Juvenile Insulin-dependent Diabetes Mellitus Research Articles

Juvenile, insulin‐dependent diabetes mellitus, type 1‐related dermatoses

Juvenile insulin-dependent diabetes mellitus type 1 (IDDM) is a well-recognized worldwide entity, the significance of which has increased because of its recent upsurging trends, warranting attention on variety of its clinical expressions, in particular, pertaining to skin, an aspect seldom taken cognizance of. Hence an endeavour to recap the related dermatoses, such as limited joint mobility syndrome including sclerodermoid (scleroderma-like) changes, xerosis, necrobiosis lipoidica diabeticorum, granuloma annulare, diabetic foot syndrome, has been made. Complexities relating to the recently explored issues of atopic dermatitis and drug hypersensitivity syndrome have also been covered adequately. In addition, the current concepts of the physiopathology of type 1 diabetes-related dermatoses are briefly recapitulated for clarity.

Relationship among psychopathological dimensions, coping mechanisms, and glycemic control in a Croatian sample of adolescents with diabetes mellitus type 1

Psychopathological factors associated with metabolic control in juvenile insulin-dependent diabetes mellitus (IDDM) deserve further investigation. This study assessed the relationship among specific psychopathological dimensions, coping mechanisms, and metabolic control in a Croatian clinical sample of adolescents with IDDM. One-hundred and one adolescents (aged 11-18) with IDDM filled out the youth self report (YSR) assessing psychopathological dimension and the scale of coping with stress (SCS). Glycemic control was estimated by the percentage of glycated hemoglobin (HbA1c). Subjects were divided into three groups according to HbA1C values: "optimal", "suboptimal control", and "at high risk". Subjects in optimal glycemic control presented with significantly lower scores in most of YSR scales compared to subjects at high risk. Moreover, they had significantly lower scores in avoidance and emotional reactivity and significantly higher scores in cognitive restructuring and problem solving SCS subscales. Regression models revealed that both internalizing and externalizing YSR scores, as well as emotional reactivity coping scores, independently contributed to explain variability of HbA1C values. Both internalizing and externalizing psychopathological dimensions, as well as emotion-oriented coping strategies, are independently associated with poor metabolic control in both boys and girls with IDDM, thus representing potential interest targets of psychotherapeutic interventions aimed at improving glycemic control in this population.

In vitro survival and RT6 expression kinetics in peripheral T cells of diabetes prone BB and Lewis rats

THE DIABETES PRONE BB (BB-DP) rat is one of the classical animal models of spontaneous auto-immune insulin-dependent diabetes mellitus (IDDM). In contrast to IDDM in the non-obese diabetic mouse and to human juvenile IDDM, disease susceptibility of BB-DP rats is tightly correlated to T cell lymphopenia that, moreover, coincides with an RT6 expression defect. 1 These experiments study comparatively the in vitro survival of T cells of different maturational stages of Lewis (LEW) and BB-DP rats, as well as investigate the kinetics of Thy-1 and RT6 expression. In the light of these data and those published previously, a hypothesis regarding the possible relations between lymphopenia and RT6 expression defect in BB-DP rats is presented.

Lipid profiles and blood pressure: are they risk factors for the development of early background retinopathy and incipient nephropathy in children with insulin-dependent diabetes mellitus?

The objective of this study is to examine the influence of lipid profiles and blood pressure on the development of microvascular complications in adolescents with insulin-dependent diabetes mellitus (IDDM) in a matched pairs study. Patients with early background retinopathy (n = 21) or microalbuminuria (n = 15) and their respective statistical twins participated in the study. Serum total cholesterol, high-density lipoprotein (HDL) cholesterol, fasting triglycerides, glycosylated haemoglobin A1c (HbA1c), and systolic and diastolic blood pressure during 3 years prior to the development of early background retinopathy or incipient nephropathy were examined. The multivariate discriminant analysis demonstrated glycaemic control and HDL cholesterol to be the most important variables related to the development of retinal lesions (84% correctness), and diastolic blood pressure to be associated with microalbuminuria (57% correctness). In addition to poor glycaemic control, different factors seem to be important for the early retinal or renal lesions of juvenile IDDM.

