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» Home » CAD » Endocrinology » Diabetes Mellitus » Diabetes Mellitus Type 2
Background
Diabetes mellitus Type 2 is a chronic metabolic disorder characterized by hyperglycemia resulting from the body’s inability to properly use insulin, known as insulin resistance, and insufficient insulin secretion from pancreatic beta cells. This type of diabetes is the most common form, accounting for approximately 90-95% of all cases of diabetes worldwide.
It is a major global health problem that significantly impacts morbidity, mortality, and healthcare costs. The prevalence of type 2 diabetes mellitus is increasing globally, and it is estimated that by 2045, there will be 700 million people affected by this disease. It is more common in adults, particularly those who are overweight or obese, have a family history of diabetes, and lead a sedentary lifestyle.
Type 2 diabetes mellitus is also more prevalent in certain ethnic groups, including African Americans, Hispanics/Latinos, Native Americans, and Asians. The long-term complications of type 2 diabetes mellitus can be severe and include microvascular complications such as retinopathy, nephropathy, and neuropathy, as well as macrovascular complications such as cardiovascular disease, stroke, and peripheral vascular disease.
Epidemiology
Prevalence: T2DM is one of the most prevalent chronic diseases worldwide, affecting an estimated 463 million adults aged 20-79 years in 2019. The prevalence of T2DM is expected to rise to 578 million by 2030 and 700 million by 2045 if current trends continue.
Age: The risk of T2DM increases with age. T2DM is most diagnosed in individuals aged 45-64 years, although the disease is increasingly affecting younger individuals.
Gender: T2DM affects men and women equally.
Ethnicity: Certain ethnic groups have a higher prevalence of T2DM, including South Asians, African Americans, Hispanics, and Native Americans.
Family History: Having a family history of T2DM is a significant risk factor for the disease.
Obesity: It is a major risk factor for T2DM, and the prevalence of T2DM is increasing in parallel with the global obesity epidemic.
Physical Inactivity: Physical inactivity is a significant risk factor for T2DM, with inactive individuals having a 30-50% higher risk of developing T2DM than active individuals.
Anatomy
Pathophysiology
Insulin Resistance: Insulin resistance is the primary defect in T2DM, and it refers to the inability of the peripheral tissues, such as muscle, liver, and adipose tissue, to respond to insulin. Insulin resistance leads to decreased glucose uptake by the muscles and liver, leading to hyperglycemia.
Beta-Cell Dysfunction: Beta-cell dysfunction occurs due to a decrease in beta-cell mass and function, leading to inadequate insulin secretion in response to glucose, which further contributes to hyperglycemia.
Increased Hepatic Glucose Production: Hepatic glucose production is increased due to increased gluconeogenesis and glycogenolysis, leading to increased glucose levels in the bloodstream.
Increased Lipolysis and Free Fatty Acid Release: In T2DM, there is increased lipolysis and free fatty acid release from adipose tissue, which leads to insulin resistance and increased hepatic glucose production.
Inflammatory Cytokines: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are elevated in T2DM, contributing to insulin resistance and beta-cell dysfunction.
Genetic Factors: There is a strong genetic component to T2DM, with several genes implicated in the pathogenesis of the disease.
Etiology
Genetics: Family history and certain genes are associated with an increased risk of developing type 2 diabetes.
Obesity: Being overweight or obese, especially with excess abdominal fat, can increase the risk of type 2 diabetes.
Physical Inactivity: Lack of physical activity may have an increased risk of developing type 2 diabetes.
Insulin Resistance: Insulin resistance, which is the body’s inability to respond properly to insulin, is a key factor in the development of type 2 diabetes.
Abnormal Glucose Production by the Liver: The liver may produce too much glucose, contributing to high blood sugar levels.
Beta-Cell Dysfunction: In type 2 diabetes, the beta cells in the pancreas that produce insulin become dysfunctional, resulting in insufficient insulin secretion.
Age: There ia an increased risk of developing type 2 diabetes with age.
Race and Ethnicity: Certain ethnic groups, including African Americans, Hispanic/Latinos, and Native Americans, have a higher risk of diabetes type 2.
Gestational Diabetes: Women with gestational diabetes during pregnancy have an increased risk of developing type 2 diabetes later in life.
Genetics
Prognostic Factors
Glycemic Control: Good glycemic control is essential for the prevention of complications associated with diabetes. HbA1c levels should be maintained below 7% to reduce the risk of microvascular complications.
Age: Older patients with type 2 diabetes are at a higher risk of developing complications such as cardiovascular disease, neuropathy, and retinopathy.
Duration of Diabetes: The longer the duration of diabetes, the greater the risk of developing complications.
Blood Pressure: High blood pressure is a significant risk factor for complications associated with diabetes, including cardiovascular disease and diabetic nephropathy.
Lipid Profile: Abnormal lipid profiles, including high LDL cholesterol, low HDL cholesterol, and elevated triglycerides, increase the risk of cardiovascular disease in patients with type 2 diabetes.
Body Mass Index (BMI): Obesity is a significant risk factor for the development of type 2 diabetes, and higher BMI is associated with a higher risk of complications.
Smoking: Smoking is a risk factor for the development of complications associated with diabetes, including cardiovascular disease and neuropathy.
Renal Function: Diabetic nephropathy is a common complication of type 2 diabetes, and patients with impaired renal function are at a higher risk of developing this complication.
Retinopathy: Diabetic retinopathy is a one of the common complications of type 2 diabetes, and patients with this complication are at a higher risk of developing other complications.
Clinical History
CLINICAL HISTORY
Age group: Diabetes mellitus can affect people of all ages, but the incidence and prevalence of the disease increase with age. Type 2 DM is more common in adults over 45 years of age, while type 1 diabetes is more commonly diagnosed in children and young adults. Gestational diabetes is typically diagnosed in pregnant women.
Physical Examination
PHYSICAL EXAMINATION
Physical examination is an essential component of the assessment of patients with type 2 diabetes mellitus. The following are some of the key aspects that should be considered during a physical examination:
Blood pressure measurement: Hypertension is a common comorbidity in patients with type 2 diabetes. Blood pressure measurement should be performed in both arms, and an average of two or more readings should be taken.
Body weight and height measurement: BMI (Body mass index) calculation should be performed.
Examination of the skin: Skin examination is important for detecting signs of insulin resistance, such as acanthosis nigricans, a skin condition characterized by dark, velvety patches in body folds and creases.
Neurological examination: Peripheral neuropathy is a common complication of type 2 diabetes. Neurological examination should be performed to detect signs of peripheral neuropathy such as loss of sensation, reduced reflexes, and muscle weakness.
