همكاران محترم مطالب زير چكيده اي از مهمترين مطالب درباره ديابت و داروهاي مورد استفاده در درمان آن مي باشد، كه تازه ترين هاي ADA و CDA برنامه كشوري كنترل ديابت مي باشد، اميد است كه قابل استفاده و مفيد واقع شود. خواهشمند است مطالب را مطالعه نموده و نظرات خود را بيان نماييد. موفق و پيروز باشيد.

Table 2. Clinical Interpretations of Plasma Glucose Concentrations

Clinical Interpretation	Glucose Concentration, mg/dL
Fasting
Within the reference range	<100
Impaired fasting glucose/prediabetes mellitus	100-125
Overt diabetes mellitus	≥126
2-hour postchallenge load (75-g oral glucose tolerance test)
Within the reference range	<140
Impaired glucose tolerance/prediabetes mellitus	140-199
Overt diabetes mellitus	≥200

Table 3. Diagnostic Criteria for Diabetes Mellitus

Symptoms of diabetes (polyuria, polydipsia, unexplained weight loss) plus casual plasma glucose concentration ≥200 mg/dL

or

Fasting plasma glucose concentration ≥126 mg/dL

or

2-hour postchallenge glucose concentration ≥200 mg/dL during a 75-g oral glucose tolerance test

Table 4. Examples of Pharmacologic Regimens for Treating Type 2 Diabetes Mellitusa

Initiate monotherapy when HbA1c levels are 6%-7% Options include: Metformin. Thiazolidinediones. Secretagogues(sulfonylurea). Dipeptidyl-peptidase 4 inhibitors. α-Glucosidase inhibitors. Monitor and titrate medication for 2-3 months Consider combination therapy if glycemic goals are not met at the end of 2-3 months Initiate combination therapy when HbA1c levels are 7%-8% Options include: Secretagogue(sulfonylurea) + metformin. Secretagogue(sulfonylurea) + thiazolidinedione. Secretagogue(sulfonylurea) + α-glucosidase inhibitor. Thiazolidinedione + metformin. Dipeptidyl-peptidase 4 inhibitor + metformin. Dipeptidyl-peptidase 4 inhibitor + thiazolidinedione. Secretagogue(sulfonylurea) + metformin + thiazolidinedione. (single pill) therapy Thiazolidinedione (pioglitazone) + metformin. Thiazolidinedione (rosiglitazone) + metformin. Thiazolidinedione(rosiglitazone) +secretagogue(glimepiride). Thiazolidinedione(pioglitazone) +secretagogue (glimepiride). Secretagogue (glyburide) + metformin. *Rapid-acting insulin analogs or premixed insulin analogs may be used in special situations. *Inhaled insulin may be used as monotherapy or in combination with oral agents and long-acting insulin analogs. *Insulin-oral medications; all oral medications may be used in combination with insulin. *therapy combinations should be selected based on the patient's self-monitoring of blood glucose profiles. Initiate/intensify combination therapy using options listed above when HbA1c levels are 8%-10% to address fasting and postprandial glucose levels. Initiate/intensify insulin therapy when HbA1c levels are: >10% Options include: • Rapid-acting insulin analog or inhaled insulin with long- acting insulin analog or NPH. • Premixed insulin analogs.

Patients with Type 2 Diabetes Mellitus Currently Treated Pharmacologically

The therapeutic options for combination therapy listed for patients naïve to therapy are appropriate for patients being treated pharmacologically. Exenatide may be combined with oral therapy in patients who have not achieved glycemic goals      Approved exenatide + oral combinations:      Exenatide + secretagogue (sulfonylurea).      Exenatide + metformin.      Exenatide + secretagogue (sulfonylurea) + metformin.      Exenatide + thiazolidinedione. Pramlintide may be used in combination with prandial insulin Add insulin therapy in patients on maximum combination therapy (oral-oral, oral-exenatide) whose HbA1c levels are 6.5%-8.5%. initiating basal-bolus insulin therapy for patients with HbA1c levels >8.5%

