirty-five participants (18 women, age 26.4+/-1.8 years; mean+/-SD) were studied with iodine-123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single photon emission tomography. Signal-averaged ECG was recorded at rest from each participant. QTc interval was computed with Bazett's correction and with the approach by Karjalainen, getting QTc and QTk intervals, respectively. Mean striatal DAT binding, as (striatum-cerebellum)/cerebellum, was 2.63+/-0.31. Mean HR, QT, QTc and QTk intervals were 66+/-9 bpm, 340+/-25 ms, 354+/-18 ms and 351+/-16 ms, respectively. HR-QT correlation was -0.63, P value of less than 0.001. HR was not related to striatal DAT binding. QTc-DAT and QTk-DAT relations were significant, r = -0.50, P = 0.004 and r = -0.59, P = 0.0002, respectively. In linear regression model, striatal DAT binding explained 35% of the variance of QTk interval (95% confidence interval: -46.9 to -13.0, P = 0.0002). This study suggests significant physiological QTc-DAT relation in young healthy adults. QTc interval measurements might carry diagnostically important information in clinical conditions, which have an effect on both striatal DAT binding and cardiac sympathetic function.
To evaluate the effect of weight loss on substrate oxidation, energy expenditure, and insulin sen... more To evaluate the effect of weight loss on substrate oxidation, energy expenditure, and insulin sensitivity we studied 12 obese subjects (body mass index 33.4 ± 1.1) before and after 6 wk ofa very-low-calorie diet (VLCD) with euglycemic insulin clamp in combination with indirect calorimetry. Body weight decreased from 105.3 ± 4.6 to 94. 1 ± 4.0 kg (P < 0.001) and fat mass from 47.2 ± 3.6 to 37.7 ± 3.0 kg(P < 0.001). Total glucose disposal during insulin clamp increased from 30.4 ± 4.3 to 38.4 ± 4.4 mol. kg lean body mass (LBM). min' (P < 0.05), insulin-stimulated glucose oxidation from 14.3 ± 4.6 to 19. 1 ± 1.4 Mmol. kg LBM. min ' (P < 0.05), and nonoxidative glucose metabolism from 16.0 ± 3.8 to 19.3 ± 3.6 imol kg LBM'. min' (NS). Lipid oxidation decreased in the basal state (P < 0.05) and during the insulin clamp (P < 0.01). The basal rate ofenergy expenditure decreased from 99. 1 ± 4.6 to 88.5 ± 2.7 Id. kg LBM. min (P < 0.05) after weight reduction. A reduction in fat mass achieved by VLCD is associated with reduced lipid oxidation and, because of substrate competition, enhanced glucose oxidation. The physiological consequence is improved insulin sensitivity.
, including 370 men engaged in sports in which weight-related performance classes are associated ... more , including 370 men engaged in sports in which weight-related performance classes are associated with weight cycling (boxers, weight lifters and wrestlers; further called as weight cyclers), and 834 matched control men with no athletic background. Outcome measure: Weight change since the age of 20 years, body mass index (BMI) and prevalence of obesity and overweight. Results: The weight cyclers gained 5.2 BMI units from age 20 years to their maximum mean weight, which was at age 58.7 years. Corresponding figures for the controls were 4.2 BMI units at 58.5 years and for other athletes 3.3 BMI units at age 62.5 years. The proportion of obese (BMIX30 kg/m 2) subjects was greatest among the weight cyclers both in 1985 and 1995. In 2001, the weight cyclers were more often obese than other athletes, but did not differ from the controls. The odds ratio for the weight cyclers to be obese compared to other athletes in 1985 was 3.18 (95% confidence intervals 2.09-4.83), and compared to the controls 2.0 (1.35-2.96). The enhanced weight gain of the weight cyclers was not accounted for by present health habits (smoking, alcohol use, use of high-fat milk or physical activity) or weight at age 20 years. Conclusions: Repeated cycles of weight loss and regain appear to enhance subsequent weight gain and may predispose to obesity. Chronic dieting with weight cycling may be harmful for permanent weight control.
Dietary fat has been reported to influence insulin sensitivity. The objective of the study was to... more Dietary fat has been reported to influence insulin sensitivity. The objective of the study was to determine how identical weight loss (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity. Forty-seven obese women [body mass index (in kg/m(2)): 32.1 +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss. The groups did not differ significantly at baseline with respect to age, body weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or 8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin sensitivity im...
