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Author: Richard D. Siegel, M.D.
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1. Goals

  • To understand how to set therapeutic goals in the individual patient with diabetes mellitus and communicate those to the patient
  • To understand the basic principles of nutrition that apply to patients with type 1 and type 2 diabetes
  • To understand the importance of exercise as a therapeutic modality in the diabetic patient and to appreciate the physiological principles involved
  • To understand the mechanism of action of oral diabetic agents, their indications and contraindications
  • To understand the various types of insulin, how these are used, and some of the complications of insulin therapy
  • To know about nonglycemic management of patients with diabetes that may lower cardiovascular risk
  • To be aware of measures that may prevent type 2 diabetes in those people at high risk of the disease
  • To understand the principles of managing the obese patient

2. Learning Objectives

  • There is no one diabetic diet. All carbohydrates will raise blood sugar levels though different glycemic excursions may exist among foods. Saturated fats should be limited while monounsaturated fats may help diabetic dyslipidemia.
  • Exercise improves glucose tolerance and insulin sensitivity and should be prescribed to all diabetics.
  • Insulin is the only treatment for type 1 diabetes. Most type 1 diabetics will use 3 or 4 shots per day or an insulin pump if the goal is intensive control. About half of the insulin should be basal (NPH/Lente, Ultralente or Glargine insulin) with the rest being boluses for meals (Regular or Lispro/Aspart insulin).
  • Type 2 diabetics who are not controlled by diet and exercise alone may require one or more medications to achieve glycemic control. Oral medications include insulin secretagogues (sulfonylureas, meglitinide), drugs which improve insulin resistance (biguanide and thiazolidinediones) and drugs which impair the absorption of carbohydrates (alpha-glucosidase inhibitors). Oral medications may be used in combination with insulin and multi-shot insulin regimens may be necessary as the disease progresses.
  • Based on recent trials suggesting that intensive control slows the progression of complications, the goal HbA1c for most diabetics should be less than 6.5 - 7% with day to day glucose being 80-120 mg/dl before meals and under 160 mg/dl in the postprandial state. Goals may be different in older patients or those with hypoglycemic unawareness.
  • Smoking cessation, control of hypertension and dyslipidemia are extremely important for lowering cardiovascular risk in diabetics.
  • Type 2 diabetes may be prevented in patients with abnormal glucose tolerance by weight loss and increased physical activity. Specific dietary components and medications may also help in diabetes prevention.
  • Treatment of obesity requires a multidisciplinary approach involving changes in behavior, diet and activity.
  • Current medications approved for obesity act by either suppression of appetite or limiting the absorption of fat calories in the small intestines. Future medications may also work to increase energy expenditure.
  • Gastric restrictive surgery is an available option for patients who are morbidly obese, especially those with co-morbidities.

3. Objectives of Therapy

3.1. Type 1 Diabetes

  • Normal growth and development
  • Normal social, economic and productive life
  • Freedom from complications of diabetes both short term (DKA, hypoglycemia) and long term (micro- and macrovascular)

3.2. Type 2 Diabetes

  • Weight as close to ideal as possible
  • Metabolism as close to physiologic as possible
  • Freedom from complications of diabetes

4. Nutrition: General Principles of Nutrition as Applied to Diabetes Mellitus

Recently the American Diabetes Association established the following as goals of nutrition therapy for persons with diabetes:

