Prevalence and clinical profile of celiac disease in type 1 diabetes mellitus in north India

Background and Aim: There is scanty data on the occurrence of celiac disease in patients with type 1 diabetes mellitus in South Asia. Our aim was to study the prevalence and clinical profile of celiac disease in patients with type 1 diabetes mellitus in a tertiary care referral centre in north India. Methods: Consecutive patients of type 1 diabetes mellitus attending the Endocrine clinic of our institute between January 2002 and December 2008 were screened using anti‐tissue transglutaminase antibodies (tTGAb), and those positive were subjected to duodenal biopsy. Clinical profile of these patients was recorded. Results: Out of 189 patients of type 1 diabetes mellitus, 21 (11.1%) were diagnosed to have celiac disease on the basis of positive serology (tTGAb) and duodenal histology. The mean age at diagnosis of diabetes was 10.81 ± 7.3 years and that of celiac disease was 13.74 ± 5.71 years, with a difference of 5.18 ± 4.75 years between the two. Only 2/21 patients with celiac disease had been diagnosed before detection of diabetes mellitus. Short stature was the commonest (52.3%) manifestation of celiac disease, followed by anemia (47.3), weight loss (42.8%), diarrhea (28.6%) and abdominal pain (14.2%). After initiating gluten free diet, 14/16 symptomatic patients had reversal of anemia, weight loss and diarrhea. Growth rate velocity improved from 2.3 ± 1.0 cm/year to 5.5 ± 2.4 cm/year in those with short stature. Conclusion: Celiac disease is highly prevalent in patients with type 1 diabetes mellitus (11.1%) and majority of them (90.5%) were diagnosed on screening. Routine screening is required for early diagnosis and combat associated co‐morbidities.     

Celiac crisis with hypokalemic paralysis in a young lady.

Celiac crisis presents as severe acute diarrhea with life-threatening metabolic derangement in a patient with celiac disease. We report a 30-year-old lady who was admitted with one-month history of worsening small bowel-type diarrhea. She developed acute quadriparesis due to refractory hypokalemia. Celiac disease was diagnosed on the basis of positive serology and histological features. She improved with aggressive correction of hypokalemia and gluten-free diet. Celiac crisis is a rare presentation of this heterogeneous disease in adulthood.     

Adult celiac disease presented with celiac crisis: severe diarrhea, hypokalemia, and acidosis

An acute severe onset of celiac disease is very uncommon in adults. We describe a patient with adult celiac disease who presented with acute diarrhea that lead rapidly to a life threatening hypokalemia and acidosis, the so-called celiac crisis. Celiac crisis, described mainly in children younger than two years of age, has become very rare due to earlier diagnosis and effective therapy of the disease. The case described is an example of the heterogeneous clinical course of celiac disease and emphasizes the need to consider it in the differential diagnosis, even in adults suffering from acute diarrhea and acidosis.     

Celiac disease--a severe disease

Celiac disease (Celiacal sprue = gluten-sensitive enteropathy = netropic sprue) is the all-life genetically determined autoimmune disease with permanent intolerance to gluten, which damages the intestinal mucous membrane and alterates the immune system. The atrophy and typical inflammatory changes of mucous membrane results in malabsorption with diarrhea, general weakness, anemia and weight loss. The clinical picture of celiac disease is considerably heterologous. Only 20-30% of patients suffer from active-classical form of the disease. Non-diagnosed, inactive forms of the disease form 70-80% of cases of celiac disease in adult individuals. The therapy is based on diet without gluten. Application of the diet usually results in clinical improvement and signs of the disease are diminished. The relapse of celiac disease occurs after a gluten load. Celiac disease and dermatitis Duhring are considered to be two equal forms how gluten enteropathy becomes manifest. Celiac disease is often associated with other autoimmune diseases (e.g. insulin-dependent diabetes mellitus, autoimmune thyreoiditis). Untreated celiac disease still represents a serious medical risk, since it is an important precancerosis. Introduction of highly sensitive methods for the determination of antibodies against endomysium and tissue transglutaminase significantly extended possibilities of diagnosis and screening for celiac disease. It became obvious that the real incidence of celiac disease including the non-diagnosed forms of the disease in the European population is greater than 1:200 to 1:250.     

Spontaneous Normalization of Anti-Tissue Transglutaminase Antibody Levels Is Common in Children with Type 1 Diabetes Mellitus

Background  

The prevalence of celiac disease among type 1 diabetes mellitus (T1DM) patients is 5–10 times higher than in the general population. Thus, evaluation of celiac serology is indicated at diagnosis of T1DM and on follow up.     

