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Aims: Impaired awareness of hypoglycaemia (IAH) has been associated with increased diabetes distress and use of sensor technology can reduce diabetes distress. The aim of this study was to examine diabetes-specific distress (emotions, cognitions, behaviours) in relation to IAH status and use of glucose sensors in people with type 1 diabetes., Methods: Individuals with type 1 diabetes from an academic diabetes outpatient clinic completed the Clarke questionnaire (to assess hypoglycaemic awareness), Problem Areas in Diabetes (PAID-5), Hypoglycaemia Fear Survey-II (HFS-II), Attitudes to Awareness of Hypoglycaemia Survey (A2A), Nijmegen Clinical Screening Instrument Survey (NCSI) and Hyperglycaemia Avoidance Scale (HAS)., Results: Of the 422 participants (51.9% male, diabetes duration 30 [16-40] years, HbA 1c 60 ± 11 mmol/mol [7.6 ± 1.0%], 351 [88.2%] used a glucose sensor; 82 [19.4%]) had IAH. Compared to individuals with normal awareness, those with IAH more often had PAID-5 scores ≥8 (35.4% vs. 21.5%, p = 0.008) and higher scores on all HFS-II subscores (total [40.2 ± 21.5 vs. 27.9 ± 17.2, p < 0.001]), HFS-II behaviour (18.5 ± 10.0 vs. 15.1 ± 8.0, p = 0.005), HFS-II worry (21.8 ± 13.5 vs. 12.7 ± 10.9, p < 0.001), HAS worries (17.5 ± 7.3 vs. 14.3 ± 7.0, p < 0.001) and NCSI hypoglycaemia items. HAS behaviour, A2A and NCSI hyperglycaemia scores did not differ between individuals with or without IAH. Restricting the analyses to individuals using a glucose sensor did not materially change the results., Conclusions: Diabetes-specific distress remains a major problem among individuals with type 1 diabetes, particularly those with IAH, despite the widespread use of (intermittently scanned) sensor technology. Further studies are needed to examine strategies to lower diabetes-specific distress in individuals with IAH., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aims: Impaired awareness of hypoglycaemia (IAH) has been reported to affect up to a third of people with type 1 diabetes. Whether the increased use of sensor technology has changed its prevalence remains unknown. The aim of this study was to investigate the current prevalence of IAH and its change over time in a cohort of individuals with type 1 diabetes., Methods: IAH was assessed using the modified Clarke questionnaire in adults with type 1 diabetes. Participants were recruited from the diabetes outpatient clinic from February 2020 through April 2021. The scores were compared to similar data collected during previous assessments in 2006, 2010 and 2016 respectively., Results: A total of 488 individuals (51.2% male) with a mean (±SD) age of 51.3 ± 15.9 years, median [Q1-Q3] diabetes duration of 30 [16-40] years and mean HbA 1c of 60 ± 12 mmol/mol (7.7 ± 1.1%) were included. Sensors were used by 85% of the study population. IAH was present among 78 (16.0%) participants, whereas 86 (17.6%) participants had a history of severe hypoglycaemia. By comparison, the prevalence of IAH equalled 32.5% in 2006, 32.3% in 2010 and 30.1% in 2016 (p for trend <0.001), while the proportion of individuals reporting severe hypoglycaemia equalled 21.2%, 46.7% and 49.8% respectively (p for trend 0.010). Comparing sequential assessments over time, the proportion of individuals with persistent IAH decreased from 74.0% and 63.6% between 2006 and 2016 to 32.5% in 2020., Conclusions: Among individuals with type 1 diabetes and high use of sensor technology, the current prevalence of IAH was 16%, about 50% lower as compared to previous years., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aim: To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes., Methods: We included people with type 2 diabetes from the Diabetes Pearl cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5-9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0-4 medications)., Results: Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3-7) in primary care and 7 (IQR 5-10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose-lowering and lipid-modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non-cardiovascular and non-glucose-lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease., Conclusions: Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Background: Hypoglycaemia is the most frequent complication of treatment with insulin or insulin secretagogues in people with diabetes. Severe hypoglycaemia, i.e. an event requiring external help because of cognitive dysfunction, is associated with a higher risk of adverse cardiovascular outcomes and all-cause mortality, but underlying mechanism(s) are poorly understood. There is also a gap in the understanding of the clinical, psychological and health economic impact of 'non-severe' hypoglycaemia and the glucose level below which hypoglycaemia causes harm., Aim: To increase understanding of hypoglycaemia by addressing the above issues over a 4-year period., Methods: Hypo-RESOLVE is structured across eight work packages, each with a distinct focus. We will construct a large, sustainable database including hypoglycaemia data from >100 clinical trials to examine predictors of hypoglycaemia and establish glucose threshold(s) below which hypoglycaemia constitutes a risk for adverse biomedical and psychological outcomes, and increases healthcare costs. We will also investigate the mechanism(s) underlying the antecedents and consequences of hypoglycaemia, the significance of glucose sensor-detected hypoglycaemia, the impact of hypoglycaemia in families, and the costs of hypoglycaemia for healthcare systems., Results: The outcomes of Hypo-RESOLVE will inform evidence-based definitions regarding the classification of hypoglycaemia in diabetes for use in daily clinical practice, future clinical trials and as a benchmark for comparing glucose-lowering interventions and strategies across trials. Stakeholders will be engaged to achieve broadly adopted agreement., Conclusion: Hypo-RESOLVE will advance our understanding and refine the classification of hypoglycaemia, with the ultimate aim being to alleviate the burden and consequences of hypoglycaemia in people with diabetes., (© 2020 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

The aim of this review was to provide an overview of developments, clinical implications and gaps in knowledge regarding the relationship between diabetes and sleep over the past 25 years, with special focus on contributions from the behavioural sciences. Multiple prospective observational and experimental studies have shown a link between suboptimal sleep and impaired glucose tolerance, decreased insulin sensitivity and the development of type 2 diabetes. While prevalence rates of suboptimal sleep vary widely according to definition, assessment and sample, suboptimal subjective sleep quality appears to be a common reality for one-third of people with type 1 diabetes and over half of people with type 2 diabetes. Both physiological and psychosocial factors may impair sleep in these groups. In turn, suboptimal sleep can negatively affect glycaemic outcomes directly or indirectly via suboptimal daytime functioning (energy, mood, cognition) and self-care behaviours. Technological devices supporting diabetes self-care may have both negative and positive effects. Diabetes and its treatment also affect the sleep of significant others. Research on the merits of interventions aimed at improving sleep for people with diabetes is in its infancy. Diabetes and sleep appear to be reciprocally related. Discussion of sleep deserves a central place in regular diabetes care. Multi-day, multi-method studies may shed more light on the complex relationship between sleep and diabetes at an individual level. Intervention studies are warranted to examine the potential of sleep interventions in improving outcomes for people with diabetes., (© 2019 Diabetes UK.)

Aims: Individual indicators of socio-economic status have been associated with glycaemic control in people with Type 2 diabetes, but little is known about the association between partner's socio-economic status and HbA 1c levels. We therefore examined the cross-sectional association between individual and partner's level of occupation on HbA 1c levels in people with Type 2 diabetes in the Netherlands., Methods: We included people with Type 2 diabetes with a partner who were treated in primary, secondary and tertiary care in the Diabetes Pearl cohort. Occupational level was classified according to International Standard Classification of Occupations (ISCO)-08 skill levels. Linear regression analyses were performed stratified for sex, and corrected for age, recruitment centre and diabetes medication., Results: In total, 3257 participants (59.8% men, mean 62.2±9.4 years) were included. For men, having a partner with an intermediate level of occupation was associated with lower HbA 1c levels [e.g. ISCO level 3: -2 mmol/mol (95% CI -4;-1) or -0.2% (95% CI -0.4;-0.1)], compared with having a partner of the highest occupational level (ISCO level 4). In women, having an unemployed partner was associated with higher HbA 1c levels [14 mmol/mol (95% CI 6; 22) or 1.3% (95% CI 0.6; 2.0)], compared with having a partner of the highest occupational level., Conclusions: Partner's occupational status provided additional information on the association between socio-economic status and HbA 1c levels in people with Type 2 diabetes. Women seemed to benefit from a partner with a higher occupational status, while men seemed to benefit from a partner with a lower status. Because of the cross-sectional nature of the present study, more research is necessary to explore this association., (© 2017 Diabetes UK.)

