Nanne Kleefstra

Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

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Publications (151)705.65 Total impact

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    ABSTRACT: . Online platforms offer opportunities for support in changing lifestyle and taking responsibility for one’s health, but engaging patients with type 2 diabetes is challenging. Previous studies have shown that patients interested in platforms were more often male, younger, and higher educated. This study aims to investigate differences in clinical and psychological characteristics between users and nonusers of a newly developed platform. Methods . A prospective study started in the Drenthe region of Netherlands. Participants in the study concerning quality of care and quality of life were additionally invited to use the platform. Results . 633 patients were registered after they opted for platform use. Of these patients, 361 (57.0%) never logged on, 184 (29.1%) were labeled “curious” users, and 88 (13.9%) were identified as “active” users. Users had lower HbA1c levels and more often hypertension compared to nonusers, and reported higher quality of life, better well-being, lower diabetes-related distress, and better medication adherence. Discussion . Platform use was associated with more favorable clinical and psychological characteristics relative to nonuse. Those with greater severity of disease, lower mood, and progression of disease used the platform the least. Other approaches need to be developed to reach these patients. Furthermore, improving the platform could also help to reach them. This trial is registered with Clinicaltrials.gov NCT01570140 .
    Full-text · Article · Jan 2016 · Journal of Diabetes Research
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    ABSTRACT: Objective: Our aim was to investigate whether trends in quality of diabetes care differ between sexes in the Netherlands from 1998 till 2013. Research design and methods: In this prospective observational cohort study quality of care was measured using process and outcome measures in patients with type 2 diabetes in primary care. Trend and absolute differences between sexes were investigated for patients <75 years. Subgroup analyses were performed in patients ≥75 years. 10-year mortality risk was assessed with the Globorisk risk equation in patients without cardiovascular diseases <75 years. Results: The number of patients increased from 2,644 in 1998 to 62,230 in 2013. In 1998, 51% of the men and 60% of the women <75 years had an HbA1c >53 mmol/mol; this decreased to approximately 29% in both sexes in 2013. Patients having a systolic blood pressure >140 mmHg decreased from 70% to 42%, and from 80% to 40% in men and women <75 years, respectively. In patients ≥75 years it decreased from 72% to 50% in men and 85% to 56% in women. Obesity increased in both sexes, whereas smoking in men and women declined in patients <75 years (men: 34% to 22%; women: 22% to 18%). The number of patients with a mortality risk >20% over 10 years decreased from 15% to 3% in men and from 18% to 3% in women. Conclusions: Quality of diabetes care has improved considerably in the period 1998-2013 in both sexes. Possibly relevant trend differences between sexes were observed for HbA1c, systolic blood pressure, BMI and smoking. The predicted mortality risk decreased over time in both sexes. Except for BMI in both age groups and systolic blood pressure in patients ≥75 years, no evident poorer risk factor control in women compared to men was found at the end of the study period.
    Preview · Article · Dec 2015 · PLoS ONE
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    ABSTRACT: We aimed to investigate whether hs-cTnT is associated with all-cause and cardiovascular mortality in stable type 2 diabetes (T2D) outpatients treated in primary care.
    No preview · Article · Dec 2015
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    ABSTRACT: Background: Past decades, there has been a constant upward projection in the prevalence of diabetes. Attempts to estimate diabetes prevalence rates based on relatively small population samples quite often result in underestimation. The aim of this study was to investigate whether the Dutch diabetes prevalence estimate of 930,000 for 2013 based on a relatively small sample still holds true when a larger population was studied using actual prevalence data. Methods: In total, data were collected from 92 primary care groups, including the total number of persons known with and without diabetes in 2013. Patients with diabetes were identified using the ICPC coding system: ICPC T90.02 (diabetes mellitus type 2), T90.01 (diabetes mellitus type 1) and T90 (diabetes mellitus). Prevalence data were compared with previous estimates made by the RIVM in 2009. Diabetes prevalence was estimated using linear extrapolation. Results: Complete data were available from 67 (73%) care groups, which together provided care for 7,922,403 subjects; 431,396 patients were coded as having diabetes, of whom 406,183 patients as type 2 diabetes. Based on these results, the extrapolated Dutch diabetes prevalence was 914,387 (5.45%). Conclusions: These results show that the previous estimate (reported in 2009), which was based on data collected in 2007, resulted in a less than 2% (~16,000) overestimation in diabetes prevalence in 2013 compared to the presented analysis. These results indicate that no upward adjustment in Dutch diabetes prevalence development is necessary. Repetitive large scale monitoring can aid in more accurate actual prevalence estimates and improved future prevalence predictions.
