1. |
- Butwicka, Agnieszka, et al.
(författare)
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Risks of psychiatric disorders and suicide attempts in children and adolescents with type 1 diabetes : a population-based cohort study
- 2015
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Ingår i: Diabetes Care. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0149-5992 .- 1935-5548.
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess the risk of psychiatric disorders and suicide attempts in children with type 1 diabetes and their healthy siblings. Research Design and Methods: We performed a population-based case cohort study of individuals born in Sweden between 1973 and 2009. Children with type 1 diabetes (n=17,122) and their healthy siblings (n=18,847) were identified and followed until their 18th birthday. Their risk of psychiatric disorders was compared with matched controls. Results: The risk of psychiatric morbidity in children with type 1 diabetes compared to the general population was tripled within 6 months after the onset of diabetes (hazard ratio, HR 3.0, 95% confidence interval, CI 2.7-3.4) and doubled within the total observation period (HR 2.1, CI 2.0-2.2). An increased risk was noted in suicide attempts (HR 1.7, CI 1.4-2.0) and in most categories of psychiatric disorders. The risk of psychiatric disorders in probands declined from HR 2.7 (CI 2.2-3.3) for those in the cohort born 1973-1986 to 1.9 (CI 1.8-2.0) in those born 1997-2009. The risk for any psychiatric disorders among siblings of patients with type 1 diabetes was estimated to be HR 1.1 (CI 1.0-1.1) and there was no increased risk in any of the specific category of disorders. Conclusions: Children with type 1 diabetes are at high risk of psychiatric disorders, which seems to be a consequence of the disease rather than due to a common familial etiology. The results support recommendations on comprehensive mental health surveillance in children with type 1 diabetes, especially in recently diagnosed children.
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2. |
- Khashan, Ali S, et al.
(författare)
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Gestational age and birth weight and the risk of childhood type 1 diabetes : a population-based cohort and sibling design study
- 2015
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Ingår i: Diabetes Care. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0149-5992 .- 1935-5548.
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We investigated the effects of gestational age, birthweight, small for gestational age (SGA) and large for gestational age (LGA) on childhood type 1 diabetes. Methods: We conducted a population-based cohort study of all singleton live births in Sweden between 1973-2009 and a sibling-control study. Perinatal data were extracted from the Swedish Medical Birth Register. Children with type 1 diabetes diagnosis were identified from the Swedish National Patient Register. Log-linear Poisson regression and conditional logistic regression were used for data analysis. Results: The study cohort consisted of 3,624,675 singleton live births (42,411,054 person-years). There were 13,944 type 1 diabetes cases during the study period. The sibling-control study consisted of 11,403 children with type 1 diabetes and 17,920 siblings. Gestational age between 33-36 weeks (RR=1.18; [95%CIs: 1.09, 1.28) and 37-38 weeks (RR=1.12; [95%CIs: 1.07, 1.17]) was associated with type 1 diabetes in the cohort study and remained significant in the sibling-control study. SGA (RR=0.83; [95%CIs: 0.75, 0.93]) and LGA (RR=1.14; [95%CIs: 1.04, 1.24]) were associated with type 1 diabetes in the cohort study. The SGA association remained unchanged in the sibling study while the LGA association disappeared. Very low birthweight was associated with a reduced risk of type 1 diabetes. Conclusions: The findings suggest a small association between gestational age and type 1 diabetes that is not likely due to familial confounding factors. Gestational age and type 1 diabetes may be related to insulin resistance due to early life growth restriction or altered gut microbiota in preterm babies.
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3. |
- Abdul-Ghani, Muhammad A., et al.
(författare)
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Fasting Versus Postload Plasma Glucose Concentration and the Risk for Future Type 2 Diabetes Results from the Botnia Study
- 2009
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 32:2, s. 281-286
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - The purpose of this study was to assess the efficacy of the postload plasma glucose concentration in predicting future risk of type 2 diabetes, compared with prediction models based oil measurement. of the fasting plasma glucose (FPG) concentration. RESEARCH DESIGN AND METHODS - A total of 2,442 subjects from the Botnia Study, who were free Of type 2 diabetes at baseline, received an oral glucose tolerance test (OGTT) at baseline and after 7-8 years of follow-up. Future risk for type 2 diabetes was assessed with area under the receiver-operating characteristic curve for prediction models based up measurement of the FPG concentration 1) with or without a 1-h plasma glucose concentration during the OGTT and 2) with or without the metabolic syndrome. RESULTS - Prediction models based on measurement of the FPG concentration were weak predictors for the risk of Future type 2 diabetes. Addition of a 1-h plasma glucose Concentration markedly enhanced prediction Of the risk of future type 2 diabetes. A cut point of 155 mg/dl for the 1-h plasma glucose concentration during the OGTT and presence Of the metabolic syndrome were used to Stratify subjects in each glucose tolerance group into low, intermediate, and high risk for future type 2 diabetes. CONCLUSIONS - The plasma glucose concentration at 1 h during the OGTT is a Strong predictor of future risk for type 2 diabetes and adds to the prediction power of models based on measurements made during the fasting state. A plasma glucose cut point of 155 mg/dl Plus the Adult Treatment Panel III criteria for the metabolic syndrome can be used to stratify nondiabetic subjects into low-, intermediate-, and high-risk groups.
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4. |
- Abdul-Ghani, Muhammad A., et al.
(författare)
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Minimal Contribution of Fasting Hyperglycemia to the Incidence of Type 2 Diabetes in Subjects With Normal 2-h Plasma Glucose
- 2010
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 33:3, s. 557-561
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To assess the relative contribution of increased fasting and postload plasma glucose concentrations to the incidence of type 2 diabetes in subjects with a normal 2-h plasma glucose concentration. RESEARCH DESIGN AND METHODS - A total of 3,450 subjects with 2-h plasma glucose concentration < 140 mg/dl at baseline were followed up in the San Antonio Heart Study (SAHS) and the Botnia Study for 7-8 years. The incidence of type 2 diabetes at follow-up was related to the fasting, 1-h, and 2-h plasma glucose concentrations. RESULTS - in subjects with 2-h plasma glucose < 140 mg/dl, the incidence of type 2 diabetes increased with increasing fasting plasma glucose (FPG) and 1-h and 2-h plasma glucose concentrations. In a multivariate logistic analysis, after adjustment for all diabetes risk factors, the FPG concentration was a Strong predictor Of type 2 diabetes in both the SAHS and the Botnia Study (P < 0.0001). However, when the 1-h plasma glucose, but not 2-h plasma glucose, concentration was added to the model, FPG concentration was no longer a significant predictor of type 2 diabetes in both Studies (NS). When subjects were matched for the level of 1-h plasma glucose concentration, the incidence Of type 2 diabetes markedly increased with the increase in 1-h plasma glucose, but the increase in FPG was not associated with a significant increase in the incidence of type 2 diabetes. CONCLUSIONS - An increase in postload glycemia in the normal range is associated with an increase in the incidence of type 2 diabetes. After controlling for 1-h plasma glucose concentration, the increase in FPG concentration is not associated with an increase in the incidence of type 2 diabetes.
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5. |
- Abdul-Ghani, Muhammad A., et al.
(författare)
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Two-Step Approach for the Prediction of Future Type 2 Diabetes Risk
- 2011
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 34:9, s. 2108-2112
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-To develop a model for the prediction of type 2 diabetes mellitus (T2DM) risk on the basis of a multivariate logistic model and 1-h plasma glucose concentration (1-h PG). RESEARCH DESIGN AND METHODS-The model was developed in a cohort of 1,562 non-diabetic subjects from the San Antonio Heart Study (SAHS) and validated in 2,395 nondiabetic subjects in the Botnia Study. A risk score on the basis of anthropometric parameters, plasma glucose and lipid profile, and blood pressure was computed for each subject. Subjects with a risk score above a certain cut point were considered to represent high-risk individuals, and their 1-h PG concentration during the oral glucose tolerance test was used to further refine their future T2DM risk. RESULTS-We used the San Antonio Diabetes Prediction Model (SADPM) to generate the initial risk score. A risk-score value of 0.065 was found to be an optimal cut point for initial screening and selection of high-risk individuals. A 1-h PG concentration >140 mg/dL in high-risk individuals (whose risk score was >0.065) was the optimal cut point for identification of subjects at increased risk. The two cut points had 77.8, 77.4, and 44.8% (for the SAHS) and 75.8, 71.6, and 11.9% (for the Botnia Study) sensitivity, specificity, and positive predictive value, respectively, in the SAHS and Botnia Study. CONCLUSIONS-A two-step model, based on the combination of the SADPM and 1-h PG, is a useful tool for the identification of high-risk Mexican-American and Caucasian individuals. Diabetes Care 34:2108-2112, 2011
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6. |
- Aburawi, Elhadi, et al.
(författare)
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Acute respiratory viral infections aggravate arterial endothelial dysfunction in children with type 1 diabetes.
