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Biomedical subjects

Jaakko Tuomilehto

Publications and source records attributed to Jaakko Tuomilehto.

At least 19 recordsLinked to original sources

Efficacy of indapamide SR compared with enalapril in elderly hypertensive patients with type 2 diabetes.

BACKGROUND: Blood pressure control is the main influential variable in reducing microalbuminuria in patients with type 2 diabetes. In this subanalysis of the Natrilix SR versus Enalapril Study in hypertensive Type 2 diabetics with micrOalbuminuRia (NESTOR) study, we have compared the effectiveness of indapamide sustained release (SR) and enalapril in reducing blood pressure and microalbuminuria in patients > or =65 years of age. METHODS: Of the 570 hypertensive patients with type 2 diabetes and persistent microalbuminuria in the NESTOR study, 187 (33%) individuals > or =65 years of age were included in this analysis. Of these, 95 patients received indapamide SR 1.5 mg and 92 patients received enalapril 10 mg, taken once daily in both cases. Adjunctive amlodipine and/or atenolol was added if required. RESULTS: The urinary albumin-to-creatinine ratio decreased by 46% in the indapamide SR group and 47% in the enalapril group. Noninferiority of indapamide SR over enalapril was demonstrated (P = .0236; 35% limit of noninferiority) with a ratio of 0.95 (95% CI: 0.68, 1.34). Mean arterial pressure decreased by 18 mm Hg and 15 mm Hg in the indapamide SR and the enalapril groups, respectively (P = .1136). The effects of both treatments seen in these elderly patients were similar to those observed in the main population, although the extent of the reduction in microalbuminuria was slightly higher. Both treatments were well tolerated, and no difference between groups was observed regarding glucose or lipid profiles. CONCLUSION: Indapamide SR is not less effective than enalapril in reducing microalbuminuria and blood pressure in patients aged >65 years of age with type 2 diabetes and hypertension.

Aged↗

Trends in lifestyle factors affecting blood pressure in hypertensive and normotensive Finns during 1982-2002.

OBJECTIVE: To assess the trends in blood pressure (BP) affecting lifestyle factors in hypertensive and normotensive Finns from 1982 to 2002. DESIGN AND SETTING: Five independent cross-sectional population surveys conducted in 1982, 1987, 1992, 1997 and 2002 in the provinces of North Karelia and Kuopio in eastern Finland and the region of Turku-Loimaa in southwestern Finland. PARTICIPANTS: Stratified random samples of men and women aged 25-64 years were drawn from the national population register. The participants (n = 28 235) were classified into four groups according to their BP level and treatment status: normotensive, unaware hypertensive, aware but untreated hypertensive, and treated hypertensive subjects. MAIN OUTCOME MEASURES: Alcohol intake, body mass index (BMI), 24-h urinary sodium and potassium excretion (a subsample of 5849 subjects) and the proportion of subjects with leisure-time physical activity (LTPA) at least three times a week. RESULTS: Mean BMI increased significantly in all groups except in untreated hypertensive women. Alcohol intake increased in all men but especially in hypertensive women (P < 0.001). The 24-h urinary sodium excretion decreased significantly in all BP groups. The proportion of subjects with a recommended level of LTPA increased significantly and similarly in all BP groups (P < 0.001). CONCLUSIONS: The unfavourable trends observed in mean BMI and alcohol intake in the entire population should be reversed in order to decrease the frequency of hypertension in Finland. The health behaviours of hypertensive subjects should be carefully monitored and modified in a more systematic and efficient way than at present.

Adult↗

Screening of 134 single nucleotide polymorphisms (SNPs) previously associated with type 2 diabetes replicates association with 12 SNPs in nine genes.

More than 120 published reports have described associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes. However, multiple studies of the same variant have often been discordant. From a literature search, we identified previously reported type 2 diabetes-associated SNPs. We initially genotyped 134 SNPs on 786 index case subjects from type 2 diabetes families and 617 control subjects with normal glucose tolerance from Finland and excluded from analysis 20 SNPs in strong linkage disequilibrium (r(2) > 0.8) with another typed SNP. Of the 114 SNPs examined, we followed up the 20 most significant SNPs (P < 0.10) on an additional 384 case subjects and 366 control subjects from a population-based study in Finland. In the combined data, we replicated association (P < 0.05) for 12 SNPs: PPARG Pro12Ala and His447, KCNJ11 Glu23Lys and rs5210, TNF -857, SLC2A2 Ile110Thr, HNF1A/TCF1 rs2701175 and GE117881_360, PCK1 -232, NEUROD1 Thr45Ala, IL6 -598, and ENPP1 Lys121Gln. The replication of 12 SNPs of 114 tested was significantly greater than expected by chance under the null hypothesis of no association (P = 0.012). We observed that SNPs from genes that had three or more previous reports of association were significantly more likely to be replicated in our sample (P = 0.03), although we also replicated 4 of 58 SNPs from genes that had only one previous report of association.

