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BACKGROUND/OBJECTIVES: Dietary pattern is central in the prevention of hypertension and blood pressure (BP)-related diseases. A diet based on healthy Nordic foods may have a favourable impact on BP. The objective was to clarify whether a Nordic alternative for a healthy food pattern would have beneficial effects on ambulatory BP in subjects with metabolic syndrome (MetS). SUBJECTS/METHODS: In total, 37 subjects were randomized to either a healthy Nordic diet or a control diet. A healthy Nordic diet embraced whole grains, rapeseed oil, berries, fruits, vegetables, fish, nuts and low-fat dairy products of Nordic origin. The mean nutrient intake in the Nordic countries formed the control diet, embracing wheat products, dairy fat-based spread and a lower intake of fruits, vegetables and fish. Diets were isoenergetic. Ambulatory BP was monitored and 24-h urine was collected before and after 12 weeks of intervention. RESULTS: After 12 weeks, ambulatory diastolic BP (-4.4mmHg; P=0.001) and mean arterial pressure (-4.2mm Hg; P=0.006) were lowered by the healthy Nordic diet compared with the control diet, whereas changes in ambulatory systolic BP did not differ significantly between diets (-3.5mmHg; P=0.122). Heart rate tended to be lower in those on the healthy Nordic diet (P=0.057). Urinary sodium and potassium excretions were unaffected by diets and consequently not associated with the healthy Nordic diet-induced lowering of BP. CONCLUSIONS: Consumption of Nordic varieties of health-enhancing foods for 12 weeks decreased diastolic ambulatory BP and mean arterial pressure in subjects with features of MetS during weight-stable condition, suggesting beneficial effects of a healthy Nordic dietary pattern on ambulatory BP. [ABSTRACT FROM AUTHOR]

Background: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome.Methods: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids.Results: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra.Conclusions: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation. [ABSTRACT FROM AUTHOR]

Background Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. Methods We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m−2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. Results Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non- HDL cholesterol (−0.18, mmol L−1 95% CI −0.35; −0.01, P = 0.04), LDL to HDL cholesterol (−0.15, −0.28; −0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (−0.04, −0.07; −0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference −84, −133; −37 ng L−1, P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, −0.23, −0.41; −0.05, P = 0.012) were associated with IL-1 Ra. Conclusions Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation. [ABSTRACT FROM AUTHOR]

Lifestyle interventions reduce the incidence of type 2 diabetes among individuals with impaired glucose tolerance (IGT). However, it is unknown whether this is due to improved insulin sensitivity or insulin secretion. We investigated at baseline insulin sensitivity and insulin secretion applying frequently sampled intravenous glucose tolerance test (FSIGT) in 87 of 101 obese middle-aged subjects with IGT randomized into an intervention or a control group in the Finnish Diabetes Prevention Study. FSIGT was repeated after 4 years in 52 people. There were no significant differences in any of the baseline anthropometric or metabolic characteristics between the groups. The 4-year weight and waist circumference decreases were greater in the intervention than in the control group (P = 0.043 and P = 0.025, respectively). At 4-year examination, insulin sensitivity (Si) tended to be higher in the intervention group (the difference between the mean values 36%; P = 0.067, and P = 0.136 after adjustment for age, sex, BMI, and baseline Si value). There was strong correlation between the 4-year changes in Si and weight (r = -0.628 and r = -0.710, for intervention and control groups; P < 0.001 for both). In the entire group, Si improved by 64% in the highest tertile of weight loss but deteriorated by 24% in those who gained weight (lowest tertile). Acute insulin response declined significantly in the control group. In conclusion, Si markedly improved by weight reduction during the 4-year follow-up of individuals with IGT. Insulin secretion remained constant for years in individuals with IGT who were able to lose weight. [ABSTRACT FROM AUTHOR]

Objective and Subjects: Dietary fibre has been suggested to interfere with endogenous cholesterol synthesis in the liver. Therefore the effects of oat bran on the proportions of cholesterol synthesis precursors (squalene, delta(8-) cholesterol, desmosterol and lathosterol), cholestanol and plant sterols (campesterol and beta-sitosterol) to cholesterol were analysed in serum of 36 hypercholesterolaemic subjects.Design: A randomized study of eight weeks duration when beta-glucan-rich oat bran (n = 20, subjects) or wheat bran (n = 16) was used as a part of a cholesterol lowering diet. Plant sterols and cholesterol synthesis precursors were analysed from frozen samples afterward.Results: In the oat-bran group, but not in the wheat bran group, serum total cholesterol declined transiently. The proportions of plant sterols and cholesterol in serum, which reflect cholesterol absorption efficiency were unchanged. However, the proportions of squalene appeared to be transiently increased during the study. Subjects with apolipoprotein E 4 allele had higher serum campesterol and sitosterol levels (suggestive of efficient cholesterol absorption) than those with homozygous apolipoprotein E 3 allele.Conclusions: Since the cholesterol precursors in serum reflecting endogenous cholesterol synthesis remained almost unchanged the reduction in the serum cholesterol level by oat bran treatment can not be ascribed to an inhibition of the endogenous cholesterol synthesis. [ABSTRACT FROM AUTHOR]

Presents the authors' response to comments to their paper published in a previous issue of the periodical 'Gut,' which described the etiology and determinants of survival of extrahepatic portal vein thrombosis. Points clarified by the authors.

Body size at birth is an indicator of the intrauterine environment. The effects of the Pro12Pro genotype and the 12Ala allele of the PPARγ-2 gene on glucose and insulin metabolism in adult life depend on body size at birth. A low birth weight is associated with insulin resistance and type 2 diabetes. The peroxisome proliferator-activated receptor-γ (PPARγs) are also regulators of adipocyte differentiation, and the PPARγ-2 gene could also contribute to the development of dyslipidemia. Therefore, the effects of the Pro12Ala polymorphisms of the PPARγ-2 gene on lipid metabolism were measured in 476 elderly persons whose birth weight was known. The Ala12 allele was associated with increased serum total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol concentrations but only among those who had birth weights below 3000 g. These interactions between the effects of the PPARγ-2 gene on adult traits and the effects of birth weight may be interpreted as examples of gene–environmental interactions, which underlie plasticity during development. [ABSTRACT FROM AUTHOR]

Objective: To study tolerance to lactose in milk chocolate among symptomatic lactose maldigesters. Design: Randomized cross-over study. Subjects: Twenty-seven adult lactose maldigesters with symptomatic lactose intolerance. Methods: A 100 g chocolate sample prepared with whole milk (12 g lactose), whole-milk powder (12 g lactose), low-lactose milk powder (2 g lactose) or lactose-free milk powder was eaten after an overnight fast. Gastrointestinal symptoms (flatulence, abdominal bloating, abdominal pain, borgorygmi and nausea) were recorded in a questionnaire during the following 8 h. Bowel movements and stool consistency were also registered during the test day. Results: The numbers of persons reporting different gastrointestinal symptoms or any of the symptoms did not differ significantly after eating the chocolate samples. No statistical differences were found in the estimated strength of the different symptoms or the total strength of all symptoms combined. Differences in the bowel frequency and stool consistency were also non-significant. Conclusions: Lactose malabsorbers with self-reported lactose intolerence did not differ in their response to milk chocolate samples containing different amounts of lactose. [ABSTRACT FROM AUTHOR]

