The pattern of incident fractures according to fracture site in people with T1D.

Higher incidences of fractures are seen in people with type 1 diabetes (T1D), but knowledge on different fracture sites is sparse. We found a higher incidence mainly for distal fracture sites in people with T1D compared to controls. It must be further studied which fractures attributed to the higher incidence rates (IRs) at specific sites. INTRODUCTION: People with T1D have a higher incidence of fractures compared to the general population. However, sparse knowledge exists on the incidence rates of individual fracture sites. Therefore, we examined the incidence of various fracture sites in people with newly treated T1D compared to matched controls. METHODS: All people from the UK Clinical Practice Research Datalink GOLD (1987-2017), of all ages with a T1D diagnosis code (n = 6381), were included. People with T1D were matched by year of birth, sex, and practice to controls (n = 6381). Fracture IRs and incidence rate ratios (IRRs) were calculated. Analyses were stratified by fracture site and sex. RESULTS: The IR of all fractures was significantly higher in people with T1D compared to controls (IRR: 1.39 (CI95%: 1.24-1.55)). Compared to controls, the IRR for people with T1D was higher for several fracture sites including carpal (IRR: 1.41 (CI95%: 1.14-1.75)), clavicle (IRR: 2.10 (CI95%: 1.18-3.74)), foot (IRR: 1.70 (CI95%: 1.23-2.36)), humerus (IRR: 1.46 (CI95%: 1.04-2.05)), and tibia/fibula (IRR: 1.67 CI95%: 1.08-2.59)). In women with T1D, higher IRs were seen at the ankle (IRR: 2.25 (CI95%: 1.10-4.56)) and foot (IRR: 2.11 (CI95%: 1.27-3.50)), whereas in men with T1D, higher IRs were seen for carpal (IRR: 1.45 (CI95%: 1.14-1.86)), clavicle (IRR: 2.13 (CI95%: 1.13-4.02)), and humerus (IRR: 1.77 (CI95%: 1.10-2.83)) fractures. CONCLUSION: The incidence of carpal, clavicle, foot, humerus, and tibia/fibula fractures was higher in newly treated T1D, but there was no difference at other fracture sites compared to controls. Therefore, the higher incidence of fractures in newly treated people with T1D has been found mainly for distal fracture sites.

Association of physical activity and sedentary time with structural brain networks-The Maastricht Study.

We assessed whether objectively measured low- and high-intensity physical activity (LPA and HPA) and sedentary time (ST) were associated with white matter connectivity, both throughout the whole brain and in brain regions involved in motor function. In the large population-based Maastricht Study (n = 1715, age 59.6 ± 8.1 (mean ± standard deviation) years, and 48% women), the amounts of LPA, HPA, and ST were objectively measured during 7 days by an activPAL accelerometer. In addition, using 3T structural and diffusion MRI, we calculated whole brain node degree and node degree of the basal ganglia and primary motor cortex. Multivariable linear regression analysis was performed, and we report standardized regression coefficients (stß) adjusted for age, sex, education level, wake time, diabetes status, BMI, office systolic blood pressure, antihypertensive medication, total-cholesterol-to-HDL-cholesterol ratio, lipid-modifying medication, alcohol use, smoking status, and history of cardiovascular disease. Lower HPA was associated with lower whole brain node degree after full adjustment (stß [95%CI] = - 0.062 [- 0.101, - 0.013]; p = 0.014), whereas lower LPA (stß [95%CI] = - 0.013 [- 0.061, 0.034]; p = 0.580) and higher ST (stß [95%CI] = - 0.030 [- 0.081, 0.021]; p = 0.250) was not. In addition, lower HPA was associated with lower node degree of the basal ganglia after full adjustment (stß [95%CI] = - 0.070 [- 0.121, - 0.018]; p = 0.009). Objectively measured lower HPA, but not lower LPA and higher ST, was associated with lower whole brain node degree and node degree in specific brain regions highly specialized in motor function. Further research is needed to establish whether more HPA may preserve structural brain connectivity.

Fasting and post-oral-glucose-load levels of methylglyoxal are associated with microvascular, but not macrovascular, disease in individuals with and without (pre)diabetes: The Maastricht Study.

