Low prevalence of latent autoimmune diabetes in adults in northern India.

AIM: To study the frequency of islet antibodies in a large cohort of clinic- and community-based patients with Type 2 diabetes in northern India. METHODS: We measured glutamic acid decarboxylase (GAD) antibodies in 618 adults with Type 2 diabetes (378 patients with diabetes attending a hospital clinic, 240 patients diagnosed in a community survey) and in 192 healthy subjects residing in north India. Islet antigen 2 (IA2) antibodies were also studied in a proportion of the patients with diabetes (n = 492) and in a control population (n = 191). GAD and IA2 antibodies were measured by immunoprecipitation of the respective (35) S-labelled recombinant antigen. RESULTS: We found that GAD antibodies were present in nine (1.5%) patients with diabetes (clinic population: 0.8%, community study: 2.5%), a prevalence similar to that among the subjects without diabetes (n = 2; 1%). IA2 antibodies were detected in seven patients with Type 2 diabetes (1.4%) and in two healthy control subjects (1.0%). The frequency of either GAD or IA2 antibodies was similar in people with and without diabetes (3.2 vs 2.1%). No subject was found to have both antibodies. Insulin requirement was higher among antibody-positive than among antibody-negative patients (GAD antibody: 33 vs 6.3%; P = 0.001; GAD or IA2 antibody: 23.1 vs 6.4%; P = 0.02); however, other clinical features were similar in the two groups. CONCLUSIONS: In the present north-Indian population with Type 2 diabetes, the overall prevalence of GAD antibodies and the prevalence of either GAD or IA2 antibodies were considerably lower than those reported in white European populations.

Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians.

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator (AIRE) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1-7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.

Effects of hypothyroidism induced by 6-n-propylthiouracil and its reversal by T3 on rat heart superoxide dismutase, catalase and lipid peroxidation.

The present study critically evaluates the effects of hypothyroid and hyperthyroid states on lipid peroxidation and two enzymes of active oxygen metabolism, namely superoxide dismutase (SOD) and catalase (CAT) in the rat heart mitochondrial and post-mitochondrial fractions. Lipid peroxidation, an index of oxidative stress, was elevated in the heart tissue in hypothyroid state but reduced upon T3 supplementation. Hyperthyroidism registered increased SOD activity in post-mitochondrial fraction. Mitochondrial SOD activity was reduced in hypothyroid state, which was further reduced by T3 administration. In contrast, different thyroid states had no effect on catalase activity in the mitochondrial fraction. The hypothyroid state however, significantly augmented catalase activity in post-mitochondrial fraction. The results suggest that the antioxidant defence status of cardiac tissue is well modulated by thyroid hormone.

Susceptibility patterns of Escherichia coli: prevalence of multidrug-resistant isolates and extended spectrum beta-lactamase phenotype.

OBJECTIVE: To study Escherichia coli (E. coli) susceptibility, prevalence of multidrug-resistant isolates and possible role of extended spectrum beta-lactamases (ESBL) in E. coli resistance. SETTING: Department of Medicine, Shifa College of Medicine, Islamabad. METHODS: Three hundred and seventy eight E. coli isolates from different sources were identified during six-month period. Susceptibility to various antibiotics was checked using standard methods. Multidrug-resistant isolates were separated. Isolates resistant to cefpodoxime and aztreonam were considered as ESBL phenotype, indicating ESBL production. RESULTS: Most of isolates were resistant to ampicillin and trimethoprim/sulfamethoxazole. Overall resistance to ciprofloxacin, ceftriaxone, cefotaxime and cefpodoxime was 49%, 34%, 36% and 38% respectively. Resistance to fourth generation cephalosporins was lower. Almost all Isolates were sensitive to amikacin, imipenem and tazobactam. Aztreonam resistance was found in 25% isolates. Similar pattern was observed for urinary E. coli isolates; 45% E. coli isolates were found to be multidrug-resistant. Nitrofurantoin showed low-level resistance both to multidrug-resistant as well as urinary isolates. Resistance to both cefpodoxime and aztreonam was found in 25% isolates suggesting ESBL production. CONCLUSION: E. coli resistance in Pakistan is much higher than reported from western literature. Multidrug-resistant isolates, including third generation cephalosporins and quinolones, are very common. ESBL production may contribute to this high level resistance against beta-lactams.