    No preview · Article · Dec 2015 · Journal of Diabetes
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    ABSTRACT: In a sham-controlled double-blind trial, we aim to establish the efficacy and safety of the local application of laser therapy in patients with diabetes, onychomycosis and risk factors for diabetes-related foot complications. Onychomycosis leads to thickened and distorted nails, which in turn lead to increased local pressure. The combination of onychomycosis and neuropathy or peripheral arterial disease (PAD) increases the risk of developing diabetes-related foot complications. Usual care for high-risk patients with diabetes and onychomycosis is completely symptomatic with frequent shaving and clipping of the nails. No effective curative local therapies exist, and systemic agents are often withheld due to concerns for side effects and interactions. The primary aim is to evaluate the efficacy of four sessions of Nd:YAG 1064 nM laser application on the one-year clinical and microbiological cure rate in a randomized, double-blind, sham-controlled design with blinded outcome assessment. Mandatory inclusion criteria are diagnosis of diabetes, risk factors for developing foot ulcers defined as a modified Simm's classification score 1 or 2 and either neuropathy or PAD. A total of 64 patients are randomized to intervention or sham treatment performed by a podiatrist. This study will be the first double-blind study that investigates the effects of local laser therapy on onychomycosis, specifically performed in patients with diabetes with additional risk factors for foot complications. Clinical trials.gov as NCT01996995 , first received 22 November 2013.
    Full-text · Article · Dec 2015 · Trials
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    ABSTRACT: Background: Continuous intraperitoneal insulin infusion (CIPII), a last-resort type 1 diabetes mellitus (T1DM) treatment, has only been investigated in small or controlled studies. We aimed to investigate glycaemia and quality of life (QoL) with CIPII versus subcutaneous (SC) insulin therapy during usual T1DM care. Methods: A prospective, observational case-control study. CIPII-treated cases were matched to SC controls. The primary endpoint was a non-inferiority assessment (pre-defined margin of -5.5 mmol÷mol) of the baseline adjusted difference in HbA1c between groups during a 26-week follow-up. Secondary outcomes included QoL, clinical and biochemical measurements. Results: In total, 183 patients were analysed (CIPII n = 39 and SC n = 144). The HbA1c difference between treatment groups was -3.0 mmol÷mol (95% CI -5.0, -1.0), being lower in the SC group. Patients using SC insulin therapy spent less percentage of time in hyperglycaemia (-9.3% (95% CI -15.8, -2.8)) and more in euglycaemia (6.9% (95% CI 1.2, 12.5) as compared with CIPII-treated patients. Besides a 3.6 U÷l (95% CI 1.2, 6.0) lower concentration of alanine aminotransferase with CIPII, no biochemical and clinical differences were present. Most QoL scores were lower at baseline among CIPII-treated patients. However, besides lower health status, there were no differences in the baseline-adjusted general and diabetes-specific QoL and treatment satisfaction. Conclusion: Although patients using CIPII had a higher glycaemic profile compared with patients using SC insulin therapy, the HbA1c difference was non-inferior. Overall, health status was lower among CIPII-treated patients, although diabetes-specific QoL and treatment satisfaction was similar to subcutaneously treated patients.
