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Biomedical subjects

David E Laaksonen

Publications and source records attributed to David E Laaksonen.

At least 19 recordsLinked to original sources
PubMed2007

Markers of absorption and synthesis of cholesterol in men with type 1 diabetes.

BACKGROUND AND METHODS: Serum cholestanol and plant sterol ratios to cholesterol, surrogate markers of cholesterol absorption, are assumed to be high in type 1 diabetes (T1D), and the ratios of cholesterol precursor sterols (markers of synthesis) are assumed to be low reflecting downregulated cholesterol synthesis. To this end, we measured serum sterols with gas-liquid-chromatography in 56 men with T1D and in 18 controls to evaluate cholesterol metabolism. Subjects were categorised into tertiles by the cholestanol to cholesterol ratio of controls indicating low to high absorption of cholesterol. RESULTS: The ratios of the synthesis markers were negatively related to the absorption markers in controls, but less consistently in T1D. The absorption markers were positively related to each other, but interrelation of the synthesis markers was less consistent in T1D. In the low absorbers the absorption markers were higher in T1D than in controls (e.g. sitosterol ratio 173 +/- 9 in T1D vs 135 +/- 11 10(2) x mmol/mol of cholesterol in controls, p < 0.05). In the high absorbers, the absorption markers were similar in T1D and controls, but the synthesis markers were higher in T1D than in controls (e.g. lathosterol ratio 154 +/- 10 in T1D vs 120 +/- 5 10(2) x mmol/mol of cholesterol in controls, p < 0.05). CONCLUSIONS: Absorption and synthesis of cholesterol are less closely related to each other in T1D than in controls, but the markers of cholesterol absorption are interrelated also in T1D. Absorption of cholesterol is higher in T1D than in controls within the range of low absorption, but similar in those with relatively high cholesterol absorption.

Adult↗
PubMed2006

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↗
PubMed2006

Cholesterol metabolism and non-cholesterol sterol distribution in lipoproteins of type 1 diabetes: the effect of improved glycemic control.

In type 1 diabetes, the ratios to cholesterol of serum absorption markers, e.g., cholestanol, are elevated and those of synthesis markers, e.g., lathosterol, are reduced suggesting perturbed cholesterol metabolism. We studied 17 subjects with type 1 diabetes in poor glycemic control at baseline to assess whether improvement of glycemic control affects lathosterol and cholestanol ratios to cholesterol and their distribution in lipoproteins. Cholesterol and the non-cholesterol sterols were assayed directly from serum, and free and ester fractions after thin-layer chromatographic separation of lipoprotein sterols with gas-liquid chromatography. After the 2-6 months follow-up, the mean value of HbA1(c) decreased from 10.8% to 8.6% (p=0.001). Even though the concentrations of serum and lipoprotein cholesterol remained unchanged, the serum lathosterol to cholesterol ratio increased by 28% (p<0.05) and the lathosterol/cholestanol proportion by 23% (p<0.05). The ratios of total and esterified lathosterol to cholesterol in serum, chylomicrons and LDL, and free lathosterol to cholesterol in serum and IDL, were negatively associated with HbA1(c) at baseline and after follow-up, suggesting that the better glycemic control, the higher was cholesterol synthesis. The absorption markers were less consistently associated with HbA1(c). About half of the serum lathosterol and cholestanol was carried in LDL and one-fourth to one-fifth in HDL, but the lathosterol ratios were roughly similar in all lipoproteins. In contrast, cholestanol accumulated in chylomicrons and HDL. Glycemic control did not affect the distributions of lathosterol and cholestanol. In conclusion, improvement in glycemic control increased cholesterol synthesis, but had no effect on cholesterol absorption as measured by the serum or lipoprotein cholestanol to cholesterol ratio. From a clinical point of view, the better the glycemic control, the more antiatherogenic cholesterol metabolism may be in type 1 diabetes.

Adult↗
PubMed2006

Interaction between cholesterol and glucose metabolism during dietary carbohydrate modification in subjects with the metabolic syndrome.

