Ethnicity and prevalence of scleroderma-like syndrome. A study of Arab and Jewish Israeli insulin-dependent diabetic children

Scleroderma-like syndrome (SLS) may represent the earliest apparent diabetes complication in insulin-dependent diabetic (IDDM) patients. To evaluate the frequency of SLS and its association with other diabetes-related pathology in our diabetic population, we studied 153 (127 Jewish and 26 Arab) IDDM patients and 45 healthy age-and gender-matched controls (25 Jewish, 20 Arab). The mean age and diabetes duration of the patients were 14.09 ± 5.1 years and 51 ± 45 months, respectively. While no diabetes-related pathology was found in the controls, SLS was detected in 47% of all patients (skin, 31.4%; arthropathy, 37.9%; both, 22%), and nephropathy, neuropathy, and retinopathy were present in 10.5%, 5.2%, and 4.6%, respectively. Independent of age, SLS directly correlated with diabetes duration (p < 0.01) and with the presence of either nephropathy or neuropathy (p < 0.009 and p < 0.005, respectively). One or more features of systemic diabetic involvement were present in 22% of patients with SLS, compared to only 7.2% in patients without SLS (p < 0.009). When patients were analyzed according to ethnicity, the frequency of skin involvement and neuropathy were found to be higher among Arab patients, particularly males (p < 0.002 and p < 0.005, respectively), and detection of one was significantly associated with the presence of the other (p < 0.001). In conclusion, our results suggest that SLS is the most common diabetic complication among Jewish and Arab IDDM patients, and its presence may reflect an inherited tendency to develop other serious diabetic complications. Ethnicity (Arab) by itself, particularly when associated with male gender, seems to accelerate neurological and dermatological diabetic involvement.     

Psychological adjustment in a french cohort of type 1 diabetic children. PEDIAB Collaborative Group

The aim of the study was to determine whether IDDM affects the course of psychological adjustment in youths. The study sample included 164 children with IDDM (mean age=10.2) and their parents compared to 164 healthy controls matched for age, sex and socioeconomic status. Adjustment was measured with the Child Behavior Checklist, a parental rating scale, validated and adapted for the French population. Two-way ANOVAs on CBCL scale scores showed that scores for both internalizing and externalizing problem behaviors and the total CBCL score were significantly raised in diabetic children (p<0.001). Further comparisons on the 8 narrow-band scale scores of the CBCL indicated increased scores for diabetic children on 6 dimensions. A significant Gender x Status (IDDM versus Controls) interaction was found, supportive of higher rates of aggressive behaviors amongst male diabetic children (p<0.01). Controlling for age, no correlation was found between CBCL total, internalizing and externalizing scores and duration of IDDM or HbA1c levels within the diabetic group. Psychological adjustment to chronic illness needs to be considered with respect to both normal developmental demands as well as in the context of the specific challenges posed by the disease.     

Cytokine overproduction in healthy first degree relatives of patients with IDDM

Summary Healthy family members of patients with insulin-dependent diabetes mellitus (IDDM) are known to share a number of immunological abnormalities with their affected relatives. Since monocyte and type 1 T-cell-derived cytokines contribute to the pathogenesis of IDDM, we studied the production of these cytokines in the healthy first degree relatives of 29 children with IDDM. We report that circulating tumour necrosis factor-α (TNF-α) and soluble interleukin-2 (sIL-2) receptor were present in increased amounts in non-diabetic family members at levels similar to those found in the diabetic children (duration of disease 3 months–5 years). Furthermore, marked hypersecretion of IL-1α and TNF-α by mitogen-stimulated peripheral blood mononuclear cells was found in both diabetic and healthy family members. Abnormalities of cytokine production in healthy relatives did not correlate with the presence of islet cell antibodies or with HLA DR type. These data indicate that healthy family members of patients with IDDM exhibit overproduction of a number of cytokines that have been implicated in diabetogenesis. [Diabetologia (1998) 41: 343–349] Received: 26 August 1997 and in revised form: 24 October 1997     

Microneurographically Determined Muscle Sympathetic Nerve Activity Levels Are Reproducible in Insulin-Dependent Diabetes Mellitus

