DIABETES MELLITUS

American Diabetes Association Guidelines 2010

Diabetes Mellitus
group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both

Etiologic Classification of Diabetes Mellitus

1. 2. 3. 4. Type 1 Diabetes Type 2 Diabetes Specific Types of Diabetes Gestational Diabetes Mellitus

Type 1 Diabetes
A. Immune Mediated accounts for 5-10% of those with diabetes results from a cellular-mediated autoimmune destruction of the -cells of the pancreas markers of the immune destruction of the -cell are usually present in 85-90% of cases commonly occurs in childhood and adolescence, but it can occur at any age, even in the 8th and 9th decades of life

Type 1 Diabetes
B. Idiopathic Diabetes patients have permanent insulopenia but have no evidence of autoimmunity occurs in minority of patients with Type 1 DM, mostly are of African and Asian ancestry strongly inherited

Type 2 Diabetes
accounts for ~90-95% of those with diabetes characterized by impaired insulin secretion, insulin resistance, excessive hepatic glucose production, and abnormal fat metabolism Risk increases with: 1. Age 2. Obesity 3. Physical Inactivity

Other specific types of diabetes

A. Genetic defects of -cell function 1. Maturity Onset Diabetes of the Young (MODY) B. Genetic defects in insulin action 1. Type A insulin resistance 2. Leprechaunism 3. Rabson-Mendenhall syndrome 4. Lipoatrophic diabetes 5. Others

Other specific types of diabetes

C. Diseases of the Exocrine Pancreas 1. Pancreatitis 2. Trauma/Pancreatectomy 3. Neoplasia 4. Cystic fibrosis 5. Hemochromatosis 6. Fibrocalculous pancreatopathy 7. Others

Other specific types of diabetes

D. Endocrinopathies 1. Acromegaly 2. Cushings Syndrome 3. Glucagonoma 4. Pheochromocytoma 5. Hyperthyroidism 6. Somatostatinoma 7. Aldosteronoma 8. Others

Other specific types of diabetes

D. Drug or Chemical Induced 1. Vacor 2. Pentamidine 3. Nicotinic Acid 4. Glucocorticoids 5. Thyroid hormone 6. Diazoxide 7. -adrenergic agonists 8. Thiazides 9. Dilantin 10. -interferon 11. Others

Other specific types of diabetes

D. Infections 1. Congenital Rubella 2. Cytomegalovirus 3. Others E. Uncommon forms of immune mediated diabetes 1. Stiff-man syndrome 2. Anti-insulin receptor antibodies 3. Others

Gestational Diabetes Mellitus

Any degree of glucose intolerance with onset or first recognition during pregnancy

Acute Complications of DM
1. Diabetic Ketoacidosis 2. Hyperglycemic hyperosmolar state

Diabetic Ketoacidosis (DKA)

results from relative or absolute insulin deficiency combined with counterregulatory hormone excess (glucagon, cathecolamines, cortisol, GH) usually occurs in patients with Type 1 DM but can develop in any person with diabetes

Manifestations of DKA
A. Symptoms Nausea/vomiting Thirst/Polyuria Abdominal pain Shortness of breath B. Physical findings Tachycardia Dehydration/hypotension Tachypnea/Kussmaul breathing/ respiratory distress Ketotic breath (fruity, with acetone smell)

Manifestations of DKA
B. Physical findings Abdominal tenderness (may resemble acute pancreatitis or surgical abdomen) Lethargy/obtundation/cerebral edema/possibly coma

Precipitating Events
1. Inadequate insulin administration 2. Infection UTI is the single most common
infection associated with diabetic ketoacidosis (pneumonia, gastroenteritis, sepsis)

3. Infarction (cerebral, coronary, mesenteric, peripheral) 4. Drugs (cocaine) 5. Pregnancy

Hyperglycemic hyperosmolar state (HHS)

characterized by hyperglycemia, hyperosmolarity, and dehydration without significant ketoacidosis relative insulin deficiency and inadequate fluid intake presents in older patients with type 2 DM and carries a higher mortality rate than DKA

Hyperglycemic hyperosmolar state (HHS)

Fingerstick glucose should be checked immediately and is usually greater than 600 mg/dL PE reflects profound dehydration, tachycardia, and altered mental status Notably absent are symptoms of nausea & vomiting, abdominal pain and Kussmaul respirations

Chronic Complications
A. Microvascular 1. Eye disease 2. Neuropathy 3. Nephropathy B. Macrovascular 1. Coronary artery disease 2. Peripheral artery disease 3. Cerebrovascular disease

