Genotype-phenotype correlation of KATP channel gene defects causing permanent neonatal diabetes in Indian patients.

BACKGROUND: There are very few reports pertaining to Indian patients with neonatal diabetes mellitus (NDM). Activating or gain of function mutations of KATP channel genes namely KCNJ11 and ABCC8 are most predominant cause of permanent neonatal diabetes mellitus (PNDM). OBJECTIVES: To identify the genotype-phenotype correlation of KATP channel gene defects in a large series of (n = 181) Indian PNDM patients. METHODS: Direct sequencing of all exons of KCNJ11 and ABCC8 genes in all 181 patients with PNDM were performed. Clinical and biochemical data were collected. RESULTS: We have identified the molecular basis of KATP -NDM in 39 out of 181 patients (22%). Of these, 20 had KCNJ11 mutations and 19 had ABCC8 mutations, thus comprising 51% of KCNJ11 and 49% of ABCC8. There were four novel mutations (D1128Tfs*16, Y1287C, S1422T, and H1537R) in ABCC8 gene. Three patients with KCNJ11 mutations had developmental delay with DEND syndrome. In patients with ABCC8 mutations developmental delay was seen in seven out of 19 (36.8%). Of this, three patients (15.7%) had DEND phenotype and four (21%) had iDEND. Of the 39 patients, 33 (84%) patients were shifted to sulfonylurea therapy (glibenclamide). Of this, 19(57.5%) patients harbored KCNJ11 mutations and 14(42.1%) ABCC8 mutations. CONCLUSIONS: This is the first largest study in NDM patients in India demonstrating the importance of KATP channel gene mutation screening in PNDM and efficacy of glibenclamide for Indian patients with KATP -PNDM. The success rate of transfer is more in patients with KCNJ11 mutations compared with those with ABCC8 mutations.

Diabetes stigma, parent depressive symptoms and Type-1 diabetes glycemic control in India.

Diabetes distress and stigma have been associated with worse patient outcomes in developed countries. However, diabetes stigma has not been studied in low and middle-income countries where clinical practices differ, diabetes awareness is lower, and families face different challenges for supporting children with Type 1 Diabetes (T1D). This study assessed the relationship between parental depression and diabetes stigma with a child's glycemic control in a clinic-based survey in Nagpur, India. The association between self-reported T1D stigma, depressive symptoms, and child's measured glycemic control (HbA1C) was assessed with data from 165 of the parents of school-aged (aged 5+) children receiving clinical T1D care at an urban nonprofit organization that provides free clinical care to children with Type-1 Diabetes (T1D) in India. Parents with moderate/severe depressive symptoms who experience stigma associated with their child's diabetes had children with significantly worse glycemic control than parents with no/mild depressive symptoms who experience the same amount of stigma. Higher reports of stigma were associated with an average of 0.65 points higher HbA1C (ß = 0.65, 95% Confidence Interval (CI): 0.18, 1.13) for parents with moderate/severe than parents with mild/no depressive symptoms. Indian parents with depressive symptoms who face social stigma associated with their child's diabetes have children with worse T1D outcomes.

Caregiving for children with type 1 diabetes and clinical outcomes in central India: The IDREAM study.

AIMS: Parental care influences outcomes for children's type 1 diabetes (T1D). There is little evidence about the impact of parental caregiving in developing countries, where fixed dose human insulin (conventional) therapy and limited self-monitoring of blood glucose are common. This article investigates whether performance of key T1D management tasks by children or their caregivers impacts hemoglobin A1c (HbA1c). METHODS: We surveyed the caregivers of 179 children with T1D routinely treated in a specialized diabetes clinic in Maharashtra, India to determine who performs key diabetes care tasks: child or parent. We used linear regression to estimate the relationship between parental caregiving and HbA1c, and how this association varies by child age and time since diagnosis. RESULTS: Caregivers of older children were less involved in care tasks, though caregivers of 11- to 18-year olds performed more care for children diagnosed for a longer duration. Parental involvement in key insulin delivery tasks was associated with lower HbA1c levels for all children. These reductions were greatest among children 11 to 14 years old and diagnosed for less than 2 years: mean HbA1c levels were 8.5% (69 mmol/mol) if the caregiver, and 14.4% (134 mmol/mol) if the child, performed the tasks (P < .05). CONCLUSION: Parents of children diagnosed with T1D early in life remain involved in care throughout the child's adolescence. Parents of children diagnosed in late childhood and early adolescence are significantly less involved in care, and this is associated with worse glycemic control. Clinics must know who performs care tasks and tailor diabetes education appropriately.

