Incidence and predictors of hypoglycaemia in type 2 diabetes - an analysis of the prospective DiaRegis registry.

BACKGROUND: Hypoglycaemia is a serious adverse effect of antidiabetic drug therapy. We aimed to determine incidence rates of hypoglycaemia in type-2 diabetic patients and identify predictors of hypoglycaemia when treatment is intensified. METHODS: DiaRegis is a prospective German registry that follows 3810 patients with type-2 diabetes referred for treatment intensification because of insufficient glycaemic control on one or two oral antidiabetic drugs. RESULTS: Out of a total of 3347 patients with data available for the present analysis 473 (14.1%) presented any severity hypoglycaemia over a follow-up of 12 months. 0.4% were hospitalized (mean of 1.3±0.6 episodes), 0.1% needed medical assistance (1.0±0.0), 0.8% needed any help (1.1±0.5) and 10.1% no help (3.4±3.7), and 8.0% had no specific symptoms (3.6±3.5). Patients with incident hypoglycaemia had longer diabetes duration, higher HbA1c and a more frequent smoking history; more had co-morbid disease conditions such as coronary artery disease, peripheral arterial disease, amputation, heart failure, peripheral neuropathy, diabetic retinopathy and clinically relevant depression at baseline. Multivariable adjusted positive predictors of incident hypoglycaemia over the follow-up were prior anamnestic hypoglycaemia, retinopathy, depression, insulin use and blood glucose self-measurement, but not sulfonylurea use as previously reported for anamnestic or recalled hypogylcaemia. On the contrary, glitazones, DPP-4 inhibitors and GLP-1 analogues were associated with a reduced risk of hypoglycaemia. CONCLUSIONS: Hypoglycaemia is a frequent adverse effect in ambulatory patients when antidiabetic treatment is intensified. Particular attention is warranted in patients with prior episodes of hypoglycaemia, microvascular disease such as retinopathy and in patients receiving insulin. On the other hand glitazones, DPP-4 inhibitors and GLP-1 analogues are associated with a reduced risk.

Asbestos exposure and malignant lymphoma: a multicenter case-control study in Germany and Italy.

AIMS: To analyze the relationship between asbestos exposure and malignant lymphoma in a multicenter case-control study conducted in Germany and Italy according to a common core protocol. METHODS: Male and female patients with malignant lymphoma (n = 1,034) between 18 and 80 years of age were prospectively recruited in six study areas in Germany (Ludwigshafen/Upper Palatinate, Heidelberg/Rhine-Neckar-County, Würzburg/Lower Frankonia, Hamburg, Bielefeld/East Westphalia, and Munich) and in two study areas in Sardinia, Italy (Cagliari and Nuoro provinces). A total of 1,173 population control subjects were drawn from population registers. In a structured personal interview, we elicited a complete occupational history, including every occupational period that lasted at least 1 year. On the basis of job task-specific supplementary questionnaires, trained experts assessed the exposure to asbestos. As a measure of cumulative asbestos exposure on a time by intensity scale, fiber-years were calculated. 12 cases (1.2%) and 12 control subjects (1.0%) had a cumulative asbestos exposure of more than 2.6 fiber-years (highest exposure category according to the 90th percentile of exposed control subjects). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression analysis adjusted for age, sex and study region. Patients with specific lymphoma sub-entities were additionally compared with the entire control group. RESULTS: We observed no statistically significant association between cumulative asbestos exposure and the risk of any lymphoma subtype. An elevated risk was found for the association between exposure to more than 2.6 fiber-years and multiple myeloma (OR = 6.0; 95% CI 1.4-25.1); however, numbers were small (n = 3 cases, all of them from Italy; n = 12 control subjects). CONCLUSIONS: Our study does not support an association between asbestos exposure and risk of malignant lymphoma.

Joint effect between regular use of non-steroidal anti-inflammatory drugs, variants in inflammatory genes and risk of lymphoma.

