Diabetes Mellitus: Symptoms, Causes, Diagnosis, and Treatment

Overview of Diabetes Mellitus

Diabetes mellitus is a chronic metabolic disorder caused by either insufficient insulin production by the pancreas or ineffective insulin action due to acquired or genetic factors, leading to elevated blood glucose levels (hyperglycemia). Persistent hyperglycemia damages multiple organ systems, particularly the blood vessels and nervous system.

Common Types of Diabetes Mellitus

Diabetes is generally categorized into three main types:
Type 1 diabetes, Type 2 diabetes, and gestational diabetes.

Type 1 Diabetes Mellitus

Type 1 diabetes, also known as insulin-dependent diabetes mellitus (IDDM), occurs when pancreatic beta cells are destroyed, leading to little or no insulin production. This results in a severe insulin deficiency, causing dangerously high blood sugar levels that can affect multiple organs.

Type 1 diabetes is less common than Type 2 and typically develops in children or young adults.

Type 2 Diabetes Mellitus

Type 2 diabetes, or non–insulin-dependent diabetes mellitus (NIDDM), is the most common form of the disease, usually occurring in middle-aged and older adults. In this condition, the body still produces insulin, but insulin resistance and progressive beta-cell dysfunction prevent effective glucose regulation.

Although Type 2 diabetes is most prevalent among individuals over 40 years old, its onset is becoming increasingly younger due to lifestyle changes.
Approximately 90–95% of all diabetes cases are Type 2. Because symptoms are often subtle or absent in the early stages, many cases remain undiagnosed until complications develop.

Gestational Diabetes Mellitus

Gestational diabetes is a temporary form of insulin resistance that develops during pregnancy, usually after the 24th week of gestation.

During pregnancy, hormonal changes — particularly increased levels of estrogen and progesterone — interfere with insulin receptor function, reducing insulin sensitivity. When the pancreas cannot produce enough insulin to overcome this resistance, blood glucose levels rise, leading to gestational diabetes.

Although gestational diabetes often resolves after childbirth, affected women require careful monitoring and treatment throughout pregnancy to prevent complications that may endanger both mother and baby.

Other Secondary Forms of Diabetes

In addition to the main types, there are secondary forms of diabetes caused by other factors such as:

• Genetic defects affecting beta-cell function,
• Endocrine disorders,
• Medication use (e.g., glucocorticoids),
• HIV/AIDS therapy, or
• Post–organ transplantation conditions.

Symptoms of Diabetes Mellitus

Common Signs and Symptoms of Diabetes

Type 1 Diabetes Symptoms

The typical clinical presentation of Type 1 diabetes is often summarized as the “four polys” syndrome:

• Polyphagia (excessive hunger)
• Polydipsia (excessive thirst)
• Polyuria (frequent urination)
• Polyweight loss (unexplained weight loss)

In addition, patients with Type 1 diabetes often experience fatigue and drowsiness due to the body’s inability to utilize glucose for energy.
They may also be prone to skin infections, tuberculosis, or other opportunistic infections.

The severity and rate of symptom onset vary among individuals, depending on how rapidly insulin production declines and how long hyperglycemia has persisted.

Type 2 Diabetes Symptoms

The symptoms of Type 2 diabetes are similar to those of Type 1 but are often less noticeable. Many individuals remain undiagnosed for several years until complications develop.

When any suspicious signs appear, it is essential to seek medical evaluation and blood testing to confirm or rule out diabetes.

Yeast infections: People with Type 2 diabetes have weakened immunity and are more prone to fungal infections. Elevated glucose levels in the blood and urine promote excessive yeast growth, particularly in moist skin folds, between fingers and toes, under the breasts, and even around or inside the genital area.

Slow wound healing: High blood sugar levels impair circulation and nerve function, resulting in delayed wound healing.

Numbness or pain in the feet is also a common symptom of diabetic neuropathy.

Gestational Diabetes Symptoms

In most cases, gestational diabetes causes no obvious symptoms.
However, some pregnant women may notice signs such as increased thirst and frequent urination.

The condition is typically diagnosed during the second or third trimester using a three-sample oral glucose tolerance test (OGTT) performed between 24 and 28 weeks of gestation, provided that the woman had no prior history of Type 1 or Type 2 diabetes.

Possible Complications of Diabetes Mellitus

Acute Complications

Acute complications often result from delayed diagnosis, inadequate treatment, or underlying infections.
They include:

Diabetic ketoacidosis (DKA): Common in Type 1 diabetes or other types during infection or stress.

Hypoglycemia (2.2–3.3 mmol/L): May occur due to medication overdose, missed or delayed meals, or excessive exercise.

Lactic acidosis: A potentially fatal metabolic complication.

Acute infections: Such as skin infections, tuberculosis, or osteomyelitis (bone infection).

