By: Dr. Hala M. Al-KhalidiFaculty of Pharmacy

King Abdulaziz University2008 - 1429

New diagnostic criteria and a new classification system, treatment for diabetes mellitus

Now many new data available, more etiological information has appeared

Updates many sources- Journals, WHO reports ADA -American Diabetes Association ACE -American College of Endocrinology AACE -American Association of Clinical Endocrinology DCCT -Diabetes Control and Complications Trial (UK)

Diabetes mellitus (DM) is a group of metabolic disorders

Characterized by hyperglycemia Poor control due Insufficient insulin associated with abnormalities in CHO, fat,

& protein metabolism Resulting in chronic complications; microvascular, macrovascular, and

neuropathic disorders.

Leading cause of blindness in adults age 20- 74

End-stage renal disease. 82,000 lower extremity amputations annually. Finally, a cardiovascular event is responsible

for 75% of deaths in individuals with type 2 DM

Interventions to prevent disease in high-risk populations have been reported for type 1 and type 2

World wide epidemic of DM is alarming CDC centers predict that incidence of DM

will rise by 37.5% in the USA, developing countries 170% over the next 30 years

Type 2 DM is increasing in both adult & children

New methods of control need to be developed

by health care providers

Cost ~ $132 billion 2002, indirect costs to disability

and mortality DM lead cause of blindness, end-stage

renal disease Annual ~82,000 lower extremity

amputations Finally, a cardiovascular event in 75% of

deaths with type-2 DM

HyperglycemHyperglycemiaia

Multiple genetic Multiple genetic defectsdefects

GENETIC PREDISPOSITION

ObesityObesity

ENVIRONMENT

Deranged insulinsecretion

PRIMARY BETA-CELLDEFECT

Inadequate glucose utilization

PERIPHERAL TISSUEINSULIN RESISTANCE

HYPERGLYCEMIAHYPERGLYCEMIA

Beta-cell exhaustion

TYPE 2 DIABETESTYPE 2 DIABETES

Pathogenesis of Type 2 DMPathogenesis of Type 2 DM

TYPE 1 DIABETES TYPE 2 DIABETES

Autoimmune 10% Children &

adolescents, or any age

Rapid/complete β-cell destruction with ketoacidosis

Insulin requiring for survival

C-peptide deficient

Obesity 90% β-cell dysfunction; may

range from insulin resistance with relative insulin deficiency to a secretory defect with or without insulin resistance, or Genetic defects

Individuals Having at Least Three Components meet the Criteria for Diagnosis;

The National Cholesterol Education Program Adult Treatment Panel (NCEP-ATP) III Guidelines

FH (i.e., parents or siblings) Obesity ( ≥20% over IBW, or [BMI] ≥25

kg/m2 Physical inactivity Race or ethnicity Hypertension (≥140/90 mm Hg in adults) HDL ≤35 mg/dl and/or a TG level ≥250

mg/dL Hx. Gestational diabetes mellitus/ delivery

baby weighing >9pd’s Hx. vascular disease polycystic ovary disease. Age Common women > men

Genetic defects in insulin action Type A insulin resistance Leprechaunism Rabson-Mendenhall syndrome Lipoatrophic diabetes

Exocrine pancreas Fibrocalculous pancreatopathy Pancreatitis Trauma / pancreatectomy

Neoplasia Cystic fibrosis Haemochromatosis Endocrinopathies Cushing's syndrome Acromegaly Phaeochromocytoma Glucagonoma Hyperthyroidism Somatostatinoma

Infections Congenital rubella Cytomegalovirus Drug- or

chemical-induced

Nicotinic acid Glucocorticoids Thyroid hormone Alpha-adrenergic

agonists Beta-adrenergic

agonists

Thiazides Dilantin Pentamidine Vacor Interferon-alpha

therapy

Gestational diabetes is CHO intolerance resulting in hyperglycaemia of variable severity with onset/ first recognition during pregnancy

Definition applies irrespective of whether or not insulin is used for treatment or the condition persists after pregnancy

Symptoms of diabetes - Polyuria - Polydipsia - Unexplained weight loss - & Casual Plasma glucose conc. ≥ 200mg/dl

(11.1mmol/L)OR

Fasting Plasma Glucose ≥ 126mg/dl (7.0mmol/L)OR

2-hr postload glucose ≥ 200mg/dl (11.1mmol/L) OGTT*(only in pregnancy) *WHO 75g anhydrous glucose in

water

8hr fasting8hr fasting

A metabolic state intermediate between normal glucose homeostasis and diabetes

Not interchangeable and represent different abnormalities of glucose regulation

TEST mg/dl

NORMALIMPAIREDFASTING GLUCOSE

IMPAIREDGLUCOSE

TOLERANCE

DIABETES

MELLITUS

FASTING PLASMA GLUC.

< 110 >110 but< 126

≥126

2HR AFTER GLUC. LOAD

<140>140 but< 200≥200

RANDOM≥200 with symptoms

Hypoglycemia (Insulin Shock). Diabetic ketoacidosis (DKA). Hyperglycemic hyperosmolar non-ketotic

coma (HHNK).

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Microvasculare Diabetic Retinopathy. Diabetic Nephropathy. Diabetic Neuropathy.. InfectionMacrovascular ischmia Periphry Diabetic gangrene Heart CAD Brain CVA or TIA’s

15

Near-normal glycemia will reduce the risk for microvascular and macrovascular disease complications

Ameliorate symptoms, to reduce mortality, and to improve quality of life.

Current evidence targets aggressive control

Avoid hypoglycemia and excess weight

The pancrease in a non-diabetic’s secretes small amount Insulin (basal secretion).

After meals a large amount of insulin is secreted (bouls secretion).

The goal of insulin therapy is to mimic this pattern of 24-hr glycaemic coverage.

Type-1 DM basal-bolus insulin therapy or pump therapy is successful.

Basal-bolus therapy in Type-2 DM is increasing.

Multiple oral agents, or oral agents with insulin to obtain goals.