    No preview · Article · Nov 2015 · The Netherlands Journal of Medicine
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    ABSTRACT: The howRu and howRwe are new short questionnaires which are meant to measure health-related quality of life and patient experience. However, validation at the individual patient level has not yet taken place. We aimed to investigate the validity of both questionnaires at the individual patient level. In this prospective validation study, patients were asked to complete both questionnaires and comment on their answers in a semi-structured in-depth interview. Based on the transcribed interviews, a panel of 45 general practitioners and 45 patients filled out the questionnaires as they thought the patients had completed them. The questionnaires were considered valid instruments when a reliable and acceptable level of agreement was reached between the patient’s score and the score of a review panel, defined as a concordance correlation coefficient (CCC) of ≥0.70. Bland-Altman plots were also made. Ninety patients were included. The CCC of the howRu total score of the review panel and patients was 0.80 (95 % CI 0.73 to 0.86). Bland-Altman plots showed a mean difference of −0.96 and the limits of agreement ranged from −2.87 to 0.95. The CCC of the howRwe total score was 0.57 (95 % CI 0.42 to 0.69). The mean difference on the Bland-Altman plots was −0.54 and the limits of agreement ranged from −3.59 to 2.52. The howRu seems to be a valid questionnaire for measuring health-related quality of life at the individual patient level. We do not advice to use the tested version of the howRwe questionnaire for assessing patient experience at the individual patient level. Trial registration The study was registered at clinicaltrials.gov NCT01830803. Registration date: 5 April 2013.
    Full-text · Article · Oct 2015 · BMC Health Services Research
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    ABSTRACT: Low concentrations of insulin-like growth factor-I (IGFI) have been reported in type 1 diabetes mellitus (T1DM), suggested to be due to low insulin concentrations in the portal vein. The aim was to describe the long-term course of IGFI concentrations among T1DM subjects treated with continuous intraperitoneal (IP) insulin infusion (CIPII). Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) insulin therapy in 2006 were followed until 2012. IGF-I measurements were performed at the start of the 2006 study, after the 6month SC- and CIPII treatment phase in 2006 and during CIPII therapy in 2012. Z-scores were calculated to compare the IGF-I concentrations with age-specific normative range values of a non-DM reference population. In 2012, IGF-I Z-scores (-0.7; 95% confidence interval -1.3, -0.2) were significantly higher than at the start of the 2006 study (-2.5; -3.3, -1.8), the end of the SC (-2.0; -2.6, -1.5) and CIPII (-1.6; -2.1, -1.0) treatment phase with a mean difference of: 1.8 (0.9, 2.7), 1.3 (0.5, 2.1) and 0.8 (0.1, 1.6), respectively. After 6years of treatment with CIPII, IGF-I concentrations among T1DM patients increased to a level that is higher than during prior SC insulin treatment and is in the lower normal range compared to a non-DM reference population. The results of this study suggest that long-term IP insulin administration influences the IGF system in T1DM. Copyright © 2015 Elsevier Ltd. All rights reserved.
    No preview · Article · Aug 2015 · Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society
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    Preview · Article · Aug 2015 · Diabetes care
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    ABSTRACT: Background: Two previous studies concluded that proenkephalin A (PENK-A) had predictive capabilities for stroke severity, recurrent myocardial infarction, heart failure and mortality in patients with stroke and myocardial infarction. Objectives: This study aimed to investigate the value of PENK-A as a biomarker for predicting mortality in patients with type 2 diabetes mellitus. Methods: Patients with type 2 diabetes mellitus were included from the prospective observational ZODIAC (Zwolle Outpatient Diabetes project Integrating Available Care) study. The present analysis incorporated two ZODIAC cohorts (1998 and 2001). Since blood was drawn for 1204 out of 1688 patients (71%), and information on relevant confounders was missing in 47 patients, the final sample comprised 1157 patients. Cox proportional hazard models were used for evaluating the relationship between PENK-A and (cardiovascular) mortality. Risk prediction capabilities were assessed with Harrell's C statistics and the integrated discrimination improvement (IDI). Results: After a follow-up period of 14 years, 525 (45%) out of 1157 patients had died, of which 224 (43%) were attributable to cardiovascular factors. Higher Log PENK-A levels were not independently associated with increased (cardiovascular) mortality. Patients with PENK-A values in the highest tertile had a 49% (95%CI 1%-121%) higher risk of cardiovascular mortality compared to patients in the reference category (lowest tertile). C-values were not different after removing PENK-A from the Cox models and there were no significant differences in IDI values. Conclusions: The associations between PENK-A and mortality were strongly attenuated after accounting for all traditional risk factors. Furthermore, PENK-A did not seem to have additional value beyond conventional risk factors when predicting all-cause and cardiovascular mortality.
