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Aims: To develop and externally validate the LIFE-T1D model for the estimation of lifetime and 10-year risk of cardiovascular disease (CVD) in individuals with type 1 diabetes., Materials and Methods: A sex-specific competing risk-adjusted Cox proportional hazards model was derived in individuals with type 1 diabetes without prior CVD from the Swedish National Diabetes Register (NDR), using age as the time axis. Predictors included age at diabetes onset, smoking status, body mass index, systolic blood pressure, glycated haemoglobin level, estimated glomerular filtration rate, non-high-density lipoprotein cholesterol, albuminuria and retinopathy. The model was externally validated in the Danish Funen Diabetes Database (FDDB) and the UK Biobank., Results: During a median follow-up of 11.8 years (interquartile interval 6.1-17.1 years), 4608 CVD events and 1316 non-CVD deaths were observed in the NDR (n = 39 756). The internal validation c-statistic was 0.85 (95% confidence interval [CI] 0.84-0.85) and the external validation c-statistics were 0.77 (95% CI 0.74-0.81) for the FDDB (n = 2709) and 0.73 (95% CI 0.70-0.77) for the UK Biobank (n = 1022). Predicted risks were consistent with the observed incidence in the derivation and both validation cohorts., Conclusions: The LIFE-T1D model can estimate lifetime risk of CVD and CVD-free life expectancy in individuals with type 1 diabetes without previous CVD. This model can facilitate individualized CVD prevention among individuals with type 1 diabetes. Validation in additional cohorts will improve future clinical implementation., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Aims: To identify physical activity trajectories, explore the factors associated with them and assess their relationship with all-cause mortality., Methods: This was a population-based longitudinal cohort study, with data from all specialist care units for type 1 diabetes in Sweden. A total of 48.921 adult patients were included, each with at least 3 registrations of physical activity, and a maximum follow-up of 14 years. The main outcomes were the longitudinal physical activity trajectories and all-cause mortality., Results: Of 48.921 patients, 55.9% were males and mean (SD) age was 39.7(16.7). Four physical activity trajectories were identified: Steady Low (10.8%), Decreaser (12.7%), Increaser (20.7%) and Steady High (55.8%). Female sex, higher education, higher income, normal BMI, fewer comorbidities and foot free from diabetic disease were significantly associated with sustained high physical activity. Compared to the steady low group, the decreaser, increaser, and steady high physical activity groups exhibited lower adjusted risk of all-cause mortality (53-73% reduction)., Conclusions: Consistently low physical activity is associated with higher all-cause mortality. This study underscores the importance of identifying patients at risk of low physical activity and tailoring personalized approaches to promote sustained physical activity in type 1 diabetes, ultimately improving outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The aim of this study was to investigate temporal trends in survival and subsequent cardiovascular events in a nationwide myocardial infarction population with and without diabetes., Methods and Results: Between 2006 and 2020, we identified 2527 individuals with type 1 diabetes, 48 321 individuals with type 2 diabetes and 243 170 individuals without diabetes with first myocardial infarction in national health care registries. Outcomes were trends in all-cause death after 30 and 365 days, cardiovascular death and major adverse cardiovascular events (ie, nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and heart failure hospitalization). Pseudo-observations were used to estimate the mortality risk, with 95% CIs, using linear regression, adjusted for age and sex. Individuals with type 1 diabetes were younger (62±12.2 years) and more often women (43.6%) compared with individuals with type 2 diabetes (75±10.8 years; women, 38.1%), and individuals without diabetes (73±13.2 years; women, 38.4%). Early death decreased in people without diabetes from 23.1% to 17.5%, (annual change -0.48% [95% CI, -0.52% to -0.44%]) and in people with type 2 diabetes from 22.6% to 19.3% (annual change, -0.33% [95% CI, -0.43% to -0.24%]), with no such significant trend in people with type 1 diabetes from 23.8% to 21.7% (annual change, -0.18% [95% CI, -0.53% to 0.17%]). Similar trends were observed with regard to 1-year death, cardiovascular death, and major adverse cardiovascular events., Conclusions: During the past 15 years, the trend in survival and major adverse cardiovascular events in people with first myocardial infarction without diabetes and with type 2 diabetes have improved significantly. In contrast, a similar improvement was not seen in people with type 1 diabetes.

Aims/hypothesis: This register-based study aimed to describe autoimmune comorbidity in children and young adults from type 1 diabetes onset, and to investigate whether such comorbidity was associated with a difference in HbA 1c or mortality risk compared with children/young adults with type 1 diabetes without autoimmune comorbidity., Methods: A total of 15,188 individuals from the Swedish National Diabetes Register, registered with type 1 diabetes before 18 years of age between 2000 and 2019, were included. Five randomly selected control individuals from the Swedish population (Statistics Sweden) were matched to each individual with type 1 diabetes (n=74,210 [346 individuals with type 1 diabetes were not found in the Statistics Sweden register at the date of type 1 diabetes diagnosis, so could not be matched to control individuals]). The National Patient Register was used to attain ICD-10 codes on autoimmune diseases and the Cause of Death Register was used to identify deceased individuals., Results: In the total type 1 diabetes cohort, mean±SD age at onset of type 1 diabetes was 9.5±4.4 years and mean disease duration at end of follow-up was 8.8±5.7 years. Of the individuals with type 1 diabetes, 19.2% were diagnosed with at least one autoimmune disease vs 4.0% of the control group. The HRs for comorbidities within 19 years from onset of type 1 diabetes were 11.6 (95% CI 10.6, 12.6) for coeliac disease, 10.6 (95% CI 9.6, 11.8) for thyroid disease, 1.3 (95% CI 1.1, 1.6) for psoriasis, 4.1 (95% CI 3.2, 5.3) for vitiligo, 1.7 (95% CI 1.4, 2.2) for rheumatic joint disease, 1.0 (95% CI 0.8, 1.3) for inflammatory bowel disease, 1.0 (95% CI 0.7, 1.2) for systemic connective tissue disorder, 1.4 (95% CI 1.1, 1.9) for uveitis, 18.3 (95% CI 8.4, 40.0) for Addison's disease, 1.8 (95% CI 0.9, 3.6) for multiple sclerosis, 3.7 (95% CI 1.6, 8.7) for inflammatory liver disease and 19.6 (95% CI 4.2, 92.3) for atrophic gastritis. Autoimmune disease in addition to type 1 diabetes had no statistically significant effect on HbA 1c or mortality risk., Conclusions/interpretation: To our knowledge, this is the first comprehensive study where young individuals with type 1 diabetes were followed regarding development of a wide spectrum of autoimmune diseases, from onset of type 1 diabetes. In this nationwide and population-based study, there was already a high prevalence of autoimmune diseases in childhood, especially coeliac and thyroid disease. The presence of autoimmune comorbidity did not have a statistically significant effect on metabolic control or mortality risk., (© 2024. The Author(s).)

Aims: To study the association between glycated haemoglobin (HbA1c) and sepsis in adults with type 1 diabetes, and to explore the relationship between HbA1c and mortality among individuals who developed sepsis., Materials and Methods: We included 33 549 adult individuals with type 1 diabetes recorded in the Swedish National Diabetes Register between January 2005 and December 2015. We used multivariable Cox regression and restricted cubic spline analyses to study the relationship between HbA1c values and sepsis occurrence and association between HbA1c and mortality among those with sepsis., Results: In total, 713 (2.1%) individuals developed sepsis during the study period. Compared with the HbA1c reference interval of 48-52 mmol/mol (6.5-6.9%), the adjusted hazard ratio for sepsis was: 2.50 [95% confidence interval (CI) 1.18-5.29] for HbA1c <43 mmol/mol; 1.88 (95% CI 0.96-3.67) for HbA1c 43-47 mmol/mol; 1.78 (95% CI 1.09-2.89) for HbA1c 53-62 mmol/mol; 1.86 (95% CI 1.14-3.03) for HbA1c 63-72 mmol/mol; 3.15 (95% CI 1.91-5.19) for HbA1c 73-82 mmol/mol; and 4.26 (95% CI 2.53-7.16) for HbA1c >82 mmol/mol. On multivariable restricted cubic spline analysis, we found a J-shaped association between HbA1c and sepsis risk, with the lowest risk observed at HbA1c of approximately 53 mmol/mol. We found no association between HbA1c and mortality among those individuals who developed sepsis., Conclusions: In our nationwide observational study of adult individuals with type 1 diabetes we found a J-shaped relationship between HbA1c and risk of sepsis, with the lowest risk at HbA1c levels about 53 mmol/mol (7.0%). HbA1c was not associated with mortality in individuals affected by sepsis., (© 2023 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

People with type 1 diabetes have a substantially increased risk of premature death. This nationwide, register-based cohort study evaluated the significance of risk factors and previous cardiovascular disease (CVD), heart failure and chronic kidney disease (CKD), for mortality in type 1 diabetes. Nationwide, longitudinal, register-based cohort study. Patients (n = 36,303) listed in the Swedish National Diabetes Register between January 1 2015 and December 31 2017 were included and followed until December 31, 2018. Data were retrieved from national health registries through each patient's unique identifier, to capture data on clinical characteristics, outcomes, or deaths, to describe mortality rates in risk groups. The mean follow-up time was 3.3 years, with 119,800 patient years of observation and 1127 deaths, corresponding to a crude overall mortality of 0.92% deaths/year. Statistically significant increased risk in multivariate analyzes was found in older age groups, in men, and in underweight or people with normal BMI, high HbA1c or blood pressure. A history of CVD, albuminuria and advanced stages of CKD was associated with an increased risk of mortality. Each combination of these conditions further increased the risk of mortality. These results emphasize the importance of risk factors and cardiovascular and renal diabetes complications. People with a combination of CKD, CVD, and heart failure, exhibit a markedly increased risk of dying prematurely. These findings provide strong arguments for optimized and individualized treatment of these groups of people with type 1 diabetes in clinical everyday life., (© 2022. The Author(s).)

