Non-linguistic comprehension, social inference and empathizing skills in autistic young adults, young adults with autistic traits and control young adults: Group differences and interrelatedness of skills.

BACKGROUND: Despite increasing knowledge of social communication skills of autistic peole, the interrelatedness of different skills such as non-linguistic comprehension, social inference and empathizing skills is not much known about. A better understanding of the complex interplay between different domains of social communication helps us to develop assessment protocols for individuals with social communication difficulties. AIMS: To compare the performances of autistic young adults, young adults with autistic traits identified in childhood and control young adults in social communication tasks measuring non-linguistic comprehension, social inference and empathizing skills. In addition, to examine associations between the different social communication measures. METHODS & PROCEDURES: Autistic young adults (n = 34), young adults with autistic traits (n = 19) and control young adults (n = 36) completed the extra- and paralinguistic scales of the Assessment Battery for Communication (ABaCo), the Faux Pas Recognition Test, Social-Pragmatic Questions (SoPra) and the Empathy Quotient (EQ). OUTCOMES & RESULTS: Group differences were found in the performance in the ABaCo, SoPra and EQ scores. Compared with the control young adults, autistic young adults scored lower. The performance of the young adults in the autistic traits group fell in between the other two groups. There were no group differences in the Faux Pas Recognition Test. The variability within the groups was large in all measurements. In the control group, there was a significant correlation between EQ and SoPra scores and between the Faux Pas and SoPra scores. In the autistic group, a significant correlation was found between Faux Pas and SoPra scores. Also, other patterns were observed but these were not statistically significant. CONCLUSIONS & IMPLICATIONS: The young adults with autistic traits fell in between the control and autistic young adults, highlighting the presence of the continuum in the terms of features of social communication. The results support other current research that suggests that theory of mind and other social communication skills may not be universally or widely impaired in all autistic individuals without cognitive deficits. Although all tasks examined social communication skills, only a small number of significant correlations were found between test scores. This highlights that clinical conclusions about a person's social communication should be based on the outcomes of different types of methods measuring different aspects of social communication. It is clear that the interrelatedness of different social communication skills needs further research. WHAT THIS PAPER ADDS: What is already known on this subject For successful communication, the ability to infer others' emotions, intentions and mental states is crucial. Autistic people have difficulty with many aspects of social communication. However, the associations between different aspects of social communication need to be better understood. What this paper adds to existing knowledge The unique contribution of this study is to compare the performance of autistic people not only with that of a control group but also with people with childhood autistic traits. This provides an understanding of the interrelatedness of different social communication skills in people with varying degrees of autistic traits. This study used four assessment methods focusing on three different social communication elements (non-linguistic comprehension, social inference and empathizing skills). These elements have complex relationships to one another, some being closely overlapping, some more distally related and some reflect more complex multifactorial elements. This study shows that although groups differ from each other in most of the assessments, the performance of different groups overlapped showing that many autistic young adults can perform well in non-linguistic and social inference tasks in structured assessment contexts. What are the potential or actual clinical implications of this work? Our findings suggest that in the assessment of social communication, self-reports and clinical assessments can be used effectively together. They can complement each other, pointing out the strengths and weaknesses of a person, leading to more personalized therapeutic interventions.

Pragmatic language development in language impaired and typically developing children: incorrect answers in context.

This study focussed on young children's incorrect answers to pragmatically demanding questions. Children with specific language impairment (SLI), including a subgroup with pragmatic language difficulties (PLD) and typically developing children answered questions targeting implicatures, based on a storybook and short verbal scenarios. Ninety-seven children participated in this study: 30 children with SLI of whom 12 had PLD, 32 typically developing children aged 5-6 years and 35 aged 7-11 years. The incorrect answers produced by the children with SLI were similar in their use of context to those of the 5-6 year old, suggesting developmental delay. The children with PLD produced significantly more irrelevant answers than both the language impaired children without PLD and the typically developing groups and had most difficulty when the context was presented solely verbally. Results are discussed in relation to a cognitive theory of communication and the clinical implications.

Linguistic and pragmatic aspects of narration in Finnish typically developing children and children with specific language impairment.