    Full-text · Article · Jul 2015 · PLoS ONE
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    ABSTRACT: Hyponatremia has been associated with an increased mortality risk in the general population. Diabetes is a condition predisposing for elevated levels of arginine vasopressin (AVP) and heart failure, both common causes of hyponatremia. These factors, however, are also associated with an increased mortality risk. We aimed to investigate whether serum sodium is associated with cardiovascular and all-cause mortality in type 2 diabetes and whether these associations could be explained by copeptin, a surrogate for AVP, or NT-proBNP, a marker for heart failure. Patients with type 2 diabetes participating in the observational ZODIAC study were included. Cox regression analyses were used to investigate the association of serum sodium with mortality. We included 1068 patients (age 67 ± 12 years, 45% male, serum sodium 142 ± 3 mmol/L). After 15 years of follow-up, 519 patients (49%) died, with 225 cardiovascular deaths (21%). In univariable analyses, serum sodium, copeptin, and NT-proBNP were all significantly associated with cardiovascular and all-cause mortality. These associations remained significant after combination of these markers in a multivariable model. Serum sodium and NT-proBNP remained significantly associated with mortality after further adjustment for potential confounders, whereas copeptin lost significance after adjustment for SCr and ACR. Low serum sodium was associated with an increased risk of cardiovascular and all-cause mortality in type 2 diabetes. Moreover, these associations were not explained by copeptin and NT-proBNP. Whether low serum sodium itself leads to poor outcome or is a marker for (unidentified) co-morbidity severity or use of specific medications remains to be elucidated. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · Jul 2015 · Atherosclerosis
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    ABSTRACT: Combined data suggest a bimodal association of alanine aminotransferase (ALT) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all-cause, cardiovascular, and non-cardiovascular mortality in patients with type 2 diabetes. A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. Cox regression analyses were performed to determine associations of log2 -transformed baseline ALT with all-cause, cardiovascular, and non-cardiovascular mortality. In 1,187 patients with type 2 diabetes (67±12 years, 45% female), ALT levels were 11 (8-16) U/l. During median follow-up for 11.1 (6.1-14.0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all-cause mortality (Hazard Ratio [HR] 0.81; 95% Confidence Interval [CI] 0.72-0.92), independently of potential confounders. This was less attributable to cardiovascular mortality (HR 0.87; 95% CI 0.72-1.05), than to non-cardiovascular mortality (HR 0.77; 95% CI 0.65-0.90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all-cause mortality was present with increasing risk for levels of ALT above normal (P=0.003). In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all-cause mortality, in particular non-cardiovascular mortality, compared to normal levels of ALT, while risk again starts to increase when levels are above normal. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    No preview · Article · Jun 2015 · European Journal of Clinical Investigation
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    ABSTRACT: We aimed to investigate whether adjustment for frailty influences the relationship of blood pressure with mortality in elderly patients with type 2 diabetes mellitus (T2DM). Patients aged 60 years and older (n = 858) were selected from a prospective observational cohort study of primary care patients with T2DM. Frailty was defined as a score less than 80 on the subscale 'physical functioning' of the RAND-36 questionnaire. After median follow-up for 14 years, multivariate Cox regression analyses were performed to evaluate the association between blood pressure and (cardiovascular) mortality. Analyses were performed in strata according to the frailty level ('physical functioning' score <80 and ≥80) and were repeated for patients older than 75 years. Frailty was highly prevalent in our study population; 629 out of 858 patients (73%) fulfilled the criterion. For patients aged at least 60 years, the hazard ratios (95% confidence interval) of a 10 mmHg increase in SBP and DBP for cardiovascular mortality in nonfrail patients were 1.38 (1.15-1.68%) and 1.60 (1.07-2.37%), respectively. No relationship was observed for frail patients. For the oldest frail elderly, the hazard ratios of SBP and DBP for all-cause mortality were 0.92 (0.87-0.98%) and 0.83 (0.73-0.93%), respectively. For the oldest nonfrail elderly, a positive relationship between SBP and all-cause mortality was observed. Frailty modifies the relationship between blood pressure and mortality in elderly patients with T2DM. Higher blood pressure was related to increased cardiovascular mortality in nonfrail patients, even in the oldest elderly, and to lower all-cause mortality in frail patients.
