Diagnosis Of Insulin-dependent Diabetes Mellitus Research Articles

Immunoreactive Trypsin(ogen) in the Sera of Children with Recent-Onset Insulin-Dependent Diabetes and Matched Controls

To evaluate the exocrine pancreatic function at the time of diagnosis of insulin-dependent diabetes mellitus, we determined immunoreactive anodal and cathodal trypsin(ogen) levels in sera from almost all children (n = 375) 0-14 years of age in Sweden in whom diabetes developed during 1 year, and in sex-, age-, and geographically matched control subjects (n = 312). The median level of anodal trypsin(ogen) was 5 (quartile range, 3-7) micrograms/L in children with newly diagnosed diabetes, compared with a median level of 7 (quartile range, 4-8) micrograms/L in control subjects (p less than 0.0001). Similarly, the median level of cathodal trypsin(ogen) was 8 (quartile range, 4-10) micrograms/L in children with diabetes, compared with a median level of 11 (quartile range, 7-15) micrograms/L in control subjects (p less than 0.0001). The median of the individual ratios between cathodal and anodal trypsin(ogen) was 1.4 in the diabetic patients and 1.7 in the control children (p less than 0.001). In a multivariate test, however, only the decrease in cathodal trypsin(ogen) concentration was associated with diabetes. The levels of trypsin(ogen)s did not correlate with levels of islet cell antibodies, present in 81% of the diabetic children. Several mechanisms may explain our findings, for example, similar pathogenetic factors may affect both the endocrine and exocrine pancreas simultaneously, a failing local trophic stimulation by insulin on the exocrine cells may decrease the trypsinogen production, and there may be an increased elimination of trypsin(ogen) because of higher filtration through the kidneys in the hyperglycemic state.

Incidence of insulin dependent diabetes in England: a study in the Oxford region, 1985-6.

To determine the incidence of insulin dependent diabetes mellitus up to the age of 21 in a geographically defined population in England with independent validation of completeness of case ascertainment. Prospective registration of newly diagnosed cases supplemented by centralised hospital discharge records and death certificates. Validation of ascertainment from general practitioners. Oxford Regional Health Authority area (population 2.4 million). All patients with insulin dependent diabetes diagnosed below age 21 during 1985-6 and resident in the region at the time of diagnosis. None. Validation of a method of case ascertainment for assessing temporal variation in incidence of insulin dependent diabetes. The overall yearly incidence of newly diagnosed insulin dependent diabetes mellitus in people under 21 was 15.6 cases/100,000 (95% confidence interval 13.6 to 17.6). Among males the incidence was 16.8 cases (14.0 to 19.7)/100,000 and among females 14.3 cases (11.6 to 17.1)/100,000. The highest incidence, in the 10-14 year age group, was 26.4 (20.9 to 31.8) new cases/100,000 population yearly. Case ascertainment was greater than 95%. The incidence of insulin dependent diabetes in England is considerably higher than reported from large scale studies. It is consistent with described patterns of geographical variation. The figures provide a baseline for assessing temporal change.

Genetic epidemiology of persistent islet cell antibodies among IDDM patients.

The persistence of cytoplasmic islet cell antibodies (ICA) more than a year after diagnosis of insulin-dependent diabetes mellitus (IDDM) was investigated in 43 families with at least two children with IDDM. The prevalence of persistent ICA among IDDM patients was 16%. Persistence of ICA appeared to be familial in that siblings with IDDM were significantly more concordant for the presence or for the absence of ICA than expected by chance (P = 0.04). Patients with persistent ICA were older on average at onset of IDDM than patients without persistent ICA after adjusting for duration of disease (P = 0.004). Persistence of ICA was not significantly associated with HLA DR type, immunoglobulin genotype, insulin allele class, sex, history of viral diseases, or prior vaccinations.

