Race affects insulin and GLP-1 secretion and response to a long-acting somatostatin analogue in obese adults.

OBJECTIVE: This study investigated (1) the effect of octreotide-LAR (Sandostatin-LAR Depot; Novartis) on the enteroinsular axis in a biracial cohort of severely obese adults, (2) whether octreotide suppression of insulin secretion occurs by both a direct beta-cell effect and through mediating a glucagon-like peptide 1 (GLP-1) response, and (3) whether differences in GLP-1 concentrations could explain racial differences in insulin concentrations. DESIGN: Prospective, open-label trial using a pre-post test design. SETTING: Single university, clinical research center. SUBJECTS: In all, 42 healthy, severely obese Caucasian and African-American (AA) adults (93% female, 64% Caucasian, age=37.8+/-1.2 y, weight=123+/-4.2 kg, BMI=44.5+/-1 kg/m(2)), recruited through physician referral and newspaper ads, participated in the study. INTERVENTIONS: Indices of beta-cell activity, insulin and GLP-1 response before and during a 75-gm oral glucose tolerance test were determined before and after 24 weeks of octreotide-LAR. RESULTS: AA exhibited higher beta-cell activity, and insulin and GLP-1 concentrations than Caucasians. Octreotide-LAR suppressed the insulin and GLP-1 levels in both groups.

Racial differences in glucagon-like peptide-1 (GLP-1) concentrations and insulin dynamics during oral glucose tolerance test in obese subjects.

Obese African-American (AA) subjects have higher resting and stimulated insulin concentrations than obese Caucasians (C), which could not be explained by the severity of obesity or the degree of insulin sensitivity. We investigated whether differences in glucagon-like peptide-1 (GLP-1), the most potent incretin that regulates insulin secretion, might explain racial differences in insulin response. Accordingly, we measured fasting and stimulated glucose, insulin, and GLP-1 levels during a 3-h oral glucose tolerance test (OGTT) in 26 obese C (age 38+/-2 y, body mass index 44+/-1 kg/m(2)) and 16 obese AA (age 36+/-2 y, BMI 46+/-2 kg/m(2)) subjects. Corrected insulin response (CIR(30)), a measure of beta-cell activity, whole body insulin sensitivity index (WBISI), and area under the curve (AUC) for insulin, GLP-1, and C-peptide/insulin ratio were computed from the OGTT. Glucose levels, fasting and during the OGTT, were similar between racial groups; 32% of the C and 31% of the AA subjects had impaired glucose tolerance. With a similar WBISI, AAs had significantly higher CIR(30) (2.3+/-0.4 vs 1.01+/-0.1), insulin response (IAUC: 23 974+/-4828 vs 14 478+/-1463), and lower insulin clearance (0.07+/-0.01 vs 0.11+/-0.01) than C (all, P<0.01). Obese AAs also had higher fasting GLP-1 (6.7+/-2.5 vs 4.5+/-1.1) and GLP-1AUC (1174.7+/-412 vs 822.4+/-191) than C (both, P<0.02). Our results indicate that obese AAs had higher concentrations of GLP-1 both at fasting and during the OGTT than obese C. The increased GLP-1 concentration could explain the greater insulin concentration and the increased prevalence of hyperinsulinemia-associated disorders including obesity and type 2 diabetes in AAs.

Lactic acidosis: a metabolic complication of hematologic malignancies: case report and review of the literature.

BACKGROUND: Lactic acidosis (LA) associated with hematologic malignancies is rare, ominous, and generally occurs in adults. Its pathogenesis is poorly understood. METHODS: The authors present one case of childhood lymphoma and two cases of childhood leukemia associated with LA, and they review the available literature. Plasma concentrations of insulin-like growth factors (IGFs), IGF binding proteins (IGFBPs), and tumor necrosis factor (TNF)-alpha were retrospectively measured to elucidate the pathogenesis of LA. RESULTS: Lactic acidosis has been reported to date in 28 cases of lymphoma and 25 cases of leukemia, including the authors' cases. Ongoing rapid cellular proliferation was indicated in all leukemia cases. The liver was involved in 43 of the 53 cases, and hypoglycemia was present in 20. The acidosis improved only if the disease responded to chemotherapy. Remission was achieved in only five of the reported cases. In the authors' three cases, LA was associated with altered concentrations of IGFs, IGFBPs, and TNF-alpha, although causality was not established. CONCLUSIONS: Lactic acidosis in association with hematologic malignancies carries an extremely poor prognosis. Because cancer cells have a high rate of glycolysis and produce a large quantity of lactate, this condition may result from an imbalance between lactate production and hepatic lactate utilization. The authors speculate that the IGF system is involved in the pathophysiology of LA in these patients. Only chemotherapy so far has been effective in correcting the acute acidosis in a few patients; however, it has not necessarily improved ultimate outcome.

