Discussion
In this cohort, an overall relationship was found in women between chronic low back pain at baseline and risk of diabetes after 11 years. The relationship was considerably stronger in women younger than 40 years. In men, no association was observed. No excess comorbidity between diabetes and chronic low back pain was found in the cohort study. The cross-sectional study did not reveal any association.
Our analysis is based on a large population-based data set, with the overwhelming majority of the participants belonging to a homogeneous ethnic group. Less than 3% of the population had a non-Caucasian background.18 The area is representative of Norway, but includes no major cities. The general income is slightly below the average in Norway.18 In the period considered here, the health system in Norway was substantially uniform, based on public services. Available information about potential confounders as BMI, physical activity and smoking made it possible to carry out essential adjustments. Former work using data from the HUNT population has shown that BMI is strongly associated with both diabetes26 and low back pain.9 BMI was categorized into four major groups representing normal weight or underweight, overweight, obesity and severe obesity. This might leave residual confounding by BMI, but separate analyses with BMI as a continuous variable indicated that this problem was very minor. Unfortunately, relatively large parts of the population did not participate in the surveys.
Taking into account the results of the validity study,19 the information supplied by the participants about diabetes most likely reflects nearly the true situation considering the previous diagnoses. It is well known, however, that a substantial proportion of those with diabetes have not received a formal diagnosis,27 although this must apply both to participants with and without low back pain. Those suffering from chronic low back pain may still have sought medical attention more frequently than the general population. If this involved drawing blood samples, diabetes may have been detected more easily, generating a false association between low back pain and risk of diabetes. Another possible source of error is reverse causation if undetected diabetes or prediabetes affects the likelihood of experiencing low back pain. Short-term effects of this kind may to some extent be checked by excluding the first part of the follow-up period from the analysis. In this study, exclusion of cases of diabetes reported to occur in the first 2 or 4 years of follow-up did not weaken the association observed among women. The total follow-up period was in any case considerably longer than in comparable studies.4 16
The diagnosis of low back pain was self-reported, but only serious cases lasting for at least 3 months were supposed to be included. Pain intensity was not recorded and pain status in the 11-year period between the HUNT2 and HUNT3 surveys is unknown.
In a Danish study of patients with type 2 diabetes matched against the general population,14 the prevalence of low back pain was significantly higher among the patients with diabetes. A cross-sectional study using National Health and Nutrition Examination Survey data from the US adult population found higher prevalence of chronic low back pain among participants with diabetes.15 In a study of Spanish twins,4 chronic back pain was found to be associated with the prevalence of type 2 diabetes in the cross-sectional analyses, with more consistent associations among women. These results are not in agreement with our cross-sectional results. In the analyses of a 2–4 year follow-up of the Spanish twins,4 low back pain was not found to increase the risk of diabetes significantly, but in women the risk estimate was elevated, suggesting a stronger association than in our study. To our knowledge, this is the only other longitudinal study reporting on associations between back pain and diabetes risk.
Studies based on other designs found mixed results regarding a potential association between diabetes and back pain. In a Swedish study based on a 4-year follow-up of a large population sample, an increased risk of frequent pain in the back, neck and/or shoulder was observed among men with diabetes without hyperlipidemia, but not among women.16 Among orthopedic patients with lumbar spinal stenosis, a higher prevalence of diabetes mellitus was found, compared with patients in the same clinic with a diagnosis of degenerative disc disease or with osteoporotic vertebral fractures.7 In a population study of twins in the UK, an association between type 2 diabetes and lumbar intervertebral disc degeneration disappeared after adjustment for BMI.5 In a patient material, markers of diabetes progression were associated with the presence of back pain.28 A Finnish cross-sectional study showed an association between chronic widespread pain including back pain and both diabetes and prediabetes.29
An earlier review of comorbidity between low back pain and other disorders included two cross-sectional studies reporting on diabetes.30 In one study, no comorbidity was found after adjustment, and in the other one, a negative association was observed. No comorbidity was found between low back pain and diabetes after adjustment in a German national survey.31
In animal models, changes in the vertebral endplates and discs were found in type 2 diabetic rats.32 In a mouse model, spinal degenerative changes in the vertebral structure were induced in a prediabetic state.33
A positive association between low back pain and risk of diabetes, as found in our study in women, could be ascribed to common underlying risk factors. However, taking into account the adjustment carried out here for BMI, physical activity and smoking, this seems unlikely. Otherwise, it is conceivable that low back pain directly affects factors that are important for later development of diabetes. Thus, low back pain may lead to less physical activity and consequently greater BMI, and in this way also an increased risk of diabetes. It is also possible that occurrence of low back pain is an early indication of underlying physiological changes that may subsequently predispose to diabetes.
