Clinical course and outcomes of type-2 diabetic patients after treatment intensification for insufficient glycaemic control - results of the 2 year prospective DiaRegis follow-up.

BACKGROUND: In cases where antidiabetic monotherapy is unable to sufficiently control glucose levels in patients with type-2 diabetes, treatment needs to be intensified. Determining factors that may be predictors for the occurrence of comorbidities in these patients is essential for improving the efficacy of clinical diabetes care. METHODS: The DiaRegis prospective cohort study included 3,810 type-2 diabetics for whom the treating physician aimed to intensify and optimise antidiabetic treatment due to insufficient glucose control. Treatment intensification was defined as increasing the dose of the originally prescribed drug, and/or selecting an alternative drug, and/or prescribing an additional drug. The aims were to monitor the co-morbidity burden of type-2 diabetic patients over a follow-up of two years, and to identify multivariable adjusted predictors for the development of comorbidity and cardiovascular events. RESULTS: A total of 3,058 patients completed the 2 year follow-up. A substantial proportion of these patients had co-morbidities such as vascular disease, neuropathy, and heart failure at baseline. After treatment intensification, there was an increased use of DPP-4 inhibitors, insulin, and GLP-1 analogues, achieving reductions in HbA1c, fasting plasma glucose, and postprandial glucose. During the 2 year period 2.5% of patients (n = 75) died, 3.2% experienced non-fatal macrovascular events, 11.9% experienced microvascular events, and 4.3% suffered onset of heart failure. Predictors for combined macro-/microvascular complications/heart failure/death were found to be age (OR 1.36; 95% CI 1.10-1.68), prior vascular disease (1.73; 1.39-2.16), and history of heart failure (2.78; 2.10-3.68). CONCLUSIONS: Determining the factors that contribute to co-morbidities during intensive glucose-lowering treatment is essential for improving the efficacy of diabetes care. Our results indicate that age, prior vascular disease, and heart failure constitute important predictors of poor cardiovascular outcomes in patients receiving such therapy.

Co-morbidity but not dysglycaemia reduces quality of life in patients with type-2 diabetes treated with oral mono- or dual combination therapy--an analysis of the DiaRegis registry.

BACKGROUND: Type-2 diabetes mellitus has a major impact on health related quality of life (HRQoL). We aimed to identify patient and treatment related variables having a major impact. METHODS: DiaRegis is a prospective diabetes registry. The EQ-5D was used to describe differences in HRQoL at baseline. Odds ratios (OR) with 95% confidence intervals (CI) were determined from univariable regression analysis. For the identification of independent predictors of a low score on the EQ-5D, multivariable unconditional logistic regression analysis was performed. RESULTS: A total of 2,760 patients were available for the present analysis (46.7% female, median age 66.2 years). Patients had considerable co-morbidity (18.3% coronary artery disease, 10.6% heart failure, 5.9% PAD and 5.0% stroke/TIA). Baseline HbA1c was 7.4%, fasting- and postprandial plasma glucose 139 mg/dl and 183 mg/dl.The median EQ-5D was 0.9 (interquartile range [IQR] 0.8-1.0). Independent predictors for a low EQ-5D were age > 66 years (OR 1.49; 95%CI 1.08-2.06), female gender (2.11; 1.55-2.86), hypertension (1.73; 1.03-2.93), peripheral neuropathy (1.62; 0.93-2.84) and clinically relevant depression (11.01; 3.97-30.50). There was no influence of dysglycaemia on the EQ-5D score. CONCLUSION: The present study suggests, that co-morbidity but not average glycaemic control reduces health related quality of life in type 2 diabetes mellitus.

Oral antidiabetic treatment in type-2 diabetes in the elderly: balancing the need for glucose control and the risk of hypoglycemia.

BACKGROUND: We aimed at identifying variables predicting hypoglycemia in elderly type 2 diabetic patients and the relation to HbA1c values achieved. DESIGN: Prospective, observational registry in 3810 patients in primary care. Comparison of patients in different age tertiles: with an age < 60 (young, n=1,253), age 60 to < 70 (middle aged, n=1,184) to those ≥ 70 years (elderly, n=1,373). Odds Ratios (OR) with 95% confidence intervals (CI) were determined from univariable and multivariable regression analyses. RESULTS: Elderly patients had a later diabetes diagnosis, a longer diabetes duration, better glucose control and more frequent co-morbid disease conditions. Overall 10.7% of patients experienced any severity hypoglycemia within the last 12 months prior to inclusion. Higher rates of hypoglycemia were observed in the elderly than in the young after adjusting for differences in HbA1c, fasting and post-prandial blood glucose (OR 1.68; 95%CI 1.16-2.45). This was particularly true for hypoglycemic episodes without specific symptoms (OR 1.74; 95%CI 1.05-2.89). In a multivariate model stroke / transitory ischemic attack, the presence of heart failure, clinically relevant depression, sulfonylurea use and blood glucose self-measurement were associated with hypoglycemic events. CONCLUSION: Elderly patients are at an increased risk of hypoglycemia even at comparable glycemic control. Therefore identified variables associated with hypoglycemia in the elderly such as heart failure, clinically relevant depression, the use of sulfonylurea help to optimize the balance between glucose control and low levels of hypoglycemia. Asymptomatic hypoglycemia should not be disregarded as irrelevant but considered as a sign of possible hypoglycemia associated autonomic failure.

