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Biomedical subjects

Olavi Ukkola

Publications and source records attributed to Olavi Ukkola.

At least 19 recordsLinked to original sources
PubMed2006

High plasma resistin level is associated with enhanced highly sensitive C-reactive protein and leukocytes.

OBJECTIVES: Resistin is a newly described hormone with a suggested role in insulin resistance. In humans, inflammatory cells seem to be the major source of resistin. The aim of this study was to find out whether plasma resistin concentration associates with carotid artery atherosclerosis and the risk factors of atherosclerosis. METHODS: Plasma resistin concentrations were measured in 525 Finnish middle-aged subjects among our population-based cohort. Intima-media thickness was measured from the internal carotid artery, the bifurcation enlargement, and the common carotid artery. RESULTS: Among all the subjects, the median resistin concentration was 7.07 ng/ml (interquartile range, 5.82-8.84), women having higher levels than men (P < 0.001) with median values of 7.56 ng/ml (6.18-9.19) and 6.67 ng/ml (5.63-8.31), respectively. Resistin level correlated negatively with mean intima-media thickness, internal carotid artery, and common carotid artery, but the association did not remain significant after adjustments. Plasma resistin concentration was associated positively with leukocytes (P < 0.001), highly sensitive C-reactive protein (P = 0.009), and IGF binding protein 1 (P < 0.001), but not with plasma insulin or glucose levels in analysis of covariance after adjustments for age, sex, and body mass index. CONCLUSIONS: The results imply that inflammatory factors are more important in the determination of plasma resistin concentration than plasma insulin or glucose values. Resistin is associated with proatherogenic inflammatory markers but not independently with early atherosclerosis.

Atherosclerosis↗
PubMed2006

Association between angiotensin-converting enzyme insertion/deletion polymorphism and treatment response in type 2 diabetic patients.

BACKGROUND: Our objective was to determine whether the angiotensin-converting enzyme insertion-deletion (ACE I/D) polymorphism affects the treatment responses in type 2 diabetic patients. METHODS: A total of 117 type 2 diabetic patients with poor metabolic control were evaluated and their treatment intensified before re-evaluation after a mean follow-up of 16.0 months. New insulin treatment was started in 61% of patients, the majority of whom used a combination of insulin and tablets. Earlier insulin treatment was continued and intensified for 9% of patients, and 19% of patients used oral treatment only. As antihypertensive treatment, 34% of patients used diuretics, 27% ACE-inhibitors, 38% beta-blockers and 21% calcium-channel blockers during the follow-up. For dyslipidemia, 6% of patients used fibrates and none used statins. RESULTS: There was a decrease in glycohemoglobin A1 levels [-2.0 (0.3) (S.E.) %], plasma total cholesterol [-0.2 (0.1) mmol/l] and plasma triglycerides [-1.2 (0.4) mmol/l], and an increase in plasma HDL cholesterol [0.07 (0.02) mmol/l] and weight [2.1 (0.5) kg] in response to intensified treatment. The changes in glycohemoglobin A1 (GHbA1) levels and HDL cholesterol were significantly associated with the ACE I/D polymorphism. The patients with the ACE I/I genotype had a greater decrease [-3.0 (0.7)] in their GHbA1 levels than the patients with I/D [-2.1 (0.5)] or D/D [-1.8 (0.4)] genotypes (P<0.03). HDL cholesterol levels increased more among the subjects homozygous for the I allele [0.21 (0.05)] than the I/D [0.04 (0.03)] or D/D [0.04 (0.03)] subjects (P<0.03). CONCLUSIONS: The results suggest that the ACE I/D polymorphism is associated with treatment responses in type 2 diabetic patients.

Journal Article↗
PubMed2006

Low plasma ghrelin concentration is an indicator of the metabolic syndrome.

BACKGROUND: Low ghrelin concentration has been associated with several features of metabolic syndrome (MS), but the relationship between ghrelin concentration and MS as a cluster of metabolic aberrations has not yet been studied. AIMS OF THE STUDY: To analyse whether ghrelin concentration is associated with MS. RESEARCH DESIGN AND METHODS: Fasting plasma ghrelin concentrations of the population-based cohort of 1037 middle-aged men and women were analysed using a commercial radioimmunoassay kit (Phoenix Peptide). MS was determined using the new International Diabetes Federation criteria. RESULTS: The prevalence of MS was 37.2%. The ghrelin concentrations were decreased in subjects with MS (635 pg/mL) compared to those without MS (687 pg/mL) (P=0.001). Ghrelin levels decreased with an increase in the number of metabolic abnormalities. Low ghrelin was a statistically significant predictor of MS in logistic regression analysis (P=0.005) so that the subjects in the 1st ghrelin quartile were at higher risk of having MS compared to the subjects in the 4th quartile (OR=1.82, 95% CI: 1.27-2.60, P=0.001). This association remained statistically significant after adjustment for age and sex (OR=1.76, 95% CI: 1.24-2.55, P=0.002). CONCLUSIONS: Metabolic syndrome is associated with low ghrelin levels suggesting a relationship of ghrelin in the metabolic disturbances of MS.

