Impact of glycaemic control, hypertension and insulin treatment on general and cause-specific mortality: an Italian population-based cohort of Type II (non-insulin-dependent) diabetes mellitus

Summary The aims of this study were to assess the impact of diabetes and associated variables (fasting plasma glucose, blood pressure, antidiabetic treatment, body mass index) on general and cause-specific mortality in an Italian population-based cohort with Type II (non-insulin-dependent) diabetes mellitus, comprising mainly elderly patients. The patients (n = 1967) who had Type II diabetes were identified in 1988 with an 80 % estimated completeness of ascertainment. In 1995, a mortality follow-up (98 % completeness) of the cohort was done amounting to a total of 11 153 person-years. Observed and expected number of deaths were 577 and 428.7, respectively, giving a standardized mortality ratio (SMR) of 1.35 (95 % CI 1.24–1.46). The most common underlying causes of death were malignant neoplasm, ischaemic heart disease and cerebrovascular diseases, which accounted for 18 %, 17.8 % and 17.5 % of deaths, respectively. Cardiovascular disease as a whole (international classification of disease ICD-9 390–459) accounted for 260 of 577 deaths (SMR 1.21, 95 % CI 1.07–1.36). In internal analysis, the most important predictors of general mortality were insulin-treatment (relative risk [RR] 1.72, 95 % CI 1.19–2.49) and a fasting plasma glucose greater than 8.89 mmol/l ([RR] 1.29, 95 % CI 1.04–1.60), whereas the most important predictors of cardiovascular diseases were insulin-treatment and hypertension. In conclusion, this population-based study showed: 1) slight mortality excess of 35 % in Type II diabetes being associated with 2) a 30 % increased mortality in subjects with baseline fasting glucose greater than 8.89 mmol/l and 3) a 40 % increased risk of death from cardiovascular diseases in hypertensive patients. [Diabetologia (1999) 42: 297–301] Received: 27 July 1998 and in final revised form: 17 November 1998     

Increased death risk and altered cancer incidence pattern in patients with isolated or combined autoimmune primary adrenocortical insufficiency

Objectives Primary adrenocortical insufficiency is mostly caused by an autoimmune destruction of the adrenal cortex. The disease may appear isolated or as a part of an autoimmune polyendocrine syndrome (APS). APS1 is a rare hereditary disorder with a broad spectrum of clinical manifestations. In APS2, primary adrenocortical insufficiency is often combined with autoimmune thyroid disease and/or type 1 diabetes. We analysed mortality and cancer incidence in primary adrenocortical insufficiency patients during 40 years. Data were compared with the general Swedish population. Design and patients A population based cohort study including all patients with autoimmune primary adrenocortical insufficiency (3299) admitted to Swedish hospitals 1964–2004. Measurements Mortality risk was calculated as the standardized mortality ratio (SMR) and cancer incidence as the standardized incidence ratio (SIR). Results A more than 2‐fold increased mortality risk was observed in both women (SMR 2·9, 95% CI 2·7–3·0) and men (SMR 2·5, 95% CI 2·3–2·7). Highest risks were observed in patients diagnosed in childhood. SMR was higher in APS1 patients (SMR 4·6, 95% CI 3·5–6·0) compared with patients with APS2 (SMR 2·1, 95% CI 1·9–2·4). Cancer incidence was increased (SIR 1·3, 95% CI 1·2–1·5). When tumours observed during the first year of follow‐up were excluded, only the cancer risk among APS1 patients remained increased. Cause‐specific cancer incidence analysis revealed significantly higher incidences of oral cancer, nonmelanoma skin cancer, and male genital system cancer among patients. Breast cancer incidence was lower than in the general population. Conclusions Our study shows a reduced life expectancy and altered cancer incidence pattern in patients with autoimmune primary adrenocortical insufficiency.     