Laparoscopic pancreatectomy for persistent hyperinsulinemic hypoglycemia of infancy.

BACKGROUND: A 4-week-old male infant (4.9 kg) with persistent hyperinsulinemic hypoglycemia of infancy (PHHI) underwent a laparoscopic pancreatectomy to evaluate its feasibility. Preoperative medications included diazoxide and glucagon to maintain adequate blood glucose levels. METHODS: Laparoscopic pancreatectomy was performed using a 5-mm cannula at the umbilicus, external fixation, transcutaneous suture-assisted gastric retraction to expose the lesser sac, and three additional 3.5-mm cannula sites. The pancreas was resected from the splenic hilum to the mesenteric vessels. The splenic vein was dissected from the under surface of the pancreas using electrocautery, and the spleen was easily preserved. Surgery time was 75 min, and minimal blood loss occurred. RESULTS: The child required no narcotic medication and tolerated a regular diet immediately after surgery. Serum glucose levels did decrease postoperatively, and the child required diazoxide, dextrose infusion, glucagon, and octreotide. On postoperative day 7, the child underwent an open near-total pancreatectomy, after which he remained asymptomatic. Essentially no scarring was found in the lesser sac, and the remaining pancreatic remnant was resected without difficulty. CONCLUSIONS: Laparoscopic pancreatectomy can be performed safely, even in a newborn patient, without prolonged operative time or unnecessary risk. The technique using external fixation and transcutaneous suture-assisted gastric retraction provides excellent exposure to the pancreas and lesser sac. In patients with PHHI, in whom reoperative additional pancreatectomy is very likely, this technique is the ideal initial surgical approach.

Heart rate variability in adolescents and adults with type 1 diabetes.

BACKGROUND: Limited data are available regarding the onset or trajectory of cardiovascular autonomic deterioration in persons with type 1 diabetes. OBJECTIVE: To describe differences in heart rate variability among adolescents with type 1 diabetes, adults with type 1 diabetes who have coexisting renal failure, and adolescent and adult controls. RESEARCH DESIGN AND METHODS: A correlational design was used to compare the status of heart rate variability in adults with type 1 diabetes and renal failure (n = 62); healthy adult controls (n = 67); adolescents with type 1 diabetes (n = 55); and healthy adolescent controls (n = 28). Convenience samples of adult patients with diabetes awaiting kidney or pancreas and kidney transplantation, and adolescents with diabetes were recruited from local university-based clinics. Volunteers served as healthy controls. The short-term R-R variability measures included in this study were changes in heart rate with deep breathing and with the Valsalva maneuver. Twenty-four hour ambulatory heart rate monitoring with power spectral analysis was also obtained to assess longterm R-R variability. RESULTS: Adult patients with type 1 diabetes awaiting transplantation had significantly poorer heart rate variability measures than any of the other three populations studied (p < .0001). Adult control values also were significantly lower than either teenage controls or youths with diabetes (p < .05). Although most long-term R-R variability measures were lower in adolescents with diabetes versus controls, only one measure of parasympathetic modulation (i.e., pNN50) was significantly lower (p = .042). There were significant negative associations between HbA1c and sympathetic modulation (i.e., low hertz) in both the adult group (r= -.406, p = .029) and the adolescent group (r= -.324, p = .025) with diabetes. CONCLUSIONS: Type 1 diabetes is associated with decreased heart rate variability, with the extent of the decrease related to the age of the individual and the severity of the disease.

Neonatal progeroid (Wiedemann-Rautenstrauch) syndrome: report of five new cases and review.

