January/February 2023

Are Prediabetes & Type 2 Diabetes Reversible?
By Hope Warshaw, MMSc, RD, CDCES, BC-ADM, FADCES
Today’s Geriatric Medicine
Vol. 16 No. 1 P. 22

Today’s Geriatric Medicine reviews the latest international consensus report on type 2 diabetes remission and provides expert guidance for dietitians and physicians who counsel these individuals.

When people are diagnosed with prediabetes or type 2 diabetes, it’s human nature for them to believe promises that there may be a “cure,” or the ability to “reverse their diabetes,” or “reset their blood sugar.” These promises proliferate on the internet, in book titles, on TV shows, on supplement labels, and more.

While it’s known that if prediabetes or type 2 diabetes is detected early and weight loss is sufficiently maintained long term through consistent healthful eating and physical activity and, for some, use of glucose-lowering and/or obesity medications and/or metabolic surgery, people can reverse or stall the progressive course of dysglycemia and type 2 diabetes.1-4 However, is it accurate to call this a “cure” or “reversal?” Perhaps for some people. But for others, as the years pass by, glucose tolerance decreases and/or weight gain or regain occurs. And eventually, glucose levels may rise high enough to meet the diagnostic criteria for prediabetes or type 2 diabetes.5

A recent longitudinal analysis of more than 50,000 medical records of adults aged 65 and older between 2010 and 2018 across the United States showed the annual progression rate (APR) from A1c-defined prediabetes to type 2 diabetes was lower (3.5%) for people with a body mass index (BMI) of 19 to 25 vs 7.6% among those with a BMI of 40 or higher. People with an A1c of 5.7% to 5.9% had an APR of 2.8% compared with those with an APR of 8.2% who had an A1c of 6% to 6.4%.4

Dietitians may wonder, “What is the most accurate word to use to define this potentially temporal normoglycemia? How should we counsel people diagnosed with prediabetes and early-onset type 2 diabetes about their glycemic status, near-future action plan, long-term follow-up, and likelihood of developing type 2 diabetes?”

The “Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes,” which updates a 2009 consensus publication,6 recently was published by the American Diabetes Association (ADA)1 and concomitantly in the journals of three international diabetes-focused organizations: The Endocrine Society, European Association for the Study of Diabetes, and Diabetes UK.

The optimal term the expert authors of the consensus report chose to describe a period of normoglycemia is “remission” after considering the terms “resolved,” “reversal,” and “cure.”1

In this article, Today’s Geriatric Medicine explains why the authors agreed on this term, how remission is defined and why a definition is needed, and when health care providers and their patients in remission should be advised on how to manage blood glucose as the years go by.

Consensus Report Findings
According to the consensus report, the authors chose the term “remission” to describe a period of normoglycemia because “remission strikes an appropriate balance, noting that diabetes may not always be active and progressive yet implying that a notable improvement [in glycemia] may not be permanent.” This term also considers that people will continue to need ongoing support to delay relapse along with regular monitoring and intervention if hyperglycemia recurs. However, the term “remission” shouldn’t be interpreted as “no evidence of disease,” as it is in the oncology field, because glycemia is rarely completely normalized with interventions. The authors also recognized that the selected term also may affect health policy decisions.

Why Did the Authors Define Remission?
The ADA 2009 consensus statement on this topic was outdated.6 “We developed a simple and standardized definition of remission in type 2 diabetes because of renewed interest in successful early treatment,” says Matthew Riddle, MD, an emeritus professor in the division of endocrinology, diabetes, and clinical nutrition at Oregon Health and Sciences University and lead author on this consensus report. “The statement was not meant to evaluate current claims or to provide direct guidance for clinical decisions, but rather to encourage more standardized methods of collecting data and assessing outcomes by [people], providers, and clinical trialists to provide better insights about who is likely to benefit most from various treatments and to support future guidance,” he says.

What Is the Definition of Remission?1
• A1c 6.5% or below and remaining at that level for at least three months without using glucose-lowering medications. This doesn’t include weight loss medications that may, by virtue of weight loss, improve glycemia. (A1c is based on the NGSP reference method).7 If a person’s A1c is considered unreliable, use a 24-hour mean glucose concentration from a continuous glucose monitor or fasting plasma glucose <126 mg/dL.

• Remission may be achieved through lifestyle changes, medical or surgical interventions, or a combination of approaches.

• An interval of at least six months after initiating lifestyle interventions is needed before an A1c check can reliably evaluate the response.

