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Aims: To identify HbA1c trajectories after the start of insulin treatment and to identify clinically applicable predictors of the response to insulin therapy., Methods: The study population comprised 1203 people with Type 2 diabetes included in the Hoorn Diabetes Care System (n = 9849). Inclusion criteria were: age ≥ 40 years; initiation of insulin during follow-up after failure to reach HbA1c levels ≤ 53 mmol/mol (7%) with oral glucose-lowering agents; and a follow up ≥ 2 years after initiating insulin. Latent class growth modelling was used to identify trajectories of HbA1c . Subjects considered to be 'off target' had HbA1c levels ≥ 53 mmol/mol (7.0%) during one-third or more of the follow-up time, and those considered to be 'on target' had HbA1c levels ≥ 53 mmol/mol (7.0%) during less than one-third of the follow-up time., Results: Four HbA1c trajectories were identified. Most people (88.7%) were classified as having a stable HbA1c trajectory of ~57 mmol/mol (7.4%). Only 24.4% of the people were on target in response to insulin; this was associated with lower HbA1c levels and a higher age at the start of insulin treatment., Conclusions: Using latent class growth modelling, four HbA1c trajectories were identified. A quarter of the people starting insulin were on target. Low HbA1c levels and advanced age at the start of insulin therapy were associated with better response to insulin therapy. Initiating insulin earlier improves the likelihood of achieving and sustaining glycaemic control., (© 2016 Diabetes UK.)

Aims: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to type 2 diabetes in humans., Methods: Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for type 2 diabetes susceptibility in up to 25 000 people (8148 with type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis., Results: rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*10⁴) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*10⁴) but again not in men (P = 0.34)., Conclusion: The present data identify DRD2/ANKK1 as a potential sex-specific type 2 diabetes susceptibility gene., (© 2014 The Authors. Diabetic Medicine © 2014 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: Self-monitoring of blood glucose (SMBG) is an important self-management tool for insulin-treated patients with Type 2 diabetes mellitus (T2DM). Its value in estimating glycaemic control in insulin-treated T2DM patients remains unclear. The relationship between glycated haemoglobin (HbA(1c)) and SMBG measures in T2DM patients treated with premixed insulin lispro mixtures or basal insulin glargine was examined., Methods: HbA(1c) and plasma equivalent glucose (PGe) data derived from SMBG profiles were pooled from five randomized clinical trials of patients with T2DM on one or more oral glucose-lowering medication +/- 0-2 insulin injections per day switching to insulin lispro mixtures (N = 317) or glargine (N = 306). Patients generated seven-point SMBG profiles three times in a 2-week period prior to each HbA(1c) measurement. Pearson's correlation coefficients (r) were calculated for PGe values and HbA(1c). Receiver-operating characteristic (ROC) curves determined the ability of sets of PGe to estimate HbA(1c) (< or > 7.0%)., Results: Mean +/- standard deviation age was 57.5 +/- 9.5 years, body mass index 31.3 +/- 5.6 kg/m(2), 52.5% were male and HbA(1c) overall was 7.4 +/- 1.0% at end-point. Among individual SMBG measures, r for HbA(1c) ranged from 0.34 to 0.49. For means of two or more PGe measures, r for HbA(1c) ranged from 0.51 to 0.59. Correlations were similar for either regimen. ROC curves were consistent with the correlation data., Conclusions: These data provide patients and clinicians information on the relationship between HbA(1c) and SMBG measurements in patients with T2DM, and support the value of frequent blood glucose measurements for assessing overall glycaemic control.

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.

Objective: To test the effectiveness at 6 and 12 months' follow-up of group cognitive behavioural therapy (CBT) compared with blood glucose awareness training (BGAT) in poorly controlled Type 1 diabetic patients and to explore the moderating effect of baseline depression., Research Design and Methods: Adults with Type 1 diabetes (n = 86) with glycated haemoglobin (HbA(1c)) >or= 8% were randomized to CBT or BGAT. Primary outcome was HbA(1c) control. Secondary outcomes were: self-care, diabetes-related distress (Problem Areas in Diabetes scale; PAID), diabetes self-efficacy (Confidence in Diabetes Self-care scale; CIDS) and depressive symptoms (Centre for Epidemiological Studies--Depression scale; CES-D). Measurements were scheduled before CBT and BGAT, and at 3, 6 and 12 months after. Differential effects were analysed for the subgroup of patients reporting low vs. high baseline levels of depression., Results: Neither CBT nor BGAT had a significant impact on HbA(1c) at 6 and 12 months' follow-up. Both interventions resulted in lower depressive symptoms (CES-D 15.7-13.3, P = 0.01) up to 12 months, but only CBT was effective in lowering HbA(1c) in patients with high baseline depression scores (HbA(1c) 9.5-8.8%) up to 1 year of follow-up (P = 0.03)., Conclusions: Our findings suggest that group CBT can effectively help Type 1 diabetic patients with co-morbid depression achieve and maintain better glycaemic outcomes.

Aims: Low-density lipoprotein cholesterol (LDL-C) levels are often fairly normal in Type 2 diabetes mellitus (DM). We anticipated that a parabolic relation between plasma triglycerides and LDL-C, as previously demonstrated in familial combined hyperlipidaemia (FCHL), might account for this phenomenon., Methods: Our hypothesis was tested in 1343 subjects derived from the general population who were studied on two occasions 6 years apart (the Hoorn study). Three groups were constructed depending on plasma triglycerides: group A (individuals with both measurements below 1.5 mmol/l), group B (one measurement below and one above 1.5 mmol/l) and group C (both measurements above 1.5 mmol/l). Diabetes status was ascertained by an oral glucose tolerance test., Results: In a mixed linear model, a significant, positive relation between triglycerides and LDL-C was observed for males in group A (beta(a) = 0.5, P < 0.001) and group B (beta(b) = 0.2, P < 0.001), whereas a significant negative relation was found for males in group C (beta(c) = -0.2, P = 0.003). The regression slopes did not differ between diabetic and non-diabetic subjects. Similar results were obtained for women, with the exception that the relation was not significantly negative in group C (beta(c) = -0.1, P = 0.4)., Conclusion: Plasma triglycerides and LDL-C are related in a parabolic fashion, not only in FCHL, but also in the general population and Type 2 DM. These findings aid our interpretation of typical dyslipidaemia and the effects of treatment that are frequently observed in hypertriglyceridaemic states.

