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Biomedical subjects

Leo K Niskanen

Publications and source records attributed to Leo K Niskanen.

12 recordsLinked to original sources

Plasma ghrelin levels after two high-carbohydrate meals producing different insulin responses in patients with metabolic syndrome.

Ghrelin is an orexigenic peptide produced in the stomach and its plasma levels are decreased acutely in response to ingested nutrients. To further clarify the role of insulin on ghrelin secretion, the present study was designed to investigate whether circulating ghrelin is affected differently by two mixtures of whole-grain breads known to produce low or high insulin responses in obese non-diabetic subjects with metabolic syndrome. After an overnight fast eight obese subjects with the metabolic syndrome (3 men and 5 women; BMI 33.7+/-0.7 kg/m(2); age 55.6+/-1.8 y) received two different meals consisting of whole-grain rye or wheat breads. The comparison group (3 men and 5 women; BMI 22.5+/-0.5 kg/m(2); age 26.0+/-0.9 y) received a wheat bread meal. Blood samples were collected postprandially at time intervals for 2 h. Feelings of hunger and satiety were analyzed using the visual analogue scales. Ghrelin concentrations decreased after bread meals in lean individuals, but not in obese individuals with the metabolic syndrome. Despite the difference in plasma insulin response, there was no difference in plasma ghrelin or feelings of hunger and satiety in patients with metabolic syndrome. After both rye and wheat bread meals, the decrease in ghrelin concentrations seen in normal-weight individuals after wheat bread meal was absent in subjects with metabolic syndrome. Despite the different plasma insulin response in obese patients, ghrelin levels did not change in response to either type of bread meals. In addition, ghrelin levels did not correlate with insulin, glucose, HOMA1-IR and satiety and hunger ratings in either study groups. This indicates that regulation of ghrelin might be altered in obese patients with metabolic syndrome independently of insulin.

Blood Glucose↗

Metabolic syndrome and depression: a cross-sectional analysis.

OBJECTIVE: To examine the prevalence of the metabolic syndrome in depressive outpatients and to identify its correlates in depression. METHOD: This cross-sectional analysis was performed on 121 depressive outpatients from January 2002 through January 2004 who were diagnosed at baseline with the Structured Clinical Interview for DSM-III-R. The metabolic syndrome was diagnosed at 6-year follow-up according to the modified criteria of the National Cholesterol Education Program. The severity of depressive symptoms was assessed at follow-up with the Beck Depression Inventory and the Hamilton Rating Scale for Depression, and general psychopathology was assessed with the Symptom Checklist-90. RESULTS: At 6-year follow-up, the prevalence of metabolic syndrome in the study group of depressive outpatients was 36% (N = 44). The syndrome was associated with a current diagnosis of major depression and overeating, but not with age or sex. CONCLUSION: The metabolic syndrome is highly prevalent among patients with a history of depression, especially those with current major depression. This may have implications for treatment. Furthermore, attention should be focused on the physical health of those suffering from depression.

Age Factors↗

Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: a prospective cohort study.

BACKGROUND: Despite abundant epidemiologic evidence, the role of elevated serum uric acid level as a cardiovascular risk factor is controversial. We assessed the predictive value of serum uric acid levels for cardiovascular and overall mortality. METHODS: A population-based prospective cohort study was performed of 1423 middle-aged Finnish men initially without cardiovascular disease, cancer, or diabetes. The main outcome measure was death from cardiovascular disease and any cause. RESULTS: The mean follow-up was 11.9 years. There were 157 deaths during follow-up, of which 55 were cardiovascular. In age-adjusted analyses, serum uric acid levels in the upper third were associated with a greater than 2.5-fold higher risk of death from cardiovascular disease than levels in the lower third. Taking into account cardiovascular risk factors and variables commonly associated with gout increased the relative risk to 3.73. Further adjustment for factors related to the metabolic syndrome strengthened the risk to 4.77. Excluding the 53 men using diuretics did not alter the results. In age-adjusted analyses, men with serum uric acid levels in the upper third were 1.7-fold more likely to die of any cause than men with levels in the lower third. Adjustment for further risk factors strengthened the association somewhat. CONCLUSIONS: Serum uric acid levels are a strong predictor of cardiovascular disease mortality in healthy middle-aged men, independent of variables commonly associated with gout or the metabolic syndrome. Serum uric acid measurement is an easily available and inexpensive risk marker, but whether its relationship to cardiovascular events is circumstantial or causal remains to be answered.

