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Aim: To examine the hypothesis that, based on their glucose curves during a seven‐point oral glucose tolerance test, people at elevated type 2 diabetes risk can be divided into subgroups with different clinical profiles at baseline and different degrees of subsequent glycaemic deterioration. Methods: We included 2126 participants at elevated type 2 diabetes risk from the Diabetes Research on Patient Stratification (IMI‐DIRECT) study. Latent class trajectory analysis was used to identify subgroups from a seven‐point oral glucose tolerance test at baseline and follow‐up. Linear models quantified the associations between the subgroups with glycaemic traits at baseline and 18 months. Results: At baseline, we identified four glucose curve subgroups, labelled in order of increasing peak levels as 1–4. Participants in Subgroups 2–4, were more likely to have higher insulin resistance (homeostatic model assessment) and a lower Matsuda index, than those in Subgroup 1. Overall, participants in Subgroups 3 and 4, had higher glycaemic trait values, with the exception of the Matsuda and insulinogenic indices. At 18 months, change in homeostatic model assessment of insulin resistance was higher in Subgroup 4 (β = 0.36, 95% CI 0.13–0.58), Subgroup 3 (β = 0.30; 95% CI 0.10–0.50) and Subgroup 2 (β = 0.18; 95% CI 0.04–0.32), compared to Subgroup 1. The same was observed for C‐peptide and insulin. Five subgroups were identified at follow‐up, and the majority of participants remained in the same subgroup or progressed to higher peak subgroups after 18 months. Conclusions: Using data from a frequently sampled oral glucose tolerance test, glucose curve patterns associated with different clinical characteristics and different rates of subsequent glycaemic deterioration can be identified. [ABSTRACT FROM AUTHOR]

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 HbA1c levels. We therefore examined the cross-sectional association between individual and partner's level of occupation on HbA1c 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 HbA1c 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 HbA1c 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 HbA1c 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. [ABSTRACT FROM AUTHOR]

Aim To test whether a low serum 25-hydroxyvitamin D level explains the greater prevalence of depression among people with Type 2 diabetes. Methods We performed a cross-sectional analysis of 527 people, aged 60-87 years, who participated in a population-based cohort study. Type 2 diabetes, impaired glucose tolerance, impaired fasting glucose and normal glucose tolerance were defined according to the 2006 WHO criteria. The Centre for Epidemiologic Studies Depression questionnaire was administered, using a cut-off score of ≥ 16 to determine clinically relevant depressive symptoms. Results Logistic regression analysis confirmed that women with impaired glucose tolerance/impaired fasting glucose and people with Type 2 diabetes did have a higher risk of depressive symptoms [unadjusted odds ratios 3.66 (95% CI 1.59 to 8.43) and 3.04 (95% CI 1.57 to 5.88), respectively], compared with people with normal glucose tolerance. Serum 25-hydroxyvitamin D level was not a mediating factor in the association between impaired glucose tolerance/impaired fasting glucose or Type 2 diabetes and depressive symptoms [unstandardized indirect effect 0.001 (95% CI −0.063 to 0.079) and 0.004 (95% CI −0.025 to 0.094), respectively]. Conclusions The study found no evidence that low vitamin D levels are a contributing factor to higher depression scores in people with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective. With depression being present in approximately 20% of people with type 2 diabetes mellitus (T2DM), we expect equally frequent prescription of antidepressants, anxiolytics, and hypnotics. Nevertheless, prescription data in people with T2DM is missing and the effect of depression on glycaemic control is contradictory. The aim of this study was to assess the prevalence of antidepressants, anxiolytics, and/or hypnotics use in a large, managed, primary care system cohort of people with T2DM and to determine the sociodemographic characteristics, comorbidities, T2DM medication, and metabolic control associated with its use. Method. The prevalence of antidepressants, anxiolytics, and/or hypnotics use in the years 2007–2012 was assessed in the Hoorn Diabetes Care System Cohort from the Netherlands. Results. From the 7016 people with T2DM, 500 people (7.1%) used antidepressants only, 456 people (6.5%) used anxiolytics and/or hypnotics only, and 254 people (3.6%) used a combination. Conclusion. We conclude that in our managed, primary care system 17% of all people with T2DM used antidepressants, anxiolytics, and/or hypnotics. Users of antidepressants, anxiolytics, and/or hypnotics were more often female, non-Caucasian, lower educated, and more often treated with insulin. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims To investigate the effects of self-monitoring of glucose in blood or urine, on diabetes-specific distress and self-efficacy, compared with usual care in people with non-insulin-treated Type 2 diabetes mellitus. Methods One hundred and eighty-one participants with non-insulin-treated Type 2 diabetes mellitus [diabetes duration ≥ 1 year, age 45-75 years, HbA1c ≥ 53.0 mmol/mol (7.0%), self-monitoring frequency < 3 times in the previous year] were randomly assigned to blood self-monitoring ( n = 60), urine self-monitoring ( n = 59) or usual care ( n = 62). Primary outcomes were between-group differences in diabetes-specific distress [Problem Areas in Diabetes scale (PAID)] and self-efficacy [Confidence in Diabetes Self-Care questionnaire (CIDS-2)] after 12 months. Secondary outcomes included changes in HbA1c, treatment satisfaction and depressive symptoms. Results There were no statistically significant between-group differences in changes in PAID and CIDS-2 after 12 months. Mean difference in PAID between blood monitoring and control was −2.2 [95% confidence interval (CI) −7.1 to 2.7], between urine monitoring and control was −0.9 (95% CI −4.4 to 2.5) and between blood monitoring and urine monitoring was −2.0 (95% CI −4.1 to 0.1). Mean difference in CIDS-2 between blood monitoring and control was 0.6 [95% CI (−2.0 to 2.1), between urine monitoring and control was 2.8 (95% CI −2.3 to 7.9)] and between blood monitoring and urine monitoring was −3.3 (95% CI −7.9 to 1.3). No statistically significant between-group differences in change in any of the secondary outcome measures were found. Conclusions This study did not find statistical or clinical evidence for a long-term effect of self-monitoring of glucose in blood or urine on diabetes-specific distress and self-efficacy in people with moderately controlled non-insulin-treated Type 2 diabetes mellitus. (Current Controlled Trials ISRCTN84568563) [ABSTRACT FROM AUTHOR]

