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Biomedical subjects

N H Cho

Publications and source records attributed to N H Cho.

At least 19 recordsLinked to original sources
PubMed2001

Prognostic role of cyclin D1 in retroperitoneal sarcomas.

PURPOSE: Cyclin D1 regulates the G1 checkpoint of the cell cycle and is overexpressed in a number of cancers. This study was designed to determine if cyclin D1 overexpression had prognostic value in patients undergoing surgery with curative intent for primary retroperitoneal soft-tissue sarcoma. METHODS: Tissue was available for analysis on 79 patients who underwent resection between September 1983 and May 1997. Clinicopathologic data and follow-up was obtained from a prospective sarcoma database and a patient and family interview. Immunohistochemical analysis was used to determine overexpression (> or = 5% of nuclei labeled). Survival was analyzed using the Kaplan-Meier method, and statistical analysis was performed by using log rank testing and the Cox regression model. RESULTS: Median follow-up was 3.5 years. On univariate analysis of disease-specific mortality, significant prognostic factors were high grade (n = 42, 53%), positive microscopic margins (n = 36, 46%) or macroscopic margins (n = 15, 19%), and cyclin D1 overexpression (n = 37, 47%). On multivariate analysis, macroscopically positive margins (P = 0.02) and the combination of high grade and cyclin D1 overexpression (P = 0.04) both were associated independently with poor survival. CONCLUSION: High grade retroperitoneal sarcomas demonstrating cyclin D1 overexpression have had an extremely poor prognosis. Continued study of multiple biological markers, exemplified by cyclin D1, may aid characterization of tumor behavior and response to treatment in this diverse group of tumors.

Analysis of Variance↗
PubMed2001

Expression of chemokine genes in human dermal microvascular endothelial cell lines infected with Orientia tsutsugamushi.

Scrub typhus, caused by Orientia tsutsugamushi, is characterized by local as well as systemic inflammatory manifestations. The main pathologic change is focal or disseminated multiorgan vasculitis, which is caused by the destruction of endothelial cells and perivascular infiltration of leukocytes. We investigated the regulation of chemokine induction in transformed human dermal microvascular endothelial cells (HMEC-1) in response to O. tsutsugamushi infection. The monocyte chemoattractant protein-1 (MCP-1) and interleukin 8 (IL-8) mRNAs were induced, and their levels showed a transitory peak at 3 and 6 h, respectively. The RANTES transcript was detected at 6 h after infection, with increased levels evident by 48 h. The induction of the MCP-1 and IL-8 genes was not blocked by cycloheximide, suggesting that de novo protein synthesis of host cell proteins is not required for their transcriptional activation. Heat- or UV-inactivated O. tsutsugamushi induced a similar extent of MCP-1 and IL-8 responses. The induction of MCP-1 and IL-8 transcripts in the endothelial cells by O. tsutsugamushi was not blocked by the inhibitors of NF-kappaB. Furthermore, the activation of NF-kappaB was not detected in HMEC-1 stimulated with O. tsutsugamushi. These results demonstrate that heat-stable molecules of O. tsutsugamushi induce the MCP-1 and IL-8 genes and the induction of the chemokine genes may be mediated by an NF-kappaB independent mechanism. We also showed that another major transcription factor, activator protein-1 (AP-1), was up-regulated in HMEC-1 after O. tsutsugamushi infection. This suggests the possible involvement of AP-1 in the chemokine gene expression.

Cells, Cultured↗
PubMed2001

How reliable is the ultrasound densitometer for community screening to diagnose osteoporosis in spine, femur, and forearm?

