Low Thiamine Levels in Children With Type 1 Diabetes and Diabetic Ketoacidosis

Rosner, Elizabeth; Strezlecki, Kenneth D.; Clark, Jeff; Lieh-Lai, Mary

doi:10.1097/pcc.0000000000000302

Cited by 27 publications

(29 citation statements)

References 16 publications

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“…In the pediatric literature, one study of 15 patients found that thiamine deficiency is common in those with DKA and that insulin administration may further reduce thiamine levels [15]. This study is the first to report on the connection between thiamine deficiency and lactic acidosis in patients with DKA.…”

Section: Discussionmentioning

confidence: 79%

The relationship between lactate and thiamine levels in patients with diabetic ketoacidosis

Moskowitz

Graver

Giberson

et al. 2014

Journal of Critical Care

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Purpose Thiamine functions as an important cofactor in aerobic metabolism and thiamine deficiency can contribute to lactic acidosis. Although increased rates of thiamine deficiency have been described in diabetic outpatients, this phenomenon has not been studied in relation to diabetic ketoacidosis (DKA). In the present study, we hypothesize that thiamine deficiency is associated with elevated lactate in patients with DKA. Materials and Methods This was a prospective observational study of patients presenting to a tertiary care center with DKA. Patient demographics, laboratory results, and outcomes were recorded. A one-time blood draw was performed and analyzed for plasma thiamine levels. Results Thirty-two patients were enrolled. Eight patients (25%) were thiamine deficient, with levels lower than 9 nmol/L. A negative correlation between lactic acid and plasma thiamine levels was found (r = −0.56, P = .002). This relationship remained significant after adjustment for APACHE II scores (P = .009). Thiamine levels were directly related to admission serum bicarbonate (r = 0.44, P = .019), and patients with thiamine deficiency maintained lower bicarbonate levels over the first 24 hours (slopes parallel with a difference of 4.083, P = .002). Conclusions Patients with DKA had a high prevalence of thiamine deficiency. Thiamine levels were inversely related to lactate levels among patients with DKA. A study of thiamine supplementation in DKA is warranted.

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Section: Discussionmentioning

confidence: 79%

The relationship between lactate and thiamine levels in patients with diabetic ketoacidosis

Moskowitz

Graver

Giberson

et al. 2014

Journal of Critical Care

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“…Thiamine deficiencies severe enough to produce beriberi are rare in the modern developed world and severe thiamine deficiency associated with severe neurological effects (Wernicke’s encephalopathy) is largely confined to alcoholic adults or other specific conditions or medical procedures (Francini-Pesenti et al, 2009; Frank, 2015; Lallas and Desai, 2014; Stroh et al, 2014; World Health Organization, 1999). Low thiamine levels in diabetics have been noted, and it has been hypothesized that consumption of high energy high carbohydrate diets may lead to low, although subclinical, thiamine levels (Kerns et al, 2015; Lonsdale, 2015; Page et al, 2011; Rosner et al, 2014). In any case, the data reported here and by Oishi et al (2004) in mouse models suggest that defects in spermatogenesis produced by low thiamine appear before other overt signs of deficiency.…”

Section: Discussionmentioning

confidence: 99%

Comparison of endpoints relevant to toxicity assessments in 3 generations of CD-1 mice fed irradiated natural and purified ingredient diets with varying soy protein and isoflavone contents

Camacho

Lewis²,

Vanlandingham

et al. 2016

Food and Chemical Toxicology

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Diet is an important variable in toxicology. There are mixed reports on the impact of soy components on energy utilization, fat deposition, and reproductive parameters. Three generations of CD-1 mice were fed irradiated natural ingredient diets with varying levels of soy (NIH-41, 5K96, or 5008/5001), purified irradiated AIN-93 diet, or the AIN-93 formulation modified with ethanol-washed soy protein concentrate (SPC) or SPC with isoflavones (SPC-IF). NIH-41 was the control for pairwise comparisons. Minimal differences were observed among natural ingredient diet groups. F0 males fed AIN-93, SPC, and SPC-IF diets had elevated glucose levels and lower insulin levels compared with the NIH-41 group. In both sexes of the F1 and F2 generations, the SPC and SPC-IF groups had lower body weight gains than the NIH-41 controls and the AIN-93 group had an increased percent body fat at postnatal day 21. AIN-93 F1 pups had higher baseline glucose than NIH-41 controls, but diet did not significantly affect breeding performance or responses to glucose or uterotrophic challenges. Reduced testes weight and sperm in the AIN-93 group may be related to low thiamine levels. Our observations underline the importance of careful selection, manufacturing procedures, and nutritional characterization of diets used in toxicological studies.

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“…Vitamin B1 (thiamine) deficiency is a frequent complication in T1D that leads to widespread tissue damage [49]. Thiamine is a well known co-factor of TKT [50], and its deficiency and low TKT activity are highly correlated.…”

Section: Discussionmentioning

confidence: 99%

Peripheral tolerance to insulin is encoded by mimicry in the microbiome

Garćıa

Paterou

Lee

et al. 2019

Preprint

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How organisms achieve sustained peripheral tolerance throughout their lifetime, a correct immune discrimination between self and non-self, remains poorly understood. Host-microbiome interactions carry fundamental information that facilitates this process. We hypothesize that commensal microbes are under evolutionary pressure to develop epitopes that, when presented along with other antigens from their own bacterial community, lead to an overall tolerogenic self classification by the host immune system. Hosts, which have co-evolved with commensals, may rely on mimotopes, bacterial epitopes that are indistinguishable from key self epitopes, as a homeostatic feedback mechanism to establish and maintain tolerance. Using a probabilistic sequence model of peptide mimicry, we show that the gut microbiome contains a set of genes that are likely to trigger identical immune responses to insulin B 9-25, a widely distributed self epitope across tissues and the primary autoantigen in type 1 diabetes. Similarities in the antigen receptor sequences determined from CD4 T cells reacting to insulin epitopes and mimotopes provide experimental evidence for mimicry. All predicted high posterior probability mimotopes belong to the transketolase superfamily, an enzyme that allows efficient harvest of commensal-derived sugar polymers and dietary fibre, an advantage during host colonisation. Microbial transketolase upregulation during infant weaning coincides in time with the peak in autoantibody development against insulin. Abundance changes in bacterial genera that carry these mimotopes have also been observed to precede disease diagnosis. Our findings suggest gut dysbiosis followed by immune response to insulin mimotopes as a primary cause of type 1 diabetes, and may contribute towards unraveling similar causal patterns in a wide variety of disorders.

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Low Thiamine Levels in Children With Type 1 Diabetes and Diabetic Ketoacidosis

Abstract: Thiamine deficiency is common in children with diabetic ketoacidosis, and this deficiency may be worsened by treatment. When metabolic acidosis persists despite appropriate treatment of diabetic ketoacidosis, other factors such as thiamine deficiency should be considered.

Cited by 27 publications

References 16 publications

The relationship between lactate and thiamine levels in patients with diabetic ketoacidosis

The relationship between lactate and thiamine levels in patients with diabetic ketoacidosis

Comparison of endpoints relevant to toxicity assessments in 3 generations of CD-1 mice fed irradiated natural and purified ingredient diets with varying soy protein and isoflavone contents

Peripheral tolerance to insulin is encoded by mimicry in the microbiome

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