Diabetes Mellitus

Initial conservative treatments may include:

1. Specialized therapeutic footwear (extra-depth shoes)
2. Management of concurrent diabetic neuropathy and/or peripheral artery disease

1. Refer all patients with diabetic retinopathy to an ophthalmologist.
2. Optimize glycemic control with antihyperglycemic treatment and lifestyle recommendations.
3. Manage ASCVD risk factors.
4. Treat hypertension if present.
5. Initiate treatment for lipid disorders as indicated.
6. Continue aspirin if indicated for another condition.
7. Screen for additional microvascular complications of diabetes.
8. Arrange follow-up eye exams at regular intervals.

Observation only; repeat dilated comprehensive eye examination every 6-12 months.

Treat as proliferative retinopathy with panretinal laser photocoagulation (PRP) and/or anti-VEGF therapy.

Intravitreal anti-VEGF therapy is the first line; consider PRP or focal and/or grid laser depending on severity of retinopathy.

Additional treatments should be utilized, including considering vitrectomy for refractory disease or severe complications.

Early detection and treatment can prevent 90% of blindness associated with diabetic retinopathy.

Patients should be educated on the importance of screening for complications of diabetes and that they may not experience symptoms until the disease is advanced.

PRP is usually preferred as it occurs in a single session, reducing the risk of loss to follow-up, and is equally effective as anti-VEGF therapy.

Pregnancy can precipitate or aggravate diabetic retinopathy in patients with both type 1 and type 2 diabetes mellitus.

Patients should undergo additional screening at the following times:

1. Prior to conception
2. Once during each trimester
3. During the first year postpartum

While panretinal photocoagulation (PRP) is safe during pregnancy, anti-VEGF therapy should be avoided due to theoretical risks to the fetus.

No, routine screening for diabetic retinopathy is not recommended for patients with gestational diabetes mellitus.

The two types of diabetes mellitus that can occur during pregnancy are gestational diabetes mellitus (GDM) and pregestational diabetes mellitus. GDM develops during pregnancy, while pregestational diabetes is present before conception.

Screening for gestational diabetes mellitus (GDM) is recommended for all individuals at 24-28 weeks' gestation. High-risk individuals should be screened at the initial prenatal visit for undiagnosed pregestational diabetes.

If medication is required for diabetes in pregnancy, insulin is recommended as the primary treatment.

Antepartum fetal surveillance is usually recommended from 32 weeks' gestation in pregnancies affected by diabetes due to the high rate of fetal complications associated with these conditions.

Patients who have had gestational diabetes mellitus (GDM) are at an elevated lifetime risk of developing diabetes mellitus and require ongoing screening for diabetes every 1-3 years after delivery.

• First trimester: Insulin sensitivity increases, leading to a risk of hypoglycemia.
• Second and third trimesters: Hormonal changes trigger progressive insulin resistance, resulting in hyperglycemia, especially after meals.

• Gestational diabetes in a previous pregnancy
• Recurrent pregnancy loss
• At least one birth of a child diagnosed with fetal macrosomia

1. Impaired pupillary tone
2. Sudomotor dysfunction
3. Dry skin
4. Heat intolerance
5. Abnormal sweating (e.g., anhidrosis, gustatory sweating)
6. Hypoglycemia unawareness

The recommended stool diagnostic studies for patients with diarrhea include:

1. Stool diagnostic studies: To identify the cause of diarrhea.
2. Esophageal barium swallow: To assess for esophageal hypermotility disorders.
3. Upper gastrointestinal endoscopy: To rule out gastric outlet obstruction and peptic ulcer disease.
4. Colonoscopy: In case of diarrhea or red flags in patients with constipation.

Management strategies for diabetic patients experiencing gastrointestinal symptoms include:

1. Optimize diabetes management: Achieve glycemic targets in diabetes mellitus (DM).
2. Treat dyslipidemia and hypertension: If present.
3. Discontinue contributing medications: If possible.
4. Consider specialist referral: For further evaluation.
5. Organ system-specific treatment:
   • Genitourinary symptoms: Refer to treatments for urinary incontinence and sexual dysfunction.
   • Diabetic gastroparesis: Refer to management strategies for diabetic gastroparesis.
   • Manage orthostatic hypotension: Include nonpharmacological and pharmacological management options.

Preventive measures for diabetic neuropathies include:

1. Educate patients: On symptoms of diabetic neuropathies.
2. Optimize diabetes management: To achieve glycemic targets in DM.
3. Encourage smoking cessation: To reduce risk factors.
4. Initiate ASCVD prevention: To prevent cardiovascular complications.

The assessments included in the screening for diabetic peripheral neuropathy are:

1. Inquire about subjective symptoms: Ask patients about any symptoms they may be experiencing.
2. Assess ankle reflexes: Check for reflex responses.
3. Perform a focused examination of sensation: Evaluate sensory function in the feet and lower extremities.

• Symptoms of diabetic gastroparesis
• Symptoms of erectile dysfunction or female sexual dysfunction
• Recurrent urinary tract infections and/or symptoms of urinary incontinence
• Peripheral dry and/or cracked skin
• Symptoms of hypotension or syncope

A resting heart rate > 100 bpm suggests cardiovascular autonomic neuropathy.

• Orthostatic vital signs should be checked.

Decreased heart rate variability can be assessed by recording an ECG either:

1. When the patient rises from seated to standing
2. Continuously while the patient takes deep breaths for 1–2 minutes

Hypoglycemia, or low blood sugar, is most often caused by insulin therapy or other medications in patients with diabetes. It can also occur due to various other factors.

A change in a patient's mental status should prompt immediate fingerstick blood glucose measurement and treatment if needed, as prolonged hypoglycemia can potentially cause acute brain damage.

Conscious patients should receive a fast-acting carbohydrate such as glucose tablets, candy, or fruit juice.

Hypoglycemia in patients with diabetes is generally defined as a blood glucose level of ≤ 70 mg/dL (≤ 3.9 mmol/L).

Administering insulin can cause life-threatening hypokalemia due to intracellular shift.

The mainstay of treatment consists of IV fluid resuscitation, electrolyte repletion, and insulin therapy.

Clinical features of DKA include polyuria, polydipsia, nausea and vomiting, volume depletion, fruity odor breath, hyperventilation, and abdominal pain.

DKA typically has an acute onset within hours, while HHS usually develops insidiously over days.

HHS is characterized by minimal or no ketone formation and more extreme volume depletion compared to DKA.

The pathogenesis of Diabetic Ketoacidosis (DKA) is triggered by acute stress (e.g., infection) leading to increased metabolic demand or insulin noncompliance, resulting in increased lipolysis and ketogenesis.

• Delirium/psychosis
• Kussmaul breathing
• Abdominal pain
• Nausea, vomiting
• Fruity (acetone) breath odor

• Hyperglycemia ≥ 200 mg/dL
• Anion gap metabolic acidosis (↑ H+, ↓ HCO3), pH < 7.3
• Decreased intracellular K+ (normal or increased serum K+)
• Hyperkaliuria (total K+ depletion)
• Hyperketonuria, hyperketonemia
• Leukocytosis

• Cerebral edema
• Cardiac arrhythmias
• Heart failure
• Mucormycosis (life-threatening)

1. Fluid resuscitation
2. Short-acting IV insulin
3. Replacement of potassium
4. Glucose supplementation in the case of hypoglycemia

• Polydipsia
• Polyuria
• Lethargy
• Focal neurological deficits
• Seizures
• Hyperglycemia (≥ 600 mg/dL)
• ↑ Serum osmolality (total > 320 mOsm/kg, calculated > 300 mOsm/kg)
• Decreased intracellular K+ (normal or increased serum K+)
• Normal serum pH and ketones
• Coma
• Death (if untreated)

1. Fluid resuscitation
2. IV insulin
3. Replacement of potassium

• Decreased glucose uptake leading to Hyperglycemia
• Increased lipolysis leading to Free fatty acids, Ketogenesis, and ketone bodies
• Increased proteolysis leading to Amino acids
• Hyperglycemia causing Osmotic diuresis, Glycosuria, Electrolyte depletion, and Dehydration, resulting in Diabetic Ketoacidosis (DKA) and Hyperosmolar Hyperglycemic State (HHS), which can lead to Coma and Death.

The most important findings of DKA include:

• Delirium/psychosis
• Dehydration
• Kussmaul respirations
• Abdominal pain/nausea/vomiting
• Fruity (acetone) breath odor

The primary goal of diabetes treatment is blood glucose control tailored to individual glycemic targets while avoiding hypoglycemia.

Comprehensive diabetes care should include:

1. Monitoring and management of ASCVD risk factors
2. Management of microvascular complications (e.g., diabetic retinopathy, nephropathy, neuropathy)
3. Management of macrovascular complications (e.g., coronary artery disease, stroke, peripheral artery disease)
4. General lifestyle modifications (e.g., smoking cessation, exercise, nutritional support)
5. Pharmacological treatment (e.g., antihyperglycemics, statins, ACE inhibitors, aspirin)

Testing for hyperglycemia is recommended for patients with classic symptoms of diabetes mellitus, and screening is advised for asymptomatic patients who are at high risk of prediabetes or diabetes, such as those with obesity and additional risk factors.

The primary treatment options for diabetes management include:

1. Insulin therapy
2. Lifestyle changes
3. Oral diabetes medications

Type 1 Diabetes Mellitus has a prevalence of approximately 1.6 million individuals in the US, accounting for about 5–10% of all patients with diabetes.

Type 1 Diabetes typically has a childhood onset, usually occurring before 20 years of age. The peak ages for onset are 4–6 years and 10–14 years.

The highest prevalence of Type 2 Diabetes Mellitus in the US is observed in Native Americans, Hispanics, African Americans, and Asian non-Hispanic Americans.

Type 2 Diabetes Mellitus typically has an adult onset, usually occurring after 40 years of age, although the mean age of onset is decreasing.

Approximately 10.5% of the adult population in the US has Type 2 Diabetes Mellitus.

The etiology of Type 1 Diabetes Mellitus involves the autoimmune destruction of pancreatic β cells in genetically susceptible individuals.

