Clinical management of diazoxide-unresponsive congenital hyperinsulinism: A single-center experience.

The most common cause of persistent hypoglycemia in newborns and children is congenital hyperinsulinism (CHI). Remarkable advancements in diagnostic tools and treatments, including novel imaging and genetic techniques, and continuous subcutaneous octreotide administration, have improved the prognosis of diazoxide-unresponsive CHI; however, in clinical practice, some issues remain. Here, we report a case series consisting of four adenosine triphosphate-sensitive potassium-associated CHI cases, discuss the practical use of new international guidelines published in 2023, and suggest clinical issues associated with CHI management. Based on the clinical experience of two diffuse and two focal CHI cases, we employed an updated treatment strategy, including genetic diagnosis to determine treatment plans, careful catheter management, switching from octreotide to long-acting somatostatin, effective utilization of a continuous glucose monitoring (CGM) device, measures for feeding problems, and individualized and systematic developmental follow-up. Particularly, our cases suggest a safe method of switching from octreotide to lanreotide, elucidate the efficacy of home-based CGM monitoring, and indicate need for personalized support for feeding problems. Severe CHI is a rare and challenging disorder; thus, further accumulation of experience according to new treatment strategies is essential in generating high-quality evidence for the development and approval of new treatment options.

Effect of feeding sodium butyrate to beef female cows during pre- and post-partum period on concentrations of glucagon-like peptides in plasma and colostrum.

The objective of this study was to evaluate the effect of feeding beef cows with sodium butyrate during the late pregnancy and early post-partum periods on concentrations of glucagon-like peptide (GLP)-1 and 2 in plasma, colostrum, and transition milk. Twelve Japanese Black female cows were fed concentrate feed without (CON; n = 6) or with (BUTY; n = 6) sodium butyrate supplementation at 1.1% of dietary dry matter from -60 d relative to the expected parturition date to 4 d after parturition. Plasma total cholesterol concentration was higher for the BUTY than for the CON (P = 0.04). In addition, plasma GLP-1 concentration was higher for the BUTY than for the CON at 3 d after calving (P < 0.05). This study showed for the first time that GLP-1 is present in the colostrum of Japanese Black cows at higher concentrations as compared to in plasma (P < 0.01). On the other hand, no treatment effect was observed for concentrations of metabolite and hormone in colostrum and transition milk. In summary, feeding beef cows with sodium butyrate during the late gestation and early post-partum period likely increases plasma GLP-1 concentrations post-partum without affecting the components of colostrum and transition milk.

Effect of Ca-octanoate supplementation on concentrations of ghrelin and ghrelin-related hormones in plasma and milk of beef cattle.

We aimed to evaluate the effect of dietary calcium (Ca)-octanoate supplementation on concentrations of ghrelin, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and insulin in plasma and milk of beef cattle during late gestation and early postpartum. Twelve Japanese Black cattle were offered concentrate without (CON, n = 6) or with Ca-octanoate supplementation at 1.5% of dietary dry matter (OCT, n = 6). Blood samples were collected at -60, -30, and -7 d relative to the expected parturition date and daily from d 0 to 3 after parturition. Milk samples were collected daily postpartum. Compared to the CON group, concentrations of acylated ghrelin increased in plasma as parturition approached in the OCT group (P = 0.02). However, concentrations of GH, IGF-1, and insulin in plasma and milk were not affected by treatment groups throughout the study. Additionally, we showed for the first time that bovine colostrum and transition milk contain acylated ghrelin at a significantly higher concentration than plasma (P = 0.01). Interestingly, concentrations of acylated ghrelin in milk were negatively correlated with those in plasma postpartum (r = -0.50, P < 0.01). Feeding Ca-octanoate increased concentrations of total cholesterol (T-cho) in plasma and milk (P < 0.05), tended to increase those of glucose in plasma at postpartum and milk (P < 0.1). We conclude that feeding Ca-octanoate in late gestation and early postpartum may contribute to increased concentrations of glucose and T-cho in plasma and milk without affecting concentrations of ghrelin, GH, IGF-1, and insulin in plasma and milk.

Phenotypic Variation in 46,XX Disorders of Sex Development due to the Fourth Zinc Finger Domain Variant of WT1: A Familial Case Report.

INTRODUCTION: The variants in the zinc finger (ZF) domains 1-3 in WT1 are one of the major causes of 46,XY disorders of sex development (DSD). Recently, variants in the fourth ZF (ZF4 variants) were reported to cause 46,XX DSD. However, all the 9 patients reported were de novo, and no familial cases were identified. CASE PRESENTATION AND RESULTS: The proband (16-year-old social female) had a 46,XX karyotype with dysplastic testes and moderate virilization in genitalia. A ZF4 variant, p.Arg495Gln, in WT1 was identified in the proband, her brother, and mother. The mother did not show any virilization with normal fertility, and the 46,XY brother developed normal puberty. CONCLUSION: The phenotypic variations due to the ZF4 variant are extremely broad in 46,XX cases.

Glucagon-like peptide 2 (GLP-2) in bovine colostrum and transition milk.

Bovine colostrum contains growth factors, cytokines, hormones, and enzymes, which have important roles in stimulating gastrointestinal development of neonatal calves. In the present study, we measured the concentration of glucagon-like peptide 2 (GLP-2), one of the gut-derived peptides secreted from intestinal L-cells, in colostrum and transition milk of Japanese black cattle. All colostrum samples were collected within 24 h after calving (d 0) and transition milk was collected at 24, 48 and 72 h relative to the time at colostrum sampling (d 1, d 2 and d 3, respectively). Concentrations of GLP-2 in colostrum were 5.53 ± 1.07 ng/mL on average (range = 0.94-9.60 ng/mL) and decreased from d 0 to 3 (P < 0.01). Furthermore, concentrations of GLP-2 in colostrum and transition milk were quadratically decreased with the elapsed time from parturition until colostrum sampling (R2 = 0.48, P < 0.01). Our results show for the first time that GLP-2 is present in bovine colostrum and transition milk and that concentrations decreased with elapsed time from parturition.