Summary Aim Little attention has been paid to the prognostic significance and tracking effect of risk factor clusters characteristic of type 2 diabetes mellitus. We studied the clustering of eight cardiovascular risk factors (smoking, high body mass index, elevated systolic blood pressure, high serum, low density lipoprotein (LDL) cholesterol, high serum LDL triglycerides, low serum, high density lipoprotein (HDL) cholesterol, high fasting blood glucose and high plasma insulin concentration) and their effect on the prognosis and the tracking effect. Methods This study is a population-based prospective follow-up of newly diagnosed type 2 diabetic subjects (n = 133, aged 45–64 years) in Eastern Finland. The following end points were used: all-cause mortality, cardiovascular mortality, and incidences of first myocardial infarction and first stroke. Furthermore, we studied the ‘tracking effect’ of the risk factor clusters during the 10-year follow-up period. Results When the clustering of risk factors typical of type 2 diabetes mellitus was taken into account, all-cause mortality increased from 28.6% to 50.0% (p < 0.05) and cardiovascular disease mortality increased from 14.3% to 50.0% (p < 0.01) depending on the number of risk factors present. The incidence of first myocardial infarction increased from 0% to 40.0% (p < 0.05) as the number of risk factors increased from 0 to 5. In survivors, the proportion of individuals with no risk factors decreased and the proportion on individuals with three to four risk factors increased during the 10-year follow-up period despite the high mortality among the group with many risk factors. Conclusions The risk factor clusters among type 2 diabetic subjects are of great predictive value and when not aggressively treated, show a relentless increase despite selective mortality. [ABSTRACT FROM AUTHOR]

Aim To examine changes in glucose metabolism (fasting and 2-h glucose) during follow-up in people with impaired fasting glucose in comparison with changes in people with isolated impaired glucose tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening-detected Type 2 diabetes at baseline, among those who participated in a diabetes prevention programme conducted in Finland. Methods A total of 10 149 people at high risk of Type 2 diabetes took part in baseline examination. Of 5351 individuals with follow-up = 9 months, 1727 had impaired glucose metabolism at baseline and completed at least one lifestyle intervention visit. Most of them (94.6%) were overweight/ obese. Results Fasting glucose decreased during follow-up among overweight/obese people in the combined impaired fasting glucose and impaired glucose tolerance group (P = 0.044), as did 2-h glucose in people in the isolated impaired glucose tolerance group (P = 0.0014) after adjustment for age, sex, medication and weight at baseline, follow-up time and changes in weight, physical activity and diet. When comparing changes in glucose metabolism among people with different degrees of glucose metabolism impairment, fasting glucose concentration was found to have increased in those with isolated impaired glucose tolerance (0.12 mmol/l, 95% Cl 0.05 to 0.19) and it decreased to a greater extent in those with screening-detected Type 2 diabetes (0.54 mmol/l, 95% Cl -0.69 to -0.39) compared with those with impaired fasting glucose (-0.21 mmol/l, 95% Cl -0.27 to -0.15). Furthermore, 2-h glucose concentration decreased in the isolated impaired glucose tolerance group (-0.82 mmol/l, 95% Cl -1.04 to -0.60), in the combined impaired fasting glucose and impaired glucose tolerance group (-0.82 mmol/l, 95% Cl -1.07 to -0.58) and in the screening-detected Type 2 diabetes group (-1.52, 95% Cl -1.96 to -1.08) compared with those in the impaired fasting glucose group (0.26 mmol/l, 95% Cl 0.10 to 0.43). Results were statistically significant even after adjustment for covariates (P < 0.001 in all models). Conclusions Changes in glucose metabolism differ in people with impaired fasting glucose from those in people with isolated impaired glucose tolerance, people with impaired fasting glucose and impaired glucose tolerance combined and people with screening-detected Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objectives: The national development programme for the prevention and care of diabetes was carried out in Finland during 2000--2010. One of the programme goals was to raise awareness of diabetes and its risk factors in the whole population through various activities, e.g. media campaigns and health fares. In addition, a targeted implementation project on the prevention of type 2 diabetes, FIN-D2D, was carried out in selected districts during 2003--2008. The aim of this analysis was to examine the changes in overall awareness of the programme and its association with self-reported lifestyle changes within the adult population during the FIN-D2D project period in the FIN-D2D area compared with the area not participating in the FIN-D2D (the control area). Study design: Health behaviour and health among the Finnish Adult Population -postal survey. Methods: The structured questionnaire mailed to a random population sample included questions on participants' sociodemographic background, medical history, health habits, and recent lifestyle changes. Awareness of the national diabetes programme was also enquired. Data (n = 10 831) from the 2004-2008 postal surveys were used for this investigation. Results: In the FIN-D2D area, 25% (347/1384) of men and 48% (797/1674) of women reported being aware of the programme. In the control area, the proportions were 20% (702/3551) and 36% (1514/4222), respectively. The overall awareness increased among both genders and in all areas during the project period, but the level of awareness was consistently higher in the FIN-D2D area. Female gender and higher age were associated with increasing awareness of the programme in both areas. Self-reported lifestyle changes were more common among women, but associated with the level of awareness of the programme more often among men than women. Conclusions: The awareness of diabetes and its risk factors increased among men and women in both implementation and control areas during the FIN-D2D project period. The activities of the implementation project may at least partly explain the differences in lifestyle changes between areas, especially among men. The results suggest that health promotion campaigns increase the population awareness about the prevention of chronic diseases and as a result, especially men may be prompted to make beneficial lifestyle changes. [ABSTRACT FROM AUTHOR]

Background/Objectives:Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism. We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake, and glucose metabolism in individuals with metabolic syndrome (MetS).Subjects/Methods:Participants were 30-65 years of age, with body mass index 27-40 kg/m2 and had MetS without diabetes. Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n=96), rich in whole-grain rye and wheat, or a control diet (n=70), for 18-24 weeks. In addition, associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled (ND+control) regression analyses at 18/24 weeks.Results:ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations (P=0.002) and positively associated with the insulin sensitivity indices Matsuda ISI (P=0.026) and disposition index (P=0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks.Conclusions:The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin sensitivity in a population with MetS. [ABSTRACT FROM AUTHOR]

