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Venous thromboembolism (VTE) is the third most common cause of cardiovascular disease. Connection between high level of physical activity (PA) and the onset of VTE is unknown. We searched the literature on the possible association between PA level, especially high levels, and the risk of VTE. A systematic review was carried out to identify relevant articles on the relation between PA level and VTE. The initial search was conducted together with the Karolinska Institutet University Library in February 2018, with follow-up searches after that. In total, 4383 records were found and then screened for exclusion of duplicates and articles outside the area of interest. In total, 16 articles with data on 3 or more levels of PA were included. Of these, 12 were cohort and 4 were case-control studies. Totally 13 studies aimed at investigating VTE cases primarily, while three studies had other primary outcomes. Of the 16 studies, five found a U-shaped association between PA level and VTE risk, although non-significant in three of them. Two articles described an association between a more intense physical activity and a higher risk of VTE, which was significant in one. Nine studies found associations between increasing PA levels and a decreasing VTE risk. Available literature provides diverging results as to the association between high levels of PA and the risk of venous thromboembolism, but with several studies showing an association. Further research is warranted to clarify the relationship between high level PA and VTE. Supplementary Information The online version of this article (10.1007/s11239-020-02372-5) contains supplementary material, which is available to authorized users.

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Venous thromboembolism (VTE) is an important cause of morbidity and mortality in Western countries. The incidence rate of VTE is estimated at 1–2 cases per 1000 annually. This study was a population-based cohort study of previously treatment naïve patients with a first occurrence of venous thromboembolism (VTE), using data from the administrative health data register of the Stockholm Region 2011–2018. Data on anticoagulant treatment was taken from the Swedish Prescribed Drug Register. We also analyzed all VTE events between 2011 and 2018. Altogether 14,849 naïve incident VTE cases were identified. In 2011 the majority of patients with a first episode of VTE were prescribed warfarin versus non-vitamin K antagonist oral anticoagulants (NOACs), 1144 versus 5. In contrast in 2018, the majority of patients were treated with NOACs, 1049 versus 59 treated with warfarin. Treatment with low molecular weight heparin only decreased from 814 to 683 patients. The frequency of all VTE events in the population increased over time from 1.88/1000 to 1.93/1000 (p = 0.072), and PE diagnoses increased from 0.69/1000 to 0.76/1000 (p = 0.003). In conclusion, during 2011–2018 there has been a shift of prescription of warfarin to a clear predominance of NOACs in the treatment of VTE in the Stockholm Region, in line with current recommendations. In the clinical situation, treatment has been simplified as monitoring of warfarin has decreased substantially. PE events increased during the time period in the population even if the increase was rather modest, while all VTE events did not increase significantly. Electronic supplementary material The online version of this article (10.1007/s11239-019-01966-y) contains supplementary material, which is available to authorized users.

Aims Compare quantitative ultrasound (QUS) of calcaneus and dual energy X-ray absorptiometry (DXA) as measurements of bone density, calculate 20-year fracture incidence in patients with T1DM and T2DM and multiple complications, and compare the methods’ predictive ability. Methods Sixty-two hospital foot clinic patients with T1DM or T2DM and complications were followed (1995–2015; 610 person-years). Clinical assessments and QUS of calcaneus were performed on all at inclusion and DXA of the spine and femoral neck on a subgroup (n = 34). Fracture incidence was assessed at follow-up and compared to incidence in the general population. We evaluated the correlation between QUS of calcaneus and DXA (Pearson’s correlation test) and the association between bone density and fracture incidence at follow-up (logistic regression). Results Bone density (QUS of calcaneus) correlated with hip bone density (DXA). Incidence of all fractures (30/62 patients; 48%) and hip fractures (6/62 patients; 10%) was higher in patients than the general population. Twelve (19%) experienced foot fracture. QUS of calcaneus predicted hip, lower leg, and foot fractures; DXA did not. Conclusions Because QUS of calcaneus predicted fractures in patients with diabetes and multiple complications, it seems appropriate to test QUS of calcaneus as a fracture risk predictor in primary care.

The risk of diabetic nephropathy (DN) can be increased by elevated intraglomerular pressure and glomerular filtration rate, leading to glomerular damage. This can be controlled by the renin-angiotensin-aldosterone (RAA) system, which has an important function regulating both systemic and intrarenal blood pressure. Smoking increases the risk of DN, but not all diabetic patients who smoke develop DN. There is a possibility that smoking has different effects depending on the different genotypes of the individual. We investigated the association of DN with seven polymorphisms in the RAA system and their possible interaction with smoking.In the present case-control study, type 1 diabetic patients with diabetes durationor =20 years, without albuminuria and without antihypertensive treatment (n=197), were included as controls. An albumin excretion rate (AER) of 20-200 microg/min (n=73) was considered as incipient DN, and an AER200 microg/min was considered as overt DN (n=48). Smoking habits were obtained from questionnaires.Homozygosity for the A allele, of the angiotensin II type 1 receptor (AGTR1) A1166C polymorphism, was associated with increased risk of overt DN (OR=3.04; 99% CI=1.02-9.06), independently of the other associated variables: age, duration of diabetes, ever smoking, HbA1c, and sex. The effect of the AA genotype was enhanced to a four times risk increase among ever-smoking patients. Two alleles of the microsatellite marker adjacent to the angiotensinogen gene were less common among nephropathy cases than among controls, but this was not significant when controlling for the same variables as above.The risk of having overt DN was increased in patients homozygous for the A1166 allele, and smoking seemed to enhance the effect of the AGTR1 genotype.

