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Introduction: Individuals with type 1 diabetes (T1D) and diabetic nephropathy (DN) experience progressive kidney function decline and high risk of cardiovascular disease (CVD) and mortality. This study explored changes in kidney function decline in new-onset DN between 2000 and 2020 and provided an updated prognosis for risk of kidney failure, CVD, and mortality., Methods: This is a register-based cohort study in T1D with new-onset DN (severely increased albuminuria) between 2000 and 2020 at Steno Diabetes Center Copenhagen, Denmark. Data were derived from electronic health records and national registers. Kidney function development was expressed as trajectories of estimated glomerular filtration rate (eGFR) and measured GFR (mGFR) using mixed-effects models. The prognosis was presented in probabilities of developing complications, stratified by sex, prior CVD, and risk factor control by using simulations based on Poisson regression analysis., Results: The cohort comprised 591 individuals with median (interquartile range [IQR]) age at DN onset of 53 (39-66) years and 57% were male. In 283 participants, mGFR were available. Plots of eGFR trajectories illustrated tendencies toward higher eGFR in more recent years; however, this was not confirmed in mGFR trajectories. Poor risk factor control, prior CVD, and male sex impacted mortality and morbidity rates negatively. For men and women with fair risk factor control and no prior CVD, the 10-year mortality rate from onset of DN was 28% and 26%, respectively. For men and women with poor risk factor control and CVD prior to DN onset, the 10-year-mortality rate was 62% for each sex., Conclusion: The results do not support an improved prognosis for T1D and DN, emphasizing the urgent need for new therapeutic approaches., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Diabetes is a major cause of end stage renal disease (ESRD), yet the natural history of diabetic kidney disease is not well understood. We aimed to identify patterns of estimated GFR (eGFR) trajectory and to determine the clinical and genetic factors and their associations of these different patterns with all-cause mortality in patients with type 2 diabetes. Among 6330 patients with baseline eGFR >60 ml/min per 1.73 m 2 in the Hong Kong Diabetes Register, a total of 456 patients (7.2%) developed Stage 5 chronic kidney disease or ESRD over a median follow-up of 13 years (incidence rate 5.6 per 1000 person-years). Joint latent class modeling was used to identify different patterns of eGFR trajectory. Four distinct and non-linear trajectories of eGFR were identified: slow decline (84.3% of patients), curvilinear decline (6.5%), progressive decline (6.1%) and accelerated decline (3.1%). Microalbuminuria and retinopathy were associated with accelerated eGFR decline, which was itself associated with all-cause mortality (odds ratio [OR] 6.9; 95% confidence interval [CI]: 5.6-8.4 for comparison with slow eGFR decline). Of 68 candidate genetic loci evaluated, the inclusion of five loci (rs11803049, rs911119, rs1933182, rs11123170, and rs889472) improved the prediction of eGFR trajectories (net reclassification improvement 0.232; 95% CI: 0.057--0.406). Our study highlights substantial heterogeneity in the patterns of eGFR decline among patients with diabetic kidney disease, and identifies associated clinical and genetic factors that may help to identify those who are more likely to experience an accelerated decline in kidney function., (Copyright © 2018 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Inuit populations have lower levels of cardiometabolic risk factors for the same level of body mass index (BMI) or waist circumference (WC) compared to Europeans in cross-sectional studies. We aimed to compare the longitudinal associations of anthropometric measures with cardiovascular disease (CVD) and all-cause mortality in Inuit and Europeans., Methods: Using pooled data from three population-based studies in Canada, Greenland and Denmark, we conducted a cohort study of 10,033 adult participants (765 Nunavik Inuit, 2960 Greenlandic Inuit and 6308 Europeans). Anthropometric measures collected at baseline included: BMI, WC, waist-to-hip-ratio (WHR), waist-to-height-ratio (WHtR) and a body shape index (ABSI). Information on CVD and death was retrieved from national registers or medical files. Poisson regression analyses were used to calculate incidence rates for CVD and all-cause mortality., Results: During a median follow-up of 10.5 years, there were 642 CVD events and 594 deaths. Slightly higher absolute incidence rates of CVD for a given anthropometric measure were found in Nunavik Inuit compared with Greenlandic Inuit and the Europeans; however, no cohort interactions were observed. For all-cause mortality, all anthropometric measures were positively associated in the Europeans, but only ABSI in the two Inuit populations. In contrast, BMI and WC were inversely associated with mortality in the two Inuit populations., Conclusions: Inuit and Europeans have different absolute incidences of CVD and all-cause mortality, but the trends in the associations with the anthropometric measures only differ for all-cause mortality. Previous findings of a lower obesity-associated cardiometabolic risk among Inuit were not confirmed., (Copyright © 2017 Elsevier B.V. All rights reserved.)