- 2004
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 27:11, s. 2733-2735
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Tidskriftsartikel (refereegranskat)abstract
- Despite improvements in therapy for children with type 1 diabetes, the prevalence of cardiovascular morbidity in adulthood due to accelerated atherosclerosis remains significant (1). Similar to other cardiovascular risk factors, the diabetic state facilitates arterial endothelial injury, a primary event in the pathogenesis of atherosclerosis (2). Although several pediatric studies have reported an association of diabetes with arterial endothelial dysfunction (3,4), pathogenic animal studies have suggested that even though this disease predisposes to endothelial dysfunction and atherosclerosis, it might not be sufficient to cause them (5). Notably, type 1 diabetes increases the propensity for both chronic and acute infections in part by weakening the immune mechanisms (6). The risk is particularly increased for respiratory tract infections, but other infections have also been associated with diabetes (7). Furthermore, diabetic patients are at greater risk for infection-related mortality (8), and the excess risk appears to be linked to cardiovascular diseases (9). In the present study, we investigated whether viral respiratory tract infections in children with type 1 diabetes might impose an additional burden on the arterial endothelial function.
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7. |
- Agardh, Carl-David, et al.
(författare)
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Improvement of the plasma lipoprotein pattern after institution of insulin treatment in diabetes mellitus
- 1982
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 5:3, s. 322-325
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Tidskriftsartikel (refereegranskat)abstract
- Plasma lipids and lipoproteins were studied in 26 nonobese diabetic patients, either newly diagnosed or unsatisfactorily controlled by oral antidiabetic treatment. Measurements were performed before and 3-4 mo after the institution of insulin treatment. In a subgroup of seven patients, the activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in postheparin plasma and the elimination rate of exogenous triglyceride were also monitored. After beginning insulin treatment, diabetic control was improved as demonstrated by decreasing levels of HbA1. Mean plasma cholesterol and triglyceride levels decreased by about 10% (P less than 0.01) and 40% (P less than 0.05), respectively. The decrease in plasma cholesterol was largely accounted for by a fall in LDL cholesterol levels (-8%, P less than 0.05), while plasma HDL cholesterol concentrations increased by about 12% (P less than 0.01). The elimination rate of exogenous triglycerides increased significantly. There was a suggestive, but not significant, increase in LPL activity while the HL activity remained unchanged. It is concluded that the improved diabetic control after institution of insulin treatment results in a significant improvement of the plasma lipoprotein profile. Since the improvement of the lipoprotein pattern is not strictly correlated to the amelioration of indices reflecting glucose transport, we suggest that the plasma lipoprotein pattern may provide an additional tool for monitoring the degree of control in diabetes mellitus.
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8. |
- Agardh, Carl-David, et al.
(författare)
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Urinary N-acetyl-beta-D-glucosaminidase activity does not predict development of diabetic nephropathy
- 1987
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 10:5, s. 604-606
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Tidskriftsartikel (refereegranskat)abstract
- Urinary activity of N-acetyl-beta-D-glucosaminidase (NAG) has been suggested as a marker for diabetic nephropathy. In this study, urinary activity of NAG was measured with an interval of 5 yr in 36 insulin-dependent diabetic subjects to evaluate its predictive value for development of diabetic nephropathy. During the observation period, 9 patients developed detectable signs of diabetic nephropathy. In these patients, urinary albumin concentration had increased to 503 +/- 185 mg/L, compared to 16 +/- 1 mg/L in patients without nephropathy (P less than .01; means +/- SE), and the fractional albumin excretion rate was 0.21 +/- 0.07 X 10(-3), compared to 0.01 +/- 0.00 X 10(-3) (P less than .01). However, the activity of urinary NAG was not different in these patients compared with the patients without nephropathy (0.69 +/- 0.15 and 0.61 +/- 0.09 U/mmol creatinine, respectively). Furthermore, no increase in the activity of urinary NAG was seen during the observation period in either group. We concluded that the urinary activity of NAG is not related to the development of microalbuminuria and therefore cannot be used as a predictor for the development of diabetic nephropathy.
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9. |
- Agardh, Elisabet, et al.
(författare)
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Adopting 3-Year Screening Intervals for Sight-Threatening Retinal Vascular Lesions in Type 2 Diabetic Subjects Without Retinopathy
- 2011
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 34:6, s. 1318-1319
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-To report the incidence of sight-threatening vascular lesions in type 2 diabetic subjects without retinopathy after adopting a 3-year interval screening program. RESEARCH DESIGN AND METHODS-In all, 1,691 type 2 diabetic subjects with no detectable retinopathy in two 50 degrees red-free fundus photographs were scheduled for follow-up with photography 3 years later. Age at diabetes diagnosis was 60 +/- 12 years, and known duration of diabetes was 6 +/- 6 years. Treatment consisted of diet only (26%), oral agents (54%), and oral agents and/or insulin (20%). Glycated hemoglobin A(1c) was 6.4 +/- 1.5%. RESULTS-Of the 1,322 subjects available for follow-up, 73% were still without retinopathy after 3 years, and 28% had developed mild or moderate retinopathy, but none developed severe nonproliferative or proliferative retinopathy. Macular edema requiring laser coagulation occurred in only one eye. CONCLUSIONS-Three-year retinal screening intervals can be recommended in subjects with mild type 2 diabetes and no retinopathy.
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10. |
- Agardh, Emilie E, et al.
(författare)
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Explanations of socioeconomic differences in excess risk of type 2 diabetes in Swedish men and women.
- 2004
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 27:3, s. 716-21
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated to what extent socioeconomic differences in type 2 diabetes risk could be explained by established risk factors (obesity, physical inactivity, smoking, and heredity) and psychosocial factors (low decision latitude at work and low sense of coherence). RESEARCH DESIGN AND METHODS: This cross-sectional study comprised 3,128 healthy Swedish men and 4,821 women, aged 35-56 years, living in the Stockholm area. An oral glucose tolerance test identified 55 men and 52 women with type 2 diabetes. The relative contribution of established and psychosocial factors to socioeconomic differences in diabetes risk was assessed by comparing analyses with adjustment for different sets of these factors. RESULTS: The relative risks (RRs) for type 2 diabetes in middle and low socioeconomic groups in men were 2.4 (95% CI 1.0-5.3) and 2.9 (1.5-5.7), respectively, and in women 3.2 (1.5-6.6) and 2.7 (1.3-5.9), respectively. In men, the RRs decreased to 1.9 (0.8-4.4) and 2.1 (1.0-4.2) after adjustment for established risk factors; no further change was found when psychosocial factors were included. In women, the RRs changed to 2.4 (1.1-5.2) and 1.6 (0.7-3.8) by including established risk factors and to 2.3 (1.0-5.1) and 1.9 (0.8-4.3) by inclusion of psychosocial factors. After adjustment for both established and psychosocial factors, the RRs were 1.4 (0.6-3.6) and 1.0 (0.4-2.5), respectively. CONCLUSIONS: In men, the excess risk of type 2 diabetes was partly explained by established risk factors (36-42%), whereas psychosocial factors had no effect. In women, most of the socioeconomic differences in type 2 diabetes were explained by simultaneous adjustment for established risk factors and psychosocial factors (81-100%).
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11. |
- Agardh, Emilie E, et al.
(författare)
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Work stress and low sense of coherence is associated with type 2 diabetes in middle-aged Swedish women.
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:3, s. 719-24
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The risk of type 2 diabetes is suggested to be increased for individuals exposed to stress. We analyzed the association of work stress by high demands, low decision latitude, and job strain (combination of high demands and low decision latitude) with type 2 diabetes. We also studied low sense of coherence (SOC) (a factor for successful coping with stressors) in association with type 2 diabetes. Finally, we investigated the combination of SOC and demands or SOC and decision latitude in association with the disease. RESEARCH DESIGN AND METHODS: This cross-sectional study recruited 4821 healthy Swedish women (aged 35-56 years) residing in five municipalities in the Stockholm area. An oral glucose tolerance test identified 52 women with type 2 diabetes. Relative risks (RRs) with 95% CIs were estimated in a logistic multiple regression analysis. RESULTS: No association was found between high demands and type 2 diabetes (RR 1.1 [CI 0.5-2.2]). Low decision latitude was associated with type 2 diabetes with a RR of 2.2 (1.0-4.8). The RR of type 2 diabetes with low SOC was 3.7 (1.2-11.2). The combination of low SOC and low decision latitude was associated with type 2 diabetes with a RR of 2.6 (1.2-5.7). Homeostasis model assessment revealed an association of 4.2 (1.2-15.0) between low SOC and insulin resistance. CONCLUSIONS: This study provided new evidence that stress factors such as low decision latitude at work and low SOC were associated with type 2 diabetes in middle-aged Swedish women.
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12. |
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13. |
- Ahrén, Bo, et al.
(författare)
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Changes in Prandial Glucagon Levels after 2-year Treatment with Vildagliptin or Glimepiride in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Monotherapy.
