The Interactions Between Diabetes Mellitus and Myelodysplastic Syndromes: Current State of Evidence and Future Directions

Hamoudeh, Eyad; Zeidan, Amer M.; Barbarotta, Lisa; Rosano, Nina

doi:10.2174/1573399811666150526151241

Cited by 8 publications

(5 citation statements)

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“…It is worth mentioning that impaired glucose metabolism in red blood cells, 45 and involvement of glucose metabolism in the erythropoiesis in MDS patients, has already been reported. [46][47][48] MCV in diabetes has been investigated but no definitive conclusions made. Although studies reported on lower MCV, 49,50 others suggested that the hyperosmolarity is associated with an increased MCV.…”

Section: Discussionmentioning

confidence: 99%

A predictive algorithm using clinical and laboratory parameters may assist in ruling out and in diagnosing MDS

et al. 2021

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We present a noninvasive Web-based app to help exclude or diagnose myelodysplastic syndrome (MDS), a bone marrow (BM) disorder with cytopenias and leukemic risk, diagnosed by BM examination. A sample of 502 MDS patients from the European MDS (EUMDS) registry (n > 2600) was combined with 502 controls (all BM proven). Gradient-boosted models (GBMs) were used to predict/exclude MDS using demographic, clinical, and laboratory variables. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were used to evaluate the models, and performance was validated using 100 times fivefold cross-validation. Model stability was assessed by repeating its fit using different randomly chosen groups of 502 EUMDS cases. AUC was 0.96 (95% confidence interval, 0.95-0.97). MDS is predicted/excluded accurately in 86% of patients with unexplained anemia. A GBM score (range, 0-1) of less than 0.68 (GBM < 0.68) resulted in a negative predictive value of 0.94, that is, MDS was excluded. GBM ≥ 0.82 provided a positive predictive value of 0.88, that is, MDS. The diagnosis of the remaining patients (0.68 ≤ GBM < 0.82) is indeterminate. The discriminating variables: age, sex, hemoglobin, white blood cells, platelets, mean corpuscular volume, neutrophils, monocytes, glucose, and creatinine. A Web-based app was developed; physicians could use it to exclude or predict MDS noninvasively in most patients without a BM examination. Future work will add peripheral blood cytogenetics/genetics, EUMDS-based prospective validation, and prognostication.

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Section: Discussionmentioning

confidence: 99%

A predictive algorithm using clinical and laboratory parameters may assist in ruling out and in diagnosing MDS

et al. 2021

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“…Multiple epidemiologic studies show that diabetic patients are more likely to develop cancer [8]. There is also evidence that COVID-19 precipitates DKA due to B-cell destruction from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) [7].…”

Section: Discussionmentioning

confidence: 99%

Diabetic Ketoacidosis in Type 1 DM: A Novel Presentation of CML

Jaggon¹,

Ntelis²,

Atalay³

et al. 2022

CRCM

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Diabetic ketoacidosis (DKA) is a life-threatening complication of diabetes characterized by metabolic acidosis, hyperglycemia, and ketosis. It most commonly occurs secondary to a precipitating event such as an infection, non-infectious illness, or insulin non-compliance. We report a case of a 28-year-old male with a history of well-controlled type 1 diabetes mellitus who began having frequent and repeated episodes of DKA. Evaluation for compliance lapses was negative. The further review noted a worsening white blood cell count over the same period, despite repeated negative infectious workups. A bone marrow biopsy revealed a hypercellular marrow with granulocyte and megakaryocyte proliferation. Testing for the BCR-ABL fusion gene was positive in 92% of cells. This led to a final diagnosis of chronic myeloid leukemia as the precipitator for repeated presentation with DKA. The two diseases do not commonly present simultaneously due to differences in median age. No previous reports of adults with DKA precipitated by CML are present in the literature. However, worsening hyperglycemia has been reported with other hematologic malignancies, particularly in the setting of acute lymphoblastic leukemia in the pediatric population. This is thought in some instances to be due to the leukemic process itself, potentially through cytokine release.

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“…The observation of abnormal threonine metabolism to 2,3-DHBA in both children and a dog with IDDM [ 38 ] raises the question as to whether or not our observations of elevated plasma 2,3-DHBA in AML with mutated IDH1/2 could be due to diabetes. The relationship between diabetes mellitus and myelodysblastic syndromes (MDS) has been examined but there is no clear evidence that diabetes is a risk factor for MDS [ 64 ]. MDS can evolve into AML [ 65 ], but only seven of our 51 patients had a previous diagnosis of MDS ( Table S1 ).…”

Section: Discussionmentioning

confidence: 99%

(2R,3S)-Dihydroxybutanoic Acid Synthesis as a Novel Metabolic Function of Mutant Isocitrate Dehydrogenase 1 and 2 in Acute Myeloid Leukemia

Idle

Seipel

Bacher

et al. 2020

Cancers

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Acute myeloid leukemia (AML) frequently harbors mutations in isocitrate 1 (IDH1) and 2 (IDH2) genes, leading to the formation of the oncometabolite (2R)-hydroxyglutaric acid (2R-HG) with epigenetic consequences for AML proliferation and differentiation. To investigate if broad metabolic aberrations may result from IDH1 and IDH2 mutations in AML, plasma metabolomics was conducted by gas chromatography–mass spectrometry (GC–MS) on 51 AML patients, 29 IDH1/2 wild-type (WT), 9 with IDH1R132, 12 with IDH2R140 and one with IDH2R172 mutations. Distinct metabolic differences were observed between IDH1/2 WT, IDH1R132 and IDH2R140 patients that comprised 22 plasma metabolites that were mainly amino acids. Only two plasma metabolites were statistically significantly different (p < 0.0001) between both IDH1R132 and WT IDH1/2 and IDH2R140 and WT IDH1/2, specifically (2R)-hydroxyglutaric acid (2R-HG) and the threonine metabolite (2R,3S)-dihydroxybutanoic acid (2,3-DHBA). Moreover, 2R-HG correlated strongly (p < 0.0001) with 2,3-DHBA in plasma. One WT patient was discovered to have a D-2-hydroxyglutarate dehydrogenase (D2HGDH) A426T inactivating mutation but this had little influence on 2R-HG and 2,3-DHBA plasma concentrations. Expression of transporter genes SLC16A1 and SLC16A3 displayed a weak correlation with 2R-HG but not 2,3-DHBA plasma concentrations. Receiver operating characteristic (ROC) analysis demonstrated that 2,3-DHBA was a better biomarker for IDH mutation than 2R-HG (Area under the curve (AUC) 0.861; p < 0.0001; 80% specificity; 87.3% sensitivity). It was concluded that 2,3-DHBA and 2R-HG are both formed by mutant IDH1R132, IDH2R140 and IDH2R172, suggesting a potential role of 2,3-DHBA in AML pathogenesis.

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The Interactions Between Diabetes Mellitus and Myelodysplastic Syndromes: Current State of Evidence and Future Directions

Cited by 8 publications

References 0 publications

A predictive algorithm using clinical and laboratory parameters may assist in ruling out and in diagnosing MDS

A predictive algorithm using clinical and laboratory parameters may assist in ruling out and in diagnosing MDS

Diabetic Ketoacidosis in Type 1 DM: A Novel Presentation of CML

(2R,3S)-Dihydroxybutanoic Acid Synthesis as a Novel Metabolic Function of Mutant Isocitrate Dehydrogenase 1 and 2 in Acute Myeloid Leukemia

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