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.

Influence of Socio-Economic and Cultural Factors on Type 1 Diabetes Management: Report from a Tertiary Care Multidisciplinary Diabetes Management Center in India.

OBJECTIVE: To study the association of socio-economic (SE) and cultural factors with HbA1c and diabetes knowledge of children, adolescents and young adults with T1DM managed in the authors' centre, as these may be unique to a country or a region. METHODS: Demographic details, SE scoring, body mass index and mean of the last two HbA1c values were recorded, in 173 eligible patients. A diabetes knowledge test (DKT) was administered. RESULTS: Median (range) age was 14.0 (3.25-25.5) y and HbA1c 8.2 ± 1.3%. The patients travelled a median of 124 (range 0.5-850) km and 2.3 (range 0.1-18.3) h each way, to reach the clinic. Only 2 children took insulin at school / college. Insulin adjustment for pre-meal blood glucose was practiced by 88%, but adjustment for meal intake by only 17% patients. Median HbA1c was lower in the participants with age > 18 y [7.7 (5.6-11.0) %] vs. < 10 y [8.3 (6.3-10.6) %, p < 0.02] or 10-18 y [(8.3 (5.9-12.6) %, p < 0.02)]. Overweight /obesity were seen in 35%. On multivariate regression, HbA1c was associated negatively with DKT score (DKTS) and age group, and DKTS was associated positively with urban residence and maternal education > class 12th. HbA1c and DKTS were not associated with income. CONCLUSIONS: Low income may be successfully compensated by other factors to obtain good glycemic control. HbA1c did not deteriorate in adolescence in contrast to world experience. Overweight is a worrisome problem. Improved societal awareness about childhood diabetes is crucial.

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.

Diazoxide toxicity in a child with persistent hyperinsulinemic hypoglycemia of infancy: mixed hyperglycemic hyperosmolar coma and ketoacidosis.

BACKGROUND: Persistent hyperinsulinemic hypoglycemia of infancy (PHHI), also known as congenital hyperinsulinism, has been known to go into spontaneous remission, with patients developing diabetes in later life. A temporary phase of hyperglycemia is, however, rarely reported. CASE PRESENTATION: We describe a 16-month-old child, a known case of diazoxide responsive PHHI, presenting with mixed hyperglycemic hyperosmolar coma and ketoacidosis with rhabdomyolysis while on diazoxide treatment. The patient required temporary cessation of diazoxide and initiation of insulin infusion, followed by a relapse of hypoglycemia again necessitating diazoxide therapy. CONCLUSIONS: Hyperosmolar coma with ketoacidosis is a rare side-effect of diazoxide therapy, documented even in patients with persistent hyperinsulinemic hypoglycemia of infancy.