Diabetes-related risk factors and survival among individuals with type 2 diabetes and breast, lung, colorectal, or prostate cancer.

Premature death in diabetes is increasingly caused by cancer. The objectives were to estimate the excess mortality when individuals with type 2 diabetes(T2D) were diagnosed with cancer, and to examine the impact of modifiable diabetes-related risk factors. This longitudinal nationwide cohort study included individuals with T2D registered in the Swedish National Diabetes Register between 1998-2019. Poisson models were used to estimate mortality as a function of time-updated risk-factors, adjusted for sex, age, diabetes duration, marital status, country of birth, BMI, blood pressure, lipids, albuminuria, smoking, and physical activity. We included 690,539 individuals with T2D and during 4,787,326 person-years of follow-up 179,627 individuals died. Overall, the all-cause mortality rate ratio was 3.75 [95%confidence interval(CI):3.69-3.81] for individuals with T2D and cancer compared to those remaining free of cancer. The most marked risk factors associated to mortality among individuals with T2D and cancer were low physical activity, 1.59 (1.57-1.61) and smoking, 2.15 (2.08-2.22), whereas HbA1c, lipids, hypertension, and BMI had no/weak associations with survival. In a future with more patients with comorbid T2D and cancer diagnoses, these results suggest that smoking and physical activity might be the two most salient modifiable risk factors for mortality in people with type 2 diabetes and cancer.

The impact of diabetes on cancer detection during the prevalence round of a national screening program for colorectal cancer.

AIMS: Diabetes is associated with a higher risk of colorectal cancer (CRC) and inferior survival after CRC. Screening may enable the early detection of CRC. We aimed to assess the impact of diabetes on cancer detection and disease stage during the prevalence round of a national CRC screening program. METHODS: We performed a register-based cohort study based on the randomized procedure for inviting Danish residents aged 50-74 years to the prevalence round of national CRC screening program in 2014-2017. By comparing the random half of the population who had been invited by 1 May 2016 with the not yet invited half, the effect of screening was assessed by the detection of CRC and disease stage among individuals with and without diabetes. Further, the impact of diabetes on the screening participation rate was calculated. RESULTS: By randomisation, 504,673 individuals had been invited to the CRC screening by 1 May 2016, and 549,359 individuals had not yet been invited. The diabetes prevalence was 10% in both groups. When comparing those not yet invited to those invited, the effect of screening on the number of detected cancers per 100,000 individuals was higher in those with diabetes (from 207 to 494 cancers) than in those without diabetes (from 147 to 364 cancers), and screening resulted in overall higher proportions of stage I cancer. Among those invited to screening, the participation rate was 9.1% lower (95% CI: 8.7%-9.5%) in individuals with versus without diabetes. CONCLUSIONS: Despite a lower participation rate, the effect of CRC screening was higher in individuals with diabetes.

Diabetic Polyneuropathy Early in Type 2 Diabetes Is Associated With Higher Incidence Rate of Cardiovascular Disease: Results From Two Danish Cohort Studies.

OBJECTIVE: Symptoms indicative of diabetic polyneuropathy (DPN) early in type 2 diabetes may act as a marker for cardiovascular disease (CVD) and death. RESEARCH DESIGN AND METHODS: We linked data from two Danish type 2 diabetes cohorts, the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Denmark) and the Danish Centre for Strategic Research in Type 2 Diabetes (DD2), to national health care registers. The Michigan Neuropathy Screening Instrument questionnaire (MNSIq) was completed at diabetes diagnosis in ADDITION-Denmark and at a median of 4.6 years after diagnosis of diabetes in DD2. An MNSIq score ≥4 was considered as indicative of DPN. Using Poisson regressions, we computed incidence rate ratios (IRRs) of CVD and all-cause mortality comparing MNSIq scores ≥4 with scores <4. Analyses were adjusted for a range of established CVD risk factors. RESULTS: In total, 1,445 (ADDITION-Denmark) and 5,028 (DD2) individuals were included in the study. Compared with MNSIq scores <4, MNSIq scores ≥4 were associated with higher incidence rate of CVD, with IRRs of 1.79 (95% CI 1.38-2.31) in ADDITION-Denmark, 1.57 (CI 1.27-1.94) in the DD2, and a combined IRR of 1.65 (CI 1.41-1.95) in a fixed-effect meta-analysis. MNSIq scores ≥4 did not associate with mortality; combined mortality rate ratio was 1.11 (CI 0.83-1.48). CONCLUSIONS: The MNSIq may be a tool to identify a subgroup within individuals with newly diagnosed type 2 diabetes with a high incidence rate of subsequent CVD. MNSIq scores ≥4, indicating DPN, were associated with a markedly higher incidence rate of CVD, beyond that conferred by established CVD risk factors.

