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Biomedical subjects

M Laakso

Publications and source records attributed to M Laakso.

At least 55 records · Page 3Linked to original sources
PubMed2002

Association of neck circumference with insulin resistance-related factors.

AIM: Overall and central obesity are associated with disorders in lipid and glucose metabolism, insulin resistance, hypertension, atherosclerosis and type 2 diabetes. Waist circumference and abdominal sagittal diameter have been suggested as the best simple anthropometric indexes of abdominal visceral fat accumulation. The aim of the present study was to test the association of neck circumference with abdominal and general obesity as well as with insulin resistance related factors. METHOD: Neck circumference was measured in addition to the traditional anthropometric measures and blood lipids, insulin and glucose concentrations and blood pressure. RESULTS: The prevalence rates of disorders in lipid or glucose metabolism and high fasting insulin concentrations were highest in the highest quintiles of all the anthropometric measures. CONCLUSION: We conclude that neck circumference is associated with the metabolic disorders related to insulin resistance. The measurement of neck circumference could be useful in clinical screening for persons at an enhanced risk for insulin resistance.

Abdomen↗
PubMed2002

Serum homocysteine, creatinine, and glucose as predictors of the severity and extent of coronary artery disease in asymptomatic members of high-risk families.

BACKGROUND: There has been no previous study to determine the severity and extent of coronary artery disease (CAD) in subjects with no diagnosis or symptoms of CAD at the time of the angiography. METHODS: Fifty-three subjects, who were siblings of patients with early onset CAD, underwent coronary angiography. Indices to describe per-patient characteristics of CAD were calculated, based on computer-aided quantitative coronary angiography. Clinical and laboratory characteristics were correlated to the angiographic parameters. RESULTS: Serum total homocysteine (rho = 0.29, P < 0.05) and creatinine (rho = 0.47, P = 0.001) levels were related to the global atheroma burden index. The median of the atheroma burden index was two times higher in the top homocysteine quartile compared to the lowest quartile. The overall atheroma burden index correlated significantly with the fasting blood glucose level in all subjects. Diabetes, especially when albuminuria was present, was a powerful risk factor. In a multivariate analysis, only age and sex were independent predictors of atheroma burden. CONCLUSIONS: Serum homocysteine and creatinine concentrations, and diabetes with albuminuria were found to be markers of the severity and extent of CAD in subjects of high-risk families without symptoms of CAD.

Biomarkers↗
PubMed2002

Acute insulin response tests for the differential diagnosis of congenital hyperinsulinism.

Mutations in genes encoding the two subunits of the beta-cell ATP-sensitive potassium channel (K(ATP)) channel (SUR1 and Kir6.2) are the major cause of congenital hyperinsulinism (CHI). In this study, the K(ATP) channel genes were screened in a population-based study that included all verified Finnish CHI patients (n = 43) in a 27-yr period. Seven different mutations were identified, which accounted for 60% of all cases. The functional consequences of the major missense mutations were studied in vivo by determining acute (1-3 min) plasma insulin and C-peptide responses to calcium (n = 18), glucose (n = 12), and tolbutamide (n = 11) in those CHI patients who were able to take part in these studies. C-peptide and insulin responses to calcium were significantly higher in the patients with SUR1-E1506K mutation, compared with patients without K(ATP) channel mutations. The patients with SUR1-V187D mutation showed a reduced response to tolbutamide but unexpectedly did not show any response to calcium stimulation. A compound heterozygous patient with Kir6.2-(-54)/K67N mutations responded to calcium but also to tolbutamide. In conclusion, our results show that a positive response in the calcium test is indicative of a K(ATP) channel mutation, but all mutations cannot be identified with this method. The insulin response to tolbutamide in patients with SUR1 mutations is impaired to different extents, depending on the genotype. The combination of calcium and tolbutamide tests is a useful tool for the detection of CHI patients with K(ATP) channel dysfunction. Our results, however, also demonstrate the complexity of these responses and the difficulties in their interpretation.

