Hypogonadotropic hypogonadism presenting with arhinia: a case report

INTRODUCTION: Arhinia, congenital absence of the nose, is a rare malformation. We present the third reported case of arhinia accompanied by hypogonadism and demonstrate that this is due to gonadotropin deficiency. CASE PRESENTATION: A 13-year-old Caucasian boy with congenital arhinia presented for evaluation of delayed puberty and micropenis. We examined genes known to be associated with hypogonadotropic hypogonadism for mutations and performed a chromosomal microarray to assess copy number variation. CONCLUSION: No mutations in KAL1, FGFR1, PROK2, PROKR2, FGF8, CHD7 and GnRHR were identified in our patient and there were no copy number variations observed that would explain the phenotype. Though studies are limited in such patients, we suggest that hypogonadotropic hypogonadism is associated with arhinia and that the two entities likely result from a common genetic cause that affects early nasal development and gonadotropin-releasing hormone neuron formation or migration

Sex Differences in Vascular Compliance in Normal-Weight but Not Obese Boys and Girls: The Effect of Body Composition

Objectives. To determine the effect of sex and obesity on vascular function in children and explore potential mechanisms that account for differences in vascular function. Methods. Participants were 61 (30 boys) normal-weight (BMI 25–75% ile for age and sex) and 62 (30 boys) obese (BMI ≥ 95% ile) children of ages 8–18 years. Measurements of large and small artery elastic index (LAEI and SAEI, resp.) and reactive hyperemia index (RHI) were obtained at rest, along with anthropometric and biochemical information. Results. In normal-weight children, LAEI was 16% higher in males than females (P = 0.04) with a similar trend for SAEI (13% higher in males, P = 0.067). In obese children, no sex-related differences in vascular measures were observed. In multivariable models, sex differences in arterial compliance were explained by higher lean mass in normal-weight boys. Fat mass predicted LAEI and SAEI in both normal-weight and obese females, but fat mass predicted arterial compliance in boys when fat mass exceeded 24 kg (37% of the sample). Conclusions. Normal-weight males have higher arterial compliance than normal-weight females due to increased lean mass, but sex-related differences were not observed among obese children due to a lack of sex-related differences in lean or fat mass

Long-term complications in youth-onset type 2 diabetes

BACKGROUND: The prevalence of type 2 diabetes in youth is increasing, but little is known regarding the occurrence of related complications as these youths transition to adulthood. METHODS: We previously conducted a multicenter clinical trial (from 2004 to 2011) to evaluate the effects of one of three treatments (metformin, metformin plus rosiglitazone, or metformin plus an intensive lifestyle intervention) on the time to loss of glycemic control in participants who had onset of type 2 diabetes in youth. After completion of the trial, participants were transitioned to metformin with or without insulin and were enrolled in an observational follow-up study (performed from 2011 to 2020), which was conducted in two phases; the results of this follow-up study are reported here. Assessments for diabetic kidney disease, hypertension, dyslipidemia, and nerve disease were performed annually, and assessments for retinal disease were performed twice. Complications related to diabetes identified outside the study were confirmed and adjudicated. RESULTS: At the end of the second phase of the follow-up study (January 2020), the mean (±SD) age of the 500 participants who were included in the analyses was 26.4±2.8 years, and the mean time since the diagnosis of diabetes was 13.3±1.8 years. The cumulative incidence of hypertension was 67.5%, the incidence of dyslipidemia was 51.6%, the incidence of diabetic kidney disease was 54.8%, and the incidence of nerve disease was 32.4%. The prevalence of retinal disease, including more advanced stages, was 13.7% in the period from 2010 to 2011 and 51.0% in the period from 2017 to 2018. At least one complication occurred in 60.1% of the participants, and at least two complications occurred in 28.4%. Risk factors for the development of complications included minority race or ethnic group, hyperglycemia, hypertension, and dyslipidemia. No adverse events were recorded during follow-up. CONCLUSIONS: Among participants who had onset of type 2 diabetes in youth, the risk of complications, including microvascular complications, increased steadily over time and affected most participants by the time of young adulthood. Complications were more common among participants of minority race and ethnic group and among those with hyperglycemia, hypertension, and dyslipidemia. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; ClinicalTrials.gov numbers, NCT01364350 and NCT02310724.)

