Type 1 Diabetes Mellitus Cohort Research Articles

A single center case series of immune checkpoint inhibitor-induced type 1 diabetes mellitus, patterns of disease onset and long-term clinical outcome.

Type 1 diabetes mellitus (T1DM) is a rare, but serious immune-related adverse event (irAE) of immune checkpoint inhibitors (ICIs). Our goal was to characterize treatment outcomes associated with ICI-induced T1DM through analysis of clinical, immunological and proteomic data. This was a single-center case series of patients with solid tumors who received ICIs and subsequently had a new diagnosis of T1DM. ICD codes and C-peptide levels were used to identify patients for chart review to confirm ICI-induced T1DM. Baseline blood specimens were studied for proteomic and immunophenotypic changes. Between 2011 and 2023, 18 of 3744 patients treated at Huntsman Cancer Institute with ICIs were confirmed to have ICI-induced T1DM (0.48%). Eleven of the 18 patients received anti-PD1 monotherapy, 4 received anti-PD1 plus chemotherapy or targeted therapy, and 3 received ipilimumab plus nivolumab. The mean time to onset was 218 days (range 22-418 days). Patients had sudden elevated serum glucose within 2-3 weeks prior to diagnosis. Sixteen (89%) presented with diabetic ketoacidosis. Three of 12 patients had positive T1DM-associated autoantibodies. All patients with T1DM became insulin-dependent through follow-up. At median follow-up of 21.9 months (range 8.4-82.4), no patients in the melanoma group had progressed or died from disease. In the melanoma group, best responses were 2 complete response and 2 partial response while on active treatment; none in the adjuvant group had disease recurrence. Proteomic analysis of baseline blood suggested low inflammatory (IL-6, OSMR) markers and high metabolic (GLO1, DXCR) markers in ICI-induced T1DM cohort. Our case series demonstrates rapid onset and irreversibility of ICI-induced T1DM. Melanoma patients with ICI-induced T1DM display excellent clinical response and survival. Limited proteomic data also suggested a unique proteomic profile. Our study helps clinicians to understand the unique clinical presentation and long-term outcomes of this rare irAE for best clinical management.

The Prevalence of Chronic Kidney Disease and Albuminuria in Patients With Type 1 and Type 2 Diabetes Attending a Single Centre.

Background Diabetes is the leading cause of chronic kidney disease worldwide. Diabetic kidney disease is one of the microvascular complications of diabetes and it involves changes in glomerular hemodynamics, interstitial fibrosis, and tubular atrophy. Early detection and management of Diabetic kidney disease (DKD) help to reduce morbidity and mortality. This study aims to assess the prevalence of nephropathy and albuminuria in the diabetic population attending an Irish tertiary care center. Methods Retrospective data collection and analysis of patients diagnosed with Type 1 diabetes mellitus(T1DM) and Type 2 diabetes mellitus (T2DM) through the Development and Integration of Accurate Mathematical Operations in Numerical Data-Processing (DIAMOND) database in a single Irish tertiary care center. An audit tool was used to collect patients' information including gender, age, type of diabetes, serum creatinine, urinary albumin excretion, albumin creatinine ratio (ACR), body mass index, and last available glycated hemoglobin (HbA1c). Results Out of 7394 subjects with T2DM, 3139 (42%) were identified with chronic kidney disease (CKD).There were 1866 subjects with positive ACR out of 3139 subjects with CKD in the T2DM cohort.This shows that 25% of subjects have diabetic kidney disease and 17% have CKD of undetermined etiology.In the T1DM cohort with 1166 subjects, 209 (18%) were identified with CKD.Out of these 209 subjects with CKD, 164 (14%) were ACR-positive.The prevalence of CKD and albuminuria were related to age in both T1DM and T2DM populations. Albuminuria showed a linear relationship with age in subjects with no known CKD, which shows that age causally relates to albuminuria independent of type and duration of diabetes. Conclusion CKD is more prevalent in patients with T2DM as compared to T1DM, whereas the prevalence of albuminuria is higher in the T1DM population.