Objective: To study the prevalence and risk factors of depressive symptoms, comparing subjects with normal glucose metabolism (NGM), impaired glucose metabolism (IGM) or Type 2 diabetes mellitus (DM2)., Research Design and Methods: Cross-sectional data from a population-based cohort study conducted among 550 residents (276 men and 274 women) of the Hoorn region, the Netherlands. Levels of depressive symptoms were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D score > or = 16). Glucose metabolism status was determined by means of fasting and post-load glucose levels., Results: The prevalence of depressive symptoms in men with NGM, IGM and DM2 was 7.7, 7.0 and 15.0% (P = 0.19) and for women 7.7, 23.1 and 19.7% (P < 0.01), respectively. Depression was significantly more common in women with IGM [odds ratio (OR) = 3.60, 95% confidence interval (CI) = 1.57 to 8.28] and women with DM2 (OR = 3.18, 95% CI = 1.31 to 7.74). In men, depression was not associated with IGM (OR = 0.90, 95% CI = 0.32 to 2.57) and non-significantly more common in DM2 (OR = 2.04, 95% CI = 0.75 to 5.49). Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms reduced the strength of these associations., Conclusions: Depressive symptoms are more common in women with IGM, but not men. Adjustment for cardiovascular risk factors, cardiovascular disease and diabetes symptoms partially attenuated these associations, suggesting that these variables could be intermediate factors.

Latent autoimmune diabetes in the adult (LADA) is a slowly progressive form of autoimmune diabetes, characterized by diabetes-associated autoantibody positivity. A recent hypothesis proposes that LADA consists of a heterogeneous population, wherein several subgroups can be identified based on their autoimmune status. A systematic review of the literature was carried out to appraise whether the clinical characteristics of LADA patients correlate with the titre and numbers of diabetes-associated autoantibodies. We found that the simultaneous presence of multiple autoantibodies and/or a high-titre anti-glutamic acid decarboxylase (GAD)--compared with single and low-titre autoantibody--is associated with an early age of onset, low fasting C-peptide values as a marker of reduced pancreatic B-cell function, a high predictive value for future insulin requirement, the presence of other autoimmune disorders, a low prevalence of markers of the metabolic syndrome including high body mass index, hypertension and dyslipidaemia, and a high prevalence of the genotype known to increase the risk of Type 1 diabetes. We propose a more continuous classification of diabetes mellitus, based on the finding that the clinical characteristics gradually change from classic Type 1 diabetes to LADA and finally to Type 2 diabetes. Future studies should focus on determining optimal cut-off points of anti-GAD for differentiating clinically relevant diabetes mellitus subgroups.

Aims: Mild cognitive deficits have been determined in both types of diabetes using neurocognitive tests. Little is known about the degree to which patients complain about their cognitive functioning. This study set out to investigate the magnitude and correlates of self-reported cognitive failure in adult out-patients with Type 1 and Type 2 diabetes., Methods: Subjective cognitive functioning was measured in 187 diabetic patients using the Cognitive Failures Questionnaire (CFQ). Demographic and clinical characteristics were retrieved from the medical records. The Patient Health Questionnaire 9 items (PHQ-9) was self-administered along with the CFQ to correct for the confounding effect of depression., Results: Analyses were based on 55 patients with Type 1 diabetes and 100 patients with Type 2 diabetes. No difference in mean CFQ score was observed between Type 1 and Type 2 diabetic patients or between Type 1 diabetic patients and healthy control subjects. Female patients with Type 2 diabetes reported significantly fewer cognitive complaints compared with female healthy control subjects. None of the demographic variables and diabetes-related complications was associated with subjective cognitive complaints. A strong positive association was found between depression symptomatology and frequency of self-reported cognitive failure., Conclusions: Our study could not confirm elevated subjective cognitive complaints in a group of Type 1 and Type 2 diabetes patients, as might be expected given the observed elevated rates of mild cognitive dysfunction in patients with diabetes. Self-reported cognitive failure appears largely determined by depressive symptomatology. Therefore, affective status should be included in any cognitive assessment procedure.

Aims: We quantified the occurrence and duration of nocturnal hypoglycaemia in individuals with Type 1 diabetes treated with continuous subcutaneous insulin infusion (CSII) or multiple-injection therapy (MIT) using a continuous subcutaneous glucose sensor., Methods: A microdialysis sensor was worn at home by 24 patients on CSII (mean HbA(1c) 7.8 +/- 0.9%) and 33 patients on MIT (HbA(1c) 8.7 +/- 1.3%) for 48 h. Occurrence and duration of nocturnal hypoglycaemia were assessed and using multivariate regression analysis, the association between HbA(1c), diabetes duration, treatment type (CSII vs. MIT), fasting and bedtime blood glucose values, total daily insulin dose and mean nocturnal glucose concentrations, and hypoglycaemia occurrence and duration was investigated., Results: Nocturnal hypoglycaemia < or = 3.9 mmol/l occurred in 33.3% of both the CSII- (8/24) and MIT-treated patients (11/33). Mean (+/- sd; median, interquartile range) duration of hypoglycaemia < or = 3.9 mmol/l was 78 (+/- 76; 57, 23-120) min per night for the CSII- and 98 (+/- 80; 81, 32-158) min per night for the MIT-treated group. Multivariate regression analysis showed that bedtime glucose value had the strongest association with the occurrence (P = 0.026) and duration (P = 0.032) of nocturnal hypoglycaemia., Conclusions: Microdialysis continuous glucose monitoring has enabled more precise quantification of nocturnal hypoglycaemia occurrence and duration in Type 1 diabetic patients. Occurrence and duration of nocturnal hypoglycaemia were mainly associated with bedtime glucose value.

Aims: To study the association between alanine aminotransferase (ALT) and the 6-year risk of the metabolic syndrome in a population-based study in Caucasian men and women., Methods: The association of ALT with the 6-year risk of the metabolic syndrome in 1097 subjects, aged 50-75 years, was assessed in the Hoorn Study with logistic regression analysis. Subjects with the metabolic syndrome at baseline, defined according to the Adult Treatment Panel III of the National Cholesterol Education Program, were excluded., Results: After 6.4 (range 4.4-8.1) years follow-up, 226 subjects (20.6%) had developed the metabolic syndrome. The odds ratio (95% confidence interval) for developing the metabolic syndrome, adjusted for age, sex, alcohol intake and follow-up duration was 2.25 (1.50-3.37) for subjects in the upper tertile compared with those in the lower tertile of ALT. This association persisted after additional adjustment for all the baseline metabolic syndrome features [1.62 (1.02-2.58)]. Among the individual components of the metabolic syndrome, ALT was significantly associated only with fasting plasma glucose at follow-up., Conclusions: These data suggest that ALT is associated with risk of the metabolic syndrome in a general population of middle-aged Caucasian men and women, further strengthening the role of ALT as an indicator for future metabolic derangement. These findings warrant further studies to elucidate the role of non-adipose tissue fat accumulation in the pathogenesis of complications related to the metabolic syndrome.