Relationship of islet cell and islet cell surface antibodies to the presentation and early course of IDDM in childhood

Islet cell (ICA) and islet cell surface (ICSA) antibodies were measured in 30 children (aged 6-17.7 years) with newly diagnosed insulin-dependent diabetes mellitus (IDDM) to determine the relationship of antibody positivity/negativity to a variety of factors both at presentation (e.g., age, severity of onset, residual insulin secretion, insulin autoantibodies) and during the first year thereafter (HbA1c, insulin antibody binding, residual insulin secretion). At diagnosis, 10 of 30 were ICA (+) and 13 ICSA (+): no differences were found between ICA (+) and (-) subjects at onset; however ICSA (+) children had a lower bicarbonate concentration than those (-) for ICSA (P less than 0.01). During the first year after diagnosis the only significant finding was that in ICA (+) patients insulin dose (units/kg) was lower at both 6 and 12 months (mean +/- SD 0.55 +/- 0.14 and 0.67 +/- 0.12 U/kg, respectively) than ICA (-)'s (0.70 +/- 0.22 and 0.96 +/- 0.38, respectively, both P less than 0.05). Those children positive for both ICA and ICSA did not differ in any way at onset or during the subsequent 12 months from those negative for both antibodies. These results suggest that, except for minor differences, the presentation and course during the first year after diagnosis of IDDM do not differ in those children positive or negative for either or both ICA and ICSA.

Insulin-dependent diabetes mellitus

‘I@z 1 or insulin-dependent diabetes mellitus (IDDM) can serve as an exercise in the definitions of disease and therapy. The clinical symptoms and signs of IDDM result from a need for exogenous insulin, but that need is the late outcome of a subclinical autoimmune process that one may view as the disease itself Hence, the insulin that saves the patient’s life is not therapy for the disease, but a partial replacement for the ravages left in the wake of the disease. The classical diagnosis of IDDM is an endstage revelation; it is usually made when the disease @ cell destruction) is over and the disease (need for insulin) begins. Definitive therapy should achieve specific and permanent abrogation of the autoimmune destruction of the p cells before disease occurs, when the inv (2) pathogenic mechanisms (what kills the p cells?); (3) minimal but reliable signs of B cell autoimmunity (when has the disease begun?), and (4) specific therapy (how can the killing of p cells be stopped?). These tissues are not trivial; the incidence of IDDM is rising and it is predicted that the cumulative incidence of IDDM will be 1% of the people alive today who reach the age of 70 111.

Seasonality in glycosylated hemoglobin in normal subjects. Does seasonal incidence in insulin-dependent diabetes suggest specific etiology?

Seasonality in the diagnosis of insulin-dependent diabetes mellitus (IDDM), i.e., increased incidence in winter, was the impetus for this study of seasonality in glycosylated hemoglobin levels in nondiabetics. Glycosylated hemoglobin levels of 35 nondiabetic children and adults were highest at the ends of autumn and winter and lowest at the ends of spring and summer (P less than 10(-4)). This result is consistent with reports of seasonal variation in blood glucose, with the highest levels occurring in winter, as well as reports that suggest an internal milieu of increased counterinsulin action in winter due to seasonality in counterinsulin hormones, dietary factors, body weight, amount of exercise, growth rates in children, and ambient temperature. IDDM is caused by the gradual destruction of the pancreatic insulin-producing cells via lymphocytic infiltration--a process that may occur over years. We conclude that a decreased carbohydrate tolerance associated with winter can explain the seasonal variation in the incidence of IDDM and that this seasonality is caused by the precipitation of overt carbohydrate intolerance in individuals with already seriously compromised insulin secretory capacity. This implies that seasonality is not very formative about the cause of the destruction of pancreatic insulin-producing cells.

Initial psychosocial impact of insulin-dependent diabetes mellitus on the pediatric client and family.

