Coexistence of impaired indices of autonomic neuropathy and diabetic nephropathy in a cohort of children with type 1 diabetes mellitus.

One hundred and twenty-nine (87%) out of a county population of 150 eligible children with type 1 diabetes mellitus (DM) and 144 age- and sex-matched control children participated in a longitudinal, epidemiological study of the evolution of diabetic microvascular disease. The mean (SD) age of the children with DM was 12.4 (+/- 3.4) years with a mean DM duration of 4.5 (+/- 3.2) years and a mean HbA1c of 11.1 (+/- 2.2)%. Two sets of measurements were made over a period of 18 months. Pupillary adaptation in darkness (PD), as an index of sympathetic dysfunction, was assessed using a portable Polaroid pupillometer. Urinary albumin excretion, as an index of incipient nephropathy, was assessed in children with DM from a fraction of all voidings during two separate 48-h periods and was expressed as urinary albumin/creatinine ratio (A/C). Heart rate variation (HRV), as an index of cardiovascular autonomic dysfunction, was assessed using a heart rate monitor and computer. Blood pressure (BP) was measured using a random zero sphygmomanometer. Reduced PD was found in 14/129 (13.8%) children with DM and in 5.8% of the controls. The diabetic children with reduced PD had longer DM duration, higher HbA1c, raised diastolic BP and higher urinary A/C than those with normal PD. Fifty percent of these children also had increased A/C and impaired HRV, in addition to impaired PD. Another group of 25/129 (19.4%) children with DM presented intermittently raised mean urinary A/C, while five children presented persistently raised A/C in both 48-h urine collections. The characteristics which differentiated the microalbuminuric group from the normoalbuminuric one were older age, longer DM duration, poorer glycemic control, reduced PD, impaired HRV and raised diastolic BP. It seems that diabetic nephropathy (DN) and autonomic neuropathy (DAN) exist in concert in childhood DM. Diabetic children with impaired indices of DN and DAN are older, pubertal and have longer DM duration and higher HbA1c values than the rest of the diabetic population.

Effects of parity on breastfeeding: a study in the rural setting in northern Thailand.

UNLABELLED: This analysis was undertaken to see whether or not previous successful breastfeeding has any influence on subsequent breastfeeding behavior. Lactational outcomes were compared between those with and without breastfeeding experience. METHODS: Amount of breast milk transferred, frequency of breastfeeding, and time spent on the breast, as well as infant's weight, were recorded on days 15, 45, 90, 180, 270, and 360 postpartum in 30 primiparae and 30 multiparae. Outcomes of the primiparae were found to be similar to those of the more experienced breastfeeding multiparous mothers with respect to infant growth, amount of breast milk transferred, and the frequency of breastfeeding or number of attachments to the breast. Though primiparae took somewhat longer to transfer similar amounts of breast milk to their infants during the initial 45 to 90 days postpartum, feed duration after 90 days was similar to that of the multiparae. Lactation performance of the rural northern Thai mothers in our sample was highly successful with or without previous breastfeeding experience. It may be that a cultural pattern of breastfeeding on demand, strong family support, and traditional practices that encourage close contact between mother and her newborn compensate for the absence of lactational experience. Unlike reports from Western countries, previous breastfeeding does not appear to be an important predictor of successful and prolonged breastfeeding in our population.

Prevalence of microvascular and neurologic abnormalities in a population of diabetic children.