Left Ventricular Structure, Tissue Composition, and Aortic Distensibility in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Intervention and Complications

Alterations in myocardial structure, function, tissue composition (e.g., fibrosis) may be associated with metabolic syndrome (MetS). This study aimed to determine the relation of MetS and its individual components to markers of cardiovascular disease in patients with type 1 Diabetes Mellitus (T1DM). A total of 978 subjects of the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications T1DM cohort (age: 49 ± 7 years, 47% female, DM duration 28 ± 5 years) underwent cardiovascular magnetic resonance. In a subset of 200 patients, myocardial tissue composition was measured with cardiovascular magnetic resonance T1 mapping after contrast administration. MetS was defined as T1DM plus 2 other abnormalities based on the American Heart Association/National Cholesterol Education Program criteria. MetS was present in 34.1% of subjects. After adjustment for age, height, scanner, study cohort, gender, smoking, mean glycated hemoglobin levels, history of macroalbuminuria and end-stage renal disease, left ventricle mass was greater by 12.3 g, end-diastolic volume was higher by 5.4 ml, and mass to end-diastolic volume ratio was higher by 5% in patients with MetS versus those without MetS (p <0.001 for all). Myocardial T1 times were lower by 29 ms in patients with MetS than those without (p <0.001). Elevated waist circumference showed the strongest associations with left ventricle mass (+10.1 g), end-diastolic volume (+6.7 ml), and lower myocardial T1 times (+31 ms) in patients with MetS compared with those without (p <0.01). In conclusion, in a large cohort of patients with T1DM, 34.1% of subjects met MetS criteria. MetS was associated with adverse myocardial structural remodeling and change in myocardial tissue composition.

Ramadan fasting in people with type 1 diabetes during COVID-19 pandemic: The DaR Global survey

ObjectivesThe DaR Global survey was conducted to determine the impact of the COVID-19 pandemic on the intentions to fast and the outcomes of fasting in <18 years versus ≥18 years age groups with type 1 diabetes mellitus (T1DM). MethodsMuslim people with T1DM were surveyed in 13 countries between June and August 2020, shortly after the end of Ramadan (23rd April–23rd May 2020) using a simple questionnaire. Results71.1% of muslims with T1DM fasted during Ramadan. Concerns about COVID-19 were higher in individuals ≥18 years (p = 0.002). The number of participants who decided not to fast plus those who received Ramadan-focused education were significantly higher in the ≥18-year group (p < 0.05). Hypoglycemia (60.7%) as well as hyperglycemia (44.8%) was major complications of fasting during Ramadan in both groups irrespective of age. ConclusionCOVID-19 pandemic had minor impact on the decision to fast Ramadan in T1DM cohort. This was higher in the age group of ≥18 years compared to those <18 years group. Only regional differences were noted for fasting attitude and behavior among T1DM groups. This survey highlights the need for Ramadan focused diabetes education to improve glucose control and prevent complications during fasting.

The association between Type 1 diabetes mellitus and periodontal diseases

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease affecting oral health. Evidence shows possible association between T1DM and periodontal diseases (PDs). We conducted a nationwide population-based study in Taiwan, with a 14-year follow-up to investigate the risk of PDs in T1DM patients. We used data from the National Health Insurance Research Database in Taiwan. The T1DM cohort was identified with newly diagnosed T1DM from 1998 to 2011. The non-T1DM cohort was frequency matched with the T1DM cohort. Participants comprised 4248 patients in the T1DM cohort and 16992 persons in the non-T1DM cohort. The T1DM patients showed an increased risk of PDs compared to non-T1DM individuals [adjusted hazard ratio (aHR)=1.45]. T1DM patients who visited the emergency room more than twice per year had a higher aHR of 13.0 for developing PDs. The aHR for PDs was 13.2 in the T1DM patients who had been hospitalized more than twice per year. T1DM patients are at higher risk of developing PDs than non-T1DM individuals. Our results further showed that the number of T1DM interventions; that is, annual emergency visits and hospitalizations were associated with increased the risk of developing PDs.

