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Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome Canadian Journal of Diabetes

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Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome Canadian Journal of Diabetes Can J Diabetes 42 (2018) S10–S15 Contents lists available at ScienceDirect Canadian Journal of Diabetes journal homepage: www.canadianjournalofdiabetes.com 2018 Clinical Practice Guidelines Definition, Classification and Diagnosis of Diabetes, Prediabetes and Metabolic Syndrome Diabetes Canada Clinical Practice Guidelines Expert Committee Zubin Punthakee MD, MSc, FRCPC, Ronald Goldenberg MD, FRCPC, FACE, Pamela Katz MD, FRCPC “Prediabetes” is a practical and convenient term referring to KEY MESSAGES impaired fasting glucose (IFG), impaired glucose tolerance (IGT) (1) or a glycated hemoglobin (A1C) of 6.0% to 6.4%, each of which places • The chronic hyperglycemia of diabetes is associated with significant long- individuals at high risk of developing diabetes and its complications. term microvascular and cardiovascular complications. • A fasting plasma glucose of ≥7.0 mmol/L, a 2-hour plasma glucose value in a 75 g oral glucose tolerance test of ≥11.1 mmol/L or a glycated hemo- globin (A1C) of ≥6.5% can predict the development of retinopathy. This Classification of Diabetes permits the diagnosis of diabetes to be made on the basis of each of these parameters. The majority of cases of diabetes can be broadly classified into • The term “prediabetes” refers to impaired fasting glucose, impaired glucose tolerance or an A1C of 6.0% to 6.4%, each of which places individuals at 2 categories: type 1 diabetes and type 2 diabetes, although some increased risk of developing diabetes and its complications. cases are difficult to classify. Gestational diabetes (GDM) refers to glucose intolerance with onset or first recognition during preg- nancy. The classification of diabetes is summarized in Table 1. Appendix 2 addresses the etiologic classification of diabetes, includ- KEY MESSAGES FOR PEOPLE WITH DIABETES ing less common forms associated with genetic mutations, dis- eases of the exocrine pancreas (such as cystic fibrosis), other diseases • There are 2 main types of diabetes. Type 1 diabetes occurs when the pan- or drug exposure (such as glucocorticoids, medications to treat HIV/ creas is unable to produce insulin. Type 2 diabetes occurs when the pan- AIDS, and atypical antipsychotics). creas does not produce enough insulin or when the body does not effectively Monogenic diabetes is a rare disorder caused by genetic defects use the insulin that is produced. of beta cell function that typically presents in young people (<25 • Gestational diabetes is a type of diabetes that is first recognized or begins during pregnancy. years of age), is noninsulin dependent and is familial, with an auto- • Monogenic diabetes is a rare disorder caused by genetic defects of beta cell somal dominant pattern of inheritance (2). Differentiating between function. type 1, type 2 and monogenic diabetes is important but can be • Prediabetes refers to blood glucose levels that are higher than normal, but difficult at the time of diagnosis in certain situations. Table 2 not yet high enough to be diagnosed as type 2 diabetes. Although not every- one with prediabetes will develop type 2 diabetes, many people will. highlights the main features of type 1 diabetes, including LADA form, • You should discuss the type of diabetes you have with your diabetes type 2 diabetes and monogenic diabetes. No diagnostic test or clinical health-care team. • There are several types of blood tests that can be done to determine if a person has diabetes and, in most cases, a confirmatory blood test is required Table 1 to be sure. Classification of diabetes • Type 1 diabetes* encompasses diabetes that is primarily a result of Definition of Diabetes and Prediabetes pancreatic beta cell destruction with consequent insulin deficiency, which is prone to ketoacidosis. This form includes cases due to an autoimmune process and those for which the etiology of beta cell destruction is Diabetes mellitus is a heterogeneous metabolic disorder char- unknown. acterized by the presence of hyperglycemia due to impairment of • Type 2 diabetes may range from predominant insulin resistance with insulin secretion, defective insulin action or both. The chronic relative insulin deficiency to a predominant secretory defect with insulin hyperglycemia of diabetes is associated with relatively specific long- resistance. Ketosis is not as common. • Gestational diabetes mellitus refers to glucose intolerance with onset term microvascular complications affecting the eyes, kidneys and or first recognition during pregnancy. nerves, as well as an increased risk for cardiovascular disease (CVD). • Other specific types include a wide variety of relatively uncommon The diagnostic criteria for diabetes are based on thresholds of conditions, primarily specific genetically defined forms of diabetes or glycemia that are associated with microvascular disease, espe- diabetes associated with other diseases or drug use (see Appendix 2. Etiologic Classification of Diabetes Mellitus). cially retinopathy. * Includes latent autoimmune diabetes in adults (LADA); the term used to describe the small number of people with apparent type 2 diabetes who appear to Conflict of interest statements can be found on page S14. have immune-mediated loss of pancreatic beta cells (5). 