Our objective was to determine whether microneurographically determined muscle sympathetic nerve activity (MSNA) levels are equally reproducible in control and insulin-dependent diabetes mellitus (IDDM) subjects. We used a retrospective review of MSNA levels in 14 IDDM and 16 control subjects who had at least two microneurographic studies in the last 8 years in our laboratory. Results showed mean MSNA levels were lower in IDDM (9.2 ± 1.2 bursts/min) than in control subjects (16.8 ± 1.7 bursts/min) (p < 0.002) but mean within individual MSNA coeffients (IDDM: 47 ± 8%; controls 30 ± 5%) and ranges of variation (IDDM: 6.6 ± 1.9; controls: 7.5 ± 1.9 bursts/min) did not differ between IDDM and control subjects. Thus, microneurographically determined MSNA levels are equally reproducible in IDDM and controls subjects. These results confirm and substantiate our previous findings of diminished MSNA in IDDM subjects.     

Alerations of lymphocyte subsets in children of diabetic mothers

Summary To investigate the impact of diabetic mothers on the maturation of the immune system in their offspring, immunophenotypic markers of major lymphocyte subpopulations were evaluated by two-colour flow cytometric analysis in 160 healthy children of diabetic mothers (100 with insulin-dependent diabetes mellitus (IDDM); 48 with gestational diabetes), including 22 neonates, 45 infants aged 8–12 months, 46 children aged 1–2 years, 29 children aged 3–6 years and 18 children aged 7–17 years. Results were compared with 21 neonates of healthy mothers from our hospital and with 110 paediatric subjects of a reference population. In neonates of diabetic mothers, percentages of total lymphocytes (p=0.044), T and B lymphocytes (p=0.004, respectively) were significantly decreased compared to our neonates of healthy mothers. By subdividing the group of neonates in offspring of mothers with IDDM (n=15) or gestational diabetes (n=7), differences compared to normal neonates were mainly observed in neonates of mothers with IDDM (T lymphocytes: p=0.006; B lymphocytes: p=0.008). In cord blood, 45.5% of neonates had antibodies to islet cells, insulin or glutamic acid decarboxylase, most likely transmitted through the placenta of the diabetic mother. No association was found between alterations of lymphocyte subsets and antibody-positivity in cord blood, nor was there any correlation of lymphocyte counts and mean HbA₁ during pregnancy, maternal age at delivery, diabetes duration, or neonatal birth weight, respectively. Comparisons among age groups from newborn infants through adolescents revealed higher percentages of total lymphocytes and lower percentages of activated T cells in children of diabetic mothers compared to children of the reference population between the age of 1 to 6 years (67–73% of the cases above and 62–77% below the interquartiles of the reference range, respectively). No significant differences in lymphocyte subpopulations between children of mothers with IDDM diabetes and gestational diabetes have been detected. In addition, there were no abnormalities of lymphocyte subsets in children who are at high risk for the development of IDDM. In summary, we suggest that the observed changes in children of diabetic mothers may reflect a cellular immune reaction to the particular maternal environment, characterized by both an abnormal metabolic state and persisting autoimmunity in the affected mother.Abbreviations ICA Islet cell antibodies - IAA insulin auto-antibodies - GAD-ab antibodies to glutamic acid decarboxylase - IDDM insulin-dependent diabetes mellitus - FITC fluorescein isothiocyanate - PE phycoerythrin     

Smoking habits and painful diabetic neuropathy

In order to assess the relationship between chronic painful diabetic neuropathy and current—or lifetime—smoking habits, the smoking history of 49 diabetic patients was investigated and compared with that of 23 diabetic patients without chronic pain (age 51.0 ± 1.9 years, mean ± SEM). Current level of nicotine intake was measured using urinary cotinine (a nicotine metabolite), and expressed as cotinine/creatinine ratio ( ), and lifetime smoking load by pack years (20 cigarettes per day for 1 year equals 1 pack year). Current pain intensity was evaluated using a visual analogue scale (VAS). The presence of chronic painful diabetic neuropathy was based on clinical history and examination. Of those patients with painful neuropathy, 26% were current smokers (age 54.2 ± 3.2 years, mean ± SEM), 31% ex-smokers (age 57.0 ± 2.9 years), and 43% lifelong nonsmokers (age 58.0 ± 2.9 years). Pain duration and intensity were similar in all three groups. levels were similar in current diabetic smokers with pain [5.0 (0.2–10.6) μg/mg] and the diabetic control group of smokers without pain [6.8 (1.8–13.3) μg/mg, NS]. There was no relationship between VAS and either levels or pack years in current smokers, or between duration of pain and pack years in diabetic current or ex-smokers. In conclusion, we found no relationship between current or previous levels of smoking and severity or duration of chronic painful diabetic neuropathy.     