The initial psychosocial impact of the diagnosis of insulin-dependent diabetes mellitus is evidenced by grief responses and crisis reactions. An overview of classic theories on grief and crisis intervention, as well as literature specific to diabetes, provides a basis for the development of appropriate nursing interventions for the pediatric diabetic client and family. The nurse, as a part of the health care team, can assess the psychosocial impact of the disease, and assist the family in the ongoing adaptation to life with diabetes. Emotional support, assistance with coping strategies and resources, patient education, tailoring of the treatment regimen, maintenance of hope, and close follow-up are essential nursing actions.

Children's Self-Reports of Psychologic Adjustment and Coping Strategies During First Year of Insulin-Dependent Diabetes Mellitus

Psychologic adjustment, assessed by self-ratings of anxiety, self-esteem, and depression, and cognitive as well as behavioral coping strategies, elicited by interview, were monitored longitudinally among school-age children with recent-onset insulin-dependent diabetes mellitus (IDDM). Our article documents the findings over the 1st yr of illness. From the start, the children viewed themselves as self-confident and emotionally comfortable. The diagnosis of IDDM created minimal emotional upheaval (which faded within 6 mo), despite this cohort's consistent report that the diet, insulin injections, and urine tests were difficult. The most prevalent cognitive strategies for coping with IDDM included wishful thinking, thoughts of forbidden foods, and resentful thoughts. Behavioral coping strategies, including information seeking, were evident from the beginning. The frequency of socially oriented coping behaviors (e.g., showing IDDM management to peers) indicated that the young patients actively tried to adapt to the illness and were more comfortable with aspects of home care than previously thought. Self-rated psychologic adjustment, psychiatric diagnosis, and illness-related coping behaviors were unrelated to one another; psychologic variables were similarly unrelated to the use of socially oriented coping strategies. Therefore, in juvenile cohorts, the presumed association between psychologic status and coping behaviors requires further examination.

Initial psychologic responses of parents to the diagnosis of insulin-dependent diabetes mellitus in their children.

As part of a prospective, longitudinal study of school-aged children with newly diagnosed insulin-dependent diabetes mellitus (IDDM), we examined how the parents adjusted to the illness. The present article documents this process for the first year of IDDM. We found no support for earlier claims that most parents resort to blatantly neurotic or psychopathologic behavior to cope. Instead, the initial strain of living with IDDM generally elicited mild and subclinical depression, anxiety, and overall distress. Mothers were more affected than fathers: they were more symptomatic (about one of four developed a mild grief reaction) and the bulk of them worried considerably about their children. However, the parents' initial emotional upheaval resolved in approximately equal to 6 mo; most mothers came to terms with IDDM by the end of the first year; and other areas of parental functioning (e.g., quality of their marriage) were not affected. Therefore, along with our previous report on how the children coped initially, the findings document the emotional resiliency of families during the first year of IDDM.

Plasma C-Peptide in Children and Adolescents with Newly Diagnosed Insulin Dependent Diabetes Mellitus

Article Plasma C-Peptide in Children and Adolescents with Newly Diagnosed Insulin Dependent Diabetes Mellitus was published on April 1, 1985 in the journal Journal of Pediatric Endocrinology and Metabolism (volume 1, issue 2-3).

Student mental health from a layman's perspective.

Abstract “Differences in Risk of Insulin-Dependent Diabetes in Offspring of Diabetic Mothers and Diabetic Fathers,” James H. Warren, et al. To examine the role of heritable factors in insulin-dependent diabetes mellitus (IDDM), we studied the incidence of IDDM-in the offspring of patients with the disease who were identified by the medical records of the Joslin Diabetes Center from 1928 to 1939. We found 187 survivors who, after the diagnosis of IDDM, had produced 419 offspring for whom information about diabetes status was available. By the age of 20, 6.1 per cent of the offspring of the 88 men had diabetes; in contrast, only 1.3 per cent of the offspring of the 99 women had the disease by the age of 20 (P < 0.05). Daughters and sons of the men with IDDM were affected equally (there were insufficient numbers of affected offspring of diabetic women to permit determination of whether the sexes were equally affected). We conclude that IDDM is transmitted less frequently to the offspring of diabetic women th...