  • Maintenance of near normal blood glucose levels by balancing food intake with insulin or oral glucose lowering medications and activity levels
  • Achievement of optimal lipid levels
  • Provision of adequate calories for normal growth and development in children; for maintaining or attaining reasonable weights for adults; to meet the increased metabolic need during pregnancy and lactation
  • Prevention, delay or treatment of nutrition - related risk factors and complications
  • Calories count
    • Obesity is present in over 80% or individuals with Type 2 diabetes, hypertrophy of adipocytes is accompanied by insulin resistance
    • Weight loss, even 5-10%, increases insulin sensitivity and improves glucose tolerance
    • For the Type 1 diabetic, normal weight and growth are essential for adequate control of glycemia
  • Carbohydrates should comprise a substantial portion of the diabetic's calories. However, not all carbohydrates are created equal.
    • "Simple sugars" - mono- and disaccharides - induce hyperglycemia when consumed alone
    • Complex carbohydrates vary in their glycemic effects
    • Fiber content of foods may alter rates of digestion and absorption of carbohydrates e.g. legumes cause a smaller increase in blood sugar level than more simple sugars
    • The general misconception that "carbohydrates" should be avoided is unfounded; the diet of the diabetic will often contain 50% or more of the calories as carbohydrates (except possibly in patients with hypertriglyceridemia)
  • Saturated fats and "trans" (partially hydrogenated) fats should be limited.
    • High fat foods are high calorie foods contributing to weight gain
    • All diabetics are prone to atherosclerosis; foods high in saturated fatty acid content or in cholesterol must be restricted
    • Some advocate a diet, especially in patients with high triglycerides and low HDL cholesterol, that is generous in monounsaturated fats such as canola oil and olive oil and lower in carbohydrates
  • There is no single diabetic diet
    • Diabetes is a heterogeneous syndrome, and no single list of foods or simplified meal plan suffices for all individuals with diabetes
    • A diabetic diet is a balanced, nutritional diet

5. Physical Activity: An Important Modality in the Treatment of Diabetes Mellitus

  • Several physiological principles of exercise of importance to diabetics
    • With exercise, we see: alterations in circulating dynamics; marked increases in blood flow to muscle beds, the diversion of flow from the splanchnic bed increments in cardiac output and the effects of training on V02
  • Biochemical changes with exercise
    • Increased uptake of glucose with increased work by skeletal muscles
    • Increased output of glucose by the splanchnic bed with exercise
    • Correlation of hepatic gluconeogenesis and glucose utilization
  • Exercise and the diabetic
    • Exercise lowers glucose in the Type 1 diabetic when insulin is aboard
    • Exercise can improve glucose tolerance (reduced insulin resistance) in obese Type 2 diabetics
    • Exercise alters the affinity of insulin for its receptors and training increases the number of insulin receptors
    • Exercise should be prescribed for all able diabetics; an exercise stress test may be necessary in older diabetics to assess for the presence of coronary artery disease if the patient will be starting a significant exercise program

6. Pharmacologic Therapy for Type 1 Diabetes

6.1. Insulin Therapy

Sources of insulin have previously included bovine, porcine and human. The insulin of choice is human insulin synthesized in the test tube by recombinant DNA technology. It is felt that the human insulin is less immunogenic than the porcine and bovine insulin which have a slightly different amino acid sequence than human insulin. Porcine and bovine insulin are no longer being manufactured as of 1999.

  • Methods of administration:
    • subcutaneous (most commonly used)
      • single injection
      • constant infusion via pump
    • intravenous: for acute or emergency situations
    • intramuscular: rarely (variable absorption rates)
  • Complications of treatment with insulin:
    • Hypoglycemia
    • Allergies (rare with newer insulin analogues)
    • Antibodies (also rare)
    • Reactions with other drugs: alcohol
  • Patterns of therapy (suggested):
    • Glargine insulin at bedtime or in the morning + rapid acting bolus insulin before each meal (four shot regimen)
    • 75/25 Lispro Mix or 70/30 Aspart Mix - twice daily (two shot regimen)
    • Insulin pump therapy which infuses lispro or aspart insulin continuously as basal insulin and is programmed for meal boluses by the patient based on carbohydrate counting at meals and snacks
    Table 1. Insulin Preparations - (A) Bolus Insulins
    Onset Peak Time Duration
    Rapid Acting
    Insulin Lispro 0.25 hrs 0.5 - 1.5 hrs 3-5 hr.
    Insulin Aspart 0.25 hr. 0.5 - 1.5 hr. 3-5 hr.
    Short Acting
    Regular 0.5 hr. 2-5 hours 5-8 hr.