Undertreatment of hypertension and hypercholesterolaemia in children and adolescents with type 1 diabetes: long-term follow-up on time trends in the occurrence of cardiovascular disease, risk factors and medications use.

The aims of the present study were, firstly, to evaluate long-term trends in the occurrence and treatment of cardiovascular disease (CVD) risk factors and the occurrence of CVD events in children with type 1 diabetes mellitus (T1DM) and, secondly, to assess the determinants of undertreatment of CVD risk factors. A retrospective cohort study was conducted in 3728 children (<19years of age) with T1DM and up to 5 age- and gender-matched diabetes-free children (reference cohort) (n=18 513) using data from the Clinical Practice Research Datalink (CPRD). Compared with diabetes-free subjects, children with T1DM had significantly higher annual prevalence rates of CVD risk factors and cardiovascular (CV) medication use 20years after the onset of diabetes (index date): hypertension: 35.2% vs. 11.4%, P < 0.001; hypercholesterolaemia: 66.7% vs. 7.14%, P<0.001; and CV medication use: 37.0% vs. 3.6%, P < 0.001. The significant differences between prevalence rates in the two cohorts started from 1year before the index date. Furthermore, 50% of the children in the T1DM cohort with hypertension and 53% with hypercholesterolaemia remained untreated with CV drugs for a period of 2-5years during the 20-year follow-up. Age was the only determinant associated with undertreated hypertension in the T1DM cohort. Children with T1DM had substantially higher prevalence rates of hypertension and hypercholesterolaemia from 1year before up to 20years after the onset of diabetes compared with nondiabetics. There is a substantial undertreatment of CVD risk factors with CV drugs. In children with T1DM, screening for CVD risk factors and adequate treatment are of the utmost importance to prevent CVD later in life.

Asthma related medication use and exacerbations in children and adolescents with type 1 diabetes.

To investigate the use of asthma medication and occurrence of asthma exacerbations up to 5 years before and after the onset of type 1 diabetes mellitus (T1DM) in children and adolescents. Children and adolescents younger than 19 years with at least 2 insulin prescriptions between 1999 and 2009 classified as T1DM cohort (n = 915) and a 4 times larger reference cohort (n = 3,590) with the same age and gender were identified from the Dutch PHARMO Record Linkage System. The date of first insulin dispensing was selected as the index date. The 5-year prevalence rate of asthma medication use in the T1DM cohort (23.2%) was significantly higher than the reference cohort (18.3%) after the onset of diabetes. No statistically significant difference between the two cohorts was observed in the use of specific types of asthma medication except for short acting muscarinic antagonists that were significantly more used in the T1DM cohort (5.5%) compared with the reference cohort (0.62%) after the onset of diabetes. The incidence rate of asthma medication use declined over time with a peak in the T1DM cohort the 1st year after the onset of diabetes. Furthermore, 1 year after the index date there was a peak in incidence rate of asthma exacerbations in both T1DM (7.8 per 1,000 person year) and reference (6.8 per 1,000 person year) cohorts. T1DM is associated with statistically significantly higher asthma medication use after the onset of T1DM, especially in the 1st year after the onset of diabetes. Pediatr Pulmonol. 2016;51:1113-1121. © 2016 Wiley Periodicals, Inc.

Childhood type 1 diabetes may increase the risk of atopic dermatitis.

