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Abstract The genomic region at 9p21 chromosome near the CDKN2A/CDKN2B genes is associated with type 2 diabetes(T2D) and cardiovascular disease(CVD). The effect of the 9p21 locus on long-term mortality in patients with T2D has yet to be determined. We examined three single nucleotide polymorphisms (SNPs) on 9p21, consistently and independently associated with T2D (rs10811661) or CVD (rs10757278, rs2383206), in relation to the risk of total and cardiovascular mortality in diabetic patients. We also aimed to replicate the previously observed interaction between rs2383206 and glycemic control on mortality. Genotypes for three SNPs were determined in 914 individuals from a prospective cohort of T2D patients of Dutch origin. Associations with mortality were assessed using Cox proportional hazard analyses. After a median follow-up of 9.5 years, 358 out of 914 patients had died. The hazard ratio (HR) for total mortality among individuals homozygous for the T2D-risk allele of rs10811661 compared to non-homozygous individuals was 0.74(95%CI 0.59-0.93). For the carriers of both CVD-risk alleles of rs10757278, the HR for total mortality was 1.31(95%CI 1.01-1.70). We found a significant interaction between rs2383206 and HbA1c on mortality, which was higher among patients with two CVD-risk alleles in the two lowest HbA1c tertiles (HR 1.68(95%CI 1.08-2.63); HR 1.48(95%CI 1.01-2.18). In conclusion, common variants on 9p21 were associated with mortality in patients with T2D in a Dutch population. The T2D SNP was inversely associated with mortality, while the CVD SNP increased the risk for mortality. We confirmed a possible, although different, synergistic relationship between HbA1c and rs2383206 on total mortality.

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 openlabel, 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that many within-class differences exist between sulfonylureas (SUs), however, whether differences exist regarding the time it takes between initiating an SU and the need to intensify treatment with insulin is unclear. The aim of this study was investigate the relationships between the three frequently used sulphonylureas, prescribed as dual therapy next to metformin, and the time needed to treatment intensification with either insulin or oral triple therapy in patients with type 2 diabetes mellitus. Methods: Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) is a prospective observational cohort study set in primary care in the Netherlands. Annually collected data on diabetes medication and clinical variables within ZODIAC are used to evaluate the primary outcome, time to insulin and secondary outcome, time to either insulin or triple oral therapy. For statistical analysis a time-dependent cox proportional hazard model was used. Results: 3507 patients were included in the analysis, with a mean age of 61 (SD 11.4) and a median HbA1c of 6.8% [IQR 6.4–7.4] (50.8 mmol/mol [IQR 46.4–57.4]).The hazard ratio (HR) for the primary endpoint was 1.10 (95% CI 0.78–1.54) for metformin/glimepiride and 0.93 (95% CI 0.67–1.30) for metformin/tolbutamide with metformin/gliclazide as reference group. The HR for the secondary outcome was 1.04 (95% CI 0.78–1.40) and 0.85 (95% CI 0.64–1.13), respectively. Conclusion: In this large Dutch primary care cohort, new users of neither gliclazide, glimepiride nor tolbutamide as dual therapy with metformin, resulted in differences in the time needed for further treatment intensification. [ABSTRACT FROM AUTHOR]

Background. Online platforms offer opportunities for support in changing lifestyle and taking responsibility for one’s health, but engaging patients with type 2 diabetes is challenging. Previous studies have shown that patients interested in platforms were more often male, younger, and higher educated. This study aims to investigate differences in clinical and psychological characteristics between users and nonusers of a newly developed platform. Methods. A prospective study started in the Drenthe region of Netherlands. Participants in the study concerning quality of care and quality of life were additionally invited to use the platform. Results. 633 patients were registered after they opted for platform use. Of these patients, 361 (57.0%) never logged on, 184 (29.1%) were labeled “curious” users, and 88 (13.9%) were identified as “active” users. Users had lower HbA1c levels and more often hypertension compared to nonusers, and reported higher quality of life, better well-being, lower diabetes-related distress, and better medication adherence. Discussion. Platform use was associated with more favorable clinical and psychological characteristics relative to nonuse. Those with greater severity of disease, lower mood, and progression of disease used the platform the least. Other approaches need to be developed to reach these patients. Furthermore, improving the platform could also help to reach them. This trial is registered with Clinicaltrials.gov NCT01570140. [ABSTRACT FROM AUTHOR]