Aims: To assess the impact of a multifaceted strategy to improve perioperative diabetes care throughout the hospital care pathway., Methods: We conducted a controlled before-and-after study in six hospitals. The purpose of the strategy was to target four predominant barriers that obstruct optimal care delivery. We provided feedback on baseline indicator performance, developed a multidisciplinary protocol and patient information, and provided professional education. After a 6-month intervention, we determined the performance changes against three outcome indicators and nine process indicators using data on 811 patients with diabetes who underwent major surgery. The progress of the interventions was monitored closely., Results: Two process indicators improved significantly in the intervention hospitals: the proportion of patients for whom glycaemic control had been evaluated preoperatively increased by 9% (P < 0.002) and the proportion of patients with blood glucose measurements within 1 h after surgery increased by 29% (P < 0.0001). Four other process indicators and all three outcome indicators improved more in the intervention hospitals than in the control hospitals, but the differences were not statistically significant. These included the proportion of patients with all glucose values at 6-10 mmol/l (+3%) and the proportion of patients with hyperglycaemia (-8%). The implementation of the multidisciplinary protocol was still ongoing after the 6-month intervention period., Conclusions: The multifaceted improvement strategy had a limited impact on the quality of perioperative diabetes care. This study demonstrates the complexity of improving perioperative diabetes care throughout the multiprofessional hospital care pathway., (© 2016 Diabetes UK.)

Aims: Person centredness is an important principle for delivering high-quality diabetes care. In this study, we assess the level of person centredness of current perioperative diabetes care., Methods: We conducted a survey in six Dutch hospitals, among 690 participants with diabetes who underwent major abdominal, cardiac or large-joint orthopaedic surgery. The survey included questions regarding seven dimensions of person-centred perioperative diabetes care., Results: Complete data were obtained from 298 participants. The survey scores were low for many of the dimensions of person centredness. The dimensions 'information', 'patient involvement' and 'coordination and integration of care' had the lowest scores. Only half the participants had received information about perioperative diabetes treatment, and approximately one-third had received information about the effect of surgery on blood glucose values, target glucose values and glucose measurement times. Similarly, half the participants had an opportunity to ask questions preoperatively, and only one-third of the participants felt involved in the decision-making regarding diabetes treatment. Most participants knew neither the caregiver in charge of perioperative diabetes treatment nor whom to contact in case of diabetes-related problems during their hospital stay., Conclusions: Current perioperative diabetes care is characterized by a lack of patient information and limited patient involvement. These results indicate that there is ample room for improving the person centredness of perioperative diabetes care., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Aims: To compare levels of diabetes distress in people with Type 2 diabetes treated in primary and secondary care and to examine demographic and clinical correlates that may explain potential differences in levels of distress between care settings., Methods: People with Type 2 diabetes from 24 primary care practices (n = 774) and three secondary care clinics (n = 526) completed the Problem Areas In Diabetes questionnaire. Data on HbA1c levels and diabetes complications were derived from medical charts. Hierarchical ordinal regression analysis was used to investigate which correlates could explain the potential differences in level of diabetes distress between care settings., Results: Diabetes distress levels and the prevalence of elevated diabetes distress were considerably lower in the participants treated in primary care (mean (SD) total diabetes distress score 8 (11); 4% of participants with a Problem Areas In Diabetes score ≥ 40) than in secondary care (mean (SD) total diabetes distress score 23 (21); 19% of participants with a Problem Areas In Diabetes score ≥ 40, P < 0.001). In addition to care setting, the following variables were also