Fibrocalculous Pancreatic Diabetes Patients Research Articles

The impact of malnutrition on secondary diabetes and calcific pancreatitis: A comprehensive review

Introduction: Malnutrition in low- and middle-income countries significantly impacts the development of secondary diabetes and calcific pancreatitis. Aim and Methods: This review summarizes the prevalence, characteristics, and findings from key studies over the past decade on the link between malnutrition and secondary diabetes, focusing on protein-deficient pancreatic diabetes (PDPD) and fibro-calculous pancreatic diabetes (FCPD). A comprehensive literature search was conducted in PubMed, Scopus, and Google Scholar for articles published between 1995 and 2023. Studies included were peer-reviewed articles focusing on the link between malnutrition and secondary diabetes, conducted in LMICs, and discussing the prevalence, clinical characteristics, and outcomes of PDPD and FCPD. Both observational and interventional studies were considered. Results: The review of studies revealed several key findings: · PDPD is characterized by lower C-peptide levels and varied responses to glibenclamide post-nutritional rehabilitation. · FCPD patients show rapid calcification, diminished exocrine and beta-cell function, and more severe exocrine deficiency compared to PDPD. · Both PDPD and FCPD patients often present with lower BMI and significant renal involvement. · Recent studies indicate improved nutritional status and prognosis of FCPD patients with enhanced medical care. · Insulin-requiring diabetes in Ethiopia is strongly linked with poor education, poverty markers, and childhood malnutrition. · Lean diabetes, linked to childhood malnutrition, is characterized by low-normal BMI, early onset, and rapid beta-cell failure. Discussion: The development of diabetes following early malnutrition can be attributed to several interconnected mechanisms involving metabolic, endocrine, and epigenetic factors. Early nutritional intervention trials are crucial to prevent glucose abnormalities and diabetes later in life. Studies highlight that improving early-life nutrition can enhance beta-cell function, reduce insulin resistance, and mitigate long-term metabolic dysfunction. Lean diabetes, linked to childhood malnutrition, presents unique challenges but can be addressed through targeted nutritional support. Conclusion: The review underscores the significant impact of malnutrition on the development of secondary diabetes and calcific pancreatitis in LMICs. Addressing malnutrition through early nutritional interventions is crucial to mitigate the risk of chronic conditions and improve metabolic health outcomes. Continued research and targeted public health strategies are essential to break the cycle of malnutrition and disease in vulnerable populations.

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.

Assessment of insulin sensitivity and secretion in patients with fibrocalculous pancreatic diabetes.

Background: Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes seen in patients with tropical chronic pancreatitis. Insulin deficiency plays a major role in the etiopathogenesis of FCPD. Limited data suggest a possible role of insulin resistance (IR) in the pathogenesis of FCPD. Sparse data exist on measures of insulin sensitivity (IS) and secretion in patients with FCPD and its comparison to type 2 diabetes mellitus (T2D) patients.Method: Eighty patients with FCPD, 36 patients with T2D and 36 healthy subjects were included. A 75 g oral glucose tolerance test (OGTT) was performed in the morning after an overnight fast. We evaluated IS and secretion using indices derived from fasting (homeostasis model assessment of insulin resistance [HOMA-IR], quantitative insulin sensitivity check index [QUICKI] and homeostasis model assessment of beta-cell function [HOMA-ß]) and OGTT (Matsuda, insulin sensitivity index by Kanauchi [ISI-K], oral glucose insulin sensitivity index [OGIS], Stumvoll, insulinogenic index and oral disposition index [ODI]) measurements of glucose and insulin.Results: HOMA-IR was significantly higher and QUICKI significantly lower in patients with FCPD and T2D than in healthy controls (P<0.001). Matsuda, ISI-K, OGIS and Stumvoll were significantly lower in patients with FCPD and T2D than in healthy controls (P<0.001), indicating reduced IS in both FCPD and T2D patients. HOMA-ß, insulinogenic index and ODI were significantly lower in patients with FCPD and T2D compared to healthy controls (P<0.001).Conclusion: FCPD is associated with reduced IS as assessed by fasting and OGTT-based indices. FCPD is also associated with a greater degree of impairment in insulin secretion than in T2D. IR may play a role in the pathogenesis of FCPD.

