Association between glucose dips and the feeling of hunger in a dietary intervention study among students with early and late chronotype-secondary analysis of a randomized cross-over nutrition trial.

Consumption of foods with high glycaemic index (GI) can cause hyperglycemia, thus increasing postprandial hunger. Since circadian rhythm differs inter-individually, we describe glucose dips after breakfast/dinner with high/medium estimated meal GI among students with early (n = 22) and late chronotype (n = 23) and examine their relation to the feeling of hunger in a secondary analysis of a randomized cross-over nutrition trial. Glucose dips reflect the difference between the lowest glucose value recorded 2-3 h postprandially and baseline, presented as percentage of average baseline level. Associations between glucose dips and the feeling of hunger were analyzed using multilevel linear models. Glucose dips were lower after medium GI meals than after high GI meals among both chronotype groups (p = 0.03). Among early chronotypes, but not among late chronotypes, glucose dip values were lower after breakfast than after dinner (-4.9 % vs. 5.5 %, p = 0.001). Hunger increased throughout the day among both chronotypes but glucose dips were not related to the feeling of hunger at the meal following breakfast. Interestingly, lower glucose dip values 2-3 h postprandially occurred particularly after medium GI meals and were seen after breakfast among early chronotypes. These glucose dips did not predict hunger at meals after breakfast.

Elevated adiponectin predicts the development of rheumatoid arthritis in subjects with obesity.

Objective The aim of the current study is to determine whether baseline serum adiponectin levels predict the development of rheumatoid arthritis (RA). Method The current report includes 3693 individuals from the Swedish Obese Subjects (SOS) study. The original SOS study is a longitudinal non-randomized controlled study aiming to assess the effect of bariatric surgery on obesity-related mortality and morbidity. Participants included in the present report had adiponectin measurement available at baseline and no prevalent RA. The diagnosis of RA was retrieved through the Swedish National Patient Register. Results During a follow-up for up to 29 years, 82 study participants developed RA. Elevated baseline adiponectin levels were associated with a higher risk of developing RA independently of other factors, including C-reactive protein (CRP) and smoking [hazard ratio (HR) 1.70, 95% confidence interval (CI) 1.12-2.60 for an increase in adiponectin of 10 mg/L, p = 0.01]. After stratifying the population according to adiponectin and CRP median at baseline, study participants with both adiponectin and CRP above the median had a higher risk of developing RA compared to subjects with adiponectin and CRP below the median (HR 2.80, 95% CI 1.25-6.31, p = 0.01). Conclusions In this cohort of subjects with obesity followed up for up to 29 years, high serum adiponectin levels at baseline were associated with an increased risk for RA. Moreover, subjects with both high adiponectin and CRP levels at baseline were at particular risk of developing RA. ClinicalTrials.gov Identifier: NCT01479452.

Anxiety boosts progression of prediabetes to type 2 diabetes: findings from the prospective Cooperative Health Research in the Region of Augsburg F4 and FF4 studies.

AIM: To investigate the association between anxiety symptoms and the progression from prediabetes to type 2 diabetes. METHODS: A sample of 1708 participants aged 31-82 years from the population-based Cooperative Health Research in the Region of Augsburg F4 and the follow-up Cooperative Health Research in the Region of Augsburg FF4 studies was included. Prediabetes was defined as impaired fasting glucose and/or impaired glucose tolerance, and anxiety status was measured by the generalized anxiety disorder-7 questionnaire. Newly diagnosed type 2 diabetes cases were identified after 6.5 years (11 102 person-years) and confirmed by medical records. Multivariate logistic regression analyses were employed to estimate the effect of prediabetes and anxiety on the incidence of type 2 diabetes with different levels of adjustments for potential confounders. The population attributable risk of type 2 diabetes in participants with prediabetes and anxiety was estimated. RESULTS: Prediabetes at baseline was prevalent in 247 participants, of whom 77 developed diabetes after follow-up, accounting for a progression rate of 31%. In participants with prediabetes, high anxiety was associated with a 3-fold increased risk of progression to type 2 diabetes in comparison with low anxiety, even after accounting for socio-demographic, lifestyle and metabolic risk factors (OR = 2.82, 95% CI = 0.95-8.37, P = 0.06). A significant proportion of incident type 2 diabetes was attributed to having anxiety in addition to prediabetes (attributable risk proportion: 0.52; 95% CI = 0.004-1.04, P = 0.05). CONCLUSIONS: Anxiety symptoms independently increase the progression risk of prediabetes to type 2 diabetes and should be routinely considered alongside the traditional risk factors in people with prediabetes.