Celiac Disease in an Adult Turkish Population with Type 1 Diabetes Mellitus

Celiac disease is a frequent cause of morbidity among patients with type 1 diabetes mellitus. In this study our objective was to determine the prevalance of celiac diasease in a Turkish adult population with type 1 diabetes mellitus. Patients included 122 type 1 diabetes cases from adult diabetes clinic. Total IgA and IgA-antiendomysial antibody (AEA) assays were performed. Patients positive for IgA-AEA were asked to undergo small intestinal biopsy. Of the 122 patients, none was IgA deficient and 3 had positive IgA-AEA results (2.45%). All three of these patients had biopsies diagnostic of celiac disease. The body mass index (BMI) values of patients with positive AEA were significantly lower than normal (P = 0.024). Among the gastrointestinal complaints there was an association between early satiety and AEA positivity (P = 0.02). None of the other gastrointestinal complaints or age, duration of diabetes, glycosylated hemoglobin values, or insulin doses used were found to be related to AEA positivity. Celiac disease has a high prevalence among Turkish paients with type 1 diabetes mellitus. Screening for IgA-AEA during routine investigations of type 1 diabetic patients is important to prevent celiac-associated symptoms.     

Type 1 diabetes and celiac disease in adults: glycemic control and diabetic complications

The prevalence of celiac disease (CD) in patients with type 1 diabetes mellitus (T1DM) is 4.5 %. Objective of the study is to investigate (1) the course of glycemic control at CD diagnosis and after the initiation of a gluten-free diet (GFD) in T1DM patients; (2) the prevalence of diabetic complications in T1DM patients with adult onset of CD. In 20 hospitals in the Netherlands, we identified T1DM patients diagnosed with CD at adult age. We retrospectively collected glycated hemoglobin (HbA1c) levels before CD diagnosis, at CD diagnosis, and the most recent HbA1c levels as well as the presence of nephropathy and retinopathy. The control group consisted of patients with T1DM and negative CD serology matched for age, gender, T1DM duration, and HbA1c levels. Thirty-one patients were eligible with a median duration of T1DM and CD of 27 years (IQR 14–37) and 3 years (IQR 1–8), respectively. The matched control group consisted of 46 patients. HbA1c levels at the moment of CD diagnosis were 7.5 % (IQR 7.1–8) [58 mmol/mol] and at the most recent visit 7.4 % (IQR 6.9–7.9, P = 0.15) [57 mmol/mol] indicating no difference. Prevalence of retinopathy was lower in T1DM + CD group compared with controls, (38.7 vs 67.4 %, P < 0.05), whereas no difference in the prevalence of nephropathy was found between the groups (P = 0.09). In conclusion, T1DM + CD patients have less retinopathy compared to T1DM patients without CD. A GFD possibly favorable affects the development of vascular complications in T1DM patients.     

Vitamin D deficiency and the associated factors in children with type 1 diabetes mellitus in southern Iran

Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder caused by destruction of beta cells of the pancreas. Several reports have suggested a connection between vitamin D deficiency and T1DM and the possible role of dietary vitamin D supplementation in reducing the risk of T1DM. There is little knowledge about the prevalence of vitamin D deficiency among Iranian children with T1DM. Serum 25-hydroxy vitamin D (25OHD) was assayed by high performance liquid chromatography in 8–18-year-old diabetic patients referred to pediatric diabetes clinics in Shiraz, Iran, during a period of 14 months. The age of the onset of T1DM, daily insulin usage, weight, height, and BMI of each patient were recorded along with levels of physical activity and sun exposure. The patients’ body composition was determined by DEXA and used in further analysis. This study was conducted on 39 diabetic boys and 46 diabetic girls aged 12.4 ± 4.2 years. Mean serum 25(OH)D3 was 18 ± 12.2 ng/dl. Serum levels of 25(OH)D3 were higher in boys than girls. 7.7 % of the boys and 30.4 % of the girls had severe vitamin D deficiency. There was a negative correlation between the age of the onset of T1DM and serum concentration of 25(OH)D3 (p = 0.006, r = ?0.17). Girls with T1DM showed a higher prevalence of severe vitamin D deficiency than boys with T1DM. Moreover, vitamin D deficiency was more prevalent in individuals with earlier onset of the disease and in those with higher fat mass index.     