The natural history of diabetic nephropathy offered an average survival of only 5-7 years. During the past decades, multiple changes in therapy and lifestyle have occurred. The prognosis of diabetic nephropathy after implementing stricter control of blood pressure (including increased use of long-term renin-angiotensin system inhibition), lipids, and glycemia, along with less smoking and other lifestyle and treatment advancements, is inadequately analyzed. To clarify this, we studied 497 patients with type 1 diabetes and diabetic nephropathy at the Steno Diabetes Center and compared them with previous data, obtained using identical criteria at our hospital. The glomerular filtration rate, measured yearly by 51Cr-EDTA plasma clearance, was a mean of 71 ml/min per 1.73 m2 at baseline. The mean glomerular filtration rate decline was significantly reduced by 19% (95% confidence interval 5-34) from previously 4.0 to 3.3 ml/min per 1.73 m2/year. During a median follow-up of 9.1 years, 29% of participants doubled their plasma creatinine or developed end-stage renal disease. Mortality risk was similar to our prior study (hazard ratio 1.05 (0.76-1.43). However, after age adjustment, as both diabetes and nephropathy onset occurred later in life, mortality was reduced by 30%. Risk factors for decline in glomerular filtration rate, death, and other renal end points were generally in agreement with prior studies. Thus, with current treatment of nephropathy in type 1 diabetes, the prognosis and loss of renal function has improved along with better control of modifiable risk factors.

Purpose: We analyzed the changes in the body mass index (BMI) distribution for urban Australian adults between 1980 and 2007., Methods: We used data from participants of six consecutive Australian nation-wide surveys with measured weight and height between 1980 and 2007. We used quantile regression to estimate mean BMI (for percentiles of BMI) and prevalence of severe obesity, modeled by natural splines in age, date of birth, and survey date., Results: Since 1980, the right skew in the BMI distribution for Australian adults has increased greatly for men and women, driven by increases in skew associated with age and birth cohort/period. Between 1980 and 2007, the average 5-year increase in BMI was 1 kg/m(2) (0.8) for the 95th percentile of BMI in women (men). The increase in the median was about a third of this, and for the 10th percentile, a fifth of this. We estimated that for the cohort born in 1960 around 31% of men and women were obese by age 50 years compared with 11% of the 1930 birth cohort., Conclusions: There have been large increases in the right skew of the BMI distribution for urban Australian adults between 1980 and 2007, and birth cohort effects suggests similar increases are likely to continue., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: To develop a multistate model and an algorithm for calculating long-term adherence to medication among patients with a chronic disease., Methods: We propose definitions of the different states of waiting, persistence, with sufficient supply to implement the prescribed dosing regimen, gaps, nonpersistence, and nonacceptance and an algorithm for transitions between states to describe long-term adherence to medication treatment. The model and algorithm are operationalized for use in a case with a retrospective cohort of patients with type 2 diabetes mellitus, with access to records of prescribed drugs from a Danish diabetes research hospital and records of filled prescriptions at Danish pharmacies from the Danish Health and Medicines Authority., Results: Calculations of long-term adherence to medication are shown for patients with type 2 diabetes mellitus on metformin and/or simvastatin. The study shows how the prevalence of patients waiting to initiate treatment, patients with supply to implement the prescribed dosing regimen, patients not accepting treatment, and patients discontinuing treatment varies over time., Conclusions: The proposed multistate model and algorithm can easily be translated and used for the calculation of adherence to medication in any chronic disease. The model and algorithm take time into account, and thus, changes in incidence rates and prevalence of the different states over time can be estimated on several time scales (calendar time, age of the patient, and time since indication for medication)., (Copyright © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