Dual X-ray absorptiometry (DXA) is the most widely used noninvasive, quantitative diagnostic method of measuring bone density, but it exhibits several limitations for the purpose of general screening and community-based study. Thus, we evaluated the feasibility of the ultrasound densitometer SoundScan Compact for screening the osteoporosis community. We compared the reliability of the SoundScan Compact's measurement to predict both osteopenia and osteoporosis at the spine, femur, and forearm measured by the XR-36. World Health Organisation criteria and Korean reference were used for the diagnosis of osteopenia and osteoporosis. Of the 1827 subjects screened in the community, we randomly selected and invited 106 subjects to our university hospital center for clinical epidemiology for further evaluation of their bone health using DXA. The site-specific relationships among speed of sound and bone mineral density at L2-L4 spine, femoral neck, trochanter, Ward's triangle, distal radius + ulna, proximal radius + ulna, and proximal radius were highly correlated with r values of 0.633, 0.632, 0.674, 0.632, 0.668, 0.78, and 0.777 respectively (all p < 0.0001). Of the 42 subjects defined as normal in the spine by SoundScan Compact's, 27 (64.3%) were also in agreement as the normal by the XR-36. However, an agreement of 43.5% (10/23) in osteopenia and 53.7% (22/41) in osteoporosis was less sensitive. Reliability tested by kappa statistics (kappa = 0.35; t = 5.3; p < 0.0001) revealed that the degree of agreement was not coincidental. On the femur, 54.8% (23/42) agreed as normal, 73.9% (17/23) as osteopenia, and 39% (16/41) as osteoporosis (kappa = 0.33; t = 5.5; p < 0.0001). Higher reliability was found in the forearm, with a kappa value of 0.48, t = 7.2, and p < 0.0001. A magnitude of agreement was also greater in the forearm, with 83.3% (35/42) agreement in normal, 52.2% (12/23) in osteopenia, and 64% (16/25) in osteoporosis. Although the SoundScan Compact's measures different bone properties and measurements are taken at different sites, it is a very useful instrument with a high correlation and high degree of variation and reliability to predict bone health at other sites such as the spine, femur, and forearm. The ultrasound densitometer such as SoundScan Compact's merits its use for community screening and in the primary care setting to detect osteopenia and osteoporosis for the purpose of early detection and prevention.

Absorptiometry, Photon↗
PubMed2001

Development of rat prostatitis model by oral administration of isoflavone and its characteristics.

Inflammation of the prostate can be induced experimentally in rats by the subcutaneous administration of estrogen. However, it is usually achieved at the price of some alteration in the sex steroid hormone balance and morphological changes in the prostate. In this study, a soy-extracted isoflavone mixture with weak estrogenic activity was administered orally in an attempt to induce prostatitis in a more physiologic way and to characterize the inflammation induced. A total of 36 male Sprague-Dawley rats, 8 weeks old, were divided into 2 groups. The control group was fed with only an AIN-76A diet containing no detectable phytoestrogen and the experimental group was fed with AIN-76A and a soy- extracted isoflavone mixture (genistein 60.0% and daidzein 19.6%), 300 mg/kg body weight for 9 weeks. The sequential body weight and prostate weight at necropsy were measured. A histologic examination and histomorphometry assessed the changes in the prostate. The serum concentrations of testosterone and dihydrotestosterone were measured to estimate the effects on the androgen level. Intraprostatic concentrations of genistein and daidzein were measured by gas chromatography/ mass spectroscopy (GC/MS). While no sign of prostate inflammation was apparent in the control group, severe inflammatory changes in the stroma, increased epithelial detachment and inflammatory exudates within the glandular lumen of the dorsolateral prostate were observed in more than 80%(15/18) of the experimental group. However, there was no significant difference in the ventral prostate between the two groups. The daidzein and genistein concentrations in both the lateral and ventral prostates were significantly higher in the experimental group than in the control group where no isoflavone was detectable. In addition, the concentrations were much higher in the dorsolateral than in the ventral prostate. Although the body weight gain was not consistent in the experimental group, there were no significant differences in the prostate weight and serum androgen level between groups. In summary, when a soy-extracted genistein and daidzein-rich isoflavone mixture was administered orally into rats, prostatic inflammation with characteristic lobe specificity developed. The present method of inducing prostatitis seems to be a more physiologic than an estrogen-induced experimental model, and sequential pharmacokinetic studies might help in establishing this model as a more valuable tool in assisting future research in this field.

Administration, Oral↗
PubMed2000

Expression of cyclin E in placentas with hydropic change and gestational trophoblastic diseases: implications for the malignant transformation of trophoblasts.

