Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.

Sustained-Release Vildagliptin 100 mg in Type 2 Diabetes Mellitus: A Review.

Dipeptidyl peptidase-4 inhibitors (DPP4Is) were introduced into the management of type 2 diabetes mellitus (T2DM) as they are insulinotropic and have no inherent risk of hypoglycemia and no effect on body weight. Currently, 11 drugs in this class are available for the management of diabetes. Although they have a similar mechanism of action, they differ from one other in their binding mechanisms, which influences their therapeutic and pharmacological profiles. Vildagliptin's overall safety and tolerability profile was comparable to placebo throughout clinical studies, and real-world data in a large group of T2DM patients corroborated this finding. Therefore, DPP4Is like vildagliptin is a secure alternative for treating patients with T2DM. Vildagliptin treatment given as a once-daily (QD) 100 mg sustained release (SR) formulation fits the criteria of adherence and compliance. This SR formulation, given once daily has the potential to provide glycemic control like the vildagliptin 50 mg twice-daily (BD) formulation. This comprehensive review discusses the journey of vildagliptin as 50 mg BD therapy as well as 100 mg SR QD therapy.

Time to reposition sulfonylureas in type 2 diabetes management in Indian context: A pragmatic practical approach.

Sulfonylureas (SU) continue to be a vital therapeutic category of oral hypoglycemic agents (OHAs) for the management of type 2 diabetes mellitus (T2DM). Physicians consider modern SU (gliclazide and glimepiride) as "safe and smart" choices for T2DM management. The presence of multiple international guidelines and scarcity of a national guideline may contribute to the challenges faced by few physicians in choosing the right therapeutic strategy. The role of SU in diabetes management is explicit, and the present consensus aims to emphasize the benefits and reposition SU in India. This pragmatic, practical approach aims to define expert recommendations for the physicians to improve caregivers' knowledge of the management of T2DM, leading to superior patient outcomes.

The INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) study: Design and methods to address mental healthcare gaps in India.

INTRODUCTION: Depression and diabetes are highly prevalent worldwide and often co-exist, worsening outcomes for each condition. Barriers to diagnosis and treatment are exacerbated in low and middle-income countries with limited health infrastructure and access to mental health treatment. The INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) study tests the sustained effectiveness and cost-effectiveness of a multi-component care model for individuals with poorly-controlled diabetes and depression in diabetes clinics in India. MATERIALS AND METHODS: Adults with diabetes, depressive symptoms (Patient Health Questionnaire-9 score≥10), and ≥1 poorly-controlled cardiometabolic indicator (either HbA1c≥8.0%, SBP≥140mmHg, and/or LDL≥130mg/dl) were enrolled and randomized to the intervention or usual care. The intervention combined collaborative care, decision-support, and population health management. The primary outcome is the between-arm difference in the proportion of participants achieving combined depression response (≥50% reduction in Symptom Checklist score from baseline) AND one or more of: ≥0.5% reduction in HbA1c, ≥5mmHg reduction in SBP, or ≥10mg/dl reduction in LDL-c at 24months (12-month intervention; 12-month observational follow-up). Other outcomes include control of individual parameters, patient-centered measures (i.e. treatment satisfaction), and cost-effectiveness. RESULTS: The study trained seven care coordinators. Participant recruitment is complete - 940 adults were screened, with 483 eligible, and 404 randomized (196 to intervention; 208 to usual care). Randomization was balanced across clinic sites. CONCLUSIONS: The INDEPENDENT model aims to increase access to mental health care and improve depression and cardiometabolic disease outcomes among complex patients with diabetes by leveraging the care provided in diabetes clinics in India (clinicaltrials.gov number: NCT02022111).

Input of stakeholders on reducing depressive symptoms and improving diabetes outcomes in India: Formative work for the INDEPENDENT Study.

AIMS: Depression and diabetes are highly comorbid, adversely affecting treatment adherence and resulting in poor outcomes. To improve treatment and outcomes for people dually-affected by diabetes and depression in India, we aimed to develop and test an integrated care model. In the formative phase of this INtegrated DEPrEssioN and Diabetes TreatmENT (INDEPENDENT) study, we sought stakeholder perspectives to inform culturally-sensitive adaptations of the intervention. METHODS: At our Delhi, Chennai, and Vishakhapatnam sites, we conducted focus groups for patients with diabetes and depression and interviewed healthcare workers, family members, and patients. These key informants were asked about experiences with diabetes and depression and for feedback on intervention materials. Data were analyzed using a grounded theory approach. RESULTS: Three major themes emerged that have bearing on adaptation of the proposed intervention: importance of family assistance, concerns regarding patient/family understanding of diabetes, and feedback regarding the proposed intervention (e.g. adequate time needed for implementation; training program and intervention should address stigma). CONCLUSIONS: Based on our findings, the following components would add value when incorporated into the intervention: 1) engaging families in the treatment process, 2) clear/simple written information, 3) clear non-jargon verbal explanations, and 4) coaching to help patients cope with stigma.

