Type 1 Diabetes Mellitus: Symptoms, Causes & Treatment
Type 1 Diabetes: This lecture reviews type 1 diabetes mellitus including its definition, symptoms, causes, risk factors, diagnosis, treatment, medications, and more!
Guest Author
Guest Author: Charlotte Watson
The lecture below was written by guest author Charlotte Watson, and the medical illustrations were created and provided by EZmed.
Pass Your Classes & Exams!
Become a member to access ALL study guides, flashcards, & PDF lectures!
Type 1 Diabetes Mellitus
Definition
Diabetes mellitus is a metabolic disorder in which the body’s ability to produce or respond to insulin is impaired, resulting in elevated blood glucose (blood sugar) levels.
The medical term for high blood glucose levels is hyperglycemia.
Diabetes mellitus comes from the Greek word “diabetes” meaning to pass through, and the Latin word “mellitus” meaning sweet.
This makes sense as sweet glucose ‘passes through’ the body and into the urine in diabetes mellitus.
Diabetes mellitus can be classified into 2 main types:
Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
This lecture will focus on type 1 diabetes mellitus (T1DM).
Type 1 diabetes is an autoimmune disease in which the body’s own immune system attacks the insulin-producing cells of the pancreas.
As a result, the pancreas produces little to no insulin and blood glucose levels will increase.
Although type 1 diabetes typically develops in younger age groups (peak age of diagnosis is approximately 13 years old), adults can also develop type 1 diabetes later in life.
Type 1 diabetes is less common than type 2 diabetes, making up only 8% of diabetes diagnoses.
Diabetes Mellitus Definition: Type 1 diabetes is an autoimmune disease in which the insulin-producing cells of the pancreas are destroyed, resulting in little to no insulin production and elevated blood glucose levels.
Overview
In this lecture, we will discuss the following about type 1 diabetes:
Definition
Signs & Symptoms
Causes
Risk Factors
Pathophysiology
Diagnosis
Treatment
Complications
Eating Disorders
Type 1 diabetes vs type 2 diabetes
The following pertinent information will also be reviewed:
Anatomy and Function of the Pancreas
Function of Insulin
Don’t miss the table at the end and leave a comment below if this lecture was helpful!
Type 1 Diabetes Mellitus: This lecture reviews type 1 diabetes definition, symptoms, causes, risk factors, pathophysiology, diagnosis, treatment, and more!
Symptoms of Type 1 Diabetes
As previously mentioned, type 1 diabetes is a condition in which the pancreas produces little to no insulin, resulting in high blood glucose levels.
Many cells require insulin for glucose uptake.
In other words, insulin helps transport glucose from the blood and into cells (see insulin function below).
Once inside the cell, glucose can then be used as energy or fuel for the cell.
Without insulin, glucose remains in the blood and blood glucose levels increase as a result.
The elevated blood glucose levels, along with the inability of cells to take up glucose, results in a number of symptoms.
The onset of symptoms is generally very rapid, occurring in just days to weeks.
Signs and symptoms of type 1 diabetes include:
Weight loss
Polyuria (Increased urine output)
Frequent urination
Polydipsia (Increased thirst)
Dry mouth
Fatigue and weakness
Polyphagia (Increased hunger or appetite)
Blurred vision
Tachycardia (Fast heart rate)
Undiagnosed patients may present in the emergency room with diabetic ketoacidosis (DKA), a serious complication of diabetes (see complications below).
Diabetes Mellitus Symptoms: Signs and symptoms of type 1 diabetes include increased thirst (polydipsia), increased appetite, weight loss, fatigue, increased urination (polyuria), blurred vision, fast heart rate (tachycardia), etc.
What Causes Type 1 Diabetes?
The cause of type 1 diabetes development is not yet known.
