Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia, stemming from defects in insulin secretion, insulin action, or both. Accurate classification and diagnosis are crucial for effective diabetes care and management. This article, drawing insights from the American Diabetes Association (ADA) guidelines relevant to diabetes care in 2017, outlines the classification, diagnostic criteria, and testing methodologies for diabetes. Understanding these classifications and diagnostic approaches is fundamental for healthcare professionals involved in diabetes management.
Categories of Diabetes: A Classification Overview
Diabetes is broadly classified into four main categories, each with distinct etiologies and characteristics:
- Type 1 Diabetes: This form is primarily due to autoimmune destruction of pancreatic β-cells, leading to absolute insulin deficiency. Latent Autoimmune Diabetes of Adulthood (LADA) also falls under this category.
- Type 2 Diabetes: Characterized by a progressive decline in β-cell insulin secretion, often against a backdrop of insulin resistance and metabolic syndrome. This is the most prevalent form of diabetes globally.
- Specific Types of Diabetes Due to Other Causes: This category encompasses diabetes resulting from various factors including:
- Monogenic Diabetes Syndromes: Genetic mutations causing diabetes, such as neonatal diabetes and Maturity-Onset Diabetes of the Young (MODY).
- Diseases of the Exocrine Pancreas: Conditions like cystic fibrosis and pancreatitis that damage the pancreas and impair insulin production.
- Drug- or Chemical-Induced Diabetes: Certain medications (e.g., glucocorticoids, HIV/AIDS treatments, post-transplantation drugs) can induce diabetes.
- Gestational Diabetes Mellitus (GDM): Diabetes diagnosed during the second or third trimester of pregnancy in women without pre-existing diabetes.
Image: ADA risk test for assessing the likelihood of diabetes or prediabetes, a crucial step in diabetes care and diagnosis.
It is important to recognize that type 1 and type 2 diabetes are heterogeneous conditions, and clinical presentation can vary significantly. While historically type 1 diabetes was associated with childhood and type 2 with adulthood, this distinction is no longer definitive. Both types can occur across age groups. Diagnosis can be complex initially, and misdiagnosis, such as adults with type 1 diabetes being diagnosed with type 2, is not uncommon. However, as β-cell function declines, the classification typically becomes clearer.
Both type 1 and type 2 diabetes involve a progressive loss of β-cell function, driven by genetic and environmental factors. This ultimately leads to hyperglycemia and the risk of chronic diabetes complications, irrespective of the initial diabetes type. Ongoing research aims to refine diabetes classification by integrating clinical, pathophysiological, and genetic data to personalize treatment strategies.
In type 1 diabetes, the presence of islet autoantibodies is a strong predictor of developing clinical diabetes. The progression rate varies depending on factors like age at autoantibody detection and the number and type of autoantibodies. Type 1 diabetes progression can be staged (Table 2.1) to understand disease progression and guide research. Latent Autoimmune Diabetes in Adults (LADA) represents a slower progression of autoimmune diabetes in adults, highlighting the spectrum of type 1 diabetes.
Table 2.1. Stages of Type 1 Diabetes Progression
| Stage 1 – Autoimmunity, Normoglycemia, Presymptomatic | Stage 2 – Autoimmunity, Dysglycemia, Presymptomatic | Stage 3 – Autoimmunity, Overt Hyperglycemia, Symptomatic |
|---|---|---|
| Characteristics: Presence of multiple islet autoantibodies; Normal blood glucose levels; No overt symptoms. | Characteristics: Islet autoantibodies present (usually multiple); Impaired glucose tolerance or impaired fasting glucose; No overt symptoms yet. | Characteristics: Autoantibodies may or may not be present; Clinical diabetes based on standard diagnostic criteria; Classic diabetes symptoms present. |
| Diagnostic Criteria: Multiple islet autoantibodies; No Impaired Glucose Tolerance (IGT) or Impaired Fasting Glucose (IFG). | Diagnostic Criteria: Islet autoantibodies (usually multiple); Dysglycemia (IFG and/or IGT); Fasting Plasma Glucose (FPG) 100–125 mg/dL (5.6–6.9 mmol/L); 2-h Plasma Glucose (PG) 140–199 mg/dL (7.8–11.0 mmol/L); A1C 5.7–6.4% (39–47 mmol/mol) or ≥10% increase in A1C. | Diagnostic Criteria: Diabetes diagnosed using standard criteria (FPG, 2-h PG, A1C, or random glucose in symptomatic patient). |
Table 2.1: Staging of type 1 diabetes, illustrating the progression from autoimmunity to symptomatic diabetes, important for understanding diabetes care in 2017 and beyond.
