Association between thyroid function, thyroid autoimmunity, and state and trait factors of depression.

OBJECTIVE: The aim of this study was to investigate whether thyroid function and thyroid peroxidase antibodies (TPOAb) are associated with depression, when using both state and trait parameters of depression. METHOD: In 1125 participants of the Nijmegen Biomedical Study, thyroid-stimulating hormone (TSH), free thyroxine (FT4), and TPOAb were measured twice. The Beck Depression Inventory (BDI), a self-reported lifetime diagnosis of depression, and the neuroticism scale of the Eysenck Personality Questionnaire Revised Short Scale (EPQ-RSS) were used to evaluate the presence of state and trait features of depression. RESULTS: We found no association between TSH and FT4 levels and BDI score, current depression, lifetime diagnosis of depression, and EPQ-RSS neuroticism score. Subjects with TPOAb had higher EPQ-RSS neuroticism scores in comparison with subjects without TPOAb, mean score 4.1 vs. 3.2 (regression coefficient 0.70; 95% CI 0.1-1.3; P-value 0.02 after adjustment for confounders). The prevalence of a lifetime diagnosis of depression was higher in subjects with positive TPOAb in comparison with participants without TPOAb: 24.2% vs. 16.7% (relative risk 1.4; 95% CI 1.0-2.1; P-value 0.04 after adjustment for confounders). CONCLUSION: Thyroid peroxidase antibodies are positively associated with trait markers of depression. The presence of TPOAb may be a vulnerability marker for depression.

The interaction between cerebrovascular disease and neuroticism in late-life depression: a cross-sectional study.

OBJECTIVE: Vascular disease and neuroticism are both risk factors for late-life depression. In this study we examined the interaction between vascular disease and neuroticism as determinants of clinically relevant depressive symptoms (CRDS) in late-life. METHODS: Multivariate logistic regression in a survey of 1396 population-dwelling people aged ≥70 years. CRDS were defined as scoring ≥16 on the CES-D. Vascular disease was categorised into four levels: none, ≥2 vascular risk factors, cardiac disease or stroke. RESULTS: Neuroticism was strongly associated with CRDS in women (OR: 1.6, 95% CI: 1.4-1.8). In men vascular disease interacted negatively but significantly with neuroticism (cardiac disease by neuroticism: OR: 0.8, 95% CI: 0.6-0.9; stroke by neuroticism: OR: 0.8, 95% CI: 0.6-0.96) when predicting CRDS. CONCLUSIONS: In men vascular disease attenuates the predictive value of neuroticism in CRDS, which might be mediated by apathy caused by cerebrovascular disease.

[Estimate of the number of new patients with type 2 diabetes mellitus in the Netherlands: at least 65,000 per year in the age group of 50 years and above]. / Schatting van het aantal nieuwe patiënten met diabetes mellitus type 2 in Nederland: ruim 65.000 per jaar in de leeftijdsgroep vanaf 50 jaar.

OBJECTIVE: To estimate the incidence of type-2 diabetes mellitus in the Netherlands, using figures which were observed in a population-based cohort study of diabetes, the Hoorn Study. DESIGN: Descriptive. METHOD: Age-specific, gender-specific and glucose-status-specific diabetes incidence figures as observed in the Hoorn Study (1989-1998) were applied to the Dutch population structure of January 1, 2000. RESULTS: Based on the fasting glucose diagnostic criteria, as recommended for clinical practice, 312,393 patients with incident type-2 diabetes were expected over 6.4 years in the 50-74 years age category, corresponding to an average of 48,811 patients per year. If data are extrapolated to the > or = 75 years age category, an additional 16,865 patients per year are expected (total: 65,676). If the 2-hour postload glucose values of the oral glucose tolerance test were also used to diagnose diabetes, these figures would be 66,001 new patients per year in the 50-74 years age group, and 22,840 in the > or = 75 years age group.