One hundred and twenty-nine (87%) of a total county population of 150 eligible diabetic children together with 144 age- and sex-matched control children participated in a longitudinal, epidemiological study of the evolution of diabetic microvascular disease. At enrollment the median (range) age of the diabetic children was 12.5 (3.7-16.8) years with a median diabetes duration of 2.9 (0.1-13.4) years and a median HbAl of 11.1 (6.8-17.9)%. Two sets of measurements were made over a period of 18 months for all indices of microvascular disease, while autonomic function was studied on one occasion. Urinary albumin excretion in diabetic children was assessed from all voidings during two timed 48-h urine collections and was expressed as urinary albumin/creatinine ratios (ACR). Blood pressure (BP) was measured using a random zero sphygmomanometer. Autonomic function was assessed by pupillary adaptation in darkness, using a portable Polaroid pupillometer, and by heart rate (HR) variation recorded by dedicated computer. Vibration sensation thresholds (VST) (as indices of peripheral neuropathy) were recorded using a Biothesiometer. Limited joint mobility (LJM) was assessed by the "prayer sign". Five (3.9%) diabetic children presented raised mean ACR in more than two of four 24-h urine collections. Fourteen (10.8%) diabetic children were identified as having persistently raised BP during both study periods. Impaired HR response in one HR test was observed in 20 (15.5%) diabetic children, while ten (7.7%) diabetic children demonstrated abnormalities in two or more HR tests. Reduced pupillary adaptation in darkness was found in eight (7.9%) diabetic children. Persistent vibration sensation impairment (VST) in lower limbs was detected in eight (6.2%) diabetic children, while LJM was present in 12 (9.3%) diabetic children. Eight of the 129 diabetic children (6.2%) were found to have abnormality in two and one in three indices of microvascular and autonomic function. Six of nine children had coexistence of impaired autonomic neuropathy and nephropathy. These nine children were diagnosed at a younger age than the rest of the diabetic population (5.1 vs 8.0 yr, p=0.002). Four of nine were aged >11 yr and five of nine had had diabetes for >5 yr. Thus, a constellation of microvascular and neurological abnormalities were demonstrable in a small proportion of diabetic children, who were younger than the rest of the population at the time of onset of their disease. Longitudinal study of this population will demonstrate the clinical significance of these findings.

Transmission of haplotypes of microsatellite markers rather than single marker alleles in the mapping of a putative type 1 diabetes susceptibility gene (IDDM6).

Allelic association methods based on increased transmission of marker alleles will have to be employed for the mapping of complex disease susceptibility genes. However, because the extent of association of single marker alleles with disease is a function of the relative frequency of the allele on disease-associated chromosomes versus non disease-predisposing chromosomes, the most associated marker allele in a region will not necessarily be closest to the disease locus. To overcome this problem we describe a haplotype-based approach developed for mapping of the putative type 1 diabetes susceptibility gene IDDM6. Ten microsatellite markers spanning a 550 kb segment of chromosome 18q21 in the putative IDDM6 region were genotyped in 1708 type 1 diabetic Caucasian families from seven countries. The most likely ancestral diabetogenic chromosome was reconstructed in a stepwise fashion by analysing linkage disequilibrium between a previously defined haplotype of three adjacent markers and the next marker along the chromosome. A plot of transmission from heterozygous parents to affected offspring of single marker alleles present on the ancestral chromosome versus the physical distance between them, was compared with a plot of transmission of haplotypes of groups of three adjacent markers. Analysing transmission of haplotypes largely negated apparent decreases in transmission of single marker alleles. Peak support for association of the D18S487 region with IDDM6 is P = 0.0002 (corrected P = 0.01). The results also demonstrate the utility of polymorphic microsatellite markers to trace and delineate extended and presumably ancient haplotypes in the analysis of common disease and in the search for identical-by-descent chromosome regions that carry an aetiological variant.

Consistency of pupillary abnormality in children and adolescents with diabetes.

Repeat measurements on pupillary adaptation to darkness were performed in a cohort of 66 children and adolescents with insulin-dependent diabetes mellitus (IDDM) (initial age 6.9-17.0 years) after a mean interval of 3.5 years, using a portable pupillometer. While there was a close correlation between the results of the two studies (r = 0.94, p < 0.001), the pupillary dilatation, the ratio of the pupil diameter to the iris diameter % (PD%), had decreased significantly (61.5% vs 62.9%, p < 0.001) over these 3.5 years in children with diabetes. The same measurements were performed on 89 healthy control children in the first study and 66 in the reassessment period and PD% was not significantly different in the two control groups. Five children with diabetes identified as having abnormal pupillary dilatation in the first study were outside the normal range 3.5 years later. In addition 4 children in whom initial testing had been normal, showed abnormality at the time of the second study. None of these children had symptoms of autonomic neuropathy. These findings suggest that abnormality in pupillary adaptation in diabetic children is consistent and increases with time and may serve as an early marker of tissue damage associated with diabetes.

