Polymorphisms in the vitamin D receptor (VDR) gene (BsmI (rs1544410), FokI (rs2228570), ApaI (rs7975232), TaqI (rs731236)) and low vitamin D concentrations have previously been associated with type 1 diabetes (T1D). Vitamin D is thought to mediate the switch from a pro-inflammatory Th1 response to an anti-inflammatory Th2 response which is protective against the development of T1D. These associations are inconsistent across studies and population groups. These associations have not been investigated in the South African black population. Thus, this observational, case-control study aims to address this knowledge gap. South African black participants with T1D (cases; n = 182) and healthy controls (n = 151) were genotyped for the four VDR polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Vitamin D levels were measured using high performance liquid chromatography (HPLC). Vitamin D levels were not significantly different between cases and controls (62.8 ± 20.7 vs. 59.5 ± 17.0 nmol/l, respectively; P = 0.122). Higher vitamin D levels were associated with the TaqI TT (P = 0.045) and FokI TT/TC (P = 0.014) genotypes in multivariate analyses. Furthermore, the TaqI TT genotype was associated with T1D status in multivariate analysis (P = 0.040). The FokI CC genotype increases the transcription of CYP24A1, resulting in vitamin D catabolism and thus decreased vitamin D concentration through the action of 24-hydroxlase. The TaqI TT genotype results in increased vitamin D potentially through calcium metabolism feedback pathways. In addition, the TaqI TT genotype is associated with T1D through a vitamin D-independent mechanism and may be in linkage disequilibrium with a true causative variant.

Type 1 diabetes (T1D) is a chronic autoimmune disease characterised by a deficiency in insulin production and consequent hyperglycaemia. A glycated haemoglobin (HbA1c) value < 53 mmol/mol (< 7%) is recommended to reduce the risk for diabetes-specific complications(1). However, most adolescents and young adults (AYAs) have an HbA1c above the target(2). Dietary behaviours, including a routine meal plan with snacks, play a significant role in self-management(3). Snacks without an insulin bolus, grazing or snacking to cope with stress contribute to out-of-target glucose levels. Although modifying AYAs’ snacking behaviours could be a low-cost, equitable, and effective approach to improving glycaemic control, there is a dearth of evidence to inform effective snacking interventions. Importantly, no brief, validated tool exists to assess snacking behaviour among individuals with T1D. This research explored the acceptability and feasibility of validating a snacking questionnaire adapted for AYAs with T1D; a crucial step before a larger validation study. Twenty-five AYAs (aged 13-20 years) with T1D and receiving diabetes care through Te Whatu Ora Southern were invited to participate in a feasibility study. Purposive sampling was used for maximum variability in participants’ demographic characteristics. All study procedures were completed remotely, with electronic questionnaires administered in the morning via a secure web platform. On days 1 and 8 of the 8-day study, participants completed a 30-item snacking questionnaire that assessed the timing and frequency of snacking and types of food or drinks consumed as a snack in the past seven days. The snacking questionnaire was adapted from questionnaires previously used in population-level surveys. An experienced diabetes dietitian ensured that items reflected foods commonly consumed by AYAs with T1D. Before recruitment, two diabetes dietitians and a young adult with T1D critically reviewed the adapted snacking questionnaire. On days 2-8, participants recalled their snacking behaviour (timing, frequency, food/drink consumed) over the previous day. The proportion of completed snacking questionnaires assessed feasibility, defined as a response rate ≥ 80%. The ease of completing the snacking questionnaires was self-reported on a Likert-type scale (1-completely agree, 5-completely disagree) to assess acceptability, defined as ≤ 20% of participants reporting the questionnaires were not easy to complete. Participants (n = 10) were aged 16.2 ± 1.69 years, 60% male, and 90% self-identified as New Zealand or Other European. All participants completed the proposed validation study. Most (95%) of the snacking questionnaires were completed. All (100%) daily snacking behaviour questionnaires were completed. All participants (100%) agreed that the questionnaires were easy to complete. The snacking behaviours questionnaire validation procedures are feasible and acceptable to New Zealand and Other European AYAs with T1D. Feasibility and acceptability must be explored among ethnically diverse AYAs before conducting a larger rigorous validation study.

