Different Regimens to Control Diabetes Mellitus

1. Overview and Goals of Treatment

2. Non-Pharmacological Regimen

• Medical Nutrition Therapy (MNT): Low glycemic index diet, controlled carbohydrate intake, reduced saturated fat.
• Physical activity: At least 150 minutes/week of moderate aerobic exercise; resistance training 2-3 times/week.
• Weight loss: Even 5-10% weight reduction significantly improves insulin sensitivity in T2DM.
• Smoking cessation: Nicotine worsens insulin resistance and microvascular risk.
• Patient self-monitoring: Self-monitoring of blood glucose (SMBG) and structured glucose profiling.

3. Oral Antidiabetic Drug Regimens (for Type 2 DM)

A. Biguanides - Metformin (First-Line Agent)

• Mechanism: Decreases hepatic glucose production, reduces intestinal glucose absorption, increases peripheral insulin sensitivity.
• Dose: Start 500 mg OD/BD with meals; titrate up to 2000-2500 mg/day.
• Advantages: No hypoglycemia risk, weight neutral/modest weight loss, cardioprotective, cheap.
• Cautions: GI side effects (take with food); contraindicated if eGFR <45 mL/min; withhold before contrast studies.
• Examples: Metformin (Glucophage), Metformin XR (Glucophage XR).

B. Sulfonylureas (Insulin Secretagogues)

• Mechanism: Stimulate pancreatic β-cells to secrete insulin by closing K⁺-ATP channels.
• Examples: Glimepiride (Amaryl), Glipizide (Glucotrol XL), Glyburide (Micronase).
• Glimepiride has the best safety profile; lowers both fasting and postprandial glucose.
• Risks: Hypoglycemia (especially in elderly, renal insufficiency), weight gain. Avoid in elderly with CVD.
• Meglitinides (e.g., Repaglinide) are short-acting secretagogues used at meal time.

C. Alpha-Glucosidase Inhibitors

• Mechanism: Inhibit α-glucosidase enzymes in the gut to slow carbohydrate absorption, reducing postprandial glucose spikes.
• Examples: Acarbose (Precose), Miglitol (Glyset).
• Notes: Mainly reduces postprandial hyperglycemia. GI side effects (flatulence, diarrhea). Contraindicated in IBD, malabsorption, bowel obstruction.
• Hypoglycemia treatment: Use oral glucose (dextrose), NOT sucrose, as acarbose blocks sucrose absorption.

D. Thiazolidinediones (TZDs / Glitazones)

• Mechanism: Activate PPAR-γ receptors → increase insulin sensitivity in skeletal muscle, liver, and adipose tissue.
• Example: Pioglitazone (Actos).
• Benefits: Durable glucose control, improves dyslipidemia.
• Risks: Weight gain, fluid retention/edema, heart failure risk (avoid in NYHA Class III-IV), fracture risk. May cause resumption of ovulation in anovulatory women.

E. DPP-4 Inhibitors (Gliptins)

• Mechanism: Inhibit dipeptidyl peptidase-4 enzyme → prevent breakdown of endogenous GLP-1 and GIP → increase insulin secretion, suppress glucagon.
• Examples: Sitagliptin (Januvia), Saxagliptin, Vildagliptin, Alogliptin.
• Advantages: Weight neutral, low hypoglycemia risk, once daily dosing, safe in CKD (with dose adjustment).
• Intermediate glucose-lowering efficacy compared to other agents.

F. GLP-1 Receptor Agonists (Incretin Mimetics)

• Mechanism: Mimic glucagon-like peptide-1 → stimulate glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying, reduce appetite.
• Examples (injectable): Liraglutide (Victoza), Semaglutide (Ozempic - weekly), Dulaglutide (Trulicity - weekly), Exenatide.
• Oral form: Oral semaglutide (Rybelsus).
• Advantages: Significant HbA1c reduction, substantial weight loss, cardiovascular benefit (liraglutide, semaglutide, dulaglutide reduce CV events and mortality).
• High efficacy agents: Dulaglutide (high-dose), Semaglutide, Tirzepatide.
• Side effects: Nausea, vomiting, GI upset (usually transient).

