Re-emergence of thiamine deficiency disease in the Pacific islands (2014-15): A case-control study.

BACKGROUND: From late 2014 multiple atolls in Kiribati reported an unusual and sometimes fatal illness. We conducted an investigation to identify the etiology of the outbreak on the most severely affected atoll, Kuria, and identified thiamine deficiency disease as the cause. Thiamine deficiency disease has not been reported in the Pacific islands for >5 decades. We present the epidemiological, clinical, and laboratory findings of the investigation. METHODOLOGY/PRINCIPAL FINDINGS: We initially conducted detailed interviews and examinations on previously identified cases to characterize the unknown illness and develop a case definition. Active and passive surveillance was then conducted to identify additional cases. A questionnaire to identify potential risk factors and blood samples to assay biochemical indices were collected from cases and asymptomatic controls. Thiamine hydrochloride treatment was implemented and the response to treatment was systematically monitored using a five-point visual analogue scale and by assessing resolution of previously abnormal neurological examination findings. Risk factors and biochemical results were assessed by univariate and multivariate analyses. 69 cases were identified on Kuria (7% attack rate) including 34 confirmed and 35 unconfirmed. Most were adults (median age 28 years [range 0-62]) and 83% were male. Seven adult males and two infants died (13% case fatality rate). Resolution of objective clinical signs (78%) or symptoms (94%) were identified within one week of starting treatment. Risk factors included having a friend with thiamine deficiency disease and drinking kava; drinking yeast alcohol reduced the risk of disease. Higher chromium (p<0·001) but not thiamine deficiency (p = 0·66) or other biochemical indices were associated with disease by univariate analyses. Chromium (p<0·001) and thiamine deficiency (p = 0·02) were associated with disease by multivariate analysis. CONCLUSIONS/SIGNIFICANCE: An outbreak of thiamine deficiency disease (beriberi) in Kiribati signals the re-emergence of a classic nutritional disease in the Pacific islands after five decades. Although treatment is safe and effective, the underlying reason for the re-emergence remains unknown. Chromium was highly and positively correlated with disease in this study raising questions about the potential role of factors other than thiamine in the biochemistry and pathophysiology of clinical disease.

Effects of Maternal Chromium Restriction on the Long-Term Programming in MAPK Signaling Pathway of Lipid Metabolism in Mice.

It is now broadly accepted that the nutritional environment in early life is a key factor in susceptibility to metabolic diseases. In this study, we evaluated the effects of maternal chromium restriction in vivo on the modulation of lipid metabolism and the mechanisms involved in this process. Sixteen pregnant C57BL mice were randomly divided into two dietary treatments: a control (C) diet group and a low chromium (L) diet group. The diet treatment was maintained through gestation and lactation period. After weaning, some of the pups continued with either the control diet or low chromium diet (CC or LL), whereas other pups switched to another diet (CL or LC). At 32 weeks of age, serum lipid metabolism, proinflammatory indexes, oxidative stress and anti-oxidant markers, and DNA methylation status in adipose tissue were measured. The results indicated that the maternal low chromium diet increased body weight, fat pad weight, serum triglyceride (TG), low-density lipoprotein cholesterol (LDL), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA), and oxidized glutathione (GSSG). There was a decrease in serum reduced/oxidized glutathione (GSH/GSSG) ratio at 32 weeks of age in female offspring. From adipose tissue, we identified 1214 individual hypomethylated CpG sites and 411 individual hypermethylated CpG sites in the LC group when compared to the CC group. Pathway analysis of the differential methylation genes revealed a significant increase in hypomethylated genes in the mitogen-activated protein kinase (MAPK) signaling pathway in the LC group. Our study highlights the importance of the MAPK signaling pathway in epigenetic changes involved in the lipid metabolism of the offspring from chromium-restricted dams.

A pilot duplicate diet study on manganese, selenium and chromium intakes in institutionalised children and adolescents from Guatemala.

