Repository hosted by TU Delft Library

Aims/hypothesis: This systematic review examines the relationship between alcohol consumption and long-term complications of type 2 diabetes. Meta-analyses could only be performed for total mortality, mortality from CHD, and CHD incidence, because the availability of articles on other complications was too limited. Materials and methods: A PubMed search through to September 2005 was performed and the reference lists of relevant articles examined. Among the relevant articles there were six cohort studies reporting on the risk of total mortality and/or fatal and/or incident CHD in alcohol non-consumers and in at least two groups of alcohol consumers. Results: Statistical pooling showed lower risks in alcohol consumers than in non-consumers (the reference category). The relative risk (RR) of total mortality was 0.64 (95% CI 0.49-0.82) in the <6 g/day category. In the higher alcohol consumption categories (6 to <18, and ≥18 g/day), the RRs of total mortality were not significant. Risks of fatal and total CHD were significantly lower in all three categories of alcohol consumers (<6, 6 to <18 and ≥18 g/day) than in non-consumers, with RRs ranging from 0.34 to 0.75. Conclusions/interpretation: This meta-analysis shows that, as with findings in the general population, moderate alcohol consumption is associated with a lower risk of mortality and CHD in type 2 diabetic populations. © Springer-Verlag 2006.3

Objective. Assessing whether the initiation of insulin therapy in patients with diabetes mellitus type 2 can be delivered as effectively in a structured transmural care model as in the more usual outpatients structure. Design. Retrospective comparative cohort study. Method. In 1997 data were collected from 52 patients with diabetes mellitus type 2 all of whom were above 40 years of age and transferred to insulin therapy in 1993: 25 in a transmural care setting and 27 in an outpatients setting, both in Amsterdam, the Netherlands. Both groups were treated according to one protocol concerning the initiation and monitoring of insulin therapy, treatment goals and follow-up. Outcome measures were: percentage of glycated haemoglobin (HbA1c), health status, self-care behaviour and patient satisfaction. In 1993 the mean age was (transmural/outpatients setting): 67.5/65.3 years; percentage of men: 32%/48%; mean duration of diabetes: 7.3/10.6 years; HbA1c: 9.1%/9.3%; mean body mass index: 27.4/29.1 kg/m2. Results. In the period 1993-1997 the mean HbA1c decreased from 9.1% to 7.2% in the transmural care group and from 9.3% to 7.6% in the outpatients care group (both: p = 0.000). The percentage of patients with poor glycaemic control (HbA1c > 8%) decreased from 60 to 8 in the transmural care group and from 59 to 15 in the outpatients care group. The percentage of patients with good glycaemic control (HbA1c < 7%) increased from 4 to 52 in the transmural care group and from 11 to 30 in the outpatients care group. No statistically significant differences were found between the patient groups with respect to health status, self-care behaviour and patient satisfaction. Conclusion. The transfer of patients with diabetes mellitus type 2 insulin therapy in a shared care setting was at least as effective as in an outpatients setting. Chemicals/CAS: Hypoglycemic Agents; Insulin, 11061-68-0

OBJECTIVE - This meta-analysis was undertaken to obtain insight regarding the shape and strength of the relationship between alcohol consumption and the risk of type 2 diabetes, the effects of adjustment for confounders, and the effect of modification by type 2 diabetes definition, sex, and BMI. RESEARCH DESIGN AND METHODS - The 15 original prospective cohort studies that were included comprise 11,959 incident cases of type 2 diabetes in 369,862 individuals who, on average, were followed for 12 years. RESULTS - After pooling the data, a U-shaped relationship was found. Compared with nonconsumers, the relative risk (RR) for type 2 diabetes in those who consumed ≤6 g/day alcohol was 0.87 (95% CI 0.79-0.95). For the moderate consumption ranges of 6-12, 12-24, and 24-48 g/day, RRs of 0.70 (0.61-0.79), 0.69 (0.58-0.81), and 0.72 (0.62-0.84) were found, respectively. The risk of type 2 diabetes in heavy drinkers (≥48 g/day) was equal to that in nonconsumers (1.04 [0.84-1.29]). In general, nonsignificant trends for larger RR reduction associated with moderate alcohol consumption were observed for women compared with men, for crude compared with multivariate-adjusted analyses, and for studies that used self-reports instead of testing for type 2 diabetes definition. No differences in RR reductions were found between individuals with low or high BMI. CONCLUSIONS - The present evidence from observational studies suggests an ∼30% reduced risk of type 2 diabetes in moderate alcohol consumers, whereas no risk reduction is observed in consumers of ≥48 g/day. © 2005 by the American Diabetes Association.