Aims: Cholesteryl ester transfer protein (CETP) exchanges neutral lipids between lipoproteins. As the role of CETP in the atherogenic process is still not fully clarified, we studied the association of CETP concentration with the prevalence of cardiovascular disease (CVD) and with intima-media thickness of the carotid artery (IMT) in subjects with normal glucose tolerance (NGT), impaird fasting glucose and/or impaired glucose tolerance (IFG/IGT) and Type 2 diabetes mellitus., Methods: Subjects (n = 566) were recruited from the 2000-2001 follow-up examination of the Hoorn study. CETP concentration was determined by immunoassay. CVD was defined as self-reported history of arterial surgery, cerebral vascular event, amputation, angina, claudication, possible infarction, measured ankle-brachial index < 0.90 or ECG abnormalities. The right common carotid artery IMT was measured by ultrasound at 10 mm proximal to the carotid bulb., Results: In men, CETP concentration was not associated with CVD, irrespective of glucose tolerance status. In women with NGT or IGT, there was also no relationship. However, in women with Type 2 diabetes, the risk of CVD was increased in those with high CETP concentration [odds ratio = 3.34 (1.56; 7.14)]. No statistically significant association was found between CETP concentration and IMT in the entire cohort., Conclusions: In an elderly Caucasian population, associations of CETP concentration with CVD were dependent on glucose tolerance status and gender. The finding that high CETP concentration was strongly associated with increased prevalence of CVD in women with Type 2 diabetes warrants further investigation.

Aims: To assess the effects of cognitive behavioural group training (CBGT) on glycaemic control, diabetes self-efficacy and well-being in Type 1 diabetes patients in persistent poor glycaemic control., Methods: In a randomized controlled trial, a total of 107 patients with Type 1 diabetes in poor glycaemic control (HbA(1c) > or = 8%) were assigned to a 6-week CBGT or blood glucose awareness training (BGAT) as control condition. The intervention was preceded by a 3-month run-in period. Glycaemic control (HbA(1c)), diabetes-specific self-efficacy (CIDS), diabetes-related distress (PAID) and depressive symptoms (CES-D), were assessed at baseline (T1), directly before (T2) and 3 months after (T3) the intervention., Results: No significant changes in HbA(1c) were found after CBGT, whilst diabetes self-efficacy increased (mean CIDS score 71.6 +/- 14.0 to 74.3 +/- 12.2) and diabetes-related distress (mean PAID score 47.0 +/- 21.6 to 42.6 +/- 20.8) and depressive symptoms decreased (mean CES-D score 16.9 +/- 12.8 to 13.5 +/- 12.6). Changes in psychological outcomes were similar for both treatment groups. Diabetes self-care behaviours improved equally. Drop-out rate, which was higher among CBGT participants, was relatively low overall (total n = 15, 17.05%), and both interventions were well-appreciated by the participants., Conclusions: CBGT was successful in improving self-efficacy, diabetes-related distress and mood at 3 months' follow-up, but not in improving glycaemic control.

Aims: Evidence strongly suggests that depression is a common complication of Type 2 diabetes mellitus. However, there is considerable room to improve the effectiveness of pharmacological antidepressant agents, as in only 50-60% of the depressed subjects with diabetes does pharmacotherapy lead to remission of depression. The aim of the present paper was to review whether polyunsaturated fatty acids (PUFA) of the omega-3 family could be used for the prevention and treatment of depression in Type 2 diabetes., Methods: MEDLINE database and published reference lists were used to identify studies that examined the associations between omega-3 PUFA and depression. To examine potential side-effects, such as on glycaemic control, studies regarding the use of omega-3 supplements in Type 2 diabetes were also reviewed., Results: Epidemiological and clinical studies suggest that a high intake of omega-3 PUFA protects against the development of depression. There is also some evidence that a low intake of omega-3 is associated with an increased risk of Type 2 diabetes, but the results are less conclusive. Results from randomized controlled trials in non-diabetic subjects with major depression show that eicosapentaenoic acid is an effective adjunct treatment of depression in diabetes, while docosahexanoic acid is not. Moreover, consumption of omega-3 PUFA reduces the risk of cardiovascular disease and may therefore indirectly decrease depression in Type 2 diabetes, via the reduction of cardiovascular complications., Conclusions: Supplementation with omega-3 PUFA, in particular eicosapentaenoic acid, may be a safe and helpful tool to reduce the incidence of depression and to treat depression in Type 2 diabetes. Further studies are now justified to test these hypotheses in patients with Type 2 diabetes.

Around 25% of the adult Type 1 diabetes population is in persistent poor glycaemic control and thus at increased risk of developing microvascular complications. We here discuss correlates of long-standing poor glycaemic control and review the efficacy of clinical strategies designed to overcome persistent poor control. Only a few studies have identified determinants and correlates of long-standing poor glycaemic control in Type 1 diabetes. There is some evidence implicating genetic factors, as well as lower economic status, and psychological factors, including lack of motivation, emotional distress, depression and eating disorders. Ways of improving glycaemic control include strategies to enable self-management, e.g. motivational strategies, coping-orientated education, psychosocial therapies, and/or intensifying insulin injection therapy plus continuous subcutaneous insulin infusion. Long-standing poor glycaemic control appears to be a heterogeneous and complex phenomenon, for which there is no simple, single solution. Comprehensive psycho-medical assessment in diabetes care may prove useful in tailoring interventions. Further research is warranted, to increase our understanding how psychosocial and biomedical factors, separately and in interaction, determine poor outcomes in Type 1 diabetes.

Aims: To determine health-related quality of life (HRQoL) in the first year following diagnosis of Type 2 diabetes among newly diagnosed patients in general practice compared with patients detected by targeted population screening., Methods: The study population consisted of 49 newly diagnosed patients in general practice and 116 screening-detected patients. HRQoL was operationalized as symptom distress, perceived health status and emotional well-being, that were assessed prospectively approximately 2 weeks, 6 months and 12 months after the diagnosis of Type 2 diabetes, with the Type 2 Diabetes Symptom Checklist (DSC-type 2), the Short Form 36 (SF-36) and the Well-Being Questionnaire (W-BQ12), respectively., Results: The DSC-type 2 total score (range 0-4) improved significantly within newly diagnosed patients in general practice (median at approximately 2 weeks, 6 months and 12 months; 0.56, 0.21, 0.26; P = 0.000) and not within screening-detected patients (0.24, 0.24, 0.29; P = 0.093). Descriptives showed that newly diagnosed patients in general practice compared with screening-detected patients had consistently worse mean scores on all SF-36 mental health subscales Social Functioning, Role Emotional, Mental Health, Vitality, and all W-BQ12 scales at each time point. The differences were statistically significant for Role Emotional, Mental Health, Vitality (SF-36), and General well-being (W-BQ12). The SF-36 General Health (F = 3.7, P = 0.028) and Vitality (F = 4.5, P = 0.012) scores of newly diagnosed patients in general practice improved significantly over time, compared with screening-detected patients., Conclusions: Newly diagnosed patients in general practice compared with screening-detected patients reported more diabetes-related symptom distress shortly after the diagnosis, and a consistently worse mental health status at each time point. Improved Vitality scores in newly diagnosed patients in general practice in the first year following diagnosis of Type 2 diabetes suggest a positive effect of diabetes treatment on HRQoL.