Chronic Complications
D. Other 1. Gastrointestinal (gastroparesis, diarrhea) 2. Genitourinary (uropathy, sexual dysfunction) 3. Dermatologic 4. Infectious 5. Cataracts 6. Glaucoma 7. Periodontal disease

Categories of Increased Risk for Diabetes

1. Impaired Fasting Glucose - FPG 100mg/dl (5.6mmol/L) to 125 mg/dl (6.9mmol/L) 2. Impaired Glucose Tolerance 2-h PG in the 75-g OGTT 140 mg/dl (7.8mmol/L) to 199mg/dl (11.0mmol/L) 3. A1C = 5.7-6.4%
Note: Individuals with IFG and/or IGT have been referred to as having pre-diabetes, indicating the relatively high risk for the future development of diabetes

Diagnostic Criteria for Diabetes Mellitus

1. A1C 6.5% - The test should be performed in a laboratory using a
method that is NGSP certified and standardized to the DCCT assay.*

OR 2. FPG 126 mg/dl (7.0mmol/L) - Fasting is defined as no caloric

intake for at least 8h.*

OR
3. 2-h plasma glucose 200mg/dl (11.1mmol/L) during an OGTT - The test should be performed as described by the World
Health Organization, using a glucose load containing the equivalent of 75g anhydrous glucose dissolved in water.*

OR

4. In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose 200mg/dl (11.1mmol/l)
*In the absence of unequivocal hyperglycemia, criteria13 should be
conrmed by repeat testing.

Criteria for testing for diabetics in asymptomatic adult individuals

1. Testing should be considered in all adults who are overweight (BMI25kg/m2) and have additional risk factors: Physical inactivity First-degree relatives with diabetes Members of high-risk ethnic populations (e.g., African American, Latino, Native American, Asian American, Pacific Islander) Women who delivered a baby weighing >9 lb or were diagnosed with GDM Hypertension (140/90 mmHg or on therapy for hypertension) HDL cholesterol level <35mg/dl (0.90mmol/L) and/or Triglyceride level >250mg/dl (2.82mmol/L) Women with polycystyic ovarysyndrome A1C 5.7%, IGT, or IFG on previous tesing Other clinical conditions associated with insulin resistance (e.g., severe obesity, acanthosis nigricans) History of CVD 2. In the absence of the above criteria, testing of diabetes should begin at age 45 years 3. If results are normal, testing should be repeated at least at 3-years intervals, with consideration of more frequent testing depending on initial results and risk status

Prevention/Delay of Type 2 DM
Patients with IGT, IFG, or an A1C of 5.7 6.4% should be referred to an effective ongoing support program for weight loss of 510% of body weight and an increase in physical activity of at least 150 min/week of moderate activity such as walking In addition to lifestyle counseling, metformin may be considered in those who are at very high risk for developing diabetes*

Prevention/Delay of Type 2 DM
Monitoring for the development of diabetes in those with pre-diabetes should be performed every year

Long-Term Treatment
The goals of therapy for type 1 or type 2 DM are: 1. Eliminate symptoms related to hyperglycemia 2. Reduce or eliminate the long-term microvascular and macrovascular complications of DM 3. Allow the patient to achieve as normal a lifestyle as possible

Diabetes Education

Nutrition

Long-Term Treatment Exercise Medications

Diabetes Self-Management Education (DMSE)

is the ongoing process of facilitating the knowledge, skill, and ability necessary for diabetes self-care this process incorporates the needs, goals, and life experiences of the person with diabetes and is guided by evidence- based standards

Diabetes Self-Management Education (DMSE)

the overall objectives are to support informed decision-making, self-care behaviors, problem-solving and active collaboration with the health care team and to improve clinical outcomes, health status, and quality of life

Nutrition
as for the general population, diet that includes fruits, vegetables, fiber-containing foods, and low fat milk is advised for weight loss, either low-carbohydrate or low-fat calorie-restricted diets may be effective in the short term (up to 1 year) must be adjusted to meet the goals of individual patients

Dietary fat intake in diabetes management

Saturated fat intake should be 7% of total calories Reducing intake of trans fat lowers LDL cholesterol and increases HDL cholesterol; therefore, intake of trans fat should be minimized

Carbohydrate intake in diabetes management

Monitoring carbohydrate, whether by carbohydrate counting, exchanges, or experience-based estimation, remains a key strategy in achieving glycemic control
the use of the glycemic index and glycemic load may provide a modest additional benefit for glycemic control over that observed when total carbohydrate is considered alone