The neonatal progeroid syndrome (NPS), or Wiedemann-Rautenstrauch, is a rare autosomal recessive disorder comprised of generalized lipoatrophy except for fat pads in the suprabuttock areas, hypotrichosis of the scalp hair, eyebrows, and eyelashes, relative macrocephaly, triangular face, natal teeth, and micrognathia. We report on 5 new patients who demonstrate phenotypic variability and who represent the single largest series of NPS reported to date. Two of the patients are from an African-American kindred, an ethnic occurrence not reported previously. The fact that there are 2 pairs of sibs among the 5 patients further supports that NPS is an autosomal recessive condition. This report also includes a review of the previously reported 16 patients and compares them with the 5 new patients. Abnormalities in endocrine and lipid metabolism were found in 3 of 5 patients. Skeletal findings in 2 of our patients demonstrated some new findings as well as the typical radiological abnormalities previously noted in NPS. It is apparent, based on the 21 cases, that mild to moderate mental retardation is common in NPS. Long term follow-up of patients with NPS should provide more information relative to their ultimate psychomotor development. NPS is usually lethal by 7 months; however, on rare occasions, patients have survived into the teens. Our 3 surviving patients range in age from 16-23 months. Variability in the phenotype of NPS is clear; however, the phenotype remains distinct enough to allow a secure diagnosis.

Diagnosis of hidden central hypothyroidism in survivors of childhood cancer.

To determine how often central hypothyroidism remains undetected by routine out-patient tests of thyroid hormone, we studied 208 pediatric cancer survivors referred for evaluation because of signs of subtle hypothyroidism or hypopituitarism. Of the 208 (68 females and 140 males), 110 had brain tumors, 14 had other head/neck tumors, 11 had solid tumors remote from head and neck, and 73 had leukemia. Patients were evaluated 1-16 yr (mean, 6.1+/-4.1 yr) after tumor diagnosis. The nocturnal TSH surge and response to TRH were measured. Of 160 patients with free T4 in lowest third of normal, 34% had central hypothyroidism (blunted TSH surge or low/delayed TSH peak or delayed TSH decline after TRH); 9% had central hypothyroidism with mild TSH elevation (mixed hypothyroidism). Another 16% had mild primary hypothyroidism (TSH, 5-15 mU/L). Of 48 with free T4 in the upper two thirds of normal, 14% had central hypothyroidism; 17% had mild primary hypothyroidism. Incidence of central, mixed, and mild primary hypothyroidism 10 yr after tumor diagnosis was significantly related to total cranial radiation dose (P < 0.0001). Of 62 patients with central hypothyroidism, 34% had not developed GH deficiency. TSH surge identified 71%, and response to TRH identified 60% of those with central hypothyroidism. More than half of the slowly growing patients who have received cranial or craniospinal radiation for childhood cancer develop subtle hypothyroidism. In our study group, 92% of patients with central hypothyroidism and 27% with mixed hypothyroidism would have remained undiagnosed using baseline thyroid function tests alone. Both TSH surge and response to TRH must be evaluated to identify all of these patients.

Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist.

OBJECTIVE: Hypothalamic obesity is a rare sequela of cranial insult, for which pathogenesis and treatment remain obscure. In rodents ventromedial hypothalamic damage causes hyperphagia, obesity, hyperinsulinism, and insulin resistance. Reduction of insulin secretion in humans may attenuate weight gain. METHODS: Eight children with intractable obesity after therapy for leukemia or brain tumors underwent oral glucose tolerance testing (OGTT) with simultaneous insulin levels before and after treatment with octreotide for 6 months. RESULTS: In comparison with a 6-month pre-study observation period, patients exhibited weight loss (+6.0 +/- 0.7 kg vs -4.8 +/- 1.8 kg; P =.04) and decrease in body mass index (+2.1 +/- 0.3 kg/m(2) vs -2.0 +/- 0.7 kg/m(2); P =.0001). Recall calorie count decreased during the 6 months of treatment (P =. 015). OGTT demonstrated biochemical glucose intolerance in 5 of 8 patients initially and in 2 of 7 at study end, whereas insulin response was decreased (281 +/- 47 microU/mL vs 114 +/- 35 microU/mL; P =.04). Percent weight change correlated with changes in insulin response (r = 0.72, P =.012) and changes in plasma leptin r = 0.76, P =.0004). CONCLUSIONS: Patients with hypothalamic obesity demonstrate excessive insulin secretion. Octreotide administration promoted weight loss, which correlated with reduction in insulin secretion on OGTT and with reduction in leptin levels. Pre-study biochemical glucose tolerance improved in several patients while they were receiving octreotide. These results suggest that normalization of insulin secretion may be an effective therapeutic strategy in this syndrome.