Incidence of malignancy in Japanese patients with rheumatoid arthritis

To determine the incidence of malignancy and site-specific malignancies in Japanese patients with rheumatoid arthritis (RA). In a prospective large observational cohort study named IORRA, 7,566 patients with RA were enrolled from April 2001 to April 2005 and were followed up to October 2005. Occurrence of malignancy was originally collected by patient reports of IORRA survey biannually from April 2001 to October 2005, and was confirmed by medical records. Standardized incidence rate (SIR) of the observed-to-expected cancer incidence and 95% confidence intervals (95% CI) were then calculated. Factors obtained at first enrollment in IORRA were assessed for association with risk of malignancy using the Cox proportional hazards model. A total of 177 malignancies in 173 patients (58 in men, 115 in women) were identified during the observation period of 25,567 person-years. The age- and sex-standardized incidence rate of malignancy was 437.1 (men, 706.8; women, 366.1) per 100,000 person-years. The SIR of malignancy was slightly excess (SIR 1.18, [95% CI 1.02–1.37]) in all patients, but 1.29 (95% CI 0.99–1.67) in men, and 1.13 (95% CI 0.94–1.36) in women. A significant excess of lymphoma (SIR 6.07, [95% CI 3.71–9.37]) and lung cancer (SIR 2.29, [95% CI 1.57–3.21]), whereas decreased incidence of colorectal cancer (SIR 0.49, [95% CI 0.26–0.83]), were found. Male gender and older age were identified as risk factors for malignancy. A slight excess in the incidence of overall malignancy and highly excess of lymphoma in Japanese RA patients was demonstrated.     

Mortality and cancer incidence among individuals with Down syndrome

BACKGROUND: Individuals with Down syndrome (DS) have a predisposition to leukemia and possibly other cancers and excess mortality from other conditions, but information on the magnitude of risk associated with specific cancers or causes of death is sparse. METHODS: Mortality experience and cancer incidence were evaluated in a combined cohort of 4872 individuals with a hospital discharge diagnosis of DS in Sweden (1965-1993) or Denmark (1977-1989) by linkage to national cancer and vital statistics registries. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) were estimated by comparison with age, sex, and calendar-year expected values. RESULTS: Individuals with DS had an increased risk of incident acute lymphocytic (SIR, 24.2; 95% confidence interval [CI], 15.2-36.6; n = 22) and acute nonlymphocytic (SIR, 28.2; 95% CI, 15.7-48.3; n = 14) leukemias. Risks of testicular cancer (SIR, 3.7; 95% CI, 1.0-9.4; n = 4) and liver cancer (SIR, 6.0; 95% CI, 1.2-17.5; n = 3) were also elevated. Individuals with DS also experienced elevated mortality attributed to stomach cancer (SMR, 6.4; 95% CI, 1.7-16.4; n = 4), dementia and Alzheimer disease (SMR, 54.1; 95% CI, 27.9-94.4), epilepsy (SMR, 30.4; 95% CI, 13.9-57.7), ischemic heart disease (SMR, 3.9; 95% CI, 2.7-5.4), other heart disease (SMR, 16.5; 95% CI, 11.0-23.7), cerebrovascular disease (SMR, 6.0; 95% CI, 3.5-9.6), infectious diseases (SMR, 12.0; 95% 6.0-21.4), and congenital anomalies (SMR, 25.8; 95% CI, 21.0-31.4). CONCLUSIONS: Individuals with DS have a substantially increased risk of mortality due to specific causes and may have an elevated risk of other incident cancers in addition to leukemia. These results provide clues regarding chromosome 21 gene involvement in diseases that complicate DS and are important for disease detection and care of affected individuals.     

Long-term mortality in a nationwide cohort of childhood-onset type 1 diabetic patients in Norway

Aims/hypothesis We examined long-term total and cause-specific mortality in a nationwide, population-based Norwegian cohort of patients with childhood-onset type 1 diabetes. Materials and methods All Norwegian type 1 diabetic patients who were diagnosed between 1973 and 1982 and were under 15 years of age at diagnosis were included (n=1,906). Mortality was recorded from diabetes onset until 31 December 2002 and represented 46,147 person-years. The greatest age attained among deceased subjects was 40 years and the maximum diabetes duration was 30 years. Cause of death was ascertained by reviews of death certificates, autopsy protocols and medical records. The standardised mortality ratio (SMR) was based on national background statistics. Results During follow-up 103 individuals died. The mortality rate was 2.2/1000 person-years. The overall SMR was 4.0 (95% CI 3.2–4.8) and was similar for males and females. For ischaemic heart disease the SMR was 20.2 (7.3–39.8) for men and 20.6 (1.8–54.1) for women. Acute metabolic complications of diabetes were the most common cause of death under 30 years of age (32%). Cardiovascular disease was responsible for the largest proportion of deaths from the age of 30 years onwards (30%). Violent death accounted for 28% of the deaths in the total cohort (35% among men and 11% among women). Conclusions/interpretation Childhood-onset type 1 diabetes still carries an increased mortality risk when compared with the general population, particularly for cardiovascular disease. To reduce these deaths, attention should be directed to the prevention of acute metabolic complications, the identification of psychiatric vulnerability and the early detection and treatment of cardiovascular disease and associated risk factors. Electronic Supplementary Materials Supplementary material is available in the online version of this article at . T. Skrivarhaug et al.: Mortality of type 1 diabetes in Norway     

