Diabetes

Diabetes is a common condition that is managed in both the inpatient and outpatient settings. The two main types of diabetes are type 1 and type 2. Highlighted below are some of the classic characteristics of type 1 and type 2 diabetes. However, these characteristics often overlap, and patients may present with mixed features.

• Type 1 diabetes is due to autoimmune beta-cell destruction that leads to absolute insulin deficiency. This includes latent autoimmune diabetes in adults (LADA). The three stages of type 1 diabetes are described in the table below. Patients typically present with symptomatic hyperglycemia (e.g., polyuria, polydipsia, and weight loss) or with diabetic ketoacidosis (DKA), Autoantibodies to insulin, glutamic acid decarboxylase (GAD-65), islet antigen 2 (IA-2), or zinc transporter 8 (ZnT8) can be used to screen for type 1 diabetes.

  Staging of Type 1 Diabetes

  	Stage 1	Stage 2	Stage 3
  Characteristics	Autoimmunity	Autoimmunity	Autoimmunity
  	Normoglycemia	Dysglycemia	Overt hyperglycemia
  	Presymptomatic	Presymptomatic	Symptomatic
  Diagnostic criteria	Multiple islet autoantibodies No IGT or IFG	Islet autoantibodies (usually multiple) Dysglycemia: IFG and/or IG FPG 100-125 mg/dL (5.6-6.9 mmol/L) 2-h 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	Autoantibodies may become absent Diabetes by standard criteria

  Abbreviations: FPG, fasting plasma glucose; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; 2-h PG, 2-h plasma glucose. Alternative additional stage 2 diagnostic criteria of 30-, 60-, or 90-min plasma glucose on oral glucose tolerance test ≥200 mg/dL (≥11.1 mmol/L) and confirmatory testing in those aged ≥18 years have been used in clinical trials. (Reference:Diagnosis and Classification of Diabetes: Standards of Medical Care in Diabetes-2024. American Diabetes Association. Diabetes Care 2024.)

• Type 2 diabetes is due to insulin resistance and progressive loss of beta-cell insulin secretion. Onset is usually gradual, with milder forms of hyperglycemia, termed prediabetes, eventually leading to symptomatic hyperglycemia.

• Other causes of diabetes include:

  • monogenic diabetes syndromes (presenting as neonatal diabetes or maturity-onset diabetes of the young [MODY])

  • drug- or chemical-induced diabetes (e.g., steroid-induced diabetes, immune checkpoint inhibitor-induced diabetes, diabetes caused by use of immunosuppressants or HIV medications)

  • diabetes due to diseases of the exocrine pancreas (e.g., cystic fibrosis, chronic pancreatitis, pancreatectomy)

  • gestational diabetes mellitus (GDM)

Key concerns in diabetes care include:

• screening and diagnosis of prediabetes/diabetes

• phenotyping (determining the type of diabetes)

• long-term (outpatient) management of blood-glucose levels and glycated hemoglobin (HbA1c)

• prevention and management of diabetic complications

• management of diabetes in hospitalized patients with infection, acute illness, and varying nutritional status

• management of glycemic emergencies (hypoglycemia, hyperglycemia, DKA, and hyperosmolar hyperglycemic nonketotic syndrome [HHS])

Screening and Diagnosis

Screening: Given the high prevalence of impaired glucose tolerance (IGT or prediabetes) and type 2 diabetes, an informal assessment of risk factors or validated tools (e.g., CANRISK diabetes risk calculator) should be considered in the screening of asymptomatic adults at risk of developing diabetes.

The United States Preventive Services Task Force (USPSTF) recommends screening for prediabetes and type 2 diabetes in all adults aged 35 to 70 years who have overweight or obesity.

The American Diabetes Association (ADA) recommendations for diabetes screening in asymptomatic adults are outlined in the following table:

Diagnosis: Diagnosis of type 2 diabetes requires two abnormal test results from the same blood sample (e.g., abnormal HbA1c and fasting plasma glucose) or in two separate test samples. If the patient presents with a clear clinical picture of hyperglycemia (e.g., polyuria, polydipsia), then a single abnormal test is sufficient to make the diagnosis. Although continuous glucose monitoring (CGM) has been widely used to monitor glucose in people with established diabetes, currently, the evidence is insufficient to support the use of CGM for screening or diagnosis of prediabetes or diabetes.