Other nutrition recommendations

Sugar alcohols and nonnutritive sweeteners are safe when consumed within the acceptable daily intake levels If adults with diabetes choose to use alcohol, daily intake should be limited to a moderate amount (one drink per day or less for adult women and two drinks per day or less for adult men)

Exercise
cardiovascular risk reduction reduced blood pressure maintenance of muscle mass reduction in body fat weight loss lowers plasma glucose increase insulin sensitivity

Recommendations
150 min/week (distributed over at least 3 days) of aerobic physical activity in patients with type 2 DM, the exercise regimen should also include resistance training should be under physicians supervision

Glycemic Control
A. Self-Monitoring Blood Glucose (SMBG) standard of care in diabetes management provide a picture of short-term glycemic control B. A1C standard method for assessing longterm glycemic control reflects average glycemic control over the previous 2-3 months

Anti-diabetic medications
A. Oral hypoglycemic agents Sulfonylureas Thiazolidinediones Biguanides Alpha-glucosidase inhibitors D-phenylalinine derivatives Combinations

Sulfonylureas
stimulate insulin secretion by interacting with the ATP-sensitive potassium channel on the beta cell Adverse reactions 1. Hypoglycemia Weight gain - results from the increased insulin levels and improvement in glycemic control

Sulfonylureas
A. First-generation sulfonylureas
1. Chlorpropamide 2. Tolazamide 3. Tolbutamide

B. Second-generation sulfonylureas
1. Glimepiride 2. Glipizide 3. Glyburide

Biguanides
reduces hepatic glucose production decreases intestinal absorption of glucose improves cell sensitivity to insulin

Metformin - weight loss - disadvantages: lactic acidosis, diarrhea, nausea

Thiazolidinediones
bind to the PPAR- (peroxisome proliferator-activated receptor) nuclear receptor Decrease insulin resistance Increase glucose utilization Examples: 1. Pioglitazone (Actos) 2. Rosiglitazone (Avandia)

Thiazolidinediones
A. Advantages Lowers insulin requirements B. Disadvantages Peripheral edema CHF weight gain fractures macular edema rosiglitazone may increase risk of MI

-Glucosidase Inhibitors
reduce postprandial hyperglycemia by delaying glucose absorption do not affect glucose utilization or insulin secretion disadvantages diarrhea, flatulence, abdominal distention Examples: 1. Acarbose 2. Miglitol

Insulin secretagogues nonsulfonylureas

interact with the ATP-sensitive potassium channel increasing insulin secretion rapid onset, short half-life Examples: 1. Repaglinide 2. Nateglinide

Insulin
Produced in the -cells of the pancreatic islets Glucose is the key regulator if insulin secretion Glucose levels >3.9mmol/L (70mg/dl) stimulate insulin synthesis

http://www.megahowto.com/how-to-get-your-body-intobalance-between-insulin-and-glucagon

Correlation of A1C with average glucose Mean plasma glucose A1C (%) 6 7 8 mg/dl 126 154 183 mmol/l 7.0 8.6 10.2

9
10 11

212
240 269

11.8
13.4 14.9

12

298

16.5

These estimates are based on ADAG data of 2,700 glucose measurements over 3 months per A1C measurement in 507 adults with type 1, type 2, and no diabetes. The correlation between A1C and average glucose was 0.92 (49). A calculator for converting A1C results into estimated average glucose (eAG), in either mg/dl or mmol/l, is available at http://professional.diabetes.org/eAG.

Summary of glycemic recommendations for non-pregnant adults with diabetes A1C Pre-prandial capillary plasma glucose <7.0%* 70130 mg/dl (3.97.2 mmol/l)

Peak postprandial capillary plasma glucose**

180 mg/dl (10.0 mmol/l)

* Referenced to a nondiabetic range of 4.06.0% using a DCCT-based assay. ** Postprandial glucose measurements should be made 12 h after the beginning of the meal, generally
peak levels in patients with diabetes.

Recommended therapy for Type 1 DM

1. use of multiple dose insulin injections (3 4 injections per day of basal and prandial insulin) or Continuous subcutaneous insulin infusion (CSII) therapy; 2. matching of prandial insulin to carbohydrate intake, premeal blood glucose, and anticipated activity; 3. for many patients (especially if hypoglycemia is a problem), use of insulin analogs

Management of Type 2 Diabetes

Glycemic Control
Diet/Lifestyle Exercise Medication
Treat associated conditions Screen for/manage complications of diabetes

Dyslipidemia Hypertension Obesity Coronary heart disease

Retinopathy Cardiovascular disease Nephropathy Neuropathy Other complications

THANK YOU!