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1.
J Psychiatr Res ; 170: 302-306, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38185076

ABSTRACT

Psychotic disorders have a strong negative impact on multiple aspects of daily life, including people's financial situation. This exploratory study examines the level of financial dissatisfaction and its correlates in a large cohort of people with psychotic disorders. Data from the first assessments of people with psychotic disorders (n = 5271) who were included in the Pharmacotherapy Monitoring and Outcome Survey (PHAMOUS; 2006-2020), which is conducted in the northern Netherlands, were used. The Manchester Short Assessment of Quality of Life (MANSA) was used to measure financial dissatisfaction. In addition, sociodemographic and psychiatric characteristics, substance use and global and social functioning were assessed. One-fifth to one-third of people with psychotic disorders report financial dissatisfaction, fluctuating over the year in which they were assessed. These proportions are considerably higher than in the general population. Cannabis and other substance use were associated with higher levels of financial dissatisfaction (small to medium effect). The other significant associations showed (very) small effect sizes. Therefore, we conclude that financial dissatisfaction in people with psychotic disorders appears to be relatively independent of other demographic and psychiatric characteristics, and global and social functioning. These findings are an important first step for increasing knowledge on financial dissatisfaction among people with psychotic disorders. The findings can also contribute to raising awareness about the topic for healthcare professionals working in this field.


Subject(s)
Psychotic Disorders , Substance-Related Disorders , Humans , Prevalence , Quality of Life , Psychotic Disorders/drug therapy , Emotions , Substance-Related Disorders/epidemiology
2.
Platelets ; 32(4): 516-523, 2021 May 19.
Article in English | MEDLINE | ID: mdl-32522065

ABSTRACT

Light transmission aggregometry (LTA) is considered the gold standard method for evaluation of platelet function. However, there are a lot of variation in protocols (pre-analytical procedures and agonist concentrations) and results. The aim of our study was to establish a national LTA protocol, to investigate the effect of standardization and to define national reference values for LTA. The SSC guideline was used as base for a national procedure. Almost all recommendations of the SSC were followed e.g. no adjustment of PRP, citrate concentration of 109 mM, 21 needle gauge, fasting, resting time for whole blood and PRP, centrifugation time, speed and agonists concentrations. LTA of healthy volunteers was measured in a total of 16 hospitals with 5 hospitals before and after standardization. Results of more than 120 healthy volunteers (maximum aggregation %) were collected, with participating laboratories using 4 different analyzers with different reagents. Use of low agonist concentrations showed high variation before and after standardization, with the exception of collagen. For most high agonist concentrations (ADP, collagen, ristocetin, epinephrine and arachidonic acid) variability in healthy subjects decreased after standardization. We can conclude that a standardized Dutch protocol for LTA, based on the SSC guideline, does not result in smaller variability in healthy volunteers for all agonist concentrations.


Subject(s)
Phototherapy/methods , Platelet Count/methods , Platelet Function Tests/methods , Healthy Volunteers , Humans , Netherlands
3.
Cogn Process ; 19(1): 95-106, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29185169

ABSTRACT

Based on the Empathizing-Systemizing (E-S) theory, it was hypothesized that the underrepresentation of female students in the physical sciences and the underrepresentation of males in the social sciences relates to differences in E-S cognitive style between the sexes. This hypothesis was tested in 115 physical science students and 155 social science students from a university in the Netherlands. The students completed visuospatial tests and the systemizing quotient-revised (SQ-R) as measures for systemizing, and a Cartoon Prediction test and the empathy quotient (EQ) as measures for empathizing. Independent of sex, the physical science students scored significantly lower than social science students on EQ (with large effect size) and 'brain type' that represents the standardized difference score between EQ and SQ-R (with large effect size). Physical science students, furthermore, scored significantly higher on the Cartoon Prediction task and one of the visuospatial tasks; however, these effects were only small of size. Unlike the scores on the SQ-R and the performance tests, the 'brain type' score of the EQ and SQ-R questionnaires was a good predictor of entry into social or physical sciences. Interestingly, the typical sex differences in more empathizing and less systemizing in females compared to males were only small for EQ and 'brain type', and absent for the SQ-R and the performance tests. This study only partially confirms the E-S theory, because typical sex differences were only minor in this selective sample and only the self-report measures predicted academic area in the absence of a role for sex.