independently related to diabetes distress: younger age, ethnic minority status, using insulin, having a higher HbA1c level, having a higher BMI and the presence of neuropathy. Other diabetes complications were not independently associated with diabetes distress., Conclusions: In primary care, lower levels of diabetes distress were reported than in secondary care. The difference in diabetes distress between care settings can be largely, but not fully, explained by specific demographic and clinical characteristics. These results need to be interpreted with caution as they are based on two separate studies, but do call into question the need to screen for diabetes distress in people with Type 2 diabetes in primary care., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Aims: Depression is common in people with diabetes, and related to higher HbA(1c) levels. Depression, however, is a heterogeneous construct that involves a variety of symptoms. As little is known about the associations of individual depressive symptoms with HbA(1c), we explored these associations in outpatients with diabetes., Methods: The study was conducted in three tertiary diabetes clinics in the Netherlands. At baseline, the presence of the nine depressive symptoms that are listed in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition was assessed with the nine-item Patient Health Questionnaire (PHQ-9). At baseline and after a 1-year follow-up, HbA(1c) was derived from the medical charts., Results: A total of 288 out of 646 subjects with diabetes (45%) reported one or more depressive symptom(s). Depressed mood (β = 0.11, P = 0.005), sleeping difficulties (β = 0.16, P < 0.001), appetite problems (β = 0.15, P < 0.001) and suicidal ideation (β = 0.14, P = 0.001) were significantly related to higher baseline HbA(1c) values. Furthermore, depressed mood (β = 0.09, P = 0.03) sleeping difficulties (β = 0.12, P = 0.004), appetite problems (β = 0.11, P = 0.01) and psychomotor agitation/retardation (β = 0.09, P = 0.04) were significantly related to higher HbA(1c) values at 1-year follow-up. Associations were more pronounced in Type 1 diabetes than in Type 2 diabetes. None of the depressive symptoms were related to change in HbA(1c) over time, except suicidal ideation., Conclusion: In people with diabetes, several individual depressive symptoms were related to higher HbA(1c) levels. These associations persisted over time. More research is needed to investigate potential mechanistic pathways., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Objective: The 5-item World Health Organization well-being index is a commonly used measure of emotional well-being, but research on psychometric properties in outpatients with diabetes is scarce. We examined psychometric and screening properties for depression of this index in a large sample of Dutch outpatients with diabetes., Methods: Patients with Type 1 (n = 384) and Type 2 (n = 549) diabetes from three outpatient clinics completed the WHO-5 index, the nine-item Patient Health Questionnaire, the Problem Areas in Diabetes survey and the Short Form-12 health survey. Internal consistency of the WHO-5 index was determined by Cronbach's alpha. The factor structure was tested by confirmatory factor analysis. Concurrent validity was assessed by correlations with the Patient Health Questionnaire, Problem Areas in Diabetes and the Short Form-12 mental component scores. Sensitivity and specificity of the WHO-5 index as depression screener were tested against two existing Patient Health Questionnaire cut-off scores for depression using receiver operating characteristic curves., Results: A one-factor structure of the WHO-5 index was verified by confirmatory factor analysis for patients with Type 1 and Type 2 diabetes. Moderate to strong correlations were observed between the WHO-5 index and the Patient Health Questionnaire scores, the Problem Areas in Diabetes scores and the Short Form-12 mental component scores (r = 0.55-0.69, P < 0.001). Receiver operating characteristic curves showed that a WHO-5 index cut-off of < 50 performed best as an indication for likely depression, with sensitivity compared with a Patient Health Questionnaire score ≥ 10 and ≥ 12 of 79% and 88%, respectively, and specificity of 88% and 76%, respectively., Conclusions: The WHO-5 index is a short, psychometrically sound measure of emotional well-being that appears suitable for use as screening test for likely depression in outpatients with Type 1 and Type 2 diabetes., (© 2012 The Author. Diabetic Medicine © 2012 Diabetes UK.)

