What is Type 2 Diabetes Mellitus – A Comprehensive Overview

Type 2 Diabetes Mellitus - A Comprehensive Overview of Symptoms, Diagnosis, Treatment - By: Dr. Ali Feili MD - www.DailyMedEd.com

Type 2 Diabetes Mellitus: Symptoms, Diagnosis, Treatment

Diabetes is a very serious metabolic condition that impairs the body’s ability to process blood glucose (also known as blood sugar), either due to body’s inability to make insulin or or development of insulin resistance.

Patients with diabetes commonly experience symptoms such as polydipsia (increased thirst), polyphagia (increased hunger) and polyuria (frequent urination).

Based on CDC’s 2017 National Diabetes Statistics Report there are 30.3 million people in the U.S. who have diabetes. Out of this group there are approximately 7.2 million of them have not been diagnosed yet.

The same report also reveals that there are a total of 84.1 million adults age 18 or older in the U.S. who have pre-diabetes.

Insulin is produced by pancreatic beta-cells and its responsibility is to act as a key for glucose to enter the cells to be metabolized and used as a source of energy.

In diabetes since glucose is not able to enter the cells, it leads to hyperglycemia (increased glucose levels in the blood).

Diabetes mellitus is categorized into two main different types:

  • Type 1 Diabetes Mellitus is typically diagnosed at a very young age and it is due to the pancreas inability to produce insulin.
  • Type 2 Diabetes Mellitus is one of the major causes of early illness and death worldwide. It is the most common form of diabetes and it accounts for over 90% of patients with diabetes.


Patients with HbA1c level of 5.7 to 6.4% or blood glucose level ranging between 100 to 125 mg/dL are referred to as having prediabetes or borderline diabetes.

Normal blood sugar levels sit between 70 and 99 mg/dL, whereas a person with diabetes will have a fasting blood sugar higher than 126 mg/dL.

The prediabetes level means that blood glucose is higher than usual (>100 mg/dL) but not so high as to constitute diabetes (<126 mg/dL).

Patients with prediabetes are, however, at risk of developing type 2 diabetes, although they do not usually experience the symptoms of full diabetes.

The risk factors for prediabetes and type 2 diabetes are similar. They include:

– Being overweight or obese,
– A family history of diabetes,
– Having a high-density lipoprotein (HDL) cholesterol level lower than 40 mg/dL or 50 mg/dL,
– History of high blood pressure,
– History of gestational diabetes or giving birth to a child with a birth weight of more than 9LBs,
– History of polycystic ovary syndrome (PCOS),
– Being of African-American, Native American, Latin American, or Asian-Pacific Islander descent,
– Over 45 years of age,
– Sedentary lifestyle.

If a doctor identifies that a person has prediabetes, they will recommend that the individual makes healthful changes that can ideally stop the progression to type 2 diabetes. Losing weight and having a more healthful diet can often help prevent the disease.

Type 2 Diabetes Mellitus:

Type 2 DM, is characterized by insulin resistance leading to increase insulin production by the pancreatic beta-cells. Basically, insulin resistance in cells results in a reduction of their ability to absorb glucose, leading to an elevation of blood glucose levels, known as hyperglycemia. This prompts the pancreas to increase it’s production of insulin in an attempt to regulate/decrease blood glucose levels.

As time goes on, the pancreas’ ability to produce insulin becomes weaker, leading to insulin resistance and a decline in the function of beta cells. This results in lower levels of insulin in the bloodstream and higher levels of glucose.

Although obesity is the most important risk factor for Type 2 DM, other important risks factors.

These important risk factors include; positive family history, ethnicity (e.g. Native Americans, African Americans, Hispanics, Asian Americans and Pacific Islanders), age and gender have also been associated with increased risk for developing Type 2 DM.

Screening for Diabetes Mellitus:

The U.S. Preventive Services Task Force (USPSTF) guidelines  recommends screening for abnormal blood glucose as part of cardiovascular risk assessment in adults aged 35 to 70 years who are overweight or obese.

This recommendation applies to adults who are seen in primary care settings and do not have obvious symptoms of diabetes.

Clinicians should consider screening earlier in persons with 1 or more of the following characteristics:
– Family history of diabetes,
– History of gestational diabetes,
– History of polycystic ovarian syndrome (PCOS),
– Those who are members of certain racial/ethnic groups (that is, African Americans, American Indians or Alaskan Natives, Asian Americans, Hispanics or Latinos, or Native Hawaiians or Pacific Islanders) because may be at increased risk for diabetes at a younger age or at a lower body mass index.

Initial Workup:

Patients with newly diagnosed diabetes require a very thorough history and physical examination.

This is done to assess the characteristics of onset of diabetes (asymptomatic laboratory finding or symptomatic polyuria and polydipsia), nutrition and weight history, physical activity, cardiovascular risk factors and current management.

