2.2 Insulin Therapy, Hyperglycemic Emergencies & Chronic Complications

1. Insulin Initiation, Intensification & Inpatient Management

Outpatient Insulin Regimens in Type 2 Diabetes

1. Basal Insulin Initiation: Indicated when HbA1c remains elevated despite 2–3 non-insulin agents or when baseline HbA1c >=10% (86 mmol/mol) or blood glucose >=300 mg/dL with catabolic features (ketosis, weight loss).
   • Starting dose: 10 units daily or 0.1–0.2 units/kg/day of long-acting basal insulin (Glargine U-100/U-300, Degludec U-100/U-200, Detemir).
   • Titration: Increase by 2 units every 3 days until fasting plasma glucose reaches 80–130 mg/dL without hypoglycemia.
2. Prandial Insulin Intensification (Basal-Plus to Basal-Bolus): If fasting glucose is at target but HbA1c remains elevated, or basal dose exceeds >0.5 units/kg/day:
   • Add 4 units or 10% of basal dose of rapid-acting insulin (Lispro, Aspart, Glulisine) before the largest meal of the day.
   • Titrate prandial dose by 1–2 units or 10–15% twice weekly based on 2-hour postprandial glucose (<180 mg/dL).
   • Expand to full basal-bolus (prandial before all 3 meals) or transition to GLP-1 RA/basal fixed-ratio combinations.

Inpatient Glycemic Management

• Target Blood Glucose: 140–180 mg/dL (7.8–10.0 mmol/L) for both critically ill ICU patients (managed with continuous IV regular insulin infusion) and non-critically ill general medical-surgical floor patients.
• Regimen Design: For non-critically ill patients with poor oral intake, administer scheduled basal insulin + correctional (sliding scale) insulin. For patients with adequate nutritional intake, administer scheduled Basal-Bolus-Correction (40–50% basal, 50–60% divided among 3 nutritional meals, plus prandial correction).
• Sliding Scale Insulin (SSI) Alone: Strongly discouraged as monotherapy; SSI monotherapy leads to glycemic volatility ("rollercoaster effect") and increased hospital complications.

2. Hyperglycemic Emergencies: DKA vs. HHS

Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS) are life-threatening acute metabolic decompensations requiring structured ICU resuscitation.

Diagnostic Comparison

Step-by-Step DKA & HHS Resuscitation Protocol

1. Fluid Resuscitation (Restoring Intravascular Volume):

   • Hour 1: Isotonic 0.9% Normal Saline (NS) at 1000–1500 mL/hr (15–20 mL/kg/hr).
   • Subsequent Hours: Assess corrected sodium: $\text{Corrected Na} = \text{Measured Na} + 1.6 \times \left(\frac{\text{Glucose} - 100}{100}\right)$.
     • If corrected Na is normal or elevated: Switch to 0.45% NaCl (Half-Normal Saline) at 250–500 mL/hr.
     • If corrected Na is low: Continue 0.9% NaCl at 250–500 mL/hr.
   • When plasma glucose reaches < 200 mg/dL in DKA (or < 300 mg/dL in HHS): Switch fluids to 5% Dextrose in 0.45% NaCl (D5 1/2 NS). This prevents hypoglycemia while allowing continued insulin infusion to close the anion gap.

2. Potassium Management (The Mandatory Gatekeeper):

   • Serum K+ is falsely elevated due to extracellular shifts from acidosis and insulin deficiency, despite total body potassium depletion (3–5 mEq/kg deficit).
   • If K+ < 3.3 mEq/L: HOLD INSULIN. Administer IV KCl 20–40 mEq/hr until K+ >=3.3 mEq/L (giving insulin when K+ <3.3 causes fatal ventricular arrhythmias and respiratory arrest from acute hypokalemia).
   • If K+ 3.3–5.2 mEq/L: Add 20–30 mEq KCl per liter of IV fluid to maintain serum K+ between 4.0–5.0 mEq/L; start insulin simultaneously.
   • If K+ > 5.2 mEq/L: Do not give K+; check serum K+ every 2 hours.

3. Insulin Administration:

   • Continuous IV Regular Insulin: 0.1 units/kg bolus IV followed by 0.1 units/kg/hr infusion (or 0.14 units/kg/hr continuous infusion without bolus).
   • Target glucose fall rate: 50–75 mg/dL/hr. If glucose does not decrease by 50 mg/dL in the first hour, double the insulin infusion rate.