Subject(s)
Cognition/physiology , Empathy/physiology , Personality/physiology , Sex Characteristics , Adolescent , Adult , Female , Humans , Male , Natural Science Disciplines , Neuropsychological Tests , Photic Stimulation , Self Report , Social Sciences , Space Perception/physiology , Students , Thinking/physiology , Visual Perception/physiology , Young Adult
5.
Anaesthesia ; 72(3): 359-369, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27987229

ABSTRACT

Biomarkers of neurological injury can potentially predict postoperative cognitive dysfunction. We aimed to identify whether classical neuronal damage-specific biomarkers, including brain fatty acid-binding protein, neuron-specific enolase and S100 calcium-binding protein ß, as well as plasma-free haemoglobin concentration as a measure of haemolysis, could be used to predict the risk of long-term cognitive decline after coronary artery bypass grafting with or without cardiopulmonary bypass. We assessed cognitive function using the CogState brief computerised cognitive test battery at 3 months and at 15 months after surgery. Blood samples were obtained pre-operatively, after sternal closure, and at 6 h and 24 h postoperatively. We found signs of cognitive decline at 3 months in 15 of 57 patients (26%), and in 13 of 48 patients (27%) at 15 months. Brain fatty acid-binding protein was already significantly higher before surgery in patients with postoperative cognitive dysfunction at 15 months, with pre-operative plasma levels of 22.8 (8.3-33.0 [0-44.6]) pg.ml-1 compared with 9.7 (3.9-17.3 [0-49.0]) pg.ml-1 in patients without cognitive dysfunction. This biomarker remained significantly higher in patients with cognitive decline throughout the entire postoperative period. At 3 months after surgery, high levels of plasma-free haemoglobin at sternal closure were associated with a negative influence on cognitive performance, as were high baseline scores on neuropsychological tests, whereas a higher level of education proved to beneficially influence cognitive outcome. We found that postoperative cognitive dysfunction at 3 months was associated with cognitive decline at 15 months after surgery, and served as a valuable prognostic factor for declines in individual cognitive performance one year later. Classical neuronal injury-related biomarkers were of no clear prognostic value.


Subject(s)
Biomarkers/blood , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , Coronary Artery Bypass/adverse effects , Aged , Cardiopulmonary Bypass/adverse effects , Coronary Artery Bypass/methods , Educational Status , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neuropsychological Tests , Postoperative Complications/diagnosis , Postoperative Complications/etiology , Postoperative Period , Prognosis , Risk Factors
6.
J Neural Transm (Vienna) ; 124(Suppl 1): 27-38, 2017 02.
Article in English | MEDLINE | ID: mdl-26471801

ABSTRACT

Spontaneous eye blink rate is modulated by task demands and internal state, and is demonstrated to reflect central dopamine activity. Also, spontaneous eye blinks are strategically timed around salient stimuli. This study investigates whether children with attention deficit hyperactivity disorder (ADHD) show reduced blink rates, blink modulation and blink timing, and whether this is influenced by stimulant medication. The electrooculogram was measured in 18 typically developing children, 16 children with ADHD off methylphenidate (Mph), and 16 children with ADHD on Mph during a rest period and during performance of a 60-min visual selective attention task. Blink rate and timing was extracted from the electrooculogram. No evidence was found for aberrant blink rate or blink modulation in children with ADHD off Mph. All groups increased blink rates from rest to task, and no group differences were found in blink rate during rest and task, or in the modulation of blink rate from rest to task. Time-on task resulted in a similar increase in blink rates in all three groups. Stimulant medication appeared not to influence blink rate and blink modulation, except that in the ADHD off Mph group the blink rate was enhanced only under conditions with performance feedback. All groups inhibited blinks before stimulus presentation and strategically timed their blinks after the stimulus. Children with ADHD off Mph showed reduced blink inhibition before the stimulus; however, given the low incidence (<1 % of the trials) and long latency this is not likely to impair their visual intake.


