Abstract-Impaired glucose metabolism (IGM) and type 2 diabetes (DM-2) are associated with high cardiovascular disease risk. Increases in peripheral and central artery stiffness may represent pathophysiologic pathways through which glucose tolerance status leads to cardiovascular disease. Peripheral artery stiffness increases with deteriorating glucose tolerance status, whereas this trend remains unclear for central artery stiffness. Therefore, we investigated the associations between glucose tolerance status and estimates of central arterial stiffness. We performed a population-based study of 619 individuals (normal glucose metabolism, nϭ261; IGM, nϭ170; and DM-2, nϭ188) and assessed central artery stiffness by measuring total systemic arterial compliance, aortic pressure augmentation index, and carotid-femoral transit time. After adjustment for sex, age, heart rate, height, body mass index, and mean arterial pressure, DM-2 was associated with decreased total systemic arterial compliance, increased aortic augmentation index, and decreased carotid-femoral transit time. IGM was borderline significantly associated with decreased total systemic arterial compliance. Respective regression coefficients (95% confidence intervals) for IGM and DM-2 compared with normal glucose metabolism were Ϫ0.05 (Ϫ0.11 to 0.01) and Ϫ0.13 (Ϫ0.19 to Ϫ0.07) mL/mm Hg for total systemic arterial compliance; 1.1 (Ϫ0.2 to 2.5) and 1.

Diabetes patients are known to have a worse quality of life than individuals without diabetes. They also have an increased risk for depressive symptoms, which may have an additional negative effect on their quality of life. This systematic review summarizes the current knowledge on the association between depressive symptoms and quality of life in individuals with diabetes. A systematic literature search using MEDLINE, Psychinfo, Social SciSearch, SciSearch and EMBASE was conducted from January 1990 until September 2007. We identified studies that compared quality of life between diabetic individuals with and without depressive symptoms. Twenty studies were identified, including eighteen cross-sectional and two longitudinal studies. Quality of life was measured as generic, diabetes specific and domain specific quality of life. All studies reported a negative association between depressive symptoms and at least one aspect of quality of life in people with diabetes. Diabetic individuals with depressive symptoms also had a severely lower diabetes specific quality of life. Generic and domain specific quality of life were found to be mild to moderately lower in the presence of depressive symptoms. Therefore, increased awareness and monitoring for depression is needed within different diabetes care settings.

OBJECTIVES: To investigate whether higher circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and a1-antichymotrypsin (ACT) are associated with worse cognitive function and decline in old age. DESIGN: Two independent population-based cohort studies. SETTING: The Rotterdam Study (mean follow-up 4.6 years) and the Leiden 85-plus Study (maximal follow-up 5 years). PARTICIPANTS: Three thousand eight hundred seventyfour individuals, mean age 72, from the Rotterdam Study, and 491 individuals, all aged 85, from the Leiden 85-plus Study. MEASUREMENTS: Both studies assessed global cognition, executive function, and memory. Linear regression analyses were used in the current study to investigate the associations between inflammatory markers and cognitive function and decline. RESULTS: In the Rotterdam Study, higher levels of CRP and IL-6 were cross-sectionally associated with worse global cognition and executive function (Po.05). ACT was not associated with cognitive function. In the Leiden 85-plus Study, estimates were similar for CRP, although not statistically significant. Higher IL-6 levels were related to a steeper annual decline in memory function in the longitudinal analysis in the Leiden 85-plus Study (Po.05). The effect of higher IL-6 levels on global and memory function decline was stronger in apolipoprotein E (APOE) e4 carriers (P-interaction 5 .01) than in those who were not (P-interaction 5 .05). In the Rotterdam Study, higher IL-6 levels were related to a steeper annual decline in global cognition in APOE e4 carriers only.CONCLUSION: Systemic markers of inflammation are only moderately associated with cognitive function and decline and tend to be stronger in carriers of the APOE e4 allele. Systemic markers of inflammation are not suitable for risk stratification. J Am Geriatr Soc 55: 708-716, 2007.

ObjectiveTo examine the association between depression and all-cause and cardiovascular mortality in people with diabetes by systematically reviewing the literature and carrying out a meta-analysis of relevant longitudinal studies.Research Design and MethodsPUBMED and PSYCINFO were searched for articles assessing mortality risk associated with depression in diabetes up until August 16, 2012. The pooled hazard ratios were calculated using random-effects models.ResultsSixteen studies met the inclusion criteria, which were pooled in an overall all-cause mortality estimate, and five in a cardiovascular mortality estimate. After adjustment for demographic variables and micro- and macrovascular complications, depression was associated with an increased risk of all-cause mortality (HR = 1.46, 95% CI = 1.29–1.66), and cardiovascular mortality (HR = 1.39, 95% CI = 1.11–1.73). Heterogeneity across studies was high for all-cause mortality and relatively low for cardiovascular mortality, with an I-squared of respectively 78.6% and 39.6%. Subgroup analyses showed that the association between depression and mortality not significantly change when excluding three articles presenting odds ratios, yet this decreased heterogeneity substantially (HR = 1.49, 95% CI = 1.39–1.61, I-squared = 15.1%). A comparison between type 1 and type 2 diabetes could not be undertaken, as only one study reported on type 1 diabetes specifically.ConclusionsDepression is associated with an almost 1.5-fold increased risk of mortality in people with diabetes. Research should focus on both cardiovascular and non-cardiovascular causes of death associated with depression, and determine the underlying behavioral and physiological mechanisms that may explain this association.

