DM tipe 1

Type 1 diabetes is a chronic illness characterized by the bodys inability to produce

insulin due to the autoimmune destruction of the beta cells in the pancreas. Onset
most often occurs in childhood, but the disease can also develop in adults in their
late 30s and early 40s.

The classic symptoms of type 1 diabetes are as follows:

Polyuria
Polydipsia

Polyphagia

Unexplained weight loss

Other symptoms may include fatigue, nausea, and blurred vision.

Diagnosis
Diagnostic criteria by the American Diabetes Association (ADA) include the following :

A fasting plasma glucose (FPG) level 126 mg/dL (7.0 mmol/L), or

A 2-hour plasma glucose level 200 mg/dL (11.1 mmol/L) during a 75-g oral glucose
tolerance test (OGTT), or

A random plasma glucose 200 mg/dL (11.1 mmol/L) in a patient with classic symptoms
of hyperglycemia or hyperglycemic crisis

Diagnosis and classification of diabetes mellitus. Diabetes Care. Jan

2010;33 Suppl 1:S62-9.
Etiologi
Type 1A DM results from autoimmune destruction of the beta cells of the pancreas
and involves both genetic predisposition and an environmental component.
Treatment
Patients with type 1 diabetes mellitus (DM) require lifelong insulin therapy. Most
require 2 or more injections of insulin daily, with doses adjusted on the basis of selfmonitoring of blood glucose levels. Long-term management requires a
multidisciplinary approach that includes physicians, nurses, dietitians, and selected
specialists.

Insulin Therapy

Types of insulin
Rapid-, short-, intermediate-, and long-acting insulin preparations are available. Various pork,
beef, and beef-pork insulins were previously used; however, in the United States, recombinant
human insulin is now used almost exclusively. Commercially prepared mixtures of insulin are
also available.
Rapid-acting insulins include lispro, glulisine, and aspart insulin. Lispro insulin is a form of
regular insulin that is genetically engineered with the reversal of the amino acids lysine and
proline at B28,29 in the B chain. Glulisine insulin substitutes glutamic acid for lysine in position
B29. Aspart insulin substitutes aspartic acid for proline in position 28 of the B chain.
These insulins are absorbed more quickly and have a rapid onset of action (5-10 minutes), a short
interval to peak action (45-75 minutes), and a short duration of action (2-4 hours). Therefore,
they can be administered shortly before eating. In addition, neutral protamine Hagedorn (NPH)
insulin will not inhibit the action of insulin lispro when the 2 agents are mixed together right
before injection; this is not true of regular insulin.
A rapid-acting inhaled insulin powder (Afrezza) for types 1 and 2 diabetes mellitus was approved
by the FDA in June 2014. It is regular insulin but is considered rapid-acting because it peaks at
12-15 minutes and returns to baseline levels at about 160 minutes. Approval was based on a
study involving over 3,000 patients over a 24-week period. In persons with type 1 diabetes, the
inhaled insulin was found to be noninferior to standard injectable insulin when used in
conjunction with basal insulin at reducing hemoglobin A1c. In persons with type 2 diabetes, the
inhaled insulin was compared to placebo inhalation in combination with oral diabetic agents and
showed a statistically significant lower hemoglobin A1c.[82, 83]
Short-acting insulin includes regular insulin. Regular insulin is a preparation of zinc insulin
crystals in solution. When it is administered subcutaneously, its onset of action occurs in 0.5
hours, its peak activity comes at 2.5-5 hours, and its duration of action is 4-12 hours.
The standard strength of regular insulin is 100 U/mL (U-100), but 500 U/mL (U-500) insulin is
increasingly used, albeit mostly in type 2 DM. Accidental prescribing of U-500 rather than U100 is a potential safety issue.[84] A study by de la Pena et al found that although the overall
insulin exposure and effects of 500 U/mL insulin are similar to those of 100 U/mL insulin, peak
concentration was significantly lower with U-500, and the effect after the peak was prolonged;
areas under the curve were similar for the 2 strengths.[85]
Both regular human insulin and rapid-acting insulin analogues are effective at lowering
postprandial hyperglycemia in various basal bolus insulin regimens used in type 1 DM. Rapidacting insulin analogues may be slightly better at lowering HbA1c and are preferred by most US
diabetologists, but the differences are clinically insignificant.[86]

