Limited joint mobility in subjects with insulin dependent diabetes mellitus: relationship with eye and kidney complications.

Three hundred and fifty seven subjects (178 males and 179 females) with insulin dependent diabetes mellitus were evaluated for the presence of limited joint mobility of the interphalangeal joints. Sixty six subjects (19%) had stage 1 and 26 subjects (7%) had stage 2 involvement of their interphalangeal joints. The presence of contractures was significantly related to mean longitudinal glycated haemoglobin (HbA1) concentrations, duration of diabetes, age of onset, mean longitudinal cholesterol concentrations and blood pressure. Limited joint mobility was also significantly associated with early diabetic retinopathy and raised albumin excretion rates. Limited joint mobility remained a significant factor in the logistic regression model for albuminuria and grade of retinopathy when controlled for smoking, cholesterol concentrations, duration of diabetes, age, gender, and blood pressure. However, limited joint mobility was only significantly associated with diabetic retinopathy when the effect of HbA1 concentrations was included in the multivariate model.     

Limited joint mobility in diabetic children: a risk factor of diabetic complications?

Limited joint mobility (LJM) was detected in 24 of 55 children with type I diabetes. Among children with longer duration of diabetes (5 years) 15 of 25 had LJM. Ten of these 15 also had preclinical diabetic retinopathy. LJM, impaired respiratory function and early retinopathy together were detected in 8 patients. Three children had early retinopathy without LJM but two of them also had impaired respiratory function. The findings were not related to the degree of metabolic control. These results confirm the great importance of connective tissue changes in childhood diabetes with respect to the early development of diabetic microvascular disease.     

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.     

Skin, joint, and pulmonary changes in type I diabetes mellitus

Three hundred seventy-five patients with diabetes mellitus were examined for the presence of sclerodermalike skin changes, limited joint mobility, and vital capacity changes. Nineteen percent of patients had vital capacities 2 SDs below the mean of predicted values. There was no significant relationship between decreased vital capacities and duration of diabetes, sclerodermalike skin changes, limited joint mobility, smoking history, proteinuria, or retinopathy. Cutaneous involvement consisting of thickening, tightening, and/or a waxy quality of the skin was noted in 190 patients (51%). The severity of skin involvement correlated positively with the patients' duration of diabetes, age, severity of joint contractures, and diabetic retinopathy. Thus, sclerodermalike skin changes appear to reflect generalized connective tissue alterations in diabetes and may indicate increased risk for diabetic microvascular complications.     

"Limited joint mobility". Diabetes-specific joint changes in diabetic children

This paper describes a case of limited joint mobility (diabetic cheiroarthropathy) observed in our pediatric diabetological outpatients department. Symptoms are limited mobility of big and small joints, thickened, waxy skin, delay in growth and maturation. Of major importance is the reference to the microvascular risk of 83% as stated by Rosenbloom in diabetes patients of Type I suffering from limited joint mobility and this signifying unfavourable prognoses.     

Limited joint mobility in insulin dependent childhood diabetes

Limited joint mobility (LJM), beginning typically in the fifth finger and moving radially, affecting interphalangeal, metacarpal-phalangeal, and large joints, is the earliest clinically apparent complication of diabetes in childhood and adolescence. It is painless and not disabling. Approximately 50% of post-adolescent patients with more than 5 years duration of diabetes are affected, with age being more important than duration of diabetes, as is the case with other complications. Growth failure is more frequent in the presence of LJM, although correlations with diabetic control have not been found. Variations in frequency in various reports, including high prevalence in controls or relatives, appear to be related to the quality of the examination; simple inspection with hands pressed flat on the table top or together in the prayer position is inadequate; passive extension must be performed. Although differential diagnosis from other conditions causing limitation of the fingers in diabetes would appear simple, LJM has been confused with other conditions which can be distinguished by the presence of pain or paresthesias, neurologic findings, disability, finger-locking, swelling, muscle atrophy, palmar skin or fascial thickening, absence of typical distribution, calcification of the vessels and, particularly, the age group affected. That the periarticular thickening found on examination and demonstrated on roentgenograms reflects generalized abnormalities is suggested by association with thick tight waxy skin, decreased pulmonary function, and association with retinopathy, nephropathy, and neuropathy, independently of duration of diabetes.(ABSTRACT TRUNCATED AT 250 WORDS)     

