Prediabetes Lifestyle Changes Can Slow Progression to Diabetes Mellitus

Abstract: Diabetes mellitus is a major cause of morbidity and mortality in the United States, increasing the risk of coronary artery disease, stroke, kidney disease, and other life-threatening illnesses. Prediabetes, defined as an elevated blood glucose level that is not yet high enough to be classified as type 2 diabetes mellitus, is often a precursor to this disease. If left untreated, patients with prediabetes are at high risk of becoming diabetic; however, studies have shown that lifestyle changes, including losing weight and increasing physical activity, can prevent or delay the onset of diabetes. This article provides an overview of prediabetes and reviews the lifestyle interventions that can play a critical role in preventing patients with this condition from developing diabetes.

Diabetes mellitus has ranked in the top 10 causes of death since at least 1980.¹ In 2010, it was ranked as the 7th leading cause of mortality, directly responsible for 69,071 deaths.² In addition, it is well known that diabetes is strongly associated with multiple comorbid conditions (Table 1), indirectly contributing to 234,051 deaths in 2010.² 

Prediabetes—also known as impaired fasting glucose (IFG), intermediate hyperglycemia, abnormal glucose tolerance, or latent diabetes—is often a precursor to diabetes. Prediabetes is defined as a hemoglobin A1c (HbA1c) level between 5.7% and 6.4% or an impaired fasting glucose (IFG) level of 100 mg/dL to 125 mg/dL. 

According to the Centers for Disease Control and Prevention, prediabetes has a high prevalence in the United States: 35% of all adults aged 20 years and older and 50% of all adults aged 65 years and older have been diagnosed with prediabetes between 2005 and 2008.³ In 2012, 86 million Americans were reported to have prediabetes, an increase from 79 million in 2010.³ 

Studies have shown that people with prediabetes who lose weight and increase their levels of physical activity can prevent or delay type 2 diabetes from evolving, and in some cases return their blood glucose levels to normal. In fact, lifestyle changes are the only treatment shown to be extremely effective for slowing or halting the progression from prediabetes to type 2 diabetes mellitus. 

Although metformin can be a beneficial medication in some patients with prediabetes, particularly those who are morbidly obese, it is more expensive and associated with shorter-acting benefits and lower quality of life than lifestyle changes. This article will provide an overview of prediabetes and review the lifestyle changes that have been found to be particularly beneficial for this condition.

ETIOLOGY

The underlying cause of prediabetes and type 2 diabetes mellitus is insulin resistance (eg, pre-receptor, receptor, and post-receptor defects). Obesity is the most common precipitating factor of insulin resistance, but other factors have been implicated. In 1 reported case, insulin resistance was attributed to infection with Helicobacter pylori.⁴ 

Several medications have been known to precipitate insulin resistance, including high-dose thiazide diuretics, beta-blockers, oral and inhaled corticosteroids, niacin, thyroid hormone, phenytoin, interferon gamma, and pentamidine.⁵ Other medications that have been reported to cause transient hyperglycemia or impaired fasting glucose levels include protease inhibitors, steroids, and atypical antipsychotics.⁶ In an 8-week randomized trial of 44 healthy postmenopausal women without diabetes, raloxifene (an oral
selective estrogen receptor modulator) caused increased insulin resistance, whereas estrogen and placebo did not.⁷ 

Glucosamine, chondroitin, and fluoroquinolones are other agents that may increase blood glucose levels.^8-12 

RISK FACTORS FOR PREDIABETES AND DIABETES 

Risk factors strongly correlated with prediabetes and diabetes mellitus include metabolic conditions, modifiable lifestyle factors, demographic factors, and pediatric factors. 

• Metabolic conditions. Obesity, metabolic syndrome, polycystic ovarian syndrome, and gestational diabetes are some of the conditions associated with diabetes and prediabetes. Many of these conditions are known to be modifiable with dietary and lifestyle changes. 

• Modifiable lifestyle factors. Poor diets, lack of exercise, and unhealthy habits (eg, smoking) are major contributors to prediabetes and diabetes. Diets associated with these conditions are characterized by increased intake of processed meats, sweetened beverages, and foods high on the glycemic index and low in cereal fiber, magnesium, and other nutrients. Lack of exercise and smoking compound the effects of a poor diet.

• Demographic factors. Genetics and socioeconomic status are 2 major demographic factors that contribute to the development of prediabetes and diabetes. Although dietary choices and other lifestyle factors are associated with certain ethnicities, genetics are also a major factor. Lower socioeconomic status contributes on multiple levels—such as lower health literacy, poorer food choices due to cost, and decreased access to quality healthcare and early interventions. 