Clinical Profile of Long-Term Survivors and Nonsurvivors with Type 1 Diabetes in India.

Objective: To compare the clinical profile of long-term survivors and nonsurvivors with type 1 diabetes (T1D) in India. Research Design and Methods: This is a retrospective study of 76 individuals with T1D who had survived for at least 40 years ("survivors") and 51 individuals with T1D who had died with shorter duration of diabetes ("non-survivors"), from diabetes clinics in different cities of India. Prevalence of complications in both groups and causes of death of the nonsurvivors were analyzed. Retinopathy was diagnosed by retinal photography; chronic kidney disease (CKD) by urinary albumin excretion (micro-or macroalbuminuria) and estimated glomerular filtration rate; peripheral vascular disease (PVD) by doppler measurement of ankle-brachial pressure index; coronary artery disease (CAD) based on history of myocardial infarction or coronary revascularization, and neuropathy by biothesiometry. Results: Mean glycated hemoglobin (8.4% ± 1.5% vs. 10.7% ± 2.2%, P < 0.001), serum low-density lipoprotein cholesterol (91 ± 29 mg/dL vs. 107 ± 22 mg/dL, P = 0.004), and systolic blood pressure (135 ± 16 mmHg vs. 153 ± 37 mmHg, P = 0.003) were lower, and high-density lipoprotein cholesterol (51 ± 11 mg/dL vs. 43 ± 15 mg/dL, P = 0.002) higher, among survivors compared to nonsurvivors. Diabetic retinopathy, CKD, neuropathy, PVD, and CAD were more frequent among nonsurvivors. CAD [25.5%] and renal failure [23.5%] were the most frequent causes of death. Conclusions: In this first report of long-term survivors with T1D from India, we report that survivors had better glycemic and blood pressure control, more favorable lipid profiles and lower prevalence of complications compared to nonsurvivors. However, there could be other protective factors as well, which merit further studies.

Management of Diabetic Foot in an Indian Clinical Setup: An Opinion Survey.

Objective The goal of this study was to evaluate foot-care practices by physicians throughout India who had participated in the Diabetic Foot Education Program (DFEP). Methods A structured questionnaire was administered to physicians throughout India, and their responses were analyzed descriptively. Results A total of 377 doctors responded to the DFEP opinion survey, including 261 doctors who belonged to independent diabetic foot clinics. Of these doctors, 44.4% reported managing fewer than five diabetic foot patients per week and 42.8% reported managing 5-10 patients per week. Most of these patients had non-ischemic foot, followed by those with ischemic and Charcot foot. About 58% of these physicians reported performing comprehensive clinical examinations and providing optimal preventive and therapeutic care in the treatment of diabetic foot, whereas only 25.7% reported performing only callus removal and changing dressings. Basic instruments to manage diabetic foot included the monofilament, tuning fork, biothesiometer, handheld Doppler, and pedometer, which were used by 76%, 75.5%, 59.5%, 27.7%, and 12.8% of doctors, respectively. The most common comorbidities were neuropathy, reported by 333 doctors, followed by peripheral vascular disease, reported by 297 doctors. Tools for diabetic foot education included posters in the clinic, used by 75% of doctors; pamphlets, used by 56.2%; videos, used by 45.2%; and diabetic foot applications, used by 36.7% of doctors. Conclusions There is a need to promote diabetic foot awareness and implement foot-care strategies to prevent diabetic foot and effectively manage this condition. Diabetic foot education programs will encourage clinicians to effectively use diagnostic tools for assessment and management of diabetic foot and to establish independent diabetic foot clinics.