    Table 1. Insulin Preparations - (B) Basal Insulins
    Onset Peak Time Duration
    Intermediate Acting
    NPH 1-3 hr. 6-12 hr. 16-24 hr.
    Lente 1-3 hr. 8-16 hr. 18-28 hr.
    Long Acting
    Ultralente 6-10 hr. 10-16 hr. 18-24 hr.
    Insulin Glargine 1-2 hr. No peak 24 hr.
    Combination Insulins
    Basal/Bolus
    • 70/30 NPH/Regular
    • 75/25 NPL/Lispro(Humalog Mix)
    • 70/30 NPA/Aspart (Novolog Mix)
  • Dietary Rules
    • Synchronize food intake with action of insulin - no missed meals!
    • Carbohydrate counting may help to determine insulin dose
  • Exercise
    • A regular pattern daily
    • Regulation of insulin with activity pattern

7. Pharmacologic Therapy for Type 2 Diabetes

7.1. Oral Hypoglycemic Agents

7.1.1. Sulfonylureas

Sulfonylureas depend on the presence of functioning beta cells in the islets of Langerhans. They enhance the ability of glucose to stimulate release of insulin from the beta cells. In some instances, the sulfonylureas may enhance the peripheral action of insulin by increasing binding or otherwise lowering the peripheral resistance to insulin; this may be secondary to improvement in glucose "toxicity" rather than a direct effect of the drugs themselves. First generation sulfonylureas (chlorpropamide, tolbutamide, tolazamide, acetohexamide) are rarely used today due to their long half lives with increased risk for hypoglycemia. Glyburide, Glipizide and Glimepiride are second and third generation sulfonylureas and are used widely.

7.1.2. Non-sulfonylurea insulin secretagogues (Repaglinide and Nateglinide)

Repaglinide and Nateglinide are short-acting glucose-lowering drug recently approved by the FDA for the treatment of type 2 diabetes alone or in combination with metformin. Their structure is different than sulfonylureas but they have a similar mechanism of action to increase insulin secretion from the pancreas acting by regulating ATP-dependent potassium channels in pancreatic beta cells which increase insulin secretion. The efficacy is similar to sulfonylureas. If the patient does not eat, the dose is skipped. These agents may have some utility in patients with poor or erratic oral intake.

7.1.3. Insulin sensitizers

The biguanide, metformin, and thiazolidinediones were introduced in the 1990s for the treatment of type 2 diabetes mellitus. These agents improve the biological response to insulin by reducing the "resistance" to insulin action seen especially in the obese adult with type 2 diabetes. These agents do not directly increase insulin secretion by the pancreas. Often patients already taking insulin who are started on these preparations will need to reduce their current dose of insulin to avoid hypoglycemia.

7.1.3.1. Metformin

The original oral hypoglycemic agent, guanidine, was introduced in 1927 and proved too toxic for human use. In the 1950's the biguanide, phenformin, became available for treatment of type 2 DM, but because it induced lactic acidosis it was withdrawn from the US market. Within the past five years another biguanide has been made available in this country. Metformin decreases blood glucose in patients with type 2 DM primarily by increasing peripheral glucose utilization and decreasing hepatic production of glucose. It does not stimulate insulin secretion. Metformin does not cause hypoglycemia when used as a single agent and is not associated with weight gain; in fact the drug is often associated with weight loss, perhaps because it induces anorexia, nausea and gastric discomfort. The drug also lowers levels of triglycerides and LDL-cholesterol. Metformin can be used alone or in combination with a sulfonylurea or insulin therapy. The drug is contraindicated in patients with renal or liver disease, alcohol abuse or cardiorespiratory insufficiency. The drug is stopped on the day of contrast dye administration and held for 48 hr. AND after a normal serum creatinine is measured.

7.1.3.2. Thiazolidinediones ("TZDs")

The thiazolidinediones decrease insulin resistance at the level of the muscle and liver to increase glucose utilization and diminish glucose production. The mechanism is not well understood. The thiazolidinediones bind and activate a nuclear transcription factor called peroxisome proliferator-activated receptor-gamma (PPAR-gamma) which is thought to be involved in insulin-responsive genes. The receptor is found in adipose tissue, muscle and liver. TZDs may have other effects on insulin action but it is unclear. Other actions of TZDs may involve reducing tumor necrosis factor-alpha expression which is felt to play a role in insulin resistance. TZDs do not stimulate insulin secretion. TZDs do not cause hypoglycemia when used as a single agent but are associated with weight gain similar to sulfonylurea agents.

