Comparison of teneligliptin and other gliptin-based regimens in addressing insulin resistance and glycemic control in type 2 diabetic patients: a cross-sectional study.

INTRODUCTION: The objective of this study was to compare the effects of teneligliptin-based regimens and other gliptin-based regimens with respect to insulin resistance and glycemic control in patients with type 2 diabetes mellitus (T2DM). METHODS: We enrolled T2DM subjects, inadequately controlled with metformin and glimepiride and taking one of the gliptins, and divided them into two groups, i.e. group 1 (teneligliptin-based regimens) and group 2 (other gliptin-based regimens). Fasting plasma insulin, adiponectin levels, homeostatic model assessment for insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), and fasting blood glucose (FBG) were measured and compared. Costs of different gliptins were noted, and mean cost of per day therapy was compared. RESULTS: Eighty-six subjects participated in this study (43 each in group 1 and group 2). No significant differences were observed in FBG, HbA1c, insulin levels, and HOMA-IR, but the trend was in favor of teneligliptin-based regimens. A significantly higher number of subjects achieved HbA1c target in group 1 (P < 0.001). Teneligliptin had significantly lower cost of per day therapy as compared to other dipeptidyl peptidase-4 inhibitors. CONCLUSION: Teneligliptin seems to be cost-effective and safer option in T2DM subjects who were not adequately controlled with metformin and sulfonylureas. However, further prospective studies are needed.

Finding the most cost-effective option from commonly used Dipeptidyl peptidase-4 inhibitors in India: a systematic study.

OBJECTIVE: To identify a preferred and cost-effective drug among Dipeptidyl peptidase-4 inhibitors (DPP4Is) for Indian patients with T2DM. METHODS: We performed a systematic literature search using standard databases for relevant literature. Original studies comparing the efficacy and/or safety of different DPP4Is were included. Two authors independently performed the literature search, screening, and collected relevant data from the selected studies. The costs of all brands of individual DPP4Is were noted and compared for lowest, highest, and average cost. Finally, we summarized the information with respect to Efficacy, safety, suitability, and cost to find the most cost-effective DPP4I. RESULTS: We found 13 eligible studies containing data on 15,720 subjects. These studies showed similar efficacy (or better) and safety with teneligliptin as compared to other DPP4Is. Teneligliptin also showed additional benefits other than the glycemic control. The average cost per tablet of teneligliptin 20 mg was markedly lower as compared to sitagliptin, vildagliptin, and other commonly used DPP4Is. Teneligliptin also outscored other commonly used DPP4Is in India in suitability and seems to have better patient compliance. CONCLUSIONS: Teneligliptin 20 mg could be considered as the preferred and most cost-effective agent among commonly used DPP4Is for the effective management of patients with T2DM in India.

Potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus: current status and future prospects.

INTRODUCTION: Based on pharmacological properties and results from clinical studies, teneligliptin has a great potential to be used as an alternate-day therapy and also the daily dose can be reduced to 10 mg. Clinical data also suggest its excellent efficacy and safety among older subjects. AREAS COVERED: We have reviewed and discussed potential approaches using teneligliptin for the treatment of type 2 diabetes mellitus (T2DM) including alternate-day therapy and reduction of dose from 20 mg to 10 mg per day. We have also discussed the potential of teneligliptin to address the needs of older patients with T2DM. EXPERT OPINION: It is an excellent option for use in older patients as studies in the geriatric population have shown encouraging results. Teneligliptin has a desirable pharmacokinetic profile that makes it a potential drug for use on an alternate-day basis. Teneligliptin has shown anti-diabetic efficacy even at a dose of 10 mg. These approaches may improve treatment satisfaction and patient compliance and can lower the cost; however, it is crucial to identify the subset of T2DM patients who can obtain maximum benefits. To verify these effects, large clinical investigations need to be planned and robust clinical evidence should be generated.

Ruminal fermentation and methane production in vitro, milk production, nutrient utilization, blood profile, and immune responses of lactating goats fed polyphenolic and saponin-rich plant extracts.

This study was conducted to evaluate the effect of a composite plant extract (CPE) rich in polyphenolics and saponins from seeds of Dolichos biflorus (horse gram), root of Asparagus racemosus (shatavari), bark of Amoora rohituka (rohitaka), and peel of Punica granatum (pomegranate) on ruminal fermentation and methanogenesis in vitro, milk production, nutrient digestibility, immune response, and blood profiles in lactating Beetal goats fed CPE at 20 g/kg diet. Dose effect of CPE was assessed using different doses (0, 10, 20, 30, and 40 g/kg substrate) to find out an optimum dose for the in vivo study. The in vivo experiment lasted 70 days including a 10-day adaptation period. In the in vitro study, dry matter (DM) and fiber degradability increased linearly (P < 0.05) and methane production and ammonia concentration decreased linearly (P < 0.05) with increasing doses of CPE. Concentrations of total VFA and proportion of propionate increased (P < 0.001) linearly, whereas proportion of acetate and acetate to propionate ratio decreased with a linear effect. Dietary CPE increased milk yield (P = 0.017) and concentrations of protein and lactose (P = 0.045) by CPE, but concentrations of fat and solid not fat in milk were not affected (P > 0.10). Somatic cell counts in milk reduced (P = 0.045) in the CPE-fed goats. Apparent digestibility of DM (P = 0.037) increased significantly and NDF (P = 0.066) tended to increase due to supplementation of CPE. Blood glucose (P = 0.028) and albumin (P = 0.007) concentrations increased, while other liver-marker metabolites and enzyme activities and superoxide dismutase activity were not altered in goats due to feeding of CPE. Concentrations of total amino acids (P = 0.010), total essential amino acids (P = 0.012), and total ketogenic amino acids (P < 0.001) were greater in the CPE-fed goats than the control goats. Cell-mediated immune response improved due to CPE feeding. This study suggests that the CPE rich in both phenolics and saponins could improve ruminal fermentation, milk production, and nutrient utilization in lactating goats with better health status while decreasing methane emission.

Mean platelet volume and glycaemic control in patients with new-onset Type 2 diabetes mellitus.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with vascular complications that are attributable to dysregulated platelet reactivity as measured by mean platelet volume (MPV). This study aimed at determining a relationship between MPV and glycaemic control in new-onset T2DM. METHODS: This was a prospective study conducted on 236 new-onset T2DM patients divided in two groups as group A, glycosylated haemoglobin A1c (HbA1c < 7.9%; n = 70) and group B, HbA1c ⩾ 8% (n = 107) who were followed up for 6 months for change in platelet and glycaemic parameters. RESULTS: At 6-month follow-up, there was a significant decrease in HbA1c and MPV (group A (HbA1c: 7.40 ± 0.40 vs 7.03 ± 0.23%, p < 0.03; MPV: 9.65 fl ± 0.74 vs 9.46 fl ± 0.71, p < 0.001) and group B (HbA1c: 10.59 ± 1.89% vs 9.29 ± 1.50%, p < 0.001; MPV: 10.89 fL ± 1.29 vs. 10.23 fL ± 1.40, p< 0.001)). The percentage decline in HbA1c was more in group B (11.81 ± 5.87 vs 4.76 ± 4.58, p < 0.01). There was a positive correlation between ΔMPV and ΔHbA1c in group B; however, we did not observe significant correlation for group A. CONCLUSION: We interpret that in people with diabetes with baseline HbA1c ⩾ 8%, with improvement in glycaemic control, there is a significant decrease in MPV. We propose that a routine MPV testing can be used as a potential marker for glycaemic control in T2DM.

Anthropometric and Pubertal Outcomes in Girls With Classical Congenital Adrenal Hyperplasia.

OBJECTIVES: To evaluate the anthropometric and pubertal outcomes, over a spectrum of treatment regimens and compliance. METHODS: We reviewed records of the patients with classical CAH seen at the endocrinology clinic of a tertiary care center between 1995 and 2016. RESULTS: 25 females were included in the study, the majority (80%) with simple virilizing variant. All patients had genital ambiguity since birth, yet 40% (10/25) presented much later with menstrual complaints. All patients received hydrocortisone, but some switched to dexa-methasone (n=7) or prednisolone (n=4). 7/9 (77.9%) girls who achieved target height, were on hydrocortisone. Menarche occurred with corticosteroid treatment in 60% (15/25) patients at a median (IQR) age of 16 (12-22) years. CONCLUSION: Hydrocortisone seems to have a beneficial effect on linear growth. Once target height is achieved, dexamethasone may be considered as an alternative.

