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An increasing number of women with urea cycle disorders (UCDs) are reaching child‐bearing age and becoming pregnant. Improved diagnostics and increased awareness of inherited metabolic diseases has also led to more previously undetected women being diagnosed with a UCD during or shortly after pregnancy. Pregnancy increases the risk of acute metabolic decompensation with hyperammonemia—which can occur in any trimester, and/or the postpartum period, and may lead to encephalopathy, psychosis, coma, and even death, if not diagnosed promptly and treated appropriately. There are also (theoretical) concerns that a maternal UCD, or its treatment, may cause potential risks for the unborn child. Currently evidence on management and outcome of pregnancies in UCDs is limited to case reports and there are no clear guidelines. In order to inform management and investigate outcomes of pregnancies in women with a UCD, we performed a retrospective review of published cases and analyzed data collected from an international online survey. We conclude that, although risk during the intra‐ and postpartum period exists, multidisciplinary management by an experienced team and a prospective plan usually result in successful pregnancy, labor, delivery, and postpartum period. No deaths were reported in mothers managed accordingly. With the exception of male neonates with Ornithine Transcarbamylase deficiency, the clinical outcome of children born to mothers with UCDs appears positive, although follow‐up is limited. The outcome for women presenting with a first acute metabolic decompensation during pregnancy or postpartum is less favorable. Deaths were associated with diagnostic delay/late management of hyperammonemia in previously undiagnosed women. [ABSTRACT FROM AUTHOR]

Aims: To compare outcomes of glucagon‐stimulated C‐peptide tests (GSCTs) in people with latent autoimmune diabetes in adults (LADA) after a 21‐month intervention with either insulin or the dipeptidyl peptidase‐4 inhibitor sitagliptin. Research design and methods: We included 64 glutamic acid decarboxylase (GAD) antibody‐positive individuals, who were diagnosed with diabetes <3 years before the study, aged 30 to 70 years, and without clinical need for insulin treatment. We stratified participants by age and body mass index (BMI) and evaluated β‐cell function by GSCT after a 48‐hour temporary withdrawal of study medication. Results: Age at randomization (mean 53 years), BMI (mean 27 kg/m2) and metabolic markers were similar between treatment arms. Glycated haemoglobin concentrations during intervention did not differ between arms. Fasting C‐peptide concentrations after the intervention were similar, as were stimulated C‐peptide levels (0.82 ± 0.63 nmol/L after insulin, 0.82 ± 0.46 nmol/L after sitagliptin; nonsignificant). Autoimmunity in the study population (estimated from GAD antibody titres and positivity/no positivity for zinc transporter 8 and islet antigen 2 antibodies) affected the evolution of the GSCT results significantly, which deteriorated in participants with high but not in those with low autoimmunity. Adjustment using analysis of covariance for the degree of autoimmunity did not alter the findings of no difference between treatment arms. Conclusions: β‐cell function after intervention was similar in patients with insulin‐ and sitagliptin‐treated LADA, regardless of the strength of autoimmunity. Further, participants with low levels of GAD antibodies did not experience progressive deterioration of β‐cell function over a 21‐month period. Taken together, these findings could be useful for clinicians' choices of treatment in people with LADA. [ABSTRACT FROM AUTHOR]

Glycogen metabolism in β-cells may affect downstream metabolic pathways controlling insulin release. We examined glycogen metabolism in human islets and in the rodent-derived INS-1 832/13 β-cells and found them to express the same isoforms of key enzymes required for glycogen metabolism. Our findings indicate that glycogenesis is insulin-independent but influenced by extracellular glucose concentrations. Levels of glycogen synthase decrease with increasing glucose concentrations, paralleling accumulation of glycogen. We did not find cAMP-elicited glycogenolysis and insulin secretion to be causally related. In conclusion, our results reveal regulated glycogen metabolism in human islets and insulin-secreting cells. Whether glycogen metabolism affects insulin secretion under physiological conditions remains to be determined. [ABSTRACT FROM AUTHOR]

Objective While impaired glucose tolerance diagnosed by the oral glucose tolerance test (OGTT) is a common trait in obese individuals, less is known about changes in levels of other metabolites. The aim was to reveal the complex alterations in metabolite levels provoked by an OGTT and its perturbation in obese individuals. Methods Gas chromatography/mass spectrometry was used to profile metabolite levels in serum from 14 obese participants (body mass index [BMI] of 43.6 ± 1.5 kg m−2 [mean ± SEM]) at 0, 30, and 120 min during a standard 2-h 75 g OGTT. Metabolite profiles from six lean individuals (BMI of 22.4 ± 2.4 kg m−2), collected from a previous study, were included for comparison. Results In the obese group, 59 metabolite profiles were determined. Among these, 16 deviated from profiles in the lean group. Deviating metabolites were categorized into three groups. Delayed reduction in levels of five fatty acids. Increased levels at 30 min of five amino acids, including isoleucine and leucine. A blunted increase at 30 min of six metabolites. Conclusions Metabolomics analysis revealed distinct differences in alterations of metabolite levels during an OGTT in obese and lean subjects. To this end, our data suggests a disrupted regulation of ketogenesis, lipolysis and proteolysis in obese individuals. [ABSTRACT FROM AUTHOR]