Fibrocalculous Pancreatic Diabetes Research Articles

Fibrocalculous Pancreatic Diabetes in a Bangladeshi Girl

Fibrocalculous pancreatic diabetes (FCPD) is atypical but unique variety of diabetes, in which chronic inflammation and pancreatic calcification lead to exocrine and endocrine failure of the pancreas, primarily occurs in tropical countries. At an early age, these diabetic children are at risk of developing disabling and life-threatening complications, putting a major human and economic burden on families and societies. Here, authors report a case of young female patient presenting with the clinical features of FCPD. BANGLADESH J CHILD HEALTH 2022; VOL 46 (2) : 89-91

A study on fibro-calculous pancreatic diabetes conducted in a tertiary medical institution in Northern Bihar

Fibro-calculous pancreatic diabetes (FCPD), which is seen in tropical areas and is caused by idiopathic nonalcoholic chronic pancreatitis, is characterized by pancreatic calcification and stomach pain. One female patient and nine male patients were identified as having FCPD. Half of the patients were under 30 years old, with an average age of 28.44±7.07. Seven individuals had diabetes for a shorter period of time than five years. Four patients reported with problems related to various infections, while six patients had osmotic complaints due to uncontrolled diabetes. With a mean waist-hip ratio of 0.89 and a mean BMI of 19.42, all of the patients were thinly built. With mean FBS of 231 mg/dl, PPBS of 469 mg/dl, and HbA1c of 11.96, all patients had uncontrolled diabetes. Microvascular issues affected 30% of the patients, while none of the patients experienced macrovascular complications. A rare type of secondary diabetes called FCPD is becoming more widespread in northern states like Bihar.

A noteworthy rarity: fibrocalculous pancreatic diabetes as an uncommon aetiology of diabetes

No abstract available

Prurigo Nodularis in Fibrocalculous Pancreatic Diabetes (FCPD)

Fibrocalculous Pancreatic Diabetes (FCPD) is a secondary form of diabetes mellitus due to chronic nonalcoholic calcific pancreatitis. Prurigo nodularis is seen in various dermatological diseases, but also seen in hematological and metabolic diseases (such as solid tumors, lymphoma, diabetes mellitus).

Fibrocalculous Pancreatic Diabetes - a Unique Differential among Diabetic.

Fibrocalculous pancreatic diabetes is a unique variant of diabetesmellitus and also known as type 3c diabetes mellitus. It is related to the patient who is young, non-alcoholic and belonging predominantly from the tropical region. It is a severe form of diabetes which can also be linked to the fact that it predisposes to malignancy.1 Among the variants of diabetes that we commonly encounter, fibrocalculous pancreatic diabetes has been rarely diagnosed in the developing countries. With the advancement of diagnostic capacity, it can be identified clinically and managed efficiently. It should be considered in patients with typical features of diabetes, abdominal pain, and pancreatic calculi. There is limited reporting of this case in Nepal because of misdiagnosis, so we are reporting a 40 years male who presented with recurrent episodes of abdominal pain with mucus mixed stool for the last 28 years and was diagnosed as fibrocalculous pancreatic diabetes. Keywords: Blood glucose; eastern Nepal; fibrocalculous pancreatic diabetes; pancreas.

Fibrocalculous pancreatic diabetes

Chronic Pancreatitis and the type of diabetes associated with it have been named as “Fibrocalcific Pancreatic Diabetes” (FCPD). Initially categorized by WHO in 1985 as a subtype of Malnutrition Related Diabetes Mellitus (MRDM), FCPD has subsequently been included as a disease of the exocrine pancreas under other specific forms of diabetes. Despite many years since its first description, the etiopathogenesis of FCPD remains obscure. While insulin secretion defects are definitely the crux of the problem, there is growing body of evidence to suggest that insulin resistance may play a key role in glucose metabolism in these individuals. Moreover, the role of free fatty acids, counter-regulatory hormones like glucagon and impact of hepatic and peripheral lipid distribution on the dynamics of insulin secretion remains to be explored. Other factors related to alterations in energy expenditure may compound the pathogenetic picture. In fact, not all people with Fibro calculous Pancreatitis will develop diabetes and a search for the exact triggers for hyperglycemia might provide the clue to this enigmatic disease pathophysiology.