AIMS: Reactive dicarbonyl compounds, such as methylglyoxal (MGO), rise during an oral glucose tolerance test (OGTT), particularly in (pre)diabetes. Fasting MGO levels are associated with chronic kidney disease (CKD) and cardiovascular disease (CVD) in patients with poorly controlled type 2 diabetes mellitus (T2DM). Yet, whether fasting or post-OGTT plasma MGO levels are associated with vascular disease in people with (pre)diabetes is unknown. METHODS: Subjects with normal glucose metabolism (n=1796; age: 57.9±8.2 years; 43.3% men), prediabetes (n=478; age: 61.6±7.6 years; 54.0% men) and T2DM (n=669; age: 63.0±7.5 years; 67.0% men) from the Maastricht Study underwent OGTTs. Plasma MGO levels were measured at baseline and 2h after OGTT by mass spectrometry. Prior CVD was established via questionnaire. CKD was reflected by estimated glomerular filtration rate (eGFR) and albuminuria; retinopathy was assessed using retinal photographs. Data were analyzed using logistic regression adjusted for gender, age, smoking, systolic blood pressure, total-to-HDL cholesterol ratio, triglycerides, HbA1c, BMI and medication use. Odd ratios (ORs) were expressed per standard deviation of LN-transformed MGO. RESULTS: Fasting and post-OGTT MGO levels were associated with higher ORs for albuminuria ≥30mg/24h [fasting: 1.12 (95% CI: 0.97-1.29); post-OGTT: 1.19 (1.01-1.41)], eGFR<60mL/min/1.73 m2 [fasting: 1.58 (95% CI: 1.38-1.82), post-OGTT: 1.57 (1.34-1.83)] and retinopathy [fasting: 1.59 (95% CI: 1.01-2.53), post-OGTT: 1.38 (0.77-2.48)]. No associations with prior CVD were found. CONCLUSION: Fasting and post-OGTT MGO levels were associated with microvascular disease, but not prior CVD. Thus, therapeutic strategies directed at lowering MGO levels may prevent microvascular disease.

Burden of disease of type 2 diabetes mellitus: cost of illness and quality of life estimated using the Maastricht Study.

AIMS: To estimate the societal costs and quality of life of people with type 2 diabetes and to compare these results with those of people with normal glucose tolerance or prediabetes. METHODS: Data from 2915 individuals from the population-based Maastricht Study were included. Costs were assessed through a resource-use questionnaire completed by the participants; cost prices were based on Dutch costing guidelines. Quality of life was expressed in utilities using the Dutch EuroQol 5D-3L questionnaire and the SF-36 health survey. Based on normal fasting glucose and 2-h plasma glucose values, participants were classified into three groups: normal glucose tolerance (n = 1701); prediabetes (n = 446); or type 2 diabetes (n = 768). RESULTS: Participants with type 2 diabetes had on average 2.2 times higher societal costs than those with normal glucose tolerance (€3,006 and €1,377 per 6 months, respectively) and had lower utilities (0.77 and 0.81, respectively). No significant differences were found between participants with normal glucose tolerance and those with prediabetes. Subgroup analyses showed that higher age, being female and having two or more diabetes-related complications resulted in higher costs (P < 0.05) and lower utilities. CONCLUSIONS: This study showed that people with type 2 diabetes have substantially higher societal costs and lower quality of life than people with normal glucose tolerance. The results provide important input for future model-based economic evaluations and for policy decision-making.

Regional differences in cell-mediated immunity in people with diabetic peripheral neuropathy.

AIM: To study cell-mediated immunity in the feet of people with type 2 diabetes with polyneuropathy. METHODS: In a cohort comprising people with type 2 diabetes with polyneuropathy (n = 17) and without polyneuropathy (n = 12) and a healthy control group (n = 12) indurations due to delayed-type hypersensitivity responses to intracutaneous Candida albicans antigen were determined in the foot and compared with those in the arm (an area relatively spared in diabetic polyneuropathy). The sizes of indurations on the foot were correlated with electromyographic measurements in the participants with diabetes. RESULTS: No differences were observed in the median size of indurations between the foot and arm in healthy controls and participants without polyneuropathy; in participants with polyneuropathy, induration sizes on the foot were smaller than on the arm: 0 (95% CI 0 to 1) vs 5 (95% CI 2 to 6) mm (P < 0.01). In participants with diabetes, larger indurations correlated with better nerve function (Spearman's rho 0.35 to 0.39). CONCLUSION: Our findings suggest that diabetic peripheral polyneuropathy negatively affects cell-mediated immunity in the foot. (Clinical Trials registry no.: NCT01370837).