Changes in weight, body mass index (BMI), and thickness of triceps and subscapular skinfolds were... more Changes in weight, body mass index (BMI), and thickness of triceps and subscapular skinfolds were studied in 17,294 adult Finns who, as part of a health survey, were examined twice after an interval of 4 to 7 (average 5.7) years. During the follow-up, the mean weight and BMI rose in men and women below the age of 50 at entry, changed little in men aged 50-70 and in women aged 50-60, and rapidly declined at later ages. Individual weight changes were generally small; about two-thirds of the participants maintained their weight within 5 kg from the initial weight. About 9 per cent of the men and 4 per cent of the women gained 10 kg or more, and 2 per cent of the men and 4 per cent of the women lost 10 kg or more in 5 years. Weight loss was associated with old age and high initial BMI, whereas weight gain was most common in the young, even in those with a high initial BMI. Young overweight subjects need most attention in prevention and treatment programmes for obesity.
Rationale: Serotonin (5-HT) is involved in the control of eating behaviour by inhibiting food int... more Rationale: Serotonin (5-HT) is involved in the control of eating behaviour by inhibiting food intake. Obese women with binge-eating disorder (OB-BED) were recently found to have reduced 5-HT transporter binding. Objectives: The aim of this study was to investigate the effect of a successful treatment on 5-HT transporters in OB-BED. Methods: The 5-HT transporter binding of seven OB-BED was measured by single-photon emission computed tomography (SPECT), by using iodine-123labelled nor-b-CIT as a tracer, before treatment and after successful treatment, when the OB-BED were asymptomatic. Treatment consisted of group psychotherapy and fluoxetine medication. The control subjects, six obese women without eating disorders, were also studied twice by using SPECT. Results: The 5-HT transporter binding of the symptomatically recovered OB-BED increased significantly (24€22%) after treatment, whereas in the control group, binding remained unchanged. Conclusions: The results tentatively suggest that 5-HT transporter binding in OB-BED is an adaptive mechanism, which can be affected by treatment. Furthermore, there seems to be a link between improved 5-HT transporter binding and reduced binge eating.
To examine the association of smoking with recurrent dieting and BMI among Finnish adults. We use... more To examine the association of smoking with recurrent dieting and BMI among Finnish adults. We used questionnaire data from 1990 on 11,055 subjects from the Finnish Twin Cohort who were 33 to 61 years of age. Multinomial logistic regression analysis was carried out using lifetime dieting as the outcome variable and smoking as the main explanatory variable, adjusted for BMI and age. Twin pairs discordant for dieting and smoking were studied to examine the effect of environmental and genetic factors. Among women, current smokers [odds ratio (OR), 1.09 to 1.41 at different ages] and former smokers (OR, 1.52 to 2.82) were more likely to have dieted recurrently than never smokers. Among men, current smokers were less likely (OR, 0.69; 95% confidence interval, 0.55, 0.87) and former smokers were more likely (OR, 1.30; 95% confidence interval, 1.05, 1.61) to have dieted recurrently at different ages. The differences between the discordant pairs were consistent with this, although not statistically significant. Recurrent dieting was associated with former smoking in both sexes and with current smoking in women.
Muscle biopsy is the gold standard for diagnosis of mitochondrial disorders because of the lack o... more Muscle biopsy is the gold standard for diagnosis of mitochondrial disorders because of the lack of sensitive biomarkers in serum. Fibroblast growth factor 21 (FGF-21) is a growth factor with regulatory roles in lipid metabolism and the starvation response, and concentrations are raised in skeletal muscle and serum in mice with mitochondrial respiratory chain deficiencies. We investigated in a retrospective diagnostic study whether FGF-21 could be a biomarker for human mitochondrial disorders. We assessed samples from adults and children with mitochondrial disorders or non-mitochondrial neurological disorders (disease controls) from seven study centres in Europe and the USA, and recruited healthy volunteers (healthy controls), matched for age where possible, from the same centres. We used ELISA to measure FGF-21 concentrations in serum or plasma samples (abnormal values were defined as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;200 pg/mL). We compared these concentrations with values for lactate, pyruvate, lactate-to-pyruvate ratio, and creatine kinase in serum or plasma and calculated sensitivity, specificity, and positive and negative predictive values for all biomarkers. We analysed serum or plasma from 67 patients (41 adults and 26 children) with mitochondrial disorders, 34 disease controls (22 adults and 12 children), and 74 healthy controls. Mean FGF-21 concentrations in serum were 820 (SD 1151) pg/mL in adult and 1983 (1550) pg/mL in child patients with respiratory chain deficiencies and 76 (58) pg/mL in healthy controls. FGF-21 concentrations were high in patients with mitochondrial disorders affecting skeletal muscle but not in disease controls, including those with dystrophies. In patients with abnormal FGF-21 concentrations in serum, the odds ratio of having a muscle-manifesting mitochondrial disease was 132·0 (95% CI 38·7-450·3). For the identification of muscle-manifesting mitochondrial disease, the sensitivity was 92·3% (95% CI 81·5-97·9%) and specificity was 91·7% (84·8-96·1%). The positive and negative predictive values for FGF-21 were 84·2% (95% CI 72·1-92·5%) and 96·1 (90·4-98·9%). The accuracy of FGF-21 to correctly identify muscle-manifesting respiratory chain disorders was better than that for all conventional biomarkers. The area under the receiver-operating-characteristic curve for FGF-21 was 0·95; by comparison, the values for other biomarkers were 0·83 lactate (p=0·037, 0·83 for pyruvate (p=0·015), 0·72 for the lactate-to-pyruvate ratio (p=0·0002), and 0·77 for creatine kinase (p=0·013). Measurement of FGF-21 concentrations in serum identified primary muscle-manifesting respiratory chain deficiencies in adults and children and might be feasible as a first-line diagnostic test for these disorders to reduce the need for muscle biopsy. Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, Molecular Medicine Institute of Finland, University of Helsinki, Helsinki University Central Hospital, Academy of Finland, Novo Nordisk, Arvo and Lea Ylppö Foundation.