Biomarkers↗

Leucine7 to proline7 polymorphism in prepro-NPY gene and femoral neck bone mineral density in postmenopausal women.

Neuropeptide Y (NPY) is a versatile neurotransmitter that has recently been shown to regulate bone metabolism in animal and in vitro studies. We studied the influence of leucine7-to-proline7 (Leu7/Pro7) polymorphism of the NPY signal peptide gene on bone mineral density (BMD) before and after a 5-year hormone replacement therapy (HRT) in 316 early postmenopausal women participating in a randomized controlled trial nested in the population-based Kuopio Osteoporosis Risk Factor and Prevention (OSTPRE) study. The participants were randomized into two treatment groups: the HRT group (n = 146) received a sequential combination of 2 mg estradiol valerate and 1 mg cyproterone acetate and calcium lactate, 500 mg/day (equal to 93 mg Ca2+) alone or in combination with vitamin D3, 100-300 IU/day. The non-HRT group (n = 170) received calcium lactate, 500 mg alone or in combination with vitamin D3, 100-300 IU/day. BMDs of the lumbar spine (L2-4) and proximal femur were measured by using dual X-ray absorptiometry (DXA). The frequency of Leu7/Pro7 polymorphism was 15.2%. At baseline, there were no significant differences in the lumbar or femoral neck BMD between the subjects who had Leu7Pro7 polymorphism and the normal subjects. After 5 years, the BMD of the femoral neck remained unaltered and that of the lumbar spine increased by 1.7% in the HRT group, whereas both BMDs were decreased by 4-5% in the non-HRT group. After 5 years, the femoral neck BMD was significantly lower in those with the wild-type NPY polymorphism than in those with Leu7/Pro7 polymorphism (P = 0.040) in the non-HRT group. In the HRT group, the changes in BMD were quite modest and not significantly modified by Leu7/Pro7 genotype. We conclude that the Leu7/Pro7 polymorphism in NPY signal gene may favorably affect femoral neck BMD in postmenopausal women.

Bone Density↗

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

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

Area Under Curve↗

Structural differences between rye and wheat breads but not total fiber content may explain the lower postprandial insulin response to rye bread.

BACKGROUND: Rye bread has a beneficial effect on the postprandial insulin response in healthy subjects. The role of rye fiber in insulin and glucose metabolism is not known. OBJECTIVE: The aim of the study was to determine the effect of the content of rye fiber in rye breads on postprandial insulin and glucose responses. DESIGN: Nineteen healthy postmenopausal women aged 61 +/- 1 y, with a body mass index (in kg/m(2)) of 26.0 +/- 0.6, and with normal glucose tolerance participated in the study. The test products were refined wheat bread (control), endosperm rye bread, traditional rye bread, and high-fiber rye bread; each bread provided 50 g available carbohydrate and was served with breakfast. Plasma glucose, insulin, glucose-dependent insulinotropic polypeptide, glucagon-like peptide 1, and serum C-peptide were measured in fasting and 8 postprandial blood samples. In vitro starch hydrolysis and the microscopic structure of the breads were also determined. RESULTS: Postprandial insulin, glucose-dependent insulinotropic polypeptide, and C-peptide responses to the rye breads were significantly lower than the response to the control; no significant differences in insulin and C-peptide responses to the rye breads were found. Glucose and glucagon-like peptide 1 responses to the rye breads were not significantly different from those to the control, except at 150 and 180 min. In vitro starch hydrolysis was slower in all rye breads than in the control, and the structure of continuous matrix and starch granules differed between the rye and control breads. CONCLUSION: Total fiber content does not explain the lower postprandial insulin response to rye bread than to wheat bread, but structural differences between rye and wheat breads might.

Blood Glucose↗

Weight loss and weight maintenance, ambulatory blood pressure and cardiac autonomic tone in obese persons with the metabolic syndrome.

BACKGROUND: Cardiac autonomic function may play a role in obesity-associated hypertension. Most studies on the effects of weight loss on blood pressure and autonomic function do not distinguish between acute or continuing weight loss and steady-state weight maintenance after weight loss. OBJECTIVES: We sought to clarify the changes in ambulatory blood pressure, heart rate and heart rate variability as assessed by spectral analysis during rapid weight loss and extended weight maintenance. PARTICIPANTS: Abdominally obese (body mass index 35.2 +/- 2.1 kg/m2, waist 114.3 +/- 9.0 cm) men and women (n = 41) with the metabolic syndrome. METHODS AND RESULTS: The 34 men and women completing the 1-year weight maintenance period lost 14.6 +/- 3.5 kg during the 9-week very-low-calorie diet and maintained a 12.5 +/- 7.5 kg weight loss to the end of the trial. Ambulatory 24-h blood pressure decreased dramatically during the diet (-9.0 +/- 8.0/-4.6 +/- 4.9 mmHg), but had risen to near baseline levels by the end of weight maintenance (-2.2 +/- 8.2 /-1.2 +/- 6.1 mmHg). Night-time heart rate decreased (-5.5 +/- 9.6 beats/min, P = 0.012), and heart rate variability total and low-frequency power measured during 5 min of controlled breathing increased by 46-56% (P = 0.003-0.09) during rapid weight loss. These changes gradually attenuated during weight maintenance, and only the change in night-time heart rate was still of borderline significance after 1 year of weight maintenance (-3.6 +/- 8.6 beats/min, P = 0.063). Heart rate variability high-frequency power tended to increase during weight loss and weight maintenance. CONCLUSION: Despite successful weight maintenance, the decrease in ambulatory blood pressure after rapid weight loss was largely transient. The increase in parasympathetic tone was more sustained, but also gradually attenuated during 1 year of weight maintenance.

Baroreflex↗

Sedentary lifestyle, poor cardiorespiratory fitness, and the metabolic syndrome.

PURPOSE: The cross-sectional associations of leisure-time physical activity (LTPA) and cardiorespiratory fitness with the metabolic syndrome (MS) were investigated in a population-based sample of 1069 middle-aged men without diabetes, cardiovascular disease, or cancer. METHODS: LTPA was assessed using a detailed quantitative questionnaire. Maximal oxygen uptake VO(2max) and core and related features of the MS were determined. A modified World Health Organization definition of the MS and factor analysis were used. RESULTS: Men who engaged in at least moderate-intensity (>or=4.5 metabolic equivalents) LTPA <1.0 h.wk-1 were 60% more likely to have the MS than those engaging in >or= 3.0 h.wk-1 even after adjustment for confounders. Low-intensity (<4.5 metabolic equivalents) LTPA was not associated with the metabolic syndrome. Men with a VO(2max) <29.1 mL x kg-1 x min-1 were almost seven times more likely to have the MS than those with a VO(2max) >or=35.5 mL.kg-1.min-1 even after adjusting for confounders. In first-order factor analysis using a promax rotation, the principal factor explained 20% of total variance and had heavy loadings for VO(2max) (-0.57) and at least moderate-intensity LTPA (-0.44), and moderate or heavy loadings for the main components of the MS. The second-order factor analysis generated a principal factor that was strongly loaded on by the main components of the MS and VO(2max) (-0.50) but not LTPA. CONCLUSION: A sedentary lifestyle and especially poor cardiorespiratory fitness are not only associated with the MS but could also be considered features of the MS. Measurement of VO(2max) in sedentary men with risk factors may provide an efficient means for targeting individuals who would benefit from interventions to prevent the MS and its consequences.