Periodontal disease in fibrocalculous pancreatic diabetes (FCPD): common complication of an uncommon disease

Periodontal disease in fibrocalculous pancreatic diabetes (FCPD): common complication of an uncommon disease

Comprehensive evaluation of patterns of hypoglycemia unawareness (HUA) and glycemic variability (GV) in patients with fibrocalculous pancreatic diabetes (FCPD): A cross-sectional study from South India.

Hypoglycemia unawareness (HUA) in patients with FCPD is common with an unclear etiology. We evaluated the prevalence, characteristics of HUA, glycemic variability (GV), its possible association with pancreatic glucagon secretion & cardiac autonomic function in patients with FCPD. A two-week ambulatory glucose profile (AGP) and cardiac autonomic function test was done in patients with FCPD (n = 60), and categorized into UNAWARE (n = 44) and AWARE (n = 16) groups based on the Hypoglycemia Unawareness Index (HUI) score. Glycaemic variability was assessed from the AGP data using Easy GV 9.0.2 software. A subset of patients from both the groups (n = 11) underwent a mixed-meal challenge test and were compared with healthy individuals (controls; n = 11). HUA was evidenced in 73% (44/60) of patients with FCPD. Significant hypoglycemia, nocturnal hypoglycemia, duration of hypoglycemia and poor cardiac autonomic functions (p = 0.01) were prominent in the UNAWARE group. The overall GV was greater in the UNAWARE group. In the UNAWARE group, significantly reduced fasting and post prandial glucagon levels negatively correlated with HUI (r = -0.74, p < 0.05) and GV-hypoglycemia indices (p < 0.05) In contrast, significantly higher post prandial glucagon levels in the AWARE group positively correlated with post prandial hyperglycemia (r = 0.61, p < 0.05). Heterogeneity in patterns of glucagon secretion were significantly associated with HUA and GV. Reduced glucagon levels contribute to greater risks of HUA, nocturnal hypoglycemia and greater GV, while hyperglucagonemia predisposes to postprandial hyperglycemia and hypoglycemia awareness in patients with FCPD.

Characteristics of children and adolescents with newly diagnosed Fibrocalculous pancreatitis diabetes (FCPD) and type 1 diabetes: A study from Eastern India

Background and aimsWe aimed to identify clinical characteristics and biochemical parameters at presentation in newly diagnosed children and adolescents with Fibrocalculous pancreatic diabetes (FCPD) and compare them with Type 1 Diabetes (T1D) children. MethodologyA retrospective chart review yielded 226 patients (below 18 years) who presented and fulfilled diagnostic criteria of diabetes mellitus. Classification of diabetes was based on American Diabetes Association (ADA), World Health Organization (WHO), International Society for Paediatric and Adolescent Diabetes (ISPAD), and Mohan's criteria and all patients underwent abdominal X-ray. ResultsA total of 31 (13.7%) patients fulfilled criteria of FCPD and 63 (27.9%) of autoantibody positive T1D. When comparing FCPD with T1D at presentation, FCPD patients were older, 14.23 years vs 11.32 years. Fewer FCPD patients presented with Diabetic Ketoacidosis (3.2% vs 34.9%), osmotic symptoms (54.8% vs 93.7%) with significantly longer median duration of symptoms (4.0 vs 1.0 months) and had more abdominal pain (58.06% vs 6.3%) & diarrhoea (38.71% vs 1.6%) as compared to patients with T1D”. FCPD patients had higher c-peptide levels (median-0.85 vs 0.61) and required higher mean dose of insulin compared to T1D (1.16 U/kg vs 1.01 U/kg). At presentation fasting plasma glucose was significantly higher in T1D than FCPD, but no difference was noted in post prandial glucose and HbA1c. ConclusionThere is a significant difference in clinical characteristics and biochemical parameters at presentation between FCPD and T1D patients with a longer symptom duration but insidious course in the former. To the best of our knowledge, this is the first study to report suitable cut-offs for age, c-peptide, duration of symptoms and insulin dose requirement which could be helpful for differentiating FCPD from T1DM patients.

