Douglas O. Sobel

Self-efficacy, Outcome Expectations, and Diabetes Self-management in Adolescents with Type 1 Diabetes

ABSTRACT. The goal of this research was to develop and evaluate measures of adolescent diabetes management self-efficacy and outcome expectations that reflect developmentally relevant, situation-specific challenges to current diabetes regimens. Self-efficacy for diabetes management, expected outcomes of adherence, adherence to the diabetes regimen, and glycemic control were assessed in 168 adolescents (ages10-16 years) with type 1 diabetes. Factor analyses indicated a single scale for self-efficacy and two distinct factors representing positive and negative outcome expectations. Reliability and predictive validity of the new scales were supported. In regression analyses, self-efficacy and the interaction of self-efficacy with expectations of positive outcomes were significantly associated with diabetes self-management adherence and glycemic control in older adolescents. The effect of self-efficacy was greatest when adolescents had stronger beliefs in the beneficial outcomes of adherence. These brief measures can be used to identify youths at risk of poor diabetes self-management. Interventions targeting self-efficacy may lead to improved diabetes self-management.

Poly I:C accelerates development of diabetes mellitus in diabetes-prone BB rat

We developed a new experimental model of accelerated diabetes mellitus in the genetically susceptible diabetes-prone BB rat with the administration of the IFN-α inducer poly I:C. With this model, there was both an increased incidence and accelerated onset of insulin-dependent-diabetes in poly I:C–treated animals compared with saline-treated controls. All twelve rats administered poly I:C (5 μg/gm body weight 3 times/wk) developed diabetes by 57 days of age (100%) compared with 1 of 27 (3.7%) saline-treated controls. Furthermore, the development of diabetes was accelerated in the poly I:C–treated group (mean age ± SE at onset 52.8 ± 0.58 days) compared with saline-treated controls (89.3 ± 2.4 days, P < 0.01). Additionally, poly I:C–treated rats had higher mean serum IFN-α levels than saline-treated rats at weeks 2 and 3 of treatment (210 vs. 27 and 183 vs. 25 U/ml, respectively, P < 0.001). Poly I:C treatment of 5 Wistar rats, the parental strain, which is not susceptible to diabetes, did not result in insulitis, diabetes, or hyperglycemia. The histopathologic findings of insulitis and decreased immunoreactive islet insulin in poly I:C–accelerated diabetic BB rats and in BB rats with spontaneous diabetes suggest a similar pathophysiology.

Poly I:C Induces Development of Diabetes Mellitus in BB Rat

Polyinosinic polycytidilic acid (poly I:C), an inducer of α-interferon, accelerates the development of diabetes in diabetes-prone (DP) BioBreeding (BB) rats. This study investigates the effect of administering poly I:C to a diabetes-resistant (DR) strain of BB rats. We compared the incidence of diabetes, the degree of insulitis, the number of NK cells, helper-inducer cells, cytotoxic-suppressor cells, Ia+ T cells, RT6.1+ T cells, and NK cell bioactivity in DR rats treated with saline and with a 5 micrograms/g body wt (poly-5) dose and a 10 micrograms/g body wt (poly-10) dose of poly I:C. The incidence of diabetes was also compared with that of DP rats receiving poly-5. We found that both doses of poly I:C significantly induce the development of diabetes in the DR BB rat. However, treatment of DR rats with the higher dose induces a greater rate of development of diabetes and earlier onset of diabetes than the lower poly-5 dose. The rate of diabetes development and the mean age of onset were similar in poly-10–treated DR and poly-5–treated DP rats. A significant degree of insulitis occurred in all the poly I:C–treated DR rats, even those not developing diabetes. Peripheral blood NK cell number was greater in poly I:C than in saline-treated rats, after 2 wk of treatment and when killed. The percentage of OX19+ peripheral blood mononuclear cells expressing RT6.1 allotype or Ia antigen were similar in poly I:C– and saline-treated rats. of diabetes in poly-10–treated DR rats and poly-5–treated DP rats is consistent with a similar mechanism of poly I:C action in the DR and DP BB rats. Although the specific mechanism is not defined, NK cell numbers are elevated with poly I:C treatment. Alterations in RT6.1+ and la+ T cells do not appear to play a role.