Factors associated with attendance at clinical follow-up of a cohort with screen-detected type 2 diabetes: ADDITION-Denmark.

AIMS: To determine the association between concurrent overall burden of disease, cardiovascular disease, cancer, self-rated health, HbA1c levels, and attendance at clinical follow-up of the Danish arm of the ADDITION-study. METHODS: Logistic regression models were used to study factors proposed being associated with attendance in clinical follow-up. We used data from clinical examinations, questionnaires and national registers at a time-point near the follow-up examination. RESULTS: A total of 1119 participants were eligible for the follow-up conducted a median of 12.8 years (IQR 11.6; 13.4) after type 2 diabetes diagnosis by screening. Concurrent high burden of disease was associated with lower attendance (OR 0.6 (95% CI: 0.4; 0.9) for high-versus no burden of disease). Concurrent cardiovascular disease and cancer showed no statistically significant association with attendance (OR 1.0 (95% CI: 0.7; 1.4)) and (OR 0.8 (95% CI: 0.6; 1.1) for (disease versus no disease). Similarly, self-rated health (OR 0.7 (95% CI: 0.5; 1.0) poor-versus good self-rated health) and HbA1c levels (OR 1.0 (95% CI: 0.9; 1.2 unit=10mmol/mol)) were not statistically significant associated with attendance. CONCLUSIONS: This study showed a lower attendance in clinical follow-up after nearly 13years among individuals with concurrent high burden of disease. No associations were found between concurrent CVD, cancer, self-rated health and Hba1c levels and attendance.

Prospective Study of Neuropathic Symptoms Preceding Clinically Diagnosed Diabetic Polyneuropathy: ADDITION-Denmark.

OBJECTIVE: To evaluate whether diabetic polyneuropathy (DPN) follows the hypothesis for the course of nerve fiber damage reflected by symptoms progressing from pure small through mixed to large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers. RESEARCH DESIGN AND METHODS: Repeated assessments of nerve fiber-specific symptoms were obtained in 518 participants of the ADDITION-Denmark study from the time of a screening-based diagnosis of type 2 diabetes using specific items of the Michigan Neuropathy Screening Instrument questionnaire. DPN was clinically assessed 13 years after inclusion. The course of symptoms reflecting dysfunction of specific nerve fibers was evaluated, and the association between symptoms and DPN was estimated using logistic regression models. RESULTS: An overall stable, yet heterogeneous course of symptoms was seen. According to the hypothesis of symptom progression, 205 (40%) participants remained free of symptoms and 56 (11%) had stable, 114 (23%) progressing, and 132 (26%) improving symptoms. Cross-sectional estimates showed a higher risk of DPN (odds ratios between 2.1 and 4.1) for participants with mixed or large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers compared with participants without symptoms. CONCLUSIONS: There was no evidence for a progressive development of nerve fiber damage in DPN reflected by symptoms going from pure small through mixed to large nerve fiber symptoms with or without symptoms of loss of function of small nerve fibers. Yet overall, neuropathic symptoms were prospectively associated with a higher risk of DPN.

Effect of duration and burden of microvascular complications on mortality rate in type 1 diabetes: an observational clinical cohort study.

