Predictors of glycemic worsening in the next year in adults with screen-detected type 2 diabetes.

Background and Aims: Identifying simple markers of risk for worsening glucose can allow care providers to target therapeutic interventions according to risk of worsening glycemic control. We aimed to determine which routine clinical measures herald near-term glycemic worsening in early type 2 diabetes(T2D). Methods: The Early Diabetes Intervention Program (EDIP) was a clinical trial in individuals with screendetected T2D [HbA1C 6.3+0.63%(45+5mmol/mol)]. During the trial some participants experienced worsening fasting blood glucose (FBG). We investigated the time course of FBG, HbA1c, weight, and other clinical factors to determine which might herald glycemic worsening over the next year. Results: Progressors (62/219, 28.5%) had higher FBG than non-progressors at baseline [118 vs 130mg/dL (6.6 vs 7.2 mmol/L), p=<0.001]. FBG was stable except in the year of progression, when progressors exhibited a large 1-year rise [mean change 14.2mg/dL(0.79 mmol/L)]. Current FBG and antecedent year change in FBG were associated with progression(p<0.01), although the magnitude of change was too small to be of clinical utility (0.19 mg/dL; 0.01 mmol/L). Current or antecedent year change in HbA1c, weight, TG or HDL were not associated with progression. In the year of glycemic worsening, rising glucose was strongly associated with a concurrent increase in weight (p<0.001). Conclusions: Elevated FBG but not HbA1c identified individuals at risk for imminent glycemic worsening; the subsequent large rise in glucose was associated with a short-term increase in weight. Glucose and weight surveillance provide actionable information for those caring for patients with early diabetes.

Inaccurate diagnosis of diabetes type in youth: prevalence, characteristics, and implications.

Classifying diabetes at diagnosis is crucial for disease management but increasingly difficult due to overlaps in characteristics between the commonly encountered diabetes types. We evaluated the prevalence and characteristics of youth with diabetes type that was unknown at diagnosis or was revised over time. We studied 2073 youth with new-onset diabetes (median age [IQR] = 11.4 [6.2] years; 50% male; 75% White, 21% Black, 4% other race; overall, 37% Hispanic) and compared youth with unknown versus known diabetes type, per pediatric endocrinologist diagnosis. In a longitudinal subcohort of patients with data for ≥ 3 years post-diabetes diagnosis (n = 1019), we compared youth with steady versus reclassified diabetes type. In the entire cohort, after adjustment for confounders, diabetes type was unknown in 62 youth (3%), associated with older age, negative IA-2 autoantibody, lower C-peptide, and no diabetic ketoacidosis (all, p < 0.05). In the longitudinal subcohort, diabetes type was reclassified in 35 youth (3.4%); this was not statistically associated with any single characteristic. In sum, among racially/ethnically diverse youth with diabetes, 6.4% had inaccurate diabetes classification at diagnosis. Further research is warranted to improve accurate diagnosis of pediatric diabetes type.

Imprecise Diagnosis of Diabetes Type in Youth: Prevalence, Characteristics, and Implications.

Classifying diabetes at diagnosis is crucial for disease management but increasingly difficult due to overlaps in characteristics between the commonly encountered diabetes types. We evaluated the prevalence and characteristics of youth with diabetes type that was unknown at diagnosis or was revised over time. We studied 2073 youth with new-onset diabetes (median age [IQR]=11.4 [6.2] years; 50% male; 75% White, 21% Black, 4% other race; overall, 37% Hispanic) and compared youth with unknown versus known diabetes type, per pediatric endocrinologist diagnosis. In a longitudinal subcohort of patients with data for ≥3 years post-diabetes diagnosis (n=1019), we compared youth with unchanged versus changed diabetes classification. In the entire cohort, after adjustment for confounders, diabetes type was unknown in 62 youth (3%), associated with older age, negative IA-2 autoantibody, lower C-peptide, and no diabetic ketoacidosis (all, p<0.05). In the longitudinal subcohort, diabetes classification changed in 35 youth (3.4%); this was not statistically associated with any single characteristic. Having unknown or revised diabetes type was associated with less continuous glucose monitor use on follow-up (both, p<0.004). In sum, among racially/ethnically diverse youth with diabetes, 6.5% had imprecise diabetes classification at diagnosis. Further research is warranted to improve accurate diagnosis of pediatric diabetes type.

Central precocious puberty: From genetics to treatment.

Central precocious puberty (CPP) results from early activation of the hypothalamic - pituitary -gonadal (HPG) axis and follows the same sequence as normal puberty. While many factors involved in pubertal initiation remain poorly understood, the kisspeptin system is known to play a key role. Currently, mutations in the kisspeptin system, MKRN3, and DLK1 have been identified in sporadic and familial cases of CPP. The diagnosis is based on physical exam findings indicating advancing puberty and on laboratory tests confirming central HPG axis activation. GnRH analogs are the mainstay of treatment and are used with the goal of height preservation. Newer extended release formulations continue to be developed. Currently there is no evidence of long-term complications associated with treatment. However, many areas remain to be explored such as targeted therapies and aspects of clinical management. Further investigation into psychological effects and additional data regarding long-term outcomes, particularly in males, is needed.