Nanne Kleefstra

Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

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Publications (112)538.5 Total impact

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    ABSTRACT: Device-guided breathing (DGB) is recommended by the American Heart Association for its blood pressure-lowering effects. Most previous studies that showed beneficial effects on blood pressure had low methodological quality and only investigated short-term blood pressure effects.
    JAMA Internal Medicine 09/2014; · 10.58 Impact Factor
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    ABSTRACT: To evaluate metabolic control and health-related quality of life (HRQOL) in a type 1 diabetes mellitus (T1DM) population.
    World journal of diabetes. 08/2014; 5(4):569-76.
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    ABSTRACT: 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.This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 07/2014; · 3.40 Impact Factor
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    ABSTRACT: 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?
    Human reproduction (Oxford, England). 05/2014;
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    ABSTRACT: The American Heart Association considers device-guided breathing as a reasonable treatment modality in their statement on non-pharmacological options for lowering blood pressure. This review discusses all randomized controlled trials that have investigated the effects of device-guided breathing on blood pressure in patients with hypertension. Thirteen studies were included in this review. In total, 627 patients were included, of which 365 patients were allocated to device-guided breathing. Only 6 studies used acceptable control groups: listening to music, meditative relaxation exercises, or a sham-device. Two sponsored trials showed beneficial effects of device-guided breathing, both used listening to music as a control group. The remaining 4 studies, which had no employees of the manufacturer listed as co-author, observed no beneficial effects on blood pressure. There is only 1 study that used a sham device as a control group. All other studies were to some extend methodologically flawed. Based on the studies with an acceptable methodological quality, there is no clear evidence supporting a short-term beneficial effect on blood pressure by using device-guided breathing.
    World journal of cardiology. 05/2014; 6(5):277-282.
  • Diabetes care 05/2014; 37(5):e115. · 7.74 Impact Factor
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    ABSTRACT: Homozygosity for a 5-leucine repeat (5L-5L) in the carnosinase gene (CNDP1) has been associated with a reduced prevalence of diabetic nephropathy in cross-sectional studies in patients with type 2 diabetes, particularly in women. Prospective studies on mortality are not available. This study investigated whether 5L-5L was associated with mortality and progression of renal function loss and to what extent this effect is modified by sex. In a prospective cohort of patients with type 2 diabetes, a Cox proportional hazard model was used to compare 5L-5L with other genotypes regarding (cardiovascular) mortality. Renal function slopes were obtained by within-individual linear regression of the estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease (MDRD) equation, and were compared between 5L-5L and other genotypes. 871 patients were included (38 % with 5L-5L). After 9.5 years of follow-up, hazards ratios (HR) for all-cause and cardiovascular mortality in 5L-5L versus other genotypes were 1.09 [95 % confidence interval (CI) 0.88-1.36] and 1.12 (95 % CI 0.79-1.58), respectively. There was a significant interaction between CNDP1 and sex for the association with cardiovascular mortality (p = 0.01), not for all-cause mortality (p = 0.32). Adjusted HR in 5L-5L for cardiovascular mortality was 0.69 (95 % CI 0.39-1.23) in men and 1.77 (95 % CI 1.12-2.81) in women. The slopes of eGFR-MDRD did not significantly differ between 5L-5L and other genotypes. The association between CNDP1 and cardiovascular mortality was sex-specific, with a higher risk in women with 5L-5L genotype. CNDP1 was not associated with all-cause mortality or change in eGFR.
    Journal of nephrology 04/2014; · 2.02 Impact Factor
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    ABSTRACT: Chromium is considered to have positive effects on insulin sensitivity and is marketed as an adjunctive therapy for inducing glucose tolerance in cases of insulin resistance ("the glucose tolerance factor"). Case reports on patients who received prolonged parenteral nutrition indeed showed that the absence of trivalent chromium caused insulin resistance and diabetes. However, whether patients with type 2 diabetes can develop a clinically relevant chromium deficiency is unclear. This review summarizes the available evidence regarding the potential effectiveness of chromium supplementation on glycemic control (Hemoglobin A1c levels) in patients with type 2 diabetes. No studies investigating the long-term safety of chromium in humans were found. All clinical trials that have been performed had a relative short follow-up period. None of the trials investigated whether the patients had risk factors for chromium deficiency. The evidence from randomized trials in patients with type 2 diabetes demonstrated that chromium supplementation does not effectively improve glycemic control. The meta-analyses showed that chromium supplementation did not improve fasting plasma glucose levels. Moreover, there were no clinically relevant chromium effects on body weight in individuals with or without diabetes. Future studies should focus on reliable methods to estimate chromium status to identify patients at risk for pathological alterations in their metabolism associated with chromium deficiency. Given the present data, there is no evidence that supports advising patients with type 2 diabetes to take chromium supplements.
