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.

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.

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.

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.

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.

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.

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.

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.

The association between glucose metabolism status, diabetes severity and a history of fractures and recent falls in participants of 50 years and older-the Maastricht Study.

In this cohort of relatively young and well-treated participants with type 2 diabetes, we found no association between diabetes status and a history of previous fractures and recent falls. Furthermore, no association between diabetes severity and previous fractures or recent falls was found. INTRODUCTION: In this study, we examined the association between glucose metabolism status and historical fractures or recent falls and the effect of diabetes severity (glucose control, insulin use, and diabetes duration) on falls and fractures in the participants with type 2 diabetes. METHODS: Cross-sectional data from 2005 participants of the Maastricht Study. Falls in the past 6 months and fractures ≥age 50 were assessed by questionnaire. Glucose metabolism status (normal glucose metabolism, impaired glucose metabolism, or type 2 diabetes) was based on the oral glucose tolerance test and medication use. RESULTS: In the completely adjusted model, the odds for a fall were not significantly higher in those with impaired glucose metabolism status (OR (95%CI) 1.28 (0.93-1.77)) or with type 2 diabetes (OR (95%CI) 1.21 (0.80-1.81)) compared with the group with normal glucose metabolism. Within the group with type 2 diabetes, there were no significant differences with regard to reported falls between participants with HbA1c >7 % (53 mmol/mol) versus HbA1c ≤7 % (OR (95%CI) 1.05 (0.58-1.90)), insulin users versus non-insulin users (OR (95%CI) 1.51 (0.79-2.89)), and with a diabetes duration >5 versus ≤5 years (OR (95%CI) 0.52 (0.46-1.47)). Similarly, neither glucose metabolism status nor diabetes severity was associated with prior fractures. CONCLUSIONS: Glucose metabolism status was not significantly associated with previous fractures and recent falls. In addition, in this cohort of relatively young and well-treated participants with type 2 diabetes, diabetes severity was not associated with previous fractures and recent falls.

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

In this 'Summary Guidance for Daily Practice', we describe the basic principles of prevention and management of foot problems in persons with diabetes. This summary is based on the International Working Group on the Diabetic Foot (IWGDF) Guidance 2015. There are five key elements that underpin prevention of foot problems: (1) identification of the at-risk foot; (2) regular inspection and examination of the at-risk foot; (3) education of patient, family and healthcare providers; (4) routine wearing of appropriate footwear; and (5) treatment of pre-ulcerative signs. Healthcare providers should follow a standardized and consistent strategy for evaluating a foot wound, as this will guide further evaluation and therapy. The following items must be addressed: type, cause, site and depth, and signs of infection. There are seven key elements that underpin ulcer treatment: (1) relief of pressure and protection of the ulcer; (2) restoration of skin perfusion; (3) treatment of infection; (4) metabolic control and treatment of co-morbidity; (5) local wound care; (6) education for patient and relatives; and (7) prevention of recurrence. Finally, successful efforts to prevent and manage foot problems in diabetes depend upon a well-organized team, using a holistic approach in which the ulcer is seen as a sign of multi-organ disease, and integrating the various disciplines involved.

Performance of prognostic markers in the prediction of wound healing or amputation among patients with foot ulcers in diabetes: a systematic review.

Prediction of wound healing and major amputation in patients with diabetic foot ulceration is clinically important to stratify risk and target interventions for limb salvage. No consensus exists as to which measure of peripheral artery disease (PAD) can best predict outcomes. To evaluate the prognostic utility of index PAD measures for the prediction of healing and/or major amputation among patients with active diabetic foot ulceration, two reviewers independently screened potential studies for inclusion. Two further reviewers independently extracted study data and performed an assessment of methodological quality using the Quality in Prognostic Studies instrument. Of 9476 citations reviewed, 11 studies reporting on 9 markers of PAD met the inclusion criteria. Annualized healing rates varied from 18% to 61%; corresponding major amputation rates varied from 3% to 19%. Among 10 studies, skin perfusion pressure ≥ 40 mmHg, toe pressure ≥ 30 mmHg (and ≥ 45 mmHg) and transcutaneous pressure of oxygen (TcPO2 ) ≥ 25 mmHg were associated with at least a 25% higher chance of healing. Four studies evaluated PAD measures for predicting major amputation. Ankle pressure < 70 mmHg and fluorescein toe slope < 18 units each increased the likelihood of major amputation by around 25%. The combined test of ankle pressure < 50 mmHg or an ankle brachial index (ABI) < 0.5 increased the likelihood of major amputation by approximately 40%. Among patients with diabetic foot ulceration, the measurement of skin perfusion pressures, toe pressures and TcPO2 appear to be more useful in predicting ulcer healing than ankle pressures or the ABI. Conversely, an ankle pressure of < 50 mmHg or an ABI < 0.5 is associated with a significant increase in the incidence of major amputation.