Objective Diabetes mellitus is associated with an increased risk of osteopenia, fracture and Charcot arthropathy. Abnormalities of the IGF system commonly observed in diabetes may underlie this “diabetic osteopathy” as IGF-I and its binding proteins (IGFBPs) have been shown to affect osteoblast and osteoclast activity. Design In type-2 diabetic and control rats we analyzed IGF-I and IGFBP-1 and -4 levels in serum, and notably, also the IGF-I levels in cortical bone, ankles and vertebrae by immunoassays. Osteopathy was assessed by radiography and dual energy X-ray absorptiometry. Results In the diabetic rats IGF-I was significantly reduced in serum and diaphyseal bone while IGFBP-1 and IGFBP-4 were increased in serum. The periosteal and endosteal diameters were increased in the diaphysis of humerus and tibia (changes similar to those in elderly humans) while bone mineral density was reduced in long bone metaphyses and vertebrae. Conclusions Our study demonstrates both systemic and local disturbances of the IGF-system in rats with type-2 diabetes, consistent with the observed enhanced endosteal erosion in long bone diaphyses, and osteopenia in metaphyses and vertebrae. Whether similar IGF-system changes contribute to osteopathy in patients with diabetes and if treatment of diabetes can reverse the osteopathy has yet to be explored.

Patients with type 1 diabetes often have low bone mineral density, but epidemiological data on fracture risk are sparse and imprecise, particularly for men.In the Swedish Inpatient Register, we identified a population-based cohort of 24,605 patients (12,551 men and 12,054 women) who were hospitalized for diabetes before age 31 years during 1975 through 1998. Follow-up for hip fracture was accomplished through cross-linkage in the Inpatient Register until the end of 1998. Censoring information was obtained from the registers of Death and Migration. Using the Kaplan-Meier method, we calculated the cumulative probability of getting a hip fracture. Standardized hospitalization ratios and their 95% CIs estimated relative risks with the age-, sex-, and calendar period-matched Swedish general population as reference.In total, 70 and 51 first hip fractures were ascertained in men and women, respectively, corresponding to a cumulative probability (both sexes) of 65.8/1,000 until age 65 years. Markedly elevated risks were observed in both men and women (standardized hospitalization ratios = 7.6 [95% CI 5.9-9.6] and 9.8 [7.3-12.9], respectively), increasing with follow-up time. Ophthalmic, nephropathic, neurological, and cardiovascular complications were indicators of particularly high risks.Both male and female type 1 diabetic patients are at increased risk for hip fracture. Although optimal preventive measures still need to be defined, the co-occurrence with other diabetes complications suggests that tighter metabolic control might reduce the risk.

We have previously demonstrated that Goto-Kakizaki (GK) rats with spontaneous type-2 diabetes and peripheral neuropathy exhibit regional osteopathic changes. In the present study on 18 GK rats and 21 control Wistar rats, the occurrence of the sensory neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP), and the autonomic neuropeptide Y (NPY) was analysed in bone and joints, dorsal root ganglia and lumbar spinal cord by immunohistochemistry and radioimmunoassay (RIA). Immunohistochemistry disclosed a predominance of immunoreactivities in vessel-related nerve fibers, although some were also seen in free terminals. While SP, CGRP and NPY in periosteum, cortical bone and synovium was confined to neuronal tissue, the bone marrow in addition exhibited an abundance of NPY-positive megakaryocytes. Apart from this cellular source of NPY, the observations suggest that the three neuropeptides analysed in bone and joints are of neuronal origin. Quantification by RIA showed a significant decrease of NPY in cortical bone (-36%), bone marrow (-66%) and ankle (-29%) of GK rats. CGRP was decreased in the spinal cord (-19%) and dorsal root ganglia (-26%) but was unchanged in bone and joints, as with SP. Given the suggested anabolic role of NPY and CGRP on bone, neuropeptidergic deficit in diabetes may prove to be an important factor underlying the development of regional osteopenia.

OBJECTIVE—Patients with type 1 diabetes often have low bone mineral density, but epidemiological data on fracture risk are sparse and imprecise, particularly for men. RESEARCH DESIGN AND METHODS—In the Swedish Inpatient Register, we identified a population-based cohort of 24,605 patients (12,551 men and 12,054 women) who were hospitalized for diabetes before age 31 years during 1975 through 1998. Follow-up for hip fracture was accomplished through cross-linkage in the Inpatient Register until the end of 1998. Censoring information was obtained from the registers of Death and Migration. Using the Kaplan-Meier method, we calculated the cumulative probability of getting a hip fracture. Standardized hospitalization ratios and their 95% CIs estimated relative risks with the age-, sex-, and calendar period–matched Swedish general population as reference. RESULTS—In total, 70 and 51 first hip fractures were ascertained in men and women, respectively, corresponding to a cumulative probability (both sexes) of 65.8/1,000 until age 65 years. Markedly elevated risks were observed in both men and women (standardized hospitalization ratios = 7.6 [95% CI 5.9–9.6] and 9.8 [7.3–12.9], respectively), increasing with follow-up time. Ophthalmic, nephropathic, neurological, and cardiovascular complications were indicators of particularly high risks. CONCLUSIONS—Both male and female type 1 diabetic patients are at increased risk for hip fracture. Although optimal preventive measures still need to be defined, the co-occurrence with other diabetes complications suggests that tighter metabolic control might reduce the risk.