Characteristics associated with polypharmacy in people with type 2 diabetes: the Dutch Diabetes Pearl cohort.

AIM: To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes. METHODS: We included people with type 2 diabetes from the Diabetes Pearl cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5-9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0-4 medications). RESULTS: Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3-7) in primary care and 7 (IQR 5-10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose-lowering and lipid-modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non-cardiovascular and non-glucose-lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease. CONCLUSIONS: Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes.

Clinical profiles of post-load glucose subgroups and their association with glycaemic traits over time: An IMI-DIRECT study.

AIM: To examine the hypothesis that, based on their glucose curves during a seven-point oral glucose tolerance test, people at elevated type 2 diabetes risk can be divided into subgroups with different clinical profiles at baseline and different degrees of subsequent glycaemic deterioration. METHODS: We included 2126 participants at elevated type 2 diabetes risk from the Diabetes Research on Patient Stratification (IMI-DIRECT) study. Latent class trajectory analysis was used to identify subgroups from a seven-point oral glucose tolerance test at baseline and follow-up. Linear models quantified the associations between the subgroups with glycaemic traits at baseline and 18 months. RESULTS: At baseline, we identified four glucose curve subgroups, labelled in order of increasing peak levels as 1-4. Participants in Subgroups 2-4, were more likely to have higher insulin resistance (homeostatic model assessment) and a lower Matsuda index, than those in Subgroup 1. Overall, participants in Subgroups 3 and 4, had higher glycaemic trait values, with the exception of the Matsuda and insulinogenic indices. At 18 months, change in homeostatic model assessment of insulin resistance was higher in Subgroup 4 (ß = 0.36, 95% CI 0.13-0.58), Subgroup 3 (ß = 0.30; 95% CI 0.10-0.50) and Subgroup 2 (ß = 0.18; 95% CI 0.04-0.32), compared to Subgroup 1. The same was observed for C-peptide and insulin. Five subgroups were identified at follow-up, and the majority of participants remained in the same subgroup or progressed to higher peak subgroups after 18 months. CONCLUSIONS: Using data from a frequently sampled oral glucose tolerance test, glucose curve patterns associated with different clinical characteristics and different rates of subsequent glycaemic deterioration can be identified.

Built environmental characteristics and diabetes: a systematic review and meta-analysis.

BACKGROUND: The built environment influences behaviour, like physical activity, diet and sleep, which affects the risk of type 2 diabetes mellitus (T2DM). This study systematically reviewed and meta-analysed evidence on the association between built environmental characteristics related to lifestyle behaviour and T2DM risk/prevalence, worldwide. METHODS: We systematically searched PubMed, EMBASE.com and Web of Science from their inception to 6 June 2017. Studies were included with adult populations (>18 years), T2DM or glycaemic markers as outcomes, and physical activity and/or food environment and/or residential noise as independent variables. We excluded studies of specific subsamples of the population, that focused on built environmental characteristics that directly affect the cardiovascular system, that performed prediction analyses and that do not report original research. Data appraisal and extraction were based on published reports (PROSPERO-ID: CRD42016035663). RESULTS: From 11,279 studies, 109 were eligible and 40 were meta-analysed. Living in an urban residence was associated with higher T2DM risk/prevalence (n = 19, odds ratio (OR) = 1.40; 95% CI, 1.2-1.6; I2 = 83%) compared to living in a rural residence. Higher neighbourhood walkability was associated with lower T2DM risk/prevalence (n = 8, OR = 0.79; 95% CI, 0.7-0.9; I2 = 92%) and more green space tended to be associated with lower T2DM risk/prevalence (n = 6, OR = 0.90; 95% CI, 0.8-1.0; I2 = 95%). No convincing evidence was found of an association between food environment with T2DM risk/prevalence. CONCLUSIONS: An important strength of the study was the comprehensive overview of the literature, but our study was limited by the conclusion of mainly cross-sectional studies. In addition to other positive consequences of walkability and access to green space, these environmental characteristics may also contribute to T2DM prevention. These results may be relevant for infrastructure planning.

Characteristics of high- and low-risk individuals in the PRIORITY study: urinary proteomics and mineralocorticoid receptor antagonism for prevention of diabetic nephropathy in Type 2 diabetes.

