Junmei Miao Jonasson

Insulin glargine use and short-term incidence of malignancies—a population-based follow-up study in Sweden

Aims/hypothesisIn the light of a report suggesting that insulin glargine may increase cancer occurrence, the EASD asked us to perform this study.MethodsWe followed 114,841 individuals who had a prescription dispensed for insulin between 1 July and 31 December 2005. From 1 January 2006 to 31 December 2007, we noted the occurrence of malignancies. Seven different nationwide registers were used to obtain information on insulin exposure, outcome and possible confounders; these were linked using the unique personal identity number assigned to every Swedish resident.ResultsAfter adjustment for age and, when appropriate, sex, users of insulin glargine alone (no other types of insulin), compared with users of types of insulin other than insulin glargine, had an RR of 1.99 (95% CI 1.31–3.03) for breast cancer, 0.93 (95% CI 0.61–1.40) for gastrointestinal cancer, 1.27 (95% CI 0.89–1.82) for prostate cancer and 1.07 (95% CI 0.91–1.27) for any type of malignancy. Adjustment for age, smoking, BMI, age at onset of diabetes, age at birth of first child, cardiovascular disease and oestrogen use gave an RR for breast cancer of 1.97 (95% CI 1.29–3.00). The 95% CIs crossed 1.0 for the RR calculated in all analyses of users of insulin glargine in combination with other types of insulin.Conclusions/interpretationIn Sweden, during 2006 and 2007, women using insulin glargine alone (no other types of insulin) had an increased incidence rate of breast cancer as compared with women using types of insulin other than insulin glargine. This result may be due to a random fluctuation; the possibilities for examining validity are limited, and no statistically significant results were obtained for any other individual cancer site or for the outcome ‘all malignancies’. No definitive conclusions regarding a possible causal relationship between insulin glargine use and the occurrence of malignancies can be drawn from the results of this study.

Bias in odds ratios by logistic regression modelling and sample size

BackgroundIn epidemiological studies researchers use logistic regression as an analytical tool to study the association of a binary outcome to a set of possible exposures.MethodsUsing a simulation study we illustrate how the analytically derived bias of odds ratios modelling in logistic regression varies as a function of the sample size.ResultsLogistic regression overestimates odds ratios in studies with small to moderate samples size. The small sample size induced bias is a systematic one, bias away from null. Regression coefficient estimates shifts away from zero, odds ratios from one.ConclusionIf several small studies are pooled without consideration of the bias introduced by the inherent mathematical properties of the logistic regression model, researchers may be mislead to erroneous interpretation of the results.

Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register

Objective To evaluate the effectiveness and safety of metformin use in clinical practice in a large sample of pharmacologically treated patients with type 2 diabetes and different levels of renal function. Design Observational study between July 2004 and December 2010, mean follow-up 3.9 years. Setting Hospital outpatient clinics and primary care in Sweden. Participants 51 675 men and women with type 2 diabetes, registered in the Swedish National Diabetes Register, and on continuous glucose-lowering treatment with oral hypoglycaemic agents (OHAs) or insulin. Main outcome measures Risks of cardiovascular disease (CVD), all-cause mortality and acidosis/serious infection, associated with each treatment regimens, were analysed in all patients and in subgroups with different estimated glomerular filtration rate (eGFR) intervals. Covariance adjustment and propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression. Results Compared with metformin in monotherapy, HRs for fatal/non-fatal CVD and all-cause mortality with all other OHAs combined (approximately 80% sulphonylureas) in monotherapy were 1.02 (95% CI 0.93 to 1.12) and 1.13 (1.01 to 1.27), while 1.18 (1.07 to 1.29) and 1.34 (1.19 to 1.50) with insulin in monotherapy, adjusting using propensity scores. Metformin, compared with any other treatment, showed reduced risks of acidosis/serious infection (adjusted HR 0.85, 95% CI 0.74 to 0.97) and all-cause mortality (HR 0.87, 95% CI 0.77 to 0.99), in patients with eGFR 45–60 ml/min/1.73 m2, and no increased risks of all-cause mortality, acidosis/serious infection or CVD were found in patients with eGFR 30–45 ml/min/1.73 m2. Conclusions Metformin showed lower risk than insulin for CVD and all-cause mortality and slightly lower risk for all-cause mortality compared with other OHA, in these 51 675 patients followed for 4 years. Patients with renal impairment showed no increased risk of CVD, all-cause mortality or acidosis/serious infection. In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects.

