IP3 Diabetes patho

Pancreas Function

Secretes insulin (β-cells), glucagon (α-cells), amylin, somatostatin, ghrelin, and digestive enzymes

Liver Function

Stores glucose as glycogen, produces glucose via gluconeogenesis and glycogenolysis

Muscle Function

Major site for insulin-mediated glucose uptake via GLUT4; stores glucose as glycogen

Adipose Function

Uptakes glucose for triglyceride synthesis; releases FFAs during lipolysis

Brain Function

Regulates appetite and satiety via leptin, ghrelin, and PYY

Endocrine Pancreas

Islets of Langerhans: α-cells (glucagon), β-cells (insulin, amylin, C-peptide), δ-cells (somatostatin), ε-cells (ghrelin)

Exocrine Pancreas

Acinar cells secrete digestive enzymes (amylase, lipase)

Insulin Source

β-cells of pancreas

Insulin Effect

↓ blood glucose via ↑ uptake and ↓ gluconeogenesis

Glucagon Source

α-cells of pancreas

Glucagon Effect

↑ blood glucose via ↑ gluconeogenesis and glycogenolysis

Classic Diabetes Symptoms

Polyuria, Polydipsia, Polyphagia

Fasting Glucose Normal

70-99 mg/dL

Fasting Glucose Pre-diabetes

100-125 mg/dL

Fasting Glucose Diabetes

≥126 mg/dL

Post-prandial Glucose Normal

<140 mg/dL

Post-prandial Glucose Pre-diabetes

140-199 mg/dL

Post-prandial Glucose Diabetes

≥200 mg/dL

HbA1c Normal

<5%

HbA1c Pre-diabetes

5.7-6.4%

HbA1c Diabetes

≥6.5%

HbA1c Purpose

Reflects average glucose over 3 months

OGTT Purpose

Measures glucose tolerance post-glucose load

Fasting Glucose Purpose

Assesses baseline glycemia

Modifiable Risk Factors

Obesity, sedentary lifestyle, dyslipidemia, smoking, hypertension, insulin resistance

Non-Modifiable Risk Factors

Age >45, family history, race/ethnicity, history of GDM or CVD, PCOS

Type 1 Diabetes

Autoimmune β-cell destruction, insulin-dependent, early onset, prone to ketoacidosis

Type 2 Diabetes

Insulin resistance + β-cell dysfunction, often obese, adult onset, not ketosis prone

Gestational Diabetes

Onset during pregnancy, resolves postpartum, ↑ risk of T2DM

Specific Diabetes Causes

MODY, pancreatitis, endocrinopathies, drug-induced

GSIS Mechanism

Glucose → ATP ↑ → K⁺ channels close → depolarization → Ca²⁺ influx → insulin exocytosis

GSIS Modulators

↑ by acetylcholine, incretins; ↓ by epinephrine

Insulin Release Stimulators

Glucose, amino acids, GLP-1, GIP, glucagon, cholecystokinin, vagal stimulation

Insulin Release Inhibitors

Somatostatin, insulin, leptin, catecholamines

Glucagon Role

Stimulates hepatic glucose production; used in hypoglycemia emergencies

Appetite Hormones

Insulin (satiety), leptin (long-term satiety), ghrelin (hunger), PYY (satiety)

Biphasic Insulin Response

Phase 1 = stored insulin (absent in T2DM); Phase 2 = newly synthesized insulin

Insulin Resistance

↓ response to insulin → ↑ hepatic glucose output, ↓ muscle uptake

β-cell Dysfunction

Progressive loss of insulin secretion

Ominous Octet

Impaired insulin secretion, insulin resistance, ↓ incretins, ↑ glucagon, ↑ hepatic glucose, ↑ SGLT2, inflammation, ↓ satiety

Vicious Cycles of Hyperglycemia

Glucotoxicity, lipotoxicity, inflammation

DKA Mechanism

Absolute insulin deficiency → ketogenesis → acidosis

HHS Mechanism

Relative insulin deficiency → severe hyperglycemia, dehydration, no acidosis

DKA vs HHS

DKA = ketones present, pH <7.3; HHS = no ketones, normal pH, severe osmolality

Chronic Complications

Microvascular (retinopathy, nephropathy, neuropathy); Macrovascular (CAD, stroke, PAD)

Molecular Mechanisms

↑ polyol flux, ↑ hexosamine pathway, ↑ PKC activation, ↑ AGE formation

Infection Risk in Diabetes

↓ WBC delivery, ↑ glucose for pathogens, ↓ oxygen delivery, ↓ collagen synthesis

Insulin Function

↑ glucose uptake, ↑ glycogenesis, ↓ gluconeogenesis, ↑ lipogenesis, ↓ lipolysis/proteolysis

Glucagon Function

↑ gluconeogenesis, ↑ glycogenolysis, ↑ lipolysis, ↑ proteolysis

Screening Adults

BMI ≥25 (≥23 in Asians) + ≥1 risk factor → screen for T2DM

Screening Children

Overweight + ≥1 risk factor (maternal DM, family history, race, insulin resistance signs)

DKA Labs

↑ glucose, ↓ pH, ↑ ketones, ↓ bicarbonate, ↑ anion gap

HHS Labs

↑ glucose (>600), ↑ osmolality (>320), normal pH, no ketones

Hypoglycemia Definition

Blood glucose <70 mg/dL ± symptoms

Hypoglycemia Symptoms

Hunger, headache, anxiety, sweating, confusion, seizures, coma

AGEs Mechanism

Non-enzymatic glycation → ROS → endothelial dysfunction → inflammation

Oxidative Stress Role

ROS damage small vessels → microvascular complications

Leptin-Ghrelin-Insulin Interplay

Leptin/insulin = satiety; ghrelin = hunger; imbalance → overeating in obesity/T2DM

HbA1c Mechanism

Glycation of hemoglobin over 120 days → reflects 3-month glucose average

HbA1c Clinical Use

Monitors long-term control; correlates with microvascular risk

Hypertriglyceridemia in DM

↑ lipolysis + ↓ TG clearance → ↑ FFAs → weight loss + high TGs