Chronic Complications

Chronic complications arise from long-term uncontrolled blood glucose and affect both large and small blood vessels:

Macrovascular complications:

• Coronary artery disease (CAD)
• Cerebrovascular disease (stroke)
• Peripheral arterial disease (PAD)

Microvascular complications:

• Diabetic foot disease
• Ocular complications such as retinopathy, cataracts, and glaucoma
• Kidney disease (diabetic nephropathy)
• Peripheral neuropathy

When to See a Doctor

If you experience any of the above symptoms, consult your healthcare provider immediately for evaluation and guidance.
Early diagnosis and treatment can prevent serious complications and help you maintain a healthier, more active life.

Causes of Diabetes Mellitus

Causes of Type 1 Diabetes

Among all Type 1 diabetes cases, approximately 95% are caused by an autoimmune mechanism (Type 1A), while the remaining 5% are of unknown origin (Type 1B).

In Type 1A diabetes, the immune system mistakenly attacks and destroys the insulin-producing beta cells of the pancreas, leading to a severe insulin deficiency. As a result, individuals with Type 1 diabetes depend on external insulin supplementation to regulate their blood glucose levels.

Causes of Type 2 Diabetes

The exact cause of Type 2 diabetes remains unclear.

In this form, the body produces insulin, but cells become resistant to its effects or fail to use it efficiently.
To compensate, the pancreas initially increases insulin production; however, over time, it loses the ability to maintain sufficient insulin output, resulting in elevated blood glucose levels and the onset of diabetes.

Common Risk Factors for Type 2 Diabetes

Several factors may increase the risk of developing Type 2 diabetes, including:

• Family history of diabetes (parents, siblings, or children with the condition)
• Personal history of gestational diabetes
• Cardiovascular disease related to atherosclerosis
• Hypertension (high blood pressure)
• Sedentary lifestyle (lack of physical activity)
• Overweight or obesity
• Impaired glucose tolerance or impaired fasting glucose
• Polycystic ovary syndrome (PCOS) in women

Causes of Gestational Diabetes

Women who are overweight, have a family history of diabetes, or have previously been diagnosed with impaired glucose tolerance are at higher risk of developing gestational diabetes.

Additionally, glucose intolerance commonly develops during the third trimester in about 3–5% of pregnancies.
Other forms of secondary diabetes may also appear due to:

• MODY (Maturity-Onset Diabetes of the Young)
• Exocrine pancreatic diseases
• Acromegaly or Cushing’s syndrome
• Viral infections that damage the pancreas

Gestational diabetes significantly increases the risk of complications and mortality for both mother and baby if not properly managed.

Risk Factors for Diabetes Mellitus

Who Is at Risk?

Individuals with the following characteristics or conditions are at increased risk of developing diabetes:

• Age 45 years or older
• Overweight or obesity
• Physically inactive lifestyle
• Family history of diabetes
• Impaired glucose regulation (prediabetes)
• Gestational diabetes history or giving birth to a baby weighing over 4.1 kg (9 lbs)
• Hypertension or cardiovascular disease
• Dyslipidemia (abnormal cholesterol levels)
• Polycystic ovary syndrome (PCOS)
• Ethnic background: African American, Hispanic/Latino, Asian American, or Native American ancestry

Other Contributing Factors

Certain lifestyle and health factors can further increase the risk of developing diabetes, such as:

• Smoking
• Obesity and lack of physical exercise
• Pregnancy (increasing the likelihood of gestational diabetes)

Diagnosis and Treatment of Diabetes Mellitus

Diagnostic Tests and Methods

Diabetes mellitus is suggested by typical symptoms and confirmed by quantitative plasma glucose testing.
The most reliable assessments include fasting plasma glucose (FPG) after 8–12 hours of fasting, or the oral glucose tolerance test (OGTT) performed 2 hours after consuming 75 g (adults) or 1.75 g/kg (children) of glucose solution.

In clinical practice, diabetes and impaired fasting glucose are often diagnosed using random plasma glucose or HbA1c measurements.

Diagnostic Criteria

Random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) with classic hyperglycemic symptoms

Fasting plasma glucose (FPG) — measured after at least 8 hours of fasting, on two separate occasions:

• < 100 mg/dL (5.6 mmol/L): Normal
• 100–125 mg/dL (5.6–6.9 mmol/L): Impaired fasting glucose (prediabetes)
• ≥ 126 mg/dL (7.0 mmol/L): Diabetes mellitus

Oral Glucose Tolerance Test (OGTT)

• < 140 mg/dL (7.8 mmol/L): Normal
• 140–199 mg/dL (7.8–11.0 mmol/L): Impaired glucose tolerance
• ≥ 200 mg/dL (11.1 mmol/L): Diabetes mellitus

HbA1c (Glycated Hemoglobin)

HbA1c reflects average blood glucose levels over the past three months and is now incorporated into standard diagnostic criteria:

• HbA1c ≥ 6.5%: Diabetes mellitus
• HbA1c 5.7–6.4%: Prediabetes or increased diabetes risk

Effective Treatment of Diabetes Mellitus

The primary goals of treatment are to control blood glucose, prevent complications, and minimize hypoglycemic episodes.