Foot examination: Foot examination is important in patients with type 2 diabetes to detect signs of diabetic foot, such as neuropathic ulcers, infections, and Charcot arthropathy.
Eye examination: Eye examination is essential for detecting diabetic retinopathy, a complication of type 2 diabetes that affects the blood vessels in the retina.
Cardiac examination: Cardiac examination is important for detecting signs of cardiovascular disease, which is a major cause of morbidity and mortality in patients with type 2 diabetes.
Kidney examination: Kidney examination should be performed to detect signs of diabetic nephropathy, a complication of type 2 diabetes that affects the kidneys.
Respiratory examination: Respiratory examination is important for detecting signs of respiratory infections that are more common in patients with type 2 diabetes.
Examination of the abdomen: Examination of the abdomen can help detect signs of diabetic gastroparesis, a complication of type 2 diabetes that affects the digestive system.
Age group
Associated comorbidity
Associated comorbidity or activity:
Diabetes mellitus is associated with many comorbidities, such as cardiovascular disease, neuropathy, nephropathy, retinopathy, and foot ulcers. People with DM are also at higher risk of infections, particularly those affecting the skin and urinary tract. Sedentary lifestyle, poor diet, and obesity are common risk factors for type 2 diabetes.
Associated activity
Acuity of presentation
Acuity of presentation:
The onset of symptoms in type 1 diabetes is usually acute, with symptoms such as increased thirst, frequent urination, weight loss, and fatigue developing over a few weeks. In contrast, type 2 diabetes may have a more insidious onset, with symptoms developing over months or years.
Some people with type 2 diabetes may be asymptomatic at the time of diagnosis, and the disease may be detected during routine screening. In gestational diabetes, symptoms may be mild or absent, and the condition is often diagnosed through screening tests during pregnancy.
Differential Diagnoses
DIFFERENTIAL DIAGNOSIS
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Modification of Environment:
Diet modification: Patients with diabetes mellitus are advised to follow a balanced diet with a restricted intake of carbohydrates, saturated and trans fats, and cholesterol. They are encouraged to consume fiber-rich foods, fresh fruits and vegetables, and whole grains.
Physical activity: Regular exercise helps in maintaining normal blood sugar levels, reducing insulin resistance, and preventing cardiovascular complications in patients with diabetes mellitus.
Administration of a Pharmaceutical Agent:
Oral hypoglycemic agents: These medications are used to lower blood glucose levels in patients with type 2 diabetes mellitus. Examples include metformin, sulfonylureas, meglitinides, DPP-4 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists.
Insulin therapy: Insulin is used in patients with type 1 diabetes mellitus and some patients with type 2 diabetes mellitus who are not able to control the blood sugar levels with oral medications.
Intervention with a Procedure:
Bariatric surgery: This procedure is recommended for patients with type 2 diabetes mellitus and obesity who are unable to control their blood sugar levels with diet and exercise, and oral medications.
Phase of Management:
Acute management: This phase involves the immediate treatment of hyperglycemia, hypoglycemia, and diabetic ketoacidosis.
Long-term management: This phase involves the long-term control of blood glucose levels and prevention of complications through lifestyle modifications, medication management, and regular monitoring of blood glucose levels.
Preventive management: This phase involves the prevention of complications in patients with diabetes mellitus through regular monitoring and management of blood pressure, lipids, kidney function, and eye and foot exams. Vaccinations for flu and pneumonia are also recommended for diabetic patients to prevent infections that can worsen the condition.
by Stage
by Modality
Chemotherapy
Radiation Therapy
Surgical Interventions
Hormone Therapy
Immunotherapy
Hyperthermia
Photodynamic Therapy
Stem Cell Transplant
Targeted Therapy
Palliative Care
Medication
insulin degludec/insulin aspart
10
units
Solution
Subcutaneous (SC)
daily once
Changing to Premix Insulin Twice Daily or Once Daily
Same unit dose and schedule as the premix or self-mix insulin
Changing to Twice Daily or Once Daily Basal Insulin
The same dosage units as the basal insulin once or twice a day
In individuals with type 2 diabetes mellitus, it is recommended as a supplement to diet and exercise to improve glycemic control
20
mg
Tablet
Orally
every morning
250mg to 2g orally daily or can be administered twice or thrice daily
Do not exceed 3g per day
Maintenance doses of more than two g/day are rarely necessary
Immediate release
Initial dose: 500 mg orally twice or 850 mg orally once daily
Increase 500 mg weekly or 850 mg every 2 weeks as tolerated
Maintenance dose: 2000 mg/day in divided doses
Maximum dose: 2550 mg/day
Take the immediate release dose 2-3 times daily with meals
In general, a lesser dose below 1500 mg/day shows little efficacy. And a dose more than 2000 mg/day are least tolerable
Extended release
Initial dose: 500 to 1000 mg orally once daily
Increment in 500 mg every week as tolerated
Do not exceed 2000 mg/day
Take the medication with evening meal
If the glycemic level is not controlled with 2000 mg once daily, divide the dosing to 1000 mg twice daily
Switch to immediate release product, even if the suitable level is not achieved
Take nateglinide as monotherapy, or in combination with metformin
120 mg orally every 8 hours
60 mg orally every 8 hours, if the patient is near to HbA1C
Take the dose before the meal (1-30 minutes)
The drug is not indicated in the treatment of patients with type 1 diabetes mellitus or diabetic ketoacidosis
If co-administered with insulin secretagogue, decrease the quantity of secretagogue
If co-administered with insulin, decrease the dose of insulin by 10-25%
If co-administered with strong CYP2C8 inhibitors, limit the maximum dose of pioglitazone to 10 mg each day
:
pioglitazone is indicated as a monotherapy or in combination with insulin/insulin secretagogues
Initially 15-30 mg orally each day with meals
Increase the dose by 15 mg, monitor carefully and do not increase the dose more than 45 mg per day
Also monitor the Alanine Transaminase level at the beginning of the treatment
Continue the check every month for 12 months, and then every 3 months thereafter
In the case of active liver disease, when ALT is more than 2.5 times the upper lower limit; do not initiate rosiglitazone
When co-administered with sulfonylurea, adjust the dose of sulfonylurea if blood glucose level decreases
:
Initially 4 mg orally each day or divided every 12 hours
