Obesity Case 1

A 45 year-old female who is “health conscious” came to your clinic for advice about healthy eating and lifestyle. She is an editor of a shopping magazine and frequently reads articles about diets, nutrients, supplements, and healthy lifestyles. She found that much of the information she recently read is contradictory, which made her confused about what to eat and do. Her mother had type 2 diabetes and died at age 61 from a fatal myocardial infarction. The death of her mother at such young age compelled her to eat healthier and to walk for 30 minutes most days of the week.

She is now eating three regular meals per day and does not eat snacks. She tries to read all of her food labels and to keep her food intake to 1,800 calories per day. Although she dines out approximately 5 days per week, she controls her food portions as much as she can. She has maintained her weight for the last 5 years. She likes good wine and drinks 1-2 glasses when she dines out. She takes several over-the-counter supplements including vitamin D, calcium, magnesium, vitamin B12, and cinnamon. She does not have any gastro-intestinal symptoms, and she sleeps 6-7 hours every night. Recent results of lab work are below.

  • Weight: 172 lbs                
  • Body mass index (BMI): 28 kg/m2 (normal, 18.5 to 24.9 kg/m2)                   
  • Waist circumference: 32 inches
  • Blood pressure: 124/72 mm Hg
  • Serum low density lipoprotein cholesterol (LDL-C): 122 mg/dL (desirable, <100 mg/dL)
  • Serum high density lipoprotein cholesterol (HDL-C): 39 mg/dL (desirable, ≥60 mg/dL)
  • Serum triglycerides (TG): 280 mg/dL (desirable, <150 mg/dL)
  • Fasting plasma glucose: 92 mg/dL (normal, 70-100 mg/dL)           
  • Glycated hemoglobin (HbA1c): 5.6% (normal, <5.7%)

She told you that she would like to follow a strict vegetarian dietary pattern since she heard that it is the best lifestyle. She would also like to follow a gluten-free diet to shed few pounds.  

 

Question 1

Regarding her current lifestyle and her intentions to change it, which of the following is correct advice?

A. Drinking 1-2 glasses (5-10 ounces) of wine daily is beneficial, especially if it is a red wine.
B. A gluten-free diet, if precisely followed, will help you to reduce few pounds.
C. Go for a strict vegan diet since it will improve your health and provide you with all the nutrients that your body needs.
D. Reducing fat in your diet to <30% of total calories will help you to control your LDL-cholesterol and prevent cardiovascular disease.
E. Reduce your caloric intake by 250 calories and vary the type of exercise you do instead of just walking every 30 minutes every day.
Incorrect!
Correct!
Correct Answer
E. Reduce your caloric intake by 250 calories and vary the type of exercise you do instead of just walking every 30 minutes every day.

Alcohol, especially red wine increases HDL-C. If a person chooses to drink alcohol, the consumption must be moderate (no more than one drink a day for women and no more than two drinks a day for men). Additionally, it is not advisable that one actually increases alcohol consumption to these levels to derive a health benefit. One drink is equal to 12 ounces of regular beer, 5 ounces of wine, or 1.5 ounces of 80-proof distilled alcohol. So, option A is incorrect as women should not exceed one drink per day.

Celiac disease or gluten sensitive enteropathy is an autoimmune disease in which there is an abnormal response to gluten, the protein contained in wheat, barley, and rye. Ingestion causes damage to the intestinal lining and malabsorption of micronutrients as well as varying degrees of symptoms, which may include diarrhea, bloating, weight loss, and fatigue. The treatment for celiac disease is a gluten-free diet. Some people without celiac disease report similar gastrointestinal symptoms when eating gluten-containing foods, although it is controversial whether these symptoms are due to the gluten itself. Regardless, gluten-free diets have become popular over the last few years, and many people are using them to lose weight. Some people lose weight because they end up eliminating high carbohydrate foods that they previously over consumed. Other people who choose to omit gluten replace gluten-containing carbohydrates with another type of carbohydrates like corn, rice, tapioca, and/or potato. In fact, many people on gluten-free diets gain weight. Since this patient does not have any gastrointestinal symptoms, she is unlikely to have gluten sensitivity. Thus, adopting a gluten-free diet is unnecessary, and option B is therefore incorrect.

A vegetarian eating plan is a relatively healthy eating pattern and has been associated with reductions in type 2 diabetes and cardiovascular risk in several observational studies. However, a strict vegan diet is associated with significant deficiency in many essential amino acids that only come from animal sources like milk, eggs, fish, meat, and poultry. If a person elects to follow a vegan diet, the diet should be supplemented with ketogenic essential amino acids to be balanced in nutrition. Therefore, option C is incorrect.

Due to the recognition of the benefit of “healthier” fats, restriction of dietary fat to Reducing daily caloric intake by 250-500 calories will help most people with overweight or obesity problems to lose weight. Since the patient in this case is overweight, a target BMI of 20-25 kg/m2may be advised to reduce her cardiovascular disease and type 2 diabetes risk. Regular physical activity, including a balanced mix of stretching, cardiovascular exercise, and progressive resistance exercise for at least 30 minutes most days of the week, has health benefits and is needed to control body weight. This new advice replaced the old recommendation of doing only aerobic exercise like walking 10,000 steps per day. Thus, option E is the correct answer.

Obesity Case 2

A 47 year-old white man of Italian descent with a strong family history of type 2 diabetes and cardiovascular disease was recently diagnosed with prediabetes. He has always been proud that he does not have any chronic disease and has never needed to take any medications, despite having a weight problem. He does not follow any specific diet plan, but is very active. He is currently doing 150 minutes of moderate intensity physical activity every week. He cooks most of his meals and rarely dines out. His meals, in general, are high in carbohydrates as he loves pasta, pizza, and bread. He also adds olive oil to most of his meals and eats fatty fish two times per week. He does not eat much red meat, but eats a lot of processed meat and cheese. During his last visit to his primary care physician, his fasting plasma glucose was 110 mg/dL (normal, 70-100 mg/dL), and his glycated hemoglobin (HbA1c) was 6.1% (normal, <5.7%). He was shocked by the results. Except for obesity, he does not have any other health problems. When your dietitian reviewed his 3-day food log, she found that he consumes approximately 2800 calories per day with total carbohydrates comprising 60% of his diet.

