Genetic glucocorticoid receptor variants differ between ethnic groups but do not explain variation in age of diabetes onset, metabolic and inflammation parameters in patients with type 2 diabetes.

Aims: The effect of excess glucocorticoid receptor (GR) stimulation through glucocorticoid medication or cortisol on glucose metabolism is well established. There are genetic GR variants that result in increased or decreased GR stimulation. We aimed to determine the prevalence of genetic GR variants in different ethnic groups in a cohort of patients with type 2 diabetes, and we aimed to determine their association with age of diabetes onset and metabolic and inflammation parameters. Methods: A cross-sectional analysis was performed in a multiethnic cohort (n = 602) of patients with established type 2 diabetes. Polymorphisms in the GR gene that have previously been associated with altered glucocorticoid sensitivity (TthIIII, ER22/23EK N363S, BclI and 9ß) were determined and combined into 6 haplotypes. Associations with age of diabetes onset, HbA1c, hs-CRP and lipid values were evaluated in multivariate regression models. Results: The prevalence of the SNPs of N363S and BclI was higher in Dutch than in non-Dutch patients. We observed a lower prevalence of the SNP 9ß in Dutch, South(East) Asian and Black African patients versus Turkish and Moroccan patients. We did not detect an association between SNPs and diabetes age of onset or metabolic parameters. We only found a trend for lower age of onset and higher HbA1c in patients with 1 or 2 copies of haplotype 3 (TthIIII + 9ß). Conclusions: The prevalence of genetic GR variants differs between patients of different ethnic origins. We did not find a clear association between genetic GR variants and age of diabetes onset or metabolic and inflammation parameters. This indicates that the clinical relevance of GR variants in patients with established type 2 diabetes is limited.

Interpretation of laboratory results after gastric bypass surgery: the effects of weight loss and time on 30 blood tests in a 5-year follow-up program.

BACKGROUND: Long-term follow-up with blood tests is essential for bariatric surgery to be a successful treatment for obesity and related co-morbidities. Adverse effects, deficiencies, and metabolic improvements need to be controlled. OBJECTIVE: We investigated the effects of time and weight loss on laboratory results in each postoperative phase after laparoscopic Roux-en-Y gastric bypass (LRYGB). SETTING: Bariatric center of excellence, general hospital, Netherlands. METHODS: We retrospectively evaluated results of 30 blood tests, preoperatively and at 6 months, 1 year, 2 years, and 5 years after LRYGB. The 2019 Dutch bariatric chart was used to define weight loss responses as outstanding (>p[percentile curve]+1 SD), average (p+1 SD to p-1 SD), and poor (

Smoking Behaviour and Beliefs About Smoking Cessation After Bariatric Surgery.

PURPOSE: Currently, bariatric surgery is the most effective intervention for treating morbid obesity and its complications. Smoking cessation is likely to improve smoking-related comorbidities and decrease postoperative complications. This study evaluated the smoking behaviour and thoughts about smoking cessation of patients more than 18 months after bariatric surgery. MATERIALS AND METHODS: A cross-sectional study was performed in patients who underwent bariatric surgery from July 2012 to December 2013. A questionnaire was used to evaluate smoking status, thoughts about the health benefits of cessation and characteristics of previous quit attempts in current and former smokers. Finally, actual bariatric surgery outcomes were evaluated in current, former and never smokers. RESULTS: Six hundred nine patients (response rate 52.0%) were included. Of them, 101 (16.6%) patients were current smokers, 239 (39.2%) former smokers and 269 (44.2%) patients were lifetime never smokers. Compared with former smokers, current smokers were less aware of the beneficial effects of smoking cessation on their general health; 66.4% of the former smokers thought smoking cessation would be much better for general health, compared with 20.6% of current smokers. Total weight loss was 2.8% higher in current smokers compared with former smokers. Actual long-term bariatric surgery outcomes were not significantly different between the groups. CONCLUSION: Despite advice to quit smoking and temporary quitting before surgery, a considerable group of bariatric surgery patients continues smoking after surgery. These patients were less aware of the beneficial effects of smoking cessation. This study emphasizes the need for better strategies to increase the number of successful cessations.

Oral health information from the dentist to the diabetologist.