BACKGROUND: Although much is known about the morphologic, cytogenetic, and clinical characters of gestational trophoblastic diseases, little information has appeared concerning the parameters related to their persistence or neoplastic transformation. Cell cycle alterations in tumor tissue were examined in this study in light of obvious changes in the clinical behavior of malignant cells. There is an increasing body of evidence suggesting that the abnormal expression of cyclins is considered one of the most important events in malignant transformation of various human cancers. Among these cell cycle regulators, the role of cyclin E in the neoplastic transformation of trophoblast populations has been poorly defined. METHODS: Using formalin fixed, paraffin embedded trophoblastic tissues, the authors investigated the expression of cyclin E by immunohistochemistry in placentas with hydropic change and gestational trophoblastic diseases. The specimens examined included tissue from 29 patients with complete hydatidiform mole, 18 patients with partial hydatidiform mole, and 6 patients with choriocarcinoma after term pregnancy or abortion. The authors also studied four cases of hydropic abortion. RESULTS: The cyclin E indexes (CEI) were as follows: 25.7% +/- 6.2% for hydropic change, 35.3% +/- 12.7% for triploid partial moles, 42.2% +/- 13.1% for diploid/tetraploid complete moles, and 63.6% +/- 9.5% for choriocarcinomas. There was a significant difference in CEI between placentas with hydropic change and partial mole (P = 0.04) and placentas with hydropic change and complete mole (P = 0.003). Choriocarcinomas had significantly higher cyclin E expression compared with placentas, partial moles, and complete moles, respectively. A significant correlation between the expression of cyclin E and S-phase fraction was observed in gestational trophoblastic diseases (rank correlation coefficient = 0.45, P < 0. 05). The relation between cyclin E expression and proliferation was abrogated in placentas with hydropic change, suggesting that cyclin E up-regulation represents a genuine aberration. CONCLUSIONS: The results of this study were consistent with the concept that cyclin E overaccumulation may play an important role in the uncontrolled proliferation and neoplastic transformation of trophoblasts.

Cell Cycle↗
PubMed2000

Androgen receptor gene mutation identified by PCR-SSCP and sequencing in 4 patients with complete androgen insensitivity syndrome.

To study the genetic defect of the human androgen receptor (hAR) gene in the complete androgen insensitivity syndrome (CAIS), we amplified each of the eight exons by PCR in genomic DNA extracted from the paraffin blocks of the resected gonads. We analyzed using SSCP, and directly sequenced the abnormally shifted bands. Mutations were found in 4 cases of CAIS. Patient 1 carried a point mutation; a G to A transition in exon 7 resulted in a change from arginine to glutamine at codon 831. Patient 2 carried a point mutation; a C to T transition in exon 7 resulted in a change from arginine to stop at codon 831. Patient 3 carried a point mutation and deletion in exon 7. A point mutation was an A to G transition that caused a glutamine to be substituted for the asparagine present at codon 819. A deletion of a G at codon 820 resulted in a frameshift and consequently in the introduction of a premature stop at codon 821. Patient 4 carried a mutation in 5' splice donor site of intron 7; a G to T transition might have caused an abnormal splicing of the exon 7. All of the mutations were found in exon 7. These mutations of hAR gene might be related to the pathogenesis of CAIS.

Adolescent↗
PubMed2000

Correlations between the intrauterine metabolic environment and blood pressure in adolescent offspring of diabetic mothers.

OBJECTIVE: To investigate associations between maternal diabetes and blood pressure (BP), obesity, impaired glucose tolerance, and serum lipids in offspring and whether these parameters correlate with metabolism during pregnancy. STUDY DESIGN: Body mass index, BP, serum glucose, and insulin during an oral glucose tolerance test, and lipid concentrations were measured in 99 offspring of diabetic mothers (ODM) and 80 members of a control group. RESULTS: ODM were more obese (body mass index 22.5 +/- 5.6 vs 20.3 +/- 4.0 kg/m(2)) and had higher systolic (8 mm Hg) and mean arterial BP (4 mm Hg) but similar diastolic BP compared with the control group. ODM had higher 2-hour glucose (6.6 +/- 1.3 vs 5.7 +/- 0.9 mmol/L) and insulin (580 +/- 544 vs 377 +/- 239 pmol/L) concentrations but lower fasting concentrations of low-density lipoprotein (2.54 +/- 0.67 vs 2.82 +/- 0.70 mmol/L) and total cholesterol (4.01 +/- 0.80 vs 4.40 +/- 0.78 mmol/L). In both groups body mass index, triglycerides, and fasting and 2-hour glucose concentrations showed correlations with BP measurements. Fasting insulin was correlated with BP readings only in the ODM. Correlations were found between second- and third-trimester maternal free fatty acid concentrations and diastolic and mean arterial BP. Third-trimester beta-hydroxybutyrate was correlated with mean arterial BP. CONCLUSIONS: In ODM, abnormalities in weight and glucose tolerance are associated with abnormal maternal metabolism. Higher BP is an additional abnormality associated with fetal overnutrition.

