Diabetes mellitus

Last updated: August 28, 2023

Summarytoggle arrow icon

Diabetes mellitus (DM) describes a group of metabolic diseases that are characterized by chronic hyperglycemia. Type 1 diabetes mellitus (T1DM) is the result of an autoimmune response that triggers the destruction of insulin-producing β cells in the pancreas and results in an absolute insulin deficiency. It often develops during childhood, manifesting with an acute onset (e.g., diabetic ketoacidosis). Type 2 diabetes mellitus (T2DM), which is much more common, has a strong genetic component as well as a significant association with obesity and a sedentary lifestyle. T2DM is characterized by insulin resistance and impaired insulin secretion due to pancreatic β-cell dysfunction, resulting in relative insulin deficiency. This type of diabetes usually remains undiagnosed for many years. Testing for hyperglycemia is recommended for patients with classic symptoms of diabetes mellitus, and screening is recommended for asymptomatic patients who are at high risk of prediabetes or diabetes (e.g., patients with obesity and additional risk factors). The diagnosis is made based on blood glucose or HbA1c levels. The main goal of treatment is blood glucose control tailored to glucose targets while avoiding hypoglycemia. Diabetes care should be comprehensive and patient-centered, and it should include monitoring and management of ASCVD risk factors, microvascular complications (e.g., diabetic retinopathy, diabetic nephropathy, diabetic neuropathy), and macrovascular complications (e.g., CAD, stroke, PAD). Management should also include general lifestyle modifications (e.g., smoking cessation, exercise, nutritional support) and pharmacotherapy (e.g., antihyperglycemics, statins, ACE inhibitors or angiotensin receptor blockers, and aspirin). The management of diabetes in children is largely similar to adults, except certain medications (sulfonylureas, dipeptidyl peptidase-4 inhibitors, SGLT-2 inhibitors, and thiazolidinediones) are not licensed for use in this age group.

See also “Diabetes in pregnancy,” “Insulin,” and “Hyperglycemic crises.”

Overviewtoggle arrow icon

Type 1 vs Type 2 diabetes mellitus
Features Type 1 DM Type 2 DM [1]
  • Negative HLA association
  • Strong familial predisposition [3]
  • Polygenic
Association with obesity
  • No
  • Yes
  • Childhood onset typically < 20 years but can occur at any age
  • Peaks at age 4–6 years and 10–14 years
  • Gradual; usually at age > 40 years
C-peptide (insulin)
  • Decreased or absent
  • Initially elevated, decreased in advanced stage
Glucose intolerance
  • Severe
  • Mild to moderate
Insulin sensitivity
  • High
  • Low
Risk of ketoacidosis
  • High
  • Low
β-cells in the islets
  • Decreased

Classic symptoms (i.e., polyuria, polydipsia, polyphagia, weight loss)

  • Common
  • Sometimes

Epidemiologytoggle arrow icon

Type 1 DM

  • Prevalence [4]
    • ∼ 1.6 million in the US
    • ∼ 5–10% of all patients with diabetes
  • Age [4]
    • Childhood onset typically < 20 years but can occur at any age
    • Peaks at age 4–6 years and 10–14 years
  • Race: highest prevalence in non-Hispanic White individuals [5]

Type 2 DM

  • Prevalence [4]
    • ∼ 10.5% of adult population in the US
    • Near 34 million individuals in the US have diabetes with 7.3 million being undiagnosed.
  • Incidence: ∼ 6.7 per 1,000 among the US adults [4]
  • Age
    • Adult onset typically > 40 years [5]
    • Mean age of onset is decreasing
  • Gender: > [4]
  • Race: highest prevalence in Native Americans, Hispanics, African Americans, and Asian non-Hispanic Americans [4]

Epidemiological data refers to the US, unless otherwise specified.

Etiologytoggle arrow icon

Type 1 DM [6][7]

“If you buy 4 DiaMonds and only pay for 3, you get 1 for free:” DR4 and DR3 are associated with Diabetes Mellitus type 1.