Objective: To investigate trends, optimal levels for cardiometabolic risk factors, and multifactorial risk control in diabetic nephropathy and end-stage kidney disease (ESKD) in patients with diabetes and matched control subjects., Research Design and Methods: This study included 701,622 patients with diabetes from the Swedish National Diabetes Register and 2,738,137 control subjects. Trends were analyzed with standardized incidence rates. Cox regression was used to assess excess risk, optimal risk factor levels, and risk according to the number of risk factors, in diabetes., Results: ESKD incidence among patients with and without diabetes initially declined until 2007 and increased thereafter, whereas diabetic nephropathy decreased throughout follow-up. In patients with diabetes, baseline values for glycated hemoglobin, systolic blood pressure (SBP), triglycerides, and BMI were associated with outcomes. Hazard ratio (HR) for ESKD for patients with type 2 diabetes who had all included risk factors at target was 1.60 (95% CI 1.49-1.71) compared with control subjects and for patients with type 1 diabetes 6.10 (95% CI 4.69-7.93). Risk for outcomes increased in a stepwise fashion for each risk factor not at target. Excess risk for ESKD in type 2 diabetes showed a HR of 2.32 (95% CI 2.30-2.35) and in type 1 diabetes 10.92 (95% CI 10.15-11.75), compared with control., Conclusions: Incidence of diabetic nephropathy has declined substantially, whereas ESKD incidence has increased. Traditional and modifiable risk factors below target levels were associated with lower risks for outcomes, particularly notable for the causal risk factors of SBP and HbA1c, with potential implications for care., (© 2022 by the American Diabetes Association.)

Background: The role of diabetes in the development of valvular heart disease, and, in particular, the relation with risk factor control, has not been extensively studied., Methods: We included 715 143 patients with diabetes registered in the Swedish National Diabetes Register and compared them with 2 732 333 matched controls randomly selected from the general population. First, trends were analyzed with incidence rates and Cox regression, which was also used to assess diabetes as a risk factor compared with controls, and, second, separately in patients with diabetes according to the presence of 5 risk factors., Results: The incidence of valvular outcomes is increasing among patients with diabetes and the general population. In type 2 diabetes, systolic blood pressure, body mass index, and renal function were associated with valvular lesions. Hazard ratios for patients with type 2 diabetes who had nearly all risk factors within target ranges, compared with controls, were as follows: aortic stenosis 1.34 (95% CI, 1.31-1.38), aortic regurgitation 0.67 (95% CI, 0.64-0.70), mitral stenosis 1.95 (95% CI, 1.76-2.20), and mitral regurgitation 0.82 (95% CI, 0.79-0.85). Hazard ratios for patients with type 1 diabetes and nearly optimal risk factor control were as follows: aortic stenosis 2.01 (95% CI, 1.58-2.56), aortic regurgitation 0.63 (95% CI, 0.43-0.94), and mitral stenosis 3.47 (95% CI, 1.37-8.84). Excess risk in patients with type 2 diabetes for stenotic lesions showed hazard ratios for aortic stenosis 1.62 (95% CI, 1.59-1.65), mitral stenosis 2.28 (95% CI, 2.08-2.50), and excess risk in patients with type 1 diabetes showed hazard ratios of 2.59 (95% CI, 2.21-3.05) and 11.43 (95% CI, 6.18-21.15), respectively. Risk for aortic and mitral regurgitation was lower in type 2 diabetes: 0.81 (95% CI, 0.78-0.84) and 0.95 (95% CI, 0.92-0.98), respectively., Conclusions: Individuals with type 1 and 2 diabetes have greater risk for stenotic lesions, whereas risk for valvular regurgitation was lower in patients with type 2 diabetes. Patients with well-controlled cardiovascular risk factors continued to display higher risk for valvular stenosis, without a clear stepwise decrease in risk between various degrees of risk factor control.

Type 1 diabetes is a chronic autoimmune disease requiring insulin treatment for survival. Prolonged duration of type 1 diabetes is associated with increased risk of microvascular complications. Although chronic hyperglycemia and diabetes duration have been considered as the major risk factors for vascular complications, this is not universally seen among all patients. Persons with long-term type 1 diabetes who have remained largely free from vascular complications constitute an ideal group for investigation of natural defense mechanisms against prolonged exposure of diabetes. Transcriptomic signatures obtained from RNA sequencing of the peripheral blood cells were analyzed in non-progressors with more than 30 years of diabetes duration and compared to the patients who progressed to microvascular complications within a shorter duration of diabetes. Analyses revealed that non-progressors demonstrated a reduction in expression of the oxidative phosphorylation (OXPHOS) genes, which were positively correlated with the expression of DNA repair enzymes, namely genes involved in base excision repair (BER) machinery. Reduced expression of OXPHOS and BER genes was linked to decrease in expression of inflammation-related genes, higher glucose disposal rate and reduced measures of hepatic fatty liver. Results from the present study indicate that at transcriptomic level reduction in OXPHOS, DNA repair and inflammation-related genes is linked to better insulin sensitivity and protection against microvascular complications in persons with long-term type 1 diabetes., (© 2021. The Author(s).)

Aims/hypothesis: Tables reporting life expectancies by common risk factors are available for individuals with type 2 diabetes; however, there is currently no published equivalent for individuals with type 1 diabetes. We aimed to develop a life expectancy table using a recently published simulation model for individuals with type 1 diabetes., Methods: The simulation model was developed using data from a real-world population of patients with type 1 diabetes selected from the Swedish National Diabetes Register. The following six important risk factors were included in the life table: sex; age; current smoking status; BMI; eGFR; and HbA 1c . For each of 1024 cells in the life expectancy table, a synthetic cohort containing 1000 individuals was created, with other risk factors assigned values representative of the real-world population. The simulations were executed for all synthetic cohorts and life expectancy for each cell was calculated as mean survival time of the individuals in the respective cohort., Results: There was a substantial variation in life expectancy across patients with different risk factor levels. Life expectancy of 20-year-old men varied from 29.3 years to 50.6 years, constituting a gap of 21.3 years between those with worst and best risk factor levels. In 20-year-old women, this gap was 18.9 years (life expectancy range 35.0-53.9 years). The variation in life expectancy was a function of the combination of risk factor values, with HbA 1c and eGFR consistently showing a negative and positive correlation, respectively, with life expectancy at any level combination of other risk factors. Individuals with the lowest level (20 kg/m 2 ) and highest level of BMI (35 kg/m 2 ) had a lower life expectancy compared with those with a BMI of 25 kg/m 2 . Non-smokers and women had a higher life expectancy than smokers and men, respectively, with the difference in life expectancy ranging from 0.4 years to 2.7 years between non-smokers and smokers, and from 1.9 years to 5.9 years between women and men, depending on levels of other risk factors., Conclusions/interpretation: The life expectancy table generated in this study shows a substantial variation in life expectancy across individuals with different modifiable risk factors. The table allows for rapid communications of risk in an easily understood format between healthcare professionals, health economists, researchers, policy makers and patients. Particularly, it supports clinicians in their discussion with patients about the benefits of improving risk factors., (© 2021. The Author(s).)

