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 function Gentic 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 virus Gestational 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 ( mmol/l) or mg/dl Imparied fasting glucose (IFG); when FPG of mg/dl or ( 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 hr, while glargine before 4- 5 hr with duration of hr, its less nocturnal hypoglycemia compared with NPH, IF given at bed time e.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 unit/kg in honey moon phase.max u/kg in sever ketosis. In type 2 D.M ; 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 life Wt 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 succharide Acarbose (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/ 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.

7-metaglip™ ; glipizide+ metformin 2.5mg/250mg 2.5mg/500mg, 5mg/500mg 8-avandamet™ rosiglitazone 1mg,2mg, 4mg/ metformin 500mg, or 2mg,4mg/1000mg