Socioeconomic inequalities in diabetes mellitus across Europe at the beginning of the 21st century

Aims/hypothesis  The aim of this study was to determine and quantify socioeconomic position (SEP) inequalities in diabetes mellitus in different areas of Europe, at the turn of the century, for men and women. Methods  We analysed data from ten representative national health surveys and 13 mortality registers. For national health surveys the dependent variable was the presence of diabetes by self-report and for mortality registers it was death from diabetes. Educational level (SEP), age and sex were independent variables, and age-adjusted prevalence ratios (PRs) and risk ratios (RRs) were calculated. Results  In the overall study population, low SEP was related to a higher prevalence of diabetes, for example men who attained a level of education equivalent to lower secondary school or less had a PR of 1.6 (95% CI 1.4–1.9) compared with those who attained tertiary level education, whereas the corresponding value in women was 2.2 (95% CI 1.9–2.7). Moreover, in all countries, having a disadvantaged SEP is related to a higher rate of mortality from diabetes and a linear relationship is observed. Eastern European countries have higher relative inequalities in mortality by SEP. According to our data, the RR of dying from diabetes for women with low a SEP is 3.4 (95% CI 2.6–4.6), while in men it is 2.0 (95% CI 1.7–2.4). Conclusions/interpretation  In Europe, educational attainment and diabetes are inversely related, in terms of both morbidity and mortality rates. This underlines the importance of targeting interventions towards low SEP groups. Access and use of healthcare services by people with diabetes also need to be improved.     

Risk of pancreatic cancer after cholecystectomy: a cohort study in Sweden

BACKGROUND: Although some experimental studies have indicated that cholecystectomy may increase the risk of pancreatic cancer, data from epidemiological studies are conflicting. AIMS: We conducted a register based retrospective cohort study to explore the relationship between cholecystectomy and pancreatic cancer. SUBJECTS: The cohort included 87 263 men and 181 049 women with a documented cholecystectomy for cholelithiasis between 1965 and 1997. METHODS: By record linkage to the nationwide and virtually complete registers of Cancer, Emigration, and Causes of Death, the cohort was followed up until the occurrence of any cancer, emigration, death, or the end of follow up, 31 December 1997, whichever came first. Relative risk was estimated by standardised incidence ratio (SIR) using the Swedish nationwide sex, age, and calendar year specific cancer incidence rates as reference. RESULTS: During the period of observation, 1053 cases of pancreatic cancer were found, among which 231 (22%) occurred within 12 months after operation. After excluding cases and person years accrued during the first two years of follow up, we observed a non-significant 6% excess risk for pancreatic cancer (95% confidence interval (CI) -2 to 14%). The relative risk did not increase with increasing follow up duration, with a SIR equal to 0.98 (95% CI 0.79-1.20) 20 years or more after operation. Patients with a comorbidity of diabetes or chronic pancreatitis had higher relative risks (SIR=1.79, 95% CI 1.39-2.28; SIR=3.17, 95% CI 1.37-6.24, respectively). After excluding patients with recorded diabetes or chronic pancreatitis, the relative risk was close to unity (SIR=1.01, 95% CI 0.94-1.09). CONCLUSIONS: Our findings do not support the hypothesis that cholecystectomy increases the subsequent risk of pancreatic cancer.     

