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Body mass index and the risk of mortality in type II diabetic patients from Verona


OBJECTIVE: The relation between body weight and mortality in type II diabetic patients has not been fully elucidated. The aim of the present study was to evaluate the impact of body weight on mortality in a well-characterized type II diabetic cohort.

RESEARCH DESIGN AND METHODS: We examined a cohort of 3398 type II diabetic patients, alive on December 1986 and followed up for 10 years, to assess mortality and its causes and to investigate the relationship between body mass index (BMI) and mortality from all and specific causes. For this purpose, survival in the different quartiles of BMI was evaluated by a Cox model, controlling for sex, age, treatment, smoking, duration of diabetes, hypertension, and fasting plasma glucose. The Cox model was applied either excluding (model 1) or including (model 2) the last three variables.

RESULTS: During the 10 ys of follow-up, 1212 deaths (639 women, 573 men) occurred in the cohort under study. Since the interaction between BMI and age was statistically significant (P = 0.002), survival was studied separately in people aged <65 and ≥65 y (median age of the cohort = 65.9 y). Under 65 y, a significantly higher all-cause mortality was observed in obese patients, that is, in the IV quartile (BMI≥30.9 kg/m2; RR = 1.74; CI 95% = 1.26–2.40), in model 1. The inclusion of hypertension, duration of diabetes, and fasting plasma glucose in the model (model 2) slightly decreased the relative risk (RR = 1.52; CI 95% = 1.10–2.11). After 65 y, higher body weight was associated with a better outcome, especially in patients belonging to the IV quartile of BMI (RR = 0.74; CI 95% = 0.62–0.90).

CONCLUSIONS: In older type II diabetic patients, a moderate excess weight predicts a better survival, while obesity is a negative prognostic factor in patients younger than 65 y. In the latter patients, the effect of obesity on mortality seems to be partly mediated by hypertension, duration of diabetes, and fasting plasma glucose.


Obesity is a common feature of type II diabetic patients; in fact, approximately two-thirds of people with type II diabetes are overweight.1 However, the relation between body weight and mortality has not been definitely established yet. Type II diabetic patients receive, as part of their treatment, the recommendation to lose weight.2 A weight loss improves insulin sensitivity and metabolic control as testified by lower glucose and HbA1c levels.3,4 While the evidence for an improvement in diabetes control after weight loss is very strong, the influence of weight and weight loss on mortality among diabetic patients remains controversial.5,6

Much of the vast literature examining the relation between body weight and mortality in nondiabetic populations supports the hypothesis of a curvilinear relation, in which the risk is increased among the very heavy and the very lean subjects.7,8,9 However, the relation observed in the general population cannot be merely extrapolated to type II diabetic patients for several reasons. First, adiposity is frequently associated with diabetes and generally precedes it.10,11 Second, as type II diabetes is a progressive disease, changes of body weight can be the results of progression and worsening of the disease. Third, drugs utilized in the treatment of diabetes can have a significant impact on body weight.12

Studies on diabetic patients are sparse and often conflicting, maybe for the heterogeneity of the diabetic population.13,14 Some investigations reported that obese patients had a better survival than nonobese patients.15 On the contrary, the WHO Multinational Study found a direct relation between body mass index (BMI) and mortality in European diabetic patients with a mean age of 47–48 y.16 Moreover, another retrospective study, carried out on 263 deceased diabetic patients, reported that weight loss was associated with a prolonged survival.5 These discrepancies could be explained, at least partly, by differences in age among the various cohorts: the excess mortality observed in overweight subjects could be confined to younger diabetic patients, similarly to the general population.17

Important unresolved questions concern the shape of the curve relating BMI and mortality, what is the optimal weight for longevity, and whether this optimal weight varies according to age or sex. The aim of the present study was to address these questions in a well-characterized type II diabetic cohort.

Subjects and methods

This investigation was performed within the framework of the Verona Diabetes Study, a population-based survey whose design, setting, and population have been described in previous publications.18 Briefly, records from diabetes clinics, family physicians, and a drug consumption database were used to identify 7148 type II diabetic patients, alive and resident in the Verona area on 31 December 1986. The present study was carried out on a cohort of 3398 patients attending the diabetes clinic, because only for this subgroup was information on BMI, smoking, glycemia, and hypertension available in the medical records. This cohort, representing 84% of all patients identified by the diabetes clinic (n = 4047), was followed up in the subsequent 10 y (1 January 1987 to 31 December 1996) to assess mortality and cause of death.19,20

In the present study, the underlying cause reported on the death certificate was considered as the cause of death; when more than one underlying cause was mentioned, the first one was chosen. Causes of death were coded according to the International Classification of Diseases, 9th edn, and grouped into all causes (codes 0–999), cardiovascular diseases (codes 390–459) and malignant neoplasms (codes 140–208).