Effectiveness of bedside investigations to diagnose peripheral artery disease among people with diabetes mellitus: a systematic review.

Non-invasive tests for the detection of peripheral artery disease (PAD) among individuals with diabetes mellitus are important to estimate the risk of amputation, ulceration, wound healing and the presence of cardiovascular disease, yet there are no consensus recommendations to support a particular diagnostic modality over another and to evaluate the performance of index non-invasive diagnostic tests against reference standard imaging techniques (magnetic resonance angiography, computed tomography angiography, digital subtraction angiography and colour duplex ultrasound) for the detection of PAD among patients with diabetes. Two reviewers independently screened potential studies for inclusion and extracted study data. Eligible studies evaluated an index test for PAD against a reference test. An assessment of methodological quality was performed using the quality assessment for diagnostic accuracy studies instrument. Of the 6629 studies identified, ten met the criteria for inclusion. In these studies, the patients had a median age of 60-74 years and a median duration of diabetes of 9-24 years. Two studies reported exclusively on patients with symptomatic (ulcerated/infected) feet, two on patients with asymptomatic (intact) feet only, and the remaining six on patients both with and without foot ulceration. Ankle brachial index (ABI) was the most widely assessed index test. Overall, the positive likelihood ratio and negative likelihood ratio (NLR) of an ABI threshold <0.9 ranged from 2 to 25 (median 8) and <0.1 to 0.7 (median 0.3), respectively. In patients with neuropathy, the NLR of the ABI was generally higher (two out of three studies), indicating poorer performance, and ranged between 0.3 and 0.5. A toe brachial index <0.75 was associated with a median positive likelihood ratio and NLRs of 3 and ≤ 0.1, respectively, and was less affected by neuropathy in one study. Also, in two separate studies, pulse oximetry used to measure the oxygen saturation of peripheral blood and Doppler wave form analyses had NLRs of 0.2 and <0.1. The reported performance of ABI for the diagnosis of PAD in patients with diabetes mellitus is variable and is adversely affected by the presence of neuropathy. Limited evidence suggests that toe brachial index, pulse oximetry and wave form analysis may be superior to ABI for diagnosing PAD in patients with neuropathy with and without foot ulcers. There were insufficient data to support the adoption of one particular diagnostic modality over another and no comparisons existed with clinical examination. The quality of studies evaluating diagnostic techniques for the detection of PAD in individuals with diabetes is poor. Improved compliance with guidelines for methodological quality is needed in future studies.

Effectiveness of revascularization of the ulcerated foot in patients with diabetes and peripheral artery disease: a systematic review.

Symptoms or signs of peripheral artery disease (PAD) can be observed in up to 50% of the patients with a diabetic foot ulcer and is a risk factor for poor healing and amputation. In 2012, a multidisciplinary working group of the International Working Group on the Diabetic Foot published a systematic review on the effectiveness of revascularization of the ulcerated foot in patients with diabetes and PAD. This publication is an update of this review and now includes the results of a systematic search for therapies to revascularize the ulcerated foot in patients with diabetes and PAD from 1980 to June 2014. Only clinically relevant outcomes were assessed. The research conformed to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, and Scottish Intercollegiate Guidelines Network methodological scores were assigned. A total of 56 articles were eligible for full-text review. There were no randomized controlled trials, but there were four nonrandomized studies with a control group. The major outcomes following endovascular or open bypass surgery were broadly similar among the studies. Following open surgery, the 1-year limb salvage rates were a median of 85% (interquartile range of 80-90%), and following endovascular revascularization, these rates were 78% (70-89%). At 1-year follow-up, 60% or more of ulcers had healed following revascularization with either open bypass surgery or endovascular techniques. Studies appeared to demonstrate improved rates of limb salvage associated with revascularization compared with the results of conservatively treated patients in the literature. There were insufficient data to recommend one method of revascularization over another. There is a real need for standardized reporting of baseline demographic data, severity of disease and outcome reporting in this group of patients.