A comparative study of the clinical profile of fibrocalculous pancreatic diabetes and type 2 diabetes mellitus

AimsThe present study aimed to compare the clinical characteristics of patients with fibrocalculous pancreatic diabetes (FCPD) and those with type 2 diabetes mellitus (T2DM) to identify the characteristics distinctive of FCPD. MethodsA total of 133 patients with FCPD were compared with 665 patients with T2DM matched for duration of diabetes. Biochemical parameters and microvascular and macrovascular complications were assessed in all patients. Multivariate regression analyses were performed to study the determinants of microvascular and macrovascular complications in both groups. ResultsThe mean duration of diabetes was 4.42 ± 5.65 years in the FCPD group and 4.51 ± 3.88 years in the T2DM group. FCPD participants were significantly younger at diagnosis and leaner than patients with T2DM. The FCPD group had higher fasting and postprandial glucose and HbA1c levels than the T2DM group. The FCPD group had significantly lower triglyceride, total cholesterol, low-density lipoprotein cholesterol, serum total calcium, hemoglobin, and serum creatinine values than the T2DM group. The prevalence of coronary artery disease, stroke, and retinopathy was significantly higher in the T2DM patients while the prevalence of distal symmetric polyneuropathy was significantly lower. On multivariate logistic regression analysis, duration of diabetes and HbA1c (OR = 1.17, P = 0 0.04) in FCPD patients and age (OR = 1.04, P < 0 0.001), duration of diabetes (OR = 1.17, P < 0 0.001) and HbA1c (OR = 1.28, P < 0.001) in T2DM patients were associated with microvascular complications. ConclusionsThere are several differences in the phenotype, biochemical parameters, and prevalence of diabetic complications between patients with FCPD and T2DM. Timely diagnosis may have implications in the follow-up and management of patients.

The Clinical Spectrum of Fibrocalculous Pancreatic Diabetes in Kashmir Valley and Comparative Study of the Clinical Profile of Fibrocalculous Pancreatic Diabetes and Type 2 Diabetes Mellitus.

Background:Fibrocalculous pancreatic diabetes (FCPD) is a secondary form of diabetes, described from several tropical countries, including India. We described the existence of this entity in the subtropical region-the Kashmir valley of the Indian subcontinent and compared the clinical characteristics of these patients with type 2 diabetes mellitus (T2DM) patients.Aim:The present study aimed to compare the clinical characteristics of patients with FCPD and those with T2DM to identify the characteristics distinctive of FCPD.Materials and Methods:A total of 124 patients with FCPD were compared with 124 patients with T2DM matched for age and duration of diabetes. Biochemical parameters and microvascular and macrovascular complications were assessed in all patients. Multivariate regression analyses were performed to study the determinants of microvascular complications in both groups.Results:FCPD patients had significantly lower serum cholesterol, serum triglyceride, and serum calcium levels but higher glycosylated hemoglobin levels compared to T2DM patients. FCPD participants were significantly leaner. The prevalence of retinopathy, neuropathy, and nephropathy was similar between the two. Five T2DM patients had documented cardiovascular disease compared to one in FCPD patients (P < 0.05). Multiple logistic regression analysis revealed glycosylated hemoglobin and duration of diabetes to be significantly associated with retinopathy and nephropathy in T2DM. Among FCPD patients, glycosylated hemoglobin showed a strong association with retinopathy as well as nephropathy. BMI showed a significant negative association with nephropathy in FCPD patients. Age and age at onset showed a strong association with neuropathy in FCPD patients while the duration of diabetes showed the association with neuropathy (P = 0.015) in T2DM.Conclusion:There are several differences in the phenotype, biochemical parameters, and prevalence of diabetic complications between patients with FCPD and T2DM.

