In this systematic study of MODY in a large pediatric US diabetes cohort, unselected by referral pattern or family history, MODY was usually misdiagnosed and incorrectly treated with insulin. Although many type 2 diabetes-like metabolic features were less common in the mutation-positive group, no single characteristic identified all patients with mutations. Clinicians should be alert to the possibility of MODY diagnosis, particularly in antibody-negative youth with diabetes.

Islet cell autoantibodies are strongly associated with the development of type 1 diabetes. The appearance of autoantibodies to one or several of the autoantigens-GAD65, IA-2, or insulin-signals an autoimmune pathogenesis of ␤-cell killing. A ␤-cell attack may be best reflected by the emergence of autoantibodies dependent on the genotype risk factors, isotype, and subtype of the autoantibodies as well as their epitope specificity. It is speculated that progression to ␤-cell loss and clinical onset of type 1 diabetes is reflected in a developing pattern of epitopespecific autoantibodies. Although the appearance of autoantibodies does not follow a distinct pattern, the presence of multiple autoantibodies has the highest positive predictive value for type 1 diabetes. In the absence of reliable T-cell tests, dissection of autoantibody responses in subjects of genetic risk should prove useful in identifying triggers of islet autoimmunity by examining seroconversion and maturation of the autoantibody response that may mark time to onset of type 1 diabetes. The complexity of the disease process is exemplified by multiple clinical phenotypes, including autoimmune diabetes masquerading as type 2 diabetes in youth and adults. Autoantibodies may also provide prognostic information in clinically heterogeneous patient populations when examined longitudinally. Diabetes 54 (Suppl. 2):S52-S61, 2005

Transferring from pediatric to adult care, experienced by more than half the sample, was associated with an increased risk of poor glycemic control at follow-up. These findings suggest that young adults need additional support when moving to adult care.

Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) are commonly believed to be a major characteristic for type 1 diabetes (T1D). We investigated the presence of GAD65Ab in healthy individuals (n ‫؍‬ 238) and first-degree relatives (FDRs) of T1D patients (n ‫؍‬ 27) who tested negative for GAD65Ab in conventional RIAs. Sera were applied to affinity columns coated with GAD65-specific mAbs to absorb anti-idiotypic antibodies (anti-Ids). The absorbed sera were analyzed for binding to GAD65 by RIAs. Both healthy individuals and FDRs present GAD65Ab that are inhibited by anti-Id, masking them in conventional detection methods. The presence of GAD65Ab-specific anti-Ids was confirmed by competitive ELISA. Remarkably, T1D patients (n ‫؍‬ 54) and Stiff Person Syndrome patients (n ‫؍‬ 8) show a specific lack of anti-Ids to disease-associated GAD65Ab epitopes. Purified anti-Ids from healthy individuals and FDRs inhibited the binding of GAD65Ab from T1D patients to GAD65. We conclude that masked GAD65Ab are present in the healthy population and that a lack of particular anti-Ids, rather than GAD65Ab per se, is a characteristic of T1D. The lack of these inhibitory antibodies may contribute to T cell activation by GAD65Ab.T ype 1 diabetes (T1D) is an autoimmune disease characterized by the presence of serologically detectable autoantibodies to multiple islet cell autoantigens. Autoantibodies to glutamate decarboxylase 65 (GAD65Ab) can be detected in the majority of new-onset T1D patients (1), in patients with latent autoimmune diabetes in adults (for review see ref.2), diabetes-related polyendocrine diseases (for review see ref.3), and in some rare neurologic diseases, notably Stiff Person Syndrome (SPS) (4), but rarely in the general population. GAD65Ab often herald the onset of T1D by months or years and are used to predict disease together with other islet cell autoantibodies (5, 6). The function of these autoantibodies and their B cells in the pathogenesis of T1D is not clear, especially as a patient with severe B cell deficiency and diabetes was reported (7). Although GAD65Ab are often considered to be an epiphenomenon resulting from the autoimmune destruction of the pancreatic ␤ cells, some studies suggest that they may be involved in antigen processing and presentation and thus modulate the immune response (8-10). This hypothesis is supported by a recent study demonstrating a pathogenic role of autoantibodies by enhancing islet cell antigen presentation to autoreactive T cells (11). Harbers et al. (11) showed that both antigen-specific CD8 ϩ T cells and antigenspecific antibodies were necessary for the development of autoimmune diabetes in transgenic mice that express a membranebound form of ovalbumin in pancreatic ␤ cells.To investigate the possible role of GAD65Ab in T1D pathogenesis, we previously injected young nonobese diabetic (NOD) mice with the GAD65-specific mAb b96.11 (12). This antibody specificity was shown earlier to be predictive of the development of T1D in humans (13). We found that this treatment i...