The 2017 Atlantic hurricane season was especially memorable for 3 major hurricanes—Harvey, Irma, and Maria—that devastated population centers across Texas, Florida, and Puerto Rico, respectively. Each storm had unique hazard properties that posed distinctive challenges for persons living with type 1 diabetes (T1D). Diabetes care specialists and educators took on leadership roles for coordinating care and establishing insulin supply lifelines for people with T1D living in the hardest-hit neighborhoods affected by these extreme storms. Strategies and resources were customized for each population. Diabetes specialists strategized to provide mutual support and shared insulins and supplies across sites.

Studies suggest that the relationship between psychosocial well-being and type 1 diabetes (T1D) is bidirectional, with T1D typically having a negative influence on psychological functioning, which in turn negatively affects the course of T1D. Here, we investigate the potential role of the capacity for mentalizing, or reflective functioning, in children and their mothers in diabetes control. We tested differences in mentalizing as assessed by the Reflective Functioning Scale in two groups of mother–son dyads with good (GDC) versus poor (PDC) diabetes control. Fifty-five boys (8–12 years old) and their mothers were recruited from the Juvenile Diabetes Foundation in Santiago, Chile. The mothers were interviewed with the Parental Development Interview and the children with the Child Attachment Interview, and both were scored for reflective functioning by using the Reflective Functioning Scale. Self-report measures of stress and diabetes outcomes were completed by the mothers and children, and levels of glycated hemoglobin (HbA1c) were assessed as an index of diabetes control. The results showed that both maternal and child reflective functioning were higher in the GDC than the PDC group and were negatively correlated with HbA1c in the total sample. Our findings suggest an important role for mentalizing in diabetes outcomes, but further prospective research is needed.

Diet is a major modifiable lifestyle factor that may affect the components of the metabolic syndrome. We aimed to investigate the association between relative proportions of macronutrients and the components of the metabolic syndrome in a population of individuals with type 1 diabetes. In all, 791 individuals without nephropathy, with plausible energy intake and known metabolic syndrome status, taking part in the Finnish Diabetic Nephropathy Study were included in the analyses. Dietary data were collected with a diet record. The association between the relative macronutrient intake and the outcome variables were analysed using multivariable nutrient density substitution models. The relative proportions of dietary macronutrients or fatty acids were not associated with the presence of the metabolic syndrome. In men, however, favouring carbohydrates over fats was associated with lower odds of the waist component, whereas favouring either carbohydrates or fats over proteins was associated with lower odds of the blood pressure component of the metabolic syndrome. In women, substituting carbohydrates for fats was associated with lower HDL-cholesterol concentration. Substituting carbohydrates or fats for alcohol or protein was, in men, associated with lower systolic blood pressure. To conclude, the relative distribution of macronutrients may have some relevance for the metabolic syndrome.

Objectives: Good glycemic control is an important goal of diabetes management. Late adolescents with type 1 diabetes (T1D) are at risk for poor glycemic control as they move into young adulthood. For a subset of these patients, this dysregulation is extreme, placing them at risk for life-threatening health complications and permanent cognitive declines. The present study examined whether deficiency in emotional decision making (as measured by the Iowa Gambling Task; IGT) among teens with T1D may represent a neurocognitive risk factor for subsequent glycemic dysregulation. Methods: As part of a larger longitudinal study, a total of 241 high-school seniors (147 females, 94 males) diagnosed with T1D underwent baseline assessment that included the IGT. Glycated hemoglobin (HbA1c), which reflects glycemic control over the course of the past 2 to 3 months, was also assessed at baseline. Of the 241,189 (127 females, 62 males, mean age=17.76, mean HbA1c=8.11) completed HbA1c measurement 1 year later. Results: Baseline IGT performance in the impaired range (per norms) was associated with greater dysregulation in glycemic control 1 year later, as evidenced by an average increase in HbA1c of 2%. Those with normal IGT scores (per norms) exhibited a more moderate increase in glycemic control, with an HbA1c increase of 0.7%. Several IGT scoring approaches were compared, showing that the total scores collapsed across all trials was most sensitive to change in glycemic control. Conclusions: IGT assessment offers promise as a tool for identifying late adolescents at increased risk for glycemic dysregulation. (JINS, 2017, 23, 204–213)

