|Year : 2022 | Volume
| Issue : 3 | Page : 238-243
Pancreatic Calcification among Children with Childhood Diabetes in Abakaliki, Nigeria: Could This Be Fibrocalculous Pancreatic Diabetes?
Maryann U Ibekwe1, Chinwe F Ogugua2, Ugo N Chikani3, Roland Ibekwe3, Emeka O Onwe2, Michael O Orji2
1 Department of Pediatrics, Ebonyi State University, Abakaliki, Nigeria
2 Department of Paediatrics, Alex Ekwueme Federal University Teaching Hospital, Abakaliki, Nigeria
3 Department of Paediatrics, University of Nigeria Teaching Hospital, Ituku Ozalla Enugu, Enugu, Nigeria
|Date of Submission||06-Jul-2021|
|Date of Decision||04-Oct-2021|
|Date of Acceptance||14-Feb-2022|
|Date of Web Publication||2-Jun-2022|
Maryann U Ibekwe
Department of Pediatrics, Ebonyi State University, Abakaliki
Source of Support: None, Conflict of Interest: None
Introduction: Tropical calcific pancreatitis is known to be associated with malnutrition and insulin-requiring diabetes mellitus. Recent studies suggest that genetic and environmental factors play a role in its etiopathogenesis. Objective: The objectives of this was were to study the prevalence, profile, and outcome of children managed for type 1 diabetes mellitus with pancreatic calcification. Materials and Methods: This was a cross-sectional study of children managed for type 1 diabetes mellitus in the pediatric endocrine unit of Federal Teaching Hospital Abakaliki, Nigeria. All patients who consented underwent ultrasonography of the pancreas. We undertook a case note review to identify factors that may be associated with pancreatic calcification. Results: Thirty-seven children were diagnosed with diabetes mellitus. The mean age was 12.3 years (5–17 years), 21 males and 16 females. Twenty of 37 (54.1%) patients were screened for pancreatic calcifications using abdominal ultrasound. Seventeen of 37 were not studied as nine of them (24.3%) died, six lost to follow-up, and two declined to participate. The mean duration of diabetes mellitus was 2.7 years (3 months–8 years). All patients were managed with a premixed twice-daily insulin regimen. Pancreatic calcification was seen in seven out of the 20 (35%) and was commoner among males and older children. The average glycosylated hemoglobin (Hba1c) was 13 and 11, and average height/weight standard deviation score was –1.9/–1.9 and –1.03/–1.02 in those with calcification and those without, respectively. Conclusion: Tropical calcific pancreatitis is common among children diagnosed with diabetes mellitus in Abakaliki, Nigeria and is associated with morbidity. Routine pancreatic ultrasound of patients with type 1 diabetes mellitus may be necessary.
Keywords: Calcification, diabetes, pancreas
|How to cite this article:|
Ibekwe MU, Ogugua CF, Chikani UN, Ibekwe R, Onwe EO, Orji MO. Pancreatic Calcification among Children with Childhood Diabetes in Abakaliki, Nigeria: Could This Be Fibrocalculous Pancreatic Diabetes?. Int J Med Health Dev 2022;27:238-43
|How to cite this URL:|
Ibekwe MU, Ogugua CF, Chikani UN, Ibekwe R, Onwe EO, Orji MO. Pancreatic Calcification among Children with Childhood Diabetes in Abakaliki, Nigeria: Could This Be Fibrocalculous Pancreatic Diabetes?. Int J Med Health Dev [serial online] 2022 [cited 2022 Jul 1];27:238-43. Available from: https://www.ijmhdev.com/text.asp?2022/27/3/238/346433
| Introduction|| |
Pancreatic calcification is an observed finding among children diagnosed with diabetes in Abakaliki, Southeastern Nigeria. Earlier terminologies such as tropical calcific pancreatitis (TCP), fibrocalculous pancreatic diabetes (FCPD), chronic calcific pancreatitis, and tropical pancreatitis have been proposed for this entity of pancreatitis calcification and diabetes. The term “fibrocalculous pancreatic diabetes (FCPD)” was introduced by the World Health Organization (WHO) Study Group report on diabetes to describe an entity of stone formation and fibrosis in the pancreatic ducts and its branches in the presence of diabetes.
TCP can be defined as a juvenile form of chronic calcific nonalcoholic pancreatitis. It is a subtype of chronic pancreatitis prevalent almost exclusively in the developing countries of the tropical world. Some of its distinctive features are younger age at onset, large intraductal calculi, and an accelerated course of the disease leading to endpoints of diabetes., TCP can be used to describe the early prediabetic stage of the disease, and the term FCPD, introduced by the WHO Group to denote the later diabetic stage. In this study, both terms are used interchangeably as they essentially refer to the same disease.
