Laser therapy for onychomycosis in patients with diabetes at risk for foot ulcers: a randomized, quadruple-blind, sham-controlled trial (LASER-1).

BACKGROUND: Patients with diabetes mellitus are at high risk for onychomycosis, which is related to the development of foot ulcers. OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of the treatment of onychomycosis with local laser therapy. METHODS: In a single-centre, randomized (1:1), quadruple-blind, sham-controlled trial, patients and microbiological confirmation with diabetes mellitus, at risk for developing diabetic foot ulcers (Sims classification score 1, 2) and a clinical suspicion on onychomycosis, were randomized to either four sessions neodymium-doped yttrium aluminium garnet (Nd-YAG) 1064 nm laser or sham treatment. The primary outcome was clinical and microbiological cure of onychomycosis after 1-year follow-up. RESULTS: From March 2015 to July 2016, 64 patients were randomized; 63 could be analysed. Trichophyton rubrum was the most detected pathogen. There was no difference in the primary outcome between laser and sham treatment. With the exception of a subungual haematoma in the fifth toenail occurring 2 weeks after laser treatment, the results suggested that treatment with Nd-YAG 1064 nm laser is safe. CONCLUSION: At this moment, there is no evidence of any effect of laser treatment for onychomycosis in patients with diabetes at increased risk for foot ulcers, at least not within 1 year after treatment.

Active participation of patients with type 2 diabetes in consultations with their primary care practice nurses - what helps and what hinders: a qualitative study.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) receiving primary care regularly visit their practice nurses (PNs). By actively participating during medical consultations, patients can better manage their disease, improving clinical outcomes and their quality of life. However, many patients with T2DM do not actively participate during medical consultations. To understand the factors affecting engagement of patients with T2DM, this study aimed to identify factors that help or hinder them from actively participating in consultations with their primary care PNs. METHODS: Two semi-structured focus groups and 12 semi-structured individual interviews were conducted with patients with T2DM (n = 20) who were undergoing treatment by primary care PNs. All interviews were transcribed verbatim and analyzed using a two-step approach derived from the context-mapping framework. RESULTS: Four factors were found to help encourage patients to actively participate in their consultation: developing trusting relationships with their PNs, having enough time in the appointment, deliberately preparing for consultations, and allowing for the presence of a spouse. Conversely, four factors were found to hinder patients from participating during consultations: lacking the need or motivation to participate, readjusting to a new PN, forgetting to ask questions, and ineffectively expressing their thoughts. CONCLUSION: Patients lacked the skills necessary to adequately prepare for a consultation and achieve an active role. In addition, patients' keen involvement appeared to benefit from a trusting relationship with their PNs. When active participation is impeded by barriers such as a lack of patient's skills, facilitators should be introduced at an early stage. TRIAL REGISTRATION: Current Controlled Trials NTR4693 (July 16, 2014).

Healthcare reimbursement costs of children with type 1 diabetes in the Netherlands, a observational nationwide study (Young Dudes-4).

BACKGROUND: Type 1 diabetes mellitus (T1DM) is one of the most common chronic diseases in children. Studies on costs related to T1DM are scarce and focused primarily on the costs directly related to diabetes. We aimed to investigate both the overall healthcare costs and the more specific costs related to the management of diabetes. METHODS: This is a retrospective and observational, nationwide cohort study of all Dutch children (aged 0-18 years) with T1DM. Data were collected from the national registry for healthcare reimbursement, in which all Dutch insurance companies combine their reimbursement data. In the Netherlands for all Dutch citizens health care is covered by law and all children are treated by hospital-based paediatricians. RESULTS: We analysed 6710 children distributed over 81 hospitals: 475 children in 6 university hospitals and 6235 children in 75 general hospitals. Total reimbursement for all children with T1DM over the period 2009 to 2011 was € 167,494,732 corresponding to an annual mean of € 55,831,577 of total costs and € 8326 euros per child. When comparing small (between 26 and 54 patients), medium (57-84 patients) and large (88-248 patients) general hospitals, costs per patient were highest in the hospitals with the highest number of T1DM patients. The costs for devices, secondary care and pharmaceutics had most impact on total expenditures. Over the study period, there was a slight decrease in per person costs. CONCLUSION: The overall health expenditure of a child with T1DM is more than € 8000 per patient per annum. Given the move towards more device-intensive multidisciplinary care for these patients, the costs of treating T1DM in children are likely to increase further in the coming years.

