Diabetes Management & Complications
Metformin, the cardiorenal agents, and the emergencies of DKA and HHS
Diagnosis and glycemic targets
Four ways to diagnose diabetes. Any one of the following establishes the diagnosis: HbA1c ≥6.5%, fasting plasma glucose ≥126 mg/dL, 2-hour OGTT ≥200 mg/dL, or a random glucose ≥200 mg/dL with classic symptoms (polyuria, polydipsia, weight loss). Confirm with a repeat test unless the patient is unequivocally hyperglycemic. Prediabetes is an A1c of 5.7–6.4% or a fasting glucose of 100–125 mg/dL.
A1c misleads when red cell turnover is abnormal (hemolysis, recent transfusion or blood loss, hemoglobinopathy, pregnancy); rely on glucose criteria in those settings.
Targets. A1c reflects roughly 3 months of average glycemia. The general target is <7% for most nonpregnant adults, <6.5% if achievable without hypoglycemia (younger, few comorbidities), and <8% for the elderly or those with extensive comorbidity or limited life expectancy, in whom hypoglycemia is the bigger danger.
Glucose-lowering therapy
Lifestyle plus metformin first. Diet, exercise, and weight loss are always foundational, and metformin is first-line pharmacotherapy. It decreases hepatic gluconeogenesis, is weight-neutral, and causes no hypoglycemia on its own; GI upset is its most common side effect. Avoid it if eGFR <30 (lactic acidosis), hold it around iodinated contrast and during acute illness, and screen for B12 deficiency with long-term use.
Pick the second drug by comorbidity, not just A1c. Established ASCVD, heart failure, or CKD favors a GLP-1 receptor agonist or SGLT2 inhibitor regardless of A1c; for heart failure or CKD, the SGLT2 inhibitor is the natural choice.
| Class | Mechanism | Strengths | Watch for |
|---|---|---|---|
| Metformin | ↓ Hepatic gluconeogenesis | Weight-neutral, no hypoglycemia | Lactic acidosis (eGFR <30), B12 deficiency, GI upset |
| GLP-1 agonists (semaglutide, liraglutide) | ↑ Glucose-dependent insulin, slow gastric emptying | Weight loss, fewer CV events, no hypoglycemia alone | Nausea; contraindicated with personal or family medullary thyroid cancer or MEN2 |
| SGLT2 inhibitors (empagliflozin, dapagliflozin) | Block proximal tubule glucose reabsorption → glucosuria | Weight loss; proven benefit in heart failure and CKD | Genital mycotic infections, euglycemic DKA, volume depletion |
| Sulfonylureas (glipizide) | Close β-cell KATP channels → insulin release | Cheap, potent | Hypoglycemia, weight gain |
| Pioglitazone | PPAR-γ agonist → ↑ insulin sensitivity | No hypoglycemia | Edema, heart failure, weight gain |
| Insulin | Replacement | Most potent; required in type 1 | Hypoglycemia, weight gain |
Euglycemic DKA on an SGLT2 inhibitor can occur with a near-normal glucose, so check ketones and the anion gap in any ill, vomiting patient taking one.
Insulin. Type 1 diabetes always requires insulin, given as basal-bolus therapy: a long-acting basal insulin (glargine, detemir) plus prandial rapid-acting insulin (lispro, aspart). In type 2, start insulin when A1c is very high (>10%), glucose is >300 mg/dL, or the patient is symptomatic or catabolic.
Morning hyperglycemia. The dawn phenomenon comes from rising early-morning cortisol and growth hormone; the Somogyi effect is rebound hyperglycemia after nocturnal hypoglycemia. A 3 a.m. glucose separates them: high in the dawn phenomenon (more or later evening basal insulin), low in Somogyi (less evening insulin).
Diabetic ketoacidosis
Recognition. DKA occurs mostly in type 1 diabetes, often triggered by infection, missed insulin, or new-onset disease. Patients have vomiting, abdominal pain, dehydration, fruity breath, and deep Kussmaul respirations. Criteria (2024 consensus) are glucose ≥200 mg/dL or known diabetes at any glucose, ketonemia (beta-hydroxybutyrate ≥3.0 mmol/L, or urine ketones 2+ or more), and acidosis with pH <7.3 or bicarbonate <18.
Fluids, insulin, potassium. Give IV isotonic crystalloid FIRST (a balanced crystalloid such as lactated Ringer is suggested, or normal saline), then an insulin drip, and replace potassium. Add potassium once serum K is <5.0; HOLD insulin if K <3.5 mEq/L.
- IV isotonic crystalloidCorrect volume first
- Insulin dripOnly if K ≥3.5 mEq/L; below that, replace K first
- Replace potassiumAdd K once serum K <5.0
- Add dextrose when glucose <250Continue insulin to close the gap
- Subcutaneous insulinOverlap with the drip before stopping it
Total body potassium is depleted even when serum K looks normal or high, because acidosis and insulin deficiency shift K out of cells. Insulin drives K back in, so give insulin only once K is ≥3.5.
Close the gap, not just the glucose. The goal is to clear ketones and close the anion gap. Glucose falls faster than ketones clear, so when glucose drops below 250 mg/dL, add dextrose to the fluids and keep the insulin drip running until the gap closes. Then transition to subcutaneous insulin with overlap to prevent rebound ketoacidosis. Bicarbonate is not routine.
Hyperosmolar hyperglycemic state
HHS usually affects older patients with type 2 diabetes, often after infection or poor access to water. Enough insulin remains to suppress ketogenesis but not hyperglycemia, so glucose climbs to 600 mg/dL or more with effective serum osmolality >300 mOsm/kg (total >320), minimal ketones (beta-hydroxybutyrate <3.0 mmol/L), pH ≥7.3 and bicarbonate ≥15, and severe dehydration with altered mental status. Mortality is higher than in DKA. Treat with aggressive IV fluids and insulin, correcting glucose and osmolality more slowly.
| Feature | DKA | HHS |
|---|---|---|
| Typical patient | Type 1, younger | Type 2, older |
| Glucose | ≥200 mg/dL, or known diabetes | ≥600 mg/dL |
| Acid-base | pH <7.3, bicarbonate <18, wide anion gap | pH ≥7.3, bicarbonate ≥15 |
| Ketones | Positive | Minimal |
| Osmolality | Variable | Effective >300 mOsm/kg |
| Clues | Fruity breath, Kussmaul breathing | Altered mental status, profound dehydration |
| Mortality | Lower | Higher |
Chronic complications and screening
Microvascular disease (retinopathy, nephropathy, neuropathy) tracks with glycemic control, so screening is scheduled and treatment starts early.
| Target | Screen | Timing | Action |
|---|---|---|---|
| Retinopathy | Dilated eye exam | At diagnosis in type 2; 5 years after diagnosis in type 1; then annually | Ophthalmology for proliferative disease or macular edema |
| Nephropathy | Urine albumin-to-creatinine ratio + eGFR | Yearly | ACE inhibitor or ARB for albuminuria; SGLT2 inhibitor |
| Neuropathy | 10-g monofilament + distal sensory exam | Yearly | Duloxetine, pregabalin, or gabapentin for pain |
| Feet | Inspection; check for peripheral artery disease | Every visit, plus daily self-exams | Protective footwear, early ulcer care |
Kidneys. Moderately increased albuminuria is a urine albumin-to-creatinine ratio of 30–299 mg/g, confirmed on repeat samples. Once albuminuria appears, give an ACE inhibitor or ARB (not both together) even if blood pressure is normal; SGLT2 inhibitors add renoprotection.
Nerves and feet. Distal symmetric "stocking-glove" polyneuropathy is the most common form; autonomic neuropathy causes gastroparesis, orthostatic hypotension, and erectile dysfunction. Lost protective sensation plus ischemia drives foot ulcers and amputations, which is why the feet are inspected at every visit.
Macrovascular risk. Cardiovascular disease is the leading cause of death in diabetes: control blood pressure (goal <130/80) and give a statin.