  • Weight: 206 lbs (93.6 kg)
  •  Height: 67 inches (170 cm)
  • Body mass index (BMI): 32 kg/m2 (normal, 18.5 to 24.9 kg/m2)
  • Waist circumference: 40 inches
  • Blood pressure: 130/80 mm Hg
  • Low density lipoprotein cholesterol (LDL-C): 98 mg/dL (desirable, <100 mg/dL)
  • High density lipoprotein cholesterol (HDL-C): 42 mg/dL (desirable, ≥60 mg/dL)
  • Triglycerides (TG): 186 mg/dL (desirable, <150 mg/dL)

His internet search led him to read the results of the diabetes prevention program, which showed that weight loss reduces type 2 diabetes risk by 58%. He stated that he was in the best shape, and he would like to reach that goal over the next 8 weeks by reducing total caloric intake to 1000-1200 calories/day and increasing his activity to 50 minutes on 5 days of the week to a total of 250 minutes/week. He came to you for advice regarding healthy eating patterns and physical activity that will help him to prevent type 2 diabetes.

Question 1

In helping this individual to achieve and maintain his target weight loss, which of the following advice is BEST?

A. Losing 0.5 to 2 lbs (0.2-0.9 kg) per 1-2 weeks is acceptable and safe.
B. Reducing caloric intake to 1200 calorie is the fastest and safest way to achieve your goal of 10% weight loss in 8 weeks.
C. When reducing caloric intake to 1200 calories, people with obesity should increase protein intake to not less than 1.5 gm/kg per day of actual body weight.
D. Exercising 30 minutes per day on 5 days per week is adequate to prevent weight regain after weight loss.
E. A diet low in fat and relatively higher in carbohydrates is frequently better that a diet low in carbohydrates and higher in fat to achieve target weight loss.
Incorrect!
Correct!
Correct Answer
A. Losing 0.5 to 2 lbs (0.2-0.9 kg) per 1-2 weeks is acceptable and safe.

For weight management, consistency is more important than speed of weight changes. Weight losses of 0.5 to 2 lbs (0.2-0.9 kg) per 1-2 weeks are acceptable and safe. You can calculate basal metabolic rate (BMR) using the Harris-Benedict equations (For men BMR = 88.362 + (13.397 x weight in kg) + (4.799 x height in cm) - (5.677 x age in years). The answer can then be multiplied by an activity factor (i.e., 1.375 for light exercise 1-3 days per week; 1.55 for moderate exercise 3-5 days per week). Using this patient as an example: BMR = 88.362 + (13.397 x 93.6) + (4.799 x 170) – (5.677 x 47) = (88 + 1254 + 816)-266 =  1892 x 1.55 = 2932- 500 = 2432 kcal. Thus, reducing caloric intake by 250-500 is reasonable and tolerated, making option A the correct response.Weight loss of around 7% significantly improves insulin sensitivity and helps individuals with prediabetes to prevent diabetes. A goal of 5-10% weight loss maintained for a year is an optimal target for patients with obesity and prediabetes.

For an individual who consumes 2800 calories per day, reducing caloric intake to 1200 calories per day may not be doable and is frequently associated with rapid weight regain.  Thus, option B is incorrect.

People who are overweight and obese may choose to increase the percentage of calorie intake from protein and decrease the percentage from carbohydrates to around 40-45% when they reduce caloric intake for weight reduction. It is particularly important to maintain the absolute protein intake at not less than 1.2 gm/kg of adjusted body weight when the total caloric intake is reduced to 1200-1500 calories to avoid protein malnutrition. Recommended protein intake is around 15-20% of total caloric intake. However, when caloric reduction is recommended for weight reduction, the use of percentages to calculate protein intake may result in a serious reduction in absolute protein intake. For this reason, individuals who seek weight reduction through caloric restriction should calculate protein intake based on gram/kg body weight. Adequate intake is 0.8 gm/kg of body weight, but for people who are overweight, 0.8-1.5 gm/kg of adjusted body weight [Adjusted Body Weight = IBW (Ideal Body Weight) + 0.25 (Current Weight - IBW) can be used to calculate appropriate intake. Thus, protein intake of 1.5 g/kg of actual body weight is too high, making option C incorrect.

Regular physical activity, including a balanced mix of stretching, cardiovascular exercise, and progressive resistance exercise for at least 30 minutes most days of the week, has health benefits and is needed to control body weight. Exercise has been shown to help overweight and obese patients to maintain weight loss over the long-term. About 60 minutes a day of moderate intensity exercise for at least 5 days/week (300 minutes/week) may be needed to prevent weight regain. Thus, option D is also incorrect.

Although a traditional weight loss diet is generally low in calories and fat, several meta-analyses comparing low-fat versus low-carbohydrates diets have consistently shown that a diet lower in calories and carbohydrates is superior to a diet low in fat and higher in carbohydrates. The percentage of carbohydrates in a weight loss diet should not be higher than 40-45%, but not less than 130 g/day. Carbohydrates of lower glycemic index like non-starchy vegetables, fruits, and whole grains are the preferred source of carbohydrates. Thus, option E is also an incorrect response. 

Obesity Case 3

  1. A 42 year-old woman who presents with a weight of 215 lbs (99 kg) and has undergone Roux-en-Y gastric bypass surgery two years prior. Postoperatively, she sustained a weight loss of 110 lb (50 kg) over 20 months, though she has gained 2.5 lbs (1 kg) in the past month. She continues to experience intermittent loose bowel movements and hair loss for the past six months.

 

  1. A 56 year-old man presents to the emergency department complaining of two days of fevers, severe abdominal pain, nausea, and an inability to tolerate food by mouth. Diverticulitis is confirmed on computerized tomography (CT) scan. Serum pre-albumin is measured to be 16 mg/dL (normal, 20-40 mg/dL)

 

  1. A 37 year-old man with history of Crohn’s disease has sustained four flares in the past year, requiring bowel rest and corticosteroids. He continues to have 5-10 bowel movements daily and has lost 15 lbs (7 kg) over the past 3 months. His current weight is 132 lbs (60 kg), with a body mass index of 20 kg/m2 .

 

  1. A 72 year-old woman with history of Chronic Obstructive Pulmonary Disease (COPD) and hypertension is transferred to the intensive care unit (ICU) for sepsis and respiratory failure two days after she was admitted to the hospital for a COPD exacerbation. She requires mechanical ventilation through an endotracheal tube. Due to hypotension, she requires continuous infusion of adrenergic agonists (pressors) and her Glomerular filtration rate has declined by 30% since admission. Her weight is 165 lbs (75 kg), and her body mass index is 26 kg/m2 (normal, 18.5 to 24.9 kg/m2).
Question 1

Which of the following clinical scenarios represents patients who are at high risk for malnutrition?