Introduction Combined data suggest a bimodal association of alanine aminotransferase ( ALT) with mortality in the general population. Little is known about the association of ALT with mortality in patients with type 2 diabetes. We therefore investigated the association of ALT with all-cause, cardiovascular and noncardiovascular mortality in patients with type 2 diabetes. Design A prospective study was performed in patients with type 2 diabetes, treated in primary care, participating in the Zwolle Outpatient Diabetes project Integrating Available Care ( ZODIAC) study. Cox regression analyses were performed to determine the associations of log2-transformed baseline ALT with all-cause, cardiovascular and noncardiovascular mortality. Results In 1187 patients with type 2 diabetes (67 ± 12 years, 45% female), ALT levels were 11 (8-16) U/L. During median follow-up for 11·1 (6·1-14·0) years, 553 (47%) patients died, with 238 (20%) attributable to cardiovascular causes. Overall, ALT was inversely associated with all-cause mortality (hazard ratio [ HR] 0·81; 95% confidence interval [ CI] 0·72-0·92), independently of potential confounders. This was less attributable to cardiovascular mortality ( HR 0·87; 95% CI 0·72-1·05), than to noncardiovascular mortality ( HR 0·77; 95% CI 0·65-0·90). Despite the overall inverse association of ALT with mortality, it appeared that a bimodal association with all-cause mortality was present with increasing risk for levels of ALT above normal ( P = 0·003). Discussion In patients with type 2 diabetes, low levels of ALT are associated with an increased risk of all-cause mortality, in particular noncardiovascular mortality, compared to normal levels of ALT, while risk again starts to increase when levels are above normal. [ABSTRACT FROM AUTHOR]

Background: Patients with diabetes are at high risk of death prior to reaching end-stage renal disease, but most models predicting the risk of kidney disease do not take this competing risk into account. We aimed to compare the performance of Cox regression and competing risk models for prediction of early- and late-stage renal complications in type 2 diabetes. Methods: Patients with type 2 diabetes participating in the observational ZODIAC study were included. Prediction models for (micro)albuminuria and 50% increase in serum creatinine (SCr) were developed using Cox regression and competing risk analyses. Model performance was assessed by discrimination and calibration. Results: During a total follow-up period of 10 years, 183 out of 640 patients (28.6%) with normoalbuminuria developed (micro)albuminuria, and 22 patients (3.4%) died without developing (micro)albuminuria (i.e. experienced the competing event). Seventy-nine out of 1,143 patients (6.9%) reached the renal end point of 50% increase in SCr, while 219 (19.2%) died without developing the renal end point. Performance of the Cox and competing risk models predicting (micro)albuminuria was similar and differences in predicted risks were small. However, the Cox model increasingly overestimated the risk of increase in SCr in presence of a substantial number of competing events, while the performance of the competing risk model was quite good. Conclusions: In this study, we demonstrated that, in case of substantial numbers of competing events, it is important to account for the competing risk of death in renal risk prediction in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

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 ZwolleOutpatient Diabetes Project Integrating Available Care (ZODIAC) study were included. Cox regression analyses with age as time scale were used to assess the relationship of baseline copeptin with CV and all-cause mortality. RESULTS--We 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 20.27 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. [ABSTRACT FROM AUTHOR]

OBJECTIVE--The aim of this study was to investigate the association between plasma COOH-terminal proendothelin-1 (CT-proET-1) and fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS--A total of 1,225 patients with type 2 diabetes participated in this prospective observational study of two combined cohorts. Three clinical end points were studied: fatal cardiovascular events, all-cause mortality, and new-onset albuminuria. After a median follow-up of 3 or 10 years, Cox proportional hazard modeling was used to investigate the association between CT-proET-1 and the end points. Harrell C statistic, the Groennesby and Borgan test, the integrated discrimination improvement (IDI), and the net reclassification improvement (NRI) were used to evaluate whether CT-proET-1 is of additional value compared with classic cardiovascular and renal risk factors. RESULTS--During follow-up, 364 (30%) patients died, 150 (42%) of whom died of cardiovascular disease; 182 (26.7%) of 688 patients with normoalbuminuria at baseline developed albuminuria. CT-proET-1 was associated with fatal cardiovascular events, all-cause mortality, and new-onset albuminuria with hazard ratios of 1.59 (95% CI 1.15-2.20), 1.41 (95% CI 1.14-1.74), and 1.48 (95% CI 1.10-2.01), respectively. Addition of CT-proET-1 to a model containing traditional risk factors leads only to improved prediction of fatal cardiovascular events. The IDI appeared significant for fatal cardiovascular events (0.82 [0.1-1.54]) and all-cause mortality (0.4 [0.05-0.92]), but not for new-onset albuminuria. CONCLUSIONS--CT-proET-1 has additional value for the prediction of fatal cardiovascular events and new-onset albuminuria in patients with type 2 diabetes, compared with conventional risk factors, but not for all-cause mortality. [ABSTRACT FROM AUTHOR]