Aims: To examine the impact of the diagnosis of Type 2 diabetes on psychological well-being and perceived health status in subjects who participated in a targeted population-screening programme., Methods: This study was conducted within the framework of a screening project in the general (aged 50-75 years) Dutch population. The final study population consisted of 259 subjects with a high-risk score on the Symptom Risk Questionnaire; 116 of whom were subsequently detected with Type 2 diabetes and 143 who were non-diabetic. The impact was assessed approximately 2 weeks (shortly) and 6 and 12 months after the diagnosis, using the 12-item Well-Being Questionnaire (W-BQ12) and the Medical Outcomes Study Short Form 36 (SF-36), respectively. Analyses of co-variance (ancova) were used., Results: Approximately 2 weeks after the diagnosis, no significant mean differences were found on either the W-BQ12 or the SF-36, between the screening-detected Type 2 diabetes subjects and the non-diabetic subjects. Six months after the diagnosis, we found lower scores in the screening-detected Type 2 diabetes subjects compared with the non-diabetic subjects on the SF-36 dimensions Role Physical (mean difference (95% CI); -8.2 (-16.2; -0.1); P = 0.046) and Role Emotional (mean difference (95% CI); -7.9 (-15.3; -0.5); P = 0.038). One year after the test results, no significant mean differences were found between both groups on either instrument (W-BQ12; SF-36)., Conclusions: The diagnosis of Type 2 diabetes has no substantial adverse or positive effect on psychological well-being and perceived health status, shortly, and 6 and 12 months after the diagnosis.

Aims: The potential importance of postprandial glucose (PPG) control in the development of complications in Type 2 diabetes is much debated. The recent American Diabetes Association (ADA) consensus statement discussed the role of postprandial hyperglycaemia in the pathogenesis of diabetic complications and concluded that the relationship between PPG excursions and the well-established risk factors for cardiovascular disease (CVD) should be further examined. Using the ADA statement as a starting point and including the more recent American College of Endocrinology guidelines on glycaemic control, a panel of experts in diabetes met to review the role of PPG within the context of the overall metabolic syndrome, in the development of complications in Type 2 diabetes., Results: Post-prandial hyperglycaemia is a risk indicator for micro- and macrovascular complications, not only in patients with Type 2 diabetes but also in those with impaired glucose tolerance. In addition, the metabolic syndrome confers an increased risk of CVD morbidity and mortality. The debate focused on the relative contributions of postprandial hyperglycaemia, the metabolic syndrome and, in particular, raised triglyceride levels in the postprandial state, to the development of cardiovascular complications of diabetes., Conclusions: The panel recommended that in the prevention and management of microvascular complications of Type 2 diabetes, targeting both chronic and acute glucose fluctuations is necessary. Lowering the macrovascular risk also requires control of (postprandial) triglyceride levels and other components of the metabolic syndrome.

Aim: To compare two intervention programmes, aimed at improving the quality of care provided for patients with Type 2 diabetes in the longer term., Methods: A retrospective comparison of data derived from two non-randomized trials with 3.5 years of follow-up. In the first intervention group 401 patients were included, 413 in the second intervention group and 105 in the reference group. The first programme focused on improving the skills and knowledge of general practitioners (GPs) with regard to Type 2 diabetes, and supported them in making organizational changes in their practice (GP care only). Centralized shared diabetes care was implemented in the second programme in which the GPs received therapy advice according to a protocol for each individual patient. The patients were also encouraged in self-management, and received structured diabetes education (Diabetes Service). The main patient outcomes were HbA1c, blood pressure and serum lipid levels. Multilevel analysis was applied to adjust for dependency between repeated observations within one patient and for clustering of patients within general practices., Results: The HbA1c levels of patients of GPs who were supported by the Diabetes Service improved significantly more than the HbA1c levels of patients receiving GP care only (-0.28% [95% confidence interval (CI) -0.45; -0.11]). In contrast, the systolic blood pressure of patients receiving GP care only decreased more than that of patients of GPs supported by the Diabetes Service [4.14 mmHg (95% CI 1.77, 6.51)]., Conclusion: A Diabetes Service, providing GPs with individual therapy advice and patient education, resulted in better glycaemic control over 3.5 years than an intervention aimed at improving the skills of GPs in combination with organizational changes in the general practice.

Aims: Oxidative modification of low-density lipoprotein (LDL) is believed to be a key step in the genesis of atherosclerotic lesions. The presence of small, dense LDL is associated with accelerated atherosclerosis and is common in diabetic patients. The aim of this study was to investigate the relationship of in vitro LDL oxidizability and circulating in vivo oxidized LDL with LDL particle size in Type 2 diabetic patients and healthy control subjects., Subjects and Methods: The study group consisted of 58 elderly well controlled Type 2 diabetic patients and 58 control subjects with normal glucose metabolism. LDL particle size was measured by high-performance gel-filtration chromatography. In vitro oxidizability of LDL was measured by monitoring conjugated diene formation and plasma levels of circulating oxidized LDL were determined by ELISA., Results: In vitro susceptibility of LDL to oxidation was not related to plasma levels of in vivo oxidized LDL, nor to LDL particle size. In the diabetic patients, but not in the control group, an inverse relation between LDL size and in vivo oxidized LDL was observed (r=-0.35, P=0.007). This relation was strengthened after controlling for LDL-cholesterol concentration (r=-0.52, P<0.001)., Conclusions: In agreement with the view that small, dense LDL accelerates atherosclerosis, an inverse relationship was observed between LDL size and circulating in vivo oxidized LDL in Type 2 diabetic patients. Our results also suggest that in vitro susceptibility to oxidation is not a suitable surrogate measure for in vivo LDL oxidation.

