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Objective: Parental diabetes history is a well-known risk factor for type 2 diabetes and considered strong evidence for a genetic basis of type 2 diabetes. Whether this relationship is affected by other known risk factors, specifically obesity, remains unclear, possibly due to a relative paucity of lean diabetic patients.Research Design and Methods: This issue was investigated using data from a high-risk population from Mexico (National Health Survey 2000, n = 27,349), with observations replicated using U.S. citizens of Mexican descent from the National Health and Nutrition Examination Survey 2001-2002 and 2003-2004 (n = 1,568).Results: As expected, positive parental diabetes was a significant risk factor for type 2 diabetes, regardless of age, sex, or adiposity level. However, positive parental diabetes conferred greater risk in leaner individuals than in their overweight peers (P = 0.001). In other words, the effect of BMI on type 2 diabetes risk was smaller in the presence of parental diabetes history.Conclusions: These findings suggest that parental diabetes is a stronger risk factor for type 2 diabetes in the absence of obesity. Thus, studies in lean diabetic patients could help identify type 2 diabetes susceptibility genes. This study reinforces the concept that parental diabetes and BMI are independent type 2 diabetes risk factors and suggests that glycemic screening may be helpful in assessing type 2 diabetes risk in individuals with parental diabetes history, regardless of their overweight status. [ABSTRACT FROM AUTHOR]

Background: Disruption in androgen profiles and testicular adrenal rest tumors in males with congenital adrenal hyperplasia (CAH) can negatively affect sexual activity and fertility. Adrenal hyperandrogenism suppresses gonadotropin secretion and testicular adrenal rest tumors (TARTS), despite being noncancerous lesions, cause obstructive azoospermia and impaired testosterone (T) production. Circulating T in men with uncontrolled CAH is often predominantly adrenal in origin, which is reflected in high androstenedione/testosterone ratios (A4/T). Therefore, decreased luteinizing hormone (LH) levels and an increased A4/T are markers of impaired fertility in these individuals., Methods: Oral tildacerfont 200 to 1000 mg once daily (QD) (n=10) or 100 to 200 mg twice daily (n=9 and 7) for 2 weeks (Study 201), and 400 mg QD (n=11) for 12 weeks (Study 202). Outcomes measured changes from baseline in A4, T, A4/T, and LH., Results: Mean T levels increased in Study 201 from 375.5 ng/dL to 390.5 ng/dL at week 2 (n=9), 485.4 ng/dL at week 4 (n=4) and 420.7 ng/dL at week 6 (n=4). In Study 202, T levels fluctuated in the normal range from 448.4 ng/dL at baseline to 412.0 ng/dL at week 12. Mean LH levels increased in Study 201 from 0.68 IU/L to 1.59 IU/L at week 2 (n=10), 1.62 IU/L at week 4 (n=5) and 0.85 IU/L at week 6 (n=4). In Study 202, mean LH levels increased from 0.44 IU/L at baseline to 0.87 IU/L at week 12. Mean A4/T decreased across both studies. In Study 201, the mean A4/T changed from a baseline of 1.28 to 0.59 at week 2 (n=9), 0.87 at week 4 (n=4), and 1.03 at week 6 (n=4). In Study 202, the A4/T decreased from baseline of 2.44 to 0.68 at week 12. Four men were hypogonadal at baseline; all experienced improved A4/T and 3/4 (75%) reached levels <1., Conclusion: Tildacerfont treatment demonstrated clinically meaningful reductions in A4 levels, and A4/T with concomitant increased LH levels indicating increased testicular T production. The data suggests improvement in hypothalamic-pituitary-gonadal axis function, but more data is required to confirm favorable male reproductive health outcomes., Competing Interests: Author AK is an employee of Rutgers University, a principal investigator for clinical trials in congenital adrenal hyperplasia with Spruce Biosciences Inc, and a consultant for Antares Pharma. Author RC is an employee of Spruce Biosciences Inc. The authors declare that this study received funding from Spruce Biosciences Inc. The funder had the following involvement with the study: participated with the study design, results and the decision to submit the findings for publication., (Copyright © 2023 Khattab and Charlton.)

