Soffia Gudbjörnsdottir

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.

Glycemic Control and Excess Mortality in Type 1 Diabetes

BACKGROUND The excess risk of death from any cause and of death from cardiovascular causes is unknown among patients with type 1 diabetes and various levels of glycemic control. We conducted a registry-based observational study to determine the excess risk of death according to the level of glycemic control in a Swedish population of patients with diabetes. METHODS We included in our study patients with type 1 diabetes registered in the Swedish National Diabetes Register after January 1, 1998. For each patient, five controls were randomly selected from the general population and matched according to age, sex, and county. Patients and controls were followed until December 31, 2011, through the Swedish Register for Cause-Specific Mortality. RESULTS The mean age of the patients with diabetes and the controls at baseline was 35.8 and 35.7 years, respectively, and 45.1% of the participants in each group were women. The mean follow-up in the diabetes and control groups was 8.0 and 8.3 years, respectively. Overall, 2701 of 33,915 patients with diabetes (8.0%) died, as compared with 4835 of 169,249 controls (2.9%) (adjusted hazard ratio, 3.52; 95% confidence interval [CI], 3.06 to 4.04); the corresponding rates of death from cardiovascular causes were 2.7% and 0.9% (adjusted hazard ratio, 4.60; 95% CI, 3.47 to 6.10). The multivariable-adjusted hazard ratios for death from any cause according to the glycated hemoglobin level for patients with diabetes as compared with controls were 2.36 (95% CI, 1.97 to 2.83) for a glycated hemoglobin level of 6.9% or lower (≤52 mmol per mole), 2.38 (95% CI, 2.02 to 2.80) for a level of 7.0 to 7.8% (53 to 62 mmol per mole), 3.11 (95% CI, 2.66 to 3.62) for a level of 7.9 to 8.7% (63 to 72 mmol per mole), 3.65 (95% CI, 3.11 to 4.30) for a level of 8.8 to 9.6% (73 to 82 mmol per mole), and 8.51 (95% CI, 7.24 to 10.01) for a level of 9.7% or higher (≥83 mmol per mole). Corresponding hazard ratios for death from cardiovascular causes were 2.92 (95% CI, 2.07 to 4.13), 3.39 (95% CI, 2.49 to 4.61), 4.44 (95% CI, 3.32 to 5.96), 5.35 (95% CI, 3.94 to 7.26), and 10.46 (95% CI, 7.62 to 14.37). CONCLUSIONS In our registry-based observational study, patients with type 1 diabetes and a glycated hemoglobin level of 6.9% or lower had a risk of death from any cause or from cardiovascular causes that was twice as high as the risk for matched controls. (Funded by the Swedish Society of Medicine and others.).

Excess Mortality among Persons with Type 2 Diabetes

BACKGROUND The excess risks of death from any cause and death from cardiovascular causes among persons with type 2 diabetes and various levels of glycemic control and renal complications are unknown. In this registry-based study, we assessed these risks according to glycemic control and renal complications among persons with type 2 diabetes. METHODS We included patients with type 2 diabetes who were registered in the Swedish National Diabetes Register on or after January 1, 1998. For each patient, five controls were randomly selected from the general population and matched according to age, sex, and county. All the participants were followed until December 31, 2011, in the Swedish Registry for Cause-Specific Mortality. RESULTS The mean follow-up was 4.6 years in the diabetes group and 4.8 years in the control group. Overall, 77,117 of 435,369 patients with diabetes (17.7%) died, as compared with 306,097 of 2,117,483 controls (14.5%) (adjusted hazard ratio, 1.15; 95% confidence interval [CI], 1.14 to 1.16). The rate of cardiovascular death was 7.9% among patients versus 6.1% among controls (adjusted hazard ratio, 1.14; 95% CI, 1.13 to 1.15). The excess risks of death from any cause and cardiovascular death increased with younger age, worse glycemic control, and greater severity of renal complications. As compared with controls, the hazard ratio for death from any cause among patients younger than 55 years of age who had a glycated hemoglobin level of 6.9% or less (≤52 mmol per mole of nonglycated hemoglobin) was 1.92 (95% CI, 1.75 to 2.11); the corresponding hazard ratio among patients older than 75 years of age or older was 0.95 (95% CI, 0.94 to 0.96). Among patients with normoalbuminuria, the hazard ratio for death among those younger than 55 years of age with a glycated hemoglobin level of 6.9% or less, as compared with controls, was 1.60 (95% CI, 1.40 to 1.82); the corresponding hazard ratio among patients older than 75 years of age or older was 0.76 (95% CI, 0.75 to 0.78), and patients 65 to 75 years of age also had a significantly lower risk of death (hazard ratio, 0.87; 95% CI, 0.84 to 0.91). CONCLUSIONS Mortality among persons with type 2 diabetes, as compared with that in the general population, varied greatly, from substantial excess risks in large patient groups to lower risks of death depending on age, glycemic control, and renal complications. (Funded by the Swedish government and others.).

