Type 1 Diabetes: Symptoms, Causes, and Management

The prevalence of type 1 diabetes mellitus (T1DM) is increasing globally, with an annual increase rate of 0.34%. By 2040, the number of people living with T1DM is projected to reach between 13.5 and 17.4 million.

Managing T1DM is complex, and the life expectancy for a 10-year-old child diagnosed with the condition is, on average, only 13 years in low-income countries. Additionally, approximately 30% of patients with T1DM develop end-stage kidney disease during their lifetime. T1DM is also associated with a poor quality of life and a significant psychological burden. The rising incidence of T1DM worldwide poses a serious challenge to public health.

This article aims to provide a comprehensive understanding of type 1 diabetes, including its symptoms, risk factors, diagnosis, and treatment options. By offering expert insights, individuals and their families can better manage this condition and improve their overall well-being.

Understanding Type 1 Diabetes

What is Type 1 Diabetes?

Type 1 diabetes mellitus (T1D) is a chronic autoimmune condition where the immune system destroys the insulin-producing beta cells in the pancreas, leading to an inability to produce insulin. This destruction happens gradually over months or even years. As a result, the body eventually has an absolute (complete) insulin deficiency. Without insulin, the body’s cells cannot use glucose for energy, leading to metabolic problems.

What is the Cause of Type 1 Diabetes?

The exact cause of T1D is not fully known, but genetics play a significant role. Its main genetic risk comes from the HLA class II genes on chromosome 6, contributing 30%-50% of the genetic risk. Other genes also play a role but have smaller effects. These include:

• Insulin gene (INS) on chromosome 11
• CTLA4 gene on chromosome 2
• PTPN22 gene on chromosome 1
• IL2RA and IFIH1 genes, among others

Additionally, certain autoantibodies in the blood can indicate that a person is at risk for, or has already developed T1D. The main autoantibodies associated with type 1 diabetes include:

• Insulin autoantibodies (IAA)
• GAD autoantibodies (GADA)
• Insulinoma antigen-2 autoantibodies (IA- 2A)
• Zinc transporter isoform 8 autoantibodies (ZnT8)

IAAs are more commonly detected in children under the age of 10, with a diagnostic sensitivity of about 50-60%. On the other hand, GADA autoantibodies are detected at relatively high rates (70-80%) across all age groups. The more autoantibodies a person has and the higher their levels, the greater their risk of developing T1D.

When Does Type 1 Diabetes Occur?

T1D can occur at any age, but it most commonly presents in children, adolescents, and young adults. There are two noticeable peaks in the age of onset:

• between 4 and 7 years old
• between 10 and 14 years old

However, it is increasingly recognized that type 1 diabetes can also develop in adults, and this adult-onset form of the disease is sometimes misdiagnosed as type 2 diabetes due to its more gradual onset and different presentation.

Studies have shown that the incidence of adult-onset type 1 diabetes is significant. For example, a study in southeastern Sweden found similar incidence rates of type 1 diabetes in individuals aged 0–19 years and those aged 40–100 years. Additionally, over half of all new cases of type 1 diabetes worldwide occur in adults, indicating that it is more prevalent than previously understood.

What are the Stages of Type 1 Diabetes?

T1D is often described as progressing through several stages before the onset of symptomatic disease. These stages are based on proposed studies and classifications from various research groups and organizations, including the JDRF (Juvenile Diabetes Research Foundation) and the American Diabetes Association (ADA).

Stage 1: Autoimmunity without Dysglycemia

In this stage, individuals have two or more islet autoantibodies, such as insulin autoantibodies (IAA), glutamic acid decarboxylase autoantibodies (GADA), and others. However, blood glucose levels remain normal. No symptoms are present, and individuals are often identified through screening in research studies or because they have a family history of T1D.

Stage 2: Autoimmunity with Dysglycemia

Individuals still have multiple islet autoantibodies but now exhibit dysglycemia, meaning abnormalities in blood glucose levels are detected through oral glucose tolerance tests (OGTT) or continuous glucose monitoring (CGM). Stage 2 of type 1 diabetes reflects early beta-cell dysfunction. Despite abnormal blood glucose levels, there are no overt symptoms of diabetes.