Subject(s)
Attention Deficit Disorder with Hyperactivity/drug therapy , Attention Deficit Disorder with Hyperactivity/physiopathology , Blinking/drug effects , Central Nervous System Stimulants/therapeutic use , Methylphenidate/therapeutic use , Analysis of Variance , Attention , Blinking/physiology , Child , Electrooculography , Feedback, Psychological , Female , Humans , Male , Neuropsychological Tests , Reaction Time , Rest , Reward , Time Factors , Visual Perception
7.
Neuropsychol Rehabil ; 26(2): 216-35, 2016.
Article in English | MEDLINE | ID: mdl-25693688

ABSTRACT

Impairments in executive functions (EF) are the core cognitive impairment in patients with Parkinson's disease (PD). Surprisingly, cognitive rehabilitation is not routinely offered to patients with PD. However, in patients with acquired brain injury (ABI), cognitive rehabilitation, in particular strategic executive training, is common practice and has been shown to be effective. In this study, we determined whether PD patients have different needs and aims with regard to strategic executive training than ABI patients, and whether possible differences might be a reason for not offering this kind of cognitive rehabilitation programme to patients with PD. Patients' needs and aims were operationalised by individually set goals, which were classified into domains of EF and daily life. In addition, patients with PD and ABI were compared on their cognitive, in particular EF, profile. Overall, PD patients' goals and cognitive profile were similar to those of patients with ABI. Therefore, based on the findings of this study, there is no reason to assume that strategic executive training cannot be part of standard therapy in PD. However, when strategic executive training is applied in clinical practice, disease-specific characteristics need to be taken into account.


Subject(s)
Cognition Disorders/rehabilitation , Cognitive Behavioral Therapy , Executive Function , Goals , Parkinson Disease/psychology , Parkinson Disease/rehabilitation , Adolescent , Adult , Aged , Brain Injuries/rehabilitation , Cognition Disorders/etiology , Female , Humans , Male , Middle Aged , Needs Assessment , Neuropsychological Tests , Parkinson Disease/complications , Reproducibility of Results , Treatment Outcome , Young Adult
9.
Anaesthesia ; 69(6): 613-22, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24750013

ABSTRACT

Coronary artery bypass surgery, performed with or without cardiopulmonary bypass, is frequently followed by postoperative cognitive decline. Near-infrared spectroscopy is commonly used to assess cerebral tissue oxygenation, especially during cardiac surgery. Recent studies have suggested an association between cerebral desaturation and postoperative cognitive dysfunction. We therefore studied cerebral oxygen desaturation, defined as area under the cerebral oxygenation curve < 40% of > 10 min.%, with respect to cognitive performance at 4 days (early) and 3 months (late) postoperatively, compared with baseline, using a computerised cognitive test battery. We included 60 patients, of mean (SD) age 62.8 (9.4) years, scheduled for elective coronary artery bypass grafting, who were randomly allocated to surgery with or without cardiopulmonary bypass. Cerebral desaturation occurred in only three patients and there was no difference in cerebral oxygenation between the two groups at any time. Among patients who received cardiopulmonary bypass, 18 (62%) had early cognitive decline, compared with 16 (53%) in the group without cardiopulmonary bypass (p = 0.50). Three months after surgery, 11 patients (39%) in the cardiopulmonary bypass group displayed cognitive dysfunction, compared with four (14%) in the non-cardiopulmonary bypass group (p = 0.03). The use of cardiopulmonary bypass was identified as an independent risk factor for the development of late cognitive dysfunction (OR 6.4 (95% CI 1.2-33.0) p = 0.027. In conclusion, although cerebral oxygen desaturation was rare in our population, postoperative cognitive decline was common in both groups, suggesting that factors other than hypoxic neuronal injury are responsible.


Subject(s)
Brain/metabolism , Cardiopulmonary Bypass , Cognition Disorders/etiology , Coronary Artery Bypass , Oxygen/metabolism , Postoperative Complications/etiology , Aged , Female , Humans , Male , Middle Aged , Oximetry , Pilot Projects
10.
Clin Exp Allergy ; 41(11): 1631-42, 2011 Nov.
Article in English | MEDLINE | ID: mdl-21801247