Effects of vildagliptin on glucose control in patients with type 2 diabetes inadequately controlled with a sulphonylurea

Aim:  To compare the efficacy and tolerability of vildagliptin vs. placebo in patients with type 2 diabetes mellitus (T2DM) who are inadequately controlled [haemoglobin A1c (HbA1c) 7.5 to 11%] with prior sulphonylurea (SU) monotherapy.

The gap between guidelines and reality: Type 2 diabetes in a national diabetes register 1996–2003

Guidelines for the treatment of risk factors in diabetes care have been updated recently, due to indisputable results from clinical end‐point trials. This study evaluates risk factor control compared with current national and international targets during the period 1996–2003 in Type 2 diabetes (DM2). Patients were registered in primary‐care and hospital outpatient clinics using computer software, or via the Internet. The clinical characteristics of the patients, treatment, HbA1c, and risk factors were reported after screening by local methods. The numbers of cases of DM2 reported were 17547 in 1996 and 57119 in 2003. The mean HbA1c decreased from 7.8 to 7.2%, while blood pressure decreased from 150/82 to 143/78 mmHg during the same period. Longitudinal analysis of results was performed in 5356 patients repeatedly reported, showing slightly lower effects. The new European treatment targets of HbA1c≤ 6.1%, blood pressure < 130/80 mmHg and total cholesterol < 4.5 mmol/l were attained by 16, 13 and 28% of the patients in 2003, respectively. The prevalence of the metabolic syndrome in 2003 was 77%. Aspirin was prescribed in 36% of cases. Lipid‐lowering, anti‐hypertensive drugs, and treatment with oral hypoglycaemic agents in combination with insulin were increasingly employed during the period studied. Risk factor control in DM2 reported to the National Diabetes Register (NDR) is slowly improving, although multiple risk factors and the metabolic syndrome are found in most patients. The majority of subjects do not achieve current target levels for HbA1c, blood pressure and blood lipids. Thus, giving up smoking and increased use of aspirin are called for, as well as more aggressive treatment of hyperglycaemia, elevated blood pressure and blood lipid levels, in accordance with updated international guidelines.

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.

New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR).

Abstract.  Eeg‐Olofsson K, Cederholm J, Nilsson PM, Zethelius B, Svensson A‐M, Gudbjörnsdóttir S, Eliasson B (Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg; Department of Public Health and Caring Sciences/Family Medicine and Clinical Epidemiology, Uppsala University, Uppsala; Department of Clinical Sciences, Lund University, University Hospital, Malmö; Department of Public Health and Caring Sciences/Geriatrics, Uppsala University, Uppsala; and Center of Registers in Region Västra Götaland, Gothenburg, Sweden) New aspects of HbA1c as a risk factor for cardiovascular diseases in type 2 diabetes: an observational study from the Swedish National Diabetes Register (NDR). J Intern Med 2010; 268: 471–482.