Introduction: Evidence on the effects of structured nutrition education is weak in adults with type 1 diabetes mellitus (T1D) with moderately impaired glycemic control. Objective was to compare the effects of different types of nutrition education programs on glycemic control, cardiovascular risk factors, quality of life, diet quality and food choices in T1D., Research Design and Methods: A 12 months randomized controlled study conducted at nine diabetes specialist centers with three parallel arms: (i) a food-based approach (FBA) including foods with low glycemic index or (ii) carbohydrate counting (CC) according to today's standard practice or (iii) individual sessions according to routine care (RC). The primary end point was difference in glycated hemoglobin A1c (HbA1c) between groups at 12 months., Results: 159 patients were randomized (FBA: 51; CC: 52; RC: 55). Mean (SD) age 48.6 (12.0) years, 57.9% females and mean (SD) HbA1c level 63.9 (7.9) mmol/mol, 8% (0.7%). After 3 months, HbA1c improved in both FBA and CC compared with RC. However, there were no significant differences at 12 months in HbA1c; FBA versus RC (-0.4 mmol/mol (1.3), 0.04% (0.1%)), CC versus RC (-0.8 mmol/mol (1.2), 0.1% (0.1%)), FBA versus CC (0.4 mmol/mol (0.3), 0.04% (0.01%)). At 12 months, intake of legumes, nuts and vegetables was improved in FBA versus CC and RC. FBA also reported higher intake of monounsaturated and polyunsaturated fats compared with RC, and dietary fiber, monounsaturated and polyunsaturated fats compared with CC (all p values <0.05). There were no differences in blood pressure levels, lipids, body weight or quality of life., Conclusions: Nutrition education using an FBA, CC or RC is equivalent in terms of HbA1c and cardiovascular risk factors in persons with T1D with moderately impaired glycemic control. An FBA had benefits regarding food choices compared with CC and RC., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To study the potential long-term benefits and possible complications of bariatric surgery in patients with type 1 diabetes (T1D)., Research Design and Methods: In this register-based nationwide cohort study, we compared individuals with T1D and obesity who underwent Roux-en-Y gastric bypass (RYGB) surgery with patients with T1D and obesity matched for age, sex, BMI, and calendar time that did not undergo surgery. By linking the Swedish National Diabetes Register and Scandinavian Obesity Surgery Registry study individuals were included between 2007 and 2013. Outcomes examined included all-cause mortality, cardiovascular disease, stroke, heart failure, and hospitalization for serious hypo- or hyperglycemic events, amputation, psychiatric disorders, changes in kidney function, and substance abuse., Results: We identified 387 individuals who had undergone RYGB and 387 control patients. Follow-up for hospitalization was up to 9 years. Analysis showed lower risk for cardiovascular disease (hazard ratio [HR] 0.43; 95% CI 0.20-0.9), cardiovascular death (HR 0.15; 95% CI 0.03-0.68), hospitalization for heart failure (HR 0.32; 95% CI 0.15-0.67), and stroke (HR 0.18; 95% CI 0.04-0.82) for the RYGB group. There was a higher risk for serious hyperglycemic events (HR 1.99; 95% CI 1.07-3.72) and substance abuse (HR 3.71; 95% CI 1.03-3.29) after surgery., Conclusions: This observational study suggests bariatric surgery may yield similar benefits on risk for cardiovascular outcomes and mortality in patients with T1D and obesity as for patients with type 2 diabetes. However, some potential serious adverse effects suggest need for careful monitoring of such patients after surgery., (© 2020 by the American Diabetes Association.)

Type 1 diabetes (T1D) is largely considered an autoimmune disease leading to the destruction of insulin-producing pancreatic β cells. Further, patients with T1D have 3-4-fold increased risk of developing micro- and macrovascular complications. However, the contribution of immune-related factors contributing to these diabetes complications are poorly understood. Individuals with long-term T1D who do not progress to vascular complications offer a great potential to evaluate end-organ protection. The aim of the present study was to investigate the association of inflammatory protein levels with vascular complications (retinopathy, nephropathy, cardiovascular disease) in individuals with long-term T1D compared to individuals who rapidly progressed to complications. We studied a panel of inflammatory markers in plasma of patients with long-term T1D with (n = 81 and 26) and without (n = 313 and 25) vascular complications from two cross-sectional Scandinavian cohorts (PROLONG and DIALONG) using Luminex technology. A subset of PROLONG individuals (n = 61) was screened for circulating immune cells using multicolor flow cytometry. We found that elevated plasma levels of soluble interleukin-2 receptor alpha (sIL-2R) were positively associated with the complication phenotype. Risk carriers of polymorphisms in the IL2RA and PTPN2 gene region had elevated plasma levels of sIL-2R. In addition, cell surface marker analysis revealed a shift from naïve to effector T cells in T1D individuals with vascular complications as compared to those without. In contrast, no difference between the groups was observed either in IL-2R cell surface expression or in regulatory T cell population size. In conclusion, our data indicates that IL2RA and PTPN2 gene variants might increase the risk of developing vascular complications in people with T1D, by affecting sIL-2R plasma levels and potentially lowering T cell responsiveness. Thus, elevated sIL-2R plasma levels may serve as a biomarker in monitoring the risk for developing diabetic complications and thereby improve patient care., (Copyright © 2020 Keindl, Fedotkina, du Plessis, Jain, Bergum, Mygind Jensen, Laustrup Møller, Falhammar, Nyström, Catrina, Jörneskog, Groop, Eliasson, Eliasson, Brismar, Nilsson, Berg, Appel and Lyssenko.)

Objective: To develop a patient-level simulation model for predicting lifetime health outcomes of patients with type 1 diabetes and as a tool for economic evaluation of type 1 diabetes treatment based on data from a large, longitudinal cohort., Research Design and Methods: Data for model development were obtained from the Swedish National Diabetes Register. We derived parametric proportional hazards models predicting the absolute risk of diabetes complications and death based on a wide range of clinical variables and history of complications. We used linear regression models to predict risk factor progression. Internal validation was performed, estimates of life expectancies for different age-sex strata were computed, and the impact of key risk factors on life expectancy was assessed., Results: The study population consisted of 27,841 patients with type 1 diabetes with a mean duration of follow-up of 7 years. Internal validation showed good agreement between the predicted and observed cumulative incidence of death and 10 complications. Simulated life expectancy was ∼13 years lower than that of the sex- and age-matched general population, and patients with type 1 diabetes could expect to live with one or more complications for ∼40% of their remaining life. Sensitivity analysis showed the importance of preventing renal dysfunction, hypoglycemia, and hyperglycemia as well as lowering HbA 1c in reducing the risk of complications and death., Conclusions: Our model was able to simulate risk factor progression and event histories that closely match the observed outcomes and to project events occurring over patients' lifetimes. The model can serve as a tool to estimate the impact of changing clinical risk factors on health outcomes to inform economic evaluations of interventions in type 1 diabetes., (© 2020 by the American Diabetes Association.)

Identification of biomarkers associated with protection from developing diabetic complications is a prerequisite for an effective prevention and treatment. The aim of the present study was to identify clinical and plasma metabolite markers associated with freedom from vascular complications in people with very long duration of type 1 diabetes (T1D). Individuals with T1D, who despite having longer than 30 years of diabetes duration never developed major macro- or microvascular complications (non-progressors; NP) were compared with those who developed vascular complications within 25 years from diabetes onset (rapid progressors; RP) in the Scandinavian PROLONG (n = 385) and DIALONG (n = 71) cohorts. The DIALONG study also included 75 healthy controls. Plasma metabolites were measured using gas and/or liquid chromatography coupled to mass spectrometry. Lower hepatic fatty liver indices were significant common feature characterized NPs in both studies. Higher insulin sensitivity and residual ß-cell function (C-peptide) were also associated with NPs in PROLONG. Protection from diabetic complications was associated with lower levels of the glycolytic metabolite pyruvate and APOCIII in PROLONG, and with lower levels of thiamine monophosphate and erythritol, a cofactor and intermediate product in the pentose phosphate pathway as well as higher phenylalanine, glycine and serine in DIALONG. Furthermore, T1D individuals showed elevated levels of picolinic acid as compared to the healthy individuals. The present findings suggest a potential beneficial shunting of glycolytic substrates towards the pentose phosphate and one carbon metabolism pathways to promote nucleotide biosynthesis in the liver. These processes might be linked to higher insulin sensitivity and lower liver fat content, and might represent a mechanism for protection from vascular complications in individuals with long-term T1D.

Concurrent type 1 diabetes (T1D) and Addison's disease (AD) is a rare combination of diseases and, in approximately one third of these patients, it is also combined with an autoimmune thyroid disease. Recently, it was shown that patients with both T1D and AD have a higher risk of premature death compared to patients with T1D alone, the most common causes of death being due to diabetic complications and cardiovascular disease. These patients receiving replacement therapies with both insulin and glucocorticoids face an increased risk of hypo- and hyperglycemia and diabetic ketoacidosis and have a higher risk of adrenal crisis than patients with AD alone. Treatment challenges include the opposing effects of insulin and glucocorticoids on glucose homeostasis and the need to balance and synchronize these two treatments. The rarity of this disease combination may explain the paucity of data on outcome and specific treatment strategies in this patient group. Based on this review, we suggest management strategies for their insulin and glucocorticoid replacement therapies and indicate future areas of research.