A. Scenarios I, II, III, and IV
B. Scenarios II and III; but not I and IV
C. Scenarios I, III, and IV; but not II
D. Scenarios III and IV; but not I and II
Incorrect!
Correct!
Correct Answer
Scenarios III and IV; but not I and II

The prevalence of malnutrition has been reported as 20-50% among hospitalized patients and is secondary to chronic disease, acute illness or exacerbation, and aging populations. Screening for malnutrition in all hospitalized patients is mandated in the United States by the Joint Commission for Accreditation of Healthcare Organizations, and addressing concerns raised regarding nutritional status is integral for patient care and improved inpatient outcomes.A large number of nutritional scoring systems have been published that identify patients at risk for malnutrition. Most of these systems involve a measure of unintentional weight loss, severity of current illness, presence of chronic illness, and gastrointestinal tract function. Three of the most commonly used models are summarized in the table below.

FIGURE 1 In Scenario I, the patient underwent bariatric surgery, and her postoperative course of intentional weight loss over 12-20 months is typical of patients following this procedure. Although reduced intestinal surface area is present following Roux-en-Y gastric bypass, frank malabsorption leading to malnutrition is a rare adverse effect of this procedure, with a prevalence of approximately 1%. Individuals who suffer from malabsorption following gastric bypass typically have weight loss that continues beyond 20 months postoperatively.  While hair loss can be a clinical sign of micronutrient deficiency, it is common following malabsorptive bariatric surgery and is nonspecific in this setting. Often hair loss for up to two years during the postoperative phase of a malabsorptive bariatric procedure cannot be attributed to a specific micronutrient deficiency.

Scenario II depicts an otherwise healthy individual with sudden onset of acute diverticulitis. Prior to this acute illness, he was well nourished. Though his dietary intake for the two days leading to hospitalization is poor and he is likely to be dehydrated, his internal nutrient stores are sufficient to compensate for this short duration of poor intake. Like many serum proteins, pre-albumin acts as an inverse acute phase reactant. Hepatic synthesis of pre-albumin is diminished during acute illness. Thus, the low serum pre-albumin levels in this scenario do not reflect low protein stores. Depending on his subsequent hospital course, he may develop malnutrition, which warrants continued evaluation. He does not presently meet criteria for malnutrition.

In Scenario III, the patient had several exacerbations of Crohn's disease, which can lead to malabsorption. In addition, individuals with gastrointestinal illness, such as Crohn's disease, may self-restrict their oral dietary intake in between flares due to persistence of abdominal pain, loose bowel movements, or fear of inducing another exacerbation. This patient lost over 10% of his body weight in the past 3 months. He also has a low body mass index and demonstrates varying tolerance of oral diet. These findings meet criteria for high nutritional risk or severe malnutrition by nearly any published classification method.

Scenario IV clearly represents an individual at high risk of malnutrition for several reasons: 1) She has a prolonged hospitalization; 2) She has acute critical illness; and 3) She has chronic illness – COPD – that can lead to malnutrition through reduced appetite, increased protein degradation, and increased autophagy secondary to chronic, low-grade systemic inflammation. She is considered at high risk for malnutrition by NUTRIC criteria, which is recommended for use in critically ill patients. Identifying patients such as the one in scenario IV emphasizes the need for aggressive provision of nutritional support for improved outcomes.

Image removed.

 

Obesity Case 4

A 54 year-old woman is scheduled for surgical neck exploration and laryngectomy for the recurrence of a laryngeal squamous cell carcinoma. She was initially treated with external beam radiation to the neck 3 years prior when she was first diagnosed. Over the past 6 months, she has lost 35 lbs, which was attributed to increased dysphagia and reduced appetite during this time. Despite strong support of family members and friends and a large supply of oral nutritional supplements at home, the patient is unable to meet her nutritional needs with oral intake. Her current weight is 93 lbs (42 kg), and her height is 65 inches (165 cm), giving her a body mass index (BMI) of 15 kg/m2 (normal, 18.5 to 24.9 kg/m2).

Her other medical history includes hypothyroidism that developed 6 months after radiation therapy and hypertension. She previously smoked one pack of cigarettes daily for 25 years, but quit 10 years prior. She has mild emphysema and only rarely requires rescue inhalers for symptoms of wheezing.

Her oral medications include levothyroxine, amlodipine, as well as opiate medications for pain. Two weeks prior to her scheduled surgery, the patient is admitted for nutritional optimization and a gastric feeding tube is placed.

Question 1

Which tube feeding regimen should be administered to this patient?

A. Standard tube feed formula (1 kcal/mL)
B. A specialized pulmonary feeding formula fortified with lipids to alter the respiratory quotient (R) and reduce CO2 production.
C. A concentrated formula (1.8 kcal/mL)
D. A semi-elemental formula
E. An immune-modulating tube feed formula, fortified with ω-3 fatty acids, arginine, glutamine, and ribonucleic acids.
Incorrect!
Correct!
Correct Answer
An immune-modulating tube feed formula, fortified with ω-3 fatty acids, arginine, glutamine, and ribonucleic acids.

The choice of tube feed formula can be daunting: a wide array of tube feed formulas are available for clinical use. In most cases, standard tube feeds are equally efficacious to specialty feed formulas, and standard feeds are the most cost effective. The use of specialized feeds is only clinically beneficial in a few specific instances. Some examples of these include the use of low carbohydrate feeds for patients with diabetes or the use of concentrated feeds with low potassium and low phosphorus for patients with renal insufficiency. Formulas with partially hydrolyzed proteins (semi-elemental) or formulas with amino acids and dipeptides as a protein source are more easily absorbed and can be used in patients with reduced intestinal absorptive area or intestinal ischemia and in pediatric populations.

For many other clinical scenarios, evidence for specialized tube feeds is lacking, or in some cases, no specific benefit has been demonstrated. For example, tube feed formulas directed for use in hepatic encephalopathy show no difference in mental status or cognition in clinical trials. In patients with pulmonary disease, use of a specialized pulmonary feeding formula that is fortified with lipids to alter the respiratory quotient (R) does not impact pulmonary function. While less CO2 is produced in the metabolism of formulas with a low R quotient, a higher amount of O2 is consumed. No differences in mortality, quality of life, or other clinically meaningful outcomes have been demonstrated with the use of specialized pulmonary formulas.Over the past few decades, dietary compounds that affect immune system function have been identified in animal studies and in human trials with purported health benefits. These include substances such as ?-3 fatty acids, glutamine, arginine, ribonucleic acids, and other antioxidant compounds.

