Death certificate coding practices related to diabetes in European countries--the 'EURODIAB Subarea C' Study.

The objective of this study was to compare and analyse coding practices for diabetes mortality data in nine European countries (Belgium, Republic of Ireland, France, Germany, Malta, The Netherlands, Northern Ireland, Scotland and Switzerland). In each country, a sample of 200 coded death certificates, which mentioned diabetes, was randomly sampled. All death certificates were recoded at the WHO Collaborating Centre for the Classification of Diseases in the French language. The results show wide differences between national coding and central coding. Discrepancies in the underlying cause of death existed at the 3-digit coding level for 26% of all death certificates and for 44% at the 4-digit level. Coding in Northern Ireland and Malta was characterized by a marked tendency to choose diabetes less frequently. In contrast, in The Netherlands and, to a lesser extent, in the Republic of Ireland and France, diabetes was more frequently selected as the underlying cause of death. Most of the differences concerned the coding of an association involving diabetes and circulatory system diseases. In some countries, these coding differences influence the reported level of diabetes mortality. For Northern Ireland and Malta, the number of certificates with diabetes as the underlying cause of death was more than doubled after central recoding and for The Netherlands, in contrast, it was almost halved. To explain the differences a number of factors are considered: a lack of information from the International Classification of Diseases (ICD), on the application of the coding rules, between-country differences in cause of death certification practices, a divergence of opinion about the causal role of diabetes when it is associated with other conditions, a lack of homogeneity between countries in data collection procedures.(ABSTRACT TRUNCATED AT 250 WORDS)     

A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group.

BACKGROUND. In primary biliary cirrhosis the hepatic lesions may result, at least in part, from the intracellular accumulation of potentially toxic endogenous bile acids. Preliminary work suggests that the administration of ursodiol (also called ursodeoxycholic acid), a hydrophilic bile acid without hepatotoxicity, leads to improvement in the condition of patients with primary biliary cirrhosis. METHODS. We conducted a two-year, multicenter, double-blind trial to compare the efficacy of ursodiol with that of placebo. Patients with biopsy-proved primary biliary cirrhosis were randomly assigned to receive either ursodiol (13 to 15 mg per kilogram of body weight per day) (n = 73) or placebo (n = 73). Treatment failure was defined as a doubling of bilirubin levels to more than 70 mumol per liter or the occurrence of a severe complication (ascites or variceal bleeding) or an adverse reaction. RESULTS. Treatment failed in 6 patients in the ursodiol group, as compared with 13 in the placebo group (P less than 0.01 by Cox regression model). A single patient in each group withdrew because of minor adverse effects. After two years of treatment, the proportion of patients with clinically overt disease decreased only in the ursodiol group (P less than 0.02). The patients treated with ursodiol had significant improvements in serum levels of bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, cholesterol, and IgM (all P less than 0.001); the antimitochondrial-antibody titer (P less than 0.01); and the Mayo risk score (P less than 0.001). Follow-up analysis of 95 liver-biopsy specimens showed a significant improvement in the mean histologic score (P less than 0.002) and in all the characteristic histologic features except fibrosis only in the group given ursodiol. CONCLUSIONS. Ursodiol is a safe and effective treatment for primary biliary cirrhosis.     

The role of non-esterified fatty acids in the deterioration of glucose tolerance in Caucasian subjects: results of the Paris Prospective Study

Summary Although an increased plasma non-esterified fatty acid (NEFA) concentration has been shown to increase insulin resistance (Randle cycle), decrease insulin secretion and increase hepatic gluconeogenesis, the effect of NEFA on the deterioration of glucose tolerance has not been studied prospectively in Caucasian subjects. Therefore, we investigated whether plasma NEFA may be regarded as predictors of deterioration of glucose tolerance in subjects with normal (NGT, n = 3671) or impaired (IGT, n = 418) glucose tolerance who were participants in the Paris Prospective study. The subjects were first examined between 1967 and 1972 and underwent two 75-g oral glucose tolerance tests 2 years apart with measurements of plasma glucose, insulin and NEFA concentrations. Glucose tolerance deteriorated from NGT to IGT or non-insulin-dependent diabetes (NIDDM) in 177 subjects and from IGT to NIDDM in 32 subjects. In multivariate analysis, high fasting plasma NEFA in NGT subjects and high 2-h plasma NEFA and low 2-h plasma insulin concentrations in IGT subjects were significant independent predictors of deterioration along with older age, high fasting and 2-h plasma glucose concentrations and high iliac to thigh ratio. When subjects were divided by tertiles of plasma NEFA concentration at baseline, there was an increase in 2-h glucose concentration with increasing NEFA in the subjects who did not deteriorate, but no effect of plasma NEFA in those who deteriorated. In subjects with IGT who deteriorated compared with those who did not 2-h plasma insulin concentration was lower but there was no evidence that this resulted from an effect of plasma NEFA. Our data suggest that a high plasma NEFA concentration is a risk marker for deterioration of glucose tolerance independent of the insulin resistance or the insulin secretion defect that characterize subjects at risk for NIDDM. [Diabetologia (1997) 40: 1101–1106] Received: 11 March 1997 and in revised form: 20 May 1997     