Thyroid hormone abnormalities at diagnosis of insulin-dependent diabetes mellitus in children

Comprehensive evaluation of thyroid hormone indices was performed in 58 children with insulin-dependent diabetes mellitus (IDDM) at the time of diagnosis and prior to insulin therapy. Two patients were found to have primary hypothyroidism, with markedly elevated TSH and very low T4, free T4, T3, and reverse T3 concentrations. The remaining 56 patients had the transient alterations in thyroid hormone indices that are characteristic of "euthyroid sick" or "low T3" syndrome. Mean TSH and reverse T3 values were significantly higher and the mean T3, T4, and free T4 levels were significantly lower than those observed in the control population. Ten of the diabetic patients had elevated TSH concentrations and normal or low free T4 values; eight had normal TSH levels and low T4 and free T4 values. The remainder of the group had thyroid indices compatible with abnormal peripheral metabolism of thyroid hormones. Elevated titers of antimicrosomal antibodies were found in 16% of the children with IDDM. We conclude that abnormal peripheral metabolism and altered hypothalamic-pituitary function are responsible for the transient changes in thyroid hormone indices in patients with untreated IDDM. The most reliable indicators of concomitant primary hypothyroidism in untreated IDDM are markedly elevated TSH and low reverse T3 values.

Differences in risk of insulin-dependent diabetes in offspring of diabetic mothers and diabetic fathers.

To examine the role of heritable factors in insulin-dependent diabetes mellitus (IDDM), we studied the incidence of IDDM in the offspring of patients with the disease who were identified by the medical records of the Joslin Diabetes Center from 1928 to 1939. We found 187 survivors who, after the diagnosis of IDDM, had produced 419 offspring for whom information about diabetes status was available. By the age of 20, 6.1 per cent of the offspring of the 88 men had diabetes; in contrast, only 1.3 per cent of the offspring of the 99 women had the disease by the age of 20 (P less than 0.05). Daughters and sons of the men with IDDM were affected equally (there were insufficient numbers of affected offspring of diabetic women to permit determination of whether the sexes were equally affected). We conclude that IDDM is transmitted less frequently to the offspring of diabetic women than to those of diabetic men. More study is required to determine whether this difference reflects a genetic mechanism or, instead, selective perinatal loss of the affected offspring of diabetic mothers.

Some thoughts on early detection and intervention in diabetes mellitus

DESPITE the fact that a casual plasma glucose ~200 mg/dl or a fasting plasma glucose > 140 mg/dl on more than one occasion; or a casual blood sugar < 140 mg/dl or fasting values < 100 mg/dl respectively either establishes or reputedly excludes a diagnosis of diabetes [l]; and that both impaired glucose tolerance (IGT) and diabetes appear to meet as many of the criteria for mass screening as hypertension [2], there has been no return to the enthusiasms of the late sixties and early seventies for campaigns of detection and early intervention in the general population. The reasons are not hard to seek. Historically diabetologists were foremost in protesting the long queues of volunteer participants referred from screening surveys to their outpatient clinics as dipstick positive for sugar in the urine or in the blood, and largely negative at follow-up. Predictive values of 28 and sometimes as low as 14% did much to discredit screening in those early days. Then paradoxically, although it was agreed that coronary heart disease in Western cultures was three times as prevalent in diabetic males and six times as prevalent in diabetic females than in corresponding non-diabetics [3], the view in Great Britain was that about 1 or 2% of the general population was diabetic, treatment did not radically alter the outcome, so why deviate resources to case detection? Subsequent experience seems to have borne out the wisdom of this view. As far as coronary heart disease is concerned, an extensive review of the results of 14 longitudinal studies in nine countries, of the relationship of asymptomatic hyperglycemia to coronary heart disease, did not reveal an association that was consistent, strong and graded [4]. It was concluded that asymptomatic hyperglycemia could not be designated an established risk factor for coronary heart disease and the major adult cardiovascular diseases. Thus there seems to be a consensus that with the exception of pregnancy, evidence is lacking that early detection and intervention are beneficial to the majority of undiagnosed diabetics in preventing either complications or mortality [5]. But old enthusiasms die hard. Perhaps in the light of insufficient evidence, especially in the absence of positive contradictory findings, we should give the old Scottish legal verdict of “not proven”; and our College should move towards renewing interest and endorsing support for further studies of early asymptomatic diabetes and IGT in the general population. The point has been made that both non-insulin dependent diabetes mellitus (NIDDM) and, more recently, most insulin dependent diabetes mellitus (IDDM) patients, pass through a phase of varying but often of substantial duration, in which IGT is present. Even if not all IGT patients proceed to diabetes, this is a familiar epidemiological situation which would seem to have excellent experimental potential for prevention. IDDM may have more appeal for the clinician than the epidemiologist but the presence of islet cell (cytoplastic) antibodies at diagnosis of IDDM [6] has potential for even earlier diagnoses. The presence of IGT in some children for periods extending up to three years,

