Cancer incidence in persons with type 1 diabetes : a five-country study of 9,000 cancers in type 1 diabetic individuals

An excess cancer incidence of 20-25% has been identified among persons with diabetes, most of whom have type 2 diabetes. We aimed to describe the association between type 1 diabetes and cancer incidence. Persons with type 1 diabetes were identified from five nationwide diabetes registers: Australia (2000-2008), Denmark (1995-2014), Finland (1972-2012), Scotland (1995-2012) and Sweden (1987-2012). Linkage to national cancer registries provided the numbers of incident cancers in people with type 1 diabetes and in the general population. We used Poisson models with adjustment for age and date of follow up to estimate hazard ratios for total and site-specific cancers. A total of 9,149 cancers occurred among persons with type 1 diabetes in 3.9 million person-years. The median age at cancer diagnosis was 51.1 years (interquartile range 43.5-59.5). The hazard ratios (HRs) (95% CIs) associated with type 1 diabetes for all cancers combined were 1.01 (0.98, 1.04) among men and 1.07 (1.04, 1.10) among women. HRs were increased for cancer of the stomach (men, HR 1.23 [1.04, 1.46]; women, HR 1.78 [1.49, 2.13]), liver (men, HR 2.00 [1.67, 2.40]; women, HR 1.55 [1.14, 2.10]), pancreas (men, HR 1.53 [1.30, 1.79]; women, HR 1.25 [1.02,1.53]), endometrium (HR 1.42 [1.27, 1.58]) and kidney (men, HR 1.30 [1.12, 1.49]; women, HR 1.47 [1.23, 1.77]). Reduced HRs were found for cancer of the prostate (HR 0.56 [0.51, 0.61]) and breast (HR 0.90 [0.85, 0.94]). HRs declined with increasing diabetes duration. Type 1 diabetes was associated with differences in the risk of several common cancers; the strength of these associations varied with the duration of diabetes.Peer reviewe

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 = 37,182). 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

HLA Genes, Islet Autoantibodies and Residual C-Peptide at the Clinical Onset of Type 1 Diabetes Mellitus and the Risk of Retinopathy 15 Years Later

HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15-34 year old individuals.The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials

Estimating the Cost of Diabetes Mellitus-Related Events from Inpatient Admissions in Sweden Using Administrative Hospitalization Data

Background and aims: To estimate short- and long-term costs of inpatient hospitalization in Sweden for major diabetes mellitus-related events. Materials and methods: Costs were estimated using administrative hospital data from the Swedish National Board of Health and Welfare, which is linked to the Swedish National Diabetes Register. Data were available for 179 749 patients with diabetes in Sweden from 1998 to 2003 (mean and median duration of 6 years' follow-up). Costing of inpatient admissions was based on Nordic diagnosis-related groups (NordDRG). Multiple regression analysis (linear and generalizing estimating equation models) was used to estimate inpatient care costs controlling for age, sex and co-morbidities. The data on hospitalizations were converted to costs (E) using 2003 exchange rates. Results: The average annual costs (linear model) associated with inpatient admissions for a 60-year-old male in the year the first event first occurred were as follows: (sic)6488 (95% CI 5034, 8354) for diabetic coma; (sic)6850 (95% CI 6514, 7204) for heart failure; (sic)7853 (95% CI 7559, 8144) for non-fatal stroke; (sic)8121 (95% CI 7104, 9128) for peripheral circulatory complications; (sic)8736 (95% CI 8474, 9001) for non-fatal myocardial infarction (MI); (sic) 10 360 (95% CI 10 085, 10 643) for ischaemic heart disease; (sic) 11411 (95% CI 10 298, 12 654) for renal failure; and (sic)14 949 (95% CI 13 849, 16 551) for amputation. On average, the costs were higher when co-morbidity was accounted for (e.g. MI with co-morbidity was twice as costly as MI alone). Conclusions: Average hospital inpatient costs associated with common diabetes-related events can be estimated using panel data regression methods. These could assist in modelling of long-term costs of diabetes and in evaluating the cost effectiveness of improving care

Estimating the Cost of Diabetes Mellitus-Related Events from Inpatient Admissions in Sweden Using Administrative Hospitalization Data

Background and aims: To estimate short- and long-term costs of inpatient hospitalization in Sweden for major diabetes mellitus-related events. Materials and methods: Costs were estimated using administrative hospital data from the Swedish National Board of Health and Welfare, which is linked to the Swedish National Diabetes Register. Data were available for 179 749 patients with diabetes in Sweden from 1998 to 2003 (mean and median duration of 6 years' follow-up). Costing of inpatient admissions was based on Nordic diagnosis-related groups (NordDRG). Multiple regression analysis (linear and generalizing estimating equation models) was used to estimate inpatient care costs controlling for age, sex and co-morbidities. The data on hospitalizations were converted to costs (€) using 2003 exchange rates. Results: The average annual costs (linear model) associated with inpatient admissions for a 60-year-old male in the year the first event first occurred were as follows: €6488 (95% CI 5034, 8354) for diabetic coma; €6850 (95% CI 6514, 7204) for heart failure; €7853 (95% CI 7559, 8144) for non-fatal stroke; €8121 (95% CI 7104, 9128) for peripheral circulatory complications; €8736 (95% CI 8474, 9001) for non-fatal myocardial infarction (MI); €10 360 (95% CI 10 085, 10 643) for ischaemic heart disease; €11 411 (95% CI 10 298, 12 654) for renal failure; and €14 949 (95% CI 13 849, 16 551) for amputation. On average, the costs were higher when co-morbidity was accounted for (e.g. MI with co-morbidity was twice as costly as MI alone). Conclusions: Average hospital inpatient costs associated with common diabetes-related events can be estimated using panel data regression methods. These could assist in modelling of long-term costs of diabetes and in evaluating the cost effectiveness of improving care.