Human leukocyte antigen (HLA)-DQ2 and -DQ8 haplotypes in celiac,celiac with type 1 diabetic,and celiac suspected pediatric cases

Celiac disease (CD) is an autoimmune enteropathy triggered by ingestion of gluten present in wheat, barley, and rye. Gluten along with environmental trigger starts an inflammatory reaction which results in damage to small intestine. Human leukocyte antigen (HLA)-DQA1∗05, -DQB1∗02, and -DQB1∗03:02 are the known risk alleles of CD. The diagnostic method for CD involves serological or intestinal biopsy, but genetic test could be implemented. HLA typing precludes the need for further diagnosis and it has high negative predictive value. The aim of this study was to make aware of HLA molecular typing for celiac disease among local laboratories and healthcare professionals. The prevalence and frequency distribution of HLA-DQ2 and -DQ8 haplotypes in 175 pediatric unrelated healthy controls, celiac patients, and CD with concurrent diabetes mellitus type 1 (DM1) was evaluated. The most common haplotype was DQ2 followed by DQ8. In control group only DQ2 was observed with frequency of 8.5%. In celiac patients 85.7% were DQ2, 11.4% were DQ8, and rest were DQ2/DQ8 (2.8%), and all had CD. In the group of CD with DM1, 31.4% had DQ2, 25% had DQ8, and 34% having both the haplotypes; while only 9 of these patients were suffering from CD. It was concluded that Celiac disease is frequently unrecognized by physicians, in part because of its variable clinical presentation and symptoms. Thus genetic testing for celiac disease could be an additive tool for diagnosis to exclude ambiguity.     

Celiac disease and autoimmune diseases or systemic disease. Six cases and a review of the literature

BACKGROUND: Celiac disease is an autoimmune disorder which may be associated with another autoimmune or systemic disease. OBJECTIVE: To determine the links between autoimmune diseases and celiac disease. PATIENTS AND METHODS: Among 31 patients with a celiac disease, we selected those who had another autoimmune or systemic disease. RESULTS: We report 6 patients with such disease association: 3 with autoimmune thyroiditis including one also with Grave's disease, 2 with systemic lupus erythematosus including one also with insulin-dependent diabetes mellitus, and 1 with temporal arteritis. CONCLUSION: The link between celiac disease and autoimmune thyroiditis or insulin-dependent diabetes mellitus seems to be real but many discrepancies are observed for the other autoimmune diseases. After a literature review, we suggest a summary of effective associations between celiac disease and autoimmune or systemic diseases.     

The prevalence of manifest and latent celiac disease in type 1 diabetes mellitus.

BACKGROUND/AIMS: Celiac disease and type 1 diabetes mellitus are both autoimmune diseases which have a common genetic predisposition. The aim of this study was to determine the prevalence of manifest and latent celiac disease in type 1 diabetic patients. METHODS: Anti-endomysium IgA was tested by indirect immunofluorescence using sections of human umbilical cord for screening in 100 adult patients with type 1 diabetes mellitus and in 80 age and sex matched controls with no known disease. Distal duodenal biopsy, human leukocyte antigen typing, urinary D-xylose excretion test, stool analysis, biochemistry profile, blood counts, serum ferritin level and small intestinal radiography were performed in anti-endomysium IgA positive cases. Small bowel biopsy specimens consistent with celiac disease were defined as manifest celiac disease, while positive antiendomysium IgA and normal intestinal histology with the presence of human leukocyte antigen class II antigens consistent with the disease were defined as latent celiac disease. RESULTS: Anti-endomysium IgA was positive in eight diabetic patients, while it was negative in all controls. Celiac disease was found in a total of six (6%) patients, four with manifest and two with latent disease. Only one patient had symptoms. CONCLUSIONS: The prevalence of celiac disease is increased in patients with type 1 diabetes mellitus. Since many patients may be asymptomatic, it is suggested that all diabetic patients should be screened for this disease.     

Biopsy-defined adult celiac disease in Asian-Canadians.

Celiac disease is thought to be a genetically based disorder reported mainly from European countries as well as countries to which Europeans have emigrated, including North America. This report documents a clinical experience of biopsy-defined celiac disease in 14 Asians diagnosed since 1988 in a single Canadian teaching hospital. Eleven were Indo-Canadians, including 10 of Punjabi descent. Other ethnic groups were also represented, including two Japanese and one Chinese patient. Abdominal pain was the most frequent presenting symptom. Anemia, particularly associated with a deficiency of iron was common, along with diarrhea and weight loss. Endoscopic studies documented lymphocytic gastric and colonic mucosal changes in over one-third of the cases while antibodies for tissue transglutaminase were positive in all patients tested. Dermatitis herpetiformis, diabetes mellitus and autoimmune liver disease were also documented. These findings indicate for the first time that adult celiac disease occurs in Asian populations living in North America, particularly in those of Punjabi descent.     