TNF-α is a pro-inflammatory cytokine that is involved in type 1 diabetes (T1D) pathogenesis. The TNFa gene is subject of epigenetic regulation in which folate and homocysteine are important molecules because they participate in the methionine cycle where the most important methyl group donor (S-adenosylmethionine) is formed. We investigated whether TNFa gene promoter methylation status in T1D patients was related to blood folate, homocysteine and TNF-α in a transversal case–control study. We studied T1D patients (n 25, mean=13·7 years) and healthy control subjects (n 25, mean=31·1 years), without T1D and/or other autoimmune diseases or direct family history of these diseases. A blood sample was obtained for determination of serum folate, plasma homocysteine and TNF-α concentrations. Whole blood was used for the extraction of DNA to determine the percentage of methylation by real-time PCR and melting-curve analysis. Results are expressed as means and standard deviations for parametric variables and as median (interquartile range) for non-parametric variables. T1D patients showed a higher TNFa gene promoter methylation (39·2 (sd 19·5) %) when compared with control subjects (25·4 (sd 13·7) %) (P=0·008). TNFa gene promoter methylation was positively associated only with homocysteine levels in T1D patients (r 0·55, P=0·007), but not in control subjects (r −0·122, P=0·872). To our knowledge, this is the first work that reports the methylation status of the TNFa gene promoter and its relationship with homocysteine metabolism in Chilean T1D patients without disease complications.

The endothelium, a thin single sheet of endothelial cells, is a metabolically active layer that coats the inner surface of blood vessels and acts as an interface between the circulating blood and the vessel wall. The endothelium through the secretion of vasodilators and vasoconstrictors serves as a critical mediator of vascular homeostasis. During the development of the vascular system, it regulates cellular adhesion and vessel wall inflammation in addition to maintaining vasculogenesis and angiogenesis. A shift in the functions of the endothelium towards vasoconstriction, proinflammatory and prothrombic states characterise improper functioning of these cells, leading to endothelial dysfunction (ED), implicated in the pathogenesis of many diseases including diabetes. Major mechanisms of ED include the down-regulation of endothelial nitric oxide synthase levels, differential expression of vascular endothelial growth factor, endoplasmic reticulum stress, inflammatory pathways and oxidative stress. ED tends to be the initial event in macrovascular complications such as coronary artery disease, peripheral arterial disease, stroke and microvascular complications such as nephropathy, neuropathy and retinopathy. Numerous strategies have been developed to protect endothelial cells against various stimuli, of which the role of polyphenolic compounds in modulating the differentially regulated pathways and thus maintaining vascular homeostasis has been proven to be beneficial. This review addresses the factors stimulating ED in diabetes and the molecular mechanisms of natural polyphenol antioxidants in maintaining vascular homeostasis.

Diabetes-induced CVD is the most significant complication of prolonged hyperglycaemia. The aim of this study was to determine whether resveratrol, a polyphenol antioxidant compound, when administered at a dose that can be reasonably obtained through supplementation could prevent the development of cardiovascular complications in older, obese, diabetic rats. Diabetes was induced in 6-month old, obese, male Wistar rats via a single intravenous dose of streptozotocin (65 mg/kg). Randomly selected animals were administered resveratrol (2 mg/kg) via oral gavage daily for 8 weeks. Body weights, blood glucose levels, food intake and water consumption were monitored, and assessments of vascular reactivity, tactile allodynia and left ventricular function were performed. Resveratrol therapy significantly improved tactile allodynia and vascular contractile functionality in diabetic rats (P<0·05). There were no significant changes in standardised vasorelaxation responses, plasma glucose concentrations, water consumption, body weight, left ventricular hypertrophy, kidney hypertrophy, heart rate or left ventricular compliance with resveratrol administration. Resveratrol-mediated improvements in vascular and nerve function in old, obese, diabetic rats were associated with its reported antioxidant effects. Resveratrol did not improve cardiac function nor mitigate the classic clinical symptoms of diabetes mellitus (i.e. hyperglycaemia, polydypsia and a failure to thrive). This suggests that supplementation with resveratrol at a dose achievable with commercially available supplements would not produce significant cardioprotective effects in people with diabetes mellitus.