- 2010
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 33:4, s. 730-732
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Tidskriftsartikel (refereegranskat)abstract
- Objective - To determine if the dipeptidyl peptidase 4 inhibitor vildagliptin more effectively than the sulfonylurea glimepiride inhibits glucagon levels during meal. Research design and methods - Glucagon responses to a standard meal were measured at baseline and study endpoint (mean 1.8 years) in a trial evaluating add-on therapy to metformin with vildagliptin 50 mg bid compared to glimepiride up to 6 mg qd in type 2 diabetes (baseline HbA1c 7.3+/-0.6%). Results - HbA(1c) and prandial glucose AUC(0-2h) were reduced similarly in both groups, while prandial insulin AUC(0-2h) increased to a greater extent by glimepiride. Prandial glucagon AUC(0-2h) (baseline 66.6+/-2.3 pmol.h/l) decreased by 3.4+/-1.6 pmol.h/l by vildagliptin group (n=137) and increased by 3.8+/-1.7 pmolh/l by glimepiride group (n=121). The between-group difference was 7.3+/-2.1 pmol.h/l (p<0.001). Conclusion - Vildagliptin therapy but not glimepiride improves post-prandial alpha-cell function, which persists for at least 2 years.
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14. |
- Ahrén, Bo, et al.
(författare)
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Characterization of GLP-1 effects on beta-cell function after meal ingestion in humans.
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 26:10, s. 2860-2864
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—Glucagon-like peptide 1 (GLP-1) is an incretin that augments insulin secretion after meal intake and is developed for treatment of type 2 diabetes. As a novel therapeutic agent, characteristics of its β-cell effects are important to establish. Previously, β-cell effects of GLP-1 have been characterized in humans during graded intravenous infusions of glucose, whereas its effects after more physiological stimuli, like meal intake, are not known. RESEARCH DESIGN AND METHODS—Eight women (aged 69 years, fasting glucose 3.7–10.3 mmol/l, BMI 22.4–43.9 kg/m2) who had fasted overnight were served a breakfast (450 kcal) with intravenous infusion of saline or synthetic GLP-1 (0.75 pmol · kg–1 · min–1), and β-cell function was evaluated by estimating the relationship between glucose concentration and insulin secretion (calculated by deconvolution of C-peptide data). RESULTS—GLP-1 markedly augmented insulin secretion, despite lower glucose. Total insulin secretion was 29.7 ± 4.2 nmol/m2 with GLP-1 versus 21.0 ± 1.6 nmol/m2 with saline (P = 0.048). GLP-1 increased the dose-response relationship between glucose concentration and insulin secretion (70 ± 26 with GLP-1 versus 38 ± 16 pmol insulin · min−1 · m2 · mmol−1 glucose · l without, P = 0.037) and augmented the potentiation factor that modulates the dose response (2.71 ± 0.42 with GLP-1 versus 0.97 ± 0.17 without, P = 0.005). The potentiation factor correlated to GLP-1 concentration (r = 0.53, P < 0.001); a 10-fold increase in GLP-1 levels produced a twofold increase in the potentiation factor. These effects of GLP-1 did not correlate with fasting glucose levels or BMI. CONCLUSIONS—Administration of GLP-1 along with ingestion of a meal augments insulin secretion in humans by a dose-dependent potentiation of the dose-response relationship between plasma glucose and insulin secretion.
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15. |
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16. |
- Ahren, Bo, et al.
(författare)
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Efficacy and safety of liraglutide added to capped insulin treatment in subjects with type 1 diabetes : The adjunct two randomized trial
- 2016
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 39:10, s. 1693-1701
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin. RESULTS Mean baseline glycated hemoglobin (HbA1c ) (8.1% [65.0 mmol/mol]) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% [3.6mmol/mol]; 1.2mg: -0.22% [2.4mmol/mol]; 0.6 mg: -0.23% [2.5mmol/mol]; placebo: 0.01% [0.1 mmol/mol]). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2mg vs. placebo and of hyperglycemia with ketosis >1.5mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01). CONCLUSIONS In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
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17. |
- Ahrén, Bo, et al.
(författare)
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Efficacy and Safety of Lixisenatide Once-Daily Morning or Evening Injections in Type 2 Diabetes Inadequately Controlled on Metformin (GetGoal-M).
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 36:9, s. 2543-2550
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEExamine the efficacy and safety of lixisenatide (20 μg once daily, administered before the morning or evening meal) as add-on therapy in type 2 diabetes patients insufficiently controlled with metformin alone.RESEARCH DESIGN AND METHODSA 24-week, randomized, double-blind, placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes (HbA1c 7-10% [53-86 mmol/mol]). Patients were randomized to lixisenatide morning (n = 255), lixisenatide evening (n = 255), placebo morning (n = 85), or placebo evening (n = 85) injections.RESULTSLixisenatide morning injection significantly reduced mean HbA1c versus combined placebo (mean change -0.9% [9.8 mmol/mol] vs. -0.4% [4.4 mmol/mol]; least squares [LS] mean difference vs. placebo -0.5% [5.5 mmol/mol], P < 0.0001). HbA1c was significantly reduced by lixisenatide evening injection (mean change -0.8% [8.7 mmol/mol] vs. -0.4% [4.4 mmol/mol]; LS mean difference -0.4% [4.4 mmol/mol], P < 0.0001). Lixisenatide morning injection significantly reduced 2-h postprandial glucose versus morning placebo (mean change -5.9 vs. -1.4 mmol/L; LS mean difference -4.5 mmol/L, P < 0.0001). LS mean difference in fasting plasma glucose was significant in both morning (-0.9 mmol/L, P < 0.0001) and evening (-0.6 mmol/L, P = 0.0046) groups versus placebo. Mean body weight decreased to a similar extent in all groups. Rates of adverse events were 69.4% in both lixisenatide groups and 60.0% in the placebo group. Rates for nausea and vomiting were 22.7 and 9.4% for lixisenatide morning and 21.2 and 13.3% for lixisenatide evening versus 7.6 and 2.9% for placebo, respectively. Symptomatic hypoglycemia occurred in 6, 13, and 1 patient for lixisenatide morning, evening, and placebo, respectively, with no severe episodes.CONCLUSIONSIn patients with type 2 diabetes inadequately controlled on metformin, lixisenatide 20 μg once daily administered in the morning or evening significantly improved glycemic control, with a pronounced postprandial effect, and was well tolerated.
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18. |
- Ahrén, Bo, et al.
(författare)
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HARMONY 3: 104-Week Randomized, Double-Blind, Placebo- and Active-Controlled Trial Assessing the Efficacy and Safety of Albiglutide Compared With Placebo, Sitagliptin, and Glimepiride in Patients With Type 2 Diabetes Taking Metformin.
- 2014
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 37:8, s. 2141-2148
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Tidskriftsartikel (refereegranskat)abstract
- To compare the efficacy and safety of weekly albiglutide with daily sitagliptin, daily glimepiride, and placebo.RESEARCH DESIGN AND METHODS: Patients with type 2 diabetes receiving metformin were randomized to albiglutide (30 mg), sitagliptin (100 mg), glimepiride (2 mg), or placebo. Blinded dose titration for albiglutide (to 50 mg) and glimepiride (to 4 mg) was based on predefined hyperglycemia criteria. The primary end point was change in HbA1c from baseline at week 104. Secondary end points included fasting plasma glucose (FPG), weight, and time to hyperglycemic rescue.RESULTS: Baseline characteristics were similar among the albiglutide (n = 302), glimepiride (n = 307), sitagliptin (n = 302), and placebo (n = 101) groups. Baseline HbA1c was 8.1% (65.0 mmol/mol); mean age was 54.5 years. The mean doses for albiglutide and glimepiride at week 104 were 40.5 and 3.1 mg, respectively. At week 104, albiglutide significantly reduced HbA1c compared with placebo (-0.9% [-9.8 mmol/mol]; P < 0.0001), sitagliptin (-0.4% [-4.4 mmol/mol]; P = 0.0001), and glimepiride (-0.3% [-3.3 mmol/mol]; P = 0.0033). Outcomes for FPG and HbA1c were similar. Weight change from baseline for each were as follows: albiglutide -1.21 kg (95% CI -1.68 to -0.74), placebo -1.00 kg (95% CI -1.81 to -0.20), sitagliptin -0.86 kg (95% CI -1.32 to -0.39), glimepiride 1.17 kg (95% CI 0.70-1.63). The difference between albiglutide and glimepiride was statistically significant (P < 0.0001). Hyperglycemic rescue rate at week 104 was 25.8% for albiglutide compared with 59.2% (P < 0.0001), 36.4% (P = 0.0118), and 32.7% (P = 0.1504) for placebo, sitagliptin, and glimepiride, respectively. Rates of serious adverse events in the albiglutide group were similar to comparison groups. Diarrhea (albiglutide 12.9%, other groups 8.6-10.9%) and nausea (albiglutide 10.3%, other groups 6.2-10.9%) were generally the most frequently reported gastrointestinal events.CONCLUSION: Added to metformin, albiglutide was well-tolerated; produced superior reductions in HbA1c and FPG at week 104 compared with placebo, sitagliptin, and glimepiride; and resulted in weight loss compared with glimepiride.
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19. |
- Ahrén, Bo, et al.
(författare)
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Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl peptidase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year.