Background: The strength of association and optimal levels for risk factors related to excess risk of death and cardiovascular outcomes in type 1 diabetes mellitus have been sparsely studied., Methods: In a national observational cohort study from the Swedish National Diabetes Register from 1998 to 2014, we assessed relative prognostic importance of 17 risk factors for death and cardiovascular outcomes in individuals with type 1 diabetes mellitus. We used Cox regression and machine learning analyses. In addition, we examined optimal cut point levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol. Patients with type 1 diabetes mellitus were followed up until death or study end on December 31, 2013. The primary outcomes were death resulting from all causes, fatal/nonfatal acute myocardial infarction, fatal/nonfatal stroke, and hospitalization for heart failure., Results: Of 32 611 patients with type 1 diabetes mellitus, 1809 (5.5%) died during follow-up over 10.4 years. The strongest predictors for death and cardiovascular outcomes were glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol. Glycohemoglobin displayed ≈2% higher risk for each 1-mmol/mol increase (equating to ≈22% per 1% glycohemoglobin difference), whereas low-density lipoprotein cholesterol was associated with 35% to 50% greater risk for each 1-mmol/L increase. Microalbuminuria or macroalbuminuria was associated with 2 to 4 times greater risk for cardiovascular complications and death. Glycohemoglobin <53 mmol/mol (7.0%), systolic blood pressure <140 mm Hg, and low-density lipoprotein cholesterol <2.5 mmol/L were associated with significantly lower risk for outcomes observed., Conclusions: Glycohemoglobin, albuminuria, duration of diabetes mellitus, systolic blood pressure, and low-density lipoprotein cholesterol appear to be the most important predictors for mortality and cardiovascular outcomes in patients with type 1 diabetes mellitus. Lower levels for glycohemoglobin, systolic blood pressure, and low-density lipoprotein cholesterol than contemporary guideline target levels appear to be associated with significantly lower risk for outcomes.

Objective: To investigate real-world costs of continuous insulin pump therapy compared with multiple daily injection (MDI) therapy for type 1 diabetes., Research Design and Methods: Individuals with type 1 diabetes and pump therapy in the Swedish National Diabetes Register (NDR) since 2002 were eligible. Control subjects on MDI were matched 2:1 using time-varying propensity scores. Longitudinal data on health care resource use, antidiabetes treatment, sickness absence, and early retirement were taken from national registers for 2005-2013. Mean annual costs were analyzed using univariate analysis. Regression analyses explored the role of sociodemographic factors. Subgroup and sensitivity analyses were performed., Results: A total of 14,238 individuals with type 1 diabetes entered in the NDR between 2005 and 2013 (insulin pump n = 4,991, MDI n = 9,247, with switches allowed during the study) were included. Mean age at baseline was 34 years, with 21 years of diabetes duration and a mean HbA 1c of 8.1% (65 mmol/mol). We had 73,920 person-years of observation with a mean follow-up of 5 years per participant. Mean annual costs were higher for pump therapy than for MDI therapy ($12,928 vs. $9,005, respectively; P < 0.001; mean difference $3,923 [95% CI $3,703-$4,143]). Health care costs, including medications and disposables, accounted for 73% of the costs for pump therapy and 63% of the costs for MDI therapy. Regression analyses showed higher costs for low education, low disposable income, women, and older age., Conclusions: Nine years of real-world data on all measurable diabetes-related resource use show robust results for additional costs of insulin pump therapy in adults by subgroup and alternative propensity score specifications. Identification of tangible and intangible benefits of pump therapy over time remain important to support resource allocation decisions., (© 2019 by the American Diabetes Association.)

Context: Patients with type 1 diabetes mellitus (T1DM) have an increased risk of Addison disease (AD) development, but prediction of those at risk is not possible., Objective: To determine whether there are early clinical indicators that may denote the development of AD in adults with T1DM., Design: Observational, matched-cohort study., Setting: Patient data from Swedish national registries [National Diabetes Register (NDR), Inpatient Register, and Prescription Drug Register]., Participants: All patients with T1DM diagnosed with concomitant AD (n = 66) among the 36,514 adult patients with T1DM in the NDR between 1998 and 2013. Each case was matched to five controls with T1DM alone (n = 330)., Main Outcome Measures: Clinical data and drug prescriptions were assessed prior to baseline (inclusion into the study) and prior to AD diagnosis. Analysis of covariance and estimated group proportions were used for comparisons., Results: Prior to baseline, cases had a higher frequency of thyroid/antithyroid drug prescription than controls (9.1% vs 1.8%). Prior to AD diagnosis, cases had higher frequencies of diabetic retinopathy (12.1% vs 2.1%), infections requiring hospital admission (16.7% vs 2.1%), thyroid/antithyroid drug prescription (28.8% vs 7.0%), and glucagon prescription (18.2% vs 6.4%). There was no difference in glycated Hb between the groups prior to baseline or prior to AD diagnosis., Conclusions: These data suggest that medical treatment of thyroid disease, a severe infection, and glucagon prescription for severe hypoglycemia should raise the suspicion of AD development in adults with T1DM. Development of diabetic retinopathy might also be associated with glucocorticoid deficiency and the development of AD among patients with T1DM., (Copyright © 2019 Endocrine Society.)

Background: People with type 1 diabetes are at elevated risk of mortality and cardiovascular disease, yet current guidelines do not consider age of onset as an important risk stratifier. We aimed to examine how age at diagnosis of type 1 diabetes relates to excess mortality and cardiovascular risk., Methods: We did a nationwide, register-based cohort study of individuals with type 1 diabetes in the Swedish National Diabetes Register and matched controls from the general population. We included patients with at least one registration between Jan 1, 1998, and Dec 31, 2012. Using Cox regression, and with adjustment for diabetes duration, we estimated the excess risk of all-cause mortality, cardiovascular mortality, non-cardiovascular mortality, acute myocardial infarction, stroke, cardiovascular disease (a composite of acute myocardial infarction and stroke), coronary heart disease, heart failure, and atrial fibrillation. Individuals with type 1 diabetes were categorised into five groups, according to age at diagnosis: 0-10 years, 11-15 years, 16-20 years, 21-25 years, and 26-30 years., Findings: 27 195 individuals with type 1 diabetes and 135 178 matched controls were selected for this study. 959 individuals with type 1 diabetes and 1501 controls died during follow-up (median follow-up was 10 years). Patients who developed type 1 diabetes at 0-10 years of age had hazard ratios of 4·11 (95% CI 3·24-5·22) for all-cause mortality, 7·38 (3·65-14·94) for cardiovascular mortality, 3·96 (3·06-5·11) for non-cardiovascular mortality, 11·44 (7·95-16·44) for cardiovascular disease, 30·50 (19·98-46·57) for coronary heart disease, 30·95 (17·59-54·45) for acute myocardial infarction, 6·45 (4·04-10·31) for stroke, 12·90 (7·39-22·51) for heart failure, and 1·17 (0·62-2·20) for atrial fibrillation. Corresponding hazard ratios for individuals who developed type 1 diabetes aged 26-30 years were 2·83 (95% CI 2·38-3·37) for all-cause mortality, 3·64 (2·34-5·66) for cardiovascular mortality, 2·78 (2·29-3·38) for non-cardiovascular mortality, 3·85 (3·05-4·87) for cardiovascular disease, 6·08 (4·71-7·84) for coronary heart disease, 5·77 (4·08-8·16) for acute myocardial infarction, 3·22 (2·35-4·42) for stroke, 5·07 (3·55-7·22) for heart failure, and 1·18 (0·79-1·77) for atrial fibrillation; hence the excess risk differed by up to five times across the diagnosis age groups. The highest overall incidence rate, noted for all-cause mortality, was 1·9 (95% CI 1·71-2·11) per 100 000 person-years for people with type 1 diabetes. Development of type 1 diabetes before 10 years of age resulted in a loss of 17·7 life-years (95% CI 14·5-20·4) for women and 14·2 life-years (12·1-18·2) for men., Interpretation: Age at onset of type 1 diabetes is an important determinant of survival, as well as all cardiovascular outcomes, with highest excess risk in women. Greater focus on cardioprotection might be warranted in people with early-onset type 1 diabetes., Funding: Swedish Heart and Lung Foundation., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aims: This study aimed to investigate the association between insulin resistance as determined by the estimated glucose disposal rate (eGDR), and survival in adults with type 1 diabetes (T1D) in Sweden., Material and Methods: Using the Swedish National Diabetes Register, indviduals with T1D were included from January 1, 2005 to December 31, 2012. Outcomes were retrieved from National healthcare registers. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated for the associations between eGDR (mg/kg/min) categorized into <4, 4 to 5.99, 6 to 7.99, and ≥8 (reference) and outcomes. Relative survival methods were used to compare survival to a matched Swedish reference population., Results: Among 17 050 included individuals with T1D, 10.5%, 20.2%, 20.5% and 48.9% had an eGDR of <4, 4 to 5.99, 6 to 7.99, and ≥8, respectively. Individuals with an eGDR <8 were older and had more comorbidities. During a median follow-up of 7.1 years, there were 946 (6%) deaths; 264 (15%), 367 (11%), 195 (6%) and 120 (1%) deaths occurred in individuals with an eGDR of <4, 4 to 5.99, 6 to 7.99 and ≥8, respectively. After adjustment for a wealth of different covariates including diabetes duration, age, sex and renal function, individuals with an eGDR <4, 4 to 5.99, and 6 to 7.99 had an increased risk of death compared to those with an eGDR ≥8 (adjusted HRs, 95% CIs, P values: 2.78, 2.04 to 3.77, <.001; 1.92, 1.49 to 2.46, <.001; 1.73, 1.34 to 2.21, <.001). Survival in individuals with an eGDR ≥8 was equal to a matched general population., Conclusions: There is a strong association between eGDR and all-cause mortality, as well as cardiovascular mortality, in individuals with T1D. Our findings may guide preventive measures by improving risk assessment in individuals with T1D., (© 2017 John Wiley & Sons Ltd.)

