Diabetes Mellitus

Prevalence

Roughly 1 in 10 adults globally are affected.

Microvascular burden

Retinopathy, nephropathy, and neuropathy drive disability.

Macrovascular burden

Diabetes markedly raises cardiovascular risk.

3.3. Gestational Diabetes Mellitus

• Glucose intolerance first recognized during pregnancy
• Raises risk of macrosomia, neonatal hypoglycemia, pre-eclampsia, and later T2DM
• Medical nutrition therapy first; insulin preferred if medication is needed

3.4. Other Specific Types

• Monogenic diabetes: MODY, neonatal diabetes
• Secondary diabetes: glucocorticoids, antipsychotics, pancreatitis, pancreatectomy, endocrinopathies such as Cushing's syndrome or acromegaly

5.1. Type 1 Diabetes Pathophysiology

1. Genetic susceptibility such as HLA-DR3 and HLA-DR4
2. Environmental trigger such as viral infection
3. Autoimmune attack on beta-cell antigens
4. Progressive beta-cell destruction
5. Absolute insulin deficiency with hyperglycemia and ketosis

5.2. Type 2 Diabetes Pathophysiology

The classic high-yield model is the ominous octet: insulin resistance, beta-cell dysfunction, reduced incretin effect, inappropriate glucagon secretion, increased renal glucose reabsorption, excess lipolysis, increased hepatic glucose production, and impaired central regulation.

6.2. Self-Monitoring of Blood Glucose

• T1DM: often 4-10 times daily
• T2DM on insulin: often 2-4 times daily
• Preprandial target: 80-130 mg/dL
• Postprandial target: <180 mg/dL

6.3. Continuous Glucose Monitoring

• Time in range goal: >70%
• Time below range: <4% under 70 mg/dL and <1% under 54 mg/dL
• Time above range: <25% over 180 mg/dL

7.1. Medical Nutrition Therapy

• Consistent carbohydrate timing and amount
• Fiber at least 14 g per 1000 kcal
• Limit saturated fat and avoid sugar-sweetened beverages
• Carbohydrate counting is essential in insulin-treated patients

7.2. Physical Activity

• 150 minutes/week of moderate aerobic activity
• Resistance training 2-3 times per week
• Adjust insulin or carbohydrate to reduce exercise-related hypoglycemia

7.3. Weight Management

• 5-10% weight loss improves glucose, BP, and lipids
• Very-low-calorie diets may induce remission in selected T2DM
• Bariatric surgery can be considered in severe obesity when medical therapy is insufficient

8.2. Insulin Regimens

• Multiple daily injections: basal insulin plus rapid-acting meal insulin
• Insulin pump (CSII): continuous basal infusion with bolus dosing

8.3. Adjunctive Therapy

Pramlintide is an amylin analogue that slows gastric emptying, suppresses glucagon, and increases satiety. It can reduce A1c modestly and may promote weight loss, but hypoglycemia risk rises if prandial insulin is not adjusted.

9.2. Insulin Secretagogues

• Sulfonylureas: glimepiride, glipizide, glyburide; high hypoglycemia risk, weight gain
• Meglitinides: repaglinide, nateglinide; shorter acting and taken with meals

9.3. Thiazolidinediones

• Pioglitazone and rosiglitazone improve insulin sensitivity
• Cause edema, weight gain, fracture risk, and can worsen heart failure

9.4. Alpha-Glucosidase Inhibitors

Acarbose and miglitol delay carbohydrate absorption. GI adverse effects are common, and hypoglycemia must be treated with glucose rather than sucrose.

9.5. DPP-4 Inhibitors

Sitagliptin, saxagliptin, linagliptin, and alogliptin raise endogenous incretin activity. They are weight neutral with low hypoglycemia risk but modest A1c lowering.

9.6. GLP-1 Receptor Agonists

Liraglutide, dulaglutide, semaglutide, and related agents lower A1c, promote weight loss, and reduce MACE in selected agents.

9.7. SGLT2 Inhibitors

Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin cause glucosuria, modest weight loss, low hypoglycemia risk, and strong cardiorenal benefit.

9.8. Pramlintide

Adjunct to insulin in T1DM or T2DM, with modest A1c lowering and weight loss but higher hypoglycemia risk unless mealtime insulin is reduced.

9.9. Insulin in Type 2 Diabetes

Use insulin for very high A1c, symptomatic hyperglycemia, failure of combination therapy, pregnancy, surgery, or acute illness. Start basal insulin and intensify if needed.

12.1. Hypoglycemia

Glucose under 70 mg/dL can cause adrenergic symptoms like tremor and sweating and neuroglycopenic symptoms like confusion or seizure.

• Rule of 15: 15 g fast carbohydrate, recheck in 15 minutes, repeat if needed
• If unconscious: give glucagon and seek emergency care

12.2. Diabetic Ketoacidosis

DKA is hyperglycemia, ketosis, metabolic acidosis, and an elevated anion gap. Treat with IV fluids, IV insulin, potassium replacement, and precipitant management.

12.3. Hyperosmolar Hyperglycemic State

HHS is severe hyperglycemia with hyperosmolarity and little or no ketosis. Fluids and electrolyte correction are especially important.

14.1. Diabetes in Pregnancy

• Preconception A1c goal often under 6.5%
• Insulin is preferred in gestational diabetes if lifestyle measures fail
• Avoid ACEi, ARB, statins, SGLT2 inhibitors, and GLP-1 RAs in pregnancy

14.2. Diabetes in CKD

• Metformin is contraindicated when eGFR is under 30
• Use renal dosing for several agents
• SGLT2 inhibitors and GLP-1 RAs are especially valuable when appropriate

14.3. Diabetes in Older Adults

• Healthy older adults often target A1c under 7.0-7.5%
• Frail patients may need less stringent goals
• Regimen simplification and hypoglycemia avoidance are key

For all patients

• Consistent carbohydrate intake, exercise, and weight management matter as much as medicines
• Check glucose as recommended and keep a log
• Recognize and treat hypoglycemia early
• During illness, stay hydrated and monitor more frequently

For insulin, SGLT2, and GLP-1 therapy

• Rotate insulin injection sites and never skip basal insulin
• Hold SGLT2 inhibitors during acute illness, surgery, or reduced intake
• GLP-1 RAs often cause nausea early, so start low and titrate slowly

GLP-1 RA Benefits

Cardiovascular benefit, weight loss, low hypoglycemia risk, and satiety.

SGLT2 Benefits

Glucosuria-based glucose lowering with heart failure and renal benefit.

High Hypoglycemia Risk

Sulfonylureas, insulin, and meglitinides are the classic high-risk classes.