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Harald Jörn Schneider, Bernhard Saller, Jens Klotsche, Winfried März, Wolfgang Erwa, Hans-Ullrich Wittchen and Günter Karl Stalla

Objective: Insulin-like growth factor-I (IGF-I) has been suggested to be a prognostic marker for the development of cancer and, more recently, cardiovascular disease. These diseases are closely linked to obesity, but reports of the association of IGF-I with measures of obesity are divergent. In this study, we assessed the association of age-dependent IGF-I standard deviation scores with body mass index (BMI) and intra-abdominal fat accumulation in a large population.

Design: A cross-sectional, epidemiological study.

Methods: IGF-I levels were measured with an automated chemiluminescence assay system in 6282 patients from the DETECT study. Weight, height, and waist and hip circumference were measured according to the written instructions. Standard deviation scores (SDS), correcting IGF-I levels for age, were calculated and were used for further analyses.

Results: An inverse U-shaped association of IGF-I SDS with BMI, waist circumference, and the ratio of waist circumference to height was found. BMI was positively associated with IGF-I SDS in normal weight subjects, and negatively associated in obese subjects. The highest mean IGF-I SDS were seen at a BMI of 22.5–25 kg/m2 in men (+0.08), and at a BMI of 27.5–30 kg/m2 in women (+0.21). Multiple linear regression models, controlling for different diseases, medications and risk conditions, revealed a significant negative association of BMI with IGF-I SDS. BMI contributed most to the additional explained variance to the other health conditions.

Conclusions: IGF-I standard deviation scores are decreased in obesity and underweight subjects. These interactions should be taken into account when analyzing the association of IGF-I with diseases and risk conditions.

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Caroline Sievers, Jens Klotsche, Lars Pieper, Harald J Schneider, Winfried März, Hans Ulrich Wittchen, Günter K Stalla and Christos Mantzoros

Objective

Although associations between testosterone and cardiovascular (CV) morbidity in women have been proposed, no large prospective study has evaluated potential associations between testosterone and mortality in women. The objective was to determine whether baseline testosterone levels in women are associated with future overall or CV morbidity and mortality.

Design

Prospective cohort study with a 4.5-year follow-up period.

Methods

From a representative sample of German primary care practices, 2914 female patients between 18 and 75 years were analyzed for the main outcome measures: CV risk factors, CV diseases, and all-cause mortality.

Results

At baseline, the study population was aged 57.96±14.37 years with a mean body mass index of 26.71±5.17 kg/m2. No predictive value of total testosterone for incident CV risk factors or CV diseases was observed in logistic regressions. Patients with total testosterone levels in the lowest quintile Q1, however, had a higher risk to die of any cause or to develop a CV event within the follow-up period compared to patients in the collapsed quintiles Q2–Q5 in crude and adjusted Cox regression models (all-cause mortality: Q2–Q5 versus Q1: crude hazard ratios (HR) 0.49, 95% confidence interval (CI) 0.33–0.74; adjusted HR 0.62, 95% CI 0.42–0.939; CV events: Q2–Q5 versus Q1: crude HR 0.54, 95% CI 0.38–0.77; adjusted HR 0.68, 95% CI 0.48–0.97). Kaplan–Meier curves revealed similar data.

Conclusions

Low baseline testosterone in women is associated with increased all-cause mortality and incident CV events independent of traditional risk factors.

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Harald Jörn Schneider, Nele Friedrich, Jens Klotsche, Sabine Schipf, Matthias Nauck, Henry Völzke, Caroline Sievers, Lars Pieper, Winfried März, Hans-Ulrich Wittchen, Günter Karl Stalla and Henri Wallaschofski

Objective

IGF1 is associated with metabolic parameters and involved in glucose metabolism. Low-IGF1 has been implicated in the etiology of glucose intolerance and subjects with pathological causes of either low- or high-IGF1 are at risk of diabetes. We hypothesized that both low- and high-IGF1 levels increase the risk of diabetes and aimed to assess the role of IGF1 in the risk of developing diabetes in a large prospective study.

Design

An analysis of two prospective cohort studies, the DETECT study and SHIP.

Methods

We measured IGF1 levels in 7777 nondiabetic subjects and assessed incident diabetes mellitus during follow-up.