ABSTRACT

BACKGROUND: Peanuts are often consumed after roasting, a process that alters the three-dimensional structure of allergens and leads to Maillard modification. Such changes are likely to affect their allergenicity. OBJECTIVE: We aimed to establish the effect of thermal treatment mimicking the roasting process on the allergenicity of Ara h 1 and a mix of 2S albumins from peanut (Ara h 2/6). METHODS: Ara h 1 and Ara h 2/6 were purified from raw peanuts and heated in a dry form for 20 min at 145°C in the presence (R+g) or absence (R-g) of glucose, and soluble proteins were then extracted. Sera obtained from 12 well-characterized peanut-allergic patients were used to assess the IgE binding and degranulation capacities of the allergens. RESULTS: Extensive heating at low moisture resulted in the hydrolysis of both Ara h 1 and Ara h 2/6. However, in contrast to Ara h 2/6, soluble R+g Ara h 1 formed large aggregates. Although the IgE-binding capacity of R+g and R-g Ara h 1 was decreased 9000- and 3.6-fold, respectively, compared with native Ara h 1, their capacity to elicit mediator release was increased. Conversely, both the IgE-binding capacity and the degranulation capacity of R-g Ara h 2/6 were 600-700-fold lower compared with the native form, although the presence of glucose during heating significantly moderated these losses. CONCLUSIONS AND CLINICAL RELEVANCE: Extensive heating reduced the degranulation capacity of Ara h 2/6 but significantly increased the degranulation capacity of Ara h 1. This observation can have important ramifications for component-resolved approaches for diagnosis and demonstrates the importance of investigating the degranulation capacity in addition to IgE reactivity when assessing the effects of food processing on the allergenicity of proteins.


Subject(s)
2S Albumins, Plant/immunology , Antigens, Plant/immunology , Glycoproteins/immunology , Hot Temperature , Peanut Hypersensitivity/immunology , Plant Proteins/immunology , 2S Albumins, Plant/chemistry , Adolescent , Adult , Animals , Antigens, Plant/chemistry , Basophil Degranulation Test , Basophils/immunology , Female , Glycoproteins/chemistry , Histamine Release/immunology , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Male , Membrane Proteins , Middle Aged , Peanut Hypersensitivity/prevention & control , Plant Proteins/chemistry , Protein Denaturation/radiation effects , Rats , Young Adult
12.
Clin Exp Allergy ; 41(2): 232-42, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21121978

ABSTRACT

BACKGROUND: Allergic diseases are increasing world-wide, and according to the hygiene hypothesis may be related to a decreased exposure to environmental bacteria. Probiotic bacteria are recognized for their immunomodulating properties, and may benefit allergy patients. In vitro studies reveal immunomodulatory effects that are strain dependent. Differential immunomodulatory in vitro capacities cannot be extrapolated directly to in vivo efficacy. Thus, in vitro screening should preferably be followed by a comparative analysis of the selected immunomodulatory strains in an in vivo setting. OBJECTIVE: We selected five Lactobacillus strains on their IL-10-inducing capacity, and evaluated the immunomodulatory properties in birch-pollen-allergic subjects outside the hayfever season, with a reduction of IL-13 as the primary outcome. METHODS: A double-blind, placebo-controlled parallel study was performed in which 62 subjects with a proven birch-pollen allergy consumed one of five different probiotic yoghurts containing four Lactobacillus plantarum strains and one Lactobacillus casei strain or a placebo yoghurt. Blood samples were collected at the start and after 4 weeks. Several immune parameters were determined in serum and peripheral blood mononuclear cell cultures (PBMC) derived from these subjects. Results A decrease in birch-pollen-specific IgE was found for four probiotic strains. L. casei Shirota reduced the number of CD16(+) /CD56(+) cells in peripheral blood mononuclear cells. For strain L. plantarum CBS125632, the decrease in IgE coincided with significant decreases in IL-5 and IL-13 production by αCD3/αCD28-stimulated PBMC cultures. CONCLUSION AND CLINICAL RELEVANCE: Subjects with seasonal allergy can be used to determine immunomodulatory responses outside the pollen season within a 4-week study period. L. plantarum CBS125632 decreased several immune markers related to allergy, and may have the potential to alleviate the severity of seasonal allergy symptoms.