Caloric restriction for 24 hours increases mean night growth hormone.

UNLABELLED: In obesity, serum growth hormone (GH) is usually low, confounding GH assessment of short obese children. We evaluated whether 24-h caloric restriction would permit better discrimination between normal GH secretion and GH deficiency (GHD) by elevating night GH levels. DESIGN AND PATIENTS: Serum was obtained every 20 minutes 2000-0800 h before and 2200-0400 h after 24 hours of caloric restriction (8% of usual calories) in 24 normal height children [14 normal (weight for height 10-90th percentile); 10 obese (weight for height > 95th percentile)] and in 31 short children (height shorter than -2.0 SD below mean for age). All samples from both nights per child were assayed for GH simultaneously to eliminate interassay variability. RESULTS: Mean GH increased significantly in all groups after caloric restriction (P < 0.01). Obese children had lower baseline mean GH and GH amplitude compared to normal (P < 0.01); GH increased into normal range after restriction. Basal GH studies in short children were not significantly below normal. Surprisingly, some with low stimulated GH increased their night GH into the normal range after caloric restriction. CONCLUSIONS: Caloric restriction for 24 h enhances night GH similarly in short and in normal children, and thus does not increase the diagnostic utility of night GH studies in non-obese short children. Caloric restriction reverses suppressed GH secretory state of obese children, perhaps by decreasing diet-dependent somatostatin inhibition of GH secretion.

Diagnosis of ACTH deficiency. Comparison of overnight metyrapone test to either low-dose or high-dose ACTH test.

Test sensitivity and accuracy of 250 microg/m(2) ACTH test, 1 microg/m(2) ACTH test, and overnight metyrapone test were evaluated in 158 children at risk for ACTH deficiency. Of 38 given high-dose ACTH, 20 had normal responses to metyrapone and to high-dose ACTH. 14 had low response to metyrapone; of these only 2 had low cortisol response (<550 nmol/l) to high-dose ACTH. Of 120 given low-dose ACTH, 64 had normal responses to metyrapone and to low-dose ACTH. All 24 with low metyrapone response had low or borderline response to low-dose ACTH. The remaining children had an inconclusive metyrapone response. In conclusion, high-dose ACTH misses most diagnoses of ACTH deficiency (21% sensitivity, 100% specificity, 63% accuracy). In contrast, the low dose ACTH test accurately diagnoses 90% of patients with ACTH deficiency (100% sensitivity, 68% specificity). The low-dose ACTH test can serve as an accurate and practical screening test for adequacy of ACTH reserve.

Genetic and immunological markers of insulin dependent diabetes in Black Americans.

ICA and GAD65 autoantibody profiles and HLA-DR and DQ analysis were performed on 43 Black juvenile onset IDDM patients and 34 unrelated Black controls from Tennessee, USA. 75% of patients were positive for GAD65 autoantibodies but only 53% had ICA; 39% both ICA and GAD65 antibodies. The strongest HLA association was with the DR3 haplotype DRB1*03 DQA1*0501 DQB1*0201 (63% of patients v 12% of controls RR = 13.0, p < 0.00002). DRB1*04 DQA1*0301 DQB1*0302, associated with IDDM in Caucasians but rare in Negroids, occurred in 27% of patients and 6% of controls (RR = 5.9, p < 0.04). All patients carried DQB1*0302 or DQB1*0201. DQB1*0602 was significantly reduced in patients (2.4% v 41%, RR = 0.036, p < 0.008) and DRB1*1501 was absent in patients (0% v 35%). The frequency of GAD65 autoantibodies in Black American IDDM patients is comparable to that in Caucasians; however ICA positivity is reduced. GAD65 antibodies may therefore be a more sensitive serological test to identify individuals in the Black American general population for markers associated with increased risk of developing IDDM. Current screening methods for predicting preclinical IDDM in Caucasians relies on a combination of immune and HLA markers of IDDM; studies of these markers in the Black Americans will make it possible to extend these options to additional genetically diverse populations.

An integral membrane protein form of brain L-glutamate decarboxylase: purification, characterization and its relationship to insulin-dependent diabetes mellitus.

A new and novel form of L-glutamate decarboxylase (GAD; EC 4.1.1.15) was purified from whole porcine brain to apparent homogeneity by a combination of column chromatographies on DE-52, ultragel AcA 34, hydroxylapatite and Sephadex G-200, and native gel electrophoresis. The purified GAD was established as an integral membrane protein based on hydrophobic interaction chromatography and membrane extraction studies. This membrane GAD (MGAD) has a native molecular weight of 120 +/- 5 kDa and is a homodimer of 60 +/- 2 kDa. Immunoprecipitation and immunoblotting tests using the sera from insulin-dependent diabetes mellitus (IDDM) patients revealed the presence of antibodies against this newly identified MGAD in IDDM. The role of MGAD in the pathogenesis of IDDM and related autoimmune disorders is also discussed.

Histologic appearance of the islet organoid.

The authors have attempted to develop a hybrid organoid capable of supporting the engraftment of human pancreatic islet tissue transplants. In this report, they we report the histologic appearance of this organoid structure for implantation periods up to 16 days. Both pancreatic duct-like and glandular cells were present inside the organoid. Insulin positive cells were identified within the pancreatic tissue. Although polymorphonuclear (PMN) cells were seen in association with tissue necrosis, the authors observed no lymphocyte infiltration in the area of the xenografted human pancreatic islet tissue in the implanted organoid. Endothelial cell growth factor induced neovascularization inside the organoid sufficient to support the engraftment of transplanted pancreatic islet tissue. This organoid model may provide an alternative for clinical pancreatic transplantation.

Comparing social learning and family systems correlates of adaptation in youths with IDDM.

Evaluated social learning and family systems theoretical models to determine (a) whether illness-specific family relations (based on social learning theory) and general family behaviors (based on family systems theory) relate uniquely to the youths' illness-specific and psychosocial adaptation, and (b) whether these types of family relations covary or whether they represent distinct aspects of family functioning. Participants included 95 youths with insulin-dependent diabetes mellitus (IDDM) and their parents. Positive and supportive family relations (illness-specific family support, general family affection, general family adaptability) as well as conflictual and nonsupportive relations (i.e., illness-specific family nonsupport, general family conflict) were assessed. Results suggest that both illness-specific and general family relations uniquely predict the youths' dietary adherence and general psychosocial adaptation. Because illness-specific and general family relations also covary, broad-based models that include both types of family functioning seem warranted.

Acid peptic disease in children with type I diabetes mellitus. A complicating relationship.

OBJECTIVE: To determine the prevalence of acid peptic disease among pediatric patients with insulin-dependent diabetes mellitus and to study the effects of acid peptic disease on treatment of insulin-dependent diabetes mellitus. DESIGN: Inception cohort and matched case-control study, with a data set derived from patient and parent interviews and inpatient and outpatient chart reviews. SETTING: LeBonheur Children's Medical Center, a university-affiliated hospital in Memphis, Tenn. PARTICIPANTS: Thirty-one patients with insulin-dependent diabetes mellitus who presented with multiple episodes of symptoms of acid peptic disease were examined by endoscopy. Thirty-one control patients with insulin-dependent diabetes mellitus and transient or no gastrointestinal complaints were matched for age, gender, race, and duration of diabetes. MEASUREMENTS: Glycosylated hemoglobin levels, stature, frequency of hospital admissions, and parental history of acid peptic disease. RESULTS: Acid peptic disease occurred with a prevalence of 7% in our population of pediatric patients with insulin-dependent diabetes mellitus. Major endoscopic findings included gastritis confirmed by upper gastrointestinal biopsy (94%), bile staining of gastric mucosa (58%), and bile pooling (52%). Patients with acid peptic disease demonstrated shorter stature, greater frequency of hospital admissions, and greater prevalence of parental acid peptic disease by history than those of controls. In the 18 months following acid peptic disease therapy, hospital admissions for diabetes-related problems decreased by 50%. CONCLUSIONS: Acid peptic disease is an underrecognized complicating factor in the treatment of diabetes. Clinical suspicion is necessary to offset compromised diabetes control, compliance to treatment regimens, and/or growth expectations associated with this disease.

Formation of pseudoislets from human pancreatic cultures.