7.1.4. Alpha-glucosidase inhibitors (Acarbose and Miglitol)

The alpha-glucosidase inhibitor, acarbose, binds with sucrases in the intestinal enterocytes and interferes with their digestion. Instead of being digested and absorbed in the upper jejunum, these complex sugars are digested in the distal jejunum and the ileum and their products are then not absorbed. This accounts for the lower postprandial glucose observed after the ingestion of acarbose in both diabetic patients and non diabetics. Since acarbose decreases postprandial glucose elevations it also decreases insulin and C-peptide postprandial levels. In patients with type 2 DM the postprandial peak of glucose rise is diminished by 40-60 mg/dl. The effect of acarbose on fasting level of glucose is much more moderate and averages 15-30 mg/dl. The primary side effects of acarbose are increased flatulence, abdominal discomfort, and occasional diarrhea. These effects are caused by formation of carbohydrates that reach the colon and are metabolized by normal flora. The side effects are dose related. Miglitol is the second drug in the class and may have a lower incidence of flatulence as a side effect.

7.1.5. Combination medications

  • Glyburide/Metformin, Glipizide GITS/Metformin, Rosiglitazone/Metformin are combination medicines which may help with compliance for patients needing multiple oral drugs to control their diabetes. Some dosing flexibility may be lost when using such combinations.

7.1.6. GLP-1 Receptor Agonists and DPP-IV Inhibitors (In Development)

Glucagon Like Peptide-1 (GLP-1) is an incretin, a peptide from the small intestine which augments insulin secretion with a meal. It also suppresses glucagon secretion, slows gastric emptying, reduces food intake and may also increase beta cell mass. Analogues of GLP-1 are in development for treatment of type 2 diabetes. Dipeptidyl peptidase-IV (DPP-IV) inactivates GLP-1. Inhibitors of DPP-IV, which would enhance the action of endogenous GLP-1, are also being developed.

7.2. Insulin in Type 2 DM

  • When used:
    • "stressful" situations: infection, vascular accident, trauma, major surgery
    • uncontrolled state: symptomatic state or blood glucose goals not achieved on oral medications (see below)
    • basal insulin may only be necessary at bedtime; bolus insulin at meals is supplemental to lower postprandial sugars
  • Complications:
    • lipogenesis (weight gain) vs. control of glycemia
    • hypoglycemia is less common in type 2 patients than type 1
Table 2. Comparison of effects of oral antidiabetic agents
Agents Sites and Action Side Effects Cost of 30 Days*
Insulin Secretagogues
  • Sulfonylureas (see above)
  • Repaglinide
  • Nateglinide
Pancreas
Increase insulin secretion
Hypoglycemia
Weight Gain
Generic glyburide $15
Glimepiride $7
Prandin $67
Biguanide
  • Metformin



Liver and peripheral tissues
Decreases hepatic glucose production
Enhances peripheral glucose uptake
GI cramping, diarrhea, anorexia, metallic taste $54
Thiazolidinediones("TZDs")
  • Rosiglitazone
  • Pioglitazone
Muscle and fat
Enhances peripheral glucose uptake
Fluid retention, liver abnormalities possible?? $75
$85
Alpha-Glucosidase Inhibitors
  • Acarbose
  • Miglitol
Small intestine
Delays carbohydrate digestion and slows glucose absorption
Flatulence, diarrhea, abdominal discomfort $46
$51
Table 3. Glycemic goals for people with diabetes
Normal Goal Action suggested
Preprandial glucose (mg/dl) < 110 80-120 < 70, >140
Bedtime or postprandial glucose (mg/dl)
HbA1c(%)
< 120
< 6
100-140
< 7
< 100, >160
> 8

