Prenatal and early life factors and type 1 diabetes.

BACKGROUND: The prevalence of type 1 diabetes is increasing worldwide, suggesting that unknown environmental factors are becoming increasingly important in its pathogenesis. AIM: The aim of the study was to investigate the possible role of a number of prenatal and perinatal factors in the aetiology of type 1 diabetes. METHODS: Mothers of patients diagnosed with type 1 diabetes (cases) and mothers of children born on the same day and of the same sex as type 1 diabetes patients (controls) were interviewed on a number of prenatal and perinatal factors of interest. RESULTS: Hand washing prior to eating, frequency of bathing and total stress score were found to be positively associated with the development of type 1 diabetes on univariate analyses. Hand-washing prior to eating and frequency of house cleaning were independently associated with an increased risk of type 1 diabetes, whilst getting dirty was associated with a reduced risk in multivariate analyses. There was no association of type 1 diabetes to removing of outdoor shoes indoors or to the age of first attendance to school or pre-school. There were also no significant associations to parental smoking, parental age, birth order, infant feeding, antibiotic use, mode of delivery or birth weight. CONCLUSION: Our data suggest that factors that affect the skin or gut microbiome might be more important than infections or factors affecting the microbiome at other sites.

Why is the Incidence of Type 1 Diabetes Increasing?

Type 1 diabetes is a condition that can lead to serious long-term complications and can have significant psychological and quality of life implications. Its incidence is increasing in all parts of the world, but the reasons for this are incompletely understood. Genetic factors alone cannot explain such a rapid increase in incidence; therefore, environmental factors must be implicated. Lifestyle factors have been classically associated with type 2 diabetes. However, there are data implicating obesity and insulin resistance to type 1 diabetes as well (accelerator hypothesis). Cholesterol has also been shown to be correlated with the incidence of type 1 diabetes; this may be mediated by immunomodulatory effects of cholesterol. There is considerable interest in early life factors, including maternal diet, mode of delivery, infant feeding, childhood diet, microbial exposure (hygiene hypothesis), and use of anti-microbials in early childhood. Distance from the sea has recently been shown to be negatively correlated with the incidence of type 1 diabetes. This may contribute to the increasing incidence of type 1 diabetes since people are increasingly living closer to the sea. Postulated mediating mechanisms include hours of sunshine (and possibly vitamin D levels), mean temperature, dietary habits, and pollution. Ozone, polychlorinated biphenyls, phthalates, trichloroethylene, dioxin, heavy metals, bisphenol, nitrates/nitrites, and mercury are amongst the chemicals which may increase the risk of type 1 diabetes. Another area of research concerns the role of the skin and gut microbiome. The microbiome is affected by many of the factors mentioned above, including the mode of delivery, infant feeding, exposure to microbes, antibiotic use, and dietary habits. Research on the reasons why the incidence of type 1 diabetes is increasing not only sheds light on its pathogenesis but also offers insights into ways we can prevent type 1 diabetes.

Amiodarone-induced type 2 thyrotoxicosis.

The authors present a case of a 55-year-old gentleman with a medical history of atrial fibrillation on amiodarone who presented with weight loss, palpitations and exertional dyspnoea. Thyroid function tests revealed thyrotoxicosis with a free thyroxine (T4) of 117 pmol/L and a thyroid-stimulating hormone (TSH) of <0.008 mIU/L. Interleukin-6 level was low. The negative TSH-receptor antibody status, the presence of a small thyroid gland with heterogeneous echotexture and decreased internal vascularity on ultrasound together with the relatively quick drop in free T4 and free tri-iodothyronine (T3) levels once prednisolone therapy was added to carbimazole suggested that this was typical of amiodarone-induced thyrotoxicosis (AIT) type 2. Subsequently, carbimazole was discontinued and treatment with prednisolone was continued. This case highlights that AIT management may be challenging and it is of paramount importance to establish the type of AIT present as this will guide management and is key to improving prognosis.

Identification of an HNF1A p.Gly292fs Frameshift Mutation Presenting as Diabetes During Pregnancy in a Maltese Family.

The diagnosis of maturity onset diabetes of the young (MODY) is a challenging process in view of the extensive clinical and genetic heterogeneity of the disease. Mutations in the gene encoding hepatocyte nuclear factor 1α (HNF1A) are responsible for most forms of monogenic diabetes in Northern European populations. Genetic analysis through a combination of whole exome sequencing and Sanger sequencing in three Maltese siblings and their father identified a rare duplication/frameshift mutation in exon 4 of HNF1A that lies within a known mutational hotspot in this gene. In this report, we provide the first description of an HNF1A-MODY3 phenotype in a Maltese family. The findings reported are relevant and new to a regional population, where the epidemiology of atypical diabetes has never been studied before. This report is of clinical interest as it highlights how monogenic diabetes can be misdiagnosed as either type 1, type 2, or gestational diabetes. It also reinforces the need for a better characterisation of monogenic diabetes in Mediterranean countries, particularly in island populations such as Malta with a high prevalence of diabetes.

Incidence of type 1 diabetes and distance from the sea: A descriptive epidemiological study.

BACKGROUND: Increasingly, environmental factors are being shown to play a role in the etiology of type 1 diabetes (T1D). One geographical feature that exerts a major effect on climate but whose relationship with T1D incidence has not been studied is distance from the sea. This study investigated any possible relationship between distance from the sea and the incidence of T1D. METHODS: Spearman correlation analysis was performed to investigate the relationship between the incidence of T1D (determined using data from the DiaMond Project) and distance from the sea. This was followed by multivariate analyses to adjust for potential cofounders. RESULTS: A significant negative association was found between T1D incidence and shortest distance from sea (r = -0.251, P = 0.01235), mean hours of sunshine (r = -0.325, P = 0.002), and mean temperature (r = -0.224, P = 0.046), and a positive association was found between T1D incidence and latitude (r = 0.434, P = 0.0001). Multivariate analysis (generalized linear model) showed that both distance from the sea and latitude were independently associated with the incidence of T1D. The association of distance from sea and the incidence of T1D remained significant even after adjusting for mean temperature (P = 0.002) and mean hours of sunshine (P = 0.005). CONCLUSIONS: The data show that there is a negative correlation between distance from the sea and the incidence of T1D, which was independent of latitude, mean temperature, and mean hours of sunshine. This suggests that environmental factors associated with climatic conditions may influence the risk of T1D.

Association of incidence of type 1 diabetes with mortality from infectious disease and with antibiotic susceptibility at a country level.

To investigate the association between country incidence of type 1 diabetes and mortality from infectious disease and antibiotic susceptibility. An ecological study to explore the relationship at a country level of the reported incidence of type 1 diabetes (DiaMond) to infectious disease mortality (World Health Organisation) and to antibiotic susceptibility (Alexander Project). There were significant negative correlations between the incidence of type 1 diabetes and mortality for all infectious diseases studied. There were also significant positive correlations between the incidence of type 1 diabetes and antibiotic susceptibilities of Strep. pneumoniae, but not to those of Haem. influenzae. Since infectious disease mortality and antibiotic susceptibility are surrogate markers for bacterial exposure, our results provide support for a negative association between bacterial exposure in a community and its incidence of type 1 diabetes. The consistency of our results as well as the highly statistically significant results of most of the associations studied reinforces the validity of our findings.