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Achtergrond Bij de behandeling van diabetespatienten met insuline worden in de dagelijkse praktijk vaak verschillende pensystemen gebruikt voor het toedienen van de basale insuline en de maaltijdinsuline. Hierbij wordt aangenomen dat patienten de voorkeur geven aan twee verschillende pensystemen en dat een en hetzelfde pensysteem zou kunnen leiden tot verwarring en daarmee foutief gebruik door de patient.

OBJECTIVE Infection commonly complicates diabetic foot ulcers and is associated with a poor outcome. In a cohort of individuals with an infected diabetic foot ulcer, we aimed to determine independent predictors of lower-extremity amputation and the predictive value for amputation of the International Working Group on the Diabetic Foot (IWGDF) classification system and to develop a risk score for predicting amputation. RESEARCH DESIGN AND METHODS We prospectively studied 575 patients with an infected diabetic foot ulcer presenting to 1 of 14 diabetic foot clinics in 10 European countries. RESULTS Among these patients, 159 (28%) underwent an amputation. Independent risk factors for amputation were as follows: periwound edema, foul smell, (non)purulent exudate, deep ulcer, positive probe-to-bone test, pretibial edema, fever, and elevated C-reactive protein. Increasing IWGDF severity of infection also independently predicted amputation. We developed a risk score for any amputation and for amputations excluding the lesser toes (including the variables sex, pain on palpation, periwound edema, ulcer size, ulcer depth, and peripheral arterial disease) that predicted amputation better than the IWGDF system (area under the ROC curves 0.80, 0.78, and 0.67, respectively). CONCLUSIONS For individuals with an infected diabetic foot ulcer, we identified independent predictors of amputation, validated the prognostic value of the IWGDF classification system, and developed a new risk score for amputation that can be readily used in daily clinical practice. Our risk score may have better prognostic accuracy than the IWGDF system, the only currently available system, but our findings need to be validated in other cohorts.

Background Healing of heel ulcers in patients with diabetes is considered to be poor, but there is relatively little information on the influence of ulcer location on ulcer healing. Methods The influence of ulcer location on time to healing of diabetic foot ulcers was analysed by multivariate Cox regression analysis for 1000 patients included in the Eurodiale study, a prospective cohort study of patients with diabetic foot disease. Results Median time to healing was 147 days for toe ulcers [(95% confidence interval (CI) 135–159 days)], 188 days for midfoot ulcers (95% CI 158–218 days) and 237 days for heel ulcers (95% CI 205–269 days) (p

Aims: Diabetic complications, and in particular diabetic foot ulcers (DFUs), are associated with low health-related quality of life (HRQoL). We evaluated whether the presence of diabetic complications also influenced the improvement of HRQoL during DFU treatment.Methods: 1088 patients presenting for DFU treatment at the centers participating in the Eurodiale study were followed prospectively up to one year. HRQoL was measured both at presentation and after healing or at end of follow up, using EQ-5D: a standardized instrument consisting of five domains and a summary index. The influence of diabetic comorbidity on the course of HRQoL was evaluated for each of the EQ-5D outcomes in multi-level linear regression analyses, adjusting for baseline characteristics.Results: HRQoL improved in all EQ-5D outcomes over the course of treatment for those DFUs that healed. The few significant differences in the development of HRQoL between patients with and without comorbidity showed a more beneficial development for patients with comorbidity in DFUs that did not heal or healed slowly.Conclusions: Comorbidity does not hamper improvement of HRQoL in DFU treatment. On the contrary, HRQoL improved sometimes more in patients with certain comorbidity with hard-to-heal ulcers. (C) 2017 Elsevier Inc. All rights reserved.

OBJECTIVE To provide a comprehensive assessment of multiorgan insulin sensitivity in lean and obese subjects with normal glucose tolerance. RESEARCH DESIGN AND METHODS The hyperinsulinemic-euglycemic clamp procedure with stable isotopically labeled tracer infusions was performed in 40 obese (BMI 36.2 ± 0.6 kg/m2, mean ± SEM) and 26 lean (22.5 ± 0.3 kg/m2) subjects with normal glucose tolerance. Insulin was infused at different rates to achieve low, medium, and high physiological plasma concentrations. RESULTS In obese subjects, palmitate and glucose Ra in plasma decreased with increasing plasma insulin concentrations. The decrease in endogenous glucose Ra was greater during low-, medium-, and high-dose insulin infusions (69 ± 2, 74 ± 2, and 90 ± 2%) than the suppression of palmitate Ra (52 ± 4, 68 ± 1, and 79 ± 1%). Insulin-mediated increase in glucose disposal ranged from 24 ± 5% at low to 253 ± 19% at high physiological insulin concentrations. The suppression of palmitate Ra and glucose Ra were greater in lean than obese subjects during low-dose insulin infusion but were the same in both groups during high-dose insulin infusion, whereas stimulation of glucose Rd was greater in lean than obese subjects across the entire physiological range of plasma insulin. CONCLUSIONS Endogenous glucose production and adipose tissue lipolytic rate are both very sensitive to small increases in circulating insulin, whereas stimulation of muscle glucose uptake is minimal until high physiological plasma insulin concentrations are reached. Hyperinsulinemia within the normal physiological range can compensate for both liver and adipose tissue insulin resistance, but not skeletal muscle insulin resistance, in obese people who have normal glucose tolerance.

