DIABETES MELLITUS THERAPY

Nutrition Therapy  Weight loss frequently is a primary goal of nutrition therapy because 80% to 90% of people with type II diabetes are obese  Diet prescriptions for type II diabetes need to take into account the higher prevalence of hyperlipidemia, atherosclerosis, and hypertension in this population.

Protein Intake Recommended protein intake for patients with type II diabetes: 0.8 g/kg body weight/day Recommended protein intake for patients with type II diabetes: 0.8 g/kg body weight/day Protein allowance amounts 12% to 20% of daily calories and should be derived from both animal and vegetable sources. Protein allowance amounts 12% to 20% of daily calories and should be derived from both animal and vegetable sources.

80% to 90% of daily calories are distributed between fat and carbohydrate intake, based on a patient's nutrition assessment and treatment goals (glucose, lipid, and weight outcomes).

Fat Intake  Reduce dietary fat to < 35% of total calories  Limit saturated fat to < 10% of total calories, and < 7% of calories in patients with elevated LDL cholesterol  Limit polyunsaturated fats to 10% of total calories  Limit daily cholesterol consumption to 300 mg  Moderately increase intake of monounsaturated fats such as canola and olive oil (up to 20% of calories). A diet high in monounsaturated fats has been shown to improve glucose control, lower triglycerides, and raise HDL levels.

Carbohydrate Intake Emphasis is placed on whole grains, starches, fruits, and vegetables to provide the necessary vitamins, minerals, and fiber in the diet. Emphasis is placed on whole grains, starches, fruits, and vegetables to provide the necessary vitamins, minerals, and fiber in the diet. The recommended daily consumption of fiber is the same for people with diabetes as for nondiabetics (20 g to 35 g). The recommended daily consumption of fiber is the same for people with diabetes as for nondiabetics (20 g to 35 g).

Carbohydrate Intake Sucrose Sucrose  A modest amount of sugar is allowed in the daily diet of patients with type II diabetes. Obese individuals usually are advised to avoid sweets because of the potential of a small portion triggering overconsumption. Fructose Fructose  A natural source of dietary fructose is fruits and vegetables.  Moderate consumption is recommended, particularly concerning foods in which fructose is used as a sweetening agent.

Alcohol Intake Moderate consumption will not adversely affect blood glucose in patients whose diabetes is well controlled. Calories from alcohol should be included as part of the total calorie intake. Moderate consumption will not adversely affect blood glucose in patients whose diabetes is well controlled. Calories from alcohol should be included as part of the total calorie intake. For patients taking insulin, one or two alcoholic beverages per day are acceptable (one alcoholic beverage = 12 oz beer, 5 oz wine, or 1[ring] oz distilled spirits; sweet drinks should be avoided) For patients taking insulin, one or two alcoholic beverages per day are acceptable (one alcoholic beverage = 12 oz beer, 5 oz wine, or 1[ring] oz distilled spirits; sweet drinks should be avoided) Patients taking insulin or sulfonylureas are susceptible to hypoglycemia if alcohol is consumed on an empty stomach. Patients taking insulin or sulfonylureas are susceptible to hypoglycemia if alcohol is consumed on an empty stomach.

Oral Antidiabetic Agents  Oral medication is initiated when 3 months of diet and exercise alone are unable to achieve or maintain plasma glucose levels within these glycemic guidelines.  If patients are symptomatic, oral antidiabetic agents or insulin should be initiated in concert with diet and exercise.

Oral Antidiabetic Agents  Current therapy for the treatment of hyperglycemia of type II diabetes includes the following oral antidiabetic agents: Sulfonylureas Sulfonylureas Biguanides: metformin Biguanides: metformin Alpha-glucosidase inhibitors: acarbose Alpha-glucosidase inhibitors: acarbose Thiazoladinediones Thiazoladinediones Meglitinides Meglitinides

Oral Antidiabetic Agents In general, oral agents are contraindicated in patients who: In general, oral agents are contraindicated in patients who: Are pregnant or lactating Are pregnant or lactating Are seriously ill Are seriously ill Have significant kidney or liver disease Have significant kidney or liver disease Have demonstrated allergic reactions. Have demonstrated allergic reactions.

