Identification of appropriate biochemical parameters and cut points to detect Maturity Onset Diabetes of Young (MODY) in Asian Indians in a clinic setting.

Maturity Onset Diabetes of the Young (MODY) is a monogenic form of diabetes which is detected by genetic testing. We looked at clinical and biochemcial variables that could help detect possible MODY among Asian Indians with youth-onset diabetes. From the diabetes electronic medical records of a diabetes care centre in Chennai in southern India, demographic, anthropometric, and biochemical details of 34 genetically confirmed MODY participants were extracted. They were compared with patients with type 1 diabetes (T1D) (n = 1011) and type 2 diabetes (T2D) (n = 1605), diagnosed below 30 years of age. Clinical and biochemical variables including body mass index (BMI), glycated hemoglobin, HDL cholesterol, and C-peptide (fasting and stimulated) were analyzed to determine whether cut points could be derived to identify individuals who could be sent for genetic testing to diagnose or rule out MODY in this ethnic group. The age at diagnosis was higher for T2D (26.5 ± 4.0 years) compared to T1D (18.2 ± 6.1 years) and MODY (17.8 ± 6.0 years). Individuals with MODY had BMI, glycated hemoglobin, total cholesterol, triglycerides, HDL cholesterol, and C-peptide levels which were intermediate between T1D and T2D. The identified probable parameters and their cut points to identify cases for MODY genetic screening were BMI 21.2-22.7 kg/m2, glycated hemoglobin 7.2-10%, HDL cholesterol 43-45 mg/dl, fasting C -peptide, 1.2-2.1 ng/ml and stimulated C-peptide, 2.1-4.5 ng/ml. Asian Indians with MODY have clinical features that are intermediate between T1D and T2D and selected biochemical parameters, especially stimulated C peptide cut points were the most useful to diagnose MODY.

Prevalence, clinical features and complications of common forms of Maturity Onset Diabetes of the Young (MODY) seen at a tertiary diabetes centre in south India.

BACKGROUND: Maturity Onset Diabetes of the Young (MODY) is a form of monogenic diabetes caused by mutations in single genes, affecting adolescents or young adults. MODY is frequently misdiagnosed as type 1 diabetes (T1). Though several studies from India have reported on the genetic aspects of MODY, the clinical profile, complications and treatments given have not been reported so far, nor compared with T1D and type 2 diabetes (T2D). AIM: To determine the prevalence, clinical features, and complications of common forms of genetically proven MODY seen at a tertiary diabetes centre in South India and compare them with matched individuals with T1D and T2D. METHODS: Five hundred and thirty individuals identified as 'possible MODY' based on clinical criteria, underwent genetic testing for MODY. Diagnosis of MODY was confirmed based on pathogenic or likely pathogenic variants found using Genome Aggregation Database (gnomAD) and American College of Medical Genetics (ACMG) criteria. The clinical profile of MODY was compared with individuals with type 1 (T1D) and type 2 (T2D) diabetes, matched for duration of diabetes. Retinopathy was diagnosed by retinal photography; nephropathy by urinary albumin excretion > 30 µg/mg of creatinine and neuropathy by vibration perception threshold > 20 v on biothesiometry. RESULTS: Fifty-eight patients were confirmed to have MODY (10.9%). HNF1A-MODY (n = 25) was the most common subtype followed by HNF4A-MODY (n = 11), ABCC8-MODY (n = 11), GCK-MODY (n = 6) and HNF1B-MODY (n = 5). For comparison of clinical profile, only the three 'actionable' subtypes - defined as those who may respond to sulphonylureas, namely, HNF1A, HNF4A and ABCC8-MODY, were included. Age at onset of diabetes was lower among HNF4A-MODY and HNF1A-MODY than ABCC8-MODY, T1D and T2D. Prevalence of retinopathy and nephropathy was higher among the three MODY subtypes taken together (n = 47) as compared to T1D (n = 86) and T2D (n = 86). CONCLUSION: This is one of the first reports of MODY subtypes from India based on ACMG and gnomAD criteria. The high prevalence of retinopathy and nephropathy in MODY points to the need for earlier diagnosis and better control of diabetes in individuals with MODY.

Strategies for participant retention in long term clinical trials: A participant -centric approaches.