At this stage of the disease, there is an approximately 60% chance of developing symptomatic type 1 diabetes within 2 years, and around a 75% chance within 4 to 5 years. The positive predictive value for developing symptomatic type 1 diabetes within 5 years is 96%.

Stage 3: Autoimmunity with Dysglycemia (Symptomatic T1D)

Research across multiple studies has established that stage 3 of type 1 diabetes is when clinical symptoms of diabetes manifest, such as polyuria (frequent urination), polydipsia (increased thirst), weight loss, and fatigue. The autoimmune destruction of beta cells has progressed to the point where the pancreas can no longer produce sufficient insulin.

Symptoms and Risk Factors of Type 1 Diabetes

What are the Symptoms of Type 1 Diabetes?

Several studies have documented the symptoms of type 1 diabetes and their prevalence among patients. The most common are known as the three P’s of diabetes. These symptoms often occur together and can appear suddenly.

Polydipsia (Excessive Thirst)

Polydipsia is characterized by an unusually high level of thirst. This excessive thirst is primarily due to elevated blood glucose levels. When blood sugar is high, the body attempts to remove the excess glucose through urine. This process requires a significant amount of water, leading to dehydration and an increased sensation of thirst.

Polyuria (Frequent Urination)

Polyuria is the production of abnormally large volumes of urine. Typically, individuals produce around 1 to 2 liters of urine daily (equivalent to about 4 to 8 cups). However, those experiencing polyuria excrete more than 3 liters of urine daily.

Polyphagia (Increased Hunger)

Polyphagia refers to an excessive feeling of hunger and increased food intake. In type 1 diabetes, the body’s cells cannot absorb glucose from the bloodstream due to a lack of insulin or insulin resistance. This means that, despite high blood glucose levels, cells are starved for energy. The body responds by increasing hunger signals, prompting individuals to eat more in an attempt to provide energy to the cells.

Other symptoms can also occur along with the three P’s, including:

• Unintended weight loss
• Fatigue
• Blurred vision
• Bed-wetting in children
• Irritability and mood changes

What are the Risk Factors of Type 1 Diabetes?

Various risk factors can increase the likelihood of developing type 1 diabetes, including:

Genetics and Family History

A family history of type 1 diabetes significantly raises the risk. The overall chance of developing this condition in the US is about 0.33% to 0.40%, and familial cases account for less than 10% of all cases. As mentioned earlier, the strongest genetic link for type 1 diabetes involves certain alleles of the HLA class II genes.

Age

Type 1 diabetes can develop at any age, but it is most commonly diagnosed during adolescence. Most research on risk factors focuses on children and teenagers due to the higher incidence rates in these age groups.

Geographical Location

The prevalence of type 1 diabetes is higher in certain countries, particularly those in Northern European countries. A 2020 study mapped the geographical distribution of T1D incidence among children in four Nordic countries, where the population is genetically similar. T1D incidence varies across Nordic countries and regions, generally decreasing with higher population density, suggesting environmental factors influence T1D incidence.

Infections

Type 1 diabetes shows a higher incidence in autumn and winter, similar to many viral infections. This seasonal pattern suggests a possible link between viral infections and the onset of diabetes.

• Respiratory infections: A 2011 study found a threefold increase in islet autoimmunity risk with frequent respiratory infections. Pneumonia, bronchitis, and respiratory syncytial virus were among the infections reported.

• Viral Infections: Enteroviruses, in particular, have long been linked to the development of type 1 diabetes. Both animal and human studies have shown associations between these viruses and the disease.

Studies from Finland, such as DiMe and DIPP, found that positive tests for enterovirus RNA and antibodies typically appear before the clinical onset of Type 1 diabetes. This suggests a potential role of enteroviruses in triggering the autoimmune response leading to type 1 diabetes.

• SARS-CoV-2: The COVID-19 pandemic has prompted the investigation into its potential link with type 1 diabetes. While some studies suggest an increase in diabetes incidence during the pandemic, the direct impact of SARS-CoV-2 on diabetes onset remains unclear.

• Other Viruses: Various other viruses, such as Rotavirus, Cytomegalovirus (CMV), and Adenovirus C, have been studied for potential associations with type 1 diabetes, but most findings are inconclusive.