This study investigates narratives of Finnish children with specific language impairment (SLI) from linguistic and pragmatic perspectives, in order to get a comprehensive overview of these children's narrative abilities. Nineteen children with SLI (mean age 6;1 years) and 19 typically developing age-matched children participated in the study. Their picture-elicited narrations were analysed for linguistic productivity and complexity, grammatical and referential accuracy, event content, the use of mental state expressions and narrative comprehension. Children with SLI showed difficulties in every aspect of narration in comparison to their peers. Only one measure of productivity, the number of communication units, did not reach statistical significance. Not only was linguistic structure fragile but also pragmatic aspects of storytelling (referencing, event content, mental state expressions and inferencing) were demanding for children with SLI. Results suggest that pragmatic aspects of narration should be taken into account more often when assessing narrative abilities of children with SLI.

Autistic adults and adults with sub-clinical autistic traits differ from non-autistic adults in social-pragmatic inferencing and narrative discourse.

LAY ABSTRACT: Previous social-pragmatic and narrative research involving autistic individuals has mostly focused on children. Little is known about how autistic adults and adults who have autistic traits but do not have a diagnosis of an autism spectrum disorder (ASD) interpret complex social situations and tell narratives about these situations. We asked 32 autistic young adults, 18 adults with autistic traits but no ASD diagnosis, and 34 non-autistic young adults to watch socially complex situations and freely tell narratives about what they thought was occurring in each situation. These narratives were analysed for how the participants had interpreted the situations and for the type of narratives they produced. We found that the groups had both similarities and differences. Regarding the differences, we found that the autistic adults and adults with autistic traits interpreted the situations differently from the non-autistic adults. The autistic adults found different aspects of the situations relevant, had different foci and placed greater importance on details than the non-autistic adults. The autistic adults and adults with autistic traits also differed from the non-autistic adults by having more detail- and event-focused narratives whereas the non-autistic adults were more likely to base their narratives on their own broad interpretations of the situations. Perceptual processing styles appeared to play a bigger role in interpreting the situations for the autistic adults and adults with autistic traits than the non-autistic adults. Our findings suggest that autistic adults and adults with autistic traits focus on different aspects in their social world than non-autistic adults.

Children with specific language impairment in Finnish: the use of tense and agreement inflections.

Children with specific language impairment (SLI) vary widely in their ability to use tense/agreement inflections depending on the type of language being acquired, a fact that current accounts of SLI have tried to explain. Finnish provides an important test case for these accounts because: (1) verbs in the first and second person permit null subjects whereas verbs in the third person do not; and (2) tense and agreement inflections are agglutinating and thus one type of inflection can appear without the other. Probes were used to compare the verb inflection use of Finnish-speaking children with SLI, and both age-matched and younger typically developing children. The children with SLI were less accurate, and the pattern of their errors did not match predictions based on current accounts of SLI. It appears that children with SLI have difficulty learning complex verb inflection paradigms apart from any problem specific to tense and agreement.

Long-term effects of growth hormone therapy on patients with Prader-Willi syndrome.

AIM: To assess the effects of recombinant human growth hormone (rhGH) treatment in children with Prader-Willi syndrome. DESIGN: A 1-year study and an observational follow-up visit 10 years later. METHODS: In 20 patients with Prader-Willi syndrome (PWS): clinical assessment, laboratory tests, body composition analysis by dual energy X-ray absorptiometry, sleep polygraphy, health-related quality of life assessed by 16D. RESULTS: Only two patients had normal growth hormone secretion at baseline. All patients were significantly shorter than their expected heights, but experienced catch-up growth during growth hormone treatment. At follow-up, 13 patients had reached adult heights and were markedly taller than historical controls. The cumulative dose of rhGH over 10 years correlated inversely with the total body fat percentage (p = 0.033). However, patients remained severely obese at 10 years. Sleep polygraphy was abnormal in more than half of the patients. Health-related quality of life of the patients remained substantially below that of normal population. CONCLUSION: Growth hormone markedly improved adult height in subjects with PWS when compared to historical data. The cumulative dose of growth hormone correlated with reduction in body fat; nevertheless, patients remained severely obese.

Processing of pragmatic communication in ASD: a video-based brain imaging study.

Social and pragmatic difficulties in autism spectrum disorder (ASD) are widely recognized, although their underlying neural level processing is not well understood. The aim of this study was to examine the activity of the brain network components linked to social and pragmatic understanding in order to reveal whether complex socio-pragmatic events evoke differences in brain activity between the ASD and control groups. Nineteen young adults (mean age 23.6 years) with ASD and 19 controls (mean age 22.7 years) were recruited for the study. The stimulus data consisted of video clips showing complex social events that demanded processing of pragmatic communication. In the analysis, the functional magnetic resonance imaging signal responses of the selected brain network components linked to social and pragmatic information processing were compared. Although the processing of the young adults with ASD was similar to that of the control group during the majority of the social scenes, differences between the groups were found in the activity of the social brain network components when the participants were observing situations with concurrent verbal and non-verbal communication events. The results suggest that the ASD group had challenges in processing concurrent multimodal cues in complex pragmatic communication situations.