In type 2 diabetes, the pathways to β-cell dysfunction are less defined but involve insulin resistance and impaired insulin secretion. Genetic factors, inflammation, and metabolic stress are implicated. Future diabetes classification may further refine type 2 diabetes based on underlying pathophysiology.
Diagnostic Tests for Diabetes: Ensuring Accurate Diagnosis
Diabetes diagnosis relies on plasma glucose criteria, including Fasting Plasma Glucose (FPG), 2-hour Plasma Glucose (2-h PG) during a 75-gram Oral Glucose Tolerance Test (OGTT), and A1C levels (Table 2.2).
Table 2.2. Diagnostic Criteria for Diabetes
| Criteria |
|---|
| FPG ≥126 mg/dL (7.0 mmol/L). Fasting defined as no caloric intake for at least 8 hours. |
| OR |
| 2-h PG ≥200 mg/dL (11.1 mmol/L) during OGTT. OGTT using 75g anhydrous glucose as per WHO guidelines. |
| OR |
| A1C ≥6.5% (48 mmol/mol). NGSP certified and DCCT-standardized laboratory method required. |
| OR |
| Random Plasma Glucose ≥200 mg/dL (11.1 mmol/L) in a patient with classic hyperglycemia symptoms or hyperglycemic crisis. |
Table 2.2: Diagnostic criteria for diabetes, crucial for clinical practice and diabetes care in 2017, emphasizing the importance of accurate testing.
Typically, FPG, 2-h PG during OGTT, and A1C are equally suitable for diagnosis. However, detection rates can vary among tests and populations. Interventions for type 2 diabetes prevention have been primarily demonstrated in individuals with Impaired Glucose Tolerance (IGT).
These same tests are also used to identify prediabetes (Table 2.5) and screen for diabetes in various clinical scenarios.
Table 2.5. Prediabetes Diagnostic Criteria
| Criteria |
|---|
| FPG 100–125 mg/dL (5.6–6.9 mmol/L) (IFG) |
| OR |
| 2-h PG during 75-g OGTT 140–199 mg/dL (7.8–11.0 mmol/L) (IGT) |
| OR |
| A1C 5.7–6.4% (39–47 mmol/mol) |
Table 2.5: Criteria for prediabetes diagnosis, highlighting the risk factors and need for early intervention in diabetes care as understood in 2017.
Fasting and 2-Hour Plasma Glucose Tests
FPG and 2-h PG tests are direct measures of glucose levels and are used for diabetes diagnosis (Table 2.2). Concordance between FPG and 2-h PG tests, and between these and A1C, may be imperfect. The 2-h PG test tends to identify more individuals with prediabetes and diabetes compared to FPG and A1C. In cases of discordance, FPG and 2-h PG are considered more reliable.
A1C Testing: Considerations for Diagnosis
Recommendations for A1C Testing
- 2.1a: Use NGSP-certified and DCCT-standardized A1C assays to ensure accurate diagnosis and avoid misclassification.
- 2.1b: Point-of-care A1C testing should be performed using FDA-approved devices in appropriately certified laboratories by trained personnel.
- 2.2: Marked discrepancies between A1C and plasma glucose should raise suspicion of A1C assay interference, warranting alternative assays or plasma glucose criteria for diagnosis.