Objective: to investigate the association between a decreased estimated glomerular filtration rate (eGFR), albuminuria and mortality in elderly patients with type 2 diabetes mellitus (T2DM).Design: prospective observational cohort study.Setting: primary care.Subjects: eight hundred and ten patients, ≥65 years with T2DM. Analyses were performed in age strata: 65–75 (n = 471), >75 (n = 339) years.Methods: Cox proportional hazard modelling was used to investigate the association between eGFR, albuminuria and all-cause and cardiovascular mortality after a median follow-up of 9.8 years.Results: an eGFR <45 and 45–60 ml/min/1.73 m2 is associated with increased cardiovascular mortality in patients of 65–75 years, hazard ratio (HR): 3.29 (1.58–6.86) and 1.78 (1.09–2.90), respectively; in those >75 years increased cardiovascular mortality was observed when eGFR was <45 ml/min/1.73 m2: 2.42 (1.47–3.69). Compared with patients of 65–75 years, an eGFR >60 ml/min/1.73 m2 and normo-albuminuria, fully adjusted HRs for cardiovascular mortality were 2.26 (1.04–4.92) and 4.86 (2.33–10.15) for those aged 65–75 years, an eGFR of 45–60 ml/min/1.73 m2 and normo-albuminuria or albuminuria, respectively; HRs were 1.33 (0.67–2.66) and 2.01 (1.02–3.94), respectively, for those >75 years.Conclusions: an eGFR of 45–60 ml/min/1.73 m2 in T2DM patients is associated with increased mortality in patients aged 65–75 years but not in those >75 years. Albuminuria is associated with increased mortality in patients >65 years. [ABSTRACT FROM AUTHOR]

To determine whether the management of type 2 diabetes mellitus in a primary care setting can be safely transferred to practice nurses. Because of the increasing prevalence of type 2 diabetes mellitus and the burden of caring for individual patients, the demand type 2 diabetes mellitus patients place on primary health care resources has become overwhelming. Randomised controlled trial. The patients in the intervention group were cared for by practice nurses who treated glucose levels, blood pressure and lipid profile according to a specified protocol. The control group received conventional care from a general practitioner. The primary outcome measure was the mean decrease seen in glycated haemoglobin (HbA1c) levels at the end of the follow-up period (14 months). A total of 230 patients was randomised with 206 completing the study. The between-group differences with respect to reduction in HbA1c, blood pressure and lipid profile were not significant. Blood pressure decreased significantly in both groups; 7·4/3·2 mm Hg in the intervention group and 5·6/1·0 mm Hg in the control group. In both groups, more patients met the target values goals for lipid profile compared to baseline. In the intervention group, there was some deterioration in the health-related quality of life and an increase in diabetes-related symptoms. Patients being treated by a practice nurse were more satisfied with their treatment than those being treated by a general practitioner. Practice nurses achieved results, which were comparable to those achieved by a general practitioner with respect to clinical parameters with better patient satisfaction. This study shows that diabetes management in primary care can be safely transferred to practice nurses. [ABSTRACT FROM AUTHOR]

