Effect of polycystic ovary syndrome on cardiac autonomic function at a late fertile age: a prospective Northern Finland Birth Cohort 1966 study

OBJECTIVES: Previous studies of women in their 20s and 30s have reported impaired autonomic function in women with polycystic ovary syndrome (PCOS). We aimed to study, for the first time, whether PCOS is associated with impaired cardiac autonomic function independent of metabolic and hormonal status in their late reproductive years. DESIGN: A prospective Northern Finland Birth Cohort 1966 (NFBC1966) study including 5889 women born in 1966 and followed through the age of 46. At that age, n=3706/5123 women (72%) answered the postal questionnaires and n=3280/5123 women (64%) participated in the clinical examination. SETTING: General community. PARTICIPANTS: The sample included women presenting both irregular menses (oligomenorrhoea or amenorrhoea) and hirsutism at age 31 (n=125) or with formally diagnosed PCOS by age 46 (n=181) and women without PCOS symptoms or diagnosis (n=1577). PRIMARY AND SECONDARY OUTCOME MEASURES: Heart rate variability parameters: the root mean square of successive R-R differences (rMSSD), spectral power densities (LF: low frequency and HF: high frequency) and baroreflex sensitivity (BRS). RESULTS: We found that parasympathetic activity (assessed by rMSSD: 19.5 (12.4; 31.9) vs 24.3 (16.1; 34.8) ms, p=0.004 and HF: 172 (75; 399) vs 261 (112; 565) ms(2), p=0.002) and BRS (6.13±3.12 vs 6.99±3.52 ms/mm Hg, p=0.036) were lower in women with PCOS compared with the controls. However, in the multivariate regression analysis, PCOS, body mass index and the free androgen index did not significantly associate with rMSSD, whereas blood pressure, insulin resistance and triglycerides did. CONCLUSIONS: We report here for the first time that late reproductive-aged women with PCOS display impaired cardiac autonomic function manifested as decreased vagal activity. Metabolic status, rather than hyperandrogenaemia and PCOS per se, was the strongest contributing factor. Given the link between cardiac morbidity and impaired autonomic function, the findings underline the importance of screening and treating metabolic abnormalities early on in women with PCOS.Peer reviewe

Hormone profiling, including anti-Mullerian hormone (AMH), for the diagnosis of polycystic ovary syndrome (PCOS) and characterization of PCOS phenotypes

Objective was to evaluate serum anti-Mullerian hormone (AMH) levels in polycystic ovary syndrome (PCOS) and in its different phenotypes in relation to clinical, endocrine and metabolic parameters using a new automated VIDAS((R)) method and to compare it with the Gen II method. Study design was multi-center study including 319 PCOS women and 109 healthy controls. Serum AMH levels measured using VIDAS((R)) were significantly higher in PCOS women than controls (pPeer reviewe

Psychological Distress Is More Prevalent in Fertile Age and Premenopausal Women With PCOS Symptoms : 15-Year Follow-Up

Context: Polycystic ovary syndrome (PCOS) is associated with increased psychological distress, obesity and hyperandrogenism being suggested as key promoters. Objectives: To investigate the prevalence of anxiety/depression and their coexistence in women with PCOS/PCOS-related symptoms at ages 31 and 46. The roles of obesity, hyperandrogenism, and awareness of PCOS on psychological distress were also assessed. Design: Population-based follow-up. Setting: Northern Finland Birth Cohort 1966 with 15-year follow-up. Participants: At age 31, a questionnaire-based screening for oligoamenorrhea (OA) and hirsutism (H): 2188 asymptomatic (controls), 331 OA, 323 H, and 125 OA plus H (PCOS). Follow-up at age 46: 1576 controls, 239 OA, 231 H, and 85 PCOS. Interventions: Questionnaire-based screening for anxiety and depression symptoms (Hopkins Symptom Checklist-25) and previously diagnosed/treated depression at ages 31 and 46. Body mass index (BMI), serum testosterone/free androgen index, and awareness of polycystic ovaries/PCOS on psychological distress were also assessed. Main Outcomes: Population-based prevalence of anxiety and/or depression in women with PCOS/PCOS-related symptoms at ages 31 and 46. Results: Anxiety and/or depression symptoms, their coexistence, and rate of depression were increased at ages 31 and 46 in women with PCOS or isolated H compared with controls. High BMI or hyperandrogenism did not associate with increased anxiety or depression symptoms. The awareness of PCOS was associated with increased anxiety. Conclusions: Women with PCOS or isolated H present more often with anxiety and/or depression symptoms and their coexistence compared with controls. High BMI or hyperandrogenism did not provoke psychological distress in PCOS. The awareness of PCOS increased anxiety but did not associate with severe anxiety or depression.Peer reviewe