Objective: We investigated the effect of early-phase insulin secretion on the incidence of type 2 diabetes in individuals with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). We examined how a lifestyle intervention affected early-phase insulin secretion (ratio of total insulin area under the curve [AUC] and total glucose AUC [AIGR] from 0 to 30 min) during a 4-year follow-up intervention trial and whether AIGR(0-30) response was modified by insulin sensitivity (IS) and obesity.Research Design and Methods: A total of 443 participants with IGT originally randomized to a lifestyle intervention or control group were studied. IS and AIGR(0-30) were estimated from an oral tolerance glucose test administered annually during the 4-year follow-up trial and were related to the risk of diabetes onset over a 6-year follow-up.Results: Lifestyle intervention resulted in higher IS (P = 0.02) and lower unadjusted AIGR(0-30) (P = 0.08) during the 4-year follow-up. A higher IS and a lower BMI during the follow-up were associated with a lower unadjusted AIGR(0-30) during the follow-up, independently of study group (P < 0.001). A greater increase in IS on the median cutoff point of a 0.69 increase was associated with higher IS-adjusted AIGR(0-30) during the follow-up (P = 0.002). In multivariate models, IS and IS-adjusted AIGR(0-30) were both inversely associated with diabetes incidence (P < 0.001). Participants who progressed to type 2 diabetes were more obese and had lower IS and Matsuda IS index-AIGR(0-30) than nonprogressors.Conclusions: Our results indicate that the reduction in the risk of developing type 2 diabetes after lifestyle intervention is related to the improvement of IS along with weight loss. Improved IS may also have beneficial effects on preservation of β-cell function. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, 207-211 (2012) Abstract Aims To investigate whether a positive family history of diabetes is associated with the effectiveness of lifestyle counselling on cardio-metabolic risk factors and glucose tolerance status in a 1-year follow-up in a cohort of Finnish men and women at high risk for Type 2 diabetes. Methods Altogether, 10 149 individuals who had high risk of Type 2 diabetes participated in the implementation programme of the national diabetes prevention programme at baseline. One-year follow-up data were available for 2798 individuals without diabetes. Family history of diabetes was based on self-report. Lifestyle interventions were individual or groups sessions on lifestyle changes. The effectiveness of lifestyle intervention was measured as changes in cardiovascular risk factors, glucose tolerance status and incidence of Type 2 diabetes. Results Family history was associated with the effectiveness of lifestyle intervention in men, but not in women. During the 1-year follow-up, body weight, BMI, systolic blood pressure, total cholesterol, LDL cholesterol and score for 10-year risk for fatal cardiovascular disease (SCORE) decreased and glucose tolerance status improved more in men without a family history of diabetes than in men with a family history of diabetes. Of the participating men and women, 10% and 5% developed Type 2 diabetes, respectively. Family history was not related to the incidence of Type 2 diabetes in either gender. Conclusions Men without a family history of diabetes were more successful in responding to lifestyle counselling with regard to cardio-metabolic measurements and glucose tolerance than those with a family history of diabetes. Similar results were not seen in women. In keeping with findings from earlier studies, the prevention of Type 2 diabetes is not influenced by a family history of diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE: In this FIN-D2D cross-sectional survey the relationship of age with HbA(1c) and fasting and 2h glucose in the oral glucose tolerance test (OGTT) was explored in apparently randomly selected healthy population. PATIENTS AND METHODS: The glycaemic parameters were measured in 1344 men and 1482 women (aged 45-74 years), and among them we excluded all subjects with known diabetes, hypertension or dyslipidaemia. The final analyses for HbA(1c) and the ratios of fasting glucose/HbA(1c) and 2h glucose/HbA(1c) included 649 men and 804 women. RESULTS: Mean age was 57 years and BMI 26.1kg/m(2) for both genders. HbA(1c) increased in both genders with age (p<0.001). For a particular fasting glucose level HbA(1c) level was higher in older age groups (p<0.001 for linearity). By contrast, a particular 2h plasma glucose value in OGTT implied significantly lower HbA(1c) in the elderly (p<0.001 for linearity). CONCLUSION: In apparently healthy population, screened with OGTT, in older individuals compared with younger ones a particular HbA(1c) value implies slightly lower fasting glucose, but relatively higher 2h glucose. These results need to be verified in different populations. The effects of age on relation between HbA(1c) and plasma glucose should be taken into account in classifying people into different dysglycaemia categories. [ABSTRACT FROM AUTHOR]

Abstract: Objective: In this FIN-D2D cross-sectional survey the relationship of age with HbA1c and fasting and 2h glucose in the oral glucose tolerance test (OGTT) was explored in apparently randomly selected healthy population. Patients and methods: The glycaemic parameters were measured in 1344 men and 1482 women (aged 45–74 years), and among them we excluded all subjects with known diabetes, hypertension or dyslipidaemia. The final analyses for HbA1c and the ratios of fasting glucose/HbA1c and 2h glucose/HbA1c included 649 men and 804 women. Results: Mean age was 57 years and BMI 26.1kg/m2 for both genders. HbA1c increased in both genders with age (p <0.001). For a particular fasting glucose level HbA1c level was higher in older age groups (p <0.001 for linearity). By contrast, a particular 2h plasma glucose value in OGTT implied significantly lower HbA1c in the elderly (p <0.001 for linearity). Conclusion: In apparently healthy population, screened with OGTT, in older individuals compared with younger ones a particular HbA1c value implies slightly lower fasting glucose, but relatively higher 2h glucose. These results need to be verified in different populations. The effects of age on relation between HbA1c and plasma glucose should be taken into account in classifying people into different dysglycaemia categories. [Copyright &y& Elsevier]

Aims The aim of this study was to investigate the prevalence of cardiovascular autonomic neuropathy in persons with previously diagnosed impaired glucose tolerance and to characterize associations between components of metabolic syndrome and cardiovascular autonomic neuropathy in the Finnish Diabetes Prevention Study cohort. Methods Two hundred and sixty-eight individuals with impaired glucose tolerance at baseline in the Finnish Diabetes Prevention Study, but not diagnosed with diabetes during follow-up,were studied for cardiovascular autonomic neuropathy. At the second annual follow-up visit after the end of lifestyle intervention,we performed deep-breathing and active orthostatic tests to detect possible parasympathetic and sympathetic dysfunction. To describe metabolic characteristics, anthropometric measurements, an oral glucose tolerance test and assessments for HbA1c, serum lipids and blood pressure were carried out. Results Prevalence of parasympathetic dysfunction was 25% and prevalence of sympathetic dysfunction was 6%, with no difference between the former intervention and control group participants or between men and women. Subjects with parasympathetic dysfunction were older, more obese (weight,waist circumference, body mass index) and had higher triglyceride concentration compared with those with normal parasympathetic function (P < 0.01 for all). Parasympathetic dysfunction was not significantly associated with other characteristics of metabolic syndrome; for example, high cholesterol, glucose and insulin levels or HbA1c. Correlations between the Expiration/Inspiration (E/I) ratio (the longest heart beat duration in expiration divided by the shortest heart beat duration in inspiration) and measures reflecting obesity were statistically significant in the pooled population and in men but not in women. Conclusions Cardiovascular autonomic neuropathy is common in persons with impaired glucose tolerance. Obesity, especially among men, seems to play an important role in the early pathogenesis of cardiovascular autonomic neuropathy. [ABSTRACT FROM AUTHOR]

Aims we analysed the Finnish Diabetes Prevention Study data in order to evaluate how the new HbA1c-based criterion compares with the oral glucose tolerance test in diagnosing Type 2 diabetes among high-risk individuals during a prospective average follow-up of 4 years. Methods In the Diabetes Prevention Study, 172 men and 350 women who were overweight and had impaired glucose tolerance at baseline were randomized into an intensive lifestyle intervention or a control group. The oral glucose tolerance test and HbA1c measurements were performed annually until the diagnosis of diabetes using the World Health Organization 1985 criteria. Results The sensitivity of the HbA1c ≥ 6.5%(≥ 48 mmol/ mol) as a diagnostic criterion for Type 2 diabetes was35%(95%CI 24%, 47%) in women and 47% (95% CI 31%, 64%) in men compared with diagnosis based on two consecutive oral glucose tolerance tests. The corresponding sensitivities for HbA1c ≥ 6.0% (≥ 42 mmol/ mol)were 67%(95% CI 55%, 77%) and 68% (95% CI 51%, 82%). The participants with HbA1c ≥ 6.5% (≥ 48 mmol/ mol) and diabetes based on the oral glucose tolerance test were more obese and had higher fasting glucose and 2-h glucose concentrations than those who had a diabetic oral glucose tolerance test but HbA1c< 6.5%(< 48 mmol/mol). There were no differences in the predictive performance of baseline fasting glucose, oral glucose tolerance test and HbA1c. Conclusions Of those with diabetes diagnosis based on two oral glucose tolerance tests during the Diabetes Prevention Study follow-up, 60% would have remained undiagnosed if diagnosis had been based onHbA1c ≥ 6.5%(≥ 48 mmol/ mol) criterion. [ABSTRACT FROM AUTHOR]