Biomarkers↗
PubMed2005

Estrogen replacement therapy increases plasma ghrelin levels.

Ghrelin is a novel peptide hormone that has GH releasing activity and also other endocrine and metabolic functions. The purpose of this study was to investigate the effects of estrogen replacement therapy on plasma active ghrelin levels in 64 hysterectomized postmenopausal women receiving peroral estrogen (PE) or transdermal estrogen therapy for 6 months. Active ghrelin was measured using commercial RIA. Estrogen therapy increased plasma active ghrelin from 479 +/- 118 to 521 +/- 123 pg/ml (P = 0.002) among all the study subjects. PE therapy increased plasma ghrelin levels from 465 +/- 99 to 536 +/- 104 pg/ml (P = 0.001). Transdermal estrogen therapy did not increase plasma ghrelin levels significantly (from 491 +/- 132 to 509 +/- 138 pg/ml; P = 0.332). The relative changes in plasma ghrelin levels were associated with the relative changes in serum estradiol concentrations (r = 0.299; P = 0.017). During the estrogen therapy, negative associations were found between plasma active ghrelin levels and several plasma lipids (total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol, total triglycerides, and very low-density lipoprotein triglycerides). As a conclusion, estrogen replacement therapy increased active plasma ghrelin levels, particularly PE therapy. Additional studies are needed to determine the possible underlying mechanisms.

Aged↗
PubMed2005

Protein tyrosine phosphatase 1B variant associated with fat distribution and insulin metabolism.

Protein tyrosine phosphatase 1B (PTPN1) affects the regulation of insulin signaling and energy metabolism. We studied whether polymorphisms in the PTPN1 gene impact body fat distribution in the HERITAGE Family Study cohort in 502 white and 276 black subjects. Insulin sensitivity index, glucose disappearance index, acute insulin response to glucose (AIR(glucose)), and the disposition index (DI) were obtained from the frequently sampled intravenous glucose tolerance test. White subjects with the G82G at the PTPN1 IVS6+G82A polymorphism had higher body fat levels (p = 0.031) and sum of eight skinfolds (p = 0.003) and highest subcutaneous fat on the limbs (p = 0.002). G82A subjects had the lowest AIR(glucose) (p = 0.005) and disposition index (p = 0.040). Interaction effects between PTPN1 and leptin receptor gene variants influenced insulin sensitivity index and AIR(glucose) (p from 0.006 to 0.010). The variant PTPN1 Pro387Leu was associated with lower fasting insulin level (p = 0.035) and glucose disappearance index (p = 0.038). In summary, PTPN1 IVS6+G82G homozygotes showed higher levels of all measures of adiposity. G82 allele heterozygotes are potentially at higher risk for type 2 diabetes. Gene-gene interactions between the PTPN1 and leptin receptor genes contributed to the phenotypic variability of insulin sensitivity. The PTPN1 Pro387Leu variant was associated with lower glucose tolerance.

Adipose Tissue↗
PubMed2005

Adiponectin polymorphisms, adiposity and insulin metabolism: HERITAGE family study and Oulu diabetic study.

