Expert Opinion by Clinicians on the Use of Insulin Therapy in People with Hepatic Impairment.

People with type 2 diabetes mellitus (T2DM) have a higher risk of developing chronic liver disease (CLD) and its complications. T2DM, obesity, and insulin resistance are all strongly associated with nonalcoholic fatty liver disease (NAFLD). Conversely, people suffering from cirrhosis have reduced glucose tolerance in approximately 60% of cases, diabetes in 20% of cases, and insulin-mediated glucose clearance is lowered by 50% as compared with those who do not have cirrhosis. An exploratory review was conducted using existing published evidence from clinical studies on dosing and titrations of individual insulin formulations in people with CLD to optimize insulin dosage titration for minimizing hypoglycemia risk.pThis article discusses current hyperglycemia treatment techniques for patients with CLD as well as the consensus recommendations on insulin use in special populations with T2DM and hepatic impairment. Based on available evidence and expert diabetologists' recommendations, careful insulin dose titration, customized glycemic targets, and frequent glucose screening are recommended for optimal glycemic management without hypoglycemia in CLD. Long-acting insulin should be avoided or used when short-acting insulin fails to provide adequate glycemic control with raised fasting blood sugar levels. While the patient's glucose profile is being evaluated, the prandial insulin dose can be lowered by 25% initially. The dose can be titrated based on the patient's postprandial glycemic expression and whether their food intake meets the Child-Pugh scores A and B categories. Titrating premixed insulins is difficult for patients in class C since their appetite and overall health are constantly compromised and in flux.

Association between Clinical Features and Magnetic Resonance Imaging Findings in Patients with Temporal Lobe Epilepsy.

BACKGROUND: Temporal lobe epilepsy (TLE) is the most common cause of partial seizures. However, there is a paucity of data on the correlation of clinical and semiological features of TLE with specific imaging findings on magnetic resonance imaging (MRI). OBJECTIVE: In this study, we sought to evaluate the association between the semiology of TLE with specific etiological findings as identified on MRI. MATERIALS AND METHODS: This was a single-center, observational study in which consecutive patients presenting with clinical features diagnostic of TLE underwent a brain MRI on a 1.5 T scanner. The data collected from the various MR parameters were then correlated with history. RESULTS: A total of 90 patients were included in the study. The mean age of the study population was 29.1 years. Females comprised 45% of the study population. Mesial temporal sclerosis (MTS) was the most common imaging finding in about 60% of patients. Four out of five patients had aura whereas 70% had automatisms. The presence of aura in TLE patients was significantly associated with MTS on MRI (p = 0.042). The presence of automatism and history of childhood febrile seizure did not have a significant association with any specific etiological findings on MRI (p = 0.254 and 0.731, respectively). Drug-refractory epilepsy was commonly associated with the presence of MTS on MRI (p = 0.004). The presence of dual pathology on MRI was associated with drug-refractory epilepsy (p = 0.031). CONCLUSIONS: The presence of aura and drug-refractory epilepsy point towards the presence of MTS. Dual pathology, on MRI, in TLE patients may be a risk factor for drug-refractory epilepsy.

LIVE INDIA: Effectiveness of Gla-100 in a Post hoc Pooled Analysis of FINE ASIA and GOAL Registries.

INTRODUCTION: Real-world evidence on insulin glargine 100 U/ml (Gla-100) initiation in Indian type 2 diabetes mellitus (T2DM) individuals is limited. The present study aimed to evaluate the effectiveness of Gla-100 in insulin-naïve T2DM participants from India. METHODS: This post hoc analysis includes real-world data of insulin-naïve Indian participants with T2DM who started Gla-100 treatment in two Asian registries: FINE ASIA and GOAL. Changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, insulin dose, and incidence of hypoglycemia from baseline to 6 months were assessed. RESULTS: A total of 955 participants with T2DM were identified and analyzed. The mean [standard deviation (SD)] age and duration of diabetes were 54.7 (9.8) years and 9.8 (6.3) years, respectively. Mean HbA1c and FPG were significantly reduced after 6 months of Gla-100 treatment [- 2.07 (1.4) %; - 94.4 (65.2) mg/dl, respectively]. HbA1c targets of < 7.0% and < 7.5% were achieved by 292 (30.6%) and 589 (61.7%) study participants, respectively. The overall incidence of hypoglycemia was low (n = 52; 5.4%); only two participants (0.2%) reported severe hypoglycemia. Insulin was titrated with a mean (SD) increment of 2.5 (5.6) U/day after 6 months, leading to a mean Gla-100 dose of 18.2 (8.9) U/day. Mean body weight remained unchanged from baseline to 6 months (- 0.1 kg). CONCLUSION: In routine clinical practice, Gla-100 significantly improved glycemic parameters after 6 months of treatment with a low risk of hypoglycemia and no weight change in participants with T2DM.

