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.

Predictors of Delayed Hyponatraemia After Surgery for Pituitary Tumour.

Delayed hyponatraemia(DH) is a common complication following trans-sphenoidal surgery(TSS) for pituitary tumour. We evaluated the prevalence of DH following TSS, and assessed the factors associated with DH, including early post-operative diabetes insipidus(EPDI). This retrospective study included 100 TSS for pituitary tumours in 98 patients, over a period of 26 months. Subjects were divided into two groups: those who developed hyponatraemia and those who did not develop hyponatraemia, during post-operative days 4 to 14. The clinical characteristics and peri-operative parameters were compared between the two groups, to identify factors predicting DH. The mean age of the patients was 42.0±13.6 years, 58 (59%) were females and 61 (61%) had functional tumours. Thirty-six patients(36%) developed DH following TSS of whom majority(58%) were diagnosed on post-operative days 7 and 8; only 8/36 (22%) were symptomatic. Syndrome of inappropriate antidiuretic hormone secretion(SIADH) was found to be the most common aetiology of DH. On logistic regression analysis, intra-operative cerebrospinal fluid(CSF) leak (OR 5.0; 95% CI 1.9-13.8; p=0.002), EPDI (OR 3.4; 95% CI 1.3-9.2; p=0.015) and peri-operative steroid use (OR 3.6; 95% CI 1.3-9.8; p=0.014) were found to be significantly associated with DH. In conclusion, EPDI, intra-operative CSF leak and peri-operative steroid use were significant predictors of DH. EPDI predicts moderate to severe hyponatraemia with 80% specificity but has low sensitivity(47%). As most patients have asymptomatic hyponatraemia, serum sodium measurement on POD 7 to 10 would be helpful to identify DH in patients at increased risk.

Cognitive impairment in type 2 diabetes and its impact on daily living and self-care: A case - Control study in Kanpur, North India.

BACKGROUND AND AIM: There have been few studies from South Asia which have shown increased prevalence of cognitive impairment (CI) in diabetes. CI may further hamper self-care and independent living. The present study was designed to evaluate the impairment in cognition and self-care among patients with type 2 diabetes. MATERIALS AND METHODS: We assessed cognitive function in 54 type 2 diabetes participants and compared them with 54 healthy controls, using Addenbrooke's Cognitive Examination-III (ACE-III) test. Assessment of self-care was done by using Katz index of independence in activities of daily living and revised Summary of Diabetes Self-Care Activities (SDSCA) measures. RESULTS: The mean age and HbA1c of cases was 64.5 ± 5.3 years and 8.8 ± 2.5%, respectively. Cognitive impairment was more prevalent among type 2 diabetes participants (Odds ratio 31.3, CI: 10-100, P < 0.0001) with mean Addenbrooke's score of 74.9 ± 11.2 compared to 86.9 ± 5.3 in controls (t-statistic = 7.09, 95% CI: 8.6 to 15.3, P < 0.0001). The adjusted Odds ratio for CI was 9.46 after adjustment for hypertension. All the sub-domains of cognition were affected. The burden of CI was more among females and in those with poor glycemic control (HbA1C > 7.5%) when compared to controls. The diabetic participants with CI had poor SDSCA scores compared to those with no CI. CONCLUSION: Diabetes may cause CI and is related to poor self-care. Considering a high prevalence of CI in diabetes, cognitive assessment should be a part of overall evaluation. ACE-III is a sensitive and convenient tool for this purpose.

Bitter experience with liquorice sweetening agent resulting in apparent mineralocorticoid excess with periodic paralysis.

Chronic liquorice ingestion is a rare cause of secondary hypertension and hypokalaemia with periodic paralysis. We report the case of a middle-aged Indian man who presented with hypertension and hypokalaemic alkalosis with recurrent bouts of periodic paralysis. Biochemical investigations revealed suppressed plasma renin and aldosterone concentrations with normal cortisol concentration. A detailed history revealed that he was addicted for the last 5 years to a form of chewing tobacco mixed with herbal preparations as a sweetening agent which on analysis revealed active principles of glycyrrhizin using the thin liquid chromatography method. The hypokalaemia resolved and hypertension control improved significantly after discontinuing liquorice consumption, and the patient was asymptomatic at 1-year follow-up. Long-term liquorice ingestion should be kept in mind as a reversible cause of hypokalaemic periodic paralysis, with a meticulous history and biochemical evaluation helping in identifying this recognisable and curable medical disorder.