Also important to know is any history of diabetes-related complications, history of hypoglycemic episodes and diabetic ketoacidosis (DKA)  frequency (type 1 diabetes only).

– HbA1c, if not measured in the past two to three months

If not measured in the past one year, measure:
– Fasting lipid panel,
Liver function tests,
– Urine protein (albumin) excretion,
– Serum creatinine,

Patients with diabetes require ongoing evaluation for diabetes-related complications. A history and physical exam should be performed two to three times yearly to obtain information on nutrition, physical activity, management of diabetes and cardiovascular risk factors, and diabetes-related complications.

Diabetes Mellitus diagnosis:

According to American Diabetes Association (ADA), the criteria for diagnosis diabetes mellitus are:

Those with classic symptoms of hyperglycemia

– The diagnosis of diabetes mellitus is easily established when a patient presents with classic symptoms of hyperglycemia (thirst, polyuria, blurry vision) and has a random blood glucose value of 200 mg/dL (11.1 mmol/L) or higher.

Those who are asymptomatic
The diagnosis of diabetes in an asymptomatic individual can be established with any of the following criteria:
– Fasting plasma glucose (FPG) values ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours.*
– Two-hour plasma glucose values of ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT).
– Hemoglobin A1c (HbA1c) values ≥6.5 % (48 mmol/mol).

Those who are at increased risk for diabetes:
– Fasting Plasma Glucose between 100 to 125 mg/dL (5.6 to 6.9 mmol/L).
– Two-hour plasma glucose value during a 75 g OGTT between 140 to 199 mg/dL (7.8 to 11.0 mmol/L).


– Lifestyle change, such as following a healthy diabetic diet, increase activity and weight loss,
– Medication,
– Using a glucometer to frequently check blood glucose levels.

These steps will help keep your blood sugar level closer to normal, which can delay or prevent complications.

Management Goals:

– Preprandial (before a meal) glucose < 100 mg/dl
– Bedtime glucose < 120 mg/dl
– HbA1c < 6.5% – Monitor HbA1c every 3 months. May monitor every 6 months for patients with controlled diabetes.
– Blood pressure < 130/80 mmHg
– LDL cholesterol < 100 mg/dl, (< 70 mg/dl with cardiovascular disease)


– Annual influenza vaccine
Pneumococcal vaccine once and repeat at age 65 (but 5 years after the 1st if received under age 65)
– Hepatitis B now recommended for all ≤ age 60 (after age 60 at high risk for hepatitis B)
– Tdap (Adult Tetanus, Diphtheria, Pertussis): OK after age 65 and no minimum time after last Td
COVID-19 vaccines and boosters

Screening for Comorbid Conditions:

– Routine blood pressure check at every doctor visit.
– Yearly dilated diabetic eye examination.
– Yearly diabetic foot examination.
– Yearly screening for increased urinary protein (albumin) excretion.
– Yearly fasting lipid panel (May obtain every five years if profile is low risk).
– Screen for hypothyroidism since it is common cause of obesity and abnormal cholesterol levels (dyslipidemia).
– Screen for tobacco use, since smoking expedites and increases the risk of vascular disease.
– Screen for depression, since this is common in patients who suffer from different chronic diseases.


Uncontrolled Type 2 Diabetes mellitus can unfortunately lead to very devastating outcomes and complications since it mainly affects the blood vessels and nerves leading to conditions such as:
– MACRO-vascular disease, where the large blood vessels become affected leading to complications such as coronary heart disease, peripheral arterial disease, and stroke .
– Micro-vascular, where the small blood vessels are affected leading to complications such as erectile dysfunction (ED), retinopathy, neuropathy and nephropathy. Diabetic retinopathy is responsible for approximately 10,000 new cases of blindness every year in the United States and is the most common microvascular complication of diabetes.
– Diabetic foot problems, which are very serious complications, leading to foot ulcers, osteomyelitis , peripheral neuropathy and charcot foot. These complications are mainly due to damages nerves and poor/delayed healing due to very  poor blood circulation.
Diabetic Ketoacidosis (DKA)  and Hyperosmolar Hyperglycemic State (HHS).

Treatment Options:




-Metformin (Glucophage)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Works primarily on the liver by inhibiting gluconeogenesis leading to decrease hepatic glucose production and therefore decrease serum glucose.
It also increases peripheral glucose uptake by increasing insulin sensitivity.

Weight loss**
-Diarrhea, nausea, vomiting & flatulence
-Lactic acidosis
Contraindicated in renal failure

GLP-1 (glucagon-like peptide-1) agonist:
-Dulaglutide (Trulicity) (weekly)
-Exenatide extended release (Bydureon bcise) (weekly)
-Exenatide (Byetta) (twice daily)
-Semaglutide (Ozempic) (weekly)
-Tirzepatide (Mounjaro) (weekly)
-Liraglutide (Victoza, Saxenda) (daily)
-Lixisenatide (Adlyxin) (daily)
-Semaglutide (Rybelsus) (taken by mouth once daily)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Increases insulin release and decrease glucagon release.
Slows gastric emptying leading to decreased food intake.