G. SGLT-2 Inhibitors (Gliflozins)

• Mechanism: Block sodium-glucose cotransporter-2 in the proximal renal tubule → increase urinary glucose excretion regardless of insulin.
• Examples: Empagliflozin (Jardiance), Dapagliflozin (Farxiga), Canagliflozin (Invokana).
• Advantages: Lower HbA1c, reduce body weight and blood pressure, marked cardiovascular benefit (reduce heart failure hospitalization and CKD progression), reduce mortality.
• 2024 ADA/AACE Guidelines specifically recommend SGLT-2 inhibitors in T2DM patients with established CVD, heart failure, or CKD regardless of metformin use or glycemic control.
• Side effects: Urogenital infections (thrush), DKA risk (rare in T2DM), polyuria.

4. Insulin Regimens

• HbA1c >8.5% with symptoms, or
• HbA1c >9.0% regardless of symptoms, or
• Type 1 DM (mandatory), or
• Pregnancy with diabetes, or
• Failure of oral agents.

Types of Insulin

Insulin Regimens

• Once daily long-acting insulin (glargine or detemir) at bedtime.
• Targets fasting hyperglycemia.
• Initial dose: 10 units or 0.1-0.2 units/kg/day.
• Can be combined with oral agents (metformin, DPP-4i, SGLT-2i, GLP-1 RA).
• Titrate dose by 2 units every 3 days until fasting glucose is at target.

• Basal insulin PLUS one injection of rapid-acting insulin for the largest meal of the day.
• Indicated when fasting glucose is controlled but HbA1c remains above target due to postprandial spikes.
• The meal with the highest postprandial glucose "delta" (Δ = 2-hr postprandial minus premeal glucose >50 mg/dL) is targeted first.

• Long-acting (basal) insulin once or twice daily + rapid-acting (bolus) insulin before each meal (3 injections/day).
• Most closely mimics normal physiological insulin secretion.
• Initial prandial dose: 0.1 units/kg per meal.
• Mandatory in Type 1 DM; used in T2DM with very high A1C (>12%) or multiple meal-related glucose excursions.
• Insulin stacking (giving correction doses before previous insulin is fully absorbed) must be avoided - it is a major cause of hypoglycemia.

• Premixed preparations (e.g., 70/30 NPH/regular, 75/25 lispro protamine/lispro) given twice daily (before breakfast and before dinner).
• Simpler than basal-bolus but less flexible; requires fixed mealtimes and carbohydrate portions.
• Good for patients with regular lifestyle who need simplification.

• Delivers programmable basal rates of rapid-acting insulin continuously + patient-activated bolus doses at mealtimes.
• Best for T1DM with difficult glycemic control; also used in T2DM.
• Eliminates need for multiple daily injections.
• Can be coupled with continuous glucose monitoring (CGM) for a "closed-loop" or hybrid artificial pancreas system.

5. Combination/Stepwise Treatment Algorithm (T2DM)

1. Lifestyle modification alone (at diagnosis if A1C <7.5%)
2. Metformin monotherapy (if A1C not at target in 3 months or A1C 7.5-9% at diagnosis)
3. Dual therapy - Add one agent based on patient profile:
   • CVD/HF/CKD present → Add SGLT-2 inhibitor or GLP-1 RA
   • Weight loss needed → GLP-1 RA or SGLT-2i
   • Hypoglycemia concern → DPP-4i, GLP-1 RA, or SGLT-2i (avoid sulfonylurea)
   • Cost concern → Sulfonylurea or TZD
4. Triple therapy - if dual therapy insufficient
5. Add basal insulin (±oral agents) when A1C >8.5-9%
6. Basal-bolus if still above target

6. Special Situations

• Type 1 DM: Basal-bolus insulin is mandatory from diagnosis; no oral agents as primary therapy.
• Gestational DM: Insulin is preferred (metformin/glyburide used off-label); target fasting <95 mg/dL, 1-hr postprandial <140 mg/dL.
• Elderly patients: Avoid sulfonylureas and TZDs; prefer DPP-4i or GLP-1 RA; target A1C 7.5-8%.
• CKD: Avoid metformin if eGFR <45; adjust SGLT-2i (eGFR >20); prefer linagliptin (no renal dose adjustment among gliptins).
• Obesity with T2DM: GLP-1 RA (semaglutide, tirzepatide) are preferred for dual benefit of glucose control + weight loss.

