Glucose variability and mood in people with type 1 diabetes using ecological momentary assessment.

OBJECTIVE: Mood fluctuations related to blood glucose excursions are a commonly reported source of diabetes-distress, but research is scarce. We aimed to assess the relationship between real-time glucose variability and mood in adults with type 1 diabetes (T1D) using ecological momentary assessments. METHODS: In this prospective observational study, participants wore a masked continuous glucose monitor and received prompts on their smartphone 6 times a day to answer questions about their current mood (Profile Of Mood States (POMS)-SF (dimensions: Anxiety, Depressive symptoms, Anger, Fatigue, Vigor)) for 14 days. Mixed model analyses examined associations over time between daily Coefficient of Variation (CV) of blood glucose and mean and variability (CV) of POMS scores. Further, within-person differences in sleep and nocturnal hypoglycemia were explored. RESULTS: 18 people with T1D (10 female, mean age 44.3 years) participated. A total of 264 out of 367 days (70.2%) could be included in the analyses. No overall significant associations were found between CV of blood glucose and mean and CV of POMS scores, however, nocturnal hypoglycemia moderated the associations between CV of blood glucose and POMS scales (mean Fatigue Estimate 1.998, p < .006, mean Vigor Estimate -3.308, p < .001; CV Anger Estimate 0.731p = 0.02, CV Vigor Estimate -0.525, p = .006). CONCLUSION: We found no overall relationship between real-time glycemic variability and mood per day. Further research into within-person differences such as sleep and nocturnal hypoglycemia is warranted.

Pregnancy Outcomes: Effects of Metformin (POEM) study: a protocol for a long-term, multicentre, open-label, randomised controlled trial in gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is a common disorder of pregnancy with health risks for mother and child during pregnancy, delivery and further lifetime, possibly leading to type 2 diabetes mellitus (T2DM). Current treatment is focused on reducing hyperglycaemia, by dietary and lifestyle intervention and, if glycaemic targets are not reached, insulin. Metformin is an oral blood glucose lowering drug and considered safe during pregnancy. It improves insulin sensitivity and has shown advantages, specifically regarding pregnancy-related outcomes and patient satisfaction, compared with insulin therapy. However, the role of metformin in addition to usual care is inconclusive and long-term outcome of metformin exposure in utero are lacking. The primary aim of this study is to investigate the early addition of metformin on pregnancy and long-term outcomes in GDM. METHODS AND ANALYSIS: The Pregnancy Outcomes: Effects of Metformin study is a multicentre, open-label, randomised, controlled trial. Participants include women with GDM, between 16 and 32 weeks of gestation, who are randomised to either usual care or metformin added to usual care, with insulin rescue in both groups. Metformin is given up to 1 year after delivery. The study consists of three phases (A-C): A-until 6 weeks after delivery; B-until 1 year after delivery; C-observational study until 20 years after delivery. During phase A, the primary outcome is a composite score consisting of: (1) pregnancy-related hypertension, (2) large for gestational age neonate, (3) preterm delivery, (4) instrumental delivery, (5) caesarean delivery, (6) birth trauma, (7) neonatal hypoglycaemia, (8) neonatal intensive care admission. During phase B and C the primary outcome is the incidence of T2DM and (weight) development in mother and child. ETHICS AND DISSEMINATION: The study was approved by the Central Committee on Research Involving Human Subjects in the Netherlands. Results will be submitted for publication in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT02947503.

A Matter of Timing-Pregnancy After Bariatric Surgery.