Objectives: We determined the incidence and prevalence of Addison's disease (AD) among persons with or without type 1 diabetes mellitus (T1DM) in nationwide, matched cohort studies., Methods: Persons with T1DM were identified from the Swedish National Diabetes Register and each was matched for age, sex, year and county to five controls randomly selected from the general population. Persons with AD were identified from the Swedish National Inpatient Register. Baseline demographics and seasonal onset variation of AD were presented by descriptive statistics. Prevalence and incidence were estimated by proportions and incidence rates, respectively. Times to AD were analyzed using the Cox proportional hazard model., Results: Between 1998 and 2013, 66 persons with T1DM were diagnosed with AD at a mean age (s.d.) of 36.4 (13.0) years among 36 514 persons with T1DM, while 32 were diagnosed with AD at a mean age of 42.7 (15.2) years among 182 570 controls. The difference in mean age at diagnosis of AD between the groups was 6.3 years ( P value = 0.036). The incidence of AD for a person with or without T1DM was therefore 193 and 18 per million person-years, respectively. The adjusted relative risk increase of developing AD in T1DM was 10.8 (95% CI: 7.1-16.5). The highest incidence of AD was observed during February-March and September-October. The prevalence of AD in persons with or without T1DM in December 2012 was 3410 and 208 per million, respectively. The odds ratio for AD in persons with T1DM vs controls was 16.5 (95% CI: 11.1-24.5)., Conclusion: The risk to develop AD among persons with T1DM is more than 10 times higher than in persons without T1DM. Persons with T1DM develop AD at a younger age. The incidence of AD may have a seasonal pattern., (© 2018 European Society of Endocrinology.)

Background: It is unknown if coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI) may offer a survival benefit in patients with type 1 diabetes (T1D) in need of multivessel revascularization., Objectives: This study sought to determine if patients with T1D and multivessel disease may benefit from CABG compared with PCI., Methods: In an observational cohort study, the authors included all patients with T1D who underwent a first multivessel revascularization in Sweden from 1995 to 2013. The authors used the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) register, the Swedish National Diabetes Register, and the Swedish National Patient Register to retrieve information about patient characteristics and outcomes. They estimated hazard ratios (HRs) adjusted for confounders with 95% confidence intervals (CIs) for all-cause and coronary heart disease mortality, myocardial infarction, repeat revascularization, stroke, and heart failure using inverse probability of treatment weighting based on propensity scores., Results: In total, 683 patients who underwent CABG and 1,863 patients who underwent PCI were included. During a mean follow-up of 10.6 years, 53% of patients in the CABG group and 45% in the PCI group died. PCI, compared with CABG, was associated with a similar risk of all-cause mortality (HR: 1.14; 95% CI: 0.99 to 1.32), but higher risks of death from coronary heart disease (HR: 1.45; 95% CI: 1.21 to 1.74), myocardial infarction (HR: 1.47; 95% CI: 1.23 to 1.78), and repeat revascularization (HR: 5.64; 95% CI: 4.67 to 6.82). No differences in risks of stroke or heart failure were found., Conclusions: Notwithstanding the inclusion of patients with T1D who might not have been able to undergo CABG in the PCI group we found that PCI, compared with CABG, was associated with higher rates and risks of coronary heart disease mortality, myocardial infarction, and repeat revascularizations. Our findings indicate that CABG may be the preferred strategy in patients with T1D in need of multivessel revascularization., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Individuals with type 1 diabetes mellitus (T1DM) have a high risk of cardiovascular complications, but it is unknown to what extent fulfilling all cardiovascular treatment goals is associated with residual risk of mortality and cardiovascular outcomes in those with T1DM compared with the general population., Methods: We included all patients ≥18 years of age with T1DM who were registered in the Swedish National Diabetes Register from January 1, 1998, through December 31, 2014, a total of 33 333 patients, each matched for age and sex with 5 controls without diabetes mellitus randomly selected from the population. Patients with T1DM were categorized according to number of risk factors not at target: glycohemoglobin, blood pressure, albuminuria, smoking, and low-density lipoprotein cholesterol. Risk of all-cause mortality, acute myocardial infarction, heart failure hospitalization, and stroke was examined in relation to the number of risk factors at target., Results: The mean follow-up was 10.4 years in the diabetes group. Overall, 2074 of 33 333 patients with diabetes mellitus and 4141 of 166 529 controls died. Risk for all outcomes increased stepwise for each additional risk factor not at target. Adjusted hazard ratios for patients achieving all risk factor targets compared with controls were 1.31 (95% confidence interval [CI], 0.93-1.85) for all-cause mortality, 1.82 (95% CI, 1.15-2.88) for acute myocardial infarction, 1.97 (95% CI, 1.04-3.73) for heart failure hospitalization, and 1.17 (95% CI, 0.51-2.68) for stroke. The hazard ratio for patients versus controls with none of the risk factors meeting target was 7.33 (95% CI, 5.08-10.57) for all-cause mortality, 12.34 (95% CI, 7.91-19.48) for acute myocardial infarction, 15.09 (95% CI, 9.87-23.09) for heart failure hospitalization, and 12.02 (95% CI, 7.66-18.85) for stroke., Conclusions: A steep-graded association exists between decreasing number of cardiovascular risk factors at target and major adverse cardiovascular outcomes among patients with T1DM. However, risks for all outcomes were numerically higher for patients with T1DM compared with controls, even when all risk factors were at target, with risk for acute myocardial infarction and heart failure hospitalization statistically significantly higher., (© 2017 The Authors.)

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.).

Aims: To describe factors associated with prevalence or absence of microvascular and macrovascular complications in people with Type 1 diabetes of very long duration and to investigate the risk factors associated with the incidence of such complications., Methods: We included individuals with Type 1 diabetes who had been entered in the Swedish National Diabetes Register between 2002 and 2004 (n = 18 450). First, risk factor distribution in people with diabetes duration of ≥ 50 years was compared between people with and without complications. Second, the incidence of complications during a 10-year follow-up period was studied in all individuals who had no complications at baseline., Results: Among people with a diabetes duration of ≥ 50 years (n = 1023), 453 (44%) had macrovascular disease, 534 (52%) had microvascular disease and 319 (31%) did not have either of the diagnoses. Factors that differed significantly between people with and without macrovascular disease were gender, age, HbA 1c , BMI, LDL cholesterol, HDL cholesterol, triglycerides, systolic blood pressure, albuminuria, antihypertensive medication and lipid-lowering medication. The same factors differed significantly between people with and without microvascular disease, with the exception of gender and HDL cholesterol. During the follow-up period, 6.1% of the study cohort were diagnosed with macrovascular disease and 19.6% with microvascular disease. Incidence of macrovascular disease was significantly associated with HbA 1c levels. Hazard ratios decreased with longer diabetes duration., Conclusions: People with Type 1 diabetes who have survived ≥ 50 years without complications are significantly younger, and have significantly lower HbA 1c levels, BMI and triglyceride levels than survivors with complications. HbA 1c level is a predictor of macrovascular disease, independently of diabetes duration., (© 2016 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Importance: The association between socioeconomic status and survival based on all-cause, cardiovascular (CV), diabetes-related, and cancer mortality in type 2 diabetes has not been examined in a setting of persons with equitable access to health care with adjustment for important confounders., Objective: To determine whether income, educational level, marital status, and country of birth are independently associated with all-cause, CV, diabetes-related, and cancer mortality in persons with type 2 diabetes., Design, Setting, and Participants: A study including all 217 364 individuals younger than 70 years with type 2 diabetes in the Sweden National Diabetes Register (January 1, 2003, to December 31, 2010) who were monitored through December 31, 2012, was conducted. A Cox proportional hazards regression model with up to 17 covariates was used for analysis., Main Outcomes and Measures: All-cause, CV, diabetes-related, and cancer mortality., Results: Of the 217 364 persons included in the study, mean (SD) age was 58.3 (9.3) years and 130 839 of the population (60.2%) was male. There were a total of 19 105 all-cause deaths with 11 423 (59.8%), 6984 (36.6%), and 6438 (33.7%) CV, diabetes-related, or cancer deaths, respectively. Compared with being single, hazard ratios (HRs) for married individuals, determined using fully adjusted models, for all-cause, CV, and diabetes-related mortality were 0.73 (95% CI, 0.70-0.77), 0.67 (95% CI, 0.63-0.71), and 0.62 (95% CI, 0.57-0.67), respectively. Marital status was not associated with overall cancer mortality, but married men had a 33% lower risk of prostate cancer mortality compared with single men, with an HR of 0.67 (95% CI, 0.50-0.90). Comparison of HRs for the lowest vs highest income quintiles for all-cause, CV, diabetes-related, and cancer mortality were 1.71 (95% CI, 1.60-1.83), 1.87 (95% CI, 1.72-2.05), 1.80 (95% CI, 1.61-2.01), and 1.28 (95% CI, 1.14-1.44), respectively. Compared with native Swedes, HRs for all-cause, CV, diabetes-related, and cancer mortality for non-Western immigrants were 0.55 (95% CI, 0.48-0.63), 0.46 (95% CI, 0.38-0.56), 0.38 (95% CI, 0.29-0.49), and 0.72 (95% CI, 0.58-0.88), respectively, and these HRs were virtually unaffected by covariate adjustment. Hazard ratios for those with a college/university degree compared with 9 years or less of education were 0.85 (95% CI, 0.80-0.90), 0.84 (95% CI, 0.78-0.91), and 0.84 (95% CI, 0.76-0.93) for all-cause, CV, and cancer mortality, respectively., Conclusions and Relevance: Independent of risk factors, access to health care, and use of health care, socioeconomic status is a powerful predictor of all-cause and CV mortality but was not as strong as a predictor of death from cancer.

