AIM: To examine the possible association between gastrointestinal symptoms and anxiety and depression in type 2 diabetes mellitus (T2DM).

METHODS: The study was a matched case-control study based on a face to face interview with designed diagnostic screening questionnaires for gastrointestinal (GI) symptoms and T2DM, Patient Health Questionnaire (PHQ-9) for depression and General Anxiety Disorders (GAD-7) for anxiety. The questionnaire consisted of questions about symptoms and signs of anxiety and depression disorders. Also, socio-demographic characteristics, life style habits and the family history of patients were collected. It was carried out from June 2010 to May 2011 among Qatari and other Arab nationals over 20 years of age at Primary Health Care Centers of the Supreme Council of Health, Qatar, including patients with diabetes mellitus and healthy subjects over 20 years of age.

RESULTS: In the studied sample, most of the studied T2DM patients with GI symptoms (39.3%) and healthy subjects (33.3%) were in the age group 45-54 years (P < 0.001). The prevalence of severe depression (9.5% vs 4.4%, P < 0.001) and anxiety (26.3% vs 13.7%, P < 0.001) was significantly higher in T2DM patients with GI symptoms than in general population. Obesity (35.7% vs 31.2%) and being overweight (47.9% vs 42.8%) were significantly higher in T2DM patients with GI symptoms than in healthy subjects (P = 0.001). Mental health severity score was higher in T2DM patients with GI symptoms than in healthy subjects; depression (8.2 ± 3.7 vs 6.0 ± 3.6) and anxiety (7.6 ± 3.3 vs 6.0 ± 3.7). The most significant GI symptom which was considerably different from controls was early satiety [odds ratio (OR) = 10.8, P = 0.009] in depressed T2DM patients and loose/watery stools (OR = 2.79, P = 0.029) for severe anxiety. Anxiety was observed more than depression in T2DM patients with GI symptoms.

CONCLUSION: Gastrointestinal symptoms were significantly associated with depression and anxiety in T2DM patients, especially anxiety disorders.

Gastrointestinal (GI) diseases are common worldwide. Although GI symptoms are very common in the general population, recent studies reported that GI complaints are commonly reported by diabetic patients, when compared with non-diabetic controls[1]. GI disturbances commonly include symptoms of stomach pain, heart burn, diarrhea, constipation, nausea and vomiting. Koch et al[2] indicated that complications involving the GI tract occur frequently and represent a major cause of morbidity in diabetes mellitus (DM). Although GI symptoms are not life threatening, the majority of those affected will cause significant burden to the health care system as well as reduced quality of life[3]. A study in Germany documented that GI symptoms were more frequent in patients with DM compared with controls[4]. Previous studies by Bener et al[5,6] stated that DM is becoming increasingly common because of the epidemic of obesity and sedentary lifestyles in the Qatar. A more recent study[7] revealed that the prevalence rate of GI disorders is high in the general community and there is a significant association with psychological disorders. But, no study has yet been conducted in Qatar to determine the prevalence of GI symptoms among the diabetic population. It is important to investigate the prevalence of GI symptoms in the diabetic population because GI symptoms affect quality of life adversely and represent a substantial cause of morbidity in patients with diabetes.

In general, GI symptoms are influenced by psychological factors such as depression and anxiety. Talley et al[8] indicated that diabetic patients with anxiety and depression had a two fold higher prevalence of GI symptoms. Moreover, a case-control study[9] in Qatar of the prevalence of psychological distress in diabetic patients showed that depression and anxiety were severe in diabetes, which is two fold higher than in non-diabetics. The three studies revealing the high prevalence of GI symptoms in general community and its association with psychological disorders and the severity of depression and anxiety in diabetics initiated the authors to examine whether these GI symptoms are more frequent in diabetic patients and to assess the association of GI symptoms with the psychological disorders. Investigation of a possible association between psychological distress and GI symptoms in diabetics has been extremely limited. The combination of psychological disorders and diabetes is common and especially harmful because it has a strong impact on psychosocial as well as medical outcomes in patients with diabetes[10]. Also, the gastrointestinal disturbances in diabetes may result from psychiatric morbidity.

In the Middle East region, we have found no studies examining the prevalence of GI symptoms and its association with psychological disorders in the diabetic population. This is the first study in Qatar investigating the prevalence of GI symptoms among the type 2 diabetes mellitus (T2DM) patients, as well as their psychosocial impact.

This is a matched case-control study performed at the primary health care centers. The survey was conducted among the population residing in the Qatar from June 2010 to May 2011. Primary health care centers are frequented by all levels of the general population as a gateway to specialized care. The study was approved by the Hamad General Hospital, Hamad Medical Corporation. All human studies have been approved by the Research Ethics Committee and performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.

