Biological responses of midge (Chironomus riparius) and lamprey (Lampetra fluviatilis) larvae in ecotoxicity assessment of PCDD/F-, PCB- and Hg-contaminated river sediments.

We evaluated the utility of chironomid and lamprey larval responses in ecotoxicity assessment of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/F)-, polychlorinated biphenyls (PCB)- and mercury (Hg)-contaminated river sediments. Sediment samples were collected from the River Kymijoki with a known industrial pollution gradient. Sediment for the controls and lamprey larvae were obtained from an uncontaminated river nearby. Contamination levels were verified with sediment and tissue PCDD/F, PCB and Hg analyses. Behaviour of sediment-exposed chironomid and lamprey larvae were measured with Multispecies Freshwater Biomonitor© utilizing quadrupole impedance conversion technique. In addition, mortality, growth and head capsule deformity incidence of chironomids were used as ecotoxicity indicators. WHOPCDD/F+PCB-TEQ in the R. Kymijoki sediments ranged from the highest upstream 22.36 ng g(-1) dw to the lowest 1.50 ng g(-1) near the river mouth. The sum of PCDD/Fs and PCBs correlated strongly with Hg sediment concentrations, which ranged from <0.01 to 1.15 µg g(-1). Lamprey tissue concentrations of PCDD/Fs were two orders and PCBs one order of magnitude higher in the R. Kymijoki compared to the reference. Chironomid growth decreased in contaminated sediments and was negatively related to sediment ∑PCDD/Fs, WHOPCDD/F+PCB-TEQ and Hg. There were no significant differences in larval mortality or chironomid mentum deformity incidence between the sediment exposures. The distinct behavioural patterns of both species indicate overall applicability of behavioural MFB measurements of these species in sediment toxicity bioassays. Chironomids spent less and lampreys more time in locomotion in the most contaminated sediment compared to the reference, albeit statistically significant differences were not detected. Lamprey larvae had also a greater activity range in some of the contaminated sediments than in the reference. High pollutant levels in lamprey indicate risks for biomagnification in the food webs, with potential health risks to humans consuming fish.

Long-lasting TMS motor threshold elevation in mild traumatic brain injury.

OBJECTIVES: Mild traumatic brain injury (mTBI) is very common, and part of the patients experience persistent symptoms. These may be caused by diffuse neuronal damage and could therefore affect cortical excitability. The motor threshold (MT), measured by transcranial magnetic stimulation (TMS), is a measure of cortical excitability and cortico-spinal tract integrity. MATERIALS AND METHODS: We used navigated TMS (nTMS) and electromyography to determine subjects' left hemisphere MTs. Nineteen subjects with mTBI (11 with persistent symptoms and eight fully recovered) and nine healthy controls were tested. The injuries had occurred on average 5 years earlier. All participants had normal brain MRIs, that is, no signs of injury. None used centrally acting medication. RESULTS: The mean MT in controls was 43.0% (SD 2.5) of maximum stimulator output. The mTBI subjects mean MT was 53.4% (SD 9.7), being higher than the controls' threshold. Subjective recovery did not correlate with MT. CONCLUSIONS: The results show chronic MT elevation in a sample of subjects with symptomatic or recovered mTBI. This suggests that mTBI may be compensated, although not fully recovered, years after the injury. While the cause for MT elevation cannot be concluded from these preliminary observations, possible explanations include decreased cortical excitability and impaired subcortical conduction.

Right visual field advantage for perceived contrast: correlation with an auditory bias and handedness.

Studies have suggested that supramodal attentional resources are biased rightward due to asymmetric spatial fields of the two hemispheres. This bias has been observed especially in right-handed subjects. We presented left and right-handed subjects with brief uniform grey visual stimuli in either the left or right visual hemifield. Consistent with the proposed asymmetry in attentional resources, right-handed subjects estimated right hemifield targets as having a higher contrast than physically identical stimuli presented in the left hemifield. Left-handed participants did not show a systematic rightward or leftward bias. However, the group of left-handed participants also took part in a dichotic listening experiment whose results showed that visual bias score correlated positively with ear-advantage in dichotic listening. Our results are consistent with the view that supramodal processing resources are biased towards the right hemispace, and that this bias is influenced by handedness.