Objective: To evaluate the effect of lipid-lowering therapy (LLT) in primary prevention on cardiovascular disease (CVD) and death in type 1 diabetes., Research Design and Methods: We used the Swedish National Diabetes Register (NDR) to perform a propensity score-based study. Propensity scores for treatment with LLT were calculated from 32 baseline clinical and socioeconomic variables. The propensity score was used to estimate the effect of LLT in the overall cohort (by stratification). We estimated risk of acute myocardial infarction, stroke, coronary heart disease, and cardiovascular and all-cause mortality in individuals with and without LLT using Cox regression. A total of 24,230 individuals included in 2006-2008 NDR with type 1 diabetes without a history of CVD were followed until 31 December 2012; 18,843 were untreated and 5,387 treated with LLT (97% statins). The mean follow-up was 6.0 years., Results: The propensity score allowed balancing of all 32 covariates, with no differences between treated and untreated after accounting for propensity score. Hazard ratios (HRs) for treated versus untreated were as follows: cardiovascular death 0.60 (95% CI 0.50-0.72), all-cause death 0.56 (0.48-0.64), fatal/nonfatal stroke 0.56 (0.46-0.70), fatal/nonfatal acute myocardial infarction 0.78 (0.66-0.92), fatal/nonfatal coronary heart disease 0.85 (0.74-0.97), and fatal/nonfatal CVD 0.77 (0.69-0.87)., Conclusions: This observational study shows that LLT is associated with 22-44% reduction in the risk of CVD and cardiovascular death among individuals with type 1 diabetes without history of CVD and underlines the importance of primary prevention with LLT to reduce cardiovascular risk in type 1 diabetes., (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Aims/hypothesis: People with type 1 diabetes have reduced life expectancy (LE) compared with the general population. Our aim is to quantify mortality changes from 2002 to 2011 in people with type 1 diabetes in Sweden., Methods: This study uses health records from the Swedish National Diabetes Register (NDR) linked with death records. Abridged period life tables for those with type 1 diabetes aged 20 years and older were derived for 2002-06 and 2007-11 using Chiang's method. Cox proportional hazard models were used to assess trends in overall and cause-specific mortality., Results: There were 27,841 persons aged 20 years and older identified in the NDR as living with type 1 diabetes between 2002 and 2011, contributing 194,685 person-years of follow-up and 2,018 deaths. For men with type 1 diabetes, the remaining LE at age 20 increased significantly from 47.7 (95% CI 46.6, 48.9) in 2002-06 to 49.7 years (95% CI 48.9, 50.6) in 2007-11. For women with type 1 diabetes there was no significant change, with an LE at age 20 of 51.7 years (95% CI 50.3, 53.2) in 2002-06 and 51.9 years (95% CI 50.9, 52.9) in 2007-11. Cardiovascular mortality significantly reduced, with a per year HR of 0.947 (95% CI 0.917, 0.978) for men and 0.952 (95% CI 0.916, 0.989) for women., Conclusions/interpretation: From 2002-06 to 2007-11 the LE at age 20 of Swedes with type 1 diabetes increased by approximately 2 years for men but minimally for women. These recent gains have been driven by reduced cardiovascular mortality.

Aim: LDL cholesterol (LDL-C) is considered an important cardiovascular disease (CVD) risk factor. Less is known in Type 1 diabetes. We assessed LDL-C and total cholesterol to HDL cholesterol ratio (TC/HDL-C) as predictors of CVD in Type 1 diabetes., Methods: The study monitored 30 778 people with Type 1 diabetes, baseline 2003-2006, to 31 December 2011. Cox regression analyses were performed with LDL-C and TC/HDL-C as predictors of fatal/non-fatal CVD. Models were adjusted for traditional CVD risk factors., Results: Hazard ratios (HR) (with 95% CI) per 1 mmol/l increase in LDL-C for CVD were 1.09 (1.01-1.18) in people without lipid-lowering medication and 1.02 (0.95-1.09) in people with lipid-lowering medication (P = 0.02 and 0.65). In people aged 40 years or older having a CVD risk factor, and in people with a history of CVD, HR was 1.07 (0.99-1.16) and 1.02 (0.92-1.13) (P = 0.07 and 0.66). HR per 1 unit increase in TC/HDL-C was 1.12 (1.05-1.20) in people without lipid-lowering medication and 1.08 (1.02-1.15) in people with lipid-lowering medication (P < 0.001 and 0.01). For people aged 40 or older and people with a history of CVD, HR was 1.16 (1.09-1.24) and 1.04 (0.95-1.14) (P < 0.001 and 0.43). Broken down into octiles, LDL-C was not a significant predictor of CVD in any group. Higher octiles of TC/HDL-C were significant predictors for CVD in people without lipid-lowering medication and in those aged 40 years or older., Conclusion: In this study of people with Type 1 diabetes in clinical practice, LDL-C was not a good predictor of CVD. We found no support for an LDL-C cut-off point < 2.6 mmol/l. TC/HDL-C seems more reliable as a marker for CVD risk when considering primary prevention., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Background: Patients with type 1 diabetes mellitus (T1DM) have a high risk of cardiovascular events., Objectives: The aim of this study was to investigate whether preoperative hemoglobin A1c (HbA1c) levels could predict cardiovascular events or death after coronary artery bypass grafting (CABG)., Methods: This was a nationwide population-based observational cohort study that included all patients with T1DM who underwent primary isolated nonemergency CABG in Sweden between 1997 and 2012, according to the Swedish National Diabetes Register and the SWEDEHEART (Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) register. We calculated the crude incidence rates and 95% confidence intervals (CIs) and used Cox regression and multivariable hazard ratios (HRs) to estimate the risk of both all-cause mortality and major adverse cardiovascular events (MACE), defined as myocardial infarction, stroke, heart failure, or repeat revascularization, in relation to HbA1c levels., Results: In total, 764 patients with T1DM were included. During a median follow-up of 4.7 years, 334 (44%) patients died or had MACE (incidence rate: 82 events/1,000 person-years). After multivariable adjustment, the HR (95% CI) for death or MACE in patients with HbA1c levels of 7.1% to 8.0%, 8.1% to 9.0%, 9.1% to 10.0%, and >10.0% were 1.34 (0.82 to 2.21), 1.59 (1.00 to 2.54), 1.73 (1.03 to 2.90), and 2.25 (1.29 to 3.94), respectively, compared with the reference category. When HbA1c was used as a continuous variable, the HR for a 1% increase in HbA1c level was 1.18, and the 95% CI was 1.06 to 1.32., Conclusions: In patients with T1DM, poor glycemic control before CABG was associated with increased long-term risk of death or MACE. (HeAlth-data Register sTudies of Risk and Outcomes in Cardiac Surgery [HARTROCS]; NCT02276950)., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: Socioeconomic status (SES) is a powerful predictor of cardiovascular disease (CVD) and death. We examined the association in a large cohort of patients with type 1 diabetes., Research Design and Methods: Clinical data from the Swedish National Diabetes Register were linked to national registers, whereby information on income, education, marital status, country of birth, comorbidities, and events was obtained. Patients were followed until a first incident event, death, or end of follow-up. The association between socioeconomic variables and the outcomes was modeled using Cox regression, with rigorous covariate adjustment., Results: We included 24,947 patients. Mean (SD) age and follow-up was 39.1 (13.9) and 6.0 (1.0) years. Death and fatal/nonfatal CVD occurred in 926 and 1378 individuals. Compared with being single, being married was associated with 50% lower risk of death, cardiovascular (CV) death, and diabetes-related death. Individuals in the two lowest quintiles had twice as great a risk of fatal/nonfatal CVD, coronary heart disease, and stroke and roughly three times as great a risk of death, diabetes-related death, and CV death as individuals in the highest income quintile. Compared with having ≤9 years of education, individuals with a college/university degree had 33% lower risk of fatal/nonfatal stroke. Immigrants had 19%, 33%, and 45% lower risk of fatal/nonfatal CVD, all-cause death, and diabetes-related death, respectively, compared with Swedes. Men had 44%, 63%, and 29% greater risk of all-cause death, CV death, and diabetes-related death., Conclusions: Low SES increases the risk of CVD and death by a factor of 2-3 in type 1 diabetes., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objective: To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes., Design: Observational study., Setting: Swedish National Diabetes Register, Sweden 2005-12., Participants: 18,168 people with type 1 diabetes, 2441 using insulin pump therapy and 15,727 using multiple daily insulin injections., Main Outcome Measures: Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases., Results: Follow-up was for a mean of 6.8 years until December 2012, with 114,135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in >80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have influenced the observed association., Conclusion: Among people with type 1 diabetes use of insulin pump therapy is associated with lower cardiovascular mortality than treatment with multiple daily insulin injections., (© Steineck et al 2015.)