Alternate-day add-on therapy with dapagliflozin in patients with type 2 diabetes mellitus: potential benefits and concerns.

INTRODUCTION: Factors such as compliance, cost and safety play a major role in achieving the long-term goal in the management of type 2 diabetes mellitus (T2DM). Dapagliflozin carries a great potential of becoming an alternate-day therapy because of its favorable pharmacological properties. AREAS COVERED: In this review, we have discussed and hypothesized the potential of dapagliflozin as an alternate-day add-on drug in T2DM patients. We have discussed the properties by virtue of which it carries a potential to become an alternate-day therapy. We have also explained the potential benefits and concerns of using this approach. EXPERT OPINION: Alternate-day add-on therapy with dapagliflozin could be a promising approach in reducing the cost, improving the treatment satisfaction and reducing the adverse effects. However, this propsed indication demands an in-depth investigation among T2DM subjects who are not able to achieve glycemic control with standard monotherapy or combination therapy. Pilot studies or some small-scale investigator-initiated trials or academic clinical trials may be carried out to explore this concept. At the same time, large industry sponsored multicenter clinical trials including pharmacoeconomic analyses may be planned to have a more detailed investigation.

Potential Role of Dexamphetamine in the Treatment of Non-alcoholic Fatty Liver Disease: Hopes and Pitfalls.

Non-alcoholic fatty liver disease (NAFLD) is one of most frequent causes of chronic liver disease. Global prevalence of NAFLD and nonalcoholic steatohepatitis (NASH) with advanced fibrosis is increasing day by day. Patients with NAFLD are more susceptible to encounter cardiovascular morbidity and mortality. Apart from lifestyle changes and dietary modifications, no effective pharmacotherapy is available to prevent the progression of NAFLD to NASH and advanced stages of hepatic fibrosis and cirrhosis. Dexamphetamine is the d-isomer of amphetamine, which acts by inhibiting monoamine reuptake and direct stimulation of dopamine and noradrenaline release. Presently, dexamphetamine is indicated for the treatment of attention deficit hyperactivity disorder and narcolepsy, but since its use was found to be associated with weight loss, it is also now used as an off-label drug for the treatment of obesity. Direct or indirect evidence is present in the form case reports, case series and from effects of related drugs to support the potential role of dexamphetamine in NAFLD. There is an urgent need to initiate preclinical and clinical studies involving robust methodology and adequate sample sizes to explore the potential of dexamphetamine in patients with NAFLD. In this review, we will discuss the therapeutic potential of dexamphetamine for the treatment of NAFLD.

Diabetes Mellitus of Pituitary Origin: A Case Report.

We describe the case report of 36-year-old female who presented to the emergency department with diabetic ketoacidosis. On detailed clinical examination, coarse facial features in the form of large fleshy nose, thick lips, prognathism, and thickening of hands and feet were noticed, suggestive of acromegaly. Subsequently, she was diagnosed with acromegaly due to somatotropinoma. Impaired glucose tolerance and diabetes mellitus are frequently associated with acromegaly. Persistent growth hormone excess impairs insulin sensitivity, increases gluconeogenesis, reduces glucose uptake in adipose tissue and muscle, and alters pancreatic ß-cell function. Rarely, diabetic ketoacidosis can be the presenting manifestation, as seen in this case.

From Psychiatry to Neurology and Endocrinology: A Case of Hypoparathyroidism.

A 31-year-old male patient developed extrapyramidal symptoms while on treatment for depression. He was investigated and found to suffer from hypoparathyroidism. He had calcification in the brain, signs and symptoms of neuromuscular irritability, and QT prolongation on electrocardiogram. He was treated with calcium carbonate and calcitriol. Although he had marked improvement, bradykinesia persisted. This report highlights the importance of maintaining a high index of suspicion for hypocalcemia, and the importance of searching for an organic basis for psychiatric symptoms.

Klinefelter Syndrome Presenting as Suicidal Attempt.

