First-degree relatives of women with polycystic ovary syndrome (PCOS) present hormonal and metabolic alterations compared to girls unrelated to PCOS. It is unknown whether glucose intolerance in the ...PCOS proband confers a more severe metabolic predisposition on their first-degree relatives.
To determine whether glucose tolerance status in women with PCOS is associated with worsened glucose metabolism and sex hormone levels in their peripubertal daughters or sisters.
Cross-sectional study.
Seven academic centers in North America, South America, and Europe.
Sixty-four pairs of women with PCOS and their daughters or younger sisters aged between 8 and 14 years were recruited. Twenty-five mothers or older sisters with PCOS were glucose intolerant (GI) and 39 were normal glucose tolerant (NGT).
Beta-cell function estimated by the insulin secretion-sensitivity index-2 (ISSI-2) during an oral glucose tolerance test and by the disposition index during a frequently sampled IV glucose tolerance test. Free testosterone and 17-hydroxyprogesterone (17-OHP) levels.
Being related to a GI PCOS proband was associated with a lower ISSI-2 (P-value = 0.032) after adjusting for ethnicity, body mass index z-score, and pubertal stage. They also had higher free testosterone (P-value = 0.011) and 17-OHP levels compared to girls with an NGT proband, the latter becoming significant after adjusting for confounders (P-value = 0.040).
Compared to first-degree female relatives of women with PCOS and NGT, first-degree relatives of women with PCOS and GI display lower beta-cell function and hyperandrogenemia, putting them at higher risk of GI and PCOS development.
Type 1 diabetes (T1D) is a complex, chronic autoimmune disease that affects over 1.6 million people in the United States. It is now understood that T1D may be undetected for many years while the ...disease progresses quietly without producing symptoms. T1D can be identified through diabetes-related autoantibody screening and staged accordingly, enabling healthcare providers to identify high-risk individuals in the early stages of the disease and either provide a stage-specific intervention or offer clinical trial opportunities to preserve beta cell function and anticipate the onset of clinical T1D. Evidence-based clinical practice guidelines currently do not exist for routine diabetes-related autoantibody screening of individuals at risk of developing T1D or of the general population. The purpose of this article is to help clinicians acquire an understanding of the rationale and protocols recommended for identifying patients at risk of developing T1D and monitoring such patients for autoimmune markers and progression of disease from Stage 1 to Stage 3 (clinical disease). Plain Language Summary: Type 1 diabetes (T1D) is a life-long condition where the body's immune system (which normally fights infection) mistakenly attacks cells in the pancreas that make insulin. Insulin allows one to use energy from food and controls blood sugar levels. Without early recognition and treatment, high blood sugar can cause serious symptoms and life-threatening complications, such as diabetic ketoacidosis (DKA). DKA happens when there is very low insulin, and if not spotted early, it can cause coma and death. T1D can occur at any age. The chance of getting T1D is higher if another family member has it. T1D progresses silently for months or years before symptoms appear such as increased thirst, frequent urination, and unintentional weight loss. Healthcare providers can now screen and identify people who are at early stages of T1D (without symptoms) with blood tests called autoantibodies. Early detection through screening allows people to 1) learn about the disease before symptoms start and insulin is needed, 2) potentially receive treatments that delay T1D progression, and 3) participate in research trials. By detecting T1D at early stages, people can connect with the right care team and develop the skills needed to manage later stage T1D. Early detection has been shown to prevent hospitalization and life-threatening conditions. Screening for T1D will help people maximize their opportunities to delay T1D onset while preparing for diabetes care. Keywords: Type 1 Diabetes, autoantibodies, screening, immunotherapy
Objective
To examine the prevalence of metabolic syndrome (MetS) in youth‐onset type 2 diabetes in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study.
Methods
Prevalence ...of MetS (ATP III definition) was compared at baseline (n = 679) and at 6 (n = 625) and 24 months (n = 545) using chi‐square tests. Laboratory data were examined between MetS classifications at each time point using ANOVA.
Results
Baseline prevalence of MetS was 75.8% and did not differ by treatment group or change over time. MetS was more common in females (83.1%) than males (62.3%; P < 0.0001) at baseline; this difference persisted over 24 months. Prevalence of MetS was similar between ethnic groups at baseline but greater in Hispanics (82.7%) vs. non‐Hispanic Whites (67.5%; P = 0.0017) and non‐Hispanic Blacks (72.7%; P = 0.0164) at 24 months. Although MetS was common in participants with hemoglobin A1c < 7.0% (74.4% at baseline; no significant change over 24 months), it was more common in those who did not maintain glycemic control at 6 months (80.3%; P = 0.0081). Elevated C‐reactive protein, ALT, IL‐6, and PAI‐1 levels were more frequent with MetS.