OBJECTIVE - Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes. Adiponectin, an adipocyte-derived plasma protein, has been found to be negatively associated with adiposity and positively associated with insulin sensitivity. Moderate alcohol consumption may increase adiponectin, which in turn causes a decrease of tumor necrosis factor (TNF)-α. A decreased TNF-α level may consequently increase insulin sensitivity. RESEARCH DESIGN AND METHODS - To test this hypothesis, we performed a randomized crossover partially diet-controlled study. A total of 23 healthy middle-aged male subjects consumed daily four glasses of whisky (40 g ethanol) or tap water with dinner during two successive periods of 17 days. RESULTS - Moderate alcohol consumption increased plasma adiponectin level (11%; P = 0.002) but did not affect plasma TNF-α level. An increase in insulin sensitivity index was observed in an insulin-resistant subgroup (21%; P = 0.11), which positively correlated with the relative alcohol-induced increase in plasma adiponectin level (r = 0.73, P = 0.02). CONCLUSIONS - The experimental results are in agreement with observational data. Moderate alcohol consumption improved insulin sensitivity in relatively insulin-resistant middle-aged men, an effect that may be mediated through alcohol-induced increases in adiponectin.

Background: Hyperhomocysteinaemia may constitute an independent risk factor for cardiovascular disease, but it is still unclear by which pathophysiological mechanisms homocysteine (tHcy) may promote atherothrombosis. The aim of this study was firstly to examine whether tHcy is associated with endothelial dysfunction, increased adherence of leukocytes, and/or chronic low-grade inflammation, as estimated from plasma levels of von Willebrand factor (vWf), soluble vascular cell adhesion molecule 1 (sVCAM-1) and C-reactive protein (CRP), respectively. Secondly we investigated whether the presence of type 2 diabetes modifies these associations. Materials and Methods: Six hundred and ten subjects of a general population of middle-aged and elderly subjects, 170 of whom had type 2 diabetes, participated in this cross-sectional study. Linear regression analyses were used to study whether tHcy was associated with vWf, sVCAM-1 and CRP, and whether the presence of diabetes modified these associations. Results: After adjustment for confounders, tHcy was significantly but weakly associated with vWf (β=0·15, P=0·05) and sVCAM-1 (β=0·082, P=0·04). tHcy was not significantly associated with CRP (β=0·02, P=0·91). The presence of diabetes did not significantly modify these associations. Conclusions: This study provides evidence that tHcy is, at most, weakly associated with endothelial dysfunction as estimated from plasma vWf, and with leukocyte adhesion as estimated from plasma sVCAM-1. tHcy was not significantly associated with chronic low-grade inflammation as estimated from plasma CRP. Our data thus suggest that the link between tHcy and atherothrombosis cannot be explained by associations of tHcy with vWf, sVCAM-1 or CRP. Chemicals/CAS: C-Reactive Protein, 9007-41-4; Cell Adhesion Molecules; Homocysteine, 454-28-4; von Willebrand Factor