Prevalence of End-Organ Damage, Beta Cell Reserve, and Exocrine Pancreas Defect in Fibrocalculous Pancreatic Diabetes: An Eastern India Perspective.

Background:Data on prevalence and burden of end-organ damage in fibrocalculous pancreatic diabetes (FCPD) from eastern India is scant. This study investigated the burden of end-organ damage and exocrine pancreatic defect in FCPD patients in Eastern India.Materials and Methods:Consecutive FCPD patients underwent evaluation of glycemic control, C-peptide, fecal elastase, body fat percent, tests for cardiac autonomic neuropathy (CAN), neuropathy, nephropathy, and retinopathy which were compared with data from type-1 diabetes (T1DM) and type-2 diabetes (T2DM).Results:Data from 101 FCPD, 41 T1DM, 40 T2DM, and 40 controls were analyzed. Body fat percent was lowest in FCPD and T1DM. Similarly, fasting and stimulated C-peptide was significantly lowest in T1DM, followed by FCPD. Significant elevations in stimulated C-peptide were observed in FCPD. Fecal elastase was lowest in FCPD. Exocrine pancreas defect in FCPD, T1DM, and T2DM was 100%, 53.66%, 27.5%, respectively. HbA1c was worst in FCPD. About 40% of FCPD patients had CAN while 13.33% had borderline CAN. Isolated parasympathetic dysfunction was the commonest (66.67%) among them. FCPD patients with CAN had lower fecal elastase, higher HbA1c, microalbuminuria, steatorrhea, neuropathy, retinopathy, and nephropathy, compared to those without CAN. On binary logistic regression, diabetes duration was a significant predictor of end-organ damage in FCPD. Fecal elastase and body fat percent were independent predictors for insulin therapy in FCPD.Conclusion:CAN is common in FCPD while exocrine pancreas defect is most severe in FCPD followed by T1DM and T2DM. Fecal elastase has an important prognostic role for insulinization in FCPD. Role of pancreatic enzyme replacement on glycemic control in diabetes with exocrine pancreas defect needs investigation.

Fibrocalculous pancreatic diabetes with hemorrhagic pericardial effusion in a female—a rare case report

Fibrocalculous pancreatic diabetes (FCPD) is a unique form of diabetes due to non-alcoholic chronic pancreatitis peculiar to tropical countries. The hallmark features are younger age of onset pain abdomen and presence of pancreatic calculi. Though etiology remains unclear but on long-term follow-up, patient may develop microvascular and macrovascular complication. Chances of progression to malignancy are also high which carries poor prognosis. We present a case of a 36-year-old female presenting with recurrent abdominal pain, diabetes and chronic calcific pancreatitis. She was diagnosed to have FCPD based on her findings. She was managed with insulin, pancreatic enzyme supplementation and analgesics for pain relief. Due to her intractable pain poorly responding to medical management, she underwent Roux-en-Y pancreaticojejunostomy but later developed massive pericardial effusion hemorrhagic in nature with pleural effusion and ascitis. Analysis showed high possibility of adenocarcinoma though the primary focus could not be confirmed as the patient developed sepsis and unfortunately succumbed to her illness. Though FCPD is a rare entity, it is important to rule out chronic calcific pancreatitis as underlying etiology in all patients of diabetes presenting with recurrent pain abdomen and also to periodically screen FCPD patients for pancreatic malignancy. This helps to prevent progression to complications by an early medical intervention. Surgical intervention may be considered an option in case of failure of medical management, though data of its usefulness is very rare.

