Prevalence and epidemiological profile of celiac disease in children with type 1 diabetes mellitus: Experience from a tertiary care center of India.

BACKGROUND: The HLA associations of celiac disease (CD) in north Indians differ from that in Europeans. Our dietary gluten is among the highest in the world. Data on CD in people with diabetes (PWD) in north India is scant. OBJECTIVE: To estimate the prevalence and clinical profile of CD in children with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Retrospective review of case records of PWD with onset ≤18 years of age, registered between 2009 and 2020, having at least one anti tissue-transglutaminase (anti-tTG) serology report. RESULTS: Of 583 registered PWD, 398 (68.2%) had celiac serology screening. A positive report was obtained in 66 (16.6%). Of 51 biopsied people, 22 (5.5%) were diagnosed to have CD, 12 in the first 2 years of diabetes onset. Symptomatic CD at diagnosis was seen in 63% (14/22). Age at diabetes onset (median [IQR] age 5.5 years, [2-12]) was lower in PWD and CD compared to PWD alone (10 years, [7-14], p < 0.016). Of 36 biopsied children with anti-tTG >100 au/ml, 20 (55.5%) had CD, while 2 out of 15 (13.3%) of those with lower anti-tTG titer had histopathology suggestive of CD. Of 23 seropositive children not diagnosed with CD, 5 of 8 with anti tTG >100 au/ml, and all 15 with lower anti-tTG, had normalization of titers over the 24 (10-41) months. CONCLUSIONS: Our prevalence of CD is comparable to international data. Celiac disease was common with younger age at onset of T1D and higher titer of celiac serology. A high proportion was symptomatic of CD at diagnosis.

Improving peptide relative quantification in MALDI-TOF MS for biomarker assessment.

Proteomic profiling by MALDI-TOF MS presents various advantages (speed of analysis, ease of use, relatively low cost, sensitivity, tolerance against detergents and contaminants, and possibility of automation) and is being currently used in many applications (e.g. peptide/protein identification and quantification, biomarker discovery, and imaging MS). Earlier studies by many groups indicated that moderate reproducibility in relative peptide quantification is a major limitation of MALDI-TOF MS. In the present work, we examined and demonstrate a clear effect, in cases apparently random, of sample dilution in complex samples (urine) on the relative quantification of peptides by MALDI-TOF MS. Results indicate that in urine relative abundance of peptides cannot be assessed with confidence based on a single MALDI-TOF MS spectrum. To account for this issue, we developed and propose a novel method of determining the relative abundance of peptides, taking into account that peptides have individual linear quantification ranges in relation to sample dilution. We developed an algorithm that calculates the range of dilutions at which each peptide responds in a linear manner and normalizes the received peptide intensity values accordingly. This concept was successfully applied to a set of urine samples from patients diagnosed with diabetes presenting normoalbuminuria (controls) and macroalbuminuria (cases).

Evaluating tools to support a new practical classification of diabetes: excellent control may represent misdiagnosis and omission from disease registers is associated with worse control.

AIMS: To conduct a service evaluation of usability and utility on-line clinical audit tools developed as part of a UK Classification of Diabetes project to improve the categorisation and ultimately management of diabetes. METHOD: We conducted the evaluation in eight volunteer computerised practices all achieving maximum pay-for-performance (P4P) indicators for diabetes; two allowed direct observation and videotaping of the process of running the on-line audit. We also reported the utility of the searches and the national levels of uptake. RESULTS: Once launched 4235 unique visitors accessed the download pages in the first 3 months. We had feedback about problems from 10 practices, 7 were human error. Clinical audit naive staff ran the audits satisfactorily. However, they would prefer more explanation and more user-familiar tools built into their practice computerised medical record system. They wanted the people misdiagnosed and misclassified flagged and to be convinced miscoding mattered. People with T2DM misclassified as T1DM tended to be older (mean 62 vs. 47 years old). People misdiagnosed as having T2DM have apparently 'excellent' glycaemic control mean HbA1c 5.3% (34 mmol/mol) vs. 7.2% (55 mmol/mol) (p<0.001). People with vague codes not included in the P4P register (miscoded) have worse glycaemic control [HbA1c 8.1% (65 mmol/mol) SEM=0.42 vs.7.0% (53mmol/mol) SEM=0.11, p=0.006]. CONCLUSIONS: There was scope to improve diabetes management in practice achieving quality targets. Apparently 'excellent' glycaemic control may imply misdiagnosis, while miscoding is associated with worse control. On-line clinical audit toolkits provide a rapid method of dissemination and should be added to the armamentarium of quality improvement interventions.

Combined measurement of diabetes mellitus immunological markers: an assessment of its benefits in adult-onset patients.

The convenience of combining the measurement of antibodies to glutamic acid decarboxylase (GADA), protein tyrosine phosphatase (IA-2A), and autoantibodies to insulin (IAA) in diabetic patients was assessed. We analysed 71 type 1 and 115 adult-onset diabetic patients. The latter were grouped into three categories according to the time of evolution to insulin dependence. The main findings were as follows: (i) in type 1 diabetes, the combined analysis of GADA and IA-2A showed a sensitivity of 87.4% and was not appreciably improved by adding IAA; (ii) out of 31 adults who required insulin immediately or within the first two years of diagnosis, 41.9, 29.0, and 6.5% were positive for at least one, two or all three, and all three markers, respectively; GADA was the most prevalent (35.5%) and IA-2A the least represented (16.1%); (iii) 34 adult patients with slow evolution to insulin dependence showed a completely different profile: 5.9% were GADA positive and 23.5% were IAA positive and no double or triple positivity was observed as all patients were IA-2A negative; and (iv) 50 type 2 patients who had not required insulin treatment showed a low incidence of GADA (4%) as the only marker present. We conclude that a combined double-antigen test for GADA and IA-2A is a useful strategy for prospective screening of type 1 diabetes. However, in adults, the profile of individual markers discloses the course to insulin dependence. Therefore, it seems advisable to measure the markers separately, to allow a better classification of these patients, and help define their treatment.

[C-peptide measurement in the classification of diabetes mellitus and in the assessment of requirements for insulin treatment]. / C-peptidmåling ved klassifikation af diabetes mellitus og ved vurdering af behov for insulinbehandling.

C-peptide and insulin are secreted in equimolar amounts from the beta-cells in the pancreas. Therefore, measurement of C-peptide in plasma can be used to estimate endogenous insulin secretion also in insulin treated diabetic subjects. From a clinical point of view, it is of especial interest to use measurements of C-peptide in the discrimination between diabetic subjects with and without insulin requirements. Such measurements are, however, difficult to interpret. Thus, plasma C-peptide values depend apart from C-peptide secretion also on C-peptide clearence, technical procedures, and during unsteady state conditions also on the C-peptide volume of distribution. In clinical practice, it is recommended only to measure basal plasma C-peptide and these values should be interpreted with caution. Generally, values below 0.2 nmol/l suggest insulin requirement while values above 0.5 nmol/l suggest non-insulin requirement. Patients with intermediate basal plasma C-peptide values should be evaluated more closely for example in hospital. Measurement of C-peptide should, however, be restricted to certain selected patients in whom the clinical classification is uncertain.