The known risk factors of atherosclerotic diseases may be involved in the development of a subara... more The known risk factors of atherosclerotic diseases may be involved in the development of a subarachnoid hemorrhage. We studied the morbidity and mortality due to subarachnoid hemorrhage among 42,862 men and women aged 20-69 years who had participated in a large health survey in Finland. During a mean follow-up of 12 years, 102 non-fatal and 85 fatal cases of subarachnoid hemorrhage were observed. The total incidence was 37 per 100,000 person-years. Smoking and hypertension were positively associated and body mass index was inversely associated with the risk of subarachnoid hemorrhage. These associations were not confounded by age or each other. No statistically significant association with risk was detected for serum cholesterol level, hematocrit content, known heart disease, or diabetes. The risk was especially elevated among lean hypertensive subjects and lean smoking subjects. The age-adjusted relative risks of subarachnoid hemorrhage for lean, hypertensive smokers were 18.3 (95% confidence interval (CI), 7.8-42.7) among women and 6.7 (95% CI, 2.3-19.7) among men as compared to the risk among subjects without these risk factors. We conclude that modifiable risk factors are predictive of subarachnoid hemorrhage, for which reason subarachnoid hemorrhage may in part be preventable. Leanness combined with arterial hypertension and/or smoking, in particular, poses a substantially elevated risk.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 1998
To analyse determinants of long-term weight maintenance we studied energy expenditure, dietary in... more To analyse determinants of long-term weight maintenance we studied energy expenditure, dietary intake, eating behaviour and psychological symptoms of 9 women (SS, BMI = 26.6) who reached their ideal weight during 1985-86 and were still an average 16.2 kg below their original weight in 1993. Controls were 42 obese, non-reducing females (OC, BMI = 34.8). Dietary intake was calculated from four-day food records. Dietary restraint was assessed by the Three-Factor Eating Questionnaire (TFEQ) and symptoms of bulimia or binge eating by Bulimic Investigatory Test, Edinburgh (BITE). Physical exercise was estimated by open interviews, resting metabolic rate (RMR) by indirect calorimetry and body composition by bioelectrical impedance. Psychological characteristics were studied using the Defense Style Questionnaire (DSQ), Beck Depression Inventory (BDI) and Symptom Checklist (SCL-90). SS had lower RMR (1320 kcal vs. 1540 kcal, p = 0.004), lower daily energy intake (1208 kcal vs. 1525 kcal, p = 0.020) and higher scores for dietary restraint (14.6 vs. 8.4, p = 0.002) than OC. Restraint scores correlated negatively with energy intake and RMR in both groups, especially in SS (r = -0.75, p = 0.021 and r = -0.87, p = 0.002, respectively). Attempts to incorporate habitual physical activities to daily life (89% vs. 39%, p = 0.011) and weekly sports hobbies (67% vs. 13%, p = 0.002) were more often reported by SS. The scores of BITE, DSQ, BDI and SCL-90 were within normal range in both groups but SS had higher scores in most measures, especially for anxiety (16.4 vs. 14.3, p = 0.045). In conclusion, long-term maintenance of weight loss was associated with highly restrained eating, regular physical activity, and perhaps with increased anxiety.
