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It is rare for young diabetic patients to develop severe complications in the first years of their disease. We describe three patients, aged 14-23 years who developed cataracts and severe retinopathy within one to five years of diagnosis of diabetes. During the same period, one patient developed peripheral neuropathy and a second severe autonomic neuropathy. Rapid development of chronic complications in these patients raises the possibility that there may be a subset of patients with unusual susceptibility to complications. We re-emphasize the need for vigilant monitoring for complications in young diabetic patients, even in the first few years of their disease. In particular, young patients with visual complaints should be evaluated carefully for evidence of treatable eye disease.

Objective: Fasting hyperglycemia is common in patients with insulin-dependent diabetes mellitus (IDDM) treated with twice-daily subcutaneous insulin regimens. We postulated that substituting human ultralente insulin for the presupper dose of intermediate-acting insulin would improve overnight glycemic control in children and adolescents with IDDM., Research Design and Methods: This 6-mo double-blind crossover study compared a conventional insulin regimen, a mixture of human NPH and regular given before both breakfast and supper (NPH), with a novel twice-daily regimen in which human ultralente replaced NPH before the evening meal (ultralente). This study was comprised of 20 children and adolescents (mean age and duration of IDDM 11.3 +/- 2.9 and 2.4 +/- 1.3 yr, respectively) from the Youth Clinic of the Joslin Diabetes Center, all of whom regularly performed self-monitoring of blood glucose (SMBG) and had been treated exclusively with human insulin (mean daily dose 0.75 +/- 0.22 U/kg). Subjects performed SMBG on a prescribed schedule with a glucose meter with an electronic memory, and recorded results of blood glucose measurements, insulin dosages, and episodes of hypoglycemia. Monthly measurements were obtained for height, weight, and HbA1, and mean daily insulin dosages and average blood glucose level before breakfast, lunch, supper, bedtime snack, and between 0200 and 0300 were calculated. Nonfasting serum lipids were measured at entry, crossover, and the end of the study., Results: After 3 mo, mean HbA, did not differ significantly (9.1 +/- 1.7 vs. 9.5 +/- 1.4%, NPH and ultralente, respectively). Mean fasting blood glucose was significantly lower on ultralente (9.6 +/- 1.9 vs. 10.3 +/- 2.2 mM, P less than 0.05, and blood glucose showed a similar trend (0.05 less than P less than 0.1) before lunch (8.9 +/- 1.7 vs. 9.8 +/- 2.6 mM. Mean blood glucose before bedtime snack was significantly lower (P less than 0.01) on NPH (8.4 +/- 1.9 vs. 10.0 +/- 2.1 mM) but did not differ significantly before supper or between 0200 and 0300. On the two regimens, growth and serum lipids were normal and similar, and no differences were observed in the incidence or severity of hypoglycemia., Conclusions: Compared with a mixed dose of regular and NPH, a similar dose of a mixture of regular and human ultralente insulin before supper caused a modest reduction in fasting blood glucose levels but was associated with higher blood glucose levels before the bedtime snack. Overall glycemic control, reflected in HbA1 values, was not significantly improved.

Cross-sectional and longitudinal findings drawn from a 4-year longitudinal study of an onset cohort of preadolescents and early adolescents with insulin-dependent diabetes and their families are presented. Patient and parent perceptions of the family environment near the time of diagnosis are used to examine patterns of adherence in the first year of illness as well as over the four follow-up years. We found that family conflict, cohesion, and organization were strongly associated with independently rated first-year adherence levels. The strongest predictor of longer term adherence was family conflict, as experienced by the patients. In addition, parents' and youngsters' perceptions of family cohesion predicted improved adherence as well as overall higher levels of patient adherence. The findings are discussed with respect to the clinical implications of discovering those family characteristics that can, shortly after diagnosis, predict short- and long-term adherence. In addition, we present planned investigations intended to further clarify paths from family perceptions to individual diabetes behaviors.

Effective diabetes management requires the commitment to take charge of one's life, and the strength to face the daily challenges the illness presents on a long-term basis. Outward Bound Programmes utilize challenging experiences in a wilderness setting to foster personal growth and responsibility, and to encourage the participants to reach beyond their limitations. Six Outward Bound courses were taught, to a total of 56 students with Type 1 diabetes, 14 to 42 years old. With appropriate precautions, the fairly strenuous programme was conducted safely. A battery of psychosocial measures, administered to the initial pilot group of eight students before the course, and again 7 to 11 months after returning home, indicated a statistically significant improvement in problem scores on the Achenbach Youth Self-Report Profile, and suggested modest improvements in diabetes adjustment, locus of control, and self-esteem. Other course participants report having had an exhilarating experience, which helped to increase their self-confidence and determination to take charge. A few have begun to break previous patterns of dysfunction. Many have acquired new insights into the causes of fluctuating blood sugars, and into the options at their disposal to optimize self-care.

