AimTo investigate the association of plasma metabolites with incident and prevalent chronic kidney disease (CKD) in people with type 2 diabetes and establish whether this association is causal... Show moreAimTo investigate the association of plasma metabolites with incident and prevalent chronic kidney disease (CKD) in people with type 2 diabetes and establish whether this association is causal.Materials and MethodsThe Hoorn Diabetes Care System cohort is a large prospective cohort consisting of individuals with type 2 diabetes from the northwest part of the Netherlands. In this cohort we assessed the association of baseline plasma levels of 172 metabolites with incident (Ntotal = 462/Ncase = 81) and prevalent (Ntotal = 1247/Ncase = 120) CKD using logistic regression. Additionally, replication in the UK Biobank, body mass index (BMI) mediation and causality of the association with Mendelian randomization was performed.ResultsElevated levels of total and individual branched-chain amino acids (BCAAs)-valine, leucine and isoleucine-were associated with an increased risk of incident CKD, but with reduced odds of prevalent CKD, where BMI was identified as an effect modifier. The observed inverse effects were replicated in the UK Biobank. Mendelian randomization analysis did not provide evidence for a causal relationship between BCAAs and prevalent CKD.ConclusionsOur study shows the intricate relationship between plasma BCAA levels and CKD in individuals with type 2 diabetes. While an association exists, its manifestation varies based on disease status and BMI, with no definitive evidence supporting a causal link between BCAAs and prevalent CKD. Show less
BackgroundEthnic differences in the progression and outcome of diabetic kidney disease (DKD) remain to be elucidated. MRI-quantified renal sinus fat volume could be a potential biomarker to help... Show moreBackgroundEthnic differences in the progression and outcome of diabetic kidney disease (DKD) remain to be elucidated. MRI-quantified renal sinus fat volume could be a potential biomarker to help investigate the changes of DKD risk in response to glucose regulation.PurposeTo evaluate whether the effect of glucose-lowering treatment on renal sinus fat volume differed in West Europeans (WE) compared to South Asians (SA), and whether ethnic-related difference exists regarding the effect of liraglutide on renal sinus fat.Study TypeRetrospective.PopulationNinety-three patients with type 2 diabetes mellitus, including 47 WE (27 males) aged 59.3 +/- 6.5 years, and 46 SA (19 males) aged 54.4 +/- 9.8 years.Field Strength/Sequence3.0 T dual-echo fast gradient-echo pulse sequence using two-point Dixon technique with a phase-correction algorithm.AssessmentChanges of renal sinus fat volume were measured by a radiologist (LL) with 4-years' experience, and were compared between the two ethnic groups, together with glycemic level, metabolic risk factors and renal function. The effects of liraglutide were assessed.Statistical TestsNormality of the data was visually evaluated by histograms and Q-Q plots. Within-group and between-group differences were analyzed using paired t-tests and analysis of covariance. Associations were analyzed by person's correlation and multiple linear regression models.ResultsRenal sinus fat decreased in SA patients (Delta% = -7.6% +/- 14.8%), but increased in WE patients (Delta% = 5.0% +/- 13.1%), with a significant difference between the two ethnic groups. In the WE group, the increase of sinus fat volume was significant in the placebo subgroup (Delta% = 6.8% +/- 12.5%), in contrast to the nonsignificant increase in the liraglutide subgroup (Delta% = 3.0% +/- 13.8%, P = 0.444).Data ConclusionRenal sinus fat accumulation responds differently to glucose regulation, showing a reduction in SA patients in contrast to a persistent accumulation in WE patients. A trend of less accumulation of sinus fat in WE patients receiving liraglutide has been observed.Evidence Level4Technical EfficacyStage 4 Show less
