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Background: Poor glycemic control prior to cancer diagnosis for patients with preexisting type 2 diabetes (T2DM) may predict a worse cancer diagnosis. We investigated the association between pre-diagnosis glycemic control and all-cause mortality in patients with T2DM who develop cancer. Methods: This prospective cohort study linked data from three sources covering 1989 to 2019: a T2DM benchmarking database, the Netherlands Cancer Registry, and the Personal Records Database. We included patients with T2DM and incident primary breast, colorectal, or prostate cancer (stage 0–III), with target glycemic control defined according to Dutch guidelines. Analysis involved estimating the association between glycemic control and all-cause mortality with Cox proportional hazard models, accounting for individual expected survival relative to the general population and relevant disease (e.g., diabetes duration and medications) and individual (e.g., age and gender) characteristics. Results: Of the 71,648 linked cases, 620 had breast cancer, 774 had colorectal cancer, and 438 had prostate cancer, with follow-up data available for 6.4 (4.2–8.4), 5.6 (2.7–7.6), and 6.3 (4.5–8.2) years, respectively. Compared with patients with pre-diagnosis glycemic control at target, the HRs and 95% confidence intervals for mortality among those with pre-diagnosis glycemic control not at target were 1.40 (1.00–1.96) for breast cancer, 1.45 (1.12–1.88) for colorectal cancer, and 1.39 (0.98–1.98) for prostate cancer. Conclusions: Among patients with T2DM in Dutch primary care, poor glycemic control before diagnosis with breast and colorectal cancer can increase mortality compared with good control. Impact: Glycemic control prior to cancer diagnosis is of prognostic value.

Albuminuria is an under-recognized component of chronic kidney disease definition, staging, and prognosis. Guidelines, particularly for hypertension, conflict on recommendations for urine albumin-to-creatinine ratio (ACR) measurement. Separately among 1 344 594 adults with diabetes and 2 334 461 nondiabetic adults with hypertension from the chronic kidney disease Prognosis Consortium, we assessed ACR testing, estimated the prevalence and incidence of ACR ≥30 mg/g and developed risk models for ACR ≥30 mg/g. The ACR screening rate (cohort range) was 35.1% (12.3%–74.5%) in diabetes and 4.1% (1.3%–20.7%) in hypertension. Screening was largely unrelated to the predicted risk of prevalent albuminuria. The median prevalence of ACR ≥30 mg/g across cohorts was 32.1% in diabetes and 21.8% in hypertension. Higher systolic blood pressure was associated with a higher prevalence of albuminuria (odds ratio [95% CI] per 20 mm Hg in diabetes, 1.50 [1.42–1.60]; in hypertension, 1.36 [1.28–1.45]). The ratio of undetected (due to lack of screening) to detected ACR ≥30 mg/g was estimated at 1.8 in diabetes and 19.5 in hypertension. Among those with ACR

Background: Nowadays, patients with chronic conditions such as type 2 diabetes mellitus (T2DM) need and want to be more active participants in their health care. This study aimed to investigate the effects of the Proactive Interdisciplinary Self-Management (PRISMA) training program on participation during consultations with practice nurses and self-efficacy of patients with T2DM in general practice. Methods: Within a randomized controlled trial, patients were followed for 6 months. They received either PRISMA in addition to usual care or usual care only. Self-efficacy was assessed using the 5-item Perceived Efficacy in Patient-Physician Interactions (PEPPI-5) scale. Consultations were video-recorded and analyzed using the Roter interaction analysis system. Multilevel analysis was carried out. Results: No differences in the PEPPI-5 were found between the intervention (n = 101) and control groups (n = 102) (U = 1,737.5, z = -0.2, P = 0.8). In addition, the groups did not differ in patient participation. However, patients who attended the PRISMA program expressed more counselling utterances (B = 0.22; standard error (SE) = 0.09). Conclusions: PRISMA did not result in higher self-efficacy or patient participation during the consultation with practice nurses at 6 months. Possibly, two training sessions are insufficient and a more powerful intervention might be needed. However, the study showed indications that patients counselled themselves more frequently during the consultation. Practice nurses could stimulate patients who are already engaged in self-counselling by further specifying their goals of behavior change. J Clin Med Res. 2020;12(2):79-89 doi: https://doi.org/10.14740/jocmr3965