AIM: To compare clinical baseline data in individuals with Type 2 diabetes and normoalbuminuria, who are at high or low risk of diabetic kidney disease based on the urinary proteomics classifier CKD273. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled international multicentre clinical trial and observational study in participants with Type 2 diabetes and normoalbuminuria, stratified into high- or low-risk groups based on CKD273 score. Clinical baseline data for the whole cohort and stratified by risk groups are reported. The associations between CKD273 and traditional risk factors for diabetic kidney disease were evaluated using univariate and logistic regression analysis. RESULTS: A total of 1777 participants from 15 centres were included, with 12.3% of these having a high-risk proteomic pattern. Participants in the high-risk group (n=218), were more likely to be men, were older, had longer diabetes duration, a lower estimated GFR and a higher urinary albumin:creatinine ratio than those in the low-risk group (n=1559, P<0.02). Numerical differences were small and univariate regression analyses showed weak associations (R2 < 0.04) of CKD273 with each baseline variable. In a logistic regression model including clinical variables known to be associated with diabetic kidney disease, estimated GFR, gender, log urinary albumin:creatinine ratio and use of renin-angiotensin system-blocking agents remained significant determinants of the CKD273 high-risk group: area under the curve 0.72 (95% CI 0.68-0.75; P<0.01). CONCLUSIONS: In this population of individuals with Type 2 diabetes and normoalbuminuria, traditional diabetic kidney disease risk factors differed slightly between participants at high risk and those at low risk of diabetic kidney disease, based on CKD273. These data suggest that CKD273 may provide additional prognostic information over and above the variables routinely available in the clinic. Testing the added value will be subject to our ongoing study. (European Union Clinical Trials Register: EudraCT 2012-000452-34 and Clinicaltrials.gov: NCT02040441).

Low vitamin D levels are not a contributing factor to higher prevalence of depressive symptoms in people with Type 2 diabetes mellitus: the Hoorn study.

AIM: To test whether a low serum 25-hydroxyvitamin D level explains the greater prevalence of depression among people with Type 2 diabetes. METHODS: We performed a cross-sectional analysis of 527 people, aged 60-87 years, who participated in a population-based cohort study. Type 2 diabetes, impaired glucose tolerance, impaired fasting glucose and normal glucose tolerance were defined according to the 2006 WHO criteria. The Centre for Epidemiologic Studies Depression questionnaire was administered, using a cut-off score of ≥ 16 to determine clinically relevant depressive symptoms. RESULTS: Logistic regression analysis confirmed that women with impaired glucose tolerance/impaired fasting glucose and people with Type 2 diabetes did have a higher risk of depressive symptoms [unadjusted odds ratios 3.66 (95% CI 1.59 to 8.43) and 3.04 (95% CI 1.57 to 5.88), respectively], compared with people with normal glucose tolerance. Serum 25-hydroxyvitamin D level was not a mediating factor in the association between impaired glucose tolerance/impaired fasting glucose or Type 2 diabetes and depressive symptoms [unstandardized indirect effect 0.001 (95% CI -0.063 to 0.079) and 0.004 (95% CI -0.025 to 0.094), respectively]. CONCLUSIONS: The study found no evidence that low vitamin D levels are a contributing factor to higher depression scores in people with Type 2 diabetes.

Individual and partner's level of occupation and the association with HbA1c levels in people with Type 2 diabetes mellitus: the Dutch Diabetes Pearl cohort.

