E. J. M. Feskens

Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM): preliminary results after one year

AIMS: Important risk factors for the progression from impaired glucose tolerance to type II diabetes mellitus are obesity, diet and physical inactivity. The aim of this study is to evaluate the effect of a lifestyle-intervention programme on glucose tolerance in Dutch subjects with impaired glucose tolerance (IGT).METHODS: A total of 102 subjects were studied, randomised into two groups. Subjects in the intervention group received regular dietary advice, and were stimulated to lose weight and to increase their physical activity. The control group received only brief information about the beneficial effects of a healthy diet and increased physical activity. Before and after the first year, glucose tolerance was measured and several other measurements were done.RESULTS: Body weight loss after 1u2009y was higher in the intervention group. The 2-h blood glucose concentration decreased 0.8±0.3u2009mmol/l in the intervention group and increased 0.2±0.3u2009mmol/l in the control group (P<0.05). Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity.CONCLUSION: A lifestyle-intervention programme according to general recommendations is effective and induces beneficial changes in lifestyle, which improve glucose tolerance in subjects with IGT. Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity.

Impact of 3-year lifestyle intervention on postprandial glucose metabolism: the SLIM study

Objectiveu2003 To determine the effect of a 3‐year diet and exercise lifestyle intervention, based on general public health recommendations, on glucose tolerance, insulin resistance and metabolic cardiovascular risk factors in Dutch subjects with impaired glucose tolerance (IGT).

Common variants in the ATP-sensitive K+ channel genes KCNJ11 (Kir6.2) and ABCC8 (SUR1) in relation to glucose intolerance : population-based studies and meta-analyses

Aimsu2003 To evaluate the relation between common variants in the ATP‐sensitive K+ channel genes and glucose intolerance.

Direct association of a promoter polymorphism in the CD36/FAT fatty acid transporter gene with Type 2 diabetes mellitus and insulin resistance

Aimsu2003 The membrane‐bound fatty acid transporter CD36/FAT may play a role in disturbed fatty acid handling as observed in the metabolic syndrome and Type 2 diabetes mellitus (T2DM). Genetic variation in the CD36 gene may contribute to the aetiology of diabetes.

Prevalence of maternally inherited diabetes and deafness in diabetic populations in the Netherlands

abnormal Valsalva ratio (in 18 patients, p < 0.001 at both comparisons, McNemar test). Abnormal handgrip test (in 73 patients) was found significantly more often than an abnormal fall in blood pressure after standing up (in 3patients, p < 0.001, McNemar test). Abnormal blood pressure tests were present only if at least one of the heart rate tests was abnormal. Data were analysed according to two different protocols. By the E U R O D I A B protocol 38 patients (18 %) had false negative results: they had normal 30/15 ratio and normal blood pressure response to standing; however, in 18 patients one, and in 20 patients, more than one of the three other tests were abnormal. According to our protocol, heart rate response to deep breathing and 30/15 ratio were examined. In this case, only three patients (1.5 %) showed false-negative results, only the Valsalva ratio being abnormal. Both heart rate responses to deep breathing and standing were abnormal in 45 of our 206 patients. However, 32 of these 45 patients had abnormal results in at least one of the three other tests as well, indicating moderate to severe autonomic involvement. Thus, evaluation of these two tests also seems to provide some possibility for the assessment of severity of autonomic dysfunction. Both protocols examined the 30/15 ratio. Evaluation of heart rate response to deep breathing instead of blood pressure response to standing seems to be a useful alternative way 1169

Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus

Aimsu2002 Thioredoxin interacting protein (TXNIP) is an attractive candidate gene for diabetes or diabetic dyslipidaemia, since TXNIP is the strongest glucose‐responsive gene in pancreatic B‐cells, TXNIP deficiency in a mouse model is associated with hyperlipidaemia and TXNIP is located in the 1q21‐1q23 chromosomal Type 2 diabetes mellitus (DM) locus. We set out to investigate whether metabolic effects of TXNIP that were previously reported in a murine model are also relevant in human Type 2 DM.

Distinct associations of complement C3a and its precursor C3 with atherosclerosis and cardiovascular disease. The CODAM study.

