Diabetes Mellitus: Management andTherapies¶
Chapter 416 | Part 12: Endocrinology and Metabolism · Part 12 – Endocrinology & Metabolism · Chapter 416
Key Clinical Points¶
- Primary goals of therapy: (1) eliminate symptoms of hyperglycemia, (2) reduce/eliminate long-term microvascular and macrovascular complications, and (3) allow for a normal lifestyle.
- Comprehensive care requires a multidisciplinary team including PCP, endocrinologist, APP, pharmacist, certified diabetes educator, nutritionist, and behavioral health professional.
- Continuous glucose monitoring (CGM) is recommended for T1DM and T2DM patients on insulin to reduce the frequency of serious hypoglycemia, especially nocturnal events.
- Medical Nutrition Therapy (MNT) goals: T2DM focuses on weight loss (target ≥5–10%) and cardiovascular risk; T1DM focuses on coordinating carbohydrate intake with insulin.
- Exercise goal: 150 min/week of moderate aerobic physical activity distributed over ≥3 days with no gaps longer than 2 days.
- HbA1c reflects average plasma glucose but does not detect glycemic variability or recent intercurrent illnesses (unlike CGM or BGM).
- Elderly patients (>65 years) require individualized goals, often prioritizing the avoidance of hypoglycemia.
- Interference: CGM devices can be affected by hydroxyurea, acetaminophen, ascorbic acid, mannitol, and sorbitol; BGM devices can be affected by uric acid, galactose, xylose, acetaminophen, L-DOPA, and ascorbic acid.
- Religious fasting (e.g., Ramadan) requires pre-fast risk assessment, patient education, and regular glucose monitoring.
- Intensive insulin therapy in T1DM aims for near-normal glycemia through multi-resource integration including education, recording, and variable regimens.
DEFINITION & OVERVIEW¶
• Primary Goals of Therapy: 1. Eliminate symptoms related to hyperglycemia. 2. Reduce or eliminate long-term microvascular and macrovascular complications. 3. Allow the patient to achieve as normal a lifestyle as possible. • Clinical Thresholds: - Symptoms typically resolve when plasma glucose is <11.1 mmol/L (200 mg/dL). • Multidisciplinary Team Approach: - Core team: PCP, endocrinologist/diabetologist, advanced practice provider (APP), pharmacist, certified diabetes educator, nutritionist, and behavioral health professional. - Specialty support: Ophthalmologists, neurologists, podiatrists, nephrologists, cardiologists, and cardiovascular/transplant surgeons.
Comprehensive Care Framework¶
• Chronic Care Model: Proactive, team-based delivery involving self-management, decision support with evidence-based guidelines, technology, and community resources. • Patient-Centered Care: Individualized plans addressing social determinants of health (financial, cultural, employment) and specific risks like MSLD in T2DM/prediabetes.
EPIDEMIOLOGY¶
• Prevalence & Risk Factors: - Obesity: Majority of T2DM patients are obese; weight loss is strongly encouraged. - Age: Approximately 1 in 4 individuals >65 years have diabetes. - Lifestyle: Sleep deprivation and shift work are risk factors for weight gain and insulin resistance. - Social Determinants: Family, financial, cultural, and employment-related issues significantly impact care quality.
ETIOLOGY & PATHOPHYSIOLOGY¶
• Insulin Requirements: - T1DM: Lack of endogenous insulin; basal insulin is essential for regulating hepatic metabolism (glycogen breakdown, gluconeogenesis, lipolysis, ketogenesis). - T2DM: Exercise-related hypoglycemia is less common but possible with insulin or secretagogues. • Exercise Physiology: - Muscle is a major site for metabolic fuel consumption; aerobic exercise increases demand. - T1DM Risk: Hyperglycemia or hypoglycemia during exercise depends on pre-exercise glucose, circulating insulin, lactate, and catecholamines. - Relative Hyperinsulinemia: Excessive insulin can reduce hepatic glucose production and increase muscle uptake → risk of hypoglycemia. • Contraindications: - Untreated proliferative retinopathy is a relative contraindication to vigorous exercise due to risk of vitreous hemorrhage or retinal detachment.
