ABSTRACT:In infants and children, elevated whole blood zinc protoporphyrin/heme (ZnPP/H) measures iron-deficient (ID) erythropoiesis. Because immature erythrocytes are less dense than mature erythrocytes, we hypothesized that the sensitivity of ZnPP/H is improved if measured in the least dense cells. Blood was collected from control suckling, mildly and severely ID suckling rats. Cord blood was collected after uncomplicated pregnancies (control), diabetic pregnancies (severe ID) and after pregnancies at-risk for iron deficiency (mild ID). ZnPP/H was measured before and after a two-step density centrifugation to obtain the lightest 6.25% of erythrocyte (top fraction). The difference between whole blood and top fraction was defined as ⌬ZnPP/H. In rats, although the whole or top ZnPP/H differed by postnatal age, ⌬ZnPP/H was greatest after the interval with least body iron accrual. In either rats or humans with mild ID, whole blood ZnPP/H was similar to, but ⌬ZnPP/H was greater than controls. In rats and newborn humans, ⌬ZnPP/H is more sensitive than whole blood ZnPP/H in identifying conditions associated with impaired erythrocyte iron delivery and may become a useful tool in measuring erythrocyte iron incorporation in early development. T here is need for a sensitive clinical index of iron-deficient (ID) erythropoiesis in growing premature infants. In premature infants, clinical practices, such as conservative transfusion criteria and erythropoietin therapy may deplete tenuous iron stores (1-4). When iron supply is limited, zinc replaces iron in the protoporphyrin IX ring to form zinc protoporphyrin (ZnPP) (5). An increased ratio of whole blood ZnPP-to-heme (ZnPP/H) reflects impaired erythrocyte iron incorporation (5,6). In older infants, whole blood zinc protoporphyrin/heme (ZnPP/H) is a more sensitive indicator of early, preanemic iron deficiency than Hb or ferritin (7). Whole blood ZnPP/H from cord blood or ill newborns also reflects iron status (4,8). ZnPP/H is higher in newborns born small for dates and offspring of mothers with insulin-treated diabetes (IDM), two conditions commonly exhibiting severely impaired tissue iron content, i.e., severe iron deficiency (severe ID) at birth (4,8). In premature infants, whole blood ZnPP/H falls in response to iron therapy (9) or with indirect delivery of iron via transfusion (3). In premature infants, whole blood ratios are inversely related to gestation (8), a clinical disadvantage because of gestation-based normal values are necessary to guide interpretation (4,8 -10).In mild ID, when Hb levels have not yet fallen, employing a more sensitive test of iron incorporation would be useful to facilitate earlier treatment. When iron demands are great and iron is limited, testing the iron status of reticulocytes, the most recently produced erythrocytes, would decrease the number of false negative assessments and improve the sensitivity of ZnPP/H to detect impaired iron incorporation. Previous work supports that measuring iron incorporation into reticulocytes (reticulocyte Hb,...

Advantages of using the OGTT for measures of diabetes risk include its accessibility and the incorporation of physiological contributions of the gut-pancreas axis in the measures of insulin response to glucose. Mathematical modeling expands the potential gains from the OGTT in physiology and clinical research. Disadvantages include individual differences in the rate of glucose absorption that modify insulin responses, imperfect control of the glycemic stimulus, and poor intraindividual reproducibility. Available research suggests the OGTT provides valuable information about the development of impaired glycemic control and β-cell function in obese youth along the spectrum of glucose tolerance.

Adults and adolescents differ in the underlying defects leading to dysglycemia, and in the nature of β-cell dysfunction across stages of dysglycemia. These results may suggest different approaches to diabetes prevention in youths versus adults.

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