Inflammation may thus be part of the pathogenesis of both diabetes34 and low back pain.35 Inflammatory pathways are involved in the pathogenesis of insulin resistance, which is associated with a state of low-grade chronic inflammation in type 2 diabetes.36 Inflammatory mediators are also involved in insulin signaling pathways.37 Obesity is characterized by a proinflammatory condition with hypertrophied adipose tissue contributing to the level of proinflammatory cytokines.38 Pain generated by inflammatory changes mediated by substances released from fat cells may also provide a possible link to increased back pain. Thus, obesity may lead to low back pain through systemic chronic inflammation.9 39 An inflammatory process has in particular been associated with Modic type 1 vertebral endplate changes seen on MRI in some low back pain patients.40
Dyslipidaemia with reduced HDL and elevated triglyceride levels are associated with insulin resistance and type 2 diabetes.41 In previous analyses among the HUNT population, the prevalence of low back pain was found to be inversely associated with HDL cholesterol and positively associated with triglycerides, with stronger associations in women than in men.42 43 This is consistent with the suggestion that low back pain may be related to lumbar artery disease, with atherosclerosis in the feeding arteries producing reduced blood supply and disc degeneration.44
Levels of sex hormones may affect the development of diabetes24 and thus be responsible for the contrast in associations with low back pain suggested in our study between women and men. Estrogens may have both anti-inflammatory and proinflammatory roles.45 Sex differences in diabetes risk have also been linked to differences in body weight,46 but this should be less important in our study since we have adjusted for BMI. Psychosocial factors may impact development of diabetes in a sex-specific manner,24 and general sex differences in pain perception47 may affect the classification of back pain. A difference in risk estimates between women and men was also found in the longitudinal analysis of low back pain as a risk factor for type 2 diabetes in the Spanish twin study.4
In this study, the association between low back pain and diabetes was stronger in younger women. For type 2 diabetes, the disease onset and progression may be different in young people.48 In the cross-sectional HUNT2 study, type 1 diabetes (including latent autoimmune diabetes in adults) must be represented in all age groups, although most of the cases are likely of type 2 diabetes.49 In contrast, our cohort study only comprises cases of diabetes diagnosed after the age of 30 years, and the vast majority will be cases of type 2 diabetes. Even in the youngest group of participants in our study, the majority of cases likely have type 2 diabetes, and type differences according to age can hardly explain the age differences in risk estimates found by us.
Although a positive association was found among women in our cohort study, no such association could be demonstrated in the cross-sectional data. Cross-sectional results do not take into account temporal relationships and may to a larger extent reflect a combination of different disease categories and underlying effects. This may also explain the heterogeneity in results considering other cross-sectional studies. It is more surprising in our study that no comorbidity was observed considering information on diabetes and low back pain collected at the same time at the end of follow-up in the cohort data. The contrast with the positive association seen among women in the standard analysis of risk may be related to the difference in time lag. The dependence of the association in women on age at baseline may also be important, with reports of back pain in the comorbidity study being made about 11 years after those considered in the standard analyses.