Adolescent↗
PubMed2002

Effect of the Pro12Ala polymorphism of the peroxisome proliferator-activated receptor gamma-2 gene on adiposity, insulin sensitivity and lipid profile in the Spanish population.

OBJECTIVE: To investigate the role of the Pro12Ala peroxisome proliferator-activated receptor (PPAR) gamma-2 polymorphism in the susceptibility to the insulin resistance syndrome and its metabolic complications in a population-based nationwide multicenter study in Spain. DESIGN: 464 unrelated adults (45.3% men and 54.7% women) aged between 35 and 64 years were randomly chosen from a nationwide population-based survey of obesity and related conditions including insulin resistance and cardiovascular risk factors. METHODS: Anthropometric determinations included: body mass index (BMI), waist-to-hip ratio, sagittal abdominal diameter; biochemical determinations included: fasting plasma glucose concentration and concentration 2 h after an oral glucose tolerance test (OGTT), total cholesterol, high and low density lipoprotein-cholesterol, triglycerides, leptin and insulin. Systolic and diastolic blood pressure were also measured. Genotyping of the PPARgamma-2 Pro12Ala polymorphism was determined by polymerase chain reaction and single strand conformation polymorphism analysis. RESULTS: The Ala12 allele frequency was higher in obese men than in lean men (0.15 vs 0.08, P=0.03). Men carriers of the Ala12 allele had a higher BMI than non-carriers (38.9% vs 21.3%; adjusted odds ratio 2.36, 95% confidence interval 1.10-5.05, P=0.03). However, despite higher BMI obese men carriers of the Ala12 allele had lower sagittal abdominal diameter than Pro12 homozygotes (24.1+/-3.2 vs 26.3+/-2.5 cm, P=0.01). The Ala12 allele was associated with lower total triglycerides levels in the overall population and it was also associated with lower fasting insulin levels and a higher insulin sensitivity by homeostasis model assessment (HOMA) in women. CONCLUSIONS: Our results suggest that the Pro12Ala polymorphism of the PPARgamma-2 gene promotes peripheral deposition of adipose tissue and increased insulin sensitivity for a given BMI. The results in women might be due to their different adipose tissue distribution.

Adipose Tissue↗
PubMed2002

Variation in the fatty acid binding protein 2 gene is not associated with markers of metabolic syndrome in patients with coronary heart disease.

BACKGROUND AND AIM: It has been suggested that the threonine (Thr) 54 allele of the intestinal fatty acid binding protein 2 (FABP2) gene is associated with insulin resistance and affects the fatty acid composition of serum lipids. Our aim was to investigate the frequency of the alanine (Ala) 54Thr polymorphism of the FABP2 gene in patients with coronary heart disease (CHD), and the association between the polymorphism and the markers of metabolic syndrome, serum lipid levels and the fatty acid profile of serum lipids. METHODS AND RESULTS: A total of 414 CHD patients (mean age 61 years, range 33-74) participated in the cross-sectional EUROASPIRE (European Action on Secondary Prevention through Intervention to Reduce Events) Study. Markers of metabolic syndrome included fasting plasma glucose concentration, serum high-density lipoprotein cholesterol and triglycerides (TG), waist circumference, the waist/hip ratio, body mass index (BMI) and blood pressure (BP). The frequency of the Thr54 allele was similar in the CHD patients (27.2%) and control subjects from two independent studies (27.8% and 28.7%). There were no significant differences in plasma glucose, serum lipids, BP, BMI, waist circumference or waist/hip ratio among the genotypes. Genotype frequency was not associated with the prevalence of diabetes or metabolic syndrome, but metabolic syndrome (as defined by National Cholesterol Education Program criteria) tended to be more frequent in subjects with the Thr/Thr genotype (p = 0.095). There were no differences in the fatty acid profiles of serum cholesteryl esters, TG or phospholipids among the genotypes. CONCLUSIONS: The Ala54Thr polymorphism of the FABP2 gene is not associated with CHD, markers of the metabolic syndrome, or the fatty acid profile of serum lipids in Finnish CHD patients.