OBJECTIVE: Limited evidence suggests the importance of inflammatory processes for the etiology of lymphomas. To further research in this area, we investigated the role of genetic variants in key inflammatory factors, non-steroidal anti-inflammatory drug [NSAID] use, and their joint effect in lymphomagenesis. METHODS: The study comprised 710 case-control pairs, matched for gender, age, and study region. We examined the association of regular NSAID use and polymorphisms in prostaglandin-endoperoxide synthase-2 (COX2), prostaglandin E synthase (PTGES), interleukin-1 alpha (IL1A), IL-1 beta (IL1B), and IL-1 receptor antagonist (IL1RA), and lymphoma risk by applying logistic regression to calculate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: Regular NSAID use was associated with a slightly reduced risk of B-NHL (OR = 0.8, 95% CI = 0.6-1.1). For T-NHL, the COX2 rs2745557 A-allele conferred a 2.2-fold (95% CI = 1.1-4.5) and homozygosis for the IL1RN rs454078 T-allele was associated with a 4.5-fold (95% CI = 1.4-13.9) elevated risk, however, based on sparse data. IL1 haplotype 5 was associated with a statistically significant 43% increased risk for B-NHL among non-regular users of NSAIDs, but a 70% decreased risk for regular users (p-value for interaction < 0.001). CONCLUSIONS: These results suggest the relevance of joint effects between NSAID use and IL1 haplotypes on the risk of B-NHL.

Solvent exposure and malignant lymphoma: a population-based case-control study in Germany.

AIMS: To analyze the relationship between exposure to chlorinated and aromatic organic solvents and malignant lymphoma in a multi-centre, population-based case-control study. METHODS: Male and female patients with malignant lymphoma (n = 710) between 18 and 80 years of age were prospectively recruited in six study regions in Germany (Ludwigshafen/Upper Palatinate, Heidelberg/Rhine-Neckar-County, Würzburg/Lower Frankonia, Hamburg, Bielefeld/Gütersloh, and Munich). For each newly recruited lymphoma case, a gender, region and age-matched (+/- 1 year of birth) population control was drawn from the population registers. In a structured personal interview, we elicited a complete occupational history, including every occupational period that lasted at least one year. On the basis of job task-specific supplementary questionnaires, a trained occupational physician assessed the exposure to chlorinated hydrocarbons (trichloroethylene, tetrachloroethylene, dichloromethane, carbon tetrachloride) and aromatic hydrocarbons (benzene, toluene, xylene, styrene). Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression analysis, adjusted for smoking (in pack years) and alcohol consumption. To increase the statistical power, patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression analysis. RESULTS: We observed a statistically significant association between high exposure to chlorinated hydrocarbons and malignant lymphoma (Odds ratio = 2.1; 95% confidence interval 1.1-4.3). In the analysis of lymphoma subentities, a pronounced risk elevation was found for follicular lymphoma and marginal zone lymphoma. When specific substances were considered, the association between trichloroethylene and malignant lymphoma was of borderline statistical significance. Aromatic hydrocarbons were not significantly associated with the lymphoma diagnosis. CONCLUSION: In accordance with the literature, this data point to a potential etiologic role of chlorinated hydrocarbons (particularly trichloroethylene) and malignant lymphoma. Chlorinated hydrocarbons might affect specific lymphoma subentities differentially. Our study does not support a strong association between aromatic hydrocarbons (benzene, toluene, xylene, or styrene) and the diagnosis of a malignant lymphoma.

Sun exposure and malignant lymphoma: a population-based case-control study in Germany.

Although some causes for malignant lymphoma are known their etiology is not well understood so far. We analyze the relationship between sun exposure and malignant lymphoma in a multicenter, population-based case-control study. Patients with malignant lymphoma (n = 710, 18-80 years) were prospectively recruited in 6 study regions in Germany. For each case, a gender, region and age-matched control was drawn from population-registers. In personal interviews, lifetime holidays spent in sunny climate, outdoor leisure activities and sunbed or sunlamp use were recorded. On basis of job task-specific supplementary questionnaires, an occupational physician assessed the cumulative working time outside. Odds ratios (OR) and 95%-confidence-intervals (CI) were calculated using conditional logistic regression analysis, adjusted for smoking and alcohol consumption. To increase statistical power, patients with specific lymphoma subentities were additionally compared with the entire control group using unconditional logistic regression. We observed a reduced overall lymphoma risk among subjects having spent vacations at sunny climates or frequently used sunbeds or sunlamps. The analysis of lymphoma subentities revealed similar results with the exception of T-NHL and follicular lymphoma which were positively associated with outdoor leisure activities. While cumulative working time outside appeared unrelated to NHL overall and most subentities, it was negatively associated with follicular lymphoma and weakly positively to HL. This data suggest that exposure to natural and artificial ultraviolet radiation may reduce the OR for lymphoma in this study population.

Tobacco and alcohol consumption and risk of lymphoma: results of a population-based case-control study in Germany.

Changing trends in lifestyle exposures are suggested to be contributing factors to the increasing incidence rates for lymphoma. We investigated the relationship between smoking and alcohol consumption and the risk of lymphoma among adult participants of a population-based case-control study recently conducted in Germany. In 710 case-control pairs, an increased risk of lymphoma was associated with a long duration of smoking (p for trend = 0.01 for men) and smoking of > 20 cigarettes per day(OR = 2.7; 95% CI = 1.4-5.2 for women). Elevated odds ratios were seen for most lymphoma subentities, albeit mostly without reaching statistical significance. A strong association was evident between smoking and multiple myeloma (OR = 2.4, 95% CI = 0.98-5.74 for men; OR = 2.9, 95% CI = 1.1-7.4 for women) and Hodgkin's lymphoma among men (OR = 3.6; 95% CI = 1.7-7.5). Alcohol consumption 10 years prior to the date of interview appeared to decrease the risk of lymphoma. Odds ratios for men who reported alcohol consumption were 53% lower (95% CI = 0.31-0.71) compared to men who drank very little or no alcohol. The same tendency was evident for women, although the association was less pronounced. The inverse relationship was also seen for low amounts of alcohol and did not appear to be restricted to specific types of beverages. Although biologic rationale for a protective effect of alcohol consumption may be given, a more in-depth analysis involving genetic markers is indicated to clarify if ethanol, other components in alcoholic beverages, or factors associated with moderate drinking reduce lymphoma risk among adults. In conclusion, this investigation suggests a positive association between tobacco smoking and lymphoma risk and finds decreased odds ratios among consumers of alcohol.

Medical history and risk for lymphoma: results of a population-based case-control study in Germany.

Since lymphomas are malignancies of cells of the immune system, associations with disorders characterised by impaired immune functions can be assumed. We investigated the relationship between a history of selected medical conditions and the risk for lymphoma including specified subentities within our population-based case-control study of lymphoma among adults conducted in Germany between 1999 and 2002. Overall, we found decreased risks for a history of repeated diarrhoea, warts, arthrosis, allergies, and appendectomy (at a younger age). Elevated risks for lymphoma correlated with tonsillectomy (at a younger age), whereas null results were found for selected auto-immune disorders in adulthood. Although the numbers are small, most of the results for the subentities corresponded with these findings. These results are compatible with the notion that persistent immunological alterations contribute to the aetiology of lymphoma, but partially inconsistent with the Th1/Th2-shift paradigm.

Population-based study of lymphoma in Germany: rationale, study design and first results.

A multi-centre, population-based case-control study of lymphoma among adults was conducted in Germany from 1999-2003. The study comprised 700 incident cases (Hodgkin lymphomas and non Hodgkin's lymphoma, NHL) in the age range 18-80 years and 700 age-, sex- and area-matched controls obtained from population registries. Diagnosis was based on the REAL/WHO classification. Information on demographic characteristics, lifestyle, medical history and occupation was obtained by in-person interviews. Each participant was asked for a 24 ml blood sample. First results are focused on basic demographic characteristics, contact to animals, childhood diseases and vaccinations. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. The ORs for lymphoma were decreased for exposure to sheep and goats (OR = 0.7; 95% CI = 0.5-0.9), for rabbits and hare (OR = 0.7; 95% CI = 0.5-0.9), measles infection (OR = 0.6; 95% CI = 0.5-0.9), Bordetella pertussis infection (OR = 0.7; 95% CI = 0.6-0.95), and tetanus vaccination (OR = 0.5; 95% CI = 0.3-0.9). Increased risk of lymphoma was associated with exposure to cattle (OR = 1.3; 95% CI = 1.03-1.7) and immunization for tuberculosis (OR = 1.5; 95% CI = 0.997-2.4). The results of this study are partly consistent with the hygiene hypothesis. The inconsistencies of some of the findings with an explanation by the Th1/Th2 paradigm, however, warrant further research and may indicate that broader explanatory concepts are needed.