The following tests can be used to both screen for and diagnose diabetes:

• fasting plasma glucose (FPG)

• 2-hour plasma glucose concentration during a 75-g oral glucose tolerance test (OGTT)

• HbA1c

Thresholds for diagnosis of IGT and type 2 diabetes based on each of these tests are provided in the following table:

Phenotyping of diabetes: All patients with new-onset diabetes should be evaluated to determine the type of diabetes. To identify less-common forms of diabetes, the patient should be evaluated for symptoms, medications, family history, and physical examination findings that may suggest genetic or secondary causes of diabetes. Targeted laboratory evaluation can be performed to further evaluate for conditions suspected after this initial clinical assessment.

Patients who present with features most consistent with type 1 diabetes (e.g., before puberty, with DKA, and/or without the typical findings of type 2 diabetes, such as obesity or acanthosis nigricans) should be tested for islet autoantibodies. This typically involves measurements of antibodies directed against glutamic acid decarboxylase 65 (GAD65), the 40K fragment of tyrosine phosphatase (IA2), insulin, and/or zinc transporter 8 (ZnT8). Levels of C-peptide can also be useful.

In older patients with typical features of type 2 diabetes, no additional testing is needed. Autoantibody and C-peptide testing as described above can be helpful in patients with atypical features.

Management of Blood Glucose

Blood-glucose testing: Patients with diabetes should regularly monitor blood glucose concentrations, typically through measurement of capillary blood glucose using lancets and glucometers (i.e., fingerstick glucose measurements). Patients with diabetes should check their blood glucose level when they are unwell or feel symptomatic for hyper- or hypoglycemia. Frequency of blood glucose monitoring depends on the individual patient’s medication regimen (e.g., testing may be omitted in patients who are not taking medications that cause hypoglycemia, while patients requiring insulin may need to test ≥4 times per day).

Continuous glucose monitoring (CGM): Measurement of interstitial fluid glucose levels using CGMs is becoming increasing popular both in patients with type 1 and type 2 diabetes. It is ideal to assess CGM metrics with data accumulated for 14 days of reading for pattern management. Time in range (TIR) is defined as the percentage of readings and time between 70-180 mg/dL (3.9-10.0 mmol/L) and is associated with the risk of microvascular complications and can be used for assessment of glycemic status. The goal TIR is >70% for most adults and >50% in older adults.

Glycated hemoglobin targets: In patients with diabetes, HbA1c should be tested at least twice annually. In general, the HbA1c target for people with diabetes is <7.0% and ideally around 6.5%. However, goals should be individualized and based on the patient’s age, comorbidities, resources, and risk for hypoglycemia. For example, in an elderly patient with established cardiovascular disease or multiple other comorbidities, the HbA1c target is less stringent (HbA1c of 7.5% to 8.5%) because the risk of harm associated with hypoglycemia outweighs the benefits gained from glycemic control.

See Figure 6.2 in the ADA Glycemic Goals and Hypoglycemia: Standards of Medical Care in Diabetes—2024 for an approach to individualization of glycemic targets and factors to consider when setting a specific glycemic target.

Management of Type 1 Diabetes

Because patients with type 1 diabetes have absolute insulin deficiency due to beta-cell destruction and require insulin, omission of insulin places patients with type 1 diabetes at risk of hyperglycemia and diabetic emergencies such as DKA.

Insulin is usually administered via multiple daily injection (MDI) or continuous subcutaneous insulin infusion (CSII) via an insulin pump. Although insulin regimens vary, the primary principles for insulin administration in patients with type 1 diabetes are as follows:

• basal insulin to cover baseline metabolic requirements (long-acting insulin analogue such as insulin glargine or via insulin pump)

• bolus insulin to cover meal-time carbohydrate intake and prevent postprandial hyperglycemia (short-acting insulin such as insulin aspart)

• correctional insulin to bring a high blood glucose level down into the target range

• Newer closed-loop systems (“artificial pancreas”) integrate the insulin pump with a continuous glucose monitor (CGM). The system adjusts basal insulin based on real-time glucose levels, but most systems still require manual entry of prandial insulin doses for meal-time coverage.

Noninsulin pharmacologic treatments (e.g., metformin and sodium-glucose cotransporter-2 [SGLT-2] inhibitors) have been investigated in many trials as potential adjuncts for treatment in type 1 diabetes. However, these adjuncts are not approved for use in type 1 diabetes at this time.