Adult↗

The metabolic syndrome and total and cardiovascular disease mortality in middle-aged men.

CONTEXT: The metabolic syndrome, a concurrence of disturbed glucose and insulin metabolism, overweight and abdominal fat distribution, mild dyslipidemia, and hypertension, is associated with subsequent development of type 2 diabetes mellitus and cardiovascular disease (CVD). Despite its high prevalence, little is known of the prospective association of the metabolic syndrome with cardiovascular and overall mortality. OBJECTIVE: To assess the association of the metabolic syndrome with cardiovascular and overall mortality using recently proposed definitions and factor analysis. DESIGN, SETTING, AND PARTICIPANTS: The Kuopio Ischaemic Heart Disease Risk Factor Study, a population-based, prospective cohort study of 1209 Finnish men aged 42 to 60 years at baseline (1984-1989) who were initially without CVD, cancer, or diabetes. Follow-up continued through December 1998. MAIN OUTCOME MEASURES: Death due to coronary heart disease (CHD), CVD, and any cause among men with vs without the metabolic syndrome, using 4 definitions based on the National Cholesterol Education Program (NCEP) and the World Health Organization (WHO). RESULTS: The prevalence of the metabolic syndrome ranged from 8.8% to 14.3%, depending on the definition. There were 109 deaths during the approximately 11.4-year follow-up, of which 46 and 27 were due to CVD and CHD, respectively. Men with the metabolic syndrome as defined by the NCEP were 2.9 (95% confidence interval [CI], 1.2-7.2) to 4.2 (95% CI, 1.6-10.8) times more likely and, as defined by the WHO, 2.9 (95% CI, 1.2-6.8) to 3.3 (95% CI, 1.4-7.7) times more likely to die of CHD after adjustment for conventional cardiovascular risk factors. The metabolic syndrome as defined by the WHO was associated with 2.6 (95% CI, 1.4-5.1) to 3.0 (95% CI, 1.5-5.7) times higher CVD mortality and 1.9 (95% CI, 1.2-3.0) to 2.1 (95% CI, 1.3-3.3) times higher all-cause mortality. The NCEP definition less consistently predicted CVD and all-cause mortality. Factor analysis using 13 variables associated with metabolic or cardiovascular risk yielded a metabolic syndrome factor that explained 18% of total variance. Men with loadings on the metabolic factor in the highest quarter were 3.6 (95% CI, 1.7-7.9), 3.2 (95% CI, 1.7-5.8), and 2.3 (95% CI, 1.5-3.4) times more likely to die of CHD, CVD, and any cause, respectively. CONCLUSIONS: Cardiovascular disease and all-cause mortality are increased in men with the metabolic syndrome, even in the absence of baseline CVD and diabetes. Early identification, treatment, and prevention of the metabolic syndrome present a major challenge for health care professionals facing an epidemic of overweight and sedentary lifestyle.

Cardiovascular Diseases↗

Metabolic syndrome and development of diabetes mellitus: application and validation of recently suggested definitions of the metabolic syndrome in a prospective cohort study.

The World Health Organization (WHO) and the National Cholesterol Education Program (NCEP) recently proposed definitions for the metabolic syndrome. Little is known of their validity, however. The authors assessed the sensitivity and specificity of the definitions of the metabolic syndrome for prevalent and incident diabetes mellitus in a Finnish population-based cohort of middle-aged men (n = 1,005) followed for 4 years since the late 1980s. Four definitions based on the WHO and NCEP recommendations were compared. All definitions identified persons at high risk for developing diabetes during the 4-year follow-up (odds ratios = 5.0-8.8). The WHO definition including waist-hip ratio > 0.90 or body mass index >or= 30 kg/m(2) was the most sensitive (0.83 and 0.67) and least specific (0.78 and 0.80) in detecting the 47 prevalent and 51 incident cases of diabetes. The NCEP definition in which adiposity was defined as waist girth > 102 cm detected only 61% of prevalent and 41% of incident diabetes, although it was the most specific (0.89 and 0.90). The WHO definition seems valid as judged by its relatively high sensitivity and specificity in predicting diabetes. The NCEP definition including waist > 102 cm also identifies persons at high risk for diabetes, but it is relatively insensitive in predicting diabetes.