    World journal of diabetes. 04/2014; 5(2):160-164.
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    ABSTRACT: Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a treatment option for patients with type 1 diabetes mellitus (T1DM). Aim of the present study was to describe the long-term course of glycaemic control, complications, health related quality of life (HRQOL) and treatment satisfaction among T1DM patients treated with CIPII. Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) therapy in 2006 were followed until 2012. Laboratory, continuous glucose monitoring, HRQOL and treatment satisfaction measurements were performed at the start of the study ,the end of the SC-, the end of the CIPII treatment phase in 2006 and during CIPII therapy in 2012. Linear mixed models were used to calculate estimated values and to test differences between the moments in time. In 2012, more time was spent in hyperglycaemia than after the CIPII treatment phase in 2006: 37% (95% CI 29, 44) vs. 55% (95% CI 48, 63), mean difference 19.8% (95% CI 3.0, 36.6). HbA1c was 65 mmol/mol (95% CI 60, 71) at the end of the SC treatment phase in 2006, 58 mmol/mol (95% CI 53, 64) at the end of the CIPII treatment phase and 65 mmol/mol (95% CI 60, 71) in 2012, respectively (p > 0.05). In 2012, the median number of grade 2 hypoglycaemic events per week (1 (95% CI 0, 2)) was still significantly lower than during prior SC therapy (3 (95% CI 2, 4)): mean change -1.8 (95% CI -3.4, -0.4). Treatment satisfaction with CIPII was better than with SC insulin therapy and HRQOL remained stable. Pump or catheter dysfunction of the necessitated re-operation in 7 patients. No mortality was reported. After 6 years of CIPII treatment, glycaemic regulation is stable and the number of hypoglycaemic events decreased compared to SC insulin therapy. Treatment satisfaction with CIPII is superior to SC insulin therapy, HRQOL is stable and complications are scarce. CIPII is a safe and effective treatment option for selected patients with T1DM, also on longer term.
    BMC Endocrine Disorders 04/2014; 14(1):30. · 2.65 Impact Factor
  • JAMA Internal Medicine 04/2014; 174(4):638. · 10.58 Impact Factor
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    ABSTRACT: Due to ongoing rise in need for care for people with chronic diseases and lagging increase in number of care providers, alternative forms of care provision and self-management support are needed. Empowering patients through an online care platform could help to improve patients' self-management and reduce the burden on the healthcare system. Access to laboratory results and educational modules on diabetes will be offered through a platform for subjects with type 2 diabetes mellitus treated in primary care. Differences in socio-demographic and clinical characteristics between subjects expressing interest vs. disinterest to use the platform will be explored. Platform usage will be tracked and compared. Patient satisfaction and quality of life will be measured by validated questionnaires and economic analyses will be performed. This study is designed to assess the feasibility of use of an online platform in routine primary healthcare for subjects with type 2 diabetes mellitus in the Netherlands, and to study effects of use of the platform on treatment satisfaction, quality of life and clinical parameters. Although providing access to a online platform is not a novel intervention, usage and effects have not yet been studied in this patient population.Trial registration: Trial registration: NCT01570140.
    BMC Endocrine Disorders 03/2014; 14(1):22. · 2.65 Impact Factor
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    ABSTRACT: The prevalence of type 2 diabetes mellitus (T2DM) is rising in the Netherlands, and health care's workload will increase. e-Health applications may increase patients' participation in their care and could help reducing workload. To explore potential users, differences in patients interested and uninterested in e-Health are characterized. A prospective cohort study was initiated in the Drenthe region of the Netherlands. This study included inviting T2DM patients to use e-Health (the e-Vita platform). Patients were offered access to clinical data, laboratory results, educational modules, and a self-management support program. Data were obtained from health record systems of general practices and questionnaires. Out of 2674 patients, 1378 (51.5%) participated in the study. Of the 1378 patients, 974 (70.7%) were interested in e-Health. Of 974, 405 (41.6%) were registered for e-Health. Interested patients were more often male, were younger, had shorter T2DM duration, and were higher educated. Of 405, 110 (27.2%) used the e-Health. No differences were found between users and nonusers of e-Health. Patients interested in e-Health were more often male, were younger, had shorter T2DM duration, and were more often higher educated. However, even in this interested group, the actual participation rate remained low. Together with characteristics and attitudes of caregivers and T2DM patients, the look and content of the e-Health platform strategies that increase interest and participation need to be developed.