Psychosocial management of diabetes in pregnancy.

This consensus based national guideline addresses the need for psychological, psychiatric and social assessment, as well as management, in antenatal women with diabetes. It builds upon the earlier Indian guidelines on psychological management of diabetes, and should be considered as an addendum to the parent guideline.

National recommendations: Psychosocial management of diabetes in India.

Although several evidence-based guidelines for managing diabetes are available, few, if any, focus on the psychosocial aspects of this challenging condition. It is increasingly evident that psychosocial treatment is integral to a holistic approach of managing diabetes; it forms the key to realizing appropriate biomedical outcomes. Dearth of attention is as much due to lack of awareness as due to lack of guidelines. This lacuna results in diversity among the standards of clinical practice, which, in India, is also due to the size and complexity of psychosocial care itself. This article aims to highlight evidence- and experience-based Indian guidelines for the psychosocial management of diabetes. A systemic literature was conducted for peer-reviewed studies and publications covering psychosocial aspects in diabetes. Recommendations are classified into three domains: General, psychological and social, and graded by the weight they should have in clinical practice and by the degree of support from the literature. Ninety-four recommendations of varying strength are made to help professionals identify the psychosocial interventions needed to support patients and their families and explore their role in devising support strategies. They also aid in developing core skills needed for effective diabetes management. These recommendations provide practical guidelines to fulfill unmet needs in diabetes management, and help achieve a qualitative improvement in the way physicians manage patients. The guidelines, while maintaining an India-specific character, have global relevance, which is bound to grow as the diabetes pandemic throws up new challenges.

Serum chromium levels in gestational diabetes mellitus.

OBJECTIVE: To measure serum chromium level in women with gestational diabetes mellitus (GDM) from Chennai, South India. MATERIALS AND METHODS: Thirty women with gestational diabetes, 60 age matched controls. INCLUSION CRITERIA: Gestational age 22-28 weeks, age group 20-35 years. EXCLUSION CRITERIA: Gestational age beyond 28 weeks, malnutrition or presence of infection. Serum chromium was measured using inductive couple plasma emission spectrometer. RESULTS: Serum chromium levels of women with GDM, 1.59+/-0.02 ng/ml (range: 0.16-4.0 ng/ml) were lower than in controls (4.58+/-0.62 ng/ml; range 0.82-5.33 ng/ml) (P < 0.001). However, there were no significant differences among cases and controls when subdivided by parity. CONCLUSIONS: Women with GDM from a South Indian city had lower levels of serum chromium compared to pregnant women without GDM. Studies may be done whether chromium supplementation is useful in this group of women.

Sleep in thyrotoxicosis.

OBJECTIVE: Pattern of sleep in hyperthyroid state / thyrotoxicosis has not been systematically studied. It is being characterized as poor without further elaboration. We analyzed the pattern of sleep in a large sample of individuals with thyrotoxicosis who came to our endocrine center in southern India. MATERIALS AND METHODS: We identified individuals with the diagnosis of 'thyrotoxicosis' from our electronic medical record database, and evaluated clinical parameters and pattern of their sleep: difficulty in falling asleep (DFA), difficulty in maintaining sleep (DMS), excess daytime sleepiness). In the first phase, univariate analysis with logistic regression was performed. Multivariate logistic regression was performed in the next phase on variables with a P-value < 0.1: these were considered as potential categories/ variables. RESULTS: In model response variable with DFA, multivariate logistic regression predicted that subjects with abnormal appetite (more 1.7 or less 2.2), change in bowel motion (loose 1.5 or constipation 2.8), in mood (easy loss of temper 3.4), change of voice -- hoarse 7.4 or moderately hoarse 3.1), tended to have higher chances of difficulty in falling asleep (DFA). Patients with tremor (yes = 5.4) had greater likelihood of difficulty in maintaining sleep (DMS). CONCLUSIONS: Individuals with hyperthyroidism/thyrotoxicosis principally had difficulty in falling asleep DFA, which was related to hyperkinetic features.

Time trends in the prevalence of diabetes mellitus: ten year analysis from southern India (1994-2004) on 19,072 subjects with diabetes.

