Type 1 diabetes: new perspectives on disease pathogenesis and treatment

During recent years, the American Diabetes Association (ADA) has published detailed guidelines and recommendations for the management of diabetes in the form of technical reviews, position statements, and consensus statements. Recommendations regarding children and adolescents have generally been included as only a minor portion of these documents. For example, the most recent ADA position statement on “Standards of Medical Care for Patients With Diabetes Mellitus” (last revised October 2003) included “special considerations” for children and adolescents (1). Other position statements included age-specific recommendations for screening for nephropathy (2) and retinopathy (3) in children with diabetes. In addition, the ADA has published guidelines pertaining to certain aspects of diabetes that apply exclusively to children and adolescents, including care of children with diabetes at school (4) and camp (5) and a consensus statement on type 2 diabetes in children and adolescents (6).

The purpose of this document is to provide a single resource on current standards of care pertaining specifically to children and adolescents with type 1 diabetes. It is not meant to be an exhaustive compendium on all aspects of the management of pediatric diabetes. However, relevant references are provided and current works in progress are indicated as such. The information provided is based on evidence from published studies whenever possible and, when not, supported by expert opinion or consensus (7). Several excellent detailed guidelines and chapters on type 1 diabetes in pediatric endocrinology texts exist, including those by the International Society of Pediatric and Adolescent Diabetes (ISPAD) (8), by the Australian Pediatric Endocrine Group (www.chw.edu/au/prof/services/endocrinology/apeg), in Lifshitz’s Pediatric Endocrinology (9–11), and by Plotnick and colleagues (12,13).

Children have characteristics and needs that dictate different standards of care. The management of diabetes in children must take the major differences between children of various ages and …

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Care of Children and Adolescents With Type 1 Diabetes A statement of the American Diabetes Association

BACKGROUND The value of continuous glucose monitoring in the management of type 1 diabetes mellitus has not been determined. METHODS In a multicenter clinical trial, we randomly assigned 322 adults and children who were already receiving intensive therapy for type 1 diabetes to a group with continuous glucose monitoring or to a control group performing home monitoring with a blood glucose meter. All the patients were stratified into three groups according to age and had a glycated hemoglobin level of 7.0 to 10.0%. The primary outcome was the change in the glycated hemoglobin level at 26 weeks. RESULTS The changes in glycated hemoglobin levels in the two study groups varied markedly according to age group (P=0.003), with a significant difference among patients 25 years of age or older that favored the continuous-monitoring group (mean difference in change, -0.53%; 95% confidence interval [CI], -0.71 to -0.35; P<0.001). The between-group difference was not significant among those who were 15 to 24 years of age (mean difference, 0.08; 95% CI, -0.17 to 0.33; P=0.52) or among those who were 8 to 14 years of age (mean difference, -0.13; 95% CI, -0.38 to 0.11; P=0.29). Secondary glycated hemoglobin outcomes were better in the continuous-monitoring group than in the control group among the oldest and youngest patients but not among those who were 15 to 24 years of age. The use of continuous glucose monitoring averaged 6.0 or more days per week for 83% of patients 25 years of age or older, 30% of those 15 to 24 years of age, and 50% of those 8 to 14 years of age. The rate of severe hypoglycemia was low and did not differ between the two study groups; however, the trial was not powered to detect such a difference. CONCLUSIONS Continuous glucose monitoring can be associated with improved glycemic control in adults with type 1 diabetes. Further work is needed to identify barriers to effectiveness of continuous monitoring in children and adolescents. (ClinicalTrials.gov number, NCT00406133.)

Continuous glucose monitoring and intensive treatment of type 1 diabetes.

Diabetes self-management education (DSME) is a critical element of care for all people with diabetes and is necessary in order to improve patient outcomes. The National Standards for DSME are designed to define quality diabetes self-management education and to assist diabetes educators in a variety of settings to provide evidence-based education. Because of the dynamic nature of health care and diabetes-related research, these Standards are reviewed and revised approximately every 5 years by key organizations and federal agencies within the diabetes education community.

A Task Force was jointly convened by the American Association of Diabetes Educators and the American Diabetes Association in the summer of 2006. Additional organizations that were represented included the American Dietetic Association, the Veteran's Health Administration, the Centers for Disease Control and Prevention, the Indian Health Service, and the American Pharmaceutical Association. Members of the Task Force included a person with diabetes; several health services researchers/behaviorists, registered nurses, and registered dietitians; and a pharmacist.

