Correction to: Mealtime insulin bolus adherence and glycemic control in adolescents on insulin pump therapy.

The Abstract section and the in the Results sections of the original version of this article, unfortunately, contained errors. The correct data are now shown in this article.

Mealtime insulin bolus adherence and glycemic control in adolescents on insulin pump therapy.

Poor self-management contributes to insufficient glycemic control in adolescents with type 1 diabetes (T1DM). We assessed the effects on glycemic control of adherence to self-measurement of blood glucose (SMBG) and insulin boluses in 90 adolescents with T1DM on insulin pump therapy over a 2-month period. We compared the number of insulin boluses and SMBGs around main meals to the "gold standard" of optimal diabetes management (SMBGs and a bolus before each main meal and SMBG before bedtime). The mean (95% CI) HbA1c levels were 2.9(1.7 to 4.0) mmol/mol lower for every additional insulin bolus and 3.1(1.6 to 4.5) mmol/mol lower for every additional SMBG. Patients performing SMBG and bolusing around each main meal had considerably lower HbA1c levels than those unable to do (95% CI for difference 4.3 to 10.4 mmol/mol and 11.5 to 20.1 mmol/mol respectively). For each additional mealtime bolus/day, the odds ratio of achieving target HbA1c levels of <58 mmol/mol was 6.73 (95% CI 2.94-15.38), after adjustment for gender, age, diabetes duration, and affective responses to SMBG in a multiple logistic regression model.Conclusion: Glycemic control in adolescents with T1DM on insulin pump therapy is strongly dependent on adherence to insulin boluses around mealtimes. What is Known: • In mixed groups of children and adolescents, insulin bolus frequency and self-monitoring of blood glucose (SMBG) frequency were determinants of HbA1c levels. • Adherence to insulin boluses and SMBG is particularly challenging in adolescents. What is New: • In adolescents on insulin pump therapy, each additional insulin bolus, particularly around mealtime, was significantly associated with approximately 3 mmol/mol lower HbA1c levels. • This beneficial effect of mealtime bolusing was strongest for the evening meal.

Diagnosing orthostatic hypotension with continuous and interval blood pressure measurement devices.

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.

Gender differences in the evaluation of care for patients with type 2 diabetes: a cross-sectional study (ZODIAC-52).

BACKGROUND: Little is known about the association between patient-related factors and patients' evaluation of care. Aim was to investigate which patient-related factors are associated with patients' evaluation of care in men and women with type 2 diabetes (T2D) in primary care. METHODS: This cross-sectional study included 1102 patients with T2D from 52 general practices. We measured patients' evaluation with the EUROPEP questionnaire and collected demographic, clinical and psychological data from questionnaires and health records. Stepwise linear regression analyses were used. RESULTS: The location where the questionnaire was completed (at home or at the general practice) was associated with all outcomes in men and women. Next to this, in men, explanatory factors for the care provider EUROPEP subscale were use of insulin, having some problems with T2D self-care and coffee consumption (R2 8.4%); coffee consumption was associated with the general practice subscale (R2 4.0%). In women, well-being, quality of life, following a general diet, and use of oral glucose-lowering drugs were associated with the care provider subscale (R2 16.8%). For the general practice subscale, well-being and age were explanatory factors (R2 9.4%). CONCLUSIONS: Only a few factors were found to be associated with patients' evaluation of care for men and women with T2D. Taken together, these factors explained only a small part of the variance of the EUROPEP scores. This explained variance was largely attributable to the location where the questionnaire was completed. We therefore advise to be aware of the possible consequences of filing-out questionnaires about patients' evaluation of care at the general practice. TRIAL REGISTRATION: NCT01570140 (Clinicaltrials.gov). Registered 29 March 2012.

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

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

Sex differences in survival of patients with type 2 diabetes in primary care (ZODIAC-50).

