Shared and distinct genetic etiologies for different types of clonal hematopoiesis.

Clonal hematopoiesis (CH)-age-related expansion of mutated hematopoietic clones-can differ in frequency and cellular fitness by CH type (e.g., mutations in driver genes (CHIP), gains/losses and copy-neutral loss of chromosomal segments (mCAs), and loss of sex chromosomes). Co-occurring CH raises questions as to their origin, selection, and impact. We integrate sequence and genotype array data in up to 482,378 UK Biobank participants to demonstrate shared genetic architecture across CH types. Our analysis suggests a cellular evolutionary trade-off between different types of CH, with LOY occurring at lower rates in individuals carrying mutations in established CHIP genes. We observed co-occurrence of CHIP and mCAs with overlap at TET2, DNMT3A, and JAK2, in which CHIP precedes mCA acquisition. Furthermore, individuals carrying overlapping CH had high risk of future lymphoid and myeloid malignancies. Finally, we leverage shared genetic architecture of CH traits to identify 15 novel loci associated with leukemia risk.

Changes of Physical Function and Quality of Life in Patients with Type 2 Diabetes after Exercise Training in a Municipality or a Hospital Setting.

INTRODUCTION: The aim was to compare changes in physical function and quality of life (QOL) after an exercise training programme to patients with type 2 diabetes mellitus (T2DM) in a municipality and a hospital setting and to compare the patients' physical function and QOL with an age- and sex-matched general population. METHODS: Patients with T2DM were stratified to exercise training in a municipality (n = 26) or a hospital (n = 46), respectively. The training was one hour twice weekly for 12 weeks. The outcomes were physical function (30 sec chair stand test (CST)) and QOL (using the SF-36). The data for the general population were collected from previous reference studies. RESULTS: Fifty-one (71%) participants completed the intervention. The CST results improved in both groups with no difference between the municipality and hospital groups (1.6 [0.1; 3.1] vs. 3.5 [2.3; 4.8] no., respectively, p = 0.062). The QOL scales physical function and general health increased more in the municipality group than in the hospital group (10.5 [2.8; 18.2] vs. -1.2 [-7.9; 5.5], respectively, p = 0.031, and 8.3 [2.3; 14.4] vs. -0.2 [-5.6; 5.1], respectively, p = 0.042). Dropout (n = 21) during the intervention was associated with reduced QOL at baseline. The patients' CST results at baseline were reduced compared to the general population (11.8 ± 3.5vs.18.9 ± 3.3, respectively, p < 0.001). All QOL scales apart from social function were reduced in the patients compared to the general population. CONCLUSION: Patients in a 12-week exercise training programme in a hospital or a municipality setting had significantly lower QOL compared to an age- and sex-matched population sample. Similar improvements in physical function were observed in patients after completion of the exercise programme irrespective of exercise setting, whereas patient exercising in a municipality setting had higher positive changes in QOL than patients undergoing the same exercise programme in a hospital setting.

Diabetes Is Associated with Musculoskeletal Pain, Osteoarthritis, Osteoporosis, and Rheumatoid Arthritis.

AIM: To investigate the associations between diabetes and musculoskeletal pain, osteoarthritis, osteoporosis, and rheumatoid arthritis. METHODS: Self-reported data were provided by the nationwide Danish National Health Survey 2013. Inclusion criteria were age ≥ 40 years and known diabetes status. The exposure variable was diabetes, and the outcome variables included musculoskeletal pain during the last 14 days in three body sites (back/lower back, limbs, and shoulder/neck), osteoarthritis, osteoporosis, and rheumatoid arthritis. Logistic regression analyses adjusted for age, gender, BMI, education, marital status, and physical activity were performed. RESULTS: 9,238 participants with diabetes were 65.6 ± 11.0 (mean ± SD) years old; 55.6% were males. 99,980 participants without diabetes were 59.2 ± 11.8 years old; 46.7% were males. Diabetes was associated with back/lower back pain (OR 1.2 (CI 95% 1.1-1.2), p < 0.001), pain in the limbs (1.4 (1.3-1.4), p < 0.001), shoulder/neck pain (1.2 (1.1-1.3), p < 0.001), osteoarthritis (1.3 (1.2-1.4), p < 0.001), osteoporosis (1.2 (1.1-1.4), p = 0.010), and rheumatoid arthritis (1.6 (1.4-1.7), p < 0.001). In participants with diabetes, physical activity was associated with reduced pain (e.g., back/lower back pain (0.7 (0.6-0.7), p < 0.001)). CONCLUSION: Diabetes was associated with elevated odds of having musculoskeletal pain. Diabetes was also associated with elevated odds of having osteoarthritis, osteoporosis, and rheumatoid arthritis. The most frequent disease in individuals with diabetes was osteoarthritis. The reported pain may have negative impacts on the level of physical activity. Health-care professionals should remember to inform patients with diabetes that musculoskeletal pain, osteoarthritis, osteoporosis, and rheumatoid arthritis are not contraindications to exercise training.

Exercise training is associated with reduced pains from the musculoskeletal system in patients with type 2 diabetes.

AIMS: To investigate the effect of exercise training on musculoskeletal pain in patients with type 2 diabetes. METHODS: The intervention was exercise twice weekly for 12 weeks. The primary outcome was musculoskeletal pain assessed using a 0-10 Numeric Rating Scale (NRS) in 11 body sites. Secondary outcomes were use of analgesics, glycaemic control and body weight. RESULTS: The participants (n = 69) were 66 ±â€¯10 years old, 38 were men and 50 completed the intervention. Pain in the limbs was more frequently reported by the participants compared to a matched general population (80.9% vs 65.3%, p = 0.007). The participants who had any pain at baseline (NRS > 0) and severe pain (NRS > 3) reported significantly decreased pain in the feet, calf muscles, knees, thighs, hips, lower back and arms after the training period. Use of analgesics was unchanged, HbA1c (mmol/mol) decreased from 60 ±â€¯15 to 54 ±â€¯11, p < 0.001 and body weight (kg) decreased from 100.5 ±â€¯19.1 to 98.6 ±â€¯17.7, p = 0.005. CONCLUSIONS: The participants with type 2 diabetes reported more frequent pain than a matched general population. The training intervention was associated with reduced musculoskeletal pain. Reduced pain may together with a positive impact on glycaemic control be an important motivational factor in patients with type 2 diabetes to perform exercise training.

Reduced Inspiratory Muscle Strength in Patients with Type 2 Diabetes Mellitus and Obstructive Sleep Apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is related to type 2 diabetes (T2DM), and it may be associated with reduced inspiratory muscle strength (IMS). The aim of this study was to investigate the IMS in patients with T2DM, with or without OSA. METHODS: Patients with T2DM with OSA (n = 33) and without OSA (n = 28) were included. The maximum IMS was tested using the POWERbreathe KH2 device. Reference IMS values were data calculated using an algorithm based on general populations and adjusted for age and gender. RESULTS: There was no difference in IMS between the OSA group (median (range) 77 (35-124) cmH2O) and the non-OSA group (84 (33-122) cmH2O) (p = 0.97). The IMS values were reduced in the OSA group compared with the reference values (92.9 (62.3-100.0) cmH2O) (p = 0.030), whereas the non-OSA group did not have reduced IMS. When the IMS values of all T2DM patients were compared with reference values, the IMS values were 79 (33-124) cmH2O and 93.8 (62.3-102.4) cmH2O, respectively (p = 0.017). CONCLUSION: No difference in IMS between patients with T2DM with or without OSA was found. However, patients with T2DM and OSA had reduced IMS compared with age- and gender-matched references whereas the non-OSA group did not have reduced IMS.