ObjectiveThe objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and... Show moreObjectiveThe objective of this study was to investigate whether placebo effect induced by pharmacological conditioning with intranasal insulin can affect glucose, insulin, C-peptide, hunger, and memory in patients with diabetes type 2 and healthy controls.MethodsPlacebo effect was induced by pharmacological conditioning. Thirty-two older patients (mean age = 68.3 years) with diabetes type 2 and age- and sex-matched thirty-two healthy older adults (mean age = 67.8 years) were randomly assigned to a conditioned or a control group. On day 1, conditioned group received six administrations of intranasal insulin with a conditioned stimulus (CS; smell of rosewood oil), whereas the control group received a placebo with the CS. On day 2, both groups received a placebo spray with the CS. Glucose, insulin, and C-peptide were repeatedly measured in blood. Hunger and memory were assessed with validated measures.ResultsIntranasal insulin stabilized dropping glucose levels in patients (B = 0.03, SE = 0.02, p = .027) and healthy men (B = 0.046, SE = 0.02, p = .021), and decreased C-peptide levels in healthy controls (B = 0.01, SE = 0.001, p = .008). Conditioning also prevented the drop of glucose levels but only in men (both healthy and patients; B = 0.001, SE = 0.0003, p = .024). Conditioning significantly decreased hunger in healthy participants (B = 0.31, SE = 0.09, p < .001). No effects were found on other measures.ConclusionsPlacebo effect induced by conditioning with intranasal insulin modifies blood glucose levels and decreases hunger in older adults, but its effects depend on health status and sex. Insulin conditioning might be beneficial for groups suffering from intensive hunger but seems not be particularly suitable for blood glucose reduction. Show less
AimsImplicit gender biases (IGBs) are unconscious evaluations about a person based on gender. IGBs of healthcare providers may affect medical decision making. This study investigated whether IGBs... Show moreAimsImplicit gender biases (IGBs) are unconscious evaluations about a person based on gender. IGBs of healthcare providers may affect medical decision making. This study investigated whether IGBs and genders of patients and general practitioners (GPs) influence diagnostics and treatment decisions in the context of diabetes type 2.MethodsNinety-nine GPs participated in this randomized online study. Implicit Associations Tasks were used to measure two IGBs, related to lifestyle (women have a healthier lifestyle than men) and communication (men are less communicative than women). Clinical decisions regarding type 2 diabetes were measured with vignettes that included a fictional male or female patient case.ResultsFemale GPs exhibited a significant lifestyle IGB (p < 0.001). GPs of both genders exhibited a significant communication IGB (p < 0.001). Several associations between IGBs and clinical decisions were found. The gender of the vignette character affected several outcomes, for example GPs were less certain in the diabetes diagnosis when the character was a woman (p < 0.001).ConclusionWe demonstrated that GPs have IGBs and these biases as well as patient's gender affect decisions of GP's when they are solving a diabetes vignette case. Future research is needed to understand the most important consequences of IGBs in the context of type 2 diabetes. Show less
Background: Low 24-h urinary potassium excretion, reflecting low potassium intake, is associated with premature mortality in the general population. Objectives: To determine whether urinary... Show moreBackground: Low 24-h urinary potassium excretion, reflecting low potassium intake, is associated with premature mortality in the general population. Objectives: To determine whether urinary potassium excretion is associated with all-cause mortality in patients with type 2 diabetes. Methods: We performed a prospective cohort study in 654 patients with type 2 diabetes in the Diabetes and Lifestyle Cohort Twente (DIALECT). Sex-specific tertiles of 24-h urinary potassium excretion were analyzed in a multivariable Cox regression model with all-cause mortality. The outpatient program of the hospital uses a continuous surveillance system by the municipal registry of death to ensure up-to-date information on the patient's status (alive or deceased). FFQs were used to study associations between urinary potassium excretion and food products. Results: Urinary potassium excretion at baseline was 84 & PLUSMN; 25 mmol/d in males and 65 & PLUSMN; 22 mmol/d in females, corresponding to estimated potassium intakes of 4250 & PLUSMN; 1270 mg/d and 3300 & PLUSMN; 875 mg/d. During a median follow-up of 5.2 (IQR: 2.7-7.9] y, 96 participants died. In a fully adjusted model, patients in the lowest sex-specific tertile had a higher risk of all-cause mortality, compared with patients in the highest sex-specific tertile (HR: 2.09; 95% CI: 1.06, 4.10; P = 0.03). Patients in the lowest sex-specific tertile consumed fewer fruits and vegetables, dairy, coffee, and potato products compared with patients in the highest sex-specific tertile (all P < 0.05). Conclusions: Low potassium intake is associated with a higher risk of all-cause mortality in Dutch patients with type 2 diabetes. Intervention studies are needed to determine whether potassium supplementation improves longevity in patients with type 2 diabetes. This trial was registered in the as NTR trial code 5855. Show less
Wang, W.Y.; Tesfay, E.B.; Klinken, J.B. van; Dijk, K.W. van; Bartke, A.; Heemst, D. van; Noordam, R. 2022
Background: There is inconsistent evidence for the causal role of serum insulin-like growth factor-1 (IGF-1) concentration in the pathogenesis of human age-related diseases such as type 2 diabetes ... Show moreBackground: There is inconsistent evidence for the causal role of serum insulin-like growth factor-1 (IGF-1) concentration in the pathogenesis of human age-related diseases such as type 2 diabetes (T2D). Here, we investigated the association between IGF-1 and T2D using (clustered) Mendelian randomization (MR) analyses in the UK Biobank. Methods: We conducted Cox proportional hazard analyses in 451 232 European-ancestry individuals of the UK Biobank (55.3% women, mean age at recruitment 56.6 years), among which 13 247 individuals developed type 2 diabetes during up to 12 years of follow-up. In addition, we conducted two-sample MR analyses based on independent single nucleotide polymorphisms (SNPs) associated with IGF-1. Given the heterogeneity between the MR effect estimates of individual instruments (P-value for Q statistic = 4.03e-145), we also conducted clustered MR analyses. Biological pathway analyses of the identified clusters were performed by over-representation analyses. Results: In the Cox proportional hazard models, with IGF-1 concentrations stratified in quintiles, we observed that participants in the lowest quintile had the highest relative risk of type 2 diabetes [hazard ratio (HR): 1.31; 95% CI: 1.23-1.39). In contrast, in the two-sample MR analyses, higher genetically influenced IGF-1 was associated with a higher risk of type 2 diabetes. Based on the heterogeneous distribution of MR effect estimates of individual instruments, six clusters of genetically determined IGF-1 associated either with a lower or a higher risk of type 2 diabetes were identified. The main clusters in which a higher IGF-1 was associated with a lower risk of type 2 diabetes consisted of instruments mapping to genes in the growth hormone signalling pathway, whereas the main clusters in which a higher IGF-1 was associated with a higher risk of type 2 diabetes consisted of instruments mapping to genes in pathways related to amino acid metabolism and genomic integrity. Conclusions: The IGF-1-associated SNPs used as genetic instruments in MR analyses showed a heterogeneous distribution of MR effect estimates on the risk of type 2 diabetes. This was likely explained by differences in the underlying molecular pathways that increase IGF-1 concentration and differentially mediate the effects of IGF-1 on type 2 diabetes. Show less
Background and Purpose:Type 2 diabetes mellitus patients have an increased fracture risk despite having higher areal bone mineral density (aBMD) measured by DXA. This apparent paradox might be... Show moreBackground and Purpose:Type 2 diabetes mellitus patients have an increased fracture risk despite having higher areal bone mineral density (aBMD) measured by DXA. This apparent paradox might be explained by the overestimation of BMD by DXA due to the higher fat mass in type 2 diabetes mellitus patients. Volumetric BMD (vBMD) as assessed by quantitative CT (QCT) is not influenced by fat mass. We assessed the association of vBMD and fasting plasma glucose in a large cohort of Chinese subjects and compared the vBMD in healthy and diabetic subjects. In addition, we compared the relation between aBMD, vBMD, glucose and fat mass in a subset of this cohort. Materials and Methods:10309 participants from the China Biobank project underwent QCT based on chest low dose CT to compute vBMD of L1 and L2 vertebrae and FPG measurements between 2018 and 2019. Among them, 1037 subjects also had spine DXA scans. Data was analyzed using linear regression models. Results: In the total cohort (5889 men and 4420 women, mean age 53 years, range 30-96), there was no significant association between vBMD and FPG after adjustment for age (women: p=0.774; men: p=0.149). 