Preferences of people with Type 2 diabetes for diabetes care: a discrete choice experiment.

AIMS: Limited knowledge exists on the preferences of people with Type 2 diabetes towards diabetes care. Consequently, these care preferences cannot yet be considered in the development of tailored diabetes care approaches. Therefore, this study aimed to assess care preferences and their determinants in people with Type 2 diabetes. METHODS: A discrete choice experiment was conducted to elicit people's preferences. People with Type 2 diabetes, treated in 30 Dutch primary care practices, were asked to choose repeatedly between two hypothetical diabetes care packages, which differed in six attributes: role division in daily diabetes care planning, lifestyle education method, type of medication management support, consultation frequency, emotional support and time spend on self-management. A mixed-logit model was used to estimate the relative importance of the included attributes. Preference heterogeneity among people with different person- and disease-related characteristics was investigated. RESULTS: In total, 288 participants completed the experiment. They preferred to plan their daily diabetes care together with a healthcare provider, to receive individual lifestyle education, medication and emotional support from a healthcare provider, one consultation visit every 3 months and to spend less time on self-management. Participants did not prefer to receive emotional support from a psychologist. Heterogeneity in preferences could partly be explained by differences in sex, education level and glucose-lowering drug use. CONCLUSION: People with Type 2 diabetes show a preference for traditional care models. Emotional support was identified by participants as the most important attribute. It is therefore important to adequately guide them when changes in diabetes care organization are implemented.

A web-based program to improve treatment adherence in patients with type 2 diabetes: Development and study protocol.

BACKGROUND: Many patients with type 2 diabetes mellitus (T2DM) sub-optimally adhere to core treatment recommendations, such as healthy diets, sufficient physical activity and pharmacological support. This paper describes the development of the web-based computer-tailored program My Diabetes Profile (MDP), incorporating identified success factors of web-based interventions, and the protocol for testing the effectiveness of this program in a randomized multicentre trial. METHODS: Formative research - including the input of a program committee, qualitative and quantitative studies with patients and health professionals and a literature search - yielded input for the development of the MDP program. MDP provides video and text tailored advice, based on determinants and salient beliefs derived from the I-Change Model, on decreasing unhealthy snack intake, increasing physical activity, and improving adherence to both oral blood glucose lowering drugs and self-administered insulin therapy. Patients with T2DM recruited by practice nurses and diabetes nurses across the Netherlands fill in online questionnaires at baseline and six-months follow-up. Participants are randomized on patient level to the intervention group (access to the MDP program) or control group (receiving care as usual). DISCUSSION: The formative research using co-creation principles proved essential in the development of the MDP program and involved various disciplines in T2DM management including target group representatives. Co-creation revealed clearly that patients needed short and attractive messages. Consequently, a mix of video and short text messages were chosen for the ultimate program format. Pilot testing was useful to further shape the program to needs of patients and professionals. TRIAL REGISTRATION: Dutch Trial Register NTR6840; Archived program website: http://www.webcitation.org/6xXz01S7X.

The association between diabetes status, HbA1c, diabetes duration, microvascular disease, and bone quality of the distal radius and tibia as measured with high-resolution peripheral quantitative computed tomography-The Maastricht Study.