OBJECTIVE: To investigate sex differences in survival of primary care treated patients with type 2 diabetes (T2D) in the Netherlands. SETTING: Primary care. PARTICIPANTS: A total of 1815 patients who participated in a prospective observational cohort study (Zwolle Outpatient Diabetes Project Integrating Available Care (ZODIAC)) were included of which 56% was female. Inclusion took place in 1998, 1999 and 2001. Vital status was assessed in 2013. MAIN OUTCOME MEASURE: Relative survival of men and women with T2D. The relative survival rate was expressed as the ratio of observed survival of patients divided by the survival of the general population in the Netherlands with comparable age. RESULTS: After 14 years, 888 (49%) patients had died. The relative survival rate was 0.88 (0.81-0.94) for men and 0.82 (0.76-0.87) for women with T2D after 14 years (p value for difference between sexes=0.169). In patients without a history of cardiovascular diseases (CVD), the relative survival was 0.99 (0.94-1.05) in men and 0.92 (0.87-0.97) in women (p value for difference between sexes=0.046). CONCLUSIONS: The survival of men and women with T2D was 12% and 18% lower, respectively, after 14 years of follow-up compared with men and women in the general population. This corresponds to a decrease in median survival of 2.2 and 3.5 years in men and women, respectively. Only for patients with T2D without a history of CVD, a significantly lower relative survival in women compared with men with T2D was found.

Within-class differences in cancer risk for sulfonylurea treatments in patients with type 2 diabetes (ZODIAC-55) - a study protocol.

BACKGROUND: Patients with type 2 diabetes (T2D) are at increased risk for developing cancer. As approximately 8% of the world's population is living with T2D, even a slight increase in cancer risk could result in an enormous impact on the number of persons developing cancer. In addition, several glucose lowering drug classes for treating patients with T2D have been associated with a difference in risk of cancer overall, and especially for obesity related cancers. In what way and to what degree cancer risk is modified by the use of different sulfonylureas (SU) is unclear. The primary aim of this study will be to evaluate within-class SU differences in obesity related cancer risk. Secondary aims will be to investigate within-class SU differences in risk for all cancers combined and site-specific cancers separately (i.e. breast, colorectal, prostate, bladder and lung cancer) and to account for duration-response relationships between individual SU use and cancer risk. METHODS: Patients will be selected from a Dutch primary care cohort of patients with T2D linked with the Dutch Cancer Registration (ZODIAC-NCR). Within this cohort study annually collected clinical data (e.g. blood pressure, weight, HbA1c) and nationwide data on cancer incidence are available. Time-dependent cox proportional hazard analyses will be performed to evaluate SU cancer risk, adjusted for potential confounders. DISCUSSION: This study will be the first prospective cohort study investigating within-class SU differences in cancer risk and could contribute to improved decision making regarding the individual drugs within the class of SUs, and possibly improve quality of life and result in an increased cost-effectiveness of healthcare in patients with T2D. TRIAL REGISTRATION: Nederlands Trialregister ( NTR6166 ), 6 Jan 2017.

Standing orthostatic blood pressure measurements cannot be replaced by sitting measurements.

As many elderly patients are not able to stand for several minutes, sitting orthostatic blood pressure (BP) measurements are sometimes used as an alternative. We aimed to investigate the difference in BP response and orthostatic hypotension (OH) prevalence between the standard postural change to the sitting and the standing position in a cross-sectional observational study. BP was measured with a continuous BP measurement device during two postural changes, from supine to the sitting and from supine to the standing position. Linear mixed models were used to investigate the differences in changes (Δ) of systolic BP (SBP) and diastolic BP (DBP) between the two postural changes. The prevalence and the positive and negative proportions of agreement of OH were calculated of the two postural changes. One hundred and four patients with a mean age of 69 years were included. ΔSBP was significantly larger in the standing position compared with the sitting between 0 and 44 s. ΔDBP was significantly larger in the sitting position compared with the standing 75-224 s after postural change. The prevalence of OH was 66.3% (95% confidence interval (CI) 57.2, 75.4) in the standing position and 67.3% (95% CI 58.3, 76.3) in the sitting position. The positive proportion of agreement was 74.8% and the negative proportion of agreement was 49.3%. A clear difference was seen in BP response between the two postural changes. Although no significant difference in prevalence of OH was observed, the positive and negative proportion of agreement of the prevalence of OH were poor to moderate, which indicates a different outcome between both postural changes.