Aged↗

Subsets of Finns with high HDL to total cholesterol ratio show evidence for linkage to type 2 diabetes on chromosome 6q.

OBJECTIVES: The purpose of this study was to examine carefully heterogeneity underlying evidence for linkage to type 2 diabetes (T2DM) on chromosome 6q from two sets of FUSION families. METHODS: Ordered subsets analysis (OSA) was performed on two sets of FUSION families. For OSA results showing significant improvement in evidence for linkage, T2DM-related phenotypes were compared between individuals with T2DM within the subset versus the complement. RESULTS: OSA analysis revealed 105 families with the highest average HDL to total cholesterol ratio (HDL ratio) that had strongly increased evidence for linkage (MLS = 7.91 at 78.0 cM; uncorrected p = 0.00002). Subjects with T2DM within this subset were significantly leaner, had lower fasting glucose, insulin, and C-peptide, and more favorable cardiovascular risk profile compared to the complement set of subjects with T2DM. OSA also revealed 33 families with the lowest average fasting insulin that had increased evidence for linkage at a second locus (MLS = 3.45 at 128 cM; uncorrected p = 0.017) coincident with quantitative trait locus linkage analysis results for fasting and 2-hour insulin in subjects without T2DM. CONCLUSIONS: These results suggest two diabetes susceptibility loci on chromosome 6q that may affect subsets of individuals with a milder form of T2DM.

Aged↗

Alcohol drinking and cognitive functions: findings from the Cardiovascular Risk Factors Aging and Dementia (CAIDE) Study.

BACKGROUND: Moderate alcohol drinking is suggested to be beneficial for cognitive functions, but the results of previous studies have varied greatly. Little is known about the effects of midlife alcohol drinking on the cognitive functions later in life. METHODS: Participants were derived from random, population-based samples studied in Eastern Finland in 1972, 1977, 1982, or 1987. A total of 1,341 participants were reexamined in 1998, after an average follow-up period of 21 years, at ages 65-79 years. RESULTS: The participants who did not drink alcohol at midlife had a poorer performance in episodic memory, psychomotor speed, and executive function in late life as compared with infrequent and frequent drinkers, adjusted for sociodemographic and vascular factors. Also late-life nondrinkers had poorer psychomotor speed and executive function. These findings were evident especially among nonsmokers. Further, no interactions between apolipoprotein E4 and alcohol or sex and alcohol were found. CONCLUSIONS: Alcohol drinking both at midlife and later is favorably related to the function in several cognitive domains, including episodic memory, psychomotor speed, and executive function, in late life. However, it is not clear whether the association is causal, what is the possible mechanism, and what would be a safe limit of drinking for the best cognitive function.

Aged↗

Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study.

BACKGROUND: Lifestyle interventions can prevent the deterioration of impaired glucose tolerance to manifest type 2 diabetes, at least as long as the intervention continues. In the extended follow-up of the Finnish Diabetes Prevention Study, we assessed the extent to which the originally-achieved lifestyle changes and risk reduction remain after discontinuation of active counselling. METHODS: Overweight, middle-aged men (n=172) and women (n=350) with impaired glucose tolerance were randomly assigned to intensive lifestyle intervention or control group. After a median of 4 years of active intervention period, participants who were still free of diabetes were further followed up for a median of 3 years, with median total follow-up of 7 years. Diabetes incidence, bodyweight, physical activity, and dietary intakes of fat, saturated fat, and fibre were measured. FINDINGS: During the total follow-up, the incidence of type 2 diabetes was 4.3 and 7.4 per 100 person-years in the intervention and control group, respectively (log-rank test p=0.0001), indicating 43% reduction in relative risk. The risk reduction was related to the success in achieving the intervention goals of weight loss, reduced intake of total and saturated fat and increased intake of dietary fibre, and increased physical activity. Beneficial lifestyle changes achieved by participants in the intervention group were maintained after the discontinuation of the intervention, and the corresponding incidence rates during the post-intervention follow-up were 4.6 and 7.2 (p=0.0401), indicating 36% reduction in relative risk. INTERPRETATION: Lifestyle intervention in people at high risk for type 2 diabetes resulted in sustained lifestyle changes and a reduction in diabetes incidence, which remained after the individual lifestyle counselling was stopped.