Background/Objectives:To examine the effects of betaine on serum lipid profile, plasma homocysteine concentration and hemostatic factors in healthy subjects.Subjects/Methods:Altogether, 63 volunteers (27±8 years, body mass index 22.6±2.4 kg/m2) participated in a placebo-controlled, randomized, parallel double-blinded study. The intervention lasted for 6 months during which the subjects consumed mineral water 500 ml/day with (betaine group, n=32) or without (control group, n=31) a 4-g betaine supplementation.Results:There was a significant interaction of time and group (general linear model) in serum total and low-density lipoprotein (LDL)-cholesterol concentrations and total-to-high-density lipoprotein (HDL)-cholesterol ratio without a significant difference between or within the groups. Concentrations of serum HDL-cholesterol, triglycerides or oxidized LDL did not change during the study. Plasma homocysteine concentration did not change in either of the groups. Plasma plasminogen activator inhibitor 1 concentration increased in the betaine group (P=0.028) and decreased in the control group (P=0.006). There was a significant interaction of time and group (general linear model) in plasma fibrinogen and blood hemoglobin concentration without a significant difference between or within the groups. There were no changes in parameters regarding the function of the liver or kidney.Conclusions:Betaine had no effect on serum lipid profile in long term in young healthy subjects. The lowering effect on plasma homocysteine concentration was weak. [ABSTRACT FROM AUTHOR]

Objective: To investigate 1-year outcomes of a national diabetes prevention program in Finland.Research Design and Methods: Altogether 10,149 individuals at high risk for diabetes were identified with the Finnish Diabetes Risk Score (FINDRISC; scoring ≥15 points), by a history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), cardiovascular disease, or gestational diabetes mellitus in 400 primary health care centers. One-year follow-up data were available for 2,798 participants who were nondiabetic at baseline (919 men and 1,879 women, aged 56.0 ± 9.9 and 54.0 ± 10.7 years [mean ± SD] with BMI 30.9 ± 4.6 and 31.6 ± 5.4 kg/m(2)).Results: The incidence of diabetes was 2.0 and 1.2% in men and women with normal glucose tolerance at baseline, 13.5 and 7.4% in those with IFG, and 16.1 and 11.3% in those with IGT, respectively. Altogether 17.5% of the subjects lost ≥ 5% weight with no sex difference. The relative risk of diabetes was 0.31 (95% CI 0.16-0.59) in the group who lost ≥ 5% weight, 0.72 (0.46-1.13) in the group who lost 2.5-4.9% weight, and 1.10 (0.77-1.58) in the group who gained ≥ 2.5% compared with the group who maintained weight.Conclusions: The FIN-D2D was the first national effort to implement the prevention of diabetes in a primary health care setting. Methods for recruiting high-risk subjects were simple and easy to use. Moderate weight loss in this very high-risk group was especially effective in reducing risk of diabetes among those participating in the program. [ABSTRACT FROM AUTHOR]

Objective: Both short and long sleep duration have frequently been found to be associated with an increased risk for diabetes. The aim of the present exploratory analysis was to examine the association between sleep duration and type 2 diabetes after lifestyle intervention in overweight individuals with impaired glucose tolerance in a 7-year prospective follow-up.Research Design and Methods: A total of 522 individuals (aged 40-64 years) were randomly allocated either to an intensive diet-exercise counseling group or to a control group. Diabetes incidence during follow-up was calculated according to sleep duration at baseline. Sleep duration was obtained for a 24-h period. Physical activity, dietary intakes, body weight, and immune mediators (C-reactive protein and interleukin-6) were measured.Results: Interaction between sleep duration and treatment group was statistically significant (P = 0.003). In the control group, the adjusted hazard ratios (HRs) (95% CI) for diabetes were 2.29 (1.38-3.80) and 2.74 (1.67-4.50) in the sleep duration groups 9-9.5 h and >or=10 h, respectively, compared with for that of the 7-8.5 h group. In contrast, sleep duration did not influence the incidence of diabetes in the intervention group; for sleep duration groups 9-9.5 h and >or=10 h, the adjusted HRs (95% CI) were 1.10 (0.60-2.01) and 0.73 (0.34-1.56), respectively, compared with that in the reference group (7-8.5 h sleep). Lifestyle intervention resulted in similar improvement in body weight, insulin sensitivity, and immune mediator levels regardless of sleep duration.Conclusions: Long sleep duration is associated with increased type 2 diabetes risk. Lifestyle intervention with the aim of weight reduction, healthy diet, and increased physical activity may ameliorate some of this excess risk. [ABSTRACT FROM AUTHOR]

Background:Insulin-like growth factor binding protein 5 (IGFBP5) binds to IGF and thus modulates IGF signaling pathway. We have shown earlier that the IGFBP5 gene was downregulated in the adipose tissue after 12-week carbohydrate diet with low insulinemic response.Objective:The aim was to examine the putative contribution of genetic variation of the IGFBP5 gene to the characteristics of metabolic syndrome and incidence of type 2 diabetes (T2DM) in the Finnish Diabetes Prevention Study (DPS).Methods:DPS is a longitudinal study where 522 subjects with impaired glucose tolerance were randomized to either lifestyle intervention group or control group. DNA was available from 507 subjects (mean body mass index (BMI) 31.2±4.5 kg/m2, age 55±7 years). The eight single-nucleotide polymorphisms (SNPs) were selected from HapMap database and genotyped by Taqman allelic discrimination protocol. The main results were confirmed in a larger cross-sectional study population (METSIM). In addition, the gene expression of IGFBP5 was studied in two previously published study populations (FUNGENUT and GENOBIN) of 124 subjects with insulin resistance (BMI 32.2±3.5 kg/m2, age 57.7±7.4 years).Results:Three out of eight IGFBP5 markers (rs9341234, rs3276 and rs11575134) were significantly associated with circulating adiponectin concentrations in men. Furthermore, mRNA expression studies of subcutaneous adipose tissue showed that mRNA concentrations of IGFBP5 correlated with adiponectin concentrations in all subjects and in women. None of the IGFBP5 SNPs were associated with T2DM.Conclusions:Our findings show that IGFBP5 has a gender-specific association with adiponectin, which may modulate the development of metabolic syndrome.International Journal of Obesity (2009) 33, 80–88; doi:10.1038/ijo.2008.196; published online 28 October 2008 [ABSTRACT FROM AUTHOR]

We have reported that the sequence variation in the tenomodulin (TNMD) gene is associated with the risk of type 2 diabetes (T2DM), central obesity and serum levels of systemic immune mediators in the Finnish Diabetes Prevention Study (DPS), which is a longitudinal lifestyle intervention study on 522 middle-aged persons with impaired glucose tolerance (IGT). The aim of this study was to investigate whether the association with T2DM, observed in the DPS could be replicated in a larger, cross-sectional population-based random sample of 5298 men (3020 with normoglycaemia, 984 with impaired fasting glucose, 436 with IGT and 811 with T2DM) from the region of Kuopio, eastern Finland. To further explore the putative mechanisms linking TNMD to T2DM and metabolic syndrome, we studied the associations of TNMD sequence variation with lipid abnormalities characteristic to metabolic syndrome. The association with T2DM risk was not replicated, but significant associations were found with serum low-density lipoprotein and total cholesterol in a body mass index-dependent manner. These associations were also observed in the men of DPS, whereas in women these associations were not significant. These results from two independent study populations suggest that the genetic variation in TNMD could modulate cholesterol metabolism in obese men.International Journal of Obesity (2008) 32, 1868–1872; doi:10.1038/ijo.2008.217; published online 4 November 2008 [ABSTRACT FROM AUTHOR]

