• Diabetes mellitus is a disorder of carbohydrate, fat, and protein metabolism.
• It occurs because of either:
  • Too little insulin secretion, or
  • Reduced tissue sensitivity to insulin.
• There are two main types:
  • Type 1 diabetes mellitus
    • Also called insulin-dependent diabetes mellitus.
    • Caused by lack of insulin secretion.
  • Type 2 diabetes mellitus
    • Also called non–insulin-dependent diabetes mellitus.
    • Initially caused by decreased sensitivity of target tissues to insulin.
    • This reduced sensitivity is called insulin resistance.
• In both types, metabolism of carbohydrates, fats, and proteins becomes abnormal.
• Insulin deficiency or insulin resistance prevents most body cells from efficiently taking up and using glucose.
• Brain cells are an important exception.
• Therefore:
  • Blood glucose increases
  • Cellular glucose utilization decreases
  • Fat utilization increases
  • Protein utilization increases

KEY CONCEPT

• Type 1 diabetes → lack of insulin secretion.
• Type 2 diabetes → insulin resistance, especially initially.
• Both cause: ↓ Effective insulin action → ↓ glucose uptake/use by most cells → ↑ blood glucose → ↑ fat and protein utilization

Conceptual Examples

• Type 1:
  ↓ Insulin secretion → cells cannot efficiently use glucose → blood glucose rises.
• Type 2:
  Insulin is present but tissues respond poorly → insulin resistance → reduced glucose utilization.
• Overall metabolic effect:
  ↓ Glucose use → body increasingly uses fat and protein for energy.

Type 1 Diabetes—Deficiency of Insulin Production By Beta Cells of the Pancreas

• Type 1 diabetes develops when pancreatic beta cells are damaged or destroyed, causing inadequate insulin production.
• Possible causes include:
  • Viral infections
  • Autoimmune destruction
  • Hereditary susceptibility
• In some people, inherited beta-cell degeneration may occur even without viral or autoimmune disease.
• Type 1 diabetes can occur at any age, but often develops in children before 14 years, so it has also been called juvenile diabetes mellitus or insulin-dependent diabetes mellitus.
• It may develop rapidly over days to weeks.
• Its three major metabolic effects are:
  • ↑ Blood glucose
  • ↑ Fat use for energy and cholesterol formation
  • ↓ Body proteins
• About 5%–10% of people with diabetes have type 1 diabetes.

Blood Glucose Concentration Rises to High Levels in Diabetes Mellitus

• Lack of insulin causes ↓ peripheral glucose use and ↑ glucose production.
• Plasma glucose may rise to about 300–1200 mg/100 mL.
• This severe hyperglycemia produces multiple harmful effects throughout the body.

Increased Blood Glucose Causes Loss of Glucose in the Urine

• When blood glucose becomes very high, more glucose is filtered by the kidneys than can be reabsorbed.
• Excess glucose therefore appears in the urine.
• Glucose usually begins to spill into urine when blood glucose exceeds about 200 mg/100 mL, called the renal threshold for glucose.
• At blood glucose levels of 300–500 mg/100 mL, more than 100 g of glucose may be lost in urine each day.

Increased Blood Glucose Causes Dehydration

• Severe hyperglycemia increases extracellular osmotic pressure.
• Water therefore moves out of cells, causing intracellular dehydration.
• Glucose in the renal tubules also causes osmotic diuresis.
• This reduces water reabsorption and causes large amounts of fluid to be lost in urine.
• The result is:
  • Polyuria → excessive urination
  • Extracellular dehydration
  • Intracellular dehydration
  • Increased thirst

Chronic High Glucose Concentration Causes Tissue Injury

• Long-term uncontrolled hyperglycemia damages blood vessels and reduces blood supply to tissues.
• This increases the risk of:
  • Heart attack
  • Stroke
  • End-stage kidney disease
  • Retinopathy and blindness
  • Limb ischemia and gangrene
• Chronic diabetes can also damage peripheral nerves and the autonomic nervous system.
• This may cause:
  • Impaired cardiovascular reflexes
  • Impaired bladder control
  • Reduced sensation in the limbs
  • Other signs of peripheral nerve damage
• The exact mechanisms are not fully understood but involve effects of high glucose and other metabolic abnormalities on vascular and other tissues.
• Hypertension from renal injury and atherosclerosis from abnormal lipid metabolism can further worsen tissue damage.

Diabetes Mellitus Causes Increased Utilization of Fats and Metabolic Acidosis

• In uncontrolled diabetes, especially type 1, the body shifts from carbohydrate use to fat use.
• This increases formation of keto acids, mainly:
  • Acetoacetic acid
  • β-hydroxybutyric acid
• These acids may be produced faster than tissues can use them.
• They accumulate and cause metabolic acidosis.
• Together with dehydration, severe acidosis can rapidly lead to diabetic coma and death without prompt insulin treatment.
• The body compensates with rapid, deep breathing, which increases CO₂ removal.
• The kidneys also:
  • Decrease bicarbonate loss
  • Produce new bicarbonate
• If blood pH falls below about 7.0, coma and death may occur within hours.
• Severe electrolyte changes in diabetic acidosis are shown in Fig. 79.11.
• Long-term excessive fat use also increases blood cholesterol and its deposition in arterial walls, promoting arteriosclerosis.

Diabetes Mellitus Causes Depletion of the Body’s Proteins

• Failure to use glucose normally causes increased use and decreased storage of protein and fat.
• Therefore, severe untreated diabetes causes:
  • Rapid weight loss
  • Asthenia → lack of energy
  • Polyphagia → excessive eating
• Without treatment, severe tissue wasting can cause death within weeks.

Treatment of Type 1 Diabetes Mellitus Requires Insulin Administration

• Type 1 diabetes requires insulin replacement to keep carbohydrate, fat, and protein metabolism as normal as possible.
• Regular insulin acts for about 3–8 hours.
• Longer-acting forms are absorbed more slowly and may act for about 10–48 hours.
• A patient may receive:
  • A longer-acting insulin for overall daily control.
  • Additional regular insulin, especially when blood glucose rises after meals.
• Insulin treatment is therefore individualized for each patient.

KEY CONCEPT

• Type 1 diabetes = beta-cell destruction → severe insulin deficiency.
• ↓ Insulin → ↑ blood glucose + ↓ glucose use + ↑ fat and protein breakdown.
• Hyperglycemia → glycosuria → osmotic diuresis → dehydration.
• Excess fat breakdown → ketone bodies → metabolic acidosis → possible coma.
• Long-term hyperglycemia damages blood vessels, kidneys, retina, nerves, and limbs.
• Treatment requires insulin replacement.

Conceptual Examples

• Hyperglycemia:
  ↓ Insulin → glucose cannot be used efficiently → blood glucose rises.
• Polyuria and thirst:
  Glucose enters urine → pulls water with it → excess urination → dehydration → increased thirst.
• Diabetic ketoacidosis:
  ↓ Insulin → ↑ fat breakdown → ↑ keto acids → metabolic acidosis → possible coma.
• Weight loss despite eating:
  ↓ Glucose use → ↑ fat and protein breakdown → weight loss + weakness despite polyphagia.
• Treatment:
  Type 1 diabetes → inadequate insulin → insulin must be given from outside the body.

Type 2 Diabetes—Resistance to the Metabolic Effects of Insulin

• Type 2 diabetes is much more common than type 1 and accounts for about 90%–95% of diabetes cases.
• It usually develops gradually and was traditionally seen after age 30 years, especially around 50–60 years.
• However, it is now increasingly seen in younger people, even those under 20 years.
• This increase is strongly related to obesity, the most important risk factor for type 2 diabetes.

Obesity, Insulin Resistance, and “Metabolic Syndrome” Usually Precede Development of Type 2 Diabetes

• Unlike type 1 diabetes, type 2 diabetes is often associated initially with high plasma insulin levels.
• This high insulin is a compensatory response to insulin resistance.
• Insulin resistance means target tissues have reduced sensitivity to insulin.
• As insulin becomes less effective:
  • Glucose utilization decreases
  • Glucose storage decreases
  • Blood glucose rises
  • Pancreatic beta cells compensate by secreting more insulin
• Insulin resistance usually develops gradually with weight gain and obesity.
• Some obese people may have fewer insulin receptors, especially in:
  • Skeletal muscle
  • Liver
  • Adipose tissue
• However, most insulin resistance appears to result from abnormalities in the intracellular signaling pathways after insulin binds its receptor.
• This impaired signaling may be related to lipotoxicity, caused by excess lipid accumulation in tissues such as skeletal muscle and liver.
• Insulin resistance commonly occurs as part of the metabolic syndrome.
• Important features include:
  • Abdominal obesity
  • Insulin resistance
  • Fasting hyperglycemia
  • ↑ Blood triglycerides
  • ↓ HDL cholesterol
  • Hypertension
• These abnormalities are closely associated with excess visceral fat around abdominal organs.
• Insulin resistance is the main cause of the increased blood glucose in this syndrome.
• Metabolic syndrome greatly increases the risk of cardiovascular disease, including atherosclerosis and organ damage.
• Insulin resistance also increases the risk of developing type 2 diabetes, which further increases cardiovascular risk.

Other Factors That Can Cause Insulin Resistance and Type 2 Diabetes

• Type 2 diabetes may also result from acquired or genetic abnormalities that impair insulin signaling, even without severe obesity (Table 79.2).
• Polycystic ovary syndrome (PCOS) is associated with:
  • Increased ovarian androgen production
  • Insulin resistance
• PCOS affects about 6% of women during reproductive life.
• About 80% of affected women have insulin resistance and hyperinsulinemia.
• In many cases, this is associated with increased visceral fat.
• Long-term risks include:
  • Diabetes mellitus
  • Increased blood lipids
  • Cardiovascular disease
• Excess glucocorticoids in Cushing syndrome can decrease tissue sensitivity to insulin and lead to diabetes.
• Excess growth hormone in acromegaly can produce a similar effect.
• Severe genetic causes of obesity and insulin resistance may also cause type 2 diabetes and other features of metabolic syndrome.

KEY CONCEPT

• Type 2 diabetes = insulin resistance first, often with compensatory high insulin.
• Obesity, especially visceral abdominal fat, is the major risk factor.
• Sequence: Obesity/visceral fat → insulin resistance → ↓ glucose use → ↑ blood glucose → compensatory ↑ insulin → type 2 diabetes
• Metabolic syndrome = abdominal obesity + insulin resistance + hyperglycemia + lipid abnormalities + hypertension.
• PCOS, Cushing syndrome, acromegaly, and genetic disorders can also cause insulin resistance.

Conceptual Examples

• Early type 2 diabetes:
  Insulin is present → tissues respond poorly → pancreas produces more insulin → hyperinsulinemia + insulin resistance.
• Obesity:
  ↑ Visceral fat → impaired insulin signaling → ↓ glucose uptake → ↑ blood glucose.
• Metabolic syndrome:
  Abdominal obesity + insulin resistance + high triglycerides + low HDL + hypertension → high cardiovascular risk.
• Hormonal cause:
  Excess cortisol or growth hormone → ↓ insulin sensitivity → insulin resistance → possible type 2 diabetes.

Prolonged, Severe Insulin Resistance May Lead to Type 2 Diabetes

• With prolonged severe insulin resistance, even high insulin levels may no longer maintain normal blood glucose.
• Early in the disease, this causes moderate hyperglycemia after carbohydrate intake.
• Later, pancreatic beta cells become dysfunctional and cannot produce enough insulin.
• As a result, hyperglycemia becomes more severe, especially after carbohydrate-rich meals.
• Some obese people with marked insulin resistance do not develop severe diabetes because their pancreas can still produce enough insulin.
• In others, prolonged high insulin production and factors related to lipid accumulation in the pancreas may damage beta-cell function.
• This can lead to full type 2 diabetes mellitus.
• Genetic factors may influence whether beta cells can maintain high insulin production for many years.

Treatment of Type 2 Diabetes By Lifestyle Modifications, Increasing Insulin Sensitivity, and Enhancing Insulin Secretion

• Lifestyle treatment usually includes:
  • Calorie restriction
  • More physical activity
  • Weight loss
  • Reduced body fat
• Long-term weight loss is difficult to maintain in many patients, so lifestyle treatment alone may have limited success.
• Drugs may be needed to control blood glucose:
  • Thiazolidinediones → increase insulin sensitivity.
  • Metformin → decreases liver glucose production.
  • Sulfonylureas → increase insulin release from the pancreas.
• In later stages, insulin administration may be required.
• GLP-1 receptor agonists:
  • Enhance insulin secretion.
  • Can produce substantial weight loss in many patients with obesity.
• GIP receptor agonists can also help treat obesity and type 2 diabetes.
• Combined GLP-1/GIP receptor agonists can produce even greater reductions in:
  • Body fat
  • Blood glucose
• DPP-4 inhibitors prevent rapid inactivation of GLP-1 and GIP.
• This prolongs incretin effects and leads to:
  • ↑ Insulin secretion
  • Better blood glucose control
• Newer treatments for obesity and type 2 diabetes have also shown benefits in reducing complications involving cardiovascular disease, chronic kidney disease, cancer, and other disorders.

Treatment of Type 2 Diabetes By Inhibition of Sodium-Glucose Transporter 2 (SGLT2)

• About 90% of filtered glucose is normally reabsorbed in the proximal tubules by SGLT2.
• Drugs called gliflozins inhibit SGLT2.
• Therefore: ↓ SGLT2 activity → ↓ renal glucose reabsorption → ↑ glucose in urine → ↓ blood glucose
• SGLT2 inhibitors are often combined with other diabetes drugs.
• Clinical trials have shown important protection against cardiovascular and kidney disease in patients with diabetes.
• Glucose remaining in renal tubules also causes osmotic diuresis.
• This may slightly reduce blood pressure.
• However, excessive diuresis can increase the risk of:
  • Dehydration
  • Hypotension
• This risk is greater in patients already taking diuretics or antihypertensive drugs.

Treatment of Type 2 Diabetes With Surgery

• In severe obesity with type 2 diabetes, diet, exercise, and drugs may not adequately reduce body fat or blood glucose.
• In these cases, bariatric surgery may be used.
• Two widely used procedures are:
  • Gastric bypass
  • Vertical sleeve gastrectomy
• These are often called metabolic surgery because many patients develop nearly complete remission of diabetes and may no longer need antidiabetic drugs.
• Improvements in blood glucose, blood lipids, and blood pressure can occur within days or weeks.
• Therefore, some benefits may occur through mechanisms beyond weight loss alone.
• The exact physiological mechanisms remain unclear.

Physiology of Diagnosis of Diabetes Mellitus

• Clinical features of type 1 and type 2 diabetes are compared in Table 79.3.
• Diabetes is commonly diagnosed using blood and urine tests.

Urinary Glucose

• Normally, a person without diabetes excretes little or no detectable glucose in urine.
• In diabetes, glucose may appear in urine in small or large amounts.
• The amount generally increases with:
  • Severity of diabetes
  • Carbohydrate intake

Fasting Blood Glucose and Insulin Concentrations

• Normal fasting blood glucose in the early morning is about 80–90 mg/100 mL.
• About 115 mg/100 mL is considered the upper limit of normal in this text.
• Fasting glucose above this level may indicate:
  • Diabetes mellitus
  • Marked insulin resistance
  • Prediabetes
• In type 1 diabetes:
  • Plasma insulin is very low or undetectable during fasting.
  • It remains very low even after a meal.
• In type 2 diabetes:
  • Plasma insulin may initially be several times higher than normal.
  • It usually rises even more after a standard glucose load.

KEY CONCEPT

• Severe insulin resistance → compensatory ↑ insulin → eventual beta-cell dysfunction → worsening type 2 diabetes.
• Treatment may target:
  • Weight and physical activity
  • Insulin sensitivity
  • Liver glucose production
  • Insulin secretion
  • Incretin pathways
  • Renal glucose reabsorption
  • Severe obesity by metabolic surgery
• Type 1 → very low insulin.
• Early type 2 → insulin may be high because of insulin resistance.

Conceptual Examples

• Progression of type 2 diabetes:
  Insulin resistance → pancreas produces more insulin → beta cells eventually fail → blood glucose rises further.
• Metformin:
  ↓ Liver glucose production → ↓ blood glucose.
• GLP-1/GIP treatment:
  ↑ Incretin action → ↑ insulin secretion + ↓ body fat + better glucose control.
• SGLT2 inhibition:
  ↓ Kidney glucose reabsorption → ↑ glucose lost in urine → ↓ blood glucose.
• Type 1 vs type 2:
  Type 1 → little or no insulin.
  Type 2 → insulin may initially be high but tissues resist its effects.

Glucose Tolerance Test

• In a normal fasting person, ingestion of 1 g glucose/kg body weight raises blood glucose from about 90 mg/100 mL to 120–140 mg/100 mL.
• Blood glucose then falls back to below the starting level within about 2 hours, as shown by the lower glucose tolerance curve in Fig. 79.12.
• In diabetes mellitus, fasting blood glucose is usually >115 mg/100 mL and often >140 mg/100 mL.
• After glucose ingestion, blood glucose rises much more than normal.
• It then returns toward the control level only after about 4–6 hours.
• It also fails to fall below the control level.
• This abnormal slow fall indicates either:
  • Insulin secretion does not increase normally, or
  • The tissues have decreased sensitivity to insulin.
• Therefore, an abnormal glucose tolerance curve can help diagnose diabetes mellitus.
• Plasma insulin measurement can help distinguish:
  • Type 1 diabetes → low or undetectable insulin
  • Type 2 diabetes → increased insulin

Glycated Hemoglobin

• When blood glucose remains high for a long time, glucose attaches to hemoglobin in red blood cells.
• This forms glycated hemoglobin, called hemoglobin A1c (HbA1c).
• The longer hyperglycemia continues, the more glucose binds to hemoglobin.
• Once hemoglobin becomes glycated, it remains glycated for the life of the red blood cell.
• Therefore, HbA1c reflects the average blood glucose exposure of red blood cells.
• Red blood cells have an average lifespan of about 120 days.
• Because red blood cells have different individual lifespans, HbA1c mainly reflects average blood glucose over the previous 3 months.
• HbA1c can therefore be used to:
  • Help diagnose diabetes mellitus
  • Assess long-term glycemic control in people with diabetes

KEY CONCEPT

• Normal glucose tolerance: glucose rises after intake → returns toward normal within about 2 hours.
• Diabetes: higher fasting glucose + greater rise after glucose → slow return over 4–6 hours.
• Type 1 → low insulin; Type 2 → insulin may be increased.
• HbA1c = average blood glucose over approximately the previous 3 months.

Conceptual Examples

• Normal person:
  Glucose drink → blood glucose rises → insulin acts normally → glucose returns toward normal within ~2 hours.
• Diabetes:
  Glucose drink → excessive rise in glucose → inadequate insulin effect → glucose stays high for 4–6 hours.
• Type 1 versus Type 2:
  Abnormal glucose tolerance + very low insulin → Type 1.
  Abnormal glucose tolerance + high insulin → Type 2 insulin resistance.
• HbA1c:
  Repeated high blood glucose for weeks → more glucose attaches to hemoglobin → higher HbA1c.

Figure 79.12 — Glucose Tolerance Curve: Normal vs Diabetes

🧠 Main idea

After a person drinks glucose:

Normal person → glucose rises a little, then quickly comes back down.
Diabetes → glucose starts high, rises much higher, and comes down very slowly.

📊 Understand the axes

X-axis = Hours

• Time after taking glucose.
• 0 hour = before glucose is given.

Y-axis = Blood glucose level (mg/100 mL)

• Moving upward = more glucose in blood.
• mg/100 mL = mg/dL.

🔴 Red line = NORMAL person

At 0 hour

Blood glucose is about:

~90 mg/dL

➡️ Normal fasting level.

During first hour

Glucose is absorbed from intestine:

Blood glucose ↑ → ~125–130 mg/dL

➡️ This rise stimulates pancreatic β-cells.

Then insulin acts

Insulin ↑ → glucose enters muscle/fat + liver stores glucose → blood glucose falls.

By about 2–3 hours, glucose returns to normal.

Why does red line fall slightly BELOW normal?

Around 3 hours it reaches about 85 mg/dL.

➡️ Insulin remains active for a short time even after much of the excess glucose has been removed.

So there is a small temporary “insulin overshoot.”

Then glucose returns toward normal again.🟢 Green line = DIABETES

At 0 hour

Blood glucose is already high:

~135–140 mg/dL

➡️ Fasting hyperglycemia.

After glucose intake

The curve rises dramatically:

~140 → >210 mg/dL

Why?

Because insulin action is inadequate:

↓ insulin / insulin resistance → ↓ glucose uptake by tissues → glucose remains in blood.

Why does the green line fall so slowly?

Even several hours later:

Blood glucose is still high (~150 mg/dL at 5 hours).

➡️ The body cannot remove glucose from blood efficiently.

So:

Normal = quick clearance
Diabetes = slow clearance

⚫ Dotted horizontal lines

Lower dotted line ≈ 90 mg/dL

Represents approximately the normal fasting/control glucose level.

The normal red curve:

starts near it → rises → later returns near it.

Upper dotted line ≈ 140 mg/dL

Shows a high glucose reference level.

The diabetic curve:

starts around this high level and remains above it for several hours.

So the dotted lines help you visually compare normal vs abnormally high glucose.

🔍 Compare both curves

Feature	🔴 Normal	🟢 Diabetes
Fasting glucose	~90	~140
Rise after glucose	Small	Large
Peak	~125–130	~215
Fall afterward	Rapid	Very slow
Back near normal	~2–3 h	Still high at 5 h
Falls below starting level?	Yes, slightly	No

⭐ KEY CONCEPT

Normal

Glucose drink → glucose ↑ → insulin ↑ → tissues take glucose → blood glucose returns to normal quickly.

Diabetes

Glucose drink → glucose ↑↑ → inadequate insulin action → glucose stays in blood → slow fall.

Easy memory

Normal curve = “UP and quickly DOWN.”
Diabetic curve = “HIGH to begin with, HIGHER after glucose, SLOW to come down.”

Acetone Breath

• In severe diabetes, especially with marked insulin deficiency, the body cannot use glucose properly.
• Therefore, the body increasingly uses fat for energy.
• Fat breakdown produces keto acids, including acetoacetic acid.
• Some acetoacetic acid is converted into acetone.
• Acetone is volatile → it evaporates into the lungs → comes out in expired air.
• Therefore, the breath may develop a characteristic fruity/acetone smell.

Easy pathway

↓ Insulin → ↑ fat breakdown → ↑ acetoacetic acid → ↑ acetone → acetone breath

• Keto acids can also be detected in the urine.
• The amount of ketones can help indicate the severity of ketosis/diabetes.
• In early type 2 diabetes, excessive ketone formation is usually uncommon because some effective insulin action remains.
• If insulin resistance becomes very severe → fat use greatly increases → ketone production can also increase in type 2 diabetes.

⭐ Key Concept

Acetone breath = increased fat breakdown and ketone production due to severe lack of effective insulin.

Relation of Treatment to Arteriosclerosis and Chronic Kidney Disease

People with diabetes may have several problems together:

↑ Blood glucose + ↑ blood pressure + ↑ cholesterol/lipids

Together, these greatly increase the risk of:

• Atherosclerosis and arteriosclerosis
• Severe coronary heart disease
• Chronic kidney disease
• Damage to small blood vessels (microcirculation)

Therefore, diabetes treatment is not only about lowering glucose.

Treatment may also target:

Blood glucose ↓ + body fat ↓ + blood pressure ↓ + blood lipids ↓

⭐ Key Concept

Good diabetes treatment controls the whole cardiovascular–metabolic risk, not glucose alone.

Insulinoma—Hyperinsulinism insulinoma is usually a tumor of the pancreatic islets of Langerhans that produces too much insulin.

Insulinoma → excessive insulin → blood glucose falls → hypoglycemia

• Excessive insulin production is much rarer than diabetes.
• About 10–15% of these adenomas may be malignant according to the text.
• Malignant tumors may spread to other parts of the body.
• Both the original tumor and metastases may produce enormous amounts of insulin.
• In extreme cases, patients may require very large amounts of glucose to prevent severe hypoglycemia.

⭐ Key Concept

Insulinoma = too much insulin → recurrent/severe hypoglycemia.

Insulin Shock and Hypoglycemia

🧠 Why is low glucose dangerous?

The brain depends heavily on glucose for energy.

Importantly:

Brain glucose uptake does NOT require insulin.

But if excessive insulin lowers blood glucose too much:

Blood glucose ↓↓↓ → brain gets insufficient glucose → brain function fails

This is called insulin shock.

It may occur because of:

Blood glucose 50–70 mg/dL

The nervous system becomes abnormally excitable.

Possible features:

• Extreme nervousness
• Trembling
• Sweating
• Sometimes hallucinations

Easy idea

Moderate hypoglycemia → brain becomes irritable/excitable.

Blood glucose 20–50 mg/dL

Hypoglycemia becomes much more severe.

May cause:

• Clonic seizures
• Loss of consciousness

Blood glucose falls even lower

Eventually:

Seizures stop → deep coma develops

This happens because the brain no longer has enough glucose to maintain normal neuronal activity.

Easy progression

Glucose ↓

→ nervousness/tremor/sweating
→ seizures
→ unconsciousness
→ coma

Diabetic coma vs hypoglycemic coma

They can sometimes appear similar, but the mechanisms are opposite.

Feature	Diabetic ketoacidotic coma	Hypoglycemic coma
Main problem	Too little insulin	Too much insulin/effect
Blood glucose	Usually high	Very low
Acetone breath	Present	Absent
Rapid, deep breathing	Present	Absent

⭐ Easy memory

Too little insulin → hyperglycemia + ketoacidosis

Too much insulin → hypoglycemia + brain failure

Treatment of Hypoglycemic Shock or Coma

This is an emergency.

The text describes immediate treatment with:

IV glucose → blood glucose rises rapidly → brain receives glucose again

The patient may improve very quickly.

Glucagon can also raise blood glucose by causing:

Liver glycogen → glucose

This process is glycogenolysis.

Epinephrine can also promote glycogenolysis, although the text describes it as less effective.

⚠️ Why immediate treatment matters

If severe hypoglycemia continues:

Brain glucose deprivation → neuronal injury → permanent CNS damage

⭐ FINAL KEY CONCEPT

Insulin deficiency → fat breakdown → ketones → acetone breath/ketoacidosis.

But:

Excess insulin → severe hypoglycemia → brain dysfunction → seizures/coma.

One-line memory

Too little insulin harms mainly through hyperglycemia + ketosis; too much insulin harms mainly through dangerous hypoglycemia.

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