Assessing social-pragmatic inferencing skills in children with autism spectrum disorder.

By utilizing the Pragma test this study investigated how sixteen five- to ten-year-old children with autism spectrum disorder (ASD) and sixteen typically developing (TD) children comprehended contextually challenging scenarios demanding 1) contextual inference with theory of mind (ToM), 2) contextual inference without ToM, 3) relevant use of language, 4) recognition of feelings, and 5) understanding false beliefs. The study also compared children's ability to explain their own correct answers. In addition, this study evaluated the sensitivity of three different methods for discriminating the children with ASD from the TD children: 1) the Pragma test, 2) the Social Interaction Deviance Composite (SIDC) of Children's Communication Checklist-2 (CCC-2), and 3) the Theory of Mind subtest of the Developmental Neuropsychological Assessment, Second edition (NEPSY-II). The results showed that children with ASD differed from TD children in questions demanding context utilization. However, the demand of mind-reading in utterance interpretation increased the difference between groups. Compared to TD children, children with ASD had more difficulties in explaining how they had used context to arrive at the correct answer. The discrimination power for detecting children with ASD from TD children was excellent in the Pragma test, good in the SIDC CCC-2 and fair in the Theory of Mind subtest of NEPSY-II. This study showed that by using contextually sensitive materials, such as the Pragma test, it is possible to detect the social-pragmatic inferencing difficulties of high-functioning children with ASD in structured test situations and not only in real-life situations or by using parental reports.

Decreased high-density lipoprotein (HDL) particle size, prebeta-, and large HDL subspecies concentration in Finnish low-HDL families: relationship with intima-media thickness.

OBJECTIVE: High-density lipoprotein (HDL) cholesterol correlates inversely with the risk of coronary heart disease (CHD). The precise antiatherogenic mechanisms of HDL subspecies are not thoroughly elucidated. We studied the relationship between carotid intima-media thickness (IMT) and HDL subspecies distribution in Finnish families with low HDL cholesterol and premature CHD. METHODS AND RESULTS: Altogether, 148 members of Finnish low-HDL families and 133 healthy control subjects participated in our study. HDL particle size was significantly smaller in affected family members (HDL < or =10th Finnish age-sex specific percentile) compared with unaffected family members and control subjects (9.1+/-0.04 nm versus 9.5+/-0.05 nm, P<0.0001, versus 9.8+/-0.03 nm, P<0.0001 [mean+/-SE]). Large HDL2b particles as well as prebeta-HDL concentration were significantly decreased among the affected family members. Mean IMT was significantly higher in the affected family members than in the control subjects (0.85+/-0.01 mm versus 0.79+/-0.01 mm; P<0.0001). Age, HDL2b, systolic blood pressure, and prebeta-HDL were significant independent determinants of mean IMT. CONCLUSIONS: The decreased levels of HDL2b and prebeta-HDL reflect the potentially efflux-deficient HDL subspecies profile in the affected low-HDL family members. Decreased HDL particle size caused by the decrease of plasma concentration of HDL2b and decreased prebeta-HDL levels correlate with increased IMT.

Use of context in pragmatic language comprehension by children with Asperger syndrome or high-functioning autism.

Utilizing relevance theory, this study investigated the ability of children with Asperger syndrome (AS) and high-functioning autism (HFA) to use context when answering questions and when giving explanations for their correct answers. Three groups participated in this study: younger AS/HFA group (age 7-9, n=16), older AS/HFA group (age 10-12, n=23) and a normally functioning control group (age 7-9, n=23). The results indicated that the younger AS/HFA group did less well when answering contextually demanding questions compared to the control group, and the performance of the older AS/HFA group fell in between the younger AS/HFA group and the control group. Both AS/HFA groups had difficulties explaining their correct answers, suggesting that they are not always aware of how they have derived answers from the context.

Answering contextually demanding questions: pragmatic errors produced by children with Asperger syndrome or high-functioning autism.