7.2.1. Non glycemic Treatments in Diabetics

  • Blood pressure
  • Treat to goal of < 130/80, < 120/75 in patients with renal disease, African Americans
  • Start with ACE inhibitors, add low dose diuretic as second drug, long acting calcium channel blocker as third drug and beta-blocker or long acting alpha blocker as fourth drug
  • Lipids- goals are for fasting lipids; postprandial lipemia is an area of current research
  • Aim for: LDL < 100
  • Triglycerides (TG) < 150-200 HDL > 45-50 (the higher, the better!)
  • Improving glycemic control will lower TGs and raise HDL
  • Statins (HMG-CoA reductase inhibitors) are best initial choice if LDL is above 130 with moderate TG elevation as they may lower LDL, TG and raise HDL with LDL lowering being the predominant effect.
  • Fibrates may be first choice for patients with primarily high TG, low HDL. Fenofibrate will lower LDL as well as very effectively lower TG and raise HDL.
  • Niacin is the most potent drug for raising HDL but may worsen glucose tolerance in some patients
  • Fish oils (DHA, EPA) may also be used to lower TG though may raise LDL in diabetics
  • Aspirin use should be recommended for all diabetics who have at least one other cardiovascular risk factor (smoking, LDL >130, low HDL, family history, hypertension, central obesity). Dose is 75-325 mg daily.

Control of blood pressure and lipids is extremely important for lowering cardiovascular risk! Postprandial glucose control may also help to lower cardiovascular risk.

7.3. Management of the Obese Patient

7.3.1. Rationale for Weight Loss

  • Increased visceral fat is associated with increased risk of diabetes mellitus, hypertension, cardiovascular disease, gall bladder disease, cancers and osteoarthritis.
  • Waist circumference over 40 in. in men and over 35 in. in women is associated with increased risk for morbidity and mortality.
  • Lowering weight moderately may lower the risk for diabetes, improve blood pressure, lower lipid concentrations and lower the risk for osteoarthritis and sleep apnea.
  • Obesity is estimated to add over $30 billion in direct costs associated with its comorbidities in the US.
  • Obesity leads to significant depression and job discrimination which causes major psychological and emotional problems in those that suffer from it.

7.3.2. Approach to Therapy

  • Body Mass Index (BMI) = weight (kg)/height (m2) or weight (lb.) x 703/ height (in2)
    BMI Definitions
    18-25 Optimal
    25-30 Overweight
    30-40 Obese
    Over 40 Morbidly Obese
  • At any given level of BMI, the risk for comorbidities increases by an increase in abdominal fat (waist circumference).
  • BMI usually correlates with percentage of body fat though in some very muscular athletes very low percentage of body fat may exist together with a BMI higher than optimal.
  • Subjects in the highest BMI category should get the most aggressive treatment.
  • For those in an optimal BMI or possibly overweight category without comorbidities, a plan should focus on prevention of weight gain by staying active and healthy eating habits.
  • All therapies for obesity will affect the balance of energy by either decreasing nutrient intake or increasing energy expenditure.
    • Behavioral modification
    • Dietary therapy
    • Physical activity
    • Pharmacologic therapy
    • Surgery

7.3.3. Goals of a Weight Loss Plan

  • Achieve a 5-10% weight loss over 6 or more months
  • Maintain weight loss over time
  • Improve one's level of fitness
  • Create a balanced eating plan for life

7.3.4. Behavioral Modification

A behavioral modification program is an essential part of any multidisciplinary plan for treating obesity. Components of behavioral modification may include:

  • Use of self monitoring logs for patients to identify what they eat, when they eat it, where food is eaten, degree of activity, triggers and emotions related to eating and degree of hunger (stomach vs. mind hunger)
  • Stimulus control such as slowing down the eating process, focusing on eating without distractions, cooking smaller portions etc.
  • Defining behavioral goals and rewarding changes in behavior (rewards other than food!)
  • Individual and group support
  • Individual psychotherapy
  • Self help programs. Patients who tend to check in frequently tend to do better over time

7.3.5. Dietary Therapy

Dietary therapy focuses on cutting caloric intake in moderate way. There are dozens (hundreds?) of different "diets". A plan should focus on creating an "eating plan for life" i.e. a day-to-day eating plan that is hopefully both satisfying and will prevent disease in the future.