IMPORTANCE Early identification of individuals at elevated risk of developing chronic kidney disease (CKD) could improve clinical care through enhanced surveillance and better management of underlying health conditions.OBJECTIVE To develop assessment tools to identify individuals at increased risk of CKD, defined by reduced estimated glomerular filtration rate (eGFR).DESIGN, SETTING, AND PARTICIPANTS Individual-level data analysis of 34 multinational cohorts from the CKD Prognosis Consortium including 5 222 711 individuals from 28 countries. Data were collected from April 1970 through January 2017. A 2-stage analysis was performed, with each study first analyzed individually and summarized overall using a weighted average. Because clinical variables were often differentially available by diabetes status, models were developed separately for participants with diabetes and without diabetes. Discrimination and calibration were also tested in 9 external cohorts (n = 2 253 540).EXPOSURES Demographic and clinical factors.MAIN OUTCOMES AND MEASURES Incident eGFR of less than 60 mL/min/1.73 m(2).RESULTS Among 4 441 084 participants without diabetes (mean age, 54 years, 38% women), 660 856 incident cases (14.9%) of reduced eGFR occurred during a mean follow-up of 4.2 years. Of 781 627 participants with diabetes (mean age, 62 years, 13% women), 313 646 incident cases (40%) occurred during a mean follow-up of 3.9 years. Equations for the 5-year risk of reduced eGFR included age, sex, race/ethnicity, eGFR, history of cardiovascular disease, ever smoker, hypertension, body mass index, and albuminuria concentration. For participants with diabetes, the models also included diabetes medications, hemoglobin A(1c), and the interaction between the 2. The risk equations had a median C statistic for the 5-year predicted probability of 0.845 (interquartile range [IQR], 0.789-0.890) in the cohorts without diabetes and 0.801 (IQR, 0.750-0.819) in the cohorts with diabetes. Calibration analysis showed that 9 of 13 study populations (69%) had a slope of observed to predicted risk between 0.80 and 1.25. Discrimination was similar in 18 study populations in 9 external validation cohorts; calibration showed that 16 of 18 (89%) had a slope of observed to predicted risk between 0.80 and 1.25.CONCLUSIONS AND RELEVANCE Equations for predicting risk of incident chronic kidney disease developed from more than 5 million individuals from 34 multinational cohorts demonstrated high discrimination and variable calibration in diverse populations. Further study is needed to determine whether use of these equations to identify individuals at risk of developing chronic kidney disease will improve clinical care and patient outcomes.

Simple SummaryA growing number of colorectal cancer survivors live with type 2 diabetes, as a result of improved cancer diagnosis and treatment. These patients might have worse glycemic control after their cancer diagnosis, which may increase the risk of cardiovascular diseases. This prospective cohort study evaluated the quality of glycemic control for colorectal cancer survivors, as compared to those without cancer in Dutch primary care for diabetes. During a 10-year follow-up for 57,330 patients, there were 705 patients diagnosed with colorectal cancer. No clinically relevant difference on the probability of reaching the target HbA1c was observed between colorectal cancer survivors and patients with no history of cancer. These results showed a robust diabetes care system, implying that the glycemic control for colorectal cancer survivors can be delegated to the primary care professionals.Cancer survivors with diabetes tend to have worse glycemic control after their cancer diagnosis, which may increase the risk of cardiovascular diseases. We aimed to investigate whether glycemic control differs between colorectal cancer (CRC) survivors and those without cancer, among patients with type 2 diabetes being treated in the Dutch primary care. The Zwolle Outpatient Diabetes project Integrating Available Care database was linked with the Dutch Cancer Registry (n = 71,648, 1998-2014). The cases were those with stage 0-III CRC, and the controls were those without cancer history. The primary and secondary outcomes were the probability of reaching the glycated hemoglobin (HbA1c) target and the mean of HbA1c during follow-up, respectively. Mixed linear modeling was applied, where the status of CRC was a time-varying variable. Among the 57,330 patients included, 705 developed CRC during follow-up. The mean probability of reaching the HbA1c target during follow-up was 73% versus 74% (p = 0.157) for CRC survivors versus those without cancer, respectively. The mean HbA1c was 51.1 versus 50.8 mmol/mol (p = 0.045) among CRC survivors versus those without cancer, respectively. We observed a clinically comparable glycemic control among the CRC survivors without cancer, indicating that glycemic control for CRC survivors can be delegated to primary care professionals.