PURPOSE: Current guidelines recommend to avoid pregnancy for 12-24 months after bariatric surgery because of active weight loss and an increased risk of nutritional deficiencies. However, high-quality evidence is lacking, and only a few studies included data on gestational weight gain. We therefore evaluated pregnancy and neonatal outcomes by both surgery-to-conception interval and gestational weight gain. MATERIALS AND METHODS: A multicenter retrospective analysis of 196 singleton pregnancies following Roux-en-Y gastric bypass, sleeve gastrectomy, and one anastomosis gastric bypass was conducted. Pregnancies were divided into the early group (≤ 12 months), the middle group (12-24 months), and the late group (> 24 months) according to the surgery-to-conception interval. Gestational weight gain was classified as inadequate, adequate, or excessive according to the National Academy of Medicine recommendations. RESULTS: Pregnancy in the early group (23.5%) was associated with lower gestational age at delivery (267.1 ± 19.9 days vs 272.7 ± 9.2 and 273.1 ± 13.5 days, P = 0.029), lower gestational weight gain (- 0.9 ± 11.0 kg vs + 10.2 ± 5.6 and + 10.0 ± 6.4 kg, P < 0.001), and lower neonatal birth weight (2979 ± 470 g vs 3161 ± 481 and 3211 ± 465 g, P = 0.008) than pregnancy in the middle and late group. Inadequate gestational weight gain (40.6%) was associated with lower gestational age at delivery (266.5 ± 20.2 days vs 273.8 ± 8.4 days, P = 0.002) and lower neonatal birth weight (3061 ± 511 g vs 3217 ± 479 g, P = 0.053) compared to adequate weight gain. Preterm births were also more frequently observed in this group (15.9% vs 6.0%, P = 0.037). CONCLUSION: Our findings support the recommendation to avoid pregnancy for 12 months after bariatric surgery. Specific attention is needed on achieving adequate gestational weight gain.

Methylome and transcriptome maps of human visceral and subcutaneous adipocytes reveal key epigenetic differences at developmental genes.

Adipocytes support key metabolic and endocrine functions of adipose tissue. Lipid is stored in two major classes of depots, namely visceral adipose (VA) and subcutaneous adipose (SA) depots. Increased visceral adiposity is associated with adverse health outcomes, whereas the impact of SA tissue is relatively metabolically benign. The precise molecular features associated with the functional differences between the adipose depots are still not well understood. Here, we characterised transcriptomes and methylomes of isolated adipocytes from matched SA and VA tissues of individuals with normal BMI to identify epigenetic differences and their contribution to cell type and depot-specific function. We found that DNA methylomes were notably distinct between different adipocyte depots and were associated with differential gene expression within pathways fundamental to adipocyte function. Most striking differential methylation was found at transcription factor and developmental genes. Our findings highlight the importance of developmental origins in the function of different fat depots.

Skin autofluorescence predicts incident type 2 diabetes, cardiovascular disease and mortality in the general population.

AIMS/HYPOTHESIS: Earlier studies have shown that skin autofluorescence measured with an AGE reader estimates the accumulation of AGEs in the skin, which increases with ageing and is associated with the metabolic syndrome and type 2 diabetes. In the present study, we examined whether the measurement of skin autofluorescence can predict 4 year risk of incident type 2 diabetes, cardiovascular disease (CVD) and mortality in the general population. METHODS: For this prospective analysis, we included 72,880 participants of the Dutch Lifelines Cohort Study, who underwent baseline investigations between 2007 and 2013, had validated baseline skin autofluorescence values available and were not known to have diabetes or CVD. Individuals were diagnosed with incident type 2 diabetes by self-report or by a fasting blood glucose ≥7.0 mmol/l or HbA1c ≥48 mmol/mol (≥6.5%) at follow-up. Participants were diagnosed as having incident CVD (myocardial infarction, coronary interventions, cerebrovascular accident, transient ischaemic attack, intermittent claudication or vascular surgery) by self-report. Mortality was ascertained using the Municipal Personal Records Database. RESULTS: After a median follow-up of 4 years (range 0.5-10 years), 1056 participants (1.4%) had developed type 2 diabetes, 1258 individuals (1.7%) were diagnosed with CVD, while 928 (1.3%) had died. Baseline skin autofluorescence was elevated in participants with incident type 2 diabetes and/or CVD and in those who had died (all p < 0.001), compared with individuals who survived and remained free of the two diseases. Skin autofluorescence predicted the development of type 2 diabetes, CVD and mortality, independent of several traditional risk factors, such as the metabolic syndrome, glucose and HbA1c. CONCLUSIONS/INTERPRETATION: The non-invasive skin autofluorescence measurement is of clinical value for screening for future risk of type 2 diabetes, CVD and mortality, independent of glycaemic measures and the metabolic syndrome.