Background: Currently, there is limited research on how having a child diagnosed with achondroplasia affects parents' lives. The purpose of the study was to investigate the experiences of parents of infants and young children less than two years of age with achondroplasia., Methods: Concept elicitation interviews were conducted with parents of children less than 2 years of age with achondroplasia in the United States and Spain. Using grounded theory methods modified for health outcomes research, a qualitative analysis of interview transcripts was conducted. Based on the qualitative analysis, a preliminary theoretical model of the experiences of parents of infants and young children with achondroplasia was developed., Results: Fifteen parents, including 14 mothers and 1 father from 15 unique families, participated in individual or focus group concept elicitation interviews in the US (n = 9) and Spain (n = 6). The qualitative analysis identified four key parent impact domains, which included caretaking responsibilities, impacts on emotional well-being, having worries and concerns about their child, and impacts on daily well-being. Frequently discussed caretaking responsibilities among parents were managing child's medical care/treatment (93%), obtaining adaptations/items for child (73%), and monitoring child to avoid complications of achondroplasia (67%). Emotional impacts included feeling stressed/overwhelmed (67%), depressed/sad (40%), and anxious/nervous (33%). Worries and concerns included worry/concern about the future (100%), concerns regarding child's physical health (87%), worry about child's social well-being (80%), concern for child's emotional well-being (73%), and worry about child being able to function independently (67%). Daily well-being impacts included family strain (60%), missed work time (47%), and missed/limited social activities (33%). Based on the qualitative findings, a preliminary theoretical model depicting the experiences of parents of infants and young children with achondroplasia was created., Conclusions: The study sheds light on the range of impacts that parents of infants and young children with achondroplasia may experience, including caretaking responsibilities, impacts on emotional well-being, worries/concerns regarding their child, and impacts on daily well-being. The theoretical model of parent experiences may provide a helpful framework for informing future research and clinical practice., (© 2021. The Author(s).)

Graves' disease is less common in prepubertal than pubertal children, and initial presentation with thyroid storm is rare. We report an 11-year-old prepubertal Hispanic girl who presented with a one-day history of respiratory distress, fever, and dysphagia. She had exophthalmos, a diffuse bilateral goiter and was agitated, tachycardic, and hypertensive. Nasal swab was positive for respiratory syncytial virus (RSV). She was diagnosed with thyroid storm and admitted to the pediatric intensive care unit. While infection is a known precipitant of thyroid storm and RSV is a common pediatric infection, to the best of our knowledge, this is the first reported case of RSV infection apparently precipitating thyroid storm in a prepubertal child.

A study was undertaken to find out the relative amounts of haem and non-haem iron absorbed from meals in which varying amounts of these substances were present. Four meals, each containing 6 mg of iron but with varying ratios of haem and non-haem iron, were fed to two groups of subjects, each group receiving two meals. The geometric mean percentage absorption of non-haem iron decreased from 18.0% (SD range 14.6-22.3%) to 6.4% (SD range 3.4-11.8%) as the non-haem iron content of the meal increased from 1.52 mg to 5.72 mg--there was therefore little variation in the actual amounts of non-haem iron absorbed from the different meals. In contrast, the geometric mean absorption of haem iron was approximately 20% from all four meals, although the haem iron content varied between 0.28 mg and 4.48 mg. The amount of haem iron absorbed was thus a linear function of the amount of haem iron in the meal. Two points emerged from the study. Firstly, the relative importance of haem iron in overall iron nutrition was confirmed. Secondly, the fact that the pattern of absorption in relation to dosage was so different for haem iron and non-haem iron suggested that a controlling mechanism for non-haem iron absorption may be located at the mucosal surface. This conclusion is based on the fact that haem iron, the percentage absorption of which was found to be independent of the size of the dose, is absorbed into the mucosal cell when still contained within the porphyrin ring and the iron thus bypasses some controlling mechanism at the mucosal border.