HLA, ESD, GLOI, C3 and HP polymorphisms and juvenile insulin dependent diabetes mellitus in Tamil Nadu (South India)

Fifty juvenile insulin dependent diabetes mellitus (JIDDM) patients of Tamil Nadu (South India) were typed for HLA-A, -B, -C, -DR, and -DQ, ESD, GLOI, C3 and HP polymorphisms. The frequencies of B8, DR3, DR4, DR53 and DQ2 antigens of the HLA system were significantly higher in the patients than in controls (relative risk, RR = 4.81; 5.14; 3.98; 3.36 and 2.53, respectively). However HLA-DR2, -DR5 and -DQ1, observed less frequently in the patient group, appear to play a role of protection against the disease (RR = 0.32; 0.30 and 0.20 respectively). HLA haplotype analysis demonstrated very high relative risk associated with two hitherto unreported haplotypes namely A3, DR1 and Cw3, DR4 (RR = 27.30 and 20.00, respectively) and also scanty distribution of the haplotypes A1, B17 and DR2, DQ1 (RR = 0.39 and 0.36 respectively) in the patient group. Among other genetic markers tested, GLOI is informative with its phenotype GLOI 2-1 showing positive association with JIDDM (RR = 4.06).

Optic Disk Risk Factors for Nonarteritic Anterior Ischemic Optic Neuropathy

The anatomic characteristics of a relatively small optic nerve head, absent to small physiologic cup, abnormal branching pattern of central retinal vessels, and a lush nerve-fiber bundle layer elevating the disk margins are associated with the occurrence of certain ischemic disease states. These diseases include the following: (1) nonarteritic anterior ischemic optic neuropathy, (2) anterior ischemic optic neuropathy of the young, (3) the papillopathy in patients with juvenile insulin-dependent diabetes mellitus, and (4) Leber's hereditary optic neuropathy. The finding of such a disk at risk should signal the possible later development of visual dysfunction. Ordinarily, when an ophthalmologist discusses risk factors in relationship to the optic disk, the topic is that of open-angle glaucoma and the predictability of the ultimate development of visual field loss. In the early 1980s, Hoyt suggested that certain disk characteristics may predispose an individual to the development of nonarteritic anterior ischemic optic neuropathy (Hoyt, W. F., unpublished data, presented at the Rocky Mountain Neuro-Ophthalmologic Society Meeting, February 1982). Specifically, in these cases he noted that the unaffected eye has a small or absent physiologic cup. Several investigators went on to confirm Hoyt's observation that these crowded disks are at risk for developing nonarteritic anterior ischemic optic neuropathy.! The hallmarks of the disk at risk are as follows: (1) relatively small optic nerve head, (2) absent to small physiologic cup, (3) increased number of branches of the central retinal vessels within the disk, and (4) a normal, healthy-appearing nerve-fiber bundle layer with heaping up of at least the superior, nasal, and inferior fibers (Fig. 1). These disks are similar in many ways to those described by Rosenberg, Savino, and GlaserS,6 as being characteristic of pseudopapilledema. Presumably, a small physiologic cup is the

Optic Disk Risk Factors for Nonarteritic Anterior Ischemic Optic Neuropathy

The anatomic characteristics of a relatively small optic nerve head, absent to small physiologic cup, abnormal branching pattern of central retinal vessels, and a lush nerve-fiber bundle layer elevating the disk margins are associated with the occurrence of certain ischemic disease states. These diseases include the following: (1) nonarteritic anterior ischemic optic neuropathy, (2) anterior ischemic optic neuropathy of the young, (3) the papillopathy in patients with juvenile insulin-dependent diabetes mellitus, and (4) Leber's hereditary optic neuropathy. The finding of such a disk at risk should signal the possible later development of visual dysfunction. Ordinarily, when an ophthalmologist discusses risk factors in relationship to the optic disk, the topic is that of open-angle glaucoma and the predictability of the ultimate development of visual field loss. In the early 1980s, Hoyt suggested that certain disk characteristics may predispose an individual to the development of nonarteritic anterior ischemic optic neuropathy (Hoyt, W. F., unpublished data, presented at the Rocky Mountain Neuro-Ophthalmologic Society Meeting, February 1982). Specifically, in these cases he noted that the unaffected eye has a small or absent physiologic cup. Several investigators went on to confirm Hoyt's observation that these crowded disks are at risk for developing nonarteritic anterior ischemic optic neuropathy.! The hallmarks of the disk at risk are as follows: (1) relatively small optic nerve head, (2) absent to small physiologic cup, (3) increased number of branches of the central retinal vessels within the disk, and (4) a normal, healthy-appearing nerve-fiber bundle layer with heaping up of at least the superior, nasal, and inferior fibers (Fig. 1). These disks are similar in many ways to those described by Rosenberg, Savino, and GlaserS,6 as being characteristic of pseudopapilledema. Presumably, a small physiologic cup is the

HLA-DQB1 typing of north east Italian IDDM patients using amplified DNA, oligonucleotide probes and a rapid DNA-enzyme immunoassay (DEIA)