Increasing participation in cervical cancer screening: Offering a HPV self-test to long-term non-attendees as part of RACOMIP, a Swedish randomized controlled trial

RACOMIP is a population‐based, randomized trial of the effectiveness and cost‐effectiveness of different interventions aimed at increasing participation in a well‐run cervical cancer screening program in western Sweden. In this article, we report results from one intervention, offering non‐attendees a high‐risk human papillomavirus (HPV) self‐test. Comparison was made with standard screening invitation routine or standard routine plus a telephone call. Women (8,800), aged 30–62, were randomly selected among women without a registered Pap smear in the two latest screening rounds. These women were randomized 1:5:5 to one of three arms: 800 were offered a high‐risk HPV self‐test, 4,000 were randomized to a telephone call (reported previously) and 4,000 constituted a control group (standard screening invitation routine). Results were based on intention to treat analysis and cost‐effectiveness was calculated as marginal cost per cancer case prevented. The endpoint was the frequency of testing. The total response rate in the self‐testing arm was 24.5%, significantly higher than in the telephone arm (18%, RR 1.36, 95% CI 1.19–1.57) and the control group (10.6%, RR 2.33, 95% CI 2.00–2.71). All nine women who tested positive for high‐risk HPV attended for a cervical smear and colposcopy. From the health‐care sector perspective, the intervention will most likely lead to no additional cost. Offering a self‐test for HPV as an alternative to Pap smears increases participation among long‐term non‐attendees. Offering various screening options can be a successful method for increasing participation in this group.

Insulin glargine use and short-term incidence of malignancies — a three-year population-based observation

Abstract Aims/hypothesis. To further investigate the association of cancer occurrence with the use of insulin glargine. Methods. We followed 114 838 individuals using insulin between 1 July and 31 December 2005. From 1 January 2006 to 31 December 2008, we noted the occurrence of malignancies (cohort I). Insulin users between 1 July and 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 (cohort II). Users of insulin during three consecutive six-month periods from 1 July 2005 to 31 December 2006 were followed for the occurrence of malignancies in 2007 and 2008 (cohort III). The Prescribed Drug Register, the Cancer Register, and the Causes of Death Register were used to obtain information on targeted person-time and outcome. We retrieved variables reflecting potential confounding factors from the Swedish National Diabetes Register, the Prescribed Drug Register, the Patient Register, the Medical Birth Register and the National Education Register. With Poisson regression we evaluated the association between insulin use and malignancy outcome with adjustment for confounders. Results. The adjusted incidence rate ratio (and 95% confidence interval) for women who used insulin glargine alone compared with those who used other types of insulin, was 1.60 (1.10–2.32) for breast cancer but included 1.0 for malignancy outcomes other than breast cancer for men and women when analyzing cohort I with follow-up in 2006–2008. For cohort II and III the corresponding incidence rate ratios were 1.38 (0.87–2.18), and 0.87 (0.41–1.85), respectively. Conclusion/interpretation. We do not see an increased risk during 2008 for breast cancer in the insulin glargine group. We need data for additional years before we can state with reasonable certainty that the increase in breast cancer incidence that we observed in Sweden in 2006 and 2007 was due to a random fluctuation or whether there is an association with the use of insulin glargine.

HbA1C and cancer risk in patients with type 2 diabetes--a nationwide population-based prospective cohort study in Sweden.

Background Diabetes is associated with increased cancer risk. The underlying mechanisms remain unclear. Hyperglycemia might be one risk factor. HbA1c is an indicator of the blood glucose level over the latest 1 to 3 months. This study aimed to investigate association between HbA1c level and cancer risks in patients with type 2 diabetes based on real life situations. Methods This is a cohort study on 25,476 patients with type 2 diabetes registered in the Swedish National Diabetes Register from 1997–1999 and followed until 2009. Follow-up for cancer was accomplished through register linkage. We calculated incidences of and hazard ratios (HR) for cancer in groups categorized by HbA1c ≤58 mmol/mol (7.5%) versus >58 mmol/mol, by quartiles of HbA1c, and by HbA1c continuously at Cox regression, with covariance adjustment for age, sex, diabetes duration, smoking and insulin treatment, or adjusting with a propensity score. Results Comparing HbA1c >58 mmol/mol with ≤58 mmol/mol, adjusted HR for all cancer was 1.02 [95% CI 0.95–1.10] using baseline HbA1c, and 1.04 [95% CI 0.97–1.12] using updated mean HbA1c, and HRs were all non-significant for specific cancers of gastrointestinal, kidney and urinary organs, respiratory organs, female genital organs, breast or prostate. Similarly, no increased risks of all cancer or the specific types of cancer were found with higher quartiles of baseline or updated mean HbA1c, compared to the lowest quartile. HR for all cancer was 1.01 [0.98–1.04] per 1%-unit increase in HbA1c used as a continuous variable, with non-significant HRs also for the specific types of cancer per unit increase in HbA1c. Conclusions In this study there were no associations between HbA1c and risks for all cancers or specific types of cancer in patients with type 2 diabetes.