High prevalence of coeliac disease in siblings of children with type 1 diabetes

Coeliac disease has been shown to occur more frequently among first-degree relatives of diabetic patients than in the general population. Our objective was to assess the prevalence of endomysium antibodies (EMA) in non-diabetic siblings of Czech diabetic children and to evaluate the effects of HLA-DQ polymorphisms in determining the genetic susceptibility to coeliac disease (CD) in these subjects. We investigated 240 siblings of diabetic children from 213 families (125 males and 115 females, aged 12.6±4.9 years, mean ± SD). All subjects were tested for the total IgA level to exclude IgA deficiency, and for endomysium IgA to disclose CD. In five IgA-deficient subjects, anti-gliadin IgG was used instead. Small bowel biopsy was offered to subjects with confirmed positive EMA. The HLA-DQA1, -DQB1 genotypes were determined using PCR-SSP. Positive EMA were found in 9/240 (3.8%) subjects (three males, six females). The biopsy confirmed CD in six children, two had a normal mucosal finding and one refused the biopsy. The HLA-DQ2 polymorphism was more frequent among siblings with EMA (seven of nine) than in siblings without EMA (33%), corrected P =0.031. Conclusion:The 3.8% frequency of coeliac disease found in siblings of diabetic children is close to the 4.3% found previously in Czech children with type 1 diabetes mellitus and is substantially higher than the rate in the healthy children population.     

Impact of glycemic control on serum lipoprotein (a) in Arab children with type 1 diabetes

BACKGROUND: Lipoprotein (a) (Lp (a)) is an independent risk factor for coronary artery disease (CAD), a major cause of death in patients with type 1 diabetes mellitus. Both type 1 diabetes and CAD represent major problems in Kuwait. Data on the effect of metabolic control on Lp (a) in diabetic children are limited and this is particularly true for Arab children. The objectives of the present study were to analyze serum Lp (a) levels in patients with type 1 diabetes compared with non-diabetic children, taking into account the effect of glycemic control. METHODS: Circulating lipids, including Lp (a), were measured in serum samples from 60 prepubertal non-diabetic children and 58 prepubertal children with type 1 diabetes. Comparisons of Lp (a) concentrations were made between the non-diabetic and diabetic children with good to fair control (glycosylated hemoglobin (GHb) <11%) and a group of diabetic children with poor control (GHb > or = 11%). RESULTS: The mean serum Lp (a) level in all diabetic children was 187.62+160.43 mg/L, compared with 162.88+156.06 mg/L in the control group. The group of children with poor glycemic control had higher median Lp (a) levels (147.50 mg/L) than either the group of diabetic children with good to fair control (95 mg/L; P<0.028) or the group of non-diabetic children (125 mg/L; P<0.04). Moreover, 38.3% of poorly controlled diabetic children had elevated Lp (a) levels > or = 250 mg/L, compared with 12.5% of diabetic children with good to fair control and 16.7% of non-diabetic children (P<0.025 and P<0.039, respectively). No association was found between Lp (a), diabetes duration and insulin dose. CONCLUSIONS: In Arab children, highest Lp (a) levels are associated with poorest metabolic control. The prevalence of Lp (a) levels associated with cardiovascular risk is higher in poorly controlled diabetic children. Increased levels of Lp (a) may be another contributing factor to the high risk for CAD in diabetic patients.     