  • A balanced low calorie diet (LCD) is usually recommended. The LCD is usually between 1200-1800 kilocalories per day (often 1200-1500 kcal/d for women, 1500-1800 kcal/d for men). It may go as low as 1000 kcal/d.
  • For every 500 kcal/d deficit (3500 kcal/wk), about 1 lb. per week should be lost.
  • Macronutrient composition may vary:
    • Carbohydrates - usually 50-60% of total kcal; emphasis is put on whole grain, complex, high fiber carbohydrates
    • Fat - 20-30% with emphasis on monounsaturated and polyunsaturated fats (including omega-3 "fish" oils); saturated and "trans" fatty acids ("partially hydrogenated" in food label identifies trans fats) should be limited to less than 7-10% of total kcal
      • Cholesterol - less than 300 mg per day
    • Protein - 15-20% emphasizing lean sources of protein, both animal and vegetarian
  • Fruits - 2-4 servings per day; Vegetables - 3-5 servings per day (aim for at least 5 servings per day between fruits and vegetables)
  • Calcium - 1000-1200 mg per day depending on age group (1200 mg for people over 50 or known osteoporosis; 1500 mg if on steroids)
  • Fiber - 20-35g per day ideally from fruits, vegetables, whole grains and legumes
  • Sodium - under 2400 mg per day (under 1800 mg if salt sensitive with hypertension, congestive heart failure, ascites)
  • Very low calorie diets (VLCD) are defined as plans with 800 kcal or fewer per day. These may be used when a more rapid weight loss is desired such as prior to an operation. VLCDs require close medical monitoring due to rapid changes in fluids and electrolytes. There is an increased risk for gallstones. Weight is often regained rapidly after a VLCD is stopped (they are usually used for no more than 3 months at a time).
  • Meal replacements, some breakfasts containing 220 calories each, and frozen entrees may be very useful as part of an LCD to help achieve a specific calorie goal since they are single servings with known caloric values.

7.3.6. Physical Activity

Physical activity is an essential part of any weight loss and maintenance plan. Physical activity is the best predictor of long term weight maintenance!!

  • Physical activity increases cardiorespiratory fitness, improves cardiovascular risk factors and reduces the risk for cardiovascular disease.
  • Activity contributes to a decrease in body fat including abdominal fat to some extent.
  • Any activity is better than none! Focusing on cutting down time sitting, watching television etc may be useful, especially for children who are overweight.
  • Individual activity plans should be established with patients incorporating activties that are enjoyable. Gyms are helpful but definitely not essential. Walking is usually the focus of most activity plans.
  • Aerobic activities such as walking, running, bicycling, aerobics etc. should be the initial focus as these will burn the most calories. An ultimate goal would be to accumulate 30 or more minutes per day for 6-7 days per week.
  • Resistance training activities can be added in to help with muscle strengthening. These should be done no more than every other day for any one muscle group.
  • To help keep weight off, a person should aim to expend 300-400 kcal/day in physical activity.
    Duration of Various Activities to Expend 150 Kilocalories for an Average 70 kg (154 lb) Adult
    Intensity Activity Approximate Duration in Minutes
    Moderate Volleyball, noncompetitive 43
    Moderate Walking, moderate pace (3 mph, 20 min/mile) 37
    Moderate Walking, brisk pace (4 mph, 15 min/mile) 32
    Moderate Table tennis 32
    Moderate Raking leaves 32
    Moderate Social dancing 29
    Moderate Lawn mowing (powered push mower) 29
    Hard Jogging (5 mph, 12 min/mile) 18
    Hard Field hockey 16
    Very Hard Running (6 mph, 10 min/mile) 13
    Source: Surgeon General's Report on Physical Activity and Health (http://www.fitness.gov/execsum/execsum.htm)

7.3.7. Pharmacologic Therapy

Pharmacologic therapy for obesity is in its "infancy" as there are currently only two approved drugs by the Food and Drug Administration for use beyond a few weeks. Medications may be very useful adjuvants to the dietary, behavioral and physical activity therapies mentioned above for patients with BMI over 30 kg/m2 or over 27 with medical complications including diabetes, hypertension, sleep apnea and hyperlipidemia. Drug therapy can be used intermittently though weight may be regained after a medication is stopped. A realistic weight loss goal with medication is 5-15% of the starting body weight (as it would be without medication) over 6-12 months.