4. Criteria for Resolution of DKA & Subcutaneous Bridging:

   • Resolution requires: Blood glucose <200 mg/dL AND at least two of: Serum $\text{HCO}_3 \ge 18\text{ mEq/L}$, Venous $\text{pH} > 7.30$, Anion gap normalized ($<= 12\text{ mEq/L}$), patient tolerating oral intake.
   • The 2-Hour Overlap Rule: Administer subcutaneous basal insulin (e.g., Glargine) 2 hours BEFORE discontinuing the IV insulin infusion. Discontinuing IV insulin without an active SQ basal depot causes rapid recurrence of ketoacidosis due to the ultra-short half-life of IV insulin (minutes).

5. Sodium Bicarbonate Utility:

   • Bicarbonate therapy is NOT recommended unless arterial pH < 6.90 (administer 100 mmol sodium bicarbonate in 400 mL sterile water with 20 mEq KCl over 2 hours). Bicarbonate carries risks of paradoxical CSF acidosis, hypocalcemia, delayed ketone clearance, and severe hypokalemia.

3. Chronic Microvascular & Macrovascular Complications

+-------------------------------------------------------------------------------------------------------------+
| COMPLICATION       | SCREENING / DIAGNOSTIC PROTOCOL             | EVIDENCE-BASED MANAGEMENT STRATEGY       |
+--------------------+---------------------------------------------+------------------------------------------+
| Diabetic Kidney    | Annual spot urine albumin-to-creatinine     | 1. ACEi (Lisinopril) or ARB (Losartan)   |
| Disease (DKD)      | ratio (UACR) + serum creatinine/eGFR;       |    if UACR >= 30 mg/g (titrate to max)   |
|                    | Microalbuminuria: UACR 30-299 mg/g;         | 2. SGLT2i (Empagliflozin/Dapagliflozin)  |
|                    | Macroalbuminuria / Overt DKD: >=300 mg/g    |    down to eGFR 20 mL/min                |
|                    |                                             | 3. Non-steroidal MRA (Finerenone) for    |
|                    |                                             |    persistent UACR >=30 mg/g with normal K|
|                    |                                             | 4. GLP-1 RA (Semaglutide) for eGFR decline|
+--------------------+---------------------------------------------+------------------------------------------+
| Diabetic           | Annual dilated funduscopic eye exam by      | Non-proliferative (microaneurysms,       |
| Retinopathy        | ophthalmologist/optometrist (Type 2: at     | cotton-wool spots, hard exudates):       |
|                    | diagnosis; Type 1: 5 years after onset);    | Strict glycemic and blood pressure control
|                    | Pregnant women: 1st trimester & postpartum  | Proliferative (neovascularization) or    |
|                    |                                             | Macular Edema: Intravitreal anti-VEGF    |
|                    |                                             | (Aflibercept, Ranibizumab) or panretinal |
|                    |                                             | photocoagulation (PRP)                   |
+--------------------+---------------------------------------------+------------------------------------------+
| Diabetic           | Annual screening using 10g Semmes-Weinstein | First-Line Pharmacotherapy for Pain:     |
| Peripheral         | monofilament (loss of protective sensation) | 1. SNRIs: Duloxetine (60-120 mg/day)     |
| Neuropathy (DSPN)  | plus 128-Hz tuning fork vibration or pinprick| 2. Gabapentinoids: Pregabalin, Gabapentin|
|                    | at dorsal hallux                            | (Avoid opioids; Tricyclic antidepressants|
|                    |                                             | like Amitriptyline effective but antichol|
|                    |                                             | inergic risks in elderly)                |
+--------------------+---------------------------------------------+------------------------------------------+
| Autonomic          | - Gastroparesis (early satiety, postprandial| - Gastroparesis: Small frequent meals,   |
| Neuropathy         |   nausea; diagnose via 4-hr solid gastric   |   low fat/fiber; Metoclopramide (short-  |
|                    |   emptying scintigraphy)                    |   term, monitor tardive dyskinesia), oral|
|                    | - Orthostatic hypotension (drop SBP >=20    |   Erythromycin                           |
|                    |   or DBP >=10 within 3 min standing)        | - Orthostasis: Compression stockings,    |
|                    | - Neurogenic bladder (urinary retention)    |   Midodrine, Droxidopa, Fludrocortisone  |
+--------------------+---------------------------------------------+------------------------------------------+
| Diabetic Foot      | Comprehensive annual visual inspection;     | Offloading pressure; aggressive surgical |
| Ulcers (DFU) &     | Palpate dorsalis pedis / posterior tibial   | debridement of necrotic tissue;          |
| Osteomyelitis      | pulses; Ankle-Brachial Index (ABI) if PAD   | Probe-to-bone test (if positive, >90% PPV|
|                    | suspected; Wagner ulcer staging             | for osteomyelitis -> perform plain X-ray |
|                    |                                             | and Foot MRI; bone biopsy gold standard) |
+--------------------+---------------------------------------------+------------------------------------------+