Major findings
The analysis of a large clinical database of primary care in Italy confirmed that excess body weight is extremely common, affecting half of the adult population. Our findings are il line with recent WHO estimates, according to which one in two citizens in Europe is overweight or obese [
2]. We also confirmed the elevated clinical burden associated with excess weight: both overweight and obesity were associated with an increasing prevalence of a large array of different chronic conditions, including cardiovascular diseases, chronic kidney disease, osteoarticular diseases, depression, sleep apnoea, and neoplasms of the gastrointestinal tract.
Glucose metabolism alterations are particularly linked to overweight and obesity: diabetes was registered in one in seven people with normal weight, one in four overweight individuals, one in three individuals with obesity class 1 and 2, and four in ten severely obese individuals. The presence of diabetes strongly influenced the likelihood of suffering from other chronic conditions. In addition, a pre-diabetes status, as indicated by the presence of impaired fasting glucose, was also associated with an elevated risk of major comorbidities, suggesting a continuum in the risk related to glucose abnormalities. Overall, our data show that the prevalence of the typical comorbidities associated with overweight and obesity is not uniform within each BMI class, and that glucose metabolism alterations help in identifying subgroups with a substantial increase in the risk of other chronic conditions. Of note, people with very severe obesity showed lower levels of total and LDL cholesterol and lower rates of some concomitant diseases, particularly coronary heart disease and cerebrovascular disease, as compared to individuals with obesity class 1 and 2. While these findings can suggest a greater attention to control major cardiovascular risk factors in the presence of more elevated BMI, the existence of a survivor bias cannot be excluded. In fact, mortality rates among very severely obese individuals tend to be higher [
22], thus determining a selection of the less severe cases.
In our study, the prevalence of chronic heart failure (CHF) clearly increased with increasing BMI. Furthermore, within each BMI class, a strong trend of increasing prevalence was observed in relation to the presence of IFG and diabetes. CHF is an important condition to monitor as it affects over 64 million people in the world, and prevalent cases and years lived with disability have increased by 91.9% and 106.0% from 1990, respectively [
23]. Previous studies have demonstrated that even metabolically healthy obese individuals (i.e. without hypertension, dyslipidemia, and dysglycemia) are at higher risk of heart failure [
24]; furthermore, heart failure prevalence in normal weight, overweight, and obese individuals increased with increasing number of metabolic abnormalities [
24]. In a pooled population-based cohort study involving 24,675 participants without a history of heart failure, 21% of incident cases of heart failure were attributable to obesity among individuals under 55 years of age and 13% among the elderly ones [
25]. The association between obesity and heart failure was confirmed in a metanalysis of 29 studies, showing a ‘J curve’ relationship between BMI and risk of heart failure, with maximum risk in the morbidly obese (OR = 1.73 (95% CI 1.30–2.31) [
26]. The metanalysis also documented an improvement in cardiac indices after intentional weight loss.
Heart failure and chronic kidney disease deserve a particular consideration. In our study, the prevalence of chronic kidney disease and heart failure clearly increased with increasing BMI. These conditions are closely interconnected, leading to the connotation of “cardiorenal syndrome” [
27], and are related to hyperglycemia. The global burden of chronic kidney disease is considerable and growing: it is estimated that around 10% of adults worldwide are affected, resulting in 1.2 million deaths and 28 million years of life lost each year [
28]. The combined effect of body mass index and metabolic status on the risk of prevalent and incident chronic kidney disease was documented in a metanalysis involving over 180,000 participants [
29]. The study showed that, compared with metabolically healthy normal weight individuals, metabolically healthy obese individuals showed a 23.5% increased risk for CKD (RR = 1.235; 95%CI: 1.027–1.484). Metabolically abnormal groups had much higher risk for CKD, with RR of 1.572 (95%CI: 1.373–1.801), 1.652(95%CI: 1.139–2.397) and 1.898(95%CI: 1.505–2.395) for unhealthy normal weight, overweight and obese individuals, respectively. A more recent metanalysis of nine prospective cohort studies with 128,773 participants confirmed that metabolically healthy overweight individuals were at increased risk for CKD (RR = 1.34; 95% CI: 1.20–1.51). In metabolically healthy obese participants, the risk of CKD further increased (RR = 1.55; 95% CI: 1.34 to 1.79), while metabolically unhealthy obese individuals showed the highest risk (RR = 2.13; 95% CI: 1.66–2.72) [
30].
Also, the prevalence of those conditions typically associated with excess body weight, such as osteoarticular diseases and sleep apnea, linearly increase with increasing body weight.
Implications for clinical practice
Our study provides an up-to-date estimate of the clinical burden of excess weight in Italy, and strongly suggests the need to intervene to limit the growth of the obesity pandemic. The study clearly shows that even moderate increases in body weight, in the range of overweight, are associated with an increased prevalence of many chronic conditions, thus suggesting the need to intervene in a timely and effective manner to counteract weight gain. The study also shows that the concomitance of excess weight and glucose metabolism alterations, even before the stage of overt diabetes, further increases the risk of comorbidities. A proactive approach is thus needed to identify glucose metabolism alterations and to address them with specific lifestyle and pharmacological interventions. These findings are particularly important for primary care, which represents the forefront of the fight against obesity, diabetes, and related comorbidities.
Strengths and limitations
Our study has strengths and limitations. Among the strengths, it should be mentioned the very large study sample, representative of the Italian adult population, providing a realistic picture of the burden associated with different levels of excess weight. The good data quality represents another important aspect, allowing a reliable estimate of the prevalence of chronic conditions associated with overweight and obesity.
The study also has limitations related to the intrinsic nature of the data, reflecting the real-world practice of GPs. In particular, missing data could, at least in theory, affect the precision of the estimates. We have tried to minimize this problem by applying validated missing imputation techniques. In this respect, the consistency of our findings with data from other epidemiological sources provides reassurance regarding the reliability of our findings. Furthermore, it is acknowledged that waist circumference represents a more accurate measure of visceral adiposity and obesity-related health risk compared to BMI [
31]. However, waist circumference was seldom reported in clinical records, precluding the possibility to use this measure in our study.