Background: Because of continuous hyperglycemia and hyperinsulinemia and the use of photosensitizing drug, hydrochlorothiazide (HCTZ), the risk of cutaneous squamous cell carcinoma (cSCC) might be increased among patients with diabetes. This study aimed to estimate the risk of cSCC among HCTZ users with type 2 diabetes, and to determine whether thiazide-like diuretics, another drug in the same class with HCTZ, would be safer. Methods: We linked the benchmarking database in Dutch primary care, the Netherlands Cancer Registry, and the Dutch Personal Records Database (1998–2019). All 71,648 patients were included, except for those who had a history of skin cancer prior to cohort entry. We used Cox modeling to estimate the HRs and 95% confidence intervals for cSCC. The model was adjusted by cumulative exposure to each antihypertensive, age, sex, smoking, body mass index, blood pressure, serum creatinine, other confounding drug use at cohort entry, and cohort entry year. Results: There were 1,409 cSCC events (23 among thiazide-like diuretics users), during a follow-up of 679,789 person-years. Compared with no HCTZ use, the adjusted HRs for HCTZ use were 1.18 (1.00–1.40) for ≤2 years, 1.57 (1.32–1.88) for 2 to 4 years, and 2.09 (1.73–2.52) for >4 years. The HR was 0.90 (0.79–1.03) for an additional year of thiazide-like diuretic use. Conclusions: In patients with diabetes, exposure to HCTZ for >2 years is associated with an increased risk of cSCC, whereas no increased risk associated with thiazide-like diuretics was observed. Impact: The potential increased risk of cSCC should be a consideration when prescribing HCTZ, with thiazide-like diuretics offering a safer alternative.

AimsWe aimed to assess and characterize sex differences in adverse drug reactions (ADRs) reported to the national pharmacovigilance centre in the Netherlands while considering differences in drug use.MethodsADRs spontaneously reported by healthcare professionals and patients to the Netherlands pharmacovigilance centre Lareb were used. Drug-ADR combinations reported at least 10 times between 2003-2016 for drugs used by 10,000 persons in that period were included. Data about the number of drug users was obtained from the National Health Care Institute. Sex-specific ADRs, like gynaecological problems, were excluded. Sex differences in specific drug-ADR combinations were tested using bivariate logistic regression analyses in which the number of drug users per sex was taken into account.ResultsIn total, 2483 drug-ADR combinations were analysed. Possibly relevant sex differences were shown in 363 combinations (15%). Most of these drug-ADR combinations were reported more often for women (322 combinations). Drugs with the highest number of ADRs that were more often reported for women included thyroid hormones (32 combinations) and antidepressants (16 combinations for the centrally acting sympathomimetics; 14 combinations for other antidepressants). Some ADRs were predominantly reported for women across a range of drugs such as headache and dizziness whereas other ADRs such as tendon ruptures and aggression were reported more often for men.ConclusionsIdentified sex differences in reported ADRs often referred to women. These differences may have various causes, including pharmacological and behavioural causes, which need to be further assessed. The results may ultimately lead to sex-specific prescribing or monitoring recommendations.

Online care platforms can support patients with type 2 diabetes (T2DM) in managing their health. However, in the use of eHealth, a low participation rate is common. The Proactive Interdisciplinary Self-Management (PRISMA) program, aimed at improving patients’ self-management skills, was expected to encourage patients to manage their disease through the use of an online platform. Therefore, the objective of the current study was to investigate whether a group education program can improve the use of an online care platform in patients with T2DM treated by primary care providers in the Netherlands. In a randomized controlled trial, patients with T2DM received either PRISMA with usual care or usual care only. During a six-month follow-up period in 2014-2015, usage (number of log-ons and time spent per session) of an online care platform (e-Vita) aimed at improving T2DM self-management was assessed. A training about the functionalities of e-Vita was offered. The sample consisted of 203 patients. No differences were found between the intervention and control groups in the number of patients who attended the platform training (interested patients) (X21=0.58; p=0.45), and the number of patients who logged on at least once (platform users) (X21=0.46; p=0.50). In addition, no differences were found between the groups in the type of users—patients who logged on twice or more (active users) or patients who logged on once (nonactive users) (X21=0.56; p=0.45). The PRISMA program did not change platform usage in patients with T2DM. In addition, only a small proportion of the patients logged on twice or more. Patients probably need other encouragements to manage their condition using an online platform.

