The elusive diagnosis of gestational diabetes.
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Diabetes, Gestational↗
Biomedical subjects
S P Chan
Publications and source records attributed to S P Chan.
Lymphoepithelial cyst of the pancreas: serum markers do not help.
We report a case of lymphoepithelial cyst of the pancreas with non-specific elevation of CA 19.9 and CEA. Pre-operative diagnosis by conventional means proved elusive, and only surgical resection and histopathology revealed the diagnosis. The origin and diagnosis are discussed by literature review.
Biomarkers, Tumor↗
Prohormone convertase 1 in obesity, gestational diabetes mellitus, and NIDDM: no evidence for a major susceptibility role.
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Aspartic Acid Endopeptidases↗
Clinicopathologic studies of thymic carcinoids in multiple endocrine neoplasia type 1.
Thymic carcinoid is part of the multiple endocrine neoplasia type 1 (MEN1) syndrome occurring predominantly in male patients who were heavy smokers, presenting most commonly in middle age. In contrast with metastatic midgut carcinoids, MEN1-related thymic carcinoid is not associated with carcinoid syndrome, nor is it associated with Cushing syndrome, in contrast with sporadic thymic carcinoids. Local invasion and metastasis are common. Prognosis is poor because of late detection, lack of effective treatment, and the aggressive nature of the tumor. All patients with thymic carcinoids should be investigated for MEN1, including thorough clinical evaluation and family studies. Anterior mediastinal lesions in MEN1 male patients should be considered thymic carcinoids until proven otherwise. All male MEN1 patients and asymptomatic gene carriers should be warned of the risk of thymic carcinoids and the possible link to smoking. Computed tomography (CT) of the chest is recommended on first screening for MEN1 in male patients more than 25 years of age, followed by yearly chest X-rays and chest CT every 3 years. Prophylactic thymectomy should be carried out during subtotal or total parathyroidectomy on MEN1 patients.
Adult↗
Correcting for ethnicity when defining large for gestational age infants in diabetic pregnancies.
The large-for-gestational-age (LGA) infant, defined as > 90th birthweight percentile, is associated with mild disturbances of maternal glucose tolerance. In the UK the same birthweight percentile charts are used for all ethnic groups when assessing LGA infants. The influence of maternal hyperglycaemia on LGA infants of Asian (Indian Subcontinent) mothers in the UK is likely to be under-reported, as Asian birthweights tend to be lower than White/Europid birthweights. We assessed the number of LGA infants born consecutively to 21 Asian and 26 White/Europid mothers with gestational diabetes mellitus (GDM), delivered between 37 and 42 weeks gestation, and also in 34 Asian and 121 White/Europid mothers with a positive screening test for GDM but a normal 75 g oral glucose tolerance test (OGTT). Large-for-gestational-age infants were identified using both the standard UK percentile charts of the Medical Research Council and percentile charts constructed from 30,418 Asian and 162,477 White/Europid singleton births, delivered between 37 and 42 weeks gestation to non-diabetic mothers delivered in the North West Thames Region of England. The standard Medical Research Council percentile charts, compared with the ethnically derived charts, identified fewer LGA Asian (7/56 vs 15/56) but more White/Europid infants (33/147 vs 21/147). When correcting for ethnicity more Asian than White/Europid GDM mothers delivered LGA infants (9/21 vs 3/26, chi 2 = 4.76, p < 0.05). The maternal 2 h OGTT plasma glucose was a significant independent contributor to birthweight in the Asian (r2 = 0.319, p < 0.0005) but not the White/Europid infants, in whom gestational age and maternal height were significant independent contributors to birthweight (r2 = 0.158, p < 0.0001). We conclude that ethnic influences are important when defining LGA infants and that mild disturbances of maternal glycaemia have a greater influence on the birthweight of Asian than White/Europid infants.
Adult↗
Clinical manifestation and outcome of tuberculosis in children with acquired immunodeficiency syndrome.
