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Johan Eriksson

Publications and source records attributed to Johan Eriksson.

30 records · Page 2Linked to original sources
PubMed2004

The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to type 2 diabetes mellitus: the Finnish Diabetes Prevention Study.

In population-based studies, dyslipidemia related to insulin resistance (high triglyceride level and low high-density lipoprotein cholesterol level) is a risk factor for type 2 diabetes. Therefore, variants in genes regulating lipid and lipoprotein metabolism are potential candidate genes for diabetes. We investigated whether the G-250A polymorphism of the hepatic lipase gene (LIPC) predicts the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. This study randomized subjects to either the intervention group (lifestyle modification aimed at weight loss, such as changes in diet and increased physical exercise) or the control group. Genotyping at position -250 of the LIPC gene was performed with PCR amplification, DraI enzyme digestion, and gel electrophoresis in 490 subjects with IGT whose DNA was available. In the entire study population, the conversion rate to type 2 diabetes was 17.8% among subjects with the G-250G genotype and 10.7% among subjects with the -250A allele (P = 0.032). In univariate analysis, the odds ratio for the G-250G genotype to predict the conversion from IGT to type 2 diabetes was 1.80 (95% confidence interval, 1.05-3.10; P = 0.034). In multivariate logistic regression analysis, the G-250G genotype predicted the conversion to diabetes independently of the study group (control or intervention), gender, weight, waist circumference at baseline, and change in weight and waist circumference. In the intervention group, 13.0% of subjects with the G-250G genotype and 1.0% of the subjects with the -250A allele converted to diabetes (P = 0.001). We conclude that the G-250G genotype of the LIPC gene is a risk factor for type 2 diabetes. Therefore, genes regulating lipid and lipoprotein metabolism may be potential candidate genes for type 2 diabetes.

Alleles↗
PubMed2004

The effects of the ACE gene insertion/deletion polymorphism on glucose tolerance and insulin secretion in elderly people are modified by birth weight.

The I allele of an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme gene (ACE) appears to be protective against the complications of type 2 diabetes. Low birth weight, a marker of an adverse intrauterine environment, is associated with higher rates of type 2 diabetes. We examined whether the ACE I/D polymorphism could explain or modify the association between low birth weight and adulthood glucose tolerance. We measured plasma glucose and insulin concentrations after an oral glucose challenge in a group of 423 men and women, ages 65-75 yr, with measurements at birth recorded. The presence of the I allele was associated with shorter duration of gestation (P = 0.006) and, relative to gestational age, higher birth weight (P = 0.008) and length (P = 0.02). The I allele was associated with lower glucose at 120 min (P = 0.04) and a greater insulin response (P = 0.03 for insulin at 30 min and P = 0.06 for insulin area under the curve) to a standard oral glucose tolerance test. However, the associations between the ACE genotype and adulthood insulin secretion were only present in people with low birth weight (P for interaction birth weight * ACE genotype on insulin at 30 min = 0.003 and on insulin area under the curve = 0.05). The ACE I allele is associated with shorter duration of gestation and higher birth weight. The association between the presence of the ACE I allele and increased indices of adult insulin secretion is confined to subjects with low birth weight. We suggest that these findings reflect interactions between genotype and intrauterine environment with resulting changes in gene expression.

Birth Weight↗
PubMed2004

Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish Diabetes Prevention Study.

Type 2 diabetes is caused by defective insulin secretion and impaired insulin action. We investigated whether common polymorphisms in the SUR1 and Kir6.2 genes are associated with increased risk of type 2 diabetes in 490 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study. The 1273AGA allele of the SUR1 gene was associated with a 2-fold risk of type 2 diabetes [odds ratio (OR), 2.00; 95% confidence interval (CI), 1.19-3.36; P = 0.009]. This silent polymorphism was in linkage disequilibrium with three promoter polymorphisms (G-2886A, G-1561A, and A-1273G), and they formed a high-risk haplotype having a 2-fold risk of type 2 diabetes (OR, 1.89; 95% CI, 1.09-3.27; P = 0.023). Subjects with both the high-risk haplotype of the SUR1 gene and the 23K allele of the Kir6.2 gene had a 6-fold risk for the conversion to diabetes compared with those without any of these risk genotypes (OR, 5.68; 95% CI, 1.75-18.32; P = 0.004). We conclude that the polymorphisms of the SUR1 gene predicted the conversion from impaired glucose tolerance to type 2 diabetes and that the effect of these polymorphisms on diabetes risk was additive with the E23K polymorphism of the Kir6.2 gene.

ATP-Binding Cassette Transporters↗
PubMed2003

Absolute asymmetric synthesis of "chiral-at-metal" Grignard reagents and transfer of the chirality to carbon.