AIMS/HYPOTHESIS: Adiponectin is an adipocytokine with lowered blood levels in obesity and Type 2 diabetes mellitus. We sought to define the specific effects of different alleles of the gene encoding adiponectin. METHODS: We studied the associations of adiponectin gene sequence variations with body fat distribution and insulin indices in 503 White and 276 Black subjects of the HERITAGE Family Study cohort and subjects from a Finnish population. RESULTS: The His111 allele frequency of the Tyr111 His polymorphism in Finnish Type 2 diabetic subjects (n=254) was higher (5.1%) than in control subjects (n=270) (2.6%; P = 0.033). In the HERITAGE cohort, the His111 allele was associated with a lower insulin sensitivity index (P = 0.018) and a higher acute insulin response to glucose (P = 0.0098) in Whites. Other variants showed associations with adiposity and plasma lipid values only in Blacks. Among Blacks, the IVS2+G62T variant was associated with body fat (P = 0.002) and total cholesterol values (P = 0.005), and the Gly15Gly variant with cholesterol (P = 0.009) and triglyceride (P = 0.05) levels. The haplotype derived from these two polymorphisms was associated with total body fat, while the IVS2+G62T and Tyr111His-haplotype was associated with body fat and disposition index. CONCLUSIONS: The carriers of the His111 allele may have a higher risk of developing Type 2 diabetes mellitus. Racial differences were found between Blacks and Whites in body composition and lipids according to ACDC genotypes. Sequence variants in the adiponectin gene appear to be associated with diabetes and diabetes-related phenotypes.

Adipocytes↗
PubMed2005

IGF-I concentrations are positively associated with carotid artery atherosclerosis in women.

BACKGROUND: Alterations in the growth hormone (GH)/insulin-like growth factor I (IGF-I) axis are associated with increased cardiovascular morbidity and mortality, but previous studies have yielded conflicting results. In addition, the T1169A polymorphism in the GH1 gene has been associated with IGF-I levels. AIMS: To investigate whether IGF-I concentrations and the T1169A polymorphism of the GH1 gene are associated with cardiovascular risk factors and the intima media thickness (IMT) of the carotid artery. METHODS: Fasting plasma IGF-I concentrations (n=1008) were measured in a large population-based OPERA (Oulu Project Elucidating Risk of Atherosclerosis) cohort. Genotype variants were determined by the restriction fragment length polymorphism method. RESULTS: Low IGF-I concentrations associated with several cardiovascular risk factors including age, adiposity, and high triglyceride, fasting insulin and C-reactive protein concentrations in the analysis of all subjects. In the multivariate models, however, IGF-I concentrations were positively associated with the mean IMT of women (ss=0.127, P=0.009) whereas the association in men was weaker and negative (ss=-0.088, P=0.034). The 1169A allele was associated with low low-density lipoprotein cholesterol in both sexes and with low systolic blood pressure levels in women. CONCLUSIONS: IGF-I concentrations were associated with several traditional cardiovascular risk factors. The observed gender difference in the association between IGF-I concentrations and carotid artery atherosclerosis warrants further study. The GH1 1169A allele may be associated with a favourable metabolic profile.

Atherosclerosis↗
PubMed2005

[Cachexia].

Explore the source record for details and available documents.

Cachexia↗
PubMed2004

Sequencing analysis of the ghrelin receptor (growth hormone secretagogue receptor type 1a) gene.

OBJECTIVES AND DESIGN: Ghrelin is a novel 28 amino acid peptide which is reported to have several endocrine and non-endocrine actions. It possesses strong growth hormone (GH)-releasing activity, which is mediated via the GH secretagogue receptor type 1a (GHS-R1a). We hypothesised that there might be functional sequential variations in the GHS-R1a gene affecting phenotypes linked to the GH/insulin-like growth factor-I (IGF-I)-axis. METHODS: To test our hypothesis we chose patients from our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study with low (n=96) and high (n=96) IGF-I levels, sequenced their GHS-R1a gene exons and performed association studies. RESULTS: We found five single-nucleotide polymorphisms (SNPs) which did not change the amino acid sequence. We were unable to detect associations between the SNPs and the IGF-I plasma concentrations, but instead we showed that SNP 171C>T was associated with the values of the area under the insulin curve (AUCIN) in an oral glucose tolerance test and with IGF-binding protein-1 (IGFBP-1) concentrations (P<0.05). SNP 477G>A was associated with the low density lipoprotein and very low density lipoprotein cholesterol plasma levels and AUCIN values (P<0.05). CONCLUSIONS: This study was the first genomic screening of the GHS-R1a gene in a population. It suggests that genetic variations in the GHS-R1a gene are not the main regulators of IGF-I levels. However, the variants may be associated with IGFBP-1 concentrations and insulin metabolism.

Amino Acid Sequence↗
PubMed2004

Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: the HERITAGE family study.

We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.

Adult↗
PubMed2003

Mutations in the adiponectin gene in lean and obese subjects from the Swedish obese subjects cohort.

