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Aims: This study aims to evaluate the stability of C‐peptide over time and to compare fasting C‐peptide and C‐peptide response after mixed‐meal tolerance test (MMTT) at T90 or T120 with C‐peptide area under the curve (AUC) in long‐standing type 1 diabetes. Methods: We included 607 type 1 diabetes individuals with diabetes duration >5 years. C‐peptide concentrations (ultrasensitive assay) were collected in the fasting state, and in a subpopulation after MMTT (T0, just prior to, T30‐T60‐T90‐T120, 30–120 min after ingestion of mixed‐meal) (n = 168). Fasting C‐peptide concentrations (in n = 535) at Year 0 and Year 1 were compared. The clinical determinants associated with residual C‐peptide secretion and the correspondence of C‐peptide at MMTT T90 / T120 and total AUC were assessed. Results: A total of 153 participants (25%) had detectable fasting serum C‐peptide (i.e ≥ 3.8 pmol/L). Fasting C‐peptide was significantly lower at Year 1 (p < 0.001, effect size = −0.16). Participants with higher fasting C‐peptide had a higher age at diagnosis and shorter disease duration and were less frequently insulin pump users. Overall, 109 of 168 (65%) participants had both non‐detectable fasting and post‐meal serum C‐peptide concentrations. The T90 and T120 C‐peptide values at MMTT were concordant with total AUC. In 17 (10%) individuals, C‐peptide was only detectable at MMTT and not in the fasting state. Conclusions: Stimulated C‐peptide was detectable in an additional 10% of individuals compared with fasting in individuals with >5 years of diabetes duration. T90 and T120 MMTT measurements showed good concordance with the MMTT total AUC. Overall, there was a decrease of C‐peptide at 1‐year follow‐up. [ABSTRACT FROM AUTHOR]

Background: The glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide may be beneficial in the regression of diabetic cardiomyopathy. South Asian ethnic groups in particular are at risk of developing type 2 diabetes.Purpose: To assess the effects of liraglutide on left ventricular (LV) diastolic and systolic function in South Asian type 2 diabetes patients.Study Type: Prospective, double-blind, randomized, placebo-controlled trial.Population: Forty-seven type 2 diabetes patients of South Asian ancestry living in the Netherlands, with or without ischemic heart disease, who were randomly assigned to 26-week treatment with liraglutide (1.8 mg/day) or placebo.Field Strength/sequence: 3T (balanced steady-state free precession cine MRI, 2D and 4D velocity-encoded MRI, 1 H-MRS, T1 mapping).Assessment: Primary endpoints were changes in LV diastolic function (early deceleration peak [Edec], ratio of early and late peak filling rate [E/A], estimated LV filling pressure [E/Ea]) and LV systolic function (ejection fraction). Secondary endpoints were changes in aortic stiffness (aortic pulse wave velocity [PWV]), myocardial steatosis (myocardial triglyceride content), and diffuse fibrosis (extracellular volume [ECV]).Statistical Tests: Data were analyzed according to intention-to-treat. Between-group differences were reported as mean (95% confidence interval [CI]) and were assessed using analysis of covariance (ANCOVA).Results: Liraglutide (n = 22) compared with placebo (n = 25) did not change Edec (+0.2 mL/s2 × 10-3 (-0.3;0.6)), E/A (-0.09 (-0.23;0.05)), E/Ea (+0.1 (-1.2;1.3)) and ejection fraction (0% (-3;2)), but decreased stroke volume (-9 mL (-14;-5)) and increased heart rate (+10 bpm (4;15)). Aortic PWV (+0.5 m/s (-0.6;1.6)), myocardial triglyceride content (+0.21% (-0.09;0.51)), and ECV (-0.2% (-1.4;1.0)) were unaltered.Data Conclusion: Liraglutide did not affect LV diastolic and systolic function, aortic stiffness, myocardial triglyceride content, or extracellular volume in Dutch South Asian type 2 diabetes patients with or without coronary artery disease.Level Of Evidence: 1 Technical Efficacy Stage: 4 J. Magn. Reson. Imaging 2020;51:1679-1688. [ABSTRACT FROM AUTHOR]

Background: Treatment of diabetes mellitus has majorly improved over the past century, however, the disease burden is high and its prevalence still expanding. Further insight in the diabetes population is imperative to improve the quality of diabetes care by enhancement of knowledge-based diabetes management strategies. To this end, in 2017 a Dutch nationwide consortium of diabetologists, paediatric endocrinologists, and diabetes patients has founded a national outpatient diabetes care registry named Dutch Pediatric and Adult Registry of Diabetes (DPARD). We aim to describe the implementation of DPARD and to provide an overview of the characteristics of patients included during the first 2 years. Methods: For the DPARD cohort with long-term follow-up of observational nature, hospital data are gathered directly from electronic health records and securely transferred and stored. DPARD provides weekly updated clinical information on the diabetes population care on a hospital-level benchmarked against the national average. Results: Between November 2017 and January 2020, 20,857 patients were included from 8 (11%) Dutch hospitals with a level of care distribution representative of all diabetic outpatients in the Netherlands. Among patients with known diabetes type, 41% had type 1 diabetes, 51% type 2 diabetes, and 8% had diabetes due to other causes. Characteristics of the total patient population were similar to patients with unknown diabetes classification. HbA1c levels decreased over the years, while BMI levels showed an increase over time. Conclusions: The national DPARD registry aims to facilitate investigation of prevalence and long-term outcomes of Dutch outpatients with diabetes mellitus and their treatment, thus allowing for quality improvement of diabetes care as well as allowing for comparison of diabetes care on an international level. [ABSTRACT FROM AUTHOR]

Aims: Data on the effect of liraglutide on glycemic endpoints in people with T2DM using multiple daily insulin injections (MDI) are scarce, especially in the context of ethnicity. Methods: This is a secondary analysis of the placebo-controlled randomized clinical "MAGNA VICTORIA" trials in Western European (WE) and South Asian (SA) people with T2DM. Participants had inadequate glycemic control despite using metformin and/or sulfonylurea derivatives and/or insulin. Participants were assigned to liraglutide (1.8 mg) or placebo for 6 months, in addition to standard care. The primary endpoint number of participants reaching target HbA1c was compared for liraglutide versus placebo in the complete dataset and MDI-treated participants using Chi-square test. Liraglutide's efficacy in WE and SA was compared using a generalized linear model. Results: Forty-five subjects were randomized to liraglutide and 51 to placebo. In each group, one participant did not complete the study. Liraglutide-treated patients reached target HbA1c more frequently: 23/45 (51%) vs 11/51 (22%), relative probability 2.4 (1.3–4.3), p = 0.002. Subgroup analysis in 43 MDI participants showed that the proportion reaching target HbA1c using liraglutide was significantly higher than in placebo: 9/22 (41%) vs 1/21 (5%), p = 0.005. There was no difference between WE and SA in terms of liraglutide efficacy (p = 0.18). Conclusions: Liraglutide treatment resulted in increased chance of reaching target HbA1c as compared to placebo. Liraglutide efficacy was sustained in participants using MDI regimens and those of SA descent. Liraglutide should be considered for T2DM people with inadequate glycemic control despite MDI. [ABSTRACT FROM AUTHOR]

Objectives Patients with diabetes mellitus are at a risk for hypoglycaemia. Besides the burden of hypoglycaemia for patients, hypoglycaemia poses an economic burden to society. The aim of this study was to calculate the per patient societal costs of hypoglycaemia among patients with type1 diabetes (T1DM) and type 2 diabetes (T2DM) on insulin therapy in the Netherlands. Methods To calculate the costs of hypoglycaemia, data from the Global Hypoglycaemia Assessment Tool (HAT) study were used. Dutch patients were selected from the HAT study database and data regarding healthcare resource use, informal care use and productivity losses were combined with Dutch unit costs to calculate the per patient 4-week costs of patients experiencing hypoglycaemia. Besides these 4-week costs, costs per hypoglycaemic event were calculated by dividing the study population total 4-week costs by the total number of events in this period. Results Mean 4-week total costs of hypoglycaemia amounted to €163 (SD, €870) in T1DM and €134 (SD, €364) in T2DM. While productivity costs were the most important cost driver of hypoglycaemia in patients with T1DM (accounting for 72% of the total costs), costs of hypoglycaemia in patients with T2DM were almost entirely driven by costs within the healthcare sector (accounting for 98% of the total costs). Mean costs of a severe hypoglycaemic event were €828 and €508 in T1DM and T2DM, respectively, whereas mean costs of a non-severe event were almost zero. Conclusions This study showed that the economic burden of severe hypoglycaemia is substantial. The prevention of hypoglycaemia could therefore not only reduce the burden for patients, but also the economic burden to society. [ABSTRACT FROM AUTHOR]

Background: Hypoglycemia is the main side effect of intensified insulin therapy in type 1 diabetes and recognized as a limitation in achieving glycemic targets. Patients with impaired awareness of hypoglycemia have a threefold to sixfold increased risk of severe hypoglycemia. Real-time continuous glucose monitoring may help patients with type 1 diabetes to achieve better glycemic control with less hypoglycemic episodes. Accordingly, one may hypothesize that particularly type 1 diabetes mellitus patients with impaired awareness of hypoglycemia will profit most from this technology with improvements in their quality of life. However, this has not yet been established. This trial aims to study the effect of real-time continuous glucose monitoring on glycemia and quality of life specifically in type 1 diabetes mellitus patients with established impaired awareness of hypoglycemia. Methods/design: This is a two-center, randomized, cross-over trial with a 12-week wash-out period in between intervention periods. A total of 52 type 1 diabetes mellitus patients with impaired awareness of hypoglycemia according to Gold et al. criteria will be randomized to receive real-time continuous glucose monitoring or blinded continuous glucose monitoring for 16 weeks. After a wash-out period, patients will cross over to the other intervention. The primary outcome measure is time spent in euglycemia. Secondary outcomes include (diabetes-specific) markers of quality of life and other glycemic variables. Discussion: It remains unclear whether patients with type 1 diabetes and impaired awareness of hypoglycemia benefit from real-time continuous glucose monitoring in real-life. This study will provide insight into the potential benefits of real-time continuous glucose monitoring in this patient population. [ABSTRACT FROM AUTHOR]

Objective. To assess the incidence of adverse pregnancy outcome in native and nonnative Dutch women with pregestational type 2 diabetes (T2D) in a multicenter study in The Netherlands. Methods. Maternal characteristics and pregnancy outcome were retrospectively reviewed and the influence of ethnicity on outcome was evaluated using independent t-test, Mann-Whitney U-test, and chi-square test. Results. 272 pregnant women (80 native and 192 non-native Dutch) with pregestational T2D were included. Overall outcome was unfavourable, with a perinatal mortality of 4.8%, major congenital malformations of 6.3%, preeclampsia of 11%, preterm birth of 19%, birth weight >90th percentile of 32%, and a Caesarean section rate of 42%. In nonnative Dutch women, the glycemic control was slightly poorer and the gestational age at booking somewhat later as compared to native Dutch women. However, there were no differences in incidence of preeclampsia/HELLP, preterm birth, perinatal mortality, macrosomia, and congenital malformations between those two groups. Conclusions. A high incidence of adverse pregnancy outcomes was found in women with pregestational T2D, although the outcome was comparable between native and non-native Dutch women. This suggests that easy access to and adequate participation in the local health care systems contribute to these comparable outcomes, offsetting potential disadvantages in the non-native group. [ABSTRACT FROM AUTHOR]