1. The modification of iron absorption from Fe(III)EDTA by agents known to promote or inhibit absorption was examined in 101 volunteer multiparous Indian women. Fe absorption from Fe(III)EDTA was compared with absorption of intrinsic food Fe in a further twenty-eight subjects. Finally the urinary excretion of radio-Fe after oral administration of 59Fe(III)EDTA was studied in twenty-four subjects and evidence of intraluminal exchange of Fe was examined. 2. Fe absorption from maize porridge fortified with Fe(III)EDTA was more than twice that from porridge fortified with FeSO4 . 7H2O. 3. Although bran decreased Fe absorption from FeSO4 . 7H2O approximately 11-fold, it had no significant effect on Fe absorption from Fe(III)EDTA. Nevertheless tea, which is a more potent inhibitor of Fe absorption, decreased absorption from Fe(III)EDTA 7-fold. 4. Fe absorption from Fe(III)EDTA given in water was only increased 40% by addition of 3 mol ascorbic acid/mol Fe but by 7-fold when the relative proportions were increased to 6:1. This enhancing effect was blunted when the Fe(III)EDTA was given with maize porridge. In these circumstances, an ascorbate:iron value of 3:1 (which doubles absorption from FeSO4 . 7H2O) produced no significant increase in Fe absorption, while a value of 6:1 produced only a 2 . 5-fold increase. 5. Fe absorption from Fe(III)EDTA was not altered by addition of maize porridge unless ascorbic acid was present. 6. Less than 1% of 59Fe administered as 59Fe(III)EDTA was excreted in the urine and there was no inverse relationship between Fe absorption and the amounts excreted (r 0 . 58, P less than 0 . 05). 7. Isotope exchange between 59Fe(III)EDTA and 59FeSO4 . 7H2O was demonstrated by finding a similar relative value for the two isotopes in urine and erythrocytes when the two labelled compounds were given together orally. This finding was confirmed by in vitro studies, which showed enhanced 59Fe solubilization from 59FeSO4 . 7H2O in maize porridge when unlabelled Fe(III)EDTA was added. 8. Although Fe absorption from Fe(III)EDTA was marginally higher it appeared to form a common pool with intrinsic food iron in most studies. It is postulated that the mechanism whereby Fe(III)EDTA forms a common pool with intrinsic food Fe differs from that occurring with simple Fe salts. When Fe is present in the chelated form it remains in solution and is relatively well absorbed because it is protected from inhibitory ligands. Simple Fe salts, however, are not similarly protected and are absorbed as poorly as the intrinsic food Fe. 9. It is concluded that Fe(III)EDTA may be a useful compound for food fortification of cereals because the Fe is well absorbed and utilized for haemoglobin synthesis. The substances in cereals which inhibit absorption of simple Fe salts do not appear to inhibit absorption of Fe from Fe(III)EDTA.

Non-haem-iron absorption from a variety of cereal and fibre meals was measured in parous Indian women, using the erythrocyte utilization of radioactive Fe method. The present study was undertaken to establish whether alteration of the phytate and polyphenol contents of sorghum (Sorghum vulgare) affected Fe absorption from sorghum meals, and to assess the influence of fibre on Fe absorption. Removing the outer layers of sorghum grain by pearling reduced the polyphenol and phytate contents by 96 and 92% respectively. This treatment significantly increased the geometric mean Fe absorption from 0.017 to 0.035 (t 3.9, P less than 0.005). The geometric mean Fe absorption from a sorghum cultivar that lacked polyphenols (albino sorghum) was 0.043, which was significantly greater than the 0.019 absorbed from bird-proof sorghum, a cultivar with a high polyphenol content (t 2.83, P less than 0.05). Fe was less well absorbed from the phytate-rich pearlings of the albino sorghum than from the pearled albino sorghum (0.015 v. 0.035 (t 8.4, P less than 0.0005]. Addition of sodium phytate to a highly Fe-bioavailable broccoli (Brassica oleracea) meal reduced Fe absorption from 0.185 to 0.037. The geometric mean Fe absorption from malted sorghum porridge was 0.024 when 9.5 mg ascorbic acid were added and 0.094 when the ascorbic acid was increased to 50 mg (t 3.33, P less than 0.005). This enhancing effect of 50 mg ascorbic acid was significantly depressed to 0.04 by tea (t 38.1, P less than 0.0005).(ABSTRACT TRUNCATED AT 250 WORDS)