Aims To test a simulation model, the MICADO model, for estimating the long-term effects of interventions in people with and without diabetes. Methods The MICADO model includes micro- and macrovascular diseases in relation to their risk factors. The strengths of this model are its population scope and the possibility to assess parameter uncertainty using probabilistic sensitivity analyses. Outcomes include incidence and prevalence of complications, quality of life, costs and cost-effectiveness. We externally validated MICADO's estimates of micro- and macrovascular complications in a Dutch cohort with diabetes (n = 498 400) by comparing these estimates with national and international empirical data. Results For the annual number of people undergoing amputations, MICADO's estimate was 592 (95% interquantile range 291-842), which compared well with the registered number of people with diabetes-related amputations in the Netherlands (728). The incidence of end-stage renal disease estimated using the MICADO model was 247 people (95% interquartile range 120-363), which was also similar to the registered incidence in the Netherlands (277 people). MICADO performed well in the validation of macrovascular outcomes of population-based cohorts, while it had more difficulty in reflecting a highly selected trial population. Conclusions Validation by comparison with independent empirical data showed that the MICADO model simulates the natural course of diabetes and its micro- and macrovascular complications well. As a population-based model, MICADO can be applied for projections as well as scenario analyses to evaluate the long-term (cost-)effectiveness of population-level interventions targeting diabetes and its complications in the Netherlands or similar countries. [ABSTRACT FROM AUTHOR]

Aims To study symptom burden among older people and its associations with change in glucose metabolism status over a 7-year period. Methods We conducted a prospective population-based cohort study among 397 older people. We used the revised Diabetes Symptom Checklist to assess symptom burden. Glucose metabolism status was determined using an oral glucose tolerance test. Analyses were adjusted for multiple confounders, including cardiovascular risk and risk of depression (Center for Epidemiological Studies Depression Scale score ≥ 16). Results Revised Diabetes Symptom Checklist total scores (range 0-100) increased slightly over time among people with normal glucose metabolism (mean difference β1.04; P = 0.04) and those with impaired glucose metabolism (β1.96; P = 0.01), but not among people with Type 2 diabetes (β0.46; P = 0.55). These associations between symptom burden and glucose status were attenuated after full adjustment for multiple confounders and remained statistically significant for those with impaired glucose status. Linear mixed models showed significant mean differences in revised Diabetes Symptom Checklist total scores over time when comparing people with Type 2 diabetes with those with normal or impaired glucose metabolism, but not when comparing subjects with impaired vs normal glucose metabolism; these results did not alter after full adjustment. Conclusions Symptom burden increased gradually over time in the people with impaired glucose metabolism and those with normal glucose metabolism, but not in patients with Type 2 diabetes over a 7-year follow-up period. [ABSTRACT FROM AUTHOR]

Diabet. Med. 29, e211-e216 (2012) Abstract Aim Glucocorticoids are efficacious anti-inflammatory agents, but, in susceptible individuals, these drugs may induce glucose intolerance and diabetes by affecting β-cell function and insulin sensitivity. We assessed whether polymorphisms in the glucocorticoid receptor gene NR3C1 associate with measures of β-cell function and insulin sensitivity derived from hyperglycaemic clamps in subjects with normal or impaired glucose tolerance. Methods A cross-sectional cohort study was conducted in four academic medical centres in the Netherlands and Germany. Four hundred and forty-nine volunteers (188 men; 261 women) were recruited with normal glucose tolerance ( n = 261) and impaired glucose tolerance ( n = 188). From 2-h hyperglycaemic clamps, first- and second-phase glucose-stimulated insulin secretion, as well as insulin sensitivity index and disposition index, were calculated. All participants were genotyped for the functional NR3C1 polymorphisms N363S (rs6195), BclI (rs41423247), ER22/23EK (rs6189/6190), 9β A/G (rs6198) and ThtIIII (rs10052957). Associations between these polymorphisms and β-cell function parameters were assessed. Results In women, but not in men, the N363S polymorphism was associated with reduced disposition index ( P = 1.06 10−4). Also only in women, the ER22/23EK polymorphism was associated with reduced first-phase glucose-stimulated insulin secretion ( P = 0.011) and disposition index ( P = 0.003). The other single-nucleotide polymorphisms were not associated with β-cell function. Finally, none of the polymorphisms was related to insulin sensitivity. Conclusion The N363S and ER22/23EK polymorphisms of the NR3C1 gene are negatively associated with parameters of β-cell function in women, but not in men. [ABSTRACT FROM AUTHOR]