We have successfully developed a technique for culturing human islet cells obtained from the cadaveric pancreata of children. Within 24-48 h of in vitro culture, collagenase-digested human pancreatic tissue formed epithelioid monolayers. Scattered within these monolayers were insulin-positive cells, as detected by immunocytochemical and dithizone staining. Treatment of the beta cell-containing epithelioid-cell monolayers with EDTA resulted in the formation of spherical cellular clusters, i.e., pseudoislets. These pseudoislets differed from isolated islets of Langerhans in that they showed a more peripheral distribution of insulin-positive cells. Our studies have demonstrated that insulin-positive cells can be detected in monolayers obtained from human pancreata 3-4 weeks after culture. When exposed to varying concentrations of glucose, these cells secreted insulin. The development of this in vitro technique for culturing human pancreatic islet tissue could provide a model for systematically studying in vitro islet function.

Peptic ulcer disease in youths with insulin-dependent diabetes mellitus: a prospective study.

Tested whether metabolic control, treatment variables, and psychosocial factors are associated with the onset of peptic ulcer disease (PUD) in 14 Ss with IDDM who later developed PUD and a matched group of 14 Ss who did not. Metabolic control was recorded 1 year before PUD diagnosis, at diagnosis, and 6 and 12 months after diagnosis. Treatment variables (adherence, insulin dose, number of injections, number of hospitalizations) and psychosocial factors (coping, stress, family relations) were assessed an average of 20 months prior to PUD diagnosis. A 2 (Group) x 4 (Time) repeated measures ANOVA revealed no between-groups differences on metabolic control. One-way ANOVAs indicated the groups did not differ on treatment variables or psychosocial factors, except that Ss in the PUD group reported more insulin injections. Research is needed regarding the correlates of PUD in Ss with well-controlled IDDM of relatively brief duration.

C4 and Bf phenotypes in black and Caucasian patients with childhood onset insulin dependent diabetes mellitus.

Certain alleles for the complement proteins, C4 and Bf, have been shown to be markers for insulin-dependent diabetes mellitus (IDDM) in samples of different racial and geographic composition. However, the same markers are not demonstrable in each group studied. Phenotyping for the complement alleles, C4 and Bf was performed on 168 Caucasian and 49 Black patients with IDDM. All of the patients were followed in Memphis, Tennessee and had onset of disease prior to age 18. The Bf*F1 allelic frequency was significantly increased for the Caucasian patients as compared to 93 healthy Caucasian controls (0.063 vs. 0.016) and for the Black IDDM patients as compared to 43 healthy Black controls (0.102 vs. 0.035). C4 phenotype frequencies showed a significant increase of the C4AQ0 (rr = 2.13) and C4A4 (rr = 2.91) phenotypes for the Caucasian IDDM patients as compared to controls, but the frequency of homozygous null C4A was not significantly increased. In addition significant negative associations of IDDM with C4A3 and C4A6 phenotypes and no association with any C4B phenotype were observed in our Caucasian patient population. Our data for Mild-South Blacks with IDDM suggest a similar positive association of IDDM with the BfF1 phenotype (rr = 3.4). However, there was no evidence among Black IDDM patients of the C4AQ0 and C4A4 associations observed in the Caucasian sample. The data support a possible association of IDDM with the C4A2 (rr = 5.86) and C4B2 (rr = 5.26) phenotypes. The hypothesis that racial admixture may account for the higher frequency of IDDM in US Blacks as compared with African Blacks has been forwarded by others.(ABSTRACT TRUNCATED AT 250 WORDS)

Coping styles in youths with insulin-dependent diabetes mellitus.

The relationships between two coping styles (i.e., use of personal and interpersonal resources; ventilation and avoidance) and two health outcomes (i.e., adherence and metabolic control) were evaluated in 135 youths with insulin-dependent diabetes mellitus (IDDM). Individual characteristics (i.e., age, duration of illness) and contextual variables (i.e., stress, family relations) were used to predict coping styles. Poor adherence to treatment, older adolescent age, and long duration of IDDM were correlated with ventilation and avoidance coping. Youths with short duration of IDDM were more likely to cope through the use of personal and interpersonal resources, although this strategy was not associated with health outcomes. A multiple regression analysis indicated that high ventilation and avoidance coping was predicted by high stress, low family cohesion, and older adolescent age. In addition, the interaction between family adaptability and duration of IDDM significantly predicted ventilation and avoidance coping.