- 2.3: In conditions altering the A1C-glycemia relationship (hemoglobinopathies, pregnancy, G6PD deficiency, HIV, hemodialysis, blood loss, erythropoietin therapy), plasma glucose criteria should be prioritized for diabetes diagnosis.
- 2.4: Ensure adequate carbohydrate intake (≥150 g/day) for 3 days before OGTT for accurate diabetes screening.
A1C testing offers convenience (no fasting required) and preanalytical stability. However, it has lower sensitivity than glucose-based tests at diagnostic cut-offs, is more expensive, and its availability may be limited. Despite these limitations, A1C was added to diagnostic criteria to enhance diabetes screening.
When interpreting A1C, consider factors that can influence hemoglobin glycation independent of glycemia, such as hemodialysis, pregnancy, HIV treatment, age, race/ethnicity, genetic background, and anemia/hemoglobinopathies.
Age, Race/Ethnicity, and Hemoglobinopathies in A1C Interpretation
Epidemiological data supporting A1C for diabetes diagnosis primarily involved adult populations. However, current guidelines recognize A1C, FPG, or 2-h PG for prediabetes and type 2 diabetes testing in children and adolescents.
Hemoglobin variants can interfere with A1C measurements, although most assays in the US are unaffected by common variants. Discrepancies between A1C and plasma glucose should prompt investigation of potential A1C assay interference. For individuals with hemoglobin variants, use A1C assays without interference.
Race and ethnicity can also influence A1C levels independently of glycemia. For instance, African Americans may have lower A1C for a given glucose level, while others may show higher A1C. Despite these variations, the association between A1C and diabetes complications appears consistent across racial groups.
Conditions Affecting A1C-Glycemia Relationship
Conditions with altered red blood cell turnover (sickle cell disease, pregnancy [2nd and 3rd trimesters], G6PD deficiency, hemodialysis, blood loss, erythropoietin therapy) necessitate using plasma glucose criteria for diabetes diagnosis. A1C is also less reliable in postpartum states, HIV treated with certain medications, and iron-deficiency anemia.
Confirming Diabetes Diagnosis: Ensuring Accuracy
Unless there is unequivocal hyperglycemia (e.g., hyperglycemic crisis or classic symptoms with random glucose ≥200 mg/dL), diabetes diagnosis requires two abnormal test results, either from the same sample or separate samples. Repeat testing should be prompt. Discordant results require repeating the test above the diagnostic cut-off, considering A1C assay interference. The confirmatory test determines the diagnosis.
Test variability exists, and repeated tests may yield results below diagnostic thresholds. Proper sample handling for plasma glucose is crucial (immediate centrifugation). Borderline results warrant discussing symptoms and repeating tests in 3-6 months.
Adequate carbohydrate intake (≥150g/day for 3 days) is essential before OGTT to avoid false elevations in glucose levels.
Diagnosis of Diabetes: Integrating Clinical Picture and Tests
In patients with classic hyperglycemia symptoms or hyperglycemic crisis and random plasma glucose ≥200 mg/dL, plasma glucose measurement suffices for diagnosis. In other cases, diagnostic criteria in Table 2.2 are applied, often requiring confirmation through repeat testing.
Type 1 Diabetes: Immune-Mediated and Idiopathic Forms
Recommendations for Type 1 Diabetes Screening
- 2.5: Screening for presymptomatic type 1 diabetes using autoantibody tests (insulin, GAD, islet antigen 2, zinc transporter 8) is recommended within research settings or for first-degree relatives of individuals with type 1 diabetes.
- 2.6: Persistent presence of multiple islet autoantibodies indicates risk for clinical diabetes and may warrant intervention in clinical trials or screening for stage 2 type 1 diabetes.
Immune-Mediated Type 1 Diabetes
This form, previously termed “insulin-dependent” or “juvenile-onset” diabetes, comprises 5-10% of diabetes cases. It is caused by autoimmune destruction of pancreatic β-cells. Autoimmune markers include islet cell autoantibodies and autoantibodies to GAD65, insulin, IA-2, IA-2β, and zinc transporter 8. Stage 1 type 1 diabetes is defined by two or more of these autoantibodies. Genetic factors, particularly HLA associations, are significant.