Evaluate anti-interleukin-1β (IL-1β) antibody, canakinumab, in patients with type 2 diabetes and ... more Evaluate anti-interleukin-1β (IL-1β) antibody, canakinumab, in patients with type 2 diabetes and impaired glucose tolerance (IGT) in whom hyperglycaemia may trigger IL-1β-associated inflammation leading to suppressed insulin secretion and β-cell dysfunction. This 4-week, parallel-group study randomized 190 patients with type 2 diabetes 2 : 1, canakinumab versus placebo, into the following treatment arms: metformin monotherapy, metformin + sulfonylurea, metformin + sulfonylurea + thiazolidinedione or insulin ± metformin. IGT population (n = 54) was randomized 1 : 1, canakinumab versus placebo. Primary efficacy assessment was change from baseline in insulin secretion rate (ISR) relative to glucose 0-2 h. Mean changes from baseline to week 4 in ISR relative to glucose at 0-2 h or other time points were not statistically significant for canakinumab versus placebo across groups. ISR (relative to glucose) at 0-0.5 h (first-phase insulin secretion) numerically favoured canakinumab versus placebo in insulin-treated patients {difference in mean change from baseline [point estimate (PE)] 3.81 pmol/min/m(2)/mmol/l; p = 0.0525} and in the IGT group (PE 3.92 pmol/min/m(2)/mmol/l; p = 0.1729). Mean change from baseline in fasting plasma glucose favoured canakinumab in the type 2 diabetes/metformin group and the IGT group; however, differences were not statistically significant. Mean change from baseline in peak insulin level and insulin AUC 0-4 h were statistically significantly higher in the canakinumab group in IGT patients. Canakinumab was well tolerated and consistent with known safety experience. The trend towards improving ISR relative to glucose 0-0.5 h in patients treated with insulin supports the hypothesis that insulin secretion can be improved by blocking IL-1β.
OBJECTIVE—Effects of weight loss on vascular function are unknown. We compared, in the face of si... more OBJECTIVE—Effects of weight loss on vascular function are unknown. We compared, in the face of similar weight loss over 3–6 months, effects of orlistat (120 mg t.i.d., n = 23) and placebo (n = 24) on in vivo endothelial function in a high-risk group of obese (BMI 32.1 ± 0.4 kg/m2) premenopausal nondiabetic women with a history of gestational diabetes. RESEARCH DESIGN AND METHODS—Forearm blood flow responses to intra-arterial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), body composition, and serum lipids were determined before and after weight loss. RESULTS—Weight loss averaged 7.3 ± 0.2 kg (8.3 ± 0.1%) and 7.4 ± 0.2 kg (8.2 ± 0.1%) of initial body weight in the orlistat and placebo groups, respectively. Forearm and body compositions changed similarly in both groups. Responses to ACh increased by 41% to the low dose (5.9 ± 0.6 vs. 8.3 ± 0.3 for flow in the experimental/control arm, P < 0.01) and by 33% to the high dose (7.6 ± 0.8 vs. 10.1 ± 0.6, P < 0.001) i...
Our objective was to determine how 8% weight loss influences subcutaneous, intra-abdominal, and l... more Our objective was to determine how 8% weight loss influences subcutaneous, intra-abdominal, and liver fat (LFAT), as well as features of insulin resistance, in obese women with high versus low LFAT. A total of 23 women with previous gestational diabetes were divided into groups of high (9.4 ± 1.4%) and low (3.3 ± 0.4%) LFAT based on their median LFAT (5%) measured with proton spectroscopy. Both groups were similar with respect to age, BMI, and intra-abdominal and subcutaneous fat. Before weight loss, women with high LFAT had higher fasting serum insulin and triglyceride concentrations than women with low LFAT. At baseline, LFAT correlated with the percent of fat (r = 0.44, P < 0.05) and saturated fat (r = 0.45, P < 0.05) of total caloric intake but not intra-abdominal or subcutaneous fat or fasting serum free fatty acids. Weight loss was similar between the groups (high LFAT −7.4 ± 0.2 vs. low LFAT −7.7 ± 0.3 kg). LFAT decreased from 9.4 ± 1.4 to 4.8 ± 0.7% (P < 0.001) in w...
In Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;... more In Parkinson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, striatal dopamine transporter (DAT) binding and cardiac sympathetic function are disturbed. In addition, heart rate (HR)-corrected cardiac repolarisation time (QTc interval), which is partly under autonomic control, is prolonged. Whether there is physiological coupling between striatal DAT binding and QTc time (QTc-DAT relation) is not known. The purpose of this study is to evaluate QTc-DAT relation in healthy young adults. Thirty-five participants (18 women, age 26.4+/-1.8 years; mean+/-SD) were studied with iodine-123 labelled 2beta-carbomethoxy-3beta-(4-iodophenyl) nortropane single photon emission tomography. Signal-averaged ECG was recorded at rest from each participant. QTc interval was computed with Bazett&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s correction and with the approach by Karjalainen, getting QTc and QTk intervals, respectively. Mean striatal DAT binding, as (striatum-cerebellum)/cerebellum, was 2.63+/-0.31. Mean HR, QT, QTc and QTk intervals were 66+/-9 bpm, 340+/-25 ms, 354+/-18 ms and 351+/-16 ms, respectively. HR-QT correlation was -0.63, P value of less than 0.001. HR was not related to striatal DAT binding. QTc-DAT and QTk-DAT relations were significant, r = -0.50, P = 0.004 and r = -0.59, P = 0.0002, respectively. In linear regression model, striatal DAT binding explained 35% of the variance of QTk interval (95% confidence interval: -46.9 to -13.0, P = 0.0002). This study suggests significant physiological QTc-DAT relation in young healthy adults. QTc interval measurements might carry diagnostically important information in clinical conditions, which have an effect on both striatal DAT binding and cardiac sympathetic function.
To evaluate the effect of weight loss on substrate oxidation, energy expenditure, and insulin sen... more To evaluate the effect of weight loss on substrate oxidation, energy expenditure, and insulin sensitivity we studied 12 obese subjects (body mass index 33.4 ± 1.1) before and after 6 wk ofa very-low-calorie diet (VLCD) with euglycemic insulin clamp in combination with indirect calorimetry. Body weight decreased from 105.3 ± 4.6 to 94. 1 ± 4.0 kg (P < 0.001) and fat mass from 47.2 ± 3.6 to 37.7 ± 3.0 kg(P < 0.001). Total glucose disposal during insulin clamp increased from 30.4 ± 4.3 to 38.4 ± 4.4 mol. kg lean body mass (LBM). min' (P < 0.05), insulin-stimulated glucose oxidation from 14.3 ± 4.6 to 19. 1 ± 1.4 Mmol. kg LBM. min ' (P < 0.05), and nonoxidative glucose metabolism from 16.0 ± 3.8 to 19.3 ± 3.6 imol kg LBM'. min' (NS). Lipid oxidation decreased in the basal state (P < 0.05) and during the insulin clamp (P < 0.01). The basal rate ofenergy expenditure decreased from 99. 1 ± 4.6 to 88.5 ± 2.7 Id. kg LBM. min (P < 0.05) after weight reduction. A reduction in fat mass achieved by VLCD is associated with reduced lipid oxidation and, because of substrate competition, enhanced glucose oxidation. The physiological consequence is improved insulin sensitivity.
, including 370 men engaged in sports in which weight-related performance classes are associated ... more , including 370 men engaged in sports in which weight-related performance classes are associated with weight cycling (boxers, weight lifters and wrestlers; further called as weight cyclers), and 834 matched control men with no athletic background. Outcome measure: Weight change since the age of 20 years, body mass index (BMI) and prevalence of obesity and overweight. Results: The weight cyclers gained 5.2 BMI units from age 20 years to their maximum mean weight, which was at age 58.7 years. Corresponding figures for the controls were 4.2 BMI units at 58.5 years and for other athletes 3.3 BMI units at age 62.5 years. The proportion of obese (BMIX30 kg/m 2) subjects was greatest among the weight cyclers both in 1985 and 1995. In 2001, the weight cyclers were more often obese than other athletes, but did not differ from the controls. The odds ratio for the weight cyclers to be obese compared to other athletes in 1985 was 3.18 (95% confidence intervals 2.09-4.83), and compared to the controls 2.0 (1.35-2.96). The enhanced weight gain of the weight cyclers was not accounted for by present health habits (smoking, alcohol use, use of high-fat milk or physical activity) or weight at age 20 years. Conclusions: Repeated cycles of weight loss and regain appear to enhance subsequent weight gain and may predispose to obesity. Chronic dieting with weight cycling may be harmful for permanent weight control.
Dietary fat has been reported to influence insulin sensitivity. The objective of the study was to... more Dietary fat has been reported to influence insulin sensitivity. The objective of the study was to determine how identical weight loss (target: loss of 8% of body weight over 3-6 mo) in women taking orlistat or placebo combined with a hypocaloric diet influences body composition and insulin sensitivity. Forty-seven obese women [body mass index (in kg/m(2)): 32.1 +/- 0.4] were randomly assigned to receive either orlistat (120 mg 3 times daily; n = 23) or placebo (n = 24) with a hypocaloric diet. Whole-body insulin sensitivity (insulin clamp technique), serum fatty acids, and body composition (magnetic resonance imaging) were measured before and after weight loss. The groups did not differ significantly at baseline with respect to age, body weight, intraabdominal and subcutaneous fat volumes, or insulin sensitivity. Weight loss did not differ significantly between the orlistat (7.3 +/- 0.2 kg, or 8.3 +/- 0.1%) and placebo (7.4 +/- 0.2 kg, or 8.2 +/- 0.1%) groups. Insulin sensitivity im...