Fibrocalculous pancreatic diabetes in Bangladeshi children and adolescents—a not so rare form of secondary diabetes

Fibrocalculous pancreatic diabetes (FCPD) is a unique form of diabetes with classic triad of abdominal pain, pancreatic calculi, and diabetes. This study was undertaken to identify the clinical characteristics in newly diagnosed children and adolescents with FCPD and compare them with children with Type 1 diabetes (T1D). The study was carried out at the Changing Diabetes in Children (CDiC) Diabetes Clinic of tertiary care hospital, BIRDEM in Bangladesh. All patients underwent abdominal X-rays and careful analysis of history of abdominal pain to differentiate the two diagnoses. Pancreatic auto antibodies were not available. Four hundred twenty-nine patients were aged under 18 years at diabetes presentation: 106 (25%) fulfilled the criteria for FCPD and 323 (75%) for T1D. When comparing FCPD with T1D at diagnosis, it was found that they were older (median age 14.0 [IQR 12.0–15.0] years vs 12.0 [IQR 10.0–14.0] years (p < .0001)). Few had a positive family history of diabetes (31% vs 48% (p = .002)). DKA was less common (4 vs 12% (p = .020)). HbA1c was higher (13.6 ± 4.2% (125 ± 22) vs 12.1 ± 3.4% (109 ± 14) (p = .001)). More FCPD patients had atypical symptoms compared to T1D (25 vs 14%, (p = .010)). The median duration of symptoms was significantly longer (3.0[1.0–6.0] vs 1.0[1.0–2.0] months (p = .0001)). Cataracts were more common in FCPD (9 vs 3% (p = .010)). The median dose of insulin was higher in FCPD patients than T1D (1.41[0.91–2.03] vs 1.02[0.78–1.48] (p = .0001)). In addition to pancreatic calcification, FCPD showed atypical symptoms with longer prodrome and higher HbA1c than T1D.

High Prevalence of Serine Protease Inhibitor Kazal Type 1 Gene Variations Detected by Whole Gene Sequencing in Patients with Fibrocalculous Pancreatic Diabetes.

Aim of Study:The aim is to study the prevalence and pattern of serine protease inhibitor Kazal type 1 (SPINK1) gene variations in patients with fibrocalculous pancreatic diabetes (FCPD) using whole gene sequencing.Materials and Methods:A total of 56 consecutive patients of FCPD were recruited for the study. Diagnosis of FCPD was based on the presence of diabetes mellitus in patients having chronic pancreatitis with radiological evidence of ductal calcifications, in the absence of other known causes for pancreatitis. Ethylenediaminetetraacetic acid samples were collected from all patients, and complete gene sequencing was performed for SPINK1 gene using Sanger technique.Results:Overall 35 patients (62.5%) were detected to have genetic alterations in SPINK1 gene. N34S polymorphism was seen in 23 participants (41.07%) out of which 3 were homozygous. N34S was seen to be in linkage disequilibrium with IVS1 − 37T>C (18/23) and IVS3-69insAAAA (19/23) polymorphisms. Seven patients (12.5%) had a 272 C>T 3'UTR polymorphism while one patient (1.8%) had a P55S polymorphism. Two patients (3.5%) had an IVS3 + 2T>C mutation which has been shown to be associated with loss of function of SPINK protein. Overall 48.2% of FCPD patients had genetic variations that were significant compared to the control population. There was no difference in anthropometric and biochemical parameters between those with or without SPINK1 gene variations.Conclusions:Variations in SPINK1 gene are frequently observed in FCPD. N34S polymorphism was the most common variation followed by intronic variations. Two patients had the pathogenic intronic IVS3 + 2T>C mutation. Whole gene sequencing of the SPINK1 gene enabled detection of an additional 7.1% of patients with significant SPINK1 gene variations as compared to targeted screening for the N34S variation.

TCF7L2 gene polymorphisms do not predict susceptibility to diabetes in tropical calcific pancreatitis but may interact with SPINK1 and CTSB mutations in predicting diabetes.