Vertebral bone density in insulin-dependent diabetic children

To determine the effect of insulin-dependent diabetes mellitus (IDDM) on bone mass, we compared the trabecular and cortical bone density in lumbar vertebrae, measured by quantitative computed tomography (CT), in 48 white diabetic patients (23 females, 25 males; 5.2 to 19.6 years of age) with those of a control group of 48 healthy subjects, matched for race, sex, and age. Patients with neuropathy, retinopathy, nephropathy, and those with recent ketoacidosis were excluded from the study. The patient and control groups did not differ in sexual or skeletal maturation, weight, height, surface area, body mass index, abdominal fat, or paraspinal musculature. In diabetic children, cortical bone density was slightly but significantly lower than in controls (3.5% lower, P less than .02); there was no difference between patients and controls regarding trabecular bone density. The decrease in cortical bone density in the diabetic group did not correlate with age, sex, duration of diabetes, or glycosylated hemoglobin levels. These results suggest that in children with uncomplicated IDDM, decreased vertebral bone density is a minor abnormality that only affects cortical bone.     

Left ventricular systolic function in middle-aged patients with diabetes mellitus

In cross-sectional studies of asymptomatic diabetic patients, multiple abnormalities in left ventricular (LV) function have been found. Long-term significance of these abnormalities is unknown because follow-up studies have not been previously performed. LV ejection fraction (EF) by radionuclide angiocardiography was examined in middle-aged control Subjects (n = 44), in patients with insulin-dependent (IDDM) (n = 32) and non-insulin-dependent (NIDDM) (n = 32) diabetes mellitus at baseline and after 4-year follow-up. At baseline, all study subjects were free from cardiovascular disease. LVEF at rest did not differ between the groups at baseline. The decrease in LVEF at rest during follow-up was 1.1 ± 1.1% (mean ± SEM) in control subjects, 3.1 ± 1.3% (p = NS, compared with control subjects) in patients with IDDM, and 7.2 ± 1.4% (p <0.01) in patients with NIDDM. At follow-up examination, abnormally low LVEF at rest (<50%) was found in 7% of control subjects, 13% of patients with IDDM (p = NS), and in 31% of patients with NIDDM (p <0.05). Compared with control subjects, the prevalence of an abnormal LVEF response to exercise (an increase by <5%, or a decrease) was higher in diabetic groups at both examinations. This prevalence increased in control subjects from 10% at baseline to 26% at follow-up examination. In patients with IDDM, the respective increase was from 43% to 52% (p = NS, compared With control subjects), and in patients with NIDDM from 53% to 73% (p = NS). Duration and metabolic control of diabetes, presence of diabetic complications, and LVEF at rest or during exercise at baseline did not differ in either diabetic group between the patients who had normal or abnormal LVEF at rest or in response to exercise at follow-up examination. No study subject experienced clinical heart failure during follow-up, but 7% of control subjects, 37% of patients (p <0.001) with IDDM, and 34% of patients (p <0.01) with NIDDM had coronary artery disease at follow-up examination. In conclusion, LVEF at rest deteriorated significantly during 4-year follow-up in patients with NIDDM but not in patients with IDDM. A high prevalence of subclinical LV systolic dysfunction became evident both in patients with IDDM and patients with NIDDM as an abnormal LVEF response to exercise both at baseline and follow-up examinations.     