Association Between Orthostatic Hypotension and Handgrip Strength With Successful Rehabilitation in Elderly Hip Fracture Patients.

OBJECTIVE: To investigate the relationship between orthostatic hypotension (OH) and muscle strength versus time to successful rehabilitation within elderly patients with hip fracture. DESIGN: A prospective, observational cohort study. Handgrip strength was measured at the day of admission and OH as soon as possible after surgery. Cox proportional hazard modeling was used to investigate the relationship between OH or handgrip strength (kg) and time to successful rehabilitation, expressed as hazard ratios (HRs). OH was defined as a decrease in systolic blood pressure of ≥20mmHg or diastolic blood pressure of ≥10mmHg after postural change (dichotomous). Handgrip strength was measured with a hand dynamometer (continuous). SETTING: General hospital. PARTICIPANTS: Patients (N=116) aged ≥70 years with a hip fracture were recruited on the day of hospital admission. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Primary outcome was time to successful rehabilitation, which was defined as discharge to patients' own homes. RESULTS: During a median follow-up period of 36 days (interquartile range, 9-57d), 103 patients (89%) were successfully rehabilitated. No statistically significant relationships were found between OH and time to successful rehabilitation (HR=1.05; 95% confidence interval [CI], .67-1.66). Also, handgrip strength and successful rehabilitation were not statistically significantly related (HR=1.03; 95% CI, .99-1.06). CONCLUSIONS: OH measured during the first days of hospitalization is not related to time to successful rehabilitation in patients with hip fracture who have undergone surgery. Although no significant relationship was seen in the present study, the width of the CIs does not exclude a relevant relationship between handgrip strength and time to successful rehabilitation.

Intraperitoneal insulin infusion: treatment option for type 1 diabetes resulting in beneficial endocrine effects beyond glycaemia.

Continuous intraperitoneal insulin infusion (CIPII) is a treatment option for patients with type 1 diabetes mellitus who fail to reach adequate glycaemic control despite intensive subcutaneous (SC) insulin therapy. CIPII has clear advantages over SC insulin administration in terms of pharmacokinetic and pharmacodynamic properties and has been shown to improve glycaemic regulation. Due to the delivery of insulin predominantly in the portal vein, as opposed to systemically, CIPII offers a unique research model to investigate the effects of insulin on endocrine and metabolic parameters in vivo. The aim of the present article is to provide an overview of the literature with respect to the effects of CIPII on glucose management, quality of life, complications and costs, with additional focus on metabolic and endocrine aspects. Finally, future use and research objectives are discussed.

Excess mortality in mothers of patients with polycystic ovary syndrome.