Increase the dose after 8-12 weeks, if inadequate response is observed
May increase the dose to 8 mg orally each day or divided every 12 hours
Monitor the Alanine Transaminase level (ALT) before initiating the treatment every month for 12 months and then every 3 months thereafter
For immediate-release tablet-
40-80 mg orally once daily with breakfast
Dose Modification
Increase the dose by 40-80 mg every 1-4 weeks if required to establish glycemic goals
Maintenance dose- 40-160 mg/day
Do not exceed more than 320 mg/day
For a dose more than 160 mg/day, administer it in a couple of divided doses
For modified-release tablet-
Initially 30 mg once daily with breakfast
Dose Modification
Increase the dose by 30 mg every 1-4 weeks if required to establish glycemic goals
Maintenance dose- 30-60 mg/day
Do not exceed more than 120 mg/day
Immediate-release tablet
Initially, 5 mg orally each day
Increase the dose by 2.5 to 5 mg per day as required based on blood glucose response
Maintenance Range
2.5-20 mg orally each day, every 12 hours
Do not exceed more than 40 mg/day
Extended-release tablet
Initially, 5 mg orally each day with breakfast
Increase the dose by 2.5 to 5 mg per day as required based on blood glucose response
Maintenance Range
5-10 mg orally each day
Do not exceed more than 20 mg/day
If the dose is more than 15 mg, divide the oral dose in every 12 hours
If CrCl<50 ml/min, use the medicine cautiously
In the case of severe hepatic impairment, avoid the medication
:
Regular tablets-
Initially, 2.5 to 5 mg orally each day
Maintenance dose- 1.25-20 mg orally each day or every 12 hours
Do not exceed 20 mg/day
For a dose of more than 10 mg/day, consider administration every 12 hours
Micronized tablets-
Initially, 1.5-3 mg orally each day
Maintenance dose- 0.75-12 mg orally each day
Do not exceed more than 12 mg/day
Patients at risk towards hypoglycemia-
Initially 0.75 mg orally each day
Transfer of insulin therapy to glyburide-
Insulin<20 units, discontinue it and start over glyburide: 2.5-5 mg/day and 1.5-3 mg/day for regular and micronized tablets respectively
Insulin 20-40 units, discontinue it and start over glyburide: 5 mg/day and 3 mg/day for regular and micronized tablets respectively
Insulin >40 units, decrease its dose and start over glyburide: 5 mg/day and 3 mg/day for regular and micronized tablets respectively
Based on patients’ response, increase the dose of glyburide by 1.25-2.5 mg and 0.75-1.5 mg/day for regular and micronized tablets respectively
When administered in combination, reduce the dose of other insulin secretagogues or sulfonylurea
When administered with strong CYP450 3A4/5 inhibitors, do not exceed 2.5 mg orally each day
In the case of renal impairment-
when CrCl <50 mL/min, do not exceed more than 2.5 mg orally each day
In the case of renal failure, when hemodialysis is required, do not exceed the oral dose of more than 2.5 mg each day
:
2.5 to 5 mg orally each day
0.6 mg (Victoza) subcutaneously each day for 1 week
Increase to 1.2 mg each day after that
If an optimum glycemic level is not achieved increase the dose to 1.8 mg each day
0.6 mg initial dose subcutaneously is only
100 mg orally each day
Indicated as an addition diet and exercise. It helps in improving glycemic control in people with type 2 diabetes
Dose Modifications
In the case of renal impairment-
when eGFR is in the range of 45 to 90 mL/min/1.73 m2 no dose adjustment is required
when eGFR is in the range of 30 to 45 mL/min/1.73 m2 50 mg orally each day
when eGFR is less than 30 mL/min/1.73 m2 25 mg orally each day
Last stage of renal failure, requiring hemodialysis/peritoneal dialysis, 25 mg orally each day
In the case of hepatic impairment, no dose adjustment is required.
Limitations
sitagliptin should not be administered to patients with type I diabetes
No dose adjustment is required in the case of linagliptin:
linagliptin is indicated for patients with diabetes mellitus type 2, along with exercise and diet to reduce the blood glucose level. It may be utilized as monotherapy or combined with other antidiabetic medications like sulfonylurea, metformin, insulin, or pioglitazone
5 mg orally each day
linagliptin should not be administered to patients with type I diabetes. It is also not meant for diabetic ketoacidosis
100 mg orally once daily. Take medicine before breakfast
Increase to 300 mg orally each day if required
If a patient can tolerate 100 mg/day and have a rate of eGFR ≥60 mL/min/1.73 m²
The drug is indicated in addition to exercise and diet. It helps improve the blood glucose level in type 2 diabetes mellitus
Dosage Modifications
In the case of renal impairment
When eGFR is more than 60 mL/min/1.73 m2 no dose adjustment is required
When eGFR ranges from 30 to 60 mL/min/1.73 m2 the dose is kept at 100 mg each day
When eGFR is less than 30 mL/min/1.73 m2 with albuminuria that is more than 300 mg/day, 100 mg dose each day for the reduction of risk of various conditions. These conditions may include end-stage kidney disease, cardiovascular death, doubling of serum creatinine level, and hospitalization for heart failure
When eGFR is less than 30 mL/min/1.73 m2, drug initiation is not recommended
5 mg orally once daily to improve the glycemic control
May increase the dose to 10 mg once daily for an additional effect, if the lower dose is tolerated
In the case of hepatic impairment, no dose adjustment is required
The drug is contraindicated in patients undergoing dialysis
The dose is decreased to 25 mg/day in case of worsen kidney condition
:
Dose is indicated in addition to exercise and diet to maintain the glycemic level in type 2 diabetic adults
It also reduces the risk of cardiovascular death in diabetic patients
10 mg orally once daily
Increase to 25 mg orally each day if required
insulin degludec shows no clinical differences in the pharmacokinetics. The comparison was done on the healthy subjects and the patients with renal and hepatic impairment
Dosing Consideration
Use the drug cautiously in patients with visual disturbance
Start off dose for insulin degludec should be same as the total daily dose or insulin unit dose (intermediate-acting)
Not indicated for the patients with di:
10 units subcutaneously each day
0.2 units/kg subcutaneously each day, increase the dose as required
Dose should be administered if there is increased risk of hypoglycemia due to co-administration of drugs
In the case of hepatic and renal impairment, risk of hypoglycemia is increased due to the drug
:
Intermediate/Long-acting insulin-
Subcutaneously, 10 units each day (generally at bedtime) to be injected
Rapid/Short-acting insulin- Start with 4 units, 0.1 unit/kg subcutaneously, 15 minutes before every meal or 10% of the basal dose
If A1C is less than 8%, decrease the dose of basal insulin by same amount
Increase the dose by a couple of units or 10-15% each week/fortnight. For this blood glucose level can be monitored by oneself.