Abnormal diurnal changes in in-vivo platelet activation in patients with atherosclerotic diseases

We measured the urinary excretion of beta-thromboglobulin in timed urine samples collected by 2 groups of healthy volunteers, (group I, N = 20, mean age 34 years, group II, N = 15, mean age 64 years) and by patients (n = 40) with symptomatic atherosclerotic diseases. Older healthy subjects were found to excrete high amounts of BTG in comparison to young subjects (302.25 ± 50.61 vs 219.65 ± 59.31 ng/day, P < 0.05). Higher (P < 0.01) levels of urinary BTG were observed in patients with coronary (427.61 ± 179.96 ng/day), cerebral (422.13 ± 223.2 ng/day) and peripheral (454.16 ± 269.05 ng/day) arterial diseases and in diabetic patients with diffuse vascular complications (613.71 ± 253.07 ng/day). The diurnal variability of BTG excretion, measured as coefficient of variation (C.V. %) of the mean daily excretion rate, was higher (P < 0.001) in atherosclerotic patients (70.59 ± 26.57) as compared with the similar values observed in the control groups of young (32.05 ± 14.54) and older subjects (26.38 ± 8.4). Comparable diurnal variabilities of the creatinine excretion rate were observed in the control groups and in patients. These data indicated that in vivo platelet activation may occur in atherosclerotic patients with a distinctive high fluctuation rate.     

Knowledge profile and control in diabetic patients

Knowledge about diabetes was assessed using a previously described interactive computer-based questionnaire in 79 patients with insulin-dependent (IDDM) and 72 with non-insulin-dependent (NIDDM) diabetes mellitus routinely attending a single diabetic clinic. Simple linear correlation of total knowledge score with glycosylated haemoglobin (HbA1c) showed no significant relationship for either IDDM (r = 0.12: p = 0.18) or NIDDM (r = 0.15: p = 0.1). However, quintile grouping of knowledge scores showed the mean HbA1c to be significantly higher in the lowest scoring NIDDM quintile (10.6 +/- 0.5: +/- SE) with respect to the pooled mean of all the higher scoring quintiles (9.0 +/- 0.3) (p = 0.027). Mean HbA1c (9.6 +/- 0.5) was also higher in the least knowledgeable IDDM quintile than any other quintile group (range 8.8-9.0) but this was not significant with respect to the pooled mean of higher scoring patients (p greater than 0.1). The mean age of the lowest scoring IDDM quintile group (60.5 +/- 13.9 years) was significantly higher (p less than 0.01) than higher scoring IDDM groups (mean age range 36.5-43.3 years) but age was not significantly related to HbA1c in IDDM subjects. IDDM showed greater knowledge of diabetes than NIDDM but ignorance in key areas was unacceptably high in both diabetic subtypes, indicating that regular knowledge assessment and educational reinforcement may be essential for good diabetic control as well as patient safety, particularly in older IDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Neuropsychological Function in Older Subjects with Non-insulin-dependent Diabetes Mellitus

Neuropsychological function was compared in three well-matched groups of subjects: Group 1, 20 diabetic patients with hypertension, mean age 69.1 ± 4.8 years, 14 males and 6 females; Group 2, 20 normotensive diabetic patients, mean age 69.0 ± 6.2 years, 14 male and 6 females; Group 3, 20 healthy community controls, mean age 68.1 ± 4.5 years, 13 males and 7 females. There were no significant differences between the groups in education or estimated IQ using the NART (National Adult Reading Test). Groups 1 and 2 did not differ significantly in duration of diabetes (mean 10.6 and 9.5 years, respectively), or mean glycosylated haemoglobin, HbA₁ (mean 9.8 and 10.6 %, respectively), or mean blood glucose before or after testing. On a battery of neuropsychological tests, sensitive to cognitive impairment in older subjects, analysis of covariance using estimated IQ as the covariate showed no significant differences between the groups on tests of recall, with (Brown-Peterson Test) and without (Kendrick Object Learning Test) interference, forward and backward digit span, concentration (serial subtraction), verbal fluency, immediate and delayed prose recall, digit symbol substitution or psychomotor speed (Kendrick Digit Copying Test). These results provide no support for an association between cognitive deficits and Type 2 diabetes mellitus in older subjects or for the view that such deficits may also be mediated by hypertension.     

