Digestive, Anorectal, and Urogenital Functions in Patients with Type 2 Diabetes Mellitus, Impaired Glucose Tolerance and Normal Glucose Tolerance: Association with Autonomic Neuropathy

Abstract

Aims Gastrointestinal disorders, including constipation and fecal incontinence, are common in type 2 diabetes mellitus (T2DM) and may derive from diabetic autonomic neuropathy, severe intestinal bacterial overgrowth, or a dysfunctional anorectal sphincter. The present study aims to characterize the correlation between these conditions.

Methods Patients with T2DM, prediabetes, and normal glucose tolerance (NGT) were included. The anorectal function was assessed with high-resolution anorectal manometry. Patients were screened for autonomic neuropathy by measuring olfactory, sweat, and erectile dysfunction as well as heart rate variability. Constipation and fecal (in-)continence were evaluated using validated questionnaires. Breath tests were used to assess severe intestinal bacterial overgrowth.

Results We included 59 participants (32 (54.2%) with T2DM, 9 (15.3%) with prediabetes, and 18 (30.5%) NGT). The presence of autonomic neuropathy, severe bacterial overgrowth, and symptoms of constipation and incontinence were comparable. HbA_1c was correlated with an increased anorectal resting sphincter pressure (r=0.31, P=0.019) and constipation symptoms (r=0.30, P=0.031). In patients with a long-standing diagnosis of T2DM, significantly higher values for maximum anorectal resting pressure (Δ=+27.81±7.84 mmHg, P=0.0015) and baseline pressure (Δ=20.50±9.74 mmHg, P=0.046) were found compared with NGT, but not with prediabetes.

Conclusions Long-standing T2DM increases anorectal sphincter activity, and constipation symptoms are associated with higher HbA_1c levels. The lack of an association of symptoms with autonomic neuropathy suggests glucotoxicity as the primary mechanism.

Key words

Type 2 diabetes - intestinal autonomic neuropathy - anorectal manometry - incontinence - constipation - small intestinal bacterial overgrowth

