Persistent pain at multiple sites—Connection to glucose derangement

diabetes research and clinical practice 84 (2009) e30–e32

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Brief report

Persistent pain at multiple sites—Connection to glucose derangement Pekka Ma¨ntyselka¨ a,*, Juhani Miettola a, Leo Niskanen b, Esko Kumpusalo a a b

Family Practice Unit, University of Kuopio & Kuopio University Hospital, P.O. Box 1777, Kuopio, FIN-70211, Finland Department of Medicine, Kuopio University Hospital, P.O. Box 1777, Kuopio, FIN-70211, Finland

article info

abstract

Article history:

The aim of this study was to analyse the prevalence of prediabetes and diabetes among

Received 2 September 2008

subjects with daily chronic widespread pain (DCWP). In the multivariate analysis, DCWP

Received in revised form

was significantly associated with prediabetes and diabetes. Persistent chronic pain at

29 January 2009

multiple sites may be an additional symptom of prediabetes and diabetes. # 2009 Elsevier Ireland Ltd. All rights reserved.

Accepted 29 January 2009 Published on line 27 February 2009 Keywords: Chronic pain Hyperglycaemia Diabetes Epidemiology Population based study

1.

Introduction

In addition to neuropathic pain, some reports have indicated an excessive occurrence of other chronic pain among patients with diabetes [1–3]. Our previous report suggested that daily chronic pain [4] and chronic pain at multiple sites [5] associate with glucose metabolism abnormalities. Daily chronic pain was defined as daily or continuous pain at any body region with duration of at least 3 months. Respectively, pain at multiple sites (widespread pain) was regarded as musculoskeletal pain at more than three sites. To our knowledge, there have not been studies which have analysed persistent chronic widespread pain as a symptom of prediabetes or diabetes.

2.

Materials and methods

The Lapinlahti 2005 study at the University of Kuopio in Finland involved all 760 adults born in 1939, 44, 49, 54, 59, 64, 69 and 74 living in one municipality in eastern Finland. Of these subjects, a total of 480 (63%) completed a health survey that consisted of a structured questionnaire, interview and a health examination [4,5]. All the relevant data were available for 469 participants including diabetes diagnosis, fasting plasma glucose (FPG) concentration, pain, age, gender and body mass index (BMI). The subjects were defined as subjects with diabetes if they reported diabetes, or if they were prescribed with long-

* Corresponding author at: Unit of Family Medicine, University of Kuopio, P.O. Box 1627, Kuopio, FIN-70211, Finland. Tel.: +358 17 174980; fax: +358 17 174981. E-mail address: [email protected] (P. Ma¨ntyselka¨). 0168-8227/$ – see front matter # 2009 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.diabres.2009.01.018

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diabetes research and clinical practice 84 (2009) e30–e32

term reimbursed medication for diabetes, or if their FPG 7.0 mmol/l, or 2-h glucose 11.1 mmol/l. We defined impaired glucose tolerance (IGT, FPG level <7.0 mmol/l and after a 2-h glucose tolerance test 7.8–11.0 mmol/l) and impaired fasting glycaemia (IFG, FPG 6.1–6.9 mmol/l and after a 2-h glucose tolerance test <7.8 mmol/l). IGT and IFG were grouped together as impaired glucose regulation (IGR). Consequently, glucose regulation categories were: normal glucose regulation (NGR), impaired glucose regulation (IGR = prediabetes) and diabetes. The presence of pain during the preceding week was recorded. The duration and frequency of pain was assessed with structured questions. Chronic pain was defined as pain lasting at least 3 months. The subjects were asked to localize pain to any of the listed 17 sites. In this study, we took into account the painful sites in the upper and lower extremities, shoulders and hips, as well as in neck and back. The total number of painful sites was summed. The subjects with chronic pain were grouped by the frequency of pain and the number of painful sites for subjects without chronic pain, for subjects with non-daily chronic pain at multiple sites or daily chronic pain at a maximum of three sites (non-daily/ non-widespread chronic pain), and for subjects with daily pain in four or more sites (daily chronic widespread pain, DCWP). We used two age groups: 30–45 years and 50–65 years. Those with BMI more than 30 kg/m2 were regarded as obese. A logistic regression analysis was used to analyse the association between chronic pain status and prediabetes or diabetes, and to control for the effects of age, gender and BMI. Subjects with prediabetes were compared to those with normal glucose regulation. Respectively, subjects with diabetes were compared to subjects without diabetes. A Pvalue of less than 0.05 was regarded as statistically significant. The Ethics Committee of Kuopio University Hospital approved the study. All the subjects provided written informed consent.

3.