OBJECTIVE-- Diabetes negatively impacts the health-related quality of life (HRQOL) of patients with type 2 diabetes. An earlier analysis showed HRQOL to be associated with mortality, which suggests that measuring HRQOL could have clinical implications. We studied the association between HRQOL and total and cardiovascular mortality in patients with type 2 diabetes during long-term follow-up and specifically focused on old age and sex differences. RESEARCH DESIGN AND METHODS-- HRQOL was measured in a prospectively followed cohort of 1,353 patients with type 2 diabetes using the RAND-36. Cox proportional hazard models were used to measure the independent effect of baseline HRQOL on mortality. RESULTS-- During a mean follow-up of 9.6 years, 570 (42%) patients died, 280 of whom died of cardiovascular disease (49%). The Physical Component Score (PCS) and the Mental Component Score (MCS) were inversely associated with total mortality, with hazard ratios of 0.988 (95% CI 0.983-0.993) and 0.990 (95% CI 0.985-0.995), respectively. A 10-point-higher score on the PCS and MCS decreased the risk for total mortality by 11 and 10%, respectively. An inverse relationship with mortality was also seen for men, women, and for patients aged >75 years. Mental health was significantly related to mortality in men but not in women. CONCLUSIONS-- Lower physical and mental HRQOL was associated with a higher total mortality and cardiovascular mortality in patients with type 2 diabetes; this is also the case when studying men and women and the elderly separately. The dimension mental health, related to depression and anxiety, was only associated with mortality in men, not in women. [ABSTRACT FROM AUTHOR]

Background The relationship between the degree of glycaemic control and mortality remains an important topic of discussion. Aim This study aimed to investigate this relationship. Design of study Prospective cohort study. Setting Primary care. Method A total of 1145 patients with type 2 diabetes were enrolled in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) in 1998. Their survival status was recorded in September 2004. Mortality ratios were calculated using standardised mortality ratios (SMRs). Associations between haemoglobin A1c (HbA1c) levels and mortality were studied with a Cox proportional hazard model. HbA1c levels were studied as continuous and as categorical variables. Results A total of 335 patients died after a median follow-up period of 5.8 years. The SMR (96% confidence interval [CI]) for total mortality was 1.86 (95% CI = 1.66 to 2.06) and 2.24 (95% CI = 1.91 to 2.61) for cardiovascular mortality. For each 1% increase in HbA1c there was a 21% increase in the hazard ratio for total mortality. When compared with the target HbA1c group (HbA1c 6.5-7%), the group with very poor glycaemic control (HbA1c >9%) had a hazard ratio of 2.21 (95% CI = 1.42 to 3.42) for total mortality. The group with normal glycaemic control (HbA1c <6.5%) had a hazard ratio of 1.00 (95% CI = 0.46 to 2.19) for total mortality. Conclusion HbA1c level was associated with mortality and this effect seemed largely attributable to patients who were in really poor glycaemic control. The absence of differences in mortality in the groups with lower HbA1c levels supports the position that there is no basis for continually decreasing the therapeutic target HbA1c level in patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Several studies have suggested an association between specific diabetes treatment and cancer mortality. We studied the association between metformin use and cancer mortality in a prospectively followed cohort. RESEARCH DESIGN AND METHODS -- In 1998 and 1999, 1,353 patients with type 2 diabetes were enrolled in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study in the Netherlands. Vital status was assessed in January 2009. Cancer mortality rate was evaluated using standardized mortality ratios (SMRs), and the association between metformin use and cancer mortality was evaluated with a Cox proportional hazards model, taking possible confounders into account. RESULTS -- Median follow-up time was 9.6 years, average age at baseline was 68 years, and average A1C was 7.5%. Of the patients, 570 died, of which 122 died of malignancies. The SMR for cancer mortality was 1.47 (95% CI 1.22-1.76). In patients taking metformin compared with patients not taking metformin at baseline, the adjusted hazard ratio (HR) for cancer mortality was 0.43 (95% CI 0.23-0.80), and the HR with every increase of 1 g of metformin was 0.58 (95% CI 0.36-0.93). CONCLUSIONS -- In general, patients with type 2 diabetes are at increased risk for cancer mortality. In our group, metformin use was associated with lower cancer mortality compared with nonuse of metformin. Although the design cannot provide a conclusion about causality, our results suggest a protective effect of metformin on cancer mortality. [ABSTRACT FROM AUTHOR]