BACKGROUND: Atypical clinical manifestations and rapid progression of tuberculous disease (TB) are well-recognized in adults with the acquired immunodeficiency syndrome (AIDS). There are few reports of children with AIDS and TB. We report the manifestations, clinical course and outcome of 12 pediatric patients with AIDS and TB. METHODS: The charts of all children admitted to our institution, from 1989 through 1994, with the diagnoses of AIDS and culture-proved TB were reviewed. RESULTS: Twelve children between the ages of 2 months and 13 years fit the criteria. The mean time between the diagnosis of AIDS and TB was 20 months. The most frequent presenting symptoms were fever (75%) and tachypnea (33%). All had negative Mantoux tests (5 tuberculin units of purified protein derivative). Extrapulmonary TB was present in 3 (25%). A source case was identified for 4 (33%). Previous pulmonary disease was present in 7 (58%). Chest roentgenograms were abnormal in 11 (91%), with diffuse interstitial infiltration the most common finding. Susceptibility tests were performed on 10 strains, 3 of which were resistant to 1 or more antituberculosis drugs. Three patients (25%) died of TB, 1 of whom was appropriately treated with antituberculosis drugs but had a strain resistant to isoniazid and rifampin. CONCLUSION: Children with AIDS and TB most frequently present with atypical manifestations of TB. A high index of suspicion is needed to correctly diagnose TB in this group of children. Early diagnosis is important because most respond well when treated appropriately.
AIDS-Related Opportunistic Infections↗
A reversible dilated cardiomyopathy due to thyrotoxicosis.
Thyrotoxicosis gives rise to a high output cardiac failure. Rarely, it can cause a dilated cardiomyopathy with severe impairment of myocardial function which improves significantly following treatment.
Antithyroid Agents↗
Aspects of metabolism in normal and gestational diabetic pregnancy.
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Diabetes, Gestational↗
Insulin secretion and sensitivity in women fulfilling WHO criteria for gestational diabetes.
Abnormalities of insulin secretion rather than insulin sensitivity are described in women fulfilling the American criteria for gestational diabetes. We examined insulin secretion and insulin sensitivity in 38 women at risk of gestational diabetes categorized according to the less stringent WHO criteria, based on the 75 g oral glucose tolerance test, performed at 24 weeks gestation. Insulin sensitivity was assessed at 28 and 36 weeks using the short insulin tolerance test. Applying WHO criteria, 18 women had GDM. Age and body mass index of the GDM and glucose tolerant women were similar (32.4 +/- 1.1 (SE) vs 32.3 +/- 1.9 yr; 28.7 +/- 1.5 vs 28.8 +/- 1.7 kg m-2, respectively). Fasting glucose was higher in the GDM women than controls (5.1 +/- 0.2 vs 4.5 +/- 0.1 mmol l-1, p < 0.025) while fasting insulin was similar (75 +/- 18 vs 90 +/- 16 pmol l-1). The 30-min insulin concentration during the OGTT was lower in the GDM women than controls (436 +/- 61 vs 788 +/- 152 pmol l-1, p < 0.05), while the insulin sensitivity at 28 (87 +/- 5 vs 76 +/- 5 mumol l-1 min) and 36 weeks (73 +/- 8 vs 76 +/- 8 mumol l-1 min) was similar. A negative correlation existed between the 30-min insulin and 120-min glucose concentration during the OGTT (Rho -0.328, p < 0.05). The WHO criteria for GDM identify women with similar abnormalities of insulin secretion as the more stringent American criteria.
Adult↗
Multiple endocrine neoplasia type 1 (MEN1) in two Asian families.
Multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disease characterized by neoplasia of the parathyroid glands, anterior pituitary and endocrine pancreas, is rarely reported in Asian populations. The MEN1 gene, mapped to chromosome 11q13 but yet to be cloned, has been found to be homogeneous in Caucasian populations through linkage analysis. Here, two previously unreported Asian kindreds with MEN1 are described; linkage analysis using microsatellite polymorphic markers in the MEN1 region was carried out. The first kindred, of Mongolian-Chinese origin, is a multigeneration family with over 150 living members, eight of whom are affected to date. The second kindred is of Chinese origin consisting of four affected members. Linkage to chromosome 11q13 was confirmed in both kindreds, supporting evidence for genetic homogeneity. A recombination in the larger kindred localizes the gene distal to marker D11S956, consistent with its placement from previous studies. We also show that it is feasible to use these markers for predictive testing, as four gene carriers were detected in 13 family members with unknown disease status in the first kindred.
Adult↗
Insulin sensitivity in non-diabetic relatives of patients with non-insulin-dependent diabetes from two ethnic groups.