T2DM is a major chronic disease with high morbidity and mortality in Qatar[9-11] and it is considered to be on the verge of an emerging diabetes epidemic. The power calculation was actually based on a reported prevalence rate of T2DM of 16.7%[6], allowing an error of 5%, level of significance (type-1 error) of 1% and with 95% confidence limits. It was computed that 453 cases and 453 controls as a sample size were needed to achieve the objective of our study. Of the 22 primary health care centers available, we selected 12 health centers at random. Of these, 9 were located in urban and three in semi-urban areas of Qatar. Finally, subjects were selected systematically 1-in-2 using a systematic sampling procedure. Each participant was provided with brief information about the study and was assured of strict confidentiality. The study excluded patients who were under 20 and over 65 years, patients with any cognitive or physical impairment and who refused to give consent to take part in the study.

Table 1 shows the socio-demographic characteristics of the studied T2DM patients with GI symptoms and healthy subjects. Most of the studied T2DM patients with GI symptoms (39.3%) and healthy subjects (33.3%) were in the age group 45-54 years (P < 0.001). The prevalence of severe depression (9.5% vs 4.4%, P < 0.001) and anxiety (26.3% vs 13.7%, P < 0.001) was significantly higher in T2DM patients with gastrointestinal symptoms compared to healthy subjects. Mental health severity score was higher in T2DM patients with GI symptoms than in healthy subjects; depression (8.2 ± 3.7 vs 6.0 ± 3.6) and anxiety (7.6 ± 3.3 vs 6.0 ± 3.7). A significant difference was observed in the age group between T2DM with GI symptoms and non-diabetic subjects (P < 0.001). Most of the studied subjects were married (83.9%), with secondary education (32.7%) and sedentary/professional jobs (30.4%).

Table 2 shows the lifestyle habits and family history of studied T2DM patients with GI symptoms and healthy subjects. Obesity (35.7% vs 31.2%) and being overweight (47.9% vs 42.8%) were significantly higher in T2DM patients with GI symptoms compared to healthy subjects (P = 0.001). Compared with healthy subjects, physical activity was significantly less frequent in T2DM patients with GI symptoms (64.9% vs 43.9%, P < 0.001) and smoking was also higher in T2DM patients (30% vs 13.9 %, P = 0.001).

Table 3 presents the comparison of gastrointestinal symptoms between studied T2DM patients with GI symptoms and healthy subjects with severe anxiety and depression. The depression and anxiety were more prevalent in T2DM patients with most of the GI symptoms compared to healthy subjects. Compared to healthy subjects, the diabetic patients were more depressed with a significant difference with anal blockage (46.5% vs 20%, P = 0.050), heartburn (41.9% vs 15%, P = 0.046), < 3 bowels/wk (51.2% vs 20%, P = 0.028), > 3 bowels/d (48.8% vs 20%, P = 0.050), early satiety (41.9% vs 5%, P = 0.003) and fecal incontinence (37.2% vs 5%, P = 0.007). The diabetic patients were significantly more anxious with GI symptoms of anal blockage (53.3% vs 35.5%, P = 0.026), heartburn (34.6% vs 17.7%; P = 0.019), loose/watery stools (26.2% vs 11.3%, P = 0.021) and postprandial illness (26.2% vs 12.9%, P = 0.042).

Table 4 shows the extracted odd ratios and confidence intervals of GI symptoms on anxiety and depression with diabetic patients vs healthy subjects. The diabetic patients with severe anxiety were significantly more different from the healthy subjects in loose/watery stools (OR = 2.79, P = 0.029), heartburn (OR = 2.45, P = 0.022), postprandial fullness (OR = 2.39, P = 0.042), anal blockage (OR = 2.07 P = 0.026) and dysphasia (OR = 1.98; P < 0.001). Similarly, diabetic depressed patients were also significantly different from non-diabetic subjects in early satiety (OR = 10.8; P = 0.009), fecal incontinence (OR =8.89; P = 0.024), heartburn (OR = 5.04; P = 0.036), < 3 bowels/wk (OR = 4.54; P = 0.038), > 3 bowels/d (OR = 4.14; P = 0.043) and anal blockage (OR = 3.77; P = 0.05).

Figure 1 reveals the distribution of severe levels of depression and anxiety in diabetic patients with GI symptoms. The prevalence of anxiety was observed more in diabetic patients with GI symptoms; upper dysmotility (24.7% vs 10.7%, P < 0.001), constipation (24.7% vs 9.3%, P < 0.001) and diarrhea (21.7% vs 10.8%, P < 0.001), while depression was higher in esophageal symptoms (20.5% vs 18.1%).

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Figure 1 Distribution of severe levels of depression and anxiety in diabetic patients with gastrointestinal symptoms (n = 453).