General and cancer mortality in a large cohort of Italian alcoholics

Background: The consumption of alcohol is an underappreciated risk factor for a wide range of conditions. Overall, it is associated with high mortality rates and causes approximately 4% of all deaths worldwide. This study aimed to evaluate the general and cancer mortality in a cohort of subjects with alcohol addiction residing in Tuscany (Central Italy). Methods: Overall, 2,272 alcoholics (1,467 men and 805 women; mean age at first examination 43.8 years ± 13.0), treated at the Alcohol Centre of Florence in the period April 1985 to September 2001, were followed until the end of the study period (median follow‐up: 9.6 years). A total of 21,855 person‐years were available for analyses. Expected deaths were estimated by using age, sex, and calendar‐specific regional mortality rates. Standardized mortality ratios (SMR) and 95% confidence intervals (CI) were calculated. Results: Six hundred and thirty‐six of the 2,272 patients (28.0%) died, yielding an SMR of 5.0 (95% CI: 4.6 to 5.4). The alcoholics had significantly elevated mortality risk from all malignant cancers (SMR = 3.8, 95% CI: 3.3 to 4.4) and a series of specific diseases (infections: SMR = 10.1, 95% CI: 4.8 to 21.1; diabetes: SMR = 3.6, 95% CI: 1.9 to 6.7; immunological system, including AIDS: SMR = 8.1, 95% CI: 4.1 to 16.2; nervous system: SMR = 3.5, 95% CI: 1.9 to 6.4; cardiovascular system: SMR = 2.4, 95% CI: 2.0 to 2.9; respiratory system: SMR = 5.8, 95% CI: 4.2 to 8.0; digestive system: SMR = 26.4, 95% CI: 22.6 to 30.8, including liver cirrhosis (SMR = 40.0, 95% CI: 33.9 to 47.1); violent causes: SMR = 6.6, 95% CI: 5.0 to 8.6). Among malignant cancers, the highest SMRs were found for cancers of the pharynx (SMR = 22.8, 95% CI: 9.5 to 54.8), oral cavity (SMR = 22.2, 95% CI: 13.2 to 37.6), liver (SMR = 13.5, 95% CI: 9.2 to 19.8), and larynx (SMR = 10.7, 95% CI: 5.8 to 19.9). Although women showed higher SMR in comparison with the general population of the area, their overall survival estimates during the follow‐up were higher than those for male alcoholics. Conclusions: This large series of Italian alcoholics showed a significant increase in total and cancer mortality in comparison with the general population, with female alcoholics reporting higher survival rates.     

Risk of adenocarcinomas of the esophagus and gastric cardia in patients with gastroesophageal reflux diseases and after antireflux surgery.

BACKGROUND & AIMS: Gastroesophageal reflux has been proposed as an important risk factor for esophageal and gastric cardia adenocarcinoma, but prospective data are lacking. Furthermore, the effect of antireflux surgery has not yet been studied. We conducted a population-based retrospective cohort study to fill these gaps. METHODS: A cohort of 35,274 male and 31,691 female patients with a discharge diagnosis of gastroesophageal reflux diseases, and another cohort of 6406 male and 4671 female patients who underwent antireflux surgery, were identified in the Swedish Inpatient Register. Follow-up was attained through record linkage with several nationwide registers. Standardized incidence ratio (SIR) was used to estimate relative risk of upper gastrointestinal cancers, using the general Swedish population as reference. RESULTS: After exclusion of the first year follow-up, 37 esophageal and 36 gastric cardia adenocarcinomas were observed among male patients who did not have surgery (SIR, 6.3, 95% confidence interval [CI], 4.5-8.7; SIR, 2.4, 95% CI, 1.7-3.3, respectively). SIR for esophageal adenocarcinoma increased with follow-up time (P = 0.03 for trend). Among male patients who had undergone antireflux surgeries, risks were also elevated (16 esophageal adenocarcinoma, SIR, 14.1, 95% CI, 8.0-22.8; 15 gastric cardia adenocarcinomas, SIR, 5.3, 95% CI, 3.0-8.7) and remained elevated with time after surgery. The cancer risk pattern in women was similar to that for men, but the number of cases were much smaller. CONCLUSIONS: Gastroesophageal reflux is strongly associated with the risk of esophageal adenocarcinoma, and to a lesser extent, with gastric cardia adenocarcinoma. The risk of developing adenocarcinomas of the esophagus and gastric cardia remains increased after antireflux surgery.     

Mortality in patients with Klinefelter syndrome in Britain: a cohort study

CONTEXT: Klinefelter syndrome is characterized by hypogonadism and infertility, consequent on the presence of extra X chromosome(s). There is limited information about long-term mortality in this syndrome because there have been no large cohort studies. OBJECTIVE: Our objective was to investigate mortality in men with Klinefelter syndrome. DESIGN AND SETTING: We obtained data about patients diagnosed with Klinefelter syndrome at almost all cytogenetics centers in Britain, as far back as records were available, and conducted a cohort study of their mortality, overall and by karyotype. PATIENTS: We assessed 3518 patients diagnosed since 1959, followed to mid-2003. OUTCOME MEASURE: The outcome measure was standardized mortality ratio (SMR). RESULTS: A total of 461 deaths occurred. There was significantly raised mortality overall [SMR, 1.5; 95% confidence interval (CI), 1.4-1.7] and from most major causes of death including cardiovascular disease (SMR, 1.3; 95% CI, 1.1-1.5), nervous system disease (SMR, 2.8; 95% CI, 1.6-4.6), and respiratory disease (SMR, 2.3; 95% CI, 1.8-2.9). Mortality was particularly raised from diabetes (SMR, 5.8; 95% CI, 3.4-9.3), epilepsy (SMR, 7.2; 95% CI, 3.1-14.1), pulmonary embolism (SMR, 5.7; 95% CI, 2.5-11.3), peripheral vascular disease (SMR, 7.9; 95% CI, 2.9-17.2), vascular insufficiency of the intestine (SMR, 12.3; 95% CI, 4.0-28.8), renal disease (SMR, 5.0; 95% CI, 2.0-10.3), and femoral fracture (SMR, 39.4; 95% CI, 4.8-142.3). Mortality from ischemic heart disease was significantly decreased (SMR, 0.7; 95% CI, 0.5-0.9). CONCLUSIONS: Patients diagnosed with Klinefelter syndrome have raised mortality from several specific causes. This may reflect hormonal and genetic mechanisms.     