A case-control study of environmental factors associated with diabetes in the under 5s.

In 1992 a national case-control study was conducted through the British Paediatric Association Surveillance Unit (BPASU) framework to evaluate both the incidence of IDDM in children under 5 in that year and the effects of various putative trigger factors in the disease pathogenesis. A total of 218 sets of matched case-control questionnaire data established that paternal IDDM (odds ratio (OR) = 16.11, 95% confidence interval (CI) 1.94-133.7, p < = 0.001) is independently associated with increased risk, and higher birth order (OR = 0.64, CI 0.44-0.94, p = 0.021) and paternal age greater than 25 years (age 25-39 OR = 0.52, CI 0.30-0.89; age 40 + OR = 0.23, CI 0.08-0.67, p = 0.009) with decreased risk of diabetes. Other factors previously implicated in the disease pathogenesis (birthweight, parental socio-economic status, infant feeding, and immunization record) showed no significant independent association with disease development.

[Average length of spontaneous labor in Chinese primigravidas]. / Durée moyenne du travail spontané chez les primipares chinoises.

OBJECTIVE: To determine if labor duration is affected by ethnicity, we measured the average length of normal spontaneous labor in recently immigrated Chinese primigravidas and compared our findings to reference primigravida populations of differing ethnicity. MATERIALS AND METHODS: In this descriptive, retrospective study of 1,006 recently immigrated low-risk Chinese primigravidas delivering singleton, vertex, term infants (37-42 weeks gestation, inclusively) without conduction anesthesia or oxytocin, the length of first-, second-, and third-stage labor, maternal age, gestational age, and infant weight was measured and compared to labor lengths previously reported for women of differing ethnicity. RESULTS: Mean first stage labor duration was 326 minutes (SD +/- 185 min, range 25-1640 min), mean second stage labor duration was 52 minutes (SD +/- 42 min, range 2-450 min), and a mean third stage labor duration was 4.6 min (SD +/- 4.5 min, range 1-62 min). Interquartile range (IQR)/median for first-, second-, and third-stage labor was 225 min/300 min, 50 min/40 min, and 3 min/3 min respectively. Weak correlations were observed between first- and second-stage labor lengths, and second- and third-stage labor lengths. Average birth weight was 3250 g (SD +/- 376 g, range 2280-4660 g). Chinese parturients showed a significantly shorter duration of first-stage (P < 0.0001) when compared to parity-matched patients of differing ethnicity. Second-stage labor in Chinese parturients was also shorter, but did not differ significantly (P = 0.185) from previously reported non-Asian controls. CONCLUSION: When compared to previously collected data from non-Chinese women, clinically significant differences in first-stage labor lengths were measured in our study population. While second-stage labor durations were also shorter, the difference was not significant. Labor management should be individualized to account for these differences, and previous reports attempting to show equivalency of labor progress regardless of ethnicity warrant reinterpretation given these findings.

Aetiopathology and genetic basis of neonatal diabetes.

A British Paediatric Association Surveillance Unit* study of neonatal diabetes determined a national incidence of 1 in 400,000 live births. Additional cases of transient neonatal diabetes were collected retrospectively. Most cases were of low birthweight at term: none had evidence of an autoimmune aetiopathogenesis. The median requirement for exogenous insulin treatment was three months. A significant number of cases developed type 2 diabetes in later life. Three of the 11 cases were found to have paternal uniparental isodisomy of chromosome 6. A further patient carried an unbalanced duplication of 6q 22-23, inherited from the father, which localised a potentially imprinted gene for diabetes to this region. The fact that low birthweight predisposes to type 2 diabetes in later life is well established, but a genetic defect that may relate both to intrauterine growth failure and the development of type 2 diabetes in later life has now been identified.