Clinical Use and Effectiveness of Lipid Lowering Therapies in Diabetes Mellitus—An Observational Study from the Swedish National Diabetes Register

Objectives To describe the use and evaluate the effectiveness of different lipid lowering therapies in unselected patients with type 1 and type 2 diabetes in clinical practice. Design Observational population-based study using the personal identification number to link information from the National Diabetes Register, the Prescribed Drug Register and the Patient register in Sweden. All patients in the NDR aged 18–75 years with diabetes more than one year were eligible, but only patients starting any lipid lowering treatment with at least three prescriptions 1 July 2006–30 June 2007 were included (n = 37182). The mean blood lipid levels in 2008 and reductions in LDL cholesterol were examined. Results Blood lipid levels were similar in patients treated with simvastatin, atorvastatin and rosuvastatin, showing similar lipid lowering effect as currently used. Users of pravastatin, fluvastatin, ezetimib and fibrate more seldom reach treatment goals. Moderate daily doses of the statins were used, with 76% of simvastatin users taking 20 mg or less, 48% of atorvastatin users taking 10 mg, 55% of pravastatin users taking 20 mg, and 76% of rosuvastatin users taking 5 or 10 mg. Conclusions This observational study shows that the LDL-C levels in patients taking simvastatin, atorvastatin or rosuvastatin are very similar as currently used, as well as their LDL-C lowering abilities. There is potential to intensify lipid lowering treatment to reduce the remaining high residual risk and achieve better fulfilment of treatment goals, since the commonly used doses are only low to moderate.

Physical activity, weight status, diabetes and dementia: a 34-year follow-up of the population study of women in Gothenburg.

Background: There is evidence of a synergistic interaction between obesity and sedentary lifestyle with respect to diabetes. Although diabetes is a known risk factor for dementia, it is unclear if both diseases have common aetiologies. Methods: A community-based sample of 1,448 Swedish women, aged 38-60 years and free of diabetes and dementia in 1968, was followed by means of up to 5 examinations spread over 34 years. 9.6% of all women developed diabetes and 11.4% developed dementia (over 40,000 person-years of follow-up for each disease). Cox proportional hazard regression was used to assess the influence of selected risk factors on both diseases, and the relation between diabetes and dementia. Results: Comparing risk factors for incident diabetes and dementia, both diseases showed a synergistic association with obesity combined with a low level of leisure time physical activity [hazard ratio (HR) for interaction = 2.7, 95% confidence interval (CI) = 1.2-6.3 for diabetes and HR = 3.3, 95% CI = 1.1-9.9 for dementia]. Development of diabetes doubled the risk for subsequent dementia (HR = 2.2, 95% CI = 1.1-4.4), which was slightly reduced upon adjustment for common risk factors. Conclusions: Shared risk factors suggest a similar aetiology for diabetes and dementia and partially explain the association between diseases.

Increasing participation in cervical cancer screening: telephone contact with long-term non-attendees in Sweden. Results from RACOMIP, a randomized controlled trial

Non‐participation is the foremost screening‐related risk factor for cervical cancer. We studied the effectiveness and cost‐effectiveness of an intervention to increase participation in the context of a well‐run screening program. Telephone contact with non‐attendees, offering an appointment to take a smear, was compared with a control group in a population‐based randomized trial in western Sweden. Of 8,800 randomly selected women aged 30–62, without a registered Pap smear in the two latest screening rounds, 4,000 were randomized to a telephone arm, another 800 were offered a high‐risk human papillomavirus (HPV) self‐test by mail (not reported in this article) and 4,000 constituted a control group. Endpoints were frequency of testing, frequency of abnormal smears and further assessment of abnormal tests. Participation during the following 12 months was significantly higher in the telephone arm than in the control group, 718 (18.0%) versus 422 (10.6%) [RR: 1.70, 95% confidence interval (CI): 1.52–1.90]. The number of detected abnormal smears was 39 and 19, respectively (RR: 2.05, 95% CI: 1.19–3.55). The respective numbers of further assessed abnormalities were 34 and 18 (RR: 1.89, 95% CI: 1.07–3.34). Twice as many high‐grade intraepithelial neoplasia (CIN2+) were detected and treated in the telephone arm: 14 and 7, respectively. Telephone contact with women who have abstained from cervical cancer screening for long time increases participation and leads to a significant increase in detection of atypical smears. Cost calculations indicate that this intervention is unlikely to be cost‐generating and this strategy is feasible in the context of a screening program.

Insulin glargine use and short-term incidence of breast cancer - a four-year population-based observation.

1National Board of Health and Welfare, Stockholm, Sweden, 2Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden, 3Equity and Health Policy, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden, 4Division of Clinical Cancer Epidemiology, Department of Oncology, The Sahlgrenska Academy, Onkologiskt Centrum, Gothenburg, Sweden, 5Division of Clinical Cancer Epidemiology, Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden, 6Diabetes Centre, Sahlgrenska University Hospital, Gothenburg, Sweden, 7Nordic School of Public Health, Gothenburg, Sweden and 8National Diabetes Register, Register Center, Västra Götaland Region, Sweden