CLINICAL FEATURES¶
• Symptom Management: Focus on long-term goals as symptoms resolve at <11.1 mmol/L (200 mg/dL). • Psychosocial Factors: - Recognition of depression, anxiety, and "diabetes distress" (negative psychological reactions to managing chronic disease). - Impact: Emotional stress can lead to non-adherence to diet, exercise, or medication. - Eating Disorders: Higher prevalence in T1DM and T2DM (e.g., binge eating, bulimia, anorexia). • Complications Screening: - Eye exam: Annual or biannual. - Foot exam: 1–2 times/year by provider; daily by patient. - Neuropathy: Annual examination. - Kidney disease: Annual testing. - Fracture risk: Assessment in older adults (consider bone mineral density).
DIFFERENTIAL DIAGNOSIS¶
• Insulin Preparation Differentiation: - Rapid-acting, injected (Aspart, Glulisine, Lispro): Onset <0.25 h; Duration 3–5 h. - Short-acting, injected (Regular): Onset 0.5–1.0 h; Duration 4–8 h. - Intermediate-acting, injected (NPH): Onset 2–4 h; Duration 10–16 h. - Long-acting, injected (Glargine): Onset 2–4 h; Duration 20–24 h. - Ultra-long-acting, injected (Degludec): Onset 1–9 h; Duration 42 h. - Rapid-acting, inhaled (Human insulin): Onset <0.25 h; Duration 3 h.
DIAGNOSTIC APPROACH¶
• Monitoring Metrics: 1. Short-term (CGM/BGM): Provides real-time data, trends, and Time in Range (TIR). 2. Long-term (HbA1c): Standard for average glucose; correlates with estimated average glucose (eAG). - HbA1c 5%: 5.4 mmol/L (97 mg/dL) - HbA1c 7%: 8.6 mmol/L - HbA1c 9%: 11.8 mmol/L - HbA1c 11%: 14.9 mmol/L • Clinical Metrics: - TIR: % time in desired range. - GMI: Glucose Management Indicator (correlates with HbA1c). - Variability: Measured by % coefficient of variation. • Interference Factors: - CGM Interference: hydroxyurea, acetaminophen, ascorbic acid, mannitol, sorbitol. - BGM Interference: uric acid, galactose, xylose, acetaminophen, L-DOPA, or ascorbic acid.
HbA1c Limitations¶
Factors affecting HbA1c accuracy include hemoglobinopathies, anemias, reticulocytosis, transfusions, uremia, hemodialysis, and vitamin deficiencies (e.g., G6PD).
MANAGEMENT & TREATMENT¶
• 1. Initial Assessment: - Determine individualized goals based on age, comorbidities, and lifestyle. - Target HbA1c: As close to normal as possible without significant hypoglycemia. • 2. Nutrition Therapy (Table 416-2): - General: High fiber, low glycemic content; Mediterranean-style diet. - Fat: Focus on monounsaturated/polyunsaturated fats; no trans fats. - Carbohydrates: Monitor for postprandial control; avoid high-fructose/sucrose beverages. - Protein: Individualized. • 3. Physical Activity: - Goal: 150 min/week moderate aerobic activity → distributed over ≥3 days (no gaps >2 days). • 4. Psychosocial Care: - Screen for depression, anxiety, and diabetes distress. • 5. Pharmacotherapy (Table 416-6): - Biguanides (Metformin): HbA1c reduction 1–2%; weight neutral; first-line. - SGLT-1/2 inhibitors: HbA1c reduction 0.5–1.0%; renal protective, CV benefit. - DPP-4 inhibitors: HbA1c reduction 0.5–0.8%; well tolerated. - Sulfonylureas: HbA1c reduction 1–2%; risk of hypoglycemia/weight gain. - TZDs (Pioglitazone): HbA1c reduction 0.5–1.4%; weight gain, edema. - GLP-1RAs: HbA1c reduction 0.5–1.0%; weight loss, CV benefit. - GLP-1/GIP (Tirzepatide): HbA1c reduction 1.8–2.4%; significant weight loss. - Pramlintide: HbA1c reduction 0.25–0.5%; postprandial control. • 6. DKA Management (Table 416-9): 1. Confirm diagnosis (↑ serum glucose, ↑ β-hydroxybutyrate, metabolic acidosis). 