For many clinical scenarios, however, the use of immune-modulating tube feed formulas remains a subject of controversy. In cases of acute critical illness, septic shock, or acute respiratory distress syndrome, initial clinical trials demonstrate benefit with specific immune-modulating formulas, while subsequent studies show no effect. In contrast, six separate, recently published trials investigating the use of arginine-fortified tube feeds among subjects with head and neck squamous cell cancer consistently demonstrate improved outcomes including reduced surgical complications, reduced fistula formation, and reduced length of hospitalization. Based on these findings, administration of tube feeds enriched with arginine is most appropriate in the patient presented here.

Question 2

In the same patient, tube feeds are started. After 36 hours, the patient develops mild lower extremity edema, and bloodwork demonstrates an electrolyte abnormality. Refeeding syndrome is suspected. 

Which of the following serum electrolyte abnormalities is most often seen in refeeding sydrome?

A. Hyperkalemia
B. Hypophosphatemia
C. Hypocalcemia
D. Hypermagnesemia
Incorrect!
Correct!
Correct Answer
B. Hypophosphatemia

Refeeding syndrome is marked by electrolyte abnormalities that occur in severely malnourished patients as nutrition support is re-introduced. In some cases, edema, diarrhea, tachycardia, and weakness can develop. Any form of nutrition including oral diet, tube feeds, or parenteral nutrition can lead to refeeding syndrome.

During times of fasting or scarce nutritional intake, circulating insulin levels are low and glucagon levels are elevated. Intracellular potassium, magnesium, and phosphate stores are continually utilized, becoming depleted. As intake of food suddenly increases, insulin levels rise significantly. Potassium, magnesium, and phosphate shift into the intracellular space, leading to low serum levels of these electrolytes.Hypophosphatemia is the most commonly described electrolyte abnormality, with a reported prevalence of 96% in a review of 27 refeeding syndrome cases. This results from a sudden increase in phosphate utilization, e.g., the intracellular phosphorylation of newly ingested glucose to glucose-6-phosphate, and through an abrupt increase in synthesis of adenosine triphosphate (ATP).

When severe, the hypophosphatemia in refeeding syndrome can lead to muscle weakness, paralysis, and even death from diaphragmatic weakness and subsequent respiratory failure. Hypokalemia and hypomagnesemia are also commonly observed in approximately half of individuals with refeeding syndrome, stimulated by intracellular shifts of these electrolytes as nutrients are given and insulin levels rise. Serum calcium levels, when corrected for low circulating levels of albumin, are usually not affected.

To avoid refeeding syndrome, nutrients should be introduced slowly, depending on the severity of malnutrition. Electrolyte disturbances can be anticipated: phosphate, potassium, and magnesium supplementation may be given along with the initial nutrition support to avoid refeeding syndrome. Thiamine, which functions as a cofactor in glucose metabolism, should also be empirically administered to address potential thiamine deficiency that can be exacerbated as dietary carbohydrate intake suddenly rises. Careful monitoring of serum electrolyte levels should guide the adjustment of electrolyte supplementation over the initial days of nutrition support in cases of severe malnutrition.

Obesity Case 5

A 28 year-old woman seeks advice about prevention of gestational diabetes mellitus. Three of her sisters have had pregnancies complicated by gestational diabetes mellitus (GDM). Although good randomized trial data evaluating whether specific diets can prevent gestational diabetes are lacking, she was advised to lose weight. Eighteen months later, the patient has not succeeded in losing any weight, but has become pregnant. She continues to follow a typical Western diet with an abundance of processed food. She walks for 20 minutes five days per week. She comes to your office at 26 weeks of gestation because her glucose tolerance test showed gestational diabetes.

Question 1

Which of the following statements reflect the best available evidence regarding which diet she should follow to control her blood sugars?

A. A Mediterranean diet followed during pregnancy will help control gestational diabetes.
B. A low fat diet will help control gestational diabetes
C. A low glycemic index (GI) diet will help control gestational diabetes.
D. Energy restriction is not recommended during pregnancy.
Incorrect!
Correct!
Correct Answer
C. A low glycemic index (GI) diet will help control gestational diabetes.

A low GI diet is typically advised as treatment for women with GDM. Although data from randomized control trials is limited, low GI diets have demonstrated benefits and no harm. In a meta-analysis, low GI diets demonstrated a lower risk of macrosomia and a lower risk of insulin usage. Additionally, low GI diets with increased dietary fiber have been shown to reduce the risk of macrosomia beyond that of a low glycemic index diet alone.

Most clinical practice guidelines recommend that women with gestational diabetes limit carbohydrate intake to 35% to 45% of total calories with a minimum of 175 g/day to avoid ketogenesis, distributed in three small- to moderate-sized meals and two to four snacks, including an evening snack. The carbohydrate choices should preferably be low glycemic index with increased dietary fiber.Energy restriction is recommended by the Endocrine Society with their guideline that women with obesity and overt or gestational diabetes reduce their calorie intake by approximately one-third (compared with their usual intake before pregnancy) while maintaining a minimum intake of 1600 to 1800 kcal/d.

For her next pregnancy, assuming that she is not diagnosed with diabetes at the conclusion of the current pregnancy, it is unclear which dietary recommendations should be given to prevent repeat gestational diabetes. Large population surveys have demonstrated that women eating the highest quantities of plant-based carbohydrate and protein and the lowest amount of saturated fat/red meat are least likely to be subsequently diagnosed with gestational diabetes mellitus (independent of body mass index). Low glycemic index and low carbohydrate diets have not been shown to be effective in preventing GDM in prospective randomized control trials. Low fat diets have been shown to reduce the risk of type 2 diabetes mellitus in persons with impaired glucose tolerance, but have not been studied in a population likely to develop GDM.

Obesity Case 6

A 55 year-old woman with a strong family history of both coronary artery disease and type 2 diabetes mellitus (T2DM) comes for evaluation. She has a 6-year history of hypertension, a long-standing problem with obesity, and pre-diabetes revealed by recent laboratory testing. She questions whether a low fat or low carbohydrate diet would be helpful in reducing her risk of coronary artery disease.