Changes in weight, body mass index (BMI), and thickness of triceps and subscapular skinfolds were... more Changes in weight, body mass index (BMI), and thickness of triceps and subscapular skinfolds were studied in 17,294 adult Finns who, as part of a health survey, were examined twice after an interval of 4 to 7 (average 5.7) years. During the follow-up, the mean weight and BMI rose in men and women below the age of 50 at entry, changed little in men aged 50-70 and in women aged 50-60, and rapidly declined at later ages. Individual weight changes were generally small; about two-thirds of the participants maintained their weight within 5 kg from the initial weight. About 9 per cent of the men and 4 per cent of the women gained 10 kg or more, and 2 per cent of the men and 4 per cent of the women lost 10 kg or more in 5 years. Weight loss was associated with old age and high initial BMI, whereas weight gain was most common in the young, even in those with a high initial BMI. Young overweight subjects need most attention in prevention and treatment programmes for obesity.
Rationale: Serotonin (5-HT) is involved in the control of eating behaviour by inhibiting food int... more Rationale: Serotonin (5-HT) is involved in the control of eating behaviour by inhibiting food intake. Obese women with binge-eating disorder (OB-BED) were recently found to have reduced 5-HT transporter binding. Objectives: The aim of this study was to investigate the effect of a successful treatment on 5-HT transporters in OB-BED. Methods: The 5-HT transporter binding of seven OB-BED was measured by single-photon emission computed tomography (SPECT), by using iodine-123labelled nor-b-CIT as a tracer, before treatment and after successful treatment, when the OB-BED were asymptomatic. Treatment consisted of group psychotherapy and fluoxetine medication. The control subjects, six obese women without eating disorders, were also studied twice by using SPECT. Results: The 5-HT transporter binding of the symptomatically recovered OB-BED increased significantly (24€22%) after treatment, whereas in the control group, binding remained unchanged. Conclusions: The results tentatively suggest that 5-HT transporter binding in OB-BED is an adaptive mechanism, which can be affected by treatment. Furthermore, there seems to be a link between improved 5-HT transporter binding and reduced binge eating.
To examine the association of smoking with recurrent dieting and BMI among Finnish adults. We use... more To examine the association of smoking with recurrent dieting and BMI among Finnish adults. We used questionnaire data from 1990 on 11,055 subjects from the Finnish Twin Cohort who were 33 to 61 years of age. Multinomial logistic regression analysis was carried out using lifetime dieting as the outcome variable and smoking as the main explanatory variable, adjusted for BMI and age. Twin pairs discordant for dieting and smoking were studied to examine the effect of environmental and genetic factors. Among women, current smokers [odds ratio (OR), 1.09 to 1.41 at different ages] and former smokers (OR, 1.52 to 2.82) were more likely to have dieted recurrently than never smokers. Among men, current smokers were less likely (OR, 0.69; 95% confidence interval, 0.55, 0.87) and former smokers were more likely (OR, 1.30; 95% confidence interval, 1.05, 1.61) to have dieted recurrently at different ages. The differences between the discordant pairs were consistent with this, although not statistically significant. Recurrent dieting was associated with former smoking in both sexes and with current smoking in women.