BACKGROUND: Diabetes care includes annual evaluation of micro- and macrovascular complications, however, oral pathologies are not included. We studied retrieving oral health information, in particular periodontal disease, from the dentist and studied the association between the reported periodontal condition and variables of both diabetes and dental care. METHODS: During their annual comprehensive diabetes evaluation, patients were asked to deliver an oral health questionnaire (OHQ) to their dentist. Based on the returned OHQs, the process of retrieving oral health information from the dentist was analyzed. In addition, reported oral health measures with special emphasis to periodontitis, using a Periodontal Screening Index (PSI), were related to diabetes-related variables. RESULTS: We included 889 patients of whom 102 patients (11%) did not visit a dentist at all and 252 (28%) were edentulous. The response rate was <50% for oral information on patients with diabetes. For the second aim, OHQs of 207 patients could be further analyzed. A moderate to high PSI-score was found in 106 patients, of whom 65% were untreated for periodontitis. Furthermore high PSI-scores were associated with poor oral hygiene, soft tissue pathologies and periodontal treatment, but not significantly with glycemic control and presence of diabetes complications. CONCLUSION: The transfer of information from the dentist to the diabetologist is far from optimal. An OHQ can be a valuable tool for the identification of patients with diabetes with poor oral health especially untreated periodontal disease, which is helpful for proper diabetes management.

Skin autofluorescence and complications of diabetes: does ethnic background or skin color matter?

AIMS: Skin autofluorescence (AF) has been associated with complications of diabetes. We evaluated the influence of skin color and ethnicity on the association between skin AF and the presence of diabetes-related complications. MATERIALS AND METHODS: In a multiethnic type 2 diabetes cohort we investigated all patients with available skin AF measurements. The associations between skin AF and hemoglobin A1c (HbA1c) and the presence of complications of diabetes were estimated, stratified for ethnicity and quartiles of ultraviolet reflectance percentage (R%). RESULTS: In total, 810 patients (438 native Dutch, 372 non-Dutch) were included. Because of too low an R%, 32% of black Africans and 19% of Hindustanis were excluded. Non-Dutch patients had lower AF values compared with Dutch patients (median AF=2.69 [interquartile range (IQR), 2.26-3.09] vs. 3.06 [IQR, 2.65-3.50] arbitrary units; P<0.001), but the R% was also lower (non-Dutch, median R%=12% [IQR, 9-15%]; Dutch, median R%=18% [IQR, 14-23%]; P=0.027). In the multivariate analysis, skin AF was only a determinant for complications in patients with R% 25(th) percentile (macrovascular, odds ratio [OR]=1.71 [95% confidence interval (CI), 1.05-2.77] vs. 1.15 [95% CI, 0.55-2.40] in the lowest quartile of R%; microvascular, OR=1.81 [95% CI, 1.20-2.75] vs. OR=0.87 [95% CI, 0.50-1.51]). A similar pattern was observed for nephropathy, neuropathy, and retinopathy separately. In non-Dutch patients AF was not a significant determinant for diabetes complication risk, whereas HbA1c was for nephropathy, retinopathy, and neuropathy. CONCLUSIONS: Skin AF measurement is a valuable tool for the assessment of micro- and macrovascular complication risk in patients with light skin color types. Even after exclusion of patients with too low a reflectance, the current performance of the AGE Reader™ (DiagnOptics Technologies BV, Groningen, The Netherlands) was insufficient in darker-skinned patients.

The longer-term effects of Roux-en-Y gastric bypass surgery on sodium excretion.

BACKGROUND: Obesity is an independent risk factor for hypertension and chronic kidney disease. During the first months after bariatric surgery, an improvement of sodium excretion has been described. The aim of this work was to study the influence of bariatric surgery on sodium excretion at more than a year after the intervention. METHODS: Patients who have undergone Roux-en-Y gastric bypass (RYGB) and who had collected a 24-h urine sample before surgery more than 12 months ago were asked to participate. A second 24-h urine sample was collected. Blood pressure and weight were measured. The difference in sodium excretion before and after surgery was calculated, and the relationship with blood pressure and weight loss was investigated. RESULTS: We included 33 patients; the median follow-up time was 21 months (range 14-41). Sodium excretion was high before surgery (median 195 mmol/day, IQR range 167-247) and decreased by 18 % after surgery (median 160 mmol/day, IQR range 118-205, p = 0.015), while there were significant improvements in body weight (% EWL 80.9 ± 21.8), systolic blood pressure (126 to 120 mmHg, p = 0.02), and diastolic blood pressure (84 to 77 mmHg, p = 0.002), even with a reduced number of antihypertensive drugs. CONCLUSIONS: After RYGB and considerable weight loss, sodium excretion remains high in the longer term. The profound improvement in blood pressure cannot be explained by reductions in sodium excretion after RYGB.