Association of early childhood diarrhea and cryptosporidiosis with impaired physical fitness and cognitive function four-seven years later in a poor urban community in northeast Brazil

To determine potential, long-term deficits associated with early childhood diarrhea and parasitic infections, we studied the physical fitness (by the Harvard Step Test) and cognitive function (by standardized tests noted below) of 26 children who had complete surveillance for diarrhea in their first 2 years of life and who had continued surveillance until 6-9 years of age in a poor urban community (favela) in Fortaleza in northeast Brazil. Early childhood diarrhea at 0-2 years of age correlated with reduced fitness by the Harvard Step Test at 6-9 years of age (P = 0.03) even after controlling for anthropometric and muscle area effects, anemia, intestinal helminths, Giardia infections, respiratory illnesses, and socioeconomic variables. Early childhood cryptosporidial infections (6 with diarrhea and 3 without diarrhea) were also associated with reduced fitness at 6-9 year of age, even when controlling for current nutritional status. Early diarrhea did not correlate with activity scores (P = 0.697), and early diarrhea remained significantly correlated with fitness scores (P = 0.035) after controlling for activity scores. Early diarrhea burdens also correlated in pilot studies with impaired cognitive function using a McCarthy Draw-A-Design (P = 0.01; P = 0.017 when controlling for early helminth infections), Wechsler Intelligence Scale for Children coding tasks (P = 0.031), and backward digit span tests (P = 0.045). These findings document for the first time a potentially substantial impact of early childhood diarrhea and cryptosporidial infections on subsequent functional status. If confirmed, these findings have major implications for calculations of global disability adjusted life years and for the importance and potential cost effectiveness of targeted interventions for early childhood diarrhea.     

Right Ventricular Diastolic Function in Children With Pulmonary Regurgitation After Repair of Tetralogy of Fallot: Volumetric Evaluation by Magnetic Resonance Velocity Mapping

Objectives. We sought to assess right ventricular diastolic function in young patients with corrected tetralogy of Fallot and pulmonary regurgitation.

Background. Pulmonary regurgitation is an important problem in repair of tetralogy of Fallot. Its effects on right ventricular diastolic function in children are unknown.

Methods. Nineteen children with repair of tetralogy of Fallot (mean age [±SD] 12 ± 3 years, mean age at operation 1.5 ± 1) and 12 healthy children were studied. Summation of magnetic resonance velocity mapping pulmonary and tricuspid volume flow curves provided right ventricular time–volume curves. Ventricular size was assessed with tomographic magnetic resonance imaging (MRI). Graded exercise testing was performed.

Results. Systematic and random differences (mean ± SD) of velocity mapping and Doppler tricuspid time to peak velocities (peak E: 1 ± 26 ms, r = 0.43; peak A: 2 ± 11 ms, r = 0.76), E/A ratios (0.04 ± 0.5, r = 0.63) and duration of pulmonary regurgitation (20 ± 35 ms, r = 0.74) were satisfactory. In 6 patients (group I), late diastolic forward pulmonary artery flow was absent; in 13 patients (group II), this flow contributed 1% to 14% to right ventricular stroke volume. Significant differences were increased deceleration time (315 ± 91 vs. 168 ± 28 ms, p < 0.001), decreased filling fraction (44 ± 11 vs. 55 ± 16%, p = 0.02) and increased peak early filling rate (378 ± 124 vs. 286 ± 112 ml/s, p = 0.018) between control subjects and group I, and increased deceleration time (230 ± 40, p = 0.03) between control subjects and group II. Pulmonary regurgitation, ventricular size and ejection fraction did not differ significantly between patient groups. Exercise function was diminished with restrictive right ventricular physiology (p < 0.001, group II vs. control subjects).

Conclusions. Impaired relaxation and restriction to filling affect diastolic right ventricular function in children with repair of tetralogy of Fallot and pulmonary regurgitation. Restrictive right ventricular physiology is associated with decreased exercise function.