Association between heart rate-corrected QT interval and coronary risk factors in 2,894 healthy subjects (the DESIR Study). Data from an Epidemiological Study on the Insulin Resistance syndrome

In the prospective Data from an Epidemiological Study on the Insulin Resistance Syndrome, 2,894 healthy subjects aged 30 to 64 years had determinations of fasting glucose, insulin, serum lipid and fibrinogen concentrations, blood pressures, body mass index, and waist-hip ratio, as well as tobacco and alcohol consumptions and physical activity. A 12-lead electrocardiogram with automatic measurement of the QT interval was recorded and the formula used for heart rate correction was based on the best-fit regression between QT and heart rate. The QT duration was influenced by glucose homeostasis in both sexes, and increased in men with physical activity; there was a dose-effect relation for men who smoked.     

Type 2 diabetes-related genetic risk scores associated with variations in fasting plasma glucose and development of impaired glucose homeostasis in the prospective DESIR study

Aims/hypothesis

Genome-wide association studies have firmly established 65 independent European-derived loci associated with type 2 diabetes and 36 loci contributing to variations in fasting plasma glucose (FPG). Using individual data from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) prospective study, we evaluated the contribution of three genetic risk scores (GRS) to variations in metabolic traits, and to the incidence and prevalence of impaired fasting glycaemia (IFG) and type 2 diabetes.

Methods

Three GRS (GRS-1, 65 type 2 diabetes-associated single nucleotide polymorphisms [SNPs]; GRS-2, GRS-1 combined with 24 FPG-raising SNPs; and GRS-3, FPG-raising SNPs alone) were analysed in 4,075 DESIR study participants. GRS-mediated effects on longitudinal variations in quantitative traits were assessed in 3,927 nondiabetic individuals using multivariate linear mixed models, and on the incidence and prevalence of hyperglycaemia at 9 years using Cox and logistic regression models. The contribution of each GRS to risk prediction was evaluated using the C-statistic and net reclassification improvement (NRI) analysis.

Results

The two most inclusive GRS were significantly associated with increased FPG (β?=?0.0011 mmol/l per year per risk allele, p _GRS-1 ?=?8.2?×?10^?5 and p _GRS-2 ?=?6.0?×?10^?6), increased incidence of IFG and type 2 diabetes (per allele: HR _GRS-1 1.03, p?=?4.3?×?10^?9 and HR _GRS-2 1.04, p?=?1.0?×?10^?16), and the 9 year prevalence (OR _GRS-1 1.13 [95% CI 1.10, 1.17], p?=?1.9?×?10^?14 for type 2 diabetes only; OR _GRS-2 1.07 [95% CI 1.05, 1.08], p?=?7.8?×?10^?25, for IFG and type 2 diabetes). No significant interaction was found between GRS-1 or GRS-2 and potential confounding factors. Each GRS yielded a modest, but significant, improvement in overall reclassification rates (NRI _GRS-1 17.3%, p?=?6.6?×?10^?7; NRI _GRS-2 17.6%, p?=?4.2?×?10^?7; NRI _GRS-3 13.1%, p?=?1.7?×?10^?4).

Conclusions/interpretation

Polygenic scores based on combined genetic information from type 2 diabetes risk and FPG variation contribute to discriminating middle-aged individuals at risk of developing type 2 diabetes in a general population.     

Dietary acid load and risk of type 2 diabetes: the E3N-EPIC cohort study

Aims/hypothesis

The objective of this study was to evaluate the prospective relationship between dietary acid load, assessed with both the potential renal acid load (PRAL) and the net endogenous acid production (NEAP) scores, and type 2 diabetes risk.

