To examine the relationship between plasma levels of the acute-phase proteins ceruloplasmin, alpha-1-antitrypsin, orosomucoid, haptoglobin and C-reactive protein (CRP), and incidence of diabetes in the population-based Malmö Diet and Cancer Study-Cardiovascular Cohort (MDCS-CC).
The study population consists of 4246 participants (aged 46-67 years, 60.8 % women) with no previous history of diabetes. Participants were followed, and incidence of diabetes was assessed by linkage with national registers and a clinical re-examination of the cohort. Cox proportional hazard regression analysis was used to compare incidence of diabetes in relation to sex-specific quartiles of the acute-phase proteins.
During a mean follow-up period of 15.6 ± 3.4 years, a total of 390 participants were diagnosed with diabetes. Orosomucoid, haptoglobin, and CRP showed a significant increased risk of diabetes after adjustment for potential confounders. However, further adjustments for fasting glucose at baseline resulted in significant association only for CRP. The multivariable-adjusted hazard ratios (HR: 4th vs. 1st quartile) were 1.18 (95 % CI: 0.83-1.67; p = 0.51), 1.19 (CI: 0.85-1.62; p = 0.10), and 1.40 (CI: 1.01-1.95; p = 0.046) for orosomucoid, haptoglobin, and CRP respectively.
The study demonstrated that there are associations between orosomucoid, haptoglobin and CRP and the risk of incidence of diabetes. However, after additional adjustment for fasting glucose levels at baseline, the association stayed significant only for CRP.
The objective of this study was to investigate the association between diabetes mellitus (DM) and the prevalence of intermittent claudication (IC). Between 1995 and 1997, all residents aged 20 years or older in Nord-Trøndelag County, Norway were mailed an invitation to participate in a health survey (HUNT 2). A total of 19,712 participants aged 40-69 years old completed and returned the questionnaire included with the invitation. They also attended an examination where brachial blood pressure was measured and non-fasting venous blood was collected. The venous blood sample was subsequently analysed for concentrations of blood lipids. Responses to 12 questions on IC were previously tested against ankle blood pressure measurements (ABPI
It was the purpose of this study to report the natural history of glucose tolerance during a five-year follow-up among elderly Finnish men, and to evaluate the role of age and body-mass index in explaining the variation in glucose tolerance both cross-sectionally and longitudinally. In the survivors of the Finnish cohorts of the Seven-Countries Study, aged 65 to 84 years at baseline, a two-hour oral glucose-tolerance test was performed according to current WHO criteria. Subjects with fasting blood glucose > 10 mmol/l were directly classified as having diabetes at baseline.--
At baseline, of the 637 men 216 had normal and 234 had impaired glucose tolerance, 187 were diabetic. At follow-up, 172 men had died; 38 (18%) of the subjects with normal glucose tolerance at baseline had either impaired glucose tolerance or diabetes; 17 (7%) of the men with initially impaired glucose tolerance had developed diabetes, and 79 (34%) were normalized. 25 (13%) and 22 (12%) of the initially diabetic subjects had reverted to impaired or normal glucose tolerance, respectively. The age was able to explain 1-2% of variation in blood glucose level in cross-sectional but not in longitudinal comparison. Body-mass index was an important predictor of abnormal glucose tolerance in previously normally responding men. By contrast, obesity did not contribute to the development of diabetes among men with impaired glucose tolerance.--
The incidence of impaired glucose tolerance was high in these elderly Finnish men as compared with studies in middle-aged Caucasoid subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
HER2/ErbB2 is a member of the epidermal growth factor receptor family. It is widely used as a tumor marker, but it also has recently been associated with insulin resistance. Both ErbB2 and diabetes have been associated with cancer; however, the relationship between ErbB2 and diabetes has not been well explored. The aim of this population-based cohort study was to assess the association between plasma ErbB2 and incidence of diabetes.
The study population included participants from the Malmö Diet and Cancer-Cardiovascular Cohort (age range 46-68 years). After excluding participants with a history of diabetes and those missing data for ErbB2 and other covariates, the final study population consisted of 4,220 individuals. Incidence of diabetes was followed through linkages to local and national registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to quartiles of ErbB2, adjusted for potential confounders.