Background Diabetes self-management education can be helpful for patients with type 2 diabetes in managing their condition. We aimed to study the effects of the group-based PRoactive Interdisciplinary Self-MAnagement (PRISMA) training program on self-reported and clinical outcomes in patients with type 2 diabetes treated in general practice. Methods Persons aged 18 years or older diagnosed with type 2 diabetes and treated in primary care were included. In a randomized controlled trial design (1:1), patients were followed for 6 months with an extension phase of 6 months. Block randomization was used. The patients with type 2 diabetes received either PRISMA in addition to usual care or usual care only. All patients completed a range of validated questionnaires (including knowledge, skills, and confidence for self-management [PAM], diabetes self-care behavior [SDSCA], health-related quality of life [EQ-5D], and emotional well-being [WHO-5]). In addition, clinical outcomes (HbA1c, body mass index, systolic blood pressure, and cholesterol levels) were collected during the routine diabetes checkups. Results Of the total sample (n = 193), 60.1% were men. The mean age was 69.9 years (SD = 9.1). No significant differences were found on self-reported outcomes between the groups at 0, 6, and 12 months. The clinical outcomes were not reported due to a large number of missing values. Conclusion PRISMA did not improve self-reported outcomes in patients with type 2 diabetes treated in primary care. It was not possible to make a statement about the clinical effects. Trial registration date: 16/07/2014, number: NL4550 (https://www.trialregister.nl/trial/4550).

Orthostatic hypotension (OH) is defined as a drop in systolic blood pressure (SBP) of >= 20 mm Hg and/or a drop in diastolic blood pressure (DBP) of >= 10 mm Hg within 3 min of standing. The international guidelines recommend ideally diagnosing OH with a continuous blood pressure (BP) measurement device, although in daily practice interval BP measurement devices are used more often. We aimed to investigate the difference in observed prevalence of OH between an interval and a continuous BP measurement device. A total of 104 patients with a mean age of 69 years were included. The prevalence of OH was 35.6% (95% CI: 26.4-44.8) with the interval BP measurement and 45.2% (95% CI: 35.6-54.8) with the continuous BP measurement device (P = .121). Lin's coefficient of concordance ranged from 0.47 to 0.59 for the drop in systolic blood pressure and from 0.33 to 0.42 for the drop in diastolic blood pressure. The positive proportion of agreement in diagnosis of OH between the interval and continuous measure was 59.5% and the negative proportion of agreement was 72.5%. Although the prevalence of OH was not significantly different between the continuous and the interval BP measurement devices using a similar amount of measurement, the concordance between interval and continuous measure is low resulting in low positive and negative proportions of agreement in the diagnosis of OH. We conclude that continuous BP measurement cannot be substituted by an interval BP measurement to diagnose OH.

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 (sic) 167,494,732 corresponding to an annual mean of (sic) 55,831,577 of total costs and (sic) 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 (sic) 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.

Objective The optimal frequency of self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes (T2DM) with stable glycemic control is unknown. This study investigated effects of 3 frequencies of SMBG on glycemic control and quality of life after 9 months in patients using one long-acting insulin injection a day. In an open-label, multi-center, primary-care, parallel (1:1:1) randomized trial in the Netherlands including patients with T2DM, HbA1c ≤ 58 mmol/mol (≤ 7.5%), stable glycemic control, treated with one insulin injection daily, three frequencies of 4-point glucose measurements (before meals and bedtime) were weekly (n = 22), every 2 weeks (n = 16) and monthly (n = 20) were compared. Results A total of 58 patients with T2DM were included by 38 general practitioners, which was lower then anticipated. There were no significant between group differences in HbA1c (mmol/mol); group C compared to A and B; − 2.7 (95% CI − 6.4, 1.0) and − 1.0 (95% CI − 4.9, 3.0) and quality of life. Baring in mind the lower than anticipated inclusion rate, there were no significant differences in HbA1c and quality of life between three different frequencies of SMBG in patients with stable glycemic control using one long-acting insulin injection. Trial registration NCT01460459, registered 10-2011, recruitment between 05-2011 and 12-2011

Background orthostatic hypotension (OH) is one out of many risk factors believed to contribute to an increased fall risk in elderly subjects but it is unclear whether an independent association between OH and falling exists. Objectives to perform an individual patient data (IPD) meta-analysis of prospective observational studies investigating the relationship between OH and falling. Design MEDLINE, EMBASE, the Cochrane Library and the abstracts of annual meetings of selected hypertension societies were searched. Both one-stage (analysing all IPD from all studies simultaneously) and two-stage (analysing IPD per study, and then pooling the results) methods were used, and both logistic and cox regression analyses were performed. The study protocol was published on PROSPERO (2015:CRD42015019178). Results from 34 selected abstracts, 6 studies were included. IPD were provided in 1,022 patients from 3 cohorts and were included in the IPD meta-analysis. The one-stage meta-analysis showed a significant relationship between OH and time to first fall incident (hazard ratio (HR) 1.52 (95% Confidence Interval (CI) 1.23-1.88)). No significant relationship between OH and falling was found in the one-stage logistic regression analysis and the two-stage logistic and cox regression analyses. Conclusions this IPD meta-analysis of prospective observational studies showed a clear and significant relationship between OH and time to first fall incident. Although the ORs of falling was not significantly different for patients with and without OH, a the cox regression analyses reporting HRs and including time to incident provided more clinically relevant information in present meta-analysis.