Statistical analysis

Significance of differences among quartiles of BMI was tested by one-way ANOVA for continuous variables and by χ2 test for categorical variables.

Multivariate survival analysis was accomplished by the Cox proportional-hazard model.21 In the Cox model the effect of BMI on all-cause and cause-specific mortality was evaluated controlling for sex, age, diabetes duration (y), treatment categories, [diet, oral hypoglycemic agents (OHA), insulin], cigarette smoking (yes/no), hypertension (yes/no), and fasting plasma glucose (mmol/l). BMI was categorized in quartiles and age was coded as a dichotomous variable (<65 and ≥65 y), using a cut-off close to the median (65.9 y). Hypertension, duration of diabetes, and fasting plasma glucose were either excluded (model 1) or included (model 2) in the multivariate analysis.

The assumption that each predictor affects mortality proportionally over the entire follow-up period was examined using graphical methods and was found to be reasonable for all the predictors considered here. The significance of the explanatory variables included in the Cox models was computed by the likelihood-ratio test.

First-order interactions between BMI and each stratifying variable were also tested. As a significant interaction between age and BMI emerged in the survival analysis (P = 0.002), statistical analysis was performed separately for patients younger and older than 65 y, after stratifying BMI (kg/m2) in quartiles: patients younger than 65 y, ≤25.4, 25.5–27.9, 28.0–30.8, ≥30.9 kg/m2; patients older than 65 y, ≤24.6, 24.7–26.9, 27.0–29.8, ≥29.9 kg/m2. Age (y) was considered also in the analyses performed separately in younger and older patients.


The main demographic and clinical characteristics of the cohort under study after stratification by age are summarized in Table 1. Younger patients had a higher proportion of men and smokers, while older patients had a higher percentage of patients with hypertension and treated with OHA; younger patients also presented slightly higher values of BMI and fasting plasma glucose.

Table 1 Demographic and clinical characteristics in type II diabetic patients older and younger than 65 y (n=3398)

During the 10 y of follow-up, 1212 deaths (639 women, 573 men) were ascertained in the population under study. As already shown,22 the main causes of deaths were cardio-vascular diseases and malignancies, which accounted for 40 and 25% of all deaths, respectively (Table 2). Mortality from malignancies was as important as cardiovascular mortality in younger patients, while in older patients deaths from cardiovascular events were twice as common as deaths from cancer.

Table 2 Number of subjects and number of events (with percentage in brackets) in each quartile in type II diabetic patients younger (n=1590) and older than 65 y (n=1808)

As already mentioned, the interaction between BMI and age was significant (P = 0.002). There were no significant interactions between BMI and the other variables considered (sex, P = 0.094; hypertension, P = 0.552; smoking, P = 0.927; and treatment, P = 0.148).

The results of the multivariate analyses are reported in Table 3. Under 65 y of age, mortality from all causes was significantly increased in the IV quartile of BMI as compared to the I quartile (model 1). When fasting glycemia, duration of diabetes, and hypertension were added (model 2), the relative risk of the IV quartile of BMI as compared to the I quartile decreased, although retaining statistical significance. After 65 y, an opposite trend was observed, higher body weight being associated with a better outcome. In older patients the inclusion or exclusion of fasting glycemia, duration of diabetes, and hypertension in the model did not affect the results substantially. Cardiovascular mortality and mortality from malignancies were not significantly related to BMI, because of an inadequate number of deaths. Anyway, they presented approximately the same pattern across BMI quartiles as compared to mortality from all causes. The only exception was cardiovascular mortality in younger patients, which was rather similar in the IV and I quartiles.

Table 3 Relative risks of death from all causes, cardiovascular diseases and malignancies as a function of BMI in type II diabetic patients younger and older than 65 y

The results did not change when early mortality, that is, in the first four years of follow-up, was excluded from the analysis. The insulin-treated patients showed a significantly (P<0.001) lower BMI (26.1±4.4 kg/m2) than diet-treated patients (27.6±4.1 kg/m2) and OHA-treated patients (28.0±4.3 kg/m2). Insulin treatment has been assumed as a marker of the severity of the disease. Therefore, in order to clarify the possible role of insulin, we repeated the analysis after excluding the patients on insulin therapy. The results were similar to those observed in the whole cohort, in both the younger and older groups of subjects.