Adult↗
PubMed2001

Apolipoprotein E gene promoter (-219G/T) polymorphism is associated with premature coronary heart disease.

The relationship of two apolipoprotein (apo) E gene polymorphisms and coronary heart disease (CHD) was investigated in 118 Finnish families with premature CHD and in 110 healthy control subjects. Affected siblings and probands with premature CHD had higher frequencies of the T allele of the -219G/T promoter polymorphism and the epsilon 4 allele (genotypes epsilon 4/3 or epsilon 4/4) of the apo epsilon 2/epsilon 3/ epsilon 4 polymorphism than those of healthy control subjects. Additionally, when the two apo E gene polymorphisms were combined, affected siblings and probands had a higher frequency of the -219T allele and the epsilon 4 allele combinations than did healthy controls. The -219T and the epsilon 4 alleles both separately and together were associated with higher levels of 2-h glucose in an oral glucose tolerance test. These results indicate that the two polymorphisms of the apo E gene have similar effects on the risk of coronary atherosclerosis in families with premature CHD. This risk was not explained by the effect of apo E gene polymorphisms on cholesterol metabolism, but their effect on cardiovascular risk factor clustering with insulin resistance may be of importance. We conclude that in addition to the epsilon 4 allele, also the -219G/T promoter polymorphism of the apo E gene is associated with early onset CHD.

Age of Onset↗
PubMed2001

Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance.

BACKGROUND: Type 2 diabetes mellitus is increasingly common, primarily because of increases in the prevalence of a sedentary lifestyle and obesity. Whether type 2 diabetes can be prevented by interventions that affect the lifestyles of subjects at high risk for the disease is not known. METHODS: We randomly assigned 522 middle-aged, overweight subjects (172 men and 350 women; mean age, 55 years; mean body-mass index [weight in kilograms divided by the square of the height in meters], 31) with impaired glucose tolerance to either the intervention group or the control group. Each subject in the intervention group received individualized counseling aimed at reducing weight, total intake of fat, and intake of saturated fat and increasing intake of fiber and physical activity. An oral glucose-tolerance test was performed annually; the diagnosis of diabetes was confirmed by a second test. The mean duration of follow-up was 3.2 years. RESULTS: The mean (+/-SD) amount of weight lost between base line and the end of year 1 was 4.2+/-5.1 kg in the intervention group and 0.8+/-3.7 kg in the control group; the net loss by the end of year 2 was 3.5+/-5.5 kg in the intervention group and 0.8+/-4.4 kg in the control group (P<0.001 for both comparisons between the groups). The cumulative incidence of diabetes after four years was 11 percent (95 percent confidence interval, 6 to 15 percent) in the intervention group and 23 percent (95 percent confidence interval, 17 to 29 percent) in the control group. During the trial, the risk of diabetes was reduced by 58 percent (P<0.001) in the intervention group. The reduction in the incidence of diabetes was directly associated with changes in lifestyle. CONCLUSIONS: Type 2 diabetes can be prevented by changes in the lifestyles of high-risk subjects.

Diabetes Mellitus, Type 2↗
PubMed2001

APOE-epsilon4 is associated with weight loss in women with AD: a population-based study.