Type 2 DM [8][9][10]

Classificationtoggle arrow icon

Classification according to the WHO and American Diabetes Association (ADA) [15][16]

Pathophysiologytoggle arrow icon

Normal insulin physiology [17]

Type 1 diabetes [6]

Type 2 diabetes

Mechanisms [5]

Progression [1]

Clinical featurestoggle arrow icon

Clinical features of diabetes mellitus
Type 1 DM Type 2 DM [1]
  • Often sudden
  • Diabetic ketoacidosis (DKA) is the first manifestation in approx. one-third of cases. [10]
  • Alternatively, children may present with acute illness and classic symptoms.
  • Typically gradual
  • The majority of patients are asymptomatic.
  • Some patients may present with a hyperglycemic crisis.
    • Elderly patients especially may present in a hyperosmolar hyperglycemic state. [20]
    • Occasionally, patients with T2DM present with DKA , which mostly affects black and Hispanic individuals. [21]
  • Symptoms of complications may be the first clinical sign of disease.
Clinical features
  • A thin appearance is typical for patients with T1DM.

Diabetes mellitus should be suspected in patients with recurrent cellulitis, candidiasis, dermatophyte infections, gangrene, pneumonia (particularly tuberculosis reactivation), influenza, genitourinary infections (UTIs), osteomyelitis, and/or vascular dementia.

Screeningtoggle arrow icon

Indications for testing [24][25]

The indications listed below are consistent with the 2023 ADA guidelines. The 2021 USPSTF guideline recommends screening in adults aged 35–70 years with overweight or obesity. [24][25][26]

Method of screening

If results are normal, repeat testing in asymptomatic patients at least every three years. Patients with prediabetes should be tested at least annually to detect progression to diabetes. [25]

Diagnosticstoggle arrow icon

Diagnostic criteria for diabetes mellitus [25]

A combination of either of the tests described below may be performed to confirm the diagnosis and the same test can be used both for screening and diagnosis. If two separate blood samples are used, the second should be obtained soon after the first.

Hyperglycemia tests [25]

Significant discrepancy between HbA1c and glucose measurements warrants investigation of the underlying cause (e.g., sickle cell trait).

Interpretation of diagnostic tests [25]
FPG 2-hour glucose value after OGTT HbA1c
Diabetes mellitus ≥ 126 mg/dL (≥ 7.0 mmol/L) ≥ 200 mg/dL (≥ 11.1 mmol/L) ≥ 6.5%
Prediabetes 100–125 mg/dL (5.6–6.9 mmol/L) = impaired fasting glucose 140–199 mg/dL (7.8–11.0 mmol/L) = impaired glucose tolerance 5.7–6.4%
Normal < 100 mg/dL (< 5.6 mmol/L) < 140 mg/dL (< 7.8 mmol/L) < 5.7%

Routine studies

Perform in all patients as part of the initial diagnostic workup and reassess at least annually.

Additional studies

These tests are not routinely indicated or required to establish a diagnosis.

While screening for T1DM with autoantibodies is not routinely recommended, it can be considered for patients with first-degree relatives with T1DM or in the setting of research trials. [25]

Consider specialist consultation if the differentiation between T2DM and T1DM is unclear.

Differential diagnosestoggle arrow icon

The differential diagnoses listed here are not exhaustive.

Managementtoggle arrow icon

General principles

Diabetes care should be patient-centered and comprehensive, including lifestyle modifications and assessment of psychosocial health. Consider social determinants of health and formulate a treatment plan together with the patient.