In this small cross-sectional study of predominantly well-treated participants with relatively short-term type 2 diabetes duration, HbA1c > 7% (53 mmol/mol) was associated with lower cortical density and thickness and higher cortical porosity at the distal radius, lower trabecular thickness at the distal tibia, and higher trabecular number at both sites. INTRODUCTION: To examine the association between diabetes status and volumetric bone mineral density (vBMD), bone microarchitecture and strength of the distal radius and tibia as assessed with HR-pQCT. Additionally-in participants with type 2 diabetes (T2DM), to examine the association between HbA1c, diabetes duration, and microvascular disease (MVD) and bone parameters. METHODS: Cross-sectional data from 410 (radius) and 198 (tibia) participants of The Maastricht Study (mean age 58 year, 51% female). Diabetes status (normal glucose metabolism, prediabetes, or T2DM) was based on an oral glucose tolerance test and medication history. RESULTS: After full adjustment, prediabetes and T2DM were not associated with vBMD, bone microarchitecture, and strength of the radius and tibia, except for lower trabecular number (Tb.N) of the tibia (- 4%) in prediabetes and smaller cross-sectional area of the tibia (- 7%) in T2DM. In T2DM, HbA1c > 7% was associated with lower cortical vBMD (- 5%), cortical thickness (- 16%), higher cortical porosity (+ 20%) and Tb.N (+ 9%) of the radius, and higher Tb.N (+ 9%) and lower trabecular thickness (- 13%) of the tibia. Diabetes duration > 5 years was associated with higher Tb.N (+ 6%) of the radius. The presence of MVD was not associated with any bone parameters. CONCLUSIONS: In this study with predominantly well-treated T2DM participants with relatively short-term diabetes duration, inadequate blood glucose control was negatively associated with cortical bone measures of the radius. In contrast, trabecular number was increased at both sites. Studies of larger sample size are warranted for more detailed investigations of bone density and bone quality in patients with T2DM.

The effects of angiotensin receptor neprilysin inhibition by sacubitril/valsartan on adipose tissue transcriptome and protein expression in obese hypertensive patients.

Increased activation of the renin-angiotensin system is involved in the onset and progression of cardiometabolic diseases, while natriuretic peptides (NP) may exert protective effects. We have recently demonstrated that sacubitril/valsartan (LCZ696), a first-in-class angiotensin receptor neprilysin inhibitor, which blocks the angiotensin II type-1 receptor and augments natriuretic peptide levels, improved peripheral insulin sensitivity in obese hypertensive patients. Here, we investigated the effects of sacubitril/valsartan (400 mg QD) treatment for 8 weeks on the abdominal subcutaneous adipose tissue (AT) phenotype compared to the metabolically neutral comparator amlodipine (10 mg QD) in 70 obese hypertensive patients. Abdominal subcutaneous AT biopsies were collected before and after intervention to determine the AT transcriptome and expression of proteins involved in lipolysis, NP signaling and mitochondrial oxidative metabolism. Both sacubitril/valsartan and amlodipine treatment did not significantly induce AT transcriptional changes in pathways related to lipolysis, NP signaling and oxidative metabolism. Furthermore, protein expression of adipose triglyceride lipase (ATGL) (Ptime*group = 0.195), hormone-sensitive lipase (HSL) (Ptime*group = 0.458), HSL-ser660 phosphorylation (Ptime*group = 0.340), NP receptor-A (NPRA) (Ptime*group = 0.829) and OXPHOS complexes (Ptime*group = 0.964) remained unchanged. In conclusion, sacubitril/valsartan treatment for 8 weeks did not alter the abdominal subcutaneous AT transcriptome and expression of proteins involved in lipolysis, NP signaling and oxidative metabolism in obese hypertensive patients.

The risks of sarcopenia, falls and fractures in patients with type 2 diabetes mellitus.

Fracture risk in patients with type 2 diabetes mellitus (T2DM) is increased, and the mechanism is multifactorial. Recent research on T2DM-induced bone fragility shows that bone mineral density (BMD) is often normal or even slightly elevated. However, bone turnover may be decreased and bone material and microstructural properties are altered, especially when microvascular complications are present. Besides bone fragility, extra-skeletal factors leading to an increased propensity to experience falls may also contribute to the increased fracture risk in T2DM, such as peripheral neuropathy, retinopathy and diabetes medication (e.g. insulin use). One of the probable additional contributing factors to the increased fall and fracture risks in T2DM is sarcopenia, the age-related decline in skeletal muscle mass, quality and function. Although the association between sarcopenia, fall risk, and fracture risk has been studied in the general population, few studies have examined the association between T2DM and muscle tissue and the risks of falls and fractures. This narrative review provides an overview of the literature regarding the multifactorial mechanisms leading to increased fracture risk in patients with T2DM, with a focus on sarcopenia and falls.