AimOrthostatic hypotension (OH) is highly prevalent in old age. The impact of OH on orthostatic complaints and falling is questionable. We wondered if the consensus definition of OH plays an essential role in the accuracy and direction of the prediction of these endpoints. We aimed to explore the relation between different definitions of OH, including relative decrease of blood pressure, and orthostatic complaints and falling. MethodsA cross-sectional study was performed with 1415 participants aged 65 years visiting a mobile fall-prevention team. The CAREFALL Triage Instrument and data on blood pressure, orthostatic complaints and previous fall incidents were collected. Multivariate binary logistic regression analyses were performed to assess the association of different definitions of OH and orthostatic complaints or falling. Ten different definitions of OH based on different relative declines of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were defined. ResultsThe 2011 consensus definition of OH was not related to orthostatic complaints (Odds Ratio (OR) 1.07 (95 % Confidence Interval (CI) 0.68-1.69)) or previous fall incidents (OR 1.08 (95%CI 0.83-1.41)). A 25 % SBP decrease was significantly related to orthostatic complaints (OR 2.81 (95%CI 1.31-6.05)) and a 25 % DBP decrease was related to previous fall incidents (OR 2.56 (95%CI 1.08-6.09)). ConclusionsWith the exception of a decrease of 25 % SBP or DBP, the clinical relevance of incidental OH blood pressure measurements seems very limited with respect to orthostatic complaints or fall incidents in elderly patients. Using relative decreases may be more appropriate in clinical practice. Geriatr Gerontol Int 2017; 17: 1881-1885

Background: Type 2 diabetes mellitus (T2DM) is a risk factor for the development of non-alcoholic fatty liver disease, which can lead to liver fibrosis and ultimately to cirrhosis. Transient elastography (TE), by using the FibroScan, and is a non-invasive ultrasonography method to measure liver elasticity. TE has been related with the degree of liver fibrosis. Objective: To investigate the applicability of TE in daily clinical practice among T2DM patients. Method: In a non-academic teaching hospital, T2DM patients without a history of liver disease the degree of liver stiffness was measured using TE. Successful measurements were defined as 10 validated measurements per patient and an interquartile range (IQR) to median ratio of ≤30%. Results: In 90 of 126 patients (71%) valid measurements were be obtained. Among the patients with invalid measurements, 33 had < 10 valid measurements and 3 had a IQR to median ratio of 2 and 39% in patients with a BMI ≥30 kg/m2. Among the 90 patients with valid liver stiffness measurements, the median liver stiffness was 6.7 [4.6-8.5] kPa with a IQR of measurements of 1.1 [0.6-1.8] kPa and IQR to median ratio of 17 (13-23)%. Conclusion: The success rate of TE measurements using the FibroScan in patients with T2DM was 71%, with a lower success rate in patients with a BMI ≥ 30 kg/m2. This diagnostic modality needs further investigation being introduced as a marker of fibrosis in daily diabetes practice.

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).