A clinical trial is the most foolproof method to evaluate the efficacy of a new intervention. Successful completion of clinical trials depends on the retention of the participants enrolled. Poor participant retention can lead to significant time and cost burden and have potentially adverse biases on the results. A high retention rate of participants is an important criterion for the validity and credibility of randomized controlled clinical trials. Many long-term trials fail due to low retention of study participants. Efforts at participant retention should start even before the first participant is recruited into the study. Retention is not only the responsibility of the investigators but also all other stakeholders in a clinical trial. In recent years, retention materials, participant camps, and introduction of national study coordinators have helped in improving retention. Quality of the relationship developed between the research staff and the study participant is a key factor for success of any trial. In our experience, in the context of resource-challenged low- and middle-income countries, we have found that it is possible to achieve high retention rates, 95%-100%. The rapport built between the investigating team and the participant plays a vital role in retention. In addition, personalized care, including listening to the participant's problems and enabling to contact investigators or study team at any time of the day, has shown benefits in retention.

Telemedicine during COVID-19 in India-a new policy and its challenges.

During the COVID-19 pandemic, a countrywide lockdown of nearly twelve weeks in India reduced access to regular healthcare services. As a policy response, the Ministry of Health & Family Welfare which exercises jurisdiction over telemedicine in India, rapidly issued India's first guidelines for use of telemedicine. The authors argue that: guidelines must be expanded to address ethical concerns about the use of privacy, patient data and its storage; limited access to the internet and weaknesses in the telecom infrastructure challenge widespread adoption of telemedicine; only by simultaneously improving both will use of telemedicine become equitable; Indian medical education curricula should include telemedicine and India should rapidly extend training to practitioner. They determine that for low- and middle-income countries (LMIC), including India, positive externalities of investing in telemedicine are ample, thus use of this option can render healthcare more accessible and equitable in future.

Quality of Life and Diabetes in India: A Scoping Review.

In recent years, numerous studies have explored the quality of life (QoL) in those with diabetes mellitus. The aim of this scoping review was to explore the current state of knowledge on QoL and its various associated factors among people with diabetes in India. Three databases were searched (PubMed, Scopus, and Medline) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. A total of 41 articles were included in the review. The included studies were largely conducted in the Southern states and mainly investigated individuals with type 2 diabetes. The World Health Organization Quality of Life (WHOQOL-BREF) and Short Form Health Survey (SF-36) were the instruments used most often. In general, the studies showed that people with diabetes had poorer QoL than those without diabetes, and women with diabetes reported poorer QoL than men, consistent with findings across the world. However, the studies had significant methodological flaws which limit the validity and generalizability of the findings. Therefore, there is an urgent need to conduct high-quality QoL studies which are representative of all states of India as well as different types of diabetes in India in order to address this gap in the evidence.

Clinical features, complications and treatment of rarer forms of maturity-onset diabetes of the young (MODY) - A review.

Maturity onset diabetes of the young (MODY) is the most common form of monogenic diabetes and is currently believed to have 14 subtypes. While much is known about the common subtypes of MODY (MODY-1, 2, 3 and 5) little is known about its rare subtypes (MODY4, 6-14). With the advent of next-generation sequencing (NGS) there are several reports of the rarer subtypes of MODY emerging from across the world. Therefore, a greater understanding on these rarer subtypes is needed. A search strategy was created, and common databases were searched, and 51 articles finally selected. INS-(MODY10) and ABCC8-(MODY12) mutations were reported in relatively large numbers compared to the other rare subtypes. The clinical characteristics of the rare MODY subtypes exhibited heterogeneity between families reported with the same mutation. Obesity and diabetic ketoacidosis (DKA) were also reported among rarer MODY subtypes which presents as a challenge as these are not part of the original description of MODY by Tattersal and Fajans. The treatment modalities of the rarer subtypes included oral drugs, predominantly sulfonylureas, insulin but also diet alone. Newer drugs like DPP-4 and SGLT2 inhibitors have also been tried as new modes of treatment. The microvascular and macrovascular complications among the patients with various MODY subtypes are less commonly reported. Recently, there is a view that not all the 14 forms of 'MODY' are true MODY and the very existence of some of these rarer subtypes as MODY has been questioned. This scoping review aims to report on the clinical characteristics, treatment and complications of the rarer MODY subtypes published in the literature.