However, there are several theories to the cause:
Infections
It is theorized that type 1 diabetes could be triggered by infections such as coxsackievirus
Autoantibodies
Another theory links type 1 diabetes to autoantibodies against beta cell antigens
Beta cells are responsible for producing insulin, and the autoantibodies destroy the beta cells
However, these autoantibodies are only present in the blood of 70-80% of patients, so it is not conclusive whether this relationship is causative
Genetics
There may also be a genetic link, with a strong association between type 1 diabetes and the presence of HLA-DR3 and HLA-DR4 antigens on chromosome 6
Type 1 Diabetes Causes: The pathophysiology and causes of type 1 diabetes include infections, autoantibodies, and genetics.
Risk Factors for Type 1 Diabetes
There are several risk factors for developing type 1 diabetes:
Family History
Family history of type 1 diabetes will increase the risk of a relative developing it by 10 times
A child’s risk of inheriting type 1 diabetes from their affected parent can vary between 1% and 9%
Family history of other autoimmune diseases (hypothyroidism, pernicious anaemia, celiac disease, etc) will increase the risk of developing type 1 diabetes
Environmental Factors
In genetically susceptible individuals, some environmental factors can trigger the development of type 1 diabetes
Obesity
Poorly-diverse gut microbiome
Diet
Breastfeeding is possibly associated with a lower risk of the infant developing type 1 diabetes
Early introduction of cow’s milk to an infant’s diet is possibility associated with a higher risk of developing type 1 diabetes
Early introduction of cereal (prior to 3 months of age) is possibility associated with a higher risk of developing type 1 diabetes
Lack of vitamin D exposure
Regular doses of vitamin D early in life have been shown to decrease the risk of developing type 1 diabetes
People in northern climates seem to be at higher risk of developing type 1 diabetes than in southern climates
Diagnosis rate of type 1 diabetes is also higher in winter months and lower in summer months
Type 1 Diabetes Risk Factors: Risk factors for developing type 1 diabetes include family history, obesity, diet, lack of vitamin D exposure, etc.
Anatomy of the Pancreas
In order to better understand the cause and pathophysiology of type 1 diabetes, let’s briefly review the anatomy and function of the pancreas and insulin.
The pancreas is an accessory organ of the abdomen.
The pancreas is located behind the stomach in the epigastric and left hypochondriac regions of the abdomen.
Anatomically, the pancreas is located along the transpyloric plane.
The transpyloric plane is an imaginary line midway between the suprasternal notch (jugular notch) and the upper border of the pubic symphysis, at approximately the level of the L1 vertebrae.
The pancreas can be divided into 5 main parts:
Head
Uncinate Process
Neck
Body
Tail
The head of the pancreas sits within the curve of the duodenum, and the tail is located by the hilum of the spleen.
The pancreas (except for the tail) is retroperitoneal - This includes the head, neck, and body.
The tail of the pancreas is intraperitoneal.
Anatomy of the Pancreas: Location and labeled parts of the pancreas including the head, uncinate process, neck, body, and tail.
Function of the Pancreas
The pancreas has both exocrine and endocrine roles:
Exocrine Function
The pancreas produces digestive enzymes which are secreted into the duodenum via the main pancreatic duct.
Pancreatic digestive enzymes include lipase, amylase, and proteases (such as trypsin and chymotrypsin).
The pancreatic digestive enzymes aid in the digestion of fats (lipase), carbohydrates (amylase), and proteins (proteases).
Endocrine Function
The pancreas produces and secretes hormones into the bloodstream.
Islets of Langerhans = Clusters of pancreatic endocrine cells that release specific hormones
Made up of 3 main types of cells:
Alpha Cells = Release glucagon
Beta Cells = Release insulin
Delta Cells = Release somatostatin
These hormones aid in glucose control.
The beta cells will be relevant in this lecture as they are responsible for producing and releasing insulin into the blood.
Function of the Pancreas: Digestive (exocrine) and hormone (endocrine) functions of the pancreas including glucagon (alpha cells), insulin (beta cells), and somatostatin (delta cells) release
Function of Insulin
As previously mentioned, insulin is produced and released by the beta cells of the pancreas.
Insulin is responsible for regulating blood glucose levels in the body by allowing the movement of glucose into cells.