Insulin-Dependent Diabetes in Colorado

To the Editor.— The efforts to establish accurate population-based data on type I diabetes are critically needed. The report on the first known effort in this country to obtain statewide epidemiologic data on earlyonset diabetes in North Dakota (1983; 249:329) was, therefore, of great interest. Similar efforts to collect statewide epidemiologic data on insulindependent diabetes mellitus (IDDM) have been ongoing in Colorado for approximately one year and in Rhode Island for approximately four years. Both research efforts are located in the state departments of health, in diabetes control programs that are funded by the Centers for Disease Control (CDC). In December 1981, the Colorado Diabetes Control Program received supplemental funding from the CDC to examine patterns of medical care and education that take place at initial diagnosis of IDDM for persons whose conditions were diagnosed after Jan 1, 1978, and who were younger than 18 years at the time of diagnosis.

Plasma testosterone and androstenedione in insulin dependent patients at time of diagnosis and during the first year of insulin treatment

Ten male patients and 6 female patients with newly diagnosed insulin dependent diabetes mellitus and significant ketosis were studied before and during the first year of insulin treatment. At onset plasma concentrations of testosterone and androstenedione were significantly (P less than 0.02) decreased in female patients when compared to healthy sex- and age-matched controls. Plasma concentrations of testosterone and androstenedione increased significantly (P less than 0.001 and P less than 0.05) in both sexes during insulin therapy. Plasma concentrations of testosterone were not significantly different from controls in both sexes after 4 days of insulin treatment and remained so during the first year of insulin treatment. Plasma concentrations of androstendeione were not significantly different from controls in both sexes after 4 days of insulin treatment, but increased to levels significantly raised in both males (P less than 0.001) and females (P less than 0.05) after 7 days and during the first year of insulin treatment.

Long-term Insulin Treatment in Two Nondiabetic Patients

TODAY the diagnosis of insulindependent diabetes mellitus seldom presents problems. However, in two patients recently seen by us, renal glucosuria had been wrongly diagnosed as diabetes mellitus 33 and 51 years earlier. Throughout this period, treatment with long-acting insulin of an unpurified type had been administered, and this therapy was withdrawn. It was considered of interest to investigate the B-cell function in nondiabetic subjects after such a long period of insulin therapy. Since it has been suggested that the presence of insulin antibodies may be a factor in the development of diabetic microangiopathy, 1 we also searched for evidence of this condition. Report of Cases Case 1.— In 1946, a 23-year-old man was found to have glucosuria, 1.5% to 4.0%; there was no ketonuria. Despite the absence of classic symptoms of diabetes mellitus and the recording of one normal glucose value, treatment was given, consisting of diet and administration of