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.

Antidiabetic pharmacotherapy and anamnestic hypoglycemia in a large cohort of type 2 diabetic patients--an analysis of the DiaRegis registry.

BACKGROUND: We aimed to identify predictors of anamnestic hypoglycaemia in type-2 diabetic patients on oral mono- or dual oral combination antidiabetic pharmacotherapy. METHODS: DiaRegis is a prospective registry in type-2 diabetic patients in primary care. Odds ratios (OR) with 95% confidence intervals were determined from univariate logistic regression. Using multivariate logistic regression analysis with stepwise backward selection at an alpha of 0.05 independent predictors of hypoglycaemia were determined. RESULTS: 3,808 patients had data on hypoglycaemia available (median age 65.9 years, 46.6% female). 10.8% had at least one anamnestic hypoglycaemic episode within the previous 12 months. Patients with hypoglycaemia received more sulfonylureas (OR 2.16; 95%CI 1.75-2.67) and less metformin (OR 0.64; 95%CI 0.50-0.82). On top of metformin, patients with thiazolidine (OR 0.50; 95%CI 0.28-0.89) and DPP-4 inhibitor use (OR 0.34; 95%CI 0.16-0.70) had a decreased risk for hypoglycaemia while it was again increased with sulfonylureas (OR 2.08; 95%CI 1.44-2.99). Age < 65 years was an independent predictor of a reduced hypoglycaemia incidence (OR 0.76; 95%CI 0.59-0.96), low HbA1c (OR 1.68; 95%CI 1.31-2.14), stroke/TIA (OR 1.72; 95%CI 1.08-2.72), heart failure (OR 1.77; 95%CI 1.28-2.45), and the use of sulfonylureas (OR 2.58; 95%CI 2.03-3.29) were independent predictors of increased risk. CONCLUSIONS: The results indicate that the risk of hypoglycaemia might be substantially reduced by carefully selecting antidiabetic pharmacotherapy in patients with type-2 diabets in primary care.

Diabetes treatment patterns and goal achievement in primary diabetes care (DiaRegis) - study protocol and patient characteristics at baseline.

BACKGROUND: Patients with type 2 diabetes are at an increased risk for disease and treatment related complications after the initial approach of oral mono/dual antidiabetic therapy has failed. Data from clinical practice with respect to this patient group are however scarce. Therefore we set up a registry in primary care documenting the course and outcomes of this patient group. METHODS: Diabetes Treatment Patterns and Goal Achievement in Primary Diabetes Care (DiaRegis) is a prospective, observational, German, multicenter registry including patients with type-2 diabetes in which oral mono/dual antidiabetic therapy has failed. Data were recorded at baseline and will be prospectively documented during visits at 6 ± 1, 12 ± 2 and 24 ± 2 months. The primary objective is to estimate the proportion of patients with at least 1 episode of severe hypoglycemia within one year. RESULTS: 313 primary care offices included 4,048 patients between June 2009 and March 2010 of which 3,810 patients fulfilled the in- and exclusion criteria. 46.7% of patients were female; patients had a median diabetes duration of 5.5 years and most were obese with respect to BMI or waist circumference. HbA1c at baseline was 7.4%, fasting plasma glucose 142 mg/dl and postprandial glucose 185 mg/dl. Co-morbidity in this patient population was substantial with 17.9% having coronary artery disease, 14.4% peripheral neuropathy, 9.9% heart failure and 6.0% peripheral arterial disease. 68.6% of patients received oral monotherapy, 31.4% dual oral combination therapy. The most frequent antidiabetic agent used as monotherapy was metformin (79.0%) followed by sulfonylureas (14.8%). CONCLUSIONS: DiaRegis is a large, prospective registry in primary diabetes care to document the course and outcomes of patients with type-2 diabetes in which the initial approach of oral mono/dual antidiabetic therapy has failed. The two year follow-up will allow for a prospective evaluation of these patients during multiple adjustments of therapy.

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.

