Introduction
Diabetes mellitus (DM) is a group of metabolic diseases characterized by increased glucose levels resulting from defects in insulin production and insulin action or both. 1 India represents 49 percent of the world’s diabetes cases, with an estimated 72 million cases in 2017.2 Diabetic Autonomic Neuropathy (DAN) is one among the complications of DM causing impaired autonomic control over cardiovascular, gastrointestinal, and genitourinary systems. Diabetic Cardiac Autonomic Neuropathy (CAN) is the most recognized component of DAN, which has positive correlation with increased morbidity and mortality.3 Gall bladder is one among affected organs in chronic diabetics. 4
Few previous studies have shown increased prevalence of gall bladder dysfunctions and its complications in diabetic patients, attributed to cholecystomegaly and impaired motility of gall bladder manifested by high fasting volume, less ejection fraction, low rate of ejection, and high residual volume of the gall bladder, which are mainly due to autonomic neuropathy commonly seen in chronic diabetics. 5, 6
This study is intended to support that ultrasonic evidence of gall bladder dysfunction can be considered as indicator of autonomic neuropathy in type 2 diabetic patients.
Materials and methods
The study was conducted in Krishna Rajendra Hospital attached to Mysore Medical College and Research Institute from 1st January 2017 to 30th June 2018 (18 Months). The study protocol was approved by the ethical and scientific committees of the institute. 100 type diabetic patients as cases and 20 age and sex matched healthy controls were selected after satisfying inclusion and exclusion criteria. Informed consent was taken from both the groups before enrolment.
Selection of cases group
Exclusion criteria
Subjects diagnosed with Type 1 DM.
Subjects with the Age <18 years and > 65 years
Subjects diagnosed to be having primary hepatobiliary disease.
Subjects who have underwent cholecystectomy.
Control group consist of age and sex matched 20 healthy volunteers were recruited to control group after taking informed consent.
Ultrasonography
An ultra-sonographic evaluation gallbladder volume was done in all subjects. Gallbladder volumes were measured in fasting and 2 hours post-prandial. Gallbladder ejection fraction was calculated using formula.
Cardiac autonomic function tests
Cardiac autonomic neuropathy in diabetic patients was assessed clinically by using simple non-invasive cardiovascular bedside tests, which included
Statistical methods
Descriptive statistical analysis has been conducted in present study. Results on continuous measurements are presented on Mean + SD and results on categorical measurements are presented in Number (%). Significance is considered at 5 % level of significance. Student t test is done to identify significance of study parameters on continuous scale between two groups on metric parameters, Chi-square/ Fisher Exact test have been used to identify the ignificance of study parameters
Statistical software: The Statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, MedCalc 9.0.1, Systat 12.0 and R environment ver.2.11.1 were used for analysis of data and Microsoft word and Excel have been used to generate graphs, tables.
Results
In these study many of subjects with type 2 diabetes and controls were between 46 – 55 years. As shown in Table 1 in these study 45% of subjects with type 2 diabetes had cardiac autonomic neuropathy as compared to 20% of controls, difference was statistically significant (p < 0.038).
As shown in Table 2, the mean fasting gall bladder volume was increased in subjects with type 2 diabetes (13.82 + 4.31 ml) compared to controls (12.39 + 3.63 ml). The mean postprandial gall bladder volume was increased in subjects with type 2 diabetes (7.84 + 3.60 ml) as compared to controls (6.62 + 2.12 ml). The mean gall bladder ejection fraction was less in subjects with type 2 diabetes (44.64 + 11.45%) as compared to controls (46.40 + 8.78%) in the present study difference was not statistically significant (p < 0.45). {Figure 1}
As shown Table 3, the mean fasting gall bladder volume was increased in type 2 diabetics with CAN (14.88 + 4.28 ml) compared to type 2 diabetics without CAN (12.96 + 4.09 ml). The mean postprandial gall bladder volume was increased in type 2 diabetics with CAN (9.21 + 4.23 ml) compared to type 2 diabetics without CAN (6.71 + 2.43 ml). The mean gall bladder ejection fraction was lower in type 2 diabetics with CAN (40.2 + 13.75%) compared to type 2 diabetics without CAN (48.2 + 7.24%) in the present study the difference was statistically significant
(p < 0.00037). {Figure 2} This shows that subjects with type 2 diabetes with CAN had higher mean fasting and postprandial gallbladder volumes and lower mean gallbladder ejection fraction showing autonomic neuropathy of gallbladder in the present study.
Table 1
Cardiac autonomic neuropathy among subjects with type2 diabetes and controls.
|
CAN |
Type 2 diabetics (n=100) |
Controls (n=20) |
|
Present |
45 (45%) |
4 (20%) |
|
Absent |
55 (55%) |
16 (80%) |
Table 2
Mean gallbladder volumes and mean ejection fraction among subjects with type 2 diabetes and controls in the present study.
Table 3
Mean gallbladder volumes and mean ejection fraction among subjects with type 2 diabetes with CAN and without CAN
Discussion
In present study mean gall bladder volume was increased in subjects with type 2 diabetes compared to controls. This is in accordance with study of AK Aggarwal et al, 7 JS Hahm et al, 8 MP Sharma et al, 9 AM Bucceri et al. 10
In present study the mean fasting gall bladder volume was increased in type 2 diabetics with CAN compared to without CAN. This is in accordance with study of Kalyani DV et al. 4
Diabetic autonomic neuropathy (DAN) is a serious and common complication of diabetes. Its association with a variety of adverse outcomes including cardiovascular deaths, cardiovascular autonomic neuropathy (CAN) is the most clinically important and well-studied form of DAN. 4 The high prevalence of gall stone disease in diabetics include; less gall bladder motility, less postprandial cholecystokinin (CCK) release, less sensitivity of gall bladder smooth muscle to CCK, less number of CCK receptors in the gallbladder wall and supersaturation of bile. Neural control of gallbladder emptying is controlled by both parasympathetic and sympathetic innervation. 7 The reason behind cholecystoparesis is vagal neuropathy. This leads to incomplete emptying of gall bladder that in turn causing cholesterol sequestration and formation of nidus. Postprandial gall bladder emptying has decreased in diabetic patients with autonomic neuropathy and has larger residual volume than control. Many studies have high prevalence of gall bladder dysfunction in diabetics. Which will lead to increased size of gall bladder and disarranged gall bladder contraction, mainly due to autonomic neuropathy seen in chronic diabetics. Increased fasting gall bladder volume and low percentage of contraction both are observed in patients of chronic diabetes mellitus attributed to autonomic neuropathy. For long time stasis of bile leads to complications e.g. cholelithiasis, cholecystitis and sludge deposition as late outcome.4
Conclusion
In the present study there is high gall bladder volume and low ejection fraction which may be due to neuropathy changes in diabetes leading to decreased gall bladder motility which conclude that gall bladder ejection fraction can be used as a marker of autonomic neuropathy in Type 2 Diabetes Mellitus.