Sulfonylureas Sulfonylureas work primarily by stimulating pancreatic insulin secretion, which in turn reduces hepatic glucose output and increases peripheral glucose disposal. Sulfonylureas work primarily by stimulating pancreatic insulin secretion, which in turn reduces hepatic glucose output and increases peripheral glucose disposal. Examples of the compounds are: Examples of the compounds are: Glimepiride (Amaryl) Glimepiride (Amaryl) Glipizide Glipizide Glyburide Glyburide Gliclazide Gliclazide

Biguanides  Metformin is a biguanide that works mainly by:  Suppressing excessive hepatic glucose production  Increasing glucose utilization in peripheral tissues to a lesser degree  It may also improve glucose levels by reducing intestinal glucose absorption

Biguanides Metformin is effective as monotherapy or in combination with sulfonylureas, alpha-glucosidase inhibitors, and insulin Metformin is effective as monotherapy or in combination with sulfonylureas, alpha-glucosidase inhibitors, and insulin Treatment with metformin has beneficial effects on plasma lipids Treatment with metformin has beneficial effects on plasma lipids Metformin therapy has been associated with weight loss or no weight gain Metformin therapy has been associated with weight loss or no weight gain

Biguanides Contraindications: Contraindications:  renal failure  significant hepaticdisease  heart failure  alcohol abuse  any hypoxic condition or history of lactic acidosis

Biguanides  Lactic acidosis is a rare complication of metformin therapy and has a high mortality rate  In any patient who is hospitalized with an acute severe illness, metformin should be temporarily discontinued

Alpha-glucosidase inhibitors Acarbose slows down the breakdown of disaccharides and polysaccharides and other complex carbohydrates into monosaccharides slows down the breakdown of disaccharides and polysaccharides and other complex carbohydrates into monosaccharides t he enzymatic generation and subsequent absorption of glucose is delayed and the postprandial blood glucose values, which are characteristically high in patients with type II diabetes, are reduce d t he enzymatic generation and subsequent absorption of glucose is delayed and the postprandial blood glucose values, which are characteristically high in patients with type II diabetes, are reduce d

Thiazolidinediones (PPAR  -agonists) They work mainly by improving peripheral insulin resistance in skeletal muscle without stimulating insulin secretion. They work mainly by improving peripheral insulin resistance in skeletal muscle without stimulating insulin secretion. They works to a lesser degree by reducing excessive hepatic glucose production. They works to a lesser degree by reducing excessive hepatic glucose production. It also results in significant reduction in total triglyceride and elevation in HDL levels. It also results in significant reduction in total triglyceride and elevation in HDL levels.

Meglitinides  Examples: repaglinide, nataglinide  It is a benzoic acid derivative and a short-acting insulin releaser.  It stimulates the release of insulin from the pancreatic beta cells by closing ATP-sensitive potassium channels.  It has no significant effect on plasma lipid levels  Rapid onset and short duration of action make multiple daily doses necessary (take it immediately before each meal!).

Monotherapy With Oral Antidiabetic Agents Obese Patients With Newly Diagnosed Diabetes With/Without Dyslipidemia  Metformin or acarbose have the advantage of not inducing weight gain, which can occur with sulfonylureas and insulin therapy.