Weight loss**
-Headache and dizziness
-Diarrhea, nausea and vomiting
Contraindicated in patients with medullary thyroid cancer or Multiple Endocrine  Neoplasia Syndrome (MEN), or with a family history of these conditions.

SGLT2 (sodium-glucose co-transporter 2) Inhibitors:
-Canagliflozin (Invokana)
-Dapagliflozin (Farxiga)
-Empagliflozin (Jardiance)
-Ertugliflozin (Steglatro)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

The SGLT2 is expressed in the proximal tubule and mediates reabsorption of approximately 90% of the filtered glucose load. SGLT2 inhibitors, block this action, causing excess glucose to be eliminated in the urine.

Weight loss**
-Increased risk of urinary tract infections and candidal vulvovaginitis

DPP-4 (dipeptidyl peptidase 4) inhibitors:
-Sitagliptin (Januvia)
-Saxagliptin (Onglyza)
-Linagliptin (Tradjenta)
-Alogliptin (Nesina)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Increases incretin levels (GLP-1 and GIP), which inhibit glucagon release and in turn increases insulin secretion, decreases gastric emptying, and decreases blood glucose levels.

AVOID combining DPP-4 inhibitors with GLP-1 agonists since they both increase insulin secretion leading to severe hypoglycemia.

-Peripheral edema
-Diarrhea, nausea and constipation

-Glipizide (Glucotrol & Glucotrol XL)
-Glyburide (Micronase, Glynase, Diabeta)
-Glimepiride (Amaryl)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Blocks the potassium (K+) channels in Beta-cells membranes of pancreas. This causes cells depolarization and influx of calcium (Ca+) into the cells, triggering insulin release.

AVOID combining with insulin since this will lead to severe hypoglycemia.

More common with glyburide, specially in patients with CKD.
Short-acting sulfonylurea such as glipizide or glimepiride, is preferred in CKD.
Weight gain

-Repaglinide (Prandin)
-Nateglinide (Starlix)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Stimulate the pancreatic Beta-cells to release insulin (similar to sulfonylureas).

-Upper respiratory tract infection

-Pioglitazone (ACTOS)
-Rosiglitazone (Avandia)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Binds and activates PPARs (peroxisome proliferator-activated receptors) a group of nuclear receptors, with greatest specificity for PPARγ (gamma), leading to increase cell sensitivity to glucose.

Weight gain
-Edema, fluid retention and subsequent heart failure
-Hepatotoxicity (liver failure)
-Increased risk of bladder cancer

Alpha-glucosidase inhibitors:
-Acarbose (Precose)
-Miglitol (Glyset) 

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Inhibits intestinal brush border alpha-glucosidase enzymes, which reduces the rate of digestion of carbohydrates. This delays glucose absorption from the gut and subsequently decreases postprandial hyperglycemia.

-Diarrhea, flatulence and abdominal pain
-Rash (rare)

Amylin agonist:
-Pramlintide (Symlin)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Slows food from moving too quickly through the stomach and helps keep after-meal glucose levels from going too high.
Suppresses appetite and may cause weight loss.
Reduces glucose production by the liver.

Weight loss**
-Loss of appetite
-Nausea and vomiting

Alpha-glucosidase inhibitors:
-Acarbose (Precose)
-Miglitol (Glyset) 

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Inhibits intestinal brush border alpha-glucosidase enzymes, which reduces the rate of digestion of carbohydrates. This delays glucose absorption from the gut and subsequently decreases postprandial hyperglycemia.

-Diarrhea, flatulence and abdominal pain
-Rash (rare)

Bile Acid Sequestrants (BAS):
-Colesevelam (Welchol)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Reduces LDL cholesterol by binding with bile acids in the digestive system; the body in turn uses cholesterol to replace the bile acids, which lowers cholesterol levels.

The exact mechanism in reducing serum glucose is unknown.

-Diarrhea, nausea, Flatulence and constipation
-Weakness and muscle pain

Rapid acting: lispro (Humalog) and aspart (NovoLog)
Regular insulin: Humulin, Novolin
Intermediate acting: NPH (Humulin N, Novolin N)
Long-acting: detemir (Levemir), glargine (Lantus)

What is Type 2 Diabetes Mellitus - A Comprehensive Overview - DailyMedEd.com

Works like endogenous insulin. Mainly used for Type 1 diabetes due to lack of insulin. Although patients with Type 2 DM make insulin, their bodies don’t respond well to it. Also overtime their pancreas burns out and stops making insulin due to excessive work.

AVOID combining with Sulfonylureas since this will lead to severe hypoglycemia.

Weight gain

Source: [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12]

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