• An interval of at least three months is needed after surgical intervention to enable A1c to stabilize.

The authors offer a caveat: “Any criterion for defining remission will necessarily be arbitrary, a point on a continuum of glycemic levels.” However, “a return to nearly normal glycemic regulation … is most likely early in the course of [type 2 diabetes] and can involve partial recovery of both insulin secretion and insulin action.”

What Population of People and Diagnoses Does This Definition Include?
• People with overweight and obesity. Weight gain, if not reversed, may not be transient. This is the most common cause of progression of dysglycemia. Weight loss through lifestyle interventions and/or weight management medication early on sometimes can restore normoglycemia, and medication can be discontinued.

• Pregnant women with gestational diabetes. In most women, glycemia returns to normal postpregnancy, yet gestational diabetes serves as a red flag for a future diagnosis of prediabetes and type 2 diabetes.

• People taking steroids. Steroid use, generally long term vs a short course, can lead to insulin resistance.

• Individuals with acute illness or undergoing stressful life experiences. These events can cause hyperglycemia, particularly in individuals who may have a propensity for glucose intolerance.

• People who experience surgical or enteral interventions that promote weight loss and metabolic control.

When and How Often Should People in ‘Remission’ Monitor Glycemia?
Recognizing that hyperglycemia frequently recurs, A1c should be measured “not less frequently than yearly.” People should be encouraged to maintain their weight loss and a healthful lifestyle. The consensus report authors highlight that people who achieve remission likely have had periods of hyperglycemia, and their bodies may have experienced the harmful effects that often lead to diabetes complications. For this reason, people should have regular medical checkups, including exams the ADA recommends in its Standards of Care.8

Role of Dietitians
Research illustrates time and again that initial weight loss and keeping as many pounds off as possible over time is the surest way to achieve and maintain remission and realize other related health benefits.9-12 “Numerous studies show that weight loss, between 3% and 10% from a starting weight, can result in remission especially if initiated early in the disease course,” says Hollie Raynor, PhD, RD, associate dean and a professor in the department of nutrition at the University of Tennessee. “What we don’t currently have is specific evidence that supports that one lifestyle or behavior change will be easier to implement or result in more health benefits than another,” Raynor says. How weight is lost, whether through lifestyle changes (ie, food choices, eating habits, and physical activity) or through metabolic surgery and/or an increasing array of weight loss medications, should be a client’s individual decision based on evidence-based information shared by his or her clinician. “The services of an RD are invaluable as a source of knowledge and support initially and in the all-important long-term monitoring and support,” Raynor says.

According to Jill Weisenberger, MS, RDN, CDCES, creator of Prediabetes Turnaround, a video course for people with prediabetes, “So many people come to RDs with a great sense of panic and urgency requesting help with drastic weight loss and radical diet changes. We need to help them understand that the underlying problems driving their prediabetes and type 2 diabetes did not occur simply with a diagnosis.”

Weisenberger encourages people to focus on what they do eat vs what they shouldn’t eat. Educate clients so they no longer fear and feel the need to avoid carbohydrate-containing foods, but rather aim to eat foods with a variety of health-boosting nutrients and phytonutrients that evidence shows can decrease insulin resistance and improve cardiometabolic health. Weisenberger recommends helping clients put their emphasis on sustainable weight loss and the implementation of incremental lifestyle changes. Expect these changes to be different for each person.

“Changes that improve A1c but are too restrictive to last will offer only temporary improvement in glucose levels,” says Hillary Wright, MEd, RD, director of nutrition counseling for the Domar Center for Mind/Body Health, in Waltham, Massachusetts, and author of The Prediabetes Diet Plan: How to Reverse Prediabetes and Prevent Diabetes Through Healthy Eating and Exercise, and other books focused on women’s health. “Encourage people to start the day with a balanced breakfast and then to eat often enough to manage hunger and reduce the risk of overeating in the evening,” Wright says.

Both Weisenberger and Wright highlight the significant benefits of various types of physical activity. “Physical activity is a natural insulin sensitizer, so encouraging clients to develop a realistic, as close to daily as possible, exercise plan that fits their lifestyle is critical to achieving and maintaining remission,” Wright says.

Weisenberger adds, “Strength training is an often-missed treatment component. Muscles utilize some of the glucose produced from a carbohydrate-containing meal, so it’s worth maintaining or building muscle to have a larger repository for that postprandial glucose.”