Aims: Insulin aspart has been shown to improve post-prandial and overall glycaemic control in people with Type 1 diabetes. We hypothesized that insulin aspart with intensified basal NPH insulin supplementation would result in better overall glycaemic control than human regular insulin with standard basal NPH insulin., Methods: The trial was conducted in 43 centres in seven countries. People with Type 1 diabetes were randomized to mealtime insulin aspart with up to four daily NPH doses if meals were > 5 h apart and a 25% increase in bedtime NPH dose (n = 187), or to mealtime human unmodified insulin with once or twice daily basal NPH insulin (n = 181). Efficacy and safety were evaluated at 12 weeks (primary evaluation period) and 64 weeks., Results: At 12 and 64 weeks there was no statistically significant difference in HbA1c between the insulin aspart and regular insulin groups: -0.09 (95% confidence interval (CI) -0.23, +0.05)% and -0.14 (-0.32, +0.04)%. Post-prandial glucose values were lower and the area under the 24-h self-monitored blood glucose curve above 7.0 mmol/l was 28% smaller with insulin aspart (35.2 +/- 3.2 vs. 48.9 +/- 3.1 mmol/l h, P = 0.0015). No significant differences were found in mild or severe hypoglycaemia, or adverse event rate. At 64 weeks treatment satisfaction was higher in the insulin aspart group (difference 1.57 (95% CI 0.49, 2.64) points, P = 0.004), while quality of life was not different., Conclusions: Improved post-prandial glycaemic control and treatment satisfaction with insulin aspart were confirmed. Intensifying basal insulin supplementation resulted in a similar HbA1c decrement as previously found with the use of insulin aspart and standard NPH insulin supplementation. This does not support routinely basal NPH insulin intensification when using rapid-acting insulin analogues in daily practice.

Aims: To determine the risk perception of Type 2 diabetes in participants in a stepwise population-screening programme., Methods: This study was carried out within the framework of a stepwise Type 2 diabetes population screening in the general (age 50-75 years) Dutch population. Main outcome measures were perceived risk of having diabetes and perceived seriousness of diabetes, based on a self-report questionnaire, completed before being informed about the diagnosis (Type 2 diabetes yes/no) of the screening procedure. Among 7736 participants, the risk perception of 217 screening-detected participants was compared with 4435 with a low-risk profile for undiagnosed Type 2 diabetes., Results: Of 7736 participants, 43.5% could not give an estimate of their risk of having diabetes, 31.2% estimated their risk to be 0% and 25.3% estimated their risk to be 10% or higher. Compared with 4435 participants with an objectively low risk profile, 217 screening-detected participants were more likely to answer 'I do not know' (52.4% vs. 40.1%, P < 0.001), perceived their risk less often to be 0% (19.3% vs. 34.7%, P < 0.001), and slightly more often perceived their risk to be 10% or higher (28.3% vs. 25.2%, P < 0.001). Overall, more than half of the total population, including both participants with a low risk profile and the screening-detected participants, perceived diabetes as a (very) serious disease. Higher age, obesity and taking anti-hypertensive drugs did not translate into a higher perceived risk., Conclusions: Among screening-detected participants the seriousness of Type 2 diabetes was generally acknowledged, whilst the perceived risk of having Type 2 diabetes was low, despite the presence of risk factors.

Aims: To longitudinally assess risk factors for diabetic polyneuropathy (DPN) severity, and to longitudinally assess risk factors for the change of DPN severity during 2-4 years of follow-up., Methods: From 1995 to 1999, 486 Type 2 diabetes patients in general practice were examined annually with regard to DPN severity and its possible risk factors. DPN severity was assessed with a clinical neurological examination (CNE) which included pinprick sense, light touch sense, vibration sense and ankle jerk. Longitudinal (multivariate) linear associations of (change of) CNE score and predicting variables were analysed using multilevel analyses., Results: In this population, 50% of participants were men and had a mean age of 65.4 years, almost one-third (31.7%) of the participants had a CNE score > 4 at baseline and were classified with DPN. CNE score significantly increased during follow-up. Among participants not graded with DPN at baseline, 21.3% progressed towards a CNE score > 4 after 3 years of follow-up. Longitudinal multivariate analyses showed that age, diabetes duration, HbA1c, height, body mass index and ankle-arm index together best predicted CNE score during follow-up. Change of CNE score during follow-up was best predicted by age, diabetes duration and HbA1c, with the latter being the strongest predictor., Conclusions: Although several factors are longitudinally associated with DPN, HbA1c, age and diabetes duration were the best predictors of CNE change during follow-up. Therefore, improving glycaemia remains an important amenable factor in preventing worsening of diabetic polyneuropathy.

Aims: To evaluate the effects of continuous intraperitoneal insulin infusion (CIPII) using implantable pumps on glycaemic control and duration of hospital stay in poorly controlled 'brittle' Dutch diabetes patients, and to assess their current quality of life., Methods: Thirty-three patients were included. Glycaemic control was retrospectively assessed with HbA(1c) levels acquired before implantation, 1 year later and at long-term follow up of 58 months. Duration of hospital stay the year before and the year following first implantation was extracted from hospital records. Determinants of long-term glycaemic response were sought. Self-report questionnaires were administered at 58 months follow-up only, to assess current psychopathology and quality of life., Results: Mean HbA(1c) decreased from 10.0 +/- 2.3% to 9.0 +/- 1.8% (P = 0.039) 1 year after implantation and stabilized at 9.0 +/- 1.6% (P = 0.023) during long-term follow-up. Median number of hospital days in the 20 patients suffering from hospital admission before implantation decreased from 45 the year before implantation to 13 the year after (P = 0.005). Patients with a higher baseline HbA(1c) showed a larger long-term response (P < 0.001). Relatively low levels for quality of life were found, as well as a higher than expected number of patients with psychiatric symptoms., Conclusions: CIPII proved effective in complex patients with a history of poor control and hospital admission. Despite a substantial long-term improvement in glycaemic control and diminished hospital stay, normal levels of glycaemic control and quality of life were not attained.

Aims: To define clinically relevant cut-off points for severe fear of self-injecting (FSI) and self-testing (FST) (phobia) in insulin-treated patients with diabetes, and to estimate the magnitude of these phobias in our research population., Methods: FSI and FST were assessed in a cross-sectional survey using the Diabetes Fear of Injecting and Self-testing Questionnaire (D-FISQ). A sample of 24 insulin-treated adult diabetic patients was selected from the high-scorers on FSI and/or FST (> or = 95th percentile). FSI and FST were re-assessed, after which patients participated in a behavioural avoidance test (BAT), thereby determining the current level of avoidance of either self-injecting or self-testing. FSI and FST scores were linked to the outcome of the BATs. Cut-off scores for severe FSI/FST were determined and extrapolated to the total study population (n = 1275)., Results: Seven patients participated in the self-injecting BAT: two patients refused to perform an extra injection. In the self-testing BAT (n = 17) four patients declined to perform the extra blood glucose self-test. Extrapolation of FSI and FST cut-off scores to the total research population showed that 0.2-1.3% of the population scored in the severe FSI range. In FST, 0.6-0.8% of the total study population obtained scores in the cut-off range., Conclusions: Severe FSI and FST, characterized by emotional distress and avoidance behaviour, seems to occur in a small group of insulin-treated patients with diabetes. The D-FISQ can be of use to health care professionals (physicians, nurse specialists) in quickly providing valuable information on levels of FSI and FST in diabetes patients.

