Type 2 diabetes mellitus
Type 2 diabetes is hyperglycemia from insulin resistance with progressive relative insulin deficiency, diagnosed by a hemoglobin A1c of 6.5% or higher, a fasting glucose of 126 mg/dL or higher, or a 2-hour oral glucose tolerance test value of 200 mg/dL or higher. First-line treatment is lifestyle modification plus metformin, with an SGLT2 inhibitor or GLP-1 receptor agonist added early for patients with atherosclerotic disease, kidney disease, or heart failure.
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What this article covers
- Overview
A progressive disorder of insulin resistance and relative insulin deficiency: hyperglycemia reflects peripheral insulin resistance plus a worsening beta-cell secretory defect, so hyperglycemia severity tracks beta-cell dysfunction.
- Epidemiology
Rising across age groups: historically a disease of middle-aged and older adults, incidence is increasing in children and adolescents alongside rising overweight and obesity.
- Risk factors
Overweight or obesity: body mass index 25 or higher (23 or higher in Asian American persons) is the central modifiable risk factor.
- Pathophysiology
Insulin resistance is the initiating defect: muscle, liver, and adipose tissue become progressively less responsive to insulin's effects on glucose and fatty acid handling.
- Clinical features
Gradual, often silent onset: most persons are asymptomatic for years, unlike the abrupt presentation typical of type 1 diabetes.
- Differential diagnosis
Type 1 diabetes mellitus: positive glutamic acid decarboxylase (GAD65) or islet antigen-2 (IA-2) autoantibodies with a low or undetectable C-peptide, unlike the antibody-negative profile of type 2 diabetes.
- Diagnosis
The clinching basis is one of three laboratory criteria, or an unequivocal glucose with symptoms: A1c 6.5% (48 mmol/mol) or higher fasting plasma glucose 126 mg/dL (7.0 mmol/L) or higher after at…
- Management
First, for every patient, initiate comprehensive lifestyle modification (weight management, dietary change, structured physical activity), which is first-line therapy regardless of subsequent pharmacologic choices.
- Complications
Microvascular disease: retinopathy, nephropathy, and peripheral or autonomic neuropathy develop from chronic hyperglycemic injury and are reduced by intensive glycemic control, as shown in the…
- Prognosis
Early intensive glycemic control confers a durable "legacy effect": long-term follow-up of intensively treated cohorts from these landmark trials shows continued reduction in cardiovascular events…
- Prevention
Lifestyle modification is the preferred preventive strategy in prediabetes: the Diabetes Prevention Program goal of at least 7% weight loss over 6 months plus 150 min/week of moderate-intensity exercise cut progression to diabetes by 58%.
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Related articles
- Type 1 diabetes mellitus
Type 1 diabetes mellitus is an insulin-deficient state from autoimmune (type 1A) or idiopathic (type 1B) destruction of pancreatic beta cells, presenting with hyperglycemia that can range from mild to life-threatening diabetic ketoacidosis. Diagnosis combines standard glycemic criteria with autoantibody testing (GAD65, IA-2), and lifelong insulin therapy, generally as a basal-bolus regimen, is required from diagnosis, with self-monitoring or continuous glucose monitoring to guide dosing.
- Insulin therapy in diabetes mellitus
Insulin therapy replaces or supplements endogenous insulin to control hyperglycemia, and is lifelong and mandatory in type 1 diabetes because of absolute beta-cell failure, while in type 2 diabetes it is added when oral and noninjectable agents fail to reach glycemic goals. First-line therapy is a basal-bolus regimen started at 0.4-1.0 units/kg/day in type 1 diabetes, or basal insulin glargine 10 units/day (or 0.1-0.2 units/kg/day) in type 2 diabetes, titrated to a fasting glucose target.
- Noninsulin antihyperglycemic drugs in type 2 diabetes mellitus
Noninsulin antihyperglycemic drugs are the oral and injectable agents used to lower glucose in type 2 diabetes mellitus once lifestyle modification alone is insufficient, chosen in a patient-centered stepwise sequence built around metformin. Metformin, titrated to 850-1000 mg PO twice daily (max 2550 mg/day), is first-line for essentially every patient; an SGLT2 inhibitor or GLP-1 receptor agonist is added next for established or high-risk atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, with further agents layered by hypoglycemia risk, weight effect, and cost.