IMPORTANCE Continuous glucose monitoring (CGM) is recommended for patients with type 1 diabetes; observational evidence for CGM in patients with insulin-treated type 2 diabetes is lacking.OBJECTIVE To estimate clinical outcomes of real-time CGM initiation.DESIGN, SETTING, AND PARTICIPANTS Exploratory retrospective cohort study of changes in outcomes associated with real-time CGM initiation, estimated using a difference-indifferences analysis. A total of 41 753 participants with insulin-treated diabetes (5673 type 1; 36 080 type 2) receiving care from a Northern California integrated health care delivery system (2014-2019), being treated with insulin, self-monitoring their blood glucose levels, and having no prior CGM use were included. EXPOSURES Initiation vs noninitiation of real-time CGM (reference group).MAIN OUTCOMES AND MEASURES Ten end points measured during the 12 months before and 12 months after baseline: hemoglobin A 1c (HbA 1c ); hypoglycemia (emergency department or hospital utilization); hyperglycemia (emergency department or hospital utilization); HbA 1c levels lower than 7%, lower than 8%, and higher than 9%; 1 emergency department encounter or more for any reason; 1 hospitalization or more for any reason; and number of outpatient visits and telephone visits. RESULTSThe real-time CGM initiators included 3806 patients (mean age, 42.4 years [SD, 19.9 years]; 51% female; 91% type 1, 9% type 2); the noninitiators included 37 947 patients (mean age, 63.4 years [SD, 13.4 years]; 49% female; 6% type 1, 94% type 2). The prebaseline mean HbA 1c was lower among real-time CGM initiators than among noninitiators, but real-time CGM initiators had higher prebaseline rates of hypoglycemia and hyperglycemia. Mean HbA 1c declined among real-time CGM initiators from 8.17% to 7.76% and from 8.28% to 8.19% among noninitiators (adjusted difference-in-differences estimate, −0.40%; 95% CI, −0.48% to −0.32%; P < .001). Hypoglycemia rates declined among real-time CGM initiators from 5.1% to 3.0% and increased among noninitiators from 1.9% to 2.3% (difference-in-differences estimate, −2.7%; 95% CI, −4.4% to −1.1%; P = .001). There were also statistically significant differences in the adjusted net changes in the proportion of patients with HbA 1c lower than 7% (adjusted difference-in-differences estimate, 9.6%; 95% CI, 7.1% to 12.2%; P < .001), lower than 8% (adjusted difference-in-differences estimate, 13.1%; 95% CI, 10.2% to 16.1%; P < .001), and higher than 9% (adjusted difference-in-differences estimate, −7.1%; 95% CI, −9.5% to −4.6%; P < .001) and in the number of outpatient visits (adjusted difference-indifferences estimate, −0.4; 95% CI, −0.6 to −0.2; P < .001) and telephone visits (adjusted difference-in-differences estimate, 1.1; 95% CI, 0.8 to 1.4; P < .001). Initiation of real-time CGM was not associated with statistically significant changes in rates of hyperglycemia, emergency department visits for any reason, or hospitalizations for any reason. CONCLUSIONS AND RELEVANCEIn this retrospective cohort study, insul...