Monotherapy With Oral Antidiabetic Agents Thin Elderly Patients Thin patients in general tend to be insulin deficient and more commonly require sulfonylureas as initial oral monotherapy Thin patients in general tend to be insulin deficient and more commonly require sulfonylureas as initial oral monotherapy Caution should be used when prescribing any medication in the elderly, and starting doses need to be lower than those in younger patients Caution should be used when prescribing any medication in the elderly, and starting doses need to be lower than those in younger patients Rosiglitazone, acarbose and metformin may also be effective as monotherapy Rosiglitazone, acarbose and metformin may also be effective as monotherapy

Monotherapy With Oral Antidiabetic Agents Patients With Acceptable Fasting Glucose Values but Elevated Glycohemoglobin Levels It suggests the likelihood of elevated postprandial glucose levels It suggests the likelihood of elevated postprandial glucose levels Acarbose would be an appropriate choice in these patients ( by reducing the postprandial glucose value) Acarbose would be an appropriate choice in these patients ( by reducing the postprandial glucose value) If acarbose is not indicated or tolerated, rosiglitazone, metformin, or sulfonylurea may be effective. If acarbose is not indicated or tolerated, rosiglitazone, metformin, or sulfonylurea may be effective.

Monotherapy With Oral Antidiabetic Agents Nonobese Individuals With Diabetes Lean patients with mild glucose intolerance can be given a trial with any of the four classes of oral agents Lean patients with mild glucose intolerance can be given a trial with any of the four classes of oral agents Sulfonylureas are likely to be a better choice for patients when blood glucose values are consistently in the 200 to 300 mg/dL range (these drugs can be titrated more rapidly to higher doses, which may be necessary in this patient group). Sulfonylureas are likely to be a better choice for patients when blood glucose values are consistently in the 200 to 300 mg/dL range (these drugs can be titrated more rapidly to higher doses, which may be necessary in this patient group).

Monotherapy With Oral Antidiabetic Agents Patients With Prolonged, Severe Hyperglycemia (Glucose Toxicity) a temporary trial of insulin therapy should be instituted for a few weeks before beginning an oral agent to reduce insulin resistance and improve endogenous insulin secretory capacity a temporary trial of insulin therapy should be instituted for a few weeks before beginning an oral agent to reduce insulin resistance and improve endogenous insulin secretory capacity start a sulfonylurea agent at the maximum dose and follow the patient carefully start a sulfonylurea agent at the maximum dose and follow the patient carefully once metabolic control is achieved the glucose toxic state improves. At this point, switching to other oral agents with less hypoglycemic potential is a reasonable alternative once metabolic control is achieved the glucose toxic state improves. At this point, switching to other oral agents with less hypoglycemic potential is a reasonable alternative

Monotherapy With Oral Antidiabetic Agents Patients With Severe Renal or Liver Dysfunction Both sulfonylureas and metformin should be used with caution Both sulfonylureas and metformin should be used with caution In patients with renal impairment, acarbose or rosiglitazone represent an excellent choice In patients with renal impairment, acarbose or rosiglitazone represent an excellent choice In patients with significant or progressive liver disease, hyperglycemia is best treated with exogenous insulin alone. In patients with significant or progressive liver disease, hyperglycemia is best treated with exogenous insulin alone.

DIABETES MELLITUS GOALS OF THERAPY (EDPG 1998) FASTING PLASMA GLUCOSE: < 100 mg/dL POSTPRANDIAL PLASMA GLUCOSE: < 135 mg/dL HbA1c: < 6,5% HbA1c: < 6,5%

DIABETES MELLITUS GOALS OF THERAPY (EDPG 1998) Total cholesterol: < 185 mg/dL Total cholesterol: < 185 mg/dL LDL-cholesterol: < 115 mg/dL LDL-cholesterol: < 115 mg/dL HDL-cholesterol: > 46 mg/dL HDL-cholesterol: > 46 mg/dL Triglycerides: < 150 mg/dL Triglycerides: < 150 mg/dL Blood pressure: < 140/85 mm Hg Blood pressure: < 140/85 mm Hg

DIABETES MELLITUS GOALS OF THERAPY Negative Urine glucose Negative Urine Ketones Symptomatic Improvement Normalize Nutrition Avoid/Prevent Complications