Background Statins play an important role in the prevention of cardiovascular disease in type 2 diabetes. Several studies have reported low adherence with statins among patients with type 2 diabetes. Studies comparing discontinuation of statins compared with discontinuation of oral anti-diabetics within the same individuals before and after initiation of oral anti-diabetic drugs are not available. The aim of this study was to describe discontinuation among patients with type 2 diabetes prescribed statins prior to and after initiation of oral anti-diabetics and to compare statin discontinuation with discontinuation of oral anti-diabetics. Methods We report an observational cohort study among patients initiating treatment with statins prior to or after initiation of oral anti-diabetics between 1999 and 2007. Patients were classified as starting statins prior to initiation (Prior users) or after initiation (After users) of anti-diabetics. Discontinuation was defined as an interval of 180 days or more between the theoretical end date of a statin/anti-diabetic prescription and the dispensing date of the next statin/anti-diabetic prescription. Results and Conclusions We included 3323 starters with oral anti-diabetic drugs in our study; 2072 patients initiated statins in the period of observation. Discontinuation rates for statins were higher compared with oral anti-diabetics (52.1 vs 15.0%). After users discontinued statin therapy more frequently compared to prior users (62.8 vs 48.2%). Discontinuation of statins is higher compared with anti-diabetic discontinuation. Patients starting statins after the initiation of oral anti-diabetic treatment are more likely to discontinue treatment than patients who initiate statins before the start of oral anti-diabetics. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

. Handberg A, Højlund K, Gastaldelli A, Flyvbjerg A, Dekker JM, Petrie J, Piatti P, Beck-Nielsen H (Aarhus Hospital and Aalborg Hospital, Aarhus University Hospital, Aarhus, Denmark; Odense University Hospital, Odense, Denmark; Institute of Clinical Physiology, CNR Pisa, Pisa, Italy; Aarhus University Hospital, Aarhus, Denmark; Vrije Universiteit Amsterdam, Amsterdam, The Netherlands; BHF Glasgow Cardiovascular Research Centre, Glasgow, UK; and San Raffaele Institute, Milan, Italy). Plasma sCD36 is associated with markers of atherosclerosis, insulin resistance and fatty liver in a nondiabetic healthy population. J Intern Med 2012; 271: 294-304. Objectives. Insulin resistance is associated with increased CD36 expression in a number of tissues. Moreover, excess macrophage CD36 may initiate atherosclerotic lesions. The aim of this study was to determine whether plasma soluble CD36 (sCD36) was associated with insulin resistance, fatty liver and carotid atherosclerosis in nondiabetic subjects. Methods. In 1296 healthy subjects without diabetes or hypertension recruited from 19 centres in 14 European countries (RISC study), we determined the levels of sCD36, adiponectin, lipids and liver enzymes, insulin sensitivity ( M/ I) by euglycaemic-hyperinsulinaemic clamp, carotid atherosclerosis as intima-media thickness (IMT) and two estimates of fatty liver, the fatty liver index (FLI) and liver fat percentage (LF%). Results. IMT, FLI, LF%, presence of the metabolic syndrome, impaired glucose regulation, insulin and triglycerides increased across sCD36 quartiles (Q2-Q4), whereas adiponectin and M/ I decreased ( P ≤ 0.01). sCD36 was lower in women than in men ( P = 0.045). Log sCD36 showed a bimodal distribution, and amongst subjects with sCD36 within the log-normal distribution (log-normal population, n = 1029), sCD36 was increased in subjects with impaired glucose regulation ( P = 0.045), metabolic syndrome ( P = 0.006) or increased likelihood of fatty liver ( P < 0.001). sCD36 correlated significantly with insulin, triglycerides, M/ I and FLI ( P < 0.05) after adjustment for study centre, gender, age, glucose tolerance status, smoking habits and alcohol consumption. In the log-normal population, these relationships were stronger than in the total study population and, additionally, sCD36 was significantly associated with LF% and IMT ( P < 0.05). Conclusions. In this cross-sectional study of nondiabetic subjects, sCD36 was significantly associated with indices of insulin resistance, carotid atherosclerosis and fatty liver. Prospective studies are needed to further evaluate the role of sCD36 in the inter-relationship between atherosclerosis, fatty liver and insulin resistance. [ABSTRACT FROM AUTHOR]

