PresenterAli Mahamoud Al-madani

SupervisorDr. Lokesh Shetty

Diabetes mellitus (DM) is a metabolic diseases in which a person has high blood sugar Level (Fasting plasma glucose level more than 126 mg/dl).

May due to,pancreas does not produce enough insulin

(Type 1 DM), or because cells do not respond (Resistant) to the insulin that is produced (Type 11 DM)

If left untreated, Diabetes can cause many life threatening complications:

• Blindness• Chronic Renal Failure= kidney failure• Atherosclerosis= heart attacks and stroke• Diabetic Neuropathy= numbness and pain to

hands and feet• Foot Ulcers• Diabetic Retinopathy & Cataract etc

Type 2 diabetes makes up about 90% of cases of diabetes of DM.

Obesity is thought to be the primary cause of type 2 diabetes in people who are genetically predisposed to the disease.

Type 2 diabetes is initially managed by increasing exercise and dietary modification.

If blood glucose levels are not adequately lowered by these measures, medications such as metformin or insulin or other Therapeutics may be needed.

A proper diet and exercise are the foundations of diabetic care, with a greater amount of exercise yielding better results.

Aerobic exercise (Exercise generates energy) leads to a decrease in HbA1c and improved insulin sensitivity.

A diabetic diet that promotes weight loss is important.

A low glycemic index diet has been found to improve blood sugar control.

If changes in lifestyle in those with mild diabetes has not resulted in improved blood sugars within six weeks, medications should then be considered

MEDICATIONThere are several classes of anti-diabetic medications available.

Metformin is generally recommended as a first line treatment as there is some evidence that it decreases mortality.

A second oral agent of another class may be used if metformin is not sufficient.

Other classes of medications include: sulfonylureas, nonsulfonylurea secretagogues, alpha glucosidase inhibitors, thiazolidinediones, glucagon-like peptide-1 analog, and dipeptidyl peptidase-4 inhibitors.

Metformin should not be used in those with severe kidney or liver problems.

Injections of insulin may either be added to oral medication or used alone in Type II DM

Most people do not initially need insulin for Management Type II DM. When Insulin used, a long-acting Insulin formulation is typically to be added at night, with oral medications being continued.

When nightly insulin is insufficient twice daily insulin may achieve better control. In those who are pregnant insulin is generally the treatment of choice.

Brief Review on Oral Hypoglycemic Agents

They are indicated only in Type II DM, when not controlled by diet & exercise.

They are best used in Patients with,1. Age above 40 years at onset of disease.2. Obesity at the time of presentation3. Duration of disease more than 5 years when

starting treatment.4. Fasting blood glucose level more than

200mg/dl5. Insulin requirement more than 40 U per day.6. No ketoacidosis or history of it or any other

complication.

Sulphonylureas (SUs)

•Interact with receptors on ß cell surface, closes K+ channels in the membrane, causing depolarisation allowing Ca to enter cells triggering release of insulin

•More insulin released•

•Reduces hepatic glucose production

•Increases glucose uptake in the peripheral tissues

Common SulphonylureasGeneric

name

Tolbutamide Gliclazide Glibenclamide Glimepiride

Brand name

Rastinon Diamicron Euglucon Amaryl

Size of tablet

500mg 80mg 2.5mg, 5mg 1,2,3 and 4mg

Doses 250mg bd – 1gram tds

40mg-160mg bd

2.5mg od – 10mg bd

1mg od – 6mg od

When taken

With or after food

Just before or during food

Just before or during food

With the first meal of the day

Duration of action

6-10 hours 10-15 hours

20-24 hours 12-24 hours

Biguanides - MetforminTablet size – 500mg, 850mgDose range – 250mg bd to 1gram tdsWhen to take – with or after food

•Mechanism of Action –Inhibits gluconeogenesis

–Stimulates peripheral glucose uptake –Enhances insulin receptor binding

–Reduces intestinal glucose absorption

Alpha Glucosidase Inhibitor - AcarboseTablet size – 50mg, 100mg

•Dose range – 50mg od up to 100mg tds•When to take – with the first mouthful of

food, swallowed or chewed

Mechanism of Action:Slows absorptions of starchy foods from the intestineHas no effect on insulin production

Meglitinide – RepaglinideTablet size – 0.5mg, 1mg and 2mgDose range – starting dose 0.5mg per meal up to qds, to a maximum dose of 4mg per meal; total daily dose not exceed 16mg.

Duration of action 3-4 hours. Maximum plasma concentration occur 60 minutes after taking tablet

Mechanism of Action:Rapidly absorbed, fast acting, short duration insulin

secretagogue

Derived from the meglitinide portion of glibenclamide binds with a different site on beta cell

Amino Acid Derivatives •Generic name - Nateglinide

•Brand name - Starlix•Tablet size – 60mg, 120mg or 180mg

•Dosage – start 60mg before meals (1-30mins). Usual maintenance dose is 120mg before meals, maximum 180mg TDS.

•Mechanism of Action–Restores early phase of insulin release

•For use in people already taking Metformin where a sulphonylurea may be inappropriate

Thiazolidinediones (glitazones)–Generic names

• RosiglitazonePioglitazone

–Brand name• AvandiaActos

–Tablet size• 4mg, 8mg15mg, 30mg

–Dose range• 4mg od – 8mg od15mg – 30mg od

Thiazolidinediones (glitazones)

Mechanism of Action

Targets insulin resistance at adipose tissue, skeletal muscle and liver by binding to specific nuclear receptors - peroxisome proliferators-activated receptor gamma agonists. Thus increases transcription of several insulin responsive genes.

Improve sensitivity to insulin in muscle, fat tissues and liver

Does not stimulate pancreatic insulin secretion

Management of Type II DM with Surgery.

Weight loss surgery in those who are obese is an effective measure to treat diabetes. Many are able to maintain normal blood sugar levels with little or no medications following surgery and long term mortality is decreased. The body mass index cutoffs for whensurgery is appropriate are not yet clear. It however is recommended that this option be considered in those who are unable to get both their

weight and blood sugar under control