OBJECTIVE: To investigate whether the APOE-epsilon4 allele is associated with weight loss in patients with AD or in nondemented elderly subjects. BACKGROUND: Weight loss has been considered a typical feature of AD. APOE-epsilon4 is a risk factor for AD and was recently proposed to be associated with weight loss in elderly women. It is not known whether APOE-epsilon4 is associated with weight loss in patients with AD or in the general population. METHODS: Weight and BMI measurements at an average interval of 3.5 years and APOE phenotype determination were performed in an elderly population (n = 980), including 46 patients with AD and 911 control subjects at the end of the follow-up. RESULTS: On average, patients with AD with the epsilon4 allele lost 1.9 +/- 4.0 kg (BMI 0.8 +/- 1.8 kg/m2) whereas epsilon4 noncarriers gained 1.2 +/- 3.8 kg (BMI 0.4 +/- 1.5 kg/m2) (both p < 0.05), after controlling for diabetes and exercise. However, when men and women were analyzed separately, weight loss was observed only in those women with AD with the epsilon4 allele. Clinically significant weight loss, defined as loss of > or = 5% of body weight, occurred more frequently in both patients with AD (30% versus 6%; p < 0.05) and control subjects (28% versus 18%; p < 0.001) carrying the epsilon4 allele. CONCLUSIONS: The APOE-epsilon4 allele may contribute to the unexplained weight loss in AD, especially in women.

Aged↗
PubMed2001

Association of angiotensin converting enzyme and plasminogen activator inhibitor-1 promoter gene polymorphisms with features of the insulin resistance syndrome in patients with premature coronary heart disease.

Polymorphisms of the angiotensin-converting enzyme (ACE) (insertion/deletion (I/D) in intron 16) and of the plasminogen activator inhibitor-1 (PAI-1) (promoter 4G/5G) genes have been linked with coronary heart disease (CHD) and/or myocardial infarction (MI). We studied the association of polymorphisms in these genes with CHD with linkage and association analyses in 118 families with premature and severe CHD and in 110 healthy controls. In linkage analysis there was no evidence for a linkage of the ACE or PAI-1 loci with CHD. However, in quantitative linkage analysis the ACE locus was linked with fasting glucose (P=0. 047) and fasting free fatty acid levels (P=0.029). In association analysis the ACE genotype frequencies of probands with CHD did not differ from those of healthy controls. Normoglycemic probands with MI and with the ACE polymorphism DD genotype had characteristics of the insulin resistance syndrome. They had higher levels of 1-h glucose (P=0.008) and 2-h free fatty acids (P=0.011) in an oral glucose tolerance test and higher levels of total (P=0.005) and very-low-density lipoprotein triglycerides (P=0.006) than probands with the ID or the II genotypes. The PAI-1 gene polymorphism was not associated with any of the variables of glucose or lipid metabolism. In conclusion, the ACE and PAI-1 gene polymorphisms are not linked with early-onset CHD. However, the ACE gene polymorphism is associated with features of the insulin resistance syndrome.

Aged↗
PubMed2001

Effect of a three-amino acid deletion in the alpha2B-adrenergic receptor gene on long-term body weight change in Finnish non-diabetic and type 2 diabetic subjects.

BACKGROUND AND OBJECTIVE: The short form (Glu9/Glu9) of the 12Glu9 deletion polymorphism of the alpha2B-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 C-peptide and glycosylated hemoglobin A1c. 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 Glu9/Glu9 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 Glu12/Glu12, Glu12/Glu9 and Glu9/Glu9 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 Glu9/Glu9 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 (Glu9/Glu9) was associated with an increase in body weight among non-diabetic subjects.

Amino Acid Sequence↗
PubMed2001

Alpha-synuclein pathology is highly dependent on the case selection.

Lewy bodies and dystrophic neurites have been considered a common substrate for dementia, but they are also frequently found in the normal elderly population. The primary component of this pathology involves alpha-synuclein. The main objective of the present study was to estimate the prevalence of alpha-synuclein pathology in aged population, and to assess its relative significance in relation to dementia. The study also investigated whether differences could be detected in alpha-synuclein pathology in relation to age, gender or concomitant Alzheimer's pathology. Furthermore, the influence of sampling strategies was analysed. Alpha-synuclein pathology was assessed using immunohistochemistry in well-characterized post-mortem material. The investigation included patients from a longitudinal study of dementia of Alzheimer's type (n = 103, 85% demented), subjects from a prospective longitudinal clinical study of ageing (n = 69, 29% demented), a cohort of consecutive clinical post-mortem cases collected for 1 year (n = 262, 12% demented), a sample of forensic post-mortem cases collected for 6 months (n = 121, 15% demented) and a sample of Brain Bank material (n = 234, 26% demented). Overall, alpha-synuclein pathology was found in 14% of all 774 subjects over 40 years of age, and this percentage varied from 8% to 27% according to sampling strategies. These results indicate that the prevalence of alpha-synuclein pathology clearly depends on the selection of material. Furthermore alpha-synuclein pathology was found in 23% of clinically demented patients and in 11% of non-demented subjects. The load of alpha-synuclein pathology was significantly greater in the demented patients versus non-demented subjects indicating that alpha-synuclein pathology is indeed of importance in the pathogenesis of dementia.