Adiponectin (also called AdipoQ, gelatin-binding protein 28, Acrp30) DNA sequence variants were determined in 96 unrelated female subjects with severe obesity (mean body mass index [BMI], 42.3 kg/m2) and in 96 non-obese female controls (mean BMI, 23.0 kg/m2) from the Swedish Obese Subjects (SOS) cohort. A single base substitution (T45G) at codon 15 of exon 2 resulting in no change in amino acid (Gly15Gly) was found in equal frequencies among obese and control subjects. However, this polymorphism was associated with serum cholesterol and waist circumference (P=.023 and.043, respectively) in the obese group. A IVS2 + G62T sequence variation was also identified, but had similar prevalence rates in obese and control subjects. Blood glucose was highest in the obese female subjects who were homozygotes for the G allele (GG) of the IVS2 + G62T polymorphism (N=56; P=.033) and all the diabetics (n=6) in this sample were in this group. IVS2 + G62T polymorphism was also associated with BMI (P=.014), diastolic blood pressure (P=.009), and sagittal diameter (P=.032). A missense point mutation at codon 111 (Tyr111His) was not associated with any obesity-related phenotypes. In conclusion, adiponectin DNA sequence variations might play a role in the complications of morbid obesity and should be further investigated.

Adiponectin↗
PubMed2003

Endocrinological activities of ghrelin: new insights.

Ghrelin is a potent endogenous growth hormone secretagogue in supraphysiological doses. It also exhibits several other endocrinological (e.g. lactotrophic and corticotrophic) activities when given intravenously. However, the significance of these effects in a normal physiological situation is still unknown, and subcutaneous administration of ghrelin seems to only increase growth hormone secretion. Interest in ghrelin research is currently focused on energy metabolism; the link between ghrelin and the regulation of both growth and energy metabolism is missing. In this paper we present an up-to-date review of the endocrinological activities of ghrelin.

Journal Article↗
PubMed2003

Temporal changes in cardiovascular autonomic regulation in type II diabetic patients: association with coronary risk variables and progression of coronary artery disease.

AIM: This research was designed to study the temporal changes in cardiovascular autonomic regulation, assessed by 24-hour heart rate (HR) variability, and the possible relation of changes in HR variability to cardiovascular risk factors and progression of coronary artery disease (CAD) among type II diabetic subjects. METHOD: In a single-center substudy of The Diabetes Atherosclerosis Intervention Study (DAIS), 53 patients assigned to fenofibrate (n = 26) or placebo (n = 27), underwent time and frequency domain and fractal analysis of HR variability, coronary risk variable analyses and quantitative coronary angiograms at baseline and after three years' follow-up. RESULTS: Twenty-four hour standard deviation of sinus intervals (SDNN) decreased from 113 +/- 35 to 94 +/- 30 msec (P < 0.001) during the three year period. Low frequency power spectral component and short-term fractal scaling exponent also decreased (P < 0.001 and P < 0.05, respectively). The reduction of SDNN was weakly related to a change in the triglyceride level (r = -0.33, P < 0.05), glucose level (r = -0.28, P < 0.05) and total cholesterol concentration (r = -0.35, P < 0.01). Furthermore, the reduction of SDNN was related to a decrease in the minimum lumen and mean segment diameter of the coronary arteries (r = 0.36, P < 0.01, and r = 0.39, P < 0.01, respectively). This association was more marked in the placebo group (r = 0.50, P < 0.01 and r = 0.44, P < 0.05, respectively) than among the patients randomized to fenofibrate (not significant for both). CONCLUSIONS: Cardiovascular autonomic regulation assessed by HR variability deteriorates rapidly in type II diabetic subjects with CAD during the time course. Impairment in HR variability is associated with changes in common coronary risk variables and with a progression of CAD.

Adult↗
PubMed2003

Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of type 2 diabetes.

Experimental studies have suggested that ghrelin plays a role in glucose homeostasis and in the regulation of blood pressure (BP). We therefore assessed the hypothesis that a low ghrelin concentration may be a risk factor for type 2 diabetes and hypertension. We also characterized the effect of the ghrelin Arg51Gln and Leu72Met mutations on ghrelin concentrations in the population-based hypertensive (n = 519) and control (n = 526) cohorts of our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study. The fasting plasma ghrelin concentrations of 1,040 subjects were analyzed using the radioimmunoassay method. Insulin sensitivity was assessed using the quantitative insulin sensitivity check index (QUICKI). Ghrelin concentrations were negatively associated with fasting insulin (P < 0.001), systolic (P = 0.026) and diastolic BP (P = 0.018), and the prevalence of type 2 diabetes (P = 0.015) and insulin resistance (P < 0.001) in the multivariate models. In the control cohort, low ghrelin was associated with hypertension (BP >140/90 mmHg) (P = 0.031). The subjects with the ghrelin 51Gln allele had lower ghrelin concentrations than the Arg51Arg homozygotes (P = 0.001). We conclude that low ghrelin is independently associated with type 2 diabetes, insulin concentration, insulin resistance, and elevated BP. Therefore, it might have some role in the etiology of type 2 diabetes and the regulation of BP. The ghrelin Arg51Gln mutation is associated with low plasma ghrelin concentrations.