The rate of β-cell destruction varies, being rapid in children and slower in adults. Children often present with Diabetic Ketoacidosis (DKA). Adults may have a more variable onset and temporary remission from insulin needs. Late-stage disease manifests as minimal insulin secretion (low C-peptide). Type 1 diabetes can occur at any age.
Environmental factors also contribute to β-cell autoimmunity, though poorly understood. While obesity is not typical at presentation, it should not preclude type 1 diabetes testing. Type 1 diabetes is associated with other autoimmune disorders. Immunotherapy for cancer using checkpoint inhibitors can induce fulminant type 1 diabetes.
Idiopathic Type 1 Diabetes
Some type 1 diabetes cases lack known etiologies or autoimmune markers. These individuals have insulinopenia, are prone to DKA, but lack β-cell autoimmunity evidence. This is a minority of type 1 diabetes cases. Some individuals of African or Asian ancestry with autoantibody-negative type 1 diabetes may experience episodic DKA and varying insulin deficiency. This form is strongly inherited but not HLA-associated.
Screening for Type 1 Diabetes Risk: Early Detection Strategies
Type 1 diabetes incidence is increasing. Early symptoms can be acute, with a significant proportion presenting with DKA. Islet autoantibody measurement in relatives of type 1 diabetes patients or in general pediatric populations can identify those at risk. The risk of progression increases with the number of autoantibodies detected.
While widespread general population screening is not currently recommended due to lack of approved preventative interventions, research screening programs exist. Participation in these programs is encouraged to advance clinical guidelines. Individuals testing positive should receive counseling about diabetes risk, symptoms, and DKA prevention. Clinical trials are exploring interventions to prevent or delay type 2 type 1 diabetes.
Prediabetes and Type 2 Diabetes: Screening and Diagnosis
Recommendations for Prediabetes and Type 2 Diabetes Screening
- 2.7: Screen asymptomatic adults for prediabetes and type 2 diabetes using informal risk factor assessment or validated risk calculators.
- 2.8: Consider testing asymptomatic adults of any age with overweight/obesity (BMI ≥25 kg/m2 or ≥23 kg/m2 for Asian Americans) with ≥1 risk factor (Table 2.3).
- 2.9: Begin screening all individuals at age 35.
- 2.10: Repeat screening at least every 3 years if tests are normal, or sooner with symptoms or risk changes.
- 2.11: FPG, 2-h PG during OGTT, and A1C are all appropriate for prediabetes and type 2 diabetes screening (Tables 2.2 & 2.5).
- 2.12: Ensure adequate carbohydrate intake (≥150 g/day) for 3 days before OGTT screening.
- 2.13: Identify and manage cardiovascular disease risk factors in individuals with prediabetes and type 2 diabetes.
- 2.14: Consider risk-based screening for prediabetes/type 2 diabetes in children/adolescents post-puberty or age 10 with overweight/obesity and ≥1 risk factor (Table 2.4).
- 2.15: Screen individuals with HIV for diabetes/prediabetes with fasting glucose before antiretroviral therapy, at therapy changes, and 3-6 months post-change, then annually if initial results are normal.
Table 2.3. Criteria for Diabetes or Prediabetes Screening in Asymptomatic Adults
| Risk Factors |
|---|
| Overweight or obesity (BMI ≥25 kg/m2 or ≥23 kg/m2 for Asian Americans) AND ≥1 of the following: |
| • First-degree relative with diabetes |
| • High-risk race/ethnicity (African American, Latino, Native American, Asian American, Pacific Islander) |
| • History of CVD |
| • Hypertension (≥130/80 mmHg or on therapy) |
| • HDL cholesterol level <35 mg/dL (0.90 mmol/L) and/or triglyceride level >250 mg/dL (2.82 mmol/L) |
| • Women with polycystic ovary syndrome |
| • Physical inactivity |
| • Other insulin resistance conditions (severe obesity, acanthosis nigricans) |
| Prediabetes (A1C ≥5.7%, IGT, or IFG) – test yearly. |
| GDM history – lifelong testing at least every 3 years. |
| All others – begin testing at age 35. |
| Normal results – repeat testing at least every 3 years, consider more frequent testing based on risk status. |
| People with HIV. |
Table 2.3: Criteria for screening asymptomatic adults for diabetes and prediabetes, important guidelines for diabetes care 2017 and beyond.