Background: Relevant safety signals in the EU are regularly communicated in so-called 'Direct Healthcare Professional Communications' (DHPCs) or European Medicines Agency (EMA) press releases. Trends of a decrease in the use of rosiglitazone following regulatory safety warnings have been described in the US. In the EU, however, relatively little is known about dispensing patterns following DHPCs or other safety signals such as EMA press releases.Objective: The objective of this study was to analyse trends in dispensing patterns of rosiglitazone and pioglitazone following DHPCs and EMA press releases in the EU member state, the Netherlands.Methods: Data for this study were obtained from the PHARMO Record Linking System, which includes drug dispensing records from community pharmacies of approximately 2.5 million individuals in the Netherlands. Over the period 1998-2008 an auto-regressive, integrated, moving average model (ARIMA) was fitted. The DHPC letters or EMA press releases were used as determinants. Adjustments were made for publication of certain literature. Stratification was performed for dispensings prescribed by general practitioners (GPs) and those prescribed by specialists.Results: For rosiglitazone, four EMA press releases and two DHPCs were issued; for pioglitazone, one DHPC was issued. The number of rosiglitazone dispensings prescribed by GPs decreased significantly after publication of DHPCs and EMA press releases concerning the risk of macular oedema and risk of fractures (both p-values 0.001). The number of rosiglitazone dispensings decreased statistically significantly after publication of EMA press releases 2 and 3 concerning cardiovascular risks but not for EMA press release 4. Adjustment for certain publications in the literature reduced the effect of communicated safety issues on the proportion of dispensings.Conclusions: Although it is difficult to disentangle the effect of DHPCs and EMA press releases from the effect of reports published in the literature, our results suggest that prescribers may react to such safety communications. [ABSTRACT FROM AUTHOR]

Objective: Numerous studies have suggested a decreased risk of cancer in patients with diabetes on metformin. Because different comparison groups were used, the effect magnitude is difficult to estimate. Therefore, the objective of this study was to further analyze whether, and to what extent, use of metformin is associated with a decreased risk of cancer in a cohort of incident users of metformin compared with users of sulfonylurea derivatives.Research Design and Methods: Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. The association between the risk of cancer in those using metformin compared with those using sulfonylurea derivatives was analyzed using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant.Results: Use of metformin was associated with a lower risk of cancer in general (hazard ratio 0.90 [95% CI 0.88-0.91]) compared with use of sulfonylurea derivatives. When specific cancers were used as end points, similar estimates were found. Dosage-response relations were identified for users of metformin but not for users of sulfonylurea derivatives.Conclusions: In our study, cumulative exposure to metformin was associated with a lower risk of specific cancers and cancer in general, compared with cumulative exposure to sulfonylurea derivatives. However, whether this should indeed be seen as a decreased risk of cancer for the use of metformin or as an increased risk of cancer for the use sulfonylurea derivatives remains to be elucidated. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Numerous studies have suggested a decreased risk of cancer in patients with diabetes on metformin. Because different comparison groups were used, the effect magnitude is difficult to estimate. Therefore, the objective of this study was to further analyze whether, and to what extent, use of metformin is associated with a decreased risk of cancer in a cohort of incident users of metformin compared with users of sulfonylurea derivatives. RESEARCH DESIGN AND METHODS--Data for this study were obtained from dispensing records from community pharmacies individually linked to hospital discharge records from 2.5 million individuals in the Netherlands. The association between the risk of cancer in those using metformin compared with those using sulfonylurea derivatives was analyzed using Cox proportional hazard models with cumulative duration of drug use as a time-varying determinant. RESULTS--Use of metformin was associated with a lower risk of cancer in general (hazard ratio 0.90 [95% CI 0.88-0.91]) compared with use of sulfonylurea derivatives. When specific cancers were used as end points, similar estimates were found. Dosage-response relations were identified for users of metformin but not for users of sulfonylurea derivatives. CONCLUSIONS--In our study, cumulative exposure to metformin was associated with a lower risk of specific cancers and cancer in general, compared with cumulative exposure to sulfonylurea derivatives. However, whether this should indeed be seen as a decreased risk of cancer for the use of metformin or as an increased risk of cancer for the use sulfonylurea derivatives remains to be elucidated. [ABSTRACT FROM AUTHOR]