- 2005
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 28:8, s. 1936-1940
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—To examine the effects of dipeptidyl peptidase-IV (DPP-4) inhibition on meal-related β-cell function and insulin sensitivity over 52 weeks in type 2 diabetes. RESEARCH DESIGN AND METHODS—In a 12-week core study, placebo (n = 51) or vildagliptin (n = 56; 50 mg OD) was added to metformin treatment (1.5–3.0 mg/day). A 40-week extension followed in 71 patients. Meal tests were performed at 0, 12, 24, and 52 weeks; glucose, insulin, and C-peptide were evaluated. RESULTS—In subjects completing 52 weeks with participation in all meal tests (n = 57), HbA1c (A1C) decreased in the vildagliptin/metformin group (VM group, n = 31) but increased in the placebo/metformin group (PM group, n = 26; between-group difference −1.0 ± 0.2%; P < 0.001; baseline of all subjects combined 7.7 ± 0.1%). Also, fasting glucose decreased in the VM group but increased in the PM group (difference −0.9 ± 0.3 mmol/l, P = 0.016; baseline 9.8 ± 0.3 mmol/l). Insulin secretion (postmeal suprabasal area under the 0- to 30-min C-peptide curve divided by the 30-min increase in glucose) was increased in the VM group but was reduced in the PM group (difference +0.011 ± 0.03 pmol/l 30 min/mmol/l, P = 0.018; baseline 0.036 ± 0.02). Insulin sensitivity during meal ingestion (oral glucose insulin sensitivity) increased in the VM group but was not altered in the PM group (difference +27 ± 4 ml · min−1 · m−2, P = 0.036; baseline 246 ± 6). Insulin secretion related to insulin sensitivity (adaptation index) increased in the VM group but decreased in the PM group (difference +3.2 ± 1.0, P = 0.040; baseline 9.1 ± 0.5). The change in adaptation index correlated to the change in A1C (r = −0.39, P = 0.004). CONCLUSIONS—This study presents evidence that DPP-4 inhibition by vildagliptin when added to metformin in type 2 diabetes over 52 weeks improves β-cell function along with improved postmeal insulin sensitivity.
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20. |
- Ahrén, Bo, et al.
(författare)
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Inhibition of dipeptidyl peptidase IV improves metabolic control over a 4-week study period in type 2 diabetes.
- 2002
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 25:5, s. 869-75
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Glucagon-like peptide-1 (GLP-1) has been proposed as a new treatment modality for type 2 diabetes. To circumvent the drawback of the short half-life of GLP-1, inhibitors of the GLP-1-degrading enzyme dipeptidyl peptidase IV (DPP IV) have been examined. Such inhibitors improve glucose tolerance in insulin-resistant rats and mice. In this study, we examined the 4-week effect of 1-[[[2-[(5-cyanopyridin-2-yl)amino]ethyl]amino]acetyl]-2-cyano-(S)-pyrrolidine (NVP DPP728), a selective, orally active inhibitor of DPP IV, in subjects with diet-controlled type 2 diabetes in a placebo-controlled double-blind multicenter study.RESEARCH DESIGN AND METHODS: A total of 93 patients (61 men and 32 women), aged 64 +/- 9 years (means +/- SD) and with BMI 27.3 +/- 2.7 kg/m(2), entered the study. Fasting blood glucose was 8.5 +/- 1.5 mmol/l, and HbA(1c) was 7.4 +/- 0.7%. Before and after treatment with NVP DPP728 at 100 mg x 3 (n = 31) or 150 mg x 5 (n = 32) or placebo (n = 30), subjects underwent a 24-h study with standardized meals (total 2,000 kcal).RESULTS: Compared with placebo, NVP DPP728 at 100 mg t.i.d. reduced fasting glucose by 1.0 mmol/l (mean), prandial glucose excursions by 1.2 mmol/l, and mean 24-h glucose levels by 1.0 mmol/l (all P < 0.001). Similar reductions were seen in the 150-mg b.i.d. treatment group. Mean 24-h insulin was reduced by 26 pmol/l in both groups (P = 0.017 and P = 0.023). Although not an efficacy parameter foreseen in the study protocol, HbA(1c) was reduced to 6.9 +/- 0.7% in the combined active treatment groups (P < 0.001). Laboratory safety and tolerability was good in all groups.CONCLUSIONS: We conclude that inhibition of DPP IV is a feasible approach to the treatment of type 2 diabetes in the early stage of the disease.
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21. |
- Ahrén, Bo
(författare)
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Insulin secretion and insulin sensitivity in relation to fasting glucose in healthy subjects.
- 2007
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 30:3, s. 644-648
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - This study evaluated insulin secretion and insulin sensitivity in healthy subjects with normal fasting glucose. RESEARCH DESIGN AND METHODS - A total of 148 healthy women (aged 53-70 years) underwent a glucose-dependent arginine stimulation test and a 2-h euglycemic-hyperinsulinemic clamp. In the arginine test, arginine (5 g) was injected intravenously under baseline (fasting) conditions and after raising the glucose levels to 15 and > 28 mmol/l. From this test, the acute insulin response (AIR) to arginine during the three glucose levels (AIR(1), AIR(2), and AIR,) were estimated. The subjects were divided into quartiles of fasting glucose (n = 37 in each group [range < 432; 4.33-4.84; 4.85-5.22; and 5:23-6.1 mmol/l, respectively). RESULTS - The results show that 1) AIR(1) was higher in subjects in the two highest quartiles (P = 0.004), 2) AIR(3) was higher in the quartile with the highest fasting glucose (P = 0.012), and 3) insulin sensitivity was reduced in subjects in the highest quartile (P = 0.026) compared with the lower quartiles. The results also show, in contrast, that AIR(2) did not show a similar trend to be increased at higher fasting glucose. CONCLUSIONS - it is concluded that 1) raised fasting glucose (albeit still within normal values) augments baseline and maximal arginine-induced insulin secretion in healthy subjects, and 2) this is associated with reduced insulin sensitivity. This suggests that high, but still normal, fasting glucose may contribute to the augmented insulin secretion in subjects with low insulin sensitivity.
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22. |
- Ahrén, Bo, et al.
(författare)
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Twelve- and 52-Week Efficacy of the Dipeptidyl Peptidase IV Inhibitor LAF237 in Metformin-Treated Patients With Type 2 Diabetes.
- 2004
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 27:12, s. 2874-2880
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE—To assess the 12- and 52-week efficacy of the dipeptidyl peptidase IV inhibitor LAF237 versus placebo in patients with type 2 diabetes continuing metformin treatment. RESEARCH DESIGN AND METHODS—We conducted a 12-week, randomized, double-blind, placebo-controlled trial in 107 patients with type 2 diabetes with a 40-week extension in those completing the core study and agreeing, together with the investigator, to extend treatment to 1 year. Placebo (n = 51) or LAF237 (50 mg once daily, n = 56) was added to ongoing metformin treatment (1,500–3,000 mg/day). HbA1c and fasting plasma glucose (FPG) were measured periodically, and standardized meal tests were performed at baseline, week 12, and week 52. RESULTS—In patients randomized to LAF237, baseline HbA1c averaged 7.7 ± 0.1% and decreased at week 12 (Δ = −0.6 ± 0.1%), whereas HbA1c did not change from a baseline of 7.9 ± 0.1% in patients given placebo (between-group difference in ΔHbA1c = −0.7 ± 0.1%, P < 0.0001). Mean prandial glucose and FPG were significantly reduced in patients receiving LAF237 versus placebo by 2.2 ± 0.4 mmol/l (P < 0.0001) and 1.2 ± 0.4 mmol/l (P = 0.0057), respectively, but plasma insulin levels were not affected. At end point of the extension, the between-group differences in change in mean prandial glucose, insulin, and FPG were −2.4 ± 0.6 mmol/l (P = 0.0001), 40 ± 16 pmol/l (P = 0.0153), and −1.1 ± 0.5 mmol/l (P = 0.0312), respectively. HbA1c did not change from week 12 to week 52 in LAF237-treated patients (n = 42) but increased in participants given placebo (n = 29). The between-group difference in ΔHbA1c after 1 year was −1.1 ± 0.2% (P < 0.0001). CONCLUSIONS—Data from this study demonstrate that LAF237 effectively prevents deterioration of glycemic control when added to metformin monotherapy in type 2 diabetes.
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23. |
- Ahuja, Vasudha, et al.
(författare)
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Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults : A Meta-analysis
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44:4, s. 1062-1069
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Forskningsöversikt (refereegranskat)abstract
- OBJECTIVE: One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard. RESEARCH DESIGN AND METHODS: We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA1c. We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3). RESULTS: Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%. CONCLUSIONS: The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.
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24. |
- Alvarsson, M, et al.