[The 46,XX male; a chromosomal form of a disorder of sex development]. / De 46,XX-man.

BACKGROUND: A disorder of sex development (abbreviated DSD) is defined as a congenital condition in which development of chromosomal, gonadal or anatomical sex is atypical. DSD is caused by a disruption of foetal sexual development, which is largely influenced by various genetic and hormonal factors. The SRY gene, located on the Y chromosome, plays a key role in sexual development. CASE DESCRIPTION: A 32-year-old male was found to be infertile because of azoospermia. His habitus was that of a male. Hormonal analysis revealed hypergonadotropic hypogonadism. Karyotyping and fluorescence in situ hybridisation (FISH) revealed a 46,XXSRY+ pattern due to an unbalanced X;Y translocation in the presence of SRY on an X chromosome, this is classified as a chromosomal form of DSD. CONCLUSION: Male infertility can be caused by DSD, even if a male habitus makes this seem unlikely at first.

Pregnancy outcomes in women with gestational diabetes mellitus diagnosed according to the WHO-2013 and WHO-1999 diagnostic criteria: a multicentre retrospective cohort study.

BACKGROUND: The World Health Organization (WHO) adopted more stringent diagnostic criteria for GDM in 2013, to improve pregnancy outcomes. However, there is no global consensus on these new diagnostic criteria, because of limited evidence. The objective of the study was to evaluate maternal characteristics and pregnancy outcomes in two cohorts in the Netherlands applying different diagnostic criteria for GDM i.e. WHO-2013 and WHO-1999. METHODS: A multicenter retrospective study involving singleton GDM pregnancies in two regions, between 2011 and 2016. Women were diagnosed according to the WHO-2013 criteria in the Deventer region (WHO-2013-cohort) and according to the WHO-1999 criteria in the Groningen region (WHO-1999-cohort). After GDM diagnosis, all women were treated equally based on the national guideline. Maternal characteristics and pregnancy outcomes were compared between the two groups. RESULTS: In total 1386 women with GDM were included in the study. Women in the WHO-2013-cohort were older and had a higher pre-gestational body mass index. They were diagnosed earlier (24.9 [IQR 23.3-29.0] versus 27.7 [IQR 25.9-30.7] weeks, p = < 0.001) and less women were treated with additional insulin therapy (15.6% versus 43.4%, p = < 0.001). Rate of spontaneous delivery was higher in the WHO-2013-cohort (73.1% versus 67.4%, p = 0.032). The percentage large-for-gestational-age (LGA) neonates (birth weight > 90th percentile, corrected for sex, ethnicity, parity, and gestational age) was lower in the WHO-2013- cohort, but not statistical significant (16.5% versus 18.5%, p = 0.379). There were no differences between the cohorts regarding stillbirth, birth trauma, low Apgar score, and preeclampsia. CONCLUSIONS: Using the new WHO-2013 criteria resulted in an earlier GDM diagnosis, less women needed insulin treatment and more spontaneous deliveries occurred when compared to the cohort diagnosed with WHO-1999 criteria. No differences were found in adverse pregnancy outcomes.

[Apparent thyrotoxicosis in a patient with multiple sclerosis: biochemical assay interference due to high dose biotin use]. / Schijnbare thyreotoxicose door gebruik van biotine in hoge dosis.

BACKGROUND: Supraphysiological doses of biotin are being tested in patients with multiple sclerosis. Biotin can cause interference with laboratory assessment of thyroid function, and therefore give a false suggestion of thyrotoxicosis. CASE DESCRIPTION: A 64-year-old patient was referred for assessment of thyrotoxicosis, due to Graves' disease. Antithyroid medication was started, but there was no effect on laboratory results. In addition, he developed symptoms which subsequently could be attributed to iatrogenic hypothyroidism. Biotin interference, when assaying TSH and thyroxin, was suspected. Upon further investigation, the patient revealed to use high doses of biotin. After discontinuation of the biotin treatment, the thyroid function test normalized. CONCLUSION: It is expected that in the future, patients with multiple sclerosis will use biotin more often. Therefore, it is important for healthcare professionals to be aware that biotin can interfere with immunoassays for thyroid hormones, to avoid misdiagnosis and unnecessary treatment for hyperthyroidism.

DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels: a systematic review and replication in a case-control sample of the Lifelines study.

AIMS/HYPOTHESIS: Epigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels. Here we present a systematic review of these studies and attempt to replicate the CpG sites (CpGs) with the most significant associations from these EWASs in a case-control sample of the Lifelines study. METHODS: We performed a systematic literature search in PubMed and EMBASE for EWASs to test the association between DNA methylation and type 2 diabetes and/or glycaemic traits and reviewed the search results. For replication purposes we selected 100 unique CpGs identified in peripheral blood, pancreas, adipose tissue and liver from 15 EWASs, using study-specific Bonferroni-corrected significance thresholds. Methylation data (Illumina 450K array) in whole blood from 100 type 2 diabetic individuals and 100 control individuals from the Lifelines study were available. Multivariate linear models were used to examine the associations of the specific CpGs with type 2 diabetes and glycaemic traits. RESULTS: From the 52 CpGs identified in blood and selected for replication, 15 CpGs showed nominally significant associations with type 2 diabetes in the Lifelines sample (p < 0.05). The results for five CpGs (in ABCG1, LOXL2, TXNIP, SLC1A5 and SREBF1) remained significant after a stringent multiple-testing correction (changes in methylation from -3% up to 3.6%, p < 0.0009). All associations were directionally consistent with the original EWAS results. None of the selected CpGs from the tissue-specific EWASs were replicated in our methylation data from whole blood. We were also unable to replicate any of the CpGs associated with HbA1c levels in the healthy control individuals of our sample, while two CpGs (in ABCG1 and CCDC57) for fasting glucose were replicated at a nominal significance level (p < 0.05). CONCLUSIONS/INTERPRETATION: A number of differentially methylated CpGs reported to be associated with type 2 diabetes in the EWAS literature were replicated in blood and show promise for clinical use as disease biomarkers. However, more prospective studies are needed to support the robustness of these findings.

New diagnostic criteria for gestational diabetes mellitus and their impact on the number of diagnoses and pregnancy outcomes.

AIMS/HYPOTHESIS: Detection and management of gestational diabetes mellitus (GDM) are crucial to reduce the risk of pregnancy-related complications for both mother and child. In 2013, the WHO adopted new diagnostic criteria for GDM to improve pregnancy outcomes. However, the evidence supporting these criteria is limited. Consequently, these new criteria have not yet been endorsed in the Netherlands. The aim of this study was to determine the impact of these criteria on the number of GDM diagnoses and pregnancy outcomes. METHODS: Data were available from 10,642 women who underwent a 75 g OGTT because of risk factors or signs suggestive of GDM. Women were treated if diagnosed with GDM according to the WHO 1999 criteria. Data on pregnancy outcomes were obtained from extensive chart reviews from 4,431 women and were compared between women with normal glucose tolerance (NGT) and women classified into the following groups: (1) GDM according to WHO 1999 criteria; (2) GDM according to WHO 2013 criteria; (3) GDM according to WHO 2013 fasting glucose threshold, but not WHO 1999 criteria; and (4) GDM according to WHO 1999 2 h plasma glucose threshold (2HG), but not WHO 2013 criteria. RESULTS: Applying the new WHO 2013 criteria would have increased the number of diagnoses by 45% (32% vs 22%) in this population of women at higher risk for GDM. In comparison with women with NGT, women classified as having GDM based only on the WHO 2013 threshold for fasting glucose, who were not treated for GDM, were more likely to have been obese (46.1% vs 28.1%, p < 0.001) and hypertensive (3.3% vs 1.2%, p < 0.001) before pregnancy, and to have had higher rates of gestational hypertension (7.8% vs 4.9%, p = 0.003), planned Caesarean section (10.3% vs 6.5%, p = 0.001) and induction of labour (34.8% vs 28.0%, p = 0.001). In addition, their neonates were more likely to have had an Apgar score <7 at 5 min (4.4% vs 2.6%, p = 0.015) and to have been admitted to the Neonatology Department (15.0% vs 11.1%, p = 0.004). The number of large for gestational age (LGA) neonates was not significantly different between the two groups. Women potentially missed owing to the higher 2HG threshold set by WHO 2013 had similar pregnancy outcomes to women with NGT. These women were all treated for GDM with diet and 20.5% received additional insulin. CONCLUSIONS/INTERPRETATION: Applying the WHO 2013 criteria will have a major impact on the number of GDM diagnoses. Using the fasting glucose threshold set by WHO 2013 identifies a group of women with an increased risk of adverse outcomes compared with women with NGT. We therefore support the use of a lower fasting glucose threshold in the Dutch national guideline for GDM diagnosis. However, adopting the WHO 2013 criteria with a higher 2HG threshold would exclude women in whom treatment for GDM seems to be effective.