Adult↗
PubMed2002

Na+-K+-ATPase alpha 2-gene and skeletal muscle characteristics in response to long-term overfeeding.

The role of Na(+)-K(+)-ATPase alpha2-gene BglII polymorphism in the changes of skeletal muscle metabolic properties after a 100-day overfeeding protocol conducted with 12 pairs of monozygotic twins is reported. The activities of oxoglutarate dehydrogenase (OGDH) and phosphofructokinase (PFK) were determined from muscle biopsies. A larger increase in the total fat mass (127 vs. 61%) (P < 0.05) and low-density lipoprotein cholesterol (20 vs. 0.7%) (P = 0.05) in 8.0/8.0-kb [3.3-kb negative (-); n = 7 pairs] than in 8.0/3.3 + 3.3/3.3-kb [3.3-kb positive (+); n = 5 pairs] subjects was observed. OGDH activity decreased in 3.3-kb(-) (-15%), whereas PFK (+26%) as well as the PFK-to-OGDH ratio (90%) increased. In contrast, among 3.3-kb(+), OGDH increased (+54%) together with a decrease in PFK (-1%) and PFK-to-OGDH ratio (-5%). These changes were significantly different between genotypes (P from <0.05 to 0.01). In conclusion, fat mass, low-density lipoprotein cholesterol, and skeletal muscle glycolytic-to-oxidative enzyme ratio increased more in the alpha2-gene 3.3-kb(-) subjects with overfeeding, suggesting more unfavorable metabolic changes compared with the 3.3-kb(+) subjects.

Adipose Tissue↗
PubMed2002

Adiponectin: a link between excess adiposity and associated comorbidities?

Adiponectin is a novel polypeptide that is highly specific to adipose tissue. In contrast to other adipocytokines, adiponectin levels are decreased in obesity and associated comorbidities, such as type 2 diabetes. Decreased expression of adiponectin is correlated with insulin resistance. It has been suggested that several agents, such as tumor necrosis factor alpha, could mediate their effects on insulin metabolism through modulating adiponectin secretion from adipocytes. The mechanisms for the development of atherosclerotic vascular disease in obese individuals are largely unknown. Several findings support the interesting hypothesis that adiponectin could be a link between obesity and related atherosclerosis. First, adiponectin levels are lower in patients with coronary artery disease. Second, adiponectin modulates endothelial function and has an inhibitory effect on vascular smooth muscle cell proliferation. Moreover, adiponectin is accumulated more preferably to the injured vascular wall than intact vessels and has been shown to suppress macrophage-to-foam cell transformation. Adiponectin may also be involved in the modulation of inflammation. Thiazolidinediones, antiatherogenic and other effects have been explained by their direct enhancing effect on adiponectin. In conclusion, adiponectin has anti-inflammatory and antiatherogeneic effects as well as multiple beneficial effects on metabolism. Therefore it is not a surprise that adiponectin therapy has been tested in animal models of obesity, and it has been shown to ameliorate hyperglycemia and hyperinsulinemia without inducing weight gain or even inducing weight loss in some studies. Unlike agents that exert their effects centrally, adiponectin's effects seem to be peripherally mediated. The evidence of an association between adiponectin and the metabolic and cardiovascular complications of obesity is growing all the time.

Adipocytes↗
PubMed2002

[Ghrelin--peptide hormone that increases appetite. It opens new possibilities for the research on energy metabolism].

Ghrelin is an endogenous ligand for the growth hormone secretagogue receptor (GHS-R) that potently stimulates growth hormone (GH) release. The discovery of ghrelin opens up a new regulatory system for GH secretion. Surprisingly, recent studies in rodents suggest that peripherally or centrally administered ghrelin, independent of GH, decreases fat oxidation and increases food intake and adiposity. In addition, plasma ghrelin levels are lower in obese human subjects. Ghrelin might participate in meal initiation and may signal to the hypothalamus when an increase in metabolic efficiency is needed.

Animals↗