Blood Glucose↗

Overweight, family history of diabetes and attending schools of lower academic grading are independent predictors for metabolic syndrome in Hong Kong Chinese adolescents.

BACKGROUND: Overweight and metabolic syndrome (MES) are emerging in both adult and paediatric populations. AIMS: To study the prevalence of and associated risk factors for the MES, using the National Cholesterol Education Program definition, among Hong Kong Chinese adolescents studying in secondary schools. METHODS: This was a cross-sectional, population-based study. A sample of 2115 Chinese adolescents was randomly selected from 14 secondary schools throughout Hong Kong. Data on anthropometric parameters, fasting blood and urine samples were collected in the school setting. Information regarding the adolescent's family history of diabetes, perinatal history, socioeconomic status and school grading was evaluated. RESULTS: The prevalence of MES was 2.4% (95% confidence interval (CI) 1.8 to 3.1), with no significant difference between boys (2.9%) and girls (2%). The prevalence of various components of MES was 32.2% (30.2 to 34.2) for hypertension, 10.9% (9.6 to 12.2) for increased triglyceride, 9.0% (7.8 to 10.2) for central adiposity, 2.4% (1.7 to 3) for low high-density lipoprotein cholesterol and 0.3% (0.1 to 0.6) for impaired fasting glucose. On multivariate analysis, overweight (odds ratio 32.2; 95% CI 13.2 to 78.4), positive family history of diabetes (4.3; 1.3 to 14.1) and studying at schools of lower academic grading (5.5; 2.2 to 13.7) were found to be independent risk factors for MES. CONCLUSION: A comparable prevalence of MES (2%) is observed in our study group Chinese adolescent girls and in US girls (2.1%), but a lower prevalence in Chinese boys (2.9%) than in US boys (6.1%). In our study, 41.8% harbour at least one component of the syndrome. Both families and schools should be alerted to this growing epidemic.

Adolescent↗

Occupational, commuting and leisure-time physical activity in relation to coronary heart disease among middle-aged Finnish men and women.

OBJECTIVE: To examine the association of different levels of occupational, commuting, and leisure-time physical activity with the risk of coronary heart disease (CHD) events. METHODS AND RESULTS: The study comprised 47,840 Finnish participants aged 25-64 years without history of CHD and stroke at baseline. During a mean follow-up of 18.9 years, 4660 new CHD events were documented. The multivariable-adjusted (age, body mass index, systolic blood pressure, total cholesterol, education, alcohol consumption, smoking, history of diabetes, and other two types of physical activity) hazard ratios (HRs) of CHD events associated with low, moderate, and high occupational activity were 1.00, 0.87, and 0.90 (P(trend)=0.019) for men, and 1.00, 0.75, and 0.80 (P(trend)<0.001) for women, respectively. The multivariable-adjusted HRs of CHD events associated with low, moderate, and high leisure-time physical activity were 1.00, 0.95, and 0.84 (P(trend)=0.026) for men, and 1.00, 0.85, and 0.77 (P(trend)=0.003) for women, respectively. Active commuting had a significant inverse association with the risk of CHD events in women but not in men. CONCLUSION: Moderate or high levels of occupational or leisure-time physical activity are associated with a reduced risk of CHD. Daily walking or cycling to and from work is associated with a decreased risk of CHD among women.

Adult↗

Diabetes associated with a low serum uric acid level in a general Chinese population.

OBJECTIVE: Serum uric acid (UA) is reported as an important marker of hypertension, coronary heart disease, and diabetes; diabetic subjects have low UA levels. The relationship between UA and fasting plasma glucose (FPG) and 2-h plasma glucose concentrations in non-diabetic subjects as well as in diabetic subjects in general population is not well known. This was investigated in a general Chinese population. METHODS: A stratified, random cluster sampling method was performed to select a representative sample of general population aged 20-74 years in Qingdao in 2002. A total of 1288 men and 2344 women participated in the survey. The mean UA concentration was calculated for small glucose intervals and the trend was tested using general linear model. RESULTS: The mean concentrations of UA were 381, 393, 371, and 345 micromol/l in men with FPG of <6.1, 6.1-6.9, > or =7.0 mmol/l (newly diagnosed diabetes), and in those with prior history of diabetes. They were 308, 322, 301, and 293 micromol/l, respectively, in women. The UA levels declined with increasing FPG levels in individuals with newly diagnosed diabetes, with standardized coefficient of -0.26 in men and -0.20 in women, after multivariate adjustment for age, body mass index, triglycerides, and cardiovascular disease history. The relationship between 2-h glucose and UA was not as clear as that for FPG. CONCLUSION: Serum UA levels tended to increase with increasing FPG levels in non-diabetic individuals, but decrease in diabetic individuals.