Hidden hunger occurs in the presence of an otherwise nutritionally or energetically appropriate diet that is deficient in essential vitamins and minerals. Guatemala has the highest rate of child malnutrition in Latin America and the prevalence of hidden hunger is high. The aim of this study was to determine the Mn, Se and Cr dietary intakes in Guatemalan institutionalised children (4-14 years), a population group at high risk of mineral deficiency. For this purpose, the contents of Mn, Se and Cr were analysed in a duplicate diet (for 7 consecutive days) by electrothermal atomisation-atomic absorption spectrophotometry following acid digestion. Mn, Se and Cr intakes from the duplicate diets were in the range of 1·3-2·31 mg/d, 58·7-69·6 µg/d and 6·32-27·57 µg/d, respectively. Mn and Cr values were below current recommended daily intakes. A cereal- and legumes-based diet is habitually consumed by this population. Local vegetables, fruits and nutritional supplements are included daily, but the consumption of fish, meat, eggs and dairy products is very infrequent or negligible. Mean daily energy intake from the 7-d diet was 8418·2 kJ (2012 kcal), with a macronutrient energy distribution of carbohydrates 69·4 %, proteins 12·3 % and fats 18·3 %. Correlations between Mn, Se and Cr intakes and energy and other nutrient intakes were also evaluated. The present findings will help establish new nutritional strategies for this and similar population groups.

Chromium, zinc and magnesium status in type 1 diabetes.

PURPOSE OF REVIEW: Chromium, zinc, and magnesium are involved in insulin signal transduction, glucose metabolism, and cellular antioxidative defense. This review details the statuses of chromium, zinc, and magnesium in type 1 diabetes patients. RECENT FINDINGS: Blood levels of trace elements (especially magnesium and zinc) were lower in type 1 diabetes patients than in controls and were even lower in type 1 diabetes patients with poor glycemic control. Studies with mouse models have shown that chromium and magnesium supplementation alleviated diabetes-induced complications and improved glycemic control. SUMMARY: Many studies indicated positive correlations between decreased levels of serum chromium, zinc, and magnesium and poor glycemic control. The supplementation of type 1 diabetes patients with zinc, magnesium, and chromium may help to control diabetes and prevent diabetes-related oxidative injuries, but require further study.

[Micronutrients and diabetes, the case of minerals]. / Micronutrientes y diabetes, el caso de los minerales.

Minerals are essential nutrients for the body, are of inorganic nature which gives them the characteristic of being resistant to heat, are involved in a lot of chemical reactions in metabolism, regulating electrolyte balance, in maintaining bone, in the process of blood clotting and the transmission of nerve impulses, particularly its role as enzyme cofactors confers a key role in various physiological processes. Glucose homeostasis involves a fine coordination of events where hormonal control by insulin plays a key role. However, the role of minerals like magnesium, zinc, chromium, iron and selenium in the diabetes is less obvious and in some cases may be controversial. This review shows the knowledge of these five elements and their correlation with diabetes.

Los minerales son nutrientes esenciales para el organismo, de naturaleza inorgánica que les confiere, entre otras características, ser resistentes al calor, participan en diversas reacciones químicas del metabolismo en donde regulan el equilibrio hidroelectrolítico, el mantenimiento óseo, en la trasmisión de los impulsos nerviosos, y durante el proceso de coagulación sanguínea, particularmente por su función como cofactores enzimáticos, tienen un papel clave en varios procesos fisiológicos. La homeostasis de la glucosa involucra una fina coordinación de eventos en donde el control hormonal por la insulina tiene un papel primordial. Sin embargo, la función de los minerales, como el magnesio, el zinc, el cromo, el hierro y el selenio en la diabetes es menos evidente y puede ser, en algún caso, controversial. Esta revisión muestra el conocimiento acerca de estos cinco elementos y su correlación con la diabetes.

High selenium impairs hepatic insulin sensitivity through opposite regulation of ROS.

Insulin resistance is the hallmark of type 2 diabetes. As an essential trace element, selenium (Se) is recommended worldwide for supplementation to prevent Se-deficient pathological conditions, including diabetes and insulin resistance. However, recent evidence has shown that supra-nutritional Se intake is positively associated with the prevalence of diabetes. In the present research, we examined the effect of high Se on insulin sensitivity, and studied possible mechanisms in rats and in rat hepatocytes. Insulin sensitivity and glucose/lipid metabolism were determined by glucose/insulin tolerance test, western blot, immunofluorescence, specific probes and other biochemical assays. We show that high Se activates selenoproteins, including glutathione peroxidase and selenoprotein P, and depletes chromium, leading to a common metabolic intersection-lipolysis in adipose tissue and influx of fatty acids in liver. Fatty acid ß-oxidation generates acetyl-CoA, which is metabolized in trichloroacetic acid cycle, supplying excessive electrons for mitochondrial oxidative phosphorylation and leading to increased "bad" reactive oxygen species (ROS) production in mitochondria and final disturbance of insulin signaling. Furthermore, high Se-activated selenoproteins also weaken insulin-stimulated "good" ROS signal generated by NAD(P)H oxidase, leading to attenuation of insulin signaling. Taken together, these data suggest that excessive intake of Se induces hepatic insulin resistance through opposite regulation of ROS.