    Journal of diabetes science and technology 02/2014; 8(2):230-237.
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    ABSTRACT: Advanced glycation end products play a pivotal role in atherosclerosis. Recently, we showed that tissue advanced glycation end products deposition, noninvasively assessed by skin autofluorescence (SAF), is increased in patients with peripheral artery disease. The aim of the present study was to establish whether SAF is associated with all-cause mortality and with fatal and nonfatal major adverse cardiovascular events (MACEs) in patients with peripheral artery disease. We performed a single-center prospective cohort study of 252 patients with peripheral artery disease (mean age, 66±11 years), recruited from the outpatient clinic (October 2007 to June 2008) who were followed until June 2013. SAF was measured with the advanced glycation end product Reader. The primary end point was all-cause mortality, and the secondary end point was fatal or nonfatal MACE, defined as cardiovascular death and nonfatal myocardial infarction or stroke. During a median follow-up of 5.1 (interquartile range, 5.0-5.3) years, 62 (25%) patients died. Fatal or nonfatal MACE occurred in 62 (25%) patients. A higher SAF was associated with increased risk for all-cause mortality (hazard ratio per unit increase, 2.01; 95% confidence interval, 1.40-2.88; P=0.0002) and fatal or nonfatal MACE (hazard ratio, 1.82; 95% confidence interval, 1.28-2.60; P=0.001), also after adjustment for cardiovascular risk factors and the use of lipid-lowering drugs (hazard ratio, 1.63; 95% confidence interval, 1.13-2.34; P=0.009 and hazard ratio, 1.50; 95% confidence interval, 1.04-2.17; P=0.03, for all-cause mortality and fatal and nonfatal MACE, respectively). SAF as a measure of advanced glycation end products deposition is independently associated with all-cause mortality and fatal or nonfatal MACE in patients with peripheral artery disease after a 5-year follow-up.
    Arteriosclerosis Thrombosis and Vascular Biology 02/2014; · 6.34 Impact Factor
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    ABSTRACT: Gliclazide has been associated with a low risk of hypoglycemic episodes and beneficial long-term cardiovascular safety in observational cohorts. The aim of this study was to assess in a systematic review and meta-analysis of randomized controlled trials the safety and efficacy of gliclazide compared to other oral glucose-lowering agents (PROSPERO2013:CRD42013004156). Medline, EMBASE, Clinicaltrials.gov, Trialregister.nl, Clinicaltrialsregister.eu and the Cochrane database. Included were randomized studies of at least 12 weeks duration with the following outcomes: HbA1c change, incidence of severe hypoglycemia, weight change, cardiovascular events and/or mortality when comparing gliclazide with other oral blood glucose lowering drugs. Bias was assessed with the Cochrane risk of bias tool. The inverse variance random effects model was used. Nineteen trials were included; 3,083 patients treated with gliclazide and 3,155 patients treated with other oral blood glucose lowering drugs. There was a considerable amount of heterogeneity between and bias in studies. Compared to other glucose lowering agents except metformin, gliclazide was slightly more effective (-0.13% (95%CI: -0.25, -0.02, I(2) 55%)). One out of 2,387 gliclazide users experienced a severe hypoglycemic event, whilst also using insulin. There were 25 confirmed non-severe hypoglycemic events (2.2%) in 1,152 gliclazide users and 22 events (1.8%) in 1,163 patients in the comparator group (risk ratio 1.09 (95% CI: 0.20, 5.78, I(2) 77%)). Few studies reported differences in weight and none were designed to evaluate cardiovascular outcomes. The methodological quality of randomized trials comparing gliclazide to other oral glucose lowering agents was poor and effect estimates on weight were limited by publication bias. The number of severe hypoglycemic episodes was extremely low, and gliclazide appears at least equally effective compared to other glucose lowering agents. None of the trials were designed for evaluating cardiovascular outcomes, which warrants attention in future randomized trials.