Klinefelter syndrome is the most common sex chromosome disorder, manifested as hypogonadism, gynecomastia, and impaired spermatogenesis. It is characterized by the presence of one or more extra X chromosomes. Patients with Klinefelter syndrome are highly susceptible to psychiatric disturbances as compared to the general population. These include personality changes, depression, and psychosis. Rarely, these psychiatric disturbances can be the presenting manifestations in these individuals. Hence, meticulous clinical examination should be performed in every patient of psychiatric illness to rule out systemic illness like hypogonadism, as the treatment of underlying medical condition can be beneficial in alleviation of the psychiatric illness.

Type 2 Autoimmune Polyglandular Syndrome Presenting with Hyperpigmentation and Amenorrhea.

A 36-year-old female presented with lethargy, anorexia, nausea, hyperpigmentation, weight loss and amenorrhea for six months. On examination, she had hyperpigmentation of face, hands and oral mucosa. Investigations revealed adrenal insufficiency and subclinical hyperthyroidism with elevated anti-thyroid peroxidase antibodies. Adrenal insufficiency in combination with Grave's disease and/or type 1 diabetes mellitus occurs in type 2 autoimmune polyglandular syndrome. It is a polygenic disorder occurring due to mutations in the human leukocyte antigen complex on chromosome 6. The patient was treated with oral hydrocortisone which led to improvement in all the symptoms.

Endometriosis at Cesarean Scar Presenting As an Acute Abdomen.

A 30-year-old female presented to the emergency department with severe abdominal pain and vomitings during her premenstrual period. Abdominal imaging revealed a mass originating from the scar of cesarean section extending into the rectus muscle. The cesarean section was performed four years back. Her history was significant for pain at the site of lesion during menses associated with disproportionate nausea. She was managed conservatively and improved. Fine needle aspiration cytology of the lesion established the diagnosis of scar endometriosis, and there was a permanent resolution of symptoms after its resection.

Suppurative thyroiditis.

Acute bacterial suppurative thyroiditis is an infrequent but life-threatening medical emergency. It needs to be considered in a patient with painful thyroid enlargement. Therapy consists of appropriate antibiotics and drainage of abscess. The disease may prove fatal if diagnosis and treatment are delayed.

Vitamin D supplementation improves simvastatin-mediated decline in exercise performance: A randomized double-blind placebo-controlled study.

BACKGROUND: The aim of the present study was to determine the effect of vitamin D supplementation on simvastatin-mediated changes in cardiorespiratory fitness and skeletal muscle mitochondrial content after exercise in adults with type 2 diabetes mellitus (T2DM). METHODS: Vitamin D-deficient T2DM patients aged 25-50 years performed moderate intensity aerobic exercise for 12 weeks and were randomized to receive simvastatin 40 mg daily, simvastatin 40 mg daily plus vitamin D 60 000 units once weekly, or vitamin D 60 000 units once weekly. The primary outcomes were cardiorespiratory fitness (peak oxygen consumption) and skeletal muscle mitochondrial content (citrate synthase activity in the vastus lateralis) following simvastatin and/or vitamin D replacement therapy. RESULTS: Twenty-eight patients completed the study. Cardiorespiratory fitness decreased by 8.4% (P < 0.05) following 12 weeks of simvastatin therapy. Vitamin D supplementation blunted the decline in cardiorespiratory fitness to 0.6% (P < 0.05 for between-group difference in change from baseline). Similarly, skeletal muscle mitochondrial content decreased by 3.6% with simvastatin, but improved by 12.1% on supplementation with vitamin D, although the between-group difference was not significant. Vitamin D alone increased cardiorespiratory fitness and mitochondrial content by 7.1% (P < 0.05) and 16.7%, respectively. CONCLUSIONS: Simvastatin tends to cause deterioration in exercise-associated cardiorespiratory fitness and skeletal muscle mitochondrial content in adults with T2DM, which is blunted by vitamin D supplementation.

Randomized controlled trial comparing 2 different starting doses of methotrexate in rheumatoid arthritis.