• Intestinal Microbiota: Emerging evidence suggests that gut microbiota composition may influence the risk of Type 1 diabetes. Studies have found differences in the gut microbiota of children with islet autoimmunity compared to healthy controls, indicating a potential role in disease development.

Dietary Factors

Nutritional factors during pregnancy, infancy, and early childhood play a complex role in the development of type 1 diabetes. While certain dietary exposures show associations with increased or decreased risk, the evidence is often mixed, and further research is needed to understand these relationships fully.

• Gluten: Higher dietary gluten intake during pregnancy was linked to a higher risk of type 1 diabetes in the Danish National Birth Cohort (DNBC), but the international TEDDY study found no association.

• Micronutrients: Maternal micronutrient intake shows inconsistent results. The Norwegian MoBa study linked iron supplements during pregnancy to a higher type 1 diabetes risk in offspring. However, Finnish (DIPP) and TEDDY studies found no association between islet autoimmunity and maternal iron intake, antioxidants, or omega-3 supplements.

• Hydrolyzed Infant Formula: The TEDDY study followed 8,676 children with increased genetic risk for T1D. The result suggests that hydrolyzed formula does not reduce, and may increase, the risk of islet autoimmunity in genetically predisposed infants.

• Solid Foods, Cereals, and Gluten: According to a 2015 study, early gluten introduction (before 3 months) significantly increased the risk of islet autoantibodies and type 1 diabetes compared to exclusive breastfeeding or introducing gluten between 3.1 and 6 months.

• Body Size in Childhood: Rapid weight gain in infancy and higher BMI in childhood are linked to increased risk of islet autoimmunity and type 1 diabetes. The association between body size and diabetes risk highlights the importance of early growth patterns.

Autoimmune Conditions

T1D is frequently associated with the following conditions:

• Hashimoto’s Thyroiditis and Graves’ Disease: Hashimoto’s thyroiditis is an autoimmune disorder where the immune system attacks the thyroid gland, leading to hypothyroidism (underactive thyroid). Meanwhile, Graves’ disease is an autoimmune disorder causing hyperthyroidism (overactive thyroid).

These diseases are present in 17% to 30% of patients with type 1 diabetes. This strong association is primarily due to the common genetic factors shared between these conditions.

• Addison’s Disease: A rare disorder in which the adrenal glands do not produce enough hormones, specifically cortisol and aldosterone. Addison’s disease and type 1 diabetes rarely co-occur. Up to 14% of patients with Addison’s disease also have T1D, while only 0.2% of those with T1D develop autoimmune Addison’s disease.

• Celiac Disease: A chronic autoimmune condition where the immune system damages the small intestine’s mucosa in response to gluten, on a genetic predisposition. Celiac disease and type 1 diabetes have a prevalence of about 8%. Over 90% of celiac disease cases are diagnosed after T1D. The condition is more frequent in children diagnosed with T1D before age four and is more common in females than males.

• Autoimmune Gastritis: A condition where the immune system attacks the stomach lining, particularly the parietal cells that produce stomach acid and intrinsic factors. This leads to decreased acid production and impaired vitamin B12 absorption, resulting in pernicious anemia. The prevalence of autoimmune gastritis in patients with type 1 diabetes is 5-10%.

Ethnicity

Certain ethnic groups have a higher incidence of type 1 diabetes. In the US, Caucasians are more prone to developing type 1 diabetes compared to African Americans and Hispanic Americans.

Diagnosis of Type 1 Diabetes

How is Type 1 Diabetes Diagnosed?

Type 1 diabetes is diagnosed through a combination of clinical evaluation and laboratory tests:

• Blood Tests: These tests measure blood sugar levels under various conditions.
• Random Blood Sugar Test: A blood sample is taken at a random time. A blood sugar level of 200 mg/dL (11.1 mmol/L) or higher suggests diabetes.
• Fasting Blood Sugar Test: Blood sugar levels are measured after an overnight fast. A fasting blood sugar level of 126 mg/dL (7.0 mmol/L) or higher indicates diabetes.
• Hemoglobin A1c Test: This test measures average blood sugar levels over the past two to three months. An A1c level of 6.5% or higher on two separate tests indicates diabetes.
• Oral Glucose Tolerance Test (OGTT): Blood sugar levels are tested before and two hours after drinking a sugary solution. A two-hour blood sugar level of 200 mg/dL (11.1 mmol/L) or higher indicates diabetes.
• Autoantibody Tests: These tests look for specific autoantibodies commonly present in T1D, such as GAD65, IA-2, and ZnT8 autoantibodies.
• C-Peptide Test: This test measures the level of C-peptide, which indicates how much insulin the pancreas is producing. Low levels of C-peptide (less than 0.2 nmol/l) suggest T1D.