For intravenous dose- 0.05 to 1 unit/ml in NS. Closely monitor the serum potassium and blood glucose during administration
Starting dosage:
2.5
mg
Subcutaneous (SC)
once weekly
4
weeks
; increase to 5 mg after 4 weeks
if more glycemic control is required, increase 2.5 mg after at least 4 weeks on the present dose
do not exceed weekly 15 mg subcutaneously (SC) once
2 mg subcutaneously every week
Start therapy-
If starting Bydureon BCise, discontinue Byetta in the patients already taking it
Discontinue immediate/extended-release exenatide product if any
Initiate the next regular dose when transiting from another extended-release exenatide product to Bydureon BCise
Patients may experience a change in blood glucose concentration within 2-4 weeks
Weekly administration can be changed if required until the last dose gets administered more than 3 days before a new day of administration
IR tablet:
Take twice daily with meals
10 mg empagliflozin total daily dose; may be increased to 25mg for additional glycemic control and 2000 mg of metformin can be increased
Switching to Synjardy
Patients using metformin should switch to a tablet containing 5 mg of empagliflozin, while maintaining the same total daily dose (TDD) of metformin
those who use empagliflozin Change to a tablet containing 500 mg of metformin and a TDD corresponding to empagliflozin
Patients who have already received metformin and empagliflozin: Switch to a tablet that has the same combined daily dosages of all the ingredients
Extended-release tablet
10 mg empagliflozin total daily dose; may be increased to 25mg for additional glycemic control and 2000 mg of metformin can be increased
Switching to Synjardy XR
Patients on metformin should switch to the XR tablet, which has a comparable TDD of metformin plus a 10 mg total daily dose of empagliflozin
Switch patients using empagliflozin to the XR tablet, which has the same TDD of empagliflozin and a TDD of metformin extended release 1000 mg
Change to an XR tablet that has the same TDD of empagliflozin and a similar TDD of metformin for patients who are already receiving treatment with these drugs
Initial dose-5mg orally in the morning daily
Maintenance doe-Can increase the dose up to 15mg every day.
50 mg of vildagliptin Orally given once or twice a day. Maximum dose is 100 mg/day
Take initial dose of 15 mg orally one time in a day prior to breakfast
insulin degludec/insulin aspart
10
units
Subcutaneous (SC)
daily once
<1 year: Not recommended
Changing to Premix Insulin Twice Daily or Once Daily
80% of the combined insulin dosage once daily
10
units
Solution
Subcutaneous (SC)
once a day
Not safe and efficacious for children less than 10 years
For more than 10 years (Victoza only)- 0.6 mg subcutaneously daily
1 week later- 0.6 mg each day. Increase the dose to 1.2 mg/day if additional glycemic level is desired
The dose is meant for children and adolescents less than 17 years
For less than 1 year, safety and efficacy are not seen
10 units subcutaneously each day
, Dosing Consideration
Not recommended for pediatrics who require a daily dose of insulin degludec less than 5 units
Not indicated for the patients with diabetic ketoacidosis
For more than 4-17 years- 0.8-1.2 unit/kg/day subcutaneously, during growth rush
Otherwise use normal adult dosing
Safety and efficacy are not seen in pediatrics
Not safe and efficacious for children less than 10 years
For more than 10 years- 2mg subcutaneously every week
Start therapy-
If starting Bydureon BCise, discontinue Byetta in the patients already taking it
Discontinue immediate/extended-release exenatide product if any
Initiate the next regular dose when transiting from another extended-release exenatide product to Bydureon BCise
Weekly administration can be changed if required until the last dose gets administered more than 3 days before a new day of administration
Age: <10 years
Safety and efficacy have not been established
Age: > 10 years
10 mg orally should be taken once every morning; increased to 25mg if required
Note:
The drug that has been approved as additions to diet and exercise for the treatment of type 2 diabetes in children aged 10 years and above
Age: <10 years
Safety and efficacy not established
Age: ≥10 years
IR tablet
Depending on the patient's current medication regimen, adjust the initial dose
Take orally twice daily with meals (i.e., divide the daily dose into 2 doses); gradually increase dosage to lessen metformin's gastrointestinal side effects
Keep track of efficacy and tolerability, and modify dosage as necessary so as not exceed over the total maximum daily dose of 25 mg of empagliflozin and 2,000 mg of metformin
In this type of condition, drug is given as monotherapy or combined with sulfonylureas
Initial dose- 25 mg orally every 8 hours with meals
Maintenance dose- 50 mg orally every 8 hours; increase the dose after 4-8 weeks
Do not increase the dose more than 100 mg orally every 8 hours
Immediate-release tablet
Initially, 2.5 mg orally each day, half an hour before breakfast
Increase the dose by 2.5 to 5 mg per day every one or the other week based on blood glucose response
Do not increase the dose to more than 20 mg/day
Future Trends
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» Home » CAD » Endocrinology » Diabetes Mellitus » Diabetes Mellitus Type 2
Diabetes mellitus Type 2 is a chronic metabolic disorder characterized by hyperglycemia resulting from the body’s inability to properly use insulin, known as insulin resistance, and insufficient insulin secretion from pancreatic beta cells. This type of diabetes is the most common form, accounting for approximately 90-95% of all cases of diabetes worldwide.
It is a major global health problem that significantly impacts morbidity, mortality, and healthcare costs. The prevalence of type 2 diabetes mellitus is increasing globally, and it is estimated that by 2045, there will be 700 million people affected by this disease. It is more common in adults, particularly those who are overweight or obese, have a family history of diabetes, and lead a sedentary lifestyle.
Type 2 diabetes mellitus is also more prevalent in certain ethnic groups, including African Americans, Hispanics/Latinos, Native Americans, and Asians. The long-term complications of type 2 diabetes mellitus can be severe and include microvascular complications such as retinopathy, nephropathy, and neuropathy, as well as macrovascular complications such as cardiovascular disease, stroke, and peripheral vascular disease.
Prevalence: T2DM is one of the most prevalent chronic diseases worldwide, affecting an estimated 463 million adults aged 20-79 years in 2019. The prevalence of T2DM is expected to rise to 578 million by 2030 and 700 million by 2045 if current trends continue.
Age: The risk of T2DM increases with age. T2DM is most diagnosed in individuals aged 45-64 years, although the disease is increasingly affecting younger individuals.
Gender: T2DM affects men and women equally.
Ethnicity: Certain ethnic groups have a higher prevalence of T2DM, including South Asians, African Americans, Hispanics, and Native Americans.
Family History: Having a family history of T2DM is a significant risk factor for the disease.
Obesity: It is a major risk factor for T2DM, and the prevalence of T2DM is increasing in parallel with the global obesity epidemic.
Physical Inactivity: Physical inactivity is a significant risk factor for T2DM, with inactive individuals having a 30-50% higher risk of developing T2DM than active individuals.