Adult↗
PubMed2001

Heart rate variability and its determinants in patients with severe or mild essential hypertension.

How cardiac autonomic nervous control is related to the severity of essential hypertension in patients receiving long-term antihypertensive therapy is not well known. The aim of this study was to examine heart rate variability (HRV), a non-invasive measure of cardiac autonomic function, in patients with long-term and medically treated mild and severe essential hypertension and healthy control subjects, and to assess the clinical determinants of HRV in these patients. Thirty-four patients with severe essential hypertension (SEHT) and 29 with mild essential hypertension (MEHT) as well as healthy age- and sex-matched control subjects were studied. HRV was assessed from 10 min ECG-recordings during paced (0.2 Hz) breathing at rest and expressed as time and frequency domain measures. In the SEHT group time (SDNN, RMSSD) and frequency domain measures (total power, low-frequency (LF) power and high-frequency (HF) power of HRV in absolute units, and LF and HF power of HRV in normalized units) of HRV were significantly lower when compared with those of the control group. The MEHT and control groups did not differ from each other with respect to time or frequency domain measures of HRV. Comparison between the hypertensive groups showed that SDNN, total power, LF power and HF power were lower in the SEHT group compared with the MEHT group (P<0.05 for all). Among hypertensive patients RR-interval, age, gender, systolic finger blood pressure and diastolic office blood pressure as well as 24-h blood pressure were significant determinants of HRV. In conclusion, we found that the severity of chronic essential hypertension seems to be related to the severity of impairment of cardiac autonomic control.

Adult↗
PubMed2001

The hormone sensitive lipase gene in familial combined hyperlipidemia and insulin resistance.

BACKGROUND: Insulin resistance in the most common familial dyslipidemia, familial combined hyperlipidemia (FCHL), could be due to variations in the hormone sensitive lipase (HSL) gene. MATERIALS AND METHODS: The coding region of the HSL gene was screened with the single strand conformation polymorphism analysis in probands of 27 FCHL families with 228 members. In addition, the C-60G promoter substitution of the HSL gene was determined by the restriction fragment length polymorphism analysis in these subjects. RESULTS: No variants in the coding region of the HSL gene were found and the allele frequencies of the C-60G promoter substitution and the silent variant (G3138A) in the 3' untranslated region did not differ between 110 control subjects and 27 probands with FCHL. However, in control women the C-60G substitution was associated with high body mass index [30.6 +/- 0.9 kg m(-2) (mean +/- SD) in subjects with the C/G genotype and 24.8 +/- 4.6 in subjects with the C/C genotype, P = 0.012], and in control men with high rates of insulin-stimulated whole body glucose uptake (70.1 +/- 14.7 vs. 56.7 +/- 14.2 micromol kg(-1) min(-1), P = 0.014). In 228 FCHL family members this substitution was associated with high low-density lipoprotein cholesterol levels in men (4.51 +/- 1.12 vs. 5.17 +/- 1.28 mmol L(-1), P = 0.049), but not in women. CONCLUSIONS: The HSL gene is not a major gene for FCHL. However, the - 60G allele of this gene may affect body weight, insulin sensitivity and serum cholesterol levels.

Adult↗
PubMed2001

Cardiovascular disease in type 2 diabetes: challenge for treatment and prevention.