Objective:Lifestyle and genetic factors interact in the development of obesity and the metabolic syndrome. The molecular mechanisms underlying the beneficial dietary modifications are, however, unclear. We aimed to examine the effect of the long-term moderate weight reduction on gene expression in adipose tissue (AT) and to identify genes and gene clusters responsive to treatment and thereby likely contributing to the development of the metabolic syndrome.Design:Randomized controlled and individualized weight reduction intervention.Subjects:Forty-six subjects with impaired fasting glycemia or impaired glucose tolerance and features of metabolic syndrome, aged 60±7 years were randomized either to a weight reduction (WR) (n=28) or a control (n=18) group lasting for 33 weeks.Measurements:Oral and intravenous glucose tolerance tests and subcutaneous AT biopsies were performed before and after the intervention. Gene expression of AT was studied using microarray technology in subgroups of WR (with weight reduction 5%, n=9) and control group (n=10). The results were confirmed using quantitative PCR.Results:In the WR group, glucose metabolism improved. Moreover, an inverse correlation between the change in S I and the change in body weight was found (r=−0.44, P=0.026). Downregulation of gene expression (P<0.01) involving gene ontology groups of extracellular matrix and cell death was seen. Such changes did not occur in the control group. The tenomodulin-gene was one of the most downregulated genes (−39±16%, P<0.0001). Moreover, its expression correlated with insulin sensitivity (r=−0.34, P=0.005) before the intervention and with body adiposity both before (r=0.42, P=0.007) and after (r=0.30, P=0.056) the intervention.Conclusion:Genes regulating the extracellular matrix and cell death showed a strong downregulation after long-term weight reduction. This likely reflects a new stable state at the molecular level in AT. Further studies are warranted to elucidate the mechanisms of these genetic factors.International Journal of Obesity (2008) 32, 292–303; doi:10.1038/sj.ijo.0803718; published online 11 September 2007 [ABSTRACT FROM AUTHOR]

Objective:To investigate whether a moderate increase in dietary sucrose intake induces different serum lipid responses in normolipidemic subjects with the ɛ2 allele compared with subjects without the ɛ2 allele.Design:Controlled, parallel study.Subjects:There were 15 subjects with the apolipoprotein E (APOE)3/2 genotype and 19 subjects with the APOE3/3 or 3/4 genotype, whose mean±s.d. age was 48±14 and 35±10 years, respectively. All subjects had normal glucose metabolism.Interventions:The subjects were instructed to increase their sucrose intake by 40 g/day for 8 weeks and to decrease the intake of saturated and unsaturated fat to maintain energy balance. Dietary adherence was monitored using food records and the actual increase in sucrose intake was 39.8±18.4 g/day. Sixteen subjects (nine with APOE3/2 genotype, seven with APOE3/3 or 3/4 genotypes) participated also in an 8 h oral fat tolerance test at the beginning and at the end of the intervention.Results:Body weight remained stable during the intervention. Sucrose intake did not have a significant effect on fasting concentrations of serum total and lipoprotein lipids, plasma glucose, serum insulin, squalene and non-cholesterol sterols in either genotype group. Neither were there any changes in postprandial lipid or insulin responses.Conclusions:Moderate increase in sucrose intake does not affect fasting or postprandial serum lipid responses in healthy subjects with or without the ɛ2 allele.Sponsorship:Academy of Finland (projects 80232, 200801) and Yrjö Jahnsson Foundation.European Journal of Clinical Nutrition (2007) 61, 1094–1101; doi:10.1038/sj.ejcn.1602620; published online 17 January 2007 [ABSTRACT FROM AUTHOR]

Objective:To examine the effects of sugar beet pectin (SBP) and polydextrose (PDX) on fasting plasma glucose concentration, serum lipid profile and postprandial glycemia in middle-aged subjects with abnormal glucose metabolism.Design:A placebo-controlled, randomized, parallel double-blinded study.Subjects and setting:Subjects were recruited via newspaper announcements. Seventy subjects were recruited of which 66 completed the study.Intervention:The intervention period lasted for 12 weeks during which the subjects consumed a drink enriched with either SBP (n=22) or PDX (n=22) or without fiber enrichment (control group, n=22). The daily dose of the drinks was 4 dl. The subjects were also given nutrition counseling. Postprandial glycemia was examined in 24 subjects (n=8 in each group) at 0 and 12 weeks after a standardized breakfast.Results:Fasting plasma glucose concentration did not change in the SBP and PDX groups, whereas it increased in the control group (P=0.007). On the contrary, the glycosylated hemoglobin A1c increased marginally but significantly (P0.05) in the intervention groups without a change in the control group. In postprandial glycemia, no differences between the groups were found. In both the SBP and PDX groups, fasting serum High-density lipoprotein (HDL)-cholesterol concentration increased (P0.05) without a change in the control group. Total to HDL-cholesterol ratio decreased in all groups (P0.05).Conclusions:It was found that SBP and PDX do not have positive effects on fasting or postprandial plasma glucose concentrations or serum lipid profile in subjects with abnormal glucose metabolism.Sponsorship:Danisco Ltd, Espoo, Finland.European Journal of Clinical Nutrition (2006) 60, 1073–1080. doi:10.1038/sj.ejcn.1602421; published online 8 March 2006 [ABSTRACT FROM AUTHOR]

Aims Ghrelin is a gut–brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). Methods DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. Results There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype ( P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10–0.79; P = 0.016). Conclusions Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Genetic variation in leptin receptor (LEPR) gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations. We wanted to evaluate the association between LEPR polymorphisms, diabetes risk and body weight in Finnish subjects with impaired glucose tolerance (IGT).Methods: We investigated the associations of the three LEPR polymorphisms (Lys109Arg, Gln223Arg, 3'UTR Del/Ins) with the conversion to type 2 diabetes and the changes in body weight in 507 individuals with IGT participating in the Finnish Diabetes Prevention Study. Participants were randomized to either an intensive diet and exercise intervention group or a control group.Results: After 3 years, the odds ratio for the development of type 2 diabetes in individuals in the control group with the Lys109Lys genotype was 2.38-fold higher than in individuals with other genotype combinations (P=0.016). Irrespective of group individuals with the Gln223Gln genotype had higher conversion to type 2 diabetes (OR 2.01 (95% CI 1.03-3.93)) than the Arg223 allele carriers (P=0.042). The risk was more pronounced in the control group than in the intervention group. Individuals having the 3'UTR Del/Del genotype had a slightly higher body weight throughout the study than those with the insertion allele (P=0.020), although no difference in weight change was observed.Conclusion: Two polymorphisms (Lys109Arg, Gln223Arg) in the extracellular domain of the leptin receptor predicted the conversion to type 2 diabetes in high-risk individuals with IGT. The Del/Ins polymorphism in the 3'UTR of LEPR was associated with body weight. [ABSTRACT FROM AUTHOR]

Impaired insulin secretion is a fundamental defect in type 2 diabetes. The aim of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the genes regulating insulin secretion (SLC2A2 [encoding GLUT2], GCK, TCF1 [encoding HNF-1alpha], HNF4A, GIP, and GLP1R) are associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in participants of the Finnish Diabetes Prevention Study. With the exception of SLC2A2, other genes were not associated with the risk of type 2 diabetes. All four SNPs of SLC2A2 predicted the conversion to diabetes, and rs5393 (AA genotype) increased the risk of type 2 diabetes in the entire study population by threefold (odds ratio 3.04, 95% CI 1.34-6.88, P = 0.008). The risk for type 2 diabetes in the AA genotype carriers was increased in the control group (5.56 [1.78-17.39], P = 0.003) but not in the intervention group. We conclude that the SNPs of SLC2A2 predict the conversion to diabetes in obese subjects with IGT. [ABSTRACT FROM AUTHOR]

