A.5 Diabetes Complications. TX DM Flashcards
A.5 Diabetes Complications. TX DM
DM 1 TX
Basal-bolus regimen
Basal insulin: Long-acting (glargine, detemir, degludec) Bolus insulin: Rapid-acting (aspart, lispro, glulisine) before meals
A.5 Diabetes Complications. TX DM
DM 2 TX Drug Classes
Metformin
SGLT2 inhibitors
GLP-1 receptor agonists
DPP-4 inhibitors
Sulfonylureas
Thiazolidinediones (TZDs)
Insulin
A.5 Diabetes Complications. TX DM
Metformin
Metformin is a biguanide that lowers blood glucose by multiple mechanisms, without causing hypoglycemia
First-line drug for Type 2 Diabetes Mellitus
↓ Hepatic gluconeogenesis
→ Metformin activates AMP-activated protein kinase (AMPK) in the liver
→ This inhibits hepatic glucose production, the main source of fasting hyperglycemia in type 2 DM
↑ Insulin sensitivity in muscle and fat → Enhances peripheral glucose uptake
↓ Intestinal glucose absorption
Promotes weight neutrality or slight weight loss
No direct effect on insulin secretion → So, no hypoglycemia
A.5 Diabetes Complications. TX DM
Metformin CI
eGFR <30 mL/min b/c ↑ risk of lactic acidosis
Unstable heart failure b/c it causes Poor perfusion = ↑ lactic acid
Acute alcohol intoxication b/c it can cause ↑ risk of lactic acidosis
Severe liver disease due to Impaired lactate clearance
Before iodinated contrast - Temporarily hold due to AKI risk
A.5 Diabetes Complications. TX DM
SGLT2 inhibitors
e.g. Empagliflozin, Dapagliflozin, Canagliflozin, Ertugliflozin
Blocking the SGLT2 transporter in the proximal renal tubule, which is responsible for 90% of glucose reabsorption in the kidney.
As a result:
↓ Glucose reabsorption → ↑ glucosuria ↓ Blood glucose levels Mild osmotic diuresis → ↓ BP and weight
They work independently of insulin, so they do not cause hypoglycemia when used alone.
Used as As 2nd-line agents after metformin
Sometimes as first-line in patients with comorbidities
A.5 Diabetes Complications. TX DM
Keys to SGLT2i
Choose empagliflozin or dapagliflozin in T2DM with CV or renal disease
Combine with metformin for synergistic effect
No risk of hypoglycemia unless combined with insulin or sulfonylureas
Monitor renal function and volume status
Educate patients on DKA symptoms, especially during illness or fasting
A.5 Diabetes Complications. TX DM
GLP-1 Receptor Agonists
e.g. Liraglutide, Semaglutide (oral and injectable), Exenatide, Dulaglutide, Albiglutide
GLP-1 receptor agonists mimic the incretin hormone GLP-1, which is secreted by the gut in response to food. These drugs activate GLP-1 receptors in various tissues to lower blood glucose.
Main actions:
↑ Glucose-dependent insulin secretion
↓ Glucagon secretion ↓ Gastric emptying (slows postprandial glucose rise) ↑ Satiety / ↓ appetite → leads to weight loss
Acts only when glucose is elevated, so no hypoglycemia unless combined with insulin or sulfonylureas.
A.5 Diabetes Complications. TX DM
GLP-1 Receptor Agonists Indications
econd-line after metformin (or first-line in selected high-risk patients)
As an alternative to insulin in patients who fear injections or weight gain
With SGLT2 inhibitors in high-risk cardiovascular or kidney patients
Semaglutide (Wegovy) approved specifically for weight loss in non-diabetics
A.5 Diabetes Complications. TX DM
GLP-1 Receptor Agonists Keys
GLP-1 RAs are weight-reducing, cardio-protective, and low risk for hypoglycemia
Liraglutide and semaglutide have the strongest evidence for CV protection
Oral form available: Semaglutide
Often preferred before insulin in overweight or cardiovascular-risk patients
A.5 Diabetes Complications. TX DM
DPP-4 inhibitors
Dipeptidyl Peptidase-4 inhibitors
e.g. Sitagliptin, Saxagliptin, Linagliptin, Alogliptin
DPP-4 inhibitors block the enzyme DPP-4, which normally degrades incretin hormones like GLP-1 and GIP.