Epidemiological investigations have examined the association between type 1 diabetes mellitus (T1DM) and atopic disease, but have obtained conflicting results. To analyse the association between T1DM and atopic dermatitis (AD) in a population-based, retrospective cohort study that investigated the hypothesis that childhood T1DM is a risk factor for subsequent AD. From claims data of the National Health Insurance programme of Taiwan, we identified 3386 patients with T1DM newly diagnosed from 1998 to 2011 and 12725 randomly selected controls without T1DM. These were frequency matched by age, sex and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the AD risk. We used Cox proportional hazards regression models to analyse the risk of AD. The overall incidence rate of AD was 1·40-fold (significantly) higher in the T1DM cohort than in the non-T1DM cohort (3·31 vs. 2·35 per 1000 person years). After adjustment for potential risk factors, the overall risk of AD remained higher in the T1DM cohort [adjusted hazard ratio (HR) 1·76, 95% confidence interval (CI) 1·29-2·39] than in those without T1DM. Compared with the non-T1DM cohort, the patients with T1DM with more emergency room visits (adjusted HR 30·1, 95% CI 18·7-48·5) or hospitalizations (adjusted HR 70·3, 95% CI 45·6-114·5) had a higher risk of subsequent AD. This nationwide, retrospective cohort study demonstrates that childhood T1DM may increase the risk of AD.

Type 1 Diabetes and Increased Risk of Subsequent Asthma: A Nationwide Population-Based Cohort Study.

The association between type 1 diabetes mellitus (T1DM) and asthma remains controversial and has led to new interest in these 2 disorders. The purpose of this study was to examine the associations among young people with T1DM and asthma and offer a clinical demonstration of the balance between Th1 and Th2 responses.We conducted a retrospective cohort study by using data from the National Health Insurance (NHI) system of Taiwan. The cohort consisted of 3545 T1DM cases and 14,180 controls established during the 1998 to 2011 period. Of the 3545 T1DM patients, 55.1% were girls and 26.5% were in the age group <8 years.The overall incidence of asthma was 47% higher in the T1DM cohort than in the control cohort (6.49 vs 4.42 per 1000 person-y), with an adjusted hazard ratio (HR) of 1.34 (95% confidence interval [CI] = 1.11–1.62). Moreover, T1DM patients who visited the emergency room (ER) more than twice for diabetes had a higher adjusted HR of 17.4 (95% CI = 12.9–23.6) of developing asthma. The adjusted HR of asthma was 38.6 (95% CI = 28.5–52.2) in T1DM patients who had been hospitalized more than twice for diabetes.We observed a significantly higher incidence of asthma in young patients with T1DM than in the general population. Among young people of T1DM with more ER visits or frequent hospitalization because of diabetes mellitus were associated with risk of asthma, may indicate that poor glycemic control significantly contributes to asthma risk.

Can exposure to environmental chemicals increase the risk of diabetes type 1 development?

Type 1 diabetes mellitus (T1DM) is an autoimmune disease, where destruction of beta-cells causes insulin deficiency. The incidence of T1DM has increased in the last decades and cannot entirely be explained by genetic predisposition. Several environmental factors are suggested to promote T1DM, like early childhood enteroviral infections and nutritional factors, but the evidence is inconclusive. Prenatal and early life exposure to environmental pollutants like phthalates, bisphenol A, perfluorinated compounds, PCBs, dioxins, toxicants, and air pollutants can have negative effects on the developing immune system, resulting in asthma-like symptoms and increased susceptibility to childhood infections. In this review the associations between environmental chemical exposure and T1DM development is summarized. Although information on environmental chemicals as possible triggers for T1DM is sparse, we conclude that it is plausible that environmental chemicals can contribute to T1DM development via impaired pancreatic beta-cell and immune-cell functions and immunomodulation. Several environmental factors and chemicals could act together to trigger T1DM development in genetically susceptible individuals, possibly via hormonal or epigenetic alterations. Further observational T1DM cohort studies and animal exposure experiments are encouraged.

Increased risk of tuberculosis in patients with type 1 diabetes mellitus: results from a population-based cohort study in Taiwan.