Development of prediction models for upper and lower respiratory and gastrointestinal tract infections using social network parameters in middle-aged and older persons -The Maastricht Study.

The ability to predict upper respiratory infections (URI), lower respiratory infections (LRI), and gastrointestinal tract infections (GI) in independently living older persons would greatly benefit population and individual health. Social network parameters have so far not been included in prediction models. Data were obtained from The Maastricht Study, a population-based cohort study (N = 3074, mean age (±s.d.) 59.8 ± 8.3, 48.8% women). We used multivariable logistic regression analysis to develop prediction models for self-reported symptomatic URI, LRI, and GI (past 2 months). We determined performance of the models by quantifying measures of discriminative ability and calibration. Overall, 953 individuals (31.0%) reported URI, 349 (11.4%) LRI, and 380 (12.4%) GI. The area under the curve was 64.7% (95% confidence interval (CI) 62.6-66.8%) for URI, 71.1% (95% CI 68.4-73.8) for LRI, and 64.2% (95% CI 61.3-67.1%) for GI. All models had good calibration (based on visual inspection of calibration plot, and Hosmer-Lemeshow goodness-of-fit test). Social network parameters were strong predictors for URI, LRI, and GI. Using social network parameters in prediction models for URI, LRI, and GI seems highly promising. Such parameters may be used as potential determinants that can be addressed in a practical intervention in older persons, or in a predictive tool to compute an individual's probability of infections.

Exploring beliefs on diabetes treatment adherence among Dutch type 2 diabetes patients and healthcare providers.

OBJECTIVE: Despite well-known beneficial effects, adherence to core elements of diabetes treatment is suboptimal. This study, conducted in the Netherlands, aimed to explore if and how treatment adherence success factors are applied in diabetes consultations, and to explore salient personal beliefs about type 2 diabetes treatment including both healthy lifestyle adaptations and pharmacotherapy. METHODS: A qualitative study using semi-structured interviews among nine Dutch healthcare providers predominantly involved in diabetes management and 19 Dutch type 2 diabetes patients. Data was systematically analysed through deductive coding analysis using Nvivo. RESULTS: Most patients visited their consultations unprepared. Patients did not or vaguely experience goal-setting in consultations, whereas healthcare providers indicated to set treatment goals. Shared-decision making was applied, however patients were rather passive collaborators as mostly healthcare providers were in charge of making treatment decisions. Despite suboptimal treatment adherence, many advantages and few disadvantages of treatment strategies were reported. Adherence self-efficacy was lower in situations outside daily routine. CONCLUSION: Treatment adherence success factors are not optimally applied, and in particular treatment adherence self-efficacy could be improved. PRACTICE IMPLICATIONS: The application of treatment adherence success factors in consultations could be improved, and personal beliefs should be addressed to improve treatment adherence and optimize counselling.

[A multidisciplinary approach in diabetic foot disease is mandatory]. / De diabetische voet vereist multidisciplinaire aanpak.

The history of two patients (66- and 53-year-old males) with diabetes and peripheral neuropathy illustrates the variety of clinical presentations and pitfalls in treatment of diabetic foot ulcers. Peripheral arterial disease and mechanical stress as a consequence of peripheral neuropathy are important risk factors for developing an ulcer and eventually loss of a limb. Revascularisation of the limb should be considered in the presence of critical limb ischaemia or in the presence of mild to severe ischaemia in combination with a deep infection. Infection is a major threat to the affected limb and requires treatment directly after taking samples for culture. After healing, education, adequate offloading and frequent foot examinations are important for secondary prevention. Presentation of these patients to a special multidisciplinary team, including a vascular surgeon, endocrinologist, rehabilitation specialist, cast technician, shoe technician and a podiatrist is mandatory, according to the Dutch guidelines on the diabetic foot.

Sedentary behaviour and bone health in children, adolescents and young adults: a systematic review-supplementary presentation.

BACKGROUND: Sedentary behaviour (SB) is a potential risk factor for suboptimal bone deposition in youth. RESULTS: Total SB was negatively associated with lower extremity bone outcomes, while no association was observed with total body bone outcomes. Insufficient evidence was found for an association between total SB and lumbar spine bone outcomes. CONCLUSION: This review highlights the heterogeneity of the available evidence and emphasizes the need for well-designed studies.