HLA-DR3 and HLA-DR4 positive patients are at increased risk of developing T1DM.

HLA-DR3 and HLA-DR4 are associated with several autoimmune conditions including:

• Hashimoto thyroiditis
• Type A gastritis
• Celiac disease
• Primary adrenal insufficiency

Risk factors for Type 2 Diabetes Mellitus include:

1. Family history of diabetes (first-degree relative)
2. High-risk race or ethnicity
3. Dyslipidemia
4. Prediabetes
5. Physical inactivity
6. Cardiovascular disease
7. Polycystic ovary syndrome
8. Hypertension
9. History of gestational diabetes
10. Poor sleep
11. Other conditions associated with metabolic syndrome and insulin resistance (e.g., overweight, obesity, acanthosis nigricans)
12. Medications known to increase the risk of diabetes (e.g., glucocorticoids, statins, thiazide diuretics, some HIV medications, second generation antipsychotics)

Type 1 Diabetes is classified as:

• Formerly known as insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes mellitus.
• Autoimmune (type 1A).
• LADA: Latent autoimmune diabetes in adults, characterized by a late onset of type 1 diabetes.

MODY (maturity-onset diabetes of the young) is a genetic form of diabetes characterized by defects in insulin secretion due to mutations in specific genes. It manifests before the age of 25 and is not associated with obesity or autoantibodies. Unlike type 1 and type 2 diabetes, MODY is inherited in an autosomal dominant manner and has multiple subtypes, with MODY II and MODY III being the most common.

In MODY II, a single mutation leads to impaired insulin secretion due to altered glucokinase function. Glucokinase acts as the glucose sensor in the beta cells, facilitating the storage of glucose in the liver, especially at high concentrations. Despite stable hyperglycemia, MODY II can often be managed with diet alone, and there is no increased risk of microvascular disease.

Pancreatogenic diabetes mellitus can occur following pancreatectomy or due to conditions that lead to the destruction of pancreatic endocrine islets. Examples include:

1. Hemochromatosis
2. Cystic fibrosis

These conditions impair the pancreas's ability to produce insulin, leading to diabetes.

Insulin is the only hormone that directly lowers blood glucose levels. It facilitates:

• Cellular uptake of glucose
• Metabolism of nutrients

By promoting these processes, insulin plays a crucial role in maintaining glycemic control and energy reserves in the body.

Several genetic syndromes are associated with diabetes mellitus, including:

• Down syndrome
• Stiff person syndrome
• Genetic defects affecting insulin synthesis
• Infections like congenital rubella infection

These conditions can lead to various forms of diabetes due to their impact on insulin production or action.

The key mechanisms involved in the development of Type 2 diabetes include:

1. Peripheral insulin resistance
2. Genetic and environmental factors
3. Central obesity leading to increased plasma free fatty acids, impairing insulin-dependent glucose uptake
4. Increased serine kinase activity in fat and skeletal muscle cells, resulting in decreased affinity of IRS-1 for PI3K and reduced GLUT4 expression
5. Pancreatic beta-cell dysfunction due to accumulation of pro-amylin, leading to decreased insulin production.

The progression of Type 2 diabetes occurs as follows:

1. Initial compensation: Insulin resistance is compensated by increased insulin and amylin secretion.
2. Progression of insulin resistance: Over time, insulin resistance worsens while the capacity for insulin secretion declines.
3. Impaired glucose tolerance: This leads to isolated postprandial hyperglycemia.
4. Manifestation of diabetes: Eventually, diabetes presents with fasting hyperglycemia.

In Type 1 diabetes, genetic susceptibility combined with environmental triggers, such as previous viral infections, leads to an autoimmune response. This results in the production of autoantibodies (e.g., anti-GAD and anti-ICA), causing progressive destruction of beta cells in the pancreatic islets, ultimately leading to absolute insulin deficiency and decreased glucose uptake in tissues.

• Onset: Often sudden; diabetic ketoacidosis (DKA) is the first manifestation in 25–50% of cases. Children may present with acute illness and classic symptoms.
• Clinical features: Classic symptoms of hyperglycemia include:
  • Polyuria (which can lead to secondary enuresis and nocturia in children)
  • Polydipsia
  • Polyphagia
  • Unexplained weight loss
  • Visual disturbances (e.g., blurred vision)
  • Fatigue
  • Pruritus

• Onset: Typically gradual; the majority of patients are asymptomatic. Some may present with a hyperglycemic crisis, especially elderly patients who may present in a hyperglycemic hyperosmolar state. Occasionally, patients with Type 2 DM present with DKA, which mostly affects Black and Hispanic individuals.
• Clinical features: Symptoms of complications may be the first clinical sign of disease.

Common skin manifestations include:

• Poor wound healing
• Increased susceptibility to infections
• Acanthosis nigricans (dark, velvety patches)
• Acrochordons (skin tags)

Diabetes mellitus should be suspected in patients with recurrent:

• Cellulitis
• Candidiasis
• Dermatophyte infections
• Gangrene
• Pneumonia (especially tuberculosis reactivation)
• Influenza
• Genitourinary infections (e.g., UTIs)
• Osteomyelitis
• Vascular dementia

The 2025 ADA guidelines recommend screening for diabetes in:

• Adults aged 35–70 years with overweight or obesity as per the USPSTF recommendations.

All individuals ≥ 35 years of age should be screened for diabetes.

Patients < 35 years of age should be screened if they are overweight or obese and have ≥ 1 risk factor such as:

• First-degree relative with diabetes
• High-risk race or ethnicity
• Physical inactivity
• Cardiovascular disease
• Polycystic ovary syndrome
• Hypertension
• Dyslipidemia
• Other conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans)
• Prediabetes or a history of gestational diabetes
• Risk-enhancing comorbidities (e.g., HIV, cystic fibrosis, post organ transplantation, pancreatitis, exposure to certain medications).

Asymptomatic patients with normal results should repeat testing at least every three years.

The diagnostic criteria for diabetes mellitus include:

• Random blood glucose level ≥ 200 mg/dL in patients with symptoms of hyperglycemia or hyperglycemic crisis
• OR ≥ 2 abnormal test results for hyperglycemia in asymptomatic individuals.

• Random blood glucose: Measured at any time, irrespective of recent meals.
• Fasting plasma glucose (FPG): Measured after more than 8 hours of fasting.

• One-step OGTT: Measures fasting plasma glucose and blood glucose 2 hours after consuming 75 g of glucose.
• Two-step OGTT: Used in the diagnosis of gestational diabetes, where nonfasting patients are given 50 g of glucose and blood glucose is measured after 1 hour.

• Increased RBC lifespan: Iron and/or vitamin B12 deficiency, splenectomy, aplastic anemia.
• Altered hemoglobin: Chronic kidney disease.
• Assay interference: Heavy alcohol use, chronic opiate use, high-dose aspirin, severe hypertriglyceridemia, uremia, hyperbilirubinemia.

• Decreased RBC lifespan: Acute blood loss, hemoglobinopathies (e.g., sickle cell trait/disease, thalassemia), cirrhosis, hemolytic anemia.
• Increased erythropoiesis: EPO therapy, reticulocytosis, pregnancy (second and third trimesters), iron supplementation.
• Altered hemoglobin: High-dose vitamin C and E supplementation.
• Assay interference: Low-dose aspirin.

A significant discrepancy warrants investigation of the underlying cause, such as the presence of sickle cell trait or other conditions affecting red blood cell lifespan or hemoglobin structure.

• BMP
• Renal function
• Electrolytes, including potassium
• Spot urinary albumin-to-creatinine ratio
• CBC with platelets
• Liver chemistries
• Lipid panel

Additionally consider:

• TSH and celiac disease panel for suspected or confirmed T1DM
• Vitamin B12 level for patients on metformin
• Calcium, phosphorous, and vitamin D level for selected patients

A high C-peptide level may indicate insulin resistance and hyperinsulinemia, which is commonly associated with Type 2 Diabetes Mellitus (T2DM).

A low C-peptide level indicates an absolute insulin deficiency, which is typically associated with Type 1 Diabetes Mellitus (T1DM).

Glucosuria may be present if the renal threshold for glucose is reached, but it is nonspecific for diabetes mellitus.

The presence of ketone bodies in urine is positive in cases of acute metabolic decompensation, such as diabetic ketoacidosis.

Microalbuminuria is an early sign of diabetic nephropathy, indicating potential kidney damage in diabetic patients.

Islet autoantibody testing is considered in patients with diagnosed diabetes mellitus if there is clinical suspicion for Type 1 Diabetes Mellitus (T1DM).

A positive result for Anti-GAD antibodies confirms the diagnosis of Type 1 Diabetes Mellitus (T1DM).

If the Anti-GAD test result is negative, it should trigger testing for other antibodies (e.g., anti-tyrosine phosphatase-related islet antigen 2 (IA-2), anti-zinc transporter 8 antibodies) and/or consultation with a specialist.

Screening for Type 1 Diabetes Mellitus (T1DM) with autoantibodies is considered in patients with presymptomatic T1DM and increased genetic risk, such as first-degree relatives with T1DM.

Differential diagnoses for diabetes include:

1. Glucagonoma
2. Somatostatinoma
3. Stress-induced hyperglycemia
4. Medication-induced hyperglycemia (Note: This list is not exhaustive.)

The main goal of diabetes management is blood glucose control, tailored to glycemic targets and regularly monitored.

Patients with Type 1 Diabetes Mellitus (T1DM) always require insulin therapy.

Type 2 Diabetes Mellitus (T2DM) may be managed with noninsulin diabetes medications and/or insulin therapy.

Recommended lifestyle modifications include:

1. Weight reduction
2. Balanced diet and nutrition (including a high-fiber diet)
3. Regular exercise
4. Smoking cessation

Routine screening for microvascular complications of diabetes should be conducted.

Recommended vaccinations for patients with diabetes include:

• Influenza
• Hepatitis B
• Zoster
• COVID-19
• Pneumococcal vaccines

ASCVD risk assessment is important for prevention, including management of hypertension and hypercholesterolemia. Patients aged 40–75 years with diabetes should initiate moderate-intensity statin therapy regardless of lipid levels.

