Diabetes mellitus
Fasting venous plasma glucose ≥ 7mmol/l(126mg/dl)Metabolic disorder , hyperglycemia, abnormality in C.H,fat, protein metabolism.
Defect in insulin secretion , insulin sensitivity or both
Type I D.M Due to Pancrease B-cell destruction result in absolute insulin defficiency .
Type 2 D.M accounts for 90% , it associated with both insulin resistance and relative insulin defficiency .
Insulin resistance : increase lipolysis ,free fatty acid production, increase hepatic glucose production and decrease skeletal muscle uptake of glucose .
Causes of D.M
Gentic defect of B-cell functionGentic defect in insulin action
Endocrine disorder ; acromegaly, cushing syndrom ,pancreatitis , cystic fibrosis , pheochromocytoma.
Drug ;thiazide , diuretic , α- interferone , glucocorticoid , oral contraceptive , diazoxide , thyroid Hr and pentamidine .
Causes of D.M
Viral infection by cytomegalo virusGestational diabetes (GDM)
Diagnosis
HbA1C≥ 6.5%
FPG ≥ 126mg/dl (7mmol/l)
OGTT ; measurement of glucose 2hr post prandial of ≥ 200mg/dl (111.1 mmol/l).
RPG ≥ 200MG/dl.
Prediabetic :
Imparied glucose tolerence (IGT); when OGTT (7.8-11 mmol/l) or 140-199mg/dl
Imparied fasting glucose (IFG); when FPG of 100-125mg/dl or (5.6-6.9 mmol/l)
Treatment
Nonpharmacology treatment :Aerobic regular exercise , wt reduction , smoking cessation, focus on regular insulin adminstration with a balanced diet to achieve healthy body wt.
Reduce saturated fat,and Carbohydrate .
Treatment
Pharmacology :Insulin :
1-rapid acting insulin ; adm. Before 10min of meals with duration 3-5 hr .e.g; (lispro, aspart, and glulisine insulins) humalog (vial + pen + car.) ,( novorapid (vial,+pen+cartridge ),novolog (vial,+pen+cartridge ), apidra (car. + opticlik pen sys.)
2-short acting ,regular insulin ; adm. Before 30min of meals with duration 3-6 hr
e.g. (humulin r (vial ) novoline r (vial , pen , cartridge and innolet) ,actrapid vial, insuman rapid (cartridge )
INSULIN
3- intermediate action(NPH) its neutral protamine hagedorn also called isophane protamine ; admin before 2-4 hr with duration 8-12hr , its may contribute to labile glucose response , nocturnal hypoglycemia and fasting hyperglycemia .
e.g. humulin N, (vial + pen) Novolin N (vial, pen , innolet) , insulitard vial , insulitard penfill, insulitard innolet
INSULIN
4-Long acting ; detemir admin before 2hr with duration of 14-24 hr , while glargine before 4-5 hr with duration of 22-24 hr , its less nocturnal hypoglycemia compared with NPH, IF given at bed timee.g. levemir™ (detemir), lantus™ (glargine )
Levemir flexpen, levemir penfill cartridges )
Lantus vial+ pen + cartildge
INSULIN
5-premixed insulin ;humalog mix 75/25(75% neutral protamine lispro , 25% lispro) (vial+pen + cartridge )
Novolog mix 70/30; 70% aspart protamine suspension and 30% aspart .
Humalog mix 50/50; (50% neutral protamine lispro and 50% lispro)
NPH regular combination ; humulin 70/30, novolin 70/30; 70% isophane , 30% regular
INSULIN
In type 1 D.M ; Insulin dose 0.5 to 0.6 unit /kg may fall to 0.1-0.4 unit/kg in honey moon phase .max 0.5-1 u/kg in sever ketosis .In type 2 D.M ; 0.7- 2.5 U/KG
Adverse effect ; hypoglycemia , wt gain.
Hypoglycemia : treated by dextrose I.V, glucagon
INNOLET
PEN
OTHER INTECTION
Other injectable preparation glucagon-like peptide 1(GLP-1) agonists :1-Exenatide (byetta)™: enhance glucose dependent insulin secretion and reduce hepatic glucose production, also it reduce appetite and reduce gastric emptying rate causing wt loss. Also inhibit glucagon secr.
2-liraglutide (victoza)™; similar in action to exenatide with longer duration
OTHER INJ.
Amylinomimetic :Pramlintide (symlin)™; neurohormone cosecreted from B- CELL with insulin , its suppress glucagon secretion ,increase satiety ( which can cause wt loss).
SULPHONYL UREA
Sulfonyl ureas: stimulate pancreatic secretion of insulin .
