insulin resistance

Introduction

insulin resistance is when cells in your muscles, fat, and liver don’t respond well to insulin and can’t easily take up glucose from blood.
as a result, your pancreas makes more insulin to help glucose enter your cells
as capacity of the pancreas to secrete insulin starts to become inadequate, blood sugars begin to rise and patients become “pre-diabetic” and can eventually develop type 2 diabetes mellitus
insulin resistance is a key component of the “metabolic syndrome” as well as obesity, inadequate aerobic exertion and can be evidenced by:
- elevated fasting insulin levels
- fasting hypertriglyceridaemia
- development of skin tags or seborrheic warts

genetic factors
- tends to be familial (this also has environmental/cultural factors as well as epigenetic factors)
- polycystic ovary syndrome (PCOS)
- rarely there are genetic syndromes:
  - Insulin receptor mutations (such as leprechaunism)
  - Type A syndrome of insulin resistance (insulin receptor mutations, signalling defects)
  - Type B syndrome of insulin resistance (antibodies against insulin receptors)
  - decreased adiponectin and leptin associated with lipodystrophies.
- genes reducing GLUT4 in muscle - 14 genes discovered in 2023 ¹⁾
ethnicity:
- African American, Alaska Native, American Indian, Asian American, Hispanic/Latino, Native Hawaiian, or Pacific Islander American ethnicity
obesity
age > 45yrs
FH type 2 diabetes in immediate family
Hx gestational diabetes
inadequate aerobic activity
obstructive sleep apnoea (OSA)
stress
Cushing's syndrome
acromegaly
medications:
- corticosteroids
- some anti-psychotic medications
- some HIV antivirals

organ tissue overgrowth
- as in polycystic ovary syndrome (PCOS)
- certain malignancies - colon, breast, endometrial
metabolic syndrome
increased expression of insulin-like growth factor receptors
- increased probability of developing:
  - skin tags (acrochordons)
  - seborrheic warts
  - acanthosis nigricans
other skin issues
- acne
- hirsutism
- androgenetic alopecia (male pattern hair loss)
- psoriasis
- hidradenitis suppurativa
- vitiligo
early pre-diabetic retinopathy
elevated serum glucose levels
- HbA1c of 5.7-6.4% suggests pre-diabetes in a non-diabetic
- fasting blood glucose of 5.6-6.9mmol/L suggests pre-diabetes in a non-diabetic
elevated fasting triglyceride levels
can also influence sex steroid production and increase free testosterone

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