STUDY QUESTION: Do diabetic parents of patients with polycystic ovary syndrome (PCOS) encounter excess mortality compared with the mortality of men and women with type 2 diabetes, recruited without selection for PCOS? SUMMARY ANSWER: Type 2 diabetes among mothers of PCOS patients results in excess mortality compared with women with diabetes from the general population. WHAT IS KNOWN ALREADY: Insulin resistance is a prominent feature of PCOS. Because of the heritable nature of PCOS, parents of these patients are also prone to develop type 2 diabetes mellitus, which might influence their life expectancy. STUDY DESIGN, SIZE, DURATION: This reverse parent-offspring study included 946 mothers and 902 fathers of patients with PCOS. PARTICIPANTS/MATERIALS, SETTING, METHODS: The medical history of the parents was primarily obtained during the initial screening of each patient and updated via questionnaires. Mortality data of these parents were compared with the mortality rates of the general Dutch population and with mortality rates of a control population consisting of 1353 men and women diagnosed with type 2 diabetes mellitus. The standardized mortality ratio (SMR) was calculated as the ratio of the observed mortality of the parents to the expected mortality in the general Dutch population. The mortality of parents with type 2 diabetes mellitus relative to controls with diabetes but not related to anyone with PCOS was standardized for age, gender and calendar period using Poisson regression. MAIN RESULTS AND ROLE OF CHANCE: In total, 302 parents were deceased in 62 693 person-years. Mothers above age 60 had a significant excess mortality of 1.50 (95% CI 1.15-1.92) compared with the general Dutch population. Moreover, mothers with diabetes had two-times higher mortality risk compared with control women with diabetes (RR 2.0, 95% CI 1.19-3.41). No excess mortality among fathers of PCOS patients was observed. LIMITATIONS, REASON FOR CAUTION: Although recall bias for family history was previously demonstrated to be minimal for long-term chronic diseases, the prevalence of diabetes in the parents was based on their daughter's self-report and was not clinically confirmed. Also, no other additional clinical data regarding the parent population were available. Prospective long-term follow-up studies should be conducted to confirm this excess mortality. WIDER IMPLICATIONS OF THE FINDINGS: Our findings justify screening for type 2 diabetes mellitus among the mothers with a daughter suffering from PCOS to ensure that timely preventive and therapeutic measures according to the appropriate guidelines can be taken. STUDY FUNDING/COMPETING INTERESTS: No particular funding was received for this study. Y.V.L., M.E.R.-S., N.K., J.R.v.L., M.v.d.B., H.J.G.B. and E.J.G.S. do not have any conflict of interest. J.S.E.L. has received fees and grant support from the following companies (in alphabetic order): Ferring, Genovum, Merck-Serono, Organon, Schering Plough and Serono. B.C.J.M.F. has received fees and grant support from the following companies (in alphabetic order): Andromed, Ardana, Ferring, Genovum, Merck Serono, Organon, Pantharei Bioscience, PregLem, Schering, Schering Plough, Serono, and Wyeth. These companies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copeptin, a surrogate marker for arginine vasopressin, is associated with declining glomerular filtration in patients with diabetes mellitus (ZODIAC-33).

AIM/HYPOTHESIS: Arginine vasopressin (AVP), the hormone important for maintaining fluid balance, has been shown to cause kidney damage in rodent models of diabetes. We investigated the potential role of AVP in the natural course of kidney function decline in diabetes in an epidemiological study. METHODS: Plasma copeptin, a surrogate for AVP, was measured in baseline samples from patients with type 2 diabetes treated in primary care and included in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort. RESULTS: Samples from 1,328 patients were available; 349 were analysed separately because they used renin-angiotensin-aldosterone system inhibition (RAASi), which influences albumin/creatinine ratio (ACR) and estimated (e)GFR. In the other 979 patients (46% men, age 68 years [58-75], ACR 1.8 mg/mmol [0.9-5.7], eGFR 67 ± 14 ml min(-1) 1.73 m(-2)) baseline copeptin (5.3 pmol/l [3.2-9.5]) was significantly associated with log e [ACR] and eGFR, even after adjustment for sex, age and risk factors for kidney function decline (standardised [std] ß 0.13, p < 0.001, std ß -0.20, p < 0.001 respectively). Follow-up data were available for 756 patients (6.5 years [4.1-9.6]). Baseline copeptin was associated with increase in ACR (std ß 0.09, p = 0.02), but lost significance after adjustment (std ß 0.07, p = 0.08). Copeptin was associated with a decrease in eGFR after adjustment (std ß -0.09, p = 0.03). The strength of the association of copeptin with change in eGFR was stronger than that of established risk factors for kidney function decline (e.g. BMI, HbA1c). In patients who used RAASi there was a significant association between baseline copeptin and ACR and eGFR, but not with change in ACR and eGFR. CONCLUSIONS/INTERPRETATION: In patients with diabetes not using RAASi a higher baseline copeptin concentration is significantly associated with higher baseline ACR and lower eGFR values and with a decline in eGFR during follow-up. This last association is independent of, and stronger than, most traditional risk factors for kidney function decline.