Methods

A total of 66,485 women from the E3N-EPIC cohort were followed for incident diabetes over 14 years. PRAL and NEAP scores were derived from nutrient intakes. HRs for type 2 diabetes risk across quartiles of the baseline PRAL and NEAP scores were estimated with multivariate Cox regression models.

Results

During follow-up, 1,372 cases of incident type 2 diabetes were validated. In the overall population, the highest PRAL quartile, reflecting a greater acid-forming potential, was associated with a significant increase in type 2 diabetes risk, compared with the first quartile (HR 1.56, 95% CI 1.29, 1.90). The association was stronger among women with BMI <25 kg/m² (HR 1.96, 95% CI 1.43, 2.69) than in overweight women (HR 1.28, 95% CI 1.00, 1.64); statistically significant trends in risk across quartiles were observed in both groups (p _trend?<?0.0001 and p _trend?=?0.03, respectively). The NEAP score provided similar findings.

Conclusions/interpretation

We have demonstrated for the first time in a large prospective study that dietary acid load was positively associated with type 2 diabetes risk, independently of other known risk factors for diabetes. Our results need to be validated in other populations, and may lead to promotion of diets with a low acid load for the prevention of diabetes. Further research is required on the underlying mechanisms.     

Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body sizeThe EPIC-InterAct study

Abstract. Beulens JWJ, van der Schouw YT, Bergmann MM, Rohrmann S, B Schulze M, Buijsse B, Grobbee DE, Arriola L, Cauchi S, Tormo M‐J, Allen NE, van der A DL, Balkau B, Boeing H, Clavel‐Chapelon F, de Lauzon‐Guillan B, Franks P, Froguel P, Gonzales C, Halkjær J, Huerta JM, Kaaks R, Key TJ, Khaw KT, Krogh V, Molina‐Montes E, Nilsson P, Overvad K, Palli D, Panico S, Ramón Quirós J, Ronaldsson O, Romieu I, Romaguera D, Sacerdote C, Sánchez M‐J, Spijkerman AMW, Teucher B, Tjonneland A, Tumino R, Sharp S, Forouhi NG, Langenberg C, Feskens EJM, Riboli E, Wareham NJ (University Medical Center Utrecht, The Netherlands; German Institute of Human Nutrition, Potsdam‐Rehbrücke, Germany; German Cancer Research Centre, Heidelberg, Germany; Basque Government, San Sebastian, CIBERESP, Spain; Institut de Biologie de Lille, Lille, France; Murcia Regional Health Council, Murcia, Spain; CIBER Epidemiologia y Salud Publica (CIBERESP), Spain; University of Oxford, Oxford, UK; National Institute of Public Health and the Environment, Bilthoven, The Netherlands; Inserm, CESP Centre for Research in Epidemiology and Population Health, Villejuif Cedex, France; Lund University, Malmö, Sweden; Imperial College, London, UK; Department of Epidemiology, Barcelona, Spain; Danish Cancer Society, Copenhagen, Denmark; University of Cambridge, Cambridge, UK; Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy; Andalusian School of Public Health, Granada, Spain; School of Public Health, Aarhus, Denmark; Cancer Research and Prevention Institute (ISPO), Florence, Italy; Università Federico II, Napoli, Italy; Consejeria de Salud y Servicios Sanitarios, Oviedo‐Asturias, Spain; Umea University, Umea, Sweden; International Agency for Research of Cancer, Lyon, France; Center for Cancer Prevention (CPO‐Piemonte), Torino, Italy; “Civile ‐ M.P. Arezzo” Hospital, Ragusa, Italy; Addenbrooke’s Hospital, Cambridge, UK; and Wageningen University, Wageningen, The Netherlands). Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body size. The EPIC–InterAct study. J Intern Med 2012; 272: 358–370. Objective: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. Design: Multicentre prospective case–cohort study. Setting: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. Subjects: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. Interventions: Alcohol consumption assessed using validated dietary questionnaires. Main outcome measures: Occurrence of type 2 diabetes based on multiple sources (mainly self‐reports), verified against medical information. Results: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.78–1.05) for 6.1–12.0 versus 0.1–6.0 g day^?1, adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.1–96.0 g day^?1 with an HR of 0.86 (95% CI: 0.75–0.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.72–0.92) for 6.1–12.0 g day^?1 (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI ≥ 25 kg m^?2) than normal‐weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.79–1.03 for 6.1–12.0 g day^?1). Wine consumption for men and fortified wine consumption for women were most strongly associated with a reduced risk of diabetes. Conclusions: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal‐weight women and men.