Item does not contain fulltext BACKGROUND: Change in albuminuria as a surrogate endpoint for progression of chronic kidney disease is strongly supported by biological plausibility, but empirical evidence to support its validity in epidemiological studies is lacking. We aimed to assess the consistency of the association between change in albuminuria and risk of end-stage kidney disease in a large individual participant-level meta-analysis of observational studies. METHODS: In this meta-analysis, we collected individual-level data from eligible cohorts in the Chronic Kidney Disease Prognosis Consortium (CKD-PC) with data on serum creatinine and change in albuminuria and more than 50 events on outcomes of interest. Cohort data were eligible if participants were aged 18 years or older, they had a repeated measure of albuminuria during an elapsed period of 8 months to 4 years, subsequent end-stage kidney disease or mortality follow-up data, and the cohort was active during this consortium phase. We extracted participant-level data and quantified percentage change in albuminuria, measured as change in urine albumin-to-creatinine ratio (ACR) or urine protein-to-creatinine ratio (PCR), during baseline periods of 1, 2, and 3 years. Our primary outcome of interest was development of end-stage kidney disease after a baseline period of 2 years. We defined an end-stage kidney disease event as initiation of kidney replacement therapy. We quantified associations of percentage change in albuminuria with subsequent end-stage kidney disease using Cox regression in each cohort, followed by random-effects meta-analysis. We further adjusted for regression dilution to account for imprecision in the estimation of albuminuria at the participant level. We did multiple subgroup analyses, and also repeated our analyses using participant-level data from 14 clinical trials, including nine clinical trials not in CKD-PC. FINDINGS: Between July, 2015, and June, 2018, we transferred and analysed data from 28 cohorts in the CKD-PC, which included 693 816 individuals (557 583 [80%] with diabetes). Data for 675 904 individuals and 7461 end-stage kidney disease events were available for our primary outcome analysis. Change in ACR was consistently associated with subsequent risk of end-stage kidney disease. The adjusted hazard ratio (HR) for end-stage kidney disease after a 30% decrease in ACR during a baseline period of 2 years was 0.83 (95% CI 0.74-0.94), decreasing to 0.78 (0.66-0.92) after further adjustment for regression dilution. Adjusted HRs were fairly consistent across cohorts and subgroups (ie, estimated glomerular filtration rate, diabetes, and sex), but the association was somewhat stronger among participants with higher baseline ACR than among those with lower baseline ACR (pinteraction

Aim: To investigate changes in body weight trajectories after the addition of individual sulphonylureas (SUs) to metformin in patients with type 2 diabetes.Materials and methods: We conducted a retrospective observational cohort study, in a primary care setting in the Netherlands. Patients aged >= 18 years with type 2 diabetes who were included in the ZODIAC cohort between 1998 and 2012 and who received metformin monotherapy at inclusion (n = 29 195), and had used metformin as monotherapy for at least 1 year before receiving dual therapy through the addition of an SU for at least 1 year were eligible for inclusion. The primary outcome was within-drug yearly change in body weight after receiving add-on therapy with individual SUs during 5 years of follow-up. The secondary outcome was within-drug yearly change in glycated haemoglobin (HbA1c). Annual changes in weight and HbA1c were estimated with linear mixed models, adjusted for age, gender and diabetes duration.Results: A total of 2958 patients were included. No significant weight changes were observed within and between any of the individual SUs after treatment intensification (p = 0.24). In addition, no significant difference in weight between the add-on therapy combinations was observed (p = 0.26). The average HbA1c the year before intensification was 7.2% (55 mmol/mol) and dropped below 7.0% (53 mmol/mol) the year after.Conclusions: In patients with type 2 diabetes treated in primary care, strict glycaemic control can be maintained with SUs used as add-on therapy to metformin, without the offset of relevant weight changes.

This study aimed to investigate the validity of the accelerometer-based DynaPort system to detect physical activity in frail, older subjects. Eighteen home-dwelling subjects (Groningen Frailty Indicator [GFI] score ≥ 4, ≥ 75 years) were included. Activities in their home environment were simultaneously observed by two researchers and measured with the DynaPort system during six consecutive hours. Primary outcome measures were the sensitivity and specificity of the DynaPort for locomotion (90% considered as sufficient agreement). Other outcome measures were overall agreement, and sensitivity and specificity for other activities. Sensitivity and specificity for locomotion were 83.3% and 100.0%, respectively. Overall agreement was 74.6%. Sensitivity was sufficient for sitting (94.4%), but not for lying and standing (59.2% and 69.6%, respectively). Specificity was sufficient for lying and standing (100.0% and 93.3%, respectively), but not for sitting (80.7%). In conclusion, the DynaPort system is not a valid method for assessing physical activity in frail, older subjects.