Methicillin-Resistant Staphylococcus aureus in Diabetic Foot Infection in India: A Growing Menace.

Diabetic foot infection (DFI) is a serious and common complication of diabetes mellitus. These infections are potentially disastrous and rapidly progress to deeper spaces and tissues. If not treated promptly and appropriately, DFI can be incurable or even lead to septic gangrene, which may require foot amputation. Mostly, these infections are polymicrobial, where Gram-positive pathogens mainly Staphylococcus aureus play a dominant causative role. Methicillin-resistant Staphylococcus aureus (MRSA) is present in 10% to 32% of diabetic infections and is associated with a higher rate of treatment failure, morbidity, and hospitalization cost in patients with DFIs. The increasing resistance of bacteria and the adverse effects pertaining to the safety and tolerability towards currently available anti-MRSA agents have limited the available treatment options for patients with DFI. Infection control, antimicrobial stewardship, and rapid diagnostics based on the microbiological culture and the antimicrobial susceptibility testing results are important components in helping curb this disturbing trend. Emphasis to revisit a vigorous research effort in order to improve the therapeutic options for the increasingly resistant and highly adaptable MRSA is the need of hour. Through this review article, we have made an attempt to explore the ongoing therapeutic trends in the management of DFI and highlighted the challenges in treatment of DFI. We have also given a brief overview of a few novel drugs that are under development to treat MRSA infections.

Mental health and well-being among type 1 diabetes caregivers in India: Evidence from the IDREAM study.

AIMS: Although more than half of the world's children with T1D live in developing countries, still little is known about how caregiving for children with T1D affects the parent/caregivers' health in low- and middle-income country settings. METHODS: Caregivers of 178 children with T1D from a specialized diabetes clinic in Maharashtra, India were surveyed. Ordered and standard logistic regression models adjusted for caregiver, household and child characteristics, were fit to estimate the association of caregiving burden (objective caregiving burden and subjective caregiving burden (Zarit Burden Inventory - tertiles)) with caregiver depression (Patient Health Questionnaire [PHQ-9]) and well-being (CDC Unhealthy Days) outcomes. RESULTS: Caregivers with high subjective caregiving burden had a 41% probability of most severe depression category (probability: 0.41, 95% CI: 0.25, 0.57) and an 39% probability of low well-being (probability: 0.39, 95% CI: 0.27, 0.51), compared to caregivers with low subjective burden. Caregivers with high subjective caregiving burden and high objective direct caregiving burden had an adjusted 30% probability of elevated depressive symptoms (PHQ≥10). CONCLUSIONS: Among Indian T1D caregivers, high subjective caregiving burden and objective direct caregiving burden were associated with a high risk for caregiver depression and poorer well-being.

Evidence-based recommendations for insulin intensification strategies after basal insulin in type 2 diabetes.

Over the time due to progressive nature of diabetes, proactive intensification of the existing insulin therapy becomes imminent as it minimizes patients' exposure to chronic hypo/hyperglycaemia and reduces weight gain while achieving individualized glycaemic targets. This review focuses on the strength of evidence behind various options for intensification, primarily the insulins as also the GLP-1 analogues. The recommendations presented here are meant to serve as a guide for the physician managing type 2 diabetes patients requiring insulin intensification upon failing of basal insulin therapy.

Clinical profile of diabetic foot in India.

The clinical profile of diabetes differs across the world on account of differences in social, economic, and cultural factors. India is referred to as the capital of type 2 diabetes. The burden of diabetes as well its complications like the diabetic foot is increasing constantly. This article on the clinical profile of the diabetic foot describes commonly observed problems in India, certain atypical features, and the successful implementation of a national project on reducing leg amputations.

The step-by-step program for reducing diabetic foot problems: a model for the developing world.

The prevalence of diabetes is increasing globally, particularly in the developing world. The diabetic foot is one of the most devastating chronic complications of diabetes. The Step-by-Step project was initiated in India, with participation from neighboring countries and Tanzania, to improve diabetes foot care in the developing world. The goal was to train health care professionals in basic foot care, improve their educational skills, and encourage them to set up minimum model diabetic foot clinics.