The studies on the risk of tuberculosis (TB) in patients with type 1 diabetes mellitus (T1DM) alone are limited. We examined this relationship using a population-based retrospective cohort study. From claims data of the National Health Insurance system of Taiwan, we identified 5195 patients with T1DM newly diagnosed from 2002 to 2011 and 20,780 randomly selected controls without T1DM, frequency matched by age, sex, and year of diagnosis. Both cohorts were followed up until the end of 2011 to evaluate the risk of TB. The overall incidence of TB was 4.07-fold higher in the T1DM cohort than in the control cohort (1.18 vs 0.29 per 1000 person-years, P < 0.001). Compared with the controls, the Cox model estimated adjusted hazard ratios (HRs) of TB in patients with T1DM were greater in men than in women (4.62 vs 3.59) and in adults than in children (4.06 vs 3.37), but not significant. The adjusted HR was much greater for those with comorbidities than those without comorbidities (14.6 vs 1.62, P < 0.001). Compared with the controls, the patients with T1DM were also more likely to develop TB with multiple emergency room visits (adjusted HR: 116.1, 95% confidence interval [CI] = 43.8–307.4) or hospitalizations (adjusted HR: 86.5, 95% CI = 33.7–222.4). Patients with T1DM are at elevated risks of developing TB with much higher HRs for those with comorbidities, within the first year of diagnosis, and with frequent emergency cares or hospitalizations.

Prevalence and natural history of histologically proven chronic liver disease in a longitudinal cohort of patients with type 1 diabetes

Although a higher prevalence of raised liver enzymes and altered echotexture on ultrasound have been reported in patients with type 1 diabetes mellitus (T1DM), the histological spectrum and natural history of chronic liver disease (CLD) in T1DM is unknown. We investigated the prevalence and outcome of histologically proven CLD in a longitudinal cohort of patients with T1DM. We identified patients who have had liver biopsy from a computerized database (DIAMOND; Hicom Technology, Brookwood, UK) containing longitudinal data for over 95% of type 1 diabetes patients from an overall catchment population of 700,000 people. Gender-matched patients with oral hypoglycemic-treated (T2OH) and insulin-treated type 2 diabetes (T2IN) who had liver biopsy formed two comparative cohorts. We collated clinical and histological data, as well as long-term outcomes of all three groups, and compared T1DM cirrhosis incidence to UK general population data. Of 4,644 patients with T1DM, 57 (1.2%) underwent liver biopsy. Of these, 53.1% of patients had steatosis, 20.4% had nonalcoholic steatohepatitis, and 73.5% had fibrosis on index liver biopsy. Cirrhosis was diagnosed in 14 patients (24.6%) during follow-up. T1DM with age under 55 years had an odds ratio of 1.875 (95% confidence interval: 0.936-3.757) for cirrhosis incidence, compared to the general population. Longitudinal liver-related outcomes were similar comparing the T1DM cohort and respective type 2 diabetes cohorts--when adjusted for important confounders, diabetic cohort type did not predict altered risk of incident cirrhosis or portal hypertension. Type 1 diabetes is associated with a previously unrecognized burden of CLD and its complications.

Direct Medical Costs for Complications Among Children and Adults with Diabetes in the US Commercial Payer Setting

