Glycemic Control and Hemoglobinopathy: When A1C May Not Be Reliable

Smaldone, Arlene

doi:10.2337/diaspect.21.1.46

Cited by 40 publications

(34 citation statements)

References 26 publications

(11 reference statements)

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“…The presence of a hemoglobin variant may be suspected in a variety of situations including a discordance between the patient's self-monitoring glucose measurements and the A1c value, an A1c result >15 %, a markedly different A1c result compared to the previous value when a different method is used to measure A1c, or the presence of anemia with abnormal red cell indices on a complete blood count. 42 …”

Section: Hemoglobin Variantsmentioning

confidence: 99%

Pitfalls in Hemoglobin A1c Measurement: When Results may be Misleading

2013

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Section: Hemoglobin Variantsmentioning

confidence: 99%

Pitfalls in Hemoglobin A1c Measurement: When Results may be Misleading

2013

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“…The level of Hb1Ac, however, does not serve as a reliable indicator of long-term hyperglycemia in all situations (8,46). Reduced activity of glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme in the pentose phosphate pathway, produces lower Hb1Ac levels than expected during hyperglycemia through reducing glucose metabolism (5).…”

Section: Vol 31 2011mentioning

confidence: 99%

CrbpI Modulates Glucose Homeostasis and Pancreas 9-cis-Retinoic Acid Concentrations

Kane

Folias

Pingitore

et al. 2011

Molecular and Cellular Biology

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Cellular retinol-binding protein type I (CrbpI), encoded by Rpb1, serves as a chaperone of retinol homeostasis, but its physiological effects remain incompletely understood. We show here that the Rbp1 ؊/؊ mouse has disrupted retinoid homeostasis in multiple tissues, with abnormally high 9-cis-retinoic acid (9cRA), a pancreas autacoid that attenuates glucose-stimulated insulin secretion. The Rbp1 ؊/؊ pancreas has increased retinol and intense ectopic expression of Rpb2 mRNA, which encodes CrbpII: both would contribute to increased ␤-cell 9cRA biosynthesis. 9cRA in Rbp1 ؊/؊ pancreas resists postprandial and glucose-induced decreases. Rbp1 (27,36). The relative amounts of apo-and holo-CrbpI facilitate cellular retinol uptake, modulate retinol storage as retinyl esters (RE), and affect retinoid homeostasis by regulating enzyme activity differentially (25, 34). Retinoic acid receptor (RAR) activation depends on CrbpI-mediated retinol uptake. CrbpI mutants with low retinol-binding affinity reduce RAR function in human mammary epithelial cells, leading to a loss of differentiation (10). Nevertheless, Rbp1 Ϫ/Ϫ mice are seemingly healthy and show no gross abnormalities characteristic of overt retinoid deficiency (13). All-trans-retinoic acid (atRA) in serum and several target tissues does not differ significantly between Rbp1 Ϫ/Ϫ and wild-type (WT) mice, likely accounting for lack of gross abnormalities (20, 29). Despite these insights, physiological effects of CrbpI remain to be elucidated fully.Retinol functions primarily through its metabolite atRA, which has diverse effects on energy metabolism. atRA induces pancreas development and differentiation into acini (18,24,28,32), but restricting dietary vitamin A in diabetes-prone rats reduces diabetes and insulitis, an effect not reversed by dosing atRA, suggesting contributions of additional retinoids (9). atRA arrests differentiation of preadipocytes into mature white adipocytes, early in the differentiation process (43, 48). Ablation of Rdh1, which encodes one of several short-chain dehydrogenases that catalyze the first and rate-limiting step in atRA biosynthesis from retinol, increases adiposity in mice fed a nonobesogenic diet (50). Dosing atRA ameliorates weight gain and represses insulin resistance in mice fed an obesogenic (high-fat) diet (3). atRA induces Ucp1, which encodes an uncoupling protein expressed in brown adipose tissue that supports thermogenesis (31).Although atRA mediates most vitamin A functions, 9-cis-RA (9cRA) occurs as an endogenous pancreas retinoid with unique actions independent of atRA (22). 9cRA, biosynthesized primarily by ␤-cells and detected only in pancreas, varies rapidly and inversely with serum glucose. 9cRA attenuates glucose-stimulated insulin secretion (GSIS): a decrease in 9cRA allows optimum glucose-stimulated insulin secretion, whereas dosing with 9cRA impairs insulin secretion and glucose tolerance. 9cRA acts, in part, through reduction of Glut2 and GK activities and through repressing expression of genes that function to pro...

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“…This parameter may be determined using several methods, including ion-exchange high-performance liquid chromatography (HPLC), boronate affinity HPLC, immunoassays and enzymatic assays (3)(4)(5)(6). Ion-exchange HPLC methods are most commonly used because they are fast, accurate and reliable.…”

Section: Introductionmentioning

confidence: 99%

“…With the expansion of ion-exchange HLPC testing, inconsistencies between the plasma glucose and HbA1c levels are sometimes identified (3)(4)(5)(6). These inconsistencies most often result from the effects of an altered blood cell life span and the presence of Hb variants (3)(4)(5)(6). The prevalence of abnormal Hb ranges from 0.04% to 6.06%, with more than 700 Hb variants reported to date, 70% of which are clinically silent (7,8).…”

Section: Introductionmentioning

confidence: 99%

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A Rare Case of Variant Hemoglobin (Hb Yahata) Suspected Based on Inconsistent Plasma Glucose and HbA1c Levels

et al. 2015

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A 52-year-old man presented for an evaluation of worsening glycemic control secondary to glucocorticoid administration. The glycated hemoglobin (HbA1c) level was 8%, and oral glucose tolerance testing revealed impaired tolerance, whereas the plasma glucose and glycoalbumin levels were normal. The results of highperformance liquid chromatography (HPLC) for HbA1c, isoelectrofocusing of the hemolysate and precise HPLC measurements of the HbA1c level supported the presence of an Hb variant, and DNA sequencing of the β-globin gene revealed Hb Yahata [β112 TGT (Cys) TAT (Tyr)] (heterozygote). In this case, the discrepancy between the plasma glucose and HbA1c levels raised suspicion of this rare Hb variant.

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Glycemic Control and Hemoglobinopathy: When A1C May Not Be Reliable

Cited by 40 publications

References 26 publications

Pitfalls in Hemoglobin A1c Measurement: When Results may be Misleading

Pitfalls in Hemoglobin A1c Measurement: When Results may be Misleading

CrbpI Modulates Glucose Homeostasis and Pancreas 9-cis-Retinoic Acid Concentrations

A Rare Case of Variant Hemoglobin (Hb Yahata) Suspected Based on Inconsistent Plasma Glucose and HbA1c Levels

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