We report on HLA-DQB1 typing in IDDM patients of north east Italian region using an enzymatic method based on the detection of hybridization reaction between PCR amplified DNA from whole blood and allele specific oligonucleotides by an antibody directed against double stranded DNA (DNA-enzyme immunoassay or DEIA). The method is reliable, simple and sensitive as the classical radioactive method with the advantage of using a universal non radioactive detection reagent. Nineteen families, each including one subject with juvenile insulin-dependent diabetes mellitus (IDDM) were analyzed. A strong association between absence of an aspartic acid (Asp) in position 57 of DQB1β chain in homozygous conditions and susceptibility to IDDM was found. In contrast with some previous observations, however, no significant association was found between Asp/non-Asp heterozygous genotype and IDDM. No patients were found with an homozygous Asp/Asp genotype, known to be protective in caucasoid population. Of particular interest was the DQB1 alleli distribution in our population sample. The non-Asp allele most frequently found in IDDM subjects was the DQB1 0201 allele and this finding was statistically significant (Pc value <0.05, relative risk = 5.01). No significant association was found for any other allele including the DQB1 0302 (Pc value = not significant although with relative risk = 3.28) previously reported as the most frequent allele in IDDM caucasoid patients.

Supratypes and ancestral haplotypes in IDDM: Potential importance of central non-HLA MHC genes

Juvenile insulin-dependent diabetes mellitus develops in susceptible children exposed to unknown environmental factors. If the genes responsible for susceptibility could be identified, it should be possible to understand the method of injury to beta cells as well as identify the infectious or other agents involved. For a decade it has been known that one or more of the susceptibility genes must be within the major histocompatibility complex (MHC). Unfortunately, there are at least 20 different genes in the complex and it has not been possible to determine which are actually responsible. Therefore, we undertook to apply a new concept and new technology to the problem. Over several years we have shown that the diabetogenic gene(s) are contained within conserved ancestral haplotypes which can then be used as markers of the DNA which must contain the gene(s), whether present in a patient or an asymptomatic carrier such as a parent. This approach avoids the confusion which has resulted from using DR3 or DR4 which are only sometimes associated with the relevant genes. The new technology involves pulsed field gel electrophoresis which allows examination of large fragments of DNA containing all of the MHC, and makes it possible to identify deletions and duplications which were otherwise undetectable. In the first instance we compared two ancestral haplotypes [1,8,3 (8.1) and 18,F1,3 (18.2)] known to contain the relevant genes, and contrasted the DNA with that of another ancestral haplotype [3,7,2(7.1)] which is known to lack these genes. We have shown that there are three major deletions common to the two carrier haplotypes but absent in the protective haplotypes.(ABSTRACT TRUNCATED AT 250 WORDS)

The significance of certain epidemiological variants in the genesis of juvenile insulin-dependent diabetes mellitus--the need for a global program of co-operation.

Published data from literature show a two-to four-fold increase in the incidence of JIDDM, in the Western hemisphere over the past decade (5% to 10-20%). WHO Expert Committee Technical Report Series No. 646 (1980) gives the risk of development of diabetes in the first two decades of life, in the sub-populations of Europe and North America, as 0.1% to 0.3%. In Japan, it is stated to be less than 0.02%; in Tamil Nadu, India, we have calculated the risk to be less than 0.01%. The incidence of JIDDM amongst diabetics in urban Southern India has remained low and static in the last decade; 0.8% and 0.84% in 1973 and 1981 respectively. This is so, despite the fact that infant and perinatal mortality rates over the past two decades have registered a sharp decline in our area. Childhood diabetes and its complications have not shown an uptrend in hospital admissions or infant mortality analysis. It is speculative that our ethnic group is lacks the genetic factor, Bf F1 (which is strongly linked with HLA B18 and IDDM) and the increased association of S1. It remains to be elucidated whether the increased susceptibility to JIDDM of Caucasian children may be associated with a genetic factor or some other exogenous factor, Such as a nutritional factor or virus infection. A plea is made to exchange groups of diabetic children and study the "behavior" of their diabetes under different environments.

Hemoglobin HbA1c: a predictor for the duration of the remission phase in juvenile insulin-dependent diabetic patients

Augmented HbA1c-concentrations in diabetics indicate retrospectively a poor metabolic control during the preceding 2-3 months. In the present study attempts have been made to use the HbA1c- concentration at the time of diagnosis as an indicator for the duration of the remission phase in 22 juvenile diabetic children. The regression analysis revealed a significant correlation between the initial HbA1c-concentrations and the duration of the remission phase defined as no glucose excretion and an insulin requirement of less than 0.5 U/kg/day (r=0.85 p:<0.001). The results suggest that the determination of the initial HbA1c-concentration may serve as a useful indicator to predict the duration of the remission phase in juvenile insulin-dependent diabetes mellitus.