Objectives: To investigate whether diabetes-specific emotional distress mediates the relationship between depression and glycaemic control in patients with Type 1 and Type 2 diabetes., Research Design and Methods: Data were derived from the baseline assessment of a depression in diabetes screening study carried out in three tertiary diabetes clinics in the Netherlands. Most recent glycated haemoglobin (HbA(1c)) measurement was obtained from medical records. The Centre for Epidemiologic Studies Depression Scale (CES-D) and Problem Areas in Diabetes scale (PAID) were used to measure depression and diabetes-specific emotional distress respectively. Linear regression was performed to examine the mediating effect of diabetes-distress., Results: Complete data were available for 627 outpatients with Type 1 (n = 280) and Type 2 (n = 347) diabetes. Analyses showed that diabetes-distress mediated the relation between depression and glycaemic control and not differently for both disease types. Post-hoc analyses revealed that patients depressed and distressed by their diabetes were in significantly poorer glycaemic control relative to those not depressed nor distressed (HbA(1c) 8.7 +/- 1.7 vs. 7.6 +/- 1.2% in those without depressive symptoms, 7.6 +/- 1.1% in depressed only and 7.7 +/- 1.1% in the distressed only, P < 0.001). Depressed patients without elevated diabetes-distress did not show a significantly increased risk of elevated HbA(1c)., Conclusions: In explaining the association between depression and glycaemic control, diabetes-specific emotional distress appears to be an important mediator. Addressing diabetes-specific emotional problems as part of depression treatment in diabetes patients may help improve glycaemic outcomes.

Aims: Depression is common in diabetes, but the scope of the problem and associated correlates are not well established in specialist diabetes care. We aimed to determine the prevalence of depression among adult outpatients with Type 1 (T1DM) or Type 2 diabetes (T2DM) using both self-report measures and a diagnostic interview, and to establish demographic and clinical characteristics associated with depressive affect., Methods: A random sample of 2055 diabetes out-patients from three diabetes clinics was invited to participate. Depressive affect was assessed using the World Health Organization-5 Well Being Index (WHO-5), the Centre for Epidemiologic Studies-Depression scale (CESD) using predefined cut-off scores, and depressive disorder with the Composite International Diagnostic Interview (CIDI). Associations between depression and patient characteristics were explored using regression analyses., Results: Seven hundred and seventy-two patients completed the depression questionnaires. About one-third of T1DM patients and 37-43% of T2DM patients reported depressive affect (WHO-5). The prevalence of depressive affect (CESD) was 25% and 30% for men and women with T1DM, and 35% and 38% for men and women with T2DM, respectively. Based on the CIDI, 8% of T1DM patients (no gender difference) and 2% of men and 21% of women with T2DM suffered from a depressive disorder. Depressive affect was associated with poor glycaemic control and proliferative retinopathy in T1DM, while non-Dutch descent, obesity and neuropathy were correlates in T2DM., Conclusions: Depressive symptoms and major depressive disorder constitute a common comorbid problem among Dutch out-patients with T1DM or T2DM and appear particularly common in migrants and women with T2DM.

Aims: According to the 'haemodynamic hypothesis', chronic hyperglycaemia induces an increase in tissue perfusion that predisposes to microangiopathy. We hypothesized that patients with longstanding diabetes mellitus (DM), who have not developed microvascular complications, would have normal tissue perfusion., Methods: In six Type 1 diabetic patients (age 43.4 +/- 1.1 years; DM duration 25.3 +/- 2.6 years.; HbA(1c) 8.5 +/- 0.7%), who had no evidence of microvascular complications, and six age- and gender-matched healthy volunteers (Control) we measured haemodynamic parameters including forearm blood flow (FBF; plethysmography) and sympathetic tone, an important regulator of blood flow, by the combination of plasma sampling (catecholamine levels), microneurography and power spectral analysis of blood pressure and heart rate., Results: FBF was increased in the diabetic compared with control subjects (4.8 +/- 1.2 vs. 2.2 +/- 0.3 ml/dl per min, P < 0.05) and forearm vascular resistance (FVR) was decreased (25 +/- 6 and 43 +/- 3 arbitrary units, P < 0.05). Heart rate was higher in diabetic subjects (77 +/- 10 vs. 57 +/- 2 beats/min, P < 0.05). All parameters of sympathetic tone were similar in diabetic and control subjects., Conclusions: In patients with Type 1 diabetes, without signs of microvascular complications and with diabetes duration of > 20 years, skeletal muscle blood flow was increased while sympathetic tone was normal. These results suggest that increased blood flow does not inevitably lead to microvascular complications and challenge the hypothesis that it has a causative role in the pathophysiology of complications.