2. Admit to hospital; ICU for severe cases. 3. Assess: Electrolytes (K+, Na+, Mg2+, Cl-, bicarbonate, phosphate), Acid-base status, Renal function. 4. Fluid Replacement: - Initial: 2–3 L of 0.9% saline or LR over first 1–3 h (10–20 mL/kg per hour). - Follow-up: 0.45% saline at 250–500 mL/h. - Switch to 5–10% glucose + 0.45% saline when blood glucose ≥ 13.9 mmol/L (250 mg/dL). 5. Insulin Administration: - IV: 0.1 units/kg bolus, then 0.1 units/kg per hour infusion. - If K+ < 3.3 mmol/L → Hold insulin until K+ corrected. - If K+ 3.5–5.0 mmol/L → Add 10–20 mEq/L to each liter of fluid. - If K+ >5.0 mmol/L → Start insulin but hold K+. 6. Identify precipitating event (infection, infarction, etc.). 7. Monitoring: Glucose every 1–2 h; Electrolytes/Anion gap every 4 h for first 24 h. 8. Clinical monitoring: BP, pulse, respiration, mental status every 1–4 h. 9. Potassium replacement: If K+ <3.5 mmol/L → add 10–20 mEq/L per hour until >3.5. 10. Resolution criteria: Glucose 8.3–11.1 mmol/L (150–200 mg/dL), normal ketones, pH, and bicarbonate ≥18 mEq/L. 11. Transition: Start long-acting insulin when eating; allow 2–4 h overlap with IV infusion.
Glycemic Management of T2DM (Flowchart 2)¶
• Step 1: Initial Plan → Individualized plan including MNT, exercise, weight loss goal 5–7%, and continuing metformin. • Path A (ASCVD/Risk): If ASCVD risk present → Add GLP-1RA or SGLT-2 inhibitor. - If HbA1c > target → Add GLP-1RA OR add SGLT-2 inhibitor or GLP-1RAs. • Path B (Heart Failure): If HFrEF/HFpEF present → Add SGLT-2 inhibitor. - If HbA1c > target → Add insulin. • Path C (CKD): If CKD present → Add SGLT-2 inhibitor. - If HbA1c > target → Add GLP-1RA. • Path D (Glycemia Focus): Options include GLP-1RA, GLP-1RA + insulin, Combination oral/injectable, Sulfonylurea, TZDs, or DPP-4 inhibitor. - If HbA1c > target → Add insulin; Re-evaluate lifestyle/nutrition/exercise. • Path E (Weight Focus): Options include GLP-1RA, Structured weight loss program, or Metabolic surgery.
PROGNOSIS & COMPLICATIONS¶
• Risk Reduction: Improvement in glycemic control reduces risk of microvascular complications. • Monitoring: Timely and consistent surveillance is required to detect, prevent, and manage DM-related complications.
SPECIAL POPULATIONS¶
• Elderly Adults (Table 416-4): - Intact Cognition/Function: HbA1c <7.0–7.5%; TIR >70% (4.4–10.0 mmol/L); CV <33%. - Other Serious Comorbidities: HbA1c <8.0%; TIR >50% (5.5–10.0 mmol/L); T1.1 0%; T1.2 0%. - Complex Comorbidities/Poor Health/Impaired Cognition: HbA1c <8.5%; TIR >40% (6.7–12.2 mmol/L). - Preprandial Targets: Non-pregnant: 4.4–7.2 (80–130); Elderly Intact: 4.4–7.2 (80–130); Elderly Other: 5.0–8.3 (90–150); Elderly Complex: 5.6–10.0 (100–180). - Postprandial Targets: Non-pregnant: <10.0 (180); Elderly Intact: <11.1 (200); Elderly Other: <13.9 (250). • Religious Fasting: - Requires pre-Ramadan risk assessment. - Education and regular glucose monitoring are critical.
KEY PEARLS & HIGH-YIELD POINTS¶
• HbA1c vs. Glucose: HbA1c is a multi-month average; CGM/BGM provides real-time data and detects variability. • SGLT-1/2 Inhibitors: Preferred in patients with Heart Failure or CKD. • Insulin Selection: Choose based on duration (e.g., Degludec for ultra-long, Glargine for long, NPH for intermediate). • DKA Management: Potassium must be >3.3 mmol/L before starting insulin; bicarbonate ≥18 mEq/L is the goal for resolution. • Tirzepatide: High efficacy (1.8–2.4% HbA1c reduction) and significant weight loss.