Conclusions
Persistent high prevalence of MetS in youth‐onset diabetes, even with excellent glycemic control, is of concern given the associated increased cardiovascular risk.
Context: We determined the relationship of metabolic syndrome (MBS) to polycystic ovary syndrome (PCOS).
Objective: We tested the hypothesis that parental MBS is related to the PCOS phenotype in ...their offspring.
Design/Setting: We phenotyped for MBS and PCOS in our General Clinical Research Center.
Patients: Girls with PCOS, 12–19 yr old (n = 36, including one pair of siblings), and their parents (35 mothers, 19 fathers) were recruited from the Pediatric Endocrinology Clinic. Healthy girls, 12–19 yr old (n = 21), were recruited as a reference population.
Interventions: We measured anthropometrics, blood pressure, fasting lipids and androgens, oral glucose tolerance, and ultrasonographically determined polycystic ovary status.
Main Outcome Measures: MBS in parents, and PCOS features in mothers, were related to the presence of PCOS features in probands.
Results: Fathers had strikingly high prevalence of excess adiposity (94% were obese or overweight) and MBS (79%). Premenopausal mothers more commonly had MBS (36%) than features of PCOS (≤22%). Polycystic ovaries in proband offspring of premenopausal mothers were associated with maternal polycystic ovaries only in a minority of cases. Proband polycystic ovary status was completely concordant to fathers’ MBS status (P = 0.008), but not their own or their mothers’ MBS status, in families whose premenopausal mothers lacked polycystic ovaries. Proband prevalence of MBS was 27.8%, 3-fold greater than expected for obesity status.
Conclusion: Familial factors related to paternal MBS seem to be fundamental to the pathogenesis of PCOS.
Objectives: Type 1 diabetes (T1D) is strongly linked with an increase in stress, depression, and anxiety. Mental health care is widely acknowledged to be an essential component of T1D clinical care. ...However, it has proven challenging to identify a successful model of mental health care for T1D. We investigated whether art therapy could be used in the psychological care of patients with T1D. Art therapy allows for the expression and exploration of complex emotions related to illness in an age-appropriate manner, and has been shown to be an effective mental health therapy in other chronic illnesses, but has not been studied in T1D.
Methods: We evaluated the effectiveness of an art therapy intervention for stress management in T1D patients. We administered a 17-question questionnaire to 22 sequential patients referred to the on-site art therapist. Mean age of the subjects was 13.1 +/- 7.5 years (range: 8-40 years) and mean duration of diabetes was 5.3 +/- 5 years. The subjects saw the art therapist a mean of 7 +/- 6.4 visits prior to completing the questionnaire.
Results: All participants found the sessions stress reducing and planned to continue with ongoing therapy and to incorporate strategies learned into diabetes self-care. The most common responses associated with art therapy were “calm,” “safe,” “feeling understood,” “less overwhelmed.” The average A1c prior to receiving art therapy was 8.7+/-1.8%, and fell to 7.7% +/- 1.5% after a mean of 7 art therapy sessions.
Conclusions: Art therapy was a well-received effective mental health treatment in reducing stress in T1D. In this sample, glucose control improved as well. Art therapy is a novel modality in the psychological care of patients living with T1D that can alleviate some of the psychological burden of the disease, a treatment that will be studied in a larger trial.
Disclosure
C. Lampron: None. R. Goland: None. N. Leibel: None.
Context: We report herein a remarkable family in which the mother of a woman with 46,XY complete gonadal dysgenesis was found to have a 46,XY karyotype in peripheral lymphocytes, mosaicism in ...cultured skin fibroblasts (80% 46,XY and 20% 45,X) and a predominantly 46,XY karyotype in the ovary (93% 46,XY and 6% 45,X).
Patients: A 46,XY mother who developed as a normal woman underwent spontaneous puberty, reached menarche, menstruated regularly, experienced two unassisted pregnancies, and gave birth to a 46,XY daughter with complete gonadal dysgenesis.