A combination of high concentrations of serum triglyceride and non-high-density-lipoprotein-cholesterol is a risk factor for cardiovascular disease in subjects with abnormal glucose metabolism--The Hoorn Study.

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.

Relation of impaired fasting and postload glucose with incident type 2 diabetes in a Dutch population: The Hoorn Study.

CONTEXT: Persons with impaired glucose tolerance (IGT) are known to have an elevated risk of developing diabetes mellitus. Less is known about diabetes risk among persons with impaired fasting glucose (IFG) or with normal glucose levels. OBJECTIVE: To determine the incidence of diabetes in relation to baseline fasting and postload glucose levels and other risk factors. DESIGN, SETTING, AND PARTICIPANTS: Population-based cohort study conducted from October 1989 to February 1992 among 1342 nondiabetic white residents of Hoorn, the Netherlands, aged 50 to 75 years at baseline, in whom fasting plasma glucose (FPG) levels and glucose levels 2 hours after a 75-g oral glucose tolerance test were measured at baseline and at follow-up in 1996-1998. MAIN OUTCOME MEASURES: Cumulative incidence of diabetes, defined according to the diagnostic criteria of the World Health Organization (WHO-1985 and WHO-1999) and the American Diabetes Association (ADA-1997), during a mean follow-up of 6.4 years, compared among participants with IFG, IGT, and normal glucose levels at baseline. RESULTS: The cumulative incidence of diabetes was 6.1%, 8.3%, and 9.9% according to the WHO-1985, ADA, and WHO-1999 criteria, respectively. The cumulative incidence of diabetes (WHO-1999 criteria) for participants with both IFG and IGT was 64.5% compared with 4.5% for those with normal glucose levels at baseline. The odds ratios for diabetes (WHO-1999 criteria), adjusted for age, sex, and follow-up duration, were 10.0 (95% confidence interval [CI], 6.1-16.5), 10.9 (95% CI, 6.0-19.9), and 39.5 (95% CI, 17.0-92.1), respectively, for those having isolated IFG, isolated IGT, and both IFG and IGT. In addition to FPG and 2-hour postload glucose levels (P<.001 for both), the waist-hip ratio also was an important risk factor for developing diabetes (P =.002). CONCLUSION: In this study, the cumulative incidence of diabetes was strongly related to both IFG and IGT at baseline and, in particular, to the combined presence of IFG and IGT.

Similar 9-year mortality risks and reproducibility for the World Health Organization and American Diabetes Association glucose tolerance categories: the Hoorn Study.

OBJECTIVE: To compare the risks of all-cause and cardiovascular disease (CVD) mortality in the American Diabetes Association (ADA) and World Health Organization (WHO) glucose tolerance categories after 9 years of follow-up in the Hoorn Study and to study the test-retest reproducibility of those categories. RESEARCH DESIGN AND METHODS: In this population-based cohort study of 2,468 elderly men and women, subjects were classified according to both the WHO and the ADA criteria. Causes of death were extracted from the medical records. Age- and sex-adjusted relative risks were estimated by Cox's proportional hazards model. Reproducibility of the diagnostic criteria was assessed in a sample of 1,109 subjects with duplicate oral glucose tolerance tests. RESULTS: Subjects with known diabetes had a four to five times higher risk of all-cause and CVD mortality compared with normal subjects (P<0.05). The relative risks of all-cause mortality were 1.67 (95% CI 1.09-2.57) and 1.56 (1.00-2.43) for newly diagnosed diabetic subjects according to the WHO and ADA criteria, respectively. The WHO and ADA criteria had similar levels of reproducibility The overall K was 0.59 (0.54-0.64) for WHO criteria and 0.61 (0.56-0.66) for ADA criteria. For the category of newly diagnosed diabetes according to WHO or ADA, the percentages of agreement for the second test compared with the first test were 77% (85/110) and 74% (74/100), respectively. CONCLUSIONS: Both sets of diagnostic criteria identify criteria-specific diabetic subjects with an increased mortality risk compared with normal subjects, and the reproducibility of both criteria is similar.

Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study.

AIMS/HYPOTHESIS: The degree of glycaemia has been shown to be associated with all-cause and cardiovascular mortality in diabetic subjects. Whether this association also exists in the general population is still controversial. We studied the predictive value of fasting plasma glucose, 2-hour post-load glucose and HbA1c in a population-based cohort of 2363 older (50-75 years) subjects, without known diabetes. METHODS: Relative risks (RR) of all-cause and cardiovascular mortality were estimated by Cox proportional hazards model, adjusting for age and sex, and additionally for known cardiovascular risk factors. RESULTS: During 8 years of follow-up, 185 subjects died; 98 of cardiovascular causes. Fasting plasma glucose was only predictive in the diabetic range, although the risks started to increase at about 6.1 mmol/l. Post-load glucose and HbA1c values were, even within the non-diabetic range, associated with an increased risk (p for linear trend < 0.05). These increased risks were mostly, but not completely, attributable to known cardiovascular risk factors. After exclusion of subjects with newly diagnosed diabetes or with pre-existent cardiovascular disease (n = 551), a 5.8 mmol/l increase of post-load glucose (corresponding to two standard deviations of the population distribution) was associated with a higher age-adjusted and sex-adjusted risk of all-cause (RR 2.24) and cardiovascular mortality (RR 3.40) (p < 0.05). After additional adjustment for known cardiovascular risk factors, these relative risks were still statistically significant, with values of 2.20 and 3.00 respectively (p < 0.05). CONCLUSION/INTERPRETATION: High glycaemic variables, especially 2-h post-load glucose concentrations and to a lesser extent HbA1c values, indicate a risk of all-cause and cardiovascular mortality in a general population without known diabetes.

The 1997 American Diabetes Association criteria versus the 1985 World Health Organization criteria for the diagnosis of abnormal glucose tolerance: poor agreement in the Hoorn Study.

OBJECTIVE: Recently, the American Diabetes Association (ADA) introduced new diagnostic criteria. These new criteria are based on fasting plasma glucose levels, avoiding the burdensome oral glucose tolerance test (OGTT). We compared the 1997 ADA criteria with the 1985 World Health Organization (WHO) criteria with respect to the prevalence of diabetes and the cardiovascular risk profile in the population of the Hoorn Study RESEARCH DESIGN AND METHODS: The Hoorn Study is a population-based survey of 2,484 men and women, aged 50-75 years. An OGTT was performed and cardiovascular risk factors were determined in 2,378 subjects without known diabetes. Subjects were categorized according to both sets of diagnostic criteria. RESULTS: Although the prevalence of diabetes was similar for both sets of criteria, 47 of 120 (39.2%) subjects who were diagnosed with diabetes according to the 1997 ADA criteria were not classified as having diabetes when using the 1985 WHO criteria. Similarly, of 285 subjects diagnosed with impaired fasting glucose by the 1997 ADA criteria, 195 (68.4%) were classified as having normal glucose tolerance by the 1985 WHO criteria. The overall agreement was poor (kappa 0.33; 95% CI 0.28-0.38). Subjects who were diagnosed as having diabetes by either set of criteria had an adverse cardiovascular risk profile, which was between the cardiovascular risk profiles of concordant normal and concordant diabetic subjects. CONCLUSIONS: In this study both sets of criteria diagnosed a similar number of diabetic subjects, but many of the subjects shifted between glucose intolerance categories. With either set of criteria, a considerable number of subjects at risk of developing diabetes and subjects carrying an increased risk of cardiovascular disease, as reflected by an adverse cardiovascular risk profile, will be missed.

Effect of physical training on QTc interval in elderly people.