Adult↗

Postprandial hyperglycaemia and cardiovascular complications of diabetes: an update.

Type 2 diabetes is characterised by a gradual decline in insulin secretion in response to nutrient loads; hence, it is primarily a disorder of postprandial glucose (PPG) regulation. However, physicians continue to rely on fasting plasma glucose (FPG) and glycosylated haemoglobin (HbA1c) levels as indicators for disease management. There is a linear relationship between the risk of cardiovascular disease (CVD) and the two-hour oral glucose tolerance test (OGTT), while a recent study confirms postprandial hyperglycaemia as an independent risk factor for CVD in type 2 diabetes. At the same time, several intervention studies have shown that treating postprandial hyperglycaemia may reduce the incidence of new cardiovascular events. Evidence supports the hypothesis that postprandial hyperglycaemia may be linked to CVD through the generation of oxidative stress. Furthermore, clinical data suggest that postprandial hyperglycaemia is a common phenomenon, even in patients who may be considered in 'good metabolic control'. Therefore, in addition to HbA1c and FPG, physicians should consider monitoring and targeting PPG in patients with type 2 diabetes.

Cardiovascular Diseases↗

Systemic exposure to Porphyromonas gingivalis predicts incident stroke.

Periodontitis has been associated with an increased risk for atherosclerosis. Prospective data concerning its association with risk of stroke, especially those measuring systemic exposure to periodontal pathogens, are scarce. We analyzed if serum antibody levels to two major periodontopathogens predict stroke. The cases and the controls were nested in a random population-based sample of 8911 subjects aged 30-59 years at baseline, who participated in a cardiovascular disease (CVD) risk factor survey in Eastern Finland in 1977 and were followed for 15 years. CVD-free controls (n=516) were matched for sex and 5-year age group with stroke cases (n=470). In subjects free from CVD at baseline (n=893), systemic exposure to Porphyromonas gingivalis increased the risk of stroke: compared to seronegative subjects, men IgA-seropositive and women IgG-seropositive for P. gingivalis had a multivariate odds ratio (OR) (95% CI) of 1.63 (1.06-2.50) and 2.30 (1.39-3.78) for stroke, respectively. Higher OR was observed in males, who had never smoked: compared to seronegative men, P. gingivalis IgA-seropositive men had a multivariate OR of 3.31 (1.31-8.40, p=0.012) for stroke. No association between antibody levels to Actinobacillus actinomycetemcomitans and stroke was found. The results suggest that the systemic exposure to P. gingivalis may predispose to incident stroke.

Adult↗

European population substructure: clustering of northern and southern populations.

Using a genome-wide single nucleotide polymorphism (SNP) panel, we observed population structure in a diverse group of Europeans and European Americans. Under a variety of conditions and tests, there is a consistent and reproducible distinction between "northern" and "southern" European population groups: most individual participants with southern European ancestry (Italian, Spanish, Portuguese, and Greek) have >85% membership in the "southern" population; and most northern, western, eastern, and central Europeans have >90% in the "northern" population group. Ashkenazi Jewish as well as Sephardic Jewish origin also showed >85% membership in the "southern" population, consistent with a later Mediterranean origin of these ethnic groups. Based on this work, we have developed a core set of informative SNP markers that can control for this partition in European population structure in a variety of clinical and genetic studies.

Arthritis, Rheumatoid↗

Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women.

AIMS: Serum gamma-glutamyltransferase (GGT) concentration may be involved in atherosclerosis. This study examined if serum GGT predicted coronary heart disease (CHD), especially differentiating non-fatal myocardial infarction (MI) and fatal CHD event, among the general population or participants with type-2 diabetes. METHODS AND RESULTS: A prospective study of 28,838 Finnish men and women aged 25-74 years was performed (1467 incident CHD cases; a median follow-up time of 11.9 years). Serum GGT cutpoints were the 25th, 50th, 75th, and 90th sex-specific percentiles. After adjustment for known cardiovascular risk factors, compared with the lowest GGT category, hazard ratios (HR) were 1.15, 1.25, 1.27, and 1.57 among men and 1.03, 1.22, 1.32, and 1.44 among women in other four GGT categories (P for trend <0.01, respectively). However, stronger associations were observed among subjects aged <60 and among alcohol drinkers. The strength of association was similar for non-fatal MI and for fatal CHD. Among subjects with type-2 diabetes, the corresponding adjusted HRs were 1.29, 1.57, 1.88, and 1.78 (P trend=0.03, men and women combined). CONCLUSION: This study suggests an independent mechanism linking serum GGT to CHD among general population. Even though the strength of association appeared to be modest among all subjects, stronger associations were observed among subjects aged <60 and among alcohol drinkers. Especially, measurement of serum GGT among type-2 diabetics may be helpful to predict the future risk of CHD.

