Beyond HbA1c: Identifying Gaps in Glycemic Control Among Children and Young People with Type 1 Diabetes Using Continuous Glucose Monitoring.

OBJECTIVES: To describe continuous glucose monitoring (CGM) derived glycemic variables, and study their association with HbA1c and socio-economic factors in young people with Type 1 diabetes mellitus (T1DM). METHODS: Ninety-two participants [age 15.7 ± 5.0 y (mean ± SD), HbA1c 8.0 ± 1.5% (mean ± SD)] wore a professional CGM sensor for 14 d. RESULTS: Median (IQR) time in range (TIR) was 41 (18)%. Participants spent 41 ± 20% of their day in hyperglycemia (>180 mg/dl), and 14 (13)% in hypoglycemia (<70 mg/dl). High glycemic variability (percent CV >36%) was seen in 92% participants. Older age at diagnosis was associated with higher TIR (ß = 0.267, p = 0.01), lower time above range (TAR) (ß = -0.352, p <0.001), but higher time below range (TBR) (ß = 0.274, p = 0.006). The use of NPH vs. glargine basal insulin was associated with higher TBR (ß = -0.262, p = 0.009) but lower TAR (ß = 0.202, p = 0.041). HbA1c showed negative correlation with TIR (r = -0.449, p <0.001) and TBR (r = -0.466, p <0.001) and positive correlation with TAR (r = 0.580, p <0.001) and mean glucose (r = 0.589, p <0.001). CONCLUSIONS: These data demonstrate wide gaps between the recommended vs. real world glycemic variables in patients with T1DM in this region on multiple daily insulin injections. CGM identifies glycemic variability and complements HbA1c in improving glycemic control.

Basic carbohydrate counting and glycemia in young people with type 1 diabetes in India: A randomized controlled trial.

OBJECTIVES: The aim of this study was to evaluate the effect on glycemic control and acceptability of basic carbohydrate counting (BCC) in children and young adults with type 1 diabetes (T1DM). METHODS: Ninety-two children and young adults (6-25 y of age) with T1DM were randomized to receive either routine nutrition education (RNE), which addressed food groups, glycemic index, and effects of food and exercise on glycemia, or learn BCC with personalized portion size education. A continuous glucose monitoring study and glycosylated hemoglobin (HbA1c) were performed at baseline and after 12 wk. The primary outcome was a change in time-in-range from baseline through 12 wk. A questionnaire on the acceptability of BCC was administered. RESULTS: At 12 wk, there was no significant difference in change in time-in-range between the two groups (BCC group: 1.2 ± 12.2; RNE group: 1.9 ± 12.3; P = 0.786). No significant changes were observed in the percentage of time that blood glucose was >180 or >250 mg/dL; <70 or <54 mg/dL; glycemic variability, percentage of nights with hypoglycemia and HbA1c. In subgroup analysis, there was a significant decrease in HbA1c in the BCC group among participants with higher maternal education (-0.5 versus 0.2, P = 0.042). The total score on the acceptability questionnaire was higher in the BCC group (P = 0.022). CONCLUSION: Among children and young adults in our region with T1DM, BCC provided flexibility in food choices and perception of greater ease of insulin adjustment. Although BCC was equivalent to RNE in terms of glycemic control, larger studies may reveal benefit in outcomes in certain subgroups.

High Frequency of Recessive WFS1 Mutations Among Indian Children With Islet Antibody-negative Type 1 Diabetes.

BACKGROUND: While the frequency of islet antibody-negative (idiopathic) type 1 diabetes mellitus (T1DM) is reported to be increased in Indian children, its aetiology has not been studied. We investigated the role of monogenic diabetes in the causation of islet antibody-negative T1DM. METHODS: We conducted a multicenter, prospective, observational study of 169 Indian children (age 1-18 years) with recent-onset T1DM. All were tested for antibodies against GAD65, islet antigen-2, and zinc transporter 8 using validated ELISA. Thirty-four islet antibody-negative children underwent targeted next-generation sequencing for 31 genes implicated in monogenic diabetes using the Illumina platform. All mutations were confirmed by Sanger sequencing. RESULTS: Thirty-five (21%) children were negative for all islet antibodies. Twelve patients (7% of entire cohort, 34% of patients with islet antibody-negative T1DM) were detected to have pathogenic or likely pathogenic genetic variants. The most frequently affected locus was WFS1, with 9 patients (5% of entire cohort, 26% of islet antibody-negative). These included 7 children with homozygous and 1 patient each with a compound heterozygous and heterozygous mutation. Children with Wolfram syndrome 1 (WS) presented with severe insulin-requiring diabetes (including 3 patients with ketoacidosis), but other syndromic manifestations were not detected. In 3 patients, heterozygous mutations in HNF4A, ABCC8, and PTF1A loci were detected. CONCLUSION: Nearly one-quarter of Indian children with islet antibody-negative T1DM had recessive mutations in the WFS1 gene. These patients did not exhibit other features of WS at the time of diagnosis. Testing for monogenic diabetes, especially WS, should be considered in Indian children with antibody-negative T1DM.