UNLABELLED: This study examined irrelevant/incorrect answers produced by children with Asperger syndrome or high-functioning autism (7-9-year-olds and 10-12-year-olds) and normally developing children (7-9-year-olds). The errors produced were divided into three types: in Type 1, the child answered the original question incorrectly, in Type 2, the child gave a correct answer, but when asked a follow-up question, he/she explained the answer incorrectly, and in Type 3, the child first gave a correct answer or explanation, but continued answering, which ultimately led to an irrelevant answer. Analyses of Type 1 and 2 errors indicated that all the children tried to utilize contextual information, albeit incorrectly. Analyses of Type 3 errors showed that topic drifts were almost non-existent in the control group, but common in the clinical group, suggesting that these children had difficulties in stopping processing after deriving a relevant answer. LEARNING OUTCOMES: The reader becomes aware of the different instances which may lead to the irrelevance of answers and get knowledge about features of answers of children with AS/HFA.

Reduced IGFBP-1 is associated with thickening of the carotid wall in type 2 diabetes.

OBJECTIVE: The aim of the present study was to assess the role of the insulin-like growth factor (IGF) system and lipids in predicting the carotid intima-media thickness (IMT) in type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 239 type 2 diabetic participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study (76 women) aged 50-75 years were examined before fenofibrate intervention. Patients underwent carotid ultrasonography for determination of IMT. IGF-I, IGF binding protein 1 (IGFBP-1), IGFBP-3, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), glucose, HbA(1c), and C-peptide were measured in fasting samples. Patients were divided in groups without (n = 168) and with (n = 71) clinical cardiovascular disease (CVD). RESULTS: Partial correlations adjusted for age, sex, BMI, and diabetes duration showed an inverse association of IGFBP-1 with C-peptide (r = -0. 24, P = 0.018) and with maximal IMT (r = -0.42, P < 0.001), whereas IGF I and IGFBP-3 correlated positively with several risk-promoting lipid parameters. In linear regression analysis controlling for age, sex, BMI, diabetes duration, and presence or absence of oral antihyperglycemic or insulin medication, determinants of IMT were age, IGFBP-1, pulse pressure, Lp(a), diabetes duration, and insulin treatment. IGFBP-1 persisted in the model for subjects with CVD. CONCLUSIONS: In summary, a decrease in IGFBP-1 is a marker of carotid IMT thickening in patients with type 2 diabetes.

Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes.

OBJECTIVE: To investigate the relationship of inflammation and endothelial activation with insulin resistance and adiposity in type 2 diabetes. METHODS AND RESULTS: Hundred and thirty-four (45 female) type 2 diabetic subjects aged 50-75 in the Fenofibrate Intervention and Event Lowering in Diabetes Study in Helsinki were examined before fenofibrate intervention. Fasting levels of circulating intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) (vascular cell adhesion molecule), ultra-sensitive C-reactive protein (CRP), human serum amyloid A (hSAA), interleukin-6 (IL-6), macrophage colony-stimulating factor (M-CSF), secretory phospholipase A(2) IIA (PLA(2)), total, HDL and LDL cholesterol, triglycerides, P-glucose, HbA1c, and serum free insulin were determined. Insulin resistance was assessed by the homeostasis model. HOMA IR correlated significantly with all measures of adiposity and markers of inflammation and endothelial dysfunction. BMI was significantly associated with inflammation and endothelial activation, but with neither lipoproteins nor glycaemic control. After controlling for age, gender and BMI, HbA1c correlated significantly with CRP, hSAA, ICAM-1, E-selectin, and HOMA IR. HDL cholesterol correlated inversely with IL-6, M-CSF, E-selectin, and HOMA IR. HbA1c, phospholipase A(2), VCAM-1, and HDL cholesterol remained independent determinants of HOMA IR in the linear regression analysis controlled for age, gender, and BMI. CONCLUSION: Endothelial activation and acute-phase reaction correlate with insulin resistance and obesity in type 2 diabetic patients.

Noun Case Suffix Use by Children with Specific Language Impairment: An Examination of Finnish.

Finnish-speaking children with specific language impairment (SLI, N = 15, M age = 5;2), a group of same-age typically developing peers (TD-A, N = 15, M age = 5;2) and a group of younger typically developing children (TD-Y, N = 15, M age = 3;8) were compared in their use of accusative, partitive, and genitive case noun suffixes. The children with SLI were less accurate than both groups of TD children in case marking, suggesting that their difficulties with agreement extend to grammatical case. However, these children were also less accurate in making the phonological changes in the stem needed for suffixation. This second type of error suggests that problems in morphophonology may constitute a separate problem in Finnish SLI.