Insulin is continuously released by the pancreatic beta cells (see above) at a low level throughout the day, which helps to:
Maintain the resting blood glucose levels at a healthy range between eating and during the night
Allow constant low-level uptake of glucose into cells for cellular processes, such as cellular growth and DNA replication
Blood sugar rises after eating a meal, and the beta cells release insulin in a biphasic pattern.
Firstly, beta cells rapidly release stored insulin from granules inside the cell
Secondly, beta cells increase insulin synthesis for a smaller, second-phase release
How Does Insulin Work?
Once the beta cells of the pancreas release insulin into the blood, insulin binds to insulin receptors on the surface of body cells.
The binding of insulin to insulin receptors on cells activates a signaling cascade which increases the recruitment of the glucose transporter GLUT4 from intracellular storage vesicles to the plasma membrane.
GLUT4 is the major transporter responsible for the uptake of glucose from the bloodstream and into the cell.
An increase in GLUT4 glucose transporters at the plasma membrane will increase glucose uptake into the cell.
The cell can then use the glucose as energy or fuel to carry out its functions.
How Does Insulin Work? Insulin receptor signaling pathway: Insulin binds to insulin receptors which increases the recruitment of GLUT4 glucose transporters to the plasma membrane. GLUT4 allows for glucose uptake into the cell.
Pathophysiology of Type 1 Diabetes
Type 1 diabetes is an autoimmune condition in which the body’s immune system attacks its own pancreatic beta cells.
More specifically, the T-cells of the immune system destroy pancreatic beta cells in genetically predisposed individuals.
As previously mentioned, the beta cells are involved in producing, storing, and releasing insulin.
This autoimmune attack damages the beta cells, preventing them from producing or releasing insulin.
Without insulin, glucose cannot be taken up from the bloodstream into cells (see above).
This results in elevated blood glucose levels called hyperglycemia.
The kidneys excrete the excess blood glucose into the urine, which can be detected as glycosuria (also called glucosuria) on a urine dipstick - More on this below!
Type 1 Diabetes Pathophysiology: Type 1 diabetes is caused by an autoimmune process in which the T cells (green) destroy the insulin-producing beta cells (yellow) of the pancreas
Diagnosis & Tests
Diagnosis of type 1 diabetes involves measuring blood glucose levels through one of the following methods:
Hemoglobin A1C
Random blood sugar test
Fasting blood sugar test
Hemoglobin A1C
Hemoglobin A1C (HbA1c) is a simple blood test that measures the patient’s average blood sugar levels over the past 2-3 months (8-12 weeks).
It measures the amount of blood glucose attached to hemoglobin (the protein in red blood cells that carries oxygen).
An A1C level of 6.5% or higher on 2 separate occasions suggests diabetes.
Random Blood Sugar Test
A blood sample can also be taken at random to assess a patient’s blood sugar level.
Regardless of when the last meal was, a blood glucose level of 200 mg/dL (11.1 mmol/L) or higher could be suggestive of diabetes.
Fasting Blood Sugar Test
A blood sample can also be taken after a period of fasting (usually overnight since midnight) to assess the blood glucose level.
Fasting blood glucose levels can be interpreted as:
Less than 100 mg/dL (5.6 mmol/L) = Normal
100-125 mg/dL (5.6-6.9 mmol/L) = Prediabetes
126 mg/dL (7 mmol/L) or higher on 2 separate tests = Diabetes
Type 1 Diabetes Diagnosis: Chart showing diagnostic criteria for normal, prediabetes, and diabetes using hemoglobin A1C, fasting blood sugar test, and random blood sugar test
Other Tests
If diagnosed with diabetes or hyperglycemia using one of the methods above, other additional tests may be performed:
Urinalysis to assess for the presence of ketones and glucose in the urine
C-peptide may be used to differentiate between different diabetes types
C-peptide is produced in the process of making insulin
Type 1 Diabetes = May see low C-peptide (no insulin produced)
Type 2 Diabetes = May see high C-peptide (insulin is produced but the cells are resistant)
Testing for diabetes autoantibodies, such as glutamic acid decarboxylase (GAD), islet cell autoantibodies, and insulin autoantibodies may further confirm an autoimmune type diabetes, especially if the presentation is atypical
Atypical type 1 diabetes presentations may include patients over 40 years old with no family history of diabetes
Upon first diagnosis of type 1 diabetes, the patient may have their thyroid checked and be tested for other autoimmune diseases, due to the strong correlation with other autoimmune diseases
Type 1 Diabetes Treatment
The treatment and management of type 1 diabetes involves the following:
Education
Insulin
Careful Glucose Monitoring
Some patients who have diabetes that is difficult to control may be referred for islet cell or pancreas transplants.