AIMS: Individual indicators of socio-economic status have been associated with glycaemic control in people with Type 2 diabetes, but little is known about the association between partner's socio-economic status and HbA1c levels. We therefore examined the cross-sectional association between individual and partner's level of occupation on HbA1c levels in people with Type 2 diabetes in the Netherlands. METHODS: We included people with Type 2 diabetes with a partner who were treated in primary, secondary and tertiary care in the Diabetes Pearl cohort. Occupational level was classified according to International Standard Classification of Occupations (ISCO)-08 skill levels. Linear regression analyses were performed stratified for sex, and corrected for age, recruitment centre and diabetes medication. RESULTS: In total, 3257 participants (59.8% men, mean 62.2±9.4 years) were included. For men, having a partner with an intermediate level of occupation was associated with lower HbA1c levels [e.g. ISCO level 3: -2 mmol/mol (95% CI -4;-1) or -0.2% (95% CI -0.4;-0.1)], compared with having a partner of the highest occupational level (ISCO level 4). In women, having an unemployed partner was associated with higher HbA1c levels [14 mmol/mol (95% CI 6; 22) or 1.3% (95% CI 0.6; 2.0)], compared with having a partner of the highest occupational level. CONCLUSIONS: Partner's occupational status provided additional information on the association between socio-economic status and HbA1c levels in people with Type 2 diabetes. Women seemed to benefit from a partner with a higher occupational status, while men seemed to benefit from a partner with a lower status. Because of the cross-sectional nature of the present study, more research is necessary to explore this association.

Design of the SALT Osteoporosis Study: a randomised pragmatic trial, to study a primary care screening and treatment program for the prevention of fractures in women aged 65 years or older.

BACKGROUND: Several drugs have become available for the treatment of osteoporosis. However, screening and treatment of patients with a high fracture risk is currently not recommended in the Netherlands, because the effectiveness of bone sparing drugs has not been demonstrated in the general primary care population. Here we describe the design of the SALT Osteoporosis study, which aims to examine whether the screening and treatment of older, female patients in primary care can reduce fractures, in comparison to usual care. METHODS: A randomised pragmatic trial has been designed using a stepwise approach in general care practices in the Netherlands. Women aged ≥65 years, who are not prescribed bone sparing drugs or corticosteroids are eligible for the study. First, women with at least one clinical risk factor for fractures, as determined by questionnaires, are randomly assigned to the intervention or control group. Second, women in the intervention group having a high fracture risk according to our screening program, including an adapted fracture risk assessment (FRAX) tool, combined with dual-energy x-ray absorptiometry (DXA), and instant vertebral assessment (IVA), are offered a structured treatment program. The women in the control group receive care as usual and will undergo the same screening as the intervention group at the end of the trial. The follow-up duration will be three years and the primary outcome is time to first incident fracture and the total number of fractures. DISCUSSION: The results of the current study will be very important for underpinnings of the prevention strategy of the osteoporosis guidelines. TRIAL REGISTRATION: ID NTR2430 . Registered 26 July 2010.

Sleep assessment using EEG-based wearables - A systematic review.

Polysomnography (PSG) is the reference standard of sleep measurement, but is burdensome for the participant and labor intensive. Affordable electroencephalography (EEG)-based wearables are easy to use and are gaining popularity, yet selecting the most suitable device is a challenge for clinicians and researchers. In this systematic review, we aim to provide a comprehensive overview of available EEG-based wearables to measure human sleep. For each wearable, an overview will be provided regarding validated population and reported measurement properties. A systematic search was conducted in the databases OVID MEDLINE, Embase.com and CINAHL. A machine learning algorithm (ASReview) was utilized to screen titles and abstracts for eligibility. In total, 60 papers were selected, covering 34 unique EEG-based wearables. Feasibility studies indicated good tolerance, high compliance, and success rates. The 42 included validation studies were conducted across diverse populations and showed consistently high accuracy in sleep staging detection. Therefore, the recent advancements in EEG-based wearables show great promise as alternative for PSG and for at-home sleep monitoring. Users should consider factors like user-friendliness, comfort, and costs, as these devices vary in features and pricing, impacting their suitability for individual needs.

Distinct associations between energy balance and the sleep characteristics slow wave sleep and rapid eye movement sleep.

