Corresponding author: Jane L. Chiang, jchiang@diabetes.org.
Type 1 diabetes is characterized by an immune-mediated depletion of β-cells that results in lifelong dependence on exogenous insulin. While both type 1 and type 2 diabetes result in hyperglycemia, the pathophysiology and etiology of the diseases are distinct and require us to consider each type of diabetes independently. As such, this position statement summarizes available data specific to the comprehensive care of individuals with type 1 diabetes. The goal is to enhance our ability to recognize and manage type 1 diabetes, to prevent its associated complications, and to eventually cure and prevent this disease.
Next Section
Incidence and Prevalence of Type 1 Diabetes
The exact number of individuals with type 1 diabetes around the world is not known, but in the U.S., there are estimated to be up to 3 million (1). Although it has long been called “juvenile diabetes” due to the more frequent and relatively straightforward diagnosis in children, the majority of individuals with type 1 diabetes are adults.
Most children are referred and treated in tertiary centers, where clinical data are more readily captured. The SEARCH for Diabetes in Youth study estimated that, in 2009, 18,436 U.S. youth were newly diagnosed with type 1 diabetes (12,945 non-Hispanic white, 3,098 Hispanic, 2,070 non-Hispanic black, 276 Asian-Pacific Islander, and 47 American Indian) (2). Worldwide, ∼78,000 youth are diagnosed with type 1 diabetes annually. Incidence varies tremendously among countries: East Asians and American Indians have the lowest incidence rates (0.1–8 per 100,000/year) as compared with the Finnish who have the highest rates (>64.2 per 100,000/year) (3). In the U.S., the number of youth with type 1 diabetes was estimated to be 166,984 (4).
The precise incidence of new-onset type 1 diabetes in those over 20 years of age is unknown. This may be due to the prolonged phase of onset and the subtleties in distinguishing the different types of diabetes. In one European study of adults aged 30–70 years, ∼9% tested positive for GAD antibodies (GADA) within 5 years of a diabetes diagnosis, consistent with other studies (5).
Adults with type 1 diabetes often receive care in primary care settings rather than with an endocrinologist. Unlike the consolidated care seen in pediatric diabetes management, the lack of consolidated care in adults makes incidence and prevalence rates difficult to characterize, and therefore they are often underestimated. The number of adults living with type 1 diabetes is increasing due to two factors: 1) the rising number of new-onset cases of type 1 diabetes in adults, including those diagnosed with latent autoimmune diabetes in adults (LADA), and 2) individuals with childhood-onset diabetes are living longer (6,7).
Previous Section
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Classification and Diagnosis
Type 1 diabetes has traditionally been diagnosed based on clinical catabolic symptoms suggestive of insulin deficiency: polyuria, polydipsia, weight loss, and marked hyperglycemia that is nonresponsive to oral agents. It is classified as an autoimmune disease with progressive β-cell destruction, resulting in a physiological dependence on exogenous insulin. Recent studies have broadened our understanding of the disease, but have made diagnosis more complex.
There is tremendous variability in the initial presentation of type 1 diabetes in both youth and adults. Children often present acutely, with severe symptoms of polyuria, polydipsia, and ketonemia. However, in adults, type 1 diabetes presents with a more gradual onset, with a clinical presentation that may initially appear consistent with type 2 diabetes. Distinguishing between type 1 and type 2 diabetes presents diagnostic challenges. Traditionally, progressive β-cell destruction has been the hallmark of type 1 diabetes, but residual C-peptide (a surrogate marker for insulin secretion) may be detected over 40 years after initial diagnosis, regardless of whether the initial diagnosis was made in childhood or in adulthood (8).
Clinical Clues
Much of the diagnosis will depend on clinical clues, but the rising incidence of overweight/obesity has also confounded the diagnosis of type 1 diabetes. A lean individual presenting with clinical symptoms without a first-degree relative with diabetes (but often with a history of distant relatives with type 1 diabetes or other autoimmune disease) is generally suggestive of type 1 diabetes. An overweight individual (of any age) with metabolic syndrome and a strong family history of type 2 diabetes may be assessed only for the development of type 2 diabetes, even though type 1 diabetes is on the differential diagnosis. Obesity does not preclude that autoimmunity and hyperglycemia will occur even amid the relatively higher levels of endogenous insulin secretion observed in obesity. In young patients aged 10–17 years with phenotypic type 2 diabetes, 10% have evidence of islet autoimmunity suggesting that type 1 diabetes was the likely diagnosis (9). Thus, although leaner individuals are more likely to be diagnosed as having type 1 diabetes, the potential for type 1 diabetes exists in those who phenotypically appear to have type 2 diabetes. If hyperglycemia persists after treatment with noninsulin agents, which is unusual in the treatment of newly diagnosed type 2 diabetes, then type 1 diabetes should be considered.