1. Education
Patient education is an important part of managing type 1 diabetes.
As previously mentioned, the pancreas produces little to no insulin in type 1 diabetes (see above).
As a result, patients with type 1 diabetes must take insulin so glucose can be transported from the blood and into cells.
Not only does the patient need to take insulin, but they must know how much.
This requires education.
Patients require an understanding of carbohydrates and glucose, so they know how much insulin they will require with meals and/or throughout the day.
Patients will be offered educational programs where they are trained on carbohydrate counting to allow self-management of their diabetes.
The training will allow the patient to independently calculate and inject the correct amount of insulin for their meal, as well as provide corrective doses if required.
Due to the increased cardiovascular risk associated with type 1 diabetes, the educational programs may also offer dietary, exercise, and lifestyle advice.
Annual reviews will also offer guidance (see annual review below).
2. Insulin
Insulin therapy is the main treatment for type 1 diabetes.
This makes sense as the pancreas is unable to produce insulin.
There are different types of insulin that can be administered, and they vary on their onset, peak, and duration.
Onset = How quickly insulin lowers blood sugar
Peak = When insulin is at maximum strength
Duration = How long insulin works to lower blood sugar
The main types of insulin include:
Rapid-Acting
insulin aspart (NovoLog), insulin lispro (Humalog)
Short-Acting
human regular (Humulin R)
Intermediate-Acting
NPH (Humulin N)
Long-Acting
detemir (Levemir), glargine (Lantus)
Ultra-Long Acting
glargine U-300
**Premixed insulin is also available, which combines intermediate and short-acting insulin.
Type 1 Diabetes Treatment: Chart showing types of insulin (rapid acting, short acting, intermediate acting, long acting, ultra-long acting) and their onset, peak, and duration.
Patients will be offered basal-bolus insulin regimens when first diagnosed.
Basal-bolus regimens involve multiple daily injections of a rapid or short acting bolus insulin administered before meals, and an intermediate or long acting insulin injection once or twice daily.
A combination of different length preparations are given in this regimen in order to mimic the normal physiological insulin release, and to maintain a stable glycemic (blood glucose) level throughout the day.
Insulin is administered subcutaneously typically in the:
Abdomen
Outer Thigh
Back of the Upper Arm
Hip
Upper Buttocks
Patients should be provided with a sharps bin to collect the used needles and related sharps.
The site of injection should be rotated regularly in order to prevent breakdown of fat beneath the skin (lipodystrophy/lipoatrophy).
Some patients prefer to use an insulin pump, allowing a continuous infusion of basal insulin, and bolus doses released at meal times, controlled by the patient.
3. Glucose Monitoring
It is important to monitor blood glucose levels to make sure they are appropriately managed.
Hemoglobin A1C
Hemoglobin A1C (HbA1c) levels should be measured by primary care staff every 3 to 6 months.
As previously mentioned, HbA1c is a simple blood test that measures the patient’s average blood sugar levels over the past 2-3 months (8-12 weeks).
A patient with type 1 diabetes should aim for a HbA1c of 6.5% (48 mmol/mol) or lower, in order to decrease the risk of cardiovascular disease, retinopathy, renal disease, etc.
Self-Monitoring
Patients are also expected to self-monitor their blood glucose levels.
This can be done in a variety of ways including:
Capillary glucose testing
Real time continuous glucose monitoring
Intermittently scanned continuous glucose monitoring (flash monitoring)
Capillary Blood Glucose Testing
Capillary blood glucose testing is a way to self-monitor blood glucose levels.