Kemppainen T, Tammi R, Tammi M,Ågren U, Julkunen R, Böhm J, Uusitupa M&Kosma V-M(2005)Histopathology46,64–72Elevated expression of hyaluronan and its CD44 receptor in the duodenal mucosa of coeliac patients: Since hyaluronan (HA) metabolism is disturbed in some malignant tumours and in inflammatory diseases, we analysed HA and its receptor CD44 as well as the expression of the Ki67 nuclear protein, a marker of cell proliferation, in histological sections of duodenal biopsies of coeliac disease patients and controls.: The study group consisted of 52 patients with coeliac disease in remission, 40 patients with newly diagnosed disease and 10 healthy control subjects. HA was detected with a specific biotinylated probe prepared from cartilage aggrecan and link protein, and CD44 with an antibody recognizing all forms of CD44 and another specific for its v6 variant. For the expression of the nuclear protein, monoclonal antibody MIB-1 was used. The percentage of HA-positive cells in surface epithelium was higher in newly diagnosed patients (13%) compared with patients in remission (11%) and controls (2%). In addition, HA intensity in the lamina propria was decreased in the newly diagnosed patients. In patients with active disease, 22–26% of the surface epithelium was CD44+, whereas the corresponding figure in patients in remission was 5%, and that of controls 1%. The more intensive MIB-1 labelling in the duodenal epithelium of coeliac patients without treatment was normalized after gluten-free diet.: The HA-positive coat on surface epithelium seen even in patients in remission suggests persistent or even permanent changes in the epithelial permeability barrier in coeliac disease. [ABSTRACT FROM AUTHOR]

Aims: The gene encoding the human aldose reductase, the first and rate- limiting enzyme of the polyol pathway of glucose metabolism, is a promising candidate gene which may contribute to diabetic microvascular complications. We investigated the association of two previously reported DNA sequence variants of this gene, the C-106T polymorphism and the (CA)n dinucleotide repeat marker, with the risk of albuminuria and retinopathy in Finnish Type 2 diabetic patients and non-diabetic control subjects. Methods The study population included 85 Finnish, middle-aged, newly diagnosed Type 2 diabetic patients and 126 non-diabetic control subjects. Genetic analyses were performed using the polymerase chain reaction, restriction fragment length polymorphism, and automated laser fluorescence scanning analyses. Microvascular complications were determined using 10-year follow- up data of urinary albumin excretion measurements and ophthalmological examinations. Results The C and Z-2 alleles of the C-106T polymorphism and the (CA)n repeat marker, respectively, were found to be more frequent in Type 2 diabetic subjects than in non-diabetic subjects. The C and Z-2 alleles were in 60% linkage disequilibrium in diabetic subjects. At the time of diagnosis, diabetic subjects with the T allele of the C-i 06T polymorphism had significantly higher urinary albumin excretion rate and prevalence of albuminuria than subjects with the C-106C genotype (prevalence of albuminuria: 33.3 vs. 13.8%, P = 0.036, odds ratio = 3.9, 95% confidence interval 1.1, 14.7). The Z-2 allele of the (CA)n repeat marker was not consistently associated with the prevalence of albuminuria. No associations were observed between the polymorphisms examined and the prevalence of retinopathy at any point of the follow-up. Conclusions The present study suggests that the C-106T polymorphism of the aldose reductase gene could be involved in the early development of microalbuminuria in Finnish Type 2 diabetic patients. [ABSTRACT FROM AUTHOR]

Objective: To describe the 1) lifestyle intervention used in the Finnish Diabetes Prevention Study, 2) short- and long-term changes in diet and exercise behavior, and 3) effect of the intervention on glucose and lipid metabolism.Research Design and Methods: There were 522 middle-aged, overweight subjects with impaired glucose tolerance who were randomized to either a usual care control group or an intensive lifestyle intervention group. The control group received general dietary and exercise advice at baseline and had an annual physician's examination. The subjects in the intervention group received additional individualized dietary counseling from a nutritionist. They were also offered circuit-type resistance training sessions and advised to increase overall physical activity. The intervention was the most intensive during the first year, followed by a maintenance period. The intervention goals were to reduce body weight, reduce dietary and saturated fat, and increase physical activity and dietary fiber.Results: The intervention group showed significantly greater improvement in each intervention goal. After 1 and 3 years, weight reductions were 4.5 and 3.5 kg in the intervention group and 1.0 and 0.9 kg in the control group, respectively. Measures of glycemia and lipemia improved more in the intervention group.Conclusions: The intensive lifestyle intervention produced long-term beneficial changes in diet, physical activity, and clinical and biochemical parameters and reduced diabetes risk. This type of intervention is a feasible option to prevent type 2 diabetes and should be implemented in the primary health care system. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVE: The short form (Glu[sup 9]/Glu[sup 9]) of the 12Glu9 deletion polymorphism of the α[sub 2B]-adrenergic receptor gene was previously found to be associated with reduced basal metabolic rate in obese subjects. We investigated the effects of this polymorphism on changes in body weight in Finnish non-diabetic and type 2 diabetic subjects during a 10 y follow-up. DESIGN: Controlled 10 y follow-up study with baseline, 5 and 10 y examinations. SUBJECTS: A total of 126 non-diabetic control subjects and 84 newly diagnosed, middle-aged type 2 diabetic patients from eastern Finland participated. MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma Cpeptide and glycosylated hemoglobin A[sub 1c]. Genotypes were determined by polymerase chain reaction followed by agarose gel electrophoresis. RESULTS: No significant differences were found in the prevalence of the 12Glu9 deletion polymorphism between non-diabetic and type 2 diabetic subjects. The non-diabetic subjects with the Glu[sup 9]/Glu[sup 9] genotype had a greater increase in their mean body weight during 5 y follow-up than the non-diabetic subjects with other genotypes (changes in body weight 0.4 ± 5.7, -0.5 ± 6.4 and 3.4 ± 4.9% for the Glu[sup 12]/Glu[sup 12], Glu[sup 9]/Glu[sup 9] and Glu[sup 9]/Glu[sup 9] genotypes, respectively, P = 0.040 for the difference between the groups). Also, the trend for the increment of body weight was statistically significant in the non-diabetic subjects with the Glu[sup 9]/Glu[sup 9] genotype (P = 0.012). The 12Glu9 polymorphism was not cross-sectionally or longitudinally associated with body weight in type 2 diabetic subjects. CONCLUSIONS: The genotype of two short alleles (Glu[sup 9]/Glu[sup 9]) was associated with an increase in body weight among non-diabetic subjects. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To study the effect of weight loss and subsequent weight maintenance or weight regain on the activities of FVII and plasminogen activator inhibitor 1 (PAI-1) and the concentration of fibrinogen over 12 months in obese women consuming a hypoenergetic, low-fat diet with or without orlistat. In addition, the relation between the changes of the activities of PAI-1 and FVII with the changes of other cardiovascular risk factors were examined. METHODS AND PROCEDURES: Design—a 12-month randomized double-blind weight reduction trial of placebo and orlistat. Subjects—51 healthy obese women (age 44 ± 0.7 y, BMI 36.2 ± 0.5 kg/m², mean ± s.e.m.) Treatment—the participants were on a hypoenergetic diet (-600 kcal daily). The diet was adjusted for actual body weight (-300 kcal) at 6 months. Women were randomized to receive either orlistat 120 mg three times daily (n=25) or placebo three times daily (n=26) for 12 months according to a double-blind protocol after a 1 month run-in period. Measurements—changes of body weight, body composition, haemostatic and other cardiovascular risk factors were measured at 3-6 month intervals. The activity of plasma PAI-1 was measured by a chromogenic method, fibrinogen by the PT-derived method and the activity of FVII by the one-stage method. RESULTS: The changes in body weight between orlistat and placebo groups were not statistically significantly different. Orlistat did not influence haemostatic factors beyond its effect on weight loss. Therefore, the results of the orlistat and placebo groups were pooled. The average weight loss at 3, 6 and 12 months was 7.6, 9.5 and 10.0 kg, respectively (P<0.001). Between 6 and 12 months, 35% of women regained weight, 24% had stable weight and 41% continued to lose weight. No changes in the mean plasma fibrinogen concentration were observed at any time point during the trial. During the first 3 months the activities of PAI-1 and FVII decreased... [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the effect of orlistat (Xenical™) treatment on body composition and resting energy expenditure (REE) during a 2 y weight-reduction programme in obese Finns. SUBJECTS: Of initially 96 obese subjects who participated in the weight-reduction programme, those 72 subjects (13 men, 59 women, body mass index (BMI) 35.9±3.9 kg/m², age 43.4±6.0 y, mean±s.d.) with the complete set of data for 2 y were included in the study. DESIGN: After a 4-week lead-in period, subjects were randomized with either orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a mildly hypoenergetic balanced diet for 1 y. This was followed by I y double-blind period with the subjects within each treatment group re-assigned to receive orlistat 120 mg t.i.d. or placebo t.i.d. in conjunction with a weight maintenance diet. MEASUREMENTS: Body composition and REE were measured after an overnight fast by a bioelectrical impedance method and indirect calorimeter, respectively. The measurements were performed at the beginning and at 3, 6, 12 and 24 months. RESULTS: During the first year, the orlistat-treated group had greater reduction of body weight and fat mass but not of fat-free mass or REE as compared to placebo. During the second year, orlistat treatment was associated with smaller regain of body weight and fat mass with no significant differences in the changes of fat-free mass or REE as compared to placebo. CONCLUSION: In addition to better weight loss and maintenance of reduced weight, orlistat treatment is associated with beneficial changes in body composition but with no excess decrease in resting energy expenditure as compared to that achieved during placebo with a dietary therapy alone. [ABSTRACT FROM AUTHOR]