Fortification of margarine with vitamin D was mandatory in Denmark during 1961–1985. The aim of the study was to assess whether gestational and early infancy exposure to margarine fortification was associated with seasonality of birth in Danish type 1 diabetes (T1D) patients. The risks of T1D in Danes born during various exposure periods around margarine fortification termination in 1985 were analyzed. As expected, the T1D hazards in males unexposed to margarine fortification and born in spring were higher than in males born in autumn: relevant hazard ratios (95% confidence intervals) in various exposure groups ranged from 1.74 (1.112/2.708) to 37.43 (1.804/776.558). There were no indications of seasonality of birth in males exposed to fortification, nor in both exposed and unexposed females. The study suggests that early life exposure to low-dose vitamin D from fortified food eliminates seasonality of birth in T1D male patients. Further studies are required to investigate the identified gender differences.

Type 1 diabetes (T1D), an autoimmune inflammatory disorder, develops as a consequence of pancreatic β-cell destruction and results in hyperglycaemia. Since current T1D therapy mainly involves insulin replacement, the aim of the present study was to evaluate the therapeutic potential of Origanum vulgare L. ssp. hirtum (Greek oregano) leaf extract rich in biophenols for the treatment of T1D. The phytochemical profile of methanolic oregano extract (MOE) and aqueous oregano extract (AOE) was determined by liquid chromatography/electrospray ion-trap tandem MS (LC/DAD/ESI-MSn), while their main compounds were quantified by HPLC with diode array detection. After establishing their potent in vitro antioxidant activity, the extracts were administered to C57BL/6 mice treated with multiple low doses of streptozotocin for diabetes induction. While prophylactic AOE therapy had no impact on diabetes induction, MOE reduced diabetes incidence and preserved normal insulin secretion. In addition, MOE scavenged reactive oxygen and nitrogen species and, therefore, alleviated the need for the up-regulation of antioxidant enzymes. MOE treatment specifically attenuated the pro-inflammatory response mediated by T helper 17 cells and enhanced anti-inflammatory T helper 2 and T regulatory cells through the impact on specific signalling pathways and transcription factors. Importantly, MOE preserved β-cells from in vitro apoptosis via blockade of caspase 3. Finally, rosmarinic acid, a predominant compound in MOE, exhibited only partial protection from diabetes induction. In conclusion, acting as an antioxidant, immunomodulator and in an anti-apoptotic manner, MOE protected mice from diabetes development. Seemingly, there is more than one compound responsible for the beneficial effect of MOE.

This study investigated the correlations between health-related quality of life and social support in adolescents with type 1 diabetes (T1DM). Participants were 102 adolescents between 12 and 17 years old, who were patients of a healthcare program in the city of Porto Alegre, south of Brazil. Two questionnaires, the KIDSCREEN-52 and the Brazilian version of Social Support Appraisals, were used to evaluate health-related quality of life and social support. Results showed good quality of life and social support levels. Strong correlations were verified between social support and three of the KIDSCREEN-52 dimensions: psychological well-being (r = .63; p < .01); peers and social support (r = .67; p < .01) and school environment (r = .64; p < .01). Analysis of linear regression showed that gender, age and social support are variables associated with health-related quality of life, explaining 52.6% of variance. Results revealed the impact of the disease to young people, and can help to find strategies to improve care in these cases.

The present study explores accuracy in estimating blood glucose levels (BGL) in children with type 1 diabetes and analyzes the kinds of symptoms and cues which they use to estimate their BGL. Forty two children with type 1 diabetes completed a SI/IC-3 scale consisting of 28 items (22 symptoms and 6 feelings), indicating those which they perceived at the time and their intensity. They estimated their BGL and gave reasons for their estimation, before having a blood glucose level analysis performed. The results indicated great variability in the accuracy of estimating BGL. They showed failures in the correct discrimination of symptoms of hypoglycemia as well as the presence of false beliefs regarding indicative symptoms of hyperglycemia, and the absence of symptoms as an indicator for euglycemia, beliefs which provoke different and frequent errors in the estimation of BGL. Correct use of external signs is shown to be related to correct estimations of normal BGL, as well as hypoglycemia and hyperglycemia. We discuss the implications these results could have on designing psychological intervention procedures for diabetics in the form of training programs to discriminate BGL accurately, taking into account these findings and previous studies completed in the same field.