Double Diabetes- Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Diabetes is a global epidemic affecting the health of at least millions of people. The co-existence of type 1 and type 2 diabetes is termed double diabetes. In this condition, an individual (especially children and young adults) with type 1 diabetes mellitus develops insulin resistance. Double diabetes is prevalent and almost synonymous with obesity and excess body weight in children and young adults. This complex metabolic condition presents symptoms of type 1 and type 2 diabetes mellitus. It is tricky to diagnose double diabetes, and newer treatment regimens are being formulated to manage the condition. It is necessary to develop universal diagnostic criteria to make it easier to recognize double diabetes at the initiation of hyperglycemia or later in the disease process.

What Is Diabetes?

Diabetes (diabetes mellitus) is a group of several metabolic disorders with characteristic clinical findings of high sugar levels in the blood for a long period. The bio reference range of blood sugar levels in the case of diabetes is; fasting blood glucose of more than 125 mg/dl, random plasma glucose of more than 200 mg/dl, and HbA1c of more than 6.5 %. In a survey conducted in the year 2017, approximately 425 million people were reported to be suffering from diabetes globally.

According to a WHO (World Health Organization) report, diabetes is the eighth leading cause of death. Primarily, diabetes is either caused due to insufficient production of the hormone insulin by the pancreas or the inability of the body's cells to respond to insulin. Based on the cause, diabetes is of two types; type 1 diabetes mellitus, and type 2 diabetes mellitus.

• Type 1 Diabetes: This type of diabetes occurs due to the loss of beta cells of the pancreatic islets leading to insufficient insulin production by the pancreas. It was earlier known as insulin-dependent diabetes or juvenile diabetes. The primary cause of type 1 diabetes mellitus is the loss of beta cells of the pancreatic islets due to the autoimmune response of the body (when the body’s immune system starts attacking healthy cells), and the cause of this autoimmune response is unknown. The disease can begin during early childhood, teenage, or adulthood.

• Type 2 Diabetes: Type 2 diabetes mellitus occurs due to a pathological condition in which the body cells fail to respond to the insulin produced by the pancreas. This inability to respond to insulin is called insulin resistance. Type 2 diabetes develops due to insulin resistance and secretory defects. Earlier, this type of diabetes was also referred to as non-insulin-dependent diabetes or adult-onset diabetes. The primary cause of this condition is an unhealthy lifestyle, including excess body weight, lack of physical exercise, and unhealthy eating habits. The age of onset is generally adulthood, but it has also been reported in obese children.

What Is Double Diabetes?

Double diabetes is a type of type 1 diabetes mellitus or a third type of diabetes mellitus in which insulin deficiency and insulin resistance co-exist. The condition affects individuals with type 1 diabetes; when they become obese, they develop insulin resistance. The increasing number of cases of obesity and diabetes in children has given rise to this new type of diabetes known as double diabetes or hybrid diabetes.

Is Double Diabetes a Common Condition?

• The exact rate of incidence of double diabetes is unknown; therefore, determining whether the condition is common or rare is also very tricky.

• An old study suggested that individuals with type 1 diabetes have a four percent chance of developing type 2 diabetes as well.

• 25 % of children with type 1 diabetes are obese, which throws them at risk of developing type 2 diabetes or insulin resistance.

• Type 1 diabetics also exhibit macrovascular complications like heart disease, stroke, etc.

• Double diabetes is equally prevalent in men and women, with a slight inclination towards men.

What Causes Double Diabetes?

Diabetes, which includes double diabetes, is not a simple and single clinical entity but rather a complex mix of metabolic disease characteristics. The development of type 1 diabetes and type 2 diabetes is affected by hereditary, environmental, and behavioral variables, resulting in double diabetes. The various factors causing double diabetes are:

• Genetic Factors: It is thought that the major genes that are independently associated with either type 1 diabetes or type 2 diabetes can act as genetic determinants for double diabetes, reducing the frequency of the major type 1 diabetes susceptibility gene while increasing the expression of type 2 diabetes genes. Several genes have been identified as having the potential to cause double diabetes by altering the mechanisms involved in both type 1 diabetes and type 2 diabetes. One of these genes, which is caused by a genetic variation in the insulin receptor substrate, is involved in insulin resistance, which is a critical component of type 2 diabetes, as well as programmed cell death, which is linked to type 1 diabetes.

• Environmental Factors: The increasing rate of obesity in children and adults is a matter of concern because it also increases the risk of several metabolic diseases along with the risk of developing type 2 diabetes (including individuals with pre-existing type 1 diabetes). A study suggested that 12.6 % of children and young adults in the united states with type 1 diabetes are also obese. Some children with type 1 diabetes have either a first-degree or second-degree relative with type 2 diabetes. “Western” food habits, along with a sedentary lifestyle, lack of physical exercise, and several other environmental factors, contribute to the development of insulin resistance in patients with type 1 diabetes.