PURPOSE: Methotrexate (MTX) remains the gold standard disease-modifying antirheumatic drug for the treatment of rheumatoid arthritis (RA). Few studies have compared different starting doses of MTX in RA. We hypothesized that starting with a higher MTX dose may be more effective but associated with more adverse effects. We compared a starting dose of 7.5 versus 15 mg per week of MTX followed by similar fast escalation. METHODS: This was an open-label (blinded assessor), parallel-group, randomized controlled trial that included RA patients aged 18 to 65 years, not on MTX, and having active disease (Disease Activity Score for 28 joints using 3 variables [DAS28(3)] ≥5.1). Patients were randomized to receive MTX at a starting dose of 7.5 mg (group 1) or 15 mg (group 2) per week. The dose of MTX was escalated by 2.5 mg every 2 weeks to a maximum of 25 mg. Patients were seen every 4 weeks, and dose escalation was continued if DAS28(3) was >2.6 and there were no laboratory abnormalities (transaminitis [>2 × upper limit of normal] or cytopenia). The primary endpoint was change in disease activity at 12 weeks (assessed by using the DAS28[3]). Secondary endpoints were patient withdrawals and episodes ofcytopenia or transaminitis. Adverse effects were ascertained by using a questionnaire. Both intention-to-treat and per-protocol analyses were performed. FINDINGS: We enrolled 100 patients (female:male ratio, 78:22) with a mean (SD) age of 43.6 (10.8) years and a disease duration of 4.7 (4.8) years. At baseline, patients had a mean DAS28(3) of 6.2 (0.7) and a Health Assessment Questionnaire score of 1.3 (0.6). Group 1 (7.5 mg) and group 2 (15 mg) included 47 and 53 patients, respectively, with no significant differences in baseline characteristics. At 12 weeks, the mean dose of MTX reached was 17.3 (4.6) mg in group 1 and 23.6 (3.0) mg in group 2 (P < 0.001). The 2 groups had a similar number of patient withdrawals. The mean change in DAS28(3) at 12 weeks in group 1 (-0.47 [0.86]) and group 2 (-0.55 [0.79]) was not significantly different (P = 0.60). The change in the Health Assessment Questionnaire score was also similar in the groups. The frequency of episodes of transaminitis (6 and 7; P = 0.8) and cytopenia (1 and 2; P = 0.9) did not differ significantly between groups 1 and 2, respectively. Results remained the same according to the per-protocol analysis. Among adverse effects, nausea was more common in group 2 compared with group 1 (relative risk, 1.6 [95% CI, 1.1-2.2]). IMPLICATIONS: There were no significant differences in efficacy between the 2 starting doses of MTX. The fast escalation of dose in both groups may have blunted any advantage of starting at a higher dose. Nausea occurred more commonly in patients started on 15 mg of MTX. We suggest longer trials to confirm our findings. ClinicalTrials.gov identifier: NCT01404429.

Non-islet cell tumor-induced hypoglycemia: a report of five cases and brief review of the literature.

UNLABELLED: We describe the clinical presentation, diagnostic and management issues in five cases of non-islet cell tumor hypoglycemia (NICTH), diagnosed at a tertiary care institute over a period of 15 years. The clinical, laboratory, and histopathological findings of these patients along with diagnostic utility of IGF2:IGF1 ratio are discussed. The mean age of presentation was 52 years, with a male predominance (3:2). Three patients presented with recurrent episodes of fasting hypoglycemia and it was detected in other two patients during hospitalization. Two patients had acromegaloid features that regressed following treatment. One patient had hypokalemia. Low levels of insulin, C-peptide, GH, and IGF1 were invariably found in all. The IGF2 level was elevated in only one patient; however, IGF2:IGF1 ratio was more than 10 in four of the five patients. The mean tumor size was 16.4 cm and mean weight was 3.6 kg. Four patients had mesenchymal tumors and one had epithelial tumor. NICTH is a rare cause of hypoglycemia. Hypoinsulinemic hypoglycemia with low IGF1 and IGF2:IGF1 ratio more than 10 is suggestive of this entity. LEARNING POINTS: NICTH should be considered in patients presenting with tumor of mesenchymal origin and hypoglycemia.Hypoinsulinemic hypoglycemia with low IGF1 is a strong biochemical evidence of NICTH.IGF2:IGF1 ratio of more than 10 is a complementary investigation in the absence of an assay facility for IGF2.