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H Dorchy

Publications and source records attributed to H Dorchy.

At least 55 records · Page 3Linked to original sources
PubMed1994

Isodisomy of chromosome 6 in a newborn with methylmalonic acidemia and agenesis of pancreatic beta cells causing diabetes mellitus.

Isodisomy (ID) is a genetic anomaly defined as the inheritance of two copies of the same genetic material from one parent. ID in an offspring is a rare cause of recessive genetic diseases via inheritance of two copies of a mutated gene from one carrier parent. We studied a newborn female with a mut(o) of methylmalonic acidemia and complete absence of insulin-producing beta cells in otherwise normal-appearing pancreatic islets, causing insulin-dependent diabetes mellitus. The patient died 2 wk after birth. Serotyping of the HLA antigens, DNA typing of HLA-B and HLA class II loci, study of polymorphic DNA markers of chromosome 6, and cytogenetic analysis demonstrated paternal ID, involving at least a 25-centiMorgan portion of the chromosome pair that encompasses the MHC. ID probably caused methylmalonic acidemia by duplication of a mutated allele of the corresponding gene on the chromosome 6 inherited from the father. It is also very likely that ID was etiologically related to the agenesis of beta cells and consequent insulin-dependent diabetes mellitus in our patient. We thus speculate on the existence of a gene on chromosome 6 involved in beta cell differentiation.

Amino Acid Metabolism, Inborn Errors↗
PubMed1994

Influence of age on the associations among insulin autoantibodies, islet cell antibodies, and HLA DAQ1*0301-DQB1*0302 in siblings of patients with type 1 (insulin-dependent) diabetes mellitus. Belgian Diabetes Registry.

In recent-onset type 1 (insulin-dependent) diabetes mellitus (IDDM), insulin autoantibodies (IAA) and islet cell antibodies (ICA) occur preferentially in young (< 10 yr) patients with the HLA DQA1*0301-DQB1*0302 risk haplotype. We investigated whether this association also exists in siblings of IDDM patients. In our group of 310 siblings, aged 0-39 yr, 6% were positive for IAA, 7% for ICA 12 Juvenile Diabetes Foundation units (JDFU) or more, 5% for ICA 20 JDFU or more, and 2% for high titer ICA (> or = 80 JDFU). The occurrence of IAA and ICA (> or = 20 JDFU) was significantly associated, with a preferential relationship to the HLA DQA1*0301-DQB1*0302 susceptibility haplotype. In the present group of siblings, IAA and DQA1*0301-DQB1*0302 were significantly associated under age 10 yr (26% positivity for IAA vs. 4% in relatives without this haplotype). In this age group, IAA were more prevalent than (high titer) ICA (6%) in the presence of the haplotype. The association between (high titer) ICA and DQA1*0301-DQB1*0302 was not restricted to subjects under age 10 yr. High titer ICA (n = 5) occurred exclusively in homozygotes for the latter haplotype and in carriers of the heterozygous DQA1*0301-DQB1*0302/DQA1*0501-DQB1*0201 high risk genotype, mostly under age 20 yr (four of five). The preferential occurrence of IAA in DQA1*0301-DQB1*0302-positive siblings under age 10 yr was caused by their high prevalence (47%) in subjects with the heterozygous high risk genotype in this age group. As in patients at onset, IAA and high titer ICA are preferentially associated with the DQA1*0301-DQB1*0302 haplotype in siblings of IDDM patients, but, unlike at onset, these associations are observed with specific genotypes only and are more pronounced in subjects under age 10 yr for IAA only. Longitudinal analysis in first degree relatives and other normal controls carrying the DQA1*0301-DQB1*0302 haplotype should assess the hypothesis that IAA qualify as earlier predictive markers for IDDM than high titer ICA.

Adolescent↗
PubMed1994

[What glycemic control can be achieved in young diabetics without residual secretion of endogenous insulin? What is the frequency of severe hypoglycemia and subclinical complications?].

BACKGROUND: Successful therapeutic management of the child and adolescent with diabetes mellitus requires insulin administration, dietary management, physical activity and physical fitness, and emotional support. The ultimate aim is to avoid long-term microvascular, renal and neurologic complications by maintaining blood glucose concentrations close to the normal range. We determined the mean annual glycosylated hemoglobin levels (HbA1c) that can be achieved in young diabetic patients without residual insulin secretion. POPULATION AND METHODS: One hundred and twenty-nine patients aged 17.7 +/- 6.4 yr (m +/- SD) were followed sequentially for 1 year by the same pediatric diebetologist. They had a diabetes duration from 2 to 27 yr (mean: 9.7). Mean age at onset of diabetes was 8.1 +/- 3.7 yr. C-peptide was undetectable in all patients. Subclinical retinopathy, neuropathy and nephropathy were looked for in all patients. HbA1c was measured by an HPLC method (normal range: 4.4-6.0%) at each visit (6.6 +/- 1.9 visits/yr/patient). RESULTS: Mean (SD) annual HbA1c levels were 6.9 +/- 1.5%, ie 115% of normal values. The frequency of monthly home blood glucose monitoring (HBGM) was between 0 and 250 measurements (77 +/- 49). HbA1c was not related to sex, ethnicity, age, and duration of diabetes. There was no difference between the 84 patients on only two or three daily insulin injections (aged 15.1 +/- 5.6 yr with a diabetes duration of 7.5 +/- 5.2 yr), and the 45 patients on four injections using the basal bolus regimen (aged 22.5 +/- 5.2 yr with a diabetes duration of 13.7 +/- 5.5 yr). The regression analysis showed a weak but significant inverse correlation between HbA1c and frequency of HBGM as well as frequency of outpatient clinic attendance. The yearly incidence rates of severe hypoglycemia were 0.10 in the two injection group and 0.31 in the four injection group without relationship to HbA1c levels. Frequency of subclinical complications was 15% for nephropathy, 31% for neuropathy and 39% for retinopathy. The minimum age at which incipient complications appear was 13 yr for one complication, 17 yr for the association of two complications, 23 yr for the association of three, after a diabetes duration of 3, 7, 15 yr, respectively. CONCLUSIONS: In 30% of young diabetic patients without residual insulin secretion, it is possible to obtain mean annual HbA1c levels within the normal range. Increased frequency of HBGM and of clinic attendance help to reduce HbA1c levels. In contrast, multiple insulin injection therapy, allowing more freedom for diet, does not necessarily improve metabolic control and is associated with a higher incidence of severe hypoglycemic episodes. Incipient complications have to be looked for by sensitive methods from puberty.

Adolescent↗
PubMed1993

Congenital absence of insulin cells in a neonate with diabetes mellitus and mutase-deficient methylmalonic acidaemia.

We report on a female neonate with diabetes mellitus and methylmalonic acidaemia, who died at age 16 days. Using immunocytochemistry, electron microscopy and in situ hybridisation, we were unable to demonstrate any insulin cells in the pancreatic islets. Methylmalonic acidaemia was caused by a methylmalonyl coenzyme A mutase apoenzyme defect. The metabolic crisis of the methylmalonic acidaemia aggravated the diabetes and may explain the failure of insulin therapy. Our results suggest that the infant suffered from a congenital absence of beta cells associated with a genetically transmitted mutase apoenzyme defect.

Autopsy↗
PubMed1992

Erythrocyte metabolic alterations in type I diabetes: relationship to metabolic control.

Erythrocytes from young type I diabetic patients (n = 11), incubated in their plasma in anaerobic conditions, exhibited higher glucose consumption than cells from controls (n = 11). This increased metabolic activity is believed to reflect erythrocyte alterations dependent on the degree of metabolic control, as glucose consumption was significantly correlated to glycosylated haemoglobin (HbA1) and to glucose levels (P < 0.05 and P < 0.01 respectively). Red cell hexokinase (HK) and pyruvate kinase (PK) activities were similar in both groups whereas phosphofructokinase (PFK) activity was slightly higher in patients' cells (P < 0.05). No difference was found between patients and controls for red cell ATP and 2.3 diphosphoglycerate (2.3 DPG) levels. However, the concentrations of these glycolytic products seem also closely related to the glucose homeostasis in diabetes. Indeed, within the diabetic group, ATP levels showed a negative relationship with glucose level (P < 0.05) and 2.3 DPG a positive relationship with HbA1 (P < 0.05). In conclusion, higher glycolytic activity is present in young diabetic red cells. This activity as well as ATP and 2.3 DPG levels are related to the degree of short- or long-term diabetic control. These findings stress the importance of a careful metabolic control to avoid haematological disturbances.

Adenosine Triphosphate↗
PubMed1991

First microangiographic abnormalities in childhood diabetes--types of lesions.

An analysis by fluorescein angiography of the first signs of retinopathy in 161 diabetic children showed that microaneurysm-like spot dilatations, microaneurysms, focal capillary dilatations, leakage, generalized capillary dilatations, retinal hemorrhages, areas of capillary non-perfusion and capillary remodelling, in decreasing order of frequency, were features of the onset of retinopathy. However, microaneurysm-like spot dilatations and both focal and generalized capillary dilatations were considered to be too subjective for use in further quantitative analysis. Retinopathy was not found in children less than 12 years of age and was detected only after at least 3 years of diabetes. The mean duration of diabetes before the occurrence of the first lesions in 118 affected eyes was 8.2 years. The mean age at which lesions occurred was 16.4 years. Although capillary non-perfusion was rarely an initial lesion, occurring after a longer duration of diabetes and at a later age than the other lesions, no significant difference could be found between the various types of lesions for either the patient's age at their onset or the duration of diabetes. The type of initial lesion was also unrelated to sex, age at the onset of diabetes, or metabolic control.

Adolescent↗
PubMed1991

[Sports and diabetes in children and adolescents].

The triad of insulin, diet and exercise has been the basis for treatment of diabetes for several decades. However, the choice of sporting activities for young diabetics requires an understanding of: a) the energy metabolism and the adaptation to physical activity in the healthy; b) the metabolic adaptation during physical activity in the diabetic child; and c) the practical recommendations concerning diet and insulin that have to be learned by the children themselves. The healthy child utilises immediately available substrates, such as ATP and creatine phosphate in much the same fashion as the adult. However, the capacity for anaerobic degradation of glycogen and glucose seems limited in the muscles of children relative to that of adults. Consequently, the adaptation to resistance exercise should be undertaken with prudence in children and adolescents. The release of insulin tends to decrease during effort. Diverse hypotheses have been proposed to explain this phenomenon. However a low concentration of insulin is required: insulin is said to play a "permissive" role. In diabetic children, an adequate insulin therapy is required to allow the full benefit of muscular activity on glucose assimilation and to reach the same level of physical performance as the non-diabetic. In the case of insufficient metabolic control, exercise can provoke severe hypoglycaemic episodes, even after muscle activity has ceased, or increase glucose levels and lead to ketoacidosis. Regular physical training induces a reduction in postexercise proteinuria measured in diabetic adolescents but its role in metabolic control remains controversial.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