The B-Subunit of Cholera Toxin Induces Immunoregulatory Cells and Prevents Diabetes in the NOD Mouse

The B-subunit of the cholera toxin molecule (CT-B) has T-cell immunomodulatory properties. Because the pathogenesis of diabetes in the nonobese diabetic (NOD) mouse model of IDDM is thought to be a Tcell-mediated process due to an imbalance of immunoregulatory and anti-islet effector cells, we examined the effect of CT-B administration on the development of diabetes in the NOD mouse and assessed whether this potential diabetes-sparing effect of CT-B is mediated by changes in immunoregulatory and/or anti-islet cytotoxic effector cell activity. The administration of either intravenous or intraperitoneal CT-B decreased the development of diabetes with no apparent drug toxicity. At 6 months of age, only 18% of CT-B vs. 75% of saline-treated animals had diabetes. Histopathological examination revealed less islet atrophy in CT-B-treated animals. The in vitro proliferative responses of mononuclear splenocytes and thymocytes to concanavalin A and lipolysaccharide and the proportion of B-cells and T-cell subsets were not altered by CT-B treatment. CT-B administration did not inhibit the primary immunization of mice to tetanus toxoid. The development of diabetes in irradiated NOD mice was slower in the animals injected with spleen cells (SC) from CT-B–treated than from saline-treated NOD mice, suggesting that CT-B decreases anti-islet effector cell activity. The injection of SC from CT-B–treated mice inhibited the adoptive transfer of diabetes by SC from diabetic mice into irradiated NOD mice, documenting that CT-B administration induces regulatory cell activity. In conclusion, CT-B administration prevents the development of diabetes in NOD mice by inhibiting the immune destruction of islets. This islet-sparing activity appears mediated, at least in part, by the induction of regulatory cells and, in turn, suppression of anti-islet effector cells, which is not associated with generalized immunosuppression or T- or B-cell depletion.

Poly I:C Induction of α-Interferon in the Diabetes-Prone BB and Normal Wistar Rats: Dose-Response Relationships

Although the administration of a fixed dose of the α-interferon (α-IFN) inducer, polyinosinic polycytidilic acid (poly I:C), accelerates the development of diabetes in DP-BB rats, no reports have characterized the dose-response relationship of poly I:C with serum alpha-IFN levels and the development of diabetes. This study examines the dose-response relationships of poly I:C with the induction of serum α-IFN and the development of diabetes in DP-BB and normal Wistar rats. Also tested in this study is the hypothesis that the lack of development of diabetes in poly I:C-treated normal Wistar rats is attributable to a deficient α-IFN response. Using poly I:C doses of 0.5, 1.5, 5, and 10 μ/g body weight, a direct dose-response relationship was observed in DP-BB rats with the serum α-IFN response. Moreover, all doses of poly I:C accelerated the onset of diabetes in BB rats. Serum α-IFN levels inversely correlated with time of onset of diabetes (P < 0.01). Also, BB rats with higher levels of serum α-IFN were associated with earlier onset of diabetes (P < 0.001). Poly I:C-induced serum α-IFN levels were significantly lower in diabetic than in nondiabetic BB rats. In normal Wistar rats, although all doses of poly I:C significantly increased serum α-IFN levels, diabetes was not induced. The results of this study indicate that poly I:C administration elevates serum α-IFN and accelerates the development of diabetes in BB rats at even very low doses. This finding in conjunction with the correlation of serum α-IFN with the onset of diabetes is consistent with a pathogenetic role of α-IFN. The absence of a diabetogenic effect of poly I:C in Wistar rats suggests that α-IFN alone cannot induce diabetes in this animal.

Interferon-tau inhibits the development of diabetes in NOD mice

Interferon-alpha (IFN-α) inhibits the development of diabetes in animal models of autoimmune diabetes. However, the mechanism of the action is not fully understood and drug toxicity could limit its potential clinical utility. Interferon-tau (IFN-τ) is another type 1 interferon, which has less toxicity but may have different biologic activity than IFN-α. This study explores the effect of IFN-τ on the diabetic process in non-obese diabetic (NOD) mice. IFN-τ by intraperitoneal, subcutaneous, or oral routes of administration decreased the development of spontaneous diabetes in NOD mice. Islet inflammation was decreased 50%. IFN-τ administration to recipient mice prevented the development of passively transferred and cyclophosphamide accelerated diabetes. IFN-τ treatment also decreased anti-islet effector activity of NOD splenic cells. Immunoregulatory activity of splenic cells was augmented by IFN-τ administration as was the number of splenic CD25+CD4+ cells. Concanavalin A (Con A)-induced release of IFN-γ was decreased in spleen cells from IFN-τ treated mice. In conclusion, IFN-τ inhibits spontaneous autoimmune diabetes and passively transferred diabetes in the NOD mouse. This diabetes sparing activity may be due to an induction of regulatory cells, possibly CD25+CD4+ T cells, which in turn inhibit anti-islet effector cell activity and the development of insulitis and diabetes. Due to the lower drug toxicity, IFN-τ could be a better drug candidate than IFN-α for experimental clinical trials.