Individual and partner's level of occupation and the association with HbA1c levels in people with Type 2 diabetes mellitus: the Dutch Diabetes Pearl cohort.

AIMS: Individual indicators of socio-economic status have been associated with glycaemic control in people with Type 2 diabetes, but little is known about the association between partner's socio-economic status and HbA1c levels. We therefore examined the cross-sectional association between individual and partner's level of occupation on HbA1c levels in people with Type 2 diabetes in the Netherlands. METHODS: We included people with Type 2 diabetes with a partner who were treated in primary, secondary and tertiary care in the Diabetes Pearl cohort. Occupational level was classified according to International Standard Classification of Occupations (ISCO)-08 skill levels. Linear regression analyses were performed stratified for sex, and corrected for age, recruitment centre and diabetes medication. RESULTS: In total, 3257 participants (59.8% men, mean 62.2±9.4 years) were included. For men, having a partner with an intermediate level of occupation was associated with lower HbA1c levels [e.g. ISCO level 3: -2 mmol/mol (95% CI -4;-1) or -0.2% (95% CI -0.4;-0.1)], compared with having a partner of the highest occupational level (ISCO level 4). In women, having an unemployed partner was associated with higher HbA1c levels [14 mmol/mol (95% CI 6; 22) or 1.3% (95% CI 0.6; 2.0)], compared with having a partner of the highest occupational level. CONCLUSIONS: Partner's occupational status provided additional information on the association between socio-economic status and HbA1c levels in people with Type 2 diabetes. Women seemed to benefit from a partner with a higher occupational status, while men seemed to benefit from a partner with a lower status. Because of the cross-sectional nature of the present study, more research is necessary to explore this association.

Sedentary behaviour and bone health in children, adolescents and young adults: a systematic review.

Sedentary behaviour (SB) is increasing in Western societies and some studies suggest a deleterious effect of SB on bone. The aim of this systematic review was to examine the association between SB and bone health in children, adolescents and young adults. Electronic databases (PubMed, MEDLINE, PsycINFO and Science Citation Index) were searched for relevant articles up to January 9, 2017. Studies were included when results on bone health (e.g. strength, mass and structure) and either subjectively (questionnaires) or objectively (accelerometry) measured SB were reported in healthy participants ≤24 years. Two reviewers independently screened titles and abstracts for eligibility, rated methodological quality and extracted data. Seventeen observational studies were included. Several studies that used DXA or quantitative ultrasound suggested that objectively measured SB was negatively associated with lower extremity bone outcomes, such as femoral neck bone mineral density. The magnitude of this negative association was small and independent of moderate-to-vigorous physical activity. In contrast to the lower extremities, there was insufficient evidence for an association of lumbar spine bone outcomes with objectively measured SB. In high-quality studies that used DXA, no association was observed between objectively measured SB and total body bone outcomes. In studies using questionnaires, none of these relationships were observed. Well-designed longitudinal studies, objectively measuring SB, are needed to further unravel the effect of SB, physical activity and their interaction on bone health.

The association between insulin use and volumetric bone mineral density, bone micro-architecture and bone strength of the distal radius in patients with type 2 diabetes - The Maastricht study.

Type 2 diabetes mellitus (T2DM) has been associated with an increased risk of fractures, despite normal to increased bone mineral density (BMD). Insulin use is one of the factors linked to this increased fracture risk. However, direct negative effects of insulin on bone quality are not expected since insulin is thought to be anabolic to bone. In this cross-sectional study the association between insulin use and volumetric BMD (vBMD), bone micro-architecture and bone strength of the distal radius, as measured with HR-pQCT, was examined. Data from 50 participants with T2DM of The Maastricht Study (mean age 62±7.5years, 44% women) was used. Participants were classified as insulin user (n=13) or non-insulin user (n=37) based on prescription data. Linear regression analysis was used to estimate the association between current insulin use and HR-pQCT derived parameters. After adjustment for age, sex, body mass index, glycated hemoglobin A1c and T2DM duration, insulin use was associated with lower total vBMD (standardized beta (ß):-0.56 (95% CI:-0.89 to -0.24)), trabecular vBMD (ß:-0.58 (95% CI:-0.87 to -0.30)), trabecular thickness (ß:-0.55 (95% CI:-0.87 to -0.23)), cortical thickness (ß:-0.41 (95% CI:-0.74 to -0.08)), log cortical pore volume (ß:-0.43 (95% CI:-0.73 to -0.13)), bone stiffness (ß:-0.39 (95% CI:-0.62 to -0.17)) and failure load (ß:-0.39 (95% CI:-0.60 to -0.17)) when compared to the non-insulin users. Insulin use was not associated with cortical vBMD, trabecular number, trabecular separation, cortical porosity and cortical pore diameter. This study indicates that insulin use is negatively associated with bone density, bone micro-architectural and bone strength parameters. These findings may partly explain the previously observed increased fracture risk in insulin users, although there may be residual confounding by other factors related to disease severity in insulin users.