As a result:
↑ Endogenous GLP-1 levels
→ ↑ Glucose-dependent insulin secretion → ↓ Glucagon secretion
Effect is glucose-dependent, so no hypoglycemia unless combined with insulin or sulfonylureas.
Unlike GLP-1 receptor agonists, DPP-4 inhibitors do not cause weight loss.
A.5 Diabetes Complications. TX DM
DPP-4 inhibitors Keys
As second-line after metformin
In combination with metformin, SGLT2i, or insulin
In patients where injectables are not desired
Monotherapy if metformin is contraindicated or not tolerated
A.5 Diabetes Complications. TX DM
Sulfonylureas
e.g. Glibenclamide (glyburide), Gliclazide, Glipizide, Glimepiride
Sulfonylureas stimulate insulin secretion from pancreatic β-cells by:
Binding to the SUR1 subunit of the K⁺-ATP channel on the β-cell membrane
→ This closes the potassium channels → Leads to cell depolarization → Opens voltage-gated Ca²⁺ channels → Calcium influx triggers insulin release
This action is independent of glucose levels, which means they can cause hypoglycemia.
A.5 Diabetes Complications. TX DM
Sulfonylureas indications
As second-line after metformin
In resource-limited settings
Short-term bridging while waiting for longer-acting agents to work
Used in patients without cardiovascular/renal comorbidities
keys:
Most common oral agent to cause hypoglycemia
Good for quick HbA1c lowering, but not disease-modifying
No cardio or renal benefit unlike GLP-1 or SGLT2 inhibitors
Shorter-acting options (e.g., glipizide) safer in elderly
A.5 Diabetes Complications. TX DM
Thiazolidinediones
Also known as “glitazones”
Examples: Pioglitazone
TZDs are insulin sensitizers. They activate the PPAR-γ (peroxisome proliferator-activated receptor gamma) nuclear receptor in adipose tissue, muscle, and liver.
Main effects:
↑ Insulin sensitivity in peripheral tissues (muscle & fat)
↓ Hepatic glucose production ↑ Glucose uptake in skeletal muscle
They do not increase insulin secretion, so they do not cause hypoglycemia when used alone.
A.5 Diabetes Complications. TX DM
Thiazolidinediones indications and keys
As second- or third-line agent in T2DM
In patients with low risk of heart failure or fluid retention
Pioglitazone is preferred due to better safety profile
keys:
TZDs are effective insulin sensitizers but take several weeks to show effect
No hypoglycemia when used alone
Pioglitazone improves lipid profile (↓TG, ↑HDL)
Monitor for edema, weight gain, and heart failure symptoms
Use with extreme caution in elderly women due to fracture risk
A.5 Diabetes Complications. TX DM
Acute Complications
Hypoglycemia
Diabetic Ketoacidosis (DKA)
Hyperosmolar Hyperglycemic State (HHS)
Lactic acidosis
A.5 Diabetes Complications. TX DM
Chronic Complications
microvascular:
Diabetic retinopathy
Diabetic nephropathy
Diabetic neuropathy
macrovascular:
Coronary artery disease (CAD)
Cerebrovascular disease
Peripheral arterial disease (PAD)
A.5 Diabetes Complications. TX DM
Hypoglycemia defintion
Hypoglycemia in patients with diabetes generally described as ≤ 3.9 mmol/L
A.5 Diabetes Complications. TX DM
Hypoglycemia Clinical
symptomatic at 2.8 mmol/L
Neurogenic/autonomic
- Increased sympathetic activity: tremor, pallor, anxiety, tachycardia, sweating, and palpitations
- Increased parasympathetic activity: hunger, paresthesias, nausea, and vomiting
Neuroglycopenic
- Agitation, confusion, behavioral changes
- Fatigue
- Seizure, focal neurological signs
Somnolence → obtundation → stupor → coma → death
A.5 Diabetes Complications. TX DM
Hypoglycemia TX
If Alert:
Oral glucose 15–20 g
Fast-acting carbohydrates (e.g., glucose tablets, candy, or fruit juice)
Patients with altered mental status (or impaired oral intake):
- IV dextrose (e.g., D50W): Repeat after 15 minutes if hypoglycemia persists; multiple doses may be required
IM glucagon
A.5 Diabetes Complications. TX DM
Hypoglycemia - Whipple’s Triad
(Diagnostic Criteria)
Symptoms of hypoglycemia
Low plasma glucose
Relief of symptoms with glucose correction
A.5 Diabetes Complications. TX DM
Why might sulfonylurea-induced hypoglycemia be prolonged?
Long half-life; stimulates endogenous insulin → requires octreotide
A.5 Diabetes Complications. TX DM
What lab test distinguishes insulinoma from factitious insulin use?
C-peptide:
↑ in insulinoma ↓ in exogenous insulin use
A.5 Diabetes Complications. TX DM
DKA definition
A condition that is primarily seen in patients with type I diabetes and is caused by insufficient insulin levels (often secondary to acute infection). Manifests with hyperglycemia (usually 300-600 mg/dL - 16.65–33.3 mmol/L.), polyuria, polydipsia, nausea, vomiting, volume depletion (e.g., dry oral mucosa, decreased skin turgor), and eventually mental status changes and coma.
A.5 Diabetes Complications. TX DM
DKA pathophys - Osmotic diuresis and hypovolemia
Insulin normally elevates cellular uptake of glucose from the blood.
In the insulin-deficient state of DKA, hyperglycemia occurs.
Hyperglycemia, in turn, leads to progressive volume depletion via osmotic diuresis.
Insulin deficiency → hyperglycemia → hyperosmolality → osmotic diuresis and loss of electrolytes → hypovolemia
A.5 Diabetes Complications. TX DM
DKA pathophys -Metabolic acidosis with increased anion gap
Insulin deficiency increases fat breakdown (lipolysis) through increased activity of hormone-sensitive lipase.
Metabolic acidosis develops as the free fatty acids generated by lipolysis become ketones, two of which are acidic (acetoacetic acid and beta-hydroxybutyric acid).
Serum bicarbonate is consumed as a buffer for the acidic ketones. Metabolic acidosis with an elevated anion gap is therefore characteristic of DKA.
Insulin deficiency → ↑ lipolysis → ↑ free fatty acids → hepatic ketone production (ketogenesis) → ketosis → bicarbonate consumption (as a buffer) → anion gap metabolic acidosis
A.5 Diabetes Complications. TX DM
DKA pathophys - Intracellular potassium deficit
As a result of hyperglycemic hyperosmolality, potassium shifts along with water from inside cells to the extracellular space and is lost in the urine.
Insulin normally promotes cellular potassium uptake but is absent in DKA, compounding the problem.
A total body potassium deficit develops in the body, although serum potassium may be normal or even paradoxically elevated.
Insulin deficiency → hyperosmolality → K+ shift out of cells + lack of insulin to promote K+ uptake → intracellular K+depleted → total body K+ deficit despite normal or even elevated serum
A.5 Diabetes Complications. TX DM
Why is there potassium deficit in DKA
There is a total body potassium deficit in DKA. This becomes important during treatment, when insulin replacement leads to rapid potassium uptake by depleted cells and patients may require potassium replacement.
A.5 Diabetes Complications. TX DM
DX DKA
BMP:
glucose < 33.3 mmol/L
Bicarbonate < 18 mmol/L
Elevated anion gap > 10 mmol/L
Urinanalysis:
Moderate-large urine ketones (ketonuria)
Glucosuria
pH:
pH ≤ 7.30 - metabolic acidosis
Electrolytes:
Hyponatremia - Due to hyperglycemia-induced osmotic shift of intracellular water into the extracellular space.
Potassium in DKA: normal or elevated (despite a total body deficit)
Magnesium levels are typically low.
Phosphorus levels may be elevated despite a total body deficit.
BUN and creatinine are often elevated - ↑ BUN and creatinine suggest AKI, which in hyperglycemic crisis is often due to osmotic diuresis and dehydration and typically responds to fluid resuscitation. Persistently elevated BUN and creatinine despite fluid resuscitation should prompt further investigation.
A.5 Diabetes Complications. TX DM
Clinical Symptoms DKA
Rapid onset (< 24 h)
Abdominal Pain - The state of ketoacidosis leads to irritation of the peritoneum. This can cause diffuse abdominal tenderness on palpation with guarding, possibly even to the extent that an acute abdominal pathology is suspected.
Fruity odor on the breath (from exhaled acetone)
Hyperventilation: long, deep breaths (Kussmaul respirations) - Respiratory compensation for the state of metabolic acidosis
A.5 Diabetes Complications. TX DM
DKA TX
Initial steps
ABCDE approach
Urgent diagnostics, e.g., POC glucose, BMP, blood gas analysis
Volume status assessment
Principal interventions
Fluid resuscitation: initially with isotonic saline (0.9% NaCl)
Potassium repletion: for potassium level < 5.3 mEq/L
Insulin therapy: initiate short-acting insulin once potassium level is > 3.3 mEq/L
IV sodium bicarbonate: only for severe refractory metabolic acidosis
Identify and treat precipitating causes (e.g., sepsis).
Consider endocrine consult and admission to the ICU.
A.5 Diabetes Complications. TX DM
DKA FLuid Therpay
First hour: isotonic saline solution (0.9% sodium chloride) at 15–20 mL/kg/hour (∼ 1000–1500 mL bolus)
Next 24–48 hours: Adjust IV fluid rate and composition according to CVP, urine output, blood glucose, and corrected sodium levels.
Check corrected sodium for hyperglycemia.
If corrected serum sodium ≥ 135 mmol/L: 0.45% NaCl
If corrected serum sodium < 135 mmol/L: 0.9% NaCl
Switch to a solution containing dextrose (e.g., D5NS) when glucose falls to ∼ 200 mg/dL (DKA) or 300 mg/dL (HHS).
A.5 Diabetes Complications. TX DM
Definition Hyperosmolar Hyperglycemic State (HHS)
Primarily affects patients with type 2 diabetes
The pathophysiology of HHS is similar to that of DKA.
However, in HHS, there are still small amounts of insulin being secreted by the pancreas, and this is sufficient to prevent DKA by suppressing lipolysis and, in turn, ketogenesis.
HHS is characterized by symptoms of marked dehydration (and loss of electrolytes) due to the predominating hyperglycemia and osmotic diuresis.
Relative insulin deficiency (enough to suppress ketogenesis but not enough to prevent hyperglycemia)
→ Marked hyperglycemia → osmotic diuresis
→ Profound dehydration
→ ↑ Plasma osmolality → altered mental status
Minimal or no ketosis (due to residual insulin activity)
A.5 Diabetes Complications. TX DM
Clinical HHS
Polyuria
Polydipsia
Recent weight loss
Nausea and vomiting
Signs of significant dehydration
Neurological abnormalities
Altered mental status
Lethargy
Coma
Other neurological examination abnormalities, e.g., blurred vision and weakness
INSIDIOUS/ gradual onset (days)
In HHS, residual insulin production prevents significant ketoacidosis leading to insidious progression (days to weeks) and profound hypovolemia and hyperglycemia (> 600 mg/dL).
A.5 Diabetes Complications. TX DM
HHS DX
HHS is the diagnosis in patients with type 2 diabetes who have hyperglycemia and hyperosmolality!
HHS: hyperglycemia, hyperosmolality, and dehydration without ketonuria
Check serum glucose to confirm hyperglycemia.
Check BMP for serum bicarbonate, anion gap, electrolytes, and renal function.
Check for the presence of ketones.
Urine ketones: Standard urine dipstick assays detect acetoacetate and acetone but not beta-hydroxybutyrate. Serum beta-hydroxybutyrate
Check blood gas analysis for pH.
Diagnostic workup to evaluate the underlying cause: HbA1c, CBC, ECG, infectious workup
A.5 Diabetes Complications. TX DM
HHS Labs
BMP:
glucose > 33.3 mmol/L
Bicarbonate: > 18 mmol/L
Normal anion gap < 10 mmol/L
serum osmolarity - Elevated > 320 mmol/kg
same tx as DKA
A.5 Diabetes Complications. TX DM
Can DKA occur with glucose <250 mg/dL?
Yes — called euglycemic DKA, often seen with SGLT2 inhibitors, pregnancy, or prolonged fasting.
A.5 Diabetes Complications. TX DM
Why might serum sodium appear low in DKA?
Pseudohyponatremia from hyperglycemia → use corrected sodium:
Corrected Na+ = measured Na+ + 1.6 for every 100mg/dL glucose > 100
A.5 Diabetes Complications. TX DM
Why is bicarbonate usually avoided?
It can cause paradoxical CNS acidosis, hypokalemia, and worsened tissue hypoxia.
A.5 Diabetes Complications. TX DM
HHS Complications
Cerebral edema (rare in adults, more in children) - Rapid correction of hyperglycemia or osmolality → Fluid shifts into brain cells → cytotoxic edema
Low serum sodium or excess hypotonic fluids can worsen it
Seizures
Thromboembolism (hyperviscosity)
Rhabdomyolysis
Acute kidney injury
A.5 Diabetes Complications. TX DM
HHS Keys
Start fluids before insulin — dehydration is more severe than in DKA
Avoid rapid correction → risk of cerebral edema
No ketosis = HHS (think “sweet but not sour”)
Use corrected Na⁺ to guide fluid choice: use corrected sodium:
Corrected Na+ = measured Na+ + 1.6 for every 100mg/dL glucose > 100
A.5 Diabetes Complications. TX DM
What is the diagnostic triad of HHS?
Severe hyperglycemia (>600 mg/dL)
Hyperosmolarity (>320 mOsm/kg)
Minimal or no ketones/acidosis
A.5 Diabetes Complications. TX DM
Why is ketosis minimal or absent in HHS?
Because patients still have enough residual insulin to suppress ketogenesis, but not enough to control hyperglycemia
A.5 Diabetes Complications. TX DM
When can you add dextrose to IV fluids in HHS?
When glucose drops to <300 mg/dL, to prevent hypoglycemia and allow continued insulin infusion to close the osmotic gap
A.5 Diabetes Complications. TX DM
Diabetic Retinopathy Definition
vascular disease of the retina that is usually asymptomatic in the early stages but can lead to visual impairment and blindness as the disease progresses.
A.5 Diabetes Complications. TX DM
3 Types of DR
Nonproliferative diabetic retinopathy (NPDR)
Proliferative diabetic retinopathy (PDR)
Diabetic macular edema (DME)
A.5 Diabetes Complications. TX DM
Describe NPDR
Retinal vessel microangiopathy → blood leaks → retinal hemorrhages
Microaneurysms
Caliber changes in veins
Intraretinal hemorrhage
Hard exudates
Retinal edema
Cotton-wool spots
Intraretinal microvascular abnormalities (IRMA)
A.5 Diabetes Complications. TX DM
TX NPDR
Mild NPDR to moderate NPDR: Observation only; repeat dilated comprehensive eye examination every 6–12 months.
Severe NPDR: Treat as proliferative retinopathy with panretinal laser photocoagulation (PRP) and/or anti-VEGF therapy.
A.5 Diabetes Complications. TX DM
Describe Proliferative diabetic retinopathy (PDR)
Retinal vessel microangiopathy → chronic retinal hypoxia → abnormal proliferation of blood vessels → traction on retina → retinal detachment
Findings of nonproliferative retinopathy are usually present.
Neovascularization is the hallmark of PDR
Fibrovascular proliferation → vitreous hemorrhage, traction retinal detachment Rubeosis iridis → secondary glaucoma
A.5 Diabetes Complications. TX DM
TX PDR
Proliferative retinopathy: PRP and/or anti-VEGF therapy
Both PRP and anti-VEGF therapy are equally effective. PRP is usually preferred as treatment occurs in a single session (reduces risk of loss to follow-up).
Anti-VEGF injections alone can be considered for patients who are highly motivated and have no barriers to follow-up.
A.5 Diabetes Complications. TX DM
Describe Diabetic Macular Edema (DME)
Retinal vessel microangiopathy → blood leaks → retinal hemorrhages → retinal infiltration with lipids and fluid → macular edema
Clinically significant retinal thickening and edema involving the macula, associated hard exudates
May occur in all stages of NPDR and PDR
A.5 Diabetes Complications. TX DM
DME TX
Center-involving macular edema
First line: Intravitreal anti-VEGF therapy
Consider PRP or focal and/or grid laser depending on severity of retinopathy.
Noncenter-involving macular edema: PRP, anti-VEGF, or focal and/or grid laser therapy may be used depending on severity of retinopathy.
Refractory disease or severe complications (e.g., tractional retinal detachment, vitreal hemorrhage): Consider vitrectomy.
A.5 Diabetes Complications. TX DM
DR Keys
DR is a microvascular complication — like nephropathy and neuropathy
VEGF = key mediator of neovascularization → target of anti-VEGF therapy
Macular edema = most common cause of vision loss in diabetics
PDR = most dangerous stage → can cause blindness
A.5 Diabetes Complications. TX DM
What’s the role of anti-VEGF in diabetic retinopathy?”
Inhibits VEGF → reduces neovascularization and vascular leakage → treats DME and PDR
A.5 Diabetes Complications. TX DM
What investigation is best to detect macular edema?
Optical Coherence Tomography (OCT)
A.5 Diabetes Complications. TX DM
Explain the pathogenesis of diabetic retinopathy.”
Hyperglycemia → endothelial damage, pericyte loss → capillary leakage and ischemia → VEGF release → neovascularization → hemorrhage and fibrosis.
A.5 Diabetes Complications. TX DM
Diabetic Nephropathy
A form of chronic kidney disease that occurs in 20–40% of patients with diabetes mellitus. Caused by glomerular damage induced by glycosylation of the basement membrane and plasma hyperfiltration.
A.5 Diabetes Complications. TX DM
Diabetic Nephropathy Risk Factors
Risk factors
Hypertension and blood pressure variability
Longstanding diabetes
Inadequate glycemic control
A.5 Diabetes Complications. TX DM
Diabetic Nephropathy Pathophysiology
Chronic hyperglycemia → glycation (also called non-enzymatic glycosylation or NEG) of the basement membrane (protein glycation) → increased permeability and thickening of the basement membrane and stiffening of the efferent arteriole → hyperfiltration (increase in GFR) → increase in intraglomerular pressure → progressive glomerular hypertrophy, increase in renal size, and glomerular scarring (glomerulosclerosis) → worsening of filtration capacity
A.5 Diabetes Complications. TX DM
Pathological Changes in Diabetic Nephropathy
Mesangial expansion
Glomerular basement membrane thickening
Glomerulosclerosis (later stages)
Diffuse hyalinization (most common) or Pathognomonic nodular glomerulosclerosis (Kimmelstiel-Wilson nodules): Glomerular capillary hypertension and hyperfiltration → increase in mesangial matrix → eosinophilic hyaline material in the area of glomerular capillary loops Can progressively consume the entire glomerulus → hypofiltration (↓ GFR)
A.5 Diabetes Complications. TX DM
Diabetic Nephropathy Clinical
Patients are usually asymptomatic in the early stages; some may report foamy urine.
Late Stage
hypertension
volume overload
A.5 Diabetes Complications. TX DM
Diabetic Nephropathy DX
Urine Albumin-Creatinine Ratio (ACR)
First morning spot urine test
30 mg/g = abnormal
Screening for diabetic kidney disease
Onset
T1DM: 5 years after diagnosis
T2DM: from the time of diagnosis
Recommended assessment
eGFR ≥ 60 mL/min/1.73 m2: Check urine albumin levels and eGFR once a year.
eGFR < 60 mL/min/1.73 m2: more frequent assessment is required; see
Diabetic kidney disease is confirmed through:
Laboratory studies showing persistent (≥ 3 months) albuminuria and/or reduced eGFR
A.5 Diabetes Complications. TX DM
Glycemic targets
Measure HbA1c at least twice yearly.
An HbA1c of < 6.5–8% is generally recommended.
HbA1c may not be an accurate method of glucose monitoring in patients with an eGFR < 30 mL/min/1.73 m2; consider continuous glucose monitoring.
Pharmacotherapy
T1DM: Insulin dosage may need to be reduced as eGFR declines
T2DM
Choice of treatment depends on eGFR;
eGFR ≥ 30 mL/min/1.73 m2
First line: metformin AND/OR an SGLT-2 inhibitor
Consider GLP-1 receptor agonist for patients: Unable to take first-line medications
eGFR < 30 mL/min/1.73 m
Discontinue metformin.
SGLT2 inhibitors can be continued but should not be initiated in patients with eGFR < 20 mL/min/1.73 m2.
Selected dipeptidyl peptidase 4 inhibitors, GLP-1 receptor agonists, insulin, thiazolidinediones, and short-acting sulfonylureas can be use
A.5 Diabetes Complications. TX DM
“What’s the earliest sign of diabetic nephropathy?”
Microalbuminuria (30–300 mg/day)
A.5 Diabetes Complications. TX DM
Which medications improve both glucose control and kidney outcomes in DN?”
SGLT2 inhibitors (e.g., empagliflozin) and GLP-1 RAs (e.g., liraglutide)
A.5 Diabetes Complications. TX DM
Is macroalbuminuria required for diagnosis of diabetic nephropathy?
❌ No — diagnosis begins with microalbuminuria
A.5 Diabetes Complications. TX DM
Should ACE inhibitors be stopped if creatinine rises?
✅ Only if creatinine rises >30% from baseline or potassium >5.5 → otherwise, continue and monitor
A.5 Diabetes Complications. TX DM
Diabetic Neuropathy Definition
progressive nerve injury caused by chronic hyperglycemia. Distal symmetric polyneuropathy and autonomic neuropathy are the most common types; less common manifestations include mononeuropathy and radiculopathy. Patients with distal symmetric polyneuropathy typically present with sensory loss of the lower extremities and may also have motor weakness, although many affected individuals are asymptomatic.
A.5 Diabetes Complications. TX DM
Diabetic Neuropathy Epidemiology
Diabetic polyneuropathy is the most common form of polyneuropathy in high-income countries. [2][3]
∼ 50% of patients with diabetes develop peripheral neuropathy. [4]
Up to 90% of patients with diabetes may develop autonomic neuropathy.
A.5 Diabetes Complications. TX DM
Diabetic Neuropathy Pathophys
Chronic hyperglycemia causes glycation of axon proteins and subsequent development of progressive sensomotor neuropathy; typically affects multiple peripheral nerves.
Chronic hyperglycemia leads to:
Sorbitol accumulation in nerves via aldose reductase Oxidative stress Ischemia from microvascular damage (vasa nervorum)
→ Axonal degeneration + demyelination
A.5 Diabetes Complications. TX DM
Peripheral Diabetic Neuropathy Clinical
Most common type — “glove and stocking” sensory loss
Affects distal limbs bilaterally
Symptoms:
Numbness
Tingling
Burning pain (worse at night)
↓ vibration, proprioception
Loss of ankle reflexes
↑ risk of foot ulcers, Charcot joints
A.5 Diabetes Complications. TX DM
Autonomic Diabetic Neuropathy
Autonomic Neuropathy
Involves involuntary functions
CV Resting tachycardia, orthostatic hypotension
GI Gastroparesis, diarrhea, constipation
GU Erectile dysfunction, neurogenic bladder
Sweat Anhidrosis or excessive sweating
A.5 Diabetes Complications. TX DM
Focal & Multifocal Neuropathies
Cranial (CN III palsy) - Ptosis, diplopia with pupil sparing
Truncal mononeuropathy - Thoracoabdominal pain or paresthesia
Limb mononeuropathy - Entrapment syndromes (e.g., carpal tunnel)
Diabetic amyotrophy - Painful asymmetric thigh weakness, weight loss (elderly men), self-limiting
A.5 Diabetes Complications. TX DM
TX for Neuropathic Pain
TCAs Amitriptyline (watch for side effects in elderly)
SNRIs Duloxetine
Gabapentinoids Gabapentin, pregabalin
Topical Capsaicin cream, lidocaine patches
A.5 Diabetes Complications. TX DM
TX for Autonomic Neuopathy
Gastroparesis: Small meals, metoclopramide or erythromycin
Orthostatic hypotension: Fludrocortisone, midodrine
Erectile dysfunction: PDE-5 inhibitors (e.g., sildenafil)
Neurogenic bladder: Intermittent catheterization, alpha-blockers
A.5 Diabetes Complications. TX DM
A patient with diabetic neuropathy has impaired sweating in the feet but excessive sweating in the upper body — how is this possible?
✅ This is a classic sign of autonomic neuropathy with compensatory hyperhidrosis in areas where innervation is preserved.
A.5 Diabetes Complications. TX DM
Can diabetic neuropathy cause diarrhea and constipation in the same patient?
✅ Yes — due to autonomic dysfunction of the GI tract, leading to erratic motility.
A.5 Diabetes Complications. TX DM
Diabetic Atherosclerosis
Prevalence: more common in patients with type 2 diabetes
Risk factors: The major determinants are metabolic risk factors, which include obesity, dyslipidemia, and arterial hypertension. Hyperglycemia may be less related to the development of macrovascular disease.
Manifestations
Coronary heart disease (most common cause of death)
Cerebrovascular disease
Peripheral artery disease (possible loss of limb)
Monckeberg arteriosclerosis
Gangrene