Pseudohypertriglyceridemia: A Novel Case with Important Clinical Implications

Pseudohypertriglyceridemia is an overestimation of serum triglyceride levels that may incorrectly lead to a diagnosis of hypertriglyceridemia. Glycerol kinase deficiency is a condition in which glycerol cannot be phosphorylated to glycerol-3-phosphate, resulting in elevated levels of serum glycerol. Laboratory assays that measure triglycerides indirectly may be affected by elevated glyerol levels and incorrectly report serum tryglyceride levels. We present a case of a novel missense mutation in the GK gene leading to isolated glycerol kinase deficiency and pseudohypertriglyceridemia in a male infant of a mother with gestational diabetes. This paper reviews glycerol kinase deficiency, describes the challenges in diagnosing pseudohypertriglyceridemia, and provides suggestions on improving diagnostic accuracy. Additionally, a potential maternal-fetal interaction between gestational diabetes and glycerol kinase deficiency is discussed

Lipoprotein abnormalities in compound heterozygous lipoprotein lipase deficiency after treatment with a low-fat diet and orlistat

BackgroundThe treatment of familial hyperchylomicronemia presenting in early childhood with episodes of pancreatitis has been ineffective, and affected patients remain at risk for pancreatitis.ObjectiveTo report on the effect of orlistat in siblings with severe inherited hyperchylomicronemia and to assess posttreatment lipoprotein concentrations and composition.MethodsSerial observations of plasma lipid levels and hospitalizations after treatment with orlistat and lipoprotein studies on a single fasting posttreatment sample.ResultsThe affected siblings inherited a lipoprotein lipase gene mutation from each of their parents: a novel mutation from their father (c.542G > C, p.G181R) and a known missense mutation from their mother (c.644G > A, p.G215E). When the boy presented to us at age 9 years of age and his sister at age 7 years, we found that addition of orlistat, a pancreatic lipase inhibitor, at a dose of 120 mg given before three low-fat meals a day was effective in reducing episodes of pancreatitis in the boy and in maintaining the triglyceride at lower levels in both children. During treatment, the children were observed to have elevations in apolipoprotein (apo)B, low-density lipoprotein particle concentration, abnormal apoB-containing subclasses, and deficiencies in apoA-I and apoA-II-containing lipoproteins, changes consistent with continuing increased cardiovascular risk.ConclusionThe data support the need for more effective long-term treatments that not only prevent pancreatitis but also offset cardiovascular risk. Orlistat can be considered effective in augmenting the effect of a low-fat diet and reducing risk for pancreatitis

Benefits and barriers to participating in longitudinal research of youth-onset type 2 diabetes: Results from the TODAY retention survey.

BACKGROUND/AIMS: Conducting longitudinal research related to chronic illness in adolescents is inherently challenging due to developmental changes and psychosocial stressors. Participants in the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial were socio-economically disadvantaged as well. This study assessed attitudes and beliefs about retention in TODAY to shed light on the factors that potentially promote and detract from the likelihood of sustained participation. METHODS: After an average 7.3 years of follow-up (range 4.9-9.5), TODAY participants completed a survey examining their perceptions of the benefits and barriers to sustained involvement in the protocol. RESULTS: The most common reasons for staying in TODAY included having a strong relationship with the medical team, getting study-provided diabetes care, access to free diabetes medicine and supplies, and being part of a large study to learn more about how to care for youth-onset type 2 diabetes. The most commonly endorsed challenges included scheduling conflicts, possibly disappointing others, difficulties getting to study visits, and the occurrence of other medical issues. CONCLUSIONS: Similar to other published reports, a supportive relationship with study staff was commonly endorsed as a benefit of engagement in the longitudinal study, suggesting that rapport, staff consistency, and relationship quality are important components of optimal retention. Moreover, our findings suggest the value of trying to remove logistical barriers, such as transportation and scheduling challenges, in order to promote long-term participation in research. Further research is recommended to evaluate factors that contribute to attrition versus retention in an a priori manner within longitudinal studies, especially protocols involving cohorts that are more vulnerable to attrition due to developmental transitions and/or socio-economic challenges. Additional efforts to optimize quantitative and qualitative measurement of barriers would also help to expand our understanding of how to optimally retain participants in longitudinal protocols

Impact of youth onset type 2 diabetes during pregnancy on microvascular and cardiac outcomes

AIMS: To examine the impact of pregnancy on microvascular and cardiovascular measures in women with youth-onset T2D. METHODS: Microvascular and cardiovascular measures were compared in in a cohort of 116 women who experienced a pregnancy of ≥ 20 weeks gestation and 291 women who did not among women in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) study. RESULTS: Cox regression models adjusted for participant characteristics at baseline including age, race/ethnicity, household income, diabetes duration, HbA1c (\u3e6%), and BMI, demonstrated those who experienced pregnancy had 2.76 (1.38-5.49; p = 0.004) fold increased risk of hyperfiltration (eGFR ≥ 135 ml/min/1.73 m), compared to those without a pregnancy. No differences were observed in rates of retinopathy (48.9% vs. 41.1%) or neuropathy (23.3% vs. 16.3%) in women who experienced pregnancy vs. women who did not, respectively. In fully adjusted models, pregnancy did not impact changes in echocardiographic or arterial stiffness compared to changes in women who were never pregnant. CONCLUSIONS: These results indicate that pregnancy increases the risk of hyperfiltration in women with youth-onset T2D, but not other micro or macrovascular complications. The rates of vascular complications are very high in youth-onset T2D potentially obscuring micro- and macrovascular changes attributable to pregnancy. CLINICAL TRIAL INFORMATION: ClinicalTrials.gov numbers,NCT01364350andNCT02310724