Increased levels of von Willebrand factor (vWf) and C-reactive protein (CRP) predict cardiovascular mortality in selected populations. It is uncertain whether vWf and CRP predict mortality in a general population and whether vWf and CRP predict mortality through similar pathways. This study investigated the association of vWf and CRP with cardiovascular and all-cause mortality among diabetic and nondiabetic subjects. An age-, sex-, and glucose tolerance-stratified sample (n=631) of a population-based cohort aged 50 to 75 years was followed prospectively for 5 years. After 5 years of follow-up, 58 subjects had died (24 of cardiovascular causes). vWf (>1.56 IU/mL) and CRP (>2.84 mg/L) levels in the upper tertile were associated with, respectively, a 3- and 2-fold increase in cardiovascular mortality after adjustment for age, sex, and glucose tolerance status. Analyses in nondiabetic and diabetic subjects separately gave similar results. After further adjustment for hypertension, levels of HDL cholesterol and triglyceride, smoking habits, ischemic heart disease, and peripheral arterial disease, the relative risks (RRs) were 3.0 (95% CI 1.2 to 7.9) for vWf and 1.4 (95% CI 0.6 to 3.5) for CRP. When both vWf and CRP were included in the latter multivariate analysis, the RRs were 3.0 (95% CI 1.1 to 7.9) for vWf and 1.3 (95% CI 0.5 to 3.4) for CRP. The association between vWf and risk of cardiovascular mortality was independent of blood group (O versus non-O) and, moreover, similar among subjects with different blood groups. Repeating the analyses for all-cause mortality gave similar results for CRP. For vWf, the RR was 2.0 (95% CI 1.1 to 3.5) after adjustment for all other risk factors. Increased levels of vWf are independently associated with cardiovascular and all-cause mortality in both diabetic and nondiabetic subjects. The association between increased levels of CRP and cardiovascular mortality was partly explained by other risk factors. Mutual adjustment of vWf and CRP did not markedly change the results, favoring the hypothesis that vWf and CRP predict mortality through different pathways.

OBJECTIVE - A nationwide retrospective study was conducted to assess the incidence of type 1 diabetes in The Netherlands among children <20 years of age in 1988-1990. The first study with a similar design covered 1978-1980. RESEARCH DESIGN AND METHODS - The capture-recapture census method was chosen for analysis of the data. A questionnaire was sent to all Dutch pediatricians and internists, and for the ascertainment, a similar questionnaire was sent out separately to members of the Dutch Diabetes Association, which is the national patient association. RESULTS - The average achieved ascertainment rate was 81%. The ascertainment-adjusted annual incidence was 13.2/100,000 for 0- to 19-year-old children, indicating an increase of 23% compared with the 1978-1980 survey; for 0- to 14-year-olds, the increase amounted to 17%. CONCLUSIONS - This study suggests a sustained increase of type 1 diabetes in The Netherlands because the cumulative incidence studied previously in the 1960-1970 birth cohorts of male army conscripts 18 years of age was also found to rise. In contrast to Northern European countries, an increase in incidence for the age category 0-4 years could not be found.

Aims: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. Methods: Four potentially functional variants in the coding region of the DRD2/ANKK1 locus (rs1079597, rs6275, rs6277, rs1800497) were genotyped and analysed for Type 2 diabetes susceptibility in up to 25 000 people (8148 with Type 2 diabetes and 17687 control subjects) from two large independent Dutch cohorts and one Danish cohort. In addition, 340 Dutch subjects underwent a 2-h hyperglycaemic clamp to investigate insulin secretion. Since sexual dimorphic associations related to DRD2 polymorphisms have been previously reported, we also performed a gender-stratified analysis. Results: rs1800497 at the DRD2/ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women (odds ratio 1.14 (1.06-1.23); P = 4.1*10-4) but not in men (odds ratio 1.00 (95% CI 0.93-1.07); P = 0.92) or the combined group. Although rs1800497 was not associated with insulin secretion, we did find another single nucleotide polymorphism in this locus, rs6275, to be associated with increased first-phase glucose-stimulated insulin secretion in women (P = 5.5*10-4) but again not in men (P = 0.34). Conclusion: The present data identify DRD2/ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene. What's new?: The rs1800497 single nucleotide polymorphism at the DRD2/ANKK1 locus was associated with a significantly increased risk for Type 2 diabetes in women but not in men. The rs6275 single nucleotide polymorphism in the DRD2 gene is associated with increased first-phase glucose-stimulated insulin secretion in women only. Our data identify DRD2/ANKK1 as a potential sex-specific Type 2 diabetes susceptibility gene. © 2014 Diabetes UK. Chemicals/CAS: glucose, 50-99-7, 84778-64-3; insulin, 9004-10-8