Background: Patients with diabetes mellitus (DM) have an increased risk of adverse outcomes after coronary artery bypass grafting (CABG). Previous studies have reported prognosis in relation to treatment with or without insulin, and not to the type of diabetes., Objectives: This study investigated long-term survival in patients with type 1 DM (T1DM) and type 2 DM (T2DM) following CABG., Methods: We included all patients from the SWEDEHEART (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) register who underwent primary isolated CABG in Sweden during 2003 through 2013. We identified patients with T1DM or T2DM in the Swedish National Diabetes Register. We calculated hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause mortality in patients with T1DM or T2DM., Results: In total, 39,235 patients were included, of whom 725 (1.8%) had T1DM and 8,208 (21%) had T2DM. Patients with TDM1 were younger (59 vs. 67 years), had reduced kidney function (31% vs. 24%), and had peripheral vascular disease (21% vs. 11%) more often than patients with TDM2 or no diabetes. During a mean follow-up of 5.9±3.2 years (230,085 person-years), 6,765 (17%) patients died. Among patients with T1DM, 152 (21%) died, and among patients with T2DM, 1,549 (19%) died. Adjusted hazard ratio (95% confidence interval) for death in patients with T1DM and T2DM, compared with patients without diabetes, were 2.04 (1.72 to 2.42), and 1.11 (1.05 to 1.18), respectively., Conclusions: Patients with T1DM had more than double the long-term risk of death after CABG compared with patients without diabetes. The long-term risk of death in patients with T2DM was only slightly increased., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objective: To examine whether previous severe hypoglycemic events were associated with the risk of all-cause mortality after major cardiovascular events (myocardial infarction [MI] or stroke) in patients with type 1 diabetes., Research Design and Methods: This study is based on data from the Swedish National Diabetes Register linked to patient-level hospital records, prescription data, and death records. We selected patients with type 1 diabetes who visited a clinic during 2002-2010 and experienced a major cardiovascular complication after their clinic visit. We estimated a two-part model for all-cause mortality after a major cardiovascular event: logistic regression for death within the first month and a Cox proportional hazards model conditional on 1-month survival. At age 60 years, 5-year cumulative mortality risk was estimated from the models for patients with and without prior diabetes complications., Results: A total of 1,839 patients experienced major cardiovascular events, of whom 403 had previously experienced severe hypoglycemic events and 703 died within our study period. A prior hypoglycemic event was associated with a significant increase in mortality after a cardiovascular event, with hazard ratios estimated at 1.79 (95% CI 1.37-2.35) within the first month and 1.25 (95% CI 1.02-1.53) after 1 month. Patients with prior hypoglycemia had an estimated 5-year cumulative mortality risk of 52.4% (95% CI 45.3-59.5) and 39.8% (95% CI 33.4-46.3) for MI and stroke, respectively., Conclusions: We have found evidence that patients with type 1 diabetes in Sweden with prior severe hypoglycemic events have increased risk of mortality after a cardiovascular event., (© 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Aims: To elucidate methodological questions in assessing the relationship between insulin treatment and cancer, since the risk of tumour growth generally increases with longer exposure time and higher dose of a growth promoting substance., Methods: Continuous hazard functions for risk of breast and prostate cancer were estimated in relation to exposure of insulin glargine among diabetic patients included in the record system, Diab-Base, as well as in the general population in Sweden., Results: In 7942 female diabetic patients, mean follow-up 7.0 years, 2014 patients initiated insulin glargine with a mean follow-up of 3.5 years. Among 11,613 men, mean follow-up 6.9 years, 2760 had a mean follow-up with glargine of 3.4 years. Risk of prostate cancer decreased significantly with longer exposure to insulin glargine (p=0.032), although average risk versus non-glargine was non-significantly higher (HR 1.37, 95% CI 0.78-2.39). The breast cancer risk did not change with longer exposure to insulin glargine (p=0.35) and the mean risk was similar for glargine and non-glargine (p=0.12). With higher dose of insulin glargine, there was an increase in risk of prostate (p=0.037) and breast cancer (p=0.019). In diabetics, the mean risk of prostate cancer was decreased (HR 0.68, 95% CI 0.59-0.79) but similar for breast cancer (HR 0.95, 95% CI 0.78-1.14) compared to the general population and did not change with longer diabetes duration (p=0.68 and p=0.53 respectively)., Conclusions: Analysing continuous hazard functions for cancer risk in relation to exposure time to an antidiabetic agent is an important complementary tool in diabetes and cancer research., (Copyright © 2011 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Aims: We assessed the association between risk factors and cardiovascular disease in an observational study of patients with Type 1 diabetes from the Swedish National Diabetes Register., Methods: A derivation sample of 3661 patients, aged 30-65 years, 6.1% with previous cardiovascular disease, baseline 2002, and 197 cardiovascular disease events when followed for 5 years until 2007. A separate validation data set of 4484 patients, baseline 2003, 201 cardiovascular disease events when followed for 4 years., Results: Adjusted hazard ratios at Cox regression for fatal/non-fatal cardiovascular disease were: diabetes duration 2.76 (2.21-3.44); onset age 1.47 (1.21-1.78); log ratio total cholesterol:HDL cholesterol 1.26 (1.09-1.45); log HbA(1c) 1.19 (1.03-1.38); log systolic blood pressure 1.17 (1.01-1.34) (1 SD increase in continuous variables); smoker 1.76 (1.27-2.46); macroalbuminuria (> 200 μg/min) 1.52 (1.10-2.10); previous cardiovascular disease 3.51 (2.54-4.84). All eight variables were used to elaborate a risk equation for 5-year cardiovascular disease risk. Regarding calibration in the derivation data set, ratio predicted 5-year risk (mean 5.4 ± 7.9%) to observed event rate was 1.0. Discrimination was sufficient, with C-statistic 0.83, sensitivity and specificity 72 and 77%, respectively, for the top quartile of predicted risk. Similarly, calibration and discrimination were adequate in the validation data set: ratio of predicted 4-year risk/observed rate 0.94, C-statistic 0.80, sensitivity and specificity 62 and 77%, respectively, for the top quartile., Conclusions: This 5-year cardiovascular disease risk model from a large observational study of patients with Type 1 diabetes in routine care showed adequate calibration and discrimination and can be useful for clinical practice. It should also be tested in patients with Type 1 diabetes from other countries., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

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.

Objective: We assessed the association between A1C and cardiovascular diseases (CVDs) in an observational study of patients with type 1 diabetes followed for 5 years., Research Design and Methods: A total of 7,454 patients were studied from the Swedish National Diabetes Register (aged 20-65 years, diabetes duration 1-35 years, followed from 2002 to 2007)., Results: Hazard ratios (HRs) for fatal/nonfatal coronary heart disease (CHD) per 1% unit increase in baseline or updated mean A1C at Cox regression analysis were 1.31 and 1.34 and 1.26 and 1.32, respectively, for fatal/nonfatal CVD (all P < 0.001 after adjustment for age, sex, diabetes duration, blood pressure, total and LDL cholesterol, triglycerides, BMI, smoking, and history of CVD). HRs were only slightly lower for CHD (P = 0.002) and CVD (P = 0.002-0.007) after also adjusting for albuminuria. Adjusted 5-year event rates of CHD and CVD increased progressively with higher A1C, ranging from 5 to 12%, as well as when subgrouped by shorter (1-20 years) or longer (21-35 years) duration of diabetes. A group of 4,186 patients with A1C 5-7.9% (mean 7.2) at baseline showed risk reductions of 41% (95% confidence intervals: 15-60) (P = 0.005) for fatal/nonfatal CHD and 37% (12-55) (P = 0.008) for CVD, compared with 3,268 patients with A1C 8-11.9% (mean 9.0), fully adjusted also for albuminuria., Conclusions: This observational study of patients in modern everyday clinical practice demonstrates progressively increasing risks for CHD and CVD with higher A1C, independently of traditional risk factors, with no J-shaped risk curves. A baseline mean A1C of 7.2% showed considerably reduced risks of CHD and CVD compared with A1C 9.0%, emphasizing A1C as a strong independent risk factor in type 1 diabetes.