AIMS/HYPOTHESIS: The role of burden and duration of multiple microvascular complications on mortality rate has not been explored in detail in type 1 diabetes. Taking complication burden and time-updated duration into account we aimed to quantify mortality rate in individuals with and without microvascular complications. METHODS: This observational clinical cohort included 3828 individuals with type 1 diabetes attending the Steno Diabetes Center Copenhagen in 2001-2013. We used information on mortality and detailed clinical measures of microvascular complications from electronic patient records. Poisson models were used to model mortality rates according to complication burden. RESULTS: During 26,665 person-years of follow-up, 503 deaths occurred. Compared with individuals without microvascular complications, the mortality rate ratio was 2.20 (95% CI 1.79, 2.69) for individuals with diabetic kidney disease, 1.72 (95% CI 1.39, 2.12) for individuals with neuropathy and 1.02 (95% CI 0.77, 1.37) for individuals with retinopathy, all adjusted for calendar time (year/month/day), age, duration of diabetes, sex, HbA1c, LDL-cholesterol, BMI, smoking status, systolic blood pressure, use of antihypertensive and lipid-lowering medication, and cardiovascular disease status. In individuals with two complications or more, the risk of mortality did not exceed the combined risk from each individual complication. Mortality rate ratios increased immediately after diagnosis of neuropathy and diabetic kidney disease. Mortality rate ratios were independent of the duration of neuropathy and retinopathy, while the mortality rate associated with diabetic kidney disease reached a stable level after approximately 3 years. CONCLUSIONS/INTERPRETATION: Neuropathy and diabetic kidney disease are strong and independent risk markers of mortality in type 1 diabetes, whereas no evidence of higher mortality rate was found for retinopathy. We found no indication that the mortality risk with multiple complications exceeds the risk conferred by each complication separately. The duration spent with microvascular complications had only a marginal effect on mortality.

Development of Microvascular Complications and Effect of Concurrent Risk Factors in Type 1 Diabetes: A Multistate Model From an Observational Clinical Cohort Study.

OBJECTIVE: Type 1 diabetes is a complex disease, and development of multiple complications over time can be analyzed only with advanced statistical methods. This study describes the development of microvascular complications and explores the effect of complication burden and important concurrent risk factors by applying a multistate model. RESEARCH DESIGN AND METHODS: We used a clinical cohort at the Steno Diabetes Center Copenhagen to study the development of diabetic kidney disease, retinopathy, and neuropathy. We extracted information from electronic patient records and estimated incidence rates of complications by concurrent complication burden. We explored the extent to which concurrent complications modify the effect of selected risk factors on the development of microvascular complications. RESULTS: We included 3,586 individuals. Incidence rate ratios in individuals with two previous complications were 3.2 (95% CI 2.3-4.5) for diabetic kidney disease, 2.1 (1.5-3.1) for retinopathy, and 1.7 (1.2-2.4) for neuropathy compared with individuals without complications. The models included diabetes duration; calendar time and age as timescales; and sex, HbA1c, lipid-lowering and antihypertensive treatment, systolic blood pressure, BMI, estimated glomerular filtration rate (eGFR), cardiovascular disease (CVD), LDL cholesterol, insulin dose (units/kg/day), and smoking status as covariates. Effects of HbA1c, diabetes duration, systolic blood pressure, BMI, eGFR, and LDL cholesterol where not modified by concurrent complication burden, whereas the effect of sex and CVD were. CONCLUSIONS: The risk of microvascular complications highly depends on the concurrent complication burden and risk factor profile in individuals with type 1 diabetes. The results emphasize attention to risk factors, regardless of existing number of complications, to prevent development of further microvascular complications.

Risk-Factor Trajectories Preceding Diabetic Polyneuropathy: ADDITION-Denmark.