(författare)
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Beneficial effects of insulin versus sulphonylurea on insulin secretion and metabolic control in recently diagnosed type 2 diabetic patients
- 2003
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 26:8, s. 2231-2237
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To evaluate whether treatment with insulin in recently diagnosed type 2 diabetes is advantageous compared with glibenclamide treatment. RESEARCH DESIGN AND METHODS - ▀-Cell function, glycemic control, and quality of life were monitored over 2 years in 39 patients with islet cell antibody-negative type 2 diabetes diagnosed 0-2 years before inclusion in a Swedish multicenter randomized clinical trial. Patients were randomized to either two daily injections of premixed 30% soluble and 70% NPH insulin or glibenclamide (3.5-10.5 mg daily). C-peptide-glucagon tests were performed yearly in duplicate after 2-3 days of temporary withdrawal of treatment. RESULTS - After 1 year the glucagon-stimulated C-peptide response was increased in the insulin-treated group by 0.14 ▒ 0.08 nmol/l, whereas it was decreased by 0.12 ▒ 0.08 nmol/l in the glibenclamide group, P < 0.02 for difference between groups. After 2 years, fasting insulin levels were higher after treatment withdrawal in the insulin-treated versus the glibenclamide-treated group (P = 0.02). HbA1c levels decreased significantly during the first year in both groups, however, at the end of the second year, HbA1c had deteriorated in the glibenclamide group (P < 0.01), but not in the insulin-treated group. The difference in evolution of HbA1c during the second year was significant between groups, P < 0.02 A questionnaire indicated no difference in well-being related to treatment. CONCLUSIONS - Early insulin versus glibenclamide treatment in type 2 diabetes temporarily prolongs endogenous insulin secretion and promotes better metabolic control.
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25. |
- Anand, Vibha, et al.
(författare)
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Islet Autoimmunity and HLA Markers of Presymptomatic and Clinical Type 1 Diabetes : Joint Analyses of Prospective Cohort Studies in Finland, Germany, Sweden, and the U.S
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44, s. 2269-2276
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To combine prospective cohort studies, by including HLA harmonization, and estimate risk of islet autoimmunity and progression to clinical diabetes.RESEARCH DESIGN AND METHODS: For prospective cohorts in Finland, Germany, Sweden, and the U.S., 24,662 children at increased genetic risk for development of islet autoantibodies and type 1 diabetes have been followed. Following harmonization, the outcomes were analyzed in 16,709 infants-toddlers enrolled by age 2.5 years.RESULTS: In the infant-toddler cohort, 1,413 (8.5%) developed at least one autoantibody confirmed at two or more consecutive visits (seroconversion), 865 (5%) developed multiple autoantibodies, and 655 (4%) progressed to diabetes. The 15-year cumulative incidence of diabetes varied in children with one, two, or three autoantibodies at seroconversion: 45% (95% CI 40-52), 85% (78-90), and 92% (85-97), respectively. Among those with a single autoantibody, status 2 years after seroconversion predicted diabetes risk: 12% (10-25) if reverting to autoantibody negative, 30% (20-40) if retaining a single autoantibody, and 82% (80-95) if developing multiple autoantibodies. HLA-DR-DQ affected the risk of confirmed seroconversion and progression to diabetes in children with stable single-autoantibody status. Their 15-year diabetes incidence for higher- versus lower-risk genotypes was 40% (28-50) vs. 12% (5-38). The rate of progression to diabetes was inversely related to age at development of multiple autoantibodies, ranging from 20% per year to 6% per year in children developing multipositivity in ≤2 years or >7.4 years, respectively.CONCLUSIONS: The number of islet autoantibodies at seroconversion reliably predicts 15-year type 1 diabetes risk. In children retaining a single autoantibody, HLA-DR-DQ genotypes can further refine risk of progression.
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26. |
- Andersen, Mette K., et al.
(författare)
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Latent Autoimmune Diabetes in Adults Differs Genetically From Classical Type 1 Diabetes Diagnosed After the Age of 35 Years
- 2010
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 33:9, s. 2062-2064
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE- We studied differences between patients with latent autoimmune diabetes in adults (LADA), type 2 diabetes, and classical type 1 diabetes diagnosed after age 35 years. RESEARCH DESIGN AND METHODS- Polymorphisms in HLA-DQB1, INS, PTPN22, and CTLA4 were genotyped in patients with LADA (n = 213), type 1 diabetes diagnosed at >35 years of age (T1D(>35y); n = 257) or <20 years of age (T1D(<20y); n = 158), and type 2 diabetes. RESULTS- Although patients with LADA had an increased frequency of HLA-DQB1 and PTPN22 risk genotypes and alleles compared with type 2 diabetic subjects, the frequency was significantly lower compared with T1D(>35y) patients. Genotype frequencies, measures of insulin secretion, and metabolic traits within LADA differed according to GAD antibody (GADA) quartiles, but even the highest quartile differed from type 1 diabetes. Having two or more risk genotypes was associated with lower C-peptide concentrations in LADA. CONCLUSIONS- LADA patients differed genetically and phenotypically from both T1D(>35y) and type 2 diabetic patients in a manner dependent on GADA levels.
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27. |
- Anderson, B. J., et al.
(författare)
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Factors associated with diabetes-specific health-related quality of life in youth with type 1 diabetes: The global teens study
- 2017
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 40:8, s. 1002-1009
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Our objective was to characterize diabetes-specific health-related quality of life (D-HRQOL) in a global sample of youth and young adults with type 1 diabetes (T1D) and to identify the main factors associated with quality of life. RESEARCH DESIGN AND METHODS The TEENs study was an international, cross-sectional study of youth, 8-25 years of age, with T1D. Participants (N= 5,887)were seen in clinical sites in 20 countries across 5 continents enrolled for 3 predetermined age groups: 8-12, 13-18, and 19-25 years of age. To assess D-HRQOL, participants completed the PedsQL DiabetesModule 3.0 and were interviewed about family-related factors. Specifics about treatment regimen and self-management behaviors were collected from medical records. RESULTS Across all age groups, females reported significantly lower D-HRQOL than didmales. The 19-25-year age group reported the lowest D-HRQOL. Multivariate linear regression analyses revealed that D-HRQOL was significantly related to HbA1c; the lower the HbA1c, the better the D-HRQOL. Three diabetes-management behaviors were significantly related to better D-HRQOL: advanced methods used to measure food intake;more frequent daily blood glucose monitoring; and more days per week that youth had 30 min of physical activity. CONCLUSIONS In all three age groups, the lower the HbA1c, the better the D-HRQOL, underscoring the strong association between better D-HRQOL and optimal glycemic control in a global sample of youth and young adults. Three diabetes-management behaviors were also related to optimal glycemic control, which represent potentially modifiable factors for clinical interventions to improve D-HRQOL as well as glycemic control.
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28. |
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29. |
- Anjana, Ranjit Mohan, et al.
(författare)
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Contrasting Associations Between Diabetes and Cardiovascular Mortality Rates in Low-, Middle-, and High-Income Countries: Cohort Study Data From 143,567 Individuals in 21 Countries in the PURE Study.
- 2020
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Ingår i: Diabetes care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:12, s. 3094-3101
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to compare cardiovascular (CV) events, all-cause mortality, and CV mortality rates among adults with and without diabetes in countries with differing levels of income.The Prospective Urban Rural Epidemiology (PURE) study enrolled 143,567 adults aged 35-70 years from 4 high-income countries (HIC), 12 middle-income countries (MIC), and 5 low-income countries (LIC). The mean follow-up was 9.0 ± 3.0 years.Among those with diabetes, CVD rates (LIC 10.3, MIC 9.2, HIC 8.3 per 1,000 person-years, P < 0.001), all-cause mortality (LIC 13.8, MIC 7.2, HIC 4.2 per 1,000 person-years, P < 0.001), and CV mortality (LIC 5.7, MIC 2.2, HIC 1.0 per 1,000 person-years, P < 0.001) were considerably higher in LIC compared with MIC and HIC. Within LIC, mortality was higher in those in the lowest tertile of wealth index (low 14.7%, middle 10.8%, and high 6.5%). In contrast to HIC and MIC, the increased CV mortality in those with diabetes in LIC remained unchanged even after adjustment for behavioral risk factors and treatments (hazard ratio [95% CI] 1.89 [1.58-2.27] to 1.78 [1.36-2.34]).CVD rates, all-cause mortality, and CV mortality were markedly higher among those with diabetes in LIC compared with MIC and HIC with mortality risk remaining unchanged even after adjustment for risk factors and treatments. There is an urgent need to improve access to care to those with diabetes in LIC to reduce the excess mortality rates, particularly among those in the poorer strata of society.
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30. |
- Apelqvist, Jan, et al.
(författare)
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Prognostic value of systolic ankle and toe blood pressure levels in outcome of diabetic foot ulcer
- 1989
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 12:6, s. 373-378
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic value of distal blood pressure measurements has been studied in 314 consecutive diabetic patients with foot ulcers. Systolic toe blood pressure was measured with a strain-gauge technique, and ankle pressure was measured with strain-gauge or Doppler techniques. Wound healing was defined as intact skin for at least 6 mo. One hundred ninety-seven patients healed primarily, 77 had amputations, and 40 died before healing had occurred. In 294 of 300 patients, it was possible to measure either ankle or toe pressure. Fourteen patients were not available for pressure measurements. Of these, 10 patients healed primarily, and 4 died before healing occurred. Both ankle and toe pressures were higher (P less than .001) among patients who healed without amputation compared with those who underwent amputation or died before healing. No differences were seen in ankle or toe pressure levels among those who had amputations or died. No patient healed primarily with an ankle pressure less than 40 mmHg. An upper limit above which amputation was not required could not be defined. Primary healing was achieved in 139 of 164 patients (85%) with a toe pressure level greater than 45 mmHg, whereas 43 of 117 patients (36%; P less than .001) healed without amputation when toe pressure was less than or equal to 45 mmHg. In conclusion, a combination of ankle and toe pressure measurements is a useful tool to predict primary healing in diabetic foot ulcers.
