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.

The seroprevalence of immunoglobulin A transglutaminase in type 1 diabetic patients of South Indian origin.

CONTEXT: Celiac disease (CD) is a commonly encountered autoimmune condition in patients with type 1 diabetes (T1D). There is sparse data on the seroprevalence of immunoglobulin A (IgA) transglutaminase (tTG) in T1D patients of South Indian origin. AIMS: To detect the prevalence of IgA tTG in T1D patients of South Indian origin. To evaluate the relation between the presence of autoimmunity and metabolic control and complications of diabetes. MATERIALS AND METHODS: We conducted a cross-sectional study on 258 T1D patients. All the patients were subjected to biochemical tests and evaluated for microvascular complications. IgA tTG was estimated by ELISA. IgA tTG levels >40 AU/ml was considered positive. RESULTS: Of the 258 participants, 12 (4.65%) were found to be positive for IgA tTG antibodies. Distribution of IgA positivity was equal in both sexes. There was a significant negative correlation of IgA tTG positivity with hemoglobin and glycated hemoglobin (HbA1c). CONCLUSIONS: The seropositivity of CD in South Indian patients with T1D has been observed to be 4.68%. This is much lower compared to studies from North India. This can be explained by both the genetic and dietary factors. The seropositivity correlated negatively with hemoglobin and HbA1c.

Pancreatic exocrine insufficiency in type 1 and type 2 diabetics of Indian origin.

BACKGROUND: Pancreatic exocrine insufficiency has been frequently described in both type 1 and type 2 diabetes. Fecal elastase test has been demonstrated to have good correlation with direct tests for exocrine function, especially in moderate to severe cases. There are no data on the prevalence of pancreatic exocrine insufficiency in Indian patients with diabetes utilizing FEC concentrations. The objective of our study is to evaluate the prevalence of pancreatic exocrine insufficiency (PEI) in type 1 and type 2 diabetes and study the impact of PEI on glycemic control and metabolic parameters in diabetes. METHODS AND MATERIALS: We conducted a cross sectional study on 89 T1D, 95 T2D patients and 90 healthy controls. Biochemical parameters including FBS, HbA1c, serum albumin and serum calcium were estimated. Fecal elastase concentrations (FEC) were estimated by ELISA. Patients with FEC <200 µg/g were considered to have pancreatic exocrine insufficiency. RESULTS: The prevalence of PEI was 31.4% in T1D, 29.4% in T2D and 4.4% in controls (P < 0.01). A significant negative correlation was observed between FEC levels and, both FBS and HbA1c in diabetic patients. There was also a significant positive correlation between BMI and FEC. There was no significant association between low FEC and other biochemical parameters. CONCLUSION: Nearly one third of patients with both T1D and T2D showed evidence of impaired exocrine function utilizing FEC test. Presence of PEI correlated with lower BMI and higher HbA1c.