• Pediatric factors. Pediatric obesity and low birth weight increased the risk of prediabetes and diabetes. Among 55 obese children (aged 4-10), 25% had impaired glucose tolerance and among 112 obese adolescents (aged 11-18), 21% had impaired glucose tolerance.¹³ 

Four percent of obese children were found to already have type 2 diabetes mellitus.¹⁴ Less intuitively, very low birth weight may be associated with higher insulin resistance and glucose intolerance in adulthood. A 2007 study compared 163 young adults (aged 18-27) who had a very low weight at birth with 169 controls (aged-matched young adults who were average for their gestational age at birth). As compared with the controls, the very-low birth weight group had a 6.7% increase in their 2-hour glucose concentration, a 16.7% increase in the fasting insulin concentration, a 40% increase in the 2-hour insulin concentration, and an 18.9% increase in the insulin-resistance index determined by homeostatic model assessment.¹⁵ 

CLINICAL EVALUATION FOR PREDIABETES

Patients with prediabetes and even diabetes may be asymptomatic; thus, all patients with risk factors for diabetes should be evaluated for the presence of abnormal blood glucose levels. This requires taking a thorough medical and family history and conducting a comprehensive physical examination. 

• Medical history. Numerous factors are important to consider when taking a patient’s family history. First, it is important to consider a patient’s past and present medication use, including the aforementioned medications that are known to increase the risk of insulin resistance and/or cause elevated blood glucose levels. 

Second, it is essential to evaluate the patient’s personal and family history—including hypertension, hyperlipidemia, obesity, recurrent yeast infections, renal disease, eye disease, neuropathy, coronary artery disease, gestational diabetes, polycystic ovarian syndrome, or prior delivery of infant with macrosomia—as these conditions are often associated with prediabetes and diabetes. 

Finally, it is essential to spend time evaluating a patient’s lifestyle, focusing on diet, exercise, alcohol intake, and use of tobacco and other substances. 

• Physical examination. A thorough evaluation may provide clues that point to prediabetes or diabetes. When examining the skin, look for changes, such as tinea (ringworm), ulcerations of the extremities, skin tags, and acanthosis nigricans. It is also important to conduct a fundoscopic examination to look for signs of retinopathy, as well as to check the extremities for sensation and proprioception. 

If prediabetes or diabetes is suspected, laboratory examination should include a hemoglobin A1c (HbA1c) test, fasting plasma glucose test, and/or 2-hour 75 g oral glucose tolerance test. When prediabetes is identified, further work-up may be needed to rule out other diagnoses (eg, Cushing syndrome, adrenal cortical adenoma, or carcinoma). 

TREATMENT FOR PREDIABETES

Once prediabetes is identified, the main goal of treatment is to prevent progression to diabetes. This is best achieved through lifestyle modifications, including dietary changes and increased physical activity, which are both considered first-line treatments. Because many patients with prediabetes are obese (body mass index [BMI] ≥30) or overweight (BMI 25 to 29.9), weight loss is often recommended. 

Weight loss has been shown to have a large impact on preventing progression to diabetes and on normalizing blood glucose levels; a recently published review of randomized trials assessing the effect diet and exercise have on prediabetes found that these interventions are effective at reducing the incidence of type 2 diabetes mellitus and in improving glycemic control even without a significant reduction in body weight.¹⁶ Furthermore, multiple trials comparing lifestyle interventions to medications showed that lifestyle interventions are significantly more effective in treating patients with prediabetes,^17,18 and may even reduce the rate of progression to diabetes. 

Diet Programs for Prediabetes

Numerous dietary interventions, such as low-carb diets, the Mediterranean diet, and the Atkins diet, have been advocated to manage prediabetes and diabetes.

• Low-carb diets. A low-carb diet restricts the number of carbohydrates consumed daily, particularly those found in grains, starchy vegetables, and sugar-sweetened foods and beverages (eg, cookies, cake, candy, and soda). Currently, there is no clear definition of how many carbs daily would constitute a low-carb diet, and a variety of factors can influence the number of allowable carbs consumed (eg, physical activity levels). The American Diabetes Association (ADA) recommends starting by restricting carbs to 45 g to 60 g per meal.¹⁹ 

A 2014 study reported that a very low carbohydrate diet (intake of between 20 to 50 carbs daily), coupled with skills to promote behavior change, improved glycemic control in patients with prediabetes and type 2 diabetes while enabling decreases or the discontinuation of certain medications.²⁰ In the study, 44% of the very low-carbohydrate group was able to discontinue 1 or more diabetes medications compared with only 11% in the medium-carbohydrate group (intake of approximately 165 carbs daily).

• Mediterranean diet. A Mediterranean diet focuses largely on plant-based foods (eg, fruits, vegetables, whole grains, legumes, and nuts), and replacing butter with healthy fats (eg, olive oil). It has been reported that the Mediterranean diet can reduce the incidence of metabolic syndrome, and in 1 study, this effect appeared to be independent of whole and abdominal obesity markers.²⁰ The investigators also noted that none of the specific items of a Mediterranean diet predicted the presence of metabolic syndrome, which they speculated could indicate that the overall diet pattern, rather than the consumption of specific food categories, had a favorable impact on metabolic syndrome.²⁰

• Atkins diet. The Atkins diet is a low-carbohydrate diet that emphasizes consumption of foods high in protein and fat. It is often used for weight loss. A criticism of this diet is that it favors fat over vegetables. 