Psychological Distress Is More Prevalent in Fertile Age and Premenopausal Women With PCOS Symptoms : 15-Year Follow-Up

Context: Polycystic ovary syndrome (PCOS) is associated with increased psychological distress, obesity and hyperandrogenism being suggested as key promoters. Objectives: To investigate the prevalence of anxiety/depression and their coexistence in women with PCOS/PCOS-related symptoms at ages 31 and 46. The roles of obesity, hyperandrogenism, and awareness of PCOS on psychological distress were also assessed. Design: Population-based follow-up. Setting: Northern Finland Birth Cohort 1966 with 15-year follow-up. Participants: At age 31, a questionnaire-based screening for oligoamenorrhea (OA) and hirsutism (H): 2188 asymptomatic (controls), 331 OA, 323 H, and 125 OA plus H (PCOS). Follow-up at age 46: 1576 controls, 239 OA, 231 H, and 85 PCOS. Interventions: Questionnaire-based screening for anxiety and depression symptoms (Hopkins Symptom Checklist-25) and previously diagnosed/treated depression at ages 31 and 46. Body mass index (BMI), serum testosterone/free androgen index, and awareness of polycystic ovaries/PCOS on psychological distress were also assessed. Main Outcomes: Population-based prevalence of anxiety and/or depression in women with PCOS/PCOS-related symptoms at ages 31 and 46. Results: Anxiety and/or depression symptoms, their coexistence, and rate of depression were increased at ages 31 and 46 in women with PCOS or isolated H compared with controls. High BMI or hyperandrogenism did not associate with increased anxiety or depression symptoms. The awareness of PCOS was associated with increased anxiety. Conclusions: Women with PCOS or isolated H present more often with anxiety and/or depression symptoms and their coexistence compared with controls. High BMI or hyperandrogenism did not provoke psychological distress in PCOS. The awareness of PCOS increased anxiety but did not associate with severe anxiety or depression.Peer reviewe

Normo- and hyperandrogenic women with polycystic ovary syndrome exhibit an adverse metabolic profile through life

Objective: To compare the metabolic profiles of normo- and hyperandrogenic women with polycystic ovary syndrome (PCOS) with those of control women at different ages during reproductive life. Design: Case-control study. Setting: Not applicable. Patient(s): In all, 1,550 women with normoandrogenic (n = 686) or hyperandrogenic (n = 842) PCOS and 447 control women were divided into three age groups: 39 years). Interventions(s): None. Main Outcome Measure(s): Body mass index (BMI), waist circumference, blood pressure, glucose, insulin, cholesterol, lipoproteins, triglycerides and high-sensitivity C-reactive protein. Result(s): Both normo- and hyperandrogenic women with PCOS were more obese, especially abdominally. They had increased serum levels of insulin (fasting and in oral glucose tolerance tests), triglycerides, low-density lipoprotein, and total cholesterol, higher blood pressure, and lower high-density lipoprotein levels independently from BMI compared with the control population as early as from young adulthood until menopause. The prevalence of metabolic syndrome was two-to fivefold higher in women with PCOS compared with control women, depending on age and phenotype, and the highest prevalence was observed in hyperandrogenic women with PCOS at late reproductive age. Conclusion(s): When evaluating metabolic risks in women with PCOS, androgenic status, especially abdominal obesity and age, should be taken into account, which would allow tailored management of the syndrome from early adulthood on. (C) 2016 by American Society for Reproductive Medicine.Peer reviewe