Table 5. New Drugs to Treat Diabetes Mellitus

Comments	Dosage	Drug Name, Generic (Brand)
Indicated as an adjunct treatment in patients taking prandial insulin who have not achieved desired glucose control. Frequent monitoring of blood glucose levels is required to titrate dosage. Contraindicated in patients with hypo-glycemia unawareness or Gastroparesis	Type 1 Diabetes Mellitus Initiated at 15 μg and titrated at 15 μg. Increments to a maintenance dosage of 30μg or 60 μg as tolerated. Reduce preprandial, rapid-acting,or short-acting insulins, including fixed-mix insulins, by 50%. Type 2 Diabetes Mellitus Initiated at 60 μg and increased to a dosage of 120 μg as tolerated. Reduce preprandial, rapid-acting or short-acting insulin, including fixed-mix insulins, by 50%.	Pramlintide (Symlin)
Not a substitute for insulin in insulin-requiring patients. Should not be used in patients with type 1 diabetes mellitus or to treat diabetic ketoacidosis. Not recommended for use in patients with end-stage renal disease or severe renal impairment (creatinine clearance <30 mL/min/1.73m2)	<Indicated as adjust treatment to improve glycemic control in patients with type2 diabetes mellitus who take metformin, sulfonylurea,or combination of metformin and a sulfonylurea, but who have not achieved adequate glycemic control. Initiated at 5 μg per dose administered twice daily any time within 60 minutes before morning and evening meals. Dosage can be increased to 10 μg twice daily after 1 month of therapy.	Exenatide (Byetta)
Administer with or without food	Initial dosage: 100 mg once daily in the morning. If creatinine clearance is 30 to 50 mL/min/1.73m2,reduce dosage to 50 mg daily. If creatinine clearance is <30 mL/min/1.73m2,reduce dosage to 25 mg daily. Maximum dosage: 100 mg once daily in the morning.	Sitagliptin (Januvia)
Administer with meals Not recommended for patients with severe renal disease.	Initial dosage: 50 mg/500 mg twice daily Maximum dosage: 50 mg/1000 mg twice daily	Sitagliptin plus Metformin (Janumet)

Table 6. Pharmacokinetics of Available Insulin Preparations

Effective Duration	Peak	Onset	Insulin, Generic Name (Brand)
Insulin, Generic Name (Brand)
<5 h	30-90 min	5-15 min	Insulin aspart injection(NovoLog)
<5 h	30-90 min	5-15 min	Insulin lispro injection(Humalog)
<5 h	30-90 min	5-15 min	Insulin glulisine injection (Apidra)
5-8 h	30-90 min	5-15 min	Insulin human (rDNA origin) Inhalation Powder (Exubera)
Short-acting
5-8 h	2-3 h	30-60 min	Regular
Intermediate, basal
10-16 h	4-10 h	2-4 h	NPH
Long-acting, basal
20-24 h	No peak	2-4 hc	Insulin glargine injection (Lantus)
5.7-23.2 h	No peak	3-8 h	Insulin detemir injection (Levemir)
Premixed
10-16 h	Dual	5-15 min	75% insulin lispro protamine suspension/25% insulin lispro injection (Humalog Mix 75/25)
10-16 h	Dual	5-15 min	50% insulin lispro protamine suspension/50% insulin lispro injection (Humalog Mix 50/50)
10-16 h	Dual	5-15 min	70% insulin aspart protamine suspension/30% insulin aspart injection (NovoLog Mix 70/30)
10-16 h	Dual	30-60 min	70% NPH/30% regular

Table 7. Oral Hypoglycemic Agents

Comments	Maximum Dosage	Initial Dosage	Drug Name, Generic (Brand)
Thiazolidinediones
Administer with or without food	45 mg once daily	15 or 30 mg once daily	Pioglitazone (Actos)
Indicated for patients: (a) with type 2 diabetes mellitus treated with combination pioglitazone +metformin, (b) with glycemia not adequately controlled with metformin alone, (c) initially responsive to pioglitazone alone but require additional glycemic control. Dosage schedule based on current dose of each Component. Consider administering in divided daily doses with meals to reduce the gastrointestinal adverse effects associated with metformin.	If inadequately controlled on metformin monotherapy: Either 15mg/500mg or 15 mg/850 mg once daily or twice daily. If initially responsive to pioglitazone monotherapy or switching from combination therapy of pioglitazone + metformin as separate tablets: Either 15 mg/500 mg twice daily or 15 mg/850 mg once daily or twice daily.		Pioglitazone + Metformin (ActoPlus Met)
Administer with or without food	8 mg once daily or 4 mg twice daily	4 mg once daily or 2 mg twice daily	Rosiglitazone (Avandia)
Dosage schedule based on current dose of each component. Administer with meals.	4 mg/1000 mg twice daily	2 mg/500 mg twice daily	Rosiglitazone + Metformin (Avandamet)
Biguanides
Administer with meals Max effective dose is 2000 mg/d	2550 mg in 3 divided doses	500 mg twice daily or 850mg once daily in the morning	Metformin (Glucophage)
Increase dosage by 500mg/d weekly If glycemic control not tightened, switch to twice daily regimen. May have better gastrointestinal tolerance than immediate-release metformin.	2000 mg once daily	500 mg once daily in the evening	Metformin extended release (Glucophage XR)
Starting doses should not exceed daily doses of glyburide or metformin already taken;dose increases can be made at 2-week intervals.	20 mg/2000 mg divided daily	1.25 mg/250 mg once daily or twice daily	Glyburide + Metformin (Glucovance)
Second Generation Sulfonylureas
Administer once daily doses with breakfast or first main meal.Doses >10 mg/d should be divided and given twice daily.s	20 mg in 1 or 2 divided doses once daily or twice daily	1.25 to 5 mg once daily	Glyburide (DiaBeta) (Micronase)
Administer once daily doses 30 min before breakfast or after first main meal Doses>15mg/d should be divided & given twice daily	40 mg in 2 divided doses	5 mg once daily; 2.5 mg once daily in elderlypatients	Glipizide (Glucotrol)
Administer with breakfast or first main meal.	8 mg once daily	1 to 2 mg once daily	Glimepiride (Amaryl)
Glinides (Short-Acting Secretagogues)
Administer 15 to 30 min before each meal	16 mg/d	Elderly patients and patients not previously treated with hypoglycemic agents or patients with hemoglobin A1c <8%: Give 0.5 mg three times daily. Patients previously treated with hypoglycemic agents or those with hemoglobin A1c >8%: Give 1 to 2 mg three times daily	Repaglinide (Prandin)
Administer 15 to 30 min before each meal	120 mg three times daily	120mg three times daily; 60 mg three times daily in elderly patients	Nateglinide (Starlix)
α-Glucosidase Inhibitorsd
Administer with first bite of each main meal. Dosage should be gradually increased as tolerated over several weeks.	100 mg three times daily	25 mg three times daily	Acarbose (Precose)
Administer with first bite of each main meal. Dosage may be gradually increased as tolerated over several weeks.	100 mg three times daily	25 mg three times daily	Miglitol (Glyset)