The goals of diabetes management include eliminating symptoms of hyperglycemia, reducing or eliminating complications, and enabling as healthy a lifestyle as possible. [24]

Lifestyle modifications [35]

Lifestyle recommendations for patients with diabetes mellitus [35]
Physical activity
  • Exercise regularly.
    • 2 ½ hours of aerobic exercise spread over ≥ 3 days per week
    • 2–3 sessions of resistance exercise per week
  • Reduce the amount of time spent sedentary and increase nonsedentary activities.
Balanced diet and nutrition
  • Refer to a registered nutritionist.
  • Individualize dietary recommendations taking into account the patient’s health status, preferences, and cultural background.
  • General recommendations include:
    • A high-fiber diet
    • Eating nonstarchy vegetables, whole foods
    • Avoiding refined sugar and grains
Weight management [39]
  • Recommend smoking cessation for all patients; offer counseling if necessary. [35]
  • Alcohol consumption [35]
    • Should be limited to a moderate intake
    • To avoid hypoglycemia, consume alcohol together with food and monitor glucose after consumption.

Physical exercise reduces blood glucose and increases insulin sensitivity.

Glycemic targets in diabetes [40][41]

  • Consider the following patient factors when setting a glycemic target:
    • Risk of hypoglycemia or other adverse effects
    • Presence of vascular complications and comorbidities
    • Patient preferences and resources
    • Disease duration and life expectancy
  • Reevaluate glycemic targets continuously and adjust if necessary.
Common glycemic targets [40]

< 7%: suitable for most patients [40][41]

Preprandial capillary glucose

80–130 mg/dL (4.4–7.2 mmol/L)

Peak postprandial capillary glucose

< 180 mg/dL (< 10.0 mmol/L)

Glycemic targets should be individualized. A target of HbA1c < 7% is generally suitable for most nonpregnant adults. [40]

Assess for past episodes or risk of hypoglycemia regularly and adjust glycemic goals accordingly. Hypoglycemia is one of the major limitations for adequate glycemic control. [40]

In patients that meet preprandial glucose targets, HbA1c above target may be due to postprandial hyperglycemia that requires prandial insulin dose adjustments.

Glycemic monitoring for DM [40][42]

HbA1c monitoring

  • HbA1c is measured at fixed intervals.
    • At least every 6 months if targets are met
    • At least every 3 months in the following situations:

Glucose monitoring

Glucose levels can be used to evaluate treatment and prevent hypoglycemia and hyperglycemia, especially in patients using insulin.

  • Self-monitoring of blood glucose (SMBG): at fixed times or as necessary
    • Indication: insulin therapy (particularly for intensive regimens)
    • Consider for any patient to assess for hypoglycemia or the impact of diet and/or exercise.
  • Continuous glucose monitoring (CGM): Interstitial glucose levels are measured continuously or intermittently using a device. [42]


  • Assess for episodes of hypoglycemia (symptomatic or asymptomatic) at every follow-up visit.
  • In patients with at least one clinically significant hypoglycemia event or asymptomatic hypoglycemia
    • Check for possible contributors, e.g., medication interaction or errors.
    • Consider relaxing the glycemic targets and adjusting management.
    • Prescribing glucagon may be beneficial for some patients.

Reassess and adjust treatment at regular intervals, e.g., every 3–6 months.

Early morning hyperglycemia

  • Early morning hyperglycemia may be caused by:
    • Dawn phenomenon
      • A physiological increase of growth hormone levels; in the early morning hours stimulates hepatic gluconeogenesis and leads to a subsequent increase in insulin demand that cannot be met in insulin-dependent patients, resulting in elevated blood glucose levels.
      • Consider measurement of nocturnal blood glucose levels before initiating insulin therapy.
      • Long-acting insulin dose may be given later or increased under careful glycemic control.
    • Somogyi effect (widely taught but unproven hypothesis)
      • Description: Nocturnal hypoglycemia ; due to evening insulin injection triggers a counterregulatory secretion of hormones , leading to elevated blood glucose levels in the morning.
      • There is no evidence to support the existence of this effect. [43][44][45]

As there is little to no evidence to support the existence of the Somogyi effect, it should not be assumed that early morning hyperglycemia is due to nocturnal hypoglycemia. Rather, it is more likely caused by nocturnal hyperglycemia with or without hypoinsulinemia and/or the early morning secretion of counterregulatory hormones (e.g., cortisol). [43][44][45]

Antihyperglycemic treatmenttoggle arrow icon

This section outlines the approach to pharmacological treatment of diabetes mellitus. See “Inpatient management of hyperglycemia” for details regarding, e.g., management of hyperglycemia in critically ill patients. See also “Perioperative medication management” for the adjustments to insulin and oral antidiabetics prior to surgery.

