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

Stadler, Marietta; Auinger, Martin; Anderwald, Christian; Kästenbauer, T; Kramar, Reinhard; Feinböck, C; Irsigler, K; Kronenberg, Florian; Prager, Rudolf

doi:10.1210/jc.2006-1058

Cited by 52 publications

(55 citation statements)

References 27 publications

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“…The life expectancy for a patient with type 1 diabetes depends heavily on the development of kidney disease and the concurrent incidence of macrovascular events (1,7,21,22). Our analyses with the self-organizing map confirmed this and provided carefully adjusted estimates for the relative risk of premature death.…”

Section: Discussionsupporting

confidence: 65%

Metabolic Phenotypes, Vascular Complications, and Premature Deaths in a Population of 4,197 Patients With Type 1 Diabetes

et al. 2008

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on behalf of the FinnDiane Study Group* OBJECTIVE-Poor glycemic control, elevated triglycerides, and albuminuria are associated with vascular complications in diabetes. However, few studies have investigated combined associations between metabolic markers, diabetic kidney disease, retinopathy, hypertension, obesity, and mortality. Here, the goal was to reveal previously undetected association patterns between clinical diagnoses and biochemistry in the FinnDiane dataset.RESEARCH DESIGN AND METHODS-At baseline, clinical records, serum, and 24-h urine samples of 2,173 men and 2,024 women with type 1 diabetes were collected. The data were analyzed by the self-organizing map, which is an unsupervised pattern recognition algorithm that produces a two-dimensional layout of the patients based on their multivariate biochemical profiles. At follow-up, the results were compared against allcause mortality during 6.5 years (295 deaths). RESULTS-The highest mortality was associated with advanced kidney disease. Other risk factors included 1) a profile of insulin resistance, abdominal obesity, high cholesterol, triglycerides, and low HDL 2 cholesterol, and 2) high adiponectin and high LDL cholesterol for older patients. The highest population-adjusted risk of death was 10.1-fold (95% CI 7.3-13.1) for men and 10.7-fold (7.9 -13.7) for women. Nonsignificant risk was observed for a profile with good glycemic control and high HDL 2 cholesterol and for a low cholesterol profile with a short diabetes duration.CONCLUSIONS-The self-organizing map analysis enabled detailed risk estimates, described the associations between known risk factors and complications, and uncovered statistical patterns difficult to detect by classical methods. The results also suggest that diabetes per se, without an adverse metabolic phenotype, does not contribute to increased mortality. Diabetes 57:2480-2487, 2008 P atients with type 1 diabetes are susceptible to severe microvascular complications such as proliferative retinopathy and chronic kidney disease, which are often accompanied by cardiovascular disease and premature death (1,2). Currently, the risk assessment and diagnostics rely on the urine albumin excretion, serum creatinine, and lipid profile (3,4). In many cases, however, the biochemical measurements are treated as independent factors without explicit attention to the overall metabolic imbalance behind the complications. Although the risk factors for cardiovascular disease and diabetes complications have been verified statistically in large clinical studies (5-7), the overall picture on the mutual relationships and their relevance for risk assessment remains fragmented.The metabolic syndrome (8) is one attempt to describe the co-occurrence of vascular complications and insulin resistance, but so far its applicability to type 1 diabetes and its exact definition remain controversial (9,10). Moreover, gradually developing conditions, such as cardiovascular disease, do not present a physiologically clear border between health and disease, so quanti...

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Section: Discussionsupporting

confidence: 65%

Metabolic Phenotypes, Vascular Complications, and Premature Deaths in a Population of 4,197 Patients With Type 1 Diabetes

et al. 2008

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“…2) [27]. Although it is well established that good metabolic control reduces the risk of macro-and microvascular endpoints and mortality [28,29], MS is an independent risk factor for the development of comorbidities: The participants with double diabetes and HbA1c below 7% (53mmol/mol) had a significantly higher prevalence of macrovascular complications than well controlled persons with T1DM without MS 7% (Fig. 2).…”