(J Am Coll Cardiol 1996;28:1827–35)>     

Glucose tolerance and insulin secretion in children of mothers with pregestational IDDM or gestational diabetes

Summary The offspring of mothers with diabetes mellitus during pregnancy are presumed to develop altered glucose homeostasis. We analysed metabolic parameters at birth and glucose tolerance and insulin secretion during oral glucose tolerance tests at 1–9 years of age in 129 children born to mothers with pregestational insulin-dependent diabetes (IDDM) and 69 infants of gestational diabetic mothers. Newborns of IDDM mothers displayed higher insulin (p < 0.001), glucose (p < 0.05), and insulin/glucose ratios (p < 0.002) than newborns of gestational diabetic mothers. During childhood, frequencies of impaired glucose tolerance (IGT) rose in infants of IDDM mothers from 9.4 % at 1–4 years to 17.4 % at 5–9 years of age, while in children of gestational diabetic mothers an increase from 11.1 % up to 20.0 % was observed. Offspring of gestational diabetic mothers displayed higher stimulated blood glucose (p < 0.025) than infants of IDDM mothers, while children of IDDM mothers showed higher stimulated insulin (p < 0.025), accompanied by increased fasting and stimulated insulin/glucose ratios (p < 0.05 and p < 0.02, respectively). Stimulated insulin in childhood was positively correlated to insulin at birth (p < 0.05). Furthermore, insulin/glucose ratio in childhood showed a positive correlation to insulin (p < 0.01) and insulin/glucose ratio at birth (p < 0.005). In conclusion, a pathogenetic role of fetal and neonatal hyperinsulinism for the development of IGT in both groups of infants of diabetic mothers is suggested, in particular for early induction of insulin resistance in the offspring of mothers with pregestational IDDM. [Diabetologia (1997) 40: 1097–1100] Received: 24 February 1997 and in revised form: 7 May 1997     

Estimating steatosis and fibrosis: Comparison of acoustic structure quantification with established techniques

AIM:To compare ultrasound-based acoustic structure quantification(ASQ) with established non-invasive techniques for grading and staging fatty liver disease.METHODS:Type 2 diabetic patients at risk of nonalcoholic fatty liver disease(n = 50) and healthy volunteers(n = 20) were evaluated using laboratory analysis and anthropometric measurements, transient elastography(TE), controlled attenuation parameter(CAP), proton magnetic resonance spectroscopy(1H-MRS; only available for the diabetic cohort), and ASQ.ASQ parameters mode, average and focal disturbance(FD) ratio were compared with:(1) the extent of liver fibrosis estimated from TE and nonalcoholic fatty liver disease(NAFLD) fibrosis scores; and(2) the amount of steatosis, which was classified according to CAP values.RESULTS:Forty-seven diabetic patients(age 67.0±8.6 years;body mass index 29.4±4.5 kg/m2)with reliable CAP measurements and all controls(age 26.5±3.2 years;body mass index 22.0±2.7 kg/m2)were included in the analysis.All ASQ parameters showed differences between healthy controls and diabetic patients(P0.001,respectively).The ASQ FD ratio(logarithmic)correlated with the CAP(r=-0.81,P0.001)and 1H-MRS(r=-0.43,P=0.004)results.The FD ratio[CAP250 d B/m:107(102-109),CAP between 250 and 300 d B/m:106(102-114);CAP between 300 and 350 d B/m:105(100-112),CAP≥350 d B/m:102(99-108)]as well as mode and average parameters,were reduced in cases with advanced steatosis(ANOVA P0.05).However,none of the ASQ parameters showed a significant difference in patients with advanced fibrosis,as determined by TE and the NAFLD fibrosis score(P0.08,respectively).CONCLUSION:ASQ parameters correlate with steatosis,but not with fibrosis in fatty liver disease.Steatosis estimation with ASQ should be further evaluated in biopsy-controlled studies.     

Myocardial blood flow and coronary flow reserve late after anatomical correction of transposition of the great arteries

Objectives. Myocardial blood flow (MBF) in children late after arterial switch operation (ASO) was investigated quantitatively by positron emission tomography (PET).

Background. In children with transposition of the great arteries (TGA), ASO is widely accepted as the management of choice. The long-term patency of coronary arteries after surgical transfer to the neo-aorta, however, remains a concern.

Methods. Twenty-two normally developed, symptom-free children were investigated by PET with nitrogen-13 ammonia at rest and during adenosine vasodilation 10 ± 1 years after ASO. A subgroup of 15 children (9 ± 1 years; group A) had simple TGA and underwent ASO within 20 days after birth while 7 (13 ± 3 years; group B) had complex TGA and underwent ASO and correction of associated anomalies later after birth. Ten young, healthy adults (26 ± 6 years) served as the control group.