Objective: To investigate the evolution of visual acuity, age-related macular degeneration (AMD), and its relation to 10-year cardiovascular mortality and risk factors in patients with newly diagnosed type 2 diabetes and control subjects.Research Design and Methods: A 10-year prospective study consisting of a representative group of 133 (70 men, 63 women) newly diagnosed type 2 diabetic patients diagnosed at health centers between 1979 and 1981 and 144 (62 men, 82 women) nondiabetic control subjects recruited from the population register was performed. The frequency of AMD was determined by grading of 45 degrees stereoscopic fundus photographs. The subjects were studied at baseline and after 5 and 10 years.Results: By the 10-year follow-up, visual acuity had declined more markedly in the diabetic patients than in the control subjects. Although the frequency of AMD was nearly the same in both groups (11-19%), it decreased visual acuity earlier in the diabetic patients than in the control group. AMD at baseline predicted 10-year cardiovascular mortality independently of adjustment for other risk factors in the diabetic patients (odds ratio [95% CI] 4.7 [1.1-19.3], P = 0.033).Conclusions: Visual acuity deteriorated earlier in newly diagnosed type 2 diabetic patients than in the control group although the cross-sectional frequency of AMD was nearly the same in both groups. Interestingly, AMD was an independent risk factor for cardiovascular mortality in type 2 diabetic patients, but the background mechanism(s) behind this association is unknown. [ABSTRACT FROM AUTHOR]

Conjugated linoleic acid (CLA) is anticarcinogenic in experimental animal studies. We studied dietary and serum CLA in Finnish patients with breast cancer in 1992-1995. Participants were consecutive women with breast cancer (68 premenopausal and 127 postmenopausal) and population-based control women (75 premenopausal and 133 postmenopausal), matched for age and area of residence. Diet was assessed by a validated food frequency questionnaire and the fatty acid composition of serum by gas-liquid chromatography. In postmenopausal women, dietary CLA, serum CLA, myristic acid, and trans-vaccenic acid were significantly lower in cases than in controls. The odds ratio for breast cancer in the highest quintile vs. the lowest was 0.4 [95% confidence interval (CI) = 0.2-0.9]for CLA, 0.3 (95% CI = 0.1-0.7) for myristic acid, and 0.3 (95% CI = 0.1-0.7) for trans-vaccenic acid in serum. The odds ratios remained similar after adjustment for known risk factors of breast cancer. A diet composed of CLA-rich foods, particularly cheese, may protect against breast cancer in postmenopausal women, but it is impossible to assess the independent effects of CLA in this study. The findings may be of relevance for food production, inasmuch as it is possible to increase CLA and its precursor trans-vaccenic acid in foods by modifying the feeding of ruminants. [ABSTRACT FROM AUTHOR]

BACKGROUND: Adipose tissue metabolism can be investigated directly in viva by microdialysis and indirectly in vitro using isolated adipocytes. The in vitro studies are relatively easy to make and they give information about specific tissue metabolism. The in vivo studies, on the other hand, are supposed to give relevant data about tissue physiology interacting with other metabolic systems at the body level. OBJECTIVE: To investigate the concordance between the results on responsiveness to stimulation of lipolysis from in viva microdialysis and in vitro isolated adipocytes. SUBJECTS: Altogether 22 massively obese otherwise healthy subjects (seven men and 15 women, age 41 (26-55) y, BMI 51.5 (37.5-73.9) kg/m², mean (range)) going through the gastric banding operation participated in the study. METHODS: The microdialysis study was done after an overnight fast at rest. Lipolysis was stimulated with isoprenaline that was perfused into the subcutaneous abdominal adipose tissue. Local blood flow was estimated by ethanol dilution method. Adipose tissue biopsy for the in vitro study was taken from subcutaneous abdominal region during the operation. Lipolysis in freshly isolated adipocytes was stimulated with different concentrations of adrenaline or isoprenaline. RESULTS: Significant positive correlations were observed between the values of relative stimulation of lipolysis in isolated adipocytes and in the microdialysis study. These correlations improved after correcting for cell size or fat mass. CONCLUSION: The microdialysis study in viva and lipolysis assay with isolated adipocytes in vitro provide concordant and complementary information of adipose tissue metabolism in the same individual. [ABSTRACT FROM AUTHOR]

Objective: To determine the role of the hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha genes in the etiology of late-onset type 2 diabetes in Finnish and Chinese subjects.Research Design and Methods: The whole coding regions of the genes encoding for HNF-1alpha and HNF-4alpha, including approximately 800 bp of the HNF-1alpha promoter, were investigated in 40 Finnish subjects (fasting C-peptide 50-570 pmol/l) and 47 Chinese subjects with type 2 diabetes by single-strand conformation polymorphism (SSCP) analysis. Frequencies of the variants of these genes were analyzed by restriction fragment-length polymorphism analysis in additional samples of 100 Finnish diabetic patients and 82 Finnish control subjects and in 58 Chinese diabetic patients and 51 Chinese control subjects.Results: No previously reported gene defects were detected, but one novel functionally silent GCC-->GCG variant (nucleotide 73, exon 10) was observed in the HNF-4alpha gene in a Chinese diabetic patient. Interestingly, the Ala98Val substitution of the HNF-1alpha gene occurred at a significantly higher frequency in 140 Finnish diabetic patients compared with 82 control subjects (P = 0.014). The Ala98Val variant was not, however, associated with abnormalities in insulin secretion evaluated by oral and intravenous glucose tolerance tests in subjects with normal (n = 295) or impaired (n = 38) glucose tolerance.Conclusions: Variants in the HNF-1alpha and HNF-4alpha genes are unlikely to play a major role in the pathogenesis of late-onset type 2 diabetes in Finnish and Chinese subjects. However, the association of the Ala98Val variant of the HNF-1alpha gene with type 2 diabetes in Finnish subjects may indicate a diabetogenic locus close to the HNF-1alpha gene. [ABSTRACT FROM AUTHOR]