    No preview · Article · Jun 2015 · Journal of Hypertension
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    ABSTRACT: Our objectives were to identify the prevalence of orthostatic hypotension (OH) in frail, elderly nursing home residents, and assess its possible association with falling and chances of successful rehabilitation. A prospective observational cohort study. A total of 290 patients participated in this study, of which 128 were admitted to the rehabilitation department. OH was defined as a drop in systolic blood pressure of >20mmHg and diastolic blood pressure of >10mmHg after postural change within 3min. The analyses regarding falling and successful rehabilitation were only performed in the rehabilitation group. Multivariate binary logistic regression analyses were used to describe risk factors related with falling. Cox proportional hazard modeling was used to investigate the relation between OH and the time to successful rehabilitation. The prevalence of OH in the studied nursing home population was 36.6% (95% CI (confidence interval): 31.1-42.1%). The prevalence varied from 28.6% (95% CI: 16.8-40.4%) in somatic patients, 36.7% (95% CI: 28.4-45.1%) in rehabilitation patients, to 40.6% (95% CI: 31.3-50.0%) in psychogeriatric patients. The association between orthostatic hypotension and previous falling was not significant; Odds ratio 0.66 (95% CI: 0.30-1.48). The Hazard ratio of the relationship between OH and successful rehabilitation was 2.88 (95% CI:1.77-4.69). OH is highly prevalent in nursing home residents. Surprisingly, patients with OH were found to have a higher chance of successful rehabilitation compared to patients without OH. If confirmed in other studies, these results may change our view of the implications of OH. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
    No preview · Article · May 2015 · Archives of gerontology and geriatrics
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    ABSTRACT: The combination of an increasing prevalence of diabetes mellitus and more people having access to smartphones creates opportunities for patient care. This study aims to investigate whether the use of the Diabetes Under Control (DBEES) mobile phone application, a digital diabetes diary, results in a change in quality of life for patients with type 1 diabetes mellitus (T1DM) compared with the standard paper diary. In this randomized controlled open-label trial, 63 patients with T1DM having access to a smartphone were assigned to the intervention group using the DBEES application (n = 31) or the control group using the standard paper diary (n = 32). Primary outcome was the change in quality of life, as measured by the RAND-36 questionnaire, between both groups. Secondary outcomes included diabetes-related distress (PAID), HbA1c, frequency of self-monitoring blood glucose, and the usability of the diabetes application (SUS). Patients had a median age (IQR) of 33 (21) years, diabetes duration of 17 (16) years, and an HbA1c of 62 ± 16 mmol/mol. No significant differences in the QOL, using the RAND-36, within and between both groups were observed after 3 months. Glycemic control, diabetes-related emotional distress, and frequency of self-monitoring of blood glucose remained within and between groups. Users reviewed the usability of DBEES with a 72 ± 20, on a range of 0-100. The use of the DBEES application in the management of patients with T1DM for 3 months yields no alterations in quality of life compared to the standard paper diary. © 2015 Diabetes Technology Society.