PLoS one 13(12), e0209225 (2018). doi:10.1371/journal.pone.0209225

Objective Dopamine agonists are the first line therapy for the treatment of prolactinomas. The aim of this study was to assess the outcome of macroprolactinomas during long-term follow-up after initial treatment with dopamine agonists. Design Retrospective follow-up study. Patients We included 72 consecutive patients (age 39 ± 17 years, men 46%) diagnosed with macroprolactinoma, and initially treated with dopamine agonists between 1980 and 2004. Results Initial presentation included headache in 49%, and visual field defects in 38% of the patients. Nine patients were already treated with dopamine agonists at presentation. Median prolactin level of the untreated patients was 460 µg/L (range 96–35,398 µg/L) at presentation. Hypopituitarism, other than hypogonadism, was present in 6% of the patients. Mean duration of follow-up was 10.2 ± 6.1 years. Additional transsphenoidal surgery was necessary in 35% of the patients, because of resistance and/or intolerance of dopamine agonists. Postoperative radiotherapy was provided to 18% of all patients. During long-term follow-up, normoprolactinemia was present in 85% of the patients, but biochemical remission (normal prolactin levels in the absence of dopamine agonists) was present in only 22% of the patients. Tumor shrinkage was evident on MRI in 57% of the patients. Hypopituitarism developed in 39% of the patients, especially in those who received additional surgery with or without radiotherapy. Conclusion Dopamine agonists are effective in normalizing prolactin values, and inducing tumor shrinkage. However, in one-third of the patients, additional therapy was necessary due to dopamine agonist resistance and/or intolerance, associated with a high incidence of hypopituitarism.

The increased risk of cardiac valve disease in patients treated for Parkinson's disease with cabergoline has raised concerns about the safety of treatment with ergot-derived dopamine agonists in patients with endocrine diseases, especially prolactinoma. Six cross-sectional studies have been published recently, of which five studies do not show an association between the treatment of prolactinoma with cabergoline during 45–79 months and clinically relevant valvular regurgitation in a total of 413 patients. Nonetheless, concern is raised because the use of cabergoline was associated in one study with an increased prevalence of moderate tricuspid regurgitation, and in two other studies with mild tricuspid regurgitation. Furthermore, the use of cabergoline was associated with increased frequencies of valvular thickening, calcifications and increased mitral tenting area. At present, the clinical relevance of these findings is still uncertain, but concern is raised with respect to the safety of the use of cabergoline in the long-term treatment of prolactinomas. Echocardiographic evaluation should be considered in patients, who require long-term treatment with cabergoline, especially in high doses. There is a need for larger, preferably prospective, studies with careful echocardiographic assessment and with longer durations of follow-up than the currently available studies.

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. (Less)

Healing of heel ulcers in patients with diabetes is considered to be poor, but there is relatively little information on the influence of ulcer location on ulcer healing.The influence of ulcer location on time to healing of diabetic foot ulcers was analysed by multivariate Cox regression analysis for 1000 patients included in the Eurodiale study, a prospective cohort study of patients with diabetic foot disease.Median time to healing was 147 days for toe ulcers [(95% confidence interval (CI) 135-159 days)], 188 days for midfoot ulcers (95% CI 158-218 days) and 237 days for heel ulcers (95% CI 205-269 days) (p 0.01). The median time to healing for plantar ulcers was 172 days (95% CI 157-187 days) and 155 days (95% CI 138-172 days) for nonplantar ulcers (p = 0.71). In multivariate Cox regression analysis, the hazard ratio for ulcer healing for midfoot and heel ulcers compared with toe ulcers was 0.77 (95% CI 0.64-0.92) and 0.62 (95% CI 0.47-0.83), respectively; the hazard ratio for ulcer healing for plantar versus nonplantar ulcers was 1 (95% CI 0.84-1.19). Other factors significantly influencing time to healing were the duration of diabetes, ulcer duration, the presence of heart failure and the presence of peripheral arterial disease.Time to ulcer healing increased progressively from toe to midfoot to heel, but did not differ between plantar and nonplantar ulcers. Our data also indicate that risk factors for longer time to healing differ from factors that affect the ultimate number of ulcers that heal (healing rate).