Follow-up care should include:

1. Periodically re-evaluating the need for further education and support.
2. Checking HbA1c at least every 3–6 months.
3. For patients requiring lipid-lowering therapy, repeating the lipid panel yearly and 4–12 weeks after any medication changes.

The goals of diabetes management include:

• Eliminating symptoms of hyperglycemia
• Reducing or eliminating complications
• Enabling as healthy a lifestyle as possible.

• 75–180 minutes of aerobic exercise spread over ≥ 3 days per week
• 2–3 sessions of resistance exercise per week
• Reduce sedentary time and increase nonsedentary activities.

• Refer to a registered nutritionist.
• Individualize dietary recommendations based on health status, preferences, and cultural background.
• General recommendations include:
  • A high-fiber diet
  • Eating nonstarchy vegetables and whole foods
  • Avoiding refined sugar and grains

• Assess BMI annually.
• For T2DM with overweight or obesity: Aim for ≥ 3% weight loss.
• Recommend dietary changes and physical activity.
• Consider weight loss drugs or metabolic surgery depending on BMI.
• Consider weight maintenance programs if weight loss is achieved.

• Recommend smoking cessation for all patients; offer counseling if necessary.
• Advise against recreational cannabis in patients with T1DM or those at risk for diabetic ketoacidosis.
• Alcohol consumption should be limited to moderate intake and consumed with food to avoid hypoglycemia.

Factors to consider include:

1. Risk of hypoglycemia or other adverse effects
2. Presence of vascular complications and comorbidities
3. Patient preferences and resources
4. Disease duration
5. Life expectancy

Continuous re-evaluation and adjustment of glycemic targets is necessary.

HbA1c should be monitored:

• At least every 6 months if targets are met.
• At least every 3 months in the following situations:
  1. If targets are not met.
  2. If treatment has recently been modified.
  3. If the patient is undergoing intensive insulin therapy.

Regular assessment of past hypoglycemic episodes or the risk of hypoglycemia is essential to adjust glycemic goals accordingly, as hypoglycemia is a major limitation to adequate glycemic control.

Self-monitoring of blood glucose is indicated for:

1. Insulin therapy (particularly for intensive regimens)
2. Assessing for hypoglycemia or the impact of diet and/or exercise.
3. Patients with T2DM on noninsulin glucose-lowering drugs who are not meeting HbA1c targets.

Continuous glucose monitoring measures interstitial glucose levels continuously or intermittently using a subcutaneous device. It:

• Improves glycemic monitoring, reducing the risk of hypoglycemia.
• Is recommended for adults with T1DM and can be used in combination with an insulin pump.
• Is advised for patients with diabetes on any form of insulin therapy.

At every follow-up visit, assess for:

• Episodes of hypoglycemia (both symptomatic and asymptomatic).
• Consider prescribing glucagon for individuals taking insulin or at high risk for hypoglycemic events.
• Check for possible contributors to hypoglycemia, such as medication interactions or errors.

Early morning hyperglycemia may be caused by:

1. Dawn phenomenon: A physiological increase in growth hormone levels in the early morning stimulates hepatic gluconeogenesis, leading to increased insulin demand that insulin-dependent patients cannot meet.
2. Somogyi effect: Nocturnal hypoglycemia due to evening insulin injection triggers counterregulatory hormone secretion, resulting in elevated blood glucose levels in the morning (though this is widely taught but unproven).

For patients with at least one clinically significant hypoglycemia event or asymptomatic hypoglycemia:

• Check for possible contributors (e.g., medication interactions or errors).
• Consider relaxing glycemic targets and adjusting management accordingly.
• Reassess and adjust treatment at regular intervals (e.g., every 3–6 months).

Insulin replacement therapy is the primary treatment for Type 1 diabetes mellitus. Treatment options include:

• Insulin pump: Consider for most patients.
• Multiple daily insulin injections, following a full basal-bolus insulin regimen.

The total daily dose (TDD) of insulin for Type 1 diabetes is usually calculated as 0.4–1.0 units/kg per day, divided into:

• 50% basal insulin
• 50% prandial insulin

Consider starting treatment with 0.5 units/kg per day.

Insulin dosage should be adjusted according to glycemic monitoring. After beginning insulin treatment, exogenous insulin demand is temporarily reduced, necessitating dosage adjustments based on the patient's activities and meals.

Alternative treatment strategies for Type 1 diabetes mellitus include:

• Noninsulin diabetes medications: Not generally used in T1DM treatment.
• Pancreas and/or islet transplantation: May improve glucose control but is not standard treatment due to the need for lifelong immunosuppressive therapy. This may be considered in patients with recurrent episodes of diabetic ketoacidosis or severe hypoglycemia despite adequate treatment.

Metformin is the first-line initial therapy for most patients without cardiovascular or kidney risk factors.

Glucose-lowering medication should be based on patient factors such as ASCVD, CKD, and other comorbidities.

Initial combination pharmacological treatment should be considered in patients with:

1. Clinical ASCVD, high ASCVD risk, heart failure, or CKD
2. HbA1c ≥ 1.5% above the glycemic target
3. Indications for insulin therapy at the time of diagnosis.

Treatment and treatment adherence should be re-evaluated every 3–6 months.

If glucose targets are not met despite adequate treatment, consider insulin therapy.

• Avoid saxagliptin in patients with heart failure.
• Should not be used in patients who also use GLP-1RAs.

Noninsulin diabetes medications are used to help manage blood glucose levels, with specific classes like Biguanides (e.g., Metformin) being frequently the first-line therapy unless contraindicated.

Oral monotherapy usually lowers HbA1c levels by approximately 1%. Every noninsulin drug added to metformin will lower the HbA1c by an additional 0.7-1.0%.

Combining sulfonylureas with insulin increases the risk for hypoglycemia, so caution is advised regarding drug interactions and incompatibilities.

Indications for insulin therapy in T2DM include:

• Patients whose glycemic targets are not met despite sufficient noninsulin diabetes medications.
• Patients with contraindications for noninsulin diabetes medications (e.g., end-stage renal failure).
• Pregestational and gestational diabetes.
• Hyperglycemic crisis.
• Consider in patients with ≥ 1 of the following:
  • Initial glucose ≥ 300 mg/dL or HbA1c > 10%.
  • Symptoms of hyperglycemia.
  • Signs of a continued catabolic state (e.g., weight loss).

The recommended approach to insulin treatment in T2DM includes:

1. Start with the simplest insulin regimen (i.e., a basal insulin regimen with once-daily injections).
2. Titrate the insulin dose according to individualized glycemic targets and tolerance.
3. Consider adding prandial insulin or switching to a mixed insulin regimen as needed.
4. Noninsulin diabetes medications may be continued once insulin treatment is started.
5. Include GLP-1 receptor agonists in the treatment strategy prior to starting insulin therapy, unless inappropriate or insulin therapy is preferred.

Screening for microvascular complications of diabetes in Type 2 Diabetes Mellitus (T2DM) should begin at the time of diabetes diagnosis and should be performed at a minimum every 12 months.

The screening modalities for diabetic complications include:

• Diabetic kidney disease: Spot urine albumin to creatinine ratio (UACR) and serum glomerular filtration rate.
• Diabetic retinopathy: Comprehensive eye exam with dilation or retinal photography (if available).

• Monofilament test
• Pinprick sensation or temperature sensation
• Vibration sense (using a tuning fork)

By recording:

• Resting heart rate
• Orthostatic vital signs
• Heart rate variability

• Check BP at every clinic appointment and encourage home monitoring for elevated BP.
• Obtain a lipid panel at the time of diabetes diagnosis and repeat every 5 years for patients < 40 years.
• Screening for cardiovascular disease is not recommended for asymptomatic individuals, but can be considered on a case-by-case basis.

• BNP or NT-proBNP for patients without known structural heart disease.
• Ankle-brachial index testing for patients ≥ 65 years of age with microvascular disease, diabetic foot complications, and/or any end-organ damage from diabetes.

The target HbA1c is < [**%] (specific value to be determined based on individual patient assessment).

• Nutrition counseling
• At least 150 minutes of moderate-intensity aerobic activity per week

• Metformin [** mg **FREQUENCY]
• GLP-1 receptor agonist: [liraglutide or semaglutide] for cardiovascular benefit and weight loss.
• SGLT2 inhibitor: [empagliflozin or dapagliflozin [** mg] once daily] for renal and cardiovascular benefit.

• DPP-4 inhibitor (e.g., sitagliptin)
• Basal insulin (consider if HbA1c remains > 10% or significant symptoms of hyperglycemia)
• Sulfonylureas (e.g., glimepiride; monitor for hypoglycemia)

HbA1c should be monitored every 3-6 months.

• Fasting lipid panel: annually
• BMP: annually, or more frequently if CKD is present
• Urine ACR: annually
• Comprehensive foot exam: annually
• Dilated eye exam: annually or every 2 years if low risk

The target blood pressure is < 140/90 mm Hg.

• Lisinopril: prescribed for patients with albuminuria or hypertension
• High-intensity statin (e.g., atorvastatin) for all patients aged ≥ 40 years
• Ezetimibe or PCSK9 inhibitors for LDL ≥ 70 mg/dL despite maximally tolerated statin
• Aspirin for ASCVD prevention

• Influenza: annually
• Pneumococcal: for all adults with diabetes
• Hepatitis B: series for all adults with diabetes aged ≤ 59 years

• Review frequency and goals for glucose monitoring.
• Reinforce signs of hypoglycemia and hyperglycemia and when to seek care.

Routine follow-up should occur in [ months]** for glycemic control, with sooner follow-up if symptomatic hyperglycemia or significant therapy adjustments are needed.

The acute complications include:

1. Hyperglycemic hyperosmolar state (HHS)
2. Diabetic ketoacidosis (DKA)
3. Life-threatening hypoglycemia: often due to inappropriate insulin therapy.

The major risk factors for macrovascular disease include:

• Obesity
• Dyslipidemia
• Arterial hypertension

Hyperglycemia is less related to the development of macrovascular disease compared to these metabolic risk factors.