Results. Resting MBF was not different between groups. After correction for the rate-pressure product as an index of cardiac work, younger children of group A had significantly higher MBF at rest compared to healthy adults (102 ± 29 vs. 77 ± 16 ml/100 g/min; p = 0.012) while flow in group B was not different from the other groups (85 ± 22 ml/100 g/min; p = NS). Hyperemic blood flows were significantly lower in both groups after ASO compared to normals (290 ± 42 ml/100 g/min for group A, 240 ± 28 for group B, 340 ± 57 for normals; p < 0.01); thus, coronary flow reserve was significantly lower in both groups after ASO compared to healthy adults (3.0 ± 0.6 for group A, 2.9 ± 0.6 for group B, 4.6 ± 0.9 for normals; p < 0.01).

Conclusions. Blood flow measurements suggest decreased coronary reserve in the absence of ischemic symptoms in children late after arterial switch repair of TGA. The global impairment of stress flow dynamics may indicate altered vasoreactivity; however, the prognostic significance of these findings needs to be determined.     

Asymptomatic cerebral infarction on brain MR images and cognitive function in elderly diabetic patients

Background: The assessment of cognitive function is of great importance in the management of elderly patients with diabetes mellitus. The purpose of the present study was to examine the effects of glucose control and asymptomatic cerebral infarction on impaired cognitive function in elderly patients with diabetes mellitus. Methods: Two hundred and thirteen elderly diabetic patients (59 men, 154 women) with a mean age of 75 years; and 40 non‐diabetic subjects participated in this study and underwent both brain magnetic resonance imaging (MRI) and several domains of cognitive function tests. Based on the brain MRI findings and neurological deficits, the subjects were divided into four groups: (i) the symptomatic cerebral infarction (CI) group; (ii) the asymptomatic CI group; (iii) the diabetic control group without any CI; and (iv) the non‐diabetic control group. Cognitive function was assessed using the mini‐mental state examination (MMSE), and the subtests of Wechsler Adult Intelligence Scale – Revised (WAIS‐R) (the digit symbol test, the backward digit span test, the similarities test, and the picture arrangement test). Attention/complex psychomotor skill and visual memory were assessed with the digit symbol substitution test, the Stroop test, and the Benton visual retention test. Results: Attention/complex psychomotor skill and visual memory were more impaired in the diabetic control group without any CI than in the non‐diabetic control group. The asymptomatic and symptomatic CI groups were significantly inferior to the non‐diabetic and diabetic controls in the digit symbol substitution test and Stroop test. The degree of cognitive impairment significantly correlated to the presence and number of small‐sized cerebral infarction, but to a less degree, large‐sized infarction. Multivariate analysis revealed that age, HbA1c, and cerebral infarction on MR images were independently associated with the impairment of complex psychomotor skill in patients with diabetes mellitus. Conclusions: The presence of asymptomatic cerebral infarction on brain MR images as well as hyperglycemia could explain the impairment of attention/complex psychomotor skill and visual memory in elderly patients with diabetes mellitus.     

Erythrocyte sodium-lithium countertransport in diabetic children: 12 months development and relationship with familial hypertension]

It has been suggested that an increased erythrocyte Na-Li countertransport (Na-Li CNT) rate in patients with IDDM is associated to the risk of developing diabetic nephropathy. Little is known, however, about the possible influence of metabolic control on Na-Li activity. Aims of the study were to evaluate Na-Li CNT at the onset of IDDM and during the remission phase and its relationship with some clinical and metabolic parameters. Twelve insulin-dependent diabetic children (6 males, 6 females; mean age 10 +/- 0.6 years) were studied at the onset and 1, 4, 12 months after the diagnosis; 6 of them had a family history of hypertension. Twelve healthy children (6 males, 6 females; mean age 12 +/- 0.3 years) served as controls. As compared to control subjects (212 +/- 24 mumol/l RBC/h), red cell Na-Li countertransport activity of diabetic children was significantly higher at the onset (354 +/- 31 mumol/l RBC/h) of IDDM and at the first month (348 +/- 36 mumol/l RBC/h). Red cell Na-Li countertransport activity returned toward normal range at the fourth (239 +/- 33 mumol/l RBC/h) and twelfth month (162 +/- 34 mumol/l RBC/h). No correlation was found between the values of red cell Na-Li countertransport activity and those of clinical and biochemical parameters at any time. Patients with hypertensive relatives showed at baseline evaluation a significantly higher red cell Na-Li countertransport activity than those without (436 +/- 28 vs 273 +/- 34 mumol/l RBC/h; p < 0.002). This difference, although not statistically significant, was still evident at the late follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular endothelial growth factor (VEGF) in children, adolescents and young adults with Type 1 diabetes mellitus: relation to glycaemic control and microvascular complications.