Time for considering other blood pressure target values in elderly patients with type 2 diabetes?

Although blood pressure control has undoubtedly proven its benefits in reducing the high cardiovascular risk in patients with type 2 diabetes mellitus (T2DM), it still remains unclear whether intensive antihypertensive treatment in old age (> 75 years) is beneficial. Many of the current guidelines recommend a systolic blood pressure (SBP) < 140 mmHg or lower, unless patients are at high risk for possible adverse events such as postural hypotension (1,2). This perspective aims to get a discussion started on the appropriate target SBP value for patients with T2DM aged older than 75 years.We would like to propose the less stringent value of< 160 mmHg in this specific population.

Glycaemic control and the risk of mortality in elderly type 2 diabetic patients (ZODIAC-20).

AIMS: Studies on macrovascular consequences of glucose control in elderly patients (>75 years) with type 2 diabetes mellitus (T2DM) are lacking. The present study aimed to investigate the relationship between HbA(1c) and mortality in this specific population. METHODS: Between 1998 and 1999, 374 primary care patients with T2DM aged older than 75 years participated in the Zwolle Outpatient Diabetes project Integrating Available Care study, a prospective observational study. Early 2009, data on mortality were collected. Updated means for annually measured HbA(1c) values were calculated after a follow-up time of 10 years. Updated mean HbA(1c) was used as a time-dependent covariate in a Cox proportional hazard model. Main outcome measures were all-cause and cardiovascular disease (CVD) mortality. Analyses were performed in strata according to diabetes duration (<5, 5-11 and ≥11 years). RESULTS: In the group with a diabetes duration <5 years, an increase of 1% in the updated mean HbA(1c) level was associated with an increase in all-cause and CVD mortality risk of 51% (95% CI 17-95%) and 72% (95% CI 19-148%), respectively. Glycaemic control was not related to mortality for patients with a diabetes duration ≥5 years. CONCLUSION: Poor glycaemic control is related to increased all-cause and CVD mortality in patients >75 years with T2DM of short duration (<5 years). DISCUSSION: Because of the observational study design, our results should be interpreted with caution. Nevertheless, they are suggestive that improving glycaemic control may be beneficial in elderly patients with T2DM, especially in those with recently diagnosed T2DM. Randomised-controlled trials are necessary to investigate whether this holds true.

Modification of diet in renal disease and Cockcroft-Gault formulas do not predict mortality (ZODIAC-6).

AIMS: An inverse relationship between estimates of renal function, with formulas such as the Modification of diet in renal disease (MDRD) study equation or the Cockcroft-Gault formula, and mortality has been suggested. These formulas both contain the variables sex, serum creatinine and age and the latter also contains body weight. We investigated whether these formulas predict mortality better than the variables they contain together in patients with Type 2 diabetes. METHODS: In 1998, 1143 primary care patients with Type 2 diabetes participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) Study, in the Netherlands. Clinical and laboratory data were collected at baseline. Life status was assessed after 6 years. We used Cox proportional hazard modelling to investigate the association between estimates of renal function (continuous data) and the variables they contain and mortality, adjusting for confounders. Both formulas were compared with models consisting of the variables present in the formulas. Predictability was assessed using Bayesian information criterion (BIC) and Harrell's C statistics. RESULTS: At follow-up, 335 patients had died. All variables, except sex, influenced mortality. Predictive capability, indicated by lower BIC values and higher Harrell's C values, was up to 10% better for models containing the separate variables as compared with Cockcroft-Gault or MDRD. CONCLUSIONS: Using estimates of renal function to assess mortality risk decreases predictability as compared with the combination of the risk factors they contain. These formulas, therefore, could be used to estimate renal function; however, they should not be used as a tool to predict mortality risk.

Increased cancer mortality in type 2 diabetes (ZODIAC-3).

