Fitness, Fatness, and Risk for Diabetes

What role do body weight and fitness level play in the risk for prediabetes among adults? Two recent studies address these questions.

Body Weight and Prediabetes

Mainous and colleagues^[1] analyzed the National Health and Nutrition Examination Survey (NHANES) III (1988-1994) and NHANES for 1999 to 2012. The analyses focused on adults aged 20 years and older without diabetes who had a normal weight (body mass index [BMI] 18.5-24.9 kg/m²).

Using data from NHANES III (1988-1994) and each 2-year NHANES cycle from 1999 to 2012, the authors calculated the prevalence of prediabetes, defined as an A1c level of 5.7% to 6.4%. They also calculated prevalence of two measures of abdominal obesity: waist circumference > 102 cm in men and > 88 cm in women, and waist-to-height ratio > 0.53 in men and 0.49 in women.

The prevalence of prediabetes among healthy-weight nondiabetic adults aged 20 years or older increased from 10.2% in 1988-1994 to 18.5% in 2012. Among individuals aged 45 years or older, the prevalence of prediabetes increased from 22.0% to 33.1%. The percentage of adults aged 20 years or older with an unhealthy waist circumference increased from 5.6% in 1988-1994 to 7.6% in 2012, and the percentage with an unhealthy waist-to-height ratio increased from 27.2% in 1988-1994 to 33.7% in 2012. Of interest, measures of abdominal obesity were not independent predictors of prediabetes in adjusted models.

Fitness and Prediabetes

The Coronary Artery Risk Development in Young Adults (CARDIA) study is a prospective, multicenter cohort study designed to investigate trends and determinants of coronary heart disease risk factors in young adults.^[2] The study began in 1985-1986, recruiting black and white women and men aged 18-30 years at baseline.

CARDIA objectively documented cardiorespiratory fitness using treadmill exercise testing to measure cardiorespiratory fitness at baseline (year 0: age 18-30 years), in early adulthood (year 7: age 25-37 years), and again at middle age (year 20: age 38-50 years), with documentation of incident prediabetes/diabetes over 25 years. Participants were classified as having prediabetes or diabetes on the basis of laboratory findings:

Prediabetes: fasting glucose level 100-125 mg/dL, 2-hour oral glucose tolerance test value 140-199 mg/dL, or A1c value 5.7%-6.4%; and
Diabetes: fasting glucose level ≥ 126 mg/dL, use of medications for diabetes treatment, 2-hour glucose tolerance test value ≥ 200 mg/dL, or A1c value ≥ 6.5%.

The outcome was incidence of prediabetes or diabetes as documented at year 7, 10, 15, 20, or 25, with adjustment for age, race, sex, field center, time-dependent cardiorespiratory fitness level, time-dependent BMI, and year 0 lifestyle factors (smoking, energy intake, alcohol intake, education, systolic blood pressure, medication for hypertension, and low-density lipoprotein and high-density lipoprotein cholesterol levels).

By year 25, 1941 participants(44.5%) had developed prediabetes and 505 participants (11.5%) had developed diabetes. Those who developed either prediabetes or diabetes were more likely to be black and male, and were more likely to take blood pressure medication; smoke; and have higher body weight, BMI, waist circumference, systolic blood pressure, low-density lipoprotein cholesterol level, daily alcohol intake, and daily energy intake. Nevertheless, even after adjustment for these differences, better fitness was independently associated with lower risk of developing incident prediabetes or diabetes.

Disturbing Trends

Obesity and diabetes go hand in hand, and both have reached epidemic proportions in the United States. However, recent reports suggest that long-term trends in obesity and diabetes rates are flattening.^[3,4,5] Although this is encouraging, flattening of trends at relatively high levels provides little relief to the beleaguered clinician or the healthcare system. The two studies examined above further dampen hopes that we may be on the downside of these epidemics, especially when they are considered together.

Prediabetes prevalence is currently estimated at 38%,^[6] but Mainous and colleagues found that it may be as high as 33% just among patients older than 45 years and who appear to be of normal weight. Furthermore, Chow and colleagues^[2] reported that 44.5% of study participants aged 18-30 years developed prediabetes within 25 years, and another 11.5% developed diabetes. These data suggest that even if obesity trends are indeed flattening, the prevalence and incidence of prediabetes continue to climb. We also learn from Mainous and colleagues that the burgeoning rates of prediabetes cannot be solely attributed to obesity or even to overweight, because their study was limited to people in the normal BMI range.

Chow and colleagues^[2] demonstrate that the association between fitness and prediabetes/diabetes risk is independent of weight and other risk factors. Although overweight and obesity unquestionably raise the risk for diabetes and cardiovascular disease, it has become increasingly clear that not all individuals with obesity are at similar cardiometabolic risk.^[7] Indeed, there has been growing interest in a phenotype known as "metabolically healthy obesity" (MHO), in which some individuals with obesity do not have the cardiometabolic risk factors normally associated with obesity and are at lower risk for diabetes, cardiovascular disease, heart failure, and mortality.^{[8,9,10,11,12,13,14,15,16]}

Consistent with the findings of Mainous and colleagues,^[1] there is also a less well-studied phenotype of metabolically unhealthy normal-weight (MUNW) individuals who appear to be at greater risk for type 2 diabetes, cardiovascular disease, heart failure, and mortality, compared with healthy normal-weight individuals.^{[14,15,16,17,18]}

MHO and MUNW may be dangerous concepts. MHO implies that there are some people with obesity who are healthy, and MUNW implies that most people with normal weight are also healthy. In both cases, adopting these terms may lead to insufficient screening for other key markers of health. Neither MHO nor MUNW account for other conditions, such as insulin resistance, inflammation, reduced kidney function, or lifestyle issues (eg, smoking and diet). Fitness is also excluded from characterizations of MHO or MUNW.

The main message is that there is much more to cardiometabolic risk than body weight. One vitally important component to health regardless of body weight is fitness level, which of course is a by-product of exercise or at least nonsedentary time. Patients as well as clinicians must strive to engage in more physical activity.

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