Inverse association of insulin antibody levels with insulin sensitivity in adults with Type 1 diabetes.

AIMS: Insulin resistance may contribute to the pathogenesis of autoimmune-mediated diabetes. Antibodies against ß-cell-associated molecules, comprising islet cell antigen (ICA), glutamic acid decarboxylase (GAD) and insulin, characterize the autoimmune process. Because the link between insulin resistance and autoimmunity might be relevant for disease progression and treatment, we hypothesized that insulin resistance associates positively with ß-cell-directed antibodies in newly diagnosed Type 1 diabetes. METHODS: Within the German Diabetes Study, an observational study including adults with newly diagnosed diabetes, 142 adults [84 men, 58 women; age 33.1 (26.4, 41.9) years; diabetes duration 6.3 (4.2, 9.1) months] positive for at least one antibody against ICA, GAD or insulin underwent hyperinsulinaemic-euglycaemic clamp tests to assess insulin sensitivity (M-value) in a cross-sectional setting. RESULTS: Insulin-directed antibodies were inversely correlated with M-values (ß = -0.039). Albeit not strong, the association persisted after adjustment for age, sex and BMI, and even after further adjustment for confounders reflecting exposure to exogenous insulin and residual ß-cell secretory capacity. Correlation network-based analyses revealed a complex interaction between levels of fasting insulin and of insulin antibodies with respect to their relationship with the M-value. GAD- or ICA-directed antibodies did not correlate with insulin sensitivity. CONCLUSIONS: In adults with recent-onset Type 1 diabetes expressing at least one ß-cell-directed antibody, insulin sensitivity is inversely related to insulin antibody titres, but not to other autoantibodies. Our finding may allow for the identification of insulin resistance in adults with high levels of insulin antibodies.

Metabolomic response to coffee consumption: application to a three-stage clinical trial.

BACKGROUND: Coffee is widely consumed and contains many bioactive compounds, any of which may impact pathways related to disease development. OBJECTIVE: To identify individual metabolite changes in response to coffee. METHODS: We profiled the metabolome of fasting serum samples collected from a previously reported single-blinded, three-stage clinical trial. Forty-seven habitual coffee consumers refrained from drinking coffee for 1 month, consumed four cups of coffee/day in the second month and eight cups/day in the third month. Samples collected after each coffee stage were subject to nontargeted metabolomic profiling using UPLC-ESI-MS/MS. A total of 733 metabolites were included for univariate and multivariate analyses. RESULTS: A total of 115 metabolites were significantly associated with coffee intake (P < 0.05 and Q < 0.05). Eighty-two were of known identity and mapped to one of 33 predefined biological pathways. We observed a significant enrichment of metabolite members of five pathways (P < 0.05): (i) xanthine metabolism: includes caffeine metabolites, (ii) benzoate metabolism: reflects polyphenol metabolite products of gut microbiota metabolism, (iii) steroid: novel but may reflect phytosterol content of coffee, (iv) fatty acid metabolism (acylcholine): novel link to coffee and (v) endocannabinoid: novel link to coffee. CONCLUSIONS: The novel metabolites and candidate pathways we have identified may provide new insight into the mechanisms by which coffee may be exerting its health effects.

Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.

BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes might have harmful effects on the kidney.

A DNA methylation biomarker of alcohol consumption.