BackgroundTropical calcific pancreatitis (TCP) is a type of chronic pancreatitis unique to developing countries in tropical regions and one of its important features is invariable progression to diabetes, a condition called fibro-calculous pancreatic diabetes (FCPD), but the nature of diabetes in TCP is controversial. We analysed the recently reported type 2 diabetes (T2D) associated polymorphisms in the TCF7L2 gene using a case-control approach, under the hypothesis that TCF7L2 variants should show similar association if diabetes in FCPD is similar to T2D. We also investigated the interaction between the TCF7L2 variants and N34S SPINK1 and L26V CTSB mutations, since they are strong predictors of risk for TCP.MethodsTwo polymorphisms rs7903146 and rs12255372 in the TCF7L2 gene were analyzed by direct sequencing in 478 well-characterized TCP patients and 661 healthy controls of Dravidian and Indo-European ethnicities. Their association with TCP with diabetes (FCPD) and without diabetes was tested in both populations independently using chi-square test. Finally, a meta analysis was performed on all the cases and controls for assessing the overall significance irrespective of ethnicity. We dichotomized the whole cohort based on the presence or absence of N34S SPINK1 and L26V CTSB mutations and further subdivided them into TCP and FCPD patients and compared the distribution of TCF7L2 variants between them.ResultsThe allelic and genotypic frequencies for both TCF7L2 polymorphisms, did not differ significantly between TCP patients and controls belonging to either of the ethnic groups or taken together. No statistically significant association of the SNPs was observed with TCP or FCPD or between carriers and non-carriers of N34S SPINK1 and L26V CTSB mutations. The minor allele frequency for rs7903146 was different between TCP and FCPD patients carrying the N34S SPINK1 variant but did not reach statistical significance (OR = 1.59, 95% CI = 0.93–2.70, P = 0.09), while, TCF7L2variant showed a statistically significant association between TCP and FCPD patients carrying the 26V allele (OR = 1.69, 95% CI = 1.11–2.56, P = 0.013).ConclusionType 2 diabetes associated TCF7L2 variants are not associated with diabetes in TCP. Since, TCF7L2 is a major susceptibility gene for T2D, it may be hypothesized that the diabetes in TCP patients may not be similar to T2D. Our data also suggests that co-existence of TCF7L2 variants and the SPINK1 and CTSB mutations, that predict susceptibility to exocrine damage, may interact to determine the onset of diabetes in TCP patients.

Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene with tropical calcific pancreatitis

BackgroundThe genetic basis of tropical calcific pancreatitis (TCP) is different and is explained by mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. However, mutated SPINK1 does not account for the disease in all the patients, neither does it explain the phenotypic heterogeneity between TCP and fibro-calculous pancreatic diabetes (FCPD). Recent studies suggest a crucial role for pancreatic renin-angiotensin system during chronic hypoxia in acute pancreatitis and for angiotensin converting enzyme (ACE) inhibitors in reducing pancreatic fibrosis in experimental models. We investigated the association of ACE gene insertion/deletion (I/D) polymorphism in TCP patients using a case-control approach. Since SPINK1 mutations are proposed a modifier role, we also investigated its interaction with the ACE gene variant.MethodsWe analyzed the I/D polymorphism in the ACE gene (g.11417_11704del287) in 171 subjects comprising 91 TCP and 80 FCPD patients and compared the allelic and genotypic frequency in them with 99 healthy ethnically matched control subjects.ResultsWe found 46% and 21% of TCP patients, 56% and 19.6% of FCPD patients and 54.5% and 19.2% of the healthy controls carrying the I/D and D/D genotypes respectively (P>0.05). No significant difference in the clinical picture was observed between patients with and without the del allele at the ACE in/del polymorphism in both categories. No association was observed with the presence or absence of N34S SPINK1 mutation in these patients.ConclusionWe conclude that the ACE insertion/deletion variant does not show any significant association with the pathogenesis, fibrosis and progression of tropical calcific pancreatitis and the fibro-calculous pancreatic diabetes.