Question 1

Which one of the following statements regarding the beneficial effect of diet in reducing cardiovascular risk and/or risk of diabetes mellitus is correct?

A. Low fat diets in women do not reduce cardiovascular disease.
B. A low fat diet is more likely than low carbohydrate diet to improve high density lipoprotein (HDL) cholesterol.
C. A low carbohydrate diet is more likely than low fat diet to improve triglycerides.
D. The macronutrient composition of the diet has not been shown to be critical for modification of coronary risk factors.
Incorrect!
Correct!
Correct Answer
C. A low carbohydrate diet is more likely than low fat diet to improve triglycerides.

In the Women's Health Initiative Dietary Modification Trial, nearly 50,000 postmenopausal women were randomly assigned to a low-fat dietary pattern or to a usual diet comparison group. The 8.3-year intervention period ended in 2005, but all participants were followed for mortality through 2013. Incidence rates for cardiovascular disease (CVD) did not differ between the intervention and comparison groups.

Several studies have compared low carbohydrate and low fat diets in obesity. In one representative study, a one-year, multicenter, controlled trial randomized 63 men and women with obesity to either a low-carbohydrate diet or a low-calorie, high-carbohydrate, low-fat (conventional) diet. Subjects on the low carbohydrate diet lost more weight than subjects on the low fat diet at 3 and 6 months, but the difference at 12 months was not significant. No differences were found between the groups in total cholesterol or low density lipoprotein (LDL) cholesterol concentrations.

The increase in HDL cholesterol concentrations and the decrease in triglyceride concentrations were greater on the low carbohydrate diet compared to the conventional diet during most of the study. In a subsequent paper from the same researchers randomizing 307 persons for two years, weight loss was similar between diet strategies, but the major lipid difference at the two-year time point was lower triglycerides in the low carbohydrate group. These lipid changes have been consistent across many studies. In such research, adherence tends to be poor with high attrition, hence a paucity of long-term (i.e., 5-year) data.A meta-analysis of 23 trials from multiple countries containing more than 2500 randomized participants concluded that both low-carbohydrate and low-fat diets lowered weight and improved metabolic risk factors. Compared with subjects on low fat diets, persons on low carbohydrate diets had a slight benefit with regard to total cholesterol and LDL, but achieved a greater increase in HDL and a greater decrease in triglycerides. Reductions in body weight, waist circumference, and other metabolic risk factors were not different between the two diets.

Obesity Case 7

An older man with obesity complicated by type 2 diabetes, and hypertension, comes for a second opinion about dietary management. His primary care physician recommends that he switch to a Mediterranean diet supplemented with mixed nuts, without worrying about energy restriction. The patient is concerned that such an approach will worsen his cardiovascular risk.

Question 1

  Which one of the following statements about the Mediterranean diet is correct?

A. The effect of the Mediterranean diet (with addition of either nuts or olive oil) on cardiovascular risk is less potent in patients with pre-existing diabetes.
B. A Mediterranean diet (with addition of either nuts or olive oil) has been shown to reduce cardiovascular events compared to a low fat diet in those with high cardiovascular risk.
C. The Mediterranean diet (with addition of either nuts or olive oil) is effective in cardiovascular risk reduction even in patients without hypertension.
D. A Mediterranean diet (with addition of either nuts or olive oil) can reduce total mortality.
Incorrect!
Correct!
Correct Answer
B. A Mediterranean diet (with addition of either nuts or olive oil) has been shown to reduce cardiovascular events compared to a low fat diet in those with high cardiovascular risk.

The latest publication from the PREDIMED trial group reported a significant reduction in major cardiovascular events, but not overall mortality, after 5 years on a Mediterranean diet. Over 7000 persons at high cardiovascular risk were enrolled and assigned to either a low fat control group or a Mediterranean diet enriched in nuts or olive oil. Energy restriction was not specifically recommended. Both of these Mediterranean-based diets were successful, and the trial was halted just over one year early because of the significance of the results. The nut-supplemented group showed a shift in their lipid patterns to less atherogenic lipid profiles and reductions in small dense low density lipoprotein (LDL).

In a sub-study from PREDIMED reporting on patients with type 2 diabetes, Mediterranean diets supplemented with virgin olive oil or nuts reduced total body weight and improved glucose metabolism to the same extent as the usually recommended low-fat diet.The diet was effective in almost all subgroups within the trial, with the notable exception of patients with normal blood pressure. Patients with diabetes saw a benefit similar to the overall group.  In contrast, lifestyle modification has been shown to prevent diabetes mellitus more consistently, but diet has been less consistent in preventing or reducing cardiovascular disease. The recent LOOK AHEAD study revealed no significant benefit of lifestyle modification on cardiovascular risk, although this paper studied only persons with pre-existing diabetes. Neither low carbohydrate diets nor addition of omega-3 fatty acids can prevent diabetes mellitus, and these diet modifications may even be associated with a higher risk of diabetes mellitus.

Obesity Case 8

A 27 year-old woman with a history of obesity, polycystic ovary syndrome (PCOS) and primary hypothyroidism is referred to you for recent weight gain. She also has a history of recurrent kidney stones. Despite her best efforts to follow a meal plan as prescribed by a registered dietitian and increasing her physical activity by hiring a personal trainer, she has gained 20 pounds in the 6 months prior to her visit with you. She reports recent trouble with portion control. She generally eats three large meals per day and craves salty snacks like potato chips and tortilla chips in the evening while watching TV.

She was evaluated by another endocrinologist who documented a normal 11 pm salivary cortisol, fasting glucose, glycated hemoglobin A1c (HbA1c), and thyroid-stimulating hormone (TSH) level. Her past medical history is unremarkable. Her only medication is levothyroxine 100 mg daily. Her family history is notable for obesity and type 2 diabetes mellitus (T2DM) in her father. Her mother had medullary thyroid cancer but is currently free of disease. She is married, but does not desire to start a family yet, wishing to focus on her personal health first.

On review of systems, she has generalized anxiety and trouble sleeping. Menses are irregular. On physical examination, her heart rate is 88 beats/minute, and her blood pressure is 125/80 mm Hg. Her body mass index (BMI) is 36 kg/m2 (normal, 18.5 to 24.9 kg/m2), and her waist circumference is 96.5 cm. She has mild facial hirsutism on the chin and upper lip. The thyroid gland is minimally enlarged, but there are no palpable nodules. An ultrasound performed 6 months ago also did not show any nodules.