Clinically confirmed type 2 diabetes mellitus and colorectal cancer risk: a population-based, retrospective cohort study

OBJECTIVES: Patients with type 2 diabetes mellitus (DM) may be at increased colorectal cancer (CRC) risk. However, existing data are inconsistent. We investigated CRC risks, overall and by anatomic subsite, within a population-based inception cohort of clinically confirmed type 2 DM subjects. METHODS: All residents of Rochester, Minnesota who first met standardized criteria for type 2 DM from 1970 to 1994 (997 men and 978 women) were identified and followed forward in time until emigration, death, or December 31, 1999. Incident CRC cases were identified by review of inpatient and outpatient medical records. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were estimated to compare CRC incidence within the type 2 DM inception cohort with previously published rates for the Rochester general population. RESULTS: Over 19,158 person-years of follow-up, 51 incident CRC cases were identified within the type 2 DM cohort, while only 36.8 cases were expected (SIR = 1.39, 95% CI 1.03-1.82). Among men, type 2 DM was associated with increased overall (SIR = 1.67, 95% CI 1.16-2.33) and proximal (SIR = 1.96, 95% CI 1.16-3.10) CRC risks; distal CRC risk was also increased, but the point estimate was not statistically significant (SIR = 1.43, 95% CI 0.82-2.32). Among women, type 2 DM was not a risk factor for overall, proximal, or distal CRC (SIR = 1.03, 95% CI 0.60-1.66; SIR = 1.17, 95% CI 0.58-2.09; and SIR = 0.74, 95% CI 0.24-1.72, respectively). Within the type 2 DM cohort, current and former cigarette smokers were at higher CRC risk (SIR = 1.77, 95% CI 1.24-2.47) than never smokers (SIR = 0.99, 95% CI 0.57-1.61) and the interaction between type 2 DM and cigarette smoking status was statistically significant (p= 0.05). CONCLUSIONS: In this population-based, retrospective cohort study, clinically confirmed type 2 DM was associated with increased CRC risk, predominantly among men. Cigarette smoking appeared to positively modify DM-associated CRC risk, which to our knowledge has not been previously reported. These data suggest that further investigation of potential interactions between endogenous and exogenous factors involved in colorectal carcinogenesis may help to clarify the magnitude and extent of CRC risk experienced by persons with type 2 DM.     

The impact of family history of diabetes and lifestyle factors on abnormal glucose regulation in middle-aged Swedish men and women

Aims/hypothesis We investigated associations between abnormal glucose regulation and family history of diabetes, separately and in combination with lifestyle risk factors.Subjects and methods This cross-sectional study comprised 3,128 men and 4,821 women, aged 35–56 years, half with a family history of diabetes. Oral glucose tolerance testing identified subjects with previously undiagnosed prediabetes (IFG, IGT) and type 2 diabetes. Information on lifestyle factors was obtained by questionnaire. Biological interaction was measured with the synergy index.Results A family history of diabetes conferred a higher odds ratio (OR) for type 2 diabetes in men (OR=3.1, 95% CI 1.7–5.6) than in women (OR=1.7, 95% CI 1.0–3.0), and the synergy index was 2.8 (95% CI 0.9–9.0), suggesting interaction between a family history of diabetes and sex. For prediabetes and diabetes combined, the synergy index was 1.7 (1.0–2.8). Exposure to only one lifestyle risk factor (obesity, physical inactivity, smoking or low sense of coherence [a psychosocial index]) increased the risk to a similar extent in men and women. Combined exposure to a family history of diabetes and lifestyle-related risk factors had a greater effect on type 2 diabetes than any of these factors alone, especially in men. However, analysis of interaction between a family history of diabetes and the lifestyle factors did not indicate any interaction for diabetes, but did indicate interaction for a family history of diabetes and obesity in women with prediabetes.Conclusions/interpretation Our data suggest a more pronounced effect of a family history of diabetes on the risk of type 2 diabetes in men than in women. While both a family history of diabetes and lifestyle risk factors had effects on type 2 diabetes, irrespective of sex, these effects did not appear to interact.     