The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Epigenetic modifications such as DNA methylation may provide novel biomarkers of alcohol use. To examine this possibility, we performed an epigenome-wide association study of methylation of cytosine-phosphate-guanine dinucleotide (CpG) sites in relation to alcohol intake in 13 population-based cohorts (ntotal=13 317; 54% women; mean age across cohorts 42-76 years) using whole blood (9643 European and 2423 African ancestries) or monocyte-derived DNA (588 European, 263 African and 400 Hispanic ancestry) samples. We performed meta-analysis and variable selection in whole-blood samples of people of European ancestry (n=6926) and identified 144 CpGs that provided substantial discrimination (area under the curve=0.90-0.99) for current heavy alcohol intake (⩾42 g per day in men and ⩾28 g per day in women) in four replication cohorts. The ancestry-stratified meta-analysis in whole blood identified 328 (9643 European ancestry samples) and 165 (2423 African ancestry samples) alcohol-related CpGs at Bonferroni-adjusted P<1 × 10-7. Analysis of the monocyte-derived DNA (n=1251) identified 62 alcohol-related CpGs at P<1 × 10-7. In whole-blood samples of people of European ancestry, we detected differential methylation in two neurotransmitter receptor genes, the γ-Aminobutyric acid-A receptor delta and γ-aminobutyric acid B receptor subunit 1; their differential methylation was associated with expression levels of a number of genes involved in immune function. In conclusion, we have identified a robust alcohol-related DNA methylation signature and shown the potential utility of DNA methylation as a clinically useful diagnostic test to detect current heavy alcohol consumption.

Circulating adiponectin concentration is inversely associated with glucose tolerance and insulin secretion in people with newly diagnosed diabetes.

AIMS: To examine the hypothesis that changes in serum adiponectin concentration inversely relate to changes in glucose tolerance and ß-cell function already during the early stage of disease progression in recently diagnosed Type 1 and Type 2 diabetes mellitus. METHODS: Participants in the prospective observational German Diabetes Study (Type 2 diabetes, n = 94; Type 1 diabetes, n = 42) underwent i.v. glucose tolerance and glucagon stimulation testing to assess pre-hepatic ß-cell function, glucose tolerance index and C-peptide secretion within the first year of diabetes diagnosis and 2 years later. Associations of changes in serum concentrations of total adiponectin, high-molecular-weight adiponectin and their ratio with changes in the aforementioned metabolic variables were calculated using linear regression. RESULTS: Among people with Type 2 diabetes, 2-year increases in high-molecular-weight adiponectin and in high-molecular-weight/total adiponectin ratio were associated with decreases in glucose tolerance index of 0.1%/min (P = 0.020) and 0.8%/min (P = 0.013), respectively. Increases in high-molecular-weight/total adiponectin ratio were related to decreases in acute C-peptide secretion of 54.6% (P = 0.020). Among people with Type 1 diabetes, 2-year increases in total adiponectin were associated with 2-year decreases in acute C-peptide secretion of 56.2% (P = 0.035). CONCLUSIONS: Increases in adiponectin concentrations in the first 2 years after diagnosis were related to a worsening of acute insulin secretion and glucose tolerance index in Type 1 and Type 2 diabetes. (Clinical Trials Registry no.: NCT01055093).

Effects of Long-Term Exercise Interventions on Glycaemic Control in Type 1 and Type 2 Diabetes: a Systematic Review.

Aim: Physical activity is one of the cornerstones in the prevention and management of diabetes mellitus, but the effects of different training forms on metabolic control still remain unclear. The aims of this review are to summarize the recommendations of 5 selected diabetes associations and to systematically review the effects of long-term supervised exercise interventions without calorie-restriction on glycemic control in people with type 1 and 2 diabetes focusing on resistance, endurance and combined training consisting of both endurance and resistance training. Methods: Literature searches were performed using MEDLINE for articles published between January 1, 2000 and March 17, 2015. Of 76 articles retrieved, 15 randomized and controlled studies met the inclusion criteria and allowed for examining the effect of exercise training in type 1 and 2 diabetes. Results: Diabetes associations recommend volume-focused exercise in their guidelines. In our analysis, all 3 training forms have the potential to improve the glycemic control, as assessed by HbA1c (absolute changes in HbA1c ranging from -0.1% to -1.1% (-1.1 to -12 mmol/mol) in resistance training, from -0.2% to -1.6% (-2.2 to -17.5 mmol/mol) in endurance training and from +0.1% to -1.5% (+1.1 to -16.4 mmol/mol) in combined training, respectively). Conclusions: There is evidence that combined exercise training may improve glycemic control to a greater extent than single forms of exercise, especially under moderate-intensive training conditions with equal training durations. In addition, intensity of training appears to be an important determinant of the degree of metabolic improvement. Nonetheless, it is still unknown to what extent exercise effects glycemic homeostasis.