The association between various smoking behaviors, cotinine biomarkers and skin autofluorescence, a marker for advanced glycation end product accumulation.

BACKGROUND: Skin autofluorescence, a biomarker for advanced glycation end products (AGEs) accumulation, has been shown to predict diabetes-related cardiovascular complications and is associated with several environmental and lifestyle factors. In the present study, we examined the association between various smoking behaviors and skin autofluorescence, as well as the association between several cotinine biomarkers and skin autofluorescence, using both epidemiological and metabolomics data. METHODS: In a cross-sectional study, we evaluated participants from the LifeLines Cohort Study and the Qatar Metabolomics Study on Diabetes (QMDiab). In the LifeLines Cohort Study smoking behavior and secondhand smoking were assessed in 8,905 individuals including 309 individuals (3.5%) with type 2 diabetes. In QMDiab, cotinine biomarkers were measured in saliva, plasma and urine in 364 individuals of whom 188 (51%) had type 2 diabetes. Skin autofluorescence was measured non-invasively in all participants using the AGE Reader. RESULTS: Skin autofluorescence levels increased with a higher number of hours being exposed to secondhand smoking. Skin autofluorescence levels of former smokers approached levels of never smokers after around 15 years of smoking cessation. Urinary cotinine N-oxide, a biomarker of nicotine exposure, was found to be positively associated with skin autofluorescence in the QMDiab study (p = 0.03). CONCLUSIONS: In the present study, we have demonstrated that secondhand smoking is associated with higher skin autofluorescence levels whereas smoking cessation has a beneficial effect on skin autofluorescence. Finally, urinary cotinine N-oxide might be used as an alternative way for questionnaires to examine the effect of (environmental) tobacco smoking on skin autofluorescence.

Skin autofluorescence, a non-invasive biomarker for advanced glycation end products, is associated with the metabolic syndrome and its individual components.

BACKGROUND: The metabolic syndrome (MetS) comprises several cardiometabolic risk factors associated with increased risk for both type 2 diabetes and cardiovascular disease. Skin autofluorescence (SAF), a non-invasive biomarker of advanced glycation end products accumulation, is associated with cardiovascular complications in subjects with diabetes. The aim of the present study was to examine the association between SAF and the presence of MetS as well as its individual components in a general population. METHODS: For this cross-sectional analysis, we included 78,671 non-diabetic subjects between 18 and 80 years of age who participated in the LifeLines Cohort Study and had SAF measurement obtained non-invasively using the AGE Reader. MetS was defined according to the revised NCEP ATP III criteria. Students unpaired t test was used to test differences between groups. Both logistic and linear regression analyses were performed in order to test associations between the individual MetS components and SAF. RESULTS: Subjects with MetS had higher SAF (2.07 ± 0.45 arbitrary units, AU) compared to individuals without MetS (1.89 ± 0.42 AU) (p < 0.001). There was a positive association between the number of MetS components and higher SAF Z-scores (p < 0.001). Individuals in the highest SAF tertile had a higher presence of MetS (OR 2.61; 95% CI 2.48-2.75) and some of the individual components compared to subjects in the lowest SAF tertile. After correction for age, gender, creatinine clearance, HbA1c and smoking status, only elevated blood pressure and low HDL cholesterol remained significantly associated with higher SAF (p = 0.002 and p = 0.001 respectively). CONCLUSION: Skin autofluorescence was associated with the presence of MetS and some of its individual components. In addition, increasing SAF Z-scores were observed with a higher number of MetS components. Prospective studies are needed to establish whether SAF can be used as an (additional) screening tool to predict both cardiovascular disease and type 2 diabetes in high-risk populations.

