Association of gestational and childhood circulating C-peptide concentrations in the hyperglycemia and adverse pregnancy outcomes follow-up study.

Aims: This study examined the association of gravida C-peptide with progeny islet function and insulin sensitivity in the Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS).

Methods: Pregnancy 3rd trimester oral glucose tolerance test (OGTT), cord blood, and offspring OGTT glucose, C-peptide and insulin at age 10-14 years were analyzed for 4,121 mother-child dyads. Gravida fasting and 1-hour C-peptide concentration correlations with cord blood and childhood C-peptide, insulin, insulinogenic index and insulin sensitivity, and insulin resistance [HOMA-IR]), were assessed by multiple linear regression.

Permanent neonatal diabetes-causing insulin mutations have dominant negative effects on beta cell identity.

Objective: Heterozygous coding sequence mutations of the INS gene are a cause of permanent neonatal diabetes (PNDM), requiring insulin therapy similar to T1D. While the negative effects on insulin processing and secretion are known, how dominant insulin mutations result in a continued decline of beta cell function after birth is not well understood.

Methods: We explored the causes of beta cell failure in two PNDM patients with two distinct INS mutations using patient-derived iPSCs and mutated hESCs.

Neurodevelopmental Programming of Adiposity: Contributions to Obesity Risk.

This review analyzes the published evidence regarding maternal factors that influence the developmental programming of long-term adiposity in humans and animals via the central nervous system (CNS). We describe the physiological outcomes of perinatal underfeeding and overfeeding and explore potential mechanisms that may mediate the impact of such exposures on the development of feeding circuits within the CNS-including the influences of metabolic hormones and epigenetic changes. The perinatal environment, reflective of maternal nutritional status, contributes to the programming of offspring adiposity.

Rare predicted loss of function alleles in Bassoon (BSN) are associated with obesity.

Bassoon (BSN) is a component of a hetero-dimeric presynaptic cytomatrix protein that orchestrates neurotransmitter release with Piccolo (PCLO) from glutamatergic neurons throughout the brain. Heterozygous missense variants in BSN have previously been associated with neurodegenerative disorders in humans. We performed an exome-wide association analysis of ultra-rare variants in about 140,000 unrelated individuals from the UK Biobank to search for new genes associated with obesity.