What Are the Signs and Symptoms of Double Diabetes?

Patients with double diabetes exhibit typical symptoms of diabetes.

Symptoms of type 1 diabetes:

• Frequent urination (polyuria).

• Excessive thirst (polydipsia).

• The excessive urge to eat (polyphagia).

• Obesity and excess body weight.

• Acanthosis nigricans (a skin condition characterized by black discoloration in the folds and creases of the body).

Symptoms of type 2 diabetes:

• Excessive weight loss.

• Presence of ketosis (raised levels of ketone bodies in the tissues).

• Diabetes-associated autoantibodies will be present.

Symptoms of double diabetes in children and adults with pre-existing type 1 diabetes:

• Patients are overweight.

• Patients will require a high dose of insulin to control their blood sugar levels.

• Hypertension or increased blood pressure.

• Presence of fat in the blood (dyslipidemia).

• Diabetes is either uncontrolled or poorly controlled.

• Polycystic ovarian syndrome in women.

Symptoms of double diabetes in children and adults with pre-existing type 2 diabetes:

• Increased autoimmune load.

• Excess body weight.

• High blood pressure.

• Acanthosis nigricans (black discoloration in the folds of the skin)

• Dyslipidemia (the presence of fat in the blood).

• Polycystic ovarian syndrome (a hormonal disorder prevalent in women of reproductive age).

How Is Double Diabetes Diagnosed?

The diagnosis of double diabetes is made in the following ways:

• Plasma Glucose: A random plasma glucose concentration above 200 mg/dL confirms high blood sugar levels and suggests diabetes mellitus.

• Hemoglobin A: Hemoglobin A or HBA1C test determines and estimates the plasma glucose levels of the past three months. HbA1c is a product of non-enzymatic irreversible glycation of the beta chain of hemoglobin by increased plasma glucose concentrations. The normal range of HbA1C is; that levels below 5.7 % are considered normal, between 5.7 % to 6.4 % is considered prediabetes, and any level above 6.5 % confirms the diagnosis of diabetes mellitus. This test also helps in evaluating the progression of microvascular complications of diabetes (retinopathy, neuropathy, and nephropathy).

• Other Laboratory Tests: These include fructosamine testing, white blood cell count, and blood and urine cultures.

• Tests to Differentiate: To help distinguish between the two types of diabetes in children, doctors should measure insulin levels and c-peptide levels and immune markers such as glutamic acid decarboxylase and autoantibodies. In addition, a detailed family history of the patient should be taken. C-peptides are produced in the pancreas along with insulin, and they are formed during the conversion of proinsulin into insulin. A c-peptide level less than 5 µU/mL confirms type 1 diabetes, whereas a fasting C-peptide level above 1 ng/dL in a patient who has had diabetes for one to two years confirms the diagnosis of type 2 diabetes. Measuring islet cell autoantibodies within six months of diagnosis can help in differentiating between type 1 and type 2 diabetes.

What Is the Treatment for Double Diabetes?

• There is no definitive therapeutic regimen formulated for double diabetes because of the complex nature of the condition.

• Since insulin resistance is the primary causative factor of double diabetes, management of this type of diabetes involves the addition of insulin sensitizers to the management regimen.

• In addition, lifestyle modifications like weight loss, healthy eating habits, and regular exercise are also encouraged.

• Because individuals with double diabetes require higher insulin doses to maintain normal blood sugar levels, an insulin titration regimen that ensures sufficient glycemic control is required.

• Increased insulin resistance and poor glycemic control create a need for alternative therapeutic methods to treat double diabetes. Drugs like Metformin and Biguanide increase the sensitivity of insulin, especially in the liver.

• Patients with double diabetes are generally obese, and the resulting insulin resistance raises their insulin demands. Along with the requirement of high insulin doses, data suggest that many patients' insulin doses are not titrated enough to attain target glucose control levels. Therefore, there is a need for a proper insulin titration regimen to control double diabetes. Titration refers to a method of determining the amount of a specific substance (insulin) in a liquid by calculating the amount of another substance needed to react with it.

Conclusion:

The co-existence of type 1 and type 2 diabetes increases the risk of complicating both types. Therefore, individuals with double diabetes are at a higher risk of developing microvascular and macrovascular complications of diabetes. Double diabetes, like type 2 diabetes, can become more severe over time if not managed correctly. If double diabetes is allowed to progress, more insulin will be required, causing weight gain and increasing the body's resistance to insulin, necessitating even more insulin. However, adopting an effective therapeutic regimen along with lifestyle modifications can help in maintaining a normal blood sugar level along with preventing further complications.