In order to assess whether heart rate-adjusted QT duration (QTc) is reduced by physical activity in an elderly population, a randomized, controlled intervention study of the effect of a 6-month intensive training program on QTc was undertaken. The participants were 229 healthy men and women, aged 60-80 years. The subjects of the intervention group trained three to four times a week at a work load of about 70% of their maximum capacity for 6 months, while the control subjects maintained their habitual activities. The main outcome measures were change in QTc and resting heart rate. For women, the mean QTc interval (ms) of the intervention group changed by -6.7 (SE 2.8) versus 0.6 (SE 2.4) in the control group (P = .05), while for men, the change in the intervention group subjects was -2.7 (SE 2.2) versus 0.4 (SE 3.1) in the control subjects (P = .39). Also, resting heart rate (beats/ min) changed in intervention group women by -4.6 (SE 1.7) as against -0.06 (SE 1.1) in the control subjects (P = .02), and in intervention group men it changed by -3.2 (SE 1.2) versus -0.9 (SE 1.5) in the control subjects (P = .25). These data indicate that regular physical activity favorably affects QTc in elderly women. A similar, but not significant, trend was observed in men. The beneficial shift in QTc may be caused by a more favorable autonomic balance through increased parasympathetic activity. The reduced resting heart rate in subjects of the intervention group supports this view. Although the reduction was relatively small, it may represent a favorable effect on cardiovascular risk.

[What are the consequences of the new American guidelines for the diagnosis of diabetes mellitus in The Netherlands?]. / Wat zijn de gevolgen van nieuwe Amerikaanse richtlijnen voor de diagnostiek van diabetes mellitus voor Nederland?

The American Diabetes Association (ADA) recently issued new guidelines for classification and diagnosis of diabetes mellitus. The main change is the decrease of the liminal value of the fasting plasma glucose level from 7.8 to 7.0 mmol/l. A fasting level of 6.1-6.9 mmol/l indicates impaired glucose tolerance (which eliminates the category 'impaired glucose tolerance', which was established on the basis of a slightly increased 2-hour glucose level after ingestion of 75 g glucose). Consequently, the ADA criteria render the oral glucose tolerance test (GTT) redundant for clinical practice. Given these criteria, the prevalence of diabetes mellitus among the general Dutch population will change only slightly, but the number of persons to be classified in a different category after their introduction is considerable: 39.2% of the ADA diabetics are not diabetics according to the current WHO classification, while 38.1% of the WHO diabetics are not diabetics according to the ADA criteria. The criteria established by the ADA accommodate clinical practice, in which the GTT is hardly used anymore. The WHO still has to decide about whether or not accepting the ADA guidelines.

Consumption of ginger (Zingiber officinale roscoe) does not affect ex vivo platelet thromboxane production in humans.

OBJECTIVES: Ginger (Zingiber Officinale Roscoe) has been claimed to exert an anti-thrombotic effect in humans as ginger extracts inhibit cyclo-oxygenase activity of platelets in vitro. Effects of ginger consumption on ex vivo platelet function, however, are contradictory. We therefore investigated whether daily consumption of raw or cooked ginger decreases platelet cyclo-oxygenase activity as assessed by ex vivo maximally stimulated platelet thromboxane B2 production. DESIGN: We carried out a randomized placebo-controlled cross-over study of 3 x 2 weeks. SUBJECTS: Eighteen healthy volunteers aged 22 +/- 3 y (mean +/- s.d.) participated in the study; there were no dropouts. INTERVENTIONS: Subjects consumed 15 g of raw ginger root, 40 g of cooked stem ginger, or placebo daily for two weeks. We took fasted venous blood samples and measured thromboxane B2 production in maximally stimulated platelet-rich plasma at days 12 and 14 of each treatment period. RESULTS: Mean decrease in thromboxane production relative to placebo was 1 +/- 9% for ginger root, and -1 +/- 8% for stem ginger, with no effect of treatment order (P = 0.984). CONCLUSIONS: We cannot confirm the putative anti-thrombotic activity of ginger in humans.