Subject(s)
Allergens/immunology , Betula/immunology , Lactobacillus plantarum/immunology , Pollen/immunology , Rhinitis, Allergic, Seasonal/immunology , Adolescent , Adult , Allergens/isolation & purification , Female , Humans , Interleukin-10/biosynthesis , Interleukin-10/immunology , Lactobacillus plantarum/isolation & purification , Male , Middle Aged , Young Adult
13.
Thorax ; 66(2): 101-7, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21047865

ABSTRACT

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is associated with a higher prevalence of antinuclear autoantibodies (ANAs). However, a significant subgroup of patients is ANA negative. It remains to be determined which patient groups carry autoantibodies. METHODS: The association of smoking behaviour, disease status, gender, age and body mass index (BMI) with the presence of autoantibodies in the serum was determined in 124 patients with COPD and 108 non-COPD control subjects. In addition, the role of B cells in autoantibody generation in COPD was investigated by sequencing the antibody repertoire of B cells in the lungs of patients with COPD and of ex-smoking and never-smoking control subjects. RESULTS: Patients with COPD had a significantly higher risk of being serum positive for ANAs (OR 3.12, 95% CI 1.68 to 5.76, p<0.001). ANAs were not significantly associated with age, smoking status, gender or pack-years of smoking. Within the COPD population, subjects with BMI <22 kg/m2 had a significantly higher risk of ANAs (OR 4.93, 95% CI 1.50 to 16.50, p=0.009) than those with normal or high BMI. The antibody repertoire of B cells in the lungs of patients with COPD had a high frequency of positively charged CDR3 residues, a feature which is associated with self-reactive antibodies. CONCLUSION: The results show that COPD is a heterogeneous disease with respect to the prevalence of ANAs. ANAs are primarily associated with the presence of COPD and with low BMI, but not with smoking and forced expiratory volume in 1 s.


Subject(s)
Antibodies, Antinuclear/blood , Body Mass Index , Pulmonary Disease, Chronic Obstructive/immunology , Smoking/immunology , Age Factors , Aged , Antibodies, Antineutrophil Cytoplasmic/blood , B-Lymphocytes/immunology , Case-Control Studies , Female , Forced Expiratory Volume/immunology , Humans , Immunoglobulin Heavy Chains/immunology , Lung/immunology , Male , Middle Aged , Pulmonary Disease, Chronic Obstructive/physiopathology , Sex Factors , Vital Capacity/immunology
14.
Diabetes Obes Metab ; 10(12): 1195-203, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18476985

ABSTRACT

OBJECTIVE: To examine the concept whether high-dose diazoxide (DZX)-mediated insulin suppression, in combination with moderate caloric restriction and increased physical activity, can establish a weight loss of at least 15% in obese hyperinsulinaemic men. DESIGN: Open, uncontrolled, 6-month pilot study. Energy intake was reduced by 30%, and walking for at least 30 min a day was strongly recommended. DZX treatment was started at 50 mg t.i.d. and increased by 50 mg per dose every 4 weeks to a maximum of 300 mg t.i.d., unless hyperglycaemia or other side-effects occurred. SUBJECTS AND METHODS: Eighteen obese hyperinsulinaemic men with a body mass index of 30-35 kg/m(2). Measurements included body weight, body composition, blood pressure, glycaemic control, insulin response, adiponectin and serum lipids. RESULTS: Body weight decreased by 9.4 kg (95% CI: 5.6-13.2 kg, p < 0.001), waist circumference reduced by 9.2 cm (95% CI: 5.3-12.9 cm, p < 0.001) and total body fat mass decreased by 23.3% (95% CI: 13.7-32.9%, p < 0.001), without a concomitant change in soft tissue lean body mass or bone mass. Fat loss was inversely related to fasting insulin levels achieved at 6 months (r = -0.76, p < 0.002). Diastolic blood pressure decreased by 10.9 mmHg (95% CI: 6.5-15.4 mmHg, p < 0.002). Fasting and postmeal peak insulin levels were reduced by about 65% (p < 0.001) and decreased to the normal range for non-obese men. Fasting and postmeal peak glucose levels increased by 0.8 +/- 0.3 mmol/l (p = 0.01) and 1.4 +/- 0.7 mmol/l (p = 0.06) respectively. Haemoglobin A1c rose by 0.5% to 5.9 +/- 0.2%. CONCLUSION: High-dose DZX-mediated insulin suppression, in combination with moderate caloric restriction and lifestyle advice, is associated with a clinically relevant degree of weight reduction. A more extensive exploration is warranted to optimize this mode of treatment and to further clarify its risks and benefits.