Adult↗

Postprandial glucose, insulin, and incretin responses to grain products in healthy subjects.

BACKGROUND: Various botanical and structural characteristics of starchy food modify the postprandial glucose and insulin responses in humans. OBJECTIVE: We investigated what factors in grain products affect human glucose and insulin responses and elucidated the mediating mechanisms. DESIGN: Ten men and 10 women [mean age: 28 +/- 1 y; mean body mass index (in kg/m(2)): 22.9 +/- 0.7] with normal glucose tolerance were recruited. The test products were whole-kernel rye bread, whole-meal rye bread containing oat beta-glucan concentrate, dark durum wheat pasta, and wheat bread made from white wheat flour. Paracetamol, a marker of the rate of gastric emptying, was added to the breads during baking. Each product provided 50 g available carbohydrate and was served in random order with breakfast (except for the beta-glucan rye bread, which was served at the last visit). Fasting and 8 postprandial blood samples were collected at intervals of 15-30 min for 3 h to determine plasma glucose, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1), serum insulin, and paracetamol concentrations. The in vitro starch hydrolysis, the structural characteristics (by light microscopy), and the molecular weight of beta-glucan in the test products were analyzed. RESULTS: Glucose responses and the rate of gastric emptying after consumption of the 2 rye breads and pasta did not differ from those after consumption of white wheat bread. However, insulin, GIP, and GLP-1 responses, except for GLP-1 responses to the rye bread containing oat beta-glucan concentrate, were lower after the consumption of rye breads and pasta than after consumption of white wheat bread. CONCLUSIONS: Postprandial insulin responses to grain products are determined by the form of food and botanical structure rather than by the amount of fiber or the type of cereal in the food. These effects may be mediated through GIP and GLP-1.

Acetaminophen↗

Low levels of leisure-time physical activity and cardiorespiratory fitness predict development of the metabolic syndrome.

OBJECTIVE: Little is known about the association of leisure-time physical activity (LTPA) and cardiorespiratory fitness with development of the metabolic syndrome, which predisposes diseases such as diabetes and atherosclerosis. We studied the associations of LTPA and cardiorespiratory fitness with development of the metabolic syndrome (World Health Organization [WHO] and the National Cholesterol Education Program [NCEP] definitions). RESEARCH DESIGN AND METHODS: LTPA over the previous 12 months, VO(2max) (ml. kg(-1). min(-1)), and cardiovascular and metabolic risk factors were assessed in a population-based cohort of 612 middle-aged men without the metabolic syndrome. RESULTS: At the 4-year follow-up, 107 men had metabolic syndrome (WHO definition). Men engaging in >3 h/week of moderate or vigorous LTPA were half as likely as sedentary men to have the metabolic syndrome after adjustment for major confounders (age, BMI, smoking, alcohol, and socioeconomic status) or potentially mediating factors (insulin, glucose, lipids, and blood pressure), especially in high-risk men. Vigorous LTPA had an even stronger inverse association, particularly in unfit men. Men in the upper third of VO(2max) were 75% less likely than unfit men to develop the metabolic syndrome, even after adjustment for major confounders. Adjustment for possible mediating factors attenuated the association. Associations of LTPA and VO(2max) with development of the metabolic syndrome, as defined by the NCEP, were qualitatively similar. CONCLUSIONS: In particular, high-risk men engaging in currently recommended levels of physical activity were less likely to develop the metabolic syndrome than sedentary men. Cardiorespiratory fitness was also strongly protective, although possibly not independent of mediating factors.

Adult↗