The Task Force was charged with reviewing the current DSME standards for their appropriateness, relevance, and scientific basis. The Standards were then reviewed and revised based on the available evidence and expert consensus. The committee convened on 31 March 2006 and 9 September 2006, and the Standards were approved 25 March 2007.

Diabetes self-management education (DSME) is the ongoing process of facilitating the knowledge, skill, and ability necessary for diabetes self-care. This process incorporates the needs, goals, and life experiences of the person with diabetes and is guided by evidence-based standards. The overall objectives of DSME are to support informed decision-making, self-care behaviors, problem-solving and active collaboration with the health care team and to improve clinical outcomes, health status, and quality of life.

Before the review of the individual Standards, the Task Force identified overriding principles based on existing evidence that would …

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National Standards for Diabetes Self-Management Education

Iatrogenic hypoglycemia causes recurrent morbidity in most people with type 1 diabetes and many with type 2 diabetes, and it is sometimes fatal. The barrier of hypoglycemia generally precludes maintenance of euglycemia over a lifetime of diabetes and thus precludes full realization of euglycemia’s long-term benefits. While the clinical presentation is often characteristic, particularly for the experienced individual with diabetes, the neurogenic and neuroglycopenic symptoms of hypoglycemia are nonspecific and relatively insensitive; therefore, many episodes are not recognized. Hypoglycemia can result from exogenous or endogenous insulin excess alone. However, iatrogenic hypoglycemia is typically the result of the interplay of absolute or relative insulin excess and compromised glucose counterregulation in type 1 and advanced type 2 diabetes. Decrements in insulin, increments in glucagon, and, absent the latter, increments in epinephrine stand high in the hierarchy of redundant glucose counterregulatory factors that normally prevent or rapidly correct hypoglycemia. In insulin-deficient diabetes (exogenous) insulin levels do not decrease as glucose levels fall, and the combination of deficient glucagon and epinephrine responses causes defective glucose counterregulation. Reduced sympathoadrenal responses cause hypoglycemia unawareness. The concept of hypoglycemia-associated autonomic failure in diabetes posits that recent antecedent hypoglycemia causes both defective glucose counterregulation and hypoglycemia unawareness. By shifting glycemic thresholds for the sympathoadrenal (including epinephrine) and the resulting neurogenic responses to lower plasma glucose concentrations, antecedent hypoglycemia leads to a vicious cycle of recurrent hypoglycemia and further impairment of glucose counterregulation. Thus, short-term avoidance of hypoglycemia reverses hypoglycemia unawareness in most affected patients. The clinical approach to minimizing hypoglycemia while improving glycemic control includes 1 ) addressing the issue, 2 ) applying the principles of aggressive glycemic therapy, including flexible and individualized drug regimens, and 3 ) considering the risk factors for iatrogenic hypoglycemia. The latter include factors that result in absolute or relative insulin excess: drug dose, timing, and type; patterns of food ingestion and exercise; interactions with alcohol and other drugs; and altered sensitivity to or clearance of insulin. They also include factors that are clinical surrogates of compromised glucose counterregulation: endogenous insulin deficiency; history of severe hypoglycemia, hypoglycemia unawareness, or both; and aggressive glycemic therapy per se, as evidenced by lower HbA 1c levels, lower glycemic goals, or both. In a patient with hypoglycemia unawareness (which implies recurrent hypoglycemia) a 2- to 3-week period of scrupulous avoidance of hypoglycemia is advisable. Pending the prevention and cure of diabetes or the development of methods that provide glucose-regulated insulin replacement or secretion, we need to learn to replace insulin in a much more physiological fashion, to prevent, correct, or compensate for compromised glucose counterregulation, or both if we are to achieve near-euglycemia safely in most people with diabetes.

https://care.diabetesjournals.org/content/diacare/26/6/1902.full.pdf

Hypoglycemia in Diabetes

Coping skills training for youth with diabetes mellitus has long-lasting effects on metabolic control and quality of life.