Insulin Resistance: Insulin resistance is the primary defect in T2DM, and it refers to the inability of the peripheral tissues, such as muscle, liver, and adipose tissue, to respond to insulin. Insulin resistance leads to decreased glucose uptake by the muscles and liver, leading to hyperglycemia.
Beta-Cell Dysfunction: Beta-cell dysfunction occurs due to a decrease in beta-cell mass and function, leading to inadequate insulin secretion in response to glucose, which further contributes to hyperglycemia.
Increased Hepatic Glucose Production: Hepatic glucose production is increased due to increased gluconeogenesis and glycogenolysis, leading to increased glucose levels in the bloodstream.
Increased Lipolysis and Free Fatty Acid Release: In T2DM, there is increased lipolysis and free fatty acid release from adipose tissue, which leads to insulin resistance and increased hepatic glucose production.
Inflammatory Cytokines: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are elevated in T2DM, contributing to insulin resistance and beta-cell dysfunction.
Genetic Factors: There is a strong genetic component to T2DM, with several genes implicated in the pathogenesis of the disease.
Genetics: Family history and certain genes are associated with an increased risk of developing type 2 diabetes.
Obesity: Being overweight or obese, especially with excess abdominal fat, can increase the risk of type 2 diabetes.
Physical Inactivity: Lack of physical activity may have an increased risk of developing type 2 diabetes.
Insulin Resistance: Insulin resistance, which is the body’s inability to respond properly to insulin, is a key factor in the development of type 2 diabetes.
Abnormal Glucose Production by the Liver: The liver may produce too much glucose, contributing to high blood sugar levels.
Beta-Cell Dysfunction: In type 2 diabetes, the beta cells in the pancreas that produce insulin become dysfunctional, resulting in insufficient insulin secretion.
Age: There ia an increased risk of developing type 2 diabetes with age.
Race and Ethnicity: Certain ethnic groups, including African Americans, Hispanic/Latinos, and Native Americans, have a higher risk of diabetes type 2.
Gestational Diabetes: Women with gestational diabetes during pregnancy have an increased risk of developing type 2 diabetes later in life.
Glycemic Control: Good glycemic control is essential for the prevention of complications associated with diabetes. HbA1c levels should be maintained below 7% to reduce the risk of microvascular complications.
Age: Older patients with type 2 diabetes are at a higher risk of developing complications such as cardiovascular disease, neuropathy, and retinopathy.
Duration of Diabetes: The longer the duration of diabetes, the greater the risk of developing complications.
Blood Pressure: High blood pressure is a significant risk factor for complications associated with diabetes, including cardiovascular disease and diabetic nephropathy.
Lipid Profile: Abnormal lipid profiles, including high LDL cholesterol, low HDL cholesterol, and elevated triglycerides, increase the risk of cardiovascular disease in patients with type 2 diabetes.
Body Mass Index (BMI): Obesity is a significant risk factor for the development of type 2 diabetes, and higher BMI is associated with a higher risk of complications.
Smoking: Smoking is a risk factor for the development of complications associated with diabetes, including cardiovascular disease and neuropathy.
Renal Function: Diabetic nephropathy is a common complication of type 2 diabetes, and patients with impaired renal function are at a higher risk of developing this complication.
Retinopathy: Diabetic retinopathy is a one of the common complications of type 2 diabetes, and patients with this complication are at a higher risk of developing other complications.
CLINICAL HISTORY
Age group: Diabetes mellitus can affect people of all ages, but the incidence and prevalence of the disease increase with age. Type 2 DM is more common in adults over 45 years of age, while type 1 diabetes is more commonly diagnosed in children and young adults. Gestational diabetes is typically diagnosed in pregnant women.
PHYSICAL EXAMINATION
Physical examination is an essential component of the assessment of patients with type 2 diabetes mellitus. The following are some of the key aspects that should be considered during a physical examination:
Blood pressure measurement: Hypertension is a common comorbidity in patients with type 2 diabetes. Blood pressure measurement should be performed in both arms, and an average of two or more readings should be taken.
Body weight and height measurement: BMI (Body mass index) calculation should be performed.
Examination of the skin: Skin examination is important for detecting signs of insulin resistance, such as acanthosis nigricans, a skin condition characterized by dark, velvety patches in body folds and creases.
Neurological examination: Peripheral neuropathy is a common complication of type 2 diabetes. Neurological examination should be performed to detect signs of peripheral neuropathy such as loss of sensation, reduced reflexes, and muscle weakness.
Foot examination: Foot examination is important in patients with type 2 diabetes to detect signs of diabetic foot, such as neuropathic ulcers, infections, and Charcot arthropathy.
Eye examination: Eye examination is essential for detecting diabetic retinopathy, a complication of type 2 diabetes that affects the blood vessels in the retina.
Cardiac examination: Cardiac examination is important for detecting signs of cardiovascular disease, which is a major cause of morbidity and mortality in patients with type 2 diabetes.
Kidney examination: Kidney examination should be performed to detect signs of diabetic nephropathy, a complication of type 2 diabetes that affects the kidneys.
Respiratory examination: Respiratory examination is important for detecting signs of respiratory infections that are more common in patients with type 2 diabetes.
Examination of the abdomen: Examination of the abdomen can help detect signs of diabetic gastroparesis, a complication of type 2 diabetes that affects the digestive system.
Associated comorbidity or activity:
Diabetes mellitus is associated with many comorbidities, such as cardiovascular disease, neuropathy, nephropathy, retinopathy, and foot ulcers. People with DM are also at higher risk of infections, particularly those affecting the skin and urinary tract. Sedentary lifestyle, poor diet, and obesity are common risk factors for type 2 diabetes.
Acuity of presentation:
The onset of symptoms in type 1 diabetes is usually acute, with symptoms such as increased thirst, frequent urination, weight loss, and fatigue developing over a few weeks. In contrast, type 2 diabetes may have a more insidious onset, with symptoms developing over months or years.
Some people with type 2 diabetes may be asymptomatic at the time of diagnosis, and the disease may be detected during routine screening. In gestational diabetes, symptoms may be mild or absent, and the condition is often diagnosed through screening tests during pregnancy.
DIFFERENTIAL DIAGNOSIS
Modification of Environment:
Diet modification: Patients with diabetes mellitus are advised to follow a balanced diet with a restricted intake of carbohydrates, saturated and trans fats, and cholesterol. They are encouraged to consume fiber-rich foods, fresh fruits and vegetables, and whole grains.
Physical activity: Regular exercise helps in maintaining normal blood sugar levels, reducing insulin resistance, and preventing cardiovascular complications in patients with diabetes mellitus.