HbA1c levels in non-diabetic older adults - No J-shaped associations with primary cardiovascular events, cardiovascular and all-cause mortality after adjustment for confounders in a meta-analysis of individual participant data from six cohort studies.

BACKGROUND: To determine the shape of the associations of HbA1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations. METHODS: The associations of HbA1c with all-cause mortality, cardiovascular mortality and primary cardiovascular events (myocardial infarction or stroke) were assessed in non-diabetic subjects ≥50 years from six population-based cohort studies from Europe and the USA and meta-analyzed. Very low, low, intermediate and increased HbA1c were defined as <5.0, 5.0 to <5.5, 5.5 to <6.0 and 6.0 to <6.5% (equals <31, 31 to <37, 37 to <42 and 42 to <48 mmol/mol), respectively, and low HbA1c was used as reference in Cox proportional hazards models. RESULTS: Overall, 6,769 of 28,681 study participants died during a mean follow-up of 10.7 years, of whom 2,648 died of cardiovascular disease. Furthermore, 2,493 experienced a primary cardiovascular event. A linear association with primary cardiovascular events was observed. Adjustment for cardiovascular risk factors explained about 50% of the excess risk and attenuated hazard ratios (95 confidence interval) for increased HbA1c to 1.14 (1.03-1.27), 1.17 (1.00-1.37) and 1.19 (1.04-1.37) for all-cause mortality, cardiovascular mortality and cardiovascular events, respectively. The six cohorts yielded inconsistent results for the association of very low HbA1c levels with the mortality outcomes and the pooled effect estimates were not statistically significant. In one cohort with a pronounced J-shaped association of HbA1c levels with all-cause and cardiovascular mortality (NHANES), the following confounders of the association of very low HbA1c levels with mortality outcomes were identified: race/ethnicity; alcohol consumption; BMI; as well as biomarkers of iron deficiency anemia and liver function. Associations for very low HbA1c levels lost statistical significance in this cohort after adjusting for these confounders. CONCLUSIONS: A linear association of HbA1c levels with primary cardiovascular events was observed. For cardiovascular and all-cause mortality, the observed small effect sizes at both the lower and upper end of HbA1c distribution do not support the notion of a J-shaped association of HbA1c levels because a certain degree of residual confounding needs to be considered in the interpretation of the results.

Low serum omentin levels in the elderly population with Type 2 diabetes and polyneuropathy.

AIMS: To investigate the hypothesis that high serum levels of omentin, an adipokine with anti-inflammatory, insulin-sensitizing and cardioprotective properties, may be related to a lower risk of diabetic sensorimotor polyneuropathy. METHODS: The association between serum omentin level and polyneuropathy was estimated in people aged 61-82 years with Type 2 diabetes (47 with and 168 without polyneuropathy) from the population-based KORA F4 study. The presence of clinical diabetic sensorimotor polyneuropathy was defined as bilateral impairment of foot vibration perception and/or foot pressure sensation. Omentin levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum omentin level was inversely associated with polyneuropathy after adjustment for age, sex, height, waist circumference, hypertension, total cholesterol, smoking, alcohol intake and physical activity [odds ratio 0.45 (95% CI 0.21-0.98); P = 0.043]. Although omentin was positively correlated with adiponectin (r = 0.55, P < 0.0001) and inversely with tumour necrosis factor-α (r = -0.30, P = 0.019), additional adjustment for adiponectin and tumour necrosis factor-α had little impact on the association. CONCLUSIONS: Serum levels of omentin are reduced in people with Type 2 diabetes and diabetic sensorimotor polyneuropathy, independently of established risk factors of polyneuropathy. This association is only partially explained by biomarkers of subclinical inflammation.

A clinical screening score for diabetic polyneuropathy: KORA F4 and AusDiab studies.

AIMS: Since screening for distal sensorimotor polyneuropathy (DSPN) in individuals with diabetes is being underused, our aim was to develop a clinical screening score for identifying individuals with DSPN. METHODS: All participants with type 2 diabetes and aged 61-82 years from the German population-based KORA F4 Study (n=177) and the Australian population-based AusDiab Study (n=244) were combined into one study sample. Risk indicators of DSPN were identified and entered into a stepwise model-selection procedure, constructing two consecutive scores with increasing complexity (a base and clinical model). RESULTS: The prevalence of DSPN was 18.2% (95% confidence interval (CI): 14.7-22.3). The base model comprised age (years), height (cm), weight (kg), pain or discomfort in the feet and/or legs (yes/no), and duration of diabetes (years), yielding an area under the receiver operating characteristics curve (AUC) of 0.80 (95% CI: 0.76-0.85). The clinical model additionally included diastolic blood pressure (mmHg) and serum creatinine levels (mmol/l). The AUC increased only marginally to 0.82 (0.77-0.87) (p for AUC comparison=0.188). The internal validation of the scores produced similar AUCs. CONCLUSIONS: The screening scores developed in this study are a simple tool to differentiate between a high and low likelihood of having DSPN among individuals with type 2 diabetes.

Diabetes in Europe: an update.

Diabetes is among the leading causes of death in the IDF Europe Region (EUR), continues to increase in prevalence with diabetic macro- and microvascular complications resulting in increased disability and enormous healthcare costs. In 2013, the number of people with diabetes is estimated to be 56 million in EUR with an overall estimated prevalence of 8.5%. However, estimates of diabetes prevalence in 2013 vary widely in the 56 diverse countries in EUR from 2.4% in Moldova to 14.9% in Turkey. Trends in diabetes prevalence also vary between countries with stable prevalence since 2002 for many countries but a doubling of diabetes prevalence in Turkey. For 2035, a further increase of nearly 10 million people with diabetes is projected for the EUR. Prevalence of type 1 has also increased over the past 20 years in EUR and there was estimated to be 129,350 cases in children aged 0-14 years in 2013. Registries provide valid information on incidence of type 1 diabetes with more complete data available for children than for adults. There are large differences in distribution of risk factors for diabetes at the population level in EUR. Modifiable risk factors such as obesity, physical inactivity, smoking behaviour (including secondhand smoking), environmental pollutants, psychosocial factors and socioeconomic deprivation could be tackled to reduce the incidence of type 2 diabetes in Europe. In addition, diabetes management is a major challenge to health services in the European countries. Improved networking practices of health professionals and other stakeholders in combination with empowerment of people with diabetes and continuous quality monitoring need to be further developed in Europe.

Anti-inflammatory cytokines and risk of type 2 diabetes.

Proinflammatory processes have been investigated extensively in the development of type 2 diabetes, but our knowledge on anti-inflammatory proteins is rather limited. This article summarizes studies that investigated associations between circulating levels of anti-inflammatory cytokines and incident type 2 diabetes preferably in prospective epidemiological studies. Adiponectin is the only known anti-inflammatory protein whose circulating levels are decreased before type 2 diabetes. In contrast, concentrations of interleukin-1 receptor antagonist (IL-1RA), transforming growth factor-ß1 (TGF-ß1) and growth differentiation factor-15 (GDF-15) are increased and indicate the presence of a compensatory, but eventually futile, counter-regulation of proinflammatory stimuli. Importantly, a proof-of-principle study using recombinant IL-1RA to improve metabolic control in patients with type 2 diabetes demonstrated that a more pronounced upregulation of this protein than that found in the natural course of diabetes development may have clinical relevance. Other interesting candidates like omentin (which shows similar associations with metabolic parameters as adiponectin), interleukin-10 (IL-10) and secreted frizzled-related protein-5 (Sfrp5) are currently less well studied with sometimes conflicting results regarding their association with type 2 diabetes. Thus, further research is required to better understand the causal role of proinflammatory cytokines, hypoadiponectinaemia and the upregulation of anti-inflammatory proteins before the onset of type 2 diabetes.

Diabetes incidence does not differ between subjects with and without high depressive symptoms--5-year follow-up results of the Heinz Nixdorf Recall Study.

AIMS: Cross-sectional studies have consistently reported evidence for an association between diabetes and depressive disorders. However, only limited prospective studies have examined this association, reporting conflicting results. In a population-based cohort study, we compared cumulative incidences of diabetes between participants with and without high depressive symptoms. METHOD: We analysed the 5-year follow-up data from the German Heinz Nixdorf Recall study of 3547 participants without diabetes at baseline [mean age 58.8 (sd 7.6) years, 47.5% male]. Depressive symptoms were defined using the Centre for Epidemiologic Studies Depression scale (cut point ≥ 17). Diabetes (diagnosed or previously undetected) was identified by self-reported physician-diagnosed diabetes, medication and high blood glucose levels. We estimated 5-year cumulative incidences with 95% confidence intervals and fitted multiple logistic regression models to calculate the odds ratios, adjusted for age, sex, physical activity, smoking, living with or without partner, and educational level. RESULTS: The cumulative incidence of diabetes was 9.2% (95% CI 6.3-12.8) in participants with high depressive symptoms at baseline and 9.0% (95% CI 8.0-10.0) in participants without these symptoms. The age- and sex-adjusted odds ratio of diabetes in participants with depressive symptoms compared with those without was 1.13 [95% CI 0.77-1.68; fully adjusted 1.11 (95% CI 0.74-1.65)]. These results did not substantially change in several additional sensitivity analyses. CONCLUSION: Our study did not show a significantly increased risk of developing diabetes in individuals with high depressive symptoms compared with those without high depressive symptoms during a 5-year follow-up period.

Myeloperoxidase is associated with incident coronary heart disease independently of traditional risk factors: results from the MONICA/KORA Augsburg study.

AIMS: Oxidative stress plays a critical role in the initiation and progression of atherosclerosis. Myeloperoxidase (MPO) is a marker of oxidative stress. We prospectively investigated whether an increased serum concentration of MPO is associated with an increased risk of incident coronary heart disease (CHD). METHODS: We conducted a population-based case-cohort study in middle-aged, healthy men and women within the MONICA/KORA Augsburg studies. Serum levels of MPO were measured in 333 subjects with (cases) and 1727 without (noncases) incident CHD. Mean follow-up time was 10.8 ± 4.6 years. RESULTS: Baseline concentrations of MPO were higher in cases compared with noncases (P ≤ 0.001 in men; P=0.131 in women). After adjustment for major cardiovascular risk factors, the hazard ratio (HR) with 95% confidence interval (CI) comparing the top with the two lower tertiles was 1.70 (95% CI, 1.25-2.30). After additional adjustment for markers of inflammation and endothelial dysfunction, the association was attenuated (HR 1.50; 95% CI, 1.08-2.09). There were no significant interactions of MPO with sex or increased weight on CHD risk. CONCLUSIONS: Elevated concentrations of the oxidative stress marker MPO were independently associated with increased risk of incident CHD. This finding deserves detailed evaluation in further studies.

Impact of weight and weight change on normalization of prediabetes and on persistence of normal glucose tolerance in an older population: the KORA S4/F4 study.

BACKGROUND AND AIMS: In a population-based cohort study with older subjects and without specific interventions, we investigated the impact of body mass index (BMI) and BMI change (as well as waist circumference and change of waist circumference) on reversion from prediabetes to normal glucose tolerance (NGT) and on long-term persistence of NGT. MATERIALS AND METHODS: Oral glucose tolerance tests were conducted at baseline and at follow-up in a cohort study in Southern Germany (KORA S4/F4; 1223 subjects without diabetes aged 55-74 years at baseline in 1999-2001; 887 subjects (73%), of whom 436 had prediabetes at baseline, participated in the follow-up 7 years later). RESULTS: BMI reduction, but not initial BMI, predicted reversion from prediabetes to NGT. The odds ratio (OR) for returning to NGT was 1.43 (95% CI: 1.18-1.73) for a BMI decrease of 1 kg m(-2), after adjustment for age, sex, baseline glucose values and lifestyle factors. Initial BMI had no effect on reversion to NGT (OR=0.98, 95% CI: 0.91-1.06, per kg m(-2)). Persistence of NGT was associated with baseline BMI (OR=0.94, 95% CI: 0.88-0.998) and BMI reduction (OR=1.16, 95% CI: 1.02-1.33, per decrease by 1 kg m(-2)). For waist circumference and change of waist circumference similar results were obtained. CONCLUSION: In older adults, weight loss strongly increased the chances of returning from prediabetes to NGT irrespective of initial BMI. Long-term persistence of NGT depended both on initial BMI and on BMI change.