291 women and 606 men fitted the diagnostic criteria of diabetes. Both women and men with diabetes had lower vBMD compared to non-diabetic subjects, but this became non-significant after adjusting for age in the total cohort (women: p=0.817; men: p=0.288) and after propensity score matching based on age (women: p=0.678; men: p=0.135). In the DXA subcohort, aBMD was significantly higher in men with diabetes after adjusting for age and this difference disappeared after further adjusting for total fat area (p=0.064). Conclusion: We did not find any effect of fasting plasma glucose or diabetes on the volumetric BMD measured with QCT after adjustment for age. Therefore, vBMD measured with QCT might be a more reliable measurement to diagnose osteoporosis and assess fracture risk than aBMD measured with DXA in diabetic patients. Show less
Hybrid e-health support was given to 11 insulin-dependent type 2 diabetes mellitus (DM2) patients, with electronic support plus a multi-disciplinary health support team. Challenges were low ICT and... Show moreHybrid e-health support was given to 11 insulin-dependent type 2 diabetes mellitus (DM2) patients, with electronic support plus a multi-disciplinary health support team. Challenges were low ICT and health literacy. After 50 weeks, attractiveness and feasibility of the intervention were perceived as high: recommendation 9.5 out of 10 and satisfaction 9.6 out of 10. Technology acceptance model (TAM) surveys showed high usefulness and feasibility. Acceptance and health behaviours were reinforced by the prolonged health results: aerobic and strength capacity levels were improved at 50 weeks, plus health related quality of life (plus biometric benefits and medication reductions, reported elsewhere). Regarding e-health theory, we conclude that iterative skill growth cycles are beneficial for long-term adoption and e-relationships. Next, the design analysis shows opportunities for additional affective and social support, on top of the strong benefits already apparent from the direct progress feedback loops used within the health coach processes. Show less
Background Lifestyle intervention studies to treat type 2 diabetes (T2D) are on the rise. However, in-depth research is lacking into the dietary changes that participants make. Methods The present... Show moreBackground Lifestyle intervention studies to treat type 2 diabetes (T2D) are on the rise. However, in-depth research is lacking into the dietary changes that participants make. Methods The present study aimed to observe the dietary intake of participants following the group program 'Reverse Diabetes2 Now' (RD2N) over 12 months. The web-based 24-h dietary recall-tool Compl-eat was used to collect dietary intake data. Results In total, 147 T2D patients were included in a cross-sectional study (n = 37 at baseline, n = 58 at 6 months, n = 52 at 12 months). A lower intake of total energy, carbohydrates and iodine was found for the groups at 6 and 12 months compared to the baseline group. The absolute consumption of total fat and saturated fat did not differ between the groups; only the percentage as total calorie consumption decreased. Consumption of vegetables and full-fat yoghurt was higher in groups at 6 and 12 months compared to the group at baseline. Consumption of bread, cakes and sweet biscuits, pasta/rice/tortillas, artificially sweetened soft drinks, and crisps were lower in the groups at 6 and 12 months compared to the group at baseline. Similar results were observed in a separate prospective study in 22 participants over 12 months following the same lifestyle-intervention. Conclusions Overall, participants shifted their dietary intake somewhat towards a healthier dietary pattern with overall lower energy and carbohydrates and more vegetables. Moreover, participants largely maintained this healthier pattern over 12 months. There were some concerns regarding iodine intake. These promising results need to be confirmed in a fully-scaled study, as well in a comparison with controls. Show less