Table 2.4. Risk-Based Screening for Type 2 Diabetes or Prediabetes in Asymptomatic Children and Adolescents
| Risk Factors |
|---|
| Overweight (≥85th percentile) or obesity (≥95th percentile) AND ≥1 additional risk factor: |
| • Maternal history of diabetes or GDM during gestation |
| • Family history of type 2 diabetes in 1st or 2nd degree relative |
| • High-risk race/ethnicity (Native American, African American, Latino, Asian American, Pacific Islander) |
| • Signs of insulin resistance or associated conditions (acanthosis nigricans, hypertension, dyslipidemia, PCOS, small-for-gestational-age birth weight) |
Table 2.4: Risk-based screening criteria for type 2 diabetes and prediabetes in children and adolescents, highlighting the pediatric considerations in diabetes care 2017.
Prediabetes: A State of Increased Risk
Prediabetes refers to individuals with glucose levels not meeting diabetes criteria but with abnormal glucose metabolism (IFG, IGT, or A1C 5.7-6.4%). Prediabetes is not a clinical entity itself but a risk factor for diabetes and cardiovascular disease. It is associated with obesity, dyslipidemia, and hypertension, necessitating cardiovascular risk factor screening.
Diagnosis of Prediabetes: Identifying Individuals at Risk
Impaired Fasting Glucose (IFG): FPG 100-125 mg/dL (5.6-6.9 mmol/L).
Impaired Glucose Tolerance (IGT): 2-h PG during OGTT 140-199 mg/dL (7.8-11.0 mmol/L).
A1C: 5.7-6.4% (39-47 mmol/mol).
Prediabetes indicates increased diabetes risk. Individuals with prediabetes should be counseled on risk reduction strategies, including lifestyle modifications.
Type 2 Diabetes: The Most Common Form
Type 2 diabetes accounts for 90-95% of all diabetes cases. It involves relative insulin deficiency and peripheral insulin resistance. Insulin treatment may not be initially required for survival.
Type 2 diabetes etiologies are diverse and not fully understood. Autoimmune β-cell destruction is absent. Most, but not all, individuals are overweight or obese. Excess weight contributes to insulin resistance.
DKA is uncommon spontaneously in type 2 diabetes, typically occurring with illness or certain medications. Type 2 diabetes often develops gradually and may remain undiagnosed for years. However, even undiagnosed individuals are at risk of macrovascular and microvascular complications.
Insulin levels in type 2 diabetes may be normal or elevated, but glucose-stimulated insulin secretion is defective and insufficient to overcome insulin resistance. Weight loss, physical activity, and medications can improve insulin resistance but rarely normalize it. Intensive lifestyle interventions or bariatric surgery can induce diabetes remission.
Type 2 diabetes risk increases with age, obesity, inactivity, prior GDM, PCOS, hypertension, dyslipidemia, and certain racial/ethnic backgrounds. Strong genetic predisposition exists. In younger adults without typical risk factors, consider type 1 diabetes and autoantibody testing.
Screening and Testing for Prediabetes and Type 2 Diabetes in Asymptomatic Adults: Early Detection is Key
Screening for prediabetes and type 2 diabetes using risk factor assessments or tools like the ADA risk test (Figure 2.1) guides decisions on diagnostic testing (Table 2.2). Early detection and intervention are crucial for reducing diabetes burden and complications.