Limited joint mobility and diabetic retinopathy demonstrated by fluorescein angiography

The association between limitation of finger joint mobility (LJM) and diabetic retinopathy demonstrable by fluorescein angiography was examined in 311 subjects aged 6–27 years. The relationship of these two complications was highly significant (P<0.0001). This was not the result of the effect of diabetes duration on both complications; interaction of LJM, retinopathy, and duration was not significant (P>0.3). The presence of LJM was predictive of associated retinopathy at the level of clinical recognition (more than ten microaneurysms); 43% of those with LJM and duration beyond 4 years had retinopathy while only 15% of this duration group without LJM had clinical retinopathy.     

Low serum TNF-alpha levels in subjects at risk for type 1 diabetes

OBJECTIVE: The aim of our study was to determine whether serum TNF-alpha levels in individuals at risk of developing type 1 diabetes, such as first-degree relatives of diabetic patients and children with incidental hyperglycemia, underwent alterations, and also to establish whether these levels might be used to identify individuals prior to insulin dependence. RESEARCH DESIGN AND METHOD: We studied 71 healthy first-degree relatives (FDR) of type 1 diabetic patients and 11 children with incidental hyperglycemia. We looked for immunogenetic (HLA class II serologic alleles and HLA-DQ alpha/beta genomic polymorphisms), immunologic (islet-cell and insulin autoantibodies) and metabolic (FPIR to IVGTT) markers of type 1 diabetic risk. Serum concentrations of TNF-alpha were quantified using IRMA. RESULTS: We found significantly lower serum TNF-alpha levels in FDR of type 1 diabetic patients (median: 54.3 pg/ml) (p=0.01) and in children with incidental hyperglycemia (median: 10.83 pg/ml) (p<0.0001) compared to controls (median: 76.56 pg/ml). No significant difference was observed between subjects with or without immunogenetic, immunologic and metabolic markers of type 1 diabetic risk. A negative correlation was found between serum TNF-alpha and HbA1c levels (r=-0.27, p=0.023). Two children with incidental hyperglycemia, whose TNF-alpha levels were very low, developed type 1 diabetes 6 and 8 months after this study. CONCLUSION: Our results are compatible with an impaired immune system in the prediabetic period and suggest that serum TNF-alpha concentrations may be considered as an immunological marker useful to identify subjects at risk of developing type 1 diabetes.     

Reduced capillary resistance in allergic patients

Fifty four of 67 allergic children (81%) had a pathologically reduced capillary resistance (CR) of less than 16 cm Hg. Five of the 13 allergic children with normal CR were treated with corticosteroids. Prednisone improved CR in one patient for at least 24 h, and this was reflected by improvement of hemorrhagic parameters such as bleeding intensity, bleeding pattern and blood loss. There was no correlation between CR and IgE levels. 90% of the symptomatic relatives of allergic children had a reduced CR, but only 44% of asymptomatic relatives. CR presents a simple additional tool for diagnosing allergy and might give hints to the carrier state of allergy.     

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.     

A FAMILY STUDY OF COELIAC DISEASE

ABSTRACT. Small intestinal biopsy was performed in all 100 firstdegree relatives of 32 index patients with childhood coeliac disease (CD) diagnosed according to the European Society for Paediatric Gastroenterology and Nutrition. CD was found in 2 relatives (2.0%), which means that first-degree relatives of coeliac children would run a tenfold increased risk of CD compared with the general population of Sweden. Five relatives had a moderately abnormal mucosa. On rebiopsy they had a normal mucosa and are therefore not classified as having CD according to current diagnostic criteria. For practical purposes it would be impossible to perform a biopsy in all first-degree relatives of coeliac patients. However, relatives with a past history of symptoms suggestive of malabsorption and relatives with present signs of malabsorption should be candidates for biopsy.     