Aims: To identify neuropathic sensory symptoms associated with a clinical neurological examination (CNE) and to investigate whether these symptoms could be used as a diagnostic or screening tool for diabetic polyneuropathy in general practice., Methods: Five hundred and eighty-eight patients with Type 2 diabetes, recruited from 26 general practices in the Netherlands, underwent a CNE and completed a diabetes symptom checklist that included 10 items on neuropathic sensory symptoms. Linear regression analyses were performed to assess the association between neuropathic symptoms and CNE. Receiver operating characteristic (ROC) curves were created to assess the diagnostic properties of neuropathic symptoms., Results: In this population, with a mean age of 66.8 years, 32% were identified with diabetic polyneuropathy according to the CNE. Variables that showed the strongest association with CNE score were age (beta = 0.41), symptoms of sensory alteration (beta = 0.27), and the item 'numbness of the feet' (beta = 0.35) in particular. ROC curves showed that prediction of diabetic polyneuropathy from these symptoms was unsatisfying. The sensitivity and specificity of daily symptoms of 'numbness of the feet' were 28% and 93%, respectively, in patients <68 years, and 22% and 92%, respectively, in patients > or =68 years., Conclusions: Identification of neuropathic sensory symptoms is not useful as a diagnostic or even a screening tool in the assessment of diabetic neuropathy in daily practice. Therefore, the results reported in this paper mandate an annual foot examination by the general practitioner.

The aim of this study was to investigate anthropometric and life-style determinants of insulinaemia. Specific fasting serum insulin (FI) was analysed in a general Caucasian population aged 50-74 years, not known to have diabetes mellitus (n = 2226, sample 1). The analysis was repeated some weeks later in a subgroup of sample 1 in which two individual measurements of FI were available (n = 540, sub-sample 2). Specific serum insulin 2 h after ingestion of 75 g glucose (2hI), also measured on two occasions, was analysed in this same subgroup after excluding 59 subjects with fasting plasma glucose >7 mmol l(-1) (n = 481, sub-sample 3). Multiple regression analyses were performed, stratified for sex, with 10log insulin as the dependent variable. All determinants were adjusted for each other. FI was positively associated with BMI and waist-hip ratio (men and women) and inversely associated with intake of fibre (women), moderate alcohol use (men), and current smoking (women). 2hI was positively associated with BMI and waist-hip ratio (men and women), and intake of fat (women). 2hI was inversely associated with physical activity and moderate alcohol use (men and women), and current smoking (men). Family history of diabetes was not associated with insulinaemia. In conclusion, various life-style factors are related to insulinaemia, independent of obesity.

To quantify the degree of fear of self-injecting insulin and self-testing of blood glucose in adult insulin-treated diabetic patients, the Diabetes Fear of Injecting and Self-testing Questionnaire (D-FISQ) was developed. The D-FISQ is a 30-item self-report questionnaire consisting of two subscales that measure Fear of Self-Injecting (FSI) and Fear of Self-Testing (FST). To test validity and internal consistency, the D-FISQ was administered to a sample of 266 insulin-treated patients (Type 1 and Type 2); four diagnosed injection phobic insulin-requiring diabetic patients also completed the D-FISQ. The minimal score was obtained on the subscales by 62% (FSI) and 57% (FST) of the population. The D-FISQ demonstrated high internal consistency, with Cronbach's as of 0.94 (D-FISQ), 0.94 (FSI), and 0.90 (FST). Spearman rho between fear of self-injecting and fear of self-testing was 0.59 (p < 0.001), justifying two separate subscales. Construct validity was confirmed by a correlation of 0.44 with Spielbergers Trait Anxiety Inventory (Spearman rho, p < 0.001). FSI-scores from the injection phobic patients were all > or =95th percentile, while three scored > or =95% on FST, indicating discriminative validity. Results confirm homogeneity and validity of the D-FISQ and suggest usefulness of this instrument in both clinical practice and research.

The aim of the present study was to assess the beta cell response to glimepiride, administered orally, during and following a hyperglycaemic clamp in 14 NIDDM patients (7 males), aged 62.5 (St. Dev. 7.7) years with a body mass index of 27.3 (2.8) kg m(-2) and HbA(Ic) of 7.0 (0.7)% at baseline, in a placebo controlled study. All patients were on stable treatment with a second generation sulphonylurea for at least 8 weeks prior to randomization and received placebo (P) or 5 mg glimepiride (G) daily for 7 days and 10 mg prior to a hyperglycaemic clamp (10.9 mmol l(-1) for 60 min, preceded by i.v. insulin infusion to stabilize fasting blood glucose levels at 4.0 mmol l(-1)). The clamp was followed by an observation period of 2 h in 5 subjects and 3.5 h in the next 9 subjects, during which blood glucose and plasma insulin, C-peptide and proinsulin levels were measured at regular intervals to determine the effect of glimepiride on the interaction between changes in glycaemia and plasma levels of beta cell products. Neither G nor P elicited a first phase insulin response. Areas under plasma insulin curve during the 1 h hyperglycaemic clamp were 94.2 (39.5) vs 69.1 (26.5) pmol.h l(-1) in G and P clamps, respectively (p = 0.002). Total areas (AUC) under the plasma insulin curve were 377 (145) vs 271 (113) pmol.h l(-1) in G and P clamps (< 0.05). Total AUCs of C-peptide were 309 (96) and 259 (102 pmol.h.(-1), in G and P clamps, respectively, p = 0.01. Total AUCs of proinsulin were 176 (77) versus 119 (56) pmol.h l(-1) in G and P clamps, respectively, p = 0.004. Five hours after G and P administration blood glucose levels were 4.7) 92.1) mmol(-1) in the G clamp vs 6.2 (1.9) mmol l(-1) in the P clamp (p = 0.001). The number of hypoglycaemic events (blood glucose < 3.0 mmol l(-1)) in the 3.5 h observation period was 3 in G clamps vs 0 in P clamps (p = ns). In conclusion, glimepiride stimulates the second phase insulin and proinsulin secretion. The lowering of blood glucose levels is not accompanied by a commensurate inhibition of the insulin secretion. Further studies are required to compare this new drug with currently available oral hypoglycaemic agents, with respect to glycaemic control and the risk of hypoglycaemia.