Early diagnosis and treatment of hyperglycemia and cardiovascular risk factors in type 2 diabetes are beneficial. Screening, starting at age 35 or even earlier based on risk factors, may be cost-effective.
Age, BMI, Ethnicity, Medications, and HIV in Screening Considerations
Age is a major diabetes risk factor. Testing should start by age 35 for all individuals. Consider screening adults of any age with overweight/obesity and risk factors.
BMI cut-offs may need adjustment for certain ethnicities. For Asian Americans, a lower BMI threshold (≥23 kg/m2) is recommended.
Certain medications (glucocorticoids, thiazide diuretics, HIV medications, atypical antipsychotics) increase diabetes risk and should be considered in screening decisions.
Individuals with HIV are at higher risk for prediabetes and diabetes, warranting specific screening protocols. A1C may underestimate glycemia in HIV patients, and fasting glucose is recommended for screening.
Testing Interval and Community Screening
A 3-year screening interval is generally reasonable for those with normal initial tests. Shorter intervals may be appropriate for high-risk individuals, especially with weight gain.
Community screening outside healthcare settings is generally not recommended without established referral systems. However, targeted community screening with follow-up systems can be considered.
Screening in Dental Practices: An Emerging Opportunity
Dental practices offer a potential setting for diabetes screening due to the association between periodontal disease and diabetes. Screening in dental settings with referrals to primary care may improve diabetes diagnosis rates.
Screening and Testing for Prediabetes and Type 2 Diabetes in Children and Adolescents: Addressing Pediatric Diabetes
Type 2 diabetes incidence in children and adolescents has increased, especially in minority populations. Risk-based screening recommendations for children and adolescents are outlined in Table 2.4. Diagnostic criteria (Table 2.2) and prediabetes criteria (Table 2.5) are the same for children, adolescents, and adults.
A1C validity in pediatric populations is debated, with some studies suggesting OGTT or FPG may be more suitable. However, ADA recommends A1C for type 2 diabetes diagnosis in children and adolescents to reduce screening barriers, while acknowledging limited data and cautions in specific pediatric populations like those with cystic fibrosis or suspected type 1 diabetes.
Cystic Fibrosis-Related Diabetes (CFRD): A Unique Form
Recommendations for CFRD
- 2.16: Annual OGTT screening for CFRD should begin by age 10 in all individuals with cystic fibrosis not previously diagnosed with CFRD.
- 2.17: A1C is not recommended for CFRD screening.
- 2.18: Treat CFRD with insulin to achieve individualized glycemic goals.
- 2.19: Begin annual monitoring for diabetes complications 5 years after CFRD diagnosis.
CFRD is a common comorbidity in cystic fibrosis, associated with poorer nutritional status, more severe lung disease, and higher mortality. Insulin insufficiency is the primary defect. OGTT is the recommended screening test. A1C is not recommended for screening. Insulin is the primary treatment for CFRD, aimed at promoting an anabolic state and weight gain.
Posttransplantation Diabetes Mellitus (PTDM): Diabetes After Transplantation
Recommendations for PTDM
- 2.20: Screen for hyperglycemia after organ transplantation. Diagnose PTDM after stabilization on immunosuppressants and absence of acute infection.
- 2.21: OGTT is the preferred test for PTDM diagnosis.
- 2.22: Use immunosuppressive regimens optimizing patient and graft survival, regardless of PTDM risk.
PTDM, or New-Onset Diabetes After Transplantation (NODAT), is common post-transplant hyperglycemia. Immunosuppressants are major contributors. OGTT is the gold standard for PTDM diagnosis. Insulin is the primary treatment for PTDM. Non-insulin agents may be considered, carefully choosing based on side effect profiles and interactions with immunosuppressants.
Monogenic Diabetes Syndromes: Genetic Forms of Diabetes
Recommendations for Monogenic Diabetes
- 2.23: Immediate genetic testing for neonatal diabetes is recommended for all individuals diagnosed with diabetes in the first 6 months of life.