  • Sympathomimetic drugs work by inhibiting appetite and causing early satiety.
    • Sibutramine is a serotonin/norepinephrine reuptake inhibitor which was approved by the FDA in 1998. It is administered once daily in the morning as 5-15 mg. It is possible that the drug may enhance thermogenesis (effect seen in animals) though it primarily causes early satiety. Side effects include dry mouth, headache, elevation in blood pressure and pulse which require monitoring, constipation and insomnia. An early response of greater than 2 kg weight loss in the first month predicts a good long term response of about 10% over 6-12 months. LDL cholesterol and triglyceride levels may improve as may HbA1c in diabetics with weight loss. The medication should be avoided in patients with known cardiac disease. It has not been associated with either pulmonary hypertension or valvular disease as were fenfluramine and dexfenfluramine which were removed from pharmacies in 1997. These latter medications suppressed appetite by stimulating the release of serotonin from nerve endings. The medication is currently approved for weight loss and maintenance for up to 2 years.
    • Sympathomimetic drugs approved for short term usage (up to 12 weeks) include phentermine, diethylproprion, benzphetamine, and phendimetrazine . These medications stimulate the release of norepinephrine from nerve endings. Dietary supplements may contain ephedra (ma huang) for weight loss which may have significant cardiac side effects and cannot be recommended for use.
  • Orlistat is a gastrointestinal lipase inhibitor which prevents about 30% of ingested fat in a meal from being absorbed. It is not systemically absorbed. The medication is meant to be taken at the beginning of each meal, 120 mg three times daily. Side effects are intestinal including flatulence, fecal incontinence, oily spotting and cramping. The degree of side effects is related initially to a person's fat intake though tend to improve after the first few weeks. Since the medication may affect the absorption of the fat-absorbable vitamins (A, D, E and K), a multivitamin must be taken with the medication at least 2 hours separately from a dose (often at bedtime). Trials have shown improvements in glycemic control in diabetics, blood pressure and serum lipid values. Orlistat is approved for weight loss and maintenance.
  • Drugs that increase energy expenditure are not approved for treatment. Ephedrine is a sympathomimetic amine with a prolonged duration of action. It has been tested together with caffeine and resulted in a 16% weight loss in one trial over 6 months which was subsequently maintained. Beta-3 adrenergic agonists have been investigated as thermogenic drugs but trials have not gone further due to poor results.
  • A number of neuropeptides involved in appetite are currently being investigated. Future medications for obesity will most likely involve these neuropeptides and their various receptors.

7.3.8. Surgery for obesity (Bariatric Surgery)

Bariatric surgery is an option to assist with weight loss for patients who are morbidly obese (BMI over 40 kg/m2) without medical complications or who have a BMI over 35 kg/m2 with co-morbidities including type 2 diabetes, hypertension, obstructive sleep apnea and hyperlipidemia.

  • Gastric bypass surgery with a Roux-en-Y procedure is the most common procedure used. It involves creating a smaller stomach "pouch" by partitioning the existing stomach and bringing up the small intestine to attach to the pouch. Much of the stomach and the duodenum is bypassed. Weight loss is likely related to early satiety in the new pouch and some malabsorption of calories with the bypassed piece of intestine. The procedure may be done laparoscopically in appropriate patients (based on prior surgical history, absolute weight and distribution of weight)
  • Other surgeries that may be done include the vertical banded gastroplasty, Lap-Band adjustable gastric banding procedure and rarely biliopancreatic bypass. An implantable gastric stimulator is currently under investigation (not FDA approved) at Tufts-NEMC as a treatment for obesity.
  • Patients may lose about 30-35% of their original weight, on average, prior to weight plateau (or 60-70% of their excess weight over ideal body weight).
  • When done by a surgeon very familiar with the surgery, operative mortality is under 1%. Complications of bariatric surgery may include anastomotic leak, infection, long term risk for vitamin deficiencies with gastric bypass procedures including iron, B12, folate and vitamin D and risk of gallstones due to rapid weight loss.
  • A multidisciplinary program prior to and after surgery is essential to educate patients in the skills necessary for long term weight maintenance. Such a program should include a strong behavioral program, medical and nutritional professionals.

8. References