Celiac sprue

Celiac sprue, celiac disease, or gluten-sensitive enteropathy, is a malabsorption disorder of the small intestine that occurs after ingestion of wheat gluten in genetically susceptible individuals. This disease is characterized by intestinal malabsorption associated with villous atrophy of the small intestinal mucosa, clinical and histological improvement after adherence to strict gluten free diet, and relapse when gluten is reintroduced. Celiac sprue has a high prevalence in Western Europe and North America where it is estimated to affect 1:120 to 1:300 individuals. The pathogenesis of celiac sprue is related to inappropriate intestinal T-cell activation in HLA-DQ2 positive individuals triggered by antigenic peptides from wheat gluten or prolamins from barley and rye. Although previously thought to be mainly a disease of childhood onset, the diagnosis is increasingly being made in adults. There are a wide variety of presentations, which range from asymptomatic forms to severe diarrhea, weight loss and nutritional deficiencies. Extraintestinal manifestations including anemia, osteopenia or neurological disorders and associated conditions such as diabetes or hypothyroidism are commonly present. The availability of highly sensitive and specific serologic markers has dramatically facilitated the diagnosis of celiac sprue. However, the demonstration of characteristic histological abnormalities in a biopsy specimen of the small intestine remains the mainstay of diagnosis. Treatment consists of life-long avoidance of dietary gluten to control symptoms and to prevent both immediate and long-term complications.     

Type 1 diabetes mellitus and celiac disease: endothelial dysfunction

Many reports indicate a hypercoagulative state in diabetes mellitus as result of endothelial damage. Experimental evidence suggests that a metabolic derangement triggers a cascade of biochemical events that lead to vascular dysfunction. The net effect is to convert the endothelium from thromboresistant to thrombogenic surface. In literature, a strong association between type 1 diabetes mellitus (DM1) and celiac disease (CD) has been reported. We do not have information about the hemostatic system in these associated conditions. Our study aims at evaluating whether the presence of CD in a group of DM1 patients is associated with a different expression of some hemostatic factors and with a different manifestation and/or progression of microvascular complications of DM1 in comparison with patients with only diabetes. Ninety-four adult DM1 patients were enrolled in the study and subsequently screened for CD. Anti-endomysial antibodies (EMA) were positive in 13 of 94 DM1 patients (13.8%). CD diagnosis was confirmed by histology and organ culture. The mean age and duration of DM1 of patients also affected by CD were similar to those of only diabetic patients, but the metabolic control and the hemocoagulative parameters were significantly different between the two groups: DM1 patients also affected by CD presented significantly lower concentrations of glycosylated hemoglobin (HbA1c) (P < 0.05), cholesterol (P < 0.001), triglycerides (P < 0.001), factor VII antigen (FVII:ag) (P < 0.005), factor VII coagulant activity (FVII:c) (P < 0.05), and prothrombin degradation fragments (F1+2) (P < 0.001), as well as higher values of activated C protein (APC) (<0.001). No retinal abnormalities and no signs of renal damage were observed in DM1 patients also affected by CD. Our results suggest a potential protective role of CD in the prothrombotic state of DM1.     

Celiac disease and chronic liver disease: Is there a relationship?

Celiac disease is a multisystem disease, and the liver is affected in a subset of patients. We herein present a case series of 25 patients with celiac disease who had evidence of cirrhosis of the liver. We retrospectively reviewed the case records of patients with celiac disease having concomitant cirrhosis. The diagnosis of celiac disease was made on the basis of the modified European Society of Pediatric Gastroenterology, Hepatology, and Nutrition criteria. Of 25 patients (nine males; mean age 28.8?±?16.6 years) with celiac disease and cirrhosis, 17 patients presented predominantly with cirrhosis, while 8 presented primarily with celiac disease. Five patients had known cause of cirrhosis (autoimmune hepatitis, three; PBC, one; hepatic venous outflow tract obstruction, one); the remaining 20 were cryptogenic. Gluten-free diet led to improvement in diarrhea and anemia and to a better control of ascites and other features of liver failure. Some patients with cryptogenic cirrhosis have coexistent celiac disease, and they show response to gluten-free diet. Patients with cryptogenic cirrhosis should be screened for celiac disease.     