Pragmatic use of language by children who develop schizophrenia in adult life.

At eleven years of age all children in a UK national birth cohort wrote short stories about the life they expected to be leading at age 25. Using a data linkage exercise, we identified those who later developed schizophrenia, affective psychosis, or other non-psychotic psychiatric disorders in later life based on the PSE CATEGO diagnostic system. The majority of these had completed the written essays. Controls from the reference population were selected, matched for gender, IQ and social and economic status. The essays were scored using well established methods for assessing pragmatic use of language, namely narrative coherence and linguistic cohesion. We hypothesised that children pre-morbid for schizophrenia (Pre-Scz) would obtain low scores on all these measures. However this general hypothesis was largely disproved by the data, although some unpredicted gender effects were found. It is concluded that thought is organised in an unexceptional way in adolescents before they develop schizophrenia, once the data are corrected for any lowering of general cognitive ability in the Pre-Scz cases.

Effects of long-term fenofibrate treatment on markers of renal function in type 2 diabetes: the FIELD Helsinki substudy.

OBJECTIVE: Although fenofibrate was associated with less progression of albuminuria in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, it is unknown if it has any effect on renal function. We explored if there were changes in commonly available markers of renal function during fenofibrate treatment in the FIELD Helsinki cohort excluding statin users. RESEARCH DESIGN AND METHODS: One hundred and seventy subjects with type 2 diabetes were randomly assigned to micronized fenofibrate (200 mg/day) or placebo for 5 years. In this substudy, we measured several markers of albumin excretion and renal function. RESULTS: After intensified treatment, blood pressure and fasting glucose decreased in both groups while A1C remained at 7.2%. Plasma creatinine increased with fenofibrate while urine creatinine remained comparable between the groups, resulting in significant decreases in both creatinine clearance and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease (MDRD)-4 and Cockroft-Gault equations in the fenofibrate group. Cystatin C increased during fenofibrate treatment. Urinary albumin-to-creatinine ratio and diurnal urine protein remained unchanged, whereas overnight urinary albumin excretion rate showed minor decreases in both groups. CONCLUSIONS: We report concomitant decreases in creatinine clearance and eGFR by fenofibrate. These changes complicate the clinical surveillance during fenofibrate treatment. We could not demonstrate the beneficial effects of fenofibrate on albumin excretion. A novel finding is the increase of cystatin C in type 2 diabetic patients during fenofibrate treatment. The clinical relevance of the changes needs to be assessed in a long-term outcome study of renal function.

ApoCIII-enriched LDL in type 2 diabetes displays altered lipid composition, increased susceptibility for sphingomyelinase, and increased binding to biglycan.

OBJECTIVE: Apolipoprotein CIII (apoCIII) is an independent risk factor for cardiovascular disease, but the molecular mechanisms involved are poorly understood. We investigated potential proatherogenic properties of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: LDL was isolated from control subjects, subjects with type 2 diabetes, and apoB transgenic mice. LDL-biglycan binding was analyzed with a solid-phase assay using immunoplates coated with biglycan. Lipid composition was analyzed with mass spectrometry. Hydrolysis of LDL by sphingomyelinase was analyzed after labeling plasma LDL with [(3)H]sphingomyelin. ApoCIII isoforms were quantified after isoelectric focusing. Human aortic endothelial cells were incubated with desialylated apoCIII or with LDL enriched with specific apoCIII isoforms. RESULTS: We showed that enriching LDL with apoCIII only induced a small increase in LDL-proteoglycan binding, and this effect was dependent on a functional site A in apoB100. Our findings indicated that intrinsic characteristics of the diabetic LDL other than apoCIII are responsible for further increased proteoglycan binding of diabetic LDL with high-endogenous apoCIII, and we showed alterations in the lipid composition of diabetic LDL with high apoCIII. We also demonstrated that high apoCIII increased susceptibility of LDL to hydrolysis and aggregation by sphingomyelinases. In addition, we demonstrated that sialylation of apoCIII increased with increasing apoCIII content and that sialylation of apoCIII was essential for its proinflammatory properties. CONCLUSIONS: We have demonstrated a number of features of apoCIII-containing LDL from hypertriglyceridemic patients with type 2 diabetes that could explain the proatherogenic role of apoCIII.

Cognitive approach to assessing pragmatic language comprehension in children with specific language impairment.