OBJECTIVE —Children with type 1 diabetes are usually asked to perform self-monitoring of blood glucose (SMBG) before meals and at bedtime, and it is assumed that if results are in target range, along with HbA 1c measurements, then overall glycemic control is adequate. However, the brief glimpses in the 24-h glucose profile provided by SMBG may miss marked glycemic excursions. The MiniMed Continuous Glucose Monitoring System (CGMS) has provided a new method to obtain continuous glucose profiles and opportunities to examine limitations of conventional monitoring. RESEARCH DESIGN AND METHODS —A total of 56 children with type 1 diabetes (age 2–18 years) wore the CGMS for 3 days. Patients entered four fingerstick blood samples into the monitor for calibration and kept records of food intake, exercise, and hypoglycemic symptoms. Data were downloaded, and glycemic patterns were identified. RESULTS —Despite satisfactory HbA 1c levels (7.7 ± 1.4%) and premeal glucose levels near the target range, the CGMS revealed profound postprandial hyperglycemia. Almost 90% of the peak postprandial glucose levels after every meal were >180 mg/dl (above target), and almost 50% were >300 mg/dl. Additionally, the CGMS revealed frequent and prolonged asymptomatic hypoglycemia (glucose CONCLUSIONS —Despite excellent HbA 1c levels and target preprandial glucose levels, children often experience nocturnal hypoglycemia and postprandial hyperglycemia that are not evident with routine monitoring. Repeated use of the CGMS may provide a means to optimize basal and bolus insulin replacement in patients with type 1 diabetes.

https://care.diabetesjournals.org/content/diacare/24/11/1858.full.pdf

Limitations of Conventional Methods of Self-Monitoring of Blood Glucose: Lessons learned from 3 days of continuous glucose sensing in pediatric patients with type 1 diabetes

OBJECTIVE: Recommendations from the Diabetes Control and Complications Trial (DCCT) indicate that adolescents with type 1 diabetes should be treated with intensive therapy involving multiple daily injections (MDI) of insulin or insulin pump therapy (continuous subcutaneous insulin infusion [CSII] to help obtain better metabolic control and prevent later complications. Interest has thus focused on insulin pump therapy to help adolescents meet this challenge. The purpose of this study was to examine responses to CSII and MDI in a large group of adolescents with established type 1 diabetes during a 12-month period and to determine whether either treatment regimen more favorably affected clinical and psychosocial outcomes. RESEARCH DESIGN AND METHODS: One-third of 75 youths aged 12-20 years who were candidates for intensive therapy chose CSII as their mode of treatment. Patients received intensive treatment and education as described by the DCCT investigators. Psychosocial data (e.g., quality of life, depression, self-efficacy, and coping) were collected at baseline and at 6-month intervals, and clinical data (e.g., HbA1c levels, adverse events) were collected every 4-6 weeks. RESULTS: Although both MDI- and CSII-treated adolescents initially exhibited improved metabolic control, this level of control was more difficult to sustain for 12 months in the MDI group (at 6 months HbA1c = 8.1, at 12 months HbA1c = 8.3), whereas average HbA1c levels in the CSII group continued to decrease during the 12 months of treatment (at 6 months HbA1c = 7.7, at 12 months HbA1c = 7.5). Despite lower HbA1c levels in CSII-versus MDI-treated patients, the rate of severe hypoglycemic events was reduced by almost 50% in the CSII group (P = 0.01). Self-reported questionnaires demonstrated that there was improvement in self-efficacy, depression, and quality of life in both MDI- and CSII-treated patients. Finally, adolescents using CSII found coping with diabetes to be less difficult than adolescents using MDI did. CONCLUSIONS: CSII is an alternative means to lower HbA1c levels and reduce the risk of hypoglycemia without adversely affecting psychosocial outcomes in adolescents with type 1 diabetes.

Continuous subcutaneous insulin infusion. A new way to lower risk of severe hypoglycemia, improve metabolic control, and enhance coping in adolescents with type 1 diabetes.