OBJECTIVE: To assess the time trends in the prevalence of diabetes at our Centre from 1994-2004 (N: 19,072 individuals) on the following parameters: age group, sex, rural or urban area and individuals with freshly diagnosed diabetes versus known diabetes. STUDY DESIGN AND SETTING: Analysis of data from electronic medical records at a referral Endocrine and Diabetes Centre in Southern India. METHODS: We have employed the period prevalence method and person-time risk to express the results. The concept of person-time risk can be estimated as the actual time-at-risk in years that all persons contributed to a study. The person-time can be estimated for each patient when a patient changed from diabetic free to diabetic patient. This can be captured for each patient from the variable onset of first diagnoses as a diabetic patient. Thus person-time is employed to derive information on the rate at which people acquire the disease. RESULTS: Between 1994 and 2004 however there is an increasing trend in the number of individuals in the young, particularly the 18-34 year group. Similarly there is a steadily increasing pattern in both urban and rural areas; the number from rural areas tended to increase compared to urban areas. The number of women with diabetes tended to increase over the 10-year period. CONCLUSION: Between 1994 and 2004 among persons with diabetes who presented at our Centre, there was a trend toward more number of younger persons, particularly women from rural areas.

Sequence analysis and homology modeling Gallus gallus glutathione S-transferase (Q08392).

Glutathione S-transferases (GST) belong to the transferase group of enzymes; GST are a family of enzymes that catalyze the addition of glutathione to endogenous or xenobiotic, often toxic electrophilic chemicals, and a major group of detoxification enzymes. We used the homology modeling technique to construct the structure of Gallus gallus GST. The amino acid sequence identity between the target protein and sequence of template protein 1ML6 (Mus musculus) was 66.2%. Based on the template structure, the protein model was constructed by using the Homology program Modeller9v1, and briefly refined by energy minimization steps; it was validated by PROCHECK. In all, 94.4% of the amino acids were in allowed regions of Ramachandran plot, showing the accuracy of the model and good stereochemical quality. Our results correlated well with the experimental data reported earlier, which proved the quality of the model. This generated model can be further used for the design and development of more potent GST inhibitors.

Malignant melanoma of the mandibular gingiva: a rare occurrence.

Primary mucosal malignant melanoma of the oral cavity is a rare tumor. It accounts for only 0.2-8% of all malignant melanomas. This malignancy commonly affects male subjects and is more frequently seen on the hard palate and maxillary gingiva. The peak age for diagnosis of oral melanoma is between 55 and 65 years. A biopsy is required to establish a diagnosis. Ablative surgery with tumor-free margins remains the treatment of choice. It has a much poorer prognosis than its counterpart on the skin. Here, we present a case of malignant melanoma of the mandibular lingual gingiva in a 55-year-old male patient. Immunohistochemistry and special stains were conducted for confirmatory diagnosis.

Built environment and diabetes.

Development of type 2 diabetes mellitus is influenced by built environment, which is, 'the environments that are modified by humans, including homes, schools, workplaces, highways, urban sprawls, accessibility to amenities, leisure, and pollution.' Built environment contributes to diabetes through access to physical activity and through stress, by affecting the sleep cycle. With globalization, there is a possibility that western environmental models may be replicated in developing countries such as India, where the underlying genetic predisposition makes them particularly susceptible to diabetes. Here we review published information on the relationship between built environment and diabetes, so that appropriate modifications can be incorporated to reduce the risk of developing diabetes mellitus.

Cluster analysis and phylogenetic relationship in biomarker identification of type 2 diabetes and nephropathy.

Cluster analysis of DNA microarray data that uses statistical algorithms to arrange the genes according to similarity in patterns of gene expression and the output displayed graphically is described in this article. Hierarchical clustering is a multivariate tool often used in phylogenetics, comparative genomics to relate the evolution of species. The patterns seen in microarray expression data can be interpreted as indications of the status of the genes responsible for nephropathy in peripheral blow cells of type 2 diabetes (T2DN). Out of 415 genes totally expressed in the 3 DNA chips it was concluded that only 116 genes expressed in T2DN and in that only 50 are functional genes. These 50 functional genes are responsible for diabetic nephropathy; of these 50, some of the genes which are more expressed and responsible are AGXT: Alanine-glyoxylate aminotransferase, RHOD: Ras homolog gene family, CAPN6: Calpain 6, EFNB2: Ephrin-B2, ANXA7: Annexin A7, PEG10: Paternally expressed 10, DPP4: Dipeptidyl-peptidase 4 (CD26, adenosine deaminase complexing protein 2), ENSA: Endosulfine alpha, IGFBP2: Insulin-like growth factor binding protein 2, 36kDa, CENPB: Centromere protein B, 80kDa, MLL3: Myeloid/lymphoid or mixed-lineage leukemia 3, BDNF: Brain-derived neurotrophic factor, EIF4A2: Eukaryotic translation initiation factor 4A, isoform 2, PPP2R1A: Protein phosphatase 2 (formerly 2A), regulatory subunit A, alpha isoform. Fifty genes and their nucleotide sequences are taken from NCBI and a phylogenetic tree is constructed using CLUSTAL W and the distances are closer to each other concluding that based on the sequence similarity and evolution the genes are expressed similarly. Literature survey is done for each gene in OMIM and the genes responsible for diabetic nephropathy are listed.