Diabet. Med. 28, 1395-1400 (2011) Abstract Aim Hypoglycaemia may have a detrimental impact on quality of life for patients with Type 2 diabetes. There are few clinical studies exploring the impact of experiencing hypoglycaemia on beliefs about diabetes and health status. The aim of this study was to explore associations between experience of hypoglycaemia and changes in diabetes beliefs and self-reported health status in patients with non-insulin-treated Type 2 diabetes using a blood glucose meter. Methods One-year prospective cohort analysis of 226 patients recruited to a randomized trial evaluating the impact of self-monitoring of blood glucose. Self-reported hypoglycaemia over 1 year was categorized into three groups: (1) no experience of hypoglycaemia; (2) blood glucose measurements < 4 mmol/l with no associated symptoms of hypoglycaemia (grade 1); and (3) symptomatic hypoglycaemia (grade 2 and 3). Measures of beliefs about diabetes (Revised Illness Perception Questionnaire) and health status (EuroQol-5D) were assessed at baseline and 1 year. Differences in mean changes over 1 year were explored with analyses of covariance. Results There was a significant increase in mean score in beliefs about personal control (1.14; 95% CI 0.14-2.14) among those experiencing grade 1 hypoglycaemia compared with those not experiencing hypoglycaemia. There were no significant differences in changes in health status between groups, with small overall changes that were inconsistent between groups. Conclusions This study does not provide support for a long-term adverse impact on beliefs about diabetes or health status from the experience of mild symptomatic hypoglycaemia, in well-controlled, non-insulin-treated patients with Type 2 diabetes using self-monitoring of blood glucose. [ABSTRACT FROM AUTHOR]

Background We hypothesized that acarbose would delay conversion from impaired glucose tolerance (IGT) to type 2 diabetes by alleviating postprandial hyperglycaemia. Our study's main objective was to investigate the effect of acarbose in IGT-persons on their 2-h plasma glucose level and beta-cell function. Subjects and Methods The study included a random sample of 45-70-year-old residents of Hoorn, Netherlands, with mean fasting plasma glucose < 7.8 mmol/L and mean 2-h plasma glucose of 8.6-11.1 mmol/L (measured by two successive oral glucose tolerance tests). After a qualification period, participants were randomized to acarbose treatment or placebo. Insulin secretion and insulin sensitivity were measured by hyperglycaemic clamp. After a 3-year treatment, analyses were performed of both the intention-to-treat and the per-protocol groups. Results Of the 12 093 residents who received postal invitations, 118 participants were randomized. The mean difference of the post-load plasma glucose after 3 years, was − 1.16 mmol/L (95% CI: − 2.03; − 0.17). The absolute risk reduction for diabetes was 6% (95% CI: − 9; 21). No effect was seen on insulin secretion and insulin sensitivity. Conclusions In patients with IGT, treatment with acarbose was associated with beneficial effects on 2-h plasma glucose levels but not with improvement of beta-cell function. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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 (βa = 0.5, P < 0.001) and group B (βb = 0.2, P < 0.001), whereas a significant negative relation was found for males in group C (βc = −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 (βc = −0.1, P = 0.4). Conclusion Plasma triglcyerides 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. [ABSTRACT FROM AUTHOR]

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 ≥ 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. [ABSTRACT FROM AUTHOR]

Background Asymptomatic peripheral arterial disease (PAD) is common amongst the elderly and is a risk factor for cardiovascular morbidity and mortality. PAD can be assessed by non-invasive tests such as the ankle/brachial pressure index (ABPI) at rest and Doppler flow velocity (DFV) scanning, but these tests may underestimate the prevalence of PAD. The aim of this study was to estimate the added value, for the detection of PAD, of the one-minute exercise test, defined as positive if the drop of the ankle systolic pressure was more than 30 mmHg. We also investigated whether the combination of the ABPI at rest and the one-minute exercise test could replace DFV scanning. Materials and methods We studied this in a random sample ( n = 631) of a 50- to 75-year-old population. Results Of these subjects 11% (66/631) had an abnormal ABPI (< 0·9) and 16% (102/631) had an abnormal DFV curve. Of this sample 72% of the subjects performed a one-minute exercise test. Of all subjects 6% (27/451) had an abnormal ABPI (< 0·9) and 12% (54/451) had an abnormal DFV curve. The one-minute exercise test revealed seven cases of PAD (beyond the 67 already identified) which were not detected by an abnormal ABPI at rest and/or DFV scanning. As a result the prevalence of PAD increased by 2%. All patients with an aortoiliac or femoropopliteal obstruction had an ABPI at rest < 0·9. The sensitivity of the combination of the ABPI at rest and the one-minute exercise test to detect abnormal DFV curves was low for crural obstructions. Conclusion The one-minute exercise test slightly improves the detection of peripheral arterial disease in the general population. [ABSTRACT FROM AUTHOR]