In response, the “new” Atkins diet enabled followers to eat more vegetables by discounting grams of fiber from the total grams of carbohydrates consumed. The benefits of either Atkins diet stem from the ability to facilitate weight loss and limit carbohydrate intake, improving blood glucose control.

Regardless of which diet a patient adopts, a healthy approach should be advocated. In general, beneficial dietary changes include decreased intake of calories, fat, and sugar, as well as increased intake of dietary fiber (14 g of fiber/1000 kcal) and whole grains (composing at least 50% of all grain intake). However, individualized nutrition counseling by a registered dietician can be beneficial in helping patients identify the best diet for them. This may be especially important for those with a BMI >35, gestational diabetes, or other risk factors and conditions that could complicate their ability to follow a diet or make glucose control more difficult. 

In one study, the incidence of diabetes at 6 years was 43.8% among those receiving dietary advice versus 67.7% in a control group (P<.03).²¹ If in-person counseling is not possible, individual telephone counseling may also reduce weight in patients with lower socioeconomic status and in ethnic minorities. 

Dietary advice was associated with reductions in insulin resistance, fasting insulin, fasting C-peptide, fasting pro-insulin, fasting blood glucose levels, BMI, blood pressure, and fasting triglyceride levels at 12 months, as well as an increase in high-density lipoprotein levels at 12 months.²²

Exercise Programs to Manage Prediabetes 

According to the American Association of Clinical Endocrinologists, aerobic exercise and strength training should be incorporated into a weight loss and maintenance plan for patients with prediabetes. A patient’s plan should include 30 to 60 minutes of moderate intensity physical activity daily for at least 5 days a week.²³ Walking appears to reduce risk of cardiovascular events in patients with prediabetes.^24,25 

Keep in mind that patients should be evaluated for contraindications or limitations on physical activity and that a plan should be created that takes into account the individual patient’s goals and limitations. 

Medications and Other Interventions 

Although lifestyle interventions are the most beneficial, medications may be indicated in some patients (Table 2). Metformin is generally the only medicine used in prediabetes, despite not being approved by the FDA for this indication. The ADA recommends using metformin to halt progression of prediabetes to full blown diabetes, especially in persons with a BMI >35.²⁶ While oral antidiabetic medications other than metformin may have a legitimate indication in the treatment of diabetes, they have limited effectiveness in the treatment of prediabetes. Additionally, they have side effect profiles that are associated with significant risks and have a much higher cost, making them unaffordable for most low-income patients.^27-45 

High-quality evidence suggests that metformin may facilitate a weight loss of at least 7%.⁴⁶ When greater weight loss is desired and lifestyle interventions are not sufficient, numerous weight loss medications can be considered, including tetrahydrolipstatin (Orlistat), lorcaserin (Belviq), phentermine and topiramate (Qsymia), and appetite suppressants. In September 2014, the FDA approved 2 new drugs for weight loss: liraglutide (Victoza), which was formerly approved only as a diabetes medication, and naltrexone/bupropion (Contrave).

Note: Lifestyle interventions, not metformin, were associated with improved health-related quality of life in a secondary analysis of the Diabetes Prevention Program trial.⁴⁵ In a study by Florez et al,⁴⁷ lifestyle interventions improve general health, physical function, bodily pain, and vitality scores when compared with placebo and metformin. These effects appear to persist at a 20-year follow-up. Mortality was improved, but was not significant. Cumulative diabetes incidence decreased by approximately 13% (P<.05) and diabetes onset was delayed by a mean of 3.6 years in the intervention groups compared with the control group.^48-50 Lifestyle changes were cost-effective in all age groups, whereas metformin was less cost-effective in general and not cost-effective in patients older than 65 years.⁵¹ 

The use of herbs and supplements by patients with diabetes and prediabetes is becoming more prevalent. Some of these include cinnamon, vitamin D, chromium, and gingko biloba extract. Of these, cinnamon showed a decrease in fasting blood glucose levels and vitamin D supplementation showed mixed evidence, with a decrease in fasting blood glucose and insulin resistance, but no difference in HbA1c levels. There does not appear to be any evidence supporting the use of chromium or gingko biloba in prediabetes.^1,52-55

The most effective treatment for prediabetes is lifestyle interventions, which is also the most cost effective and has virtually no harmful side effects—good news for primary care physicians and their patients. Patients with prediabetes who change their eating habits and increase their physical activity can prevent or delay the onset of type 2 diabetes. In some cases, patients can even regain normal blood glucose levels. Slowing or halting the progression from prediabetes to diabetes mellitus type 2 has an enormous impact on both the patient’s quality of life as well as the use of precious healthcare dollars. This is an opportunity to head off one of the most common deadly and costly diseases.