Complications associated with diabetes are a major contributor to the burden of the disease. To better inform decision modelling, there is a need for cost estimates of specific diabetes-related complications, stratified by diabetes type and patient age group. To obtain direct medical costs of managing and treating diabetes-related complications over a 2-year period, for adults and children with type1 diabetes mellitus (T1DM) or type2 diabetes mellitus (T2DM), using data from a large commercially insured US subscriber database. We examined records from a large US multi-payer claims database to identify patients with any diabetes-related complications included in nine pre-specified categories, filed between January 2009 and September 2010, and with pre-index evidence of T1DM or T2DM. Patients were required to have continuous health plan enrolment 12months before and 24months after each index complication. Patients were classified into cohorts based on their diabetes type and age status at the time of the complication. The direct medical cost associated with each complication was calculated for the 12- and 24-month follow-up periods. Mean paid and allowed total costs were calculated and inflation-adjusted to the year 2011. Of the 119,715 patients who met the inclusion criteria, 211 (0.2%) were categorized as children with T1DM, 55 (0.05%) as children with T2DM, 6,227 (5.2%) as adults with T1DM and 113,222 (94.6%) as adults with T2DM. The respective mean cohort ages were 13.5, 14.9, 48.5 and 58years. Proteinuria/albuminuria was the most common complication for T1DM and T2DM child cohorts, with this complication occurring in almost one third of these children. Among the child cohorts, renal disease accounted for the highest mean paid cost for T1DM patients (US$6,053) whereas for T2DM patients, the complication associated with the highest mean paid cost was lactic acidosis (US$25,053). For the adult T1DM cohort, the complications with the highest occurrence and highest mean total paid cost were non-proliferative retinopathy (40.3%) and renal disease (US$28,076), respectively. Similarly, for the adult T2DM cohort, these complications were neuropathy (26.8%) and peritoneal dialysis (US$32,826). With the continuing and increasing interest in child and adult T1DM and T2DM, stakeholders will need relevant and timely information to guide treatment decision making. This cost research may directly inform the economic models that are often developed to better identify, understand and manage key economic considerations that drive the costs of this chronic disease.

Modern-Day Clinical Course of Type 1 Diabetes Mellitus After 30 Years' Duration

Clinical treatment goals of type 1 diabetes mellitus (T1DM) have changed since the Diabetes Control and Complications Trial (DCCT) demonstrated reduced long-term complications with intensive diabetes therapy. There have been few longitudinal studies to describe the clinical course of T1DM in the age of intensive therapy. Our objective was to describe the current-day clinical course of T1DM. An analysis of the cumulative incidence of long-term complications was performed. The DCCT (1983-1993) assigned patients to conventional or intensive therapy. Since 1993, the DCCT has been observational, and intensive therapy was recommended for all patients. The Pittsburgh Epidemiology of Diabetes Complications (EDC) study is an observational study of patients with T1DM from Allegheny County, Pennsylvania. The study population comprised the DCCT T1DM cohort (N = 1441) and a subset of the EDC cohort (n = 161) selected to match DCCT entry criteria. In the DCCT, intensive therapy aimed for a near-normal glycemic level with 3 or more daily insulin injections or an insulin pump. Conventional therapy, with 1 to 2 daily insulin injections, was not designed to achieve specific glycemic targets. Main outcome measures included the incidences of proliferative retinopathy, nephropathy (albumin excretion rate >300 mg/24 h, creatinine level >or=2 mg/dL [to convert to micromoles per liter, multiply by 88.4], or renal replacement), and cardiovascular disease. After 30 years of diabetes, the cumulative incidences of proliferative retinopathy, nephropathy, and cardiovascular disease were 50%, 25%, and 14%, respectively, in the DCCT conventional treatment group, and 47%, 17%, and 14%, respectively, in the EDC cohort. The DCCT intensive therapy group had substantially lower cumulative incidences (21%, 9%, and 9%) and fewer than 1% became blind, required kidney replacement, or had an amputation because of diabetes during that time. The frequencies of serious complications in patients with T1DM, especially when treated intensively, are lower than that reported historically.