Type 2 diabetes increases the risk of cardiovascular disease (CVD) two- to fourfold compared with the risk in non-diabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors (small, dense low-density lipoprotein [LDL] particles, low high-density lipoprotein [HDL] cholesterol, high triglycerides, elevated blood pressure, obesity, central obesity, hyperinsulinaemia, hyperglycaemia, etc.), the cause for an excess risk of CVD remains unknown. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol and blood pressure is similarly beneficial in diabetic and non-diabetic subjects. The treatment of hyperglycaemia reduces micro- and macrovascular complications in type 2 diabetic patients. Beta-blocking agents, angiotensin-converting enzyme inhibitors, aspirin, and thrombolytic therapy are also effective in the treatment of CVD amongst diabetic patients.

Adrenergic beta-Antagonists↗
PubMed2001

Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1.

Patients with autosomal dominant polycystic kidney disease (ADPKD) have an increased occurrence of cardiac valve abnormalities. However, the prevalence of cardiac abnormalities in patients with a uniform genotype of ADPKD has not been previously reported. We performed M-mode and color Doppler echocardiography on 109 patients from 16 families with polycystic kidney disease type 1 (PKD1). Findings were compared with those of 73 unaffected family members and 73 healthy controls. Mitral valve prolapse was found in 26% of patients with PKD1, 14% of unaffected relatives, and 10% of control subjects. The prevalence of hemodynamically significant mitral regurgitation (grade 2 or 3) was 13%, 4%, and 3%, respectively. Prevalences of grade 2 or 3 aortic regurgitation (8%, 4%, and 3%, respectively) and tricuspid regurgitation (4%, 6%, and 7%, respectively) were not significantly different among the three groups. Left ventricular hypertrophy (LVH) was found in 19% of subjects with PKD1, 6% of unaffected relatives, and 4% of control subjects. Systolic blood pressure and severity of renal insufficiency were related to mitral regurgitation and LVH in subjects with PKD1. The prevalence of cardiac valve abnormalities did not differ between unaffected relatives and control subjects. Mitral valve prolapse is a characteristic finding in patients with PKD1. Conversely, mitral regurgitation and LVH are likely to be secondary to elevated blood pressure in these patients.

Adolescent↗
PubMed2001

Postprandial responses of individual fatty acids in subjects homozygous for the threonine- or alanine-encoding allele in codon 54 of the intestinal fatty acid binding protein 2 gene.

BACKGROUND: The affinity of intestinal fatty acid binding protein (FABP) for fatty acids is regulated by the polymorphism at codon 54 of the FABP2 gene (alanine-to-threonine shift). We found earlier that the threonine-encoding allele (Thr54) is associated with an increased postprandial lipemic response. OBJECTIVE: We studied the postprandial responses of individual fatty acids in subjects homozygous for the Thr54 or alanine-encoding allele (Ala54). DESIGN: Oral-fat-loading tests were performed in 8 subjects homozygous for Thr54 and in 7 subjects homozygous for Ala54. RESULTS: The postprandial responses of most of the 14-18-carbon fatty acids in chylomicron and VLDL triacylglycerols were significantly elevated in the Thr54 homozygotes whereas the relative increases in these fatty acids were not significantly different in both groups. The amounts of 20- and 22-carbon polyunsaturated fatty acids started to increase later than the amounts of shorter ones after the test meal, and the differences between the groups were mostly insignificant. The responses of chylomicron fatty acids correlated positively with postprandial insulin response in the Thr54 homozygotes and inversely in the Ala54 homozygotes. VLDL fatty acid responses correlated with fasting triacylglycerol concentrations in the Ala54 homozygotes but not in the Thr54 homozygotes. CONCLUSION: The threonine-encoding allele of the FABP2 gene is associated with an increased postprandial response of 14-18-carbon fatty acids but not with changes in the relative amounts of individual fatty acids introduced to chylomicron triacylglycerols.

Aged↗