8. Considerations for Oral Therapy in Patients With Type 2 Diabetes Mellitus

Comments	Monitoring	Possible Adverse Effects	Primary Mechanism	Drug Class
Response plateaus after half max dose Glipizide and glimepiride may be preferred in old patients.	FPG at 2 wk HbA1c at 3 m	Hypoglycemia Weight gain	Stimulates insulin release	Sulfonylureas
Less associated weight gain than with sulfonylureas & thiazolidinediones; weight loss may occur helps limit weight gain in combination therapy Max effective dosage is 2g/d Contraindications: Serum creatinine >1.5mg/dL(men), >1.4mg/dL(women) Congestive heart failure drug therapy Hepatic disease Alcohol abuse	Serum creatinine at Initiation FPG at 2wk A1c at 3m	Dose-related diarrhea (usually self-limiting in 7-10 days) Lactic acidosis iin patients with renal compromise	Inhibits hepatic glucose output	Biguanides
Administer with first bite of each meal Use slow titration to avoid gastrointestinal adverse effects(eg, 25 mg once daily for 2w;then 25 twice daily for 2 w;then 25 mg three times daily for 8w;max dosage is 100mg three times daily) Must use glucose if hypoglycemia occurs.	PPG at initiation HbA1c at 3 months	Dose-related diarrhea, abdominal pain, flatulence	Delays carbohydrate absorption to decrease postprandial hyperglycemia	α-Glucosidase Inhibitors
Decrease in glucose may not be pparent for 4w.Max efficacy of dose may not be observed for 4-6m. Contraindications: ALT >2.5 times the upper limit of normal Hepatic disease Alcohol abuse NYHA class III or IV	AST&ALT at baseline Monitor for signs of fluid overload	Edema Weight gain Congestive heart failure	Enhances insulin sensitivity	Thiazolidine-diones
Commonly used for basal-bolus dosing schedules	FPG at 2w HbA1c at3m PPG at initiation	Hypoglycemia	Stimulates insulin secretion	Glinides
Reduce dosage in patients with renal insufficiency. No weight gain or markedly reduced incidence of hypoglycemia	PPG at initiation FPG at 2w HbA1c at3m	Not clinically significant	Restores GLP-1 and GIP levels	DPP-4 Inhibitors

Table 9. Effect of Oral Therapies on Hemoglobin A1c Levels in Patients With Diabetes Mellitus

Hemoglobin A1c Reduction, %	Drug Therapy
Monotherapy
0.9 to 2.5	Sulfonylureas
1.1 to 3.0	Biguanide (metformin)
1.5 to 1.6	Thiazolidinediones
0.6 to 1.3	α-Glucosidase inhibitors
0.8	Dipeptidyl-peptidase 4 inhibitors
Noninsulin Injectables
0.43 to 0.56	Pramlintide
0.8 to 0.9	Exenatide
Combination Therapy
1.7	Sulfonylurea + metformin
1.4	Sulfonylurea + rosiglitazone
1.2	Sulfonylurea + pioglitazone
1.3	Sulfonylurea + acarbose
1.4	Repaglinide + metformin
0.7	Pioglitazone + metformin
0.8	Rosiglitazone + metformin
0.7	Dipeptidyl-peptidase 4 inhibitor + metformin
0.7	Dipeptidyl-peptidase 4 inhibitor + pioglitazone