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31. |
- Arnlöv, Johan, et al.
(författare)
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Impact of BMI and the metabolic syndrome on the risk of diabetes in middle-aged men
- 2011
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 34:1, s. 61-65
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE- The existence of an obese subgroup with a healthy metabolic profile and low diabetes risk has been proposed; yet long-term data are lacking. We aimed to investigate associations between combinations of BMI categories and metabolic syndrome and risk of type 2 diabetes in middle-aged men. RESEARCH DESIGN AND METHODS- At age 50, cardiovascular risk factors were assessed in 1,675 participants without diabetes in the community-based Uppsala Longitudinal Study of Adult Men (ULSAM) study. According to BMI/metabolic syndrome status, they were categorized as normal weight (BMI <25 kg/m(2)) without metabolic syndrome (National Cholesterol Education Program criteria, n = 853), normal weight with metabolic syndrome (n = 60), overweight (BMI 25-30 kg/m(2)) without metabolic syndrome (n = 557), overweight with metabolic syndrome (n = 117), obese (BMI >30 kg/m(2)) without metabolic syndrome (n = 28), and obese with metabolic syndrome (n = 60). We investigated the associations between BMI/metabolic syndrome categories at baseline and diabetes incidence. RESULTS- After 20 years, 160 participants had developed diabetes. In logistic regression models adjusting for age, smoking, and physical activity, increased risks for diabetes were observed in the normal weight with metabolic syndrome (odds ratio 3.28 [95% CI] 1.38-7.81; P = 0.007), overweight without metabolic syndrome (3.49[2.26-5.42]; P < 0.001), overweight with metabolic syndrome (7.77 [4.44-13.62]; P < 0.001), obese without metabolic syndrome (11.72 [4.88-28.16]; P < 0.001), and obese with metabolic syndrome (10.06 [5.19-19.51]; P < 0.001) categories compared with the normal weight without metabolic syndrome category. CONCLUSIONS- Overweight or obese men without metabolic syndrome were at increased risk for diabetes. Our data provide further evidence that overweight and obesity in the absence of the metabolic syndrome should not be considered a harmless condition.
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32. |
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33. |
- Arnqvist, Hans, et al.
(författare)
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Impact of HbA(1c) Followed 32 Years From Diagnosis of Type 1 Diabetes on Development of Severe Retinopathy and Nephropathy: The VISS Study
- 2022
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Ingår i: Diabetes Care. - : AMER DIABETES ASSOC. - 0149-5992 .- 1935-5548. ; 45:11, s. 2675-2682
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To evaluate HbA(1c) followed from diagnosis, as a predictor of severe microvascular complications (i.e., proliferative diabetic retinopathy [PDR] and nephropathy [macroalbuminuria]). RESEARCH DESIGN AND METHODS In a population-based observational study, 447 patients diagnosed with type 1 diabetes before 35 years of age from 1983 to 1987 in southeast Sweden were followed from diagnosis until 2019. Long-term weighted mean HbA(1c) (wHbA(1c)) was calculated by integrating the area under all HbA(1c) values. Complications were analyzed in relation to wHbA(1c) categorized into five levels. RESULTS After 32 years, 9% had no retinopathy, 64% non-PDR, and 27% PDR, and 83% had no microalbuminuria, 9% microalbuminuria, and 8% macroalbuminuria. Patients with near-normal wHbA(1c) did not develop PDR or macroalbuminuria. The lowest wHbA(1c) values associated with development of PDR and nephropathy (macroalbuminuria) were 7.3% (56 mmol/mol) and 8.1% (65 mmol/mol), respectively. The prevalence of PDR and macroalbuminuria increased with increasing wHbA(1c), being 74% and 44% in the highest category, wHbA(1c) >9.5% (>80 mmol/mol). In comparison with the follow-up done after 20-24 years duration, the prevalence of PDR had increased from 14 to 27% and macroalbuminuria from 4 to 8%, and both appeared at lower wHbA(1c) values. CONCLUSIONS wHbA(1c) followed from diagnosis is a very strong biomarker for PDR and nephropathy, the prevalence of both still increasing 32 years after diagnosis. To avoid PDR and macroalbuminuria in patients with type 1 diabetes, an HbA(1c) <7.0% (53 mmol/mol) and as normal as possible should be recommended when achievable without severe hypoglycemia and with good quality of life.
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34. |
- Axelsson, Stina, et al.
(författare)
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Cellular and Humoral Immune responses in Type 1 Diabetic patients participating in a Phase III GAD-alum Intervention Trial
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:11, s. 3418-3424
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEGAD formulated in aluminum hydroxide (GAD-alum) has previously been shown to induce preservation of residual insulin secretion in recent-onset type 1 diabetes, but recent phase II and III GAD-alum trials failed to reach primary outcomes. The European phase III study was therefore closed after 15 months, and only a minority of patients completed the 30 months of follow-up.RESEARCH DESIGN AND METHODSThis study aimed to characterize cellular and humoral responses in the Swedish patients (n = 148) participating in the phase III trial, receiving four (4D) or two (2D) GAD-alum doses or placebo. Serum GAD(65) antibody (GADA) levels, GADA IgG1-4 subclass distribution, cytokine secretion, and proliferative responses in peripheral blood mononuclear cells (PBMCs) were analyzed.RESULTSThe GAD(65)-induced cytokine profile tended to switch toward a predominant Th2-associated profile over time both in the 2D and 4D group. The groups also displayed increased GADA levels and PBMC proliferation compared with placebo, whereas GADA IgG subclass distribution changed in 4D patients.CONCLUSIONSBoth 2D and 4D patients displayed GAD(65)-specifc cellular and humoral effects after GAD-alum treatment, but at different time points and magnitudes. No specific immune markers could be associated with treatment efficacy.
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35. |
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36. |
- Balintescu, A., et al.
(författare)
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Glycemic Control and Risk of Sepsis and Subsequent Mortality in Type 2 Diabetes
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 45:1, s. 127-133
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To investigate the nature of the relationship between HbA1c and sepsis among individuals with type 2 diabetes, and to assess the association between sepsis and all-cause mortality in such patients. RESEARCH DESIGN AND METHODS We included 502,871 individuals with type 2 diabetes recorded in the Swedish National Diabetes Register and used multivariable Cox regression and restricted cubic spline analyses to assess the association between time-updated HbA1c values and sepsis occurrence between 1 January 2005 and 31 December 2015. The association between sepsis and death was examined using multivariable Cox regression analysis. RESULTS Overall, 14,534 (2.9%) patients developed sepsis during the study period. On multivariable Cox regression analysis, compared with an HbA1c of 48–52 mmol/mol (6.5–6.9%), the adjusted hazard ratio for sepsis was 1.15 (95% CI 1.07–1.24) for HbA1c <43 mmol/mol (6.1%), 0.93 (0.87–0.99) for HbA1c 53–62 mmol/mol (7.0–7.8%), 1.05 (0.97–1.13) for HbA1c 63–72 mmol/mol (7.9–8.7%), 1.14 (1.04–1.25) for HbA1c 73–82 mmol/mol (8.8–9.7%), and 1.52 (1.37–1.68) for HbA1c >82 mmol/mol (9.7%). In the cubic spline model, a reduction of the adjusted risk was observed within the lower HbA1c range until 53 mmol/mol (7.0%), with a hazard ratio of 0.78 (0.73–0.82) per SD; it increased thereafter (P for nonlinearity <0.001). As compared with patients without sepsis, the adjusted hazard ratio for death among patients with sepsis was 4.16 (4.03–4.30). CONCLUSIONS In a nationwide cohort of individuals with type 2 diabetes, we found a U-shaped association between HbA1c and sepsis and a fourfold increased risk of death among those developing sepsis. © 2021 by the American Diabetes Association.
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37. |
- Basu, Samar, et al.
(författare)
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Type 1 diabetes is associated with increased cyclooxygenase- and cytokine-mediated inflammation
- 2005
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 28:6, s. 1371-1375
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The extent of involvement of cyclooxygenase (COX)-mediated inflammation in type 1 diabetes is unknown, and the association between the COX- and cytokine-mediated inflammatory responses in type 1 diabetes is not fully understood. RESEARCH DESIGN AND METHODS: Plasma high-sensitivity C-reactive protein (CRP), 24-h urinary and plasma 15-keto-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin F(2alpha) [PGF(2alpha)] and an indicator of COX-mediated inflammation), serum amyloid protein A (SAA), and interleukin (IL)-6 (indicators of inflammation) were measured in 38 subjects with type 1 diabetes and 41 healthy age- and sex-matched control subjects. RESULTS: The inflammatory indicators (urinary 15-keto-dihydro-PGF(2alpha), P < 0.01; IL-6, P < 0.04) were increased in men with diabetes. CRP and SAA did not show any significant difference between the diabetic and the control subjects. Urinary levels of 15-keto-dihydro-PGF(2alpha) correlated with the degree of glycemic control, HbA(1c) (r = 0.42, P < 0.0005). No correlation was found between the duration of diabetes and the inflammatory biomarkers or metabolic measurements. CONCLUSIONS: These results suggest that an early low-grade inflammatory process reflected by elevated levels of PGF(2alpha) and IL-6 is involved in type 1 diabetes. Thus, both COX- and cytokine-mediated inflammatory pathways are significantly related to type 1 diabetes.