Administration of a Pharmaceutical Agent:
Oral hypoglycemic agents: These medications are used to lower blood glucose levels in patients with type 2 diabetes mellitus. Examples include metformin, sulfonylureas, meglitinides, DPP-4 inhibitors, SGLT2 inhibitors, and GLP-1 receptor agonists.
Insulin therapy: Insulin is used in patients with type 1 diabetes mellitus and some patients with type 2 diabetes mellitus who are not able to control the blood sugar levels with oral medications.
Intervention with a Procedure:
Bariatric surgery: This procedure is recommended for patients with type 2 diabetes mellitus and obesity who are unable to control their blood sugar levels with diet and exercise, and oral medications.
Phase of Management:
Acute management: This phase involves the immediate treatment of hyperglycemia, hypoglycemia, and diabetic ketoacidosis.
Long-term management: This phase involves the long-term control of blood glucose levels and prevention of complications through lifestyle modifications, medication management, and regular monitoring of blood glucose levels.
Preventive management: This phase involves the prevention of complications in patients with diabetes mellitus through regular monitoring and management of blood pressure, lipids, kidney function, and eye and foot exams. Vaccinations for flu and pneumonia are also recommended for diabetic patients to prevent infections that can worsen the condition.
insulin degludec/insulin aspart
10
units
Solution
Subcutaneous (SC)
daily once
Changing to Premix Insulin Twice Daily or Once Daily
Same unit dose and schedule as the premix or self-mix insulin
Changing to Twice Daily or Once Daily Basal Insulin
The same dosage units as the basal insulin once or twice a day
In individuals with type 2 diabetes mellitus, it is recommended as a supplement to diet and exercise to improve glycemic control
20
mg
Tablet
Orally
every morning
250mg to 2g orally daily or can be administered twice or thrice daily
Do not exceed 3g per day
Maintenance doses of more than two g/day are rarely necessary
Immediate release
Initial dose: 500 mg orally twice or 850 mg orally once daily
Increase 500 mg weekly or 850 mg every 2 weeks as tolerated
Maintenance dose: 2000 mg/day in divided doses
Maximum dose: 2550 mg/day
Take the immediate release dose 2-3 times daily with meals
In general, a lesser dose below 1500 mg/day shows little efficacy. And a dose more than 2000 mg/day are least tolerable
Extended release
Initial dose: 500 to 1000 mg orally once daily
Increment in 500 mg every week as tolerated
Do not exceed 2000 mg/day
Take the medication with evening meal
If the glycemic level is not controlled with 2000 mg once daily, divide the dosing to 1000 mg twice daily
Switch to immediate release product, even if the suitable level is not achieved
Take nateglinide as monotherapy, or in combination with metformin
120 mg orally every 8 hours
60 mg orally every 8 hours, if the patient is near to HbA1C
Take the dose before the meal (1-30 minutes)
The drug is not indicated in the treatment of patients with type 1 diabetes mellitus or diabetic ketoacidosis
If co-administered with insulin secretagogue, decrease the quantity of secretagogue
If co-administered with insulin, decrease the dose of insulin by 10-25%
If co-administered with strong CYP2C8 inhibitors, limit the maximum dose of pioglitazone to 10 mg each day
:
pioglitazone is indicated as a monotherapy or in combination with insulin/insulin secretagogues
Initially 15-30 mg orally each day with meals
Increase the dose by 15 mg, monitor carefully and do not increase the dose more than 45 mg per day
Also monitor the Alanine Transaminase level at the beginning of the treatment
Continue the check every month for 12 months, and then every 3 months thereafter
In the case of active liver disease, when ALT is more than 2.5 times the upper lower limit; do not initiate rosiglitazone
When co-administered with sulfonylurea, adjust the dose of sulfonylurea if blood glucose level decreases
:
Initially 4 mg orally each day or divided every 12 hours
Increase the dose after 8-12 weeks, if inadequate response is observed
May increase the dose to 8 mg orally each day or divided every 12 hours
Monitor the Alanine Transaminase level (ALT) before initiating the treatment every month for 12 months and then every 3 months thereafter
For immediate-release tablet-
40-80 mg orally once daily with breakfast
Dose Modification
Increase the dose by 40-80 mg every 1-4 weeks if required to establish glycemic goals
Maintenance dose- 40-160 mg/day
Do not exceed more than 320 mg/day
For a dose more than 160 mg/day, administer it in a couple of divided doses
For modified-release tablet-
Initially 30 mg once daily with breakfast
Dose Modification
Increase the dose by 30 mg every 1-4 weeks if required to establish glycemic goals
Maintenance dose- 30-60 mg/day
Do not exceed more than 120 mg/day
Immediate-release tablet
Initially, 5 mg orally each day
Increase the dose by 2.5 to 5 mg per day as required based on blood glucose response
Maintenance Range
2.5-20 mg orally each day, every 12 hours
Do not exceed more than 40 mg/day
Extended-release tablet
Initially, 5 mg orally each day with breakfast
Increase the dose by 2.5 to 5 mg per day as required based on blood glucose response
Maintenance Range
5-10 mg orally each day
Do not exceed more than 20 mg/day
If the dose is more than 15 mg, divide the oral dose in every 12 hours
If CrCl<50 ml/min, use the medicine cautiously
In the case of severe hepatic impairment, avoid the medication
:
Regular tablets-
Initially, 2.5 to 5 mg orally each day
Maintenance dose- 1.25-20 mg orally each day or every 12 hours
Do not exceed 20 mg/day
For a dose of more than 10 mg/day, consider administration every 12 hours
Micronized tablets-
Initially, 1.5-3 mg orally each day
Maintenance dose- 0.75-12 mg orally each day
Do not exceed more than 12 mg/day
Patients at risk towards hypoglycemia-
Initially 0.75 mg orally each day
Transfer of insulin therapy to glyburide-
Insulin<20 units, discontinue it and start over glyburide: 2.5-5 mg/day and 1.5-3 mg/day for regular and micronized tablets respectively
Insulin 20-40 units, discontinue it and start over glyburide: 5 mg/day and 3 mg/day for regular and micronized tablets respectively
Insulin >40 units, decrease its dose and start over glyburide: 5 mg/day and 3 mg/day for regular and micronized tablets respectively
Based on patients’ response, increase the dose of glyburide by 1.25-2.5 mg and 0.75-1.5 mg/day for regular and micronized tablets respectively
When administered in combination, reduce the dose of other insulin secretagogues or sulfonylurea
When administered with strong CYP450 3A4/5 inhibitors, do not exceed 2.5 mg orally each day
In the case of renal impairment-
when CrCl <50 mL/min, do not exceed more than 2.5 mg orally each day
In the case of renal failure, when hemodialysis is required, do not exceed the oral dose of more than 2.5 mg each day
:
2.5 to 5 mg orally each day
0.6 mg (Victoza) subcutaneously each day for 1 week
Increase to 1.2 mg each day after that
If an optimum glycemic level is not achieved increase the dose to 1.8 mg each day
0.6 mg initial dose subcutaneously is only
100 mg orally each day
Indicated as an addition diet and exercise. It helps in improving glycemic control in people with type 2 diabetes
Dose Modifications
In the case of renal impairment-
when eGFR is in the range of 45 to 90 mL/min/1.73 m2 no dose adjustment is required
when eGFR is in the range of 30 to 45 mL/min/1.73 m2 50 mg orally each day
when eGFR is less than 30 mL/min/1.73 m2 25 mg orally each day
Last stage of renal failure, requiring hemodialysis/peritoneal dialysis, 25 mg orally each day
In the case of hepatic impairment, no dose adjustment is required.