Lys(B28)Pro(B29) human insulin analogue (Lispro) is a newly developed monomeric insulin analogue with a rapid onset and short duration of action. The aim of the study was to compare the thresholds for the counterregulatory responses during a stepwise euglycaemic/hypoglycaemic clamp for insulin lispro (LP), human (H), and porcine (P) insulin in a randomized order in 12 healthy male volunteers (age 22.4 +/- 1.7 years, BMI 21.9 +/- 1.7 kg m-2). A euglycaemic period of 2 h was followed by three hypoglycaemic levels of 60 min each; from 150-210 min at 3.5 mmol l-1, 240-300 min at 3.0 mmol l-1 and 330-390 min at 2.5 mmol l-1. Plasma insulin levels during the 50 mU kg-1 h-1 infusions and blood glucose levels were not significantly different. The glucose requirements (mean +/- SD) during the last part of the euglycaemic period (90-120 min) tended to be higher during LP compared to those during H and P; 2239 +/- 702 and 1929 +/- 769, 1957 +/- 725 mg kg-1, P = 0.067, respectively. The thresholds (blood glucose level at which a sustained elevation of the counterregulatory hormones as compared to the mean at normoglycaemia level 4.0 mmol l-1, occurs) for the various hormones were very similar during LP, H, and P insulin infusions and occurred at 253.8 +/- 56.7, 256.3 +/- 55.3 and 257.5 +/- 70.0 min for adrenaline; 241.4 +/- 80.3, 260.5 +/- 82.5 and 225.0 +/- 75.9 min for noradrenaline; 307.5 +/- 65.5, 304.1 +/- 74.1 and 322.5 +/- 40.4 min for cortisol; 263.8 +/- 50.3, 255.0 +/- 63.6 and 249.6 +/- 50.9 min for growth hormone; 236.3 +/- 78.2, 200.0 +/- 73.1 and 226.3 +/- 65.5 for pancreatic polypeptide. The autonomic and neuroglycopenic symptoms were elicited at 240 and 300 min, respectively. In conclusion, our data indicate a tendency to a higher biological activity of approximately 10% for Lispro insulin. During a stepwise euglycaemic/hypoglycaemic clamp, the counterregulatory hormone responses to insulin lispro, human insulin, and porcine insulin were similar.

Only sparse and contradictory data are available on peripheral somatic nerve function in relation to the total range of glucose tolerance. A random sample (n = 708) of people, stratified by age, sex, and glucose tolerance, from a Caucasian population aged 50 to 74 years was invited to undergo an examination including measures of large-fibre nerve function (ankle and knee reflexes, vibration sense, vibratory perception threshold (VPT) at the foot) and one measure of small-fibre function (thermal discrimination threshold (TDT) at the foot). A total of 267 subjects with a normal glucose tolerance (NGT), 167 with impaired glucose tolerance (IGT), 90 with newly diagnosed diabetes mellitus (NDM), and 73 with previously known diabetes (KDM) were included. KDM was associated with the highest prevalence of large-fibre nerve dysfunction. Within the range from NGT to NDM, most large-fibre function measures showed a decline with decreasing glucose tolerance. The TDT showed a decrease with an increase in fasting and post-load insulin levels (p < 0.05). We conclude that glucose intolerance is associated with impaired peripheral large-fibre nerve function, an association which seems to apply even in the non-diabetic range. Higher insulin levels were associated with a better small-fibre nerve function.

The purpose of the study was to assess the reliability of mydriatic 60 degrees fundus photography in a retinopathy screening programme for Type 2 diabetic patients in a primary health care setting. In 323 eligible consecutive Type 2 diabetic patients above 40 years of age, attending a regional shared care diabetes project, mydriatic wide angle fundus photography was compared with standardized fundoscopy in dilated pupils as the recommended test for the detection of diabetic retinopathy. Fundus photography included two black and white transparencies per eye visualizing the central and nasal retinal field. Fundoscopy findings and pictures were scored according to modified Wisconsin criteria. Fundoscopy revealed in 95/646 eyes (14.7%) some degree of diabetic retinopathy. Sensitivity and specificity of fundus photography (omitting ungradable transparencies) were 97% for the diagnosis of any diabetic retinopathy (DRP). All patients with moderate and severe DRP (Wisconsin grade 3 and worse) according to fundoscopy were detected by fundus photography. In conclusion, mydriatic wide angle 60 degrees fundus photography, making two pictures per eye, can be applied effectively and reliably in the detection of diabetic retinopathy in patients with Type 2 diabetes.

The Hoorn study has investigated the prevalence of impaired glucose tolerance (IGT) and diabetes in a random sample of the population, 50-75 years of age, in the small Dutch town of Hoorn. The percentage of the population identified as having IGT was 10.3%, while 8.4% had diabetes. The prevalence of both diabetes and IGT was higher in older subjects (70-74 years of age) than in younger subjects (50-54 years of age), suggesting that age is a major determinant of the prevalence of IGT and diabetes in a population. A prospective study of the development of non-insulin dependent diabetes mellitus (NIDDM) in the subjects identified as having IGT was then initiated. Preliminary results for the 158 subjects who have been followed for a mean of 2 years indicated that 28.5% (95% confidence interval, 15-42%) have progressed to NIDDM within this period. The progression rate calculated from this value is 13.8%/year (95% confidence interval, 3.5-24%/year). Analysis of possible determinants of conversion has revealed that 2-hour plasma glucose levels greater than 9.4 mmol/litre and increased fasting proinsulin levels are predictive of progression to NIDDM. This suggests that beta cell dysfunction, rather than increased insulin resistance, is responsible for the development of NIDDM.

The aim of our study was to assess the long-term (24 months) efficacy of a comprehensive weight reduction programme as compared to that of a conventional programme. The Comprehensive Programme comprised, besides the Conventional Programme (diet counselling), behavioural modification and exercise training. The 2-year follow-up period was completed by 53 patients (19M/34F; 88.3%). The differences (95% confidence intervals; CI) between the change in body weight of patients in the Comprehensive Programme compared to the Conventional Programme after 6 and 24 months of treatment were -2.2 (-4.0, -0.3) kg, p = 0.03 and -1.3 (-3.3, 0.7) kg, p = 0.21, respectively. In comparison to the Conventional Programme, the Comprehensive Programme resulted in a greater decrease (95% CI) of HbA1c after 6 months: -0.8 (-1.2, -0.2)%, p = 0.01, but not after 2 years: -0.4 (-1.0, 0.1)%, p = 0.12. The effects on blood pressure and serum lipids of the Comprehensive Programme and the Conventional Programme were comparable. Changes in body weight at 6 months correlated well with changes in HbA1c, fasting plasma insulin, and blood pressure, whereas at 24 months no such correlation was found with HbA1c. Pretreatment variates that were associated with the greatest 2-year weight loss were a high HbA1c value, a low energy per cent carbohydrate intake and a low percentage of obese subjects within the family. In conclusion, the long-term outcome of the Comprehensive Programme was not different from that of the Conventional Programme. The achieved body weight reduction was associated with a sustained fall in blood pressure, but with only a transient beneficial effect on the glycaemic control in the Type 2 diabetic patient.