Type 1 diabetes mellitus

Insulin replacement therapy [32]

Educate patients on calculating insulin requirements throughout the day and in accordance with activities and meals. [32]

Other treatment strategies [32]

Type 2 diabetes mellitus

Approach [32]

Metformin should be part of every patient's treatment, unless contraindicated, and continued for as long as it is tolerated, as it is safe, effective, widely available, and has been shown to reduce cardiovascular events and mortality. [32]

Noninsulin antidiabetics

Noninsulin antidiabetics for the treatment of type 2 diabetes mellitus [32]
Drug class


Important considerations
Dipeptidyl peptidase-4 inhibitor
SGLT-2 inhibitors
GLP-1 receptor agonists

Oral monotherapy usually lowers HbA1c levels by ∼ 1%. Every noninsulin drug added to metformin will lower the HbA1c by an additional ∼ 0.7–1.0%. [32]

Beware of drug interactions and drug incompatibilities; combining sulfonylureas with insulin increases the risk of hypoglycemia. [48]

Many oral antidiabetic drugs should be avoided in patients undergoing surgery or experiencing severe illness. Instead, insulin therapy may be initiated.

Indications for insulin therapy in T2DM [32]

Approach to insulin treatment in T2DM [32]

GLP-1 receptor agonists should be part of the treatment strategy prior to starting insulin treatment in patients with T2DM, unless they are not appropriate or insulin therapy is preferred.

If treatment goals are not met in a patient on a basal insulin regimen, combination therapy with basal insulin and injectable GLP-1 receptor agonists may be considered.

Screening for complications of diabetestoggle arrow icon

Screening for microvascular complications of diabetes

Screening for macrovascular complications of diabetes [37]

  • Check BP at every clinic appointment and encourage patients with elevated BP to measure blood pressure at home.
  • Obtain a lipid panel at the time of diabetes diagnosis and repeat every 5 years for patients < 40 years.
  • Screening for cardiovascular disease is not recommended for asymptomatic individuals. [37][55]

Complicationstoggle arrow icon

Acute complications

Long-term complications [56]

Macrovascular disease (atherosclerosis)

Microvascular disease

Strict glycemic control is crucial in preventing microvascular disease.

Necrobiosis lipoidica [58]

Other complications

Insulin purging [63]

We list the most important complications. The selection is not exhaustive.

Prognosistoggle arrow icon

Special patient groupstoggle arrow icon

For management in pregnancy, see “Diabetes in pregnancy.”

Diabetes mellitus in children

The following recommendations are for children and adolescents with T1DM and T2DM. Management of other forms of diabetes in children (e.g., diabetes associated with transplantation or cystic fibrosis) is not addressed here.

Screening [25][36][64]

For screening modalities, see “Diagnostics” below.

Diagnostics [25]

Management [34][36]

Diabetes management in children is generally similar to adults, with the following modifications.

Screening and management of associated conditions [36]

Educate all individuals involved in the care of the patient (e.g., family members, school, and childcare personnel) about the treatment plan. [36]

Antidiabetic treatment [36]

Adolescents should be supported by clinicians to gradually take over diabetes management from caregivers. [36]

Patients with T2DM presenting with diabetic ketoacidosis should be treated with insulin alone. Metformin may be added after acidosis resolves. [36]

T2DM is rare in children under 10 years of age; consider consulting a specialist to determine treatment, as neither metformin nor GLP-1 receptor agonists are FDA-approved for use in this age group.

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Referencestoggle arrow icon

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