DM (1)
DM (1)
Diabetes Mellitus
Diabetes mellitus (DM) is a group of metabolic diseases characterized by
hyperglycemia resulting from defects in insulin secretion, insulin action, or both (1).
Pathophysiology
There are two main types of diabetes: type 1 and type 2.
1-Type 1 diabetes (accounts for <10%), is caused by destruction of the insulin-
producing β-cells of the pancreas (2) (leading to absolute deficiency of insulin
secretion) (3).
2-Type 2 diabetes (accounts for about 90%), results from lack of sufficient insulin
production and/or lack of sensitivity to the effects of insulin (insulin resistance) (2).
Clinical presentation
1. Symptom severity and onset help differentiate type 1 from type 2 DM.
a. Type 1 DM typically presents with an abrupt onset and an acute
presentation (3).
b. Symptoms in individuals with type 2 DM generally develop gradually,
with some patients being asymptomatic or having only mild symptoms upon
diagnosis (3).
Diagnosis (5, 6)
Criteria for the diagnosis of DM include any one of the following:
1. Hemoglobin A1C ≥6.5%.
2. Fasting (defined as no caloric intake for at least 8 hours) plasma glucose ≥126
mg/dL (7.0 mmol/L).
3. Two-hour plasma glucose ≥200 mg/ dL (111.1 mmol/L) during an oral glucose
tolerance test (OGTT) .
35
4. A random plasma glucose concentration ≥200 mg/dL (111.1 mmol/L) in a
patient with classic symptoms of diabetes (Polyuria, polydipsla, unexplained
weight loss).
Note: The diagnosis must be confirmed by repeating the test, preferably the same
test (7).
Treatment
1- There are three major components to the treatment of diabetes: diet, drugs
(insulin and antidiabetic agents ), and exercise (7).
2-Appropriate treatment requires goal setting for glycemia, blood pressure, and
lipid levels (5). The American Diabetes Association (ADA) metabolic goals for
adults with diabetes mellitus are listed in Table 2 (8).
Note: Lower systolic targets, such as ,<130 mmHg, may be appropriate for certain individuals,
such as younger patients,if it can be achieved without undue treatment burden (8).
B-Twice daily injections (before breakfast and before the evening meal) of pre-
mixed preparations of short- and intermediate-acting insulin provide a
convenience for many patients. Two-thirds of the daily dose given in the
morning (with about two thirds given as long-acting insulin and one-third as
36
short-acting) and one-third in the evening (with approximately one-half given as
long-acting insulin and one-half as short-acting).
Hypoglycemia(7)
Definition
Blood glucose concentration <60 mg/dL: Patient may or may not be symptomatic
Blood glucose <40 mg/dL: Patient is generally symptomatic
Blood glucose <20 mg/dL: Can be associated with seizures and coma
37
Diabetic Ketoacidosis(DKA) (9)
Definitions
Is a condition characterized by hyperglycemia (serum glucose > 250 mg/dL,
ketosis, and metabolic acidosis (serum bicarbonate <15 mmol/L with increased
anion gap).
Precipitating events(9)
Inadequate insulin administration, Infection ,Infarction and stressful conditions .
5-if the patient is stable, glucose level is 150–200 mg/dL, and acidosis is
resolved. Insulin infusion may be decreased, long-acting insulin is given as soon
as patient is able to eat. Allow for a 2–4 hour overlap in insulin infusion and SC
long-acting insulin injection..
38
3-Table 4 lists classes of drugs for type 2 DM (6).
3-A reasonable treatment algorithm for initial therapy uses metformin as initial
therapy because of its efficacy, known side-effect profile, and relatively low cost
(Fig. 1). Metformin has the advantage that it promotes mild weight loss, and
improves the lipid profile slightly (9). However, type 2 DM is a progressive
disorder and ultimately requires multiple therapeutic agents and often insulin (9).
2 (SGLT-2) Inhibitor
39
Figure 1 : Glycemic management of type 2 diabetes. Agents that
can be combined with metformin include insulin secretagogues,
thiazolidinediones, α-glucosidase inhibitors, DPP-IV inhibitors, and GLP-1
receptor agonists.
Treatment of complications
1-Retinopathy
• Early retinopathy may reverse with improved glycemic control. More advanced
disease may requires laser therapy (4).
2-Neuropathy (4).
A- Peripheral neuropathy is the most common complication in type 2 DM
outpatients. Paresthesias, numbness, or pain may be predominant symptoms.
Pharmacologic therapy include duloxetine(the preferred one), low-dose
TCAs, anticonvulsants (e.g., gabapentin, pregabalin), , topical capsaicin, and
various analgesics, , including tramadol and NSAIDS.
40
E-Erectile dysfunction: is common, and initial treatment should include one of
the oral medications (e.g., sildenafil, vardenafil, tadalafil).
3-Nephropathy (4).
• Glucose and blood pressure control are most important for prevention of
nephropathy.
• ACE inhibitors and ARBs have shown efficacy in preventing the clinical
progression of renal disease in patients with type 2 DM.
References
1- Cooper, Daniel H.; Krainik, Andrew J.; Lubner, Sam J.; Reno, Hilary E. L. Washington Manual of
Medical Therapeutics, The, 35th Edition 2016
2-Nadia Bukhari , David Kearney .Fasttrack therapeutics . First edition 2009 by pharmaceutical press.
3-Leon Shargel , Alan H. Mutnick . Comprehensive pharmacy review. Fifth edition 2007.
4- Roger Walker. Clinical Pharmacy and Therapeutics. Fifth edition 2012.
5- Joseph T. DiPiro, Robert L. Pharmacotherapy: A Pathophysiologic Approach, 8th Edition. Copyright 2011.
6- Rick D .Kellerman,David P.Rakel. Conn’s Current Therapy. Copyright 2019
7-Caroline S. Zeind ,Michael G. Carvalho.Applied Therapeutic,The Clinical Use Of Drugs.11th Edition 2018
8- Stuart H Ralston, Ian D Penman, Mark WJ Strachan, Richard P Hobson. Davidson's Principles and Pracrtice of
Medicines . 23nd Edition 2018..
9- Dan L. Longo, et al, eds. Harrison's Principles of Internal Medicine, 20th Edition. 2018 .
10- American Diabetes Association. Standards of Medical Care in Diabetes 2014. Diabetes Care Volume 37,
Supplement 1, January 2014.
41