Lower verbal intelligence is associated with diabetic complications and slower walking speed in people with Type 2 diabetes: the Maastricht Study.

AIMS: To determine the association of verbal intelligence, a core constituent of health literacy, with diabetic complications and walking speed in people with Type 2 diabetes. METHODS: This study was performed in 228 people with Type 2 diabetes participating in the Maastricht Study, a population-based cohort study. We examined the cross-sectional associations of score on the vocabulary test of the Groningen Intelligence Test with: 1) determinants of diabetic complications (HbA1c , blood pressure and lipid level); 2) diabetic complications: chronic kidney disease, neuropathic pain, self-reported history of cardiovascular disease and carotid intima-media thickness; and 3) walking speed. Analyses were performed using linear regression and adjusted in separate models for potential confounders and mediators. Significant age- and sex-adjusted associations were additionally adjusted for educational level in a separate model. RESULTS: After full adjustment, lower verbal intelligence was associated with the presence of neuropathic pain [odds ratio (OR) 1.18, 95% CI 1.02;1.36], cardiovascular disease (OR 1.14, 95% CI 1.01;1.30), and slower walking speed (regression coefficient -0.011 m/s, 95% CI -0.021; -0.002 m/s). These associations were largely explained by education. Verbal intelligence was not associated with blood pressure, glycaemic control, lipid control, chronic kidney disease or carotid intima-media thickness. CONCLUSIONS: Lower verbal intelligence was associated with the presence of some diabetic complications and with a slower walking speed, a measure of physical functioning. Educational level largely explained these associations. This implies that clinicians should be aware of the educational level of people with diabetes and should provide information at a level of complexity tailored to the patient.

Diagnosis and assessment of peripheral arterial disease in the diabetic foot.

Approximately half of all patients with a diabetic foot ulcer have co-existing peripheral arterial disease. Identifying peripheral arterial disease among patients with foot ulceration is important, given its association with failure to heal, amputation, cardiovascular events and increased risk of premature mortality. Infection, oedema and neuropathy, often present with ulceration, may adversely affect the performance of diagnostic tests that are reliable in patients without diabetes. Early recognition and expert assessment of peripheral arterial disease allows measures to be taken to reduce the risk of amputation and cardiovascular events, while determining the need for revascularization to promote ulcer healing. When peripheral arterial disease is diagnosed, the extent of perfusion deficit should be measured. Patients with a severe perfusion deficit, likely to affect ulcer healing, will require further imaging to define the anatomy of disease and indicate whether a revascularization procedure is appropriate.

Importance of factors determining the low health-related quality of life in people presenting with a diabetic foot ulcer: the Eurodiale study.

AIM: To identify the factors responsible for the low health-related quality of life associated with foot ulcers and the relative importance of these factors. METHODS: A total of 1232 patients with a new foot ulcer, who presented at one of the 14 centres in 10 European countries participating in the Eurodiale study, were included in this cross-sectional study. Patient and ulcer characteristics were obtained as well as results from the Euro-Qol-5D questionnaire, a health-related quality of life instrument with five domains (mobility, self-care, usual activities, pain/discomfort and anxiety/depression). To analyse the relative importance of comorbidities and ulcer- and patient-related factors for health-related quality of life, linear regression models were used to calculate the relative contributions of each factor to the fit (R(2) ) of the model. RESULTS: Patients reported poor overall health-related quality of life, with problems primarily in the mobility and pain/discomfort domains. Among the comorbidities, the inability to stand or walk without help was the most important determinant of decreased health-related quality of life in all five domains. Among ulcer-related factors, ulcer size, limb-threatening ischaemia and elevated C-reactive protein concentration also had high importance in all domains. The clinical diagnosis of infection, peripheral arterial disease and polyneuropathy were only important in the pain/discomfort domain. CONCLUSIONS: The factors that determine health-related quality of life are diverse and to an extent not disease-specific. To improve health-related quality of life, treatment should not only be focused on ulcer healing but a multifactorial approach by a specialized multidisciplinary team is also important.

Evidence-based management of PAD & the diabetic foot.

