Type 2 diabetes

What is it?

Glucose (blood sugar) is the main source of energy for the body's cells, and most of it comes from food. For glucose to enter cells it needs insulin, a hormone secreted by the pancreas.

In type 2 diabetes the muscle, liver and fat cells do not respond to insulin as they should (insulin resistance), and over time the pancreas cannot secrete enough to compensate, so glucose stays in the blood instead of being used by the cells.

Type 2 differs from type 1, in which the immune system destroys the insulin-producing cells, and from gestational diabetes, which appears during pregnancy. See the comparison between the two types.

How does it develop?

1. 1
   Insulin resistanceMuscle, liver and fat tissue respond more weakly to insulin.
2. 2
   CompensationThe pancreas secretes larger amounts of insulin to keep sugar normal, and tests may remain normal at this stage.
3. 3
   Beta cell strainThe ability of the pancreatic beta cells to keep up with the growing need gradually declines.
4. 4
   Rising sugarSugar first rises to the level of prediabetes and then reaches the threshold of diabetes.
5. 5
   Long-term effectChronic elevation damages blood vessels and nerves, affecting the eyes, kidneys, heart and feet.

The disease goes beyond the two-part “resistance + reduced secretion”: increased hepatic glucose production, impaired action of gut incretin hormones, increased lipolysis and increased renal glucose reabsorption also contribute. This is why different drug classes target different points in this network; SGLT2 inhibitors, for example, act on the kidney, and GLP-1 agonists act on the incretin axis.

Causes

There is no single direct cause. Type 2 results from an interplay of genetic predisposition and lifestyle-related factors. We therefore distinguish the direct mechanism that raises sugar from the risk factors that make it more likely to occur.

The known mechanism

• Insulin resistance with a progressive failure of insulin secretion from beta cells.

Genetic factors

• Family history raises the risk; the disease is linked to a large number of genes, each with a small effect.

Environmental and lifestyle factors

• Excess weight, especially around the abdomen, and physical inactivity, two of the main contributors to insulin resistance.

Not fully understood

• Why some people develop it without obvious risk factors, and exactly how genes interact with the environment — questions still under study.

Risk factors

Symptoms

When do symptoms appear?

Type 2 develops slowly over years, and many people affected notice no symptoms, so it is sometimes found by chance in a routine test or when a complication appears.

For this reason periodic screening is advised for people with risk factors even in the absence of symptoms.

How is it diagnosed?

This section explains how the doctor reaches the diagnosis; it is not a tool for self-diagnosis.

Medical history

• Symptoms and their duration, family history, current medicines, and previous gestational diabetes.

Clinical examination

• Weight, waist circumference, blood pressure and foot examination.

Tests

• HbA1c or fasting blood glucose or oral glucose tolerance test, or random glucose with clear symptoms.

Diagnosis usually needs two abnormal results, from the same sample or on two different days, unless there are clear symptoms with a very high glucose.

The doctor may request antibody tests to distinguish type 1 from type 2 when in doubt, especially in younger adults or those who are not overweight. HbA1c may also be inaccurate with some haemoglobin variants, anaemia or pregnancy, in which case glucose measurements are relied on.

Related tests

For diagnosis:

• Hemoglobin A1cLab test
• Fasting plasma glucoseLab test
• Oral glucose tolerance testLab test
• Random plasma glucoseLab test

For follow-up and detecting complications:

• Creatinine & eGFRLab test
• Urine albumin-to-creatinine ratioLab test
• Lipid profileLab test

Treatment

The treatment categories usually used are listed here; this is not a prescription. The doctor chooses the plan according to each person's condition; do not change any medicine or dose without a specialist.

Lifestyle

• Structured diabetes education and an individual meal plan.
• Regular physical activity and reducing long periods of sitting.
• Weight loss when needed; losing 5% or more of body weight improves glucose control in many people.

Medicines (categories)

• Metformin is a common starting point for many people.
• SGLT2 inhibitors and GLP-1 agonists are preferred when there is heart or kidney disease or according to weight goals.
• Other classes such as DPP-4 inhibitors and sulfonylureas, and insulin when needed.

Procedures and surgery

• Obesity (metabolic) surgery is an option for some people with obesity according to specific criteria decided by a specialist team.

Follow-up

• Regular visits to assess sugar, blood pressure, kidneys, eyes and feet — see the follow-up section.

Rehabilitation

• Generally not applicable, but people with complications such as foot ulcers or amputation may need specialised rehabilitation.

Choice of medicine depends on heart and kidney status, weight, hypoglycaemia risk, side effects and cost. SGLT2 inhibitors and GLP-1 agonists are used for their heart and kidney benefits proven in large trials in specific groups, sometimes regardless of the HbA1c level.

Follow-up

The doctor determines the suitable frequency for each person, and it may differ from this table.

Complications

Short-term

• Hypoglycaemia, especially with insulin or sulfonylurea medicines.
• Severe, persistent high sugar with dehydration, which may develop into an emergency.

Long-term

• Heart disease, coronary artery disease and stroke.
• Chronic kidney disease.
• Retinopathy.
• Neuropathy.
• Foot problems and ulcers.

Rare

• Diabetic ketoacidosis is more common in type 1 but can occur in type 2.

Serious

• Lower limb amputation resulting from untreated foot ulcers or infections.
• Kidney failure.
• Loss of vision.

Prevention

What reduces risk

• Losing excess weight, even by a moderate amount.
• Regular physical activity.
• Healthy nutrition that reduces free sugars and sweetened drinks.

Early detection

• The American Diabetes Association recommends screening adults from age 35, and earlier for those who are overweight with other risk factors.

Living with it

Food

• There is no single ideal diet for everyone; the basis is an individual plan rich in vegetables, legumes and whole grains while reducing free sugars and sweetened drinks.

Activity

• At least 150 minutes a week of moderate activity, with resistance exercise two or three times a week, and breaking up long periods of sitting.

Sleep

• Lack of sleep and sleep disturbance affect glucose control, and the doctor assesses symptoms of sleep apnoea when present.

Medicines

• Stick to the plan, and ask the doctor what to do on sick days or when unable to eat.

Ramadan fasting

• Needs an individual assessment with the doctor weeks before Ramadan to estimate the risk and adjust medicine timing and doses when needed, according to the IDF-DAR guidelines.

Follow-up

• Keeping to the schedule of regular check-ups detects complications early, when they are easier to treat.

Why & how

Common questions

What is science studying now?

• Available now

  Medicines with heart and kidney benefits

  Large trials have shown that some SGLT2 inhibitors and GLP-1 agonists reduce cardiac events or slow the decline of the kidneys in specific groups, so they have become part of the guidelines.¹⁰

• Available now

  Artificial intelligence in retinal screening

  In 2018 the IDx-DR system received FDA authorisation as the first artificial intelligence system to give a screening decision for retinopathy without a doctor needing to interpret the image, in a specific screening context.²⁷

• Preliminary research

  Dividing diabetes into subgroups

  A Swedish study in 2018 proposed dividing adult diabetes into five clusters that differ in risk and complications. The idea is promising for precision medicine, but it has not yet been adopted to guide treatment.²⁸