Background: C-reactive protein (CRP), procalcitonin (PCT) and pro-adrenomedullin (MR-proADM) are inflammation markers associated with long-term mortality risk. We compared the associations and predictive capacities of CRP, PCT and MR-proADM with cardiovascular and all-cause mortality in patients with type 2 diabetes.Methods: This study included primary care treated patients with type 2 diabetes participating in the ZODIAC cohort study. A total of 1005 out of 1688 patients (60%) had complete baseline variables. Baseline CRP, PCT and MR-proADM were assessed in relation to cardiovascular and all-cause mortality with Cox proportional hazard analyses. Hazard Ratios (HR) were adjusted for age, gender, BMI, smoking, systolic blood pressure, cholesterol-HDL ratio, duration of diabetes, HbA(1c), history of cardiovascular diseases, albumin-creatinine ratio and creatinine. Risk prediction capabilities were assessed with Harrell's C statistics and proportion of explained variance (R-2).Results: After a median follow-up of 11 years, 472 (47%) of 1005 patients had died. The likelihood ratio test showed that CRP and MR-proADM significantly improved prediction in cardiovascular mortality [HRs 1.20 (95% CI 1.09-1.33) and 1.56 (95% CI 1.06-2.30)] and in all-cause mortality [HRs 1.10 (95% CI: 1.03-1.18) and 1.31 (95% CI 1.02-1.69)]. Harrell's C values and R-2 measures showed slightly improved discrimination for cardiovascular mortality in patients without macrovascular disease (C: 0.80 to 0.81; R-2: 0.50 to 0.52) and MR-proADM (C: 0.80 to 0.82; R-2: 0.50 to 0.52).Conclusions: CRP and MR-proADM, but not PCT, were independently associated with cardiovascular and all-cause mortality. In patients without macrovascular diseases, CRP and MR-proADM slightly improved discrimination, in absolute sense, of patients at risk for cardiovascular mortality. (C) 2016 Published by Elsevier Ireland Ltd.

Context: In type 1 diabetes mellitus, low levels of insulin-like growth factor -1 (IGF-1) and IGF binding protein-3 (IGFBP-3) and high levels of GH and IGFBP-1 are present, probably due to portal vein insulinopenia.Objective: To test the hypothesis that continuous ip insulin infusion (CIPII) has a more pronounced effect than sc insulin therapy on regulation of the GH-IGF-1 axis.Design: This was a prospective, observational case-control study. Measurements were performed twice at a 26-week interval.Setting: Two secondary care hospitals in the Netherlands participated in the study.Patients: There were a total of 184 patients, age-and gender-matched, of which 39 used CIPII and 145 sc insulin therapy for the past 4 years.Outcomes: Primary endpoint included differences in IGF-1. Secondary outcomes were differences in GH, IGFBP-1, and IGFBP-3.Results: IGF-1 was higher with CIPII as compared to SC insulin therapy: 124 mu g/liter (95% confidence interval [CI], 111-138) vs 108 mu g/liter (95% CI 102-115) (P = .035). Additionally, IGFBP-3 concentrations were higher and IGFBP-1 and GH concentrations were lower with CIPII as compared to SC insulin therapy: 3.78 mg/liter (95% CI, 3.49 - 4.10) vs 3.31 mg/liter (95% CI, 3.173.47) for IGFBP-3, 50.9 mu g/liter (95% CI, 37.9 - 68.2) vs 102.6 mu g/liter (95% CI, 87.8 - 119.8) for IGFBP-1 and 0.68 mu g/liter (95% CI, 0.44 - 1.06) vs 1.21 mu g/liter (95% CI, 0.95-1.54) for GH, respectively. In multivariate analysis, IGF-1 had no significant association with HbA1c.Conclusions: The GH-IGF-1 axis may be affected by the route of insulin administration with CIPII counteracting dysregulation of the GH-IGF1 axis present during sc insulin therapy.

Objective: Hypertension, orthostatic hypotension and orthostatic hypertension (OHT) are highly prevalent in old age. The associations in the very elderly and frail patients between blood pressure, and especially orthostatic changes in blood pressure, and mortality are unclear. We aimed to investigate the relationships between orthostatic changes in blood pressure, blood pressure and mortality in nursing home residents.Design and methods: A prospective observational cohort study. Cox proportional hazard modelling was used to investigate the relation between orthostatic hypotension, OHT, the various blood pressure variables and mortality with adjustment for confounders. In the case of significant associations in the models, risk prediction capabilities were assessed with Harrell's C statistics and the proportion of explained variance (R-2).Results: Two hundred and ninety patients with a mean age of 80.8 (SD 9.9) years participated in this study. The overall mortality risk increased by 17% [95% confidence interval (CI): 2-34%] for every 10-mmHg increase in DBP. Adding DBP did not change Harrell's C values and increased R-2 with 0.03 or less. Only in patients at the psychogeriatric department, orthostatic hypotension was associated with an increased all-cause mortality risk [hazard ratio (HR) 1.71 (95% CI: 1.08-2.71%)]. The HR of OHT in this patient group was 0.61 (95% CI: 0.32-1.19%).Conclusion: DBP was related to all-cause mortality in a nursing home population. Orthostatic hypotension was related to all-cause mortality in the most frail group of nursing home patients. The predictive capabilities of both DBP and orthostatic hypotension are rather small with respect to mortality. A beneficial effect of OHT could not be excluded on the basis of the width of the CI.