Role of trace elements in parenteral nutrition support of the surgical neonate.

BACKGROUND: Parenteral nutrition (PN) has transformed the outcome for neonates with surgical problems in the intensive care unit. Trace element supplementation in PN is a standard practice in many neonatal intensive care units. However, many of these elements are contaminants in PN solutions, and contamination levels may, in themselves, be sufficient for normal metabolic needs. Additional supplementation may actually lead to toxicity in neonates whose requirements are small. METHODS: An electronic search of the MEDLINE, Cochrane Collaboration, and SCOPUS English language medical databases was performed for the key words "trace elements," "micro-nutrients," and "parenteral nutrition additives." Studies were categorized based on levels of evidence offered, with randomized controlled trials and meta-analyses accorded the greatest importance at the apex of the data pool and case reports and animal experiments the least importance. Articles were reviewed with the primary goal of developing uniform recommendations for trace element supplementation in the surgical neonate. The secondary goals were to review the physiologic role, metabolic demands, requirements, losses, deficiency syndromes, and toxicity symptoms associated with zinc, copper, chromium, selenium, manganese, and molybdenum supplementation in PN. RESULTS: Zinc supplementation must begin at initiation of PN. All other trace elements can be added to PN 2 to 4 weeks after initiation. Copper and manganese need to be withheld if the neonate develops PN-associated liver disease. The status of chromium supplementation is currently being actively debated, with contaminant levels in PN being sufficient in most cases to meet neonatal requirements. Selenium is an important component of antioxidant enzymes with a role in the pathogenesis of neonatal surgical conditions such as necrotizing enterocolitis and bronchopulmonary dysplasia. Premature infants are often selenium deficient, and early supplementation has shown a reduction in sepsis events in this age group. CONCLUSION: Appropriate supplementation of trace elements in surgical infants is important, and levels should be monitored. In certain settings, it may be more appropriate to individualize trace element supplementation based on the predetermined physiologic need rather than using bundled packages of trace elements as is the current norm. Balance studies of trace element requirements should be performed to better establish clinical recommendations for optimal trace element dosing in the neonatal surgical population.

Urinary chromium loss associated with diabetes is offset by increases in absorption.

The results of the current study indicate that diabetic rats have increased urinary Cr loss as a result of their diabetes; however, this increased urinary Cr loss is offset by increased absorption of Cr. Insulin resistant, obese rats have alterations in the rates of Cr transport and distribution compared to lean rats but have similar levels of urinary Cr loss and Cr absorption. Thus, any increases in urinary Cr loss associated with insulin resistance or diabetes are offset by increased absorption. Given that dietary chromium is normally absorbed with only approximately 1% efficiency, suitable Cr exists in the diet so that a standard diet possesses sufficient chromium to allow for the increases in absorption associated with diabetes. Consequently, supplementing the diet with nutritionally relevant quantities of chromium is not anticipated to have any beneficial effects. Similarly, beneficial effects on plasma variables, such as cholesterol, triglycerides, and insulin concentrations, from supra-nutritional doses of Cr(III) complexes should not arise from alleviation of chromium deficiency. These beneficial effects must arise from pharmacological effects of high dose Cr(III) administration.

Chromium in parenteral nutrition: too little or too much?

Although guidelines for routine parenteral supplements of chromium (Cr) were published, there remain major concerns about the infusion of excess Cr. In addition, little information is available on appropriate dosage for intravenous usage. Cr functions as a regulator of insulin action. In humans, the 3 reported cases of Cr deficiency developed peripheral neuropathy, weight loss, and hyperglycemia. Supplementation of Cr to the parenteral nutrition (PN) solution corrected these abnormalities. For parenteral Cr, concerns arise from the high levels found in sera (up to 40-fold higher) and tissues (10- to 100-fold higher) and their effects on kidneys: In 15 children receiving long-term PN, the glomerular filtration rate was lower than that of non-PN controls and was inversely correlated with Cr indices. Furthermore, in a randomized blinded prospective protocol involving 75 newborns, the group receiving the recommended dose of Cr showed higher levels of creatinine that were positively correlated with Cr intake. Of note, Cr contaminants in PN solutions can increase the amount delivered by 10%-100%. A possible method for estimating adequate Cr to be provided IV is to calculate the amount physiologically absorbed in healthy people. This amount is 10 to 100 times less than the daily recommended parenteral Cr in adults. The accumulated scientific data presented here point to a serious need to lower the recommended amount of parenteral Cr.