Adult↗

How well does the metabolic syndrome defined by five definitions predict incident diabetes and incident coronary heart disease in a Chinese population?

We evaluate the ability of the metabolic syndrome (MetS) defined by five definitions for predicting both incident CHD and diabetes combined, diabetes alone, and CHD alone in a Chinese population. The screening survey for type 2 diabetes was conducted in 1994. A follow-up study of 541 high-risk non-diabetic individuals who were free of CHD at baseline was carried out in 1999 in Beijing area. The MetS was defined by the World Health Organization (WHO), European Group for the Study of Insulin Resistance (EGIR), American College of Endocrinology (ACE), the International Diabetes Federation (IDF), and the National Cholesterol Education Program and the American Heart Association (AHA) (updated NCEP) criteria. From a multiple logistic regression adjusting for age, sex, education, occupation, smoking, family history of diabetes, and total cholesterol, the relative risk of the ACE-defined MetS for incident diabetes alone (67 cases) was 2.29 (95% CI, 1.20-4.34). The MetS defined by the five definitions was associated with a 1.8-3.9 times increased risk for both incident CHD and diabetes combined (59 cases), and with a 1.9-3.0 times for total incident diabetes (126 cases). None of the five definitions predicted either incident CHD alone (177 cases) or total incident CHD (236 cases). In conclusion, the MetS defined by the current definitions appears to be more effective at predicting incident diabetes.

Adult↗

Six year incidence and progression of diabetic retinopathy: results from the Mauritius diabetes complication study.

AIMS: To determine the incidence, progression and risk factors for diabetic retinopathy in the multiethnic population of Mauritius. METHOD: A longitudinal, population-based study was conducted in Mauritius, during 1987, 1992 and 1998. Participants identified through the study as having diabetes (both known and newly diagnosed, by self-report and oral glucose tolerance test) and one in four participants with impaired glucose tolerance (IGT) underwent complications screening in 1992 and 1998. Retinal photographs were taken using a TRC-50VT retinal camera in three fields of the right eye (centred on the optic disc; macula (temporal to the optic disc); and nasal to disc). Photographs were graded according to a simplified version of the Wisconsin grading system. RESULTS: The 6-year incidence of diabetic retinopathy was 23.8% (sight-threatening in 0.4%). Among those with known diabetes mellitus (KDM) and free of retinopathy at baseline the incidence of non-proliferative diabetic retinopathy (NPDR) was 29.2% and proliferative diabetic retinopathy (PDR) was 1.0%. Among those with newly diagnosed diabetes mellitus (NDM) at baseline the incidence of NPDR was 19.1% (no incident cases of PDR were found). Independent risk factors for retinopathy using the baseline population characteristics were duration of diabetes and fasting plasma glucose. CONCLUSIONS: This is one of the few recent population-based studies of diabetic retinopathy undertaken in a developing nation. The incidence of retinopathy in Mauritius was high among those with NDM at baseline, with one in five developing retinopathy over 6 years. These results support the concept that screening for diabetes is important.

Adult↗

Tag SNP selection for Finnish individuals based on the CEPH Utah HapMap database.

The pattern and nature of linkage disequilibrium in the human genome is being studied and catalogued as part of the International HapMap Project [:2003 Nature 426:789-796]. A key goal of the HapMap Project is to enable identification of tag single nucleotide polymorphisms (SNPs) that capture a substantial portion of common human genetic variability while requiring only a small fraction of SNPs to be genotyped [International HapMap Consortium, 2005: Nature 437:1299-1320]. In the current study, we examined the effectiveness of using the CEU HapMap database to select tag SNPs for a Finnish sample. We selected SNPs in a 17.9-Mb region of chromosome 14 based on pairwise linkage disequilibrium (r(2)) estimates from the HapMap CEU sample, and genotyped 956 of these SNPs in 1,425 Finnish individuals. An excess of SNPs showed significantly different allele frequencies between the HapMap CEU and the Finnish samples, consistent with population-specific differences. However, we observed strong correlations between the two samples for estimates of allele frequencies, r(2) values, and haplotype frequencies. Our results demonstrate that the HapMap CEU samples provide an adequate basis for tag SNP selection in Finnish individuals, without the need to create a map specifically for the Finnish population, and suggest that the four-population HapMap data will provide useful information for tag SNP selection beyond the specific populations from which they were sampled.

Chromosome Mapping↗