It involves using a lancet to pinprick the finger in order to draw a small amount of blood onto a test strip.
The test strip can then be analyzed by a handheld glucose monitor.
Testing should be done at least 4 times a day (before each meal and before bed).
Testing may need to be done more frequently in times of illness, or if there are recurring episodes of hypoglycemia/hyperglycemia.
Real Time Continuous Glucose Monitoring and Intermittently Scanned Continuous Glucose Monitoring (Flash Monitoring)
Both real time and flash continuous glucose monitors allow the patient’s blood sugar to be checked by a small sensor, rather than by pin pricking the fingers.
The sensor is worn all day and night, and allows the blood sugar levels to be read on a bluetooth connected smartphone.
The real time monitor automatically syncs blood glucose readings to a mobile device throughout the day, whereas the flash device requires the phone to ‘scan’ a sensor on the skin to take the blood glucose reading.
Even with a continuous glucose monitor, the patient must still check their capillary glucose levels regularly to ensure their device recordings are accurate.
Blood Glucose Targets
Blood glucose targets are seen below:
Fasting glucose of 90-126 mg/dL (5-7 mmol/L)
Plasma glucose level of 72-126 mg/dL (4-7 mmol/L)
Aim for plasma glucose level of 90-162 mg/dL (5-9 mmol/L), 90 minutes after eating
Annual Review
Patients with diabetes in the UK will be invited to an “annual review” with a member of the multidisciplinary team at their primary care practice.
This will involve a full screen of the patient’s diabetic history, how they are managing their diabetes, and a full examination.
The examination will involve measuring the patient’s weight, abdominal circumference, and BMI (body mass index) to assess cardiovascular risk.
A full cardiovascular and peripheral vascular exam will also be completed, along with inspection of injection sites, the feet, and blood tests to check kidney function.
The patient must also be seen in a yearly eye clinic to check for diabetic retinopathy.
Urinalysis will also be done to check for ketones and glucose in the urine.
Sick Day Rules
A patient with type 1 diabetes must abide by what are known as “sick-day rules”.
Stress, such as acute illness, increases the level of cortisol produced and released by the adrenal glands.
This causes the blood glucose levels to increase without increased oral intake.
The patient must continue with their normal insulin regimen and check their blood sugar levels more frequently.
Ketones in the blood should also be checked, as there is an increased risk of diabetic ketoacidosis (DKA) when the patient is sick.
If the blood sugar is higher than expected when given their normal insulin dose, a corrective dose must be given.
Complications of Type 1 Diabetes
Complications of type 1 diabetes occur when blood glucose levels are not managed correctly.
Short Term Complications
Short term complications of type 1 diabetes include hypoglycemic and hyperglycemic episodes:
Hypoglycemic Episodes
Hypoglycemic episodes can occur as a result of:
Too much insulin is given for the meal that was eaten
Too much insulin was given in the setting of recent exercise
Exercise can increase insulin sensitivity
Less insulin may be needed
Hyperglycemic Episodes
Hyperglycemic episodes can occur as a result of:
Not enough insulin is given for the meal that was eaten
Non-compliance to the insulin regime
Diabetic Ketoacidosis (DKA)
When blood sugar levels are too high for too long
Leads to a buildup of ketones in the body
Leads to hyperglycemia and acidosis
Serious complication
Often requires hospital admission
Long Term Complications
Long term complications of uncontrolled type 1 diabetes can cause a range of microvascular and macrovascular complications including:
Microvascular (related to small blood vessels)
Small blood vessels can become damaged by the sustained inappropriately high blood sugar
This can lead to:
Diabetic Retinopathy (Eyes) - May cause loss of vision in both eyes
Diabetic Nephropathy (Kidneys) - May require dialysis
Diabetic Neuropathy (Nerves) - Diabetic peripheral neuropathy has a high mortality rate due to infection
Macrovascular (related to large blood vessels)
High blood sugar can cause plaque formation in blood vessels
This can increase the risk of:
Cardiovascular Disease
Heart Attack (Myocardial Infarction)
Stroke
Peripheral Vascular Disease (PVD)
Type 1 Diabetes Complications: Microvascular complications include diabetic retinopathy, nephropathy, and neuropathy. Macrovascular complications include cardiovascular disease, heart attack, stroke, and peripheral vascular disease (VD)
Type 1 Diabetes with Disordered Eating (T1DE)
It is worth being aware of the implications of a patient with type 1 diabetes withholding their insulin injections.
