A retrospective analysis of a societal experiment among the Danish population suggests that exposure to extra doses of vitamin A during fetal development may lower type 2 diabetes mellitus (T2DM) risk later in life.

Vitamin A deficiency has been associated with impaired fetal pancreatic development and increased risk of developing type 2 diabetes mellitus (T2DM). In 1962, mandatory margarine fortification with vitamin A was increased by 25 % in Denmark. We aimed to determine whether offspring of mothers who had been exposed to the extra vitamin A from fortification during pregnancy had a lower risk of developing T2DM in adult life, compared with offspring of mothers exposed to less vitamin A. Individuals from birth cohorts with the higher prenatal vitamin A exposure (born 1 December 1962-31 March 1964) and those with lower prenatal exposure (born 1 September 1959-31 December 1960) were followed up with regard to development of T2DM before 31 December 2012 in the Danish National Diabetes Registry and National Patient Register. Logistic and Cox regression analyses were performed to determine the risk of T2DM by vitamin A exposure level. A total of 193 803 individuals were followed up until midlife. Our results showed that individuals exposed prenatally to extra vitamin A from fortified margarine had a lower risk of developing T2DM than those exposed to lower levels: OR 0·88; 95 % CI 0·81, 0·95, P=0·001, after adjustment for sex. Fetal exposure to small, extra amounts of vitamin A from food fortification may reduce the risk of T2DM. These results may have public health relevance, as they demonstrate that one of the most costly chronic diseases may be prevented by food fortification - a simple and affordable public health nutrition intervention.

Intake of Total and Subgroups of Fat Minimally Affect the Associations between Selected Single Nucleotide Polymorphisms in the PPARγ Pathway and Changes in Anthropometry among European Adults from Cohorts of the DiOGenes Study.

BACKGROUND: Although the peroxisome proliferator-activated receptor γ (PPARγ) pathway is central in adipogenesis, it remains unknown whether it influences change in body weight (BW) and whether dietary fat has a modifying effect on the association. OBJECTIVES: We examined whether 27 single nucleotide polymorphisms (SNPs) within 4 genes in the PPARγ pathway are associated with the OR of being a BW gainer or with annual changes in anthropometry and whether intake of total fat, monounsaturated fat, polyunsaturated fat, or saturated fat has a modifying effect on these associations. METHODS: A case-noncase study included 11,048 men and women from cohorts in the European Diet, Obesity and Genes study; 5552 were cases, defined as individuals with the greatest BW gain during follow-up, and 6548 were randomly selected, including 5496 noncases. We selected 4 genes [CCAAT/enhancer binding protein ß (CEBPB), phosphoenolpyruvate carboxykinase 2, PPARγ gene (PPARG), and sterol regulatory element binding transcription factor 1] according to evidence about biologic plausibility for interactions with dietary fat in weight regulation. Diet was assessed at baseline, and anthropometry was followed for 7 y. RESULTS: The ORs for being a BW gainer for the 27 genetic variants ranged from 0.87 (95% CI: 0.79, 1.03) to 1.12 (95% CI: 0.96, 1.22) per additional minor allele. Uncorrected, CEBPB rs4253449 had a significant interaction with the intake of total fat and subgroups of fat. The OR for being a BW gainer for each additional rs4253449 minor allele per 100 kcal higher total fat intake was 1.07 (95% CI: 1.02, 1.12; P = 0.008), and similar associations were found for subgroups of fat. CONCLUSIONS: Among European men and women, the influence of dietary fat on associations between SNPs in the PPARγ pathway and anthropometry is likely to be absent or marginal. The observed interaction between rs4253449 and dietary fat needs confirmation.

Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects. AIM: We conducted a case-cohort study to investigate the associations of SNPs in candidate genes with weight change during an average of 6.8 years of follow-up and to examine the potential effect modification by glycemic index (GI) and protein intake. METHODS AND FINDINGS: Participants, aged 20-60 years at baseline, came from five European countries. Cases ('weight gainers') were selected from the total eligible cohort (n = 50,293) as those with the greatest unexplained annual weight gain (n = 5,584). A random subcohort (n = 6,566) was drawn with the intention to obtain an equal number of cases and noncases (n = 5,507). We genotyped 134 SNPs that captured all common genetic variation across the 15 candidate genes; 123 met the quality control criteria. Each SNP was tested for association with the risk of being a 'weight gainer' (logistic regression models) in the case-noncase data and with weight gain (linear regression models) in the random subcohort data. After accounting for multiple testing, none of the SNPs was significantly associated with weight change. Furthermore, we observed no significant effect modification by dietary factors, except for SNP rs7180849 in the neuromedin ß gene (NMB). Carriers of the minor allele had a more pronounced weight gain at a higher GI (P = 2 x 10⁻7). CONCLUSIONS: We found no evidence of association between SNPs in the studied hypothalamic genes with weight change. The interaction between GI and NMB SNP rs7180849 needs further confirmation.