Background. Evidence is accumulating that the vitamin D endocrine system has physiological functions beyond bone health including a role in the regulation of blood pressure. Effects of poor vitamin D status on blood pressure may be mediated by elevated parathyroid hormone (PTH) levels. Aim. To evaluate whether serum 25-hydroxyvitamin D [25(OH)D] and PTH levels are independently associated with blood pressure in a population-based study of older men and women. Methods. Subjects were participants of the Longitudinal Aging Study Amsterdam, aged 65 years and older. In 1205 participants, serum 25(OH)D and PTH levels were determined and diastolic and systolic blood pressure were measured. Linear and logistic regression analyses were performed with adjustments for age, sex, region, season, lifestyle factors (physical activity, smoking, alcohol intake), and waist circumference. Results. Serum 25(OH)D was not significantly associated with diastolic (beta 0.00, P = 0.98) or systolic (beta 0.06, P = 0.11) blood pressure. In contrast, higher ln-PTH levels were significantly associated with higher diastolic (beta 1.93, P = 0.03) and systolic (beta 4.67, P = 0.01) blood pressure. Higher PTH levels were associated with a substantially higher prevalence of hypertension (OR 2.00, 95% CI 1.31–3.06 for the highest versus the lowest quartile), whereas 25(OH)D showed no significant association (OR 0.89, 95% CI 0.47–1.69 for the lowest versus the highest 25(OH)D category). Conclusion. These results indicate that PTH is a potentially modifiable determinant of blood pressure in the general elderly population. Serum 25(OH)D, however, was not associated with blood pressure, possibly due to the relatively high levels in our population. [ABSTRACT FROM AUTHOR]

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. Diabet. Med. 24, 430 – 435 (2007) [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective. Homocysteine and cardiovascular autonomic function are both predictors of cardiovascular disease and death, particularly in patients with diabetes. The mechanism by which homocysteine causes disease is unknown. The objective of our study was to determine whether hyperhomocysteinaemia is associated with impaired cardiovascular autonomic function in an age-, sex-, and glucose tolerance-stratified sample of an elderly Caucasian population. Methods. We studied 609 subjects, 252 with normal glucose metabolism, 173 with impaired glucose metabolism, and 184 with type 2 diabetes. Cardiac cycle duration (RR interval) and continuous finger arterial pressure were measured under three conditions: during (i) spontaneous breathing, (ii) six deep breaths over 1 min, and (iii) an active change in position from lying to standing. From these readings, 10 parameters of autonomic function were assessed (three Ewing tests, six heart rate variability tests and one test of baroreflex sensitivity). These 10 measurements were summarized in a single cardiovascular autonomic dysfunction score (CADS). Results. Comparing values of autonomic function measures in the lowest versus the highest quartile of homocysteine revealed no significant association between homocysteine level and autonomic function in the whole study group, nor in the individual glucose tolerance groups. Multiple adjustment for age, sex, waist-to-hip ratio, serum creatinine, use of antihypertensives and fasting insulin, confirmed this result. We found no evidence of effect modification of glucose tolerance status on the association between homocysteine and autonomic dysfunction ( P for interaction for CADS = 0.79). Conclusions. There is no evidence for an association between homocysteine levels and cardiovascular autonomic function in either diabetic or nondiabetic subjects. Cardiovascular autonomic dysfunction does not help explain why hyperhomocysteinaemia is related to cardiovascular mortality. [ABSTRACT FROM AUTHOR]

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 ω-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 ω-3 PUFA and depression. To examine potential side-effects, such as on glycaemic control, studies regarding the use of ω-3 supplements in Type 2 diabetes were also reviewed. Results Epidemiological and clinical studies suggest that a high intake of ω-3 PUFA protects against the development of depression. There is also some evidence that a low intake of ω-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 ω-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 ω-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. [ABSTRACT FROM AUTHOR]

Spijkerman AMW, Henry RMA, Dekker JM, Nijpels G, Kostense PJ, Kors JA, Ruwaard D, Stehouwer CDA, Bouter LM, Heine RJ. (VU University Medical Center, Amsterdam and Erasmus University Medical Center, Rotterdam, The Netherlands; and Royal Netherlands Embassy, Washington, DC, USA). Prevalence of macrovascular disease amongst type 2 diabetic patients detected by targeted screening and patients newly diagnosed in general practice: the Hoorn Screening Study.J Intern Med2004;256: 429–436.Screening for type 2 diabetes has been recommended and targeted screening might be an efficient way to screen. The aim was to investigate whether diabetic patients identified by a targeted screening procedure differ from newly diagnosed diabetic patients in general practice with regard to the prevalence of macrovascular complications.Cross-sectional population-based study.Population study, primary care.Diabetic patients identified by a population-based targeted screening procedure (SDM patients), consisting of a screening questionnaire and a fasting capillary glucose measurement followed by diagnostic testing, were compared with newly diagnosed diabetic patients in general practice (GPDM patients). Ischaemic heart disease and prior myocardial infarction were assessed by ECG recording. Peripheral arterial disease was assessed by the ankle-arm index. Intima-media thickness of the right common carotid artery was measured with ultrasound.A total of 195 SDM patients and 60 GPDM patients participated in the medical examination. The prevalence of MI was 13.3% (95% CI 9.3–18.8%) and 3.4% (1.0–11.7%) in SDM patients and GPDM patients respectively. The prevalence of ischaemic heart disease was 39.5% (95% CI 32.9–46.5%) in SDM patients and 24.1% (15.0–36.5%) in GPDM patients. The prevalence of peripheral arterial disease was similar in both groups: 10.6% (95% CI 6.9–15.9%) and 10.2% (4.7–20.5%) respectively. Mean intima-media thickness was 0.85 mm (±0.17) in SDM patients and 0.90 mm (±0.20) in GPDM patients. The difference in intima-media thickness was not statistically significant.Targeted screening identified patients with a prevalence of macrovascular complications similar to that of patients detected in general practice, but with a lower degree of hyperglycaemia. [ABSTRACT FROM AUTHOR]

