Type 2 Diabetes Mellitus – Diagnosis, Management, Treatment and Complications

Diabetes Mellitus Type 2:

Diabetes Mellitus is metabolic disorder that causes blood sugar (glucose) levels to rise higher than normal (hyperglycemia). 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. Type 2 Diabetes Mellitus is characterized by insulin resistance leading to increase insulin production by the Beta-cells of the pancreas. Over time, the insulin secretory capacity of the pancreas becomes unable to overcome insulin resistance, resulting in progressive deterioration of Beta-cell function and steady decrease in plasma insulin and subsequently an increase in plasma glucose. Although obesity is the most important risk factor for Type 2 Diabetes Mellitus, other important risks factors such as; 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 Diabetes Mellitus.

 

Diagnostic Criteria based on ADA guidelines:

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

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 eight hours.*
– Two-hour plasma glucose values of ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT)
– A1C values ≥6.5 percent (48 mmol/mol)

Categories of increased risk for diabetes:
– FPG between 100 and 125 mg/dL (5.6 to 6.9 mmol/L).
– Two-hour plasma glucose value during a 75 g OGTT between 140 and 199 mg/dL (7.8 to 11.0 mmol/L).
– Persons with 5.7 to 6.4 percent (39 to 46 mmol/mol), (6.0 to 6.4 percent [42 to 46 mmol/mol] in the International Expert Committee report) are at highest risk, although there is a continuum of increasing risk across the entire spectrum of A1C levels less than 6.5 percent (48 mmol/mol).

 

Initial Workup:

Patients with newly diagnosed diabetes require a history and physical examination 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, history of diabetes-related complications, hypoglycemic episodes, diabetic ketoacidosis (DKA) frequency (type 1 diabetes only), and current management.
– Glycated hemoglobin A1C (HgbA1C), 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.

 

Managing diabetes:

– Lifestyle change (healthy nutrition, increase activity and weight loss)
– Medication
– Blood sugar monitoring
These steps will help keep your blood sugar level closer to normal, which can delay or prevent complications.

 

Management Goals:

© American Diabetes Association.

– Preprandial glucose < 100 mg/dl
– Bedtime glucose < 120 mg/dl
– A1C < 7% (many now using 6.5%) – Monitor A1C every 3 months. May monitor every 6 months for patients with controlled diabetes.
Numerous aspects must be considered when setting glycemic targets. The ADA proposes optimal targets, but each target must be individualized to the needs of each patient and his or her disease factors.
– Blood pressure < 130/80
– LDL cholesterol < 100 mg/dl, (< 70 mg/dl with cardiovascular disease)

 

Immunization:

– Influenza yearly
– 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

 

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 as it can contribute to abnormal cholesterol levels (dyslipidemia)
– Screen for tobacco use
– Screen for depression (more prevalent in patients with chronic disease)

 

Complications:

– Macrovascular (e.g. coronary heart disease and stroke)
– Microvascular (e.g. retinopathy, neuropathy and nephropathy)
– Diabetic foot problems (e.g. ulcers, osteomyelitis, Charcot foot)
Ketoacidosis (DKA) and Hyperosmolar Hyperglycemia State (HHS)

 

Medications:




DRUG CLASS

MECHANISM OF ACTION

SIDE EFFECTS

Biguanides:
-Metformin (Glucophage)

-Works primary in liver. It decreases gluconeogenesis and increases glycolysis leading to decrease serum glucose
-Increases peripheral glucose uptake by increasing insulin sensitivity.
-Lactic acidosis
Contraindicated in renal failure
-Diarrhea, nausea, vomiting and flatulence
Weight loss**
 

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

 

-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

 

Hypoglycemia**
Weight gain

GLP-1 (glucagon-like peptide-1 agonist) analogs:
-Liraglutide (Victoza)
-Albiglutide (Tanzeum)
-Dulaglutide (Trulicity)
-Exenatide (Byetta)
-Exenatide ER (Bydureon)

-Increases insulin release and decrease glucagon release
-Slows gastric emptying and decreased food intake
-Headache and dizziness
-Diarrhea, nausea and vomiting
Weight loss**
SGLT2 (sodium-glucose co-transporter 2) Inhibitors:
-Canagliflozin (Invokana)
-Dapagliflozin (Farxiga)
-Empagliflozin (Jardiance)

-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. Ketoacidosis
-Hypotension
-Increased risk of urinary tract infections and candidal vulvovaginitis
Weight loss**
DPP-4 (dipeptidyl peptidase 4) inhibitors:
-Sitagliptin (Januvia)
-Saxagliptin (Onglyza)
-Linagliptin (Tradjenta)
-Alogliptin (Nesina)
-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.

 

-Peripheral edema
-Diarrhea, nausea and constipation
Meglitinides:
-Repaglinide (Prandin)
-Nateglinide (Starlix)

-Stimulate the pancreatic Beta-cells to release insulin (similar to sulfonylureas) -Headache
-Hypoglycemia
-Upper respiratory tract infection
Thiazolidinediones:
-Pioglitazone (ACTOS)
-Rosiglitazone (Avandia)

-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) 

 

-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 Analogue:
-Pramlintide (Symlin)

 

-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.

 

 

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

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

-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
 

Insulin:
Rapid acting: lispro (Humalog) and aspart (NovoLog)

Regular insulin: Humulin, Novolin

Intermediate acting: NPH (Humulin N, Novolin N)

Long-acting: detemir (Levemir), glargine (Lantus)

 

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

 

-Hypoglycemia
Weight gain


Armando Hasudungan

**REFERENCES for This Article:

 

SUPPLEMENTARY MATERIALS:

Diabetes Follow-up Mnemonic (questions you should ask your diabetic patients at each visit)

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