What Is Type 2 Diabetes? Causes, Complications, and Treatment

Insulin Resistance: The Core Defect

In a healthy individual, after a meal causes blood glucose to rise, the pancreatic beta-cells secrete insulin. Insulin acts as a key, binding to receptors on muscle, liver, and fat cells to allow glucose to enter those cells for energy production or storage. In type 2 diabetes, this signaling pathway breaks down: cells become resistant to insulin's signal, failing to take up glucose efficiently despite adequate or even elevated insulin levels. This state is called insulin resistance.

Initially, the pancreatic beta-cells compensate by secreting more insulin to overcome the resistance, keeping blood glucose within a normal range. Over time—often over years or even decades—the beta-cells become exhausted from the sustained overproduction demand and gradually lose their capacity to secrete sufficient insulin. This progressive beta-cell failure causes blood glucose to rise into the diabetic range. By the time type 2 diabetes is diagnosed, patients have typically lost 50–70% of their beta-cell function.

Risk Factors and Epidemiology

Type 2 diabetes is one of the fastest-growing health crises globally, affecting over 500 million adults worldwide, with projections suggesting this number will exceed 700 million by 2045. The condition disproportionately affects people in low- and middle-income countries, where rapid urbanization, dietary changes, and reduced physical activity have driven epidemic-level increases.

The major risk factors include overweight and obesity (particularly central/abdominal adiposity), physical inactivity, a diet high in refined carbohydrates and ultra-processed foods, older age, and family history of diabetes. Certain ethnic groups—including South Asian, East Asian, Hispanic/Latino, Black African, and Afro-Caribbean populations—have a significantly higher genetic predisposition. Other risk factors include previous gestational diabetes, polycystic ovary syndrome (PCOS), prediabetes, and the use of certain medications such as glucocorticoids and atypical antipsychotics.

Diagnosis: HbA1c and Blood Glucose Tests

Diabetes is diagnosed using one of four criteria, with a confirmatory repeat test required if the person is asymptomatic: a fasting plasma glucose of 7.0 mmol/L (126 mg/dL) or higher; a 2-hour plasma glucose of 11.1 mmol/L (200 mg/dL) or higher during an oral glucose tolerance test (OGTT); a random plasma glucose of 11.1 mmol/L or higher with classic symptoms of hyperglycemia; or an HbA1c of 48 mmol/mol (6.5%) or higher.

HbA1c (glycated hemoglobin) measures the percentage of hemoglobin molecules that have glucose attached, reflecting average blood glucose levels over the preceding 2–3 months. It is widely used both for diagnosis and for monitoring long-term glycemic control. Prediabetes is defined as HbA1c of 39–47 mmol/mol (5.7–6.4%), fasting glucose of 5.6–6.9 mmol/L, or an impaired 2-hour glucose tolerance test result. Identifying prediabetes creates an opportunity for intensive lifestyle intervention that can prevent or delay progression to type 2 diabetes.

Long-Term Complications

Chronically elevated blood glucose damages blood vessels and nerves throughout the body, producing a range of serious complications categorized as microvascular (affecting small vessels) and macrovascular (affecting large vessels). Diabetic neuropathy—the most common microvascular complication—affects over half of people with long-standing diabetes, causing symptoms ranging from numbness and tingling in the extremities to severe burning pain, and in autonomic forms, affecting heart rate, digestion, and bladder function. Peripheral neuropathy combined with peripheral arterial disease (a macrovascular complication) is the leading cause of non-traumatic lower limb amputations.

Diabetic retinopathy is the leading cause of new cases of blindness in working-age adults in developed countries. High blood glucose damages the retinal capillaries, causing leakage, microaneurysm formation, and eventually proliferative retinopathy with new vessel formation that can lead to vitreous hemorrhage and retinal detachment. Diabetic nephropathy begins with microalbuminuria (small amounts of protein in the urine) and can progress over decades to end-stage renal disease requiring dialysis or transplantation. On the macrovascular side, type 2 diabetes doubles the risk of cardiovascular disease, including heart attack and stroke, and dramatically increases the risk of peripheral artery disease.

Treatment: From Lifestyle to Insulin

Treatment follows a stepwise escalation approach. Lifestyle modification—regular physical activity, a balanced diet emphasizing whole foods and fiber, and weight loss if overweight—remains the foundation of management at every stage. Structured weight-loss programs achieving 10–15% body weight loss have been shown to put type 2 diabetes into remission in a significant proportion of patients, particularly those with shorter disease duration.

Metformin remains the first-line oral medication in most guidelines due to its efficacy, safety, low cost, and potential cardiovascular and longevity benefits. When metformin is insufficient, additional agents are added based on individual cardiovascular and renal risk profiles. SGLT-2 inhibitors (e.g., empagliflozin, dapagliflozin) and GLP-1 receptor agonists (e.g., semaglutide, liraglutide) have demonstrated not only glucose-lowering but also significant cardiovascular and renal protective effects, transforming how diabetes complications are managed. As beta-cell function continues to decline, basal insulin therapy is eventually introduced. The goal of treatment is to maintain HbA1c below 53 mmol/mol (7%) to minimize the risk of complications while avoiding hypoglycemia.

Diabetes Remission

Type 2 diabetes remission—defined as HbA1c below the diagnostic threshold for at least three months without glucose-lowering medication—is achievable for many patients, particularly those who have had diabetes for fewer than six years, have preserved beta-cell function, and achieve substantial weight loss. The landmark DiRECT trial demonstrated that an intensive dietary weight management program delivered in primary care achieved remission in 46% of participants at 12 months and 36% at 24 months. Bariatric (metabolic) surgery achieves even higher remission rates, with 30–63% of patients in remission at 5 years, and is now recommended in guidelines for patients with a BMI above 35 with type 2 diabetes, or above 30 in Asian populations.