Pancreatic Calcification among Children with Childhood Diabetes in Abakaliki, Nigeria: Could This Be Fibrocalculous Pancreatic Diabetes?

Pancreatic Calcification among Children with Childhood Diabetes in Abakaliki, Nigeria: Could This Be Fibrocalculous Pancreatic Diabetes?

224-LB: A Study to Evaluate the Glucagon and Incretin Responses and Identify the Role of Extrapancreatic Glucagon in Patients with Fibrocalcific Pancreatic Diabetes

Aim: The aim of this study is to evaluate glucagon and incretin responses in patients with FCPD. Methods: Nine FCPD patients and six age- and body mass index-matched healthy controls were subjected to 75 g oral glucose tolerance test (OGTT) followed by isoglycemic intravenous glucose infusion (IIGI). Blood samples were analyzed for incretins and glucagon at nine pre-specified time-points over 3 h and the area under curve was calculated. Results: Glucagon was significantly higher during OGTT compared to IIGI in FCPD patients (98.8 ± 13 pg/ml vs. 63.4 ± 7 pg/ml, P = 0.03) and was also higher when compared to controls (98.8 ± 13 pg/ ml vs. 65.8 ± 18 pg/ml, P = ns). FCPD patients showed very low basal and stimulated c-peptide (0.43 ± 0.14 ng/ml and 1.09 ± 0.3 ng/ ml, respectively) and pancreatic polypeptide (12.3 ± 0.0pg/ml and 12.0 ± 0.6 pg/ml, respectively) levels. Glucagon-like peptide-1 (GLP-1) was significantly higher in cases on OGTT when compared to controls (44.5 ± 9.2 pM vs. 12.8 ± 7.5 pM, P = 0.02). Oxyntomodulin was also insignificantly higher in cases on OGTT when compared to controls (1252 ± 350 pg/ml vs. 859.8 ± 165 pg/ml, P = 0.43). GIP was lower in cases on IIGI when compared to controls (52.9 ± 23.9 pg/ml vs. 144.5 ± 36.1 pg/ml, P = 0.045) and there was blunted response on OGTT as well (106.8 ± 40.3 pg/ml vs. 557.8 ± 96.4 pg/ml, P = 0.003). Discussion: We found hyperglucagonemia in FCPD on OGTT, which was suppressed on IIGI. Increase in L-cell products: GLP-1 and oxyntomodulin and a good correlation between glucagon and GLP-1 during OGTT were suggestive of extrapancreatic glucagon production probably from L-cell. The blunted GIP could probably be due to: inadequate pancreatic enzyme supplements, a selective PC-2 enzyme up-regulation or a negative feedback regulation from extrapancreatic glucagon. Conclusion: Extrapancreatic glucagon does exist in FCPD and may contribute to postprandial hyperglycemia and lower GIP levels. Disclosure A. Shankar: None.

Fibrocalculous pancreatic diabetes (FCPD)presenting as regression of puberty–a rare presentation of a rare disease

Here we present a case of young female who presented to us with secondary amenorrhea causing regression of puberty which is quite uncommon as a presentation of FCPD which is occasionally encountered in our day to day clinical practice. The aim of this communication is to keep a high index of suspicion and to keep FCPD as a possible aetiology which can lead to regression of puberty.