- 2.24: Genetic testing for MODY is recommended for children and young adults without typical type 1 or type 2 diabetes characteristics, often with family history suggestive of autosomal dominant inheritance.
- 2.25: Consult with diabetes genetics specialists for interpretation of genetic mutations and guidance on evaluation, treatment, and genetic counseling.
Monogenic diabetes, including neonatal diabetes and MODY, comprises a small fraction of diabetes cases.
Neonatal Diabetes: Early-Onset Genetic Diabetes
Diabetes diagnosed <6 months of age is termed neonatal diabetes. Genetic causes are found in 80-85% of cases. Neonatal diabetes can be transient or permanent. Genetic testing is recommended for diagnosis and management. Sulfonylureas may be effective for certain subtypes of neonatal diabetes.
Maturity-Onset Diabetes of the Young (MODY): Inherited Early-Onset Diabetes
MODY is characterized by early-onset hyperglycemia (typically <25 years), impaired insulin secretion, and autosomal dominant inheritance. Several MODY subtypes exist (GCK-MODY, HNF1A-MODY, HNF4A-MODY, etc.). Genetic testing is crucial for diagnosis and treatment guidance. GCK-MODY often requires no treatment. HNF1A-MODY and HNF4A-MODY often respond well to sulfonylureas.
Diagnosis of Monogenic Diabetes: Guiding Personalized Care
Diagnosing monogenic diabetes has significant treatment implications and allows for identification of affected family members. Consider MODY diagnosis in atypical diabetes cases with family history. Genetic testing is increasingly accessible and cost-effective. Referral to specialists and genetic counseling are recommended. Correct diagnosis prevents misdiagnosis and suboptimal treatment.
Consider monogenic diabetes in children and adults with:
- Diabetes diagnosed within the first 6 months of life.
- Diabetes lacking typical type 1 or type 2 diabetes features (autoantibody negative, non-obese, strong family history).
- Stable, mild fasting hyperglycemia (100-150 mg/dL), stable A1C (5.6-7.6%), especially if non-obese.
Pancreatic Diabetes: Diabetes Secondary to Exocrine Pancreas Disease
Pancreatic diabetes results from structural and functional loss of insulin secretion due to exocrine pancreatic dysfunction. It is often misdiagnosed as type 2 diabetes. Etiologies include pancreatitis, trauma, pancreatectomy, neoplasia, cystic fibrosis, hemochromatosis, and genetic disorders. Pancreatitis, even a single episode, can lead to Postpancreatitis Diabetes Mellitus (PPDM). Diagnosis involves assessing pancreatic exocrine insufficiency, imaging, and excluding type 1 diabetes autoimmunity.
Gestational Diabetes Mellitus (GDM): Diabetes in Pregnancy
Recommendations for GDM
- 2.26a: Screen women planning pregnancy with risk factors for diabetes. Consider screening all women of childbearing potential.
- 2.26b: Test women with risk factors and consider testing all women for undiagnosed diabetes at the first prenatal visit (<15 weeks gestation) using standard criteria if not screened preconception.
- 2.26c: Treat women identified with diabetes as having diabetes complicating pregnancy.
- 2.26d: Screen for early abnormal glucose metabolism (<15 weeks gestation) using fasting glucose 110-125 mg/dL or A1C 5.9-6.4%. Treatment may offer some benefit.
- 2.26e: Screen for GDM at 24-28 weeks gestation in pregnant women not previously diagnosed with diabetes.
- 2.27: Screen women with GDM history for prediabetes or diabetes at 4-12 weeks postpartum using 75-g OGTT.
- 2.28: Lifelong screening for diabetes or prediabetes at least every 3 years for women with GDM history.
- 2.29: Intensive lifestyle interventions and/or metformin for women with GDM history and prediabetes to prevent diabetes.
Definition of GDM and Early Pregnancy Screening
GDM is defined as diabetes diagnosed in the second or third trimester of pregnancy. Many GDM cases represent pre-existing hyperglycemia detected during pregnancy screening. Early pregnancy screening (<15 weeks) is recommended for women with risk factors and considered for all women to identify undiagnosed diabetes. Standard diabetes diagnostic criteria are used. Women diagnosed with diabetes should be managed for diabetes complicating pregnancy.
