Insulin resistance with progressive beta-cell dysfunction; most common form of diabetes.
Also known as: T2DM, type 2 diabetes, adult-onset diabetes, NIDDM, insulin resistance
Overview
Chronic metabolic disorder characterized by peripheral insulin resistance and progressive pancreatic beta-cell dysfunction, leading to hyperglycemia. Accounts for ~90-95% of all diabetes cases.
Epidemiology
Affects ~37 million Americans (11% of adults); ~96 million have prediabetes. Disproportionately affects Hispanic, Black, Native American, and South Asian populations. Increasing incidence in adolescents paralleling childhood obesity epidemic.
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Pancreatic disease — Chronic pancreatitis, hemochromatosis, pancreatic cancer; may cause secondary diabetes
Drug-induced hyperglycemia — Glucocorticoids, atypical antipsychotics, HIV protease inhibitors, immunosuppressants
Diagnostic workup
Diagnostic criteria
A1c ≥6.5%, fasting glucose ≥126 mg/dL (8-hr fast), 2-hr OGTT ≥200 mg/dL (75 g load), or random ≥200 mg/dL with symptoms. Prediabetes: A1c 5.7-6.4%, fasting 100-125, OGTT 140-199.
Labs
Screening: USPSTF recommends screening adults 35-70 with overweight/obesity; ADA recommends starting at age 35 for all, earlier with risk factors
A1c ≥6.5%, fasting glucose ≥126 mg/dL, 2-hr OGTT ≥200 mg/dL, or random ≥200 mg/dL with symptoms
Confirm with repeat testing unless unequivocal hyperglycemia
Lipid panel, comprehensive metabolic panel, urine albumin/creatinine ratio
TSH, LFTs (NAFLD screening), CBC
Imaging
Not routine for diagnosis
Dilated retinal exam at diagnosis and annually
Consider liver imaging if AST/ALT elevated (NAFLD evaluation)
Diagnostic algorithm
flowchart TD
A[New T2DM diagnosis<br/>A1c ≥6.5%] --> B[Lifestyle modification<br/>+ Metformin]
B --> C{Comorbidities?}
C -->|ASCVD| D[Add GLP-1 RA<br/>semaglutide, liraglutide]
C -->|HF or CKD| E[Add SGLT2i<br/>empagliflozin, dapagliflozin]
C -->|Obesity| F[Add GLP-1 RA<br/>or tirzepatide]
C -->|None| G[Continue metformin<br/>reassess A1c in 3 mo]
D --> H{At A1c goal?}
E --> H
F --> H
G --> H
H -->|No| I[Add second agent<br/>DPP-4i, SU, TZD, basal insulin]
I --> J{A1c >9% or symptomatic?}
J -->|Yes| K[Initiate basal insulin<br/>± prandial]
H -->|Yes| L[Continue regimen<br/>recheck q3-6mo]
T2DM treatment algorithm — choice of second agent driven by comorbidities (ADA 2025).
Sulfonylurea — glipizide, glimepiride, glyburide: inexpensive but cause hypoglycemia and weight gain
Thiazolidinedione — pioglitazone: insulin sensitizer; weight gain, edema, HF exacerbation, bladder cancer concern
Insulin: indicated if A1c >10%, glucose >300, symptomatic hyperglycemia, or failure of oral/injectable agents; basal insulin (glargine, detemir, degludec) first, then add prandial
Bariatric/metabolic surgery: BMI ≥35 or ≥30 with inadequate glycemic control; can induce remission
Complications
Microvascular: retinopathy (leading cause of adult blindness in US), nephropathy (leading cause of ESRD), neuropathy (peripheral, autonomic, mononeuropathies)
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants.