Gestational diabetes mellitus (GDM) has historically been perceived as a medical complication of pregnancy that also serves as a harbinger of maternal risk of developing type 2 diabetes mellitus (T2DM) in the future. In recent decades, a growing body of evidence has detailed additional lifelong implications that extend beyond T2DM, including an elevated risk of ultimately developing cardiovascular disease. Furthermore, the risk factors that mediate this lifetime cardiovascular risk are evident not only after delivery but are present even before the pregnancy in which GDM is first diagnosed. The concept thus emerging from these data is that the diagnosis of GDM enables the identification of women who are already on an enhanced track of cardiometabolic risk that starts early in life. Studies of the offspring of pregnancies complicated by diabetes now suggest that the earliest underpinnings of this cardiometabolic risk profile may be determined in utero and may first manifest clinically in childhood. Accordingly, from this perspective, GDM is now seen as a chronic metabolic disorder that holds implications across the life span of both mother and child.

Diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD) and progresses faster in males than in females. We identify sex-based differences in kidney metabolism and in the blood metabolome of male and female individuals with diabetes. Primary human proximal tubular epithelial cells (PTECs) from healthy males displayed increased mitochondrial respiration, oxidative stress, apoptosis, and greater injury when exposed to high glucose compared with PTECs from healthy females. Male human PTECs showed increased glucose and glutamine fluxes to the TCA cycle, whereas female human PTECs showed increased pyruvate content. The male human PTEC phenotype was enhanced by dihydrotestosterone and mediated by the transcription factor HNF4A and histone demethylase KDM6A. In mice where sex chromosomes either matched or did not match gonadal sex, male gonadal sex contributed to the kidney metabolism differences between males and females. A blood metabolomics analysis in a cohort of adolescents with or without diabetes showed increased TCA cycle metabolites in males. In a second cohort of adults with diabetes, females without DKD had higher serum pyruvate concentrations than did males with or without DKD. Serum pyruvate concentrations positively correlated with the estimated glomerular filtration rate, a measure of kidney function, and negatively correlated with all-cause mortality in this cohort. In a third cohort of adults with CKD, male sex and diabetes were associated with increased plasma TCA cycle metabolites, which correlated with all-cause mortality. These findings suggest that differences in male and female kidney metabolism may contribute to sex-dependent outcomes in DKD.

The developmental theory of health and disease posits that exposures in early life preprogram offspring to develop chronic disease by associations with developmental pathways.¹ Maternal nutrition, gestational weight gain, and diabetes status in pregnancy are risk factors for childhood obesity and its complications.^2-5 Rates of maternal diabetes in pregnancy have increased over the last 20 years, in part being driven by the increasing rates of childhood type 2 diabetes. Researchers among the Pima Indian population, which included a mix of type 2 diabetes and gestational diabetes exposure, reported an increased risk for type 2 diabetes and obesity in offspring.⁶ The SEARCH study⁷ supported these observations, revealing that maternal diabetes and obesity exposure attributed to 47% of type 2 diabetes risk to offspring. In a small case-control study,⁴ exposure to maternal type 2 diabetes was associated with a 14-fold increased risk of childhood type 2 diabetes, while gestational diabetes exposure was associated with a 4-fold increased risk.

BACKGROUND: Despite prevention efforts, type 2 diabetes mellitus continues to increase in incidence among First Nations children and is associated with early and aggressive complications. We aimed to determine the experiences of adolescents living with type 2 diabetes and the barriers to living well with type 2 diabetes that adolescents perceived. METHODS: We recruited adolescents with type 2 diabetes mellitus from the pediatric diabetes clinic in Winnipeg, Manitoba, to participate in a day-long facilitated focus group discussion. Group discussions were recorded and transcribed verbatim. We used interpretive description methodology to inform the thematic analysis of the transcripts. RESULTS: Eight adolescents with a mean age of 15 years participated. Five adolescents identified as female; most were Indigenous (7/8). The mean duration since diagnosis of diabetes was 2.5 years. Adolescents reported struggling with acceptance of their diagnosis, with the stigma and shame associated with the diagnosis and with daily self-management tasks. Three themes were developed from the focus group discussions: bearing witness, the “weight” of diabetes and support (lack of support). INTERPRETATION: Adolescents with diagnoses of type 2 diabetes experience associated stigma and shame, which are substantial barriers to self-care. A broader understanding of their lived experience, including the socioecological and emotional context, could help to improve health care provision and intervention strategies for this population.

In addition to benefits for bone health, vitamin D is implicated in muscle function in children and adults. Aims: To determine if vitamin D dosage positively correlated with gross motor development at 3 and 6 months of age. We hypothesized that higher doses would be associated with higher scores for gross motor skills. Methods: A consecutive sample of 55 healthy, term, and breastfed infants from Montreal, Canada were recruited from a randomized trial of vitamin D supplementation between 2009 and 2012. Infants were randomized to 400 International Units (IU) (n = 19), 800 IU (n = 18) or 1,200 IU (n = 18) vitamin D₃/day. Motor performance at 3 and 6 months was quantified by the Alberta Infant Motor Scale (AIMS). Plasma vitamin D₃ metabolites were measured by tandem mass spectrometry. Results: AIMS scores did not differ at 3 months. However, total AIMS scores and sitting subscores were significantly higher at 6 months in infants receiving 400 IU/day compared to 800 IU/day and 1,200 IU/day groups (p < .05). There were weak negative correlations with length and C-3 epimer of 25(OH)D. Conclusions: In contrast to our hypothesis, gross motor achievements were significantly higher in infants receiving 400 IU/day vitamin D. Our findings also support longer infants being slightly delayed.