Serum ferritin concentrations were found to be raised, often considerably, in 58 of 76 black patients with primary liver cancer (PLC). No correlation could be demonstrated between the serum ferritin concentration and several other measurements, including the following: hepatic iron stores measured chemically, the size of the tumour, serum transaminase values, and the presence or absence of cirrhosis in the non-tumorous liver. There was, however, a negative correlation between serum ferritin and alpha-foetoprotein concentrations. Ferritin was purified from PLC tissue obtained from three patients at necropsy and the distribution of isoferritins was determined by isoelectric focusing. Acidic isoferritins similar to those previously found in PLC tissue were obtained. Their acidic nature was confirmed chromatographically using DEAE cellulose. Because the serum ferritin in patients with PLC probably consists of a mixture of normal and acidic isoferritins, it is likely that the serum assay used in the present study underestimated the actual concentrations present. With the development of an assay which utlises a specific antibody against acidic PLC isoferritins, serum ferritin may prove to be a second marker for PLC.

1. The feasibility of improving iron nutrition by fortifying cane sugar with Fe and ascorbic acid was studied. 2. It was found to be possible to add a number of Fe salts together with ascorbic acid to sugar without affecting its appearance or storage properties. 3. The absorption of Fe from fortified sugar eaten with maize-meal porridge or made into jam or biscuits was measured in ninety-four volunteer multiparous Indian women using the 59-Fe erythrocyte utlization method. 4. The absorption of Fe from sugar fortified with ascorbic acid and ferrous sulphate and eaten with maize-meal porridge was increased about twofold in the ratio, ascorbic acid:Fe was 10:1 by weight. If the ratio was increased to 20:2, Fe absorption was increased a further threefold. 5. Sugar fortified with soluble Fe salts, including FeSO4.7H2O, discoloured both tea and coffee; sugar fortified with ferric orthophosphate did not have this effect. 6. Fe from FePO4.H2O was poorly absorbed when added with sugar to maize-meal porridge, and also when added with adequate quantities of ascorbic acid. This form of Fe was absorbed much less well than was the intrinsic Fe present in the maize. 7. When sugar fortified with FePO4.H2O and ascorbic acid was added to maize-meal porridge before cooling or was made into jam there was a several-fold increase in the amount of Fe absorbed.

The effect of tea on iron absorption was studied in human volunteers. Absorption from solutions of FeCl3 and FeSO4, bread, a meal of rice with potato and onion soup, and uncooked haemoglobin was inhibited whether ascorbic acid was present or not. No inhibition was noted if the haemoglobin was cooked. The effect on the absorption of non-haem iron was ascribed to the formation of insoluble iron tannate complexes. Drinking tannin-containing beverages such as tea with meals may contribute to the pathogenesis of iron deficiency if the diet consists largely of vegetable foodstuffs.

Serum ferritin concentrations were measured in 651 Black male miners who originated from rural areas throughout southern Africa and who were aged between 17 and 57 years. The mean serum ferritin concentration of 229 microgram/l was above the normal range reported for White subjects, and in 52,8% of the subjects the values were greater than 200 microgram/l. The serum ferritin concentration rose with age, as did the proportion of subjects in each age group who exhibited high values (more than 200 microgram/l). The lowest mean ferritin concentration (112 microgram/l) as well as the lowest proportion of high values (22,9%) were found in subjects from the most northerly area studied. Similarly, the highest mean proportion of high values (66,3%) was seen in the most southerly group studied. Calculations from the present data suggest that the degree of iron overload is currently greater in rural than in urban Black male subjects.