— Hope Warshaw, MMSc, RD, CDCES, BC-ADM, FADCES, is owner of Hope Warshaw Associates, LLC, a diabetes- and nutrition-focused consultancy based in Asheville, North Carolina. She’s a book author and freelance writer who specialized for many years in diabetes care and provides diabetes counseling through 9am.health. Warshaw served as the 2016 president of ADCES and currently serves as the 2022–2023 chair of the Academy of Nutrition and Dietetics Foundation.

References
1. Riddle MC, Cefalu WT, Evans PH, et al. Consensus report: definition and interpretation of remission in type 2 diabetes. Diabetes Care. 2021;44(10):2438-2444.

2. DeFronzo RA, Eldor R, Abdul-Ghani M. Pathophysiologic approach to therapy in patients with newly diagnosed type 2 diabetes. Diabetes Care. 2013;36(Suppl 2)S127-S138.

3. Schwartz SS, Epstein S, Corkey BE, Grant SF, Gavin JR, Aguilar RB. The time is right for a new classification system for diabetes: rationale and implications of the Beta-cell-centric classification schema. Diabetes Care. 2016;39(2):179-186.

4. Koyama AK, McKeever Bullard K, Pavkov ME, Park J, Mardon R, Zhang P. Progression to diabetes among older adults with hemoglobin A1C-definted prediabetes in the US. JAMA Network Open. 2022;5(4):e228158.

5. American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Supp 1):S17-S38.

6. Buse JB, Caprio S, Cefalu WT, et al. How do we define cure of diabetes? Diabetes Care. 2009;32(11):2133-2135.

7. Harmonizing hemoglobin A1c testing. NGSP website. http://www.ngsp.org/. Accessed May 12, 2022.

8. American Diabetes Association Professional Practice Committee. 4. Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S46-S59.

9. DPP Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-875.

10. Look AHEAD Research Group. Eight-year weight losses with an ILI: the Look AHEAD study. Obesity. 2014;22(1):5-13.

11. Lean MEJ, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019;7(5):344-355.

12. American Diabetes Association Professional Practice Committee. 3. Prevention and delay of type 2 diabetes and associated comorbidities: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S39-S45.

Prediabetes & Diabetes Prevalence

According to CDC estimates, the number of people in the United States aged 18 and older who have diabetes and prediabetes has skyrocketed.1

Of the total population, 37 million people (11.3%) have diabetes. Of this subpopulation, nearly 29 million people have been diagnosed, while it’s estimated that 8.5 million have diabetes but remain undiagnosed. Using the estimate that 90% to 95% of people with diabetes have type 2 diabetes, roughly 33 to 35 million adults have type 2 diabetes.

Of the total US population (nearly 260 million), 38% of the adult population (96 million) have prediabetes. Of adults aged 65 and older, 49% (26.4 million) have prediabetes.

The picture also is grim for youth aged 12 to 19. Earlier this year, authors using data from the National Health and Nutrition Examination Survey found a rise in prediabetes prevalence from 12% in 1999–2002 to 28% in 2015–2018.2 This increase was observed across many subgroups including sex, race and ethnicity, parental education level, family income, food security, and BMI subgroups.

Prediabetes shouldn’t be considered a condition in its own right but rather a risk factor for the progression to type 2 diabetes and cardiovascular disease. Prediabetes is associated with obesity (especially abdominal or visceral obesity), dyslipidemia with high triglycerides and/or low HDL cholesterol, and hypertension. The diagnosis of prediabetes (see Table “Defined by the Numbers”) also should trigger screening for cardiovascular risk factors.3

Health Care Providers Often Drop the Ball
These surprising stats beg the question: What are health care providers doing about screening, diagnosing, managing, and referring people with prediabetes and type 2 diabetes for diabetes care and education?

The answer is not much. A large retrospective study conducted among more than 21,000 patients who were eligible for prediabetes screening found that while about two-thirds of the population was screened, only 5% of people were diagnosed.4 No one who was diagnosed received appropriate treatment. In communicating the study results, a senior news writer for the American Medical Association wrote, “Even though the US Preventive Services Task Force has issued straightforward recommendations to screen for prediabetes, fewer than two-thirds of people get screened at their primary care visits, and vanishingly few get a diagnosis or treatment.”5-7 The author refers to this as “near the top of medicine’s missed opportunities.”

— HW

References
1. National Diabetes Statistics Report. Centers for Disease Control and Prevention website. https://www.cdc.gov/diabetes/data/statistics-report/index.html. Accessed May 12, 2022.

2. Liu J, Li Y, Zhang D, Yi SS, Liu J. Trends in prediabetes among youths in the US from 1999 through 2018. JAMA Pediatrics. 2022;176(6):608-611.