CONTEXT: Epidemiologically, an inverse relationship between body mass index (BMI) and sleep duration is observed. Intra-individual variance in the amount of slow wave sleep (SWS) or rapid eye movement (REM) sleep has been related to variance of metabolic and endocrine parameters, which are risk factors for the disturbance of energy balance (EB). OBJECTIVE: To investigate inter-individual relationships between EB (EB= energy intake-energy expenditure∣, MJ/24 h), SWS or REM sleep, and relevant parameters in normal-weight men during two 48 h stays in the controlled environment of a respiration chamber. SUBJECTS AND METHODS: A total of 16 men (age 23±3.7 years, BMI 23.9±1.9 kg m(-2)) stayed in the respiration chamber twice for 48 h to assure EB. Electroencephalography was used to monitor sleep (2330-0730 hrs). Hunger and fullness were scored by visual analog scales; mood was determined by State Trait Anxiety Index-state and food reward by liking and wanting. Baseline blood and salivary samples were collected before breakfast. Subjects were fed in EB, except for the last dinner, when energy intake was ad libitum. RESULTS: The subjects slept on average 441.8±49 min per night, and showed high within-subject reliability for the amount of SWS and REM sleep. Linear regression analyses showed that EB was inversely related to the amount of SWS (r=-0.43, P<0.03), and positively related to the amount of REM sleep (r=0.40, P<0.05). Relevant parameters such as hunger, reward, stress and orexigenic hormone concentrations were related to overeating, as well as to the amount of SWS and REM sleep, however, after inclusion of these parameters in a multiple regression, the amount of SWS and REM sleep did not add to the explained variance of EB, which suggests that due to their individual associations, these EB parameters are mediator variables. CONCLUSION: A positive EB due to overeating, was explained by a smaller amount of SWS and higher amount of REM sleep, mediated by hunger, fullness, State Trait Anxiety Index-state scores, glucose/insulin ratio, and ghrelin and cortisol concentrations.

Observational and experimental studies on sleep duration and aggression: A systematic review and meta-analysis.

Short sleep duration has been linked to higher levels of aggression. To synthetize all available research on this association, a systematic review and meta-analysis was performed. We included observational and experimental studies, using various measures of sleep duration and aggression. Eighty eligible papers were identified, describing 82 studies comprising a total number of 76.761 participants. Meta-analysis of results was possible for 60 studies. Pooled observational results on the association between sleep duration and aggression showed a correlation estimate of -0.16 (95%CI -0.19, -0.12; I2 = 83.9%) and an odds ratio estimate of 1.83 (95%CI 1.47, 2.28; I2 = 0.0%). For experimental studies, the pooled Standardized Mean Difference after manipulation of sleep duration was -0.37 (95%CI -0.80, 0.05; I2 = 89.05%) for controlled designs and -0.34 (95%CI -0.54, -0.14; I2 = 89.05%) for pre-post designs. Effect estimates were stronger for individuals with psychological vulnerabilities and younger persons. Exclusion of studies with low methodological quality strengthened the effect estimate in experimental but not in observational studies. To conclude, short sleep duration is associated with higher levels of aggression, with observational research strongly supporting the association and experimental studies providing mixed results. More well-designed prospective and experimental studies are needed to establish causality and optimize treatment, especially for individuals with psychological vulnerabilities.

Neighborhood walkability, physical activity and changes in glycemic markers in people with type 2 diabetes: The Hoorn Diabetes Care System cohort.

Studies investigating neighborhood walkability and physical activity in people with type 2 diabetes (T2D) mainly used self-report measures, and only few studies assessed the association with glycemic control. This study assessed the associations between objectively measured (i.e. GIS based) and subjectively measured (i.e. questionnaire-based) neighborhood walkability and changes in glycemic markers in people with T2D, and whether this association was mediated by device-measured physical activity (PA), in the Diabetes Care System Cohort (n = 1230). Neither objective or subjectively measured walkability was associated with glycemic control. In mediation analyses we observed no overall mediation by PA.

Sleep duration and body-weight development during puberty in a Dutch children cohort.

BACKGROUND: Short sleep duration is associated with obesity during childhood and adulthood. OBJECTIVE: The objective of our study was to investigate the relationship between sleep duration and body mass index (BMI) from Tanner stages 1 to 5 in a Dutch children cohort. DESIGN: In 98 children, anthropometric measurements and leptin concentrations were measured from age 7 to 16 years; body composition, physical activity (Baecke questionnaire), hours television viewing and self-reported sleep duration were measured yearly from age 12 to 16 years. Moreover, the polymorphisms of the FTO gene (rs9939609) and parental BMI's were determined. RESULTS: At Tanner stages 1-5 sex differences were observed in height, body weight, waist circumference, fat mass per squared meter height and leptin concentrations per kg fat mass. Inverse relationships were observed between the change in BMI (kg m(-2)) and the change in hours of sleep per night (h) from Tanner stages 1 to 4 (r=-0.68, P<0.001), from Tanner stages 2 to 5 (r=-0.35, P<0.05) and from Tanner stages 1 to 5 (r=-0.33, P<0.05). Univariate analysis of variance showed that with progressive Tanner stages, BMI increases and sleep duration decreases in an interrelated way independent of possible confounders (R(2)=0.38, P<0.02). CONCLUSION: Changes in BMI during puberty were inversely related to changes in sleep duration, independent of possible confounders.