Groen, N.; Leenders, F.; Mahfouz, A.; Munoz-Garcia, A.; Muraro, M.J.; Graaf, N. de; ... ; Carlotti, F. 2021
The maintenance of pancreatic islet architecture is crucial for proper beta-cell function. We previously reported that disruption of human islet integrity could result in altered beta-cell identity... Show moreThe maintenance of pancreatic islet architecture is crucial for proper beta-cell function. We previously reported that disruption of human islet integrity could result in altered beta-cell identity. Here we combine beta-cell lineage tracing and single-cell transcriptomics to investigate the mechanisms underlying this process in primary human islet cells. Using drug-induced ER stress and cytoskeleton modification models, we demonstrate that altering the islet structure triggers an unfolding protein response that causes the downregulation of beta-cell maturity genes. Collectively, our findings illustrate the close relationship between endoplasmic reticulum homeostasis and beta-cell phenotype, and strengthen the concept of altered beta-cell identity as a mechanism underlying the loss of functional beta-cell mass. Show less
Introduction South Asians with diabetes have more severe diabetic retinopathy (DR) and cardiovascular complications than white Caucasians. However, how big this gap is and the relation with the... Show moreIntroduction South Asians with diabetes have more severe diabetic retinopathy (DR) and cardiovascular complications than white Caucasians. However, how big this gap is and the relation with the severity of DR has not been studied. Here, we quantify the difference in time from diabetes diagnosis until a first non-fatal Major Adverse Cardiovascular Event (TUF MACE) in different DR groups in South Asians and Europeans. Methods 3831 adults with type 2 diabetes, 1358 South Asians and 2473 Europeans, treated in our diabetes clinic between 2006 and 2017 were included. Data on risk factors, diabetes duration, age of diagnosis and diabetes complications were collected from the diabetes-specific database and analysed using descriptive statistics and Cox regression. DR was graded in 3 categories, and non-fatal MACE was pre-specified. Results Prevalence of non-fatal MACE was the same when DR was absent, increased with increasing severity of DR in both ethnic groups, but was more frequent in South Asians with DR (mild: 50 vs. 42% and severe 62 vs. 46%. Classic risk factors only differed in relation to smoking habits, which were significantly lower in South Asians. After correction for classic risk factors and age at diabetes diagnosis TUF MACE was significantly shorter in South Asians, an effect also seen in the no-DR group (4.1 yrs. HR 1.5, 95% CI 1.3-1.8 and 7.4 yrs. earlier, HR 2.0, 95% CI 1.6-2.6 for no-DR and severe DR, respectively). Conclusions When adjusted for age at diabetes diagnosis, we show that time until first non-fatal MACE in South Asians is significantly shorter compared to Europeans and increases from no- to severe DR. Show less
Aims To investigate changes in physical activity (PA) and psychological factors during societal lockdown in people with type 2 diabetes.Methods A cross-sectional study among Dutch adults with type... Show moreAims To investigate changes in physical activity (PA) and psychological factors during societal lockdown in people with type 2 diabetes.Methods A cross-sectional study among Dutch adults with type 2 diabetes. Data were collected using online questionnaires. A multivariate multinomial logistic regression was performed with change in PA during societal lockdown as outcome and perceived change in stress, anxiety, perceived risk for COVID-19 infection, emotional well-being and former PA status as determinants.Results Five hundred and sixty seven respondents filled out the questionnaire, 536 were included in the final analysis: mean age of 65.9 +/- 7.9 years; mean diabetes duration 13.3 +/- 8 years; 54% men; 47% reported no change in PA, 27% became less active and 26% became more active during societal lockdown. Participants who were more likely to become less active were participants who experienced more stress (OR: 2.27; 95% CI 1.25-4.13) or less stress (OR: 2.20; 95% CI 1.03-4.71). Participants who were more likely to become more active were participants who experienced more stress (OR: 2.31; 95% CI 1.25, 4.26). Participants with higher emotional well-being (OR: 0.98; 95% CI 0.97, 0.99) were less likely to become less active than to report no change in PA.Conclusions Changes in PA in people with type 2 diabetes during societal lockdown are associated with changes in psychological factors such as perceived stress and emotional well-being. People with diabetes and their caregivers should be aware of these possible changes. Show less