Aims/hypothesis: We determined the shape of the metabolic memory of HbA1c and its contribution to retinopathy, as well as the importance of reducing HbA1c to prevent progression of retinopathy., Methods: The relative risk contribution of HbA1c values at different points in time to current progression of retinopathy was determined in the DCCT patients., Results: HbA1c 2 to 3 years earlier had the greatest relative risk contribution to current progression of retinopathy. HbA1c up to 5 years earlier made a greater contribution than current values, while values from 8 years earlier still had an important impact. When HbA1c had been at 8% for a long period and was subsequently lowered to 7%, the salutary effects did not begin to appear until 2 to 3 years after lowering. The hazard function for a constant level of HbA1c increased with time. The numbers needed to treat when reducing HbA1c from 8.3% to 8% from diagnosis was estimated to be 1,688 for the first 3 years and 13 for the period 9 to 12 years. Survival functions when reducing HbA1c from 8% to 7% show that pre-study glycaemic control dominates the effect on progression of retinopathy during the first years of a trial., Conclusions/interpretation: The most harmful effect of hyperglycaemia on progression of retinopathy in type 1 diabetes initially increases, but declines after roughly 5 years. The salutary effect of reducing HbA1c accelerates with time and becomes greater in clinical practice than has been previously understood. Clinical trials should preferably be designed for long periods or include patients with low previous glycaemic exposure to distinguish trial effects from those of the metabolic memory.

Background: The use of rapid-acting insulin analogs and regular insulin differs considerably in countries throughout the world. We therefore studied how glycemic control has been affected by using insulin lispro in clinical practice over 5 years in 14 hospitals in Sweden., Methods: We used a time period when most patients had not changed the basal insulin, but only the mealtime insulin. Accordingly the most recent years were not suitable since many patients had changed basal insulin from NPH to glargine or determir. We therefore analyzed the metabolic consequences on glycosylated hemoglobin (HbA1c) when changing from regular insulin to insulin lispro from 1997 and during the following 5 years. We studied 1,069 patients with diabetes taking NPH insulin as basal insulin and at least three daily injections of regular insulin, of whom 423 changed their mealtime insulin to insulin lispro and 646 controls who continued with regular insulin., Results: Patients changing to insulin lispro on average decreased by 0.19% units more in HbA1c than those remaining on regular insulin. The effect was most pronounced in patients with high HbA1c even after controlling for regression to the mean. A beneficial effect of insulin lispro was also indicated since patients had the same level of HbA1c during a long period of time with regular insulin but then dropped when changing to insulin lispro., Conclusions: This study indicates that insulin lispro has had a beneficial and persisting effect on glycemic control when used in patients with diabetes on multiple daily injections of insulin in clinical practice.

Objective: This study was designed to investigate the clinical characteristics of a large type 1 diabetic population and to evaluate the degree of fulfillment of recently updated treatment goals., Research Design and Methods: The Swedish National Diabetes Register was initiated in 1996 as a tool for quality assurance in diabetes care. A1C levels, treatment, and risk factors were analyzed in two cross-sectional samples of 9,424 patients in 1997 and 13,612 patients in 2004 and in a smaller longitudinal sample from 1997 to 2004., Results: Mean A1C decreased from 8.2 +/- 1.3% in 1997 to 8.0 +/- 1.2% in 2004 (P < 0.001). The proportion of patients reaching A1C <7.0% increased from 17.4 to 21.2% in 2004. A slow but significant improvement in blood pressure levels was seen, but only 61.3% reached the blood pressure goal of <130/80 mmHg in 2004. Lipid control improved, and the use of lipid-lowering drugs increased. Among patients treated with lipid-lowering agents, 38% reached the goal of total cholesterol <4.5 mmol/l, and 48% reached the goal of LDL cholesterol <2.5 mmol/l. Successful long-term glycemic and blood pressure control were both independently predicted by low BMI and the absence of microalbuminuria in 1997., Conclusions: In this large cohort of type 1 diabetic patients, there was a slow improvement in glycemic and risk factor control from 1997 to 2004, although the gap between the clinical results and current Swedish and American treatment goals is still unsatisfactory. It is crucial that additional measures be taken to improve risk factor control in type 1 diabetic patients.

This case-control study was designed to analyse predictors of the effects on HbA1c levels in 4001 type 1 and type 2 diabetic patients after changing their insulin treatment. Patients from 15 outpatient diabetic clinics were treated with basal insulin and multiple injections of short-acting insulin. The effects on HbA1c of changing from NPH insulin to insulin glargine as basal insulin were studied, compared to patients continuing with NPH insulin. The following possible predictors were examined with multiple regression analysis: age, sex, type and duration of diabetes, smoking, metformin use, insulin requirement, number of basal doses per day, BMI and HbA1c at baseline. The difference between the two regression functions yielded the effect of switching treatment to insulin glargine compared to continuing with NPH insulin. Male gender, low BMI and high baseline HbA1c levels were significant predictors for a greater decrease in HbA1c when changing to insulin glargine. For example, for men with a BMI of 25 and an HbA1c of 8.0%, there was a calculated mean benefit in HbA1c of 0.26 percentage points by changing to insulin glargine, whereas women with a BMI 30 had no benefit of such a change. Thus, changing to insulin glargine had best effect in male patients with low BMI. This is one of the first studies designed to find responders to insulin treatment. Analyses of predictors may prove useful in order to tailor insulin treatment in diabetic patients in clinical practice. The clinical effects need to be confirmed in other studies and randomised controlled trials.

Aims: To compare the effects on glycaemic control after using continuous subcutaneous insulin infusion (CSII) or insulin glargine., Methods: Data were obtained from 17 diabetes outpatient clinics in Sweden, employing the same diabetes data management system. Type 1 diabetic patients using multiple dose injections were included prior to starting on either CSII (n = 563) or glargine (n = 513). The median duration of therapy was 25 months for CSII and 6 months for glargine. The comparison between the treatment modalities was carried out by multiple regression analysis and logistic regression analysis in an attempt at reducing the influence of confounding factors., Results: The mean HbA1c decrease was 0.59 +/- 1.19% for CSII and 0.20 +/- 1.07% for glargine (P < 0.001, when assessed by logistic regression). An additional 0.1% lower HbA1c would be expected if glargine had been optimized with basal insulin 40-60% of the daily dose. The more pronounced effect of CSII was achieved with a lower daily dosage of insulin. In a multiple regression analysis with a change of HbA1c as the dependent variable, the following variables were significant: choice of treatment (P < 0.001), HbA1c prior to treatment (P < 0.001) and BMI prior to treatment (P < 0.01)., Conclusion: Both regimes improved metabolic control, but CSII resulted in significantly higher reduction in HbA1c than after insulin glargine treatment, particularly in those individuals who had higher levels of HbA1c at baseline.

A prospective study of normoalbuminuric diabetic patients was performed between 1997 and 2002 on 4097 type 1 and 6513 type 2 diabetic patients from the Swedish National Diabetes Register (NDR); mean study period, 4.6 years. The strongest independent baseline risk factors for the development of microalbuminuria (20-200 microg/min) were elevated HbA(1c) and diabetes duration in both types 1 and 2 diabetic patients. Other risk factors were high BMI, elevated systolic and diastolic BP in type 2 patients, and antihypertensive therapy in type 1 patients. A subsequent larger cross-sectional study in 2002 showed that established microalbuminuria was independently associated with HbA(1c), diabetes duration, systolic BP, BMI, smoking and triglycerides in types 1 and 2 diabetic patients, and also with HDL-cholesterol in type 2 patients. Relatively few types 1 and 2 patients with microalbuminuria achieved treatment targets of HbA(1c) < 6.5% (21-48%), BP < 130/85 mmHg (33-13%), cholesterol < 5 mmol/l (48-46%), triglycerides < 1.7 mmol/l (83-48%) and BMI < 25 kg/m(2) (50-18%), respectively. In conclusion, high HbA(1c), BP and BMI were independent risk factors for the development of microalbuminuria in types 1 and 2 diabetic patients. These risk factors as well as triglycerides, HDL-cholesterol and smoking were independently associated with established microalbuminuria. Treatment targets were achieved by a relatively few patients with microalbuminuria.