Objective: Most studies on treatment of microprolactinoma have focused on clinical and biochemical outcome rather than on functional and mental well-being. We evaluated this topic in female patients with microprolactinoma, because other pituitary adenomas are associated with decreased quality of life. Design: We conducted a cross-sectional study. Patients and methods: To assess the impact of treatment for microprolactinoma on subjective well-being, quality of life was investigated in 55 female patients (mean age 45 ± 10 years), treated for microprolactinoma in our center, using four validated, health-related questionnaires: Short-Form-36 (SF-36), Nottingham Health Profile (NHP), Multidimensional Fatigue Inventory (MFI-20), and Hospital Anxiety and Depression Scale (HADS). Patient outcomes were compared with those of 183 female controls with equal age distributions. Results: Anxiety and depression scores were increased when compared with controls for all subscales as measured by HADS, and fatigue for all but one subscale as measured by MFI-20. Patients treated for microprolactinoma had worse scores on social functioning, role limitations due to physical problems (SF-36), energy, emotional reaction, and social isolation (NHP) when compared with control subjects. Important independent predictors of quality of life were reproductive status and anxiety and depression scores according to the HADS. Conclusion: Quality of life is impaired in female patients treated for microprolactinoma, especially due to increased anxiety and depression. These increased anxious and depressive feelings might be due to possible effects of hyperprolactinemia on the central nervous system. Failure to recognize this association may adversely affect patient–doctor relationships.

Ever since the first descriptions of adrenal insufficiency following exogenous supplementation physicians dread to abolish perioperative glucocorticosteroid supplementation. Now, 55 years after the first publications we can challenge those first reports. However, these cases have resulted in the supplementation of supraphysiological doses of glucocorticosteroids to patients that use exogenous corticosteroids: the so-called perioperative glucocorticosteroid supplementation or "(gluco)corticosteroids stress scheme". It is very questionable whether a dose that exceeds the normal daily production of 5.7 mg cortisol per square meter of body surface area is necessary to prevent perioperative hypotension. Retrospective, prospective and randomised studies, though all methodologically flawed, are discussed and show that continuation of the "basal" amount of glucocorticosteroids is Sufficient to Counterbalance surgical stress. The current and rather defensive strategy of perioperative supraphysiological glucocorticosteroid supplementation is not embedded in medical evidence. Additionally, high doses of glucocorticosteroids have disadvantages that should not be ignored. (c) 2007 European Federation of Internal Medicine. Published by Elsevier B.V All rights reserved.

OBJECTIVE Growth hormone release in response to all known stimuli of GH secretion is blunted in obese subjects. Several studies, using dl-fenfluramine (dl-FF) as a serotoninergic tool, suggest that brain serotonin plays a role in the pathogenesis of this phenomenon. However, the effect of dl-FF appears to be dependent on the stimulus used to induce GH release. Furthermore, dl-FF has catecholamingergic properties apart from its capacity to stimulate serotonin release and to block its re-uptake. In this study, we investigated whether subchronic treatment with the highly selective serotoninergic drug dexfenfluramine (d-FF) affects the GH response to galanin or GHRH in obese subjects. DESIGN The study had a randomized, cross-over, placebo controlled design. d-FF was administered in a dose of 15 mg twice daily during 6 days. On days 5 and 6 of treatment (with either d-FF or placebo) an i.v. bolus injection of 100 μg hGHRH(1-44) or a continuous infusion of p-galanin (40 pmol/kg/min over 40 minutes) were administered in randomized order. All tests were performed in the follicular phase of two consecutive menstrual cycles. PATIENTS Eight obese women (body mass index (BMI) 34.5 ± 3.6 kg/m2); 7 normal weight (BMI 21.9 ± 1.9 kg/m2) age-matched control women. All women had a regular menstrual cycle. None used oral contraceptive drugs. MEASUREMENTS GH response to either stimulus was measured both during treatment with d-FF and during treatment with placebo. RESULTS The GH response to galanin and the response to GHRH were significantly smaller in obese subjects. d-FF significantly reduced the galanin induced GH secretion in obese subjects, but not in normal weight controls. It did not significantly affect GH release in response to GHRH in either group. CONCLUSION This study confirms that GH secretion in response to stimuli with varying mechanisms of action is blunted in obese subjects. A decrease of central serotonin mediated neurotransmission does not appear to play a role in the pathogenesis of this phenomenon.

To determine the influence of ulcer location on ulcer healing in diabetic foot disease, as especially heel ulcers are considered poorly healing ulcers.