Background: The precise relationship between the lipid profile and mortality in elderly patients with type 2 diabetes mellitus (T2DM) remains unclear. The aim of this study was to investigate the relationship between the lipid profile over time, and mortality in elderly patients with T2DM. Methods and Findings: In 1998, 881 primary care patients with T2DM aged 60 years and older participated in the ZODIAC study, a prospective observational study. The cohort was divided into two age categories: 60-75 years and older than 75 years. Updated means of all lipid profile indices were calculated after a median follow-up time of 9.8 years. These values were used as time dependent covariates in a Cox proportional hazard model. The cholesterol-HDL ratio and LDL-cholesterol were positively related to both all-cause and cardiovascular mortality in the low age group. In contrast, except for the triglyceride level, none of the other lipid profile indices were related to all-cause mortality in patients aged over 75 years. The mortality risk decreased by 17% (95%CI: 5% to 27%) for each 1 mmol/L higher serum level of triglycerides. The relationships between the various lipid profile indices and cardiovascular mortality were not significant. However, the results were different after stratification for diabetes duration. In the subgroup of elderly patients with a diabetes duration of 8 years and longer, higher lipids were predictive of increased cardiovascular mortality. The main limitation of this study is its observational design, which prevents us drawing conclusions about causality. Conclusion: Although the lipid profile was not predictive in the overall group of elderly patients, higher lipids were related to increased cardiovascular mortality in patients with diabetes of long duration. In order to make valid recommendations concerning lipid-lowering treatment, a randomized controlled trial or a meta-analysis concerning this specific population is mandatory. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Skin autofluorescence is a noninvasive measure of the level of tissue accumulation of advanced glycation end products, representing cumulative glycemic and oxidative stress. Recent studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as the predictive value of skin autofluorescence for total and cardiovascular mortality in type 2 diabetes. Our aim was to investigate the predictive value of skin autofluorescence for the development of microvascular complications in type 2 diabetes. RESEARCH DESIGN AND METHODS -- At baseline, skin autofluorescence of 973 type 2 diabetic patients with well-controlled diabetes was noninvasively measured with an autofluorescence reader. The aggregate clinical outcome was defined as the development of any diabetes-associated microvascular complication of 881 surviving patients, which was assessed at baseline and at the end of follow-up. Single end points were the development of diabetes-associated retinopathy, neuropathy, and (micro)albuminuria. RESULTS -- After a mean follow-up period of 3.1 years, baseline skin autofluorescence was significantly higher in patients who developed any microvascular complication, neuropathy, or (micro)albuminuria but not in those who developed retinopathy. Multivariate analyses showed skin autofluorescence as a predictor for development of any microvascular complication along with A1C, for development of neuropathy along with smoking, and for development of (micro)albuminuria together with sex, A1C, and diabetes duration. Skin autofluorescence did not have predictive value for the development of retinopathy, albeit diabetes duration did. CONCLUSIONS -- Our study is the first observation of skin autofluorescence measurement as an independent predictor of development of microvascular complications in type 2 diabetes. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Chromium treatment has been reported to improve glycemic control and insulin sensitivity in specific populations of patients with type 2 diabetes. The aim of this study was to determine the effect of chromium treatment on glycemic control in a Western population of insulin-dependent patients with type 2 diabetes. RESEARCH DESIGN AND METHODS -- In this 6-month double-blind study, patients with an HbA1c (AIC) >8% and insulin requirements of >50 units/day were randomly assigned to receive treatment with placebo or 500 or 1,000 µg chromium daily in the form of chromium picolinate. The primary efficacy parameter was a change in A1C. Secondary end points were changes in lipid profile, BMI, blood pressure, and insulin requirements. RESULTS--In this per-protocol analysis (n = 46), the decrease in A1C was approximately equal across the three groups (0.4%). All patients had a BMI >25 kg/m². No differences were found in the secondary end points. We found a weak relationship between an increasing serum chromium concentration and improvement of the lipid profile. CONCLUSIONS--There is no evidence that high-dose chromium treatment is effective in obese Western patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Simple Summary: A 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. [ABSTRACT FROM AUTHOR]

The article presents a cross-sectional observational study which examined the prevalence of orthostatic hypotension (OH) in older people with type 2 diabetes in the Netherlands. The study assessed the link between OH, orthostatic complaints, type 2 diabetes and the high fall risk using multiple binary logistics regression analyses. There was no correlationbetween OH and orthostatic complaints and falls, while OH is prevalent in diabetic patients.