BACKGROUND: It is unclear whether there is a relationship between type two diabetes and cancer mortality. It also is unclear whether obesity and body mass index (BMI) are associated with cancer in type 2 diabetes patients. PATIENTS AND METHODS: In 1998, 1,145 patients with type two diabetes mellitus were enrolled in the Zwolle Outpatient Diabetes project Intergrating Available Care (ZODIAC) study. In this project, general practitioners (GPs) were assisted by hospital-based diabetes specialist nurses. Vital status was assessed in September 2004. The cancer mortality rate was evaluated using standardized mortality ratio (SMR) and its association with BMI (kg/m2) and obesity (>30 kg/m2) with the Cox proportional hazard ratio. RESULTS: The median follow-up time was 5.8 years. A total of 335 patients had died, of whom 70 died from malignancy. The SMR for cancer mortality was 1.38 (95% CI 1.07-1.75). BMI and obesity were not associated with cancer death. CONCLUSION: An increased cancer mortality rate was found in type two diabetes mellitus patients but there was no significant association between BMI or obesity and cancer mortality.

Association between body mass index and obesity-related cancer risk in men and women with type 2 diabetes in primary care in the Netherlands: a cohort study (ZODIAC-56).

OBJECTIVE: To investigate the relationship between body mass index (BMI) and obesity-related cancers in men and women with type 2 diabetes (T2D). DESIGN: Observational cohort study. SETTING: Primary care. PARTICIPANTS: A total of 52 044 patients with T2D who participated in the ZODIAC (Zwolle Outpatient Diabetes project Integrating Available Care) study between 1998 and 2012 was included (49% women). A dataset of these patients was linked to available information of the Netherlands Cancer Registry to obtain data on cancer incidents. PRIMARY OUTCOME MEASURES: Analyses were performed for the total group of obesity-related cancers and for non-sex-specific and sex-specific obesity-related cancers (in men: advanced prostate cancer, in women: ovarian, endometrial and postmenopausal breast cancer). RESULTS: The median follow-up period in all analyses was 3.1 (1.7-5.0) years in men and 3.1 (1.7-5.1) in women. During follow-up, 689 men and 914 women were diagnosed with an obesity-related cancer. In men, BMI was associated with a higher risk of the total group of obesity-related cancers and non-sex-specific obesity-related cancers (HR (per 5 kg/m2 increase) 1.12 (95% CI 1.02 to 1.23) and HR 1.18 (95% CI 1.06 to 1.31)). No association was found with prostate cancer. In women, an association between BMI and all obesity-related cancers combined and sex-specific obesity-related cancers was present (HR 1.15 (95% CI 1.08 to 1.22) and HR 1.22 (95% CI 1.14 to 1.32)). No association with non-sex-specific cancers was found in women. CONCLUSIONS: BMI is associated with obesity-related cancers in men with T2D, except with advanced prostate cancer. The results of this study provide reason to reconsider the classification of advanced prostate cancer as an obesity-related cancer, at least in T2D. In women, BMI is associated with the total group of obesity-related cancers and with sex-specific obesity-related cancers.

[Cinnamon: not suitable for the treatment of diabetes mellitus]. / Kaneel: niet geschikt als behandeling voor diabetes mellitus.

OBJECTIVE: To identify published studies evaluating the effects of cinnamon on glycaemic control. DESIGN: Literature search. METHOD: The Medline database was searched using all possible combinations of the words and medical subject headings (MeSH) 'cinnamon', 'diabetes mellitus', 'HbA1C' and 'glucose'. All human or animal studies in which cinnamon was administered as intervention were included. RESULTS: Several animal studies and 5 randomized placebo-controlled trials in humans were found. Most of the animal studies described beneficial effects of cinnamon on glycaemic control. One placebo-controlled trial in patients with type 2 diabetes found that cinnamon intake was associated with favourable effects on fasting plasma glucose. None of the studies reported an improvement in HbA1C. A study in patients with type 1 diabetes found that cinnamon had no effect. CONCLUSION: Based on the currently available evidence, cinnamon should not be recommended for the improvement ofglycaemic control.