The effects of rivastigmine on processing speed and brain activation in patients with multiple sclerosis and subjective cognitive fatigue.

BACKGROUND: Cognitive decline and fatigue are typical in multiple sclerosis (MS). However, there is no official medication for either of these symptoms. OBJECTIVE: The purpose of this study was to estimate the effects of a single dose of rivastigmine on processing speed and associated brain activity in patients with MS and subjective cognitive fatigue. METHODS: Fifteen patients with MS and subjective cognitive fatigue and 13 healthy controls (HCs) matched for age, gender and education performed a neuropsychological assessment and functional (f)MRI. A modified version of the Paced Visual Serial Addition Test (mPVSAT) was used as the behavioural task during fMRIs. After the first scanning session, both groups were randomly divided into two subgroups receiving either rivastigmine or placebo. A single dose of rivastigmine or placebo was administrated double-blindly and 2.5 hours later the scanning was repeated. RESULTS: At baseline, the patients with MS showed slower processing speed in mPVSAT compared with the HCs. They also demonstrated stronger bilateral frontal activation after sustained cognitive effort than the HCs. Performance improvement and a further activation increase in the left anterior frontal cortex and additional activation in the right cerebellum were observed in patients who received rivastigmine but not in patients on placebo, or in HCs with placebo or rivastigmine. CONCLUSION: These preliminary findings suggest that rivastigmine may improve cognitive processing speed by enhancing compensatory brain activation in patients with MS.

Hemispatial neglect reflected on visual memory.

PURPOSE: Recent studies of hemispatial neglect have revealed both lateralized and nonlateralized attention mechanisms contributing to the syndrome. In addition, neglect patients show impaired spatial working memory and diminished working memory capacity. The aim of this study was to investigate, how neglect would be reflected in their performances in commonly used clinical visual memory tests. METHODS: Twelve patients with right hemisphere lesions and left neglect and twelve matched controls were assessed with the Behavioural Inattention Test, the visual reproduction of the WMS-R, the object memory test, the Rey figure test and the list learning test. Visuo-spatial span was explored with the Corsi block test. RESULTS: The severity of neglect was significantly associated with the naming of objects from the left side, with the copying of the Rey figure and with the immediate visual reproduction of the WMS-R. In comparison to the matched controls, the patients named and copied fewer items from both sides and showed impaired immediate and delayed recall of visual material, more so from the left side. After recovery, patients were still impaired in their visual search, whereas their immediate reproduction of visual material was no longer significantly different from the control subjects. The deficit in delayed recall of visual material persisted and was lateralized to the left side of the recollected memories. The role of hemianopia was analyzed. CONCLUSIONS: Patients with neglect exhibited spatial working memory bias and diminished nonlateralized attention capacity in encoding and immediate recall. The deficit in delayed recall was lateralized to the left side of memorized material.

Comparison of the Behavioural Inattention Test and the Catherine Bergego Scale in assessment of hemispatial neglect.

The objective of the study was to correlate visual and behavioural assessments of hemispatial neglect caused by cerebrovascular accident. We assessed 17 consecutive right-hemisphere stroke patients with hemispatial neglect: the Catherine Bergego Scale (CBS) was used to evaluate neglect in spontaneous behaviour and the conventional subtests of the Behavioural Inattention Test (BIT C) were used to assess visual neglect. The proportional severity of both visual and behavioural neglect was calculated in each individual patient. Dissociations were found between mild neglect in visual screening tasks and moderate or severe neglect in behaviour, although in most patients, neglect was equally evident in both tests. Only the line bisection subtest from the BIT correlated significantly with the CBS, yet both tests showed good internal consistency. The line bisection test and several items of the CBS were especially sensitive in detecting the combination of visual field deficit and hemispatial neglect. In conclusion, we propose that visual fields should always be assessed in patients with neglect because neglect may be exacerbated by a visual field deficit and this can cause prolonged functional disability in everyday life situations. Specific rehabilitation methods might also be needed in neglect with or without hemianopia.

Bone mineral content in young adults with active or inactive juvenile idiopathic arthritis and in controls.