Aims/hypothesis: The pathogenesis of vascular complications in type 1 diabetes is poorly understood, but may involve chronic, low-grade inflammation. We investigated the association of markers of inflammation with vascular complications in type 1 diabetes. Methods: A cross-sectional nested case-control study of the follow-up data of the EURODIAB Prospective Complications Study. This study included 543 individuals (278 men) with type 1 diabetes diagnosed at <36 years of age. Cases (n=348) had complications of diabetes, controls (n=195) had no complications. Results: C-reactive protein, interleukin-6 and tumour necrosis factor-α levels, which were combined in an inflammatory marker Z-score, were associated with albuminuria, retinopathy and cardiovascular disease. Conclusions/interpretation:We have shown that markers of inflammation are strongly and independently associated with microvascular complications and cardiovascular disease in type 1 diabetes. These data suggest that strategies to decrease inflammatory activity may help to prevent the development of vascular complications in type 1 diabetes.

1C-reactive protein (CRP) has been shown to be associated with type 2 diabetes, but whether CRP has a causal role is not yet clear. We examined the association in the Rotterdam Study, a population-based prospective cohort study. The association of baseline serum CRP and incident diabetes during follow-up was investigated, and a meta-analysis was conducted on the BMI-adjusted relation of CRP and diabetes. Furthermore, the association of CRP haplotypes with serum CRP and risk of diabetes was assessed. The ageand sex-adjusted hazard ratio for diabetes was 1.41 (95% CI 1.29 -1.54) per 1 SD increase in natural logarithm of CRP, and it was 1.88, 2.16, and 2.83 for the second, third, and fourth quartiles of CRP, respectively, compared with the first quartile. The risk estimates attenuated but remained statistically significant after additional adjustment for obesity indexes, which agreed with the results of the meta-analysis. The most common genetic haplotype was associated with a significantly lower CRP level compared with the three other haplotypes. The risk of diabetes was significantly higher in the haplotype with the highest serum CRP level compared with the most common haplotype (OR 1.45, 95% CI 1.08 -1.96). These findings support the hypothesis that serum CRP enhances the development of diabetes. Diabetes 56:872-878, 2007 P rospective studies have shown that C-reactive protein (CRP), which is a general marker of systemic inflammation, is associated with the risk of diabetes (1-9). CRP is produced by hepatocytes, and its gene expression is regulated by tumor necrosis factor-␣ and interleukin-6, which are secreted by adipocytes (10). As a result, obese individuals who have more and larger adipocytes also have higher baseline serum CRP. Because diabetes is more common in obese individuals, an association is expected between serum CRP and diabetes. However, some studies found that obesity does not explain the association of CRP with diabetes completely, suggesting an independent role for CRP in the development of diabetes (1,5,9).Twin and familial studies have shown a substantial hereditability for CRP level (11), and a recent study found a strong association of serum CRP with genetic variations in the CRP promoter region (12). Four haplotypes broadly represent the CRP gene variation in the European population (13). Therefore, an association of CRP haplotypes with serum CRP and the incidence of diabetes may point to a contribution of CRP in the development of diabetes.We studied the association of serum CRP with the risk of diabetes in the Rotterdam Study, a prospective population-based cohort study among participants aged Ն55 years. Furthermore, we conducted a meta-analysis, which included our own study, to clarify whether CRP serum level is associated with diabetes, independent of obesity indexes. Finally, to investigate a potential role of CRP in the development of diabetes, we studied the association of genetic CRP haplotypes with the risk of diabetes. RESEARCH DESIGN AND METHODSThis study was conducted within t...

Prediabetes, T2DM, and measures of hyperglycemia are independently associated with impaired microvascular function in the retina and skin. These findings support the concept that microvascular dysfunction precedes and thus may contribute to T2DM-associated cardiovascular disease and other complications, which may in part have a microvascular origin such as impaired cognition and heart failure.

This study shows that setting and registry characteristics have an important influence on the outcome of multimorbidity studies. We recommend provision of at least information about the setting, the (list of) conditions included, the data collection method, and the time frame used, when reporting about the size and nature of multimorbidity.