Diabetic foot ulceration (DFU) is associated with high morbidity and mortality, and represents the leading cause of hospitalization in patients with diabetes. Peripheral arterial disease (PAD), present in half of patients with DFU, is an independent predictor of limb loss and can be difficult to diagnose in a diabetic population. This review focuses on the evidence for therapeutic strategies in the management of patients with DFU. We highlight the importance of timely referral of patients presenting with a new foot ulcer to a multidisciplinary team, which includes vascular surgeons and interventional radiologists.

Efficacy and safety of IV/PO moxifloxacin and IV piperacillin/tazobactam followed by PO amoxicillin/clavulanic acid in the treatment of diabetic foot infections: results of the RELIEF study.

OBJECTIVE: The aim was to compare the efficacy and safety of two antibiotic regimens in patients with diabetic foot infections (DFIs). METHODS: Data of a subset of patients enrolled in the RELIEF trial with DFIs requiring surgery and antibiotics were evaluated retrospectively. DFI was diagnosed on the basis of the modified Wagner, University of Texas, and PEDIS classification systems. Patients were randomized to receive either intravenous/oral moxifloxacin (MXF, N = 110) 400 mg q.d. or intravenous piperacillin/tazobactam 4.0/0.5 g t.d.s. followed by oral amoxicillin/clavulanate 875/125 mg b.d. (PIP/TAZ-AMC, N = 96), for 7-21 days until the end of treatment (EOT). The primary endpoint was clinical cure rates in the per-protocol (PP) population at the test-of-cure visit (TOC, 14-28 days after EOT). RESULTS: There were no significant differences between the demographic characteristics of PP patients in either treatment group. At TOC, MXF and PIP/TAZ-AMC had similar efficacy in both the PP and intent-to-treat (ITT) populations: MXF: 76.4 % versus PIP/TAZ-AMC: 78.1 %; 95 % confidence interval (CI) -14.5 %, 9.0 % in the PP population; MXF: 69.9 % versus PIP/TAZ-AMC: 69.1 %; 95 % CI -12.4 %, 12.1 % in the ITT population. The overall bacteriological success rates were similar in both treatment groups (MXF: 71.7 % versus PIP/TAZ-AMC: 71.8 %; 95 % CI -16.9 %, 10.7 %). A similar proportion of patients (ITT population) experienced any adverse events in both treatment groups (MXF: 30.9 % versus PIP/TAZ-AMC: 31.8 %, respectively). Death occurred in three MXF-treated patients and one PIP/TAZ-AMC-treated patient; these were unrelated to the study drugs. CONCLUSION: Moxifloxacin has shown favorable safety and efficacy profiles in DFI patients and could be an alternative antibiotic therapy in the management of DFI. CLINICAL TRIAL: NCT00402727.

Prevention of the metabolic syndrome in IGT subjects in a lifestyle intervention: results from the SLIM study.

BACKGROUND AND AIMS: The Study on Lifestyle intervention and Impaired glucose tolerance Maastricht (SLIM), a randomized controlled trial, directed at diet and physical activity in impaired glucose tolerant subjects was effective to improve glucose tolerance and prevent type 2 diabetes. The aim of this study was to determine the effects of the SLIM lifestyle intervention on the incidence and prevalence of the metabolic syndrome (MetS) during the active intervention and four years thereafter. METHODS AND RESULTS: MetS was diagnosed according to the NCEP ATP III criteria. At baseline, 66.4% of all participants (n = 146, age 57 ± 7 years, BMI 29.7 ± 3.6, 51.3% female) fulfilled the criteria for MetS. No significant difference in MetS prevalence was observed between the intervention (63.9%) and control group (68.9%). At the end of active intervention (average duration 4.2 ± 2.0 years), prevalence of MetS was significantly lower in the intervention group (52.6%, n = 57) compared to the control group (74.6%, n = 59) (p = 0.014). Furthermore, in participants without MetS at baseline, cumulative incidence of MetS was 18.2% in the intervention group at the end of active intervention, compared to 73.7% in the control group (Log-rank test, p = 0.011). Four years after stopping active intervention, the reduced incidence of MetS was maintained (Log-rank test, p = 0.002). CONCLUSION: In conclusion, a combined diet-and-exercise intervention to improve glucose tolerance, not only prevented type 2 diabetes, but also reduced the prevalence of MetS and prevented MetS development, showing the long-term impact of lifestyle intervention on cardiovascular risk reduction.