OBJECTIVE—The aim of this study was to compare the prevalence of being overweight in black and white children and adolescents at onset of insulin-treated diabetes during two time periods: 1979–1989 (period I) and 1990–1998 (period II). RESEARCH DESIGN AND METHODS—All black children <19 years of age diagnosed with diabetes and treated with insulin at onset admitted to the Children’s Hospital of Pittsburgh between January 1979 and December 1998 were matched with white children by sex, age at onset, and year of diagnosis. Data were obtained from a review of medical records. Overweight was defined as BMI ≥85th percentile for age and sex. Islet cell autoantibodies were measured. RESULTS—The prevalence of being overweight increased from 12.6% (period I) to 36.8% (period II) (P = 0.0003); in whites from 2.9 to 16.6% (P = 0.04) and in blacks from 22 to 55% (P = 0.001); and in the age-group <11 years from 7.3 to 22.2% (P = 0.04) and age 11–18 years from 20 to 50% (P = 0.006). In children with at least one antibody, the prevalence of being overweight increased from 5.1 to 24.4% (P = 0.001). In the multivariate logistic regression, period of diagnosis (period II), race (black), age at onset (≥11 years old), and absence of autoimmunity were associated with being overweight. CONCLUSIONS—At onset of the disease, the prevalence of being overweight has tripled from the 1980s to the 1990s, following the trend in the general population. Weight gain may be an accelerating factor for onset of insulin-treated diabetes and may have contributed to the increased incidence of diabetes in youth seen in some populations.

Objective: We examined the reproducibility of the oral glucose tolerance test (OGTT) in overweight children and evaluated distinguishing characteristics between those with concordant vs. discordant results. Design: Sixty overweight youth (8–17 yr old) completed two OGTTs (interval between tests 1–25 d). Insulin sensitivity was assessed by the surrogate measures of fasting glucose to insulin ratio, whole-body insulin sensitivity index, and homeostasis model assessment of insulin resistance, and insulin secretion by the insulinogenic index with calculation of the glucose disposition index (GDI). Results: Of the 10 subjects with impaired glucose tolerance (IGT) during the first OGTT only three (30%) had IGT during the second OGTT. The percent positive agreement between the first and second OGTT was low for both impaired fasting glucose and IGT (22.2 and 27.3%, respectively). Fasting blood glucose had higher reproducibility, compared with the 2-h glucose. Youth with discordant OGTTs, compared with those with concordant results, were more insulin resistant (glucose/insulin 2.7 ± 1.4 vs. 4.1 ± 1.8, P = 0.006, whole-body insulin sensitivity index of 1.3 ± 0.6 vs. 2.2 ± 1.1, P = 0.003, and homeostasis model assessment of insulin resistance 10.6± 8.1 vs. 5.7 ± 2.8, P = 0.001), had a lower GDI (0.45 ± 0.58 vs. 1.02 ± 1.0, P = 0.03), and had higher low-density lipoprotein cholesterol (117.7 ± 36.6 vs. 89.9 ± 20.1, P = 0.0005) without differences in physical characteristics. Conclusions: Our results show poor reproducibility of the OGTT in obese youth, in particular for the 2-h plasma glucose. Obese youth who have discordant OGTT results are more insulin resistant with higher risk of developing type 2 diabetes mellitus, as evidenced by a lower GDI. The implications of this remain to be determined in clinical and research settings.

OBJECTIVE: Previous studies showed that inhibiting lymphocyte costimulation reduces declining β-cell function in individuals newly diagnosed with type 1 diabetes. We tested whether abatacept would delay or prevent progression of type 1 diabetes from normal glucose tolerance (NGT) to abnormal glucose tolerance (AGT) or to diabetes and the effects of treatment on immune and metabolic responses.RESEARCH DESIGN AND METHODS: We conducted a phase 2, randomized, placebo-controlled, double-masked trial of abatacept in antibody-positive participants with NGT who received monthly abatacept/placebo infusions for 12 months. The end point was AGT or diabetes, assessed by oral glucose tolerance tests.RESULTS: A total of 101 participants received abatacept and 111 placebo. Of these, 81 (35 abatacept and 46 placebo) met the end point of AGT or type 1 diabetes diagnosis (hazard ratio 0.702; 95% CI 0.452, 1.09; P = 0.11) The C-peptide responses to oral glucose tolerance tests were higher in the abatacept arm (P < 0.03). Abatacept reduced the frequency of inducible T-cell costimulatory (ICOS)+ PD1+ T-follicular helper (Tfh) cells during treatment (P < 0.0001), increased naive CD4+ T cells, and also reduced the frequency of CD4+ regulatory T cells (Tregs) from the baseline (P = 0.0067). Twelve months after treatment, the frequency of ICOS+ Tfh, naive CD4+ T cells, and Tregs returned to baseline.CONCLUSIONS: Although abatacept treatment for 1 year did not significantly delay progression to glucose intolerance in at-risk individuals, it impacted immune cell subsets and preserved insulin secretion, suggesting that costimulation blockade may modify progression of type 1 diabetes.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programs are being increasingly emphasized. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody–positive (IAb+) children and adults who are at risk for (confirmed single IAb+) or living with (multiple IAb+) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in nonspecialized settings. To inform this monitoring, JDRF, in conjunction with international experts and societies, developed consensus guidance. Broad advice from this guidance includes the following: 1) partnerships should be fostered between endocrinologists and primary care providers to care for people who are IAb+; 2) when people who are IAb+ are initially identified, there is a need for confirmation using a second sample; 3) single IAb+ individuals are at lower risk of progression than multiple IAb+ individuals; 4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; 5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and 6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasizes significant unmet needs for further research on early-stage type 1 diabetes to increase the rigor of future recommendations and inform clinical care.

Given the proven benefits of screening to reduce diabetic ketoacidosis (DKA) likelihood at the time of stage 3 type 1 diabetes diagnosis, and emerging availability of therapy to delay disease progression, type 1 diabetes screening programmes are being increasingly emphasised. Once broadly implemented, screening initiatives will identify significant numbers of islet autoantibody-positive (IAb⁺) children and adults who are at risk of (confirmed single IAb⁺) or living with (multiple IAb⁺) early-stage (stage 1 and stage 2) type 1 diabetes. These individuals will need monitoring for disease progression; much of this care will happen in non-specialised settings. To inform this monitoring, JDRF in conjunction with international experts and societies developed consensus guidance. Broad advice from this guidance includes the following: (1) partnerships should be fostered between endocrinologists and primary-care providers to care for people who are IAb⁺; (2) when people who are IAb⁺ are initially identified there is a need for confirmation using a second sample; (3) single IAb⁺ individuals are at lower risk of progression than multiple IAb⁺ individuals; (4) individuals with early-stage type 1 diabetes should have periodic medical monitoring, including regular assessments of glucose levels, regular education about symptoms of diabetes and DKA, and psychosocial support; (5) interested people with stage 2 type 1 diabetes should be offered trial participation or approved therapies; and (6) all health professionals involved in monitoring and care of individuals with type 1 diabetes have a responsibility to provide education. The guidance also emphasises significant unmet needs for further research on early-stage type 1 diabetes to increase the rigour of future recommendations and inform clinical care. Graphical Abstract