A 52-week extension study of switching from gemigliptin vs sitagliptin to gemigliptin only as add-on therapy for patients with type 2 diabetes who are inadequately controlled with metformin alone.

We investigated the long-term efficacy and safety of gemigliptin and the efficacy and safety of gemigliptin treatment after once-daily treatment with sitagliptin 100 mg, in patients with type 2 diabetes. This was a 28-week extension of a 24-week, randomized, double-blind, parallel study of gemigliptin or sitagliptin added to ongoing metformin therapy. After randomization to sitagliptin 100 mg qd (S), gemigliptin 25 mg bid (G1) or gemigliptin 50 mg qd (G2) and after completing 24 weeks of treatment, 118 patients switched from gemigliptin 25 mg bid to 50 mg qd (G1/G2), 111 patients continued gemigliptin 50 mg qd (G2/G2) and 106 patients switched from sitagliptin 100 mg qd to gemigliptin 50 mg qd (S/G2). All 3 treatments reduced glycated haemoglobin (HbA1c) (S/G2,-0.99% [95% CI -1.25%, -0.73%]; G1/G2, -1.11% [95% CI -1.33%, -0.89%]; G2/G2, -1.06% [95% CI -1.28%, -0.85%]). The percentage of patients achieving HbA1c < 6.5% was 27.6% in the G1/G2 group at both Week 24 and Week 52, and ranged from 27.3% to 32.7% in the G2/G2 group (difference in proportions, 5% [95% CI -6%, 17%]), while it increased from 6.8% to 27.3% from Week 24 to Week 52 in the S/G2 group (difference in proportions, 20% [95% CI 7%, 34%]). Addition of gemigliptin 50 mg qd to metformin was shown to be efficacious for 52 weeks. Switching from sitagliptin 100 mg to gemigliptin 50 mg showed consistent glyacemic control over the previous treatment.

The performance and reproducibility of late-night salivary cortisol estimation by enzyme immunoassay for screening Cushing disease.

OBJECTIVE: Our study aimed to establish a local reference range for late-night salivary cortisol (LNSC) using enzyme immunoassay (EIA) and to study the intra-individual reproducibility of LNSC. METHODS: Prospective study involving 30 healthy subjects (HS) with body mass index (BMI) <25 kg/m2, 37 obese/overweight subjects (OS) with BMI >25 kg/m2 and 28 patients with Cushing disease (CD). Salivary sampling was performed on 2 consecutive nights and assayed by EIA. The reference range was established using LNSC values of HS, and receiver operating characteristic (ROC) curves were used to determine diagnostic cutoffs. RESULTS: The mean LNSC level of CD was significantly higher than HS and OS (CD: 16.96 ± 9.11 nmol/L, HS: 1.30 ± 0.95 nmol/L, and OS 1.21 ± 0.78 nmol/L). A cutoff of 2.92 nmol/L differentiated CD from HS with 100% sensitivity and 96.7 % specificity, and a cutoff of 5.04 nmol/L yielded a specificity of 100% with a sensitivity of 96.4% to distinguish CD from OS. There was more intra-individual variability in HS (55%) than in CD (49%) and OS (22%). There was no difference in the sensitivity and specificity derived from the ROCs using day 1 values or the higher of the 2 LNSCs. CONCLUSIONS: In our cohort, we found that LNSC assayed by EIA showed good sensitivity and specificity to screen patients suspected to have CD. Although intra-individual variability was significant, it did not hamper the diagnostic performance of the test.

Peak bone mineral density and its determinants in an Asian Indian population.

Data on peak bone mineral density (BMD) and its determinants in Asian Indians are limited. We studied the peak BMD and its determinants in Asian Indians. A total of 1137 young (age: 25--35yr) healthy volunteers of either sex (558 men and 579 women) were recruited for dietary evaluation, analyses of serum calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D [25(OH)D], and intact parathyroid hormone (iPTH) levels, and measurement of BMD with dual-energy X-ray absorptiometry. In men and women, peak bone mass (PBM) at the femoral neck, femoral trochanter, total femur, and lumbar spine was achieved between 25 and 30yr of age, whereas PBM at the femoral intertrochanter occurred between 30 and 35yr of age. Peak BMD was lower than that of Caucasians by 15.2--21.1% in men and 14.4--20.6% in women. On stepwise multiple regression, height and weight were the most consistent predictors of BMD at all sites in both groups. In men, 25(OH)D positively predicted BMD at the hip, whereas in women, serum iPTH negatively predicted BMD at the femoral trochanter and total femur. The study concluded that Asian Indians have significantly lower peak BMD than Caucasians and that weight and height are the most consistent predictors of BMD at all sites in both men and women.

High prevalence of hypovitaminosis D in young healthy adults from the western part of India.

OBJECTIVE: Data on the prevalence of hypovitaminosis D in Indians living in the western part of the country are limited. The authors aimed to study the vitamin D status and dