What's diabetes type 2?
The biology of diabetes type 2
Insulin Resistance (Early Stage)
Primary feature: The body's cells—especially in the muscle, fat (adipose), and liver
tissues—become resistant to insulin.
●​ Normal Process:​
After eating, blood glucose rises → pancreas releases insulin → insulin binds
to receptors on cells → glucose enters cells → blood glucose levels
normalize.​
●​ In Type 2 Diabetes:​
The cells don’t respond properly to insulin (insulin resistance). As a result,
glucose cannot efficiently enter the cells, so it remains in the bloodstream.​
●​ Mechanism:​
○​ Insulin receptor signaling is impaired.​
○​ This may be due to:​
■​ Inflammation​
■​ Accumulation of intracellular fat (lipotoxicity)​
■​ Oxidative stress​
■​ Genetic factors​
Compensatory Hyperinsulinemia
Response: The pancreas (beta cells) compensates by producing more insulin to
overcome resistance.
●​ This phase can last for years, keeping blood glucose relatively normal.​
●​ However, the excess demand overworks the pancreas.​
Beta-Cell Dysfunction and Failure
Progression: Over time, the beta cells in the pancreas begin to dysfunction and die.
●​ Reduced insulin secretion → blood glucose starts to rise chronically
(hyperglycemia).​
●​ Caused by:​
○​ Chronic high glucose (glucotoxicity)​
○​ High fat levels (lipotoxicity)​
○​ Inflammatory cytokines​
○​ Endoplasmic reticulum stress in beta cells​
Hepatic Glucose Overproduction
Liver dysfunction: The liver becomes insulin resistant and continues to produce
glucose even when not needed.
●​ Normally, insulin suppresses hepatic glucose production after meals.​
●​ In type 2 diabetes, this suppression fails, contributing to fasting
hyperglycemia.​
Altered Incretin Effect
Gut hormones (incretins) like GLP-1 and GIP, which help stimulate insulin release
after meals, are less effective.
●​ This reduces post-meal insulin secretion.​
●​ It contributes further to high postprandial (after-meal) glucose levels.​
Increased Glucose Reabsorption in Kidneys
The kidneys reabsorb more glucose instead of excreting it in urine.
●​ Normally, when glucose levels are high, kidneys help lower it by excreting
excess.​
●​ In diabetes, SGLT2 transporters in the kidneys reabsorb more glucose,
worsening hyperglycemia.​
Lipid Metabolism Disturbance
Type 2 diabetes often involves dyslipidemia (abnormal fat levels).
Insulin resistance promotes the release of free fatty acids from adipose tissue.​
Leads to:​
a.​ Fat buildup in liver and muscle​
b.​ Increased VLDL (very low-density lipoproteins)​
c.​ Lower HDL ("good" cholesterol)​
d.​ More small, dense LDL particles (atherogenic)
How does one get TYPE II diabetes?
●​ Genetic Predisposition – Family History
○​ If you have a parent, sibling, or close relative with Type II diabetes,
your risk is higher.
○​ Certain genes affect how your body makes or uses insulin.
○​ Genetics don’t guarantee diabetes but make you more susceptible if
combined with unhealthy lifestyle factors.
○​ Example: identical twins have a higher chance of both having diabetes
than fraternal twins.
●​ Poor Diet – High Sugar/Fat Intake
○​ Diets rich in refined sugars, processed foods, and saturated fats lead to
weight gain and higher blood sugar levels.
○​ Sugary drinks, fast food, and snacks cause repeated spikes in blood
glucose → pancreas works overtime to make insulin.
○​ Over time, cells stop responding to insulin → insulin resistance.
○​ Lack of fiber, whole grains, fruits, and vegetables increases the risk.
●​ Lack of Physical Activity
○​ Physical activity helps:
■​ Burn glucose for energy.
■​ Improve insulin sensitivity (cells respond better to insulin).
○​ Without exercise, more glucose stays in the bloodstream.
○​ Sedentary lifestyles → weight gain → worsen insulin resistance.
●​ Obesity – Especially Abdominal Fat
○​ Excess body fat, especially around the abdomen, increases
inflammation and hormones that interfere with insulin’s action.
