Effect of General Adiposity and Central Body Fat Distribution on the Circulating Metabolome: A Multicohort Nontargeted Metabolomics Observational and Mendelian Randomization Study.

Obesity is associated with adverse health outcomes, but the metabolic effects have not yet been fully elucidated. We aimed to investigate the association between adiposity and circulating metabolites and to address causality with Mendelian randomization (MR). Metabolomics data were generated with nontargeted ultraperformance liquid chromatography coupled to time-of-flight mass spectrometry in plasma and serum from three population-based Swedish cohorts: ULSAM (N = 1,135), PIVUS (N = 970), and TwinGene (N = 2,059).

Non-targeted urine metabolomics and associations with prevalent and incident type 2 diabetes.

Better risk prediction and new molecular targets are key priorities in type 2 diabetes (T2D) research. Little is known about the role of the urine metabolome in predicting the risk of T2D. We aimed to use non-targeted urine metabolomics to discover biomarkers and improve risk prediction for T2D.

Open Randomized Multicenter Study to Evaluate Safety and Efficacy of Low Molecular Weight Sulfated Dextran in Islet Transplantation.

Background: When transplanted human pancreatic islets are exposed to blood during intraportal infusion, an innate immune response is triggered. This instant blood-mediated inflammatory reaction (IBMIR) activates the coagulation and complement cascades and leads to the destruction of 25% of all transplanted islets within minutes, contributing to the need, in most patients, for islets from more than 1 donor. Low molecular dextran sulfate (LMW-DS) has been shown in experimental settings to inhibit IBMIR.

Glucose challenge metabolomics implicates medium-chain acylcarnitines in insulin resistance.

Insulin resistance (IR) predisposes to type 2 diabetes and cardiovascular disease but its causes are incompletely understood. Metabolic challenges like the oral glucose tolerance test (OGTT) can reveal pathogenic mechanisms. We aimed to discover associations of IR with metabolite trajectories during OGTT.

The Impact of Continuous Positive Airway Pressure on Circulating IGF-1 in Patients With Obstructive Sleep Apnea.

Study Objectives: Obstructive sleep apnea (OSA) is a disease with metabolic and cardiovascular consequences and is associated with decreased serum concentrations of insulin-like growth factor-1 (IGF-1). The aim of this study was to investigate whether continuous positive airway pressure (CPAP) will increase serum IGF-1 concentration in patients with OSA.

Methods: Patients with moderate to severe OSA were recruited from a sleep clinic and serum IGF-1 was measured before initiation of CPAP and at follow-up after 4.

Correction: Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study.

[This corrects the article DOI: 10.1371/journal.pgen.

Effect of Insulin Resistance on Monounsaturated Fatty Acid Levels: A Multi-cohort Non-targeted Metabolomics and Mendelian Randomization Study.

Insulin resistance (IR) and impaired insulin secretion contribute to type 2 diabetes and cardiovascular disease. Both are associated with changes in the circulating metabolome, but causal directions have been difficult to disentangle. We combined untargeted plasma metabolomics by liquid chromatography/mass spectrometry in three non-diabetic cohorts with Mendelian Randomization (MR) analysis to obtain new insights into early metabolic alterations in IR and impaired insulin secretion.

Non-targeted metabolomics combined with genetic analyses identifies bile acid synthesis and phospholipid metabolism as being associated with incident type 2 diabetes.

Aims/hypothesis: Identification of novel biomarkers for type 2 diabetes and their genetic determinants could lead to improved understanding of causal pathways and improve risk prediction.

Methods: In this study, we used data from non-targeted metabolomics performed using liquid chromatography coupled with tandem mass spectrometry in three Swedish cohorts (Uppsala Longitudinal Study of Adult Men [ULSAM], n = 1138; Prospective Investigation of the Vasculature in Uppsala Seniors [PIVUS], n = 970; TwinGene, n = 1630). Metabolites associated with impaired fasting glucose (IFG) and/or prevalent type 2 diabetes were assessed for associations with incident type 2 diabetes in the three cohorts followed by replication attempts in the Cooperative Health Research in the Region of Augsburg (KORA) S4 cohort (n = 855).

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)).

Defining the role of common variation in the genomic and biological architecture of adult human height.

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability.