Prevention and management of foot problems in diabetes: A Summary Guidance for Daily Practice 2015, based on the IWGDF guidance documents.

Foot problems complicating diabetes are a source of major patient suffering and societal costs. To prevent, or at least reduce, the adverse effects of foot problems in diabetes, the International Working Group on the Diabetic Foot (IWGDF; www.iwgdf.org) was founded in 1996, consisting of experts from almost all the disciplines involved in the care of patients with diabetes and foot problems. An important output of the IWGDF is the international consensus guidance, continuously updated since 1999. To date, the publications have been translated into 26 languages, and more than 100,000 copies have been distributed globally. The "Summary Guidance for Daily Practice" summarises the essentials of prevention and management of foot problems in persons with diabetes for clinicians who work with these patients on a daily basis. This guidance is the result of a long and careful process that started with the empaneling in 2013 of five working groups consisting of 49 international experts. These experts performed seven targeted systematic reviews to provide the evidence supporting the five chapters of the IWGDF Guidance on prevention; footwear and offloading; diagnosis, prognosis and management of peripheral artery disease; diagnosis and management of foot infections; interventions to enhance healing. In total almost 80,000 studies were detected by our literature review. After review of the title and abstract the reviewers of the different working groups selected only studies that fulfilled a minimal set of quality criteria and ended up with 429 articles for complete quality analysis. The GRADE system was used to translate the evidence from the studies into recommendations for daily clinical practice. The rating of each recommendation takes into account both the strength and the quality of the evidence. The IWGDF Guidance 2015 makes a total of 77 recommendations on prevention and management of foot problems in diabetes. These recommendations were condensed by the editorial board into this "Summary Guidance". Encouraging and aiding clinicians to follow the evidence-based recommendations of the IWGDF Guidance 2015, and in particular the principles outlined in the "Summary Guidance", will likely result in a worldwide reduction in, and better outcomes of, foot problems in persons with diabetes, helping to reduce the morbidity and mortality associated with this major health problem.

Minor amputation does not negatively affect health-related quality of life as compared with conservative treatment in patients with a diabetic foot ulcer: An observational study.

BACKGROUND: Health-related quality of life (HRQoL) is poor in patients with persistent diabetic foot ulcers and poor HRQoL predicts worse outcomes in these patients. Amputation is often considered a treatment failure, which is why conservative treatment is generally preferred over amputation. However, it is unclear whether minor amputation negatively affects HRQoL compared with conservative treatment in patients with diabetic foot ulcers. METHODS: In the cohort of the multicenter, prospective, observational Eurodiale study, we determined difference in change of HRQoL measured by EQ-5D between patients with a diabetic foot ulcers that healed after conservative treatment (n = 676) and after minor amputation (n = 145). Propensity score was used to adjust for known confounders, attempting to overcome lack of randomization. RESULTS: Baseline HRQoL was not significantly different between patients treated conservatively and undergoing minor amputation. In addition, there was no difference in the change of HRQoL between these groups. In patients who healed 6 to 12 months after the first visit, HRQoL on the anxiety/depression subscale even appeared to improve more in those who underwent minor amputation. CONCLUSIONS: Minor amputation was not associated with a negative impact on HRQoL in patients with a diabetic foot ulcers. It may therefore not be considered treatment failure in terms of HRQoL but rather a viable treatment option. A randomized controlled trial is warranted to further examine the influence of minor amputations on health-related quality of life.