Results

There were 464 cases of incident diabetes during 32 229 person-years (time of follow-up in the DETECT study and SHIP: 4.5 and 5 years respectively). There was no heterogeneity between both studies (P>0.4). The hazard ratios (HRs) of incident diabetes in subjects with IGF1 levels below the 10th or above the 90th age- and sex-specific percentile, compared to subjects with intermediate IGF1 levels, were 1.44 (95% confidence interval (CI) 1.07–1.94) and 1.55 (95% CI 1.06–2.06) respectively, after multiple adjustment. After further adjustment for metabolic parameters, the HR for low-IGF1 became insignificant. Analysis of IGF1 quintiles revealed a U-shaped association of IGF1 with risk of diabetes. Results remained similar after exclusion of patients with onset of new diabetes within 1 year or with borderline glucose or HbA1c levels at baseline.

Conclusions

Subjects with low- or high-IGF1 level are at increased risk of developing diabetes.

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Sarah M Leistner, Jens Klotsche, Christina Dimopoulou, Anastasia P Athanasoulia, Josefine Roemmler-Zehrer, Lars Pieper, Jochen Schopohl, Hans-Ulrich Wittchen, Günter K Stalla, Stephany Fulda and Caroline Sievers

Objectives

Several studies reported decreased quality of life (QoL) and sleep as well as increased rates of depression for patients with pituitary adenomas. Our aim was to explore to what extent differences in depression and sleep quality contribute to differences in QoL between patients with pituitary adenomas and controls.

Design

A cross-sectional case–control study.

Setting

Endocrine Outpatient Unit of the Max Planck Institute of Psychiatry, Munich, Department of Internal Medicine, Ludwig-Maximilians-University, Munich, and the Institute of Clinical Psychology and Psychotherapy, Technical University, Dresden.

Participants

Patients with pituitary adenomas (n=247) and controls (from the DETECT cohort, a large epidemiological study in primary care patients) matched individually by age and gender (n=757).

Measurements

Sleep quality was assessed with the Pittsburgh Sleep Quality Index (PSQI) and QoL was measured by the generic EQ-5D and calculated by the time trade-off- and VAS-method. Depression was categorized as ‘no depression’, ‘subclinical depression’, and ‘clinical depression’ according to the Beck Depressions Inventory for patients and the Depression Screening Questionnaire for control subjects.

Statistical analyses

General linear and generalized, logistic mixed models as well as proportional odds mixed models were calculated for analyzing differences in baseline characteristics and in different subgroups.

Results

Patients with pituitary adenomas showed decreased QoL (VAS index: 0.73±0.19) and sleep (PSQI score: 6.75±4.17) as well as increased rates of depression (subclinical or clinical depression: 41.4%) compared with their matched control subjects (VAS index: 0.79±0.18, PSQI score: 5.66±4.31, subclinical or clinical depression: 25.9%). We have shown that a substantial proportion of the reduced QoL (48% respectively 65%) was due to the incidence of depression and reduced sleep quality.

Conclusions

These findings emphasize the importance of diagnosing depressive symptoms and sleep disturbances in patients with pituitary disease, with the ultimate goal to improve QoL in patients with pituitary adenomas.

Free access

Harald Jörn Schneider, Jens Klotsche, Bernhard Saller, Steffen Böhler, Caroline Sievers, David Pittrow, Günther Ruf, Winfried März, Wolfang Erwa, Andreas M Zeiher, Sigmund Silber, Hendrik Lehnert, Hans-Ullrich Wittchen and Günter Karl Stalla

Objective

We aimed at investigating the association of age-dependent IGF-I SDS with diabetes, dyslipidemia, hypertension, and heart diseases, in a large patient sample.

Background

IGF-I has been suggested to be associated with several diseases and a prognostic marker for the development of cardiovascular diseases and risk factors. The findings, though, have been inconsistent possibly due to the methodological factors.

Methods

We studied 6773 consecutive primary care patients, aged 18+ years, in a cross-sectional, epidemiological study in primary care, Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment study. All patients underwent a standardized clinical diagnostic and laboratory assessment. IGF-I levels were measured with an automated chemiluminescence assay system. We calculated the odds ratios (OR) for diseases in quintiles of IGF-I, and additionally analyzed the association of age-dependent IGF-I SDS with these conditions.

Results

After multiple adjustments for confounders, we found increased ORs for coronary artery disease in patients with high IGF-I. Women, but not men, with low IGF-I also showed increased ORs for coronary artery disease. Dyslipidemia was positively associated with IGF-I. Type 2 diabetes showed a curvilinear association with IGF-I SDS.

Conclusions

The findings suggest the existence of multiple and complex interactions between IGF-I and several health conditions. The complex nature of disease- and subgroup-specific associations along with the methodological factors can be held responsible for divergent findings in previous studies.