Drug Induced Diabetes Mellitus in Pediatric Acute Lymphoblastic Leukemia: Approach to Diagnosis and Management.

Corticosteroids and l -asparaginase used in the treatment of pediatric acute lymphoblastic leukemia (ALL) can cause drug-induced diabetes mellitus (DIDM). DIDM can lead to dyselectrolytemia, a higher risk of infections including cellulitis, bacteremia, fungemia, and a higher incidence of febrile neutropenia and may have an impact on the outcome of ALL. Literature on the management of DIDM among children with ALL is sparse and the diagnostic criteria for pediatric diabetes should be carefully applied considering the acute and transient nature of DIDM during ALL therapy. Insulin remains the standard of care for DIDM management and the choice of Insulin regimen (stand-alone Neutral Protamine Hagedorn or basal bolus) should be based on the type and dose of steroids used for ALL and the pattern of hyperglycemia. A modest glycemic control (postmeal 140 to 180 mg/dL, premeal <140 mg/dL) to prevent complications of hyperglycemia, as well as hypoglycemia, would be the general approach. This review is intended to suggest evidence-based practical guidance in the diagnosis and management of DIDM during pediatric ALL therapy.

Long-Term Outcomes of Paediatric-Onset Craniopharyngioma: A Retrospective Analysis from a Tertiary Care Centre in North India.

Background: Craniopharyngiomas are associated with long-term morbidity in the form of hormone deficiencies, visual deficits, and hypothalamic obesity. Objective: To study the long-term outcomes, including cure rates, endocrine dysfunction, visual dysfunction, hypothalamic obesity, and mortality in pediatric-onset craniopharyngiomas. Methods: A retrospective data analysis of pediatric (onset <18 years) craniopharyngioma diagnosed between 2003 and 2018. Data were collected from electronic hospital records, case files, and direct patient interviews. Results: The mean age at presentation was 10.4 ± 4.5 years (n = 62). The median duration of symptoms at diagnosis was 6 months (3-13 months). At presentation, central diabetes insipidus was present in four (6.5%), central hypothyroidism in 27 (43.5%), secondary adrenal insufficiency in 20 (32%) and delayed puberty in 15 (24%) patients. Hypothalamus was involved in 59/60 patients (98%). At last visit, 22.6% were obese in comparison to 4.6% at presentation, and anterior pituitary deficiency was present in 90% of the patients. Sixty-one percent patients (n = 62) had delayed puberty and 67% (n = 53) had short-stature. Out of 35 short children, nine (14%) children who received growth hormone had significant increase in height SD score (-3.8 (1.4) at start vs. -2.9 (1.2) at last follow-up; P = 0.008). Tumor progression was significantly less in the group that received RT compared to those who did not (8% vs. 39%; P = 0.002). Conclusion: Childhood-onset craniopharyngioma results in significant morbidity. The prevalence of pituitary hormones deficiency, visual deficits, and obesity are high at long-term follow-up. Incomplete tumor removal is also frequent. Thus, long-term monitoring is necessary for the timely management of the morbidities associated with craniopharyngioma.

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.

Neonatal Diabetes Mellitus: Novel Mutations.

OBJECTIVE: To describe the spectrum of neonatal diabetes mellitus (NDM), document new mutations, and review published Indian literature on the etiology of NDM. METHODS: Retrospective analysis of the clinical and genetic profile of 12 NDM patients. RESULTS: Eight patients presented with NDM before the age of 6 mo. Three other patients, including 2 siblings presented in later part of infancy. An additional patient was diagnosed at age 5 y with the same etiology as her infant sibling. Four patients had transient diabetes [TNDM:1 each with a mutation in KCNJ11 and INS gene, 2 with ABCC8 mutation], 7 had permanent diabetes [PNDM: 2 siblings with complete glucokinase deficiency, 2 siblings with thiamine responsive megaloblastic anemia (TRMA), 1 with Immune dysregulation, Polyendocrinopathy, Enteropathy, X-linked (IPEX) syndrome and 2 with Wolcott Rallison syndrome, (WRS)]. Four patients had 5 novel mutations. Genetic etiology could not be established in 1 patient with features of insulin resistance. Poorly controlled blood glucose in the TRMA patient led to hyperglycemia-induced hemichorea-hemiballismus, a rare manifestation in children. CONCLUSIONS: The authors describe 5 novel mutations, in the EIF2AK3, ABCC8, and GCK genes, a homozygous mutation at the ABCC8 locus presenting as TNDM, an obscure phenotype of the GCK gene mutation, and hyperglycemia-induced hemichorea-hemiballismus in a patient with TRMA. In India, PNDM is most commonly due to WRS similar to Middle Eastern countries with high consanguinity rates.