    No preview · Article · May 2015 · Journal of diabetes science and technology
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    Preview · Article · May 2015 · Journal of the American Society of Hypertension
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    ABSTRACT: The Perception of Self-Monitoring of Blood Glucose (P-SMBG) scale was developed and validated to assess perceptions of self-monitoring of blood glucose (SMBG) in insulin-treated patients with diabetes. An initial 68-item version of the P-SMBG has been evaluated by a panel of professionals and patients. A sample of 375 patients tested the revised scale. Factor analysis suggested a 19-item scale and a 2-factor structure, separating negatively and positively worded items. Cronbach's alpha was .84 and .72, and the intraclass correlation coefficient was .66 and .57, respectively for both factors. Item-total correlations were in the range of .23-.66. Convergent/divergent validity was confirmed for the negatively worded items. The final P-SMBG scale (21 items) can be used to assess positive and negative perceptions of SMBG in insulin-treated patients with diabetes.
    Full-text · Article · Apr 2015 · Journal of Nursing Measurement
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    ABSTRACT: The hormone somatostatin inhibits growth hormone release from the pituitary gland and is theoretically linked to diabetes and diabetes related complications. This study aimed to investigate the relationship between levels of the stable somatostatin precursor, N-terminal prosomatostatin (NT-proSST), with mortality in type 2 diabetes (T2DM) patients. In 1,326 T2DM outpatients, participating in this ZODIAC prospective cohort study, Cox proportional hazards models were used to investigate the independent relationship between plasma NT-proSST concentrations with all-cause and cardiovascular mortality. Median concentration of NT-proSST was 592 [IQR 450-783] pmol/L. During follow-up for 6 [3-10] years, 413 (31%) patients died, of which 176 deaths (43%) were attributable to cardiovascular causes. The age and sex adjusted hazard ratios (HRs) for all-cause and cardiovascular mortality were 1.48 (95%CI 1.14 - 1.93) and 2.21 (95%CI 1.49 - 3.28). However, after further adjustment for cardiovascular risk factors there was no independent association of log NT-proSST with mortality, which was almost entirely attributable to adjustment for serum creatinine. There were no significant differences in Harrell's C statistics to predict mortality for the models with and without NT-proSST: both 0.79 (95%CI 0.77 - 0.82) and 0.81 (95%CI 0.77 - 0.84). NT-proSST is unsuitable as a biomarker for cardiovascular and all-cause mortality in stable outpatients with T2DM.
    Full-text · Article · Apr 2015 · BMC Endocrine Disorders
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    ABSTRACT: Zelfcontrole is een belangrijk hulpmiddel om strikte glucoseregulatie te bereiken. Er is echter geen overeenstemming over het gebruik van de 1e of 2e bloeddruppel bij de uitvoering van zelfcontrole.
    No preview · Article · Apr 2015
  • Dennis Schrijnders · Nanne Kleefstra · Gijs W D Landman
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    ABSTRACT: In a recent issue of Diabetologia, Riefflin et al published the results of their investigation into the effects of glibenclamide (known as glyburide in the USA and Canada) on insulin secretion in patients at different levels of glucose control [1]. We acknowledge that these results provide further evidence for the unique side-effect profile of glibenclamide. Unfortunately, in the discussion section, the results were repeatedly extrapolated to sulfonylureas as a class. For example, the final conclusion ends with ‘This emphasises the need for cautious titration when using sulfonylureas as second-line agents after metformin when attempting to maintain tight glucose control.’ The results of this study are largely confirmatory, given the overwhelming existing evidence that glibenclamide is associated with a higher risk of hypoglycaemia [2]. This extrapolation completely ignores important and clinically relevant within-class differences among sulfonylureas. It is well known that of all the s ...
    No preview · Article · Mar 2015 · Diabetologia

Publication Stats

2k Citations
705.65 Total Impact Points

Institutions

  • 2012-2015
    • Universitair Medisch Centrum Groningen
      • Department of Internal Medicine
      Groningen, Groningen, Netherlands
  • 2004-2015
    • University of Groningen
      • • Department of Internal Medicine
      • • Department of General Practice
      Groningen, Groningen, Netherlands
  • 2010-2014
    • Netherlands eScience Center
      Amsterdamo, North Holland, Netherlands
  • 2009-2011
    • Isala Klinieken
      • Department of Internal Medicine
      Zwolle, Overijssel, Netherlands