Autonomic function in a cohort of children with diabetes.

129 diabetic children in Avon County participated in a longitudinal study of the evolution of microvascular disease together with 129 age- and sex-matched controls. Diabetic children had mean (+/- SD) age 12.7 (+/- 3.4) years (range: 3.7-16.8), mean (+/- SD) diabetes duration 3.9 (+/- 3.2) years (range: 0.1-13.4) and mean (+/- SD) HbA1 11.1% (+/- 2.2) (range: 6.5-18.2). Cardiovascular autonomic function was studied by four heart rate (HR) tests using a computerized system of HR monitoring. As a group, diabetic children had higher mean HR (p = 0.0004) and reduced max/min HR ratio while standing (p = 0.001), compared with the control children. HR ratio while standing was the only variable related to diabetes duration (r = -0.20, p = 0.018), while no correlation of HR variables with glycaemic control was found. Twenty diabetic children (15.5%) had one abnormal HR test. Ten diabetic children (7.7%) demonstrated abnormality in two or more HR tests. When compared with the other diabetic children in the cohort, these ten children were found to be younger in age (mean age: 9.4 vs 12.0 yr, p = 0.05), but did not otherwise differ in terms of diabetes duration or glycaemic control. No pubertal or sex effect in the development of diabetic autonomic neuropathy was detected. These findings suggest that autonomic function may be impaired early in childhood diabetes, independent of the duration of the disease or the quality of glycaemic control.

Consistency of microvascular and autonomic abnormalities in diabetes.

The progression of early measures of microvascular disease and autonomic neuropathy were studied in a group of 81 children with insulin dependent diabetes mellitus over a mean interval of 4.2 years. Repeated measurements were made of blood pressure, albumin excretion, joint mobility, and pupillary dilatation in darkness. Over the years between the first and the second study, systolic and diastolic blood pressure showed positive tracking correlations (r = 0.38 and r = 0.32) with a small but significant deviation from normality; albumin/creatinine ratio was significantly increased (0.79 v 0.55); a greater number of children were identified in the second study as having limitation of mobility of the fifth metacarpophalangeal joint; and pupillary dilatation in darkness significantly decreased (61.5% v 62.9%); 62% of the children with one or more abnormal measurements in the first study were found to have measurements outside the normal ranges in the second study, indicating a consistency in observations over time. It remains to be seen with what accuracy these measurements predict adult onset clinical disease.

Further evidence for an imprinted gene for neonatal diabetes localised to chromosome 6q22-q23.

Transient neonatal diabetes mellitus (TNDM) is a rare form of childhood diabetes which usually resolves in the first 6 months of life but which predisposes to type 2 diabetes of adult onset. We recently reported paternal uniparental isodisomy of chromosome 6 (UPD6) in two children with TNDM and proposed that there may be an imprinted gene important in the aetiology of diabetes on chromosome 6. We now describe two unrelated families which independently suggest that the gene is imprinted, is paternally expressed and maps to 6q22-q23. One family has a duplication while the other, with familial TNDM, shows linkage to a marker in this region.

Research ethics committee audit: differences between committees.

The same research proposal was submitted to 24 district health authority (DHA) research ethics committees in different parts of the country. The objective was to obtain permission for a multi-centre research project. The study of neonatal care in different types of unit (regional, subregional and district), required that four health authorities were approached in each of six widely separated health regions in England. Data were collected and compared concerning aspects of processing, including application forms, information required, timing and decision-making. The key finding was that ethics committees received and processed the applications variably, reflecting individual factors and local problems. To improve consensus and facilitate multicentre studies, standard forms and instructions are suggested and the establishment of a national committee or advisory group advocated.