Question 1

  The most appropriate choice of pharmacotherapy for this patient is which of the following?

A. Orlistat
B. Phentermine/topiramate ER
C. Liraglutide
D. NaltrexoneER/bupropion ER
E. Phentermine
Incorrect!
Correct!
Correct Answer
D. NaltrexoneER/bupropion ER

Increasing fat mass is always due to a positive energy balance. In addition to ongoing meal-planning and physical activity, pharmacotherapy plays a role in helping patients adhere to nutrition therapy. Scientifically, there is a growing armamentarium of medications for obesity.

Practically, as of 2017, obesity medications are not covered by the federal government or many third party payers. This results in patients having to incur the cost of medications out-of-pocket. This severely restricts patient access to needed care. Phentermine is an adrenergic agonist. It is approved for short-term use for the treatment of obesity (generally considered 3 months). Although it was originally labelled as having the potential for being habit-forming, tolerance-building, and addictive, we now know it is not. Phentermine is the most commonly used weight management medication because it is generic and cheap. It is safe and effective, but its side effect profile includes hyperadrenergic signs and symptoms. Phentermine use may cause an increase in the heart rate, jitteriness, shakiness, anxiety, palpitations, insomnia, dry mouth, constipation, and anxiety. Therefore, phentermine should be avoided in people who have underlying anxiety.

Phentermine in combination with topiramate is available as Qsymia® in the United States. This combination of medications allows for the phentermine dose to be lower. Although the phentermine dose is lower in Qsymia, its use would still be a concern in a patient with anxiety. Topiramate causes cleft-lip and cleft-palate malformations in women who take it during pregnancy. Topiramate is therefore absolutely contraindicated in women desiring pregnancy. There is also increased risk of nephrolithiasis with topiramate therapy thus not the preferred medication.

Orlistat is a pancreatic lipase inhibitor. For it to be effective, an orlistat capsule has to be taken with each meal containing fat. Orlistat acts entirely within the lumen of the gut. Lipase inhibition causes fat malabsorption. Fat malabsorption in turn may cause loose stools, oily stools, fecal incontinence, and anal leakage. Most of the symptoms of fat malabsorption go away with daily ingestion of soluble fiber (i.e., psyllium seeds), and the ingestion of 500 mg of calcium carbonate with each orlistat capsule.  Calcium carbonate saponifies any oily residue and prevents its irritating effects. The combination of both psyllium and calcium carbonate makes most of the untoward symptoms of fat malabsorption due to orlistat go away, and patients may tolerate it. Over time, orlistat may lead to fat-soluble vitamin malabsorption, and it is recommended to prescribe a multivitamin to be taken apart from meals. Orlistat is probably not the best option due to her regular intake of high fat snacks as well as the increased risk of calcium oxalate stones. In addition, orlistat can block the absorption of levothyroxine, and its dosing would need to be separated from the thyroid medication making it a less optimal choice. Furthermore, orlistat is the only approved weight loss medication that does not work on appetite control which is her primary barrier to dietary adherence.

Liraglutide, 3 milligrams daily, is marketed as Saxenda® in the United States. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist. It delays gastric emptying, improves insulin secretion in response to postprandial hyperglycemia in people with diabetes, suppresses glucagon release from the pancreas, and stimulates central receptors that promote early satiety. Liraglutide, being a polypeptide, must be injected subcutaneously. It is formulated as a daily injection and is the most costly of the weight-management medications available as of 2017. Liraglutide may cause nausea and other gastrointestinal symptoms. For patients with obesity and hyperglycemic derangements, it may be the preferred option. Due to carcinogenicity studies in rodents, liraglutide is contraindicated in patients with a personal or family history of medullary thyroid cancer or multiple endocrine neoplasia type 2 so this option is incorrect.

The best choice of agents for this patient is the combination of buproprion and naltrexone. Bupropion is a mood stabilizer that also decreases addictive and compulsive behavior. Naltrexone is an opioid receptor blocker and decreases the pleasure of meal intake. The combination of these medications helps to decrease food intake and reduce cravings. The naltrexone component predictably causes nausea, and therefore, the dose is gradually titrated from one tablet daily to two tablets twice daily over time. Most patients tolerate an increase of one tablet a day, once a week.

Obesity Case 9

A 71 year-old Caucasian American female with a history of obesity disease, Type 2 Diabetes, hyperlipidemia with a recent hospitalization for abdominal pain and found to have Nonalcoholic fatty liver on US abdomen, is now in the clinic for a follow up. 

 

Question 1

Lifestyle intervention and modification including exercise, diet and weight loss is the first line treatment and prevention of non-alcoholic fatty liver disease. What pharmacologic agent shows an improvement in liver histology?

A. Insulin
B. Metformin
C. Liraglutide
D. Sitagliptin
Incorrect!
Correct!
Correct Answer
C. Liraglutide

Nonalcoholic fatty liver disease is very frequent in type 2 diabetes, with increased risk of further development of liver fibrosis. Study has showed treatment with liraglutide at a daily dose of 1.2 mg induced a significant reduction in liver fat content in patients with uncontrolled type 2 diabetes; this effect was due to reduction in body weight.[i]

GLP1 agonists have been reported to significantly decrease liver enzyme levels in patients with type 2 diabetes. The GLP-1 analog, Liraglutide has led to clinically significant NASH resolution and exenatide have stopped liver fibrosis progression.[ii]

 

[i] Jean-Michel Petit, et al. Effect of Liraglutide Therapy on Liver Fat Content in Patients with Inadequately Controlled Type 2 Diabetes: The Lira-NAFLD Study. The Journal of Clinical Endocrinology & Metabolism, Volume 102, Issue 2, 1 February 2017, Pages 407–415

[II]. Debra AG, et al. Liraglutide’s use in treatment of non-alcoholic fatty liver: an evaluation of the non-alcoholic steatohepatitis study. Hepatobilary Surg Nutr. 2016 Dec; 5(6): 515–518.