IGF-1 and IGF-Binding Proteins and Bone Mass, Geometry, and Strength: Relation to Metabolic Control in Adolescent Girls With Type 1 Diabetes

Children and adolescents with poorly controlled type 1 diabetes mellitus (T1DM) are at risk for decreased bone mass. Growth hormone (GH) and its mediator, IGF-1, promote skeletal growth. Recent observations have suggested that children and adolescents with T1DM are at risk for decreased bone mineral acquisition. We examined the relationships between metabolic control, IGF-1 and its binding proteins (IGFBP-1, -3, -5), and bone mass in T1DM in adolescent girls 12–15 yr of age with T1DM (n = 11) and matched controls (n = 10). Subjects were admitted overnight and given a standardized diet. Periodic blood samples were obtained, and bone measurements were performed. Serum GH, IGFBP-1 and -5, glycosylated hemoglobin (HbA1c), glucose, and urine magnesium levels were higher and IGF-1 values were lower in T1DM compared with controls (p < 0.05). Whole body BMC/bone area (BA), femoral neck areal BMD (aBMD) and bone mineral apparent density (BMAD), and tibia cortical BMC were lower in T1DM (p < 0.05). Poor diabetes control predicted lower IGF-1 (r2 = 0.21) and greater IGFBP-1 (r2 = 0.39), IGFBP-5 (r2 = 0.38), and bone-specific alkaline phosphatase (BALP; r2 = 0.41, p < 0.05). Higher urine magnesium excretion predicted an overall shorter, lighter skeleton, and lower tibia cortical bone size, mineral, and density (r2 = 0.44–0.75, p < 0.05). In the T1DM cohort, earlier age at diagnosis was predictive of lower IGF-1, higher urine magnesium excretion, and lighter, thinner cortical bone (r2 ≥ 0.45, p < 0.01). We conclude that poor metabolic control alters the GH/IGF-1 axis, whereas greater urine magnesium excretion may reflect subtle changes in renal function and/or glucosuria leading to altered bone size and density in adolescent girls with T1DM.

Long-Term Mortality and Incidence of Renal Dialysis and Transplantation in Type 1 Diabetes Mellitus

We investigated long-term mortality and requirement of renal replacement therapy (RRT) in type 1 diabetes mellitus (T1DM) to study risk factors and late complication incidence of T1DM in a prospective cohort study at Lainz Hospital, Vienna, Austria. In 1983-1984, T1DM patients [n = 648; 47% females, 53% males; age, 30 +/- 11 yr; T1DM duration, 15 +/- 9 yr; body mass index, 24 +/- 4 kg/m(2); glycated hemoglobin (HbA1c), 7.6 +/- 1.6%] were stratified into HbA1c quartiles [1st, 5.9 +/- 0.5% (range, 4.2-6.5%); 2nd, 6.9 +/- 0.3% (6.6-7.4%); 3rd, 7.9 +/- 0.3% (7.5-8.4%); and 4th, 9.6 +/- 1.3% (8.5-14.8%)]. Twenty years later, both endpoints (death and RRT) were investigated by record linkage with national registries. At baseline, creatinine clearance, blood pressure, and body mass index were comparable among the HbA1c quartiles, whereas albuminuria was more frequent in the 4th quartile (+15%; P < 0.03). After the 20-yr follow-up, 13.0% of the patients had died [rate, 708 per 100,000 person-years (95% confidence interval, 557-859)], and 5.6% had received RRT [311 per 100,000 person-years (95% confidence interval, 210-412)]. Patients with the highest HbA1c values (4th quartile) had a higher mortality rate and a greater incidence of RRT (P < 0.04). In the Cox proportional hazards analysis, age, male gender, increased HbA1c, albuminuria, and reduced creatinine clearance were predictors of mortality (P < 0.05). Predictors of RRT were albuminuria (P < 0.001), reduced creatinine clearance (P < 0.001), and belonging to the 4th HbA1c quartile (P = 0.06). In Kaplan-Meier analysis, mortality was linearly associated with poor glycemia, whereas RRT incidence appeared to rise at a HbA1c threshold of approximately 8.5%. In the Lainz T1DM cohort, 13.0% mortality and 5.6% RRT were directly associated with and more frequently found in poor glycemia, showing that good glycemic control is essential for the longevity and quality of life in T1DM.