Aims: Despite high-dose s.c. insulin therapy, some Type 2 diabetes mellitus (DM) patients remain in poor metabolic control. We investigated whether a period of euglycaemia using i.v. insulin, followed by continuous subcutaneous insulin infusion (CSII), would ameliorate the deleterious effects of hyperglycaemia on insulin sensitivity and result in sustained, improved metabolic control., Methods: In a prospective observational study, eight Type 2 DM patients with severe insulin resistance (insulin dose 1.92 +/- 0.66 U/kg per day (mean +/-sd)), in poor metabolic control (HbA(1c) 12.0 +/- 1.7%), were treated with i.v. insulin for 31 +/- 10 days aimed at euglycaemia, followed by CSII therapy for 12 months, using insulin lispro. Before and after 28 +/- 6 days of i.v. insulin treatment, insulin sensitivity was measured by a hyperinsulinaemic euglycaemic clamp., Results: Euglycaemia was reached after 12 +/- 6 days of i.v. insulin treatment. Subsequently, the i.v. insulin dose required to maintain euglycaemia decreased from 1.7 +/- 0.9 to 1.1 +/- 0.6 U/kg per day (P < 0.005). Whole body glucose uptake increased from 12.7 +/- 5.7 to 22.4 +/- 8.8 micromol/kg per min (P < 0.0005). HbA(1c) decreased to 8.9 +/- 1.2% after 28 +/- 6 days, to 7.1 +/- 0.6% after 6 months and to 8.3 +/- 1.4% after 12 months (P < 0.001 vs. pretreatment, for all). Lipid profile improved and plasminogen activator inhibitor type 1 levels decreased significantly. Mean body weight did not change., Conclusions: In Type 2 diabetic patients, who are poorly controlled despite high-dose s.c. insulin treatment, a period of 2 weeks of euglycaemia achieved by i.v. insulin reverses hyperglycaemia-induced insulin resistance and substantially improves metabolic control. Subsequent CSII treatment, using insulin analogues, appears to maintain improved metabolic control for at least 1 year. This approach is promising but needs further evaluation.

Aims: Glibenclamide attenuates the protective responses to opening of vascular ATP-sensitive potassium (K(ATP)) channels during ischaemia. Therefore, glibenclamide treatment of Type 2 diabetes mellitus may have hazardous cardiovascular effects when used under conditions of ischaemia. Glimepiride and metformin seem to lack such characteristics. Based on these data, we hypothesized that, in contrast to glibenclamide, chronic treatment of Type 2 diabetic patients with glimepiride or metformin will not impair the vasodilator function of K(ATP) opening in vivo., Methods: Two groups of 12 Type 2 diabetes mellitus patients participated in a double-blind randomized cross-over study consisting of two 8-week periods, in which treatment with orally administered glibenclamide (15 mg/day) was compared with either glimepiride or metformin (6 mg and 1500 mg/day, respectively). At the end of each treatment period, the increase in forearm blood flow (FBF, venous occlusion plethysmography) in response to intra-arterial administered diazoxide (K(ATP) opener), acetylcholine (endothelium-dependent vasodilator) and dipyridamole (adenosine-uptake blocker) and to forearm ischaemia was measured., Results: There were no significant differences in vasodilator responses to diazoxide, acetylcholine, dipyridamole and forearm ischaemia after glibenclamide compared with glimepiride and metformin., Conclusions: Chronic treatment of Type 2 diabetes mellitus with glimepiride or metformin has similar effects on vascular K(ATP) channels compared with chronic glibenclamide treatment.