C. A. Baan

Ethnic aspects of emotional distress in patients with diabetes-the Amsterdam Health Monitor Study

Depression and anxiety are relatively common in patients with diabetes, but it is unclear whether migrant patients with diabetes are at increased risk for emotional distress. We determined levels of emotional distress in patients with diabetes with a Turkish, Moroccan or Dutch ethnic background and compare distress levels with healthy control subjects. Among patients with diabetes, we examined demographic and clinical correlates of higher levels of emotional distress.

Policy evaluation in diabetes prevention and treatment using a population-based macro simulation model: the MICADO model

To test a simulation model, the MICADO model, for estimating the long‐term effects of interventions in people with and without diabetes.

Modelling integrated care for diabetes based on observational data: the MICADO model

Background and aims: TCF7L2 is both an activator and an inhibitor of transcription and the most highly associated type 2 diabetes gene known to date. It influences beta cell survival and function, i.e. incretin hormonal effects, insulin processing and secretion. However, its target genes in pancreatic islets are not fully described and the molecular mechanism whereby it propagates its effects on islet function is not known. The aim of this study is to identify the molecular mechanisms through which TCF7L2 influence beta cell survival and function. Materials and methods: Wister rat primary islets and INS-1 (832/13) cells were incubated with siRNA against Tcf7l2, both Tcf7l2 and TP53INP1 or both TCF7L2 and TP53 in 5.5 mM and 14.3 mM glucose. TCF7L2 activity, p53 activity and target gene expression (using qPCR) were measured after siRNA treatment. INS-1 cell apoptosis was measured by DNA degradation levels, caspase-3/7 levels and by using antibodies against Annexin V, and 7-AAD, visualized using confocal microscopy. Rat islet viability was estimated measuring metabolic rate. Rat islet apoptosis was estimated by measuring Caspase-3/7 level. Results: The type 2 diabetes associated genes TP53INP1, FTO, GIPR and ADAMTS9 were identified as TCF7L2 potential target gene using chromatin immunoprecipitation on microarrays. In INS-1 cells, siRNA mediated Tcf7l2 knock down (69.5 %) resulted in decreased TCF7L2 activity (91%) and differential expression of the target genes: Tp53 (14.5% increase), TP53INP1 (65.9% increase) and ADAMTS9 (82.8% decrease). TCF7L2 knockdown also lead to reduced cell viability (65%) and increased apoptosis (113%). The TCF7L2 induced cell death was replicated in rat primary islets. When restoring (decreasing) the Tp53inp1 expression level in TCF7L2 depleted islets, the decrease in cell viability and increase in apoptosis were prevented, suggesting that the Tcf7l2 effect is mediated via Tp53inp1. Furthermore, p53 depletion prohibited TCF7L2 down regulation induced cell death and elevation of Tp53inp1 expression in both INS-1 cells and rat primary islets. Conclusion: The type 2 diabetes associated genes TP53INP1 and ADAMTS9 are target genes of TCF7L2 in pancreatic islets. TCF7L2 induced apoptosis and decreased cell viability are mediated through activation of p53 and increased p53INP1 expression.

Cost-effectiveness of centralised and partly centralised care compared to usual care for patients with type 2 diabetes