Pancreatic Autoantibodies
Pancreatic autoantibodies are characteristic of type 1 diabetes. Highly sensitive laboratory measurements capture ∼98% of individuals with autoantibodies at diagnosis (10). Unfortunately, most commercial laboratories do not have reliably sensitive or specific assays that measure all five autoantibodies: GADA, islet cell antibodies (ICA), insulin autoantibodies (IAA), protein tyrosine phosphatase antibodies (ICA512 or IA2A), and zinc transporter protein (ZnT8). Thus, it may be inappropriate to report a patient as autoantibody negative. Another cause of “false-negative” autoantibodies is testing far out from diagnosis as antibody titers diminish over time (Fig. 1). It appears that there is an increased incidence of type 1 diabetes in ethnic populations where autoantibody markers may be of variable utility, such as in Asians where autoantibodies are often negative (11–15).
Figure 1
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Figure 1
The percentage of antibody-positive subjects is affected by the duration of type 1 diabetes for GADA (A) and IA2A (B). Given an increase in the scatter (due to lower numbers of subjects), the x-axis is truncated at a duration of 30 years. Reproduced with permission from Tridgell et al. (16).
Family History
Type 1 diabetes has a genetic predilection and, in some cases, can be predicted in family members. The overall prevalence of type 1 diabetes in the U.S. is ∼0.3%, but if a first-degree relative has diabetes, the empiric risk of being affected is ∼5% (17,18), representing a 15-fold increase among family members. Studies evaluating children at risk for developing type 1 diabetes have shown that the presence of more than two autoantibodies was associated with a nearly 70% risk for disease development within 10 years and 84% within 15 years (19). Evaluating at-risk individuals in the clinical setting is not yet recommended due to limited clinical interventions; however, ongoing research studies are identifying at-risk individuals through genetic testing in both the lower-risk general population and in the higher-risk population of relatives of people with type 1 diabetes.
Recommendations
Diagnosis
The American Diabetes Association’s (ADA’s) diagnostic criteria for type 1 and type 2 diabetes are the same (Table 1). (A)
Consider measurement of pancreatic autoantibodies to confirm the diagnosis of type 1 diabetes. (B)
View this table:
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Table 1
Criteria for the diagnosis of diabetes
Identification of At-Risk Relatives
Inform type 1 diabetic patients of the opportunity to have their relatives tested for type 1 diabetes risk in the setting of a clinical research study. (B)
Previous Section
Next Section
Initial Evaluation and Follow-up
General Considerations
All patients with type 1 diabetes need age-appropriate care, with an understanding of their specific needs and limitations. Infants and toddlers are approached quite differently from adolescents; the needs of young adults may vary from middle-aged or older adults. Regardless of age, the patient’s needs are the same: an individualized care plan with ongoing education and support, ongoing assessment for acute and chronic complications, and access to medical providers with type 1 diabetes expertise. Just as patients change, the therapeutic approach should change and should be evaluated at each visit and modified as needed.
Type 1 diabetes care must be an iterative process, adapted as the needs of the individual evolve. Clinical assessments for type 1 diabetes in children and adults should incorporate age-appropriate and complication-focused evaluations, based on the likelihood that an abnormality will be present. For example, a young adult with low cardiovascular disease (CVD) risk and no complications may need more of an assessment of lifestyle adjustment as opposed to an older adult with longer duration of the disease who may need more evaluation of vascular and neurological issues.
Transition of Care From Pediatric to Adult Providers
As youth transition into emerging adulthood, the supportive infrastructure often abruptly disappears and glycemic control tends to deteriorate. The ADA recognizes that this is a challenging time and recommends a strong, practical transition plan to anticipate the upcoming changes. A successful transition plan should be initiated early (e.g., early teenage years) and include ongoing dialogue between the family and youth. The discussion should include fin
Corresponding author: Jane L. Chiang, jchiang@diabetes.org.