3. Mainous AG, Rooks BJ, Wright RU, Sumfest JM, Carek PJ. Diabetes prevention in a U.S. healthcare system: a portrait of missed opportunities. Am J Prev Med. 2022;62(1):50-56.

4. Prediabetes and type 2 diabetes: screening. U.S. Preventive Services Task Force website. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/screening-for-prediabetes-and-type-2-diabetes#fullrecommendationstart. Accessed April 27, 2022.

5. Gregg EW, Moin T. New USPSTF recommendations for screening for prediabetes and type 2 diabetes. JAMA. 2021;326(8):701-703.

6. Smith TM. Of medicine’s missed opportunities, diabetes prevention nears the top. American Medical Association website. https://www.ama-assn.org/delivering-care/diabetes/medicine-s-missed-opportunities-diabetes-prevention-nears-top. Accessed April 27, 2022.

7. American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S17-S38.

Screening Criteria for Asymptomatic Adults1

The following criteria for screening reflect the US Preventive Services Task Force’s updated recommendations in 2021.2,3

It’s important to note that the diagnosis of prediabetes and type 2 diabetes in children and adolescents is dramatically increasing.4 Review risk-based screening for type 2 diabetes or prediabetes in this population as recommended by the American Diabetes Association.1

1. According to the American Diabetes Association, screening for prediabetes and diabetes should be considered for adults with overweight or obesity (body mass index ≥25 kg/m2 or ≥23 kg/m2 in Asian Americans) and who have one or more of the following risk factors:

• first-degree relative with diabetes;

• high-risk race/ethnicity (eg, African American, Latino, Native American, Asian American, Pacific Islander);

• history of cardiovascular disease;

• hypertension (≥140/90 mm Hg or on medication for hypertension);

• women with polycystic ovary syndrome;

• physical inactivity; and

• other clinical conditions associated with insulin resistance (eg, severe obesity, acanthosis nigricans).

2. Patients with prediabetes (A1c ≥5.7% [39 mmol/mol], impaired glucose tolerance, or impaired fasting glucose) should be tested yearly.

3. Women who were diagnosed with gestational diabetes should have lifelong testing at least every three years.

4. For all other patients, testing should begin at age 35.

5. If results are normal, testing should be repeated at a minimum of three-year intervals, with consideration of more frequent testing depending on initial results and risk status.

6. People with HIV.

— HW

References
1. American Diabetes Association Professional Practice Committee. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S17-S38.

2. Lean MEJ, Leslie WS, Barnes AC, et al. Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial. Lancet Diabetes Endocrinol. 2019;7(5):344-355.

3. American Diabetes Association Professional Practice Committee. 3. Prevention and delay of type 2 diabetes and associated comorbidities: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S39-S45.

4. DPP Research Group. Long-term effects of lifestyle intervention or metformin on diabetes development and microvascular complications over 15-year follow-up: the Diabetes Prevention Program Outcomes Study. Lancet Diabetes Endocrinol. 2015;3(11):866-875.

Case Study & Commentary

Does V.S.’s current data and status meet the definition of remission? Review the case, then read the commentary.

V.S. is a 51-year-old Brazilian woman who immigrated to the United States in 2005 and became a US citizen in 2019. She runs an independent house cleaning business and is active in her work. In 2005, she weighed 145 lbs; she’s 5' 5" tall. She says she’s always struggled with her weight and was on a medication prescribed by a “nutrition doctor” when living in Brazil and in the United States to maintain her weight. She didn’t know the name of the medication but says she stopped taking it in 2012 and started to slowly gain weight once again.

In 2007, V.S. became pregnant with her daughter and soon developed gestational diabetes. She went on insulin the last month of her pregnancy. After her daughter was born, her diabetes “disappeared and her blood glucose went back to normal,” she says. She received no follow up on her glucose levels or weight management counseling.

In February 2021, V.S. visited her doctor. Her weight was nearly 220 lbs. She received lab work and a follow up call and was told she had prediabetes with an A1c of 6.8%. (This A1c is diagnostic for type 2 diabetes. See the following commentary and the table “Defined by the Numbers.”) She wasn’t prescribed a glucose-lowering medication and was told she needed to go on a low-calorie diet. She went to see a nutritionist and was encouraged to make changes to her eating and drinking habits. “I stopped drinking beer (about three cans per day after work), regular soda, and juice.” V.S. says she also stopped eating sugary foods, including cake, candies, and chocolates. In approximately one year, V.S. lost 50 lbs.