Subject(s)
Caloric Restriction , Diazoxide/therapeutic use , Diet, Reducing , Insulin Antagonists/therapeutic use , Obesity/diet therapy , Weight Loss/physiology , Adult , Body Composition/drug effects , Dose-Response Relationship, Drug , Humans , Insulin/blood , Life Style , Male , Middle Aged , Obesity/blood , Pilot Projects , Treatment Outcome
15.
Eur J Neurol ; 15(5): 487-92, 2008 May.
Article in English | MEDLINE | ID: mdl-18355310

ABSTRACT

BACKGROUND: Motor symptoms form the hallmark of Parkinson's Disease (PD), although features like depression are often present. Depression rating scales [e.g. Montgomery-Asberg Depression Rating Scale (MADRS)] used in PD measure affective, cognitive and somatic symptoms. An important clinical question is which items of the MADRS are likely to be influenced by PD symptoms. METHODS: Depression was assessed in 43 PD patients who scored below the cut-off of the MADRS and who differed widely in motor severity. RESULTS: Parkinson's Disease patients scored relatively highest on Concentration difficulties, Reduced sleep and Inner tension. Reduced sleep, Lassitude and Suicidal thoughts were associated with motor severity and specifically with Bradykinesia, Rigidity and Axial impairment, however not with Tremor. To avoid a possible influence on our results of coincidentally included PD patients with a depression, all associations between somatic MADRS items and motor severity were corrected for the influence of affective symptoms of depression. All associations remained significant. DISCUSSION: In conclusion, the items Reduced sleep and Lassitude of the MADRS are likely to be influenced by motor symptoms. The high score on Concentration difficulties is suggested to be a reflection of cognitive dysfunction in PD. Thus, when assessing depression in PD, using a depression rating scale like the MADRS, adjusted cut-off scores are required.


Subject(s)
Depression/diagnosis , Depression/etiology , Parkinson Disease/complications , Adult , Aged , Disability Evaluation , Female , Humans , Male , Middle Aged , Psychiatric Status Rating Scales , Severity of Illness Index
16.
Neth J Med ; 66(3): 103-9, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18349465

ABSTRACT

BACKGROUND: Obesity can be associated with biochemical evidence of isolated hypogonadotropic hypogonadism (IHH) in men. Prevalence and severity of IHH in obese men are not exactly known. OBJECTIVE: To assess the prevalence of IHH in obese men. DESIGN AND SUBJECTS: Cross-sectional study of 160 obese men, BMI >30 kg/m2, who applied for medical or surgical treatment of obesity in a general teaching hospital. MAIN OUTCOME MEASURES: Total and calculated free testosterone (TT and FT) in relation to body mass index (BMI). RESULTS: Mean age of the study population was 43.3 +/- 0.8 years (mean +/- SEM), BMI ranged from 30.0 to 65.7 kg/m2. TT and FT levels were inversely related to BMI (-0.48, p<0.0001). Total testosterone was subnormal in 57.5% and free testosterone in 35.6% of the subjects. The group of men with IHH was more obese, had higher Hba IC levels and had a 2.6 higher risk for cardiovascular disease. Decreased libido and erectile dysfunction were 7.1 and 6.7 times as common in IHH than in eugonadal obese men. CONCLUSION: Reduced T levels, well into the hypogonadal range, are common in male obesity. Assessment of its clinical implications, and a search for the best mode of treatment are warranted.


Subject(s)
Hypogonadism/etiology , Obesity/complications , Adolescent , Adult , Aged , Body Mass Index , Cardiovascular Diseases/etiology , Cross-Sectional Studies , Erectile Dysfunction/etiology , Humans , Hypogonadism/blood , Hypogonadism/epidemiology , Hypogonadism/physiopathology , Libido , Male , Middle Aged , Netherlands/epidemiology , Obesity/blood , Obesity/epidemiology , Obesity/physiopathology , Prevalence , Risk Factors
17.
Diabetes Obes Metab ; 8(5): 517-23, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16918586