Reference Tables¶
TABLE 416-1 Guidelines for Ongoing, Comprehensive Medical Care for Individuals with Diabetes • Individualized glycemic…¶
Harrison's 22e, p.3205
| 416 | Diabetes Mellitus: Management and Therapies Alvin C. Powers, Kevin D. Niswender, Michael R. Rickels |
|---|---|
TABLE 416-1 Guidelines for Ongoing, Comprehensive Medical Care for Individuals with Diabetes
- • Individualized glycemic goal and therapeutic plan with an emphasis on shared
decision-making
• Blood glucose measurement using continuous glucose monitoring (CGM) or
capillary fingerstick device
• HbA testing (2–4 times/year)
1c
• Lifestyle management in the care of diabetes, including:
• Diabetes self-management education and support
• Nutrition therapy
• Physical activity
• Psychosocial care, including evaluation for depression, anxiety, diabetes
distress
• Detection, prevention, or management of diabetes-related complications,
including:
• Diabetes-related eye examination (annual or biannual; Chap. 417)
• Diabetes-related foot examination (1–2 times/year by provider; daily by
patient; Chap. 415)
• Diabetes-related neuropathy examination (annual; Chap. 415)
• Diabetes-related kidney disease testing (annual; Chap. 417)
• Screen for other diabetes-related complications (annual; see Table 417-1)
• Assessment of fracture risk in older adults with diabetes (consider
measurement of bone mineral density)
• Manage or treat diabetes-relevant conditions, including:
• Blood pressure (assess 2–4 times/year; Chap. 417)
• Lipids (1–2 times/year; Chap. 417)
• Consider screening individuals with type 2 diabetes or prediabetes for
metabolic dysfunction–associated steatotic liver disease if other risk
factors are present
• Consider antiplatelet therapy with low-dose aspirin (Chap. 417)
• Immunizations, including influenza, pneumococcal, hepatitis B,
coronavirus, and respiratory syncytial virus (>60 years of age) (Chap. 6)
TABLE 416-2 Nutritional Recommendations for Adults with Diabetes or Prediabetes a General dietary guidelines •…¶
Harrison's 22e, p.3206
- General dietary guidelines
• Vegetables, fruits, whole grains, legumes, low-fat dairy products and food
higher in fiber and lower in glycemic content; optimal diet composition and
eating pattens are not known.
Fat in diet (optimal percentage of diet is not known; should be individualized)
• Encourage Mediterranean-style diet rich in monounsaturated and
polyunsaturated fatty acids.
• Minimal or no trans fat consumption.
Carbohydrate in diet (optimal percentage of diet is not known; should be
individualized)
• Monitor carbohydrate intake in regard to calories and set limits for meals to
reduce postprandial glycemia.
• Consider limiting overall carbohydrate intake in adults with diabetes as this
may improve glycemia.
• Avoid fructose- and sucrose-containing beverages and minimize consumption
of foods with added sugar that may displace healthier, more nutrient-dense
food choices and elevate postprandial glycemia.
• Estimate grams of carbohydrate in diet for flexible insulin dosing (type 1
diabetes and insulin-dependent type 2 diabetes).
• Consider using glycemic index to predict how consumption of a particular
food may affect blood glucose.
Protein in diet (optimal percentage of diet is not known; should be individualized)
Other components
• Reduced-calorie and nonnutritive sweeteners may be useful.
• Routine supplements of vitamins, antioxidants, or trace elements not
supported by evidence.
• Vitamin D and calcium supplemental as recommended to promote bone
health.
• Sodium intake as advised for general population (<2300 mg/d).
• Minimize disruption to sleep and eating patterns (chrononutrition), and note
risk of hypoglycemia associated with religious fasting.