Type 1 diabetes is characterized by an immune-mediated depletion of β-cells that results in lifelong dependence on exogenous insulin. While both type 1 and type 2 diabetes result in hyperglycemia, the pathophysiology and etiology of the diseases are distinct and require us to consider each type of diabetes independently. As such, this position statement summarizes available data specific to the comprehensive care of individuals with type 1 diabetes. The goal is to enhance our ability to recognize and manage type 1 diabetes, to prevent its associated complications, and to eventually cure and prevent this disease.
Next Section
Incidence and Prevalence of Type 1 Diabetes
The exact number of individuals with type 1 diabetes around the world is not known, but in the U.S., there are estimated to be up to 3 million (1). Although it has long been called “juvenile diabetes” due to the more frequent and relatively straightforward diagnosis in children, the majority of individuals with type 1 diabetes are adults.
Most children are referred and treated in tertiary centers, where clinical data are more readily captured. The SEARCH for Diabetes in Youth study estimated that, in 2009, 18,436 U.S. youth were newly diagnosed with type 1 diabetes (12,945 non-Hispanic white, 3,098 Hispanic, 2,070 non-Hispanic black, 276 Asian-Pacific Islander, and 47 American Indian) (2). Worldwide, ∼78,000 youth are diagnosed with type 1 diabetes annually. Incidence varies tremendously among countries: East Asians and American Indians have the lowest incidence rates (0.1–8 per 100,000/year) as compared with the Finnish who have the highest rates (>64.2 per 100,000/year) (3). In the U.S., the number of youth with type 1 diabetes was estimated to be 166,984 (4).
The precise incidence of new-onset type 1 diabetes in those over 20 years of age is unknown. This may be due to the prolonged phase of onset and the subtleties in distinguishing the different types of diabetes. In one European study of adults aged 30–70 years, ∼9% tested positive for GAD antibodies (GADA) within 5 years of a diabetes diagnosis, consistent with other studies (5).
Adults with type 1 diabetes often receive care in primary care settings rather than with an endocrinologist. Unlike the consolidated care seen in pediatric diabetes management, the lack of consolidated care in adults makes incidence and prevalence rates difficult to characterize, and therefore they are often underestimated. The number of adults living with type 1 diabetes is increasing due to two factors: 1) the rising number of new-onset cases of type 1 diabetes in adults, including those diagnosed with latent autoimmune diabetes in adults (LADA), and 2) individuals with childhood-onset diabetes are living longer (6,7).
Previous Section
Next Section
Classification and Diagnosis
Type 1 diabetes has traditionally been diagnosed based on clinical catabolic symptoms suggestive of insulin deficiency: polyuria, polydipsia, weight loss, and marked hyperglycemia that is nonresponsive to oral agents. It is classified as an autoimmune disease with progressive β-cell destruction, resulting in a physiological dependence on exogenous insulin. Recent studies have broadened our understanding of the disease, but have made diagnosis more complex.
There is tremendous variability in the initial presentation of type 1 diabetes in both youth and adults. Children often present acutely, with severe symptoms of polyuria, polydipsia, and ketonemia. However, in adults, type 1 diabetes presents with a more gradual onset, with a clinical presentation that may initially appear consistent with type 2 diabetes. Distinguishing between type 1 and type 2 diabetes presents diagnostic challenges. Traditionally, progressive β-cell destruction has been the hallmark of type 1 diabetes, but residual C-peptide (a surrogate marker for insulin secretion) may be detected over 40 years after initial diagnosis, regardless of whether the initial diagnosis was made in childhood or in adulthood (8).
Clinical Clues
Much of the diagnosis will depend on clinical clues, but the rising incidence of overweight/obesity has also confounded the diagnosis of type 1 diabetes. A lean individual presenting with clinical symptoms without a first-degree relative with diabetes (but often with a history of distant relatives with type 1 diabetes or other autoimmune disease) is generally suggestive of type 1 diabetes. An overweight individual (of any age) with metabolic syndrome and a strong family history of type 2 diabetes may be assessed only for the development of type 2 diabetes, even though type 1 diabetes is on the differential diagnosis. Obesity does not preclude that autoimmunity and hyperglycemia will occur even amid the relatively higher levels of endogenous insulin secretion observed in obesity. In young patients aged 10–17 years with phenotypic type 2 diabetes, 10% have evidence of islet autoimmunity suggesting that type 1 diabetes was the likely diagnosis (9). Thus, although leaner individuals are more likely to be diagnosed as having type 1 diabetes, the potential for type 1 diabetes exists in those who phenotypically appear to have type 2 diabetes. If hyperglycemia persists after treatment with noninsulin agents, which is unusual in the treatment of newly diagnosed type 2 diabetes, then type 1 diabetes should be considered.