We examined whether the adherence to major dietary patterns at baseline of 5824 nondiabetic Danes (30-60 y) enrolled in the nonpharmacological Inter99 intervention predicted changes in fasting plasma glucose (FPG) and postchallenge 2-h plasma glucose (2h-PG) concentrations during a 5 y period and whether a potential association was dependent on baseline glucose tolerance status. Through principal component analysis, a score for a traditional dietary pattern (characterized by higher intakes of high-fat sandwich spreads, red meat, potatoes, butter and lard, low-fat fish, sandwich meat, and sauces) and a score for a modern dietary pattern (characterized by higher intakes of vegetables, fruit, vegetable oil/vinegar dressing, poultry, pasta, rice, and cereals) were estimated for each person at baseline. Random effect models adjusting for relevant confounders were used to estimate changes in repetitive measures of FPG and 2h-PG. A higher modern score (of 1 SD) predicted an annual decrease in 2h-PG of 0.015 mmol/L (P < 0.01) regardless of glucose tolerance status. For individuals with isolated impaired glucose tolerance, a higher traditional score (of 1 SD) predicted an annual increase in 2h-PG of 0.083 mmol/L (P < 0.0001). In conclusion, glucose tolerance status did not, in general, affect the predictive effect of the dietary patterns. The study suggests that the risk of worsening 2h-PG concentrations may be smaller for individuals with a high modern dietary pattern score characterized by high intakes of vegetables, fruit, vegetable oil/vinegar dressing, poultry, pasta, rice, and cereals.

Purpose: To examine the age- and gender-specific prevalence and describe the common phenotype of early age-related maculopathy (ARM) and late-stage age-related macular degeneration (AMD) among the Inuit in Greenland., Design: Population-based cross-sectional study., Participants: All > or =60-year-olds born in Greenland and living in the communities of Nuuk and Sisimiut, Greenland., Methods: The presence and form of early (ARM) and late age-related macular disease (AMD) were determined by grading color fundus photographs using the international classification and grading system for ARM and AMD., Main Outcome Measures: Prevalences of ARM and AMD were assessed by masked grading of fundus photographs., Results: Overall, 695 persons were included in the study (response rate, 74.8%). Prevalence of any ARM was 52.3%. Age-related maculopathy was present in the worse eye in 50.0%, 58.8%, and 44.7% of age groups 60 to 69, 70 to 79, and > or =80, respectively. Prevalence of any AMD was 9.5%. Any AMD was present in the worse eye in 3.9%, 14.6%, and 43.2% of age groups 60 to 69, 70 to 79, and > or =80. Prevalences of pure geographic atrophy (GA) in one or both eyes, exudative degeneration in one or both eyes, and GA in one eye and exudative degeneration in the other eye were 2.3%, 6.1%, and 1.1%, respectively., Conclusions: The prevalence of ARM is higher than in most other populations studied, and the prevalence of AMD in the oldest age group is higher than in most other populations studied. The prevalence of exudative degeneration is higher than the prevalence of GA, in contrast to findings in some of the Nordic countries-particularly Iceland-and earlier observations in Greenland.

Background: The level of albuminuria is related to progression of diabetic nephropathy, and patients with nephrotic range albuminuria have advanced renal structural changes and the fastest decline in glomerular filtration rate (GFR). We have previously demonstrated that the rate of decline in GFR is diminished in patients obtaining remission of nephrotic range albuminuria, but information is scarce concerning the impact of remission of nephrotic range albuminuria on the long-term prognosis., Methods: At the Steno Diabetes Center, we performed a prospective cohort study of all type 1 diabetic patients with nephrotic range albuminuria (N= 125), who had annual measurement of GFR [(51)chromium-ethylenediaminetetraacetic acid ((51)Cr-EDTA) plasma clearance] carried out for at least 3 years. Patients were followed from onset of nephrotic range albuminuria until death or the end of year 2003. Nephrotic range albuminuria was defined as persistent albuminuria above 2.5 g/24 hours, remission of nephrotic range albuminuria was defined as sustained albuminuria <0.6 g/24 hours for at least 1 year., Results: Nephrotic range albuminuria occurred in 90 men and 35 women, age [mean (SD)] 34 (8) years, duration of diabetes 22 (8) years, and follow-up time from onset of nephrotic range albuminuria [median (range)] 12.4 (3.0 to 24.9) years. Remission was induced in 32 patients (26%), 25 predominantly treated with angiotensin-converting enzyme (ACE) inhibitors, seven with non-ACE inhibitors. The remission lasted 5.5 (1.0 to 22.4) years. At the end of follow-up, 25% in the remission group and 74% in the no remission group had reached the composite end point of end-stage renal disease (ESRD) (dialysis, transplantation) or death. A Cox proportional hazard regression analysis with gender and age as fixed covariates and remission as time-dependent covariate revealed that obtaining remission was associated with a lower risk of dialysis, transplantation, or death, relative risk (95% CI) 0.28 (0.13 to 0.59), P= 0.001, whereas older age at onset of nephrotic range albuminuria (per 10-year increase) was associated with higher risk of reaching the end point, 1.42 (1.08 to 1.87), P= 0.01., Conclusion: Our prospective study suggests that remission of nephrotic range albuminuria in type 1 diabetic patients, induced by aggressive antihypertensive treatment with and without ACE inhibitors, is associated with a slower progression in diabetic nephropathy and a substantially improved survival.