TABLE 416-3 Relationship of HbA 1c and Estimated Average Glucose (eAG)¶
Harrison's 22e, p.3207
| HEMOGLOBIN A (%) 1C |
ESTIMATED AVERAGE GLUCOSE (AVERAGE, RANGE) | |
|---|---|---|
| mmol/L | mg/dL | |
| 5 | 5.4 (4.2–6.7) | 97 (76–120) |
| 7.0 (5.5–8.5) | ||
| 7 | 8.6 (6.8–10.3) | 154 (123–185) |
| 10.2 (8.1–12.1) | ||
| 9 | 11.8 (9.4–13.9) | 212 (170–249) |
| 13.4 (10.7–15.7) | ||
| 11 | 14.9 (12.0–17.5) | 269 (217–314) |
| 16.5 (13.3–19.3) |
TABLE 416-4 Glycemic Goals for Adults with Diabetes a¶
Harrison's 22e, p.3209
| INDEX OF GLYCEMIC CONTROL | ADULTS (NONPREGNANT) | ELDERLY ADULTS WITH INTACT COGNITION AND FUNCTIONAL STATUS |
ELDERLY ADULTS WITH OTHER SERIOUS COMORBIDITIESb |
ELDERLY ADULTS WITH COMPLEX COMORBIDITIES, POOR HEALTH, OR IMPARIED COGNITIONc |
|---|---|---|---|---|
| HbA 1c |
<7.0% (53 mmol/mol) | <7.0–7.5% (53–57 mmol/mol) | <8.0% (64 mmol/mol) | <8.5% (64 mmol/mol) with avoidance of hypoglycemia |
| >70% within 3.9–10.0 mmol/L (70–180 mg/dL)c <4% <1% ≤36% |
>70% within 4.4–10.0 mmol/L (80–180 mg/dL)c <1% <1% <33% |
>50% within 5.5–10.0 mmol/L (100–200 mg/dL)c 0% 0% N/A |
||
| Preprandial capillary blood glucose | 4.4–7.2 mmol/L (80–130 mg/dL) |
4.4–7.2 mmol/L (80–130 mg/dL) |
5.0–8.3 mmol/L (90–150 mg/dL) |
5.6–10.0 mmol/L (100–180 mg/dL) |
| <10.0 mmol/L (<180 mg/dL) | <11.1 mmol/L (200 mg/dL) | <13.9 mmol/L (250 mg/dL) |
TABLE 416-5 Properties of Insulin Preparations a PREPARATION Rapid-acting, injected¶
Harrison's 22e, p.3209
| PREPARATION | TIME OF ACTION | ||
|---|---|---|---|
| ONSET, h | PEAK, h | EFFECTIVE DURATION, h |
|
| Rapid-acting, injected | |||
| Aspartb | <0.25 | 0.5–1.5 | 3–5 |
| Glulisine | <0.25 | 0.5–1.5 | 3–5 |
| Lisproc | <0.25 | 0.5–1.5 | 3–5 |
| Short-acting, injected | |||
| 0.5–1.0 | 2–3 | ||
| Rapid-acting, inhaled | |||
| Inhaled human insulin | <0.25 | 1–2 | 3 |
| Intermediate-acting, injected | |||
| 2–4 | 4–10 | ||
| Long-acting or Ultralong-acting, injected | |||
| Degludec | 1–9 | —e | 42f |
| Glargineg | 2–4 | —e | 20–24 |
| Examples of insulin combinationsh | |||
| <0.25 | Duali | ||
| <0.25 | Duali | ||
| <0.25 | Duali | ||
| 0.5–1 | Duali | ||
| Combination of long-acting insulin and GLP-1RA |
See text |
TABLE 416-6 Agents Used for Treatment of Type 1 or Type 2 Diabetes Oral Biguanides c ∗¶
Harrison's 22e, p.3211
| MECHANISM OF ACTION |
EXAMPLESa | HBA 1C REDUCTION (%)b |
AGENT-SPECIFIC ADVANTAGES |
AGENT-SPECIFIC DISADVANTAGES |
CONSIDERATIONS | |
|---|---|---|---|---|---|---|
| Oral | ||||||
| Biguanidesc∗ | ↓ Hepatic glucose production, ↑ insulin sensitivity, influence gut function |
Metformin | 1–2 | Weight neutral, do not cause hypoglycemia, inexpensive, extensive experience, modest ↓ CV events |
Diarrhea, nausea, lactic acidosis, vitamin B 12 deficiency |
Renal insufficiency (see text for GFR <30 mL/min), CHF, radiographic contrast studies, hospitalized patients, acidosis |
| ↑ Renal glucose excretion |
Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin, bexagliflozin, sotagliflozin (SGLT-1/2 inhibitor) |
0.5–1.0 | Renal protective, ↓ CV events, ↓ heart failure, do not cause hypoglycemia, modest ↓ weight and blood pressure |
Increased risk genital mycotic infections and necrotizing fasciitis of perineum; polyuria, dehydration; increased risk of euglycemic DKAf (see text); exacerbate tendency to hyperkalemia |
||
| Dipeptidyl peptidase-4 inhibitorsc∗∗∗ |
Prolong endogenous GLP-1 action; ↑ insulin, ↓ glucagon |
Alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin |
0.5–0.8 | Well tolerated, do not cause hypoglycemia |
Angioedema/urticarial and immune-mediated dermatologic effects; rarely associated with pancreatitis |
Reduced dose with renal insufficiency |
| ↑ Insulin secretion | Glimepiride, glipizide, gliquidone, glyburide |