Type 1 diabetes is diagnosed when tests show elevated blood sugar levels and the presence of specific autoantibodies.

Can Type 1 Diabetes be Misdiagnosed?

T1D can be misdiagnosed, particularly in adults. Misdiagnosis is more common in cases of late-onset T1D, where the condition is often mistaken for type 2 diabetes (T2D) due to similar symptoms.

A study by the Diabetes Alliance for Research in England (DARE) reported that 38% of individuals diagnosed with type 1 diabetes after the age of 30 were initially misdiagnosed with type 2 diabetes and did not receive necessary insulin treatment.

Testing for autoantibodies and C-peptide levels is recommended to differentiate between type 1 and type 2 diabetes. Although up to 30% of patients with type 1 diabetes may test negative for autoantibodies, a low C-peptide level can help confirm the diagnosis.

Management and Treatment of Type 1 Diabetes

How is Type 1 Diabetes Treated?

Type 1 diabetes treatment focuses on managing blood sugar levels and preventing complications. The primary treatments include:

Insulin Therapy

Here’s a table summarizing the different types of insulin used in the treatment of type 1 diabetes:

Data source: CDC and Mayo Clinic

As for the method of administration, insulin can’t be taken orally. Stomach enzymes would break down the insulin, making it ineffective in lowering blood sugar levels. Therefore, insulin must be administered through injections or an insulin pump.

Insulin pumps exclusively use rapid-acting insulin. Some pumps use external tubing to deliver insulin from the pump to the infusion site, while others use a pod that is applied directly to the skin and controlled wirelessly. Insulin pumps are programmed with adjustable settings for basal rates, insulin-to-carbohydrate ratios, correction factors, and target glucose ranges.

Blood Sugar Monitoring

Depending on the type of insulin therapy selected or required, individuals may need to check and record their blood sugar levels at least four times a day. The American Diabetes Association recommends testing blood sugar levels before meals and snacks, at bedtime, before exercising or driving, and whenever low blood sugar is suspected.

• Continuous Glucose Monitoring (CGM): This involves attaching a water-resistant disposable sensor to the back of the upper arm or abdomen, lasting between 3 to 14 days. The sensor can be scanned with a reader to display current interstitial fluid glucose levels and trends over the past eight hours.CGM devices can store up to 90 days of data, which can be shared via smartphone applications, often including alerts for hypoglycemia. Some CGM systems integrate with insulin delivery devices to halt insulin if a drop in blood sugar is detected or predicted. Currently, four major CGMs are approved by the FDA in the US. These are:

• • Medtronic
  • Dexcom
  • FreeStyle Libre
  • Eversense

• Hybrid Closed Loop (HCL) Systems: HCL systems, also known as automated insulin delivery systems or artificial pancreas systems, are advanced technologies used in managing diabetes, particularly type 1 diabetes. These systems combine continuous glucose monitoring (CGM) and insulin pump technology with sophisticated algorithms to automate insulin delivery, helping maintain blood glucose levels within a target range. The system automatically adjusts insulin delivery based on CGM readings, reducing the user’s need for manual adjustments. It includes alarms and alerts for hypo- or hyperglycemia and failsafe mechanisms to prevent over- or under-delivery of insulin. While the system automates many aspects of diabetes management, users still need to input information such as carbohydrate intake during meals and calibration of the CGM.

Other Medications

Additionally, people with type 1 diabetes may be prescribed other medications, including:

• High Blood Pressure Medications: For patients with type 1 diabetes, several classes of medications are commonly prescribed to manage high blood pressure. These include:

• ACE Inhibitors (ACEi): These medications help relax blood vessels by preventing the formation of angiotensin, a chemical that narrows blood vessels. Common examples are lisinopril and enalapril.