Safety of Insulin Degludec/Insulin Aspart in Patients with Diabetes Mellitus over a Period of 1 Year during Routine Clinical Care in India: SMART (Study of Management of Diabetes with Ryzodeg™ Treatment).

This post-authorization study was conducted to evaluate the safety of insulin degludec/insulin aspart (IDegAsp) in adult patients with diabetes mellitus (DM) during routine clinical care under a real-world setting in India. Eligible patients received IDegAsp for a minimum of 12 months during routine clinical management. Data were collected at 0, 3, 6, and 12 months. In total, 1029 adult patients with DM were included; 65.2% (n = 671) were men; mean age was 55.0 ± 12.2 years, and the mean duration of diabetes mellitus was 10.8 ± 7.4 years. Thirty adverse events were reported in 23 patients (2.2%) during the follow-up: two adverse events in two patients were serious with fatal outcomes, which were unrelated to IDegAsp use. At baseline, there were 176 confirmed hypoglycemic events in 67 (6.7%) patients while they were on their previous treatment options. At 12 months of treatment with IDegAsp, 11 confirmed hypoglycemic events were reported in 11 (1.1%) patients since the previous visit; there were no reported episodes of severe hypoglycemia. Mean glycosylated hemoglobin value reduced from 9.5% ± 1.8% at baseline to 7.7% ± 1.1% at 12 months. This study showed the safety of IDegAsp in patients with diabetes mellitus over a period of 1 year during routine clinical care.

Optical Coherence Tomography Findings in Patients of Parkinson's Disease: An Indian Perspective.

BACKGROUND: Parkinson's disease (PD) is one of the most common neurodegenerative movement disorders and its incidence is increasing worldwide along with population aging. Previous clinical and histologic studies suggest that the neurodegenerative process, which affects the brain, may also affect the retina of PD patients. OBJECTIVE: The objective of this study was to determine the thickness changes of retina nerve fibers and macular volume with optical coherence tomography (OCT) in PD patients. MATERIALS AND METHODS: The spectral domain OCT was used to assess the thickness of retinal nerve fiber layer (RNFL) and macular volume from 34 PD patients and 50 healthy age-matched controls. RESULTS: Compared with healthy age-matched controls, the RNFL thickness of PD patients was much thinner (P < 0.05) in all retinal quadrants, with temporal thinning being more than nasal thinning. Macular volumes were diminished in both perifoveal and outer macular regions in all sectors (P < 0.05) with preserved foveal volume. The degree of tissue loss corroborated with the severity of disease as objectively assessed by standardized rating scales (UPDRS). CONCLUSION: There is generalized retinal nerve degeneration in patients of PD and the degree of loss correlated with the severity and duration of disease.

Deletion mapping of chromosome 1 in early onset and late onset breast tumors--a comparative study in eastern India.

Younger women exhibit more aggressive pathologic features of breast cancer (BC) compared to their older counterparts. Young age has been shown to be an independent predictor of adverse prognosis. These findings have raised the question of whether these differences are also present at the genetic level. Twenty-five early onset (age < or = 40 years) tumors including 4 bilateral tumors, and 26 late onset (>40 years) breast tumors, including 2 bilateral tumors, were examined for loss of heterozygosity (LOH) at chromosome 1 using 11 polymorphic microsatellite markers. A comparative study revealed high frequencies of LOH in chr. 1p36 (61%), 1p31.3 (40%), 1p21.3 (50%) and 1q22-23.2 (56%) in a younger group, and chr. 1p36 (46%), 1p34.2 (48%), and 1q22-23.2 (52%) in an older group. These differences in LOH frequency in these two age groups were significant for chr. 1p21.3 (p = 0.025) only. These data suggest that the deletion pattern in early onset breast tumors is not fully identical to late onset breast tumors. Similar differential deletion patterns of LOH in the 5 highly deleted regions were seen in premenopausal and postmenopausal groups. An association was seen between LOH at chr. 1p34.2 and chr. 1q22-23.2 and higher grade of the tumors in older women. Among the highly deleted regions, the deletion at chr. 1p36 was found to occur early in both groups because of common allelic loss in the bilateral tumors.

Altered serum levels of adipokines and insulin in probable Alzheimer's disease.

Cerebral hypometabolism of glucose, weight loss, and decreased food intake are characteristic features of sporadic Alzheimer's disease (AD). A systematic study on the serum levels of adipokines and insulin, the major hormones regulating energy metabolism, food intake, and body weight, in sporadic AD is necessary. The present study compares the serum levels of leptin, adiponectin, and insulin, measured by commercially available immuno-assay kits, between controls and sporadic AD subjects. The results show a conspicuous decrease in the level of leptin, a dramatic rise in the level of adiponectin, and also a statistically significant increase in insulin level, in the blood of AD subjects, with respect to controls. The changes in the serum levels of adiponectin and insulin in AD are positively correlated with the severity of dementia. Likewise, the serum level of leptin in AD subjects is negatively correlated with the degree of dementia. The changes in the levels of adipokines and insulin have implications in the amyloid pathology, neurodegeneration, and hypometabolism of glucose existing in the AD brain.