1–2 | Short onset of action, lower postprandial glucose, inexpensive |
Hypoglycemia, weight gain |
||
| Insulin secretagogues: Nonsulfonylureasc∗∗∗ |
↑ Insulin secretion | Nateglinide, repaglinide |
0.5–1.0 | Short onset of action, lower postprandial glucose |
Hypoglycemia | Renal/liver insufficiency (except repaglinide) |
| ↓ Insulin resistance, ↑ glucose utilization |
Pioglitazone, rosiglitazone |
0.5–1.4 | Lower insulin requirements |
Peripheral edema, CHF, weight gain, fractures, macular edema |
||
| α-Glucosidase inhibitorsc∗∗ |
↓ GI glucose absorption |
Acarbose, miglitol |
0.5–0.8 | Reduce postprandial glycemia |
GI flatulence, elevated liver function tests |
Renal/liver insufficiency |
| Parenteral/Oral (GLP-1RA-related agents) | ||||||
| ↑ Insulin, ↓ glucagon, slow gastric emptying, satiety |
Dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide (oral formulation available) |
0.5–1.0 | Weight loss, do not cause hypoglycemia (unless combined with another insulin secretagogue or insulin); ↓ CV events, modest renoprotection |
Nausea, GI intolerance; possibly associated with pancreatitise, possibly worsen retinopathy |
||
| GLP-1/GIP receptor agonistc∗∗∗ |
↑ Insulin, ↓ glucagon, slow gastric emptying, satiety |
Tirzepatide | 1.8-2.4 | Weight loss, do not cause hypoglycemia (unless combined with insulin secretagogue or insulin); ↓ CV events |
Nausea, GI intolerance, possibly associated pancreatitise, possibly worsen retinopathy |
Renal disease, agents that also slow GI motility; medullary carcinoma of thyroid, pancreatic disease, history of gastroparesis |
| Parenteral | ||||||
| Slow gastric emptying, ↓ glucagon |
Pramlintide | 0.25–0.5 | Reduce postprandial glycemia, weight loss |
Injection, nausea, ↑ risk of hypoglycemia with insulin |
||
| Insulinc,d∗∗∗∗ | ↑ Glucose utilization, ↓ hepatic glucose production, and other anabolic actions |
See text and Table 416-4 |
Not limited | Known safety profile | Injection, weight gain, hypoglycemia |
Can be combined with most other agents |
| ↓ Insulin resistance, ↑ insulin secretion |
Low-calorie, carbohydrate- controlled diet, exercise |
1–3 | Other health benefits | Compliance difficult, long-term success of sustained weight loss low |
TABLE 416-7 Laboratory Values in Diabetic Ketoacidosis (DKA), Hyperglycemic Hyperosmolar State (HHS), and Euglycemic…¶
Harrison's 22e, p.3217
| DKA | HHS | EUGLYCEMIC DKAc | |
|---|---|---|---|
| Glucose,a mmol/L (mg/dL) | 11.1–33.3 (250–600) | 33.3–66.6 (600–1200) | 5.5-13.9 (100–250)c |
| 125–135 | 135–145 | ||
| Potassiuma,b | Normal to ↑ | Normal | Normal to ↑ |
| Normal | Normal | ||
| Chloridea | Normal | Normal | Normal |
| Normal | Normal | ||
| Creatinine | Slightly to moderately ↑ | Moderately ↑ | Slightly ↑ |
| >300 | >300 | ||
| Serum/urine ketonesa | >++ | +/– | >++ |
| >3.0 | <1.0 | ||
| Serum bicarbonate,a meq/L | <18 | >18 | <18 |
| 6.8–7.3 | >7.3 | ||
| Arterial Pco,a mmHg 2 |
20–30 | Normal | 20–30 |
| ↑ | Normal to slightly ↑ |
TABLE 416-8 Manifestations of Diabetic Ketoacidosis Symptoms¶
Harrison's 22e, p.3217
| Symptoms Nausea/vomiting Thirst/polyuria Abdominal pain Shortness of breath Precipitating events Inadequate insulin administration Infection (pneumonia/UTI/ gastroenteritis/sepsis) Infarction (cerebral, coronary, mesenteric, peripheral) Pancreatitis Drugs (cocaine) Pregnancy |
Physical Findings Tachycardia Dehydration/hypotension Tachypnea/Kussmaul respirations/ respiratory distress Abdominal tenderness (may resemble acute pancreatitis or surgical abdomen) Lethargy/obtundation/cerebral edema/possibly coma |
|---|---|
TABLE 416-9 Management of Diabetic Ketoacidosis (DKA) 1. Confirm diagnosis ( ↑ serum glucose, ↑ serum β…¶
Harrison's 22e, p.3218
-
- Confirm diagnosis (↑ serum glucose, ↑ serum β-hydroxybutyrate, metabolic
acidosis).