Plasma ErbB2 was significantly and positively associated with glucose, insulin, and HbA1c after being adjusted for potential confounding factors. During a mean ± SD follow-up period of 20.20 ± 5.90 years, 615 participants (14.6%) were diagnosed with new-onset diabetes. Individuals with high levels of ErbB2 had a significantly higher risk of diabetes than those with low levels of ErbB2. The multivariable-adjusted hazard ratio was 1.31 (95% CI 1.03-1.66; P
INTRODUCTION: Elevated levels of coagulation factor VII (FVII) have been associated with increased risk for myocardial infarction (MI). The R353Q polymorphism of the FVII gene has been shown to modify plasma levels of FVII, and has in some studies also been associated with reduced risk for MI. OBJECTIVES: To examine the R353Q polymorphism of the FVII gene and the relation to myocardial infarction (MI), cardiovascular disease (CVD), and diabetes, and furthermore, to elucidate the association between the polymorphism and plasma levels of FVII coagulant activity (FVIIc), FVII antigen (FVIIag), activated FVII (FVIIa), and serum choline-containing phospholipids (PC). METHODS: In 560 elderly men characterised as hypercholesterolemic in 1972, we examined the R353Q polymorphism by melting curve analysis after real-time PCR. In a subgroup of 205 individuals, FVIIc, FVIIag, FVIIa, and PC were analysed. RESULTS: There were no significant associations between genotype and the disease states, although we observed a lower number of MI cases among subjects with the Q allele, compared to the RR individuals (14% vs. 19%). FVIIag and FVIIc levels were lower in RQ compared to RR subjects, whereas for FVIIa the opposite was observed (p
OBJECTIVES: To examine the long-term incidence of diabetes in relation to coffee consumption in Swedish women. DESIGN: Prospective longitudinal cohort study. SETTING: City of Göteborg, Sweden. SUBJECTS: A random population sample of 1361 women, aged 39-65 years, without prior diabetes or cardiovascular disease took part in a screening study in 1979-1981 with questionnaires, physical examination and blood sampling. MAIN OUTCOME MEASURES: The development of diabetes until 1999 was identified by questionnaires in a second screening and the Swedish hospital discharge register. RESULTS: Altogether, there were 74 new cases of diabetes. The risk of developing diabetes was 475 per 100 000 person-years in women who consumed two cups of coffee or less per day, 271 in women who consumed three to four cups per day, 202 with a consumption of five to six cups per day, and 267 in drinkers of seven cups or more per day. Associated hazard ratios, after adjustment for age, smoking, low physical activity, education and body mass index were 0.55 (0.32-0.95), 0.39 (0.20-0.77) and 0.48 (0.22-1.06) for daily consumption of three to four, five to six and seven cups or more, respectively, with a consumption of less than two per day as reference. Additional adjustment for serum cholesterol and triglycerides attenuated the relation between coffee and diabetes slightly, indicating a possible mediating effect on the effect of coffee by serum lipids. CONCLUSIONS: The findings of the present study support the hypothesis that coffee consumption protects from the development of diabetes in women.
The predictive effect of various insulin resistance indexes for risk of cardiovascular diseases (CVD) or type 2 diabetes (T2DM) is still unclear.
One thousand and forty-nine 71-years-old male subjects from the Swedish ULSAM study, mean follow-up 9 years. All subjects performed the euglycemic insulin clamp for M/I [glucose disposal/mean insulin], and 75-g oral glucose tolerance test for Ceder-IR: 1/glucose uptake rate/[mean glucose×log mean insulin]; Matsuda-IR: 1/10,000/square root [glucose0×insulin0×glucose120×insulin120]; Belfiore-IR: 1/([glucose0+glucose120]/normal mean glucose×[insulin0+insulin120]/normal mean insulin)+1); and HOMA-IR: [glucose0×insulin0]/22.5.
Bland-Altman plots showed best agreement between M/I versus Belfiore-IR and Ceder-IR with mean difference near zero, -0.21 to -0.46, while -0.68 to -0.77 for the other indexes. ISI-Ceder was the strongest predictor for incident nonfatal/fatal ischemic heart disease (CHD) or CVD at Cox regression in all subjects, and for incident T2DM at logistic regression in 1024 subjects with no baseline T2DM, with significantly higher hazard ratios or odds ratios than with all other indexes, also with best model fit, after adjusting for clinical characteristics and the traditional cardiovascular risk factors, including metabolic syndrome for CVD risk.
Ceder-IR performed strongest as independent predictor for incidences of CHD/CVD and T2DM.
This study explored whether complement factor 3 (C3) in plasma is associated with incidence of diabetes in a population-based cohort. We also identified genetic variants related to C3 and explored whether C3 and diabetes share common genetic determinants.
C3 was analyzed in plasma from 4368 nondiabetic subjects, 46 to 68 years old, from the Malmö Diet and Cancer Study. Incidence of diabetes was studied in relationship to C3 levels during 17.7± 4.4 years of follow-up. Genotypes associated with C3 were identified in a genome-wide association study. Diabetes Genetics Replication and Meta-Analysis and the European Genetic Database were used for in silico look-up.
In all, 538 (12.3%) subjects developed diabetes during 18 years of follow-up. High C3 was significantly associated with incidence of diabetes after risk factor adjustments (hazard ratio comparing 4th vs 1st quartile, 1.54 (95% confidence interval, 1.13 to 2.09; P = 0.005). C3 was associated with polymorphisms at the complement factor H locus (P
The diagnostic criteria and the clinical usefulness of the metabolic syndrome (MetSy) are currently questioned. The objective was to describe the structure of MetSy and to evaluate its components for prediction of diabetes type 2 (T2DM).
This was a case-referent study nested within a population-based health survey. Among 33,336 participants, we identified 177 initially non-diabetic individuals who developed T2DM after 0.1 to 10.5 years (mean, 5.4 years), and, for each diabetes case, two referents matched for sex, age, and year of health survey. Baseline variables included oral glucose tolerance test, BMI, blood pressure, blood lipids, adipokines, inflammatory markers, insulin resistance, and beta-cell function. Exploratory and confirmative factor analyses were applied to hypothesize the structure of the MetSy. The prediction of T2DM by the different factors was evaluated by multivariate logistic regression analysis.
A hypothetical five-factor model of intercorrelated composite factors was generated. The inflammation, dyslipidemia, and blood pressure factors were predicitive only in univariate analysis. In multivariable analyses, two factors independently and significantly predicted T2DM: an obesity/insulin resistance factor and a glycemia factor. The composite factors did not improve the prediction of T2DM compared with single variables. Among the original variables, fasting glucose, proinsulin, BMI, and blood pressure values were predictive of T2DM.
Our data support the concept of a MetSy, and we propose five separate clusters of components. The inflammation and dyslipidemia factors were not independently associated with diabetes risk. In contrast, obesity and accompanying insulin resistance and beta-cell decompensation seem to be two core perturbations promoting and predicting progression to T2DM.