The aim of the present study was to develop a Type 2 diabetes symptom checklist for use in clinical and epidemiological research, which can measure differences in symptom severity between patients and detect changes over time within patients. Face and content validity of items and dimension structure were based on literature and experiences of diabetologists. Two Likert scales were used to measure symptom frequency and perceived burden. Reliability, responsiveness and validity were studied in 185 Type 2 diabetic patients. Factor-analysis confirmed the predesigned dimension structure with 34 items, distributed over 6 dimensions. The internal consistency with Cronbach alpha coefficients between 0.76 and 0.95 and test-retest reliability with Pearson product-moment correlation coefficients between 0.79 and 0.94 were satisfactory. The ability to detect change over time (responsiveness) was estimated in stable subjects, using sample size calculations. A minimal detectable mean change of 0.07-0.58 points in total score on the 10-point scale within a group of 100 subjects suggests an impressive responsiveness. Significant differences in symptom severity score were found between patients with different co-morbidity status and treatment modes, indicating satisfactory construct validity of the dimension structure. The Type 2 Diabetes Symptom Checklist was found to be a useful diabetes-specific symptom severity assessment method for clinical and epidemiological studies.

Efficacy and acceptability of the Medi-Jector II, compared with conventional syringes, was evaluated in a cross-over study (two 4-week periods) in 14 adult insulin-dependent diabetic patients. In 6 out of these 14 patients the clinical diagnosis of needle phobia was confirmed by anxiety tests for trait (45.8 +/- 12.8 (SD) versus 34.0 +/- 6.2; p less than 0.05) and state (50.3 +/- 10.9 versus 28.9 +/- 5.2, p less than 0.05). Five patients (one needle-phobic) dropped out, all for Medi-Jector-related problems. No significant differences were found in body weight, insulin dosage, and number of hypoglycaemic reactions. HbA1 after the Medi-Jector period was significantly higher than after the conventional period (9.8 +/- 1.2 (SE) versus 9.1 +/- 1.1 (SE)%; p less than 0.05). The questionnaire, evaluating the Medi-Jector, revealed poor acceptance of the device (7/9 patients' general impression being moderate or bad). The use of the Medi-Jector in comparison with conventional injections caused the patients to complain about: more immediate pain (4/9 patients), delayed pain (often: 4/9, sometimes: 2/9), more insulin leakage (6/9), more bleeding (6/9), and more haematomas (5/9). Except for 'often occurring delayed pain' (4/5 needle-phobics versus 0/4 non-needle-phobics; p less than 0.05), needle-phobic patients scored the questionnaire similarly to the other patients. We conclude that the use of the Medi-Jector II did not cause a major short-term loss of metabolic control, but that the device was not well accepted by our patients, independent of the existence of needle phobia.

In ten patients with insulin-dependent diabetes we compared postprandial blood glucose levels and plasma free insulin concentrations after the administration of insulin mixtures with two commonly used injection techniques. The morning dose of insulin was administered once using a 13 mm needle, inserted perpendicularly, and once with a 20 mm needle, inserted deep subcutaneously just above the muscle fascia at an angle dependent on the skinfold thickness. Plasma free insulin concentrations and postprandial blood glucose levels were virtually identical for either technique. We conclude, therefore, that the simpler perpendicular method is the technique of choice, saving the diabetics much unnecessary anxiety over a daily procedure.

The efficacy and acceptability of multiple daily insulin injections (three preprandial injections of short-acting insulin (NovoPen) plus once daily extended-acting insulin) were compared with those of twice daily injections of short- and intermediate-acting insulin. Sixteen Type 1 diabetic patients participated in a cross-over study (6-month treatment periods). Total areas under 24-h plasma free insulin curves, assessed at the end of each study period, were not significantly different, but a greater area under this curve was found for the pen-injector regimen from 1200 to 1600 h (150 +/- 15 (SE) vs 106 +/- 7 mU l-1 h, p less than 0.01). Home blood glucose profiles showed significantly lower values with pen-injector therapy after lunch (7.1 +/- 0.6 vs 8.4 +/- 0.4 mmol l-1, p = 0.05) and before and after dinner (6.4 +/- 0.6 vs 8.8 +/- 0.5 mmol l-1, p less than 0.005, and 7.5 +/- 0.7 vs 9.4 +/- 1.1 mmol l-1, p less than 0.05). Mean daily blood glucose concentration was also lower (7.1 +/- 0.4 vs 8.2 +/- 0.5 mmol l-1, p less than 0.05). HbA1, fructosamine, hypoglycaemic reactions, and body weight were not significantly different. Thirteen patients decided to continue with pen-injector therapy at the end of the study.

The efficacy and psychosocial effects of multiple daily insulin injections (three preprandial injections of short-acting insulin (NovoPen) and once daily, bedtime extended-acting insulin) were compared with those of twice daily combinations of short- and intermediate-acting insulin, in a randomized crossover study (two 6-month periods), in 16 adult diabetic patients. HbA1 was not significantly different for the two treatment modalities (8.2 +/- 0.4 vs 7.6 +/- 0.4%). With the pen-injector regimen significantly less state anxiety (36.0 +/- 2.5 vs 39.5 +/- 2.7; p less than 0.05) was found than with the conventional syringe regimen. The patients tended to experience a better self-concept as having diabetes (32.0 +/- 2.1 vs 37.7 +/- 3.0; p less than 0.06), as well as less external ('chance') orientation (18.5 +/- 1.2 vs 20.7 +/- 1.6; p = 0.09) with the pen-injector regimen. A subgroup of patients with lower trait anxiety scores experienced less state anxiety during the pen-injector regimen than during twice daily insulin injections (30.6 +/- 2.6 vs 34.3 +/- 2.7; p less than 0.05). However, this subgroup tended to be less positive about injecting insulin during the pen-injector regimen (34.8 +/- 3.6 vs 29.6 +/- 4.0; p less than 0.08). The subgroup with higher trait anxiety scores experienced a better self-concept as having diabetes (35.3 +/- 2.3 vs 40.1 +/- 2.6; p less than 0.05) and a tendency towards less physician orientation (15.8 +/- 1.8 vs 19.6 +/- 2.7; p less than 0.07) with the pen-injector regimen. Thirteen patients continued with the pen-injector regimen.