Results: Evaluation of the Y chromosome in the daughter and both parents revealed that the daughter inherited her Y chromosome from her father. Molecular analysis of the genes SOX9, SF1, DMRT1, DMRT3, TSPYL, BPESC1, DHH, WNT4, SRY, and DAX1 revealed normal male coding sequences in both the mother and daughter. An extensive family pedigree across four generations revealed multiple other family members with ambiguous genitalia and infertility in both phenotypic males and females, and the mode of inheritance of the phenotype was strongly suggestive of X-linkage.
Conclusions: The range of phenotypes observed in this unique family suggests that there may be transmission of a mutation in a novel sex-determining gene or in a gene that predisposes to chromosomal mosaicism.
We report herein a remarkable family in which the mother of a woman with 46,XY complete gonadal dysgenesis was found to have a 46,XY karyotype in peripheral lymphocytes, mosaicism in cultured skin ...fibroblasts (80% 46,XY and 20% 45,X), and a predominantly 46,XY karyotype in the ovary (95% 46,XY and 5% 45,X).
Objectives: To study the real-world effect of hybrid closed loop systems (HCLS) on glycemic control and quality of life (QoL) in pediatric patients with T1D.
Methods: Patients 2-20 years old with T1D ...for ≥ 1 year were recruited when starting t:slim x2 with CIQ (TS) or Omnipod 5 (O5). We collected time in range (TIR), time low (BG <70 mg/dl), A1c, and QoL survey responses at baseline and 3 months. Kruskal-Wallis rank sum test and chi-squared test were used for data analysis.
Results: Baseline data is in Figure 1. TIR improved by 7% after 3 months of HCLS use (p=0.004). Time low was unchanged after 3 months (p=0.3). Figure 2 shows results by subject.
Discussion: In this real-world study, HCLS improved TIR at 3 months without change in hypoglycemia. Data collection, enrollment, and analysis are ongoing with more results (A1c, QoL surveys) expected shortly.
Disclosure
C.V. Tillotson: None. P.H. Nichols: None. K. Mofford: None. N. Leibel: None. R. Gandica: None.
Funding
National Institutes of Health (5T32DK065522-18)
A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) ...(2.5 mg/kg) preserved β-cell function and reduced HbA1c for 1 year in new-onset type 1 diabetes. Subjects (N = 89) were randomized to 1) ATG and pegylated granulocyte colony-stimulating factor (GCSF), 2) ATG alone, or 3) placebo. Herein, we report 2-year area under the curve (AUC) C-peptide and HbA1c, prespecified secondary end points, and potential immunologic correlates. The 2-year mean mixed-meal tolerance test–stimulated AUC C-peptide, analyzed by ANCOVA adjusting for baseline C-peptide, age, and sex (n = 82) with significance defined as one-sided P < 0.025, was significantly higher in subjects treated with ATG versus placebo (P = 0.00005) but not ATG/GCSF versus placebo (P = 0.032). HbA1c was significantly reduced at 2 years in subjects treated with ATG (P = 0.011) and ATG/GCSF (P = 0.022) versus placebo. Flow cytometry analyses demonstrated reduced circulating CD4:CD8 ratio, increased regulatory T-cell:conventional CD4 T-cell ratios, and increased PD-1+CD4+ T cells following low-dose ATG and ATG/GCSF. Low-dose ATG partially preserved β-cell function and reduced HbA1c 2 years after therapy in new-onset type 1 diabetes. Future studies should determine whether low-dose ATG might prevent or delay the onset of type 1 diabetes.
We evaluated the performance of the iLet bionic pancreas (BP) in non-Hispanic White individuals (here referred to as "Whites") and in Black, Hispanic, and other individuals (here collectively ...referred to as "Minorities").
A multicenter, randomized controlled trial evaluated glycemic management with the BP versus standard of care (SC) in 161 adult and 165 pediatric participants with type 1 diabetes over 13 weeks.
In Whites (n = 240), the mean baseline-adjusted difference in 13-week HbA1c between the BP and SC groups was -0.45% (95% CI -0.61 to -0.29 -4.9 mmol/mol; -6.6 to -3.1; P < 0.001), while this difference among Minorities (n = 84) was -0.53% (-0.83 to -0.24 -6.0 mmol/mol; -9.2 to -2.8; P < 0.001). In Whites, the mean baseline-adjusted difference in time in range between the BP and SC groups was 10% (95% CI 7-12; P < 0.001) and in Minorities was 14% (10-18; P < 0.001).
The BP improves glycemic control in both Whites and Minorities and offers promise in decreasing health care disparities.
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