A clinical decision support system using multilayer perceptron neural network to assess well being in diabetes.

BACKGROUND: Diabetes mellitus is an increasingly common life-style disorder whose management outcomes are measured in symptomatic, biochemical as well as psychological areas. Well being as an outcome of treatment is being increasingly recognized as a crucial component of treatment. There is little published literature on psychosocial outcomes and the factors influencing them. Therefore we have developed a neural network system which is trained to predict the well being in diabetes, using data generated in real life. MATERIAL AND METHODS: We developed a Multi Layer Perceptron Neural Network model, which had been trained by back propagation algorithm. Data was used from a cohort of 241 individuals with diabetes. We used age, gender, weight, fasting plasma glucose as a set of inputs and predicted measures of well-being (depression, anxiety, energy and positive well-being). RESULTS: It was observed that female patients report significantly higher levels of depression than their male counter parts. Some slight high or no significant differences are observed between males and female patients with regard to the number of persons with whom they share their anxieties and fears regarding diabetes. There is not much difference has been observed in energy levels of both males and females. Also, Males have higher pwb value when compared with the female counterparts. Also, this may be due to women tend to react more emotionally to disease and hence experience more difficulty in coping with it. The present sample of women being predominantly house wives may be worrying more about their health and its problems. Also, it is observed that, gender differences are significant with regard to total general well-being. With five inputs (age, sex, weight, fasting plasma glucose, bias), four outputs are four (depression, anxiety, energy and positive well-being) the momentum rate was 0.9, the learning rate 0.7, using a sample of 50. the maximum individual error is 0.001 when the number of iterations were 500, number of hidden layers is 1 and the number of units in the hidden layer are 6, the normalized system error was 470.57. With input samples of 100, 150 and 200, keeping the other variables constant, the normalized system error was 419.61, 359.67 and 332.32 respectively. Similar values are found for the normalized system error when the number of units in the hidden layer have been increased to 7, 8 and 9 respectively. With two hidden layers, and with each hidden layer containing 6,7 ,8, 9, 10, 11 units for the samples 50, 100, 150, and 200, the same values of normalized system error was found. Women having weight between 40 kgs and 85kgs had higher levels of depression than men who had weight between 39kgs and 102 kgs. CONCLUSION: We have developed a prototype neural network model to predict the psychosocial well-being in diabetes, when biological or biographical variables are given as inputs. When greater data was fed to the system, the normalized system error can be reduced.

Psychosocial aspects of women with polycystic ovary syndrome from south India.

BACKGROUND: Polycystic ovary syndrome (PCOS), though initially manifesting with reproductive and cosmetic symptoms is a harbinger of insulin resistance syndrome. It is associated with psychological distress in both management as well as in its etiology. There are no Indian studies on psychological stress in women with PCOS. METHODS: Ninety nine women who presented with PCOS to the Endocrinology clinic were administered Goldberg's GHQ 28 (General Health Questionnaire) to assess psychological status, along with clinical, hormonal and ultrasound evaluation. RESULTS: Fifty four percent had a GHQ28 score >8. Among them 38% had a family size <4, 72% had obesity, 70% had hirsutism, 72% had a waist circumference >88 cm and 69% had a F/G score >4 . All these variables were statistically significant; p < 0.05 using Chi-square test. CONCLUSION: Women presenting with PCOS had increased psychological distress, which was related to smaller size of family, and more severe physical manifestations of the condition.

Psychiatric co-morbidity & diabetes.

Diabetes mellitus as well as psychiatric disorders are common. These may occur with one another and/or one may worsen the other. Psychological stress may follow screening for diabetes, as well as when diabetes is first identified. Acting through the hypothalamo-pituitary-adrenal axis, stress may initiate or worsen hyperglycaemia. Depression may be a risk factor for the development of diabetes; it also commonly occurs in subjects with diabetes. Identification and management are both important in preventing the disability. A variety of antipsychotic medications, especially the newer agents can induce weight gain, dyslipidaemia, insulin resistance and diabetes. Therefore in choosing a drug, one must consider the risk factors and screen for metabolic syndrome. Subjects with type 1 diabetes can have cognitive dysfunction, eating disorders and developmental disturbances. Physicians caring for people with diabetes must be trained to recognize and manage co-morbid psychiatric conditions that commonly occur. A biopsychosocial disease model for both conditions can leverage the social strengths and medical knowledge in developing countries.