1-glipizide(minodiab) 5mg , 10mg , the duration about up to 20hr.( Metabolized by liver) , glipizide XL (slow release form)
(Daily before breakfast or lunch)
2-glyburide(glibenclamide ) 1.25, 2.5,5 mg , duration up to 24hr, (liver +renal ) ,daily during or after breakfast.
3-glimepiride (amaryl)™ 1,2,3,4,6 mg , duration up to 24hr (metabolized by liver). Given shortly before breakfast.
SULPHONYL UREA
4-Gliclazide (diamicron)™ 30,40,80mg , diamicron MR , taken daily with breakfast .Adverse effect of sulphonyl urea
Hypoglycemia specialy with longer half lifeWt gain
Less common haemolytic anemia , GIT upset, and cholestasis
MEGLITINIDE
Meglitinides: short acting insulin secretory , they should be adminstered 30 min before meal . If a meal is skipped , the medication should also be skipped .1- repaglinide (prandin)™ ( novonorm )™; 0.5,1,2mg , given three to four times daily .
2-nateglinide (starlix)™ ; 60mg,120mg,180mg
Also three times daily
BIGUANIDE
Biguanide ; increase isulin sensitivity of both hepatic and peripheral , reduce LDL, triglyceride and increase HDL. ALSO decrease glucose absorption in GIT.
Metformin (500,850,1000mg )
Adverse effect ; GIT (stomach upset, abdominal discomfort, anorexia and diarrhea , also lactic acidosis in renal impariment.
How to minimized GIT adverse effect?
Glucophage XR (extended release ) and take the medicine with food .
GLITAZONE
Thiozolidinediones (glitazone );It enhance insulin sensitivity in muscle , liver and fat tissue indirectly and need insulin for their action
1-pioglitazone (Actos )™(15,30,45mg) with duration 24hr , also decrease triglyceride without increase in LDL.
2- rosiglitasone (avandia )™ 2,4,8mg with duration 24hr , an increase in LDL will occur.
GLUTAZONE
Adverse effect of glitazone ; water retention due to sodium retention , odema, wt gain, hepatic toxicity , increase risk of upper and lower limb .α –glucosidase inhibitor
α –glucosidase inhibitor ; inhib. Of breakdown of sucrose and complex carbohydrate to mono succharideAcarbose (precose )™ and miglitol (glycet)™
25,50,,100mg taken 1-3 times daily .
Adverse effect ; flatulence , abdominal discomfort, bloating and diarrhea.
DPP-4 -I
DPP-4-Inhibitor : dipeptidyl peptidase-4 enzyme –inhibitor(glipitin) ; these agent able to prolong half life of endogenous incretin hr. that required for decrease glucagon level , stimulate insulin secretion .
Sitagliptine (januvia)™ 25,50,100mg. Given once daily , reduce dose in renal impairment.
Alogliptin (vipidia)™ 6.25, 12.5,25mg also once daily and reduce dose in renal impairment
DPP4-I
Saxagliptin (onglyza)™ ; 2.5,5mg once daily .linagliptine(trajenta)™ ; 5mg once daily
Vildagliptin (galvus )™ ; 50mg twice daily
All above group need dose adjusment in case of mixed with sulphonyl urea and insulin , in add. alogliptine + metformin + pioglitazone need adjustment bec. Risk of hypoglycemia.
DPP4-I
Adverse effect ; mild hypoglycemia if use alone , urticaria , facial oedema , Rare steven –johnson syndrom , pancreatitis , (saxagliptine rare associated with decrease lymphocyte count and cause infection )SOD.GLUCOSE CO-TRANS.2-I
Na- glucose co transporter 2 inhibitor ;Inhibit glucose reabsorption in renal and increase urinary glucose excretion .
Canagliflozin (invokana)™ ; 100mg, 300mg 1x1
Dapagliflozin(forxiga)™; 5mg, 10mg 1x1
Empagliflozin (jardiance)™ ; 10mg, 25mg 1x1
Most adverse eff. UTI, thirst, polyurea.
MIXED PREPARATION ROR TYPE 2 D.M
1- glucovance™ (glibenclamide+metformin)1.25/250,2.5/500,5/500
2- vipdomet ™ 12.5mg of alogliptine+ 1000mg of metformin .
3-jentadueto™ linagliptine 2.5mg/850mg or 1000mg
4-komboglyze™ saxagliptine 2.5mg/850 or 1000mg
5-janumet™ sitagliptine 50mg/500mg, or 1000mg met.
6-galvumet™, eucreas™ vildagliptin 50mg/850 or 1000 mg met.