 

 

 

Nonalcoholic fatty liver disease is very frequent in type 2 diabetes, with increased risk of further development of liver fibrosis. Study has showed treatment with liraglutide at a daily dose of 1.2 mg induced a significant reduction in liver fat content in patients with uncontrolled type 2 diabetes; this effect was due to reduction in body weight.[i]

GLP1 agonists have been reported to significantly decrease liver enzyme levels in patients with type 2 diabetes. The GLP-1 analog, Liraglutide has led to clinically significant NASH resolution and exenatide have stopped liver fibrosis progression.[ii]

 

[i] Jean-Michel Petit, et al. Effect of Liraglutide Therapy on Liver Fat Content in Patients with Inadequately Controlled Type 2 Diabetes: The Lira-NAFLD Study. The Journal of Clinical Endocrinology & Metabolism, Volume 102, Issue 2, 1 February 2017, Pages 407–415

[II]. Debra AG, et al. Liraglutide’s use in treatment of non-alcoholic fatty liver: an evaluation of the non-alcoholic steatohepatitis study. Hepatobilary Surg Nutr. 2016 Dec; 5(6): 515–518.

Obesity Case 10

A 35-year-old man comes to the office for a routine follow-up examination. He has type 2 diabetes mellitus, hypertension, obstructive sleep apnea and hyperlipidemia. Medications are losartan, metformin, CPAP and rosuvastatin. He is 180 cm (5 ft 8 in) tall and weighs108 kg (238lb); BMI is 33 kg/m2. Vital signs are within normal limits. Physical examination is normal except for generalized obesity. The patient says he wants to lose weight.

Question 1

Which of the following is the most appropriate recommendation in order to improve metabolic disturbances associated with his weight?

A. decrease between 3.2 kg (7.1lb) and 4.3 kg (9.5lb)
B. decrease between 5.4 kg (11.9 lb) and 10.8 kg (23.8 lb)
C. decrease between 14 kg (31 lb) and 15.2 kg (35.7 lb)
D. decrease between 17.2 kg (38.1 lb) and 21.6 kg (47.6 lb)
E. decrease between 24.8 kg (54.7 lb) and 27 kg (59.5 lb)
Incorrect!
Correct!
Correct Answer
B. decrease between 5.4 kg (11.9 lb) and 10.8 kg (23.8 lb)

Weight loss of 5 to 10 percent of your total body weight is likely to produce health benefits, such as improvements in blood pressure, blood cholesterol, and blood sugars and is recommended in person that have already comorbidities. A 2011 study published in Diabetes Care found that people who lost between 5 and 10 percent of their body weight experienced both a boost in beneficial HDL cholesterol and a decrease in triglycerides.

There’s scientific evidence that many obesity-related conditions improve with a 5-10 percent weight-loss as follow

  1. A 5-10 percent weight-loss can result in a five point increase in HDL cholesterol. This deserves applause as raising HDL by these few points can lower the risk of an individual developing heart disease.
  2. By losing 5-10 percent of one’s weight, blood pressure, both systolic and diastolic, decrease by 5 mmHg on average.
  3. Research has shown that a 5-10 percent weight-loss can decrease HbA1c by half a point on average.
  4. It has been shown that a 5-10 percent weight-loss may improve sleep apnea and sometimes if the apnea was not very severe, one can be weaned from the CPAP breathing machine.

 

Weight loss of 5 to 10 percent of your total body weight is likely to produce health benefits, such as improvements in blood pressure, blood cholesterol, and blood sugars and is recommended in person that have already comorbidities. A 2011 study published in Diabetes Care found that people who lost between 5 and 10 percent of their body weight experienced both a boost in beneficial HDL cholesterol and a decrease in triglycerides.

There’s scientific evidence that many obesity-related conditions improve with a 5-10 percent weight-loss as follow

  1. A 5-10 percent weight-loss can result in a five point increase in HDL cholesterol. This deserves applause as raising HDL by these few points can lower the risk of an individual developing heart disease.
  2. By losing 5-10 percent of one’s weight, blood pressure, both systolic and diastolic, decrease by 5 mmHg on average.
  3. Research has shown that a 5-10 percent weight-loss can decrease HbA1c by half a point on average.
  4. It has been shown that a 5-10 percent weight-loss may improve sleep apnea and sometimes if the apnea was not very severe, one can be weaned from the CPAP breathing machine.

Obesity Case 11

A 63-year-old African American male with a history of obesity, T2DM, CKD3b and recent NSTEMI was referred for cardiometabolic risk optimization.

Medications: atorvastatin 80mg, lisinopril 20mg, aspirin 162mg, metformin 1000mg bid, metoprolol 50mg daily, duloxetine 20mg daily

Diet:

  1. Heavy in starchy and refined carbohydrates, “meat & potatoes,” and casseroles
  2. Doesn’t snack much and avoids sweets or baked goods during the day and evening but eats fruit for dessert
  3. No sugar-sweetened beverages and rare alcohol

Exercise: states he has always been physically active with his work but has been in cardiac rehab three times weekly for the past 6 weeks

Sleep: has OSA treated with cpap

Exam: BMI 37 and waist circumference 111cm; BP 140/90; pulse 66

Labs: HbA1c 7.6%, eGFR 44, total cholesterol 145, HDLc 45 mg/dL, trig 160 mg/dL, LDLc 68 mg/dL, albumin 4, ALT 35, platelets 300,000, urine albumin:creatinine 320

Question 1

In addition to adding a SGLT2inh for cardiovascular and renal benefits, which medication approved for the chronic therapy of obesity would be preferred?

A. Naltrexone/bupropion ER
B. Liraglutide 3mg
C. Phentermine/topiramate ER
D. Orlistat
Incorrect!
Correct!
Correct Answer
B. Liraglutide 3mg

The GLP-1 analog, liraglutide, previously approved for the treatment of type 2 diabetes mellitus (T2DM), is also approved as a weight loss agent at a dose of 3 mg daily. In the SCALE diabetes trial, there was an average of about 4% placebo-subtracted weight loss and HbA1c reduction of 1% more than placebo and statistically better in both regards than the 1.8-mg dosing[1]. Liraglutide at all doses consistently improves cardiometabolic risk factors including lipids and blood pressure with slightly increased heart rate. A pooled post hoc analysis of the phase 3 trials involving liraglutide 3 mg suggested possible cardiovascular benefit but with small numbers of events and wide confidence intervals[2]. Further reassurance of cardiovascular safety, and perhaps benefit, could be drawn from the benefits shown in the LEADER trial of 1.8-mg liraglutide in patients with T2DM and high-risk (and high prevalence of established) CVD[3].