Target Blood Glucose Levels

• Pre-meal plasma glucose: 80–130 mg/dL (4.4–7.2 mmol/L)
• Post-meal peak (1–2 hours after eating): < 180 mg/dL (10 mmol/L)
• HbA1c: < 7%

Non-Pharmacological Management

1. Diet and Nutrition Therapy

A balanced diet should be individualized based on body weight, caloric needs, lifestyle, and treatment regimen. Recommended macronutrient distribution:

• 45–65% carbohydrates
• 25–35% fats (saturated fat < 7%)
• 10–35% protein

2. Physical Activity

Regular physical activity improves insulin sensitivity, enhances glycemic control, and reduces cardiovascular risk by helping maintain or reduce body weight.

• Exercise for 30–45 minutes per session,
• 3–5 days per week (approximately 150 minutes per week)
• Moderate intensity (e.g., brisk walking, cycling)

3. Vaccinations

All diabetic patients should receive:

• Pneumococcal vaccination (once in a lifetime)
• Annual influenza vaccination

Pharmacological Treatment

Type 1 Diabetes

Requires insulin therapy for survival and metabolic control.

Type 2 Diabetes

Managed with oral hypoglycemic agents and/or injectable medications.
Insulin may be added when three or more oral agents fail to achieve adequate glucose control.

Oral Hypoglycemic Agents

1. Sulfonylureas

Stimulate pancreatic beta cells to release insulin and enhance tissue insulin sensitivity.
They lower blood glucose effectively but often require combination therapy for long-term control.

2. Short-Acting Insulin Secretagogues (Glinides)

Includes repaglinide and nateglinide.
These agents stimulate rapid insulin release around meals, effectively reducing postprandial glucose spikes with lower hypoglycemia risk compared to sulfonylureas.

3. Biguanides

Metformin decreases plasma glucose by inhibiting hepatic glucose production (gluconeogenesis and glycogenolysis).
It is typically the first-line medication for Type 2 diabetes.

4. Thiazolidinediones (TZDs)

Examples: troglitazone, rosiglitazone, pioglitazone.
They reduce insulin resistance in peripheral tissues but are associated with serious side effects, such as fluid retention and heart failure risk.

5. Alpha-Glucosidase Inhibitors

These drugs delay carbohydrate absorption in the intestine, reducing postprandial glucose levels.
However, they are less effective and may cause flatulence, bloating, or diarrhea, leading to discontinuation in some patients.

6. Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

Examples: alogliptin, linagliptin, saxagliptin, sitagliptin.
They increase incretin activity, promoting insulin release and reducing glucagon secretion.

7. Sodium–Glucose Cotransporter-2 (SGLT2) Inhibitors

Examples: canagliflozin, dapagliflozin, empagliflozin.
They block glucose reabsorption in the proximal renal tubule, causing glucosuria and lower blood glucose levels.
Empagliflozin has been shown to reduce cardiovascular events in high-risk diabetic patients.

Injectable Glucose-Lowering Agents

1. GLP-1 Receptor Agonists

Examples: liraglutide, dulaglutide, albiglutide.
They stimulate glucose-dependent insulin secretion and slow gastric emptying, helping control postprandial glucose.

2. Amylin Analogs (Pramlintide)

Pramlintide, an analog of the pancreatic hormone amylin, helps reduce post-meal glucose by:

• Suppressing postprandial glucagon secretion
• Delaying gastric emptying
• Promoting a feeling of satiety

It is administered by injection, often in combination with insulin.

Lifestyle and Prevention of Diabetes (Diabetes Mellitus)

Healthy Lifestyle Habits to Help Control Diabetes Progression

Lifestyle management:

Follow your doctor’s treatment plan and take medications as prescribed.

Maintain a positive lifestyle and minimize stress.

Engage in regular and appropriate physical activity.

Contact your doctor immediately if any unusual symptoms appear during treatment.

Schedule regular medical checkups to monitor your health status, disease progression, and to allow your doctor to adjust treatment when necessary.

Keep an optimistic attitude. Mental well-being greatly influences diabetes control—talk to trusted people, share your thoughts with family members, keep pets, read books, or do anything that helps you feel relaxed and happy.

Choose lifestyle and self-care activities that best fit your specific health condition.

Dietary recommendations:

• Adopt a diet low in saturated fats and cholesterol.
• Consume a moderate amount of carbohydrates, preferably from whole grains rich in dietary fiber.

Effective Ways to Prevent Diabetes

To prevent diabetes and lower your risk, consider the following measures:

• Maintain a healthy, balanced diet suited to your energy needs.
• Exercise regularly to improve physical fitness and maintain a healthy body weight.
• Quit smoking and avoid excessive alcohol consumption.
• Get regular diabetes screenings, especially if you have risk factors such as obesity, family history, or high blood pressure.