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38. |
- Battaglia, Manuela, et al.
(författare)
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Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes
- 2020
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 43:1, s. 5-12
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Tidskriftsartikel (refereegranskat)abstract
- The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.
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39. |
- Behall, KM, et al.
(författare)
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Consumption of both resistant starch and beta-glucan improves postprandial plasma glucose and insulin in women
- 2006
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 29:5, s. 976-981
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - Consumption of a meal high in resistant starch or soluble fiber (P-glucan) decreases peak insulin and glucose concentrations and areas under the curve (AUCs). The objective was to determine whether the effects of soluble fiber and resistant starch on glycemic variables are additive. RESEARCH DESIGN AND METHODS - Ten normal-weight (43.5 years of age, BMI 22.0 kg/m(2)) and 10 overweight women (43.3 years of age, BMI 30.4 kg/m(2)) consumed 10 tolerance meals in a Latin square design. Meals (1 g carbohydrate/kg body wt) were glucose a ne or muffins made with different levels of soluble fiber (0.26, 0.68, or 2.3 g beta-glucan/100 g muffin) and three levels of resistant starch (0.71, 2.57, or 5.06 g/100 g muffin). RESULTS - Overweight subjects had plasma insulin concentrations higher than those of normal-weight subjects but maintained similar plasma glucose levels. Compared with low beta-glucan-low resistant starch muffins, glucose and insulin AUC decreased when beta-glucan (17 and 33%, respectively) or resistant Starch (24 and 38%, respectively) content was increased. The greatest AUC reduction occurred after meals containing both high beta-glucan-high resistant Starch (33 and 59% lower AUC for glucose and insulin, respectively). Overweight women were somewhat more insulin resistant than control women. CONCLUSIONS - Soluble fiber appears to have a greater effect on postprandial insulin response while glucose reduction is greater after resistant starch from high-amylose cornstarch. The reduction in glycemic response was enhanced by combining resistant starch and soluble fiber. Consumption of foods containing moderate amounts of these fibers may improve glucose metabolism in both normal and overweight women.
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40. |
- Benedict, Christian, et al.
(författare)
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Impaired Insulin Sensitivity as Indexed by the HOMA Score Is Associated With Deficits in Verbal Fluency and Temporal Lobe Gray Matter Volume in the Elderly
- 2012
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:3, s. 488-494
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVEImpaired insulin sensitivity is linked to cognitive deficits and reduced brain size. However, it is not yet known whether insulin sensitivity involves regional changes in gray matter volume. Against this background, we examined the association between insulin sensitivity, cognitive performance, and regional gray matter volume in 285 cognitively healthy elderly men and women aged 75 years from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study.RESEARCH DESIGN AND METHODSInsulin sensitivity was calculated from fasting serum insulin and plasma glucose determinations using the homeostasis model assessment of insulin resistance (HOMA-IR) method. Cognitive performance was examined by a categorical verbal fluency. Participants also underwent a magnetic resonance imaging (MRI) brain scan. Multivariate analysis using linear regression was conducted, controlling for potential confounders (sex, education, serum LDL cholesterol, mean arterial blood pressure, and abdominal visceral fat volume).RESULTSThe HOMA-IR was negatively correlated with verbal fluency performance, brain size (S1), and temporal lobe gray matter volume in regions known to be involved in speech production (Brodmann areas 21 and 22, respectively). No such effects were observed when examining diabetic (n = 55) and cognitively impaired (n = 27) elderly subjects as separate analyses.CONCLUSIONSThese cross-sectional findings suggest that both pharmacologic and lifestyle interventions improving insulin signaling may promote brain health in late life but must be confirmed in patient studies.
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41. |
- Berhan, Yonas, et al.
(författare)
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Impact of Parental Socioeconomic Status on Excess Mortality in a Population-Based Cohort of Subjects With Childhood-Onset Type 1 Diabetes
- 2015
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 38:5, s. 827-832
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to analyze the possible impact of parental and individual socioeconomic status (SES) on all-cause mortality in a population-based cohort of patients with childhood-onset type 1 diabetes.RESEARCH DESIGN AND METHODS: Subjects recorded in the Swedish Childhood Diabetes Registry (SCDR) from 1 January 1978 to 31 December 2008 were included (n =14,647). The SCDR was linked to the Swedish Cause of Death Registry (CDR) and the Longitudinal Integration Database for Health Insurance and Labour Market Studies (LISA).RESULTS: At a mean follow-up of 23.9 years (maximum 46.5 years), 238 deaths occurred in a total of 349,762 person-years at risk. In crude analyses, low maternal education predicted mortality for male patients only (P = 0.046), whereas parental income support predicted mortality in both sexes (P < 0.001 for both). In Cox models stratified by age-at-death group and adjusted for age at onset and sex, parental income support predicted mortality among young adults (≥18 years of age) but not for children. Including the adult patient’s own SES in a Cox model showed that individual income support to the patient predicted mortality occurring at ≥24 years of age when adjusting for age at onset, sex, and parental SES.CONCLUSIONS: Exposure to low SES, mirrored by the need for income support, increases mortality risk in patients with childhood-onset type 1 diabetes who died after the age of 18 years.
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42. |
- Besser, Rachel E J, et al.
(författare)
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Lessons From the Mixed-Meal Tolerance Test Use of 90-minute and fasting C-peptide in pediatric diabetes
- 2013
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 36:2, s. 195-201
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Mixed-meal tolerance test (MMTT) area under the curve C-peptide (AUC CP) is the gold-standard measure of endogenous insulin secretion in type 1 diabetes but is intensive and invasive to perform. The 90-minMMTT-stimulated CP andgt;= 0.2 nmol/L (90CP) is related to improved clinical outcomes, and CP andgt;= 0.1 nmol/L is the equivalent fasting measure (FCP). We assessed whether 90CP or FCP are alternatives to a full MMTT. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-CP was measured during 1,334 MMTTs in 421 type 1 diabetes patients aged, 18 years at 3, 9, 18, 48, and 72 months duration. We assessed: 1) correlation between mean AUC CP and 90CP or FCP; 2) sensitivity and specificity of 90CP andgt;= 0.2 nmol/L and FCP andgt;= 0.1 nmol/L to detect peak CP andgt;= 0.2 nmol/L and the equivalent AUC CP; and 3) how the time taken to reach the CP peak varied with age of diagnosis and diabetes duration. less thanbrgreater than less thanbrgreater thanRESULTS-AUC CP was highly correlated to 90CP (r(s) = 0.96; P andlt; 0.0001) and strongly correlated to FCP (r(s) = 0.84; P andlt; 0.0001). AUC CP andgt;= 23 nmol/L/150 min was the equivalent cutoff for peak CP andgt;= 0.2 nmol/L (98% sensitivity/97% specificity). A 90CP andgt;= 0.2 nmol/L correctly classified 96% patients using AUC or peak CP, whereas FCP andgt;= 0.1 nmol/L classified 83 and 85% patients, respectively. There was only a small difference seen between peak and 90CP (median 0.02 nmol/L). The CP peak occurred earlier in patients with longer diabetes duration (6.1 min each 1-year increase in duration) and younger age (2.5 min each 1-year increase). less thanbrgreater than less thanbrgreater thanCONCLUSIONS-90CP is a highly sensitive and specific measure of AUC and peak CP in children and adolescents with type 1 diabetes and offers a practical alternative to a full MMTT. Diabetes Care 36:195-201, 2013
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43. |
- Besser, Rachel E J, et al.
(författare)
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Urine C-Peptide Creatinine Ratio Is a Noninvasive Alternative to the Mixed-Meal Tolerance Test in Children and Adults With Type 1 Diabetes
- 2011
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Ingår i: DIABETES CARE. - : American Diabetes Association Inc. - 0149-5992 .- 1935-5548. ; 34:3, s. 607-609
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-Stimulated serum C-peptide (sCP) during a mixed-meal tolerance test (MMTT) is the gold standard measure of endogenous insulin secretion, but practical issues limit its use. We assessed urine C-peptide creatinine ratio (UCPCR) as an alternative. RESEARCH DESIGN AND METHODS-Seventy-two type 1 diabetic patients (age of diagnosis median 14 years [interquartile range 10-22]; diabetes duration 6.5[2.3-32.7]) had an MMTT. sCP was collected at 90 min. Urine for UCPCR was collected at 120 min and following a home evening meal. RESULTS-MMTT 120-min UCPCR was highly correlated to 90-min sCP (r = 0.97; P andlt; 0.0001). UCPCR andgt;= 0.53 nmol/mmol had 94% sensitivity/100% specificity for significant endogenous insulin secretion (90-min sCP andgt;= 0.2 nmol/L). The 120-min postprandial evening meal UCPCR was highly correlated to 90-min sCP (r = 0.91; P andlt; 0.0001). UCPCR andgt;= 0.37 nmol/mmol had 84% sensitivity/97% specificity for sCP andgt;= 0.2 nmol/L. CONCLUSIONS-UCPCR testing is a sensitive and specific method for detecting insulin secretion. UCPCR may be a practical alternative to serum C-peptide testing, avoiding the need for inpatient investigation.