Acute stress and food-related reward activation in the brain during food choice during eating in the absence of hunger.

BACKGROUND: Stress results in eating in the absence of hunger, possibly related to food reward perception. HYPOTHESIS: Stress decreases food reward perception. AIM: Determine the effect of acute stress on food choice and food choice reward-related brain activity. SUBJECTS: Nine females (BMI = 21.5 + or - 2.2 kg/m(2), age = 24.3 + or - 3.5 years). PROCEDURE: Fasted subjects came twice to randomly complete either a rest or stress condition. Per session, two functional MRI scans were made, wherein the subjects chose the subsequent meal (food images). The rewarding value of the food was measured as liking and wanting. Food characteristics (for example, crispiness, fullness of taste and so on), energy intake, amount of each macronutrient chosen, plasma cortisol and Visual Analog Scale (VAS) hunger and satiety were measured. RESULTS: Fasted state was confirmed by high hunger (80 + or - 5 mm VAS). Breakfast energy intake (3 + or - 1 MJ) and liking were similar in all conditions. Wanting was lower postprandially (Delta = -0.3 items/category, P<0.01). Breakfast decreased hunger (-42 mm VAS, P<0.01). Postprandially, energy intake (-1.1 MJ), protein intake (-14.7 g) and carbohydrate intake (-32.7 g all P<0.05) were lower. Fat intake was not different (-7.3, P = 0.4). Putamen activity was not lower postprandially. Cortisol levels were increased in the stress condition (Area under the curve of cortisol: DeltaAUC = +2.2 x 10(4) nmol min(-1) l(-1), P<0.05). Satiety was lower after breakfast (-8 mm VAS, P<0.01). Postprandial energy intake, protein intake and carbohydrate intake were relatively higher compared with the rest condition, resulting from more choice for crispiness and fullness of taste (P<0.05). Brain activation was reduced in reward areas: amygdala, hippocampus and cingulate cortex (AUC = -13.33, -1.34, -2.56% blood oxygen level dependent (BOLD) s for choosing breakfast and AUC = -9.31, -1.25, -2.34%BOLD s<0.05 for choosing the second meal). Putamen activation was decreased postprandially (AUC = -1.2%BOLD s, P<0.05). CONCLUSION: Reward signaling and reward sensitivity were significantly lower under stress, coinciding with increased energy intake from food choice for more crispiness and fullness of taste. The changes in putamen activation may reflect specifically decreased reward prediction sensitivity.

Poor sleep quality at baseline is associated with increased aggression over one year in forensic psychiatric patients.

OBJECTIVE: In forensic psychiatric patients, sleep problems as well as impulsivity and aggression are highly prevalent, yet studies on their association over time are lacking. This study investigates the association between sleep quality and changes in impulsivity and aggression in forensic psychiatric patients over one year. METHODS: Data were drawn from an ongoing prospective observational study in adult forensic psychiatric patients admitted to a forensic treatment facility between October 2006 and January 2018. Validated self-reports and observational instruments were used to assess sleep quality, impulsivity and aggression upon admission to the hospital and after one year. Linear regression analyses were performed to examine the association between sleep quality, impulsivity and aggression. All models were adjusted for baseline values of outcome measures, demographic features and general psychopathology. RESULTS: Data from 83 men (age 37.7 ± 11.7 years) with completed consecutive measurements were analyzed. Poor sleep quality was associated with increased self-reported aggression (ß = 1.08; 95% CI, 0.38-1.78). This association was positively confounded by general psychopathology, indicating that sleep quality is specifically related to self-reported aggression instead of being part of general psychopathology (adjusted ß = 1.18; 95% CI, 0.39-1.97). Poor sleep quality was not associated with changes in self-reported impulsivity, clinician-rated impulsivity or clinician-rated hostility in this population. CONCLUSION: Poor sleep quality was associated with an increase in self-reported aggression over one year in male forensic psychiatric patients. Early evaluation and treatment of sleep problems in (forensic) psychiatric patients may play an important role in reducing the risk of aggressive behavior.

