Diabetes Mellitus: Management and Therapies¶
Chapter 416 | Part 12: Endocrinology and Metabolism
KEY CLINICAL POINTS¶
- Comprehensive diabetes care includes glycemic control, lifestyle management, and prevention of complications.
- Individualized glycemic targets (e.g., HbA1c <7%) are essential, with adjustments for elderly or comorbid patients.
- Insulin therapy is critical for type 1 diabetes and advanced type 2 diabetes, with newer agents like GLP-1RAs and SGLT-2 inhibitors offering cardiovascular benefits.
- CGM and AID systems improve glycemic control and reduce hypoglycemia risks in type 1 diabetes.
- Management of acute complications (DKA/HHS) requires fluid resuscitation, insulin, and electrolyte correction.
1. DEFINITION & OVERVIEW¶
Diabetes mellitus (DM) is a metabolic disorder characterized by hyperglycemia due to defects in insulin secretion, action, or both. Management focuses on glycemic control, complication prevention, and lifestyle modification. The goals include eliminating hyperglycemia-related symptoms, preventing microvascular/macrovacular complications, and enabling a normal lifestyle.
Table 416-1: Guidelines for Ongoing, Comprehensive Medical Care¶
| Individualized glycemic goal and therapeutic plan | Blood glucose measurement | HbA1c testing | Lifestyle management | Psychosocial care | Complication screening |
|---|---|---|---|---|---|
| Shared decision-making | CGM/BGM | 2–4 times/year | Nutrition, exercise, diabetes education | Depression/anxi ety screening | Annual eye/foot/kidney exams |
1.1 Pathophysiology¶
Type 1 DM: Autoimmune destruction of pancreatic β -cells leading to absolute insulin deficiency. Type 2 DM: Insulin resistance with relative β -cell dysfunction. Gestational diabetes: Hyperglycemia during pregnancy without prior diabetes.
1.2 Clinical Spectrum¶
DM encompasses a spectrum of conditions with varying etiologies and severity. Management requires individualized approaches based on type, comorbidities, and patient preferences.
2. EPIDEMIOLOGY¶
Global prevalence of diabetes is rising, with ~9.4% of adults (463 million) affected. Type 2 DM accounts for ~90% of cases. Risk factors include obesity, family history, and metabolic syndrome. Elderly populations face higher risks due to age-related insulin resistance and comorbidities.
2.1 Demographics¶
Predominant in urban areas; higher prevalence in South Asia and the Pacific. Age-adjusted incidence peaks in middle age, with increasing prevalence in older adults.
2.2 Complications¶
Microvascular (retinopathy, nephropathy, neuropathy) and macrovascular (CVD, stroke) complications are major contributors to morbidity/mortality.
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Type 1 DM: Autoimmune destruction of β -cells. Type 2 DM: Insulin resistance with β -cell dysfunction. Genetic predisposition and environmental triggers (e.g., obesity, infections) contribute to pathogenesis.
3.1 Insulin Resistance¶
Central to type 2 DM, driven by visceral adiposity, inflammation, and hepatic glucose output. Insulin resistance impairs glucose uptake in muscle and adipose tissue.
3.2 β -Cell Dysfunction¶
Progressive loss of β -cell mass/function due to oxidative stress, lipotoxicity, and immune-mediated damage. GLP-1 and incretin hormones mitigate this.
4. CLINICAL FEATURES¶
Symptoms include polyuria, polydipsia, weight loss, and fatigue. Chronic complications manifest as neuropathy, retinopathy, and nephropathy. Acute complications (DKA/HHS) present with severe hyperglycemia, ketosis, and metabolic acidosis.
Table 416-7: Laboratory Values in DKA, HHS, and Euglycemic DKA¶
| Parameter | DKA | HHS | Euglycemic DKA |
|---|---|---|---|
| Glucose (mmol/L) | 11.1–33.3 | 33.3–66.6 | 5.5–13.9 |
| Sodium (mmol/L) | 125–135 | 135–145 | |
| Potassium | Normal to › | Normal | Normal to › |
| Serum bicarbonate (meq/L) | <18 | >18 | <18 |
| Arterial pH | 6.8–7.3 | >7.3 | 6.8–7.3 |
| Serum b-hydroxybutyrate | >3.0 | <1.0 | >3.0 |
4.1 Chronic Complications¶
Microvascular: Diabetic retinopathy, nephropathy, neuropathy. Macrovascular: Coronary artery disease, stroke, peripheral artery disease.
4.2 Acute Complications¶
DKA: Hyperglycemia, ketosis, metabolic acidosis. HHS: Hyperosmolar state without ketosis, severe dehydration, and altered mental status.
5. DIFFERENTIAL DIAGNOSIS¶
Differentiate DM from other causes of hyperglycemia (e.g., Cushing’s syndrome, pancreatic tumors, drug-induced hyperglycemia). Consider gestational diabetes and other endocrine disorders.
5.1 Non-Diabetic Hyperglycemia¶
Cushing’s syndrome, hyperthyroidism, acromegaly, and drug-induced (e.g., glucocorticoids, atypical antipsychotics).
5.2 Gestational Diabetes¶
Screening via OGTT in high-risk pregnancies. Distinguishes from type 2 DM with postpartum resolution.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnosis requires fasting plasma glucose, OGTT, or HbA1c. Confirm with repeated testing. Monitor for complications via eye, foot, and kidney exams.
Table 416-4: Glycemic Goals for Adults with Diabetes¶
| Index of Glycemic Control | Adults (Nonpregnant) | Elderly with Intact Cognition | Elderly with Other Serious Comorbidities | Elderly with Complex Comorbidities |
|---|---|---|---|---|
| HbA1c (%) | <7.0 | <7.0–7.5 | <8.0 | <8.5 |
| CGM Metrics | 70–180 mg/dL | 80–180 mg/dL | 100–200 mg/dL | 120–220 mg/dL |
| Time below 70 mg/dL | <4% | <1% | 0% | 0% |
| Time below 54 mg/dL | <1% | <1% | 0% | 0% |
| Glucose Variability | £36% | <33% | N/A | N/A |
6.1 Diagnostic Criteria¶
FPG ≥ 126 mg/dL, 2-h OGTT ≥ 200 mg/dL, or HbA1c ≥ 48 mmol/mol (6.5%).
6.2 Complication Screening¶
Annual eye exam, foot exam, and urine albumin-to-creatinine ratio. Monitor for retinopathy, neuropathy, and CKD.
7. MANAGEMENT & TREATMENT¶
Lifestyle modification (diet, exercise) is foundational. Pharmacologic agents include metformin, GLP-1RAs, SGLT-2 inhibitors, and insulin. Acute management of DKA/HHS requires fluid resuscitation, insulin, and electrolyte correction.
Table 416-6: Agents Used for Treatment of Type 1 or Type 2 Diabetes¶
| Mechanism of Action | Examples | HbA1c Reduction (%) | Advantages | Disadvantages | Considerations |
|---|---|---|---|---|---|
| Biguanides | Metformin | 1–2 | Weight neutral, inexpensive | GI side effects | Renal insufficiency |
| SGLT-2 Inhibitors | Canagliflozin | 0.5–1.0 | Renal protective | Genital infections | Avoid in CKD |
7.1 Lifestyle Management¶
Nutrition therapy, physical activity, and diabetes education are critical. Weight loss goals of 5–7% are recommended for type 2 DM.
7.2 Pharmacologic Agents¶
Metformin (first-line for type 2 DM), GLP-1RAs (cardiovascular benefits), SGLT-2 inhibitors (kidney protection), and insulin for advanced disease.
7.3 Insulin Therapy¶
Basal/bolus regimens, CSII, and AID systems. Insulin adjustments based on CGM and BGM data.
8. PROGNOSIS & COMPLICATIONS¶
Poor glycemic control increases risk of microvascular/macrovacular complications. Mortality from DKA/HHS is <1% with prompt treatment. Long-term complications include retinopathy, nephropathy, and neuropathy.
8.1 Long-Term Outcomes¶
HbA1c reduction by 1% lowers microvascular risk by 25% and macrovascular risk by 16%. Early intervention improves outcomes.
8.2 Acute Complications¶
DKA mortality <1% with aggressive management. HHS has higher mortality (up to 15%) due to comorbidities.
9. SPECIAL CONSIDERATIONS¶
Pregnancy, elderly, and pediatric populations require tailored approaches. Insulin is preferred in pregnancy. Elderly patients need cautious glycemic targets to avoid hypoglycemia.
9.1 Pregnancy¶
Gestational diabetes management with diet/insulin. Insulin is preferred due to teratogenic risks of oral agents.
9.2 Elderly Patients¶
Individualized HbA1c targets (<7.5–8.0%) with emphasis on avoiding hypoglycemia. Monitor for frailty and polypharmacy.
10. KEY POINTS & CLINICAL PEARLS¶
- Comprehensive diabetes care integrates glycemic control, lifestyle, and complication prevention. 2. Insulin remains the cornerstone for type 1 and advanced type 2 diabetes. 3. GLP-1RAs and SGLT-2 inhibitors reduce cardiovascular risk. 4. Acute hyperglycemia requires fluid resuscitation and insulin. 5. Individualized glycemic targets are critical to avoid hypoglycemia in vulnerable populations.