OBJECTIVE: To study cardiometabolic risk-factor trajectories (in terms of levels and changes over time) preceding diabetic polyneuropathy (DPN) 13 years after a screen-detected diagnosis of type 2 diabetes. RESEARCH DESIGN AND METHODS: We clinically diagnosed DPN in a nested case-control study of 452 people in the Danish arm of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION). By linear regression models, we estimated preceding risk-factor trajectories during 13 years. Risk of DPN was estimated by multivariate logistic regression models of each individual's risk-factor trajectory intercept and slope adjusting for sex, age, diabetes duration, height, and trial randomization group. RESULTS: Higher baseline levels of HbA1c (odds ratio [OR] 1.76 [95% CI 1.37; 2.27] and OR 1.68 [95% CI 1.33; 2.12] per 1% and 10 mmol/mol, respectively) and steeper increases in HbA1c over time (OR 1.66 [95% CI 1.21; 2.28] and OR 1.59 [95% CI 1.19; 2.12] per 1% and 10 mmol/mol increase during 10 years, respectively) were associated with DPN. Higher baseline levels of weight, waist circumference, and BMI were associated with DPN (OR 1.20 [95% CI 1.10; 1.31] per 5 kg, OR 1.27 [95% CI 1.13; 1.43] per 5 cm, and OR 1.24 [95% CI 1.12; 1.38] per 2 kg/m2, respectively). CONCLUSIONS: Both higher levels and slopes of HbA1c trajectories were associated with DPN after 13 years. Our findings indicate that the rate of HbA1c increase affects the development of DPN over and above the effect of the HbA1c level. Furthermore, this study supports obesity as a risk factor for DPN.

Prevalence and geographical distribution of insulin pump therapy in the Central Denmark Region and its association with metabolic parameters.

AIMS: Insulin treatment in type 1 diabetes encompasses multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII). Both population-based studies and comparative studies regarding CSII use are sparse. The aim of the current study was to describe the prevalence and distribution of CSII use among adults with type 1 diabetes in the Central Denmark Region and to compare metabolic control in CSII-treated patients to those treated with MDI. METHODS: A database was constructed using the Danish Adult Diabetes Registry in 2014/2015 in combination with an audit of the patients' medical records. RESULTS: 3909 adults with type 1 diabetes patients were included. The proportion of patients treated with CSII differed significantly between the 8 regional hospitals from 12.0% to 31.1%. CSII users had a significantly lower HbA1c compared to MDI treated patients (7.6% (60 mmol/mol) versus 8.0% (64 mmol/mol)) in unadjusted analyses. After adjustment for clinically relevant characteristics the difference between CSII and MDI-treated patients was attenuated, but remained statistically significant. CONCLUSION: The distribution of CSII differed markedly between hospitals and CSII users had better glycemic control, even after adjustment for sex, age, BMI, diabetes duration, smoking, use of lipid-lowering and blood pressure-lowering medication.

[Reducing postpolypectomy bleeding in colon and rectum]. / Forebyggelse af postpolypektomiblødning i colon og rectum.

Postpolypectomy bleeding is the most common complication of colonoscopic polypectomy. When the Danish colorectal cancer screening programme is fully implemented it will generate approximately 40,000 colonoscopies and thousands of polypectomies, all with a bleeding risk. In that context we find it important to give evidence-based recommendations regarding techniques used to prevent postpolypectomy bleeding. A literature search was conducted for studies that investigate the various techniques used and recommendations are given.

The B1-cell subpopulation is diminished in patients with relapsing-remitting multiple sclerosis.

B cell subsets in newly diagnosed untreated, relapsing-remitting multiple sclerosis (MS) patients were examined. The fraction of CD20(+) B cells was significantly increased in MS. Among subsets of B cells, MS patients had increased frequency of naïve cells, but reduced frequency of memory and B1 cells. The frequencies of B1 cells were inversely correlated with the time since last attack. B1 cells resembled the phenotype of either lymphocytes (CD11b(-) B1 cells) or monocytes (CD11b(+) B1 cells) and a small fraction of cells was CD3(+)CD20(+) by confocal microscopy.