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44. |
- Bhavadharini, B., et al.
(författare)
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White Rice Intake and Incident Diabetes: A Study of 132,373 Participants in 21 Countries
- 2020
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Ingår i: Diabetes care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:11, s. 2643-2650
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Previous prospective studies on the association of white rice intake with incident diabetes have shown contradictory results but were conducted in single countries and predominantly in Asia. We report on the association of white rice with risk of diabetes in the multinational Prospective Urban Rural Epidemiology (PURE) study. RESEARCH DESIGN AND METHODS Data on 132,373 individuals aged 35-70 years from 21 countries were analyzed. White rice consumption (cooked) was categorized as <150, >= 150 to <300, >= 300 to <450, and >= 450 g/day, based on one cup of cooked rice = 150 g. The primary outcome was incident diabetes. Hazard ratios (HRs) were calculated using a multivariable Cox frailty model. RESULTS During a mean follow-up period of 9.5 years, 6,129 individuals without baseline diabetes developed incident diabetes. In the overall cohort, higher intake of white rice (>= 450 g/day compared with <150 g/day) was associated with increased risk of diabetes (HR 1.20; 95% CI 1.02-1.40;Pfor trend = 0.003). However, the highest risk was seen in South Asia (HR 1.61; 95% CI 1.13-2.30;Pfor trend = 0.02), followed by other regions of the world (which included South East Asia, Middle East, South America, North America, Europe, and Africa) (HR 1.41; 95% CI 1.08-1.86;Pfor trend = 0.01), while in China there was no significant association (HR 1.04; 95% CI 0.77-1.40;Pfor trend = 0.38). CONCLUSIONS Higher consumption of white rice is associated with an increased risk of incident diabetes with the strongest association being observed in South Asia, while in other regions, a modest, nonsignificant association was seen.
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46. |
- Birkeland, Kare I., et al.
(författare)
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Insulin degludec in type 1 diabetes : a randomized controlled trial of a new-generation ultra-long-acting insulin compared with insulin glargine
- 2011
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 34:3, s. 661-665
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.RESEARCH DESIGN AND METHODS: In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m(2)) received subcutaneous injections of IDeg(A) (600 mu mol/L; n = 59), IDeg(B) (900 mu mol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes.RESULTS: At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 +/- 0.8%), IDeg(B) (8.0 +/- 1.0%), and IGlar (7.6 +/- 0.8%), as was FPG (8.3 +/- 4.0, 8.3 +/- 2.8, and 8.9 +/- 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52-1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65-1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25-0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44-1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.CONCLUSIONS: In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.
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47. |
- Birukov, Anna, et al.
(författare)
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Immunoglobulin G N-Glycosylation Signatures in Incident Type 2 Diabetes and Cardiovascular Disease
- 2022
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 45:11, s. 2729-2736
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE N-glycosylation is a functional posttranslational modification of immunoglobulins (Igs). We hypothesized that specific IgG N-glycans are associated with incident type 2 diabetes and cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS We performed case-cohort studies within the population-based European Prospective Investigation into Cancer and Nutrition (EPIC)–Potsdam cohort (2,127 in the type 2 diabetes subcohort [741 incident cases]; 2,175 in the CVD subcohort [417 myocardial infarction and stroke cases]). Relative abundances of 24 IgG N-glycan peaks (IgG-GPs) were measured by ultraperformance liquid chromatog-raphy, and eight glycosylation traits were derived based on structural similarity. End point–associated IgG-GPs were preselected with fractional polynomials, and prospective associations were estimated in confounder-adjusted Cox models. Diabetes risk associations were validated in three independent studies. RESULTS After adjustment for confounders and multiple testing correction, IgG-GP7, IgG-GP8, IgG-GP9, IgG-GP11, and IgG-GP19 were associated with type 2 diabetes risk. A score based on these IgG-GPs was associated with a higher diabetes risk in EPIC-Potsdam and independent validation studies (843 total cases, 3,149 total non-cases, pooled estimate per SD increase 1.50 [95% CI 1.37–1.64]). Associations of IgG-GPs with CVD risk differed between men and women. In women, IgG-GP9 was inversely associated with CVD risk (hazard ratio [HR] per SD 0.80 [95% CI 0.65–0.98]). In men, a weighted score based on IgG-GP19 and IgG-GP23 was associated with higher CVD risk (HR per SD 1.47 [95% CI 1.20–1.80]). In addition, several derived traits were associated with cardiometabolic disease incidence. CONCLUSIONS Selected IgG N-glycans are associated with cardiometabolic risk beyond classic risk factors, including clinical biomarkers.
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48. |
- Bizzotto, Roberto, et al.
(författare)
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Processes Underlying Glycemic Deterioration in Type 2 Diabetes : An IMI DIRECT Study
- 2021
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Ingår i: Diabetes Care. - : American Diabetes Association. - 1935-5548 .- 0149-5992. ; 44:2, s. 511-518
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We investigated the processes underlying glycemic deterioration in type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: A total of 732 recently diagnosed patients with T2D from the Innovative Medicines Initiative Diabetes Research on Patient Stratification (IMI DIRECT) study were extensively phenotyped over 3 years, including measures of insulin sensitivity (OGIS), β-cell glucose sensitivity (GS), and insulin clearance (CLIm) from mixed meal tests, liver enzymes, lipid profiles, and baseline regional fat from MRI. The associations between the longitudinal metabolic patterns and HbA1c deterioration, adjusted for changes in BMI and in diabetes medications, were assessed via stepwise multivariable linear and logistic regression. RESULTS: Faster HbA1c progression was independently associated with faster deterioration of OGIS and GS and increasing CLIm; visceral or liver fat, HDL-cholesterol, and triglycerides had further independent, though weaker, roles (R2 = 0.38). A subgroup of patients with a markedly higher progression rate (fast progressors) was clearly distinguishable considering these variables only (discrimination capacity from area under the receiver operating characteristic = 0.94). The proportion of fast progressors was reduced from 56% to 8-10% in subgroups in which only one trait among OGIS, GS, and CLIm was relatively stable (odds ratios 0.07-0.09). T2D polygenic risk score and baseline pancreatic fat, glucagon-like peptide 1, glucagon, diet, and physical activity did not show an independent role. CONCLUSIONS: Deteriorating insulin sensitivity and β-cell function, increasing insulin clearance, high visceral or liver fat, and worsening of the lipid profile are the crucial factors mediating glycemic deterioration of patients with T2D in the initial phase of the disease. Stabilization of a single trait among insulin sensitivity, β-cell function, and insulin clearance may be relevant to prevent progression.
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49. |
- Bojestig, M, et al.
(författare)
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Reduction of ACE activity is insufficient to decrease microalbuminuria in normotensive patients with type 1 diabetes
- 2001
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Ingår i: Diabetes Care. - 0149-5992 .- 1935-5548. ; 24:5, s. 919-924
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - To study whether administration of 1.25 and 5.0 mg ramipril daily, compared with placebo treatment, reduces the urinary albumin excretion rate (UAER) in normotensive patients with type 1 diabetes. RESEARCH DESIGN AND METHODS - Ramipril was administered double blind at two different doses(1.25 [n = 19] and 5.0 mg [n = 18]), and compared with placebo [n = 18] after a single-blind placebo period of 1-4 weeks. The patients (total, n = 55, women, n = 14) were followed for 2 years. To document an effect on the renin-angiotensin system, ACE activity and plasma-renin activity (PRA) were measured. In addition, 24-h ambulatory blood pressure (BP) was recorded at baseline and repeated after 1 and 2 years using a Spacelab 90207 ambulatory BP recording device (Spacelab, Redmont, CA). RESULTS - Both doses of ramipril were sufficient to reduce ACE activity and to increase PRA significantly as compared with placebo (P < 0.05 for both). On the other hand, neither ambulatory nor clinic BP was affected by either dose of ramipril compared with the placebo group. There was no progression of UAER in the placebo group during the 2 years of the study. Analysis of covariance showed no differences in UAER between the three treatment groups at year 1 (P = 0.94) or year 2 (P = 0.97), after adjusting for baseline. Furthermore, there were no statistically significant changes from baseline UAER within any of the three treatment groups. CONCLUSIONS - Treatment with ramipril did not affect microalbuminuria or clinic or ambulatory BP in this study. On the basis of the present study, we question the clinical use of ACE inhibitors in stably normotensive patients with type 1 diabetes and microalbuminuria in whom a concomitant reduction in BP is not demonstrated.
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50. |
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