Objective: 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).Design: 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 6 month 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.Results: 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; -33, -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.Conclusion: After 6 years 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. (C) 2015 Elsevier Ltd. All rights reserved.

Rationale & Objective Chronic kidney disease (CKD) is complicated by abnormalities that reflect disruption in filtration, tubular, and endocrine functions of the kidney. Our aim was to explore the relationship of specific laboratory result abnormalities and hypertension with the estimated glomerular filtration rate (eGFR) and albuminuria CKD staging framework. Study Design Cross-sectional individual participant-level analyses in a global consortium. Setting & Study Populations 17 CKD and 38 general population and high-risk cohorts. Selection Criteria for Studies Cohorts in the CKD Prognosis Consortium with data for eGFR and albuminuria, as well as a measurement of hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, or calcium, or hypertension. Data Extraction Data were obtained and analyzed between July 2015 and January 2018. Analytical Approach We modeled the association of eGFR and albuminuria with hemoglobin, bicarbonate, phosphorus, parathyroid hormone, potassium, and calcium values using linear regression and with hypertension and categorical definitions of each abnormality using logistic regression. Results were pooled using random-effects meta-analyses. Results The CKD cohorts (n = 254,666 participants) were 27% women and 10% black, with a mean age of 69 (SD, 12) years. The general population/high-risk cohorts (n = 1,758,334) were 50% women and 2% black, with a mean age of 50 (16) years. There was a strong graded association between lower eGFR and all laboratory result abnormalities (ORs ranging from 3.27 [95% CI, 2.68-3.97] to 8.91 [95% CI, 7.22-10.99] comparing eGFRs of 15 to 29 with eGFRs of 45 to 59 mL/min/1.73 m 2), whereas albuminuria had equivocal or weak associations with abnormalities (ORs ranging from 0.77 [95% CI, 0.60-0.99] to 1.92 [95% CI, 1.65-2.24] comparing urinary albumin-creatinine ratio > 300 vs < 30 mg/g). Limitations Variations in study era, health care delivery system, typical diet, and laboratory assays. Conclusions Lower eGFR was strongly associated with higher odds of multiple laboratory result abnormalities. Knowledge of risk associations might help guide management in the heterogeneous group of patients with CKD. © 2018. This is the authors’ accepted and refereed manuscript to the article. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ "

BACKGROUND: Guideline-adherent prescribing for treatment of multiple risk factors in type 2 diabetes (T2D) patients is expected to improve clinical outcomes. However, the relationship to Health-Related Quality of Life (HRQoL) is not straightforward since guideline-adherent prescribing can increase medication burden.OBJECTIVES: To test whether guideline-adherent prescribing and disease-specific medication burden are associated with HRQoL in patients with T2D.METHODS: Cross-sectional study including 1,044 T2D patients from the e-VitaDM/ZODIAC study in 2012 in the Netherlands. Data from the diabetes visit, such as laboratory and physical examinations and prescribed medication, and from two HRQoL questionnaires, the EuroQol 5 Dimensions 3 Levels (EQ5D-3L) and the World Health Organization Well-Being Index (WHO-5) were collected. Twenty indicators assessing prescribing of recommended glucose lowering drugs, statins, antihypertensives and renin-angiotensin-aldosterone system (RAAS)-inhibitors and potentially inappropriate drugs from a validated diabetes indicator set were included. Disease-specific medication burden was assessed using a modified version of the Medication Regimen Complexity Index (MRCI). Associations were tested with regression models, adjusting for age, gender, diabetes duration, comorbidity, body mass index and smoking.RESULTS: The mean MRCI was 7.1, the median EQ5D-3L-score was 0.86 and the mean WHO-5 score was 72. Seven indicators included too few patients and were excluded from the analysis. The remaining thirteen indicators focusing on recommended start, intensification, current and preferred use of glucose lowering drugs, statins, antihypertensives, RAAS inhibitors, and on inappropriate prescribing of glibenclamide and dual RAAS blockade were not significantly associated with HRQoL. Finally, also the MRCI was not associated with HRQoL.CONCLUSIONS: We found no evidence for associations between guideline-adherent prescribing or disease-specific medication burden and HRQoL in T2D patients. This gives no rise to refrain from prescribing intensive treatment in T2D patients as recommended, but the interpretation of these results is limited by the cross-sectional study design and the selection of patients included in some indicators.