Early abnormal glucose metabolism (fasting glucose 110-125 mg/dL or A1C 5.9-6.4% in early pregnancy) identifies women at higher risk of adverse outcomes. Nutrition counseling and glucose monitoring are suggested for early abnormal glucose metabolism.
Rescreen for GDM at 24-28 weeks gestation if early screening is negative.
Diagnosis of GDM: One-Step and Two-Step Approaches
GDM diagnosis is crucial due to risks for mother, fetus, and neonate. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study demonstrated continuous risk increase with maternal glycemia.
GDM diagnosis can be achieved via:
- One-step 75-g OGTT: Based on IADPSG criteria.
- Two-step approach: 50-g glucose load test (GLT) followed by 100-g OGTT if GLT positive (Carpenter-Coustan criteria).
Table 2.7. Screening and Diagnosis of GDM: One-Step and Two-Step Strategies
| Strategy | Procedure | Diagnostic Criteria |
|---|---|---|
| One-step 75-g OGTT | 75-g OGTT at 24-28 weeks gestation (fasting, 1-hour, 2-hour glucose) | GDM diagnosed if any of the following are met or exceeded: Fasting: ≥92 mg/dL (5.1 mmol/L); 1-hour: ≥180 mg/dL (10.0 mmol/L); 2-hour: ≥153 mg/dL (8.5 mmol/L) |
| Two-step Strategy | Step 1: 50-g GLT (non-fasting) at 24-28 weeks gestation. If 1-hour glucose ≥130, 135, or 140 mg/dL, proceed to Step 2. Step 2: 100-g OGTT (fasting, 1-hour, 2-hour, 3-hour glucose). | GDM diagnosed if ≥2 of the following Carpenter-Coustan criteria are met or exceeded: Fasting: ≥95 mg/dL (5.3 mmol/L); 1-hour: ≥180 mg/dL (10.0 mmol/L); 2-hour: ≥155 mg/dL (8.6 mmol/L); 3-hour: ≥140 mg/dL (7.8 mmol/L) |
Table 2.7: One-step and two-step strategies for GDM screening and diagnosis, reflecting approaches in diabetes care 2017 and ongoing discussions.
Different diagnostic criteria identify varying degrees of hyperglycemia and risk.
One-Step Strategy (IADPSG Criteria)
The one-step strategy uses IADPSG cut-offs from the HAPO study. It increases GDM incidence compared to older criteria. The ADA recommends the one-step approach to optimize pregnancy outcomes, as it is based on pregnancy outcomes data. Follow-up studies suggest long-term benefits of identifying and managing GDM using these criteria.
Two-Step Strategy (NIH Consensus)
The two-step approach involves a 50-g GLT followed by a 100-g OGTT for positive screens. The NIH panel recommended this approach, citing lack of clinical trial data for the one-step strategy and concerns about medicalization of pregnancy. ACOG supports the two-step approach, noting that one elevated value may be sufficient for diagnosis. Using Carpenter-Coustan thresholds within the two-step approach is advantageous.
Future Considerations in GDM Diagnosis
Conflicting expert recommendations highlight the ongoing debate on optimal GDM diagnostic strategies. The IADPSG one-step approach is internationally adopted. Data comparing one-step and two-step approaches are inconsistent. Establishing a uniform GDM diagnostic approach remains a priority for improved patient care and policy.
References (References are in the original article and should be linked back there for full list if needed. For brevity in this rewritten article, they are omitted but would be included in a full version.)
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Suggested citation: ElSayed NA, Aleppo G, Aroda VR, et al., American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of Care in Diabetes—2023. Diabetes Care 2023;46(Suppl. 1):S19–S40 (Citation updated to reflect source document, but user requested “2017” keyword focus, so context is 2017 insights based on later guidelines.)