Muscle biopsy is the gold standard for diagnosis of mitochondrial disorders because of the lack o... more Muscle biopsy is the gold standard for diagnosis of mitochondrial disorders because of the lack of sensitive biomarkers in serum. Fibroblast growth factor 21 (FGF-21) is a growth factor with regulatory roles in lipid metabolism and the starvation response, and concentrations are raised in skeletal muscle and serum in mice with mitochondrial respiratory chain deficiencies. We investigated in a retrospective diagnostic study whether FGF-21 could be a biomarker for human mitochondrial disorders. We assessed samples from adults and children with mitochondrial disorders or non-mitochondrial neurological disorders (disease controls) from seven study centres in Europe and the USA, and recruited healthy volunteers (healthy controls), matched for age where possible, from the same centres. We used ELISA to measure FGF-21 concentrations in serum or plasma samples (abnormal values were defined as &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;200 pg/mL). We compared these concentrations with values for lactate, pyruvate, lactate-to-pyruvate ratio, and creatine kinase in serum or plasma and calculated sensitivity, specificity, and positive and negative predictive values for all biomarkers. We analysed serum or plasma from 67 patients (41 adults and 26 children) with mitochondrial disorders, 34 disease controls (22 adults and 12 children), and 74 healthy controls. Mean FGF-21 concentrations in serum were 820 (SD 1151) pg/mL in adult and 1983 (1550) pg/mL in child patients with respiratory chain deficiencies and 76 (58) pg/mL in healthy controls. FGF-21 concentrations were high in patients with mitochondrial disorders affecting skeletal muscle but not in disease controls, including those with dystrophies. In patients with abnormal FGF-21 concentrations in serum, the odds ratio of having a muscle-manifesting mitochondrial disease was 132·0 (95% CI 38·7-450·3). For the identification of muscle-manifesting mitochondrial disease, the sensitivity was 92·3% (95% CI 81·5-97·9%) and specificity was 91·7% (84·8-96·1%). The positive and negative predictive values for FGF-21 were 84·2% (95% CI 72·1-92·5%) and 96·1 (90·4-98·9%). The accuracy of FGF-21 to correctly identify muscle-manifesting respiratory chain disorders was better than that for all conventional biomarkers. The area under the receiver-operating-characteristic curve for FGF-21 was 0·95; by comparison, the values for other biomarkers were 0·83 lactate (p=0·037, 0·83 for pyruvate (p=0·015), 0·72 for the lactate-to-pyruvate ratio (p=0·0002), and 0·77 for creatine kinase (p=0·013). Measurement of FGF-21 concentrations in serum identified primary muscle-manifesting respiratory chain deficiencies in adults and children and might be feasible as a first-line diagnostic test for these disorders to reduce the need for muscle biopsy. Sigrid Jusélius Foundation, Jane and Aatos Erkko Foundation, Molecular Medicine Institute of Finland, University of Helsinki, Helsinki University Central Hospital, Academy of Finland, Novo Nordisk, Arvo and Lea Ylppö Foundation.
The known risk factors of atherosclerotic diseases may be involved in the development of a subara... more The known risk factors of atherosclerotic diseases may be involved in the development of a subarachnoid hemorrhage. We studied the morbidity and mortality due to subarachnoid hemorrhage among 42,862 men and women aged 20-69 years who had participated in a large health survey in Finland. During a mean follow-up of 12 years, 102 non-fatal and 85 fatal cases of subarachnoid hemorrhage were observed. The total incidence was 37 per 100,000 person-years. Smoking and hypertension were positively associated and body mass index was inversely associated with the risk of subarachnoid hemorrhage. These associations were not confounded by age or each other. No statistically significant association with risk was detected for serum cholesterol level, hematocrit content, known heart disease, or diabetes. The risk was especially elevated among lean hypertensive subjects and lean smoking subjects. The age-adjusted relative risks of subarachnoid hemorrhage for lean, hypertensive smokers were 18.3 (95% confidence interval (CI), 7.8-42.7) among women and 6.7 (95% CI, 2.3-19.7) among men as compared to the risk among subjects without these risk factors. We conclude that modifiable risk factors are predictive of subarachnoid hemorrhage, for which reason subarachnoid hemorrhage may in part be preventable. Leanness combined with arterial hypertension and/or smoking, in particular, poses a substantially elevated risk.
Eating and Weight Disorders - Studies on Anorexia, Bulimia and Obesity, 1998
To analyse determinants of long-term weight maintenance we studied energy expenditure, dietary in... more To analyse determinants of long-term weight maintenance we studied energy expenditure, dietary intake, eating behaviour and psychological symptoms of 9 women (SS, BMI = 26.6) who reached their ideal weight during 1985-86 and were still an average 16.2 kg below their original weight in 1993. Controls were 42 obese, non-reducing females (OC, BMI = 34.8). Dietary intake was calculated from four-day food records. Dietary restraint was assessed by the Three-Factor Eating Questionnaire (TFEQ) and symptoms of bulimia or binge eating by Bulimic Investigatory Test, Edinburgh (BITE). Physical exercise was estimated by open interviews, resting metabolic rate (RMR) by indirect calorimetry and body composition by bioelectrical impedance. Psychological characteristics were studied using the Defense Style Questionnaire (DSQ), Beck Depression Inventory (BDI) and Symptom Checklist (SCL-90). SS had lower RMR (1320 kcal vs. 1540 kcal, p = 0.004), lower daily energy intake (1208 kcal vs. 1525 kcal, p = 0.020) and higher scores for dietary restraint (14.6 vs. 8.4, p = 0.002) than OC. Restraint scores correlated negatively with energy intake and RMR in both groups, especially in SS (r = -0.75, p = 0.021 and r = -0.87, p = 0.002, respectively). Attempts to incorporate habitual physical activities to daily life (89% vs. 39%, p = 0.011) and weekly sports hobbies (67% vs. 13%, p = 0.002) were more often reported by SS. The scores of BITE, DSQ, BDI and SCL-90 were within normal range in both groups but SS had higher scores in most measures, especially for anxiety (16.4 vs. 14.3, p = 0.045). In conclusion, long-term maintenance of weight loss was associated with highly restrained eating, regular physical activity, and perhaps with increased anxiety.