BACKGROUND: Pragmatic language impairment in children with specific language impairment has proved difficult to assess, and the nature of their abilities to comprehend pragmatic meaning has not been fully investigated. AIMS: To develop both a cognitive approach to pragmatic language assessment based on Relevance Theory and an assessment tool for identifying a group of children with pragmatic language impairment from within an specific language impairment group. METHODS & PROCEDURES: The authors focused on Relevance Theory's view of the role of context in pragmatic language comprehension using questions of increasing pragmatic complexity in different verbal contexts (scenarios with and without pictures and a story with supporting pictures). The performances of the children with and without pragmatic impairment on the most pragmatically demanding Implicature questions were examined. This study included 99 children: 27 with specific language impairment (including nine pragmatically impaired children) and two groups of typically developing children (32 children aged 5-6 years and 40 children aged 7-11 years). OUTCOMES & RESULTS: The specific language impairment group performed similarly to their peers when utilizing context in inferring referents, inferring semantic meaning, and generating Implicatures, only when the answer was provided by pictorial context. Both the children with specific language impairment and the 5-6 year olds were not yet competent at utilizing verbal context when answering the most pragmatically demanding questions (targeting Implicature). On these questions the children with pragmatic language impairment performed significantly poorer than the rest of the specific language impairment group and performance scores on Implicature questions were found to identify accurately the children with pragmatic language impairment from the rest of the specific language impairment group (sensitivity = 89%). CONCLUSIONS: Children's ability to infer and integrate information in the comprehension of pragmatic meaning was found to be influenced by the available context. As children become more competent they are able to utilize verbal context and integrate information. Children with specific language impairment and those with pragmatic language impairment were found to be developmentally delayed at making inferences, but children with pragmatic language impairment had particular difficulty in integrating contextual information. Findings support the view that a cognitive approach to assessing pragmatic comprehension deficits could provide clinicians with a useful tool.

Answering questions and explaining answers: a study of Finnish-speaking children.

This research explores, within the framework of Relevance Theory, how children's ability to answer questions and explain their answers develops between the ages of 3 and 9 years. Two hundred and ten normally developing Finnish-speaking children participated in this study. The children were asked questions requiring processing of inferential meanings and routines, and were asked to explain their correct answers to elicit understanding about their awareness of how they had derived the answers from the context. The results indicated that the number of correct answers increased rapidly between the ages of 3 years and 4-5 years. Familiarity of context had a significant effect on young children's ability to answer questions. Becoming aware of the information used in inferencing developed gradually over time between the ages of 3 and 9. Analysis of the children's incorrect answers and explanations showed that, as children develop, their unsophisticated answer strategies diminish and they increasingly utilize context even in incorrect answers and explanations.

Long-term effects of fenofibrate on carotid intima-media thickness and augmentation index in subjects with type 2 diabetes mellitus.

OBJECTIVES: The aim of this substudy was to ascertain whether long-term treatment with fenofibrate reduces surrogate measures of atherosclerosis, biomarkers of inflammation, and endothelial activation in patients with type 2 diabetes. BACKGROUND: Some fibrates may decrease cardiovascular events, improve endothelial function, and reduce levels of acute-phase proteins. In the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) study, fenofibrate failed to decrease the primary end point of coronary events in patients with type 2 diabetes. METHODS: A total of 170 patients with type 2 diabetes of the FIELD Helsinki cohort were randomly assigned to micronized fenofibrate 200 mg/day or placebo in a double-blind design. Carotid intima-media thickness (IMT) and the augmentation index (a measure of large artery stiffness) were measured at baseline and at second- and fifth-year visits. Plasma levels of interleukin (IL)-6, C-reactive protein (CRP), serum amyloid A (SAA), secretory phospholipase A2 IIA (SPLA2), E-selectin, vascular cellular adhesion molecule (VCAM)-1, and intercellular adhesion molecule (CAM)-1 were determined by commercial enzyme-linked immunosorbent assay kits at the same visits. RESULTS: IMT and the augmentation index increased similarly in both treatment groups during the study. Plasma levels of CRP, IL-6, SPLA2, SAA, VCAM-1, ICAM-1, and E-selectin remained unchanged in both groups. CONCLUSIONS: Fenofibrate treatment was not associated with beneficial changes in IMT, augmentation index, or biomarkers of inflammation and endothelial function. (Fenofibrate Intervention and Event Lowering in Diabetes; NCT00132886).