• Angiotensin II Receptor Blockers (ARBs): These block the action of angiotensin, keeping blood vessels open. Examples include losartan and candesartan.

• Calcium Channel Blockers (CCBs): These prevent calcium from entering cells of the heart and blood vessels, leading to relaxation and lowered blood pressure. Amlodipine and verapamil are typical examples.

• Diuretics: Also known as water pills, these help eliminate excess sodium and water from the body. Hydrochlorothiazide is a commonly used diuretic.

• Beta-Blockers: These reduce heart rate and the force of contraction, which lowers blood pressure. Metoprolol and carvedilol are common beta-blockers.

• Aspirin: This is generally recommended for adults with diabetes who are at an increased risk for cardiovascular disease (CVD). This typically includes men over 50 and women over 60 who have additional risk factors such as a family history of CVD, hypertension, smoking, dyslipidemia, or albuminuria.

• Cholesterol-lowering Drugs: Statins are the primary class of medications used for this purpose. They help lower LDL (bad) cholesterol, raise HDL (good) cholesterol, and reduce triglycerides. They are also associated with a reduction in the risk of heart attack and stroke. Common statins prescribed include:

• • Atorvastatin (Lipitor)
  • Rosuvastatin (Crestor)
  • Simvastatin (Zocor)
  • Pravastatin (Pravachol)
  • Lovastatin (Mevacor)
  • Fluvastatin (Lescol)
  • Pitavastatin (Livalo)

If statins alone do not achieve the desired cholesterol levels, other medications might be used in combination. These include:

• Ezetimibe: This drug specifically blocks cholesterol absorption in the intestines and is approved for use in children with familial hypercholesterolemia (FH). In adults, combining ezetimibe with statin therapy has been shown to lower LDL-C levels further effectively.

• Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Inhibitors: The only FDA-approved PCSK9 inhibitors are alirocumab and evolocumab. Clinical studies indicate that these inhibitors are well-tolerated and significantly lower LDL-C in individuals with hyperlipidemia and diabetes mellitus, even when added to maximally tolerated statin therapy. Moreover, they do not affect glycemic control or increase the risk of diabetes in non-diabetic individuals and can reduce the incidence of cardiovascular events.

• Bile Acid Sequestrants: Examples of this drug are cholestyramine and colesevelam. Bile acid sequestrants prevent the reabsorption of bile acids, promoting the conversion of cholesterol to bile salts and reducing overall cholesterol levels. Cholestyramine has been shown to lower cholesterol by 8.5% compared to placebo but is often poorly tolerated due to side effects like abdominal pain and nausea. Colesevelam, a newer bile acid sequestrant, effectively lowers LDL-C with fewer adverse effects and holds promise for individuals with type 1 diabetes.

• Fibrates: This drug is primarily used to lower triglyceride levels and increase HDL-C levels. Studies have shown that fibrates are both safe and effective in reducing triglyceride levels in children. However, they are less effective in lowering LDL-C.

• Niacin: This vitamin enhances HDL-C levels by inhibiting the liver’s production of VLDL-C. The cholesterol in VLDL particles, VLDL-C, contributes to the overall amount of cholesterol in the blood. Elevated levels of VLDL-C are associated with an increased risk of cardiovascular diseases, as VLDL can be converted into LDL in the bloodstream. Niacin is infrequently prescribed for pediatric patients due to common side effects such as flushing, impaired glucose tolerance, liver failure, and myopathy.

Patients must work with their healthcare providers to develop a personalized treatment plan based on their risk factors and health profile.

How Is Type 1 Diabetes Managed?

Managing type 1 diabetes involves a combination of insulin therapy, lifestyle adjustments, and regular monitoring. Here are some key lifestyle adjustments for effective management:

Diet and Nutrition

Below are general guidelines on which foods to eat, based on various studies and recommendations from health organizations.