Two new six-coordinate Grignard reagents, cis-[(p-CH(3)C(6)H(4))MgBr(dme)(2)] (1) and cis-[MgCH(3)(thf)(dme)(2)]I (2), have been synthesized and their crystal structures have been determined. Both reagents are cis-octahedral and therefore chiral. They crystallize as conglomerates and racemize rapidly in solution. By utilizing these properties, the absolute asymmetric synthesis of specifically the Delta or the Lambda enantiomer was achieved for both Grignard reagents. Enantiopure 1 and 2 were then reacted with butyraldehyde or benzaldehyde to give the corresponding alcohol in up to 22 % enantiomeric excess. At -60 degrees C, the Grignard reagents crystallize as racemic phases instead of conglomerates. Consequently, the crystal structures of rac-cis-[(p-CH(3)C(6)H(4))MgBr(dme)(2)].DME (3) and rac-cis-[MgCH(3)(thf)(dme)(2)]I (4) could be determined.

Journal Article↗
PubMed2003

Serum insulin-like growth factor (IGF)-I and IGF-binding protein-1 in elderly people: relationships with cardiovascular risk factors, body composition, size at birth, and childhood growth.

The IGF system is important in regulation of fetal and childhood growth. In later life, IGF-I and IGF-binding protein-1 (IGFBP-1) have been implicated in the pathogenesis of arteriosclerosis. They are, thus, potential candidates in explaining the link between early growth and adult cardiovascular disease. We measured fasting serum IGF-I and IGFBP-1 concentrations in 394 men and women from a cohort of 7086 individuals, born between 1924 and 1933 in Helsinki, Finland, whose weight and height were recorded at birth and from 7 to 15 yr of age. They also underwent clinical examination, including measurement of body fat using bioimpedance, blood pressure, glucose tolerance, and plasma insulin and fibrinogen concentrations. Serum IGF-I was positively correlated with fasting glucose (r = 0.10, P = 0.06) and fibrinogen (r = 0.19, P = 0.0001) concentrations and blood pressure (systolic and diastolic r = 0.10, P </= 0.05) and inversely with percentage body fat (r = -0.13, P = 0.01) and waist circumference (r = -0.11, P = 0.03). IGFBP-1 was inversely correlated with adult body mass index (BMI) (r = -0.46, P < 0.0001), fasting glucose and insulin concentrations, and blood pressure. There were correlations between the adult level of IGFBP-1 and birth weight (r = 0.11, P = 0.03) and ponderal index (weight/length(3)) at birth (r = 0.13, P = 0.01), but IGF-I was not related to birth measurements. There were interactive effects between childhood height or BMI and adult BMI on IGF-I and IGFBP-1 in adulthood. Tall height and high BMI at 7 yr were associated with low IGF-I (P = 0.03 for height and P = 0.003 for BMI) and high IGFBP-1 (P = 0.02 and P = 0.06) in adulthood but only in those subjects whose current BMI was below median. On further analysis these interactive effects were particularly strong for height in childhood and adult lean BMI (lean body mass/height(2)). Among men and women of below-average lean BMI, tall height at 7 yr was associated with low adult IGF-I (P = 0.007) and high IGFBP-1 (P = 0.0004) concentrations [interaction (7-yr height x adult lean BMI); P = 0.008 for IGF-I and 0.001 for IGFBP-1]. There is no evidence that reduced fetal growth programs IGF-I concentrations in old age. An association between small size at birth and low IGFBP-1 concentrations may in part reflect fetal programming effects on insulin resistance. Given the anabolic effects of the GH-IGF-I axis, subjects with tall height in childhood but low adult lean body mass may be at risk of late-life GH-IGF-I axis dysfunction. Prospective studies should address whether this group is susceptible to type 2 diabetes, coronary heart disease, and osteoporosis.

Adolescent↗
PubMed2003

Birthsize, gestational age and adrenal function in adult life: studies of dexamethasone suppression and ACTH1-24 stimulation.

OBJECTIVE: Several studies show that low birthweight is associated with long-term alterations in the function of the hypothalamic-pituitary-adrenal axis (HPAA). We recently reported that the relationship between birthweight and fasting serum cortisol concentrations differed according to the gestational age of the babies, suggesting that both hypercortisolism and hypocortisolism could be a consequence of impaired fetal growth. We have now extended these findings by examining the relationship between birthweight, gestational age and tests of adrenal suppression and stimulation. DESIGN: Prospective birth cohort study. SUBJECTS AND METHODS: We studied 165 women (mean age 71.3 Years) born at term in Helsinki, Finland, between 1924 and 1933, whose body size and gestational age at birth were recorded. These women underwent an overnight 0.25 mg dexamethasone suppression test followed by a 1 microg ACTH(1-24) stimulation test. RESULTS: In all women combined, low birthweight was associated with lower total (P=0.03) and free (P=0.02) cortisol concentrations following dexamethasone. However, these relationships were dependent on gestational age at birth, interactions between the effects of birth size and gestational age on dexamethasone responsiveness being statistically significant. To demonstrate these interactions, we divided the study population into two groups according to gestational age. In subjects born at 40 weeks of gestation or more, low birthweight was strongly associated with enhanced dexamethasone suppression (P=0.003 for total and P=0.0004 for free cortisol), while in subjects born before 40 weeks of gestation there was no association. There was, however, no correlation between birth size and the adrenal response to ACTH(1-24). CONCLUSIONS: These findings reinforce our suggestions that events during prenatal life may lead to both up-regulation and down-regulation of the HPAA.