Results

Of the study subjects 12% (N = 54) had diabetes and 20% (N = 94) had prediabetes. The diagnosis of diabetes was based on self-reported diabetes or reimbursed medication in 36 subjects, on a 2-h glucose tolerance test in 12 subjects, and on the fasting glucose level in 6 subjects. A total of 252 study subjects did not have chronic pain. Nondaily/non-widespread chronic pain was found in 38% (N = 176) of the subjects. The prevalence of DCWP was 9% (N = 41). Of the subjects who had no chronic pain, 18% (N = 46) had prediabetes and 6% (N = 16) had diabetes. Respectively, of the subjects with non-daily/non-widespread pain 20% (N = 36) had prediabetes and 14% (N = 25) had diabetes. The corresponding figures were 29% (N = 12) and 32% (N = 13) for those with DCWP. DCWP was significantly associated with prediabetes (NGR as a reference category) in both univariate and multivariate analyses (Table 1). Also age and BMI displayed an association with prediabetes in both models. There was a significant association between DCWP and diabetes in both univariate and multivariate analysis (Table 2). Similarly non-daily/non-widespread chronic pain, age and BMI were associated with diabetes.

4.

Discussion

This study indicates that daily chronic widespread pain is associated with threefold risk of prediabetes and sixfold increased risk of diabetes. This connection has been hitherto surprisingly little studied. Due to the rather small sample size and restricted geographical area, the results are of a preliminary nature. Several subjects in our study had previously undiagnosed diabetes. The prevalence of diabetes was comparable with a previous larger population study from Finland [6]. A painful diabetic neuropathy is an unlikely reason for our findings although the duration of diabetes increases the

Table 1 – Prevalence of prediabetes, and association of chronic pain status, age, gender and BMI with prediabetes (versus normal glucose regulation). Number (total)

Prevalence

Univariate analysis

Multivariate analysisa

N

N (%)

Odds ratio (95% CI)

Odds ratio (95% CI)

Chronic pain status No chronic pain Non-daily/non-widespread pain Daily widespread pain

236 151 28

46 (19.5) 36 (23.8) 12 (42.9)

1.00 1.29 (0.79–2.12) 3.10 (1.37–7.00)

1.00 1.05 (0.62–1.76) 2.74 (1.15–6.52)

Age (years) 30–45 50–65

177 238

22 (12.4) 72 (30.3)

1.00 3.06 (1.81–5.17)

1.00 2.48 (1.43–4.28)

Gender Male Female

198 217

45 (22.7) 49 (22.6)

1.00 0.99 (0.63–1.57)

1.00 0.89 (0.55–1.45)

BMI (kg/m2) 30 >30

307 108

54 (17.6) 40 (37.0)

1.00 2.76 (1.69–4.49)

1.00 2.43 (1.46–4.05)

a

Adjusted for age, gender and BMI.

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diabetes research and clinical practice 84 (2009) e30–e32

Table 2 – Prevalence of diabetes, and association of chronic pain status, age, gender and BMI with diabetes (versus normal glucose regulation and prediabetes). Number (total)

Prevalence

Univariate analysis

Multivariate analysisa

N

N (%)

Odds ratio (95% CI)

Odds ratio (95% CI)

Chronic pain status No chronic pain Non-daily/Non-widespread pain Daily widespread pain

252 176 41

16 (6.3) 25 (14.2) 13 (31.7)

1.00 2.44 (1.26–4.72) 6.85 (2.99–15.71)

1.00 2.14 (1.09–4.22) 5.65 (2.36–13.52)

Age (years) 30–45 50–65

187 282

10 (5.3) 44 (15.6)

1.00 3.27 (1.60–6.68)

1.00 2.27 (1.08–4.80)

Gender Male Female

229 240

31 (13.5) 23 (9.6)

1.00 0.68 (0.38–1.20)

1.00 0.56 (0.31–1.03)

BMI (kg/m2) 30 >30

336 133

29 (8.6) 25 (18.8)

1.00 2.45 (1.38–4.37)

1.00 1.94 (1.05–3.58)

a

Adjusted for age, gender and BMI.

frequency of neuropathic pain. Our previous study suggested that elevated plasma glucose level per se is associated with chronic pain, but less is known about other types of pain [4]. Recent studies have suggested that also prediabetic states can evoke dysfunction and pathological changes in peripheral small nerve fibres resulting in bodily pain. These processes may be related to oxidative stress and changes in cytokine levels caused by elevated glucose concentration [7]. The cooccurrence of persistent widespread pain and hyperglycaemia with or without clinical diabetes may be related to lowered physical activity, cardio-respiratory fitness and disturbed energy balance. The assessment of a patient with widespread pain could include screening for diabetes and its precursor states. While pain may have a negative impact on management of diabetes, the assessment of diabetes patients should include also a general assessment of pain, not only that caused by evident neuropathy. DCWP and glucose regulation derangement may have some common pathophysiological features probably related to chronic tissue inflammation. Our results emphasize the need for further studies into the pathophysiology and management options of chronic pain.

Conflict of interest There are no conflicts of interest.

Acknowledgements We express our gratitude to the participating Lapinlahti residents, our research staff and the staff members of the

Lapinlahti Primary Health Care Centre and the Kuopio University Hospital Laboratory. This study was financially supported by Lapinlahti Municipality and the Development Programme for the Prevention and Care of Diabetes in Finland (DEHKO/D2D) through the Northern Savo Hospital District.

references

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