OBJECTIVE Quality of life is an important criterion for assessing outcomes of treatment in chronic illness related to psychosocial well-being. The purpose of this study was to evaluate the factors that influence quality of life in adolescents with IDDM. RESEARCH DESIGN AND METHODS Self-reports were obtained from 52 adolescents (age 13-20 years, mean 16.1 ± 1.9 [mean ± SD], diabetes duration 8.2 ± 3.4 years, 49% female) using the following scales: Diabetes Quality of Life for Youths, Children9s Depression Inventory, Issues in Coping with Diabetes, Diabetes Family Behavior Scale, Family Adaptability and Cohesion, Self-Efficacy for Diabetes, and the Adolescent Coping Orientation. Metabolic control was measured by HbA 1c . RESULTS Teenagers whose diabetes had the greater impact (R 2 = 0.48) and were less satisfied (R 2 = 0.45) felt that management was more difficult ( r = 0.56) and that diabetes was more upsetting ( r = 0.63). They also used fewer rebellion strategies for coping ( r = −0.44), had lower diabetes self-efficacy ( r = −0.36), and had more depressive symptoms ( r = 0.61). Higher impact was also associated with higher family warmth and caring ( r = −0.54) and lower family adaptability ( r = −0.42). Teenagers who were more worried (R 2 = 0.37) about their diabetes felt that management was more difficult ( r = 0.40) and that diabetes was more upsetting ( r = 0.58), and they used less rebellion ( r = −0.49) and more ventilation ( r = 0.42) to cope, had lower diabetes ( r = −0.40) and medical ( r = −0.30) self-efficacy, were more depressed ( r = 0.55), and their families were less warm and caring ( r = −0.33). HbA 1c levels were not associated with quality of life or any other psychosocial factors except in teenagers who perceived their families as providing more guidance and control. These teenagers had lower HbA 1c values than those whose families were less involved. CONCLUSIONS Even teenagers who are successfully achieving HbA 1c goals of therapy may perceive diabetes as having a negative impact on their lives, be depressed, and find diabetes difficult to manage. Diabetes treatment teams need to pay equal attention to the psychosocial needs to the quiet, nonrebellious teen with well-controlled diabetes from a supportive family as they do to the rebellious adolescent with poorly controlled diabetes.

Personal and Family Factors Associated With Quality of Life in Adolescents With Diabetes

OBJECTIVE Given the urgent need to develop effective programs that improve the ability for adolescents to achieve metabolic control equivalent to programs studied in the Diabetes. Control and Complications Trial, we have undertaken a clinical trial to determine if a behavioral intervention (coping skills training [CST]) combined with intensive diabetes management can improve metabolic control and quality of life in adolescents implementing intensive therapy regimens. RESEARCH DESIGN AND METHODS A total of 65 youths between the ages of 13 and 20 years, who elected to initiate intensive insulin therapy, were randomly assigned to one of two groups: the intensive management with CST group and the intensive management without CST group. CST consists of a series of small group efforts designed to teach adolescents the coping skills of social problem-solving, social skills training, cognitive behavior modification, and conflict resolution. Data were collected at pre-intervention and at 3 months following the use of the Self-Efficacy for Diabetes scale, Children9s Depression Inventory, Issues in Coping with IDDM scale, and the Diabetes Quality of Life: Youth scale. Clinical data (HbA 1c , adverse effects) were collected monthly. RESULTS The experimental and control groups were comparable on all measures at baseline. Results show that adolescents who received CST had lower HbA 1c and better diabetes self-efficacy and were less upset about coping with diabetes than adolescents receiving intensive management alone. In addition, adolescents who received the CST found it easier to cope with diabetes and experienced less of a negative impact of diabetes on quality of life than those who did not receive CST. CONCLUSIONS CST is useful in improving not only an adolescent9s metabolic control, but also their quality of life. As more pediatric providers aim for improved control, in adolescents with diabetes, the addition of this behavioral intervention may be helpful in achieving metabolic and life goals.

Elizabeth A. Boland

Papers

Coping skills training for youth with diabetes mellitus has long-lasting effects on metabolic control and quality of life.

Limitations of Conventional Methods of Self-Monitoring of Blood Glucose: Lessons learned from 3 days of continuous glucose sensing in pediatric patients with type 1 diabetes

Continuous subcutaneous insulin infusion. A new way to lower risk of severe hypoglycemia, improve metabolic control, and enhance coping in adolescents with type 1 diabetes.

Personal and Family Factors Associated With Quality of Life in Adolescents With Diabetes

Short-term effects of coping skills training as adjunct to intensive therapy in adolescents