Surgery: Pancreas transplantation or islet cell transplantation are two options for management of type 1 diabetes offered to very select patients and should not be considered part of routine care.

Teplizumab is an anti-CD3-antibody that is approved to delay the onset of stage 3 type 1 diabetes in adults and pediatric individuals (aged 8 years and older) with stage 2 type 1 diabetes. However, teplizumab is not used to manage hyperglycemia in type 1 diabetes.

Management of Type 2 Diabetes

The three main approaches to managing diabetes and blood-glucose levels are:

• comprehensive lifestyle management

• pharmacologic therapy

• surgery

Lifestyle management: Lifestyle management is a key component of diabetes management, and all patients diagnosed with diabetes should make lifestyle changes, including the following:

• diabetes self-management education and support

• nutritional/dietary changes

• increase of physical activity and weight loss (when appropriate)

• smoking-cessation counseling (when applicable)

• psychosocial care

Pharmacologic therapy: Types of pharmacologic treatment for type 2 diabetes include:

• oral agents (e.g., metformin, SGLT-2 inhibitors, sulfonylureas, and meglitinides)

• injectable agents that are not insulin (e.g., glucagon-like peptide-1 [GLP-1] analogues or glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists.)

• insulin

As with glycemic targets, choice of pharmacologic agents should be individualized. Metformin is typically recommended as the first-line agent, with more individualization possible when choosing second-line therapies. For example, an overweight 60-year-old man with heart failure will derive greater benefit from an SGLT-2 inhibitor than a sulfonylurea.

Surgery: Metabolic surgery is a potential treatment option in patients with type 2 diabetes and BMI ≥40 kg/m² (BMI ≥37.5 in Asian Americans) and in adults with BMI 35.0-39.9 (32.5-37.4 in Asian Americans) who do not achieve durable weight loss and improvement in comorbidities (including hyperglycemia) with reasonable nonsurgical methods. In the appropriate patient, increasing evidence indicates that metabolic surgery is associated with improved cardiovascular outcomes and sustained glycemic control, compared with lifestyle and pharmacologic treatments alone.

For more information on metabolic surgery, see the Obesity section in this rotation guide.

Diabetic Complications

Diabetic complications can be classified as microvascular and macrovascular disease. Microvascular disease comprises nephropathy, retinopathy, and neuropathy. Macrovascular complications include coronary artery disease, cerebrovascular disease, and peripheral vascular disease.

Management of patients with diabetes requires regular assessment for potential complications and management of cardiovascular risk factors. Due to the autoimmune nature of type 1 diabetes, additional screening should be performed in this patient group for other autoimmune diseases.

Hypoglycemia in Diabetes

Hypoglycemia is defined as blood-glucose concentration below 70 mg/dL (<3.9 mmol/L). However, some patients experience symptoms before blood-glucose concentrations are so low. Symptoms can be classified as adrenergic (autonomic; e.g., sweating, shaking, palpitations) or neuroglycopenic (due to alterations in brain function; e.g., hunger, difficulty concentrating, confusion). Common risk factors of hypoglycemia include:

• incorrect insulin or long-acting sulfonylurea administration

• variation in carbohydrate intake

• suppression of glucose production in the liver by alcohol

• vigorous or prolonged exercise

• intercurrent illness

• end-stage kidney disease

• cognitive impairment or dementia

• socioeconomic issues such as food insecurity or homelessness

Hypoglycemic unawareness occurs when patients no longer experience adrenergic symptoms but directly experience neuroglycopenic symptoms. Usually, neuroglycopenic symptoms occur at a lower blood-glucose concentration. Patients with hypoglycemic unawareness are at risk for more-severe complications. Hypoglycemic unawareness can potentially be corrected by strict avoidance of hypoglycemia for 2 to 3 months.

Treatment:

• Nonsevere hypoglycemia (patient is conscious and capable of self-management) can be treated with fast-acting oral glucose (15 g) such as fruit juice or glucose gel.

• Severe hypoglycemia (patient is unconscious or unable to perform self-management) needs to be treated with intramuscular (IM) or nasal glucagon and potentially IV glucagon.

• All patients should be encouraged to consume sources of long-acting carbohydrates when able and acute hypoglycemia has been corrected.

Review and address risk factors for hypoglycemia to prevent future hypoglycemic events. Consider CGM, which can be helpful for detecting and preventing hypoglycemia, especially those with hypoglycemia unawareness and/or on insulin therapy.