Postpartum glucose follow-up and lifestyle management after gestational diabetes mellitus: general practitioner and patient perspectives.

BACKGROUND: Incidence of type 2 diabetes is high after gestational diabetes mellitus (GDM). We aimed to evaluate the adherence to follow-up six-weeks postpartum visits in secondary care after GDM and glucose monitoring in primary care longer than 12-14 months after delivery and the years thereafter. In addition, we examined the women's lifestyle after delivery. METHODS: A cross-sectional follow-up survey among women with a history of GDM and their general practitioners (GP). Rates of attendance at the six-weeks postpartum visit and glucose testing were obtained from hospital records, over the period 2011-2012. Rates of annual follow-up postpartum glucose testing were assessed by a survey among their GP's. Lifestyle of the women on diet and exercise was assessed by questionnaire in 2015. RESULTS: In total 197 women were eligible for the study. Of these, 156 (79%) attended the six-weeks postpartum visit at the diabetes outpatient clinic and in 145 (93%) of these women glucose testing was performed. In total 77 (39%) women responded to the invitation to participate in this study and filled in the lifestyle questionnaire. About one third of the women met the recommendations for sufficient physical activity. A majority of them did not fulfil the Dutch guidelines on healthy diet - fruit intake 35.1%, vegetables intake 7.8%. Of the 74 invited GP's, 61 responded (82%), only 12 (20%) reported that they had performed a follow-up glucose testing within >12-14 months postpartum. Of these women, five were tested only in the first year of follow-up, five also in the second year, and two were tested for three consecutive years. CONCLUSIONS: Despite the high attendance rate of six-weeks postpartum visit and glucose testing, we observed low rates of longer-term follow-up regarding postpartum glucose testing. Moreover, we found a suboptimal adherence to healthy lifestyle for women with a history of GDM.

Neonatal and obstetric outcomes in diet- and insulin-treated women with gestational diabetes mellitus: a retrospective study.

BACKGROUND: To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment - diet-only versus additional insulin therapy - were based on the 2010 national Dutch guidelines. METHODS: Retrospective study of the electronic medical files of 820 singleton GDM pregnancies treated between January 2011 and September 2014 in a university and non-university hospital. Pregnancy outcomes were compared between regular care treatment regimens -diet-only versus additional insulin therapy- and pregnancy outcomes of the Northern region of the Netherlands served as a reference population. RESULTS: A total of 460 women (56 %) met glycaemic control on diet-only and 360 women (44 %) required additional insulin therapy. Between the groups, there were no differences in perinatal complications (mortality, birth trauma, hyperbilirubinaemia, hypoglycaemia), small for gestational age, large for gestational age (LGA), neonate weighing >4200 g, neonate weighing ≥4500 g, Apgar score <7 at 5 min, respiratory support, preterm delivery, and admission to the neonatology department. Neonates born in the insulin-group had a lower birth weight compared with the diet-group (3364 vs. 3467 g, p = 0.005) and a lower gestational age at birth (p = 0.001). However, birth weight was not different between the groups when expressed in percentiles, adjusted for gestational age, gender, parity, and ethnicity. The occurrence of preeclampsia and gestational hypertension was comparable between the groups. In the insulin-group, labour was more often induced and more planned caesarean sections were performed (p = 0.001). Compared with the general obstetric population, the percentage of LGA neonates was higher in the GDM population (11.0 % vs.19.9 %, p = <0.001). CONCLUSIONS: Neonatal and obstetric outcomes were comparable either with diet-only or additional insulin therapy. However, compared with the general obstetric population, the incidence of LGA neonates was significantly increased in this GDM cohort.

Association of Skin Autofluorescence Levels With Kidney Function Decline in Patients With Peripheral Artery Disease.