OBJECTIVE: Non-insulin-dependent diabetes is a heterogeneous disorder, the basis of which may differ in different ethnic groups. In order to investigate early metabolic abnormalities occurring during the development of the condition we assessed insulin secretion and insulin action in subjects predisposed to the later development of non-insulin-dependent diabetes from two different ethnic groups. DESIGN: Subjects were studied on two separate occasions by an oral glucose tolerance test and a short insulin tolerance test. PATIENTS: Twenty-four glucose-tolerant first-degree relatives of patients with non-insulin-dependent diabetes (12 of European and 12 of Asian origin) were compared with 24 ethnically matched control subjects with no family history of diabetes. MEASUREMENTS: Insulin, proinsulin, glucose and intermediary metabolites were measured during a 75-g oral glucose tolerance test. Insulin sensitivity was assessed using a 15-minute insulin tolerance test (0.05 units/kg). RESULTS: Asian relatives compared to Asian controls had significantly higher fasting levels of immunoreactive insulin (83 +/- 17 vs 40 +/- 6 pmol/l, P < 0.05), which were not due to increased proinsulin. Blood glycerol concentrations were elevated (83 +/- 9 vs 51 +/- 4 mumol/l, P < 0.005), but fasting glucose and non-esterified fatty acid (NEFA) concentrations were similar. Relatives of European origin did not differ from their European controls in any of these measurements. The glucose response to oral glucose was similar in relatives and controls, irrespective of ethnic group. The insulin responses were non-significantly greater in relatives from both ethnic groups. Proinsulin levels were not significantly different. Asian relatives had higher circulating glycerol and NEFA levels after oral glucose than Asian controls, but these differences were not observed in the European group. Insulin sensitivity was reduced in the Asian relatives compared to their controls (183 +/- 7 vs 139 +/- 12 mumol/l/min, P < 0.01) but there was no difference in insulin sensitivity between the European relatives and European controls (167 +/- 11 vs 160 +/- 11 mumol/l/min). CONCLUSIONS: First-degree relatives of non-insulin-dependent diabetic patients of Asian, but not of European, origin are insulin insensitive in terms of both glucose metabolism and lipolysis, and have true hyperinsulinaemia. This suggests that insulin insensitivity may be an early abnormality in the development of non-insulin-dependent diabetes in the Asian population.
Adult↗
Insulin insensitivity is associated with a decrease in postprandial thermogenesis in normal pregnancy.
Insulin sensitivity and postprandial thermogenesis were investigated at various stages of pregnancy to assess if changes in insulin sensitivity contribute to energy conservation during pregnancy. Cross-sectional and longitudinal studies were undertaken. Sixteen control non-pregnant women were compared with 10 women in the second trimester (2nd) and thirteen women in the third trimester (3rd) of uncomplicated pregnancy. Six women were studied at all three time points. The slope of plasma glucose decline following a bolus of intravenous insulin was used as an index of insulin sensitivity. Resting energy expenditure was measured with continuous indirect calorimetry. Postprandial thermogenesis was measured as the change in energy expenditure for the 2 h after a mixed meal. Results are expressed as mean +/- SEM or median (interquartile range). Insulin sensitivity was lower as pregnancy progressed (non-pregnant control 181 (177-205) vs 2nd 111 (100-112) vs 3rd 96 (80-109) mumol l-1 min-1, p < 0.001). Fasting insulin levels were significantly higher in the third trimester but not in the second trimester (non-pregnant control 1.9 (1.5-6.0) vs 2nd 3.1 (2.8-5.2) vs 3rd 8.6 (4.8-9.7) mU l-1, p < 0.05). Meal stimulated insulin levels were higher in the second and third trimesters compared to non-pregnant women (insulin area over 2 h, postmeal, non-pregnant control 78 +/- 10 vs 2nd 92 +/- 14 vs 3rd 145 +/- 14 mU l-1 h-1, p < 0.005). Postprandial thermogenesis was lowest in the third trimester (non-pregnant control 103 +/- 5 vs 2nd 74 +/- 8 vs 3rd 48 +/- 8 kJ, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Disseminated histoplasmosis mimicking miliary tuberculosis: a case report.
A 35-year-old Chinese man who was known to have insulin-dependent diabetes mellitus was admitted for fever and weight loss. During his hospital stay, he fell to his death from his ward at the twelfth floor. The clinical features, radiological findings and gross organ changes at autopsy closely simulated miliary tuberculosis. Histology, however, revealed extensive necrosis of the adrenal glands, lungs, spleen, kidneys and thyroid associated with the presence of Histoplasma capsulatum organisms. This case highlights the similarity both clinically and pathologically between histoplasmosis and tuberculosis and emphasizes the need to be aware of this infection in a nonendemic area among patients with a compromised immune system.
Adult↗
Abnormalities of intermediary metabolism following a gestational diabetic pregnancy.