Dermatoglyphic alterations associated with acute rheumatic fever in children

The dermatoglyphic configurations of 78 children with acute rheumatic fever were compared with those of 46 first-degree relatives and 1,310 normal subjects. Of the children with acute rheumatic fever, 75% had an ulnar deviation of the axial triradius. In about 40% of this group, the ulnar deviation was associated with a concomitant distal displacement, which resulted in a significantly higher mean maximal angle atd (P less than .001) and significantly lower mean ab and td ridge counts (P less than .001) relative to normal control values. The palmar dermatoglyphics of patients with acute rheumatic fever were more closely related to the configurations of first-degree relatives than to normal controls. The dermatoglyphic profiles of six patients were nearly identical to those of their first-degree relatives, all of whom had a history of acute rheumatic fever. Presence of abnormal dermatoglyphic profiles in a large proportion of children with acute rheumatic fever supports the hypothesis that certain individuals have a genetic predisposition to this disease.     

Pupil size in diabetes.

Sympathetic function was studied in 101 diabetic children and 102 age and sex matched control children, as part of a longitudinal study of the evolution of microvascular disease in the population of diabetic children and adolescents in Avon County. The median (range) age of the diabetic population was 13.5 (6.0-17.2) years, the duration of diabetes was 4.0 (0.4-13.9) years, and glycated haemoglobin (HbA1) was 10.9 (7.0-18.1)%. Pupillary adaptation in darkness, as an index of sympathetic neuropathy, was measured using a Polaroid portable pupillometer. Diabetic children had a significantly smaller median pupillary diameter, measured as the pupil/iris ratio and expressed as a percentage, than control children (median (range) 62.9 (50.3-72.1) v 65.9 (52.2-73.8)). Pupillary diameter was significantly related to diabetes duration (r = -0.22), HbA1 (r = -0.34), systolic blood pressure (r = -0.25), diastolic blood pressure (r = -0.49), and mean albumin/creatinine ratio on random urine samples (r = -0.26). Pupillary diameter was not related to age (r = -0.1). Eight (7.9%) diabetic and four (3.9%) control children were identified as having abnormal pupillary dilation in darkness. In comparison with the rest of the diabetic population, these diabetic children had longer diabetes duration and poorer glycaemic control. Polaroid pupillometry has demonstrated subclinical autonomic neuropathy in a population of diabetic children and adolescents. These abnormalities were related to poor metabolic control, long diabetes duration, and also to other indices of microvascular disease.     

The Prevalence of Microalbuminuria in Diabetic Children and Adolescents and Its Relation to Puberty

The albumin excretion rate (AER) was studied in two groups of diabetic children and adolescents. Twenty-four-hour AER was studied in 75 children with diabetes for 5 years, in 49 children with diabetes for 10 years, in 55 children with diabetes for 10–20 years and in 21 age matched healthy controls. Overnight AER was studied in 129 diabetic children and adolescents with a duration of diabetes varying from 1–14 years. Diabetics exhibited a wide range of AER-values and when expressed per body surface area, diabetic children had significantly higher AER compared to controls. Log transformed AER-values were significantly correlated to age and body surface area in diabetics but not in controls. In the diabetics, log AER was also correlated to systolic and diastolic blood pressure but not to HbA_1c. 20% of the 0 diabetics had AER values exceeding the upper value for healthy controls which was 18.5 μg/min. 31/35 of them were older than 12 years. In both groups of diabetics, 5% had AER-values exceeding those reported to be predictive for later development of overt nephropathy, the youngest being 16 years old. When comparing diabetic children 0–12 years (i.e. before the maximal growth spurt of puberty) to those older than 12 years, at the same duration of diabetes, the latter group had significantly higher AER-values. No sex difference was found in either age group. It is concluded that after puberty diabetic patients also show evidence of incipient diabetic nephropathy. Thus, routine screening for microalbuminuria is recommended also in pediatric diabetes care after 12 years of age.     