Prevalence of diabetic complications in fibrocalculous pancreatic diabetic patients and type 2 diabetic patients: A cross-sectional comparative study

Objective To determine the prevalence of diabetes-related complications in subjects with fibrocalculous pancreatic diabetes (FCPD) and compare them with subjects with type 2 diabetes mellitus matched for age, sex, and duration of diabetes. Methods The study group comprised of 277 FCPD patients and 277 age, sex, and duration of diabetes-matched type 2 diabetic patients. All the study subjects underwent a detailed clinical examination, and fasting blood samples were obtained for biochemical studies. Peripheral Doppler was used for diagnosis of peripheral vascular disease (PVD). Vibratory perception threshold (VPT) was determined using biothesiometry for diagnosis of neuropathy. Diagnosis of coronary artery disease (CAD) was based on medical history and 12-lead resting ECG. Retinal photographs were used for diagnosis of retinopathy using a modified version of Early Treatment Diabetic Retinopathy Study (ETDRS) grading system. Results FCPD patients had lower body mass index (BMI) ( P<.001), systolic blood pressure ( P<.0001), diastolic blood pressure ( P<.001), serum cholesterol ( P<.001), serum triglyceride ( P<.001), and serum creatinine ( P<.01) but higher glycosylated hemoglobin ( P<.001) levels compared to patients with type 2 diabetes. Prevalence of CAD was significantly higher among type 2 diabetic patients (11.9%) compared to FCPD patients (5.1%), P<.003. There was no significant difference in the prevalence of other diabetic complications between the two study groups (type 2 diabetes vs. FCPD: retinopathy—37.2% vs. 30.1%, PVD—4.3% vs. 4.7%, Neuropathy—25.3% vs. 20.9%, Nephropathy—15.0% vs. 10.1%). Multiple logistic regression analysis revealed the following risk factors for diabetes complications among type 2 diabetic subjects—retinopathy: BMI ( P=.028), duration of diabetes ( P<.001), and glycosylated hemoglobin ( P=.026); nephropathy: diastolic blood pressure ( P=.016) and glycosylated hemoglobin ( P=.040); neuropathy: age ( P<.001), duration of diabetes ( P=.003), and glycosylated hemoglobin ( P=.001). Among subjects with FCPD, systolic blood pressure ( P=.013), glycosylated hemoglobin ( P=.021), and duration of diabetes ( P<.001) were associated with retinopathy; BMI ( P=.057), glycosylated hemoglobin ( P=.010), and duration of diabetes ( P=.024) with nephropathy and age ( P=.011) and BMI ( P=.010) with neuropathy. Conclusion: The prevalence of retinopathy, nephropathy, neuropathy, and PVD was similar among FCPD patients and type 2 diabetic patients, but the prevalence of CAD was lower among FCPD patients.

Histopathology and immunohistochemistry of pancreatic islets in fibrocalculous pancreatic diabetes

The histopathology of Fibrocalculous Pancreatic Diabetes (FCPD) has been extensively studied, but there are no reports on alteration in patterns of hormone secreting cells using immunohistochemistry in islets of FCPD patients. In this study, we report on the histopathology and immunohistochemistry of islets of FCPD patients and its possible correlation with the clinical picture. Pancreatic biopsies were carried out in six patients with FCPD at the time of surgery for abdominal pain. Routine histopathology and immunohistochemistry studies were carried out with six primary antibodies namely insulin, glucagon, pancreatic polypeptide (PP), somatostatin, vasoactive intestinal peptide and gastrin. Histopathology of the pancreas showed a spectrum of changes ranging from moderate to severe atrophy, fibrosis of the parenchyma and degeneration of the ducts. Nesidioblastosis was present in three patients. Immunohistochemical studies showed a decrease in the number of islets but some patients showed evidence of hyperplasia. There was an overall decrease in the percent of insulin cells and the positivity in the islets correlated with plasma C-peptide levels and the duration of diabetes. There was no consistent relationship with glucagon with some patients showing increased and other decreased positivity. There was a marked decrease in PP and somatostatin positivity, the significance of which is not clear. The reduction, but partial preservation of insulin positivity is consistent with the ketosis resistance shown by patients with Fibrocalculous Pancreatic Diabetes.