Aims: The purpose of this study was to investigate, within the context of the Danish Breast Cancer Cooperative Group (DBCG) programmes, whether a dedicated surgical approach had a significant bearing on the outcome of breast cancer treatment., Methods: From 1 January 1980 to 31 December 1990, patients below 70 years of age with operable breast cancer from Odense University Hospital (n=743) were compared with those from the rest of Denmark (denoted rest-DK) (n=15,419). All patients were treated according to nationwide DBCG guidelines and reported to the DBCG Data Centre. The potential median observation time was 11.2 years (range 6.0-16.9). Patients underwent mastectomy or breast conserving therapy, and high risk lymph-node positive patients had adjuvant systemic therapy with or without radiotherapy., Results: Comparing total patients series, overall survival (OS) was significantly superior in patients from Odense compared with rest-DK (P=0.02), with 10-year OSs of 62% (95% CI: 58-65%) and 56% (55-57%), respectively. In subgroups, the OS of low-risk node negative patients (protocol A) in Odense compared with rest-DK was significantly better (P=0.02); 10-year OS was 78% (73-84%) versus 72% (70-73%). Among the high-risk pre-menopausal patients (protocol B), the OS was significantly better in Odense (P=0.009); 10-year OS was 67% (60-75%) versus 53% (51-55%) in rest-DK. Post-menopausal high-risk patients (protocol C) did not differ significantly in OS between Odense and rest-DK (P=0.61). Locoregional control in the Odense series was superior compared with rest-DK. More lymph nodes were recovered and examined from the axilla in the Odense series than in rest-DK, a median of 10 vs. 6 nodes. In the Odense series, a significantly higher proportion of pre-menopausal patients had positive lymph nodes, predominantly one to three positive nodes, and subsequently a lower proportion of pre-menopausal patients had negative lymph nodes compared with rest-DK (P=0.02), indicating a more accurate staging in Odense vs. rest-DK. The survival benefit among the patients from Odense cannot be explained by stage migration alone, but seems to represent a true survival advantage. Overall mortality was significantly lower in the Odense series compared with rest-DK. Whether or not this difference could be explained by lower background mortality in the Odense series or was caused by superior treatment is discussed., Conclusions: The extent of surgery seems important for locoregional tumour control and accurate axillary lymph-node staging. In combination, these might lead to superior recurrence-free and overall survival, although differences in background mortality cannot be ignored. Surgery, therefore, might represent a risk factor by itself.

There is a considerable variation among specialists in the use of liver biopsy for the diagnosis of alcoholic cirrhosis, which is often based solely on clinical findings, sometimes supplemented with blood tests. To assess the diagnostic accuracy that may be achieved by this approach, we related items of the history, symptoms and signs, and routine blood tests to the presence/absence of cirrhosis in a unique, previously established, consecutive series of 303 alcohol-abusing men, in whom liver biopsy was performed irrespective of the clinical and biochemical findings. Using logistic regression analyses, we created a clinical, a combined clinical and biochemical, and a pure biochemical diagnostic model. The probability of cirrhosis in patients with the specified characteristics was estimated, the diagnostic accuracy was assessed as functions of diagnostic thresholds for cirrhosis defined by the probability of cirrhosis varying between 0 and 1,and confidence intervals were estimated by bootstrap sampling. The clinical model, including facial teleangiectasia, vascular spiders, white nails, abdominal veins, fatness, and peripheral edema, could be used with high diagnostic accuracy and it was clearly superior to the biochemical model. Adding biochemical findings to the clinical model improved the accuracy of the clinical model only slightly. We conclude that cirrhosis may be diagnosed in alcohol-abusing men with a high accuracy using selected, properly weighted clinical observations only.