Result of 3 years of screening for preclinical phase of juvenile insulin-dependent diabetes mellitus

We screened 1,000 individuals for pre-type I diabetes mellitus: 927 were first degree relatives of patients treated at our institution, 31 other had related autoimmune diseases, 42 had fortuitously discovered slight hyperglycemia. Islet cell antibodies were present in 31 subjects, 13 adults and 18 children. Among these 18 children, 7 also had complement-fixing islet cell antibodies, and 5 anti-insulin antibodies. All but one initially had a normal insulin response to intravenous glucose. The child with the abolished response, as well as another whose insulin secretion fell down during the study period, became diabetic. Based on these preliminary data, we are developing large scale family screening of pre-type I diabetes.     

HLA-DQA1*05-DQB1*0201 positivity predisposes to coeliac disease in Czech diabetic children

The aims of this study were to estimate the prevalence of coeliac disease (CD) in Czech children with insulin dependent diabetes mellitus (IDDM), and to determine the contribution of HLADQA1 and DQB1 to CD susceptibility among diabetic children. We screened 345 children with IDDM (186 boys and 159 girls, aged 0 to 18 y) for coeliac disease using the IgA endomysial antibodies (EMA) test. In all EMA-positive children, small bowel biopsy was performed to confirm CD. To determine the role of the HLA-DQA1*05-DQB1*0201 (DQ2) and the DQA1*03-DQB1*0302 (DQ8) molecules in CD susceptibility among diabetic children, the HLA-DQA1-DQB1 was genotyped in all EMA-positive, and in 186 of EMA-negative diabetic patients. EMA positivity was found in 15/345 (4.3%) diabetic children. The diagnosis of CD was established in 14/345 (4.1%) children based on a bioptic finding of villous atrophy, while the remaining EMApositive patient had a normal bioptic finding, being diagnosed as a potential CD. The HLA DQA1*05-DQB1*0201 (DQ2) molecule conferred a significant risk of CD among diabetic children (odds ratio = 4.1, CI 95% 1.1-15), being found more frequently in diabetic children with CD (80%) than in diabetic children without CD (49%). Conclusion: The high prevalence of CD (4.1%) found in Czech children with IDDM emphasizes the need for their regular screening. We suggest that this CD screening protocol may be individualized according to the DQA1*05-DQB1*0201 positivity.     

小儿系统性红斑狼疮的特点

目的了解小儿系统性红斑狼疮(SLE)的特点。 方法对85例SLE儿的临床资料进行分析。 结果85例中起病年龄10a以上者66例(77．6％),男女比为16．1,12例(14．1％)家族中有结缔组织病史。最常见的表现是抗核抗体(ANA)阳性(91．8％)、血沉增快(90．6％)、肾脏受累(82．3％)、发热(82．3％)、低补体血症(81．2％)、蝶形红斑(69．4％)、关节症状(62．3％)及血液系统损害(62．3％)。18例(21．2％)起病时表现为单一系统损害。6例(7．0％)肾损害始终为唯一临床表现。经激素联合免疫抑制剂治疗,随访0．5～23a,临床缓解或病情波动者49例,无1例进入慢性肾功能衰竭,死亡9例,失访27例。 结论本病临床表现多样,肾损害发生率高,早期正规治疗疗效显著。     

Ophthalmologic complications of insulin-dependent diabetes mellitus in children and adolescents

Diabetes mellitus is a major cause of visual impairment and blindness. Cataracts and retinal vascular abnormalities (retinopathy) are the major defects occurring in the eyes. The frequency of these defects increases with the duration of diabetes. Many believe that the occurrence of eye disease in children with diabetes is rare. Blurry vision, an early manifestation of cataractogenesis, occurs in nearly all children with diabetes. Retinopathy, which is extremely rare prior to puberty, occurs in 70-90% of adolescents with diabetes of more than 10 years' duration. Proliferative retinopathy and blindness due to diabetes also occur in adolescents. Regular, careful ophthalmologic examinations by retinal specialists are indicated for the adolescents at risk. Those at risk are adolescent females with HLA DR3 and DR4 as well as those with limited joint mobility. Early recognition is essential to prevent the blindness that follows untreated proliferative retinopathy.