Pancreatitis in fibrocalculous pancreatic diabetes mellitus is not associated with common mutations in the trypsinogen gene

A distinct type of pancreatitis associated with diabetes, termed fibrocalculous pancreatic diabetes (FCPD), has been reported in tropical developing countries including Bangladesh. The molecular basis for autosomal dominant hereditary pancreatitis (HP) has recently been attributed to mutations in exons 2 and 3 of the trypsinogen gene. We have investigated the hypothesis that mutations in the aforementioned exons of this gene might also predispose to FCPD. Seventy Bangladeshi and 50 South Indian unrelated FCPD patients and seven South Indian families with FCPD probands were studied. Pancreatic calcification was confirmed by abdominal X-ray, ultrasound and/or ERCP. Established mutations of exons 2 and 3 of the trypsinogen gene were studied in these subjects by PCR-RFLP analysis and DNA sequencing. The mutations found in hereditary pancreatitis were not observed in this collection of FCPD subjects, and complete DNA sequencing of exons 2 and 3 of the fourth cationic trypsinogen gene also excluded any new mutations. These results indicate that chronic pancreatitis of FCPD is unlikely to be caused by common mutations in the trypsinogen gene.

Ketosis resistance in fibrocalculous pancreatic diabetes: II. Hepatic ketogenesis after oral medium-chain triglycerides

A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not become ketotic even in adverse conditions. It is not clear whether this ketosis resistance is due to reduced, fatty acid release from adipose tissue or to impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and compared it with that in matched insulin-dependent diabetes mellitus (IDDM) patients and healthy controls. After oral MCTs, FCPD patients, showed only a mild increase in blood 3-hydroxybutyrate (3-HB) concentrations (median: fasting, 0.13 mmol/L; peak, 0.52) compared with IDDM patients (fasting, 0.44; peak, 3.39) and controls (fasting, 0.04; peak, 0.75). Plasma nonesterified fatty acid (NEFA) concentrations were comparable in the two diabetic groups (FCPD: fasting, 0.50 mmol/L; peak, 0.79; IDDM: fasting, 0.91; peak, 1.04). Plasma C-peptide concentrations were low and comparable in the two diabetic groups. Plasma glucagon concentrations were higher in IDDM patients in the fasting state, but declined to levels comparable to those in FCPD patients after oral MCTs. Plasma carnitine concentrations were comparable in the two groups of patients. It is concluded that the failure to stimulate ketogenesis under these conditions could be partly due to inhibition of a step beyond fatty acid entry into the mitochondria.

Autonomic Dysfunction in Non‐insulin‐dependent Diabetes Mellitus and Fibrocalculous Pancreatic Diabetes in South India

The prevalence of cardiovascular autonomic dysfunction in non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and fibrocalculous pancreatic diabetes (FCPD) was assessed by a standard battery of autonomic dysfunction tests involving heart rate responses and blood pressure responses. Three hundred and thirty-six patients with NIDDM and 40 patients with FCPD were studied. Logistic regression analysis was done to look for risk factors associated with autonomic dysfunction. Abnormalities of autonomic function tests were detected in 120 NIDDM patients (35.7 %) and 9 FCPD patients (22.5 %). There was no significant difference in severity of autonomic dysfunction between NIDDM and FCPD groups. There was an increase in prevalence of autonomic dysfunction with age and duration of diabetes both in NIDDM and FCPD. In the 0–5 years duration group, 28.2 % of NIDDM and 16.6 % of FCPD had evidence of disordered autonomic function and these figures increased to 56.2 % and 60 % respectively, after 16–20 years duration of diabetes. Logistic regression analysis showed that only peripheral dysfunction was associated with autonomic dysfunction in NIDDM patients (r = 0.66, p = 0.02).

Autonomic dysfunction in non-insulin-dependent diabetes mellitus and fibrocalculous pancreatic diabetes in south India.