Limitations
sitagliptin should not be administered to patients with type I diabetes
No dose adjustment is required in the case of linagliptin:
linagliptin is indicated for patients with diabetes mellitus type 2, along with exercise and diet to reduce the blood glucose level. It may be utilized as monotherapy or combined with other antidiabetic medications like sulfonylurea, metformin, insulin, or pioglitazone
5 mg orally each day
linagliptin should not be administered to patients with type I diabetes. It is also not meant for diabetic ketoacidosis
100 mg orally once daily. Take medicine before breakfast
Increase to 300 mg orally each day if required
If a patient can tolerate 100 mg/day and have a rate of eGFR ≥60 mL/min/1.73 m²
The drug is indicated in addition to exercise and diet. It helps improve the blood glucose level in type 2 diabetes mellitus
Dosage Modifications
In the case of renal impairment
When eGFR is more than 60 mL/min/1.73 m2 no dose adjustment is required
When eGFR ranges from 30 to 60 mL/min/1.73 m2 the dose is kept at 100 mg each day
When eGFR is less than 30 mL/min/1.73 m2 with albuminuria that is more than 300 mg/day, 100 mg dose each day for the reduction of risk of various conditions. These conditions may include end-stage kidney disease, cardiovascular death, doubling of serum creatinine level, and hospitalization for heart failure
When eGFR is less than 30 mL/min/1.73 m2, drug initiation is not recommended
5 mg orally once daily to improve the glycemic control
May increase the dose to 10 mg once daily for an additional effect, if the lower dose is tolerated
In the case of hepatic impairment, no dose adjustment is required
The drug is contraindicated in patients undergoing dialysis
The dose is decreased to 25 mg/day in case of worsen kidney condition
:
Dose is indicated in addition to exercise and diet to maintain the glycemic level in type 2 diabetic adults
It also reduces the risk of cardiovascular death in diabetic patients
10 mg orally once daily
Increase to 25 mg orally each day if required
insulin degludec shows no clinical differences in the pharmacokinetics. The comparison was done on the healthy subjects and the patients with renal and hepatic impairment
Dosing Consideration
Use the drug cautiously in patients with visual disturbance
Start off dose for insulin degludec should be same as the total daily dose or insulin unit dose (intermediate-acting)
Not indicated for the patients with di:
10 units subcutaneously each day
0.2 units/kg subcutaneously each day, increase the dose as required
Dose should be administered if there is increased risk of hypoglycemia due to co-administration of drugs
In the case of hepatic and renal impairment, risk of hypoglycemia is increased due to the drug
:
Intermediate/Long-acting insulin-
Subcutaneously, 10 units each day (generally at bedtime) to be injected
Rapid/Short-acting insulin- Start with 4 units, 0.1 unit/kg subcutaneously, 15 minutes before every meal or 10% of the basal dose
If A1C is less than 8%, decrease the dose of basal insulin by same amount
Increase the dose by a couple of units or 10-15% each week/fortnight. For this blood glucose level can be monitored by oneself.
For intravenous dose- 0.05 to 1 unit/ml in NS. Closely monitor the serum potassium and blood glucose during administration
Starting dosage:
2.5
mg
Subcutaneous (SC)
once weekly
4
weeks
; increase to 5 mg after 4 weeks
if more glycemic control is required, increase 2.5 mg after at least 4 weeks on the present dose
do not exceed weekly 15 mg subcutaneously (SC) once
2 mg subcutaneously every week
Start therapy-
If starting Bydureon BCise, discontinue Byetta in the patients already taking it
Discontinue immediate/extended-release exenatide product if any
Initiate the next regular dose when transiting from another extended-release exenatide product to Bydureon BCise
Patients may experience a change in blood glucose concentration within 2-4 weeks
Weekly administration can be changed if required until the last dose gets administered more than 3 days before a new day of administration
IR tablet:
Take twice daily with meals
10 mg empagliflozin total daily dose; may be increased to 25mg for additional glycemic control and 2000 mg of metformin can be increased
Switching to Synjardy
Patients using metformin should switch to a tablet containing 5 mg of empagliflozin, while maintaining the same total daily dose (TDD) of metformin
those who use empagliflozin Change to a tablet containing 500 mg of metformin and a TDD corresponding to empagliflozin
Patients who have already received metformin and empagliflozin: Switch to a tablet that has the same combined daily dosages of all the ingredients
Extended-release tablet
10 mg empagliflozin total daily dose; may be increased to 25mg for additional glycemic control and 2000 mg of metformin can be increased
Switching to Synjardy XR
Patients on metformin should switch to the XR tablet, which has a comparable TDD of metformin plus a 10 mg total daily dose of empagliflozin
Switch patients using empagliflozin to the XR tablet, which has the same TDD of empagliflozin and a TDD of metformin extended release 1000 mg
Change to an XR tablet that has the same TDD of empagliflozin and a similar TDD of metformin for patients who are already receiving treatment with these drugs
Initial dose-5mg orally in the morning daily
Maintenance doe-Can increase the dose up to 15mg every day.