Clinical and immunological features of celiac disease in patients with Type 1 diabetes mellitus

Celiac disease (CD) is one of the most frequent autoimmune disorders occurring in Type 1 diabetes mellitus (T1DM). The prevalence of CD in T1DM varies from 3 to 16%, with a mean prevalence of 8%. The clinical presentation of CD in T1DM is classified as symptomless in approximately half of cases, but a more accurate analysis often discloses a wide array of symptoms suggestive of CD. Both T1DM and CD show the same genetic background and an abnormal small intestinal immune response with inflammation and a variable grade of enteropathy. Serological screening for CD should be performed in all T1DM patients by means of antibodies to tissue transglutaminase at T1DM onset. T1DM patients found to be celiacs must be treated by a gluten-free diet. Potential CD cases (especially when asymptomatic) should be kept on a gluten-containing diet with a careful clinical and antibody follow-up, since many of them will not develop villous atrophy.     

Optimal Frequency to Screen Celiac Disease amongst Patients with Type 1 Diabetes Mellitus: A Multicenter Study

AimsCeliac disease (CD) is frequent amongst patients with type 1 diabetes mellitus (T1DM). Since there is a disagreement on the optimal interval and frequency to perform screening tests for CD among diabetic patients, this study aimed to evaluate these issues amongst patients with T1DM.MethodsThis retrospective cohort study was conducted in seven referral diabetic centers in different cities of Iran from January 2020 to January 2021. Data belonging to 106 patients who were affected by both T1DM and CD was collected. The time interval between CD diagnosis and diabetes (IBCD), the age of diabetes onset, and any associated diseases, symptoms, and family history of T1DM and CD were recorded and analyzed.ResultsResults show that 45% of the patients with CD were diagnosed during the first year of diabetes onset; furthermore, 18% and 16% of the patients with CD were diagnosed in the second or third year after being diagnosed with diabetes. In addition, another 18% of patients with CD were diagnosed during the fourth till the eighth year after diabetes onset. Moreover, there was a negative relationship between the age of T1DM diagnosis and IBCD. Most participants were asymptomatic at the time of CD diagnosis.ConclusionsScreening tests to detect CD amongst patients with T1DM should continue for at least eight years after the initial T1DM diagnosis, especially those affected at a younger age.     

Prevalence of mitochondrial diabetes in southwestern Finland: a molecular epidemiological study

Mitochondrial diabetes and deafness (MIDD) is a subtype of diabetes mellitus (DM) that most commonly results from the m.3243A > G mutation in mitochondrial DNA (mtDNA). Sensorineural hearing loss is a typical accompanying feature. Previous studies have suggested a prevalence of ~1–1.5 % for MIDD. We studied the molecular epidemiology of MIDD among young (aged 18–45 years) adults in a defined population in southwestern Finland. Of the identified cohort of 1,532 patients with DM, we received blood samples of 299 patients and analyzed them for the m.3243A > G mutation and for mtDNA haplogroups. We found three DM patients (1.0 %) with the m.3243A > G mutation. All the three patients with DM and m.3243A > G also had severe hearing impairment that required use of hearing aid. MtDNA haplogroup U was more prevalent among patients with maternal family history of DM. We conclude that among young adults, ~1 % of all DM is associated with the m.3243A > G mutation. We suggest that all patients with both DM and hearing impairment, at least in this age group, should undergo investigation for this mutation. Furthermore, our results suggest that mtDNA haplogroup U is associated with maternal family history of DM.     

Prevalence of celiac disease in children with type 1 diabetes: A review

Background and aimsDiabetes mellitus is a chronic disease and a major health threat. Comorbidity of celiac disease and diabetes is associated with many complications in children, and if not diagnosed in time in diabetes children, caused complications, including gastrointestinal disorders, most importantly, growth disorders. Thus, this study aims to summarize the evidence about prevalence of celiac disease in children with type 1 diabetes through a systematic review approach.MethodsA literature review was conducted within databases. Observational studies that assessed the prevalence of celiac disease in diabetes children, were included. We assess the quality of included studies with STROBE checklist. Data extraction and assessment has guided by PRISMA checklist. Also, the data has reported by Garrard’s table.Results31 studies included that assessed 63,349 children with type 1 diabetes. Anemia, osteoporosis, and neurological disorders reported. Studies showed two main type of tests for diagnosis of CD included serological and intestinal biopsy. The prevalence of CD based serologic tests was higher than of intestine biopsy (1.4%–24.5% VS 1.1%–16.6%). In addition, the prevalence of celiac disease was different between populations.ConclusionsCeliac disease is an important comorbidity in children with type 1 diabetes, especially because of the similarity between CD symptoms and neuropathic and gastrointestinal symptoms of diabetes. Screening the diabetes children for celiac disease by serological tests and then intestinal biopsy is recommended.