Incidence of diabetes in children and adolescents in Dhaka, Bangladesh

Bangladesh has limited information regarding incidence of type 1 diabetes (T1D) and type 2 diabetes (T2D) in young people. The objective of this study was to measure minimum incidence of T1D and T2D, and record other types of new-onset diabetes in children and adolescents <20 years (y), in Dhaka District, Bangladesh, from 2011-2018. Retrospective study using clinical records from Diabetic Association of Bangladesh clinics. Cases were classified by clinical evaluation. 725 cases were diagnosed. 482 (66.5%) had T1D, 205 (28.3%) T2D, 14 (1.9%) fibrocalculous pancreatic diabetes, and 24 (3.3%) other types. Male:female ratios for T1D/T2D were 1:1.6 (p<0.0001) (T1D) and 1:1.4 (p<0.01) respectively. T1D cases by age-group were 7.3% (0-4y), 19.9% (5-9y), 43.6% (10-14y) and 29.3% (15-19y). Mean±SD ages of onset were 12.3±4.2y (T1D) and 13.1±2.4y (T2D). Annual T1D mean incidences/100,000 were 1.22 [95%CI: 0.85-1.58] (<15y) and 1.25 [0.94-1.57] (<20y), and for T2D 0.52 [0.33-0.73] (<20y). T1D incidence <15y was 1.04 [0.69-1.39] in 2011 and 1.42 [1.04-1.80] in 2018 (p=0.08). T2D incidence rose from 0.22 [0.80-0.36] (2011) to 0.57 [0.36-0.77] (2018), an annualized increase of 12% [8-22%] (p=0.001). Ascertainment was estimated as 95%. T1D was most common, but T2D, FCPD and other forms also occur. T2D incidence increased during the study period.

Unusual type of diabetes: fibrocalculous pancreatic diabetes.

A 34-year-old Thai man complained about recurrent upper abdominal pain, polyuria, and a 5-kg weight loss in 6 months. He had no history of steatorrhea, jaundice, gallstones, alcohol intake, or cassava consumption. Physical examination was unremarkable except for his body mass index of 17.6 kg/m². The plasma glucose level was 672 mg/dL with normal serum amylase and lipase. Laboratory investigation showed serum osmolality of 287 mOsm/kg, bicarbonate 22 mEq/L and negative for serum ketone. Fibrocalculous pancreatic diabetes (FCPD) was diagnosed from a plain abdominal X-ray study showing multiple large calcifications over a pancreatic area (A). Computerized tomography of the abdomen revealed a large tubular calcification in dilated pancreatic duct during entering the duodenum (B). Scattered calcifications along the pancreatic duct were also noted (C). A genetic study revealed a SPINK1 N34S heterozygous mutation. His hyperglycemia responded well to insulin therapy. FCPD, a late stage of tropical chronic pancreatitis (TCP), is classified as a secondary cause of diabetes resulting from pancreatic dysfunction. The clinical picture consists of a triad of pancreatic calcification, abdominal pain, and diabetes. Its distinctive features are young age at onset, lean or underweight, ketosis-resistant diabetes, presence of large intraductal pancreatic calculi, and reported mainly in tropical developing countries. An etiology was previously thought to relate to malnutrition; however, a strong association with SPINK1 mutation is noted. The major morbidities are recurrent abdominal pain, steatorrhea, and malnutrition, while the majority of death is associated with diabetic nephropathy and pancreatic cancer. Treatment includes pancreatic enzyme supplementation, insulin therapy, and surgical drainage.

Incretins in fibrocalculous pancreatic diabetes: A unique subtype of pancreatogenic diabetes.

