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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. [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]

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/Objective:Early insulin secretion following a meal is representative for normal physiology and may depend on meal composition. To compare the effects of a fat-rich and a carbohydrate-rich mixed meal on insulinogenic index as a measure of early insulin secretion in normoglycemic women (NGM) and in women with type 2 diabetes mellitus (DM2), and to assess the relationship of anthropometric and metabolic factors with insulinogenic index.Subjects/Methods:Postmenopausal women, 76 with NGM and 64 with DM2, received a fat-rich meal and a carbohydrate-rich meal on separate occasions. Early insulin response was estimated as insulinogenic index (△insulin0–30 min/△glucose0−30 min) for each meal. Associations of fasting and postprandial triglycerides, body mass index, waist and hip circumference and alanine aminotransferase with insulinogenic indices were determined.Results:Women with NGM present with higher insulinogenic index than women with DM2. The insulinogenic index following the fat-rich meal (△I30/△G30 (fat)) was higher than the index following the carbohydrate-rich meal (△I30/△G30 (CH)) (P<0.05 in women with DM2, and not significant in women with NGM). In women with DM2, homeostasis model assessment for insulin resistance was positively associated with △I30/△G30 (CH). In women with NGM, waist circumference was independently and inversely associated with △I30/△G30 (fat) and with △I30/△G30 (CH); hip circumference was positively associated with △I30/△G30 (fat).Conclusions:The insulinogenic index following the fat-rich meal was higher than following the isocaloric carbohydrate-rich meal, which might favorably affect postprandial glucose excursions, especially in women with DM2. The association between a larger waist circumference and a lower meal-induced insulinogenic index in women with NGM requires further mechanistic studies.European Journal of Clinical Nutrition (2009) 63, 398–404; doi:10.1038/sj.ejcn.1602953; published online 7 November 2007 [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]

The association between depression and insulin resistance has been investigated in only a few studies, with contradictory results reported. The aim of this study was to determine whether the association between symptoms of depression and insulin resistance varies across glucose tolerance status and between men and women. Cross-sectional data from a population-based cohort study in Hoorn, a medium-sized town in the Netherlands, were analysed. The study sample consisted of 541 men and women aged 55–75 years, of whom 260 had NGT, 164 had IGT and 117 had established type 2 diabetes mellitus. Main outcome measures were insulin resistance defined by the homeostasis model assessment for insulin resistance (HOMA-IR) and symptoms of depression using the Centre for Epidemiologic Studies Depression Scale (CES-D). In the total sample, we found a weak positive correlation between the depressive symptoms CED-D scores and HOMA-IR scores ( r s = 0.156, p < 0.001). Even weaker associations were found in subjects with NGT ( r s = 0.041, p=0.509), in subjects with IGT ( r s = 0.112, p = 0.160) and in subjects with type 2 diabetes ( r s = 0.007, p = 0.942). The association between depressive symptoms and insulin resistance was similar for men and women. We found only weak associations between depressive symptoms and insulin resistance, which did not differ among different glucose metabolism subgroups or between men and women. [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]