OBJECTIVE: To obtain information on bone mineral content (BMC) in juvenile idiopathic arthritis (JIA) in young adulthood. METHODS: BMC measurements of 116 young adults with JIA and controls were performed at the lumbar spine and the proximal femur by dual-energy X-ray absorptiometry (DXA). RESULTS: Patients were divided into the JIA-active group (n = 73) and the JIA-inactive group (n = 43). Fifty-five per cent of men and 30% of women had their disease in remission. Forty-eight per cent in the JIA-active group and 16% in the JIA-inactive group had used glucocorticoids (p < 0.001). Mean BMC in the femoral neck was 5.76 (SD 0.21) g for men and 4.74 (SD 0.10) g for women in the JIA-active group; 5.84 (SD 0.23) g for men and 4.59 (SD 0.06) g for women in the JIA-inactive group; and 6.65 (SD 0.20) g for men and 4.78 (SD 0.07) g for women in the controls. Both JIA groups had lower BMC values in the femoral neck than the controls (p < 0.001), but a statistically significant difference was found among men (p = 0.006). There was no significant difference in mean BMC in the lumbar spine between the JIA groups and the controls, nor between men and women. Glucocorticoid use, weight and also height among women were associated statistically significantly with BMC in the femoral neck. CONCLUSIONS: Young adults, especially men, with JIA have reduced BMC values in the femoral neck. Glucocorticoid use and weight, but not disease activity, seem to be associated with lower BMC. However, osteoporosis is rare.

Rehabilitation of hemispatial neglect: A randomized study using either arm activation or visual scanning training.

PURPOSE: Hemispatial neglect, a failure to orient to the contralateral side of the lesion, is a disabling disorder after stroke. Previously arm activation combined with visual training or visual scanning training were found effective in rehabilitation of hemispatial neglect. The aim of this study was to determine whether left arm activation alone could be sufficient to produce a long lasting amelioration of neglect comparable to the effect obtained with traditional visual scanning training. METHODS: Twelve neglect patients less than six months from stroke were randomized either into 20-30 hours of left arm activation training or 10 hours of traditional visual scanning training as a part of a comprehensive rehabilitation program. All patients received 48~hours of therapy during the 3-week rehabilitation. RESULTS: Visual neglect of the arm activation group recovered significantly in the conventional subtests of the Behavioural Inattention Test both post-rehabilitation and at 6-months follow-up. The improvement of the visual scanning training group was almost significant at the end of the rehabilitation and significant by the follow-up. The behavioural neglect observed in the Catherine Bergego Scale was alleviated nearly significantly at the post-rehabilitation in both groups. The effect was maintained in the arm activation group at 6-months. CONCLUSION: The arm activation training appears beneficial even without supplementary visual neglect rehabilitation, although the traditional visual scanning training may have further effects in cognition.

Physical activity modifies the effect of SNPs in the SLC2A2 (GLUT2) and ABCC8 (SUR1) genes on the risk of developing type 2 diabetes.

Single nucleotide polymorphisms (SNPs) in two genes regulating insulin secretion, SLC2A2 (encoding GLUT2) and ABCC8 (encoding SUR1), were associated with the conversion from impaired glucose tolerance (IGT) to type 2 diabetes (T2D) in the Finnish Diabetes Prevention Study (DPS). We determined whether physical activity (PA), assessed annually with a questionnaire, modified the association of SNPs in SLC2A2 and ABCC8 with the conversion to T2D in the combined intervention and control groups of the DPS. Finnish overweight subjects with IGT (N = 479) were followed for an average of 4.1 yr. The interaction of the SNPs with the change in PA on the conversion to T2D was assessed using Cox regression with adjustments for the other components of the intervention (dietary changes, weight reduction). The carriers of the common homozygous genotype of rs5393, rs5394, or rs5404 of SLC2A2 and rs3758947 of ABCC8 who were in the lower third of the change in moderate-to-vigorous PA during the follow-up had a 2.6- to 3.7-fold increased risk of developing T2D compared with the upper third, whereas the rare allele carriers seemed to be unresponsive to changes in moderate-to-vigorous PA (for the interaction of genotype with change in PA, P = 0.022-0.027 for the SNPs in SLC2A2, and P = 0.007 for rs3758947). We conclude that moderate-to-vigorous PA may modify the risk of developing T2D associated with genes regulating insulin secretion (SLC2A2, ABCC8) in persons with IGT.