[Assessment of renal function according to the NHG protocol 'Diabetes mellitus type 2': risk of overestimating the number of diabetes patients with renal dysfunction]. / Bepaling van de nierfunctie volgens de NHG-standaard 'diabetes mellitus type 2': kans op overschatting van het aantal diabetespatiënten met nierfunctieproblemen.

OBJECTIVE: To evaluate the consequences of the new Dutch College of General Practitioners (NHG) protocol 'Diabetes mellitus type 2', which recommends using either the Cockcroft-Gault (CG) formula or the 'Modification of diet in renal disease' (MDRD) study formula to determine the estimated glomerular filtration rate (eGFR) as an indicator of renal function, in a cohort of patients with type-2 diabetes. DESIGN: Inventory. METHOD: The eGFR was calculated using the CG formula, the body-mass index (BMI-)corrected CG formula and the MDRD formula in 6224 patients with type-2 diabetes who entered the 'Zwolle outpatient diabetes project integrating available care' (ZODIAC) study in 2005. RESULTS: Using the CG and MDRD formulas, 31% and 63% of patients, respectively, had an eGFR of 30-59 ml/min (units for MDRD are ml/ min/1.73 m2) for which referral is advisable. In addition, 1% and 11%, respectively, had an eGFR <30 ml/min (reference: >90 ml/min), for which referral is necessary. Most patients aged >70 years (or > 50 years using the BMI-corrected CG formula) had an eGFR <60 ml/min. CONCLUSIONS: Reduced eGFR can be a sign of renal dysfunction but, using these formulas, can also be partly explained by advanced age. Therefore other factors should be considered when interpreting the results ofeGFR before it is concluded that the patient has kidney disease and the associated increased risk of cardiovascular disease.

[Measuring the blood pressure in both arms is of little use; longitudinal study into blood pressure differences between both arms and its reproducibility in patients with diabetes mellitus type 2]. / Weinig nut van bloeddrukmeting aan beide armen; longitudinale studie naar interarmbloeddrukverschillen en de reproduceerbaarheid daarvan bij patiënten met diabetes mellitus type 2.

OBJECTIVE: To determine the prevalence of inter-arm blood pressure differences > 10 mmHg in patients with diabetes mellitus type 2 (DM2) and to determine whether these differences are consistent over time. DESIGN: Descriptive. METHOD: In an evaluation study of 169 DM2 patients from 5 general practices in 2003 and 2004, different methods of oscillatory measurement were used to investigate inter-arm blood pressure differences > 10 mmHg systolic or diastolic. These methods were: one measurement in each arm non-simultaneously (method A), one measurement simultaneously (B) and the mean of two simultaneous measurements (C). RESULTS: With method A an inter-arm blood pressure difference was found in 33% of patients. This percentage diminished to 9 with method C. In 44% (n = 7) of the patients in whom method C detected a relevant blood pressure difference, this difference was not found with method A. In 79% of patients the inter-arm blood pressure difference was not reproduced after one year. CONCLUSION: In daily practice, one non-simultaneous blood pressure measurement in each arm (method A) was of little value for identification of patients with inter-arm blood pressure differences. The reproducibility was poor one year later. Bilateral blood pressure measurement is therefore of little value.

Orthostatic hypotension does not predict recurrent falling in a nursing home population.

OBJECTIVE: Most studies regard orthostatic hypotension (OH) as a causal factor for falls. However, the evidence is lacking for this assumption. We aimed to investigate the relationship between orthostatic hypotension and fall incidents in nursing home residents. METHODS: A total of 249 patients was included in a prospective observational cohort study of nursing home residents. Falls were prospectively registered. Cox proportional hazard modelling and the conditional frailty model were used to analyse the relationship between OH and (recurrent) falling. RESULTS: Among the 249 patients, 450 falls were recorded during follow-up and OH was present in 93 out of 249 patients. No significant associations were found between OH and the first fall incident (Hazard Ratio (HR) 1.01 (95% Confidence Interval (CI) 0.60-1.69) and recurrent falling (HR 1.21 (95%CI 0.65-2.24)). CONCLUSIONS: Although falling and OH were both highly prevalent in nursing home residents, no relationship between OH and falling was found.