Adolescent↗
PubMed2000

Expression of chemokine genes in murine macrophages infected with Orientia tsutsugamushi.

Scrub typhus, caused by Orientia tsutsugamushi infection, is characterized by local as well as systemic inflammatory manifestations. Inflammation is initiated by O. tsutsugamushi-infected macrophages and endothelial cells in the dermis. We investigated the regulation of chemokine induction in macrophage cell line J774A.1 in response to O. tsutsugamushi infection. The mRNAs for macrophage inflammatory proteins 1alpha/beta (MIP-1alpha/beta), MIP-2, and macrophage chemoattractant protein 1 were induced within 30 min, and their levels showed a transitory peak for 3 to 12 h. However, the lymphotactin, eotaxin, gamma interferon-inducible protein 10, and T-cell activation gene 3 mRNAs were not detected by RNase protection assays. Heat-killed O. tsutsugamushi induced a similar extent of chemokine responses. Induction of the chemokine genes was not blocked by the eukaryotic protein synthesis inhibitor cycloheximide, suggesting that de novo synthesis of host cell protein is not required for these transcriptional responses. The induction of chemokine mRNAs by O. tsutsugamushi was blocked by the inhibitors of NF-kappaB activation. Furthermore, O. tsutsugamushi induced the nuclear translocation and activation of NF-kappaB. These results demonstrate that heat-stable molecules of O. tsutsugamushi induce a subset of chemokine genes and that induction involves activation of the transcription factor NF-kappaB.

Animals↗
PubMed1999

Pathological difference between retractile and cryptorchid testes.

PURPOSE: We compared testicular biopsies from retractile and cryptorchid testes to determine the histological effect of testicular retraction and the necessity of treatment for retractile testes. MATERIALS AND METHODS: A total of 61 testicular biopsies were performed during orchiopexy in 36 boys 1.3 to 9.8 years old (mean age 5.4) with retractile testes (unilateral in 11, bilateral in 50) and 115 testicular biopsies were done in 83 patients with cryptorchidism (unilateral in 51, bilateral in 64) 0.5 to 14.9 years old (mean age 3.7). Parameters for germ and Sertoli cells were determined in each group. RESULTS: Mean average spermatogonial number (S/T value) and Sertoli cell index were statistically different between retractile and cryptorchid testes with values of 2.96+/-1.33 versus 0.61+/-0.87 and 26.81+/-6.75 versus 23.04+/-5.85, respectively. Average tubular degeneration phase V to VII ratio was 0.23+/-0.18 for retractile testes and 0.22+/-0.17 for cryptorchid testes which was not statistically different. CONCLUSIONS: Similar tubular degeneration phase V to VII values between retractile and cryptorchid testes indicate histological change in retractile testes and suggest the need for hormonal or surgical therapy for those patients with retractile testes lacking spontaneous descent.

Biopsy↗
PubMed1999

Protective immunity of microsphere-based mucosal vaccines against lethal intranasal challenge with Streptococcus pneumoniae.

Mucosal vaccination of capsular polysaccharide (PS) of Streptococcus pneumoniae and subsequent creation of the first line of immunological defense in mucosa were examined. Mucosal as well as systemic antibody responses to PS were evoked by peroral or intranasal immunization of BALB/c mice with PS-cholera toxin B subunit (CTB) conjugates entrapped in the alginate microspheres (AM). The bacterial colonization at the lung mucosa was most profoundly inhibited (<95%) by intranasal immunization with the naked conjugate (PS-CTB). The mice vaccinated orally with encapsulated conjugate [AM(PS-CTB)] showed significant reduction on the level of pneumococcal bacteremia (<99%). Eighty percent of the mice perorally immunized with AM (PS-CTB) were protected from lethal intranasal challenge with S. pneumoniae, whereas more than 60% of the mice in the other control groups died of infection. Our novel approach may prove to be important in the development of a mucosal vaccine that will provide protection of mucosal surfaces of host.

Animals↗
PubMed1999

T2-weighted fast spin-echo MR findings of adenocarcinoma of the uterine cervix: comparison with squamous cell carcinoma.