There have been TCP reports from different parts of the world and mainly from the tropics and India. The prevalence varies worldwide from 5–12/100000 per year in the USA to 114–200/1000000 per year in Southern India.,Zuidema in 1959 reported the first series of patients with pancreatic calculi and clinical features of undernutrition occurring in the lower socioeconomic strata of society.,, Since then, there have been several other reports of FCPD in Nigeria and some parts of Africa,,
The etiology of TCP is not clear. As it was first reported, several hypotheses have been entertained from environmental to genetic factors. Environmental factors such as malnutrition were once thought to play a significant role, as the majority of the patients had malnutrition.,,,
Other important proposed etiology includes cassava/cyanogen toxicity of the pancreas.,, Cassava root is rich in carbohydrates but deficient in proteins and is a staple food in the Eastern part of Nigeria. The results from candidate gene studies established that several genetic components are involved in the pathophysiology of TCP., It was hypothesized in 1896 that premature trypsinogen activation is the cause of pancreatitis. Therefore, mutation of the cationic trypsinogen is the pathogenic mediator for TCP. The serine protease inhibitor Kazal-type 1 (SPINK1) is a potent antiprotease that is thought to be a major inactivation factor of intra-pancreatic trypsin activity. SPINK1 has been associated with defense mechanisms that prevent premature activation of trypsin within the pancreas. Therefore, mutation of the SPINK1 gene has been shown to have the strongest genetic risk factor in TCP., We do not know yet if genetic mutation might be implicated in the pancreatic calcification seen in children with diabetes in Abakaliki. The classical imaging findings in TCP include ductal dilatation and intraductal calculi, which occur in 80%, whereas pancreatic atrophy may be seen in 50% of the patient. The calculi are usually located in the main pancreatic duct and may measure up to 5 cm in size.
Aims and objectives
The aim of this work was to evaluate the prevalence, profile, and outcome of children diagnosed with type 1 diabetes mellitus who had pancreatic calcifications.
This study was carried out in Abakaliki in Southeastern Nigeria. It has the natural vegetation of the guinea savannah and experiences the equatorial types of climate with an average temperature of 27°C. The inhabitants are mainly Izzi of Igbo ethnicity. A quarter of the children and adolescents diagnosed with diabetes mellitus come from the Izzi tribe.
| Subjects and Methods|| |
This was a cross-sectional study of children, which was carried out between January 2010 and December 2018. All children with diabetes mellitus and managed by the pediatric endocrine unit of Federal Teaching Hospital Abakaliki were eligible for the study. Patients were enrolled consecutively from the pediatric endocrinology clinics. Parental consent and assent from children above 7 years were obtained. All children seen in this study were diagnosed with type 1 diabetes and placed on premix insulin (30% soluble insulin and 70% Protamine Hagedorn). Injections are administered in the morning and evening. On average, each patient does blood glucose testing at least twice a day. Ultrasonography of the pancreas was used in identifying pancreatic calcifications in the patients. Obtained demographic information from each patient includes age, gender, socioeconomic class, and clinical characteristics. Social class was obtained using the Oyedeji classification. It is based on the use of parental income to assign scores. The scores, which represent a scale of 1–5, are derived from each parent’s educational attainment and occupation. The mean value of the educational qualification and occupation of each parent is determined. The mean of these four values is calculated to the nearest whole number, and the social class is scored. A score of 1 is regarded as the highest social class, whereas a score of 5 is the lowest social class. The anthropometry, including height and weight measurement, was done using standard methods. The glycosylated hemoglobin (HbA1c) was measured immunochemically in the clinic using DCA 2000+ (Bayer Corporation, Leverkusen, Germany). The instrument is standardized against the Diabetes Control and Complication Trial (DCCT) method. Researchers assured quality control by using standard solutions. Data were analyzed by using the Statistical Package for the Social Sciences (SPSS) software program, version 20.0. The mean, standard deviation, and Z score (standard deviation score) were calculated. The continuous variables were compared using the Student’s t test. A value of P < 0.05 was considered significant.
Ethical approval was obtained from the ethical review committee of the Federal Teaching Hospital Abakaliki.
| Results|| |
Thirty-seven patients were seen over the study period, of which 21 were males and 16 were females, with a mean age of 12.3 years (5–17 years) and modal age of 17 years. Over this period, nine (24.3%) patients died and six lost to follow-up. Of the remaining 22 patients, two patients declined to participate, and only 20 of them were screened for pancreatic calcifications using plain abdominal radiograph and abdominal ultrasound scan. Pancreatic calcification was seen in 7 (35%) of children who were screened by ultrasound and plain abdominal radiograph, whereas 13 (65%) had no calcification in their pancreas. The findings of ultrasonography [Figure 1] showed an increased parenchymal echogenicity with areas of diffused calcifications in the pancreas, whereas the findings of plain radiograph [Figure 2] of the abdomen showed multiple diffuse radio-opaque calculi in the region of the pancreas (first and second lumbar vertebrae) and also taking the shape of the pancreas. Few dilated pancreatic ducts were seen in the ultrasonography of these patients. [Table 1] shows the demographic characteristics of patients with pancreatic calcifications and those without. There were more males with calcifications in their pancreas (P = .27). The average age of diagnosis of diabetes mellitus in the group with calcification was 14.1 years. It was higher than those without calcification (11.3 years) but not statistically significant. The average duration of diabetes, 2.6 years and 2.7 years, was similar in both groups. The average height (HT)/weight (WT) standard deviation score (SDS) was –1.9/–1.9 and –1.03/–1.02 in those with calcification and those without, respectively (P = .08 and .05) [Table 2]. There was an increase in insulin requirement but higher average random blood glucose measurement of morning and evening in those with calcification. The average HbA1c was generally poor but more marked in the calcification group than without calcification (P = .08) [Figure 3]. The majority of the patients belonged to the lower socioeconomic group, but all the patients with calcification belonged to class 5, which is the lowest and is statistically significant (P = .05).