AIMS: To evaluate serum levels of vascular endothelial growth factor (VEGF) in a large group of children, adolescents and young adults with Type 1 diabetes mellitus to investigate whether increased VEGF concentrations are associated with long-term glycaemic control and microvascular complications. METHODS: The study involved 196 patients with Type 1 diabetes mellitus (age range 2-24 years, onset of diabetes before the age of 12 years, duration of disease longer than 2 years), without clinical and laboratory signs of microvascular complications; they were divided into three groups (group 1 - n = 37, age < 6 years; group 2 - n = 71, age 6-12 years; group 3 - n = 88, age > 12 years). Fifty-three adolescents and young adults (age 16.1-29.7) with different grades of diabetic retinopathy and microalbuminuria were also selected (group 4). A total of 223 healthy controls were matched for age and sex with each group of patients with diabetes mellitus. RESULTS: VEGF serum levels were significantly increased in pre-school and pre-pubertal children with diabetes as well as in pubertal patients compared to controls. VEGF concentrations were markedly increased in adolescents and young adults with microvascular complications compared with both healthy controls and diabetic patients without retinopathy or nephropathy. Multivariate analysis showed that elevation of VEGF in serum was an independent correlate of complications. One-year mean HbA1c values were significantly correlated with VEGF concentrations (r = 0.372; P < 0.01). Children with HbA1c levels greater than 10% had significantly higher VEGF concentrations when compared with matched patients whose HbA1c levels were lower than 10%. In poorly controlled diabetic children (HbA1c > 10%), long-term (2 years) improvement of glycaemic control (aiming at HbA1c < 7%) resulted in a significant reduction of VEGF levels. CONCLUSIONS: VEGF serum concentrations are increased in prepubertal and pubertal children with diabetes. Glycaemic control influences VEGF serum levels. Severity of microvascular complications is associated with marked increase of VEGF concentrations in the serum of these patients.     

Proinflammatory cytokines are increased in type 2 diabetic women with cardiovascular disease

Diabetics have a much greater morbidity and mortality due to cardiovascular disease (CVD) than nondiabetics. Furthermore, diabetic women have a 3.8-fold greater risk for CVD compared to diabetic men. Inflammation is now considered a risk factor for CVD and it has been demonstrated that inflammation also plays a role in diabetes. One component of inflammation that has reported to be increased in patients with diabetes only and CVD only are proinflammatory cytokines, particularly interleukin-6 (IL-6), tumor necrosis factor (TNF-), and interleukin-1 (IL-1β). This study was performed to test the hypothesis that these proinflammatory cytokines were increased in women with CVD and further increased in diabetic women with CVD compared to nondiabetic women with CVD and healthy age-matched controls. We found that IL-6 was increased in diabetic women with CVD compared to healthy age-matched controls (1.41=0.48 to 0.33±0.06 pg/ml, P<.05). IL-6 was also increased in diabetic women without CVD compared to healthy age-matched controls, but not significantly (0.96±0.27 to 0.33±0.06 pg/ml). We found that TNF- was increased in diabetic women with and without CVD compared to healthy age-matched controls, but not significantly (4.53±1.38 to 3.93±0.53 to 2.33±0.89 pg/ml). IL-1β was not significantly different among any of the four groups of women. These results indicate that both IL-6 and TNF- are chronically increased in diabetic women with and without CVD compared to nondiabetic women. The additive concentration of cytokines in diabetes and CVD suggests a common inflammatory state in both diabetes and CVD.