Boels, A.M.; Rutten, G.; Cleveringa, F.; Avendonk, M. van; Vos, R. 2021
IntroductionMany individuals with type 2 diabetes mellitus (T2DM) experience "psychological insulin resistance". Consequently, it could be expected that insulin therapy may have negative effects on... Show moreIntroductionMany individuals with type 2 diabetes mellitus (T2DM) experience "psychological insulin resistance". Consequently, it could be expected that insulin therapy may have negative effects on psychological outcomes and well-being. Therefore, this study compared health status and psychosocial functioning of individuals with T2DM using only oral antihyperglycemic agents (OHA) and on insulin therapy (with or without OHA).Materials and MethodsIn this cross-sectional study, we used baseline data of a cluster randomized controlled trial conducted in 55 Dutch general practices in 2005. Health status was measured with the Short Form (SF)-36 (scale 0-100) and psychosocial functioning with the Diabetes Health Profile (DHP, scale 0-100). To handle missing data, we performed multiple imputation. We used linear mixed models with random intercepts per general practice to correct for clustering at practice level and to control for confounding.ResultsIn total, 2,794 participants were included in the analysis, their mean age was 65.8 years and 50.8% were women. Insulin-users (n = 212) had a longer duration of T2DM (11.0 versus 5.6 years) and more complications. After correcting for confounders and multiple comparisons, insulin-users reported significantly worse outcomes on vitality (SF-36, adjusted difference -5.7, p=0.033), general health (SF-36, adjusted difference -4.8, p=0.043), barriers to activity (DHP, adjusted difference -7.2, p<0.001), and psychological distress (DHP, adjusted difference -3.7, p=0.004), all on a 0-100 scale.DiscussionWhile previous studies showed similar or better health status in people with type 2 diabetes receiving insulin therapy, we found that vitality, general health and barriers to activity were worse in those on insulin therapy. Although the causality of this association cannot be established, our findings add to the discussion on the effects of insulin treatment on patient-reported outcomes in daily practice. Show less
Background: Most risk assessment models for type 2 diabetes (T2DM) have been developed in Caucasians and Asians; little is known about their performance in other ethnic groups.Objective(s): We... Show moreBackground: Most risk assessment models for type 2 diabetes (T2DM) have been developed in Caucasians and Asians; little is known about their performance in other ethnic groups.Objective(s): We aimed to identify existing models for the risk of prevalent or undiagnosed T2DM and externally validate them in a multi-ethnic population currently living in the Netherlands.Methods: A literature search to identify risk assessment models for prevalent or undiagnosed T2DM was performed in PubMed until December 2017. We validated these models in 4,547 Dutch, 3,035 South Asian Surinamese, 4,119 African Surinamese, 2,326 Ghanaian, 3,598 Turkish, and 3,894 Moroccan origin participants from the HELIUS (Healthy Life in an Urban Setting) cohort study performed in Amsterdam. Model performance was assessed in terms of discrimination (C-statistic) and calibration (Hosmer-Lemeshow test). We identified 25 studies containing 29 models for prevalent or undiagnosed T2DM. C-statistics varied between 0.77-0.92 in Dutch, 0.66-0.83 in South Asian Surinamese, 0.70-0.82 in African Surinamese, 0.61-0.81 in Ghanaian, 0.69-0.86 in Turkish, and 0.69-0.87 in the Moroccan populations. The C-statistics were generally lower among the South Asian Surinamese, African Surinamese, and Ghanaian populations and highest among the Dutch. Calibration was poor (Hosmer-Lemeshow p < 0.05) for all models except one.Conclusions: Generally, risk models for prevalent or undiagnosed T2DM show moderate to good discriminatory ability in different ethnic populations living in the Netherlands, but poor calibration. Therefore, these models should be recalibrated before use in clinical practice and should be adapted to the situation of the population they are intended to be used in. Show less
Aims Short-term weight loss may lead to remission of type 2 diabetes but the effect of maintained weight loss on cardiovascular disease (CVD) is unknown. We quantified the associations between... Show moreAims Short-term weight loss may lead to remission of type 2 diabetes but the effect of maintained weight loss on cardiovascular disease (CVD) is unknown. We quantified the associations between changes in weight 5 years following a diagnosis of diabetes, and incident CVD events and mortality up to 10 years after diagnosis.Materials and methods Observational analysis of the ADDITION-Europe trial of 2730 adults with screen-detected type 2 diabetes from the UK, Denmark and the Netherlands. We defined weight change based on the maintenance at 5 years of weight loss achieved during the year after diabetes diagnosis, and as 5-year overall change in weight. Incident CVD events (n = 229) and all-cause mortality (n = 225) from 5 to 10 years follow-up were ascertained from medical records.Results Gaining >2% weight during the year after diabetes diagnosis was associated with higher hazard of all-cause mortality versus maintaining weight [hazard ratio (95% confidence interval): 3.18 (1.30-7.82)]. Losing >= 5% weight 1 year after diagnosis was also associated with mortality, whether or not weight loss was maintained at 5 years: 2.47 (0.99-6.21) and 2.72 (1.17-6.30), respectively. Losing >= 10% weight over 5 years was associated with mortality among those with body mass index <30 kg/m(2) [4.62 (1.87-11.42)]. Associations with CVD incidence were inconclusive.Conclusions Both weight loss and weight gain after screen-detected diabetes diagnosis were associated with higher mortality, but not CVD events, particularly among participants without obesity. The clinical implications of weight loss following a diagnosis of diabetes probably depend on its magnitude and timing, and may differ by body mass index status. Personalization of weight loss advice and support may be warranted. Show less
Aims Whether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2... Show moreAims Whether diabetes increases venous thromboembolism (VTE) is unclear. Any greater risk may relate to insulin resistance, but many studies did not differentiate between type 1 diabetes and type 2 diabetes for VTE risk.Methods Retrospective cohort study of the Royal College of General Practitioners Research and Surveillance Centre, comprising over 530 primary care practices. We determined whether type 1 diabetes and/or type 2 diabetes are independent risk factors for VTE. The index date was 1 January 2009, individuals were followed to 31 December 2018, or censoring. Cox proportional hazard regression analysis was used to investigate the risk of VTE in people with type 1 diabetes and type 2 diabetes relative to no diabetes. The primary outcome was occurrence of VTE. The model was adjusted for potential confounders for VTE.Results There were 7086 people with type 1 diabetes and 95,566 with type 2 diabetes, diagnosed before 1 January 2009. The non-diabetes group consisted of 1,407,699 people. In the unadjusted analysis, there was no increased risk of VTE with type 1 diabetes (HR 1.00, 95% CI 0.76-1.33) but there was for type 2 diabetes (HR 2.70, 95% CI 2.57-2.84). In the fully adjusted model, VTE risk was increased in type 1 diabetes (HR 1.46, 95% CI 1.11-1.92), but not with type 2 diabetes (HR 1.06, 95% CI 0.98-1.14).Conclusions Type 1 diabetes was associated with a greater risk for VTE while type 2 diabetes was not. Further work is needed to determine the reason(s) for this. Show less