The purpose of this study was to investigate the differences in MR findings of adenocarcinoma (AC) and squamous cell carcinoma (SCC) of the uterine cervix and to compare MR findings with pathologic findings. MR images of 17 patients with pathologically proven AC, using a fast spin-echo (FSE) T2-weighted image (T2WI) with pelvic phased-array coil on a 1.5-T unit, were retrospectively evaluated. After measurement of the signal intensity (SI) ratios of the region of interest between tumors and gluteus maximus muscle, we compared the ratios of AC with those of 16 patients with SCC. AC showed relatively high SI on FSE T2WI with multiseptated lesions in four cases and hydrometrocolpos in three cases. The mean SI ratio was 3.82 +/- 1.68 in AC and 2.35 +/- 0.42 in SCC (p < 0.0001, t-test). Multiple tumorous glands with cytoplasmic and intraglandular mucin or serous fluid were pathologically found in AC, but SCC revealed the compact cellularity of stratified squamous tumor cells. The cervical AC showed higher SI than SCC on FSE T2WI with occasional multiseptated lesions and hydrometrocolpos. If the SI ratio of the tumor was more than 3.0, AC could be diagnosed with a sensitivity of 68.8% and a specificity of 100%.

Adenocarcinoma↗
PubMed1998

Novel mucosal immunization with polysaccharide-protein conjugates entrapped in alginate microspheres.

A novel mucosal immunization was examined using biocompatible and biodegradable alginate microspheres containing a conjugate of polysaccharide antigen and cholera toxin B subunit (CTB). In order to prepare the alginate microspheres with diameters of less than 5 microm, a new diffusion-controlled interfacial gelation technique was developed. Also, in order to improve the mucosal immune response, a pneumococcal capsular polysaccharide type 19 (PS19) was conjugated to the CTB (PS19-CTB). This conjugate was subsequently encapsulated into the alginate microspheres. The loading content of PS19-CTB to the alginate microspheres was 60%. An in vitro sustained release pattern was observed with the antigen-loaded microspheres, showing 80% antigen release within one day. Mucosal and systemic immunities following oral immunization with the alginate microspheres were studied. Balb/c mice were immunized perorally three times at intervals of two weeks. Peroral immunization with 25 microg of PS19-CTB entrapped in the alginate microspheres evoked both the mucosal IgA and systemic IgM responses to PS19 in small intestine and in sera, respectively. The results suggest that both the mucosal and systemic antibody responses could be induced by oral administration of the PS19-CTB antigen entrapped in alginate microspheres.

Alginates↗
PubMed1998

Underexpression of cyclin-dependent kinase (CDK) inhibitors in cervical carcinoma.

Recent studies have revealed a new family of tumor suppressor genes that directly implicate aberrant cell cycle regulation in tumorigenesis. The general function of these gene products is that they prevent cell cycle progression by directly interfering with cyclin/cyclin-dependent kinase (CDK) activation. The importance of these genes is that they are potent inhibitors of CDK. Among these cell cycle inhibitors, p21(WAF1/CIP1) and p16 have been thoroughly studied. However, the role of p21(WAF1/CIP1) and p16 in the tumorigenesis of the uterine cervix has been poorly defined. We used immunohistochemical techniques to study the expression of these cell cycle inhibitors in formalin-fixed, paraffin-embedded cervical tissue to explore the relationship between cyclin/CDK inhibitors and cervical carcinoma. Cervical tissues were analyzed from 46 patients with cervical carcinoma, 30 cases with cervical intraepithelial neoplasia (CIN) and 22 control cases who underwent hysterectomy due to benign gynecologic disease at Yonsei University College of Medicine. All CDK inhibitors were strongly expressed in the reverse cell hyperplasia and koilocytes, whereas they revealed significantly decreased expression in neoplastic tissues (P < 0.05). P16 revealed higher expressions in cases associated with human papillomavirus (HPV) (t test, P < 0.05) than in cases lacking any type of HPV. Our results were consistent with the concept that underexpression of CDK inhibitors may play an important role in neoplastic transformation in cervical carcinoma.

Adult↗
PubMed1998

Short stature in Korean women: a contribution to the multifactorial predisposition to gestational diabetes mellitus.