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 -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 -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. [ABSTRACT FROM AUTHOR]

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. 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. 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). 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. Diabet. Med. (2004) [ABSTRACT FROM AUTHOR]

Background The aim of the study was to examine, by measurement of specific indicators of free radical-mediated oxidation of LDL, whether there is evidence of increased in vivo oxidation of LDL in type 2 diabetic patients, and to investigate their associations with carotid intima media thickness (IMT). Methods In native LDL, we quantified five different products of LDL oxidation reflecting various stages of LDL oxidative modification in 38 individuals with well- or moderately controlled type 2 diabetes (HbA1c ≤ 8.5%) and 38 gender-matched subjects with normal glucose metabolism. Baseline conjugated dienes (BCD), 7-OH-glycero-phosphocholine (7-OH-GPC), lyso-phosphatidylcholine (lyso-PC), and ketocholesterol were determined in LDL, and circulating in vivo oxidized apolipoprotein B100 (Ox-apoB) was measured in plasma. The IMT of the carotid artery was measured by ultrasound. Results Borderline higher carotid IMT values were observed in individuals with diabetes (0.88 ± 0.14 vs 0.83 ± 0.11 mm, p = 0.06). LDL-ketocholesterol (45.5 ± 19.4 vs 37.1 ± 13.8 nmol/mmol LDL-cholesterol, p < 0.05) and Ox-apoB (25.3 ± 5.5 vs 22.2 ± 5.8 U/mmol LDL-cholesterol, p < 0.05) were significantly increased in diabetic patients. The concentration of BCD, 7-OH-GPC and lyso-PC in LDL did not differ between diabetic patients and control subjects. No significant correlations were demonstrated between the measured indicators of LDL oxidation and carotid IMT. Conclusion Levels of BCD, 7-OH-GPC and lyso-PC, that is, intermediary products of LDL oxidation, were not significantly elevated, but ketocholesterol and Ox-apoB, that is, stable end products of the oxidation process, were increased in diabetic patients. We conclude that in vivo oxidation of LDL is increased, even in subjects with well- or moderately controlled type 2 diabetes. Copyright © 2004 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract 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. Diabet. Med. 20, 563–567 (2003). [ABSTRACT FROM AUTHOR]

Objectives: Amongst nondiabetic individuals, a high serum homocysteine concentration is an independent but relatively weak risk factor for coronary events. However, it is not known whether homocysteine increases risk of coronary events in type 2 diabetes. Therefore, we examined the combined effect of homocysteine and type 2 diabetes on risk of fatal and nonfatal coronary events.Subjects: We assessed the 10-year risk of coronary events associated with homocysteine amongst diabetic (n = 140) and nondiabetic (n = 361) individuals.Design: We did this in the Hoorn Study, a population-based study of glucose tolerance and related complications in Caucasian men and women aged 50-75 years.Results: The incidence rate for coronary events was 2.63 (29 of 140) per 100 person-years amongst diabetic and 1.29 (42 of 361) amongst nondiabetic individuals. Amongst diabetic individuals, risk of coronary events increased 28% for each 5-micromol L(-1) increment of homocysteine (hazard ratio, 1.28; 95% CI, 1.02-1.58). This risk was independent of age, sex, hypertension, total cholesterol, HDL-cholesterol, cigarette smoking, body mass index and glomerular filtration rate. In nondiabetic participants, homocysteine was not associated with an increased risk of coronary events (hazard ratio for each 5-micromol L(-1) increment of homocysteine, 0.86; 0.52-1.41).Conclusions: These data suggest that homocysteine is significantly associated with coronary events in individuals with type 2 diabetes, independent of traditional cardiovascular risk factors. Investigation of the effect of treatment with vitamin B on prognosis of individuals with type 2 diabetes is warranted. [ABSTRACT FROM AUTHOR]

Abstract 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. Diabet. Med. 20, 210–215 (2003). [ABSTRACT FROM AUTHOR]