Glycemic Control and Long-term Complications in Pediatric Onset Type 1 Diabetes Mellitus: A Single-center Experience from Northern India.

OBJECTIVE: To study glycemic control, mortality and long-term complications in children with type 1 diabetes (T1D). DESIGN: Cross-sectional study. SETTING: Referral centre at a government teaching hospital. PARTICIPANTS: Patients with T1D with age £18 years at onset. METHODS: We retrospectively collected demographic data from computer records from 1991 to 2015. Prospective study for outcomes was conducted between 2012 and 2016. MAIN OUTCOME MEASURES: Mortality rate, glycosylated hemoglobin (HbA1c), and microvascular complication rate. RESULTS: The proportion of T1D patients (n=512) <5 years of age at onset was 18.6% between 1995 and 2004, and 24.2% in 2005-2014 (P<0.001). Twenty eight patients had died out of 334 whose living status was known (mortality 1.1 per 100 patient-years over 2549 patient-years follow up). Median (range) HbA1c (n=257) was 8.3% (5.1-15.0%). At least one episode of severe hypoglycemia (coma/seizure/inability to assist self) had occurred in 22.8% patients over two years. Hypertension was present in 11.7% patients. Microvascular complications screen in 164 eligible patients [median (range) age 20 (8-45) y and duration of diabetes 9.1 (5-30) y] showed diabetic nephropathy in 3.0%, proliferative retinopathy in 3.6% and LDL cholesterol >100 mg/dL in 34% patients. CONCLUSIONS: The mortality rate and prevalence of hypertension were high, given the short duration of diabetes of the patients. The proportion of patients with age ≤5 years at onset of diabetes has increased at our center.

The impact of free medical supplies and regular telephonic contact on glycemic control in Indian children and adolescents with type 1 diabetes.

BACKGROUND/OBJECTIVE: The effect of economic assistance to underprivileged families with type 1 diabetes has never been described. Such a study is relevant as logistic and cultural factors may preclude an anticipated good outcome. The objective of the study is to determine the impact of economic and educational intervention on hemoglobin A1c (HbA1c) and diabetes knowledge. METHODS: Eighty-five consecutive participants were prospectively provided insulin and glucose strips for 1 year. From the 6th to 12th month, patients were randomized such that half of them (telephone group) received proactive telephonic advice by a diabetes educator, while the non-telephone group received usual care. HbA1c and diabetes knowledge were measured at baseline, 6 and 12 months. RESULTS: Significant improvement was seen in HbA1c with provision of free diabetes supplies, when patients were compared with their own HbA1c values during the prior 36 months (baseline [8.38 ± 2.0%], at 3 months [8.0 ± 1.6%] and at 6 months [8.1 ± 1.5%, P = 0.0106]). Knowledge score increased from baseline (48 ± 15) to 6 months (58 ± 13, P < 0.001). No difference was seen between the telephone and non-telephone groups in HbA1c from the 6th to 9th and 12th month. The knowledge score showed significant improvement in the telephone group during the proactive telephonic advice study compared with the non-telephone group (P = 0.002). CONCLUSIONS: The provision of free medical supplies improved HbA1c and diabetes knowledge. Intensive telephone contact improved knowledge, not HbA1c. These results provide important background for policy makers and diabetes management teams.

Validation of a diabetes knowledge test for Indian children, adolescents and young adults with type 1 diabetes mellitus.