2. Admit to hospital; intensive care setting may be necessary for severe DKA
(see text). Mild to moderate DKA can be treated in a step-down unit with
close nursing and laboratory monitoring.
3. Assess:
Serum electrolytes (K+, Na+, Mg2+, Cl–, bicarbonate, phosphate)
Acid-base status—pH, HCO–, PCO, β-hydroxybutyrate
3 2
Renal function (creatinine, urine output)
4. Replace fluids: 2–3 L of 0.9% saline or lactated Ringer’s over first 1–3 h
(10–20 mL/kg per hour); subsequently, 0.45% saline at 250–500 mL/h; change
to 5–10% glucose and 0.45% saline or lactated Ringer’s at 150–250 mL/h when
blood glucose reaches 250 mg/dL (13.9 mmol/L). For treatment of euglycemic
DKA, start 5% or 10% dextrose infusion and insulin treatment when 0.9% saline
is started; adjust dextrose infusion to prevent hypoglycemia.
5. Administer short-acting regular insulin: IV (0.1 units/kg), then 0.1 units/
kg per hour by continuous IV infusion; increase two- to threefold if no
response by 2–4 h. In mild to moderate DKA, subcutaneous rapid-acting
insulin may be used with close monitoring (0.1 unit/kg rapid-acting insulin
analogue subcutaneously and then 0.1 unit/kg every 1 h or 0.2 unit/kg every
2 h). Continue insulin treatment and 5% or 10% dextrose infusion to prevent
hypoglycemia. If the initial serum potassium is <3.3 mmol/L (3.3 meq/L), do
not administer insulin until the potassium is corrected.
6. Assess patient: What precipitated the episode (noncompliance, infection,
trauma, pregnancy, infarction, cocaine)? Initiate appropriate workup for
precipitating event (cultures, CXR, ECG, etc.).
7. Measure blood glucose every 1–2 h; measure electrolytes (especially K+,
bicarbonate, phosphate) and anion gap every 4 h for first 24 h.
8. Monitor blood pressure, pulse, respirations, mental status, fluid intake and
output every 1–4 h.
9. Replace K+ if ECG, urine flow, and creatinine are normal. If K+ <3.5 mmol/L,
administer 10–20 mmol/L per hour until K+ >3.5 mmol/L. If K+ 3.5–5 mmol/L,
administer 10–20 mmol/L in each liter of IV fluid to keep serum K+ between
4 and 5 mmol/L. If K+ >5.0 mmol/L, start insulin but hold K+. Recheck K+ every
2 h to determine when to start K+ replacement.
10. Continue above until patient is stable, glucose goal is 8.3–11.1 mmol/L
(150–200 mg/dL), normal plasma ketone and pH, and bicarbonate ≥18 mmol/L.
Insulin infusion may be decreased to 0.02–0.1 unit/kg per hour. Resolution of
euglycemic DKA should be based on bicarbonate, not glucose, correction;
see text.
11. Administer long-acting insulin as soon as patient is eating. Allow for a 2- to
4-h overlap in insulin infusion and SC long-acting insulin injection.
- Confirm diagnosis (↑ serum glucose, ↑ serum β-hydroxybutyrate, metabolic