Table 10. Major clinical trials Using Statins in Patients with Diabetes Mellitus

Outcome (Relative Risk Reduction)	No. Subjects	Mean Baseline LDL-C mg/dL	Medication (Dosage)	Trial
Total mortality (43%) Major coronary heart disease event (55%)	202	186	Simvastatin (10-40 mg once daily by mouth)	4S
Major coronary heart disease event (13%) Expanded end point (25%)	586	136	Pravastatin (40 mg once daily by mouth)	CARE
Major coronary heart disease event (27%) Any major cardiovascular event (22%)	5963	124	Simvastatin (40 mg once daily by mouth)	HPS
Acute coronary heart disease event (36%) Any major cardiovascular event (48%)	2838	117	Atorvastatin (10 mg once daily by mouth)	CARDS
Major coronary heart disease event (16%) Total cardiovascular events and procedures (23%)	2532	128	Atorvastatin (10 mg once daily by mouth)	ASCOT-LLA
Primary end point: death from any cause, myocardial infarction, documented unstable angina requiring rehospitalization, revascularization (performed at least 30 days after randomization), and stroke (16%) Secondary end point: death due to coronary heart disease, myocardial infarction, revascularization (25%)	4162 diabetic and nondiabetic subjects	......	Pravastatin (40 mg once daily by mouth) vs atorvastatin (80 mg once daily by mouth)	PROVE-IT
First major cardiovascular event, defined as death from coronary heart disease, nonfatal non–procedure-related myocardial infarction, resuscitation after cardiac arrest, or fatal or nonfatal stroke (22%, diabetic and nondiabetic subjects)	10001 diabetic and nondiabetic subjects	<130	Atorvastatin (10 mg once daily by mouth vs 80 mg once daily by mouth)	TNT
Coronary death, acute myocardial infarction,cardiac arrest with resuscitation (11%, diabetic and nondiabetic subjects)	1069 diabetic subjects (8888 total)	121	Atorvastatin (80mg once daily by mouth) vs atorvastatin (20 mg once daily by mouth)	IDEAL
Intensively treated patients had no change in atheroma burden, whereas moderately treatedpatients showed progression	654 diabetic and nondiabetic subjects	150	Atorvastatin (80mg once daily by mouth) vs pravastatin 40mg once daily by mouth)	REVERSAL
Regression of coronary atherosclerosis determined by intravascular ultrasound (6.8%,median reduction)	28 diabetic subjects191total	130	Rosuvastatin (40mg once daily by mouth)	ASTEROID

Table 11. Major Clinical Trials Using Fibrates in Patients with Diabetes Mellitus

Outcome (Relative Risk Reduction)	No. Subjects	Medication (Dosage)	Trial
Acute coronary heart disease events (22%) Stroke (31%)	633 diabetic subjects (2531 total)	Gemfibrozil (600mg twice daily by mouth)	VA-HIT
Acute coronary heart disease events (23%)	713	Fenofibrate (200mg/d)	DAIS
Acute coronary heart disease events (19%) Nonfatal myocardial infarction (24%)	9795	Fenofibrate (200mg once daily by mouth)	FIELD

Table 12. Insulin initiation and titration algorithm

Mean of self-monitoring FPG values from preceding 2 days	Increase of insulin dosage(Iu/day)
>=180 mg/dl ( 10 mmol/l)	8
140-180 mg/dl ( 7.8-10 mmol/l)	6
120-140 mg/dl (6.7-7.8 mmol/l)	4
100-120 mg/dl (5.6- 6.7 mmol/l)	2

Table 13. Potential strategy for insulin initiation and advancement

1. start 10 units NPH, glargin or detemir at bedtime. 2. continue metformin. Stop all other antihyperglycemic medication. 3. Have patient check daily FBG.. 4. Increase insulin doses according to table12. 5. If A1c meets goal(usually <7%),continue with single daily injection of insulin. 6. If A1c is above goal, and FBG has been 100-120mg/dl for at least 2 mounth,have patient check BG before breakfast, lunch, dinner, and bedtime. *Initiate 1-3 additional insulin injections per day, according to the following:      If pre-lunch BG is above 180mg/dl (10 mmol/l), add pre-breakfast insulin aspart, lispro or glulisine.      If pre-dinner BG is above 180mg/dl (10 mmol/l), add pre-lunch insulin aspart, lispro or glulisine.      If pre-bedtime BG is above 180mg/dl (10 mmol/l), add pre-dinner insulin aspart, lispro or glulisine

Table 14. Assessment guidelines

Every visite	Blood pressure / Weight / Visual foot examination
Quarterly	Hemoglobin A1c
Biannual	Dental examination
Annualy	Albumin/creatinin ratio(unless proteinuria is documented) Pedal pulses and neurologic examination Dilated eye examination(by trained expert) Examine patient for factors linked to clinical depression Blood lipids Assessment of diabetes knowledge and ability to provide self-care, including: Self monitoring blood glucose(SMBG) Meal planning and nutrition Physical activity Weight management