|Figure 2: Plain abdominal radiograph showing widespread punctate calcification of the pancreas involving the head, the body, and the tail|
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|Table 2: Clinical and demographic characteristics of patients: comparison among the patients with and without pancreatic calcification|
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|Figure 3: Graph showing the differences in the HBA1C values of the two groups|
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| Discussion|| |
This study has shown that a significant proportion of children with diabetes mellitus in Abakaliki have calcified pancreas as 35% of studied patients have pancreatic calcifications. The etiology of the calcified pancreas is not known. Several studies have postulated environmental factors like cassava consumption as etiology in TCP. Cassava, the staple food of the patients studied, is known to contain cyanogenic glycosides and a proposed pathogenic factor in TCP. This cassava theory lacks experimental support; also, TCP has been reported in regions of the world where cassava is not consumed in the diet. These environmental factors have not been proven as an etiologic cause; however, they may play a background role in gene modulation. The typical ultrasound reported in this study shows a raised parenchymal echogenicity with areas of calcification. This is similar to the report from Uganda in a case report. The anthropometric indices of the patients studied were generally poor. The explanation could be multifactorial, considering the poor socioeconomic status and the burden of diabetes mellitus disease. No significant differences were observed in the height and weight of the two groups studied; however, the group of patients with calcification appeared more stunted and lighter than those without calcification. Again reports from previous work have highlighted the role of malnutrition in its etiopathogenesis,,, The basis for this was the initial consistent observation of protein-energy malnutrition in patients with TCP, which led researchers to conclude that malnutrition may play a role in the etiopathogenesis of TCP. On the contrary, TCP has been observed in those with a high socioeconomic background where malnutrition is least likely. Also, TCP is not known in some countries where there is poor socioeconomic status. The studies on monkeys fed on high carbohydrate and low protein diets failed to develop pancreatic calcification., These findings generally refute the protein-calorie hypothesis as the etiology of TCP. Most studies report that patients with TCP are very often emaciated. It is not certain if the weight loss resulted from the disease burden or a cause. We do not have data regarding the premorbid anthropometric indices of these patients. It has also been argued that malnutrition could be the effect and not the cause. However, studies tend to suggest that the disease burden might be a cause of malnutrition.
Those without calcification have a height and weight SDS of 1.03, which appears to have better height and weight indices than those with calcification. It goes to compare with studies that pancreatic calcification in type I diabetes is associated with malnutrition. It needs to be proven if malnutrition was present before the onset of the disease or if the disease brought about the malnutrition.
A striking difference is seen in the long-term diabetes control between the two groups. There is a weak significant difference in the HbA1c of the two groups, with the better HbA1c seen in those without calcification. This indicates that there might be an association between an increased disease burden and poor diabetes control. The data revealed that pancreatic calcification tends to occur more in older children when compared with those without calcification. Although the mean age of diagnosis in our cohort is 12.30 years, the average duration of diabetes is 2.7 years in both groups. In this study, the average HbA1c of 12 indicates that the diabetes control is generally poor as compared with the DCCT. The differences appear to be worse in those with calcification.
Generally, the majority of the patients belong to the poor socioeconomic class of 4–5, which is considered by the Oyedeji classification to belong to low socioeconomic strata. The patients with TCP were in social class 5, which according to the Oyedeji classification belongs to the lowest socioeconomic class. The lower socioeconomic class is likely associated with poor nutrition, food scarcity, ignorance, and these can account for the lower anthropometric indices seen in the patients with calcification. There is strong evidence of poverty being more pronounced in those with calcification. Other studies have shown that poor socioeconomic status might play a role in the poor outcome of type 1 diabetes. The cause of calcification in this group of patients cannot be ascertained. However, there is a strong association of poor diabetes control, low socioeconomic class, and male gender found in children with TCP in this study. It is possible that the patients who presented with calcification may have a unique form of diabetes secondary to TCP, thus leading to end-stage FCPD. We do know that FCPD is a rare type of secondary diabetes due to chronic tropical non-alcoholic calcific pancreatitis, which has been widely described exclusively in developing tropical countries; however, the etiology is still largely unknown.
| Conclusion|| |
Calcified pancreas is common among children with diabetes in Abakaliki. The etiology of this condition is unknown; however, there is a strong association with poor diabetes control, low socioeconomic class, and male gender. FCPD is common in the Tropics, and all children diagnosed with diabetes mellitus should routinely have an ultrasound of the pancreas to aid in the diagnosis of the form of diabetes they have.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2]