Increased risk of left sided colon cancer in patients with diverticular disease.

Certain similar epidemiological characteristics suggest a common aetiology for colon cancer and diverticulosis of the colon. The hypothesis that patients with diverticulosis are at increased risk of developing colon cancer was tested in a retrospective, population based, cohort study in Sweden. A total of 7159 patients (2478 men and 4681 women) who had been given a hospital discharge diagnosis of diverticulosis or diverticulitis of the colon between 1965 and 1983 were followed up during 1985 by means of record linkage procedures. After excluding the first 2 years of follow up, there was not a significant increase in risk (SIR) overall for colon cancer (SIR = 1.2; 95% confidence intervals (CI) 0.9, 1.6) or for rectal cancer (SIR = 1.1; 95% CI 0.7, 1.7). The observed number of right sided colon cancers was as expected (SIR = 0.9; 95% CI 0.5, 1.5). In contrast, an increased risk of left sided colon cancer was found both overall (SIR = 1.8; 95% CI 1.1, 2.7) and consistently in men and women as well as in different age groups. This risk increased the longer the follow up (p value for trend < 0.001). These results do not support the hypothesis of a common aetiology in diverticular disease and colonic cancer but suggest a causal relationship between diverticular disease and cancer of the left colon.     

Mortality amongst participants in Vasaloppet: a classical long-distance ski race in Sweden

OBJECTIVE: The aim of this study was to assess mortality amongst participants in long-distance ski races during the Vasaloppet week. We considered the 90 km races for men and 90 or 30 km for women. The vast majority of the participants in these races are not competing on the elite level. It is assumed, however, that they have to undergo regular physical training during a long period of time in order to successfully finish the race. DESIGN: The cohort study consisted of 49 219 men and 24 403 women, who participated in any of the races during 1989-1998. All subjects were followed up in the National-Cause-of-Death-Register until 31 December 1999. We computed the standardized mortality ratios (SMRs) adjusting for age and calendar year. RESULTS: Overall, 410 deaths occurred, compared with 850.6 expected, yielding an SMR of 0.48 [95% confidence interval (CI) 0.44-0.53]. Low SMRs were found in all age groups in both men and women and in all groups after categorization by finishing time and number of races. The lowest SMRs were found amongst older participants and in those who participated in several races. A decreased mortality was observed in all major diagnostic groups, namely cancers (SMR = 0.61; 95% CI 0.52-0.71), diseases of the circulatory system (SMR = 0.43; 95% CI 0.35-0.51), and injuries and poisoning (SMR = 0.73; 95% CI 0.60-0.89). For lung cancer the SMR was 0.22, but even after exclusion of lung cancer the all-cancer mortality was low (SMR = 0.72; 95% CI 0.59-0.86). CONCLUSIONS: We conclude that participants in long-distance skiing races, which demand prolonged regular physical training, have low mortality. The extent to which this is due to physical activity, related lifestyle factors, genetics or selection bias is yet to be assessed.     

White blood-cell count and the risk of impaired fasting glucose or Type II diabetes in middle-aged Japanese men

Aims/hypothesis: To investigate the association between white blood-cell (WBC) count and the development of diabetes, independent of cigarette smoking. Methods: We examined 2953 Japanese men who were office workers and between 35 and 59 years of age and who did not have impaired fasting glucose (IFG) (a fasting glucose concentration of 6.1–6.9 mmol/l), Type II (non-insulin-dependent) diabetes mellitus (a fasting glucose concentration of ≥ 7.0 mmol/l or more or receipt of hypoglycaemic medication), medication for hypertension, and a history of cardiovascular disease. Fasting glucose concentrations were measured at annual health examinations from May 1994 through May 2000. Results: After controlling for potential predictors of diabetes, the relative risk for IFG or Type II diabetes mellitus compared with a WBC count of less than 5.3 · 10⁹ cells/l was 1.2 (95 %-CI, 0.6–2.3), 1.6 (CI, 0.8–3.1), and 2.5 (CI, 1.2–5.1) among non-smokers (p for trend = 0.009): and 1.0 (CI, 0.4–2.5), 2.3 (CI, 1.0–5.1), and 3.1 (CI, 1.4–7.1) among ex-smokers (p for trend = 0.001) with WBC counts of 5.3–6.1, 6.2–7.2, and 7.3 · 10⁹ cells/l or more, respectively. Among current smokers, the respective multivariate-adjusted relative risks for IFG or Type II diabetes mellitus were 1.1 (CI, 0.6–2.1), 1.4 (CI, 0.8–2.4), and 1.2 (CI, 0.7–2.1) (p for trend = 0.460). Conclusion/hypothesis: Although the selection of a rigorously normoglycaemic cohort might have had an influence on these observations, higher WBC counts seem to predict the development of IFG or Type II diabetes mellitus, primarily in non-smokers. [Diabetologia (2002) 45: 42–48] Received: 16 July 2001 and in revised form: 13 September 2001     