ABSTRACT

INTRODUCTION: Weight gain appears to be unavoidable in patients with type 2 diabetes who are switched from oral agents to insulin therapy. Peripheral hyperinsulinism induced by the use of long-acting insulin may be the key to explain this adverse effect. AIM: The aim of this study was to investigate whether a regimen free of long-acting insulin can provide long-term glycaemic control without causing weight gain. PATIENTS AND METHODS: This is an uncontrolled, 1-year study comprising 58 patients with type 2 diabetes and secondary failure, age 30-75 years, BMI 25-35 kg/m(2), HbA1c > 7.5% and fasting C-peptide level > 0.3 mmol/l. All patients were treated with the GAME regimen, a combination of glimepiride administered at 20:00 hours for nocturnal glycaemic control, insulin aspart three times daily for meal-related glucose control and metformin. RESULTS: Seventy-one per cent of the patients were considered evaluable. HbA1c decreased from 10.0 +/- 0.3 to 7.4 +/- 0.1% (p < 0.001). Fifty-nine per cent reached HbA1c levels

Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/analogs & derivatives , Weight Gain/drug effects , Adult , Aged , Blood Glucose/metabolism , Body Mass Index , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/physiopathology , Drug Therapy, Combination , Female , Glycated Hemoglobin , Hemoglobins/metabolism , Humans , Insulin/therapeutic use , Insulin Aspart , Male , Metformin/therapeutic use , Middle Aged , Sulfonylurea Compounds/therapeutic use , Treatment Failure , Treatment Outcome
18.
Diabetes Obes Metab ; 7(3): 211-5, 2005 May.
Article in English | MEDLINE | ID: mdl-15811136

ABSTRACT

BACKGROUND: Morbid obesity is associated with increased estradiol production as a result of aromatase-dependent conversion of testosterone to estradiol. The elevated serum estradiol levels may inhibit pituitary LH secretion to such extent that hypogonadotropic hypogonadism can result. Normalization of the disturbed estradiol-testosterone balance may be beneficial to reverse the adverse effects of hypogonadism. AIM: To examine whether aromatase inhibition with Letrozole can normalize serum testosterone levels in severely obese men with hypogonadotropic hypogonadism. PATIENTS AND METHODS: Ten severely obese men, mean age 48.2 +/- 2.3 (s.e.) years and body mass index 42.1 +/- 2.6 kg/m(2), were treated with Letrozole for 6 weeks in doses ranging from 7.5 to 17.5 mg per week. RESULTS: Six weeks of treatment decreased serum estradiol from 120 +/- 20 to 70 +/- 9 pmol/l (p = 0.006). None of the subjects developed an estradiol level of less than 40 pmol/l. LH increased from 4.5 +/- 0.8 to 14.8 +/- 2.3 U/l (p < 0.001). Total testosterone rose from 7.5 +/- 1.0 to 23.8 +/- 3.0 nmol/l (p < 0.001) without a concomitant change in sex hormone-binding globulin level. Those treated with Letrozole 17.5 mg per week had an excessive LH response. CONCLUSION: Short-term Letrozole treatment normalized serum testosterone levels in all obese men. The clinical significance of this intervention remains to be established in controlled, long-term studies.


Subject(s)
Aromatase Inhibitors/therapeutic use , Hypogonadism/blood , Nitriles/therapeutic use , Obesity, Morbid/blood , Testosterone/blood , Triazoles/therapeutic use , Dose-Response Relationship, Drug , Drug Administration Schedule , Estradiol/blood , Gonadotropins, Pituitary/blood , Humans , Hypogonadism/drug therapy , Letrozole , Male , Middle Aged , Obesity, Morbid/drug therapy , Pilot Projects , Sex Hormone-Binding Globulin/analysis
19.
Diabetes Obes Metab ; 7(3): 239-45, 2005 May.
Article in English | MEDLINE | ID: mdl-15811140