Is microalbuminuria progressive?

In 1990, 81 children and adolescents with insulin dependent diabetes were studied for early signs of diabetic nephropathy. Nine patients were identified as having microalbuminuria (incipient nephropathy). These subjects were re-examined three years later. In five of these cases, the second examination revealed normal albumin excretion; in three of the four cases in whom microalbuminuria persisted, the rate of albumin excretion had decreased. The general improvement in albumin excretion rates in the initially microalbuminuric group could not be explained by improved glycaemic control nor interventional drug treatment. The lack of progression in this microalbuminuric group from the original prevalence study suggests that this method of identifying early nephropathy in childhood may not be valid or that the progression of incipient nephropathy in childhood is more irregular or slower than in later life.

Urinary heparan sulphate proteoglycan excretion is abnormal in insulin dependent diabetes.

Urinary excretion of heparan sulphate proteoglycan (HSPG), the main anionic component of the glomerular basement membrane (GBM), was estimated in 30 adolescents and young adults with insulin dependent diabetes (IDDM), 10 with microalbuminuria and 20 sex matched, diabetic controls of similar age without evidence of microalbuminuria. A further 10 non-diabetic control subjects were also examined. Both groups of patients with diabetes had significantly elevated excretion of HSPG when compared to normal individuals. There was no difference in HSPG excretion between diabetic subjects with and without microalbuminuria.

Foot pathology in insulin dependent diabetes.

OBJECTIVES: Foot pathology is a major source of morbidity in adults with diabetes. The aim of this study was to determine if children with insulin dependent diabetes have an increased incidence of foot pathology compared with non-diabetic children. DESIGN: Questionnaire, clinical examination, and biomechanical assessment. SUBJECTS: 67 diabetic children and a comparison group matched for age, sex, and social class. RESULTS: We found significantly more foot pathology in the children with diabetes (52 children) than the comparison group (28 children); with more biomechanical anomalies (58 children with diabetes, 34 comparison group); and a higher incidence of abnormal skin conditions (53 children with diabetes, 27 comparison group). Forty two children with diabetes had received foot health education compared with 27 in the comparison group, but the study revealed ignorance and misconceptions among the diabetic group, and previous contact with a podiatrist was minimal. CONCLUSIONS: The survey suggests that children with diabetes have an increased incidence of foot pathology justifying greater input of podiatric care in the hope of preventing later problems.

Maternal behaviour and socio-economic influences on the bacterial content of infant weaning foods in rural northern Thailand.

The bacterial contamination of infant weaning foods was examined in the context of a longitudinal study of lactation and infant growth, the Chiang Mai Lactation Study. Sixty-two mother-infant pairs were selected by random sampling from a rural area outside the city of Chiang Mai and studied for 48 hours in their homes on six occasions over the first year of life. Data on food hygiene practices and maternal factors were related to the total bacterial count per gram and coliform content of weaning foods. Bottle feeding, premastication, and mashing were significantly related to an increased bacterial content of weaning foods, while boiling foods to make soups, preparing in and feeding from a banana leaf, and using boiled water to prepare foods all reduced their bacterial content. Storage also increased the bacterial contamination in foods and foods were more highly contaminated in the rainy season. Maternal age and education were also related to some feeding practices. By promoting the feeding of traditional, but less contaminated weaning foods, an intervention is put forward which would aim to reduce weaning food contamination and thereby reduce incidence of diarrhoea in this area of Northern Thailand.

Screening for diabetic microalbuminuria in routine clinical care: which method?

The measurement of albumin/creatinine ratios and simple albumin concentrations in early morning urine specimens were evaluated to establish which was the best screening test for those likely to have microalbuminuria by the reference standard analysis of timed overnight urine specimens. The measurement of an albumin/creatinine ratio with a cut off of > or = 2.0 mg/mmol was found to be suitable with a specificity of 93% and sensitivity of 97%.