Lipid but not glycaemic parameters predict total mortality from Type 2 diabetes mellitus in Canterbury,New Zealand

A cohort of 447 subjects with Type 2 diabetes mellitus (208 male, 239 female; age range 30–82, median 62 years; and of predominantly European origin) was characterized in a clinic survey in 1989. Individual status (dead or alive) at 1 June 1995 was ascertained. Mortality rates were compared with the general New Zealand population by calculating standardized mortality ratios (SMR) and the hazard ratio (HR) of prognostic factors evaluated with Cox’s proportional hazards model. At 6 years, 289 subjects were confirmed as alive and 133 as dead; only 25 were untraceable. Six-year survival for the cohort was 70 % (95 % CI 66–74). SMR was 2.53 (95 % CI 1.99–2.68) for the female cohort and 2.03 (95 % CI 1.60–2.59) for the male cohort. Factors assessed at baseline (1989) that were independently prognostic of total mortality included age, male sex, pre-existing coronary artery disease (CAD) (HR 2.2, 95 % CI 1.5–3.3) and plasma cholesterol (HR for 1.4 mmol l⁻¹ change: 1.49, 95 % CI 1.2–1.9). HDL-cholesterol was protective in women (HR for 0.4 mmol l⁻¹ change: 0.72, 95 % CI 0.51–1.00) but not men. Glycated haemoglobin was not a significant predictor of total mortality. Predictors of CAD mortality (in those subjects free of CAD in 1989) included plasma cholesterol (HR for 1.4 mmol l⁻¹ change: 1.86 95 % CI 1.20–2.89), glycated haemoglobin (HR for 1.8 % change: 1.9 95 % CI 1.04–3.47), male sex, peripheral vascular disease, and smoking. There is therefore increased mortality in Type 2 diabetic subjects in Canterbury, New Zealand. HDL-cholesterol is protective against total mortality in females. © 1998 John Wiley & Sons, Ltd.     

Fasting blood glucose and cancer risk in a cohort of more than 140,000 adults in Austria

Aims/hypothesis We investigated relations between fasting blood glucose and the incidence of cancer.Methods A population-based cohort of more than 140,000 Austrian adults (63,585 men, 77,228 women) was followed over an average of 8.4 years. Incident cancer (other than non-melanoma skin cancers) was ascertained by a population-based cancer registry (n=5,212). Cox proportional-hazards models were used to estimate hazard rate ratios (HR) stratified for age and adjusted for smoking, occupational group and body mass index.Results The highest fasting blood glucose category (≥7.0 mmol/l) was weakly associated with all cancers combined (HR 1.20; 95% CI, 1.03–1.39 in men and 1.28; 95% CI, 1.08–1.53 in women) relative to the reference level (4.2–5.2 mmol/l). The strongest association was found for liver cancer in men (HR 4.58; 95% CI, 1.81–11.62). Positive associations between fasting hyperglycaemia (6.1–6.9 or ≥7.0 mmol/l) and cancer incidence were also observed for non-Hodgkin’s lymphoma in men, and for colorectal and bladder cancer in women. Breast cancer in women diagnosed at or after age 65 was also associated with fasting blood glucose ≥7.0 mmol/l. Positive associations with glucose values >5.3 mmol/l were noted for thyroid cancer, gallbladder/bile duct cancer and multiple myeloma in men and women combined.Conclusions/interpretation These findings provide further evidence that elevated blood glucose is associated with the incidence of several types of cancer in men and women.     