Studies evaluating endocrine and exocrine functions in fibrocalculous pancreatic diabetes (FCPD) are scarce. Insulin, C-peptide, glucagon, incretin hormones (glucagon-like peptide 1 [GLP-1] and gastric inhibitory peptide [GIP]), and dipeptidyl peptidase IV (DPP-IV) were estimated in patients with FCPD (n = 20), type 2 diabetes mellitus (T2DM) (n = 20), and controls (n = 20) in fasting and 60 minutes after 75 g glucose. Fasting and post-glucose C-peptide and insulin in FCPD were lower than that of T2DM and controls. Plasma glucagon decreased after glucose load in controls (3.72, 2.29), but increased in T2DM (4.01, 5.73), and remained unchanged in FCPD (3.44, 3.44). Active GLP-1 (pmol/L) after glucose load increased in FCPD (6.14 to 9.72, P = <.001), in T2DM (2.87 to 4.62, P < .001), and in controls (3.91 to 6.13, P < .001). Median active GLP-1 in FCPD, both in fasting and post-glucose state (6.14, 9.72), was twice that of T2DM (2.87, 4.62) and 1.5 times that of controls (3.91, 6.13) (P < .001 for all). Post-glucose GIP (pmol/L) increased in all: FCPD (15.83 to 94.14), T2DM (21.85 to 88.29), and control (13.00 to 74.65) (P < .001 for all). GIP was not different between groups. DPP-IV concentration (ng/mL) increased in controls (1578.54, 3012.00) and FCPD (1609.95, 1995.42), but not in T2DM (1204.50, 1939.50) (P = .131). DPP-IV between the three groups was not different. Fecal elastase was low in FCPD compared with T2DM controls. In FCPD, basal C-peptide and glucagon are low, and glucagon does not increase after glucose load. GLP-1, but not GIP, in FCPD increases 1.5 to 2 times as compared with T2DM and controls (fasting and post glucose) without differences in DPP-IV.

Intra-abdominal fat estimation by bio-electrical impedance analysis in patients with fibrocalculous pancreatic diabetes compared with BMI matched type 2 diabetic subjects and healthy controls

Background and aimsIntra-abdominal adipose tissue (IAAT) is a major contributor to insulin resistance (IR) in type 2 diabetes mellitus (T2D). Prior studies have demonstrated evidence of IR in fibrocalculous pancreatic diabetes (FCPD). However, no data exists on IAAT estimation in FCPD. Hence, we compared IAAT area among FCPD patients and an equal number of body mass index (BMI) matched T2D patients and healthy controls. MethodsWe recruited 60 patients with FCPD between January 2019 and February 2020. Body composition analysis was performed via bio-electrical impedance analysis. ResultsThe mean ages were 37.82 ± 10.07, 51.02 ± 9.9, and 30.7 ± 11.51 years for patients in the FCPD, T2D, and control groups, respectively. The mean BMI of patients in the three groups was 20.65 ± 2.01, 20.83 ± 1.49, and 20.91 ± 1.59 kg/m2, respectively (P = 0.684). The mean IAAT area of patients in the FCPD, T2D, and control groups was 67.93 ± 43.38, 117.78 ± 48.03, and 100.52 ± 42.31 cm2, respectively. IAAT was significantly lower in patients with FCPD compared with those in the other two groups (P < 0.0001). In the entire cohort, IAAT showed significant positive correlation with age (r = 0.20), abdominal circumference (r = 0.80), waist hip ratio (r = 0.75), and LDL level (r = 0.25) (P < 0.05). ConclusionsPatients with FCPD have significantly lower IAAT compared to BMI matched T2D subjects and healthy controls. IAAT does not appear to be a major contributor to insulin resistance observed in patients with FCPD.

Fibrocalculous pancreatic diabetes.

Fibrocalculous pancreatic diabetes (FCPD) is a unique form of diabetes reported from tropical countries, associated with both endocrine and exocrine disease of the pancreas. The pre-diabetic phase of the disease is called tropical chronic pancreatitis (TCP). Currently FCPD is classified as a secondary form of diabetes called pancreatic diabetes, because essentially the disease is caused by pancreatic damage. There is an overlap of these subjects with idiopathic, non-alcoholic pancreatitis. This review will cover the etiopathogenesis, diagnosis and management of this clinical condition. FCPD could lead to endocrine dysfunction (diabetes and its complications) as well as exocrine dysfunction, and is associated with a higher risk of pancreatic cancer, for which early detection is important.