OBJECTIVE: The aim of this study was to compare intermediary metabolism in glucose tolerant women with previous gestational diabetes and control women without a history of gestational diabetes. SUBJECTS: Fifteen women with previous gestational diabetes and 15 controls individually matched for race, age and body mass index were included. Only subjects with normal glucose tolerance were included in this study. METHODS: Plasma glycerol, 3-OH butyrate, non-esterified fatty acids (NEFA), glucose and insulin were measured fasting and following a 75 g oral glucose load. RESULTS: The women with previous gestational diabetes and their matched controls were of similar racial origin, age and body mass index. There was no difference between those with previous gestational diabetes and controls in fasting glycerol, 3-OH butyrate, NEFA, glucose or insulin concentrations. Following the oral glucose load, glycerol, 3-OH butyrate and NEFA concentrations fell in both groups. However, compared with controls at 120 minutes, those with previous gestational diabetes had significantly higher concentrations of glycerol (median 57, range 24-216 vs 27, range 8-89 mumols/l, P less than 0.005) and 3-OH butyrate (9, range 1-18 vs 5, range 2-11 mumols/l, P less than 0.01). NEFA concentrations were similar in the two groups. Despite similar glucose concentrations during the oral glucose tolerance test the insulin response during the first 60 minutes following oral glucose was significantly reduced in the subjects with previous gestational diabetes when compared with controls (insulin area, 0-60 minutes; 2172, range 788-4767 vs 2830, range 996-4784 pmol min/l, P less than 0.05). CONCLUSIONS: Women with a previous history of gestational diabetes, despite having normal glucose tolerance, have defective insulin release with resultant abnormalities of intermediary metabolism.
3-Hydroxybutyric Acid↗
Postprandial thermogenesis is reduced in polycystic ovary syndrome and is associated with increased insulin resistance.
OBJECTIVE: In order to investigate the possible causes and effects of obesity in polycystic ovary syndrome resting energy expenditure, postprandial thermogenesis and insulin resistance were measured in 14 polycystic ovary syndrome subjects and in 14 controls. DESIGN: A cross-sectional study of a selected group of patients was performed. PATIENTS: Seven of the PCOS subjects were obese and seven lean. Controls were individually matched for age, race, weight, body mass index (BMI) lean body mass and percentage fat. The obese, but not lean, polycystic ovary syndrome subjects had a greater waist:hip ratio than controls (median (range) obese PCOS 0.865 (0.823-0.960) vs obese control 0.804 (0.823-0.940), P less than 0.025). MEASUREMENTS: Metabolic rate was measured by continuous indirect calorimetry and insulin sensitivity was assessed by a short insulin tolerance test. RESULTS: The resting energy expenditure (REE) was similar in PCOS subjects and controls (median (range), 6796 (5489-7774) vs 6833 (4893-8492) kJ/day). REE correlated with LBM in the PCOS group (r = 0.83, P less than 0.00) and the control group (r = 0.82, P less than 0.001). Postprandial thermogenesis was reduced in polycystic ovary syndrome (obese: median 45.4 (range 33.6-100.0) vs 86.5 (67.2-109.2) kJ (P less than 0.05); lean: 79.4 (73.5-108.4) vs 89.9 (76.0-109.2) kJ (P less than 0.05). Fasting insulin (9.7 +/- 3.6 vs 4.4 +/- 0.8 mU/l, P less than 0.05) and postprandial incremental insulin rise (163 +/- 31 vs 116 +/- 15 mU/l, P less than 0.025) were higher in polycystic ovary syndrome. Insulin sensitivity was reduced in polycystic ovary syndrome (obese: median 136 (range 92-169) vs 173 (109-225) mumol/l/min (P less than 0.05); lean: 161 (138-225) vs 194 (161-253) mumol/l/min (P less than 0.05)). The reduction in insulin sensitivity correlated with the reduced postprandial thermogenesis in the polycystic ovary syndrome group (r = 0.75, P less than 0.01). CONCLUSION: These results confirm previous reports of hyperinsulinaemia and insulin resistance in polycystic ovary syndrome. Furthermore, polycystic ovary syndrome subjects have a reduced postprandial thermogenesis which is related statistically to the reduced insulin sensitivity. The decreased postprandial thermogenesis may predispose women with polycystic ovary syndrome to weight gain.
Adult↗
Ethnic differences in insulin secretion in women at risk of future diabetes.