Microvascular disease typically arises 5-10 years after the onset of diabetes.

The pathophysiology involves:

• Chronic hyperglycemia leading to:
  • Nonenzymatic glycation of proteins and lipids
  • Thickening of the basal membrane
  • Progressive functional impairment and tissue damage

The manifestations of microvascular disease include:

• Diabetic nephropathy
• Diabetic retinopathy and glaucoma
• Diabetic neuropathy, including diabetic gastroparesis
• Diabetic foot

Necrobiosis lipoidica is an inflammatory granulomatous disorder of the skin characterized by collagen degeneration and lipid accumulation. It has a >60% association with diabetes mellitus and is more common in females than males.

The rash is characterized by circumscribed, erythematous plaques with atrophic centers and irregular margins. Common sites include the pretibial region, and it is usually asymptomatic. Ulcerations with subsequent scarring may occur.

Histopathology of necrobiosis lipoidica shows necrobiotic palisading granuloma, with lymphohistiocytic infiltration including plasma cells, foam cells, and giant cells. There is also wall thickening and occlusion of small blood vessels, and destruction of collagen fibers in the entire corium.

Treatment for necrobiosis lipoidica may include corticosteroids, which can be effective, particularly through intralesional corticosteroid injections.

Mucormycosis, also known as zygomycosis, is a serious fungal infection that can occur in patients with diabetes, particularly those with uncontrolled blood sugar levels. It is characterized by the rapid progression of tissue necrosis and can affect various body parts, including the sinuses, brain, and lungs.

Chronic hyperglycemia leads to altered metabolism of glucose and fatty acids, resulting in microangiopathy, endothelial dysfunction, and autonomic neuropathy. These changes can cause cardiomyocyte hypertrophy, myocardial fibrosis, ventricular dilation, and ultimately lead to systolic and/or diastolic heart failure.

Diabetic cardiomyopathy is a disorder of the myocardium seen in patients with diabetes. It may present with features of heart failure, which can occur with or without the presence of cardiovascular disease (CVD) and hypertension.

Osmotic damage in diabetes occurs in tissues with high aldolase reductase activity and low or absent sorbitol dehydrogenase activity, such as the eyes and peripheral nerves. This can lead to complications like cataracts and neuropathy.

Limited joint mobility syndrome, formerly known as diabetic cheiroarthropathy, is characterized by stiffness of the small joints of the hand, tight waxy skin on the dorsal surface of the fingers, and positive tests indicating contractures in the joints, such as the prayer sign and tabletop test.

Hyporeninemic hypoaldosteronism in diabetic patients is characterized by hypotension, hyponatremia, and type 4 renal tubular acidosis. It is commonly caused by diabetic nephropathy or chronic interstitial nephritis.

Diabetic fatty liver disease is a condition where excess fat accumulates in the liver of diabetic patients, which can lead to liver dysfunction and is associated with metabolic syndrome and increased cardiovascular risk.

Diabetes can impair the immune response, leading to an increased risk of infections. This is due to factors such as hyperglycemia, which can affect white blood cell function and the body's ability to fight off pathogens.

Insulin purging is the act of attempting to lose weight by purposefully not injecting insulin after meals. It is commonly practiced by young patients with type 1 diabetes who have eating disorders, using it as an alternative to fasting, vomiting, and other weight loss methods.

The consequences of insulin purging include self-induced insulin deficiency, poor glycemic control, increased risk of hyperglycemic crises, and weight loss without weight gain due to the anabolic effect of insulin being inhibited.

Common complications of diabetes mellitus that can result in death include myocardial infarction, end stage renal failure, blindness, nontraumatic lower limb amputation, and cardiovascular disease.

The prognosis of diabetes mellitus primarily depends on glycemic control and the treatment of comorbidities such as hypertension and dyslipidemia.

Screening for T1DM in children is recommended for those with first-degree relatives who have T1DM.

Children should be screened for T2DM if they are age ≥ 10 years or after puberty begins, have a BMI ≥ 85th percentile, and have at least one additional risk factor such as being born to mothers with pregestational or gestational diabetes, conditions associated with insulin resistance, or specific race/ethnicity.

• Thyroid disease screening
• Celiac disease screening
• Dyslipidemia screening for children ≥ 2 years with acceptable glycemic control
• Annual screening for associated mental health problems
• Psychosocial distress screening from age 7-8 years
• Disordered eating screening from age 10-12 years

The goal blood pressure is < 90th percentile or < 130/80 mm Hg for children aged 13 years and older.

The following regimens are suitable for children ≥ 10 years of age:

• Metformin
• Insulin
• GLP-1 receptor agonists (e.g., exenatide extended-release, liraglutide)

Diabetes management in children is generally similar to adults, with modifications including:

• Screening for associated conditions
• Age-specific mental health screenings
• Preconception counseling for adolescent girls
• Education for caregivers about the treatment plan

If glycemic targets are not achieved with metformin and basal insulin, consider:

• Switching to an insulin pump
• Adding prandial insulin
• Adding GLP-1 receptor agonists

Patients should be treated with insulin alone. Metformin may be added after the acidosis resolves.

Consult a specialist to determine treatment, as neither metformin nor GLP-1 receptor agonists are FDA-approved for use in this age group.

Hyperglycemia in hospitalized patients is defined as a blood glucose level > 140 mg/dL.

Common causes include:

• Underlying diabetes mellitus
• Medications (e.g., glucocorticoids, thiazide diuretics)
• Parenteral nutrition
• Stress (e.g., due to surgery, trauma, or sepsis)

Hyperglycemia is associated with longer hospital stays and worse outcomes.

A key consideration is to avoid potentially life-threatening hypoglycemia, which can occur as a complication of insulin therapy.

Medications that can cause hyperglycemia include:

• Glucocorticoids
• Fluoroquinolones
• Beta blockers
• Thiazide diuretics and loop diuretics
• Heparin
• Calcineurin inhibitors
• Tricyclic antidepressants
• Antipsychotic drugs
• Lithium
• HIV-protease inhibitors
• Thyroid hormones (e.g., levothyroxine)
• Estrogen (contraceptives)
• Sympathomimetic drugs (e.g., dobutamine)
• Derivatives of nicotinic acid

Initial management steps for patients with potential hyperglycemic crises include:

1. Rule out hyperglycemic crises.
2. Identify and treat the underlying cause, such as:
   • Underlying diabetes
   • Glucose intolerance
3. Obtain a thorough patient history to understand contributing factors.

Indications for initiating an insulin regimen include:

1. Persistently elevated blood glucose ≥ 180 mg/dL in critically ill patients and/or those with pre-existing diabetes.
2. Persistently elevated blood glucose > 140 mg/dL in noncritically ill patients without pre-existing diabetes.

The glycemic targets are as follows:

In patients receiving intravenous insulin, blood glucose should be checked every 30–120 minutes.

Consider consulting an endocrinology or glucose management team if glucose levels are difficult to control.

Check point-of-care glucose every 4–6 hours in patients who are NPO or receiving continuous enteral feeding.

All patients with T1DM require insulin therapy.

Patients with T2DM require insulin therapy if blood glucose is ≥ 180 mg/dL on ≥ 2 occasions in 24 hours.

For patients with inadequate or no oral intake, a basal insulin or a basal-bolus insulin regimen is recommended.

Patients with adequate oral intake should receive a basal-bolus insulin regimen.

Check POC glucose every 4–6 hours for patients who are NPO or on continuous enteral feeding.

The glycemic target for patients with diabetes is 100–180 mg/dL.

Patients without preexisting diabetes mellitus with persistently elevated blood glucose > 140 mg/dL should be considered for insulin therapy.

Scheduled insulin therapy, such as a basal-bolus insulin regimen, is recommended for patients without preexisting diabetes mellitus with persistent blood glucose ≥ 180 mg/dL.

Blood glucose ≥ 180 mg/dL on ≥ 2 occasions in 24 hours.

Continuous intravenous insulin infusion (IIP) is preferred.

IIP should be avoided in the following situations:

1. Rapid normalization of glucose expected
2. Patients close to transfer to a general ward
3. Terminally-ill patients
4. Patients who are eating

The glycemic target is 140–180 mg/dL.

Point-of-care (POC) glucose should be monitored hourly in patients on continuous insulin infusion.

Consider insulin therapy if blood glucose levels are ≥ 140 mg/dL.

A basal-bolus regimen is preferred, especially for patients receiving dexamethasone.

POC glucose should be checked every 4–6 hours.

Adjust the insulin regimen if changing the glucocorticoid dose, tailoring treatment based on individual factors such as blood glucose level and severity of hyperglycemia.

Perform POC glucose testing every 4-6 hours for 24-48 hours. Discontinue screening if glucose levels are < 140 mg/dL for 48 hours in nondiabetic patients.

Insulin therapy is indicated if blood glucose is > 180 mg/dL once or if blood glucose is 140–180 mg/dL on ≥ 2 occasions.

An adapted basal-bolus insulin regimen or NPH insulin regimen is preferred. Regular insulin can also be added to parenteral nutrition solutions, and correctional insulin should be included for both enteral and parenteral nutrition.

POC glucose should be monitored every 4–6 hours.

Provide diabetes-specific formulas of enteral or parenteral nutrition to help manage blood glucose levels, as these patients are at high risk of hypoglycemia.

Identify and treat the underlying stressor, while glycemic management remains similar to standard diabetes care.

The decision to reduce or discontinue a drug associated with hyperglycemia should be made on an individual basis, with glycemic management similar to standard diabetes care.

Patients with T1DM require basal insulin even if feeding is discontinued.

The criteria for considering the continuation of CSII include:

• The patient demonstrates the capacity to use the pump correctly.
• No contraindications for CSII are present, such as:
  • Inability to participate actively in blood sugar management
  • Altered state of consciousness
  • Diabetic Ketoacidosis (DKA)
  • Severe illness (e.g., sepsis)
  • Need for MRI
  • Suicidal ideation

If CSII is discontinued, a basal-bolus insulin regimen is recommended. Every patient switched from CSII to another insulin regimen should receive basal insulin.

The acute management checklist for hyperglycemia includes:

1. Rule out hyperglycemic crisis.
2. Rule out sepsis and other reversible causes of hyperglycemia.
3. Check HbA1c.
4. Hold any medications that may be contributing to hyperglycemia.
5. Ensure the patient is on the correct diet (e.g., consistent carbohydrate).
6. Start insulin therapy if indicated.
7. Order monitoring parameters.
8. Order hypoglycemia treatment protocol.
9. Consider endocrine consult or hyperglycemia team consult if glucose is difficult to control despite appropriate insulin regimen.

The ABCDE approach involves a systematic evaluation focusing on:

1. Airway - Ensure the airway is clear.
2. Breathing - Assess respiratory function.
3. Circulation - Evaluate circulatory status.
4. Disability - Check neurological status (e.g., mental status).
5. Exposure - Examine the patient for any other signs or symptoms.

Essential laboratory tests include:

• Serum glucose to confirm hyperglycemia
• Serum osmolality
• Urinalysis for ketones
• Serum ẞ-hydroxybutyrate
• Blood gas analysis
• Basic Metabolic Panel (BMP)
• Complete Blood Count (CBC) with differential
• Serum lipase
• HbA1c
• Urine toxicology screen
• Urine pregnancy test in individuals who can become pregnant
• 12-lead ECG
• Chest x-ray

A glucose level of < 200 mg/dL does not rule out DKA in these patients.

The diagnostic criteria for DKA include:

• Glucose ≥ 200 mg/dL
• pH < 7.3
• HCO3 < 18 mEq/L
• Ketones (β-hydroxybutyrate ≥ 3.0 mmol/L or urine strip ≥ 2+)

Severe DKA is characterized by:

• pH < 7.0
• HCO3- < 10 mEq/L
• β-OHB > 6.0 mmol/L
• Altered mental status (AMS)

The diagnostic criteria for HHS include:

• Glucose ≥ 600 mg/dL
• Calculated osmolality > 300 mOsm/kg (or total > 320 mOsm/kg)
• pH ≥ 7.3
• HCO3- ≥ 15 mEq/L
• Minimal or no ketones

Red flag features include:

• Altered mental status (AMS), lethargy, and/or coma
• Hyperventilation
• Signs of significant dehydration
• Signs of cerebral edema
• Severe abdominal pain
• Nausea and/or vomiting in patients with diabetes

The management checklist for DKA includes:

1. IV access
2. Identify and treat life-threatening causes (e.g., MI, sepsis)
3. IV fluid resuscitation with 0.9% NaCl or LR at 500-1000 mL/hour
4. Replete K+ and maintain levels at 4-5 mEq/L
5. Replete other electrolytes as indicated
6. Start continuous insulin infusion once serum K+ is > 3.5 mEq/L
7. Hourly POC glucose checks

Consider IV sodium bicarbonate.

Add dextrose to IV fluids once POC glucose is < 250 mg/dL.

Monitor BMP, serum osmolality, and blood gas.

Consider ICU admission for severe DKA or HHS, altered mental status (AMS), or hemodynamic instability.

Common causes of DKA include:

1. Lack of or insufficient insulin replacement therapy
2. Undiagnosed, untreated diabetes mellitus
3. Treatment failure in known diabetics (e.g., insulin pump failure, forgotten insulin injection)
4. Poor adherence to insulin therapy
5. Inability to afford treatment
6. Use of expired insulin
7. Increased insulin demand due to stress (infections, surgery, trauma, etc.)
8. Drugs (e.g., glucocorticoid therapy, cocaine use, alcohol abuse)

Diabetic ketoacidosis (DKA) is most commonly seen in patients with type 1 diabetes mellitus, accounting for approximately 30% of cases as an initial manifestation.

Insulin deficiency leads to hyperglycemia, which causes hyperosmolality. This results in osmotic diuresis and loss of electrolytes, ultimately leading to hypovolemia.

Insulin deficiency increases lipolysis, leading to the production of free fatty acids. These fatty acids are converted into acidic ketones, which consume serum bicarbonate as a buffer, resulting in an elevated anion gap metabolic acidosis.

In DKA, potassium shifts from inside cells to the extracellular space due to hyperglycemic hyperosmolality, and the lack of insulin prevents potassium uptake into cells. This results in a total body potassium deficit, although serum potassium levels may appear normal or even elevated.

During treatment of DKA, insulin replacement can lead to rapid potassium uptake by depleted cells, which may necessitate potassium replacement to prevent hypokalemia.

In HHS, there are still small amounts of insulin being secreted by the pancreas, which is sufficient to prevent DKA by suppressing lipolysis and ketogenesis. In contrast, DKA typically occurs with little to no insulin secretion.

Key clinical features of HHS include:

• Polyuria
• Polydipsia
• Recent weight loss
• Nausea and vomiting
• Signs of significant dehydration
• Neurological abnormalities
• Altered mental status
• Lethargy
• Coma
• Other neurological examination abnormalities, such as blurred vision and weakness.

DKA has a rapid onset, typically occurring in less than 24 hours, whereas HHS has a more gradual onset.

Patients with known diabetes who present with nausea and/or vomiting should be immediately assessed for DKA or HHS.

DKA has a rapid onset occurring in less than 24 hours, while HHS has an insidious onset that can take days to weeks.

Common symptoms of DKA include:

• Polyuria
• Polydipsia
• Nausea and vomiting
• Dehydration
• Fruity breath
• Severe abdominal pain
• Kussmaul breathing

In DKA, patients are usually alert, whereas in HHS, patients typically have an altered mental status.

Essential laboratory tests for diagnosing DKA include:

1. Serum glucose to confirm hyperglycemia.
2. BMP for serum bicarbonate, anion gap, electrolytes, and renal function.
3. Ketone testing (serum and urine).
4. Blood gas analysis for pH.
5. Additional tests like HbA1c, CBC, ECG, and infectious workup to evaluate underlying causes.

The diagnostic criteria for HHS include:

• Hyperglycemia: Blood glucose ≥ 600 mg/dL
• Hyperosmolality: Calculated effective serum osmolality > 300 mOsm/kg or total serum osmolality > 320 mOsm/kg
• Absence of ketonemia and acidosis

The diagnostic criteria for DKA include:

• Hyperglycemia: Blood glucose ≥ 200 mg/dL and/or history of diabetes
• Ketosis: Serum ẞ-hydroxybutyrate ≥ 3.0 mmol/L and/or ≥ 2+ on urine strip
• Metabolic acidosis: pH < 7.3 and/or bicarbonate < 18 mEq/L

Bicarbonate levels < 18 mEq/L (< 18 mmol/L) indicate metabolic acidosis in DKA.

An elevated anion gap (> 12 mEq/L) is often observed in DKA, indicating the presence of metabolic acidosis.

Moderate to large urine ketones (≥ 2+) indicate ketonuria in DKA.

A serum ẞ-hydroxybutyrate level of ≥ 3.0 mmol/L is considered elevated in DKA.

A blood gas pH < 7.30 indicates acidosis in DKA.

Normal serum osmolality in a stuporous patient rules out HHS; elevated osmolality (> 320 mOsm/kg) may indicate DKA.

Common electrolyte abnormalities in DKA include hyponatremia, normal or elevated potassium, low magnesium, and potentially elevated phosphorus levels.

Corrected sodium should be checked in hyperglycemia to account for the dilutional effect of high glucose levels on serum sodium.

Use the measured serum sodium concentration rather than the corrected serum sodium concentration.

Additional diagnostics include:

• HbA1c
• Urine pregnancy test
• Diagnostics for AMS: CT head, Toxicology screen
• Diagnostics for sepsis: CBC with differential, Serum lactate
• Diagnostics for myocardial infarction: 12-lead ECG
• Diagnostics for acute abdomen: Abdominal imaging, Serum lipase, Serum transaminases

In all patients presenting with a hyperglycemic crisis, rule out:

• Infection
• Myocardial infarction
• Pancreatitis

The initial steps in management include:

1. ABCDE approach
2. Urgent diagnostics (e.g., POC glucose, BMP, blood gas analysis)
3. Volume status assessment

Principal interventions include:

1. Fluid resuscitation: initially with normal saline (0.9% NaCl) or lactated Ringer's solution
2. Potassium repletion: for baseline potassium level ≤ 5.0 mEq/L
3. Insulin therapy: Initiate short-acting insulin as soon as possible once potassium level is > 3.5 mEq/L

Pregnancy and SGLT2-inhibitors can cause euglycemic DKA, which is characterized by high anion gap metabolic acidosis with normal or near-normal glucose levels.

IV sodium bicarbonate should be considered only for severe refractory metabolic acidosis, specifically when the pH is less than 7.0.

It is important to identify and treat precipitating causes such as sepsis in patients experiencing hyperglycemic crises.

The goal of therapy is to resolve hyperglycemia, ketonemia, and acidosis in DKA, and to address hyperglycemia and hyperosmolarity in HHS.

Monitoring should include:

1. Hourly vital signs
2. Mental status assessment
3. Hydration status
4. POC glucose every 1-2 hours until resolution
5. Blood gas and BMP with electrolytes every 2-4 hours
6. For HHS, serum osmolality every 2-4 hours
7. For DKA, serum ẞ-hydroxybutyrate every 4 hours
8. Regular monitoring of volume status, serum glucose, serum electrolytes, and acid-base status.

Pregnant patients with DKA should be assessed by both an endocrinologist and an obstetrician due to the potential for a high-risk pregnancy.

Noninsulin agents should be avoided in patients with Type 1 Diabetes Mellitus (T1DM).

Cerebral edema should be considered in patients exhibiting symptoms such as headache, mental status deterioration, seizures, and pupillary changes, especially if there has been an overly rapid correction of serum osmolality.

Admission is indicated for all patients with HHS and for most patients with DKA.

ICU admission should be considered for patients with:

• Persistently altered mental status or hemodynamic instability
• Severe DKA (Diabetic Ketoacidosis) or HHS (Hyperglycemic Hyperosmolar State)
• Underlying critical illness (e.g., sepsis, myocardial infarction)

Patients with mild DKA may be considered for discharge if they meet all the following conditions:

1. Resolved acidosis
2. No concerning precipitating cause
3. Toleration of oral hydration and nutrition
4. Adequate basal-bolus insulin regimen
5. Ability to adhere to discharge instructions, including outpatient follow-up

The initial fluid resuscitation protocol is as follows:

• First 2-4 hours: Administer 0.9% NaCl or balanced crystalloid solutions (e.g., lactated Ringer's solution) at 500–1000 mL/hour.
• Next 8-12 hours: Continue with 0.9% NaCl or crystalloid solution to replace 50% of the remaining fluid deficit.
• Adjust IV fluid rate and composition based on CVP, urine output, blood glucose, and corrected sodium levels within the first 24–48 hours.

Electrolyte repletion, particularly potassium, should be managed as follows:

• Ensure potassium levels are > 3.5 mEq/L before initiating insulin therapy.
• Initiate potassium replacement if levels are ≤ 5.0 mEq/L.
• Maintain serum potassium between 4–5 mEq/L.
• Monitor potassium levels 2 hours after starting insulin and every 2–4 hours thereafter, using caution in anuric patients.

During fluid resuscitation, it is crucial to carefully monitor for signs of fluid overload, especially in patients with comorbidities such as:

• Congestive heart failure
• Chronic kidney disease

Potassium levels must be greater than 3.5 mEq/L before administering insulin, as insulin can lower serum potassium and potentially cause severe hypokalemia.

Insulin is essential to halt lipolysis and ketoacidosis in patients with DKA.

Ensure blood glucose levels decline by less than 90-120 mg/dL/hour to prevent cerebral edema.

Check glucose levels every 1-2 hours and adjust the insulin infusion rate as needed.

• Glucose < 200 mg/dL
• Venous pH ≥ 7.30
• Serum bicarbonate ≥ 18 mEq/L
• Serum ketone < 0.6 mmol/L
• Normal serum osmolality (i.e., calculated < 300 mOsm/kg)
• Normal mental status

• Blood glucose < 250 mg/dL
• Urine output > 0.5 mL/kg/hour

1. Stop dextrose infusion.
2. Administer a basal-bolus insulin regimen (~ 50% basal insulin and 50% prandial insulin).
3. Estimate total daily dose (TDD) based on:
   • Prior outpatient regimen in patients previously on insulin (adjust as needed)
   • Weight-based estimates in insulin-naive patients (e.g., 0.3–0.6 units/kg/day)
   • IV insulin hourly requirement (e.g., quantity used in the preceding 6 hours)
4. Continue IV insulin for 1–2 hours after initiating subcutaneous insulin.

• Alcoholic ketoacidosis
• Lactic acidosis
• Starvation ketoacidosis
• Toxin ingestion

Other causes include sepsis and acute pancreatitis.

All other causes of altered mental status must be considered, including intoxication, endocrine disorders, gastroenteritis, myocardial infarction, pancreatitis, and other causes of high anion gap metabolic acidosis.

Important complications include:

1. Cerebral edema
2. Cardiac arrhythmias
3. Heart failure
4. Respiratory failure
5. Mucormycosis (Mucor and Rhizopus species)
6. Hypoglycemia
7. Hypokalemia

This list is not exhaustive but highlights significant risks.

Common examination findings include:

• Microaneurysms
• Caliber changes in veins
• Intraretinal hemorrhage
• Hard exudates
• Retinal edema
• Cotton-wool spots
• Intraretinal microvascular abnormalities (IRMA)

The hallmark of proliferative diabetic retinopathy (PDR) is neovascularization.

Vision loss may result from:

• Macular edema
• Vitreous hemorrhage
• Retinal detachment
• Neovascular glaucoma

For severe diabetic retinopathy, treatment options include:

• Panretinal photocoagulation (PRP)
• Anti-VEGF therapy
• Focal and/or grid laser therapy
• Management of diabetes and underlying ASCVD risk factors

Vitrectomy may be required for patients with complications such as tractional retinal detachment or vitreous hemorrhage.

Proliferative diabetic retinopathy is characterized by:

• Neovascularization: Formation of new, abnormal blood vessels, often appearing congested and tangled.
• Optic disc changes: The optic disc may appear lighter in color, with numerous blood vessels emerging from it.
• Background changes: The fundus may show a brown background with lighter, ill-defined areas around the optic disc.
• Presence of white spots: Small white spots can be scattered in the peripheral areas of the fundus, indicating possible exudates or hemorrhages.

Tractional retinal detachment in proliferative diabetic retinopathy indicates:

• Severe progression of the disease, where abnormal blood vessels pull on the retina.
• Visual impairment risk: This condition can lead to significant vision loss if not treated promptly.
• Appearance: The fundus appears dark red with a raised area representing the detachment, and the optic disc may not be clearly visible.

Neovascularization in proliferative diabetic retinopathy is significant because:

• Indicates advanced disease: It shows that the retinopathy has progressed to a more severe stage.
• Risk of complications: These new blood vessels are fragile and can lead to bleeding, scarring, and retinal detachment.
• Visual prognosis: The presence of neovascularization is associated with a higher risk of vision loss, necessitating close monitoring and potential treatment.

Neovascularization of the iris is the abnormal growth of blood vessels on the iris, and it is also known as rubeosis iridis.

Approximately 80% of patients with type 1 diabetes will develop retinopathy after 15 years.

Approximately 40% of patients requiring insulin will develop retinopathy within 5 years of diagnosis.

Diabetic retinopathy is the most common cause of visual impairment and blindness in patients aged 20–74 years.

The development and progression of diabetic retinopathy is associated with:

• Poor glycemic control
• Increased duration of diabetes
• Presence of diabetic nephropathy

• Usually asymptomatic
• Symptoms of associated complications may include:
  • Macular edema
  • Vitreous hemorrhage
  • Retinal detachment
• Other symptoms may include:
  • Blurred vision
  • Floaters
  • Photopsia
  • Scotoma
  • Sudden, painless vision loss

• Type 1 Diabetes: Screening should begin within 5 years of the onset of the disease.
• Type 2 Diabetes: Screening should occur at the time of diagnosis.
• Interval: Generally, screening should be done every year. Less frequent screening (e.g., every 2 years) may be considered for patients with a normal initial eye exam and good glycemic control, in consultation with an ophthalmologist or optometrist.

The purpose of a comprehensive eye examination is to assess disease severity, determine treatment approach, assess response to treatment, and exclude differential diagnoses of sudden vision loss. This includes performing a slit lamp examination and fundoscopy with pupil dilation.

Features of Moderate NPDR include:

• ≥ 1 capillary microaneurysms
• ≥ 1 of the following:
  • Capillary microaneurysms (to a greater extent than in mild NPDR)
  • Intraretinal hemorrhages
  • Hard exudates
  • Cotton wool spots
  • Mild intraretinal microvascular abnormalities or signs of ischemia

Findings associated with Severe NPDR include:

• ≥ 1 of the following:
  • In all 4 retinal quadrants: capillary microaneurysms, dot intraretinal hemorrhages
  • In ≥ 2 retinal quadrants: signs of ischemia (e.g. venous beading)

• In ≥ 1 retinal quadrant: moderate intraretinal microvascular abnormalities
• Neovascularization
• Criteria for high-risk PDR not met

• Neovascularization on the optic disc or within 1 disc diameter
• Neovascularization elsewhere in the eye, if accompanied by vitreous and/or preretinal hemorrhage

• Within 500 microns of the center of the macula
• Retinal thickening
• Hard exudates (if associated with adjacent retinal thickening)
• Within 1 disc diameter of the center of the macula: any zone of retinal thickening ≥ 1 disc size in any area

• Center-involving DME: ≥ 1 mm diameter retinal thickening in a central subfield
• Noncenter-involving DME: ≥ 1 mm diameter retinal thickening that does not involve a central subfield

• Usually asymptomatic.
• May present with edema.
• Warning signs include polyhydramnios or large-for-gestational age infants (greater than 90th percentile).

• Screening for GDM should occur at 24–28 weeks' gestation for all individuals without pregestational diabetes.
• High-risk individuals should be screened for undiagnosed pregestational diabetes in the first trimester.

• Prenatal patient education on nutrition and physical activity.
• Strict glycemic control during pregnancy through:
  1. Diet
  2. Medication (usually insulin)
• Regular monitoring of fetal growth and wellbeing (e.g., ultrasound).

• Early delivery if glycemic control is poor or complications occur.
• Cesarean delivery if estimated fetus weight > 4500 g.
• Tight control of blood glucose during delivery (e.g., insulin infusion).

Maternal complications include:

• Hypertensive pregnancy disorders
• Urinary tract infections (UTI)
• Birth complications

Fetal and neonatal complications include:

• Diabetic embryopathy
• Diabetic fetopathy

• In most cases, GDM resolves after pregnancy.
• Increased risk of developing Type 2 Diabetes Mellitus (T2DM) (~ 50% over 10 years).
• Screen for diabetes 4–12 weeks postpartum (one-step OGTT) and repeat every 1–3 years.
• Increased risk of gestational diabetes recurring in subsequent pregnancies (~ 50%).

• Indications: Any preexisting indication for diabetes screening.
• Modality: Perform either HbA1c testing (before 15 weeks' gestation) or fasting blood glucose at the initial prenatal visit.
• Follow-up: If screen positive, manage as pregestational diabetes; if negative, perform routine screening for GDM.

HbA1c is not reliable after 15 weeks' gestation due to rapid red blood cell turnover that occurs during pregnancy.

The recommended screening modality for GDM at 24-28 weeks' gestation is the Oral Glucose Tolerance Test (OGTT).

If a screening test for GDM is positive, the individual should be managed as having gestational diabetes mellitus (GDM).

For individuals who screen negative for GDM, no further testing is necessary unless clinical features of diabetes mellitus (DM) develop.

Most pregnant individuals with diabetes are referred to specialists such as endocrinology or maternal-fetal medicine for management.

• Initiate routine prenatal care.
• Offer supportive services (e.g., social work, diabetes education).
• Address coexisting conditions related to diabetes (e.g., obesity, hypertensive pregnancy disorders, ASCVD).
• Discuss glycemic control in pregnancy.
• Initiate antepartum fetal surveillance based on risk factors.

• HbA1c
• Thyroid function tests
• ECG
• Diabetic retinopathy screen
• 24 hour urine profile (if no baseline)

• Advise that most individuals can control GDM with diet and exercise.
• Refer to a dietitian to plan meals and snacks.
• Recommend 30 minutes of moderate-intensity exercise at least 5 days a week.
• Review glycemic control and start antihyperglycemic treatment in pregnancy if lifestyle changes alone are insufficient.

Good glycemic control during pregnancy reduces the risk of maternal and fetal complications.

Consider cesarean delivery.

The target serum glucose is < 110 mg/dL.

Reduce insulin doses immediately after delivery to one-third to one-half of previous levels.

Initiate standard postpartum care including postpartum contraception, encourage breastfeeding, and offer lifestyle recommendations for patients with diabetes mellitus.

Assess for resolution of GDM using the one-step OGTT.

Advise weight loss and exercise, and consider metformin.

Screen for diabetes every 1–3 years.

Advise patients to optimize weight, nutrition, and glucose control before conception.

Near physiologic glucose control decreases the risk of complications of diabetes in pregnancy.

HbA1c should be monitored monthly during pregnancy.

The target for HbA1c during pregnancy is < 6%.

The target for fasting glucose during pregnancy is 70–95 mg/dL.

1 hour postprandial target is 110–140 mg/dL and 2 hour postprandial target is 100-120 mg/dL.

Blood glucose levels < 70 mg/dL are generally considered too low and indicate hypoglycemia.

Insulin is recommended for all patients requiring medication to control diabetes during pregnancy.

The starting dose for gestational diabetes is 0.7–1.0 units/kg/day.

Insulin requirements may decrease in the first trimester, increase in the second and third trimesters, and typically increase if antenatal corticosteroids for fetal maturation are used.

Oral antidiabetic medications can be used off-label for patients unwilling or unable to take insulin during pregnancy.

Diabetic embryopathy is defined as any anomaly in an embryo associated with maternal diabetes, typically developing during the main embryonic period.

• Onset: First trimester
• Pathophysiology: Hyperglycemia leads to inhibition of myo-inositol uptake, which causes abnormalities in the arachidonic acid-prostaglandin pathway, resulting in congenital anomalies and early pregnancy loss.

Pregestational diabetes poses a greater risk of complications than gestational diabetes.

• First trimester: Complications are more common in pregestational diabetes.
• Second and third trimesters: Complications are equally associated with both pregestational and gestational diabetes.

Common cardiovascular defects include:

Clinical features of caudal regression syndrome include:

• Lower limb deformities or foot deformities (e.g., club foot)
• Anorectal malformations
• Aplasia or hypoplasia of the sacrum and/or lumbosacral spine
• Mild to severe motor function impairment and paralysis
• Flat buttocks and shallow gluteal clefts
• Bowel and bladder dysfunction (e.g., neurogenic bladder, bladder incontinence)
• Vertebral anomalies (e.g., hemivertebrae)

The cause of caudal regression syndrome is unknown, but maternal diabetes is a known risk factor. The clinical features vary based on the level of the spinal lesion and disease severity.

Gastrointestinal defects include:

Diabetic fetopathy is defined as any anomaly in a fetus associated with maternal diabetes, caused by fetal hyperinsulinemia during gestation. It occurs due to maternal hyperglycemia leading to fetal hyperglycemia, which stimulates the fetal pancreas and results in fetal hyperinsulinemia.

Diabetic fetopathy typically onset during the second and third trimesters of pregnancy.

Key manifestations of diabetic fetopathy include:

• Fetal macrosomia (growth defect)
• Neonatal hypoglycemia
• Neonatal polycythemia
• Neonatal hypocalcemia and hypomagnesemia
• Respiratory defects (e.g., acute respiratory distress syndrome)
• Cardiovascular defects (e.g., transient hypertrophic cardiomyopathy)

Maternal hyperglycemia leads to fetal hyperglycemia, which causes beta cell hypertrophy and hyperfunctioning in the fetus. This results in fetal and neonatal hyperinsulinemia, leading to transient hypoglycemia after birth when the maternal glucose supply stops.

Transient hypertrophic cardiomyopathy is characterized by the thickening of one or both of the ventricular walls and the interventricular septum. Its pathophysiology involves maternal hyperglycemia leading to fetal hyperglycemia and hyperinsulinemia, which increases fat and glycogen in fetal myocardial cells, resulting in thickened ventricular walls and potential left ventricular outflow obstruction.

Supportive care for symptomatic infants includes:

1. Intravenous fluids
2. Beta blockers

Symptoms typically resolve as plasma insulin normalizes.

Preventive measures include:

1. Weight management
2. Diet and exercise advice
3. Testing individuals with indications for diabetes screening

In the first trimester, it is recommended to:

• Follow a healthy diet
• Engage in regular exercise

The main complications associated with diabetic foot include:

• Ulcers
• Infections
• Foot deformities

These complications arise from the effects of diabetes on the peripheral nervous system and microvasculature.

Foot ulcers are significant because up to one-third of patients with diabetes develop them. They are associated with increased rates of hospitalization, amputation, and death. Notably, 80% of patients with diabetes requiring a lower limb amputation had a preceding foot ulcer.

The risk factors for developing diabetic foot complications include:

1. Poor glycemic control: Chronic hyperglycemia leads to sensorimotor neuropathy.
2. Long-term comorbidities
3. Peripheral neuropathy
4. Peripheral arterial disease (PAD)
5. Long-term tobacco use

Patients with diabetes should take the following preventive measures to avoid diabetic foot complications:

• Daily foot examinations
• Proper foot care
• Glycemic control
• Regular attendance at scheduled diabetic foot screenings

Diabetic foot ulcers are classified into three types:

1. Neuropathic ulcers: Caused by neuropathy, such as peripheral sensory neuropathy and autonomic neuropathy.
2. Ischemic ulcers: Resulting from peripheral artery disease (PAD) and microvascular changes.
3. Neuroischemic ulcers: A combination of both neuropathy and ischemic changes, which are increasingly common and now comprise half of all diabetic foot ulcers.

The clinical features of diabetic foot ulcers include:

• Skin breakdown with or without surrounding tissue necrosis.
• Neuropathic ulcers typically occur at sites of repetitive stress or trauma, such as bony abnormalities, often on the bottom of the foot (e.g., Malum perforans over the metatarsal heads or heel).
• Ischemic and neuroischemic ulcers often appear on the toes or lateral foot.
• Ulcers are usually painless.
• They may be preceded by signs of infection, trauma, or calluses.
• Underlying risk factors may include signs of diabetic peripheral neuropathy (e.g., sensory loss, motor weakness) and features of PAD (e.g., cool foot with no palpable pulses).

1. Assess for any signs of diabetic foot infection.

2. Evaluate for peripheral neuropathy.

3. Perform diagnostics for Peripheral Artery Disease (PAD).

4. Consider imaging for underlying diabetic foot osteomyelitis.

The management of diabetic foot ulcers includes:

1. Management of underlying causes
2. Optimize diabetes management to meet glycemic targets
3. Management of Peripheral Artery Disease (PAD) if present, including surgical or endovascular revascularization procedures
4. Treat any associated diabetic foot infections
5. Specialized footwear
6. Mechanical offloading from pressure points
7. Wound care in consultation with a wound care specialist
8. Dressings to promote wound healing
9. Debridement, including removal of surrounding calluses
10. Negative pressure wound therapy
11. Hyperbaric oxygen therapy
12. Biologic therapies, such as platelet-derived growth factor
13. Amputation if necessary

Follow-up is essential, with assessments at 1-4 week intervals and lifelong follow-up by foot care specialists.

Antibiotics are not indicated for diabetic ulcers unless there are signs of wound infection. This is due to the high risk of infection associated with diabetic foot ulcers, which occurs in approximately 50% of cases.

Diabetic foot ulcers have a high risk of infection due to the negative effects of diabetes on immunity and microvasculature, which can impair healing and increase susceptibility to infections.

Patients with diabetic foot ulcers should be followed up at 1-4 week intervals to assess healing progress. They should also receive lifelong follow-up by foot care specialists to prevent complications.

The management of diabetic foot ulcers frequently requires a multidisciplinary team, which may include:

• Podiatrist
• Wound care specialist
• Vascular surgeon
• Endocrinologist

Infection is the main risk factor for amputation in patients with diabetes.

The most common causative pathogens in diabetic foot infections are Staphylococci and streptococci spp.

The clinical features of diabetic foot infections include:

• Edema
• Induration
• Erythema
• Tenderness
• Warmth
• Purulent exudate

The severity of diabetic foot infections is classified as follows:

• Mild: Superficial infection with ≤ 2 cm of erythema
• Moderate: Deep infection or > 2 cm of erythema
• Severe: Any degree of infection plus systemic inflammatory response syndrome

• CBC, CRP, ESR
• Wound cultures via biopsy or curettage
• Diagnostics for Peripheral Artery Disease (PAD) and polyneuropathy
• Assessment for diabetic foot osteomyelitis (e.g., probe to bone test, imaging)
• For patients with severe infections, obtain diagnostic studies for sepsis.

Patients should be admitted if they have any of the following criteria:

1. Severe infection
2. Chronic limb-threatening ischemia
3. Barriers to follow-up
4. Little response to outpatient management

• Infection severity
• Local resistance patterns
• Recent antibiotic use
• Risk factors for MRSA infection and/or Pseudomonas aeruginosa
• Route of administration

Osteomyelitis should be suspected in any patient with an ulcer and any of the following features:

• Clinical features of skin and soft tissue infection (e.g., erythema, edema)
• Ulcer size > 2 cm² and/or ulcer depth > 3 mm

A positive probe-to-bone test indicates potential underlying osteomyelitis. This clinical test involves inserting a sterile blunt probe into the ulcer; if the probe makes direct contact with the bone, it suggests the presence of infection in the bone tissue.

Common clinical features indicating osteomyelitis include:

• Exposed bone tissue
• Positive probe-to-bone test
• Chronic ulcers that are treatment-resistant
• Ulcers overlying a bony prominence
• Markedly increased ESR (> 70 mm/hour)
• Unexplained leukocytosis

Recommended diagnostic approaches for suspected osteomyelitis include:

1. Obtain serial plain radiographs
2. MRI to assess soft tissues and bones for infection and fluid accumulation

The treatment plan for osteomyelitis includes:

• Optimizing diabetes management
• Antibiotics to address infection
• Possible surgery to remove infected tissue or bone

Diabetic neuropathy can lead to foot deformities such as hammer toes and claw toes, increasing the risk of developing foot ulcers. This occurs due to:

• Loss of intrinsic muscle volume
• Thickening of the plantaraponeurosis

• Flexible hammer toe: Joint deformity can be manually corrected.
• Fixed (rigid) hammer toe: Joint deformity cannot be manually corrected.

Factors that can prolong insulin absorption time include:

1. Cold injection site
2. Obesity
3. Peripheral injection site
4. Superficial subcutaneous injection

Factors that can shorten insulin absorption time include:

1. Manipulative therapy (e.g., massages)
2. Deep subcutaneous injection
3. Injection into the abdominal skin around the navel

Indications for insulin therapy include:

1. Type 1 diabetes mellitus
2. Type 2 diabetes mellitus (if noninsulin antidiabetic drugs are insufficient)
3. End-stage renal failure (doses titrated according to glomerular filtration rate)
4. Exocrine pancreatic insufficiency with secondary diabetes
5. Gestational diabetes mellitus
6. Acute hyperkalemia (using regular insulin and glucose solution)

• Hypoglycemia
• Weight gain
• Lipodystrophy at the injection site
• Hypokalemia
• Allergic or hypersensitivity reactions
• Edema
• Pain and erythema at the injection site

• Thiazide diuretics and loop diuretics
• Heparin
• Glucocorticoids
• Immunosuppressive drugs (e.g., calcineurin inhibitors)
• Tricyclic antidepressants
• Antipsychotic drugs
• Lithium
• HIV-protease inhibitors
• Thyroid hormones
• Estrogen (contraceptives)
• Sympathomimetic drugs that interact with the ẞ1-adrenergic receptor (e.g., dobutamine)
• Derivatives of nicotinic acid

• Analgesics (e.g., NSAIDs, tramadol)
• Antibiotics (e.g., cotrimoxazole and other sulfonamides, fluoroquinolones)
• Antimalarial drugs (e.g., mefloquine, quinine)
• MAO inhibitors

• Insulin regimens should be tailored individually to each patient.
• Treatment of Type 1 Diabetes Mellitus (T1DM) requires intensive insulin therapy with a multi-injection regimen or insulin pump.
• There are various options for patients with Type 2 Diabetes Mellitus (T2DM).
• Certain diabetes medications (e.g., sulfonylureas) should be stopped when insulin therapy is started.
• Hospital standards vary; specialists should be involved early.

• Acute stage:

  • Swelling
  • Warmth
  • Erythema
  • Mild-to-moderate pain due to reduced sensation from peripheral neuropathy.

• Chronic stage:

  • Painless bony deformities
  • Midfoot collapse (rocker-bottom foot deformity)
  • Osteolysis
  • Fractures

The first-line diagnostic tool for diabetic neuropathic arthropathy is x-ray. MRI may be used in cases of diagnostic uncertainty.

In cases of diagnostic uncertainty, a bone biopsy can be considered to distinguish diabetic neuropathic arthropathy from diabetic foot osteomyelitis.

The Kocker-bottom deformity is characterized by the collapse of the arch of the foot, often seen in patients with Charcot foot due to diabetic neuropathic arthropathy.

Key prevention strategies include:

1. Optimize glycemic control.
2. Encourage smoking cessation.
3. Screen patients ≥ 50 years old for peripheral artery disease (PAD) using an ankle-brachial index (ABI).
4. Identify and treat dermatological conditions that increase ulcer risk, such as onychomycosis and calluses.
5. Educate patients on the importance of regular diabetic foot screenings and daily self-monitoring, including foot examination and skin/nail care.
6. Advise against self-treatment of calluses/corns and recommend proper footwear.

Patients at high risk of ulceration should wear specialized therapeutic footwear that fits properly and meets safety criteria to prevent foot injuries and complications.

Patients should engage in daily self-monitoring practices that include:

1. Foot examination.
2. Skin and nail care.
3. Avoiding self-treatment of calluses/corns.
4. Selecting socks with no seams or wearing socks with seams inside out to prevent rubbing.
5. Choosing appropriate footwear and avoiding walking barefoot or wearing open-toed/open-heeled shoes.

Annually.

At every visit.

1. Focused history to identify new symptoms, risk factors, and diabetic complications.

2. Inspection of the skin for breakdown, calluses, and signs of infection.

3. Evaluation of bones for deformities.

4. Focused examination of sensation using the 10g monofilament test.

5. Palpation of pedal pulses.

Symptoms such as burning, pain, numbness, and claudication should be monitored.

Risk factors such as cigarette smoking should be assessed.

Diabetic gastroparesis is a complication of long-term diabetes characterized by delayed gastric emptying not associated with mechanical obstruction. Main symptoms include nausea, vomiting, abdominal discomfort, and early satiety.

The risk factors for diabetic gastroparesis include inadequate glycemic control (sustained hyperglycemia > 200 mg/dL) and obesity.

Diabetic gastroparesis is diagnosed by exclusion and confirmed through scintigraphic gastric emptying studies.

The mainstay of treatment for diabetic gastroparesis includes:

1. Glycemic control
2. Dietary modifications
3. Avoidance of medications and substances that delay gastric emptying
4. Prokinetic agents to improve gastric emptying
5. Antiemetics for symptom relief
6. For refractory symptoms, options may include surgery, gastric electric stimulation, or parenteral feeding.

Diabetic gastroparesis affects 5% of patients with type 1 diabetes and 1% of patients with type 2 diabetes in the US.

The pathophysiology of diabetic gastroparesis involves:

• Poor glycemic control leading to neuronal damage
• Impaired neural control of gastric function, including dysfunction of interstitial cells of Cajal, abnormal myenteric neurotransmission, smooth muscle dysfunction, and vagal dysfunction
• Resulting in impaired antral motor coordination.

Common symptoms include:

• Nausea and/or vomiting
• Bloating
• Upper abdominal pain
• Loss of appetite
• Early satiety

Examination findings may include:

• Abdominal distension
• Epigastric tenderness
• Succussion splash

1. Perform clinical evaluation to exclude differential diagnoses of gastroparesis.
2. Assess for clinical features of neurological diseases, autoimmune disease, or eating disorders.
3. Review medication list for medications that delay gastric emptying (e.g., opioids).
4. Ask about history of bariatric surgery.
5. Consider laboratory studies, as indicated.
6. Obtain upper endoscopy to exclude mechanical obstruction.
7. Perform confirmatory testing to observe delayed gastric emptying.

• HbA1c: to assess glycemic control
• TSH: to assess for hypothyroidism
• CBC: to evaluate for infection or malignancy
• Additional studies may be needed to rule out differential diagnoses of gastroparesis, including diagnostic studies for chronic pancreatitis.

The preferred confirmatory test for delayed gastric emptying is scintigraphic gastric emptying.

At least 48 hours prior to confirmatory testing, medications that affect gastric emptying should be stopped, and strict glucose control should be initiated to prevent false negative or false positive results.

Alternative causes of gastroparesis include:

• Idiopathic
• Postsurgical (e.g., after vagotomy or bariatric surgery)
• Medication-induced (e.g., opioids)
• Neurologic disorders (e.g., Parkinsonism)
• Infiltrative disorders (e.g., amyloidosis)

Differential diagnoses for abdominal pain related to gastroparesis include:

• GERD
• Acute or chronic pancreatitis
• Malignancy
• Eating disorders (e.g., avoidant restrictive food intake disorder)
• Cyclic vomiting syndrome or cannabinoid hyperemesis syndrome
• Thyroid disorders

• Optimize treatment of diabetes to achieve glycemic targets.
• Initiate dietary modifications in consultation with a nutritionist, including small, frequent meals that are low in fat and fiber.
• Avoid substance use such as tobacco and alcohol.
• Consider acupuncture for symptomatic relief.

The first-line pharmacotherapy for improving symptoms and gastric emptying in diabetic gastroparesis is metoclopramide.

Diabetic gastroparesis can complicate diabetes management by causing:

• Poor absorption of oral antidiabetic drugs.
• Difficulties with timing insulin doses due to delayed food absorption.
• Some antidiabetic medications may delay gastric emptying, necessitating careful selection of drugs.

Recommended dietary modifications include:

1. Small, frequent meals.
2. Low in fat and fiber.
3. Small particle size foods.

When prescribing antidiabetic medications to patients with diabetic gastroparesis, it is important to:

• Select medications carefully, as some can delay gastric emptying.
• Consider alternatives for medications associated with delayed gastric emptying, such as GLP-1 agonists and pramlintide.

For severe symptoms, the recommended dosage is IV/IM metoclopramide, but specific dosages should be determined based on clinical guidelines and patient needs.

For mild to moderate symptoms, oral metoclopramide is recommended, with specific dosages to be determined based on clinical guidelines.

Gastric electric stimulation (GES) involves providing high-frequency electrical pulses to the stomach through implanted leads to enhance gastric emptying. Evidence supporting its use has been mixed.

Parenteral nutrition should be considered in advanced disease, and continuing oral feeding alongside parenteral nutrition can reduce morbidity and mortality.

• Electrolyte imbalance
• Malnutrition
• Increased risk of postprandial hypoglycemia due to delayed food absorption

Diabetic kidney disease is a chronic kidney disease (CKD) caused by chronic hyperglycemia and is a major cause of end-stage renal disease (ESRD).