Abstract Background It is unclear whether homocysteine itself is causal in the pathogenesis of cardiovascular disease. Alternatively or additionally, the association between homocysteine and cardiovascular disease may be because of its metabolic precursor, S-adenosylhomocysteine, or of the ratio of S-adenosylmethionine to S-adenosylhomocysteine. Therefore, it is relevant to know how these moieties are interrelated, and whether, as is the case for homocysteine, they are influenced by blood levels of folate, cobalamin or vitamin B6 . Design We cross-sectionally studied a population-based cohort of 97 Caucasian subjects aged 60–85 years. Concentrations of homocysteine, S-adenosylhomocysteine, S-adenosylmethionine, folate, cobalamin and vitamin B6 were measured in fasting blood samples. Results In multiple regression analysis, homocysteine was associated with vitamin B12 (per 50 pmol L-1 increase of cobalamin, change in homocysteine, –0·70 mmol L-1 ; 95% CI, -1·30 to -0·10 mmol L-1 ) and folate (per 100 nmol L-1 increase in erythrocyte folate, change in homocysteine, –0·68 mmol L-1 ; 95% CI -1·28 to -0·08 mmol L-1 ). S-adenosylhomocysteine, S-adenosylmethionine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine were not associated with serum folate, cobalamin or vitamin B6, nor with erythrocyte folate. Furthermore, plasma homocysteine showed a negative correlation with the ratio of S-adenosylmethionine to S-adenosylhomocysteine in plasma (r = -0·27; P < 0·01) but not in erythrocytes. Conclusions In contrast to homocysteine, the plasma concentrations of S-adenosylhomocysteine and the ratio of S-adenosylmethionine to S-adenosylhomocysteine were not associated with the folate, cobalamin and vitamin B6 concentrations in the present study. If these precursors in part explain why homocysteine is associated with... [ABSTRACT FROM AUTHOR]

Abstract Background Several studies have reported differences in the mortality risk between diabetic subjects detected by screening and known diabetic patients. We studied mortality in relation to diabetes duration, and the contribution of other cardiovascular risk factors to the elevated risk. Materials and methods Participants were type 2 diabetic subjects (n = 174) of a population-based cohort study. Of these, 95 were diagnosed by screening. Known diabetic subjects were grouped into two categories of diabetes duration, with a median duration of 2·4 and 11·2 years, respectively. We assessed the contribution of classical cardiovascular risk factors (dyslipidaemia, hypertension, and prior myocardial infarction), and of new cardiovascular risk factors (microalbuminuria, von Willebrand factor, sVCAM-1 and C-reactive protein) to the mortality risk during nearly 10 years of follow up. Cox's proportional hazards model was used to study the association of diabetes duration and mortality. Results The age- and sex-adjusted relative risks of mortality were 2·06 (95% C.I. 1·04–4·10) and 3·19 (1·64–6·20) for the patients with short- and long-term diabetes compared with the screening-detected diabetic subjects, respectively. Adjustment for cardiovascular risk factors resulted in a reduction of mortality risk in both groups: 1·13 (0·51–2·50) and 2·39 (1·18–4·83), respectively. Mortality risk significantly increased with increasing diabetes duration, even after multiple adjustment (P -value for trend ranged from < 0·001–0·018). Conclusions Mortality risk increased with increasing diabetes duration. In subjects with short diabetes duration the mortality risk could largely be attributed to other risk factors. In subjects with a longer diabetes duration, however, the elevated mortality risk was independent of these cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

Increased plasma levels of soluble adhesion molecules are associated with an increased risk of atherothrombosis. The pathophysiological mechanisms responsible for these associations are not known. The aim of the present study was to investigate the association of soluble intercellular adhesion molecule-1 (sICAM-1) concentration and risk of cardiovascular and all-cause mortality among individuals with and without type 2 diabetes. In addition, we assessed potential pathophysiological mechanisms by which sICAM-1 may promote mortality. Six hundred and thirty-one subjects taken from a general population of the middle-aged and elderly participated in this prospective cohort study. Baseline data collection was performed from 1989 to 1992; subjects were followed until 1 January 2000. Subjects who died had higher levels of sICAM-1 than those who survived (506(164) vs. 477(162) ng mL-1 , respectively). After adjustment for age, gender and glucose tolerance status, subjects with sICAM-1 levels in the upper quartile (≥550 ng mL-1 ) had a relative risk of cardiovascular mortality of 2·05 (95% confidence interval, 1·10–3·81) compared to subjects with sICAM-1 levels in the other quartiles. Further adjustment for classical cardiovascular risk factors or indicators of (sub)clinical atherosclerosis, endothelial dysfunction, inflammation and renal function did not materially alter this relative risk. A high sICAM-1 level was more frequent in subjects with type 2 diabetes than in subjects with a normal glucose tolerance (33·3 vs. 17·8%). Individuals with a plasma concentration of sICAM-1 higher than 550 ng mL-1 had a cardiovascular mortality risk that was twice that of individuals with a lower concentration. Classical cardiovascular risk factors (sub)clinical atherosclerosis, endothelial dysfunction and inflammation do not explain this excess risk. [ABSTRACT FROM AUTHOR]