Semilente insulin is like regular insulin and is a rapid-acting insulin with a slightly slower onset
of action. It contains zinc insulin microcrystals in an acetate buffer. It is not readily available in
the United States.
Intermediate-acting insulins include NPH insulin, a crystalline suspension of human insulin with
protamine and zinc. NPH provides a slower onset of action and longer duration of action than
regular insulin does. The onset of action usually occurs at 1-2 hours, the peak effect is noted at 412 hours, and the duration of action is normally 1424 hours.
Lente insulin is a suspension of insulin in buffered water that is modified by the addition of zinc
chloride. This insulin zinc suspension is equivalent to a mixture of 30% prompt insulin zinc
(Semilente) and 70% extended insulin zinc (Ultralente). It is not used in the United States.
Long-acting insulins used in the United States include insulin glargine and insulin detemir.
Insulin glargine has no peak and produces a relatively stable level lasting more than 24 hours. In
some cases, it can produce a stable basal serum insulin concentration with a single daily
injection, though patients requiring lower doses typically are given twice-daily injections. Insulin
detemir has a duration of action that may be substantially shorter than that of insulin glargine but
longer than those of intermediate-acting insulins.
A new ultralong-acting basal insulin, insulin degludec, which has a duration of action of up to 42
hours, has been developed. It awaits approval by the US Food and Drug Administration (FDA).
[87]

Mixtures of insulin preparations with different onsets and durations of action frequently are
administered in a single injection by drawing measured doses of 2 preparations into the same
syringe immediately before use. The exceptions are insulin glargine and insulin detemir, which
should not be mixed with any other form of insulin. Preparations that contain a mixture of 70%
NPH and 30% regular human insulin (eg, Novolin 70/30 and Humulin 70/30) are available, but
the fixed ratios of intermediate-acting to rapid-acting insulin may restrict their use.
82. Tucker M. FDA Approves Inhaled Insulin Afrezza for Diabetes. Medscape Medical
News. Available at http://www.medscape.com/viewarticle/827539.. Accessed July 14,
2014.
83. Afrezza (insulin inhaled) prescribing information [package insert]. Valencia CA, United
States: MannKind Corporation; June, 2014.
84. US Food and Drug Administration. Mixups between Insulin U-100 and U-500 (April
2008). FDA Patient Safety News. Available at
http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/psn/transcript.cfm?show=79. Accessed
January 28, 2012.
85. de la Pena A, Riddle M, Morrow LA, et al. Pharmacokinetics and pharmacodynamics of
high-dose human regular u-500 insulin versus human regular u-100 insulin in healthy
obese subjects. Diabetes Care. Dec 2011;34(12):2496-501.

86. Garg S, Ampudia-Blasco FJ, Pfohl M. Rapid-acting insulin analogues in Basal-bolus

regimens in type 1 diabetes mellitus. Endocr Pract. May-Jun 2010;16(3):486-505.
87. Birkeland KI, Home PD, Wendisch U, Ratner RE, Johansen T, Endahl LA, et al. Insulin
Degludec in Type 1 Diabetes: A randomized controlled trial of a new-generation ultralong-acting insulin compared with insulin glargine. Diabetes Care. Mar 2011;34(3):6615.

DM tipe 2

Signs and symptoms

Many patients with type 2 diabetes are asymptomatic. Clinical manifestations include the
following:

Classic symptoms: Polyuria, polydipsia, polyphagia, and weight loss

Blurred vision

Lower-extremity paresthesias

Yeast infections (eg, balanitis in men)

Diagnosis
Diagnostic criteria by the American Diabetes Association (ADA) include the following :

A fasting plasma glucose (FPG) level of 126 mg/dL (7.0 mmol/L) or higher, or
A 2-hour plasma glucose level of 200 mg/dL (11.1 mmol/L) or higher during a 75-g oral
glucose tolerance test (OGTT), or

A random plasma glucose of 200 mg/dL (11.1 mmol/L) or higher in a patient with classic
symptoms of hyperglycemia or hyperglycemic crisis

Treatment

Early initiation of pharmacologic therapy is associated with improved glycemic control and
reduced long-term complications in type 2 diabetes. Drug classes used for the treatment of type 2
diabetes include the following:

Biguanides
Sulfonylureas

Meglitinide derivatives

Alpha-glucosidase inhibitors

Thiazolidinediones (TZDs)

Glucagonlike peptide1 (GLP-1) agonists

Dipeptidyl peptidase IV (DPP-4) inhibitors

Selective sodium-glucose transporter-2 (SGLT-2) inhibitors

Insulins

Amylinomimetics

Bile acid sequestrants

Dopamine agonists

Diagnosis and classification of diabetes mellitus. Diabetes Care. Jan 2010;33 Suppl
1:S62-9.