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Diabetes Mellitus Type 2Published by: Domus Medica | SSMGLast published: 2017Diabète sucré de type 2Published by: SSMG | Domus MedicaLast published: 20171st tests to order
HbA1c
Test
Confirm with a repeat HbA1c or another diabetes diagnostic test. If using two separate test samples, it is recommended that the second test be performed without delay.[2] HbA1c reflects degree of hyperglycemia over the preceding 2-3 months (as opposed to glucose, which provides an acute measure).[2] Unlike glucose measurement, it uses a standardized assay, is unaffected by recent food intake, stress, illness, or activity, and there is no requirement for patients to fast.[2] However, HbA1c is a more expensive test, not as widely available, and requires a whole blood sample for diagnosis (although point-of-care assays using capillary blood can be used for disease monitoring).[2]
Some variability in HbA1c results is possible as a result of such factors as increased red blood cell turnover (e.g., sickle cell anemia), factors related to ancestry, or laboratory variation.[2] The American Diabetes Association recommends that blood glucose criteria (and not HbA1c) should be used to diagnose diabetes in people with hemoglobinopathies including sickle cell disease, in women who are pregnant (second and third trimesters and the postpartum period), and those with glucose-6-phosphate dehydrogenase deficiency, HIV, hemodialysis, recent blood loss or transfusion, or on erythropoietin therapy.[2] Marked discordance between measured HbA1c and plasma glucose levels should raise the possibility of HbA1c assay interference (causes of which include hemoglobin variants, severe hypertriglyceridemia, and severe hyperbilirubinemia).[2]
Result
≥6.5% (≥48 mmol/mol)
fasting plasma glucose
Test
Order after a minimum 8-hour fast. Confirm an elevated result with an HbA1c (which can be done on the same sample), a second fasting plasma glucose, or another diabetes diagnostic test.[2]
Result
≥126 mg/dL (≥7.0 mmol/L)
2-hour plasma glucose
Test
Plasma glucose is measured 2 hours after 75 g oral glucose load.[2]
Patients should be advised to consume a varied diet with at least 150 g of carbohydrate on the 3 days prior to testing, as fasting and carbohydrate restriction can falsely increase plasma glucose levels.[2] May be particularly useful when diagnosing older adults.[35]
Result
≥200 mg/dL (≥11.1 mmol/L)
random plasma glucose
Test
Confirms diagnosis in the presence of symptoms of hyperglycemia or hyperglycemic crisis (e.g., polyuria, polydipsia, and unexplained weight loss).[2]
Result
≥200 mg/dL (≥11.1 mmol/L)
Tests to consider
urine ketones
Test
Urine ketones should be checked if patients are symptomatic of hyperglycemia (polyuria, polydipsia, weakness) and volume depletion (dry mucous membranes, poor skin turgor, tachycardia, hypotension, and, in severe cases, shock) at diagnosis or throughout course of disease. Diabetic ketoacidosis (DKA) is a common presentation of type 1 diabetes, but can also occur in type 2 diabetes, particularly in ethnic and racial minorities, or if there is an underlying infection.[2][107] It should be noted that clinical overlap between DKA and hyperosmolar hyperglycemic state (HHS) has been reported in more than one third of people with hyperglycemic crises, thus traces of urinary ketones and mild-to-moderate ketonemia may also be present in HHS.[3][105]
Result
positive in instances of ketoacidosis
random C-peptide
Test
Not done routinely for diagnosis of diabetes, but may be useful in differentiating type 1 and type 2 diabetes when performed in conjunction with a glucose test.[108] Absolute insulin deficiency is a key feature of type 1 diabetes, which results in low (<0.6 ng/mL [<200 pmol/L]) or undetectable levels of plasma C-peptide.[108] C-peptide values are only meaningful when considered with a corresponding glucose measurement; in the presence of hypoglycemia, a low C-peptide may simply indicate appropriate insulin suppression and does not necessarily signify a problem with insulin production. C-peptide results must also be interpreted in clinical context of disease duration, comorbidities, and family history.[109] Although C-peptide can be helpful in evaluating the endogenous production of insulin, both type 1 and type 2 diabetes can be associated with insulinopenia, and endogenous insulin production can be detected in some individuals with type 1 diabetes for prolonged periods of time after diagnosis, especially in individuals diagnosed in adulthood.