Patients (>90% type 1 diabetes) using real time- continuous glucose monitoring (RT-CGM) for more than 3 months were asked to complete a questionnaire on type and duration of diabetes, self-reported complications, subjective reasons for RT-CGM use, source of payment for RT-CGM, personal income, time on the sensor, but also information such as perceived burden of diabetes, admissions for severe hypoglycaemia or ketoacidosis before and since commencing RT-CGM use. Of the 150 patients supplied with the questionnaire it was completed by 89%. Compliance was high with 77% reporting RT-CGM use ≥75% of the time. The proportion of patients having an HbA1c of ≤7% increased from 33% to 73% (p<0.001). Severe hypoglycaemia and hospital admissions for hypoglycaemia and ketoacidosis also decreased significantly. Patient satisfaction with the device was high. The impact of living with diabetes in daily life improved from 4.1 to 3.4 (p<0.001). The hypoglycaemia alarm was most appreciated.In summary, we confirm that RT-CGM can be a valuable tool to support patients in the self-management of their type 1 diabetes in real life practice if they are willing and able to use the device at least 75% of the time. [ABSTRACT FROM PUBLISHER]

Background: South Asians have a high risk to develop type 2 diabetes, which may be related to substantial ectopic fat deposition. Since glucagon-like peptide-1 analogues can reduce ectopic fat accumulation, the aim of the present study was to assess the effect of treatment with liraglutide for 26 weeks on ectopic fat deposition and HbA1c in South Asian patients with type 2 diabetes. Methods: In a placebo-controlled trial, 47 South Asian patients with type 2 diabetes were randomly assigned to treatment with liraglutide (1.8 mg/day) or placebo added to standard care. At baseline and after 26 weeks of treatment we assessed abdominal subcutaneous, visceral, epicardial and paracardial adipose tissue volume using MRI. Furthermore, myocardial and hepatic triglyceride content were examined with proton magnetic resonance spectroscopy. Results: In the intention-to-treat analysis, liraglutide decreased body weight compared to placebo (− 3.9 ± 3.6 kg vs − 0.6 ± 2.2 kg; mean change from baseline (liraglutide vs placebo): − 3.5 kg; 95% CI [− 5.3, − 1.8]) without significant effects on the different adipose tissue compartments. HbA1c was decreased in both groups without between group differences. In the per-protocol analysis, liraglutide did decrease visceral adipose tissue volume compared to placebo (− 23 ± 27 cm2 vs − 2 ± 17 cm2; mean change from baseline (liraglutide vs placebo): − 17 cm2; 95% CI [− 32, − 3]). Furthermore, HbA1c was decreased by liraglutide compared to placebo (− 1.0 ± 0.8% (− 10.5 ± 9.1 mmol/mol)) vs (− 0.6 ± 0.8% (− 6.1 ± 8.8 mmol/mol)), with a between group difference (mean change from baseline (liraglutide vs placebo): − 0.6% (− 6.5 mmol/mol); 95% CI [− 1.1, − 0.1 (− 11.5, − 1.5)]). Interestingly, the decrease of visceral adipose tissue volume was associated with the reduction of HbA1c (β: 0.165 mmol/mol (0.015%) per 1 cm2 decrease of visceral adipose tissue volume; 95% CI [0.062, 0.267 (0.006, 0.024%)]). Conclusions: While the intention-to-treat analysis did not show effects of liraglutide on ectopic fat and HbA1c, per-protocol analysis showed that liraglutide decreases visceral adipose tissue volume, which was associated with improved glycaemic control in South Asians. Trial registration NCT02660047 (clinicaltrials.gov). Registered 21 January 2016 [ABSTRACT FROM AUTHOR]