Two-Year Outcomes of Patients Treated With Aliskiren Under Clinical Practice Conditions: Non-Interventional Prospective Study.

The authors investigated the long-term effectiveness and safety of aliskiren (ALIS) with particular attention on its association with dual blockade of the renin-angiotensin system (RAS). The open, prospective 3A Registry (N=8723) in Germany assigned patients in a 4:1:1 ratio to ALIS, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), or non-RAS drugs. Patients taking ALIS compared with those taking ACE inhibitors/ARBs or non-RAS had more comorbidities and risk factors, were taking more antihypertensive agents, and had higher blood pressure (BP) values at entry. At 2 years, BP reduction from baseline was similar in all groups (mean, -20.5/-9.9 mm Hg). A total of 2.3% of patients died, 0.5% had myocardial infarction, 0.6% had stroke, 2.9% were hospitalized, and 5.5% had any event (not significant between groups). ALIS alone or combined with another RAS inhibitor was well tolerated and effective in lowering BP in typical unselected patients with hypertension. Given the methodical limitations of the design, the study cannot be used to confirm or refute safety concerns for dual RAS blockade as suggested by the Aliskiren Trial in Type 2 Diabetes Using Cardio-Renal Endpoints (ALTITUDE) trial.

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.

Hypoglycaemia is more frequent in type 2 diabetic patients with co-morbid vascular disease: an analysis of the DiaRegis registry.

BACKGROUND: Patients with type-2 diabetes are at risk for treatment- and disease-related complications. Little is known about the interrelation of hypoglycaemia and co-morbid vascular disease (VD), defined as coronary heart disease, stroke and peripheral arterial disease. HYPOTHESIS: Hypoglycaemia is associated with co-morbid VD in diabetic patients. METHODS: DiaRegis is a prospective registry that included patients with type-2 diabetes in 2009/2010. Metric variables are displayed as median and quartiles. For the comparison of patients with or without VD Odds Ratios (OR) were determined from univariate analyses and adjusted for differences in patient characteristics (multivariable analysis). RESULTS: Data on hypoglycaemia and VD within the last 12 months were available for 3741 patients (98.2%) with a median (IQR) age of 65.9 (57.6-72.9) years; 46.7% were female. VD patients (n = 909; 24.3%) were older (70.7 vs 63.9 years; p < 0.0001), less often female (33.6% vs 50.9%; p < 0.0001) and had had diabetes for a longer duration (6.4 vs 5.4 years; p < 0.0001). Mean cholesterol (total, HDL and LDL) was also slightly lower (p < 0.0001). Glycaemic control (HbA1c, fasting and postprandial glucose) was comparable. VD patients received less metformin (80.7 vs 85.2%; p < 0.01) and more sulfonylureas (31.8 vs 27.6%; p < 0.05). There was an increased incidence of symptomatic hypoglycaemia with or without requiring help and with a need for medical assistance. After adjusting a number of baseline variables the rates of symptomatic hypoglycaemias with help remained significantly increased (OR 3.73 (95% CI 1.31-10.65) in patients with VD. CONCLUSIONS: As hypothesized there is a strong association between the incidence of hypoglycaemia and vascular disease at comparable glycaemic control, which confirms prior randomized controlled trial data suggesting an interrelationship between hypoglycaemia and vascular disease.

Guideline adherence in cardiovascular risk assessment and analysis in 15,000 hypertensive German patients in real life: results of the Prospective 3A Registry.

The benefit obtained from antihypertensive treatment is related more to overall cardiovascular risk reduction than to blood pressure levels. Accurate implementation of cardiovascular diagnostics is a key step toward assessment of cardiovascular risk. In the 3A Registry study, data about patient history, concomitant diseases, diagnostic procedures, and medications were prospectively collected. A total of 14,738 patients recruited by 899 physicians in 2008 and 2009 were analyzed. Assessment of cardiovascular risk factors and subclinical end-organ damage (SOD) showed broad differences in the implementation of European Society of Hypertension/European Society of Cardiology recommendations. Electrocardiograms were available in 59% of patients, cholesterol in 71.4%, and glucose in 69.7%. Almost all patients (99.6%) had creatinine measurements performed and microalbuminuria was measured in 8.5%. Metabolic syndrome (MS) had been evaluated in 59.7%. Implementation of diagnostic guidelines was highest in hypertensive patients with diabetes, followed by patients with known cardiovascular disease and established chronic renal insufficiency. For hypertensive patients without known comorbidities, the authors estimated that up to 29% had missed SOD (detection rate <50%) and 13% missed MS due to incomplete assessment of risk factors. This large registry study shows that assessment for cardiovascular risk factors and SOD is incomplete. Major efforts are required to improve comprehensive hypertension management as recommended by current guidelines.

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.