Pancreatic Autoantibodies
Pancreatic autoantibodies are characteristic of type 1 diabetes. Highly sensitive laboratory measurements capture ∼98% of individuals with autoantibodies at diagnosis (10). Unfortunately, most commercial laboratories do not have reliably sensitive or specific assays that measure all five autoantibodies: GADA, islet cell antibodies (ICA), insulin autoantibodies (IAA), protein tyrosine phosphatase antibodies (ICA512 or IA2A), and zinc transporter protein (ZnT8). Thus, it may be inappropriate to report a patient as autoantibody negative. Another cause of “false-negative” autoantibodies is testing far out from diagnosis as antibody titers diminish over time (Fig. 1). It appears that there is an increased incidence of type 1 diabetes in ethnic populations where autoantibody markers may be of variable utility, such as in Asians where autoantibodies are often negative (11–15).
Figure 1
View larger version:
In this page In a new window
Download as PowerPoint Slide
Figure 1
The percentage of antibody-positive subjects is affected by the duration of type 1 diabetes for GADA (A) and IA2A (B). Given an increase in the scatter (due to lower numbers of subjects), the x-axis is truncated at a duration of 30 years. Reproduced with permission from Tridgell et al. (16).
Family History
Type 1 diabetes has a genetic predilection and, in some cases, can be predicted in family members. The overall prevalence of type 1 diabetes in the U.S. is ∼0.3%, but if a first-degree relative has diabetes, the empiric risk of being affected is ∼5% (17,18), representing a 15-fold increase among family members. Studies evaluating children at risk for developing type 1 diabetes have shown that the presence of more than two autoantibodies was associated with a nearly 70% risk for disease development within 10 years and 84% within 15 years (19). Evaluating at-risk individuals in the clinical setting is not yet recommended due to limited clinical interventions; however, ongoing research studies are identifying at-risk individuals through genetic testing in both the lower-risk general population and in the higher-risk population of relatives of people with type 1 diabetes.
Recommendations
Diagnosis
The American Diabetes Association’s (ADA’s) diagnostic criteria for type 1 and type 2 diabetes are the same (Table 1). (A)
Consider measurement of pancreatic autoantibodies to confirm the diagnosis of type 1 diabetes. (B)
View this table:
In this window In a new window
Table 1
Criteria for the diagnosis of diabetes
Identification of At-Risk Relatives
Inform type 1 diabetic patients of the opportunity to have their relatives tested for type 1 diabetes risk in the setting of a clinical research study. (B)
Previous Section
Next Section
Initial Evaluation and Follow-up
General Considerations
All patients with type 1 diabetes need age-appropriate care, with an understanding of their specific needs and limitations. Infants and toddlers are approached quite differently from adolescents; the needs of young adults may vary from middle-aged or older adults. Regardless of age, the patient’s needs are the same: an individualized care plan with ongoing education and support, ongoing assessment for acute and chronic complications, and access to medical providers with type 1 diabetes expertise. Just as patients change, the therapeutic approach should change and should be evaluated at each visit and modified as needed.
Type 1 diabetes care must be an iterative process, adapted as the needs of the individual evolve. Clinical assessments for type 1 diabetes in children and adults should incorporate age-appropriate and complication-focused evaluations, based on the likelihood that an abnormality will be present. For example, a young adult with low cardiovascular disease (CVD) risk and no complications may need more of an assessment of lifestyle adjustment as opposed to an older adult with longer duration of the disease who may need more evaluation of vascular and neurological issues.
Transition of Care From Pediatric to Adult Providers
As youth transition into emerging adulthood, the supportive infrastructure often abruptly disappears and glycemic control tends to deteriorate. The ADA recognizes that this is a challenging time and recommends a strong, practical transition plan to anticipate the upcoming changes. A successful transition plan should be initiated early (e.g., early teenage years) and include ongoing dialogue between the family and youth. The discussion should include fin
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