Both habitual short sleepers and long sleepers are at greater risk of obesity: a population-based 10-year follow-up in women.

Objective: To assess how change in sleep duration is related to subsequent obesity.

Methods: In this 10-year follow-up, 4903 non-pregnant participants answered a questionnaire on sleeping habits, obesity, and lifestyle factors (questions identical to baseline questionnaire). Habitual normal sleepers were defined as sleeping 6-9 h/night at both baseline and follow-up, whereas women sleeping <6 h/night or ≥9 h/night at both occasions were defined as habitual short sleepers and habitual long sleepers, respectively.

Can costs of screening for hypertension and diabetes in dental care and follow-up in primary health care be predicted?

Aim: The purpose was to assess the direct costs of screening for high blood pressure and blood glucose in dental care and of follow-up in primary health care and, based on these data, arrive at a prediction function. Study population. All subjects coming for routine check-ups at three dental health clinics were invited to have blood pressure or blood glucose measurements; 1,623 agreed to participate.

Low serum adiponectin concentrations are associated with insulin sensitivity independent of obesity in Sudanese subjects with type 2 diabetes mellitus.

Aims: Prevalence of Type 2 diabetes mellitus among Sudanese population was found to be 3.4% and associated with high rates of complications and obesity. Different adipocytokines are secreted from adipose tissues, among them adiponectin, which was shown to have insulins ensitizing properties and anti-inflammatory, anti-atherogenic effect.

Long-term reproductive and metabolic consequences of PCOS.

Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic consequences. The review of findings indicate that the long-term reproductive outcomes of women with PCOS are surprisingly similar compared to women with normal ovaries, and that they have an ovarian reserve possibly superior to women with normal ovaries. The typical features of PCOS, specifically the anovulatory cycles tend to normalize over time, but in spite of a decrease over time, free androgen levels remain elevated compared to age-matched control subjects.

Islet engraftment and revascularization in clinical and experimental transplantation.

Proper revascularization after transplantation is assumed to be crucial for appropriate islet graft function. We developed a novel noninvasive imaging method, based on adenoviral transduction of islets with a hypoxia responsive reporter gene, for continuous in vivo monitoring of hypoxia in islet grafts in a mouse model. In addition, morphological data were obtained from a deceased patient previously subject to intraportal transplantation.

Sleep apnea and glucose metabolism: a long-term follow-up in a community-based sample.

Background: It has been suggested that sleep-disordered breathing (SDB) is a risk factor for diabetes, but long-term follow-up studies are lacking. The aim of this community-based study was to analyze the influence of SDB on glucose metabolism after > 10 years.

Methods: Men without diabetes (N = 141; mean age, 57.

Seasonal variations of insulin sensitivity from a euglycemic insulin clamp in elderly men.

Introduction: Seasonal variations in hemoglobin-A1c have been reported in diabetic patients, but the underlying mechanisms have not been elucidated.

Aims: To study if insulin sensitivity, insulin secretion, and fasting plasma glucose showed seasonal variations in a Swedish population-based cohort of elderly men.

Methods: Altogether 1117 men were investigated with a euglycemic insulin clamp and measurements of fasting plasma glucose and insulin secretion after an oral glucose tolerance test.

Prevalence of the metabolic syndrome in women with a previous diagnosis of polycystic ovary syndrome: long-term follow-up.

Objective: To examine the prevalence of the metabolic syndrome (MetS) according to the scientific statement of the American Heart Association and the US National Cholesterol Education Program/Adult Treatment Panel III in middle-aged Swedish women previously diagnosed with polycystic ovary syndrome (PCOS) in comparison with age-matched healthy controls.

Design: Long-term follow-up study.

Setting: Department of Obstetrics and Gynecology, Uppsala University.

Prompt reversal of a severe complement activation by eculizumab in a patient undergoing intentional ABO-incompatible pancreas and kidney transplantation.

We describe the presumably first intentional ABO-incompatible deceased-donor kidney and pancreas transplantation with a severe antibody-mediated rejection during a rebound of isoagglutinins. Rejection was successfully treated with eculizumab, which inhibits the terminal pathway of complement. Complement analysis (C3, C3d,g, and a modified assay of classical complement-related hemolytic function) documented complement activation and confirmed that eculizumab completely blocked complement function.