Aims/hypothesis. Coffee contains several substances that may affect glucose metabolism. The aim of this study was to evaluate the relationship between habitual coffee consumption and the incidence of IFG, IGT and type 2 diabetes. Methods. We used cross-sectional and prospective data from the population-based Hoorn Study, which included Dutch men and women aged 50–74 years. An OGTT was performed at baseline and after a mean follow-up period of 6.4 years. Associations were adjusted for potential confounders including BMI, cigarette smoking, physical activity, alcohol consumption and dietary factors. Results. At baseline, a 5 cup per day higher coffee consumption was significantly associated with lower fasting insulin concentrations (-5.6%, 95% CI -9.3 to -1.6%) and 2-h glucose concentrations (-8.8%, 95% CI -11.8 to -5.6%), but was not associated with lower fasting glucose concentrations (-0.8%, 95% CI -2.1 to 0.6%). In the prospective analyses, the odds ratio (OR) for IGT was 0.59 (95% CI 0.36–0.97) for 3–4 cups per day, 0.46 (95% CI 0.26–0.81) for 5–6 cups per day, and 0.37 (95% CI 0.16–0.84) for 7 or more cups per day, as compared with the corresponding values for the consumption of 2 or fewer cups of coffee per day (p=0.001 for trend). Higher coffee consumption also tended to be associated with a lower incidence of type 2 diabetes (OR 0.69, CI 0.31–1.51 for ≥7 vs ≤2 cups per day, p=0.09 for trend), but was not associated with the incidence of IFG (OR 1.35, CI 0.80–2.27 for ≥7 vs ≤2 cups per day, p=0.49 for trend). Conclusions/interpretation. Our findings indicate that habitual coffee consumption can reduce the risk of IGT, and affects post-load rather than fasting glucose metabolism. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Fat distribution as measured by waist-to-hip ratio has been shown to be an important independent predictor of glucose intolerance. Few studies, however, have considered the contributions of the waist and hip circumferences independently. The aim of this study was to investigate the independent associations of waist and hip circumference with diabetes in a large population-based study, and to investigate whether they also apply to other major components of the metabolic syndrome (hypertension and dyslipidemia). In addition, as previous studies were performed in older persons, we investigated whether these associations were present across adult age groups. METHODS:: Weight, height, waist and hip circumferences were measured in 11?247 participants of the nationally representative Australian Diabetes, Obesity and Lifestyle (AusDiab) Study. HDL-cholesterol, triglycerides, fasting and 2-h postload glucose were determined, and diastolic and systolic blood pressure was measured. After exclusion of persons already known to have diabetes, hypertension or dyslipidemia, logistic and linear regression were used to study cross-sectional associations of anthropometric variables with newly diagnosed diabetes, hypertension and dyslipidemia, and with continuous metabolic measures, all separately for men (n=3818) and women (n=4582). Analyses were repeated in the same population stratified for age. RESULTS:: After adjustment for age, body mass index and waist, a larger hip circumference was associated with a lower prevalence of undiagnosed diabetes (odds ratio (OR) per one s.d. increase in hip circumference 0.55 (95% CI 0.41-0.73) in men and 0.42 (0.27-0.65) in women) and undiagnosed dyslipidemia (OR 0.58 (0.50-0.67) in men and 0.37 (0.30-0.45) in women). Associations with undiagnosed hypertension were weaker (OR 0.80 (0.69-0.93) in men and 0.88 (0.70-1.11) in women). As expected, larger waist circumference was associated with higher prevalence of these conditions. Similar associations were found using continuous metabolic variables as outcomes in linear regression analyses. Height partly explained the negative associations with hip circumference. When these analyses were performed stratified for age, associations became weaker or disappeared in the oldest age groups (age =75?y in particular), except for HDL-cholesterol. CONCLUSION:: We found independent and opposite associations of waist and hip circumference with diabetes, dyslipidemia and less strongly with hypertension in a large population-based survey. These results emphasize that waist and hip circumference are important predictors for the metabolic syndrome and should both be considered in epidemiological studies. The associations were consistent in all age groups, except in age =75?y. Further research should be aimed at verifying hypotheses explaining the ‘protective’ effect of larger hips.International Journal of Obesity (2004) 28, 402-409. doi:10.1038/sj.ijo.0802567 Published online 13 January 2004 [ABSTRACT FROM AUTHOR]