An onset cohort of adolescents and children with insulin-dependent diabetes mellitus was studied over a 4-year period. Individual patient psychosocial and demographic factors were assessed at study inception and used to examine aspects of adherence over the follow-up. We found that initial assessment of patient coping (defense level, adaptive strength, and locus of control) and adjustment at study inception were predictive of the level of patient adherence to diabetic regimen over the 4 years of study. Psychosocial variables predicted adherence outcomes independent of patient age. This was found for three domains of adherence, i.e., diet, insulin adjustment, and metabolic monitoring, and for the composite index derived from the separate adherence scales. Preadolescents (ages 9-12) at study entry were more adherent than patients who were already adolescent (ages 13-16) when diagnosed. Using multiple regression, three factors (age, adjustment, ego defense level) accounted for 47% of the variance in adherence. No factors were predictive of change in adherence during the follow-up. Thus, psychosocial characteristics of diabetic children assessed shortly after diagnosis predicted typical or average adherence over a 4-year period. Identification of such characteristics may be useful in developing strategies for intervention early in the course of illness.

Currently, there are three markers that are being studied with the potential to give a high positive predictive value for the development of type I diabetes (insulin-dependent diabetes caused by autoimmune beta-cell destruction) and that can be utilized to predict the disease in susceptible relatives: 1) high-titer cytoplasmic islet cell antibodies, 2) insulin autoantibodies detected with fluid-phase radiobinding assays, and 3) first-phase insulin release after intravenous glucose less than 1st percentile. With the combination of these assays, it seems to be possible to identify first-degree relatives with a high probability of developing type I diabetes within a limited time span (i.e., less than 10 yr). The ability to predict type I diabetes with selected assays will allow trials for prevention of diabetes and trials to assess whether prediction will decrease morbidity and mortality at onset of diabetes.

Transient hyperglycemia may represent the earliest manifestation of IDDM. In a series of 30 children referred for transient hyperglycemia, 8/30 (27%) developed IDDM within 10 months of their initial evaluation. Three children with detectable cytoplasmic islet cell antibodies (ICA) and/or positive insulin autoantibodies (CIAA) all developed IDDM, compared to 21% of ICA negative children and 13% who were CIAA negative. Of those with impaired glucose tolerance, 6/11 (55%) developed IDDM, as did 1/14 with normal OGTT. Of the children with a low "K rate" on IVGTT, 75% developed IDDM, compared to 1/13 with a normal "K rate". All four children (100%) whose first phase (1' + 3') insulin secretion never exceeded the first percentile developed IDDM within nine months, while no child with first phase insulin secretion above the first percentile (0/16) developed IDDM during 19 +/- 9 months (mean +/- SD) of follow-up. Thus, in our experience the oral glucose tolerance test is a less accurate predictor of impending IDDM; immunological abnormalities have the highest positive predictive value, while the first phase insulin secretion during an intravenous glucose tolerance test has the highest negative predictive value and the greatest overall accuracy of prediction.

A group of 57 children with recent onset of insulin-dependent diabetes mellitus was studied over 18 months. Compliance with the prescribed diabetic treatment deteriorated over this period. Adolescents (aged 13 to 15 years) were less compliant than preadolescents (aged 9 to 12 years). Initial patient reports of self-esteem, perceived competence, social functioning, behavioral symptoms, and their adjustment to diabetes predicted subsequent compliance behaviors. The findings highlight the linkage of child personality and adjustment with self-care of diabetes, and suggest that psychosocial assessment soon after diabetes is diagnosed may help identify patients at risk for later compliance problems.

Cross-sectional findings drawn from the first year of a 4-year longitudinal study of preadolescent and early adolescent insulin-dependent diabetics and their families are presented. Using direct observation techniques and a specially designed coding system, the family interactions of 56 families with a recently diagnosed diabetic child are compared with those of 49 families with a child of similar age and sex, who has had a recent, serious acute illness. The two samples are contrasted in terms of each family member's (mother, father, and child) enabling and constraining interactions, controlling for social class differences. The findings reveal that the diabetic children and their parents expressed significantly more enabling (e.g., focusing, problem solving, active understanding) speeches than comparable members of the acute illness group. In addition, there are indications of particular constraining interactions (devaluing) occurring between fathers and diabetic children. Several alternative interpretations are offered to account for these results, together with plans for future research directions to investigate these hypothesized explanations.

Insulin-producing beta-cells were selectively absent from the islets of Langerhans in postmortem specimens from two patients with Wolfram's syndrome. In families with multiple cases of this syndrome, we found a very high concordance rate (r = .910, P less than .001) among siblings for age at onset of diabetes mellitus. Taken together with the lack of markers for an autoimmune process, these findings suggest that diabetes mellitus in this syndrome results from genetically programmed selective beta-cell death.