The prevalence of type 2 diabetes in people with psychiatric disorders: an umbrella review protocol.

BACKGROUND: Many epidemiological studies have investigated the prevalence of type 2 diabetes in individuals with a psychiatric disorder. In an umbrella review, we aim to systematically summarize existing systematic reviews examining the prevalence of type 2 diabetes in people with a psychiatric disorder. When information is available in the identified systematic reviews, comparisons with control groups without a psychiatric disorder will be made. Furthermore, we aim to assess the quality of the included systematic reviews. METHODS: The umbrella review will be based on a comprehensive systematic search of systematic reviews of observational (cross-sectional or longitudinal) studies investigating the prevalence of type 2 diabetes in people with a psychiatric disorder. Four electronic databases (Embase, PsycINFO, PubMed, and the Cochrane Database of Systematic Reviews) will be searched. Retrieved papers will be screened for eligibility by two independent reviewers. Furthermore, the reference lists of all included publications will be screened. Data will be extracted by using an a priori developed data extraction form and two independent reviewers will assess the risk of bias in the included systematic reviews using with the Risk of Bias in Systematic Reviews (ROBIS) tool. A narrative data-synthesis and a subsequent meta-analysis based on the primary studies will be made. DISCUSSION: For each psychiatric disorder, the data regarding the prevalence of type 2 diabetes will be summarized and discussed. When possible, comparisons with control groups will be reported and discussed. Finally, future implications and recommendations for clinical care will be presented. SYSTEMATIC REVIEW REGISTRATION: This protocol was submitted for registration with the International Prospective Register of Systematic Reviews (PROSPERO) on December 9, 2019 (registration number: pending).

Risk and management of pre-diabetes.

Type 2 diabetes mellitus (T2DM) is associated with a two- to four-fold increased risk of developing cardiovascular disease (CVD) and microvascular complications, which may already be present before diagnosis. It is, therefore, important to detect people with an increased risk of T2DM at an early stage. In order to identify individuals with so-called 'pre-diabetes', comprising impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), current guidelines have developed definitions based on fasting plasma glucose, two-hour glucose concentrations and haemoglobin A1c. Subjects with pre-diabetes are at an increased risk of developing T2DM and CVD. This elevated risk seems similar according to the different criteria used to define pre-diabetes. The risk of progression to T2DM or CVD does, however, depend on other risk factors such as sex, body mass index and ethnicity. Based on the risk factors to develop T2DM, many risk assessment models have been developed to identify those at highest risk. These models perform well to identify those at risk and could be used to initiate preventive interventions. Many studies have shown that lifestyle modification and metformin are effective in preventing the development of T2DM, although lifestyle modification seems to have a more sustainable effect. In addition, lifestyle modification seems more effective in those with IGT than those with IFG. In this review, we will describe the different definitions used to define pre-diabetes, progression from pre-diabetes to T2DM or other vascular complications, risk factors associated with progressions and the management of progression to T2DM, ending with clinical recommendations.

Associations between sleep duration and sleep debt with insulin sensitivity and insulin secretion in the EGIR-RISC Study.