Gastrointestinal symptoms are reportedly common in diabetic patients and symptoms are also frequent in individuals without DM. Therefore, this study determined whether these GI symptoms are more frequent in the diabetic population of Qatar and also assessed the association between GI disorders and psychological distress. The potential association between GI symptoms and psychological distress in diabetes has not been studied in this region. It is important to assess the effect of GI symptoms on the psychological profile for individual symptoms in diabetic patients because the co-occurrences of psychological disorders and gastrointestinal symptoms contribute to a high medical utilization in primary health care settings. Co-morbidity seems to play an essential role in increasing symptoms. The study detected higher levels of gastrointestinal symptoms in the diabetic population with depression and anxiety compared to the general population. However, patients with diabetes are almost twice as likely to suffer from anxiety and depression than the general population[16].

In the study sample, the prevalence of severe depression (9.5% vs 4.4%, P < 0.001) and anxiety (26.3% vs 13.7%) was significantly higher in diabetic patients than in the healthy population. Koloski et al[17] reported that psychological distress is linked to having persistent GI symptoms and frequently seeking health care. More than half of the diabetic patients (58.3%) evaluated reported at least two or more troublesome GI symptoms, which is very close to the figure reported in a study by Talley et al[18] (40%), with a significant difference with the healthy subjects. An increased prevalence of GI symptoms in patients with diabetes was reported in the study sample which is in agreement with previous studies[1,19]. In a Chinese diabetic population[20], it was found that 70% of them had GI symptoms which was much higher than in their non-diabetic controls. The difference in GI symptoms prevalence among studies depends on the specific diabetic population. The majority of the diabetic patients (39.3%) with gastrointestinal symptoms were observed in the age group 45-54 years.

In our diabetic population, patients were more depressed with the GI symptoms of anal blockage (46.5% vs 20.0%), heartburn (41.9% vs 12.5%), < 3 bowels/wk (51.2% vs 18.8%), > 3 bowels/d (48.8% vs 20.0%), early satiety (41.9% vs 5%) and fecal incontinence (37.2% vs 5%) compared to healthy subjects. In a study by Kolaski et al[17], it was found that increased levels of psychological distress were associated with persistent GI symptoms, in particular abdominal pain, constipation and bloating, which is similar to our study results. De Kort et al[21] indicated that GI symptoms were considerably higher in the diabetic population with 17.9% for diarrhea, 16.1% for constipation, 19.6% for bloating and 12.5% for early satiety. Bytzer et al[19] showed an increased prevalence of diarrhea or constipation (15.6%), bloating (12.3%) and early satiety (54%) in diabetic patients. Even the odd ratios revealed that early satiety (OR = 10.8), fecal incontinence (OR = 8.89), heartburn (OR = 5.04), < 3 bowels/wk (OR = 4.54), > 3 bowels/d (OR = 4.14) and anal blockage (OR = 3.77) were significantly different in diabetic depressed patients from healthy subjects. These data show that gastrointestinal symptoms were more closely related to psychiatric disturbances. On the other hand, it is also possible that unpleasant GI symptoms lead to increased anxiety and depression.

Even so, the studied diabetic patients were significantly more anxious with the GI symptoms of anal blockage (53.3% vs 35.5%), heartburn (34.6% vs 17.7%), loose/watery stools (26.2% vs 11.3%) and postprandial illness (26.2% vs 12.9%) and they were significantly different from their counterparts. It is documented that psychological vulnerability is associated with a poorer outcome for people with chronic GI symptoms[22]. In studied diabetic patients with severe anxiety, odd ratios revealed that loose/watery stools (OR = 2.79), heart burn (OR = 2.45), postprandial fullness (OR = 2.39), anal blockage (OR = 2.07) and dysphasia (OR = 1.98) symptoms remained significantly different from healthy subjects. Odd ratios reported in a study revealed that suffering diabetes was associated with suffering a mental disorder[23]. Gastrointestinal symptoms negatively affect health related quality of life in diabetes and clinicians should consider psychological factors in the treatment of GI symptoms.

The study findings show that psychological distress may be one important underlying component of the condition and should be considered by physicians in their treatment of patients. One study suggests that physicians could usefully explore the fear and anxiety of patients about their symptoms to reduce subsequent health care seeking[24]. In our diabetic population, psychological factors seem to affect GI symptoms to a large extent and should be taken into account when considering treatment of these symptoms. The current high prevalence of type 2 diabetes is likely to result in a heavy burden of diabetes complications; this will pose a significant challenge to individuals, communities and health care systems during the coming decades.

The study findings revealed that all GI symptoms occur frequently in diabetic patients compared with community controls. Also, GI symptoms in diabetes are strongly linked to depression and anxiety. The study has observed a significantly increased prevalence of the GI symptoms like anal blockage, heartburn, < 3 bowel/wk, < 3 bowels/d and fecal incontinence in depressed diabetic patients compared to healthy subjects. Anxiety, loose/watery stools, heartburn, postprandial fullness, anal blockage and dysphasia were significantly different from controls. Further studies are recommended to clarify the potential causal relationship between GI symptoms and psychological factors in diabetes.

The authors would like to thank the Hamad Medical Corporation for their support and ethical approval (ref: RP#7100/07).