The main results of the present study were: (1) The pattern of the association between obesity and mortality is different in younger and older type II patients: under the age of 65 y, obesity (patients in the IV quartile, ie with BMI ≥30.9 kg/m2) was a significant negative prognostic factor, whereas in older age overweight and obesity were associated with a decreased risk of dying. (2) Hyperglycemia, duration of diabetes, and hypertension played a role as obesity-related mechanisms of damage only in younger patients.

In the general population, the relationship between body weight and mortality has been extensively investigated.7,8,9,23,24,25,26 A U-shaped relation has been reported by most authors with the highest mortality among lean and obese individuals. Some,25,26 but not all,7,24 authors have found that when smoking is controlled for and early mortality excluded, the U-shaped pattern turns into a monotonically increasing trend. Moreover, age has been shown to modulate the relation between BMI and mortality: the increase in mortality associated with overweight is remarkable in young individuals but this effect declines with age,17 and in older subjects, aged over 85 y, a low BMI is associated with a larger risk of death than a high BMI.27

The present study suggests that these findings apply to type II diabetic subjects, as in a cohort of nearly 3500 type II diabetic subjects followed up for 10 y, mortality tended to increase with BMI in patients aged less than 65 y and to decrease in older patients. In younger patients, hyperglycemia, duration of diabetes, and hypertension, which can be considered not mere confounders but possible intermediate mechanisms of the obesity-related damage, seemed to play a role in mediating mortality linked to obesity. It has been reported that obesity can increase the probability of having diabetes diagnosed earlier in life.28 Thus, in some way obesity is a ‘cause’ of diabetes duration. Moreover, it has to be remembered that obesity usually clusters with several cardiovascular risk factors such as dyslipidemia, procoagulant state, inflammatory cytokines, etc, which may contribute to increasing the risk of mortality.29

In elderly subjects, the reduced risk of mortality associated with excess weight, was not affected by hyperglycemia, duration of diabetes, or hypertension. The decreasing risk of dying observed in older age could be merely the result of a previous selection, or the effect of other factors, such as the use of estrogen in postmenopausal women. However, the protective effect of exogenous estrogen, recorded in observational studies,30 was not confirmed by a randomized clinical trial.31 On the other hand, the higher risk of dying associated with low BMI may be a result of either a concomitant nondiagnosed illness, that is, occult cancer, or to a more severe diabetes, that is, patients treated by insulin. This does not seems to be the case because the results of mortality did not substantially change when either the early mortality (first 4 y)32,33 or insulin-treated patients were excluded from the analysis.

Thus, the present results might suggest that the treatment of obesity should be more aggressive in younger patients in order to reduce mortality, but, of course, the present research is an observational study that by its nature cannot allow inferences on the efficacy of treatment; only a randomized clinical trial can address this issue.34

A limitation of the present analysis is that BMI does not take into account the role of central obesity, an important predictor of both insulin resistance and mortality.35,36 It may be that in diabetic populations the waist-to-hip ratio is a stronger predictor of mortality than BMI. Furthermore, we could not distinguish between intentional and unintentional weight loss, which have been shown to affect mortality in opposite ways.37

In conclusion, we documented that in type II diabetic patients overweight is associated with mortality under the age of 65 y, whereas a moderate excess weight predicts a better survival in patients older than 65 y. These observations can have important clinical implications because they indicate that in younger type II diabetic patients obesity might have a worse prognostic significance than in older patients. Further investigations are needed to elucidate the effect of body weight loss on survival in different age groups.


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This work was supported by grants from the Italian National Research Council, the Italian Ministry of University and Scientific and Technological Research, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Regione Veneto. The kind support of the following pharmaceutical companies is acknowledged: Astra-Zeneca, Aventis, Bayer, Fournier Pierrel Pharma, GSK, Laboratori Guidotti, Roche, Servier Italia, A. Menarini, Merck Sharp & Dohme, Pfizer Italiana, Novo Nordisk Farmaceutici, Neopharmed and Lifescan.

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Zoppini, G., Verlato, G., Leuzinger, C. et al. Body mass index and the risk of mortality in type II diabetic patients from Verona. Int J Obes 27, 281–285 (2003).

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  • BMI
  • type II diabetes
  • age
  • mortality

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