BACKGROUND: Carbohydrate modification based on rye bread and pasta enhances early insulin secretion in subjects with the metabolic syndrome. OBJECTIVE: Because the actions of insulin and cholesterol metabolism are interrelated, the question is raised of whether it is possible to alter cholesterol metabolism by means of dietary carbohydrate modification. DESIGN: We investigated the 12-wk effects of dietary carbohydrate modification on cholesterol synthesis and absorption by measuring the ratios of surrogate markers of precursor (cholestenol, desmosterol, and lathosterol) and absorption (cholestanol and plant sterols) sterols to cholesterol and their association to glucose metabolism in 74 subjects with the metabolic syndrome. The subjects were randomly assigned to diets with rye bread and pasta (RPa) or oat, wheat bread, and potato (OWPo) as the main carbohydrate source (34% and 37% of energy intake, respectively). RESULTS: During the study, serum cholesterol concentrations remained unchanged. Cholesterol synthesis was lower (6-10% for cholestenol and lathosterol; P < 0.05) and absorption higher (9%; P < 0.05 for sitosterol) with the OWPo diet than at baseline. With the RPa diet, cholesterol absorption was lower and synthesis higher than with the OWPo diet. The increment in the glucose area under the curve with the RPa diet was positively related to baseline cholesterol synthesis (eg, lathosterol; r = 0.480, P < 0.05) and negatively to absorption (for cholestanol; r = -0.520, P < 0.05). In the combined group, the changes in the cholestanol ratio and the insulinogenic index were interrelated (r = -0.464, P < 0.001). CONCLUSIONS: Carbohydrate modifications had dissimilar effects on cholesterol metabolism. Consumption of RPa, as compared with OWPo, may be clinically more favorable because it seems to inhibit the absorption of cholesterol, a factor crucial in the development of arterial atherosclerosis.

Adult↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2005

C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study.

AIMS: Cut-offs for C-reactive protein concentrations have been recommended for risk stratification, but little is known about how these cut-offs predict cardiovascular risk in population-based cohorts. We therefore assessed the association of C-reactive protein levels with cardiovascular mortality in a population-based cohort of 2321 middle-aged men stratified by the presence of cardiovascular disease (CVD) at baseline. METHODS AND RESULTS: C-reactive protein concentrations were categorized according to current recommendations (1 and 3 mg/L). During the 15 year follow-up, 77 men without CVD and 121 men with CVD at baseline died of CVD. In men without CVD at baseline (n=1476), age-adjusted cardiovascular mortality was 4.1-fold higher (95% CI 2.1-8.2) for C-reactive protein levels between 3.0 and 9.9 mg/L at baseline than for C-reactive protein levels <1.0 mg/L. In men with CVD at baseline (n=845), the corresponding age-adjusted cardiovascular mortality was 3.3-fold higher (95% CI 2.0-5.3). Adjustment for conventional CVD risk factors attenuated the risk somewhat. Further adjustment for dietary and lifestyle factors and factors related to insulin resistance did not affect the association. Classification of C-reactive protein by tertiles gave qualitatively similar results, but identified twice as many men at high risk. C-reactive protein levels also predicted overall mortality. CONCLUSION: Currently, recommended cut-offs for C-reactive protein levels identify men at risk for cardiovascular and overall death independently of conventional and other risk factors in a population-based sample of middle-aged men with and without CVD at baseline. Lower cut-offs may better identify men at high risk for cardiovascular death, but improvement of current recommendations will require standardization of C-reactive protein assays.

Adult↗
PubMed2005

Prediction of cardiovascular mortality in middle-aged men by dietary and serum linoleic and polyunsaturated fatty acids.

BACKGROUND: Substitution of dietary polyunsaturated for saturated fat has long been recommended for the primary prevention of cardiovascular disease (CVD), but only a few prospective cohort studies have provided support for this advice. METHODS: We assessed the association of dietary linoleic and total polyunsaturated fatty acid (PUFA) intake with cardiovascular and overall mortality in a population-based cohort of 1551 middle-aged men. Dietary fat composition was estimated with a 4-day food record and serum fatty acid composition. RESULTS: During the 15-year follow-up, 78 men died of CVD and 225 of any cause. Total fat intake was not related to CVD or overall mortality. Men with an energy-adjusted dietary intake of linoleic acid (relative risk [RR] 0.39; 95% confidence interval [CI], 0.21-0.71) and PUFA (RR, 0.38; 95% CI, 0.20-0.70) in the upper third were less likely to die of CVD than men with intake in the lower third after adjustment for age. Multivariate adjustment weakened the association somewhat. Mortality from CVD was also lower for men with proportions of serum esterified linoleic acid (RR, 0.42; 95% CI, 0.21-0.80) and PUFA (RR, 0.25; 95% CI, 0.12-0.50) in the upper vs lower third, with some attenuation in multivariate analyses. Serum and to a lesser extent dietary linoleic acid and PUFA were also inversely associated with overall mortality. CONCLUSIONS: Dietary polyunsaturated and more specifically linoleic fatty acid intake may have a substantial cardioprotective benefit that is also reflected in overall mortality. Dietary fat quality seems more important than fat quantity in the reduction of cardiovascular mortality in men.