Evaluate anti-interleukin-1β (IL-1β) antibody, canakinumab, in patients with type 2 diabetes and ... more Evaluate anti-interleukin-1β (IL-1β) antibody, canakinumab, in patients with type 2 diabetes and impaired glucose tolerance (IGT) in whom hyperglycaemia may trigger IL-1β-associated inflammation leading to suppressed insulin secretion and β-cell dysfunction. This 4-week, parallel-group study randomized 190 patients with type 2 diabetes 2 : 1, canakinumab versus placebo, into the following treatment arms: metformin monotherapy, metformin + sulfonylurea, metformin + sulfonylurea + thiazolidinedione or insulin ± metformin. IGT population (n = 54) was randomized 1 : 1, canakinumab versus placebo. Primary efficacy assessment was change from baseline in insulin secretion rate (ISR) relative to glucose 0-2 h. Mean changes from baseline to week 4 in ISR relative to glucose at 0-2 h or other time points were not statistically significant for canakinumab versus placebo across groups. ISR (relative to glucose) at 0-0.5 h (first-phase insulin secretion) numerically favoured canakinumab versus placebo in insulin-treated patients {difference in mean change from baseline [point estimate (PE)] 3.81 pmol/min/m(2)/mmol/l; p = 0.0525} and in the IGT group (PE 3.92 pmol/min/m(2)/mmol/l; p = 0.1729). Mean change from baseline in fasting plasma glucose favoured canakinumab in the type 2 diabetes/metformin group and the IGT group; however, differences were not statistically significant. Mean change from baseline in peak insulin level and insulin AUC 0-4 h were statistically significantly higher in the canakinumab group in IGT patients. Canakinumab was well tolerated and consistent with known safety experience. The trend towards improving ISR relative to glucose 0-0.5 h in patients treated with insulin supports the hypothesis that insulin secretion can be improved by blocking IL-1β.
OBJECTIVE—Effects of weight loss on vascular function are unknown. We compared, in the face of si... more OBJECTIVE—Effects of weight loss on vascular function are unknown. We compared, in the face of similar weight loss over 3–6 months, effects of orlistat (120 mg t.i.d., n = 23) and placebo (n = 24) on in vivo endothelial function in a high-risk group of obese (BMI 32.1 ± 0.4 kg/m2) premenopausal nondiabetic women with a history of gestational diabetes. RESEARCH DESIGN AND METHODS—Forearm blood flow responses to intra-arterial infusions of acetylcholine (ACh) and sodium nitroprusside (SNP), body composition, and serum lipids were determined before and after weight loss. RESULTS—Weight loss averaged 7.3 ± 0.2 kg (8.3 ± 0.1%) and 7.4 ± 0.2 kg (8.2 ± 0.1%) of initial body weight in the orlistat and placebo groups, respectively. Forearm and body compositions changed similarly in both groups. Responses to ACh increased by 41% to the low dose (5.9 ± 0.6 vs. 8.3 ± 0.3 for flow in the experimental/control arm, P < 0.01) and by 33% to the high dose (7.6 ± 0.8 vs. 10.1 ± 0.6, P < 0.001) i...
Our objective was to determine how 8% weight loss influences subcutaneous, intra-abdominal, and l... more Our objective was to determine how 8% weight loss influences subcutaneous, intra-abdominal, and liver fat (LFAT), as well as features of insulin resistance, in obese women with high versus low LFAT. A total of 23 women with previous gestational diabetes were divided into groups of high (9.4 ± 1.4%) and low (3.3 ± 0.4%) LFAT based on their median LFAT (5%) measured with proton spectroscopy. Both groups were similar with respect to age, BMI, and intra-abdominal and subcutaneous fat. Before weight loss, women with high LFAT had higher fasting serum insulin and triglyceride concentrations than women with low LFAT. At baseline, LFAT correlated with the percent of fat (r = 0.44, P < 0.05) and saturated fat (r = 0.45, P < 0.05) of total caloric intake but not intra-abdominal or subcutaneous fat or fasting serum free fatty acids. Weight loss was similar between the groups (high LFAT −7.4 ± 0.2 vs. low LFAT −7.7 ± 0.3 kg). LFAT decreased from 9.4 ± 1.4 to 4.8 ± 0.7% (P < 0.001) in w...
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