    PLoS ONE 01/2014; 9(2):e82880. · 3.73 Impact Factor
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    ABSTRACT: Oxidative stress plays an underlying pathophysiologic role in the development of diabetes complications. The aim of this study was to investigate peroxiredoxin 4 (Prx4), a proposed novel biomarker of oxidative stress, and its association with and capability as a biomarker in predicting (cardiovascular) mortality in type 2 diabetes mellitus. Prx4 was assessed in baseline serum samples of 1161 type 2 diabetes patients. Cox proportional hazard models were used to evaluate the relationschip between Prx4 and (cardiovascular) mortality. Risk prediction capabilities of Prx4 for (cardiovascular) mortality were assessed with Harrell's C statistic, the integrated discrimination improvement and net reclassification improvement. Mean age was 67 and the median diabetes duration was 4.0 years. After a median follow-up period of 5.8 years, 327 patients died; 137 cardiovascular deaths. Prx4 was associated with (cardiovascular) mortality. The Cox proportional hazard models added the variables: Prx4 (model 1); age and gender (model 2), and BMI, creatinine, smoking, diabetes duration, systolic blood pressure, cholesterol-HDL ratio, history of macrovascular complications, and albuminuria (model 3). Hazard ratios (HR) (95% CI) for cardiovascular mortality were 1.93 (1.57 - 2.38), 1.75 (1.39 - 2.20), and 1.63 (1.28 - 2.09) for models 1, 2 and 3, respectively. HR for all-cause mortality were 1.73 (1.50 - 1.99), 1.50 (1.29 - 1.75), and 1.44 (1.23 - 1.67) for models 1, 2 and 3, respectively. Addition of Prx4 to the traditional risk factors slightly improved risk prediction of (cardiovascular) mortality. Prx4 is independently associated with (cardiovascular) mortality in type 2 diabetes patients. After addition of Prx4 to the traditional risk factors, there was a slightly improvement in risk prediction of (cardiovascular) mortality in this patient group.
    PLoS ONE 01/2014; 9(2):e89719. · 3.73 Impact Factor
  • Diabetes care 12/2013; 36(12):e217. · 7.74 Impact Factor
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    ABSTRACT: Background: Studies investigating interventions, aimed at improving patient satisfaction by exploring the patient's request for help, show conflicting results. Objective: To investigate whether writing down the request for help on a request card, prior to the consultation improves patient satisfaction. Methods: This study was a single-blind randomized controlled trial, in which the patients were blinded to the intervention. Patients were recruited in two rural practices (five GPs) and one urban practice (four GPs) in The Netherlands. Consecutive patients with a new request for help were asked to participate. All patients received general information about patient satisfaction. After randomization, patients in the intervention group were asked to fill in a card with their request(s) for help; the general practitioners started the consultations with these questions. We used the 'Professional Care' subscale of the Consultation Satisfaction Questionnaire (CSQ) to examine the effect of the intervention on patient satisfaction. Secondary outcomes were patient satisfaction measured with the patient's VAS score, the GP's VAS score on satisfaction, consultation time, the other subscales of the CSQ, and the number of consultations during follow-up. Results: There was no difference in patient satisfaction (CSQ, VAS) between both groups. We also did not find any differences between the other subscales of the CSQ. Conclusion: A beneficial effect of the use of a 'request card' by the patient on patient satisfaction of the consultation could not be demonstrated.