Adult↗
PubMed2005

Dietary carbohydrate modification enhances insulin secretion in persons with the metabolic syndrome.

BACKGROUND: The metabolic syndrome markedly increases the risk of type 2 diabetes and cardiovascular disease, but the influence of dietary modification on insulin and glucose metabolism independent of weight loss is still poorly understood. OBJECTIVE: Our aim was to test whether carbohydrate dietary modifications improve insulin sensitivity and secretion and glucose tolerance in overweight or obese persons with the metabolic syndrome, even in the absence of weight loss. DESIGN: We assessed the effect of carbohydrate modification on insulin and glucose metabolism in 72 overweight or obese men and women with the metabolic syndrome, as determined according to the National Cholesterol Education Program criteria. The subjects were randomly assigned to 12-wk diets in which either rye bread and pasta or oat and wheat bread and potato were the main carbohydrate sources (34% and 37% of energy intake, respectively). RESULTS: Body weight did not significantly change in either group during the trial. No significant difference was observed in the changes in fasting glucose and insulin concentrations or in glucose and insulin areas under the curve between the groups during a 2-h oral-glucose-tolerance test. The insulinogenic index (an index of early insulin secretion) increased more in the rye bread and pasta group than in the oat and wheat bread and potato group (33.2% compared with 5.5%; P = 0.026). In the combined groups, an enhanced insulinogenic index was associated with improved glucose tolerance, whereas weight gain worsened glucose tolerance. Moreover, even modest weight gains abolished the relative improvement in the insulinogenic index in the rye bread and pasta group compared with the oat and wheat bread and potato group (P for the interaction between weight change and group = 0.019). CONCLUSIONS: Rye bread and pasta-based carbohydrate modification enhances early insulin secretion in persons with the metabolic syndrome, which may lower the risk of deteriorating glucose tolerance and development of type 2 diabetes.

Adult↗
PubMed2005

Physical activity in the prevention of type 2 diabetes: the Finnish diabetes prevention study.

Clinical trials have demonstrated that lifestyle changes can prevent type 2 diabetes, but the importance of leisure-time physical activity (LTPA) is still unclear. We carried out post hoc analyses on the role of LTPA in preventing type 2 diabetes in 487 men and women with impaired glucose tolerance who had completed 12-month LTPA questionnaires. The subjects were participants in the Finnish Diabetes Prevention Study, a randomized controlled trial of lifestyle changes including diet, weight loss, and LTPA. There were 107 new cases of diabetes during the 4.1-year follow-up period. Individuals who increased moderate-to-vigorous LTPA or strenuous, structured LTPA the most were 63-65% less likely to develop diabetes. Adjustment for changes in diet and body weight during the study attenuated the association somewhat (upper versus lower third: moderate-to-vigorous LTPA, relative risk 0.51, 95% CI 0.26-0.97; strenuous, structured LTPA, 0.63, 0.35-1.13). Low-intensity and lifestyle LTPA and walking also conferred benefits, consistent with the finding that the change in total LTPA (upper versus lower third: 0.34, 0.19-0.62) was the most strongly associated with incident diabetes. Thus increasing physical activity may substantially reduce the incidence of type 2 diabetes in high-risk individuals.

Diabetes Mellitus, Type 2↗
PubMed2004

The metabolic syndrome and smoking in relation to hypogonadism in middle-aged men: a prospective cohort study.