AIM: Extremes in sleep duration play an important role in the development of type 2 diabetes. We examined the associations between sleep duration and sleep debt with estimates of insulin sensitivity and insulin secretion. METHODS: Data were derived from the European multi-centre EGIR-RISC study. Sleep duration and sleep debt were derived from a sleep questionnaire asking about sleeping time during the week and during the weekend. Insulin sensitivity and insulin secretion were estimated from a 2-hour Oral Glucose Tolerance Test, with samples every 30 minutes. Associations between sleep duration and sleep debt with insulin sensitivity and insulin secretion, were analysed by multiple linear regression models corrected for possible confounders. RESULTS: Sleep data were available in 1002 participants, 46% men, mean age 48 ± 8 years, who had an average sleep duration of 7 ± 1 hours [range 3-14] and an average sleep debt (absolute difference hours sleep weekend days minus weekdays) of 1 ± 1 hour [range 0-8]. With regard to insulin sensitivity, we observed an inverted U-shaped association between sleep duration and the Stumvoll MCR in (mL/kg/min), with a corrected ß (95% CI) of 2.05 (0.8; 3.3) and for the quadratic term -0.2 (-0.3; -0.1). Similarly, a U-shaped association between sleep duration and log HOMA-IR in (µU/mL), with a corrected ßs of -0.83 (-1.4; -0.24) and 0.06 (0.02; 0.10) for the quadratic term. Confounders showed an attenuating effect on the associations, while BMI mediated 60 to 91% of the association between sleep duration and insulin sensitivity. No significant associations were observed between sleep duration with insulin secretion or between sleep debt with either insulin sensitivity or insulin secretion. CONCLUSIONS: Short and long sleep duration are associated with a lower insulin sensitivity, suggesting that sleep plays an important role in insulin resistance and may provide the link with development of type 2 diabetes.

Leptin-adiposity relationship changes, plus behavioral and parental factors, are involved in the development of body weight in a Dutch children cohort.

BACKGROUND: The development of body weight is determined by different factors, namely genetic, behavioral, parental and physiological. OBJECTIVE: To investigate whether genetic, behavioral, parental and physiological factors are involved and the extent of involvement in the development of body weight at ages 12 and 13 y in a Dutch children cohort. METHODS: In a Dutch cohort of 94 children at ages 12 and 13 y, we determined anthropometric measurements, body composition, leptin concentrations, TFEQ scores, physical activity, as well as 3 polymorphisms, and in the parents we determined anthropometric measurements and TFEQ scores. RESULTS: 11% of the children in the cohort were classified as overweight. The genotype frequency distributions of the PPARy2, GRL and CNTF genes at ages 12 and 13 y were not significantly different for the overweight children compared to the lean children. Overweight children showed higher dietary restraint and disinhibition scores. Overweight children's parents had a higher BMI, dietary restraint and disinhibition scores, compared to lean children's parents. A peak in leptin concentrations between 7 and 13 y was shown at 12 y. In lean boys, the decrease in leptin concentrations between 12 and 13 y was related to an increase in fat free mass. At the age of 12 y predominantly the physiological factors were predictors for body weight, and at the age of 13 y both the physiological and behavioral factors were predictors for body weight. CONCLUSION: We conclude from this longitudinal study, that leptin appeared to play an important role in the development of body weight during puberty, in addition to behavioral and parental factors.

Incretin responses to oral glucose and mixed meal tests and changes in fasting glucose levels during 7 years of follow-up: The Hoorn Meal Study.

We conducted the first prospective observational study in which we examined the association between incretin responses to an oral glucose tolerance test (OGTT) and mixed meal test (MMT) at baseline and changes in fasting glucose levels 7 years later, in individuals who were non-diabetic at baseline. We used data from the Hoorn Meal Study; a population-based cohort study among 121 subjects, aged 61.0±6.7y. GIP and GLP-1 responses were determined at baseline and expressed as total and incremental area under the curve (tAUC and iAUC). The association between incretin response at baseline and changes in fasting glucose levels was assessed using linear regression. The average change in glucose over 7 years was 0.43 ± 0.5 mmol/l. For GIP, no significant associations were observed with changes in fasting glucose levels. In contrast, participants within the middle and highest tertile of GLP-1 iAUC responses to OGTT had significantly smaller increases (actually decreases) in fasting glucose levels; -0.28 (95% confidence interval: -0.54;-0.01) mmol/l and -0.39 (-0.67;-0.10) mmol/l, respectively, compared to those in the lowest tertile. The same trend was observed for tAUC GLP-1 following OGTT (highest tertile: -0.32 (0.61;-0.04) mmol/l as compared to the lowest tertile). No significant associations were observed for GLP-1 responses following MMT. In conclusion, within our non-diabetic population-based cohort, a low GLP-1 response to OGTT was associated with a steeper increase in fasting glucose levels during 7 years of follow-up. This suggests that a reduced GLP-1 response precedes glucose deterioration and may play a role in the etiology of type 2 diabetes mellitus.