Summary Table

Intraoperative Regimen to Control Diabetes Mellitus

1. Why Intraoperative Glucose Control Matters

• Hyperosmolarity and osmotic diuresis
• Impaired wound healing
• Increased susceptibility to infection (especially deep sternal wound infections after cardiac surgery)
• Worsened neurological outcome after cerebral ischemia
• Increased postoperative mortality

2. Target Blood Glucose Intraoperatively

Blood glucose: 85-180 mg/dL (target <180 mg/dL, avoid <85 mg/dL)

3. Pre-Intraoperative Preparation (Immediately Relevant)

4. Intraoperative Regimen - Main Methods

A. Intravenous Insulin Infusion (Gold Standard for Major Surgery / T1DM)

• Predictable, rapid absorption
• Can be titrated up or down immediately
• SC and IM insulin absorption is unreliable during surgery due to poor tissue perfusion

• Add regular insulin (100 units) to 100 mL of 0.9% Normal Saline → concentration = 1 unit/mL
• Use a dedicated IV line - do NOT run alongside other intraoperative fluids/drugs to avoid unintended rate changes

Units/hour = Plasma glucose (mg/dL) ÷ 150

• T1DM: Start at 0.5-1 unit/hour
• T2DM or poorly controlled/septic patients: Start at 2-3 units/hour or more
• Adjust infusion up or down based on hourly glucose monitoring

• Run a separate infusion of 5-10% Dextrose at 75-100 mL/hour to prevent hypoglycemia
• If blood glucose drops below 100 mg/dL → administer supplemental dextrose bolus

• Insulin drives potassium into cells → hypokalaemia risk
• Add 20 mEq KCl to each litre of maintenance fluid in patients with normal renal function and normal baseline K⁺

• Check blood glucose every 30-60 minutes intraoperatively in patients on IV insulin infusions
• An intra-arterial catheter is recommended for major cases to allow repeated sampling without additional punctures

B. Variable-Rate IV Insulin Infusion ("Sliding Scale IV")

C. Glucose-Insulin-Potassium (GIK) Infusion

• Typical mixture: 500 mL of 10% dextrose + 10-15 units regular insulin + 10-20 mEq KCl
• Infused at 100 mL/hour
• Simpler but less flexible - cannot independently adjust glucose and insulin rates
• Historically used in cardiac surgery; now largely replaced by separate infusions for better titration

D. Subcutaneous Insulin (Minor/Short Procedures Only)

• Give 1/3 to 1/2 of the usual daily NPH/intermediate-acting insulin dose subcutaneously on the morning of surgery
• Omit any short-acting/prandial insulin
• Monitor blood glucose every 1-2 hours
• Limitations: Unreliable absorption under anaesthesia (poor perfusion), cannot be rapidly reversed

E. Continuous Insulin Pump (CSII) - For Pump-Dependent T1DM Patients

• Continue the patient's own insulin pump at the programmed basal rate intraoperatively
• Monitor blood glucose hourly from the pre-operative area
• Turn off the pump if blood glucose falls below 110 mg/dL
• Give correction boluses via pump for blood glucose >180 mg/dL
• If pump placement interferes with the surgical field → switch to IV insulin infusion

5. Regimen by Patient Type

6. Monitoring Frequency

7. Key Principles - Summary

1. Target BG: 85-180 mg/dL - avoid both hypoglycaemia and marked hyperglycaemia
2. IV regular insulin infusion is preferred over SC/IM for major surgery
3. Always co-infuse dextrose when running insulin to prevent hypoglycaemia
4. Always supplement potassium (20 mEq/L) as insulin shifts K⁺ intracellularly
5. Dedicated IV lines for insulin and dextrose - no mixing with other fluids
6. Hourly glucose monitoring is mandatory with IV insulin infusion
7. SGLT-2 inhibitors must be stopped 3-4 days preoperatively due to euglycaemic DKA risk
8. Do NOT use tight control (<110 mg/dL) - associated with worse outcomes in clinical trials
9. The insulin infusion formula units/hr = plasma glucose ÷ 150 is a starting guide only - individual needs vary greatly
10. Stress, sepsis, hypothermia, and catecholamine infusions all alter insulin requirements dramatically