Objective Type 2 diabetes mellitus is a metabolic disorder characterized by insulin resistance. Previous studies in patients demonstrated that plasma levels of cathepsin D (CTSD), which is... Show moreObjective Type 2 diabetes mellitus is a metabolic disorder characterized by insulin resistance. Previous studies in patients demonstrated that plasma levels of cathepsin D (CTSD), which is optimally active in the acidic environment of lysosomes, correlate with insulin resistance. As plasma pH is slightly reduced in type 2 diabetic patients and we have previously shown that plasma CTSD activity is causally linked to insulin levelsin vivo, it is likely that the activity of CTSD in plasma will be increased in type 2 diabetes compared to healthy individuals. However, so far the interaction between CTSD activity and levels to postprandial metabolic derangements in type 2 diabetes is not known. Methods Eighteen type 2 diabetes and 16 age-matched healthy males were given 2 consecutive standardized mixed meals, after which blood samples were collected. Plasma metabolic parameters as well as CTSD levels and activity were measured, and changes in plasma pH was assessed. Results In line with the elevation of plasma free fatty acids (FFA) levels in male type 2 diabetics patients, plasma pH in type 2 diabetic individuals was decreased compared to male healthy individuals. While plasma CTSD levels were similar, plasma CTSD activity was increased in male type 2 diabetic compared to male healthy individuals. Besides, plasma CTSD activity rather than levels significantly correlated with indicators of type 2 diabetes (HbA1c, HOMA-IR and glucose). Furthermore, FFA was also independently associated with plasma CTSD activity (standardized beta = 0.493, p = 0.007). Conclusions Despite similar plasma CTSD levels, type 2 diabetic male individuals showed increased plasma CTSD activity compared to healthy males, which was independently linked to plasma FFA levels. Our data therefore point toward plasma CTSD as a metabolic regulator in male type 2 diabetes. Show less
Introduction With increased duration of type 2 diabetes, most people have a growing need of glucose-lowering medication and eventually might require insulin. Presumptive evidence is reported that... Show moreIntroduction With increased duration of type 2 diabetes, most people have a growing need of glucose-lowering medication and eventually might require insulin. Presumptive evidence is reported that early detection (eg, by population-based screening) and treatment of hyperglycemia will postpone the indication for insulin treatment. A treatment legacy effect of population-based screening for type 2 diabetes of about 3 years is estimated. Therefore, we aim to compare insulin prescription and glycemic control in people with screen-detected type 2 diabetes after 10 years with data from people diagnosed with type 2 diabetes seven (treatment legacy effect) and 10 years before during care-as-usual.Research design and methods Three cohorts were compared: one screen-detected cohort with 10 years diabetes duration (Anglo-Danish-Dutch study of Intensive Treatment in People with Screen-Detected Diabetes in Primary care (ADDITION-NL): n=391) and two care-as-usual cohorts, one with 7-year diabetes duration (Groningen Initiative to Analyze Type 2 Diabetes Treatment (GIANTT) and Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC): n=4473) and one with 10-year diabetes duration (GIANTT and ZODIAC: n=2660). Insulin prescription (primary outcome) and hemoglobin A1c (HbA1c) of people with a known diabetes duration of 7 years or 10 years at the index year 2014 were compared using regression analyses.Results Insulin was prescribed in 10.5% (10-year screen detection), 14.7% (7-year care-as-usual) and 19.0% (10-year care-as-usual). People in the 7-year and 10-year care-as-usual groups had a 1.5 (95% CI 1.0 to 2.1) and 1.8 (95% CI 1.3 to 2.7) higher adjusted odds for getting insulin prescribed than those after screen detection. Lower HbA1c values were found 10 years after screen detection (mean 50.1 mmol/mol (6.7%) vs 51.8 mmol/mol (6.9%) and 52.8 mmol/mol (7.0%)), compared with 7 years and 10 years after care-as-usual (MDadjusted: 1.6 mmol/mol (95% CI 0.6 to 2.6); 0.1% (95% CI 0.1 to 0.2) and 1.8 mmol/mol (95% CI 0.7 to 2.9); and 0.2% (95% CI 0.1 to 0.3)).Conclusion Population-based screen-detected type 2 diabetes is associated with less need for insulin after 10 years compared with people diagnosed during care-as-usual. Glycemic control was better after screen detection but on average good in all groups. Show less