Predictive value of health-related fitness tests for self-reported mobility difficulties among high-functioning elderly men and women.

BACKGROUND AND AIMS: The functional independence of elderly populations deteriorates with age. Several tests of physical performance have been developed for screening elderly persons who are at risk of losing their functional independence. The purpose of the present study was to investigate whether several components of health-related fitness (HRF) are valid in predicting the occurrence of self-reported mobility difficulties (MD) among high-functioning older adults. METHODS: Subjects were community-dwelling men and women, born 1917-1941, who participated in the assessment of HRF [6.1-m (20-ft) walk, one-leg stand, backwards walk, trunk side-bending, dynamic back extension, one-leg squat, 1-km walk] and who were free of MD in 1996 (no difficulties in walking 2- km, n=788; no difficulties in climbing stairs, n=647). Postal questionnaires were used to assess the prevalence of MD in 1996 and the occurrence of new MD in 2002. Logistic regression analysis was used as the statistical method. RESULTS: Both inability to perform the backwards walk and a poorer result in it were associated with risk of walking difficulties in the logistic model, with all the statistically significant single test items included. Results of 1-km walk time and one-leg squat strength test were also associated with risk, although the squat was statistically significant only in two older birth cohorts. Regarding stair-climbing difficulties, poorer results in the 1-km walk, dynamic back extension and one-leg squat tests were associated with increased risk of MD. CONCLUSIONS: The backwards walk, one-leg squat, dynamic back extension and 1-km walk tests were the best predictors of MD. These tests are recommended for use in screening high-functioning older people at risk of MD, as well as to target physical activity counseling to those components of HRF that are important for functional independence.

Association of the Leu72Met polymorphism of the ghrelin gene with the risk of Type 2 diabetes in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study.

AIMS: Ghrelin is a gut-brain regulatory peptide stimulating appetite and controlling energy balance. In previous studies, the Leu72Met polymorphism of the ghrelin gene has been associated with obesity and impaired insulin secretion. We investigated whether the Leu72Met polymorphism is associated with the incidence of Type 2 diabetes in subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study (DPS). METHODS: DPS was a longitudinal intervention study carried out in five participating centres in Finland. A total of 522 subjects with IGT were randomized into either an intervention or a control group and DNA was available from 507 subjects. The Leu72Met polymorphism was screened by the restriction fragment length polymorphism method. RESULTS: There were no differences in clinical and anthropometric characteristics among the genotypes at baseline. IGT subjects with the Met72 allele were at higher risk of developing Type 2 diabetes than subjects with the Leu72Leu genotype (P = 0.046). Our data also demonstrated that IGT subjects with the common Leu72Leu genotype developed Type 2 diabetes less frequently under intervention circumstances than subjects with the Met72 allele (OR = 0.28, 95% CI 0.10-0.79; P = 0.016). CONCLUSIONS: Subjects with the Leu72Leu genotype had a lower risk for the development of Type 2 diabetes. This was observed particularly in the study subjects who underwent an intensive diet and exercise intervention. Defective first-phase insulin secretion related to the Met72 allele might be one factor contributing to the conversion to Type 2 diabetes.

Association of sequence variations in the gene encoding adiponectin receptor 1 (ADIPOR1) with body size and insulin levels. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: Adiponectin is a circulating peptide derived from adipose tissue. It mediates its insulin-sensitising and anti-atherogenic effects on target tissues through two known receptors, adiponectin receptors 1 and 2 (ADIPOR1; ADIPOR2), which are encoded by the genes ADIPOR1 and ADIPOR2. Our aim was to study the association of ADIPOR1 gene variations with body size and risk of type 2 diabetes in subjects with impaired glucose tolerance, who participated in the Finnish Diabetes Prevention Study (DPS). SUBJECTS AND METHODS: We selected seven single nucleotide polymorphisms (SNPs) of the ADIPOR1 gene to perform association studies with anthropometrics and metabolic parameters at baseline, and with the risk of type 2 diabetes during the 3-year follow-up in the DPS study population. Both single SNP analysis and haplotype effects were studied. RESULTS: Three out of seven markers studied (rs10920534, rs22757538 and rs1342387) were significantly associated with various body size measurements including weight, height, waist and hip circumference, sagittal diameter and body mass index. Furthermore, three markers (rs10920534, rs12045862 and rs7539542), of which two were different from those associating with body size, were linked to fasting and 2-h insulin levels, particularly in men at baseline. The haplotype analysis with five markers revealed seven major haplotypes in the DPS study population. The haplotype effects on body size measures were in line with those of single SNP analysis. However, none of the markers were associated with the risk of type 2 diabetes. CONCLUSIONS/INTERPRETATION: Our findings suggest that ADIPOR1 has a putative role in the development of body size, and that traits for central adiposity and insulin resistance may be dissociated from each other.