INTRODUCTION: Diabetes knowledge has a large impact on glycemic control. There is a pressing need for creation of validated tests of knowledge for different ethnic groups. OBJECTIVE: To create and validate a diabetes knowledge test (DKT) for young Indians with type 1 diabetes mellitus (T1DM). METHODS: We created a 34 item Hindi language DKT, with basic (19-questions) and advanced (15-questions) components. It was administered to 77 consecutive patients who had previously received in-hospital diabetes education. We hypothesized that the test scores would be higher for patients residing in urban regions, for patients with higher maternal education, and those with lower HbA1c. Cronbach's alpha (α) was used to calculate the test reliability. RESULTS: The DKT score was significantly higher in families with higher (>class 12th) maternal formal education compared with lower [70.0 (95% C.I. 67.2-73.5) vs 54.2 (95% C.I. 44.0-57.3), p<0.001] and urban residence compared with rural [68.5 (95% C.I. 63.4-70.6) vs 54.5 (95% C.I. 42.5-61.7), p<0.001]. It had negative correlation with HbA1c (r=-0.268, p=0.019). The Cronbach's α was 0.87 for the entire test, and for the basic and advanced components was 0.78 and 0.74 respectively. CONCLUSION: The DKT India is a valid and reliable instrument to evaluate diabetes knowledge in Hindi speaking Indian children, adolescents and young adults with T1DM.

Cutaneous mucormycosis as a presenting feature of type 1 diabetes in a boy - case report and review of the literature.

BACKGROUND: Mucormycosis is a potentially fatal complication of diabetes. The rhino-orbito-cerebral form is the most common presentation, however, rarely other types can also be seen. CASE PRESENTATION: We describe the case of a 4½ -year-old boy not previously known to be a diabetic who presented to the plastic surgery department for gangrene of the left middle finger with surrounding erythema and induration. After the diagnosis of diabetes and initial treatment, pus from the wound showed broad aseptate hyphae suggestive of mucormycosis which was further confirmed on culture. Aggressive surgical debridement including amputation, antifungal treatment and glycemic control achieved a complete cure. CONCLUSIONS: Cutaneous mucormycosis is a rare complication of type 1 diabetes mellitus and can even be seen at the onset of diabetes. High index of suspicion, timely antifungal treatment and aggressive surgical debridement usually lead to recovery in the localized form of the disease.

Sun exposure, UV irradiance and serum 25-hydroxycholecalciferol in pregnant women in rural north India.

OBJECTIVE: To document the effect of season and environmental pollution on UVB irradiance; and to estimate cutaneous vitamin D synthesis in village women in different seasons. DESIGN: Radiant UVB energy was measured by a spectroradiometer in different seasons and, in April and May, on successive days in open areas at the city outskirts, at a crowded inner-city area and the villages of our participants. Clothing, outdoor activity pattern and serum 25-hydroxycholecalciferol (25(OH)D) levels were documented. SETTING: Rural north India, latitude 26·8°N. SUBJECTS: Pregnant women (n 139, aged 20-40 years). RESULTS: UVB irradiance ranged from 56 µW/cm2 in January to 470 µW/cm2 in June. Proportion of skin exposed was 18·5 % in summer and 9·5 % in winter. Mean (sd) daily duration of sun exposure was 3·2 (0·2) h during winter and 2·1 (0·4) h during summer. Cutaneous vitamin D synthesis was estimated to be 19·25 µg (770 IU) during winter and 37·25 µg (1490 IU) during summer. Mean (sd) serum 25(OH)D was 28 (15) nmol/l during winter (92 % of participants with 50 nmol/l). Mean (sd) UVB irradiance at peak summer was significantly higher at the open areas and in the villages than at the inner-city location (340 (45) and 310 (60) v. 250 (50) µW/cm2, P=0·03). CONCLUSIONS: In our population, at latitude 26·8°N, poor skin exposure is a limiting factor in all seasons. During winter, low UVB radiation energy also contributes. Particulate pollution limits UVB irradiance. Vitamin D supplementation during winter may be necessary.

Acute Respiratory Distress Syndrome: A Rare Complication in Pediatric Diabetic Ketoacidosis.

Cerebral edema (CE) and non cardiogenic pulmonary edema (acute respiratory distress syndrome, ARDS) are life-threatening complications of diabetic ketoacidosis (DKA). In contrast to CE complicating DKA, which is primarily reported in pediatric patients, ARDS is rarely described in this age group. Here, the authors present a child with DKA who developed both cerebral edema and ARDS during the course of her management. It is feasible that severe acidosis, hypotension, azotemia, hypoalbuminemia and the superimposed aggressive intravenous fluid administration were important risk factors for the development of cerebral edema and ARDS in the index patient. The report highlights the importance of early diagnosis and aggressive therapy in the management of ARDS, and summarizes the published literature on this rarely reported complication of pediatric DKA.