Comorbidities in patients with persistent or chronic immune thrombocytopenia

There is a paucity of epidemiological data on the risk of comorbidities in adults with persistent or chronic immune thrombocytopenia (ITP). In this study, we compared the rates of cataracts, diabetes, renal failure, vascular events, lymphoma, and leukemia among patients with and without persistent or chronic ITP. Using administrative data, adult patients with medical claims for ITP from January, 2000 through September, 2006 were identified. An age- and gender-matched comparison cohort without evidence of ITP was randomly selected. The incidence rate ratio (IRR) of each comorbidity among ITP patients relative to the comparison group was estimated using Poisson regression, adjusting for baseline covariates. A total of 3,131 patients with persistent or chronic ITP were identified, and 9,392 were selected for the comparison cohort. The adjusted IRRs were as follows: diabetes 1.73 (95% CI 1.36–2.20), renal failure 2.05 (95% CI 1.67–2.51), any vascular event 1.70 (95% CI 1.41–2.05), lymphoma 5.91 (95% CI 2.61–13.37), leukemia 19.83 (95% CI 5.84–67.34), and mortality 4.21 (95% CI 3.06–5.79). There was no increased risk for cataract or myocardial infarction in the ITP cohort. Patients with persistent or chronic ITP are at increased risk for several comorbidities including hematologic malignancies, relative to a matched comparison cohort.     

Cancer in rheumatoid arthritis: occurrence, mortality, and associated factors in a South European population

OBJECTIVES: To estimate the prevalence, incidence, mortality, and predictors of cancer in patients with rheumatoid arthritis (RA). METHODS: We compared the incidence of cancer and the mortality by cancer in a cohort of 789 randomly selected RA patients (1999-2005) with the expected ones in the general population. We estimated standardized incidence ratios (SIR) and standardized mortality ratios (SMR) by indirect age and sex standardization. Additionally, we analyzed by generalized linear models the association of various predictors with cancer incidence, obtaining incidence rate ratios (IRR) with 95% confidence intervals (CI). RESULTS: The SIR of cancer in RA is 1.23 (95% CI: 0.78-1.85). By cancer type, there is an increased risk of leukemia, non-Hodgkin's lymphoma, and lung cancer in RA compared with the general population of the same sex and age. The SMR of cancer is 1.0 (95% CI: 0.53-1.7). By cancer type, RA patients with lung or kidney cancer have higher mortality than expected. Being male, elderly, with longstanding disease, and having used any cytotoxic drugs apart from methotrexate are confirmed as predictive factors for cancer. Additional independent predictors are increases in blood leukocyte counts (IRR per 3000 u/mm3 increase: 1.88 (95% CI: 1.6 -2.1)) and decreases in serum hemoglobin (IRR per 2 g/l decrease: 1.88 (95% CI: 1.19 -2.94)). CONCLUSIONS: The overall incidence and mortality of cancer in RA is not greater than the expected, although there is an increased risk of hematopoietic and lung cancers in RA patients compared with the general population. Hemoglobin and leukocyte counts may help to identify RA patients at risk for cancer.     

Familial components of the multiple metabolic syndrome: the ARIC Study

Summary The association of a parental history of diabetes mellitus and hypertension with the multiple metabolic syndrome (MMS) was studied in a population survey of middle-aged adults. The eligible population was drawn from the baseline examination of the Atherosclerosis Risk in Communities Study, a population-based, bi-ethnic, multi-centre cohort study. The MMS was defined as a multivariate, categorical phenotype of co-occurring diabetes, hypertension, and dyslipidaemia. MMS cases (n = 356) were compared to disorder-free control subjects (n = 6797) with respect to their parental history of diabetes and hypertension. MMS cases were more likely to report a history of diabetes in both parents (odds ratio [OR] 4.7, 95 % confidence interval (CI) 1.5–14.7) or a history of hypertension in both parents (OR 1.9, 95 % CI 1.1–3.0) than control subjects, adjusting for BMI, waist-to-hip ratio, age, gender, and ethnicity/centre. A parental history of diabetes and hypertension in both parents was associated with the greatest increase in odds of MMS (OR 8.3, 95 % CI 3.0–22.8). A dose-response relationship between the number of parental disorders (one; two; three to four) and the odds of MMS was observed (OR 1.2, 95 % CI 0.9–1.7; OR 2.0, 95 % CI 1.4–2.8; OR 4.0, 95 % CI 2.5–6.2). Based on the marked associations observed between a parental history of MMS components and the clustering of these metabolic disorders in the offspring generation, we conclude that genetic and/or non-genetic familial influences play a role in the development of the multiple metabolic syndrome. [Diabetologia (1997) 40: 963–970] Received: 20 February 1997 and in revised form: 2 May 1997