Is orthostatic hypotension related to falling? A meta-analysis of individual patient data of prospective observational studies.

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.

Lifestyle and emotional well-being in men and women with type 2 diabetes (e-VitaDM-4; ZODIAC-48).

BACKGROUND: Whether lifestyle is associated with well-being in patients with type 2 diabetes (T2D) is largely unknown. Uncovering and clarifying associations between these constructs may lead to new strategies for improving both. OBJECTIVES: The aim was to investigate the relationship between lifestyle and well-being, focussing on gender differences. METHODS: This cross-sectional study included 1085 patients with T2D that participated in the e-Vita part of the Zwolle outpatient diabetes project integrating available care (ZODIAC) study. Patients were included from May 2012 until September 2014 from 52 general practices. Emotional well-being was assessed with the World Health Organization-5 well-being index (WHO-5). Lifestyle information on body mass index, smoking, physical activity and alcohol use was extracted from self-reported questionnaires. Multiple linear regression analyses were used. RESULTS: After adjustment for other lifestyle factors, physical activity, smoking and drinking 22-35 alcohol consumptions per week were associated with the WHO-5 score in men and physical activity and smoking were associated with the WHO-5 score in women. In the fully adjusted analyses for the total study population, physical activity and smoking were still associated with the WHO-5 score (b = 1.1, P < .001 and b =-3.1, P = .018, respectively). In the fully adjusted analyses stratified to gender only physical activity was associated with the WHO-5 score (in men: b =0.8, P = .006, in women: b = 1.4, P = .001). CONCLUSION: This study shows a negative, non-clinically relevant association between smoking and emotional well-being in the total population with T2D and a positive, non-clinically relevant association between physical activity and emotional well-being in both men and women with T2D.

The clinical relevance of orthostatic hypotension in elderly patients.

AIM: Orthostatic 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. METHODS: A 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. RESULTS: The 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)). CONCLUSIONS: With 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.

Patient Activation in Type 2 Diabetes: Does It Differ between Men and Women?

Background. Aim was to investigate whether the degree of patient activation of patients with type 2 diabetes (T2D) is different between men and women. Furthermore, we investigated which factors are associated with patient activation in men and women. Methods. This cross-sectional study included 1615 patients with T2D from general practices. Patient activation was measured with the Patient Activation Measure (PAM) questionnaire. Multivariate linear regression analyses were used to investigate the association between gender and patient activation. Stratified analyses according to gender were performed to investigate which factors are associated with patient activation. Results. No association between gender and PAM score was found after adjustment for all selected confounders (p = 0.094). In men, lower age (p = 0.001), a higher WHO-5 score (p < 0.001), and a lower BMI (p = 0.013) were associated with a higher PAM score. In women, a higher WHO-5 score (p < 0.017) and the absence of macrovascular complications (p < 0.031) were associated with a higher PAM score. Conclusion. There is no difference in the degree of patient activation of men and women with T2D. Age, well-being, and BMI were found to be associated with patient activation in men, whereas well-being and macrovascular complications were found to be associated with patient activation in women.

Addition of sulphonylurea to metformin does not relevantly change body weight: a prospective observational cohort study (ZODIAC-39).

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.

Inflammation biomarkers and mortality prediction in patients with type 2 diabetes (ZODIAC-27).

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, HbA1c, 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.

Orthostatic changes in blood pressure and mortality in a nursing home population.

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). 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 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.

Validity of an Accelerometer-Based Activity Monitor System for Measuring Physical Activity in Frail Older Adults.

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.