Role of skeletal muscle-fibre type in regulation of glucose metabolism in middle-aged subjects with impaired glucose tolerance during a long-term exercise and dietary intervention.

AIM: The aim of this study was to investigate the role of skeletal muscle fibre type in the regulation of glucose metabolism in middle-aged obese subjects with impaired glucose tolerance (IGT) during a 2-year exercise and dietary intervention. METHODS: Muscle biopsies (musculus vastus lateralis) were taken from 22 subjects belonging to the intervention group of the Finnish Diabetes Prevention Study [1]. According to their myosin heavy chain (MHC) profile at the baseline, the subjects were divided into two groups: IGT(slow) (n=10) with a high proportion of MHC I isoforms and IGT(fast) (n=12) with a high proportion of MHC II isoforms in the vastus lateralis muscle. The intervention consisted of dietary counselling, strength and power training and/or aerobic exercise. The amount of exercise was the same in both groups; the exercise frequency was 5.1+/-2.7 h/week in the IGT(slow) and 5.1+/-2.8 h/week in the IGT(fast) group. RESULTS: Fasting glucose (p<0.05), 2-h glucose (p<0.05), fasting insulin (p<0.05), haemoglobin A1c (HbA(1c)) (p<0.01) and insulin resistance (p<0.05) [homeostasis model assessment for insulin resistance (HOMA-IR)] decreased in the IGT(fast) group, whereas only the 2-h glucose and HbA(1c) concentrations decreased in the IGT(slow) group. The amount of the glycogen synthase kinase-3-alphabeta (GSK-3-alphabeta) decreased in the IGT(fast) group (p<0.05). Exercise training increased the lactate dehydrogenase (LDH) (p<0.01), LDH-1 (p<0.05) and citrate synthase (CS) (p<0.05) activities in the vastus lateralis muscle in the IGT(slow) group, but only the CS activity (p<0.05) in the IGT(fast) group. CONCLUSIONS: The glucose metabolism improved both in the IGT(slow) and IGT(fast) group during the 2-year exercise and dietary intervention. The change was more prominent in the IGT(fast) group than in the IGT(slow) group, associated with the decrease of the GSK-alphabeta protein expression in skeletal muscle. The exercise training improved both glycolytic and oxidative capacity in the vastus lateralis muscle. The glycolytic capacity improved in the IGT(slow) group and the oxidative capacity in both groups.

Improved fibrinolysis by an intensive lifestyle intervention in subjects with impaired glucose tolerance. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of lifestyle intervention on the levels of plasminogen activator inhibitor (PAI-1) and fibrinogen in subjects participating in the Finnish Diabetes Prevention Study (DPS). METHODS: In five DPS centres, 321 subjects with impaired glucose tolerance (intervention group, n=163; control group, n=158) had their PAI-1 and fibrinogen levels measured at baseline and at the 1-year follow-up. Additional 3-year follow-up assessments were carried out in a sample of 97 subjects in one of the DPS centres (Turku). The intervention programme included an intensive lifestyle intervention aiming at weight reduction, healthy diet and increased physical activity. RESULTS: During the first intervention year, PAI-1 decreased by 31% in the intervention group but showed no change in the control group (p<0.0001). In the Turku subgroup, the decrease in PAI-1 persisted throughout the 3-year follow-up. Changes in PAI-1 were associated with the number of lifestyle changes made during the first year (p=0.008). Weight reduction was the most important factor explaining the decrease in PAI-1. Changes in fibrinogen levels did not differ between the groups. CONCLUSIONS/INTERPRETATION: In addition to the previously reported reduction in the risk of type 2 diabetes in DPS participants with impaired glucose tolerance, the intensive dietary and exercise intervention had beneficial long-term effects on fibrinolysis as indicated by the reduced levels of PAI-1. These results suggest that elevated PAI-1 levels in obese subjects with impaired glucose tolerance are mostly reversible by lifestyle changes, especially those geared to weight reduction.

Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: The Finnish Diabetes Prevention Study.

OBJECTIVE: Genetic variation in leptin receptor (LEPR) gene has been reported to associate with insulin and glucose metabolism and adiposity in different study settings and various populations. We wanted to evaluate the association between LEPR polymorphisms, diabetes risk and body weight in Finnish subjects with impaired glucose tolerance (IGT). METHODS: We investigated the associations of the three LEPR polymorphisms (Lys109Arg, Gln223Arg, 3'UTR Del/Ins) with the conversion to type 2 diabetes and the changes in body weight in 507 individuals with IGT participating in the Finnish Diabetes Prevention Study. Participants were randomized to either an intensive diet and exercise intervention group or a control group. RESULTS: After 3 years, the odds ratio for the development of type 2 diabetes in individuals in the control group with the Lys109Lys genotype was 2.38-fold higher than in individuals with other genotype combinations (P=0.016). Irrespective of group individuals with the Gln223Gln genotype had higher conversion to type 2 diabetes (OR 2.01 (95% CI 1.03-3.93)) than the Arg223 allele carriers (P=0.042). The risk was more pronounced in the control group than in the intervention group. Individuals having the 3'UTR Del/Del genotype had a slightly higher body weight throughout the study than those with the insertion allele (P=0.020), although no difference in weight change was observed. CONCLUSION: Two polymorphisms (Lys109Arg, Gln223Arg) in the extracellular domain of the leptin receptor predicted the conversion to type 2 diabetes in high-risk individuals with IGT. The Del/Ins polymorphism in the 3'UTR of LEPR was associated with body weight.

Recovery of somatosensory deficits in acute stroke.

OBJECTIVES: To study the recovery of somatosensory deficits after acute stroke. MATERIAL AND METHODS: A detailed clinical examination of sensation, median nerve somatosensory evoked potentials (SEP), quantitative sensory tests (QST), and subjective evaluation were performed in five acute stroke patients at three control time points up to 12 months after the stroke. RESULTS: The deficit recovered at least partially in all patients, mostly within 3 months after stroke. The improvement in warm and vibration detection thresholds occurred between 3 and 12 months. The SEP improved both by 3 and 12 months. CONCLUSION: The recovery of subjective sensory disturbance occurred in line with the improvement of the clinical sensory tests and QST. The most sensitive measure for somatosensory dysfunction at the early phase was graphesthesia. In our patients, initially normal SEP with a sensory deficit resulted in excellent clinical recovery, whereas initially absent SEP did not necessarily predict poor outcome.

The development of bone mineral density and the occurrence of osteoporosis from 15 to 20 years of disease onset in patients with rheumatoid arthritis.

OBJECTIVE: To ascertain the occurrence of osteoporosis and the development of central bone mineral density (BMD) in long-term rheumatoid arthritis (RA) METHODS: BMD of the lumbar spine (L2-L4) and the femoral neck were measured by dual-energy X-ray absorptiometry in a cohort of 59 patients (49 women and 10 men) with rheumatoid factor-positive RA followed up for 20 years. BMD measurements were obtained at the 15- and 20-year follow-up visits. RESULTS: At the 15-year check-up the mean age was 61 (SD 13)for men and 54 (SD 11) years for women. Bone densitometry of these patients revealed decreased BMD at both lumbar spine and femoral neck, the mean T-scores being -1.1 [95%CI: -1.6 to -0.6] and -1.3 [95%CI: -1.6 to -1], respectively). Eighteen (31 %) patients thus had osteoporosis (BMD T -score < or = -2.5) and 32 (54%) patients were osteopenic (BMD T-score -1.0 to -2.5). However, when compared with reference values, the decreases in central bone mineral in this patient group were of low degree; the mean Z-score -0.2 [95%CI: -0.7 to 0.2] at the lumbar spine and -0.5 [95%CI: -0.8 to -0.3] at the femoral neck, respectively. After the subsequent five years the mean Z-score increased 0.45 [95%CI: 0.32 to 0.58] at the lumbar spine and the mean T-score decreased -0.20 [95%CI: -0.32 to -0.08] at the femoral neck. ESR, Larsen score, gender and cumulative dose of prednisolone during the 5 year follow-up and HAQ-index were used as explanatory parameters of BMD change between the 15- and 20-year follow-ups. None of these parameters explained the BMD change. CONCLUSION: We conclude that in long-term RA central bone densities seemed to be only moderately decreased after 15 years from eruption of RA. No essential change in central BMD was found after the consecutive 5 years.

Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: Impaired insulin secretion has a strong genetic component. In this study we investigated whether the 12Glu9 polymorphism in the gene encoding the alpha2B-adrenergic receptor ( ADRA2B) is associated with insulin secretion and/or the incidence of Type 2 diabetes in individuals with impaired glucose tolerance. METHODS: We investigated a total of 506 subjects with impaired glucose tolerance participating in the Finnish Diabetes Prevention Study (DPS). Participants were randomly assigned to an intervention group or a control group. Anthropometric measurements and an oral glucose tolerance test were performed at baseline and at annual follow-up. In a subgroup of patients (n=83), a frequently sampled intravenous glucose tolerance test (FSIGT) was performed at baseline. RESULTS: All patients had similar anthropometric measurements and insulin and glucose levels at baseline. Multiple logistic regression analysis revealed significant interaction (p=0.003) between study group and genotype across the entire study population. In the control group, subjects with the Glu9 allele had an increased risk of developing Type 2 diabetes compared with subjects with the Glu12/12 genotype (odds ratio [OR]=2.68, 95% CI 1.02-7.09, p=0.047 for Glu12/12, and OR=5.17, 95% CI 1.76-15.21, p=0.003 for Glu9/9). This increased risk was not observed in the intervention group, who showed significant weight loss during the trial. In the subgroup who underwent the FSIGT, subjects with the Glu9/9 genotype showed the lowest acute insulin response (p=0.005 for trend). CONCLUSIONS/INTERPRETATION: The 12Glu9 polymorphism of ADRA2B is associated with impaired first-phase insulin secretion and may predict the development of Type 2 diabetes in subjects with impaired glucose tolerance who are not subjected to a lifestyle intervention.

Common polymorphisms in the genes regulating the early insulin signalling pathway: effects on weight change and the conversion from impaired glucose tolerance to Type 2 diabetes. The Finnish Diabetes Prevention Study.

AIMS/HYPOTHESIS: Type 2 diabetes is a complex disorder with strong heritability. The aim of our study was to investigate whether common polymorphisms in the genes regulating the early insulin signalling pathway (insulin; A-23T, insulin-like growth factor 1 receptor [IGF-1R]; GAG1013GAA, plasma cell membrane glycoprotein 1 [PC-1]; K121Q, insulin receptor substrate [IRS-1]; G972R, insulin receptor substrate 2 [IRS-2]; G1057D and phosphatidylinositol 3-kinase p85 alpha [PI3K]; M326I) affect the weight change and development of Type 2 diabetes in the Finnish Diabetes Prevention Study. METHODS: We screened for the polymorphisms in 490 overweight subjects with impaired glucose tolerance whose DNA was available from the Finnish Diabetes Prevention Study. These subjects were randomly allocated into a control group and an intervention group characterised by intensive, individualised diet and exercise. RESULTS: In carriers of the GAA1013GAA genotype of IGF-1R, the R972 allele of IRS-1 and the D1057D genotype of IRS-2, lifestyle intervention did not lead to significant differences in weight loss between the intervention and control groups, implying a role of these risk genotypes in the regulation of body weight. We observed a statistically significant difference in the conversion rate from IGT to diabetes between the genotypes of the IGF-1R gene (GAG1013GAG: 18.6%, GAG1013GAA: 10.4%, GAA1013GAA: 19.5%, p=0.033). Common polymorphisms in the insulin, PC-1 and PI3K genes did not regulate weight change or conversion to diabetes. CONCLUSIONS/INTERPRETATION: The common polymorphisms of the IGF-1R, IRS-1 and IRS-2 genes may modify the weight change response to a lifestyle intervention but not the conversion from IGT to Type 2 diabetes, whereas IGF-1R may also regulate the risk of developing Type 2 diabetes.