OBJECTIVE: Skin autofluorescence (SAF), a measure of advanced glycation end product accumulation, is associated with kidney function. We investigated the association of SAF with rate of kidney function decline in a cohort of patients with peripheral artery disease. APPROACH AND RESULTS: We performed a post hoc analysis of an observational longitudinal cohort study. We included 471 patients with peripheral artery disease, and SAF was measured at baseline. Primary end point was rate of estimated glomerular filtration rate (eGFR) decline. Secondary end points were incidence of eGFR <60 and <45 mL/min/1.73 m(2) and rapid eGFR decline, defined as a decrease in eGFR of >5 mL/min/1.73 m(2)/y. During a median follow-up of 3 years, the mean change in eGFR per year was -1.8±4.4 mL/min/1.73 m(2)/y. No significant difference in rate of eGFR decline was observed per 1 arbitrary unit increase in SAF (-0.1 mL/min/1.73 m(2)/y; 95% confidence interval, -0.7 to 0.5; P=0.8). Analyses of the secondary end points showed that there was an association of SAF with incidence of eGFR <60 and <45 mL/min/1.73 m(2) (hazard ratio, 1.54; 95% confidence interval, 1.13-2.10; P=0.006 and hazard ratio, 1.76; 95% confidence interval, 1.20-2.59; P=0.004, respectively), but after adjustment for age and sex, significance was lost. There was no association of SAF with rapid eGFR decline. CONCLUSIONS: In conclusion, in this cohort of patients with peripheral artery disease, elevated SAF was associated with lower baseline eGFR. Although SAF has previously been established as a predictor for cardiovascular disease and mortality, it did not predict the rate of kidney function decline during follow-up in this study.

Arterial Stiffness Is Positively Associated With 18F-fluorodeoxyglucose Positron Emission Tomography-Assessed Subclinical Vascular Inflammation in People With Early Type 2 Diabetes.

OBJECTIVE: Type 2 diabetes is accompanied by premature atherosclerosis and arterial stiffness. The underlying association remains incompletely understood. The possible relationship between subclinical arterial inflammation assessed by (18)F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and arterial stiffness was investigated in patients with early type 2 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes (n = 44), without cardiovascular disease and any type of antidiabetic medication, were studied (median age 63 years [interquartile range 54-66], men:women 27:17). Arterial inflammation was quantified as the FDG uptake maximal standardized uptake value (SUVmax). SUVmax was corrected for the prescan glucose level. A target-to-background ratio (TBR) was calculated by dividing the SUVmax of the arteries by the SUVmean of the caval veins (blood pool). TBRs were calculated for four individual segments (carotid arteries, ascending aorta and aortic arch, descending and abdominal aorta, and iliac and femoral arteries) and averaged for the total aortic tree (meanTBR). Arterial stiffness was assessed as central systolic blood pressure (cSBP), carotid-femoral pulse wave velocity (PWV), and augmentation index (AIx). RESULTS: The meanTBR was significantly associated with PWV (R = 0.47, P = 0.001) and cSBP (R = 0.45, P = 0.003) but not with AIx. TBR of each separate segment was also significantly associated with PWV and cSBP. In a multiple linear regression model including age, sex, BMI, hemoglobin A1c (HbA1c), hs-CRP, cholesterol, cSBP, and PWV, PWV was the strongest determinant of meanTBR. CONCLUSIONS: In patients with type 2 diabetes, FDG-PET/CT-imaged subclinical arterial inflammation is positively associated with determinants of arterial stiffness.

Gestational Diabetes Mellitus:current knowledge and unmet needs.

Gestational diabetes mellitus (GDM) is a global health concern, not only because its prevalence is high and on the increase, but also because of the potential implications for the health of mothers and their offspring. Unfortunately, there is considerable controversy in the literature surrounding the diagnosis and treatment of GDM, as well as the possible long-term consequences for the offspring. As a result, worldwide there is a lack of uniformly accepted diagnostic criteria and the advice regarding the treatment of GDM, including diet, insulin therapy, and the use of oral blood glucose-lowering agents, is highly variable. In this review we provide an overview of the important issues in the field of GDM, including diagnostic criteria, different treatment regimens available, and the long-term consequences of GDM in the offspring.