OBJECTIVE-- To investigate the relationship between health-related quality of life (HRQOL) and mortality in type 2 diabetes. RESEARCH DESIGN AND METHODS-- In 1998, 1,143 primary care patients with type 2 diabetes participated in the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) study. At baseline, HRQOL was assessed with the RAND-36 and, after almost 6 years, life status was retrieved. Cox proportional hazards modeling was used to investigate the association between HRQOL (continuous data) and mortality with adjustment for selected confounders (smoking, age, sex, diabetes duration, A1C, renal function, BMI, blood pressure, HDL cholesterol, and macrovascular complications). RESULTS-- The Physical Component Summary of the RAND-36 was inversely associated with mortality (hazard ratio [HR] 0.979 [95% CI 0.966-0.992]), as were two separate RAND-36 dimensions. CONCLUSIONS-- This study found that HRQOL is an independent marker of mortality and emphasizes the importance of looking beyond clinical parameters in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The Netherlands will face a shortage of general practitioners (GPs) in the near future. In order to maintain quality of care for the increasing number of patients with type 2 diabetes (DM2), treatment of DM2 in the primary care setting is increasingly taken over by practice nurses (PNs). In a randomized controlled study, we investigated whether medical treatment (including prescriptions according to protocol), quality of life (SF-36), diabetes related complaints (DSC-R), and patient satisfaction (PEQD) were at least equal to care provided by GPs; 206 patients from five general practices participated. The intervention group was treated by PNs and the control group received "standard" care from their own GPs. After fourteen months, the care in the two groups was comparable according to the clinical parameters (HbA1c, blood pressure (BP) and lipid profile). In the group which was treated by the PNs, significantly more patients were referred to specialists including the ophthalmologist according to protocol (71% vs. 37% (p<0.01)). Furthermore, more action was undertaken when the patient had critical foot problems (57% vs. 27% (p<0.01)), and medication dosages were raised more often when considered necessary, except for lipid lowering drugs (hypoglycaemic agents: 83% vs. 50% (p<0.01); antihypertensive agents: 50% vs. 29% (p<0.01)). The overall quality of life and the number of complications related to diabetes were equal in the two groups. Patients were more satisfied with the care they received from the PNs than with the care provided by the GP (PEQD score: 66 vs. 52 (p<0.01)). This study allows the conclusion that PNs who work with strict protocols are capable to offer effective cam to patients with DM2 in a primary care setting. PNs follow the quality guidelines, as formulated by the Dutch General Practitioners' College, more consistently than GPs, saving GPs time, whilst providing care of good quality. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor about the association between the characteristics of general practitioners and their patients with type 2 diabetes.

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. [ABSTRACT FROM AUTHOR]

Background and aims Hyponatremia has been associated with an increased mortality risk in the general population. Diabetes is a condition predisposing for elevated levels of arginine vasopressin (AVP) and heart failure, both common causes of hyponatremia. These factors, however, are also associated with an increased mortality risk. We aimed to investigate whether serum sodium is associated with cardiovascular and all-cause mortality in type 2 diabetes and whether these associations could be explained by copeptin, a surrogate for AVP, or NT-proBNP, a marker for heart failure. Methods Patients with type 2 diabetes participating in the observational ZODIAC study were included. Cox regression analyses were used to investigate the association of serum sodium with mortality. Results We included 1068 patients (age 67 ± 12 years, 45% male, serum sodium 142 ± 3 mmol/L). After 15 years of follow-up, 519 patients (49%) died, with 225 cardiovascular deaths (21%). In univariable analyses, serum sodium, copeptin, and NT-proBNP were all significantly associated with cardiovascular and all-cause mortality. These associations remained significant after combination of these markers in a multivariable model. Serum sodium and NT-proBNP remained significantly associated with mortality after further adjustment for potential confounders, whereas copeptin lost significance after adjustment for SCr and ACR. Conclusion Low serum sodium was associated with an increased risk of cardiovascular and all-cause mortality in type 2 diabetes. Moreover, these associations were not explained by copeptin and NT-proBNP. Whether low serum sodium itself leads to poor outcome or is a marker for (unidentified) co-morbidity severity or use of specific medications remains to be elucidated. [ABSTRACT FROM AUTHOR]