The other medications are not preferred for reducing CV risk in this patient with established ascvd and CKD3b though could be considered[4]. Orlistat reduces cardiovascular risk factors and has no cardiovascular safety concerns but has not shown cardiovascular event reduction and is not as beneficial for this patients glycemic control and renal benefits. Sympathomimetics, like phentermine in the combination of phentermine/topiramate ER, are to be used in caution for patients at increased cardiovascular risk. While the cardiovascular safety of phentermine/topiramate ER is not established, data from the phase 3 trials are reassuring thus far[5]. Weight loss with naltrexone/bupropion ER is accompanied by improvements of several cardiometabolic parameters, though blood pressure generally remained higher than placebo in trials. A cardiovascular outcome trial was initiated for naltrexone/bupropion ER with reassuring early data, though with high discontinuation rate, but the trial had to be terminated due to public compromise of that data; thus, the cardiovascular safety has not been determined[6].

 

[1] Davies MJ, et al. Efficacy of liraglutide for weight loss among patients with type 2

diabetes: the SCALE Diabetes Randomized Clinical Trial. JAMA 2015;314(7):687–699

[2] Davies MJ, et al. Liraglutide and cardiovascular outcomes in adults with overweight

or obesity: a post hoc analysis from SCALE randomized controlled trials. Diabetes Obes

Metab 2018;20:734–739

[3] Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J

Med 2016;375(4):311–322.

[4]Garvey WT, et al. American Association of Clinical Endocrinologists and American

College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care

of Patients with Obesity. Endocr Pract 2016;22(suppl 3):1–203

[5] Ritchey ME, et al. Cardiovascular safety during and after use of phentermine and

topiramate. J Clin Endocrinol Metab 2019;104(2):513–522. doi:10.1210/jc.2018-01010.

[6] Nissen SE, et al. Effect of naltrexone-bupropion on major adverse cardiovascular

events in overweight and obese patients with cardiovascular risk factors: a randomized

clinical trial. JAMA 2016;315(10):990–1004

The GLP-1 analog, liraglutide, previously approved for the treatment of type 2 diabetes mellitus (T2DM), is also approved as a weight loss agent at a dose of 3 mg daily. In the SCALE diabetes trial, there was an average of about 4% placebo-subtracted weight loss and HbA1c reduction of 1% more than placebo and statistically better in both regards than the 1.8-mg dosing[1]. Liraglutide at all doses consistently improves cardiometabolic risk factors including lipids and blood pressure with slightly increased heart rate. A pooled post hoc analysis of the phase 3 trials involving liraglutide 3 mg suggested possible cardiovascular benefit but with small numbers of events and wide confidence intervals[2]. Further reassurance of cardiovascular safety, and perhaps benefit, could be drawn from the benefits shown in the LEADER trial of 1.8-mg liraglutide in patients with T2DM and high-risk (and high prevalence of established) CVD[3].

The other medications are not preferred for reducing CV risk in this patient with established ascvd and CKD3b though could be considered[4]. Orlistat reduces cardiovascular risk factors and has no cardiovascular safety concerns but has not shown cardiovascular event reduction and is not as beneficial for this patients glycemic control and renal benefits. Sympathomimetics, like phentermine in the combination of phentermine/topiramate ER, are to be used in caution for patients at increased cardiovascular risk. While the cardiovascular safety of phentermine/topiramate ER is not established, data from the phase 3 trials are reassuring thus far[5]. Weight loss with naltrexone/bupropion ER is accompanied by improvements of several cardiometabolic parameters, though blood pressure generally remained higher than placebo in trials. A cardiovascular outcome trial was initiated for naltrexone/bupropion ER with reassuring early data, though with high discontinuation rate, but the trial had to be terminated due to public compromise of that data; thus, the cardiovascular safety has not been determined[6].

 

[1] Davies MJ, et al. Efficacy of liraglutide for weight loss among patients with type 2

diabetes: the SCALE Diabetes Randomized Clinical Trial. JAMA 2015;314(7):687–699

[2] Davies MJ, et al. Liraglutide and cardiovascular outcomes in adults with overweight

or obesity: a post hoc analysis from SCALE randomized controlled trials. Diabetes Obes

Metab 2018;20:734–739

[3] Marso SP, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J

Med 2016;375(4):311–322.

[4]Garvey WT, et al. American Association of Clinical Endocrinologists and American

College of Endocrinology Comprehensive Clinical Practice Guidelines for Medical Care

of Patients with Obesity. Endocr Pract 2016;22(suppl 3):1–203

[5] Ritchey ME, et al. Cardiovascular safety during and after use of phentermine and

topiramate. J Clin Endocrinol Metab 2019;104(2):513–522. doi:10.1210/jc.2018-01010.

[6] Nissen SE, et al. Effect of naltrexone-bupropion on major adverse cardiovascular

events in overweight and obese patients with cardiovascular risk factors: a randomized

clinical trial. JAMA 2016;315(10):990–1004

Obesity Case 12

A 47-year-old woman with primary hypothyroidism and osteoarthritis of the right knee presented to the clinic for follow-up.  She is trying to lose weight in preparation for right knee surgery.  The weight loss has plateaued on a low-calorie meal plan.  Her exercise is limited by chronic knee pain.  She tracks her calories and daily steps.  After the discussion about the risks and benefits of weight loss medications, she was started on phentermine/topiramate extended-release daily.  She returns three months later and has lost 3% of her body weight since the last visit.  On physical examination, her BMI is 34 kg/m². She has decreased range of motion of right knee. Otherwise, the physical examination is unremarkable.

Question 1

Which of the following is true for cardiometabolic risk markers after weight loss?

A. Increase in hs-CRP and decrease in adiponectin
B. Increase in both hs-CRP and adiponectin
C. Decrease in both hs-CRP and adiponectin
D. Decrease in hs-CRP and an increase in adiponectin
Incorrect!
Correct!
Correct Answer
D. Decrease in hs-CRP and an increase in adiponectin

The effect of phentermine/topiramate extended-release on cardiometabolic risk factors include lowering of hs-CRP and an increase in adiponectin.  There is a reduction in systolic and diastolic blood pressure, reduction in triglycerides, total cholesterol and LDL cholesterol, and an increase in HDL cholesterol with weight loss.

The effect of phentermine/topiramate extended-release on cardiometabolic risk factors include lowering of hs-CRP and an increase in adiponectin.  There is a reduction in systolic and diastolic blood pressure, reduction in triglycerides, total cholesterol and LDL cholesterol, and an increase in HDL cholesterol with weight loss.