Aims/hypothesis. There is accumulating evidence that depression is common in people with Type 2 diabetes. However, most prevalence-studies are uncontrolled and could also be inaccurate from selection-bias, as they are conducted in specialized treatment settings. We studied the prevalence and risk factors of co-morbid depression in a community-based sample of older adults, comparing Type 2 diabetic patients with healthy control subjects. Methods. A large (n=3107) community-based study in Dutch adults (55–85 years of age) was conducted. Pervasive depression was defined as a CES-D score greater than 15. Diagnosis of Type 2 diabetes was obtained from self-reports and data from general practitioners. Results. A number of 216 patients (7%) were identified as having Type 2 diabetes. The prevalence of pervasive depression was increased in people with Type 2 diabetes and co-morbid chronic disease (20%) but not in patients with Type 2 diabetes only (8%), compared with the healthy control subjects (9%). Regression analyses in diabetic patients yielded that being single, being female, having functional limitations, receiving instrumental support and having an external locus of control were associated with higher levels of depression. Conclusions/interpretation. The Results suggest that the prevalence of pervasive depression is increased in patients with Type 2 diabetes and co-morbid disease(s), but not in patients with Type 2 diabetes only. Functional limitations that often accompany co-morbid chronic disease could play an essential role in the development of depression in Type 2 diabetes. These findings can enable clinicians and researchers to identify high-risk groups and set up prevention and treatment programs. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. Type 2 diabetes is not only associated with hyperglycaemia, but also with disorders of lipid metabolism. The aim of this study was to investigate the association of triglyceride and non-HDL-cholesterol concentrations with cardiovascular disease in subjects with normal and abnormal glucose metabolism. Methods. Subjects were 869 men and 948 women aged 50 to 75 who participated in the Hoorn Study, a population-based cohort study that started in 1989. Glucose metabolism was determined by a 75 g OGTT. High fasting triglyceride and non-HDL-cholesterol concentrations were defined as above the median of the study population. Results. After 10 years of follow-up, the age- and sex-adjusted hazard ratios for cardiovascular disease were 1.35 (1.11–1.64) and 1.71 (1.40–2.08) for high triglycerides and high non-HDL-cholesterol, respectively, after mutual adjustment. After stratification for glucose metabolism status, the hazard ratios for cardiovascular disease for non-HDL-cholesterol were 1.70 (1.31–2.21) in normal glucose metabolism and 1.56 (1.12–2.18) in abnormal glucose metabolism. Triglycerides were not a risk factor in subjects with normal glucose metabolism, with a hazard ratio of 0.94 (0.73–1.22), but in subjects with abnormal glucose metabolism, the hazard ratio for cardiovascular disease was 1.54 (1.07–2.22). In subjects with abnormal glucose metabolism, the hazard ratio for the combined presence of high triglycerides and non-HDL-cholesterol was 2.12 (1.35–3.34). Conclusion. Our data suggest that in people with abnormal glucose metabolism, but not in those with normal glucose metabolism, high triglyceride concentration could be associated with the risk of cardiovascular disease, particularly in people with high non-HDL-cholesterol. [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]

Aims/hypothesis. The sulphonylurea receptor is a subunit of the ATP-sensitive potassium channel in the pancreatic beta cell. Mutations at nt –3 of the splice acceptor site of exon 16 and a silent mutation in exon 18 of the gene for the sulphonylurea receptor (SUR1) associate with Type II (non-insulin-dependent) diabetes mellitus in several independent populations. We investigated whether these gene variants associate with changes in the pattern of glucose-stimulated insulin secretion.¶Methods. Subjects who had normal glucose tolerance (n = 67) and subjects with an impaired glucose tolerance (n = 94), originating from two independent studies, were included in the study. Beta-cell function and insulin sensitivity were assessed by the hyperglycaemic clamp.¶Results. Frequencies of the exon 16 –3t allele in the normal and impaired glucose tolerant groups were 46 % and 44 % respectively (p = NS). The more rare exon 18 T allele showed frequencies of 5 and 7 % respectively (p = NS). We observed an approximately 25 % reduced second-phase insulin secretion in carriers of the exon 16 –3t allele in both groups (p < 0.05). Estimates of insulin sensitivity did not show differences between carriers and non-carriers. The variant in exon 18 and the combined presence of variants in exon 16 and exon 18 were not associated with differences in insulin secretion or insulin sensitivity in our study groups.¶Conclusion/interpretation. The diabetes associated exon 16 –3t variant of the SUR1 gene associates with a functional change of the beta cell as reflected by reduced second-phase insulin secretion in response to a standardized hyperglycaemia in normal and impaired glucose tolerant subjects. [Diabetologia (2000) 43: 515–519] [ABSTRACT FROM AUTHOR]

Presents a letter to the editor concerning lack of association between gene variants in the ALMS1 gene and type 2 diabetes mellitus.