50 mg of vildagliptin Orally given once or twice a day. Maximum dose is 100 mg/day
Take initial dose of 15 mg orally one time in a day prior to breakfast
insulin degludec/insulin aspart
10
units
Subcutaneous (SC)
daily once
<1 year: Not recommended
Changing to Premix Insulin Twice Daily or Once Daily
80% of the combined insulin dosage once daily
10
units
Solution
Subcutaneous (SC)
once a day
Not safe and efficacious for children less than 10 years
For more than 10 years (Victoza only)- 0.6 mg subcutaneously daily
1 week later- 0.6 mg each day. Increase the dose to 1.2 mg/day if additional glycemic level is desired
The dose is meant for children and adolescents less than 17 years
For less than 1 year, safety and efficacy are not seen
10 units subcutaneously each day
, Dosing Consideration
Not recommended for pediatrics who require a daily dose of insulin degludec less than 5 units
Not indicated for the patients with diabetic ketoacidosis
For more than 4-17 years- 0.8-1.2 unit/kg/day subcutaneously, during growth rush
Otherwise use normal adult dosing
Safety and efficacy are not seen in pediatrics
Not safe and efficacious for children less than 10 years
For more than 10 years- 2mg subcutaneously every week
Start therapy-
If starting Bydureon BCise, discontinue Byetta in the patients already taking it
Discontinue immediate/extended-release exenatide product if any
Initiate the next regular dose when transiting from another extended-release exenatide product to Bydureon BCise
Weekly administration can be changed if required until the last dose gets administered more than 3 days before a new day of administration
Age: <10 years
Safety and efficacy have not been established
Age: > 10 years
10 mg orally should be taken once every morning; increased to 25mg if required
Note:
The drug that has been approved as additions to diet and exercise for the treatment of type 2 diabetes in children aged 10 years and above
Age: <10 years
Safety and efficacy not established
Age: ≥10 years
IR tablet
Depending on the patient's current medication regimen, adjust the initial dose
Take orally twice daily with meals (i.e., divide the daily dose into 2 doses); gradually increase dosage to lessen metformin's gastrointestinal side effects
Keep track of efficacy and tolerability, and modify dosage as necessary so as not exceed over the total maximum daily dose of 25 mg of empagliflozin and 2,000 mg of metformin
In this type of condition, drug is given as monotherapy or combined with sulfonylureas
Initial dose- 25 mg orally every 8 hours with meals
Maintenance dose- 50 mg orally every 8 hours; increase the dose after 4-8 weeks
Do not increase the dose more than 100 mg orally every 8 hours
Immediate-release tablet
Initially, 2.5 mg orally each day, half an hour before breakfast
Increase the dose by 2.5 to 5 mg per day every one or the other week based on blood glucose response
Do not increase the dose to more than 20 mg/day
Diabetes mellitus Type 2 is a chronic metabolic disorder characterized by hyperglycemia resulting from the body’s inability to properly use insulin, known as insulin resistance, and insufficient insulin secretion from pancreatic beta cells. This type of diabetes is the most common form, accounting for approximately 90-95% of all cases of diabetes worldwide.
It is a major global health problem that significantly impacts morbidity, mortality, and healthcare costs. The prevalence of type 2 diabetes mellitus is increasing globally, and it is estimated that by 2045, there will be 700 million people affected by this disease. It is more common in adults, particularly those who are overweight or obese, have a family history of diabetes, and lead a sedentary lifestyle.
Type 2 diabetes mellitus is also more prevalent in certain ethnic groups, including African Americans, Hispanics/Latinos, Native Americans, and Asians. The long-term complications of type 2 diabetes mellitus can be severe and include microvascular complications such as retinopathy, nephropathy, and neuropathy, as well as macrovascular complications such as cardiovascular disease, stroke, and peripheral vascular disease.
Prevalence: T2DM is one of the most prevalent chronic diseases worldwide, affecting an estimated 463 million adults aged 20-79 years in 2019. The prevalence of T2DM is expected to rise to 578 million by 2030 and 700 million by 2045 if current trends continue.
Age: The risk of T2DM increases with age. T2DM is most diagnosed in individuals aged 45-64 years, although the disease is increasingly affecting younger individuals.
Gender: T2DM affects men and women equally.
Ethnicity: Certain ethnic groups have a higher prevalence of T2DM, including South Asians, African Americans, Hispanics, and Native Americans.
Family History: Having a family history of T2DM is a significant risk factor for the disease.
Obesity: It is a major risk factor for T2DM, and the prevalence of T2DM is increasing in parallel with the global obesity epidemic.
Physical Inactivity: Physical inactivity is a significant risk factor for T2DM, with inactive individuals having a 30-50% higher risk of developing T2DM than active individuals.
Insulin Resistance: Insulin resistance is the primary defect in T2DM, and it refers to the inability of the peripheral tissues, such as muscle, liver, and adipose tissue, to respond to insulin. Insulin resistance leads to decreased glucose uptake by the muscles and liver, leading to hyperglycemia.
Beta-Cell Dysfunction: Beta-cell dysfunction occurs due to a decrease in beta-cell mass and function, leading to inadequate insulin secretion in response to glucose, which further contributes to hyperglycemia.
Increased Hepatic Glucose Production: Hepatic glucose production is increased due to increased gluconeogenesis and glycogenolysis, leading to increased glucose levels in the bloodstream.
Increased Lipolysis and Free Fatty Acid Release: In T2DM, there is increased lipolysis and free fatty acid release from adipose tissue, which leads to insulin resistance and increased hepatic glucose production.
Inflammatory Cytokines: Inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) are elevated in T2DM, contributing to insulin resistance and beta-cell dysfunction.
Genetic Factors: There is a strong genetic component to T2DM, with several genes implicated in the pathogenesis of the disease.
Genetics: Family history and certain genes are associated with an increased risk of developing type 2 diabetes.
Obesity: Being overweight or obese, especially with excess abdominal fat, can increase the risk of type 2 diabetes.
Physical Inactivity: Lack of physical activity may have an increased risk of developing type 2 diabetes.
Insulin Resistance: Insulin resistance, which is the body’s inability to respond properly to insulin, is a key factor in the development of type 2 diabetes.
Abnormal Glucose Production by the Liver: The liver may produce too much glucose, contributing to high blood sugar levels.
Beta-Cell Dysfunction: In type 2 diabetes, the beta cells in the pancreas that produce insulin become dysfunctional, resulting in insufficient insulin secretion.
Age: There ia an increased risk of developing type 2 diabetes with age.
Race and Ethnicity: Certain ethnic groups, including African Americans, Hispanic/Latinos, and Native Americans, have a higher risk of diabetes type 2.
Gestational Diabetes: Women with gestational diabetes during pregnancy have an increased risk of developing type 2 diabetes later in life.
Glycemic Control: Good glycemic control is essential for the prevention of complications associated with diabetes. HbA1c levels should be maintained below 7% to reduce the risk of microvascular complications.
Age: Older patients with type 2 diabetes are at a higher risk of developing complications such as cardiovascular disease, neuropathy, and retinopathy.
Duration of Diabetes: The longer the duration of diabetes, the greater the risk of developing complications.
Blood Pressure: High blood pr