ABSTRACT

BACKGROUND: It has been suggested that diazoxide (DZX)-mediated insulin suppression may be useful to promote weight loss in obese subjects. AIM: To assess the DZX-dose range that is safe to use in obese hyperinsulinaemic men. METHODS: Assessment of DZX efficacy and safety was based on plasma glucose and insulin responses to a standardized 500-kcal breakfast, taken on the sixth day of treatment. Basic information regarding the potential efficacy of DZX treatment was first evaluated in an open-label study in five non-obese men. Subsequently, a double-blind, randomized, placebo-controlled study was performed in 12 obese but otherwise healthy men, comparing placebo treatment with DZX in doses of 50, 75 and 100 mg three times daily for 6 days. RESULTS: In non-obese subjects, DZX 50 mg decreased peak insulin levels by +/-28% and raised peak glucose concentration from 7.1 +/- 0.6 to 7.8 +/- 0.6 mmol/l (p < 0.05). DZX 100 mg reduced peak insulin levels by 45% and caused a rise in peak glucose levels from 7.1 +/- 0.6 to 9.0 +/- 0.9 mmol/l (p < 0.05). In obese men, the 50 and 75 mg doses had no significant effects on glucose or insulin levels. DZX 100 mg reduced the peak insulin levels and insulin area under the curve by +/-20% (p < 0.05) but did not affect fasting or postprandial glucose levels. The relatively limited insulin-suppressive effects in obese subjects were attributed to the low plasma DZX levels that were achieved in this group. For comparable doses, plasma DZX levels were about 30% lower in obese than in non-obese men. Plasma DZX levels were highly dependent on dose (p < 0.001) and body weight (p < 0.001). Ninety-two percent of the total variability in DZX levels was explained by these two parameters. CONCLUSION: DZX-mediated insulin suppression is dose dependent in normal and in obese men. However, the efficacy of DZX is much less in obese than in non-obese subjects. This is attributed to weight-dependent differences in distribution volume that lead to markedly lower plasma DZX levels in obese subjects. Weight-adjusted doses will be needed to achieve biologically effective plasma DZX levels. Extrapolation of the data suggests that effective insulin suppression in obese men will at least require a daily dose of 3.2-4.2 mg/kg.


Subject(s)
Diazoxide/administration & dosage , Insulin/blood , Obesity/drug therapy , Sodium Chloride Symporter Inhibitors/administration & dosage , Adult , Area Under Curve , Blood Glucose/analysis , Body Weight , Depression, Chemical , Diazoxide/blood , Diazoxide/therapeutic use , Diuretics , Dose-Response Relationship, Drug , Double-Blind Method , Humans , Male , Middle Aged , Obesity/blood , Obesity/physiopathology , Postprandial Period , Sodium Chloride Symporter Inhibitors/blood , Sodium Chloride Symporter Inhibitors/therapeutic use
20.
Diabetes Obes Metab ; 6(2): 114-9, 2004 Mar.
Article in English | MEDLINE | ID: mdl-14746576

ABSTRACT

BACKGROUND: Patients with type 2 diabetes who are failing on oral agents will generally gain a large amount of body fat when switched to insulin treatment. This adverse effect may be related to chronic hyperinsulinism induced by long-acting insulin compounds. AIM: To test the concept that regain of glycaemic control can be achieved without causing weight gain, using a regimen free of long-acting insulin. METHODS: In a 3-month open-label pilot study including 25 patients with moderate overweight and secondary failure, we investigated whether nocturnal glycaemic control could be achieved with glimepiride administered at 20:00 hours. The starting dose was 1-2 mg, with subsequent titration up to a maximum of 6 mg. Rapid-acting insulin analogues were used three times daily to regain postprandial glucose control. RESULTS: Glycaemic control at 3 months was established with glimepiride in a dose of 4.4 +/- 0.3 mg/day (mean +/- standard error of the mean), and a total daily insulin dose of 24.1 +/- 2.6 IU. Fasting glucose levels decreased from 12.7 +/- 0.6 mmol/l to 8.1 +/- 0.3 mmol/l (p < 0.001), and target levels were reached in 14 of 25 patients (56%). Mean HbA1c decreased from 10.5 +/- 0.4 to 7.7 +/- 0.2% (p < 0.001). Symptomatic nocturnal hypoglycaemia was not reported. Body weight did not change (85.7 +/- 3.6 kg vs. 85.7 +/- 3.3 kg, p = 0.99). CONCLUSION: The data suggest that this new approach may be useful in about 50% of type 2 diabetes patients presenting with failure on maximal oral treatment.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Sulfonylurea Compounds/therapeutic use , Weight Gain , Blood Glucose/analysis , C-Peptide/blood , Diabetes Mellitus, Type 2/blood , Drug Administration Schedule , Drug Therapy, Combination , Female , Humans , Male , Metformin/therapeutic use , Middle Aged , Pilot Projects
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