Result
normal or high
autoantibodies
Test
Not done routinely for diagnosis of diabetes, but is an option for differentiating type 1 and type 2 diabetes.[2]
Autoantibodies to glutamic acid decarboxylase (GAD), tyrosine phosphatase 2 (IA-2), and zinc transporter 8 (ZnT8) can help to identify individuals with immune-mediated diabetes, although these antibodies fade with time after the onset of illness.[2]
Result
presence suggests immune-mediated diabetes
urinary albumin to creatinine ratio (ACR)
Test
Indicates nephropathy and suggests possible other microvascular damage. Monitored at least yearly.[2] Albuminuria is an independent definition of chronic kidney disease (CKD) even if estimated glomerular filtration rate (eGFR) is ≥60 mL/minute/1.73 m². Detecting albuminuria is important because early intervention can prevent progression of CKD.[114]
ACR may be assessed with a random urine sample.[2] To confirm moderately increased albuminuria (previously known as microalbuminuria) or severely increased albuminuria (previously known as macroalbuminuria), 2 of 3 specimens collected within 3-6 months should be abnormal.[2]
Exercise within 24 hours of specimen collection, infection, fever, congestive heart failure, significant hyperglycemia or hypertension, and menstruation may increase urinary ACR independently of kidney damage.[2]
Result
may be normal or increased; normal to mildly increased: <30 mg/g; moderately increased: 30-299 mg/g; severely increased: ≥300 mg/g
serum creatinine and estimated GFR (eGFR)
Test
Checks for chronic kidney disease (CKD), which may be present at diagnosis.[2] Reduced eGFR without albuminuria is frequently reported in people with type 2 (and type 1) diabetes and has become more common over time with increasing prevalence of diabetes; such patients usually have a better renal prognosis than those with overt albuminuria.[2]
A 2021 task force convened by the National Kidney Foundation and the American Society of Nephrology recommended the adoption of the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation (2021) that estimates kidney function without a race variable.[111] [ Glomerular Filtration Rate Estimation (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Equation with Creatinine, without Race (2021) Opens in new window ] This replaces the original CKD-EPI equation which was previously widely used to estimate kidney function with an adjustment for black race.[111]
Result
may show CKD, defined as eGFR <60 mL/minute/1.73 m² (persistent for at least 3 months)
fasting lipid profile
Test
Dyslipidemia is common in type 2 diabetes, especially low HDL and high triglycerides.[2]
Result
may show high LDL, low HDL, and/or high triglycerides
ECG
Test
All patients with symptoms or signs suggestive of coronary artery disease should have a resting 12-lead ECG (although a normal ECG does not rule out coronary artery disease). Patients with an abnormal resting ECG may require further cardiac investigation. See Diabetic cardiovascular disease.
Result
may indicate cardiac ischemia
B-type natriuretic peptide (BNP)/N-terminal prohormone B-natriuretic peptide (NT-proBNP)
Test
Can be considered to screen asymptomatic adults with diabetes for heart failure (HF).[2] If abnormal natriuretic peptide levels are detected, echocardiography is recommended. Identification, risk stratification, and early treatment of risk factors in people with diabetes and asymptomatic stages of HF reduce the risk for progression to symptomatic HF.[2]
Result
elevated in HF
ankle-brachial index (ABI)
Test
A noninvasive tool to detect peripheral arterial disease (PAD), which has a high prevalence in patients with diabetes. The American Diabetes Association recommends that ABI should be performed in patients with symptoms of PAD and/or those with decreased or absent foot pulses.[2] It also recommends screening for PAD using ABI in asymptomatic people in whom a diagnosis may help further intensify pharmacologic therapies. These include people with any of the following characteristics: age ≥65 years; diabetes with duration ≥10 years; comorbid microvascular disease; clinical evidence of foot complications; or any end-organ damage from diabetes.[2]
Result
≤0.9 is abnormal
toe-brachial index (TBI)
Test
Due to the potential for calcification of the arteries from atherosclerotic peripheral vascular disease (which falsely elevates ABI), toe pressure testing is often done as an adjunct to ABI testing.[113]
Result
≤0.7 is abnormal
dilated retinal examination
Test
Patients should be referred to an eye specialist (e.g., ophthalmologist or optometrist) at the time of diagnosis of type 2 diabetes. Patients with type 2 diabetes may have been undiagnosed for many years and have a significant risk of retinopathy at the time of diagnosis.[2]
Result
may show retinopathy
liver function test (LFT)
Test
Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (MASLD; previously known as nonalcoholic fatty liver disease) commonly coexist. LFTs are recommended by the American Diabetes Association for comprehensive medical evaluation at initial diagnosis.[2] Alanine aminotransferase and aspartate aminotransferase levels, along with patient age and platelet count, can also be used to calculate fibrosis 4 (FIB-4) index.[2] [ Cirrhosis probability in hepatitis C (FIB-4) Opens in new window ]
Result
liver enzymes may be elevated
platelet count
Test
Platelet count is required for calculation of fibrosis-4 (FIB-4) index. All patients, even those with normal liver enzymes, should be screened and risk-stratified for clinically significant fibrosis (defined as moderate fibrosis to cirrhosis) secondary to metabolic dysfunction-associated steatotic liver disease (MASLD; previously known as nonalcoholic fatty liver disease) using FIB-4 index (derived from age, alanine aminotransferase, aspartate aminotransferase, and platelets).[2] [ Cirrhosis probability in hepatitis C (FIB-4) Opens in new window ]
Result
thrombocytopenia may be present in patients with chronic liver disease
noninvasive tests of liver elasticity
Test
Type 2 diabetes mellitus and metabolic dysfunction-associated steatotic liver disease (MASLD; previously known as nonalcoholic fatty liver disease) commonly coexist. All patients with type 2 diabetes or prediabetes, even those with normal liver enzymes, should be screened and risk-stratified for clinically significant fibrosis (defined as moderate fibrosis to cirrhosis) secondary to MASLD using a calculated FIB-4 index (derived from age, alanine aminotransferase, aspartate aminotransferase, and platelets).[2] [ Cirrhosis probability in hepatitis C (FIB-4) Opens in new window ]
Patients with a FIB-4 ≥1.3 should have additional risk stratification by liver stiffness measurement with transient elastography, or by measurement of enhanced liver fibrosis (ELF), a blood biomarker.[2] Those at higher risk for significant liver fibrosis (i.e., as indicated by FIB-4, liver stiffness measurement, or ELF) should be referred to a gastroenterologist or hepatologist for further evaluation and management.[2] The FIB-4 score has limitations in patients age ≥65 years, where its specificity decreases, potentially leading to overestimation of fibrosis.[112] To mitigate this, age-adjusted cutoffs may be necessary.
Result
serologic marker and ultrasound-based elastography evidence of fibrosis
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