Effect of weight loss on inflammation in patients with mild obstructive sleep apnea.

BACKGROUND AND AIMS: Inflammation may be one mediating mechanism for cardiovascular diseases in obstructive sleep apnea (OSA). However, little is known about subclinical inflammation or the effect of lifestyle intervention on inflammation in early stages of OSA. The aim of this substudy of an existing randomized controlled trial, with post hoc analyses, was to determine the impact of lifestyle changes aimed at weight reduction on inflammatory biomarkers in overweight patients with mild OSA. METHODS AND RESULTS: Patients were randomized to supervised intensive lifestyle intervention group (N=28) or to control group (N=31), which received routine lifestyle advices. Circulating concentrations of pro- and anti-inflammatory mediators were measured before and after the 1-year intervention. The concentrations of two pro-inflammatory mediators, high-sensitivity C-reactive protein (hsCRP) and interleukin (IL)-6, decreased significantly in both groups. Although the changes in inflammatory biomarkers favored the supervised lifestyle intervention, the only significant reduction observed between the groups was for the anti-inflammatory IL-1 receptor antagonist (IL-1RA). The change in hsCRP was associated with apnea-hypopnea index, and improving night-time oxygen saturation was related to tumor necrosis factor alpha. IL-1RA and IL-6 were associated with insulin metabolism. CONCLUSION: Weight loss resulted in reductions in concentrations of some pro- and anti-inflammatory mediators in overweight patients with mild OSA, overall favoring the supervised lifestyle intervention. These findings suggest that more intensive treatment of obesity in OSA patients might be well-justified.

Sleep disturbances and depressed mood: a harmful combination associated with increased leptin levels in women with normal weight.

Leptin, involved in energy regulation and contributor to cardiovascular disease, has been implicated to play a role in depression and sleep disturbances, two closely intertwined conditions. Previous results investigating leptin level alterations either in sleep disorders or in depression have been inconsistent. We investigate the association between leptin levels and the different combinations of depressed mood and sleep disturbances in 1369 subjects (706 men, 663 women), derived from the population-based MONIKA/KORA study. As leptin regulation is known to differ by sex and weight, analyses were performed in normal weight and overweight men and women separately. We found a highly significant association between leptin levels and the combination of depressed mood and sleep disturbances in normal-weight women (BMI ≤ 25) (p<0.01). No associations were found in men and in overweight women. Our results suggest that leptin regulation in depressed mood and sleep disturbances very much depend on sex and weight.

Association between social isolation and inflammatory markers in depressed and non-depressed individuals: results from the MONICA/KORA study.

INTRODUCTION: Depressed individuals not only suffer from chronic low grade inflammation, but also exhibit an inflammatory hyper-responsiveness to acute stress. We investigate whether chronic stress also induces an exaggerated inflammatory response in individuals with increased depression features. As model for chronic stress, social isolation was chosen. METHODS: Interleukin (IL)-6 and hs-CRP levels were assessed in 1547 subjects (847 men and 700 women), derived from the population-based MONICA/KORA study. Standardized questionnaires were used to assess depressed mood (depression and exhaustion subscale) and social isolation (social network index). The relationship between the two inflammatory markers, social isolation and depressed mood was examined taking into account interactions social isolation × depressed mood using multivariable linear regression models, adjusted for age, BMI, smoking, alcohol, and physical activity. Analyses were performed in men and women separately. RESULTS: We observed a significant interaction between depressed mood and social isolation regarding IL-6 and hs-CRP, respectively in men (p-value=0.02 for IL-6 and <0.01 for hs-CRP), evidencing a substantial synergistic effect of social isolation, and depressed mood on inflammatory responses. Furthermore, depressed and socially isolated men had highly significantly elevated IL-6 levels (geometric mean: 3.76 vs. 1.92 pg/ml, p-value <0.01) and heightened hs-CRP levels (geometric mean: 2.01 vs. 1.39 mg/l, p=0.08) in comparison with non-depressed and socially integrated men. In women, no significant associations were seen. CONCLUSION: The interaction of depressed mood and social isolation elicits a substantial synergistic impact on inflammatory markers in men, but not in depressed women.