The plasma glucose and insulin responses to oral glucose were studied in 44 women who had previously had gestational diabetes, but had reverted to normal glucose tolerance. Twenty were White, 14 Black, and 10 Asian. A group of race-, age- and weight-matched controls was also studied. Fasting values of glucose and insulin did not differ significantly between the study group and controls. During the 2 h 75-g OGTT the White and Black previously gestational-diabetic women had similar plasma glucose values to their controls, while the Asian previously gestational-diabetic women had significantly higher glucose values at 30 min (9.2 +/- 0.6 (+/- SE) vs 7.1 +/- 0.3 mmol l-1, p less than 0.02) and at 60 min (8.6 +/- 0.8 vs 6.2 +/- 0.4 mmol l-1, p less than 0.02). Compared with their race-matched controls, the White previously gestational-diabetic women had significantly lower insulin values at 60 min (median 41 range 2-91) vs 56 (15-118) mU l-1, p less than 0.05), and the Black previously gestational-diabetic women had lower values at both 30 min (17 (4-116) vs 53 (22-197) mU l-1) and 60 min (36 (4-148) vs 99 (12-169) mU l-1, p less than 0.05). The insulin values were similar during the OGTT in the Asian previously gestational-diabetic women and their controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Phylogenetic analysis of 48 papillomavirus types and 28 subtypes and variants: a showcase for the molecular evolution of DNA viruses.
Papillomaviruses are attractive models for studying the molecular evolution of DNA viruses because of the large number of isolates that exhibit genomic diversity and host species and tissue specificity. To examine their relationship, we selected two amino acid sequences, one of 52 residues within the early gene E1 and the other of 44 residues within the late gene L1, which allowed insertion- and deletion-free alignment of all accessible papillomavirus sequences. We constructed phylogenetic trees from the amino acid and corresponding nucleotide sequences from 28 published and 20 newly determined animal and human papillomavirus (HPV) genomic sequences by using distance matrix, maximum-likelihood, and parsimony methods. The trees agreed in all important topological aspects. One major branch with two clearly separated clusters contained 11 HPV types associated with epidermodysplasia verruciformis. A second major branch had all the papillomaviruses involved in genital neoplasia and, in distant relationship, the cutaneous papillomaviruses HPV type 2a (HPV-2a), HPV-3, and HPV-10 as well as the "butcher's" papillomavirus HPV-7 and two simian papillomaviruses. Four artiodactyl (even-toed hoofed mammal) papillomaviruses, the cottontail rabbit papillomavirus, and avian (chaffinch) papillomavirus type 1 formed a third major branch. Last, four papillomaviruses exhibited little affinity to any of these three branches; these were the cutaneous types HPV-1a, HPV-4, and HPV-41 and B-group bovine papillomavirus type 4. The phylogeny suggests that some branches of papillomavirus evolution are restricted to particular target tissues and that a general process of long-term papillomavirus-host coevolution has occurred. This latter hypothesis is still conjectural because of bias in the current data base for human types and the paucity of animal papillomavirus sequences. The comparison of evolutionary distances for the most closely related types with those of 28 subtypes and variants of HPV-2, HPV-5, HPV-6, HPV-16, and HPV-18 supports the type as a natural taxonomic unit, with subtypes and variants being expressions of minor intratype genomic diversity similar to that found in the natural populations of all biological species. An exception to this seems to be HPV-2c, which has an evolutionary distance from HPV-2a of the intertype magnitude and may eventually have to be regarded as a distinct type. We describe an experimental approach that estimates the taxonomic and phylogenetic positions of newly identified papillomaviruses without viral isolation and complete genomic sequencing.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Results of long-term follow-up after compensated fixed-dose therapy for thyrotoxicosis.
To evaluate the effects of simple compensated fixed-dose iodine-131 therapy for thyrotoxicosis, the long-term results for 74 patients treated with a fixed dose of iodine-131 ranging from 5 to 12 mCi (185 to 444 MBq) were evaluated in the first 2 years of a trial. The dose selected was loosely based on the gross size of the thyroid gland. Routine antithyroid drug therapy was given for a minimum of 3 months after iodine-131 therapy. The mean (+/- SD) duration of follow-up was 74.5 +/- 42 months. The results indicated that roughly 25% of patients treated in this way will become hypothyroid after 5 years and that 85% are cured (need no further therapy during the follow-up period) using a single dose of iodine-131. Of those cured using a single iodine-131 dose, 81% were no longer receiving drugs after 6 months and 85% after 1 year. Such a regimen seems currently to be among the best available where prolonged periods of medication-free euthyroidism after therapy are sought.
Female↗