We examined the associations between demographic characteristics including short stature and the prevalence of gestational diabetes mellitus (GDM) in Korean women. In this study, a total of 9005 pregnant women underwent universal screening for GDM. Oral glucose tolerance tests (100 g OGTT) were performed in positive screenees (1 h plasma glucose > or = 7.2 mmol/l) and GDM was diagnosed using National Diabetes Data Group criteria. Women with GDM were older and heavier than those with a positive screen and normal OGTT, as well as those with a negative screen. However, height of women with GDM was significantly shorter than those with a positive screen and normal OGTT, and a negative screen. When the study subjects were stratified according to height quartiles, the plasma glucose at the screening test decreased as height increased. Furthermore, the prevalence of GDM was highest in the shortest quartile (< or = 157 cm) group; the odds ratio for GDM was two times greater compared with the highest quartile (> or = 163 cm) group, even after controlling for age and body mass index (BMI). In addition, multiple logistic regression analysis revealed that greater prepregnancy BMI, age, weight gain, a parental history of diabetes mellitus, and shorter maternal height were directly and independently associated with the prevalence of GDM. We have found that short stature is an independent risk factor for GDM in the racially homogeneous population of Seoul, Korea. It is suggested that this propensity may be conveyed primarily by environmental influences. However, genetic factors may also modify the response to the environmental insult. Our findings also emphasize the heterogeneity of factors which predispose to GDM.

Adult↗
PubMed1998

Detection of human papillomavirus in warty carcinoma of the uterine cervix: comparison of immunohistochemistry, in situ hybridization and in situ polymerase chain reaction methods.

Warty carcinoma of the uterine cervix is a very rare specific variant of invasive squamous cell carcinoma, usually described as a hybrid feature of condyloma with invasive squamous cell carcinoma. Besides having the koilocytes and maturation of squamous epithelium, there is unequivocal stromal invasion. The feathery surface seems to be characteristic of warty carcinoma, differentiating it from condylomata acuminata or verrucous carcinoma. Using in situ polymerase chain reaction (IS-PCR) and in situ hybridization (ISH) as well as an immunohistochemical technique (IHC), we determined the amplification and expression of several human papilloma virus (HPV) types (6, 11, 33, 16 and 18) in nine warty carcinomas of the uterine cervix. We found amplified HPV predominantly in the nuclei of the feathery surface in all cases only when IS-PCR was applied, while it was detected only in five (55.6%) or six cases (66.7%) by conventional IHC or ISH, respectively. We found multiple types in the same lesion in six cases (66.7%) by IS-PCR, in comparison with ISH which detected a lower incidence (22.2%). This finding of coinfection is more consistent with that seen in low-grade squamous intraepithelial lesions (LSILs) of the uterine cervix than in high SIL. It is important to be aware of these distinct lesions in postmenopausal women with their characteristic feathery and thin surface, as well as a hybrid form of exophytic condyloma and stromal invasion, and frequent coinfection of multiple different HPVs as a type of LSILs.

Adult↗
PubMed1998

Long-term effects of the intrauterine environment. The Northwestern University Diabetes in Pregnancy Center.

We sought to test the hypothesis that long-term postnatal development may be modified by metabolic experiences in utero. We enrolled offspring of women with pregestational diabetes (this included type 1 and type 2 diabetes) and gestational diabetes in a prospective study from 1977 to 1983. Fetal beta-cell function was assessed by measurement of amniotic fluid insulin (AFI) concentration at 32-38 weeks' gestation. Postnatally, offspring were seen yearly for neuropsychological testing, measurement of anthropometrics, and modified glucose tolerance testing. Neuropsychological control subjects were followed longitudinally. Additional control subjects had anthropometrics measured once, and a random subset of these had a single oral glucose challenge at 10-16 years. The rates of major neuropsychological disturbances in our cohort did not differ significantly from national estimates. However, aberrant maternal metabolism was associated with poorer intellectual performance and psychomotor development. The macrosomia observed at birth in offspring of diabetic mothers (ODM) resolves by 1 year of age. Obesity recurs in childhood; and by 14-17 years, the mean BMI is 24.6 +/- 5.8 kg/m2 in ODM versus 20.9 +/- 3.4 kg/m2 in control subjects. Obesity in adolescence is associated with sex, mother's weight, and AFI concentration. Impaired glucose tolerance (IGT) is found in 36% of ODM and is also associated with elevated amniotic fluid insulin in utero. In confirmation of our original hypothesis, aberrant maternal metabolism is associated with poorer intellectual and psychomotor development, obesity, and IGT in offspring. Excessive insulin secretion in utero, as assessed by AFI concentration, is a predictor of both obesity and IGT in adolescence. This study is a long-term prospective evaluation of the effects of maternal diabetes on pregnant women and their offspring. In this article, we report the results of the correlations between indexes of maternal and fetal metabolism during pregnancy and the offspring's subsequent physical, metabolic, and psychological development from birth through adolescence.

Adolescent↗