Adrenal Cortex↗
PubMed2003

Promoter polymorphisms of the TNF-alpha (G-308A) and IL-6 (C-174G) genes predict the conversion from impaired glucose tolerance to type 2 diabetes: the Finnish Diabetes Prevention Study.

High levels of cytokines are risk factors for type 2 diabetes. Therefore, we investigated whether the promoter polymorphisms of the tumor necrosis factor-alpha (TNF-alpha; G-308A) and interleukin 6 (IL-6; C-174G) genes predict the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. Altogether, 490 overweight subjects with IGT whose DNA was available were randomly divided into one of the two treatment assignments: the control group and the intensive, individualized diet and exercise intervention group. The -308A allele of the TNF-alpha gene was associated with an approximate twofold higher risk for type 2 diabetes compared with the G-308G genotype (odds ratio 1.80, 95% CI 1.05-3.09; P = 0.034). Subjects with both the A allele of the TNF-alpha gene and the C-174C genotype of the IL-6 gene had a 2.2-fold (CI 1.02-4.85, P = 0.045) higher risk of developing type 2 diabetes than subjects without the risk genotypes. We conclude that the -308A allele of the promoter polymorphism (G-308A) of the TNF-alpha gene is a predictor for the conversion from IGT to type 2 diabetes. Furthermore, this polymorphism seems to have a gene-gene interaction with the C-174C genotype of the IL-6 gene.

Analysis of Variance↗
PubMed2003

Predictive properties of impaired glucose tolerance for cardiovascular risk are not explained by the development of overt diabetes during follow-up.

OBJECTIVE: To evaluate the relationship of impaired glucose tolerance (IGT) at baseline to coronary heart disease (CHD) incidence, and cardiovascular disease (CVD) and total mortality at follow-up, and to analyze whether the relationship is independent of the subsequent development of diabetes during follow-up. RESEARCH DESIGN AND METHODS: A baseline screening survey for diabetes was performed in 1987 using a 2-h 75-g oral glucose tolerance test. A total of 1234 men and 1386 women aged 45-64 years, who were free of diabetes at baseline, were followed up for 10 years. During the follow-up, 153 subjects had an incident CHD event, 224 died, and 100 deaths were due to cardiovascular causes. Multivariate adjusted (adjusted for age, sex, waist-to-hip ratio, systolic blood pressure, cholesterol, HDL cholesterol, and smoking) hazard ratio (HR) was estimated using Cox regression analysis. RESULTS: In subjects who had IGT at baseline and who did not progress to diabetes during the follow-up, the multivariate adjusted HR (95% CI) was 1.49 (0.95-2.34) for CHD incidence, 2.34 (1.42-3.85) for CVD mortality, and 1.65 (1.13-2.40) for all-cause mortality. CONCLUSIONS: Baseline IGT was an independent risk predictor for cardiovascular morbidity and mortality and for total mortality, which was not confounded by the subsequent development of overt diabetes.

Cardiovascular Diseases↗
PubMed2003

The Finnish Diabetes Prevention Study (DPS): Lifestyle intervention and 3-year results on diet and physical activity.

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

Diabetes Mellitus, Type 2↗
PubMed2002

Size at birth, gestational age and cortisol secretion in adult life: foetal programming of both hyper- and hypocortisolism?

OBJECTIVE: Recent studies have suggested that lifelong programming of the hypothalamic-pituitary-adrenal (HPA) axis in utero is an important mechanism in explaining the link between small size at birth and adult cardiovascular disease. However, direct evidence from human birth cohorts has so far been contradictory. We set out to study reasons for this discrepancy by examining the relationship between adult HPA axis function and birthweight and body proportions at birth in a group of elderly subjects with detailed birth records. DESIGN: Birth cohort study. SUBJECTS: Four hundred and twenty-one men and women (mean age 69.5 years, range 65.1-75.8 years) born at term in Helsinki, Finland, during 1924-33, with body size and gestational age at birth recorded. MEASUREMENTS: Fasting serum cortisol and cortisol-binding globulin concentrations. The concentration of free cortisol was estimated by their ratio. RESULTS: There was no significant correlation between fasting cortisol concentrations and birthweight in either men or women. However, there was a weak inverse association between fasting cortisol and length at birth in women but not in men. There was also a significant positive association between cortisol and ponderal index in both genders. We found that the association between foetal growth on fasting total and free cortisol concentrations differed in subjects born at different gestational ages. In subjects born before 39 weeks of gestation, both total and free cortisol showed inverse correlations with birthweight (P = 0.02 and P = 0.09, respectively) and length at birth (P = 0.001 and P = 0.02), whereas in subjects born after 40 weeks of gestation there were positive correlations with birthweight (P = 0.06 and P = 0.002) and ponderal index at birth (P = 0.003 and P = 0.003). The interactions between birthweight and gestational age were statistically significant (P = 0.01 for total and P = 0.003 for free cortisol). CONCLUSIONS: These data suggest that the relationship between size at birth and cortisol concentrations in adult life is different in subjects born at different gestational ages: both hyper- and hypocortisolism may arise as a consequence of foetal programming of the hypothalamic-pituitary-adrenal axis during intrauterine life.

Adult↗