○​ Fat cells in the belly area are more metabolically active, producing
substances that cause insulin resistance.
○​ People with a high waist circumference are at greater risk even if their
weight is in the normal range.
●​ Age (Risk Increases After 45)
○​ As you age, muscle mass declines while fat increases → makes it
harder to maintain healthy blood sugar.
○​ Older adults may exercise less and gain weight more easily.
○​ The pancreas may also become less efficient at producing insulin over
time.
●​ Ethnic Background
○​ Some ethnic groups have genetic variations or patterns of fat
storage that raise their diabetes risk:
○​ African Americans, Hispanic/Latino Americans, Native
Americans, Asian Americans, Pacific Islanders.
○​ These groups also face higher rates of insulin resistance at
lower body weights compared to other populations.
○​ May also be influenced by cultural diets, socioeconomic factors,
and access to healthcare.
Gestational Diabetes
Symptoms
●​ Frequent urination – High blood sugar causes kidneys to remove
excess glucose through urine.​
●​ Increased thirst – More urination leads to dehydration, triggering thirst.​
●​ Increased hunger – Cells can’t absorb glucose properly, so the body
craves more fuel.​
●​ Fatigue – Without enough glucose entering cells, the body lacks
energy.​
●​ Blurred vision – High blood sugar can cause fluid changes in the eyes,
affecting focus.​
●​ Slow-healing cuts or wounds – Poor circulation and immune response
delay healing.​
●​ Frequent infections – High sugar levels weaken immune defenses.​
●​ Tingling, numbness, or pain in hands or feet – Nerve damage
(neuropathy) results from prolonged high blood sugar.​
●​ Darkened skin in certain areas – Insulin resistance can lead to skin
changes like acanthosis nigricans.​
●​ Unexplained weight loss – In rare cases, the body burns fat/muscle
when it can’t use glucose.
Treatments
Healthy Diet
●​ Emphasize low glycemic index foods (e.g., whole grains, vegetables).
●​ Reduce refined sugar, saturated fats, and processed foods.
●​ Watch portion sizes and avoid skipping meals.
Regular Physical Activity
●​ At least 150 minutes of moderate-intensity aerobic exercise per week
(walking, cycling).
●​ Strength training 2–3 times a week improves insulin sensitivity.
Weight Loss
●​ Losing 5–10% of body weight can significantly lower blood sugar.
●​ Weight loss improves insulin function and may even lead to remission.
Medications
●​ If lifestyle changes aren’t enough, medications are prescribed to help lower
blood sugar:
Insulin Therapy
●​ May be needed if oral medications are insufficient or during illness/stress.
●​ Used more commonly in later stages of Type 2 diabetes.
●​ Administered by injection (pen, syringe) or pump.
Bariatric (Metabolic) Surgery
●​ For severely obese patients (BMI ≥35) who can’t control diabetes with
lifestyle/meds.
●​ Can lead to remission of Type 2 diabetes in many patients.
●​ Types include gastric bypass, sleeve gastrectomy.
Key Goals of Treatment
●​ Keep HbA1c (average blood sugar) below target (usually <7%).
●​ Control blood pressure and cholesterol to reduce heart disease risk.
●​ Prevent complications: eye, kidney, nerve, heart problems.
Data US
Complications
●​ Short-term:
○​ Hyperglycemia (high blood sugar) → fatigue, blurred vision, frequent
urination
○​ Hypoglycemia (low blood sugar, especially from meds) → shaking,
confusion, fainting​
●​ Long-term:
○​ Heart disease and stroke – 2–4x higher risk
○​ Kidney failure – damage to blood vessels in kidneys (diabetic
nephropathy)
○​ Vision loss – diabetic retinopathy can lead to blindness
■​ Damage to the blood vessels in the retina (the light-sensitive
layer at the back of your eye) caused by long-term high blood
sugar.
○​ Nerve damage – especially in feet/hands (neuropathy)
○​ Amputations – due to poor circulation and infections
○​ Slow wound healing – increases infection risk
How to prevent
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