Risk Prediction of Cardiovascular Disease in Type 2 Diabetes: A risk equation from the Swedish National Diabetes Register

OBJECTIVE—Risk prediction models obtained in samples from the general population do not perform well in type 2 diabetic patients. Recently, 5-year risk estimates were proposed as being more accurate than 10-year risk estimates. This study presents a diabetes-specific equation for estimation of the absolute 5-year risk of first incident fatal/nonfatal cardiovascular disease (CVD) in type 2 diabetic patients with use of A1C and clinical characteristics. RESEARCH DESIGN AND METHODS—The study was based on 11,646 female and male patients, aged 18–70 years, from the Swedish National Diabetes Register with 1,482 first incident CVD events based on 58,342 person-years with mean follow-up of 5.64 years. RESULTS—This risk equation incorporates A1C, as in the UK Prospective Diabetes Study risk engine, and several clinical characteristics: onset age of diabetes, diabetes duration, sex, BMI, smoking, systolic blood pressure, and antihypertensive and lipid-reducing drugs. All predictors included were associated with the outcome (P < 0.0001, except for BMI P = 0.0016) with Cox regression analysis. Calibration was excellent when assessed by comparing observed and predicted risk. Discrimination was sufficient, with a receiver operator curve statistic of 0.70. Mean 5-year risk of CVD in all patients was 12.0 ± 7.5%, whereas 54% of the patients had a 5-year risk ≥10%. CONCLUSIONS—This more simplified risk equation enables 5-year risk prediction of CVD based on easily available nonlaboratory predictors in clinical practice and A1C and was elaborated in a large observational study obtained from the normal patient population aged up to 70 years.

Mortality and Cardiovascular Disease in Type 1 and Type 2 Diabetes

BACKGROUND Long‐term trends in excess risk of death and cardiovascular outcomes have not been extensively studied in persons with type 1 diabetes or type 2 diabetes. METHODS We included patients registered in the Swedish National Diabetes Register from 1998 through 2012 and followed them through 2014. Trends in deaths and cardiovascular events were estimated with Cox regression and standardized incidence rates. For each patient, controls who were matched for age, sex, and county were randomly selected from the general population. RESULTS Among patients with type 1 diabetes, absolute changes during the study period in the incidence rates of sentinel outcomes per 10,000 person‐years were as follows: death from any cause, ‐31.4 (95% confidence interval [CI], ‐56.1 to ‐6.7); death from cardiovascular disease, ‐26.0 (95% CI, ‐42.6 to ‐9.4); death from coronary heart disease, ‐21.7 (95% CI, ‐37.1 to ‐6.4); and hospitalization for cardiovascular disease, ‐45.7 (95% CI, ‐71.4 to ‐20.1). Absolute changes per 10,000 person‐years among patients with type 2 diabetes were as follows: death from any cause, ‐69.6 (95% CI, ‐95.9 to ‐43.2); death from cardiovascular disease, ‐110.0 (95% CI, ‐128.9 to ‐91.1); death from coronary heart disease, ‐91.9 (95% CI, ‐108.9 to ‐75.0); and hospitalization for cardiovascular disease, ‐203.6 (95% CI, ‐230.9 to ‐176.3). Patients with type 1 diabetes had roughly 40% greater reduction in cardiovascular outcomes than controls, and patients with type 2 diabetes had roughly 20% greater reduction than controls. Reductions in fatal outcomes were similar in patients with type 1 diabetes and controls, whereas patients with type 2 diabetes had smaller reductions in fatal outcomes than controls. CONCLUSIONS In Sweden from 1998 through 2014, mortality and the incidence of cardiovascular outcomes declined substantially among persons with diabetes, although fatal outcomes declined less among those with type 2 diabetes than among controls. (Funded by the Swedish Association of Local Authorities and Regions and others.)

Glycaemic control of Type 1 diabetes in clinical practice early in the 21st century: an international comparison

Improving glycaemic control in people with Type 1 diabetes is known to reduce complications. Our aim was to compare glycaemic control among people with Type 1 diabetes using data gathered in regional or national registries.