• Carbohydrate Management: Carbohydrate counting is essential for matching insulin doses to carbohydrate intake to maintain stable blood glucose levels. To reduce spikes in blood glucose, it is recommended to prefer foods with low glycemic index (GI). A meta-analysis found that low-GI diets improve glycemic control, as reflected by reductions in HbA1c levels compared to high-GI diets. Recommended low-GI foods include:

• • Whole Grains: Oats, quinoa, barley, and whole wheat products. These have a lower GI and provide sustained energy release.
  • Fruits and Vegetables: Non-starchy vegetables (spinach, kale, broccoli) and fruits like berries, apples, and pears. These are high in fiber and low in GI.

• Protein Intake: Protein has minimal impact on blood glucose levels and is important for muscle repair and overall health. Studies have shown that incorporating protein into meals can slow the absorption of glucose, thereby preventing spikes in blood sugar levels after eating. Foods high in protein include:

• • Lean Meats: Chicken, turkey, and lean cuts of beef.
  • Fish: Especially fatty fish like salmon and mackerel, which are high in omega-3 fatty acids.
  • Plant-Based Proteins: Lentils, beans, tofu, and tempeh.

• Healthy Fats: Diets rich in monounsaturated fats (MUFAs) can improve lipid profiles and reduce cardiovascular risk in people with diabetes. Studies have shown that incorporating MUFAs into the diet, particularly from plant-based sources like olive oil, nuts, and avocados, can have significant cardiometabolic benefits.

• Fiber-Rich Foods: Studies have shown that dietary fiber intake can significantly benefit glycemic control in individuals with type 1 diabetes. For example, the Coronary Artery Calcification in Type 1 Diabetes (CACTI) study found an inverse correlation between dietary fiber intake and HbA1c levels, indicating better blood sugar control among participants with higher fiber consumption. Additionally, fiber intake was associated with improvements in other cardiovascular risk factors such as BMI, waist circumference, and blood pressure. Fiber-rich foods include:

• • Whole Grains: Brown rice, whole wheat bread, and oats.
  • Vegetables: Brussels sprouts, sweet potatoes, and carrots.
  • Fruits: Apples, oranges, and strawberries.

• Hydration: Staying hydrated is crucial for maintaining blood glucose levels. Avoid sugary drinks to prevent spikes in blood sugar.

Regular monitoring and diet adjustments based on blood glucose readings are essential for optimal management.

Physical Activity

Exercise has been shown to benefit individuals with type 1 diabetes in various ways significantly. Here are some key findings from recent studies:

• Improved Glycemic Control: A meta-analysis demonstrated that regular exercise can improve HbA1c levels, indicating better long-term blood glucose control. The study found that both aerobic and combined aerobic and resistance exercises were effective in reducing HbA1c levels in both adults and children with T1D.

• Enhanced Vascular Health: Research published in Diabetes Care found that regular exercise training improved vascular endothelial function in individuals with T1D. Improved endothelial function is crucial as it can reduce the risk of cardiovascular complications, common in diabetes.

• Reduction in Insulin Resistance: Exercise can also help reduce insulin resistance, making it easier for the body to use insulin effectively. This not only helps in better blood glucose management but also reduces the overall insulin requirement.

• Cardiovascular Benefits: Regular physical activity lowers cardiovascular risk factors such as LDL cholesterol, blood pressure, and BMI. These changes contribute to a lower risk of heart disease, which is a significant concern for individuals with diabetes.

• Improved Metabolic and Lipid Profiles: Exercise has been shown to improve metabolic profiles by lowering triglycerides and increasing HDL cholesterol levels. This helps in better overall management of diabetes and the reduction of associated risks.

Overall, incorporating regular physical activity, including both aerobic and resistance exercises, is highly beneficial for individuals with T1D.

What is the Difference Between Type 1 and Type 2 Diabetes?

Type 1 and type 2 diabetes are two distinct forms of diabetes mellitus that differ in their causes, development, and management. Here’s a detailed comparison of type 1 diabetes versus type 2 diabetes:

Takeaway

Type 1 diabetes is a complex and chronic condition that requires comprehensive understanding and management. It is primarily caused by an autoimmune reaction that destroys insulin-producing beta cells in the pancreas, leading to insulin deficiency. This condition can be influenced by genetic predispositions and environmental triggers, though the exact causes are still under investigation.

While type 1 diabetes poses significant challenges, advancements in medical treatments and a comprehensive approach to lifestyle management can help individuals with type 1 diabetes lead healthy and fulfilling lives.