When V.S. visited her doctor in early 2022, she weighed about 167 lbs. She says she was disappointed when her doctor said nothing about her weight loss. Her doctor checked her A1c and said, “Your blood test result was very good with an A1c of 6.2%.” She says her doctor told her she’s no longer at risk of type 2 diabetes and wasn’t offered information about continued follow up. V.S. checks her blood glucose a few times a week. She says her fasting levels are in the high 90s; otherwise, they’re usually in the 80s.

Commentary
This case, unfortunately, illustrates what often happens today in clinical practice.1-3 What follows is accurate information on the diagnosis, treatment, and follow-up that V.S. should have received.

• Proper diagnosis: V.S. should have been diagnosed with type 2 diabetes with an A1c of 6.8%; her post–weight loss A1c of 6.2% demonstrates good glycemic management (defined as an A1c of 7% or lower) that was impacted by nearly 50 lbs of weight loss and/or healthful food choices, physical activity, and improved insulin sensitivity.

• Proper treatment: Initially, with an A1c of 6.8%, V.S.’s doctor not only should have diagnosed her with type 2 diabetes but also should have provided education about the glucose levels and A1c measurements diagnostic for prediabetes and type 2 diabetes. In addition, her doctor should have given her blood glucose management goals for type 2 diabetes. He also should have, if she was able and willing, referred her for medical nutrition therapy and diabetes self-management education and support.

When V.S. returned to her doctor after losing almost 50 lbs, he should have praised her for her successful weight loss and encouraged her to keep as many of those pounds off as possible to help prevent type 2 diabetes disease progression. Her doctor also should have offered or encouraged her to seek weight management support to do so. Moreover, her doctor should not have told her that she’s no longer at risk of type 2 diabetes. Based on the American Diabetes Association’s standards of care, her doctor should have prescribed a glucose-lowering medication (eg, metformin) to address her insulin resistance and continued elevated glucose levels.4,5

• Proper follow-up: With V.S.’s history of gestational diabetes and a type 2 diabetes diagnosis, her doctor should have counseled her and recommended she seek regular comprehensive diabetes care and follow-up that includes evaluation for chronic complications.6

— HW

References
1. American Diabetes Association Professional Practice Committee. 3. Prevention and delay of type 2 diabetes and associated comorbidities: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Supp 1):S39-S45.

2. Mainous AG, Rooks BJ, Wright RU, et al. Diabetes prevention in a U.S. healthcare system: a portrait of missed opportunities. Am J Prev Med. 2022;62(1):50-56.

3. Harmonizing hemoglobin A1c testing. NGSP website. http://www.ngsp.org/. Accessed May 12, 2022.

4. American Diabetes Association Professional Practice Committee. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S125-S143.

5. Aroda VR, Ratner RE. Metformin and type 2 diabetes prevention. Diabetes Spectrum. 2018;31:(4):336-342.

6. American Diabetes Association Professional Practice Committee. 4. Comprehensive medical evaluation and assessment of comorbidities: standards of medical care in diabetes-2022. Diabetes Care. 2022;45(Suppl 1):S46-S59.

Additional Consensus & Position Statements

Shortly before press time, the American College of Lifestyle Medicine published two additional statements.1,2 The consensus statement is endorsed by the American Association of Clinical Endocrinologists, supported by the Academy of Nutrition and Dietetics, and cosponsored by the Endocrine Society.1 Its objective is to guide clinicians in “using diet” to achieve remission of type 2 diabetes in adults with the concluding statement: “Diet as a primary intervention to [type 2 diabetes] is most effective in achieving remission when emphasizing whole, plant-based foods with minimal consumption of meat and other animal products.” This statement’s definition of remission is similar to the international consensus report detailed in this article.3

— HW

References
1. Rosenfeld RM, Kelly JH, Agarwal M, et al. Dietary interventions to treat type 2 diabetes in adults with a goal of remission: an expert consensus statement from the American College of Lifestyle Medicine. Am J Lifestyle Med. 2022;16(3):342-362.

2. Kelly J, Karlsen M, Steinke G. Type 2 diabetes remission and lifestyle medicine: a position statement from the American College of Lifestyle Medicine. Am J Lifestyle Med. 2022;14(4):406-419.

3. Riddle MC, Cefalu WT, Evans PH, et al. Consensus report: definition and interpretation of remission in type 2 diabetes. Diabetes Care. 2021;44(10):2438-2444.