Circulating metabolites and the risk of type 2 diabetes : a prospective study of 11,896 young adults from four Finnish cohorts

Aims/hypothesis Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case-control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults. Methods NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24-45 years). Associations between baseline metabolites and risk of developing diabetes during 8-15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up. Results Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59-1.50; p Conclusions/interpretation Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.Peer reviewe

Circulating metabolites and the risk of type 2 diabetes: a prospective study of 11,896 young adults from four Finnish cohorts

Aims/hypothesis Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case-control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults. Methods NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24-45 years). Associations between baseline metabolites and risk of developing diabetes during 8-15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up. Results Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59-1.50; p< 0.0009). Among the strongest biomarkers of diabetes risk were branched-chain and aromatic amino acids (OR 1.31-1.33) and triacylglycerol within VLDL particles (OR 1.33-1.50), as well as linoleic n-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years). Conclusions/interpretation Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk

Understanding the complexity of glycaemic health: systematic bio-psychosocial modelling of fasting glucose in middle-age adults; a DynaHEALTH study

© The Author(s) 2018. Background: The prevention of the risk of type 2 diabetes (T2D) is complicated by multidimensional interplays between biological and psychosocial factors acting at the individual level. To address the challenge we took a systematic approach, to explore the bio-psychosocial predictors of blood glucose in mid-age. Methods: Based on the 31-year and 46-year follow-ups (5,078 participants, 43% male) of Northern Finland Birth Cohort 1966, we used a systematic strategy to select bio-psychosocial variables at 31 years to enable a data-driven approach. As selection criteria, the variable must be (i) a component of the metabolic syndrome or an indicator of psychosocial health using WHO guidelines, (ii) easily obtainable in general health check-ups and (iii) associated with fasting blood glucose at 46 years (P < 0.10). Exploratory and confirmatory factor analysis were used to derive latent factors, and stepwise linear regression allowed exploration of relationships between factors and fasting glucose. Results: Of all 26 variables originally considered, 19 met the selection criteria and were included in an exploratory factor analysis. Two variables were further excluded due to low loading (<0.3). We derived four latent factors, which we named as socioeconomic, metabolic, psychosocial and blood pressure status. The combination of metabolic and psychosocial factors, adjusted for sex, provided best prediction of fasting glucose at 46 years (explaining 10.7% of variation in glucose; P < 0.001). Regarding different bio-psychosocial pathways and relationships, the importance of psychosocial factors in addition to established metabolic risk factors was highlighted. Conclusions: The present study supports evidence for the bio-psychosocial nature of adult glycemic health and exemplifies an evidence-based approach to model the bio-psychosocial relationships. The factorial model may help further research and public health practice in focusing also on psychosocial aspects in maintaining normoglycaemia in the prevention of cardio-metabolic diseases.European Union’s Horizon 2020 research and innovation programme, grant agreement No 633595

Gamma-glutamyl Transferase as a Marker of Alcohol Abuse: Effects of Moderate Drinking, Obesity and Increasing Age on Reference Intervals