In men, hypoandrogenism is associated with features of the metabolic syndrome. It is not known whether men with the metabolic syndrome are at a higher risk of developing hypogonadism. We therefore assessed whether the metabolic syndrome predicts development of hypogonadism 11 yr later in 651 middle-aged Finnish men participating in a population-based cohort study. Men with the metabolic syndrome at baseline as defined by the World Health Organization (n = 114, 20%) had a 2.6-fold increased risk of developing hypogonadism as defined by total testosterone levels less than 11 nmol/liter at the 11-yr follow-up independent of age, smoking, and other potential confounders. Further adjustment for body mass index (OR, 2.0; 95% CI, 1.1-3.8) or baseline total testosterone levels (OR, 1.9; 95% CI, 1.0-3.4) attenuated the association. The association of the metabolic syndrome with hypogonadism as defined by calculated free testosterone levels less than 225 pmol/liter was similar, but weaker. The adjusted decrease in testosterone concentrations during the 11-yr follow-up was also greater in men with than without the metabolic syndrome. Smokers had a nonsignificantly lower risk of developing hypogonadism during follow-up, whereas a decrease in smoking increased the risk of hypogonadism. The metabolic syndrome predisposes to development of hypogonadism in middle-aged men. Prevention of abdominal obesity and the accompanying metabolic syndrome in middle age may decrease the risk of hypogonadism in men, especially in those who quit smoking.

Blood Glucose↗
PubMed2004

Inflammation, abdominal obesity, and smoking as predictors of hypertension.

Development of hypertension has been linked to chronic low-grade inflammation. However, it is not known whether this connection is mediated by features of the metabolic syndrome or smoking, or their changes, which themselves have been linked to inflammation. We studied the predictive value of highly sensitive C-reactive protein (hs-CRP), smoking, and abdominal obesity to the development of hypertension in an 11-year follow-up of a population-based study cohort comprising 379 middle-aged normotensive men. During the follow-up, 124 men (33%) developed hypertension. Men with hs-CRP > or =3.0 mg/L were 2.8x (95% confidence interval, 1.2 to 6.6) more likely to develop hypertension than with hs-CRP <1.0 mg/L even after adjustment for features of the metabolic syndrome, lifestyle factors, and their changes. Cigarette smoking was also associated with development of hypertension independently of inflammation and other confounders. Waist girth increased more in men who quit smoking than in other men. An increase in waist girth during follow-up strongly predicted incident hypertension. The decrease in smoking was not associated with a lower risk of hypertension in age-adjusted analyses. Hypertension is preceded by low-grade chronic inflammation in middle-aged white men independently of smoking or features of the metabolic syndrome. Furthermore, smoking may be a risk factor for hypertension. Although stopping smoking is beneficial with respect to health outcomes, the subsequent increase in weight and waist girth associated with smoking cessation may offset the decrease in the risk of hypertension that one may otherwise expect.

Alcohol Drinking↗
PubMed2004

Serum linoleic and total polyunsaturated fatty acids in relation to prostate and other cancers: a population-based cohort study.

Dietary and serum fatty acid composition has been implicated in the pathogenesis of prostate and other cancers, but findings have been conflicting. Cohort studies reporting serum fatty acid composition are lacking. We assessed the association of fatty acid composition determined from dietary records and serum with incident cancer of the prostate and any site in a population-based cohort of 2,002 middle-aged Finnish men who were free of cancer at baseline and during the first 4 years of follow-up. During 12.6 years of follow-up, 46 men developed prostate cancer and 151 any cancer. Men with proportions of serum nonesterified [risk ratio (RR) 0.28; 95% confidence intervals (CI) 0.12-0.66] and esterified linoleic acid (RR 0.37; 95% CI = 0.16-0.86) and total polyunsaturated fatty acids (RR 0.30; 95% CI = 0.12-0.71) in the upper third were less than 1/3 as likely to develop prostate cancer during follow-up. Adjustment for possible confounders like socioeconomic status, physical activity, obesity and insulin concentrations did not attenuate the association. Similar but weaker associations with any cancer were found. Dietary linoleic acid intake also tended to be inversely associated with incident prostate cancer (age-adjusted RR for the upper vs. lower third 0.55; 95% CI = 0.26-1.14, p for the trend 0.097). Substitution of linoleic acid for saturated fat in middle-aged men consuming a high saturated-fat diet may decrease the risk of prostate and other cancers, although it is possible that some of the effect may be mediated by nutrients closely associated with vegetable fats.

Blood Glucose↗
PubMed2004

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↗
PubMed2004

Exercise training modulates heat shock protein response in diabetic rats.