Type 1 diabetes with disordered eating (T1DE), also known as diabulimia, is an eating disorder in which patients with type 1 diabetes stop taking insulin in order to lose weight.
T1DE may also be associated with other eating disorder behaviors as well.
T1DE puts the patient at great risk of developing diabetic ketoacidosis and other diabetic complications described above.
Therefore, it is vital to identify patients with T1DE and provide the support they need.
Before You Go….
Leave a comment down below if you enjoyed the lecture!
SAVE TIME studying and PASS your classes - Get free lectures and videos sent right to your inbox below!
References: Oram R.; Understanding the Extremely Early Onset of Type 1 Diabetes; University of Exeter Medical School; Jan 2017 - March 2024; Accessed Feb 2023; https://www.diabetes.org.uk/research/our-research-projects/south-west/understanding-the-extremely-early-onset-of-type-1-diabetesFerri F.F.; Ferri’s Clinical Advisor 2023, E-Book; Elsevier Health Sciences; Last Updated 2022; Accessed Feb 2023; https://www.clinicalkey.com/student/content/book/3-s2.0-B9780323755733002687CDC; Living with Diabetes - Managing Sick Days; Centers for Disease Control and Prevention; Last Reviewed Feb 2022; Accessed Feb 2023; https://www.cdc.gov/diabetes/managing/flu-sick-days.htmlRad A., Osika A.; Pancreas; Kenhub; Last Reviewed July 2022; Accessed Feb 2023; https://www.kenhub.com/en/library/anatomy/the-pancreasSapra A., Bhandari P.; Diabetes Mellitus; NIH National Library of Medicine; National Center for Biotechnology Information; StatPearls Publishing; Last Updated June 2022; Accessed Feb 2023; https://www.ncbi.nlm.nih.gov/books/NBK551501/Nicholson E., May NG., Kar P.; Type 1 Diabetes; BMJ Best Practice; BMJ Publishing Group Ltd 2023; Last Updated Jul 2021; Accessed Feb 2023; https://bestpractice.bmj.com/topics/en-gb/25/history-exam#riskFactorsDiabetes UK; Type 1 Diabetes; Accessed Feb 2023; https://www.diabetes.org.uk/diabetes-the-basics/types-of-diabetes/type-1Diabetes UK; Technology and Diabetes; Accessed Feb 2023; https://www.diabetes.org.uk/guide-to-diabetes/diabetes-technologySmith-Marsh D., Zeller W.P.; Type 1 Diabetes Complications; Endocrineweb; Last Updated Jan 2017; Accessed Feb 2023; https://www.endocrineweb.com/conditions/type-1-diabetes/type-1-diabetes-complicationsDiabetes UK; Diabulimia and Diabetes; Accessed Feb 2023; https://www.diabetes.org.uk/guide-to-diabetes/life-with-diabetes/diabulimiaNICE; Diabetes - Type 1; NICE Clinical Knowledge Summaries (CKS); Last Updated Jan 2023; Accessed Feb 2023; https://cks.nice.org.uk/topics/diabetes-type-1/Johns Hopkins Medicine; The Pancreas; Accessed Feb 2023; https://www.hopkinsmedicine.org/health/conditions-and-diseases/the-pancreasAmerican Diabetes Association; Insulin Basics; Accessed Feb 2023; https://diabetes.org/healthy-living/medication-treatments/insulin-other-injectables/insulin-basicsCDC; Types of Insulin; Centers for Disease Control and Prevention; Last Reviewed Dec 2022; Accessed Feb 2023; https://www.cdc.gov/diabetes/basics/type-1-types-of-insulin.html