SAT-650 Novel Insights into the Entero-Insular Axis in Fibrocalcific Pancreatic Diabetes: An Isoglycemic Intravenous Glucose Infusion (IIGI) Study from India

In tropical countries including India, one of the common causes for young onset diabetes mellitus (DM) is “Fibro Calcific Pancreatic Diabetes” (FCPD) characterized by progressive pancreatic destruction. Despite this, glucagon has been found to be elevated in FCPD (1,2). The L-Cells in gut produce glucagon like peptide- 1 (GLP-1) and oxyntomodulin which are products of glucagon gene, thus raising probability of extra-pancreatic glucagon in FCPD. To test this hypothesis we performed 75grams oral glucose tolerance test (OGTT) followed by IIGI on separate days on nine FCPD and six healthy subjects. The latter procedure ensured matched glucose levels achieved during OGTT. Glucagon and incretins were measured at nine pre-specified time points. We found an increase in L-Cell products: GLP-1 (44.5±9.2pM vs. 12.4±4.5pM, p=0.02) and Oxyntomodulin (1252±350pg/ml vs. 859.8±165pg/ml, p=0.43) along with significant rise in glucagon during OGTT (98.8±13pg/ml vs. 63.4±7pg/ml, p=0.03) despite flat basal & stimulated C-peptide (0.43±0.14ng/ml and 1.09±0.3ng/ml, respectively) and Pancreatic polypeptide (12.3±0.0pg/ml and 14.7±1.7pg/ml, respectively) levels.Paradoxically, gastric inhibitory polypeptide (GIP) levels were low in FCPD (106.8±40.3pg/ml vs. 557.8±96.4pg/ml, p=0.003). We speculate that the hyperglucagonemia is extra-pancreatic (L-Cell) in origin and may also contribute to the dichotomous incretin response in FCPD.

Fibrocalculous Pancreatic Diabetes.

Fibrocalculous pancreatic diabetes (FCPD) is an uncommon form of diabetes occurring in underprivileged developing countries of the world. We attempt to review the latest evidence on epidemiology, secular trends, etiopathogenic mechanisms, and treatment modalities of FCPD with particular reference to studies from the past decade. There has been little new data on FCPD over the past decade even from countries where it was considered to be prevalent. There appears to be a decline in prevalence of the condition of late. There is also some evidence to show that the condition develops due to as yet unknown environmental influences acting on a background of genetic susceptibility. FCPD is a severe form of diabetes and may be a premalignant condition. FCPD deserves more attention than it currently receives, because of its unique clinical features and management strategies, and its propensity to develop pancreatic adenocarcinoma.

Comparison of CGM-Derived Measures of Glycemic Variability Between Pancreatogenic Diabetes and Type 2 Diabetes Mellitus.

To compare glycemic variability (GV) indices between patients with fibrocalculous pancreatic diabetes (FCPD) and type 2 diabetes mellitus (T2D) using continuous glucose monitoring (CGM). We measured GV indices using CGM (iPro™2 Professional CGM, Medtronic, USA) data in 61 patients each with FCPD and T2D who were matched for glycated hemoglobin A1c (HbA1c) and duration of diabetes. GlyCulator2 software was used to estimate the CGM-derived measures of GV (SD, mean amplitude of glycemic excursion [MAGE], continuous overall net glycemic action [CONGA], absolute means of daily differences [MODD], M value, and coefficient of variance [%CV]), hypoglycemia (time spent below 70 mg/dL, AUC below 70 mg/dL, glycemic risk assessment diabetes equation hypoglycemia, Low Blood Glucose Index), and hyperglycemia (time spent above 180 mg/dL at night [TSA > 180], AUC above 180 mg/dL [AUC > 180], glycemic risk assessment diabetes equation hyperglycemia, High Blood Glucose Index [HBGI], and J index). The correlation of GV indices with HbA1c, duration of diabetes, and demographic and biochemical parameters were also assessed. All the CGM-derived measures of GV (SD, MAGE, CONGA, MODD, and %CV), except M value, were significantly higher in the FCPD group than in the T2D group (P < 0.05). Measures of hyperglycemia (TSA >180, AUC >180, HBGI, and J index) were significantly higher in the FCPD group than in the T2D group (P < 0.05). The measures of hypoglycemia were not significantly different between the two groups. All the hyperglycemia indices showed a positive correlation with HbA1c in both groups. FCPD is associated with higher GV than is T2D. The findings of higher postprandial glycemic excursions in patients with FCPD could have potential therapeutic implications.