Clinical experience with insulin detemir, biphasic insulin aspart and insulin aspart in people with type 2 diabetes: Results from the North East India cohort of the A1chieve study.

BACKGROUND: The A1chieve, a multicentric (28 countries), 24-week, non-interventional study evaluated the safety and effectiveness of insulin detemir, biphasic insulin aspart and insulin aspart in people with T2DM (n = 66,726) in routine clinical care across four continents. MATERIALS AND METHODS: Data was collected at baseline, at 12 weeks and at 24 weeks. This short communication presents the results for patients enrolled from North East, India. RESULTS: A total of 730 patients were enrolled in the study. Four different insulin analogue regimens were used in the study. Patients had started on or were switched to biphasic insulin aspart (n = 518), insulin detemir (n = 88), insulin aspart (n = 74), basal insulin plus insulin aspart (n = 19) and other insulin combinations (n = 30). At baseline glycaemic control was poor for both insulin naïve (mean HbA1c: 9.5%) and insulin users (mean HbA1c: 9.2%) groups. After 24 weeks of treatment, both groups showed improvement in HbA1c (insulin naïve: -1.6%, insulin users: -1.5%). SADRs including major hypoglycaemic events or episodes did not occur in any of the study patients. CONCLUSION: Starting or switching to insulin analogues was associated with improvement in glycaemic control with a low rate of hypoglycaemia.

Serum Homocysteine, Dehydroepiandrosterone Sulphate and Lipoprotein (a) in Alzheimer's Disease and Vascular Dementia.

Alzheimer's disease (AD) and vascular dementia (VAD) are the major forms of dementia affecting elderly people, in which the levels of many metabolites are altered in cerebrospinal fluid (CSF) and serum. These metabolites could be risk factors or potential biomarkers, but the significance of some of these are not clearly understood in the context of the disease pathogenesis. In the present study serum levels of homocysteine, dehydroepiandrosterone sulphate (DHEA-S) and lipoprotein (a) or Lp(a) have been measured by ELISA using commercial kits in AD (n = 40), VAD (n = 40) and age matched control subjects (n = 40). The data are compared by ANOVA and post-hoc analysis. The serum homocysteine is markedly elevated compared to control both in AD and VAD subjects, but to a significantly higher extent in the latter. Lp(a) is increased in the serum of VAD subjects only compared to control. Likewise, serum DHEA-S level is lowered in AD but not in VAD compared to control. The analysis of the present data and those published by others suggest that alterations in homocysteine and Lp(a) in serum are indicators of vascular pathology in AD or VAD, while the lowering of serum DHEA-S is a consequence of AD pathology.

Suggested use of vaccines in diabetes.

Diabetes has emerged as a disease of major public health importance in India affecting the rich and the poor alike. Conventionally, comprehensive diabetes management is aimed at preventing micro and macro vascular complications. However, morbidity and mortality due to infections are also significant. In developing countries like India, the concept of adult immunization is far from reality. Recently the H1N1 pandemic has triggered the necessity for considering immunization in all age groups for the prevention of vaccine-preventable fatal infectious diseases. Considering the economics of immunization in a developing country, providing free vaccines to all adults may not be a practical solution, although the free universal immunization program for children is in existence for several decades. There is no consensus on the use of vaccines in diabetes subjects in India. However, there are some clinics offering routine pneumococcal, influenza and other vaccinations. Patients with diabetes have a deranged immune system making them more prone for infections. Hospitalization and death due to pneumococcal disease and influenza are higher in diabetes patients. They, like other healthy individuals, have a normal humoral response to vaccination with clinically significant benefits. The American Diabetes Association, Advisory Committee on Immunization Practices, Centers for Disease Control and Prevention, World Health Organization, United Kingdom Guidelines and a number of other scientific organizations have well defined guidelines for vaccination in diabetes. In this article we make some suggestions for clinicians in India, regarding use of vaccines in subjects with diabetes.

Evaluation of the efficacy and safety of fexofenadine in the management of chronic idiopathic urticaria: a prospective study with 512 patients.

Five hundred and twelve patients with chronic idiopathic urticaria (CIU) were treated with fexofenadine at a dose on 180 mg/day. Maximum number of patients were between 20 to 40 years of age and female to male ratio was 1.45:1. The severity of itching was calculated on a scale of 0 to 4 and was recorded by the patients. The mean daily total symptom score (TSS) was measured as sum of the patients' pruritus and number of wheal scores (0 to 7). A mean TSS was determined for each week. Baseline TSS came down to '0' by 4 weeks in all groups except those with TSS 4. There was no correlation between the baseline TSS and degree of improvement. Of 512, 14 (2.73%) patients did not complete the study. The commonest adverse effect was headache (9.04%). There was no report of drowsiness or cardiac arrhythmia. In no patient fexofenadine had to be withdrawn because of its adverse effects.