The prevalence of cardiovascular autonomic dysfunction in non-insulin-dependent (Type 2) diabetes mellitus (NIDDM) and fibrocalculous pancreatic diabetes (FCPD) was assessed by a standard battery of autonomic dysfunction tests involving heart rate responses and blood pressure responses. Three hundred and thirty-six patients with NIDDM and 40 patients with FCPD were studied. Logistic regression analysis was done to look for risk factors associated with autonomic dysfunction. Abnormalities of autonomic function tests were detected in 120 NIDDM patients (35.7%) and 9 FCPD patients (22.5%). There was no significant difference in severity of autonomic dysfunction between NIDDM and FCPD groups. There was an increase in prevalence of autonomic dysfunction with age and duration of diabetes both in NIDDM and FCPD. In the 0-5 years duration group, 28.2% of NIDDM and 16.6% of FCPD had evidence of disordered autonomic function and these figures increased to 56.2% and 60% respectively, after 16-20 years duration of diabetes. Logistic regression analysis showed that only peripheral dysfunction was associated with autonomic dysfunction in NIDDM patients (r = 0.66, p = 0.02).

Comparison of anti-human insulin antibodies detection by commercial enzyme-linked immunosorbent assay kit, displacement enzyme-linked immunosorbent assay and radioimmunoassay, in Thai diabetic patients

Antibodies specific to human insulin, in sera of Thai diabetic patients and normal healthy individuals, were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit, displacement ELISA and radioimmunoassay (RIA). Among 36 insulin-treated patients, the antibodies were detected in 22, 23 and 20 individuals, by RIA, commercial ELISA kit and displacement ELISA, respectively. Among those who had never previously received insulin therapy, RIA showed positive results in 5/11 patients with insulin-dependent diabetes mellitus (IDDM) and 1 2 patients with fibrocalculous pancreatic diabetes (FCPD); but were negative in all 26 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 30 normal healthy individuals. The commercial ELISA kit could detect such insulin autoan-tibodies (IAA) in 4 11 IDDM, 3 26 NIDDM, 2 2 FCPD patients and 4 30 normal controls; while the displacement ELISA showed positive IAA detection in 5 11 IDDM, 2 26 NIDDM, 2 2 FCPD and 2 30 normal controls. By using RIA as the ‘gold standard’, the commercial ELISA kit had 92.86% sensitivity, 87.01% specificity, 88.57% accuracy, 72.22% positive predictive value and 97.10% negative predictive value; while these indices for the displacement ELISA were 85.71%, 90.01%, 89.52%, 77.42% and 94.59%, respectively.

Nutritional profile of fibrocalculous pancreatic diabetes and primary forms of diabetes seen in Southern India

Plasma levels of retinol binding protein (RBP), prealbumin, total protein, albumin, transferrin and ferritin were estimated in three groups of diabetic patients seen at a diabetes centre in S. India. The groups consisted of patients with fibrocalculous pancreatic diabetes (FCPD), non-insulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM). Mean RBP levels were lower in FCPD and IDDM patients compared to controls but this did not reach statistical significance. Prealbumin levels were normal in FCPD patients, but low in IDDM compared to controls (P less than 0.005) and NIDDM (P less than 0.05). FCPD patients had lower transferrin levels compared to controls (P less than 0.05). There were no differences in the levels of total protein, albumin and ferritin in any of the study groups. The study shows that biochemical evidence of undernutrition is seen in FCPD and IDDM patients while NIDDM patients are not significantly different from non-diabetic control subjects.

Anthropometric studies in diabetes in the Tropics

Anthropometric studies were carried out in three groups of diabetics seen in southern India, namely fibrocalculous pancreatic diabetes (FCPD) (n = 49) (a subtype of malnutrition related diabetes), insulin dependent diabetes mellitus (IDDM) (n = 55) and non-insulin dependent diabetes mellitus (NIDDM) (n = 104). Both FCPD and IDDM had significantly lower body mass index, skinfold thickness (triceps, biceps, subscapular and suprailiac), mid-arm circumference and fat mass compared to controls and NIDDM patients, (p less than 0.001 for all parameters). FCPD and IDDM males did not show any significant differences in any of the anthropometric parameters studied. Among the females, FCPD had lower triceps skinfold measurements (p = 0.007) and mid-arm circumferences (p less than 0.05) compared to IDDM patients. Patients with NIDDM did not show any significant difference compared to the control group. This study shows that both FCPD and IDDM patients have lower body mass and fat mass compared to NIDDM patients and control subjects.