Background and aims: Due to an ever increasing number of type 2 diabetes patients, innovations to control the increasing health care use and costs are needed. Results of diabetes care programs on the costs or (cost-) effectiveness are heterogeneous. The aim of this study is to compare the cost-effectiveness of two diabetes care models with usual care for type 2 diabetes patients from the societal perspective. Materials and methods: An economic evaluation was performed alongside a clinical trial. In two distinct regions of the Netherlands, two diabetes care models were implemented with different levels of centralized organizational structures. One of them was centralized care (CC) with a central organization and coordination of the care between all care providers and the use of a central database. Patients receive an annual extended diabetes assessment at the Diabetes Care Centre, in addition to the care by patients general practitioner (GP). GPs receive feedback about their performance. Partly centralized care (PC) focuses on adherence to type 2 diabetes guidelines. An online clinical database is used to monitor mean values of risk factors. All assessments were performed in patients GP practice. Usual care (UC) has a decentralized organisation structure and patients GP is responsible for the diabetes care. Clinical outcome measure was risk of a coronary heart disease (CHD) calculated with the UKDPS risk engine. Cost-effectiveness analysis was performed from the societal perspective comparing patients receiving CC (n=313), PC (n=293) and UC (n=485) during one year of follow-up. Missing costs and effects data were imputed using multiple imputation. Differences in costs, effects and cost-effectiveness between the diabetes care groups were analysed using bootstrapping techniques. Results: Differences in changes in CHD risk over 12 months of follow-up between the three groups were statistically insignificant and clinically irrelevant. Compared to UC, health care costs during the follow-up period were lower in CC (-1300 (95% CI: -2300 to -570)) and PC (-960 (95% CI: -1890 to -100)). Costs from the societal perspective showed the same trend, although not statistically significant. Conclusion: Clinical outcomes did not differ between the different care models. Lower health care costs were observed in (partly) centralized care compared to usual care, mainly due to substitution of secondary health care use by primary health care use. This suggests that centralizing the diabetes care results in equal outcomes at lower health care costs.Background and aims: Metabolic disruptions characterized by high hepatic lipid content (HLC) are associated with impairments in whole body glucose homeostasis. To gain insight on the role of hepatic lipids in the metabolic performance in the absence artificial metabolic stresses we measured non- invasively and longitudinally the HLC and profile in mice during adult devel - opment by Magnetic Resonance (MR) Spectroscopy in vivo . In parallel, mice were challenged with insulin and glucose tolerance tests. Materials and methods: Male (N=10) and female (N=10) C57Bl/6J mice were studied at 3 (3Mo), 7 (7Mo) and 10 months (10Mo) of age. Mice were scanned in a 14.1 T magnet with a 1 H quadrature surface coil over the abdo - men. Localized 1 H spectra were acquired from a 8 μl volume with stimulated echo acquisition mode sequence and the HLC expressed as the percent of to - tal 1 H MR signal, with corrections for spin-spin relaxation effects. Additional spectra were acquired from the same volume with suppression of the water signal to enable the detection and quantification of all the lipid protons. The lipid profile was characterized by the following indices: saturated component (SC); unsaturated fatty acyl chains (UFA); mean number of double bonds per fatty acyl chain (ndb/FA), mean number of poly-unsaturated double bonds per fatty acyl chain (PUdb/FA) and per UFA (PUdb/UFA); mean chain length (MCL). OGTTs (1.5 g/Kg) and i.p. insulin tolerance tests (ITTs) were per - formed after a 6h-fast. Plasma insulin was determined by ELISA and insulin sensitivity estimated with the quantitative insulin check index (QUICKI) as the inverse of the log 10 sum of fasting insulin (μIU/ml) and fasting glucose (mg/dl). Data are expressed as mean ± SEM. Statistical significance was ac - cepted for a P < 0.05 (one-way ANOVA with Newman-Keuls post test) and correlations assessed by the Pearson r coefficient. Results: In males, the HLC at 3Mo was 1.35 ± 0.15%, increasing to 3.06 ± 0.38% at 7Mo, not different from 2.70 ± 0.31% at 10Mo. Females had higher HLC at 3Mo (2.63 ± 0.19%) but no further changes henceforward (2.31 ± 0.20% at 7Mo; 2.36 ± 0.20% at10 Mo). In males, the SC and MCL of hepatic lipids increased with age, with a trend for decreased PUdb/FA and PUdb/ UFA with no changes in ndb/FA or UFA content. Females showed the same trends. Glycemia 3h-post ITT and 2h-post OGTT was lower in females, while QUICKI was higer. These scores were preserved until 10Mo in females. In males, glycemia 2-h post OGTT increased with age and the area above the curve (AAC) for the ITT decreased. In males, but not females, higher body weight correlated with hepatic lipid accumulation ( r = 0.7); worse ITT scores correlated with higher body weight ( r = -0.6) and HLC ( r = -0.7) and lower Pudb/UFA ( r = 0.5); worse OGTT scores correlated with higher HLC ( r = 0.4). Conclusion: In male mice, loss of insulin sensitivity correlated with weight gain, HL accumulation and lower poly-unsaturation. Glucose intolerance was specifically associated with HLC, suggesting a deleterious effect of lipids on the adaptation of hepatic metabolism to the fed state. This behaviour was not observed in females even if they showed similar HLC. In fact, the poly- unsaturation of HL in females didn’t change with HLC, suggesting a positive effect of PUFA on preserving the hepatic metabolic performance.

Cost-effectiveness of preventive interventions in Diabetes Mellitus and its (macrovascular) complications: A systematic literature review

PDB30 COST-EFFECTIVENESS OF PREVENTIVE INTERVENTIONS IN DIABETES MELLITUS AND ITS (MACROVASCULAR)COMPLICATIONS: A SYSTEMATIC LITERATURE REVIEW Vijgen SMC, Hoogendoorn M, Baan C, de Wit A, Limburg W, Feenstra TL National Institute for Public Health and the Environment, Bilthoven, The Netherlands INTRODUCTION: Diabetes Mellitus is one of the major chronic diseases in Western societies, causing considerable comorbidity of cardiovascular diseases and premature death. Because of the variety of risk factors for diabetes mellitus and different macrovascular complications, the set of potentially interesting interventions is quite large. For policy makers with limited budgets, the question thus arises in what area of diabetes prevention, health care money is spent most effectively. OBJECTIVE: The aim of the present study was to review the literature on economic evaluation of interventions for prevention of diabetes Type-2 or its macrovascular complications, to describe their results and to identify the interventions that require additional research. METHODS: A systematic review of the literature was conducted. The interventions were classified by type of prevention. The characteristics of the selected studies (with life years gained or quality adjusted life years as an outcome measure) were described in a database, to generate summary tables. To be included, studies had to give a full economic evaluation of effects of the intervention. All studies were scored for quality using the BMJ checklist. RESULTS: In total 23 studies with life years gained or quality adjusted life years as an outcome measure were selected. Two studies focused on primary prevention, one on screening, and 20 studies evaluated interventions for the prevention of macrovascular complications. CONCLUSIONS: Tight blood pressure control is a cost effective intervention compared to less tight control. Medication to reduce both overweight and hyperglycemia was found to be cost saving to moderately cost-effective. Primary prevention of Type-2 diabetes also appeared to be cost-effective and cost saving, but further research is needed because only two studies were available. The results of medication interventions to reduce overweight, to reduce hyperglycemia, and to reduce dyslipidemia vary considerably, warranting further economic analysis to identify costeffective strategies.