The hemostatic system in patients with type 2 diabetes with and without cardiovascular disease.

The contribution of the hemostatic system in the development of cardiovascular disease (CVD) in patients with type 2 diabetes is not completely defined. The aim of this study was to elucidate associations of hemostatic factors with the development of CVD in patients with type 2 diabetes. Patients with type 2 diabetes without CVD (n = 113), with CVD (n = 94), and controls without CVD (n = 100) were enrolled in this study. Several hemostatic markers were measured. A disturbed hemostatic balance in patients with type 2 diabetes was observed as illustrated by hypofibrinolysis and increased levels of von Willebrand factor (vWF) and plasminogen-activator inhibitor 1 (PAI-1). Patients with type 2 diabetes with CVD have more thrombin generation compared to patients without CVD. This hemostatic imbalance might contribute to the development of CVD in patients with type 2 diabetes.

Prescription of physical activity is not sufficient to change sedentary behavior and improve glycemic control in type 2 diabetes patients.

OBJECTIVE: To assess the impact of personalized exercise prescription on habitual physical activity and glycemic control in sedentary, insulin treated type 2 diabetes patients during a 2-y intervention period. RESEARCH DESIGN AND METHODS: 74 patients were randomized to the intervention (n=38) or control (n=36) group. The intervention group was stimulated to increase daily physical activity through regular, structured, and personalized exercise prescription by a physical therapist over the 2-y intervention period. RESULTS: Physical activity levels at work or in leisure time were not modulated by the exercise prescription intervention. In accordance, no changes in body composition, glycemic control, medication use or risk factors for cardiovascular disease were observed. CONCLUSIONS: Long-term behavioral intervention programs, providing individualized exercise prescription, are not sufficient to change sedentary behavior and/or improve glycemic control in insulin treated, type 2 diabetes patients.

The inflammation and coagulation cross-talk in patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disorder with a high prevalence of cardiovascular disease due to accelerated atherosclerosis, as well as an increased risk of venous thromboembolism. Many of these clinical features have been attributed to the high prevalence of autoantibodies that are directed against phospholipid-bound antigens and that induce prothrombotic effects and disturb endothelial cell function. We conducted a case-control study in a cohort of female patients with SLE and in age-matched and sex-matched normal individuals. Patients had significantly higher levels of plasma inflammatory markers, but their overall coagulation status assessed by prothrombin fragment 1 + 2 and D-dimer plasma levels was not different from controls. Resistance against activated protein C (APC), assessed by a thrombin generation-based as well as an activated partial thromboplastin time-based method, however, was increased in patients. This defect was neither due to factor V Leiden carriership or to the use of oral contraceptives. This acquired form of APC resistance was due to proinflammatory changes associated with lower plasma levels of free protein S. In conclusion, acquired APC resistance may be an important determinant of the risk of thrombosis in patients with SLE, probably due to an active cross-talk between inflammation and coagulation systems.

Bayesian pharmacokinetics of lithium after an acute self-intoxication and subsequent haemodialysis: a case report.

We report a case of a 39-year-old male with bipolar affective disorder who was admitted to hospital with an intentional acute lithium intoxication resulting in renal insufficiency. The patient had previously been treated with lithium, risperidone, fluoxetine and lorazepam, and successfully titrated to lithium levels of 0.7 mmol/l. After overdosing, the lithium level was 5.89 mmol/l and haemodialysis was initiated. A full pharmacokinetic time profile of lithium was obtained. After successful haemodialysis treatment, lithium levels recovered below toxic levels of 1.5 mmol/l in 53 hr. Without intervention non-toxic levels were not expected to have been reached within 6 days, based on computer simulation of predialysis levels. The patient was discharged 6 days after admission without residual symptoms. It was concluded that the lithium intoxication resulted from a combination of lithium overdose and subsequent renal insufficiency due to the overdose. A possible fluoxetine-risperidone interaction was not considered clinically apparent.