The effect of plant stanol ester on serum cholesterol is dose-dependent. However, it is not clear what the dose is beyond which no additional benefit can be obtained. Therefore, we determined the dose-response relationship for serum cholesterol with different doses of plant stanol ester in hypercholesterolemic subjects. In a single-blind design each of 22 men or women consumed five different doses of plant stanol [target (actual) intake 0 (0), 0.8 (0.8), 1.6 (1.6), 2.4 (2.3), 3.2 (3.0) g/d] added as plant stanol esters to margarine for 4 wk. The order of dose periods was randomly determined. Serum total cholesterol concentration decreased (calculated in reference to control) by 2.8% (P = 0.384), 6.8% (P < 0.001), 10.3% (P < 0.001) and 11.3% (P < 0.001) by doses from 0.8 to 3.2 g. The respective decreases for LDL cholesterol were 1.7% (P = 0. 892), 5.6% (P < 0.05), 9.7% (P < 0.001) and 10.4% (P < 0.001). Although the decreases were numerically greater with 2.4 and 3.2 g doses than with the 1.6 g dose, these differences were not significant (P = 0.054-0.516). Serum plant stanols rose slightly, but significantly with the dose (P < 0.001). Apolipoprotein B concentration was decreased significantly already at the dose of 0.8 g (8.7%, P < 0.001). Apolipoprotein E genotype did not affect the lipid responses. We conclude that significant reduction of serum total and LDL cholesterol concentrations is reached with the 1.6-g stanol dose, and increasing the dose from 2.4 to 3.2 g does not provide clinically important additional effect. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate the independent and combined effects of the Trp64Arg polymorphism of the β[sub 3]-adrenergic receptor (β[sub 3]AR) gene and the (-3826) A→G polymorphism of the uncoupling protein 1 (UCP1) gene on body weight change in type 2 diabetic and non-diabetic control subjects during a 10 y follow-up study. DESIGN: Controlled 10 y follow-up study with baseline, 5 and 10y examinations. SUBJECTS: 70 newly diagnosed, middle-aged type 2 diabetic patients and 123 non-diabetic control subjects from eastern Finland. MEASUREMENTS: Anthropometric measurements, blood pressure, oral glucose tolerance test, plasma insulin, plasma C-peptide and HbA[sub 1c]. Genotypes by polymerase chain reaction followed by enzymatic digestion. RESULTS: No significant differences were found in the frequencies of the two polymorphisms between diabetic and control subjects. The polymorphisms were not cross-sectionally or longitudinally associated with body weight or BMI in diabetic or control subjects. When the diabetic and control subjects were analysed together, the change in the mean body weight was significantly greater among the subjects with both polymorphisms (n = 11) than among those with no polymorphisms (n= 103; change in weight 6.5±2.5% vs -0.2±0.8%, P=0.036, and change in Body Mass Index 8.5 ± 2.6% vs 2.0 ± 0.8%, P = 0.060, mean ± s.e.m.). CONCLUSIONS: The simultaneous existence of the two polymorphisms was associated with a tendency to gain weight suggesting a synergistic effect of these polymorphisms on body weight gain. [ABSTRACT FROM AUTHOR]

Objective: Low levels of selenium have been associated with a higher risk of cardiovascular diseases and cancer in humans. Since 1984, selenium supplementation through fertilizers has been employed in Finland to increase the very low concentration of selenium in the nation's food supply. As a result, the selenium concentration of Finnish foods became one of the highest in Europe. A decade after selenium supplementation began, the association between toenail selenium and the risk of breast cancer was examined.Design: Case-control study.Setting: Eastern Finland.Subjects: 289 pre- and postmenopausal breast cancer cases and 433 community controls. The diagnosis was unknown at the time the toenail samples were collected.Results: The mean toenail selenium concentration was 0.80 mg/kg in premenopausal cases and 0.84 mg/kg in premenopausal controls: and 0. 77 mg/kg in postmenopausal cases and 0.80 mg/kg in postmenopausal controls. The odds ratio (OR) comparing the highest with the lowest quintiles of toenail selenium concentration was 1.1 (95% CI 0.4-3.2) in premenopausal women and 0.7 (95% CI 0.3-1.5) in postmenopausal women. The intake of retinol, beta-carotene, vitamin E and vitamin C did not change the association between toenail selenium and breast cancer.Conclusions: A decade after selenium supplementation, selenium seems not to be an important factor in the etiology of breast cancer, neither in premenopausal nor postmenopausal women.Sponsorship: This work was supported by the EVO funds from the Kuopio University Hospital and by research grants from the Academy of Finland, Yrjö Jahnsson Foundation and Juho Vainio Foundation. European Journal of Clinical Nutrition (2000) 54, 98-103 [ABSTRACT FROM AUTHOR]

Sympathetic activation has been considered as a link between insulin resistance, hyperinsulinemia, and hypertension. However, little is known about the association between insulin sensitivity and autonomic regulation or about the effect of acute hyperinsulinemia on cardiac sympathovagal balance. The aim of this study was to investigate heart rate variability (HRV) during the euglycemic-hyperinsulinemic clamp in nondiabetic offspring of patients with type 2 diabetes. We studied 35 nondiabetic offspring of patients with type 2 diabetes and 19 control subjects. Probands were chosen from a 10-year follow-up study of patients with well-characterized type 2 diabetes according to their fasting C-peptide level (selected from both ends of the distribution) and from control subjects to form three groups: 1) a group including subjects who were offspring of type 2 diabetic patients with low C-peptide levels (deficient insulin secretion group [IS group], n = 17), 2) a group including subjects who were offspring of type 2 diabetic patients with high C-peptide levels (insulin-resistant group [IR group], n = 18), and 3) a control group without a history of type 2 diabetes in first-degree relatives (n = 19). HRV was assessed at baseline and at the steady state during the euglycemic-hyperinsulinemic clamp. Rates of whole-body glucose uptake (M value) were lower in the IR group than in the IS group and the control group (41+/-3 vs. 54+/-2 vs. 60+/-4 micromol x kg(-1) x min(-1), P < 0.01 and P < 0.01, respectively). In all groups, heart rate increased significantly during hyperinsulinemia. In the IR group, insulin infusion increased total power of HRV [from 7.70+/-0.15 to 8.05+/-0.15 ln(ms2), P < 0.01] and the low frequency-to-high frequency ratio (from 0.62+/-0.14 to 1.14+/-0.18, P < 0.01) and decreased power of the high frequency spectral component (from 5.73+/-0.17 to 5.43+/-0.16 ln(ms2), P < 0.05), whereas in other groups, changes in HRV were not significant. We conclude that the HRV response to acute hyperinsulinemia in the offspring of type 2 diabetic probands was likely to be modulated by the type 2 diabetic phenotype of the parent. In insulin-resistant subjects, autonomic dysfunction may be an earlier defect than hitherto acknowledged. [ABSTRACT FROM AUTHOR]

Objective: To study barriers in following nutritional advice among coronary heart disease patients in relation to dietary fat intake.Design: A cross-sectional study using 4-day food records and a questionnaire with regard to barriers to or difficulties in following dietary advice.Subjects: Altogether, 362 male subjects with coronary heart disease from two separate patient populations (91 + 271) were included in the study, with the mean age of 50 years and 60 years, respectively. The patients were classified into low (< or = 30 E%) or high (> 30 E%) fat intake groups. The patients with low dietary fat intake obtained on an average 10 E% less energy from fat as compared to the high dietary fat intake group.Results: Overall, most patients with coronary heart disease reported difficulties in following nutritional advice when eating in social situations. Patients with high dietary fat intake reported more frequently than patients with low fat intake that they eat like other people without thinking about what they eat. On the other hand, there were no differences between the high and low fat intake groups in the barriers: eating at work, food price, shopping, taste or knowledge of nutrition.Conclusions: Our results suggest that the sensitivity to social influence is an important factor explaining noncompliance with dietary advice among patients with high dietary fat intake. [ABSTRACT FROM AUTHOR]