Section: Discussionmentioning

confidence: 97%

Prevalence and comorbidities of double diabetes

Merger

Kerner²,

Stadler

et al. 2016

Diabetes Research and Clinical Practice

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Statement of all funding sources: BMBF Kompetenznetz Diabetes mellitus (FKZ 01GI1106); DZD; EFSD, BMBF Kompetenznetz Adipositas (FKZ01GI1130)Conflicts of interest The authors have no conflict of interest to declare.Key words: double diabetes, T1DM, diabetes mellitus type 1, insulin resistance, diabetic nephropathy, macroangiopathy, microangiopathy, coronary heart disease, LADA Novelty statement: The outlined paper analyzes 392 diabetes centers with 31119 patients with autoimmune diabetes for the prevalence and comorbidities of double diabetes. We could show for the first time that insulin requirement or insulin resistance is an independent risk factor for patients with type 1 diabetes and that even in well controlled diabetes an additional metabolic syndrome is a major risk factor for developing macrovascular as well as microvascular complications. Aim of this cross sectional study is to better estimate the prevalence of MS in T1DM, and to assess its association with comorbidities. AbbreviationsMethods: Data of 31119 persons with autoimmune diabetes mellitus were analyzed for signs of MS and presence of late complications. Double diabetes was defined as T1DM coexisting with MS (obesity, hypertension, dyslipidemia). Multiple linear or logistic regression analyses were performed to identify associations between double diabetes and late complications.Results: 25.5% (n=7926) of persons with T1DM presented additionally the MS. Persons with double diabetes showed significantly more macrovascular comorbidities (coronary heart disease 8.0 versus 3.0% w/o MS, stroke 3.6 versus 1.6%, diabetic foot syndrome 5.5% versus 2.1%).Also microvascular diseases were increased in people with double diabetes (retinopathy 32.4% versus 21.7%, nephropathy 28.3% versus 17.8%). Both macrovascular and microvascular comorbidities were increased independent of glucose control, even if patients with good metabolic control (HbA1c <7.0%, 53mmol/mol) showed significantly less macrovascular (coronary heart disease 2.3% versus 1.8%, p<0.0001) and microvascular problems (retinopathy 8.7% versus 6.6%, p<0.0001).Conclusions: Double diabetes seems to be an independent and important risk factor for persons with T1DM in developing macrovascular and microvascular comorbidities. Therefore, patients should be identified and development of MS should be avoided. Longtermstudies are needed to observe the effect of insulin resistance on patients with autoimmune diabetes.

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“…Outliers (> three standard deviations) were excluded casewise (n=6). Predictors of IGI(60 min) at a significance level of p<0.1 remained in the model, as described in detail elsewhere [16,19]. The final model was verified by backward stepwise linear multiple regression analysis.…”

Section: Statisticsmentioning

confidence: 99%

Beta cell (dys)function in non-diabetic offspring of diabetic patients

et al. 2009

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Aims/hypothesis The first-degree offspring of patients with type 2 diabetes are prone to develop type 2 diabetes, and have both insulin resistance and beta cell impairment. However, it is still unclear whether both pathophysiological features are inseparably combined and which is the outstanding determinant in the offspring. Methods Glucose metabolism, insulin sensitivity (calculated as M value divided by insulin [M/I]) and beta cell function were studied in the offspring of individuals with type 2 diabetes (n=187; 57% females; age 43.8±8.1 years; BMI 26.8±4.5 kg/m 2 ) and in individuals without a family history of type 2 diabetes (controls, n=519, 55% females; age 43.4± 8.2 years; BMI 26.4± 3.7 kg/m 2 , no significant differences between the groups for any characteristic) by performance of 75 g OGTT and 2 h hyperinsulinaemic (40 mU min −1 m −2 )-isoglycaemic clamp tests. Beta cell function was evaluated by calculating insulinogenic index (IGI) from C-peptide AUC:glucose AUC ratios from the first hour of OGTT (IGI[60 min]) and from the total OGTT (IGI[120 min]). Results During the OGTT, the offspring of individuals with type 2 diabetes showed 4-14% higher plasma glucose from 30 to 120 min (p<0.05) and 20-29% higher serum insulin from 90 to 120 min, but decreased IGI(60 min) and IGI (120 min) (p<0.05). M/I was 11% lower in the offspring of affected individuals than in controls (p<0.01). To study the offspring of patients with type 2 diabetes with insulin sensitivity similar to that of the control group, the offspring of affected patients were divided into M/I quartiles. Those in the third M/I quartile showed M/I values and major anthropometric characteristics similar to those of the controls, but insulin AUC and C-peptide AUC values were lower in the first hour and the total OGTT (p<0.05). The third M/I quartile had lower IGI values at 60 min and 120 min: 11% and 14% lower, respectively (p<0.02). Conclusions/interpretation The first-degree offspring of type 2 diabetic patients show insulin resistance and beta cell dysfunction in response to oral glucose challenge. Beta cell impairment exists in insulin-sensitive offspring of patients with type 2 diabetes, suggesting beta cell dysfunction to be a major defect determining diabetes development in diabetic offspring.

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

Abstract: 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.

Cited by 52 publications

References 27 publications

Metabolic Phenotypes, Vascular Complications, and Premature Deaths in a Population of 4,197 Patients With Type 1 Diabetes

Metabolic Phenotypes, Vascular Complications, and Premature Deaths in a Population of 4,197 Patients With Type 1 Diabetes

Prevalence and comorbidities of double diabetes

Beta cell (dys)function in non-diabetic offspring of diabetic patients

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