To explore the natural course of beta cell function in recent onset diabetes, a subgroup (n=157) of all incident cases (n=879) 15-34 years old, 1992-1993 in Sweden, and with positivity for at least one autoantibody of islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A) were followed prospectively for the first four years with annual analysis of C-peptide. The aim was to relate the course of beta cell function, measured as C-peptide, in early diabetes with the presence of different islet autoantibodies at diagnosis. We found that patients positive for ICA alone (n=11) had significantly higher C-peptide levels both at diagnosis and during the first three years compared with the other patients (n=146; p=0.022, p
AIMS/HYPOTHESIS: We aimed to evaluate how an aetiology-based classification, as recommended in the ADA and WHO guidelines for classification of diabetes mellitus, matches clinical judgement in the Diabetes Incidence Study in Sweden (DISS), a study covering incident cases of diabetic patients aged 15 to 34 years. METHODS: During a 1-year period (1998), blood samples were taken at diagnosis and 4 months (median) thereafter. Patients were classified according to clinical judgement by the reporting physicians and assessments of islet antibodies (ICA, GADA, and IA-2A) and plasma C-peptide. RESULTS: In 1998, 422 patients were registered in DISS. Among the 313 patients participating in the follow-up, most with clinical Type 1 diabetes (185/218, 85%, 95% CI 79-89%) were islet antibody positive (ab+) at diagnosis. In addition, 14 out of 58 (24%, 14-37%) with clinical Type 2 diabetes and 21 out of 37 (57%, 40-73%) with unclassifiable diabetes were antibody positive at diagnosis. Further to this, 4 out of 33 (12%, 3-28%) were antibody negative with clinical Type 1 diabetes and 4 out of 44 (9%, 3-22%) with Type 2 had converted to antibody positive at follow-up. Among those who were constantly antibody negative, 10 out of 29 (34%, 18-54%) with clinical Type 1 and 1 out of 16 (6%, 0-30%) with unclassifiable diabetes had fasting plasma C-peptide concentrations below the normal range (
Glutamic acid decarboxylase antibodies (GADA) is the most important factor for prediction of insulin therapy within 3 years in young adult diabetic patients not classified as Type 1 diabetes on clinical grounds.
BACKGROUND: Differentiation between Type 1 and Type 2 diabetes in adults is difficult at diagnosis. In this study we tested the hypothesis that autoantibodies at diagnosis are predictive for insulin treatment within 3 years in patients initially not classified as Type 1 diabetes. METHODS: In a nationwide population-based study, blood samples were obtained from 764 patients, all diagnosed with diabetes during a 2-year period. At diagnosis, 583 (76%) were classified as Type 1, 110 (14%) as Type 2 and 71 (9.3%) could not be classified. RESULTS: Among patients not classified as Type 1 diabetes, 52 (47%) of Type 2 and 42 (59%) of unclassified patients were positive for islet cell antibodies (ICA), glutamic acid decarboxylase antibodies (GADA) or tyrosine phosphatase antibodies (IA-2A). These patients (n=94) had lower body mass index (BMI) (p
AIMS: To test the hypothesis that there is lower prevalence of islet antibodies in subjects with newly diagnosed Type 1 diabetes mellitus in young adulthood than in children is associated with less severe diabetes at time of diagnosis. METHODS: This investigation was based on a nationwide study (Diabetes Incidence Study in Sweden) of 15-34-year-old newly diagnosed diabetic subjects. During 1992-1993, all diabetic subjects (excluding secondary and gestational diabetes) were reported on standardized forms, with information about clinical characteristics at diagnosis. The study examined islet cell antibodies (ICA) by indirect immunofluorescence, and autoantibodies to glutamic acid decarboxylase (GADA), tyrosine phosphatase-like antigen (IA-2A) and insulin (IAA) as well as C-peptide by radioimmunoassay. RESULTS: Blood samples were available from 78 patients with diabetic ketoacidosis (DKA) and 517 non-acidotic patients. The prevalence of ICA (63% vs. 57%), GADA (63% vs. 66%), IA-2A (35% vs. 44%) and IAA (20% vs. 15%) were very similar in patients with or without DKA. The median levels of the four autoantibodies did not differ between the two groups. High blood glucose (P
AIM: To identify clinical, immunological and biochemical factors that predict remission, and its duration in a large cohort of young adults with Type 1 diabetes mellitus (DM). METHODS: In Sweden, 362 patients (15-34 years), classified as Type 1 DM were included in a prospective, nation-wide population-based study. All patients were followed at local hospitals for examination of HbA(1c) and insulin dosage over a median period after diagnosis of 5 years. Duration of remission, defined as an insulin maintenance dose 12 months. Among patients with antibodies (ab(+)), bivariate analysis suggested that adult age, absence of low BMI, high plasma C-peptide concentrations, lack of ketonuria or ketoacidosis at diagnosis and low insulin dose at discharge from hospital were associated with a high possibility of achieving remission. Multiple regression showed that normal weight (BMI of 20-24.9 kg/m(2)) was the only factor that remained significant for the possibility of entering remission. In survival analysis among ab(+) remitters, a low number of islet antibodies, one or two instead of three or four, were associated with a long duration of remissions. CONCLUSION: In islet antibody-positive Type 1 DM, normal body weight was the strongest factor for entering remission, whilst a low number of islet antibodies was of importance for the duration.
Institute of Medical Sciences, Uppsala University, Uppsala Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences, UmeÃ¥ University, UmeÃ¥ Department of Clinical and Experimental Medicine, LinkÃ¶ping University, LinkÃ¶ping Department of Medicine, Karolinska University Hospital Huddinge, Karolinska Institutet, Stockholm, Sweden.
Diabet. Med. 28, 156-161 (2011) ABSTRACT: Aims After initiation of treatment in Type 1 diabetes, a period with lower insulin requirement often follows, reflecting increased insulin sensitivity and improved insulin secretion. We explored if efficiency of proinsulin processing is associated with the remission phenomenon. Methods Seventy-eight patients with new-onset Type 1 diabetes were followed prospectively for 3 years. Daily insulin dosage, HbA(1c) , plasma glucose, proinsulin, C-peptide, glucagon concentrations and islet antibodies were determined at diagnosis and after 3, 6, 9, 12, 18, 24, 30 and 36 months. We studied remission, defined as an insulin dose = 0.3 U kg(-1) 24 h(-1) and HbA(1c) within the normal range, in relation to the above-mentioned variables. Results A rise and subsequent decline in plasma proinsulin and C-peptide concentrations was observed. Forty-five per cent of the patients experienced remission at one or more times, characterized by higher proinsulin and C-peptide levels, and lower proinsulin/C-peptide ratios, indicating more efficient proinsulin processing, compared with those not in remission. Non-remission also tended to be associated with higher glucagon values. Patients entering remission were more often men, had higher BMI at diagnosis, but did not differ at baseline with respect to islet antibody titres compared with patients with no remission. Conclusions Remissions after diagnosis of Type 1 diabetes were associated with lower proinsulin/C-peptide ratios, suggesting more efficient proinsulin processing, and tended to have lower glucagon release than non-remissions. This indicates that, in remission, the residual islets maintain a secretion of insulin and glucagon of benefit for control of hepatic glucose production.