1. Iron absorption from maize (Zea mays) and sorghum (Sorghum vulgare) beer was more than twelve-fold greater than from a gruel made from the constituents used to prepare the beer. 2. The effect of changes occurring during brewing were investigated. These changes include a decrease in the solid content, and the formation of 30 ml ethanol/1 and 5 ml lactic acid/1. 3. The presence of solid material was found to inhibit Fe absorption markedly, especially when the solid content was 100 g/l or more. 4. The presence of ethanol potentiated Fe absorption but the effect was only modest in gruels with a high solid content. 5. Fe absorption from a 2 ml lactic acid/l solution was four-fold greater than from a hydrochloric acid solution of the same pH. When lactic acid was added to a gruel containing 200 g solids/l the mean absorbtion rose from 0.4 to 1.2 %. 6. In a direct comparison, Fe absorption from beer was significantly better than from a gruel of similar pH containing lactic acid. 7. The results suggest that at least three factors are responsible for the enhanced Fe absorption from maize and sorghum beer. These include the removal of solids during fermentation and the presence of ethanol and of lactic acid in the final brew. 8. In order to reproduce the way in which beer is brewed domestically in Fe containers, a study was done in which beer was prepared in the presence of Fe wire. Under such circumstances Fe was rapidly dissolved and the final Fe concentration of the brew was 89 mg/l. However, the nature of the Fe-containing compound or compounds was not elucidated.

The iron status of 320 Indian women living in Chatsworth, Durban, who had volunteered for iron absorption studies, was assessed using a number of measurements. These included: radio-iron absorption, the transferrin saturation, the serum ferritin concentration and the haemoglobin concentration. In the sample as a whole, the prevalence of iron deficiency anaemia (haemoglobin concentration less than 12 g/dl, with two or more abnormal measurements of iron status) was 14,4%. A further 26% had depleted iron stores (serum ferritin less than 12 micrograms/l) and 8,4% also had evidence of iron-deficient erythropoiesis (serum ferritin less than 12 micrograms/l and transferrin saturation below 16%). A profile of iron status based on the cumulative frequency distribution of iron stores showed that the sample, with calculated median iron stores of 150 mg and lower and upper 10 percentiles of -355 mg and 655 mg respectively, was significantly more iron deficient than a sample of women studied in Washington State, USA. Of interest was the observation that all measurements of iron status were better in the older age groups, presumably as a result of the cessation of menstruation. In addition, there was evidence that the duration of menstruation, as volunteered in a brief history, had a significant effect on several measurements of iron status. This was particularly true of the serum ferritin concentration and radio-iron absorption, both of which reflect the size of the iron stores.

There is still controversy concerning the effects of increasing the dietary intake of iron on iron nutrition. This debate has not only centered on the question of efficacy but also on that of safety. At particular potential risk are those individuals with disorders such as idiopathic haemochromatosis, who absorb iron excessively from the diet. Data obtained in the present study and in several other investigations suggest that subjects homozygous for the mutant gene responsible for the disorder would develop clinical features of the disease at a younger age were the dietary iron intake to be increased. Iron stores in affected heterozygotes would increase but the size of the stores would probably equilibrate long before they had reached massive proportions. While these conclusions are drawn from a number of studies, there are enough unanswered questions to make it mandatory for any future fortification programmes, whether they be directed at the entire population or only at certain segments of it, to be carefully monitored. This can currently be achieved with serial plasma ferritin measurements, since the concentrations mirror the size of iron stores in the body.

In Bantu subjects with iron overload iron is visible in skeletal muscle cells and in the tissue histiocytes which lie between these cells. In the present study the concentrations of ;muscle' iron were measured chemically in subjects with varying hepatic storage iron concentrations. The results indicate that the concentrations of storage iron in ;muscle' are much lower than those in the liver. However, the muscle mass is so large that the total amount of iron present is at least equal to that in the liver in subjects with normal body stores. The concentrations of iron in ;muscle' are raised in subjects with iron overload but the degree to which they rise is far less than occurs in the liver; a thirtyfold increase in hepatic iron concentrations is associated with only a sixfold increase in ;muscle' iron. Experiments in rats revealed that storage iron in ;muscle' represents a relatively non-miscible pool which responds very little to acute changes in the iron environment.

Studies of the ascorbic acid status in two subjects with idiopathic haemochromatosis and in 12 with transfusional siderosis showed that all had decreased levels of white cell ascorbic acid. The urinary excretion of ascorbic acid was also diminished in those subjects in whom such measurements were made. The administration of ascorbic acid was followed by only a small rise in the urinary ascorbic acid output, while the oxalic acid levels (measured in two subjects) showed a significant rise. These findings resemble those described in siderotic Bantu, and support the thesis that increased iron stores lead to irreversible oxidation of some of the available ascorbic acid.