1499-2671 © 2018 Canadian Diabetes Association. The Canadian Diabetes Association is the registered owner of the name Diabetes Canada. https://doi.org/10.1016/j.jcjd.2017.10.003 Z. Punthakee et al. / Can J Diabetes 42 (2018) S10–S15 S11 Table 2 Clinical features distinguishing type 1 diabetes, type 2 diabetes and monogenic diabetes Clinical features Type 1 diabetes Type 2 diabetes Monogenic diabetes Age of onset (years) Most <25 but can occur at any age (but not Usually >25 but incidence increasing in Usually <25; neonatal diabetes <6 months* before the age of 6 months) adolescents, paralleling increasing rate of obesity in children and adolescents Weight Usually thin, but, with obesity epidemic, >90% at least overweight Similar to general population can have overweight or obesity Islet autoantibodies Usually present Absent Absent C-peptide Undetectable/low Normal/high Normal Insulin production Absent Present Usually present First-line treatment Insulin Noninsulin antihyperglycemic agents, Depends on subtype gradual dependence on insulin may occur Family history of diabetes Infrequent (5%–10%) Frequent (75%–90%) Multigenerational, autosomal pattern of inheritance DKA Common Rare Rare (except for neonatal diabetes*) DKA, diabetic ketoacidosis. * Neonatal diabetes is a form of diabetes with onset <6 months of age, requires genetic testing, and may be amenable to therapy with oral sulfonylurea in place of insulin therapy (3). criteria can reliably make this distinction, but additional testing may risk scoring for type 1 diabetes may provide marginal additional be helpful in atypical presentations if knowing the specific diag- information over clinical features and autoantibodies, but it is too nosis may alter management. One monogenic form to highlight is early to know its utility in clinical practice (13). Clinical judgement neonatal diabetes, which typically presents by 6 months of age and with safe management and ongoing follow up is a prudent approach is indistinguishable from type 1 diabetes in its clinical features, but for all people diagnosed with diabetes, regardless of the type. may be amenable to therapy with oral sulfonylurea in place of insulin therapy. For this reason, all infants diagnosed before 6 months of age should have genetic testing. In addition, all people with a diag- Diagnostic Criteria nosis of type 1 diabetes should be reviewed to determine if diag- nosis occurred prior to 6 months of age and, if so, genetic testing Diabetes should be performed (3). Obesity and physical signs of insulin resistance (e.g. acanthosis The diagnostic criteria for diabetes are summarized in Table 3 nigricans) are more common in children and adolescents with (1). These criteria are based on venous samples and laboratory type 2 diabetes than type 1 diabetes. In adults, a systematic review methods (14). A fasting plasma glucose (FPG) level of 7.0 mmol/L < of clinical indicators identified age at diagnosis of diabetes 30 to correlates most closely with a 2-hour plasma glucose (2hPG) value < 40 years, and time to needing insulin 1 to 2 years as more pre- of ≥11.1 mmol/L in a 75 g oral glucose tolerance test (OGTT), and dictive of type 1 diabetes than body mass index (BMI) (4). The presence of autoimmune markers, such as anti-glutamic acid decarboxylase (GAD) or anti-islet cell (ICA) autoantibodies, may be Table 3 helpful in identifying type 1 diabetes and rapid progression to insulin Diagnosis of diabetes requirement (5), but levels wane over time and they do not have sufficient diagnostic accuracy to be used routinely (6). In cases where FPG ≥7.0 mmol/L Fasting = no caloric intake for at least 8 hours it is difficult to distinguish between type 1, type 2 and monogenic or diabetes, presence of 1 or more autoantibodies (GAD and ICA) indi- A1C ≥6.5% (in adults) cates type 1 diabetes with a need for insulin replacement therapy; Using a standardized, validated assay in the absence of factors that affect the however, the absence of autoantibodies does not rule out type 1 accuracy of the A1C and not for suspected type 1 diabetes (see text) diabetes. If the person has clinical features suggestive of mono- or 2hPG in a 75 g OGTT ≥11.1 mmol/L genic diabetes (familial diabetes with autosomal dominant pattern or of inheritance >2 generations, onset <25 years, not having obesity), Random PG ≥11.1 mmol/L genetic testing for monogenic diabetes may be performed (7). Random = any time of the day, without regard to the interval since the last While very low C-peptide levels measured after months of meal clinical stabilization may favour type 1 diabetes (8), they are not In the absence of symptomatic hyperglycemia, if a single laboratory test result helpful in acute hyperglycemia (9,10). Combined use of autoanti- is in the diabetes range, a repeat confirmatory laboratory test (FPG, A1C, body testing and C-peptide measurement at diagnosis may have 2hPG in a 75 g OGTT) must be done on another day.
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