    The European journal of general practice 11/2013;
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    ABSTRACT: Objective The mid region fragment of pro-adrenomedullin (MR-proADM) is a marker of endothelial dysfunction and has been associated with a variety of diseases. Our aim was to investigate whether MR-proADM is associated with new-onset albuminuria, cardiovascular (CV) and all-cause mortality in patients with type 2 diabetes treated in primary care.Research Design and Methods Patients with type 2 diabetes participating in the observational ZODIAC study were included. Cox regression analyses were used to assess the relation of baseline MR-proADM with new-onset albuminuria, cardiovascular and all-cause mortality. Risk prediction capabilities of MR-proADM for new-onset albuminuria, cardiovascular and all-cause mortality were assessed with Harrell's C and the integrated discrimination improvement (IDI).ResultsIn 1,243 patients (mean age 67 (± 12) years) the median follow-up was 5.6 [IQR 3.1-10.1] years, 388 (31%) patients died, with 168 (12%) CV deaths. Log2 MR-proADM was associated with CV (hazard ratio (HR) 1.96, 95%CI 1.27-3.01), and all-cause mortality (HR 1.78, 95%CI 1.34-2.36) after adjusting for age, gender, BMI, smoking, systolic blood pressure, cholesterol-HDL ratio, duration of diabetes, HbA1c, ACEi/ARB, history of CV diseases, log serum creatinine, and log albumin-to-creatinine-ratio. MR-proADM slightly improved mortality risk prediction. The age and sex adjusted, but not multivariate adjusted, MR-proADM levels were associated with new-onset albuminuria.ConclusionsMR-proADM was associated with cardiovascular and all-cause mortality in patients with type 2 diabetes after a median follow-up of 5.6 years. There was no independent relationship with new-onset albuminuria. In the availability of an extensive set of risk factors, there was little added effect of MR-proADM in risk prediction of cardiovascular and all-cause mortality.
    Diabetes care 10/2013; · 7.74 Impact Factor
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    ABSTRACT: Objectives: To study vitamin B12 concentrations in patients with type 2 diabetes with and without metformin use and to identify risk factors and consequences of low vitamin B12 concentrations. Research design and methods: This study had a cross-sectional design. During eight weeks all patients with type 2 diabetes visiting the diabetic outpatient clinic of the Isala Clinics in Zwolle were approached for participation. Participation included measurement of haemoglobin, mean corpuscular volume and vitamin B12 levels. Data on neuropathy were retrospectively searched for in the patient records. Vitamin B12 deficiency was defined as serum B12 concentrations.
    The Netherlands Journal of Medicine 09/2013; 71(7):386-90. · 2.38 Impact Factor
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    ABSTRACT: OBJECTIVE Copeptin, a surrogate marker for arginine vasopressin, has been associated with cardiovascular (CV) events and mortality in patients with type 2 diabetes complicated by end-stage renal disease or acute myocardial infarction. For stable outpatients, these associations are unknown. Our aim was to investigate whether copeptin is associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care.RESEARCH DESIGN AND METHODS Patients with type 2 diabetes participating in the observational Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses with age as time scale were used to assess the relationships of baseline copeptin with CV and all-cause mortality.RESULTSWe included 1,195 patients (age 67 ± 12 years, 44% male). Median baseline copeptin concentration was 5.4 (interquartile range [IQR] 3.1-9.6) pmol/L. After a median follow-up of 5.9 (IQR 3.2-10.1) years, 345 patients died (29%), with 148 CV deaths (12%). Log2 copeptin was associated with CV (hazard ratio 1.17 [95% CI 0.99-1.39]; P = 0.068) and all-cause mortality (1.22 [1.09-1.36]; P = 0.001) after adjustment for age, sex, BMI, smoking, systolic blood pressure, total cholesterol to HDL ratio, duration of diabetes, HbA1c, treatment with ACE inhibitors and angiotensin receptor blockers, history of CV diseases, log serum creatinine, and log albumin to creatinine ratio; however, copeptin did not substantially improve risk prediction for CV (integrated discrimination improvement 0.14% [IQR -0.27 to 0.55%]) and all-cause mortality (0.77% [0.17-1.37%]) beyond currently used clinical markers.CONCLUSIONS We found copeptin to be associated with CV and all-cause mortality in patients with type 2 diabetes treated in primary care. Intervention studies should show whether the high CV risk in type 2 diabetes can be reduced by suppression of vasopressin, for example by reducing salt intake.
    Diabetes care 06/2013; · 7.74 Impact Factor

Publication Stats

860 Citations
538.50 Total Impact Points

Institutions

  • 2010–2014
    • Universitair Medisch Centrum Groningen
      • Department of Internal Medicine
      Groningen, Groningen, Netherlands
  • 2007–2013
    • Isala Klinieken
      • Department of Internal Medicine
      Zwolle, Overijssel, Netherlands
  • 2006–2010
    • University of Groningen
      • Department of Internal Medicine
      Groningen, Province of Groningen, Netherlands