^* contributed equally

Publication History

Received: 10 October 2022
Received: 23 February 2023

Accepted: 28 February 2023

Accepted Manuscript online:
06 March 2023

Article published online:
17 May 2023

• References

• 1 Vinik AI, Maser RE, Mitchell BD. et al. Diabetic autonomic neuropathy. Diabetes Care 2003; 26: 1553-1579 DOI: 10.2337/diacare.26.5.1553.
• 2 Bytzer P, Talley NJ, Leemon M. et al. Prevalence of gastrointestinal symptoms associated with diabetes mellitus: A population-based survey of 15,000 adults. Arch Intern Med 2001; 161: 1989-1996 DOI: 10.1001/archinte.161.16.1989.
• 3 Du YT, Rayner CK, Jones KL. et al. Gastrointestinal symptoms in diabetes: Prevalence, assessment, pathogenesis, and management. Diabetes Care 2018; 41: 627-637 DOI: 10.2337/dc17-1536.
• 4 Fillmann HS, Llessuy S, Marroni CA. et al. Diabetes mellitus and anal sphincter pressures: An experimental model in rats. Dis Colon Rectum 2007; 50: 517-522 DOI: 10.1007/s10350-006-0838-1.
• 5 Lejeune D, Melange M, Daumerie C. et al. Comparative value of anorectal manometry and electrocardiography in the diagnosis of diabetic autonomic neuropathy. Gastroenterol Clin Biol 1986; 10: 554-557
• 6 Epanomeritakis E, Koutsoumbi P, Tsiaoussis I. et al. Impairment of anorectal function in diabetes mellitus parallels duration of disease. Dis Colon Rectum 1999; 42: 1394-1400 DOI: 10.1007/bf02235035.
• 7 Russo A, Sun WM, Sattawatthamrong Y. et al. Acute hyperglycaemia affects anorectal motor and sensory function in normal subjects. Gut 1997; 41: 494-499 DOI: 10.1136/gut.41.4.494.
• 8 Lee TH, Bharucha AE. How to perform and interpret a high-resolution anorectal manometry test. J Neurogastroenterol Motil 2016; 22: 46-59 DOI: 10.5056/jnm15168.
• 9 Guillaume A, Salem AE, Garcia P. et al. Pathophysiology and therapeutic options for fecal incontinence. J Clin Gastroenterol 2017; 51: 324-330 DOI: 10.1097/mcg.0000000000000797.
• 10 Ghoshal UC, Ghoshal U. Small intestinal bacterial overgrowth and other intestinal disorders. Gastroenterol Clin North Am 2017; 46: 103-120 DOI: 10.1016/j.gtc.2016.09.008.
• 11 Rana SV, Malik A, Bhadada SK. et al. Malabsorption, orocecal transit time and small intestinal bacterial overgrowth in type 2 diabetic patients: A connection. Ind J Clin Biochem 2017; 32: 84-89 DOI: 10.1007/s12291-016-0569-6.
• 12 Adamska A, Nowak M, Pilacinski S. et al. Small intestinal bacterial overgrowth in adult patients with type 1 diabetes: Its prevalence and relationship with metabolic control and the presence of chronic complications of the disease. Pol Arch Med Wewn 2016; 126: 628-634 DOI: 10.20452/pamw.3501.
• 13 George NS, Sankineni A, Parkman HP. Small intestinal bacterial overgrowth in gastroparesis. Dig Dis Sci 2014; 59: 645-652 DOI: 10.1007/s10620-012-2426-7.
• 14 Linde JM, Nijman RJM, Trzpis M. et al. Urinary incontinence in the Netherlands: Prevalence and associated risk factors in adults. Neurourol Urodyn 2017; 36: 1519-1528 DOI: 10.1002/nau.23121.
• 15 American Diabetes Association. 2. Classification and diagnosis of diabetes: Standards of medical care in diabetes-2021. Diabetes Care 2021; 44: S15-S33 DOI: 10.2337/dc21-S002.
• 16 Jorge JM, Wexner SD. Etiology and management of fecal incontinence. Dis Colon Rectum 1993; 36: 77-97 DOI: 10.1007/bf02050307.
• 17 Vaizey CJ, Carapeti E, Cahill JA. et al. Prospective comparison of faecal incontinence grading systems. Gut 1999; 44: 77-80 DOI: 10.1136/gut.44.1.77.
• 18 Agachan F, Chen T, Pfeifer J. et al. A constipation scoring system to simplify evaluation and management of constipated patients. Dis Colon Rectum 1996; 39: 681-685 DOI: 10.1007/bf02056950.
• 19 Abrams P, Andersson KE, Apostolidis A. et al. 6th International Consultation on Incontinence. Recommendations of the International Scientific Committee: Evaluation and treatment of urinary incontinence, pelvic organ prolapse and faecal incontinence. Neurourol Urodyn 2018; 37: 2271-2272 DOI: 10.1002/nau.23551.
• 20 Losurdo G, Leandro G, Ierardi E. et al. Breath tests for the non-invasive diagnosis of small intestinal bacterial overgrowth: A systematic review with meta-analysis. J Neurogastroenterol Motil 2019; DOI: 10.5056/jnm19113.
• 21 Rezaie A, Buresi M, Lembo A. et al. Hydrogen and methane-based breath testing in gastrointestinal disorders: The North American Consensus. Am J Gastroenterol 2017; 112: 775-784 DOI: 10.1038/ajg.2017.46.
• 22 Benichou T, Pereira B, Mermillod M. et al. Heart rate variability in type 2 diabetes mellitus: A systematic review and meta-analysis. PLoS One 2018; 13: e0195166 DOI: 10.1371/journal.pone.0195166.
• 23 Gouveri E, Katotomichelakis M, Gouveris H. et al. Olfactory dysfunction in type 2 diabetes mellitus: An additional manifestation of microvascular disease?. Angiology 2014; 65: 869-876 DOI: 10.1177/0003319714520956.
• 24 Hummel T, Kobal G, Gudziol H. et al. Normative data for the “Sniffin’ Sticks” including tests of odor identification, odor discrimination, and olfactory thresholds: An upgrade based on a group of more than 3,000 subjects. Eur Arch Otorhinolaryngol 2007; 264: 237-243 DOI: 10.1007/s00405-006-0173-0.
• 25 Markendeya N, Martina V, Mathew A. et al. Sweat function in the diabetic foot. Indian J Dermatol Venereol Leprol 2004; 70: 18-19
• 26 Rosen RC, Riley A, Wagner G. et al. The international index of erectile function (IIEF): A multidimensional scale for assessment of erectile dysfunction. Urology 1997; 49: 822-830 DOI: 10.1016/s0090-4295(97)00238-0.
• 27 Kouidrat Y, Pizzol D, Cosco T. et al. High prevalence of erectile dysfunction in diabetes: A systematic review and meta-analysis of 145 studies. Diabet Med 2017; 34: 1185-1192 DOI: 10.1111/dme.13403.
• 28 Aitchison M, Fisher BM, Carter K. et al. Impaired anal sensation and early diabetic faecal incontinence. Diabet Med 1991; 8: 960-963 DOI: 10.1111/j.1464-5491.1991.tb01537.x.
• 29 Nieves-Cintron M, Flores-Tamez VA, Le T. et al. Cellular and molecular effects of hyperglycemia on ion channels in vascular smooth muscle. Cell Mol Life Sci 2021; 78: 31-61 DOI: 10.1007/s00018-020-03582-z.
• 30 Heitmann PT, Rabbitt P, Schloithe A. et al. Relationships between the results of anorectal investigations and symptom severity in patients with faecal incontinence. Int J Colorectal Dis 2019; 34: 1445-1454 DOI: 10.1007/s00384-019-03331-0.
• 31 Simren M, Stotzer PO. Use and abuse of hydrogen breath tests. Gut 2006; 55: 297-303 DOI: 10.1136/gut.2005.075127.
• 32 O'Donnell MP, Fox BW, Chao PH. et al. A neurotransmitter produced by gut bacteria modulates host sensory behaviour. Nature 2020; 583: 415-420 DOI: 10.1038/s41586-020-2395-5.
• 33 Snelson M, de Pasquale C, Ekinci EI. et al. Gut microbiome, prebiotics, intestinal permeability and diabetes complications. Best Pract Res Clin Endocrinol Metab 2021; 35: 101507 DOI: 10.1016/j.beem.2021.101507.
• 34 Papaefstathiou E, Moysidis K, Sarafis P. et al. The impact of diabetes mellitus on Lower urinary tract symptoms (LUTS) in both male and female patients. Diabetes Metab Syndr 2019; 13: 454-457 DOI: 10.1016/j.dsx.2018.11.009.
• 35 Caballero AE, Nordstrom BL, Liao B. et al. Individualized HbA1c target selection and achievement in the Multinational Observational Study Assessing Insulin Use (MOSA1c) type 2 diabetes study. J Diabetes Complications 2021; 35: 108011 DOI: 10.1016/j.jdiacomp.2021.108011.