Väitöstutkimuksen tavoite oli selvittää alkoholinkulutuksen, lihavuuden ja iän aiheuttamia vaikutuksia GGT-arvoihin (gammaglutamyylitransferaasi). GGT on maksaentsyymi, jota on jo kauan käytetty alkoholin suurkulutuksen osoittimena kliinisessä työssä. Aikaisemmin ei ole ollut tarkkaa tietoa, minkälainen alkoholinkulutuksen määrä nostaa seerumin GGT-pitoisuutta ja mitkä muut tekijät vaikuttavat GGT-tasoa nostavasti. Tutkimuksen mukaan lihavuus ja alkoholi nostavat GGT-arvoja yhdessä huomattavasti enemmän kuin kumpikaan yksin, mikä heijastaa myös suurentunutta maksavaurioriskiä potilailla, joilla on ylipainoa. Tämän vuoksi terveydenhuollossa on tärkeää ottaa huomioon sekä alkoholin käyttötottumukset että ylipaino ja tutkittavan ikä, kun määritellään GGT:n normaaliarvoja. Tutkimuksessa määritettiin alkoholin suurkuluttajien GGT-arvot ja niitä verrattiin sekä kohtuukäyttäjien ja täysraittiiden arvoihin. Tämän lisäksi tutkimusväestö jaettiin painoindeksin (BMI) mukaisiin ryhmiin sekä ikäluokkiin. Kohtuukäyttäjillä, jotka olivat ylipainoisia tai lihavia, GGT-arvot kasvoivat erityisen selvästi verrattuna normaalipainoisten raittiiden henkilöiden arvoihin. Naisilla kasvavan BMI:n ja alkoholin kohtuukäytön vaikutus GGT-arvoihin oli pienempi kuin miehillä. Viiterajojen ylärajat, jotka saatiin normaalipainoisista raittiista henkilöistä koostuvasta aineistosta, olivat huomattavasti alemmat kuin viiteväestöllä, jolle ei BMI-luokittelua oltu tehty. Lisäksi GGT:n herkkyys alkoholin liikakäytön osoittimena muuttui merkittävästi, kun viiteväestö jaettiin BMI:n mukaisiin luokkiin. GGT-aktiivisuudet lisääntyivät myös kasvavan iän myötä 70 vuoteen asti. Suurkuluttajilla ja raittiilla kontrolleilla, jotka oli jaettu ikäluokkiin, GGT-arvot olivat selvästi paremmin verrannollisia keskenään kuin aineistossa, jossa ikäjaottelua ei oltu tehty. Lisäksi miehillä kohtuukäyttäjien arvot kaikissa ikäryhmissä olivat suurempia kuin täysraittiiden vastaavien ryhmien arvot, kun taas naisilla ero oli merkitsevä ainoastaan 18-30-vuotiaiden ryhmässä. Suomessa alkoholin suurkulutus aiheuttaa koko ajan lisääntyviä kansanterveydellisiä ja sosiaalisia ongelmia sekä merkittäviä kansantaloudellisia kustannuksia. Tämän vuoksi on tärkeää tunnistaa alkoholiongelmat mahdollisimman varhaisessa vaiheessa ja kehittää entistä tehokkaampia ja herkempiä laboratoriomenetelmiä suurkulutuksen tunnistamiseksi.Excessive alcohol consumption is a major cause of health problems throughout the Western world, and the need for objective clinical tools for detecting alcohol abuse in its early phase has been widely acknowledged. Gamma-glutamyl transferase (GGT) is a liver-derived enzyme, which has long been used as a marker of excessive alcohol consumption, but the amount of drinking needed to elevate GGT levels has remained unknown. Also, it has been suggested that GGT levels may be elevated by factors such as obesity and increasing age in addition to alcohol consumption, although the magnitude of such effects have remained unclear. The relationships between alcohol consumption, obesity, age and GGT values are studied here in a large number of heavy drinkers and apparently healthy reference individuals, classified as fol-lows: subjects reporting no alcohol consumption (abstainers), subjects reporting 1­40 grams of ethanol consumed per day (moderate drinkers) and subjects reporting 40-­540 grams of ethanol con-sumed per day (heavy drinkers). The reference population was further classified according to body mass index (BMI) into underweight (BMI30), and by age into those under 18 years, 18-­30 years, 3-0­50 years, -50­70 years and over 70 years. GGT activity was markedly higher in the heavy drinkers than in the moderate drinkers (p The data show that serum GGT is a highly sensitive indicator of ethanol consumption, although its diagnostic value could be improved by using reference data based solely on abstainers of normal weight, or else BMI-specific reference intervals. Also, the fact that GGT activity responds to etha-nol in an age-dependent manner should be considered in the clinical use of GGT measurements for detecting alcohol consumption disorders