Complement C3 is a novel risk factor for cardiovascular disease (CVD), but the underlying mechanism is currently unknown. We determined the associations of the anaphylatoxin C3a, the activation product of C3, and of C3 itself with estimates of atherosclerosis and CVD. We studied associations of C3a and C3 with carotid intima-media thickness (cIMT), ankle-arm blood pressure index (AAIx) and CVD in cross-sectional analyses among 545 participants of the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) study (62% men, 59.4 ± 6.9 years) and examined effect modification by smoking. We conducted linear and logistic regression analyses with adjustments for age, sex, glucose metabolism status, lipids, adiposity, renal function, blood pressure, pack-years smoked, physical activity, use of medication and investigated mediation by inflammation. C3a was independently associated with cIMT (β=0.032 mm, [95% confidence interval: 0.004; 0.060]) and AAIx (β=-0.022, [-0.043; -0.001]), but C3 was not. Effect modification by smoking was only observed for CVD (P(smoking*C3a)=0.008, P(smoking*C3)=0.018), therefore these associations were stratified for smoking behaviour. Both C3a (odds ratio [OR] =2.96, [1.15; 7.62]) and C3 (OR =1.98, [1.21; 3.22]) were independently associated with CVD in heavy smokers. The association of C3 with CVD was independent of C3a. Low-grade inflammation did partially explain the association of C3a with AAIx, but not the other observed associations. This suggests that C3a and C3 have distinct roles in pathways leading to CVD. C3a may promote atherosclerosis and additionally advance CVD in heavy smokers. Conversely, C3 may be associated with CVD in heavy smokers via pathways other than atherosclerosis.

The alternative complement pathway is longitudinally associated with adverse cardiovascular outcomes The CODAM study

The alternative pathway of complement activation is highly reactive and can be activated spontaneously in the vasculature. Activation may contribute to vascular damage and development of cardiovascular disease (CVD). We aimed to investigate functional components of the alternative pathway in cardiovascular risk. We studied 573 individuals who were followed-up for seven years. At baseline, we measured the enhancer properdin; the rate-limiting protease factor D (FD); and a marker of systemic activation, Bb. Using generalised estimating equations, we investigated their longitudinal associations with cardiovascular events (CVE, N=89), CVD (N=159), low-grade inflammation (LGI), endothelial dysfunction (ED) and carotid intima-media thickness (cIMT). Furthermore, we investigated associations with incident CVE (N=39) and CVD (N=73) in 342 participants free of CVD at baseline. CVE included myocardial infarction, stroke, cardiac angioplasty and/or cardiac bypass. CVD additionally included ischaemia on an electrocardiogram and/or ankle-brachial index < 0.9. In adjusted analyses, properdin was positively associated with CVE (per 1SD, longitudinal OR=1.36 [1.07; 1.74], OR for incident CVE=1.53 [1.06; 2.20]), but not with CVD. Properdin was also positively associated with ED (β=0.13 [95%CI 0.06; 0.20]), but not with LGI or cIMT. FD and Bb were positively associated with LGI (per 1SD, FD: β=0.21 [0.12; 0.29], Bb: β=0.14 [0.07; 0.21]), and ED (FD: β=0.20 [0.11; 0.29], Bb: β=0.10 [0.03; 0.18]), but not with cIMT, CVE or CVD. Taken together, this suggests that the alternative complement pathway contributes to processes of vascular damage, and that in particular a high potential to enhance alternative pathway activation may promote unfavourable cardiovascular outcomes in humans.

Subscapular skinfold thickness distinguishes between transient and persistent impaired glucose tolerance: Study on Lifestyle‐Intervention and Impaired Glucose Tolerance Maastricht (SLIM)

Aims To assess whether adding anthropometric measurements to an oral glucose tolerance test (OGTT) can help to distinguish between transient and persistent impaired glucose tolerance (IGT).

Impact of 3-year lifestyle intervention on postprandial glucose metabolism

Objectiveu2003 To determine the effect of a 3‐year diet and exercise lifestyle intervention, based on general public health recommendations, on glucose tolerance, insulin resistance and metabolic cardiovascular risk factors in Dutch subjects with impaired glucose tolerance (IGT).