Strenuous exercise induces oxidative stress and modification of intracellular proteins. Exercise training, however, upregulates endogenous antioxidant defenses and heat shock protein (HSP) expression. In diabetes, perturbations in the endogenous antioxidant and HSP protection have been reported. The aim of this study was to examine the effect of 8 wk of endurance training on HSP expression and oxidative stress markers in the skeletal muscle, heart, and liver of streptozotocin-induced diabetic (SID) and nondiabetic control rats. Induction of diabetes decreased HSP72 expression in heart, liver, and vastus lateralis muscles. SID increased heme oxygenase-1, an oxidative stress-inducible HSP, in liver, red gastrocnemius muscle, and vastus lateralis muscle and glucose-regulated protein 75 in liver. SID increased HSP90 levels in the heart, but levels decreased in the liver. Diabetes induced oxidative stress marker protein carbonyl levels and tissue inflammation. Although endurance training increased the expression of HSP72 in all of the tissues examined, this induction was less pronounced in diabetic rats than in nondiabetic controls. Furthermore, endurance training induced the activation and expression of transcriptional regulator heat shock factor-1 only in nondiabetic control animals. In summary, diabetes may increase susceptibility to oxidative damage and impair HSP protection, but endurance training may offset some of the adverse effects of diabetes by upregulating tissue HSP expression. Our results suggest that diabetes impairs HSP protection, possibly via transcriptionally mediated mechanisms.

Animals↗
PubMed2004

Epidemiology and treatment of the metabolic syndrome.

Recent definitions of the metabolic syndrome from the World Health Organization (WHO) and National Cholesterol Education Program (NCEP) have given us a clearer picture of the prevalence of the metabolic syndrome and the risks it poses for cardiovascular disease and type 2 diabetes. Solid epidemiological and trial evidence support lifestyle changes as the main modifiable risk factors, including abdominal obesity, sedentary lifestyle and a diet rich in saturated fat and low in fiber content, in the treatment of individual components of the metabolic syndrome. Physical activity may prevent the metabolic syndrome as defined by the WHO and NCEP, but the evidence for lifestyle changes using these definitions is still sparse. No trials on the treatment of the metabolic syndrome to prevent diabetes have been published. However, both the Finnish Diabetes Prevention Study and the Diabetes Prevention Program found that moderate lifestyle interventions in persons with impaired glucose tolerance, a condition related to the metabolic syndrome. decreased the incidence of type 2 diabetes by 58%. Some drugs may also prevent diabetes. Further research on lifestyle modifications in the prevention and treatment of the metabolic syndrome, and on how best to promote lifestyle changes, is needed. In the meantime, efforts to curb obesity and overweight, increase physical activity and improve compliance with current dietary recommendations should continue.

Cardiovascular Diseases↗
PubMed2004

The effect of home biofeedback training on stress incontinence.

BACKGROUND: To compare the effectiveness of pelvic floor training (PFT) with the aid of a home biofeedback device to PFT alone for urodynamic stress urinary incontinence (SUI) in women after a 1-year follow-up. METHODS: A randomized study comparing two conservative interventions was conducted in an outpatient clinic of a university hospital. Thirty-five consecutive women were randomized to either the PFT with home biofeedback group or the PFT alone group. The intensive training period lasted 12 weeks. After 1 year, 33 women could be evaluated according to the protocol. At the 1-year visit pelvic floor muscle activity was measured and the need for surgical intervention was evaluated. Logistic multivariate analysis was used to predict response to the PFT. RESULTS: In the home biofeedback training group 11/16 (68.8%) avoided surgery vs. 10/19 (52.6%) in the PFT alone group. The difference was not statistically significant. In the nonoperated home biofeedback group the increase in pelvic floor muscle activity (p = 0.005 in supine, p = 0.005 in standing) and the decrease in leakage index (p = 0.05) was significant after 12 weeks and pelvic floor activity remained constant. By contrast, in the nonoperated PFT group the increase in pelvic floor muscle activity after 12 weeks predicted a good result for conservative treatment. CONCLUSIONS: This randomized controlled trial suggests that the home biofeedback method in PFT has a good success rate of 68.8%. The change achieved in leakage index after 12 weeks of training predicted an effective outcome for conservative treatment.

Adult↗