Effects of intraperitoneal insulin versus subcutaneous insulin administration on sex hormone-binding globulin concentrations in patients with type 1 diabetes mellitus.

AIMS: Elevated sex hormone-binding globulin (SHBG) concentrations have been described in patients with type 1 diabetes mellitus (T1DM), probably due to low portal insulin concentrations. We aimed to investigate whether the route of insulin administration, continuous intraperitoneal insulin infusion (CIPII), or subcutaneous (SC), influences SHBG concentrations among T1DM patients. METHODS: Post hoc analysis of SHBG in samples derived from a randomized, open-labeled crossover trial was carried out in 20 T1DM patients: 50% males, mean age 43 (±13) years, diabetes duration 23 (±11) years, and hemoglobin A1c (HbA1c) 8.7 (±1.1) (72 (±12) mmol/mol). As secondary outcomes, testosterone, 17-ß-estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were analyzed. RESULTS: Estimated mean change in SHBG was -10.3nmol/L (95% CI: -17.4, -3.2) during CIPII and 3.7nmol/L (95% CI: -12.0, 4.6) during SC insulin treatment. Taking the effect of treatment order into account, the difference in SHBG between therapies was -6.6nmol/L (95% CI: -17.5, 4.3); -12.7nmol/L (95% CI: -25.1, -0.4) for males and -1.7nmol/L (95% CI: -24.6, 21.1) for females, respectively. Among males, SHBG and testosterone concentrations changed significantly during CIPII; -15.8nmol/L (95% CI: -24.2, -7.5) and -8.3nmol/L (95% CI: -14.4, -2.2), respectively. The difference between CIPII and SC insulin treatment was also significant for change in FSH 1.2U/L (95% CI: 0.1, 2.2) among males. CONCLUSIONS: SHBG concentrations decreased significantly during CIPII treatment. Moreover, the difference in change between CIPII and SC insulin therapy was significant for SHBG and FSH among males. These findings support the hypothesis that portal insulin administration influences circulating SHBG and sex steroids.

Health-related quality of life, rehabilitation and mortality in a nursing home population.

BACKGROUND: Health-related quality of life (HRQOL) in nursing home residents is generally low. The purpose of this study was to investigate the associations between HRQOL and two clinically relevant outcome measures, all-cause mortality and successful rehabilitation, in a nursing home population. METHODS: In an observational prospective cohort study in a nursing home population, HRQOL was assessed with the RAND-36. A total of 184 patients were included, 159 (86%) completed the RAND-36 and were included in the study. A Cox proportional hazard model was used to investigate the independent association between HRQOL, rehabilitation and mortality with adjustment for confounders. Risk prediction capabilities were assessed with Harrell's C statistics and the proportion of explained variance (R2). RESULTS: The median age (interquartile range) was 79 (75-85) years. The health dimensions vitality (HR 0.88 (95% CI 0.77-0.99)) and mental health (HR 0.86 (95% CI 0.75-0.98)) were inversely associated and role functioningphysical (HR 1.08 (95%CI 1.02-1.15)) was positively associated with mortality. The Harrell's C value and the R2 were ≤ 0.02 and ≤ 0.03 higher in the adjusted models with the dimensions role functioning- physical, mental health or vitality compared with the models without these dimensions. None of the health dimensions or summary scales were related to successful rehabilitation. CONCLUSION: HRQOL was significantly associated with mortality for three dimensions, but partly in opposite directions. Additional value of HRQOL in mortality prediction is very limited. There were no independent associations between HRQOL and successful rehabilitation. Although HRQOL is an important outcome, this study did not provide evidence for an association between HRQOL and successful rehabilitation.