BackgroundDecreased large artery function, as reflected by increased brachial artery pulse pressure and increased carotid artery diameter and stiffness, may contribute to the increased mortality risk that is observed in subjects with impaired glucose tolerance. We therefore investigated the association between brachial artery pulse pressure and carotid artery diameter and stiffness, which are estimates of central artery stiffness and arterial remodelling, respectively, and mortality in subjects with a recent history of impaired glucose tolerance. DesignA prospective, population-based cohort study. We measured brachial artery pulse pressure by oscillometric blood pressure measurements, and common carotid artery diameter and distensibility and compliance coefficients by ultrasound in 140 subjects with a recent history of impaired glucose tolerance. During a median 6·6-year follow-up, 16 subjects died. ResultsBrachial artery pulse pressure and common carotid artery diameter were positively related to all-cause mortality [hazard ratios per standard deviation, 1·7 (1·2–2·5) and 2·1 (1·3–3·3), respectively]. Results were similar after adjustment for gender, age, waist-to-hip ratio, body mass index, total cholesterol concentration, pre-existent cardiovascular disease, and hypertension, and after additional mutual adjustment. Common carotid artery distensibility and compliance coefficients were not statistically significantly associated with mortality. ConclusionsAmong subjects with a recent history of impaired glucose tolerance, brachial artery pulse pressure and common carotid artery diameter are independently associated with mortality risk. Stiffness of the central arteries may explain the association between pulse pressure and mortality risk. The association between carotid diameter and mortality risk is more likely to reflect arterial remodelling in response to atherosclerosis than that in response to increased local... [ABSTRACT FROM AUTHOR]

Abstract. Hoogeveen EK, Kostense PJ, Jakobs C, Rauwerda JA, Dekker JM, Nijpels G, Bouter LM, Heine RJ, Stehouwer CDA (University Hospital Vrije Universiteit, Amsterdam). Hyperhomocysteinaemia is not associated with isolated crural arterial occlusive disease: the Hoorn Study. J Intern Med 2000; 247: 442–448. Objectives. Hyperhomocysteinaemia is an independent risk factor for peripheral arterial disease (PAD). The localization of peripheral arterial disease is clinically relevant, because proximal (aortoiliac and femoropopliteal) disease is associated with a particularly poor overall prognosis, whereas isolated distal (i.e. crural) disease is associated with a better overall prognosis. The aim of the study was to investigate whether the strength of the association between hyperhomocysteinaemia and peripheral arterial disease differs according to the localization of the anatomical obstruction. Design. Fasting serum total homocysteine (tHcy) was measured in an age-, sex- and glucose-tolerance stratified random sample (n = 631) of a 50- to 75-year-old general Caucasian population. History of a peripheral arterial reconstruction was recorded. Aortoiliac, femoropopliteal and crural arterial obstructions were registered by means of Doppler flow velocity curves. Results. The median serum tHcy level was 12.2 µmol L–1 (interquartile range: 10.0–15.3) in men and 10.7 µmol L–1 (interquartile range: 9.0–13.3) in women. The prevalences of aortoiliac, femoropopliteal and crural obstructions were 2.1%, 2.7% and 11.9%, respectively. After adjustment for age, sex, systolic blood pressure, current smoking, serum cholesterol and diabetes mellitus, the odds ratios (95% confidence interval) per 5 µmol L–1 tHcy increment were 1.41 (1.05–1.89) for aortoiliac, 1.03 (0.70–1.52) for femoropopliteal and 0.82 (0.59–1.15) for crural obstructions. Finally, diabetes mellitus, HbA1c and current smoking were significantly associated with crural and femoropopliteal disease, whereas systolic blood pressure was significantly associated with aortoiliac obstructions. Conclusions. The present study indicates that hyperhomocysteinaemia is associated with aortoiliac but not with isolated crural arterial occlusive disease. [ABSTRACT FROM AUTHOR]

Objective: Distal somatic polyneuropathy is a major contributing factor in the pathogenesis of chronic foot infections and ulcers, and may lead to lower limb amputations. Both metabolic and vascular abnormalities may contribute to the development of impaired nerve function. We therefore assessed the association between hyperhomocysteinaemia, a risk factor for cardiovascular disease, and polyneuropathy.Design, Setting and Subjects: We studied an age-, sex- and glucose-tolerance-stratified random sample of a 50- to 75-year-old general Caucasian population in the Hoorn Study (N = 629). Any polyneuropathy (N = 95) was defined as the absence of at least two of the three following sensory modalities or reflexes of either foot: light touch sense, ankle reflex and vibration sensation. Definite polyneuropathy (N = 25) was present if, in addition, the vibration perception threshold of the right big toe was abnormal.Results: The prevalence of any polyneuropathy was 12.4% (33 of 266) in subjects with normal glucose tolerance (NGT), 12.6% (21 of 167) in those with impaired glucose tolerance (IGT), and 25.3% (41 of 162) in those with type 2 diabetes. The prevalence of definite polyneuropathy was 2.6% (7 of 266) in subjects with NGT, 2.4% (4 of 167) in those with IGT and 8.7% (14 of 161) in type 2 diabetic subjects. Polyneuropathy was associated with known risk factors such as diabetes, hyperglycaemia and body height. After adjustment for age, sex, HbA1c and hypertension, the odds ratio (95% CI) for any polyneuropathy per 5 micromol L-1 (about 1 SD) serum total homocysteine increment was 1.00 (0.72-1.39). After adjustment for age and sex, it was 0.62 (0.21-1.89) for definite polyneuropathy.Conclusion: Although a weak relation (as judged from the confidence intervals) cannot be excluded, we conclude that hyperhomocysteinaemia is probably not related to risk of distal somatic polyneuropathy. [ABSTRACT FROM AUTHOR]