Teenagers with poor metabolic control already have a higher risk of microvascular complications as young adults

Aims: To evaluate how HbA1c in adolescents with type 1 diabetes affects microvascular complications in young adults. Methods: All individuals registered in the Swedish paediatric diabetes quality registry (SWEDIABKIDS) 13-18 years of age, and as adults registered in the Swedish National Diabetes Registry (NDR) in both the years 2011 and 2012 were included, in total 4250 individuals. Results: Of the individuals with mean HbA1c &amp;gt;78 mmol/mol in SWEDIABKIDS 83.4% had retinopathy, 15.8% had microalbuminuria and 4.9% had macroalbuminuria in NDR. The logistic regression analysis showed that the OR to develop macroalbuminuria as a young adult was significantly higher in the group with mean HbA1c &amp;gt;78 mmol/mol in SWEDIABKIDS (p &amp;lt; 0.05). Among the patients with mean HbA1c above 78 mmol/mol in both registries there was a significantly higher proportion that had retinopathy, microalbuminuria (p &amp;lt; 0.001) and/or macroalbuminuria (p &amp;lt; 0.01) compared to the group with HbA1c below 57 mmol/mol in both registries. Only 6.5% of the persons in this study were over 30 years of age. Conclusions: Paediatric diabetes teams working with teenagers must be aware of the impact of good metabolic control during adolescence, and should intensify the care during this vulnerable period of life to reduce the risk of microvascular complications in young adults.Funding Agencies|Ostergotland County Council; Futurum the Academy for Health and Care; Jonkoping County Council; FORSS- Medical Research Council of Southeast Sweden</p

Hazard ratios (HR) with 95% confidence intervals (CI) for all cancer in overweight and obese patients with type 2 diabetes, compared to patients with normal weight, using several models for adjustment with covariates.

<p>Model 1: adjustment for gender and also stratification by quartiles of age in order to avoid violation by age of the proportional hazards assumption at Cox regression analysing all cancer.</p><p>Model 2: Diabetes duration and HbA1c added as covariates, except for gender and stratification by age quartiles.</p><p>Model 3: Insulin treatment also added as covariate, except for gender, duration, HbA1c, and stratification by age quartiles.</p><p>Hazard ratios (HR) with 95% confidence intervals (CI) for all cancer in overweight and obese patients with type 2 diabetes, compared to patients with normal weight, using several models for adjustment with covariates.</p

Long-term sustained autoimmune response to beta cell specific zinc transporter (ZnT8, W, R, Q) in young adult patients with preserved beta cell function at diagnosis of diabetes.

The aim of this study was to examine whether autoantibodies to: ZnT8-Tryptophan (ZnT8WA), ZnT8-Arginine (ZnT8RA) or ZnT8-Glutamine (ZnT8QA) correlated with C-peptide or other autoantibodies and to assess diagnostic sensitivity of ZnT8WRQA. Specimens from 270 newly diagnosed diabetic subjects (age 15--34 years) and after five 5 years duration of disease were examined. Four linear regression models were used to dissect the importance of different factors from diagnosis for the respective difference of (logZnT8WA), (logZnT8RA) and (logZnT8QA); A) unadjusted model for: initial C-peptide, age, BMI, gender, clinical classification, ICA, GADA, IA-2A, (ZnT8WA/ZnT8RA/ZnT8QA); B) C-peptide corrected for clinical factors; C) C-peptide corrected for autoantibodies; D) C-peptide corrected for all factors. The least decrease of ZnT8WA was observed in patients with high initial C-peptide in all models A) p = 0.054; B) p = 0.021; C) p = 0.047 and D) p = 0.017. A less statistically significant decrease of ZnT8RA was observed in patients with high initial C-peptide in A) p = 0.038 and C) p = 0.047, but this finding was not confirmed in B or D. The decrease of ZnT8QA levels was not related to C-peptide in any model but correlated to age D) p = 0.049. Furthermore, patients with unclassifiable diabetes showed the least decrease in D) p = 0.035. ZnT8WA, ZnT8RA or ZnT8QA were identified as a single autoantibody in 3.8% (10/266) of patients, thereby increasing diagnostic sensitivity from 79.3% (211/266) to 83.1% (221/266). In conclusion, high initial C-peptide was the most important factor even after adjusting for other factors in patients positive for ZnT8WA or ZnT8RA to remain autoantibody positive five 5 years after diagnosis

Hazard ratios (HR) with 95% confidence intervals (CI) for all cancer and specific types of cancer, comparing overweight or obese patients with normal weight patients as reference, classified based on baseline BMI values, given for all patients with type 2 diabetes and separately in men and women.

<p>*Adjusted for age, HbA1c, smoking, diabetes duration, diabetes medication (insulin yes or no).</p><p>First incident of all cancer was defined by means of ICD-10 codes (C00-C97, D00-D09, D37-D48) and the following specific types of cancer were also investigated: the first incident of gastrointestinal cancer (ICD-10 code C15–C25), colorectal cancer (C18–C21), breast cancer in all women (C50) as well as in women over 55 years at baseline (C50), and prostate cancer in men (C61). For cancer of specific sites, we included only tumors that were histopathologically classified as adenocarcinoma (WHO/HS/CANC/24.1 histology code 096).</p><p>Hazard ratios (HR) with 95% confidence intervals (CI) for all cancer and specific types of cancer, comparing overweight or obese patients with normal weight patients as reference, classified based on baseline BMI values, given for all patients with type 2 diabetes and separately in men and women.</p