The role of NK cell activity in the pathogenesis of poly I:C accelerated and spontaneous diabetes in the diabetes prone BB rat

The development of insulin dependent diabetes mellitus (IDDM) and diabetes in the diabetes prone (DP) BB rat animal model of IDDM is thought to be due to an autoimmune process. Natural killer (NK) cells have been implicated but not proven to play a pathogenetic role in BB rats due to the increased NK cell number and activity found in these animals. We have recently reported that poly I:C, an inducer of cytokines and a potent enhancer of NK cell function, accelerates the development of diabetes in DP BB rats and induces diabetes in diabetes resistant (DR) BB rats. Since we have further demonstrated that poly I:C administration to BB rats increases NK cell number and levels of inducers of NK cell activity, interferon-alpha and IL-6 which is described therein, we tested the hypothesis that NK cell activity plays an important role in poly I:C accelerated disease. The role of NK cells in poly I:C accelerated diabetes and spontaneous diabetes was examined by determining whether selective depletion of NK cells using a rat NK cell specific antibody (anti-NKR-P1 antibody) alters the development of diabetes. The treatment of BB rats with anti-NKR-P1 antibody resulted in a significantly lower mean NK cell activity of splenic mononuclear cells than that found in control animals. However, the development of diabetes and degree of insulitis was not significantly different between treatment groups. BB rats administered anti-NKR-P1 antibody with poly I:C had a lower mean splenocyte NK cell activity and lower mean NK cell number within the peripheral blood and inflamed islets than rats administered poly I:C alone. However, anti-NKR-P1 antibody administration did not alter the accelerated development of diabetes or the degree of insulitis in poly I:C treated animals. These data document that NK cells do not play a major role in the pathogenesis of poly I:C accelerated diabetes or spontaneous diabetes in the DP BB rat.

Use of Fructosamine Test in Diabetic Children

Objective The goal of this study was to assess the effect of glucose and the contribution of the aldimine component on the measurement of fructosamine, the relationship of serum fructosamine with glycosylated plasma proteins, as measured by a new high-performance liquid chromatography methodology (Glyc PP-HPLC) and by an affinity chromatography (Glyc PP), and the ability of serum fructosamine to assess acute, short-term (1–2 wk), and long-term (2–3 mo) glycemic control. Research Design and Methods The measurement of fructosamine was unaltered by the addition of up to 27.5 mM glucose or by the elimination of the aldimine component of serum specimens by dialysis. Fructosamine was generated in vitro by incubating serum aliquots. This generation was dependent on time, glucose concentration, and temperature. Results Fructosamine (n = 27) correlated well with Glyc PP (r = 0.76, P < 0.01) and significantly less with Glyc PP-HPLC (r = 0.46, P < 0.01). Although oral glucose ingestion increased serum glucose acutely by 200% fructosamine was unchanged at each time interval. Improving glycemic control decreased the mean serum fructosamine concentration from 3.68 (baseline) to 3.28 mM (P < 0.01) at 1 wk and to 3.13 mM (P < 0.01) at 2 wk. HbA1c correlated with fructosamine (r = 0.59) and Glyc PP-HPLC (r = 0.47) but correlated best with Glyc PP (r = 0.83). Conclusions These results indicate the fructosamine assay is unaltered by serum glucose, solely measures the ketoamine component, correlates well with glycosylated plasma proteins measured by aminophenylboronic acid column chromatography, is unaffected by acute changes of serum glucose, and may be used to monitor changes in glycemic control over a 1-wk interval.

Parenting goals: Predictors of parent involvement in disease management of children with type 1 diabetes

The purpose of this study was to develop a measure of diabetes-specific parenting goals for parents of children with type 1 diabetes and to examine whether parenting goals predict a change in parenting involvement in disease management. An independent sample of primary caretakers of 87 children aged 10 to 16 years with type 1 diabetes completed the measure of parenting goals (diabetes-specific and general goals); both parent and child completed measures of parent responsibility for diabetes management at baseline and 6 months. Parents ranked diabetes-specific parenting goals as more important than general parenting goals, and rankings were moderately stable over time. Parenting goals were related to parent responsibility for diabetes management. The relative ranking of diabetes-specific parenting goals predicted changes in parent involvement over 6 months, with baseline ranking of goals predicting more parental involvement at follow-up. Parenting goals may play an important role in family management of type 1 diabetes.

Health attitudes, beliefs, and risk behaviors among adolescents and young adults with type 1 diabetes

Decision making about engaging in health-promoting and health-compromising behaviors among adolescents and young adults with type 1 diabetes is an important but understudied topic. The purpose of this study was to describe the health attitudes, beliefs, risk behaviors, and general psychological functioning of adolescents and young adults with diabetes and to compare these psychosocial aspects of health to those of adolescents and young adults without diabetes. Fifty-three adolescents and young adults with type 1 diabetes and 53 demographically matched controls were recruited from 2 pediatric teaching hospitals and administered a confidential self-report questionnaire consisting of individual survey items and standardized scales. Compared to healthy adolescents and young adults, adolescents and young adults with diabetes had more frequent thoughts about health and sickness, rated their health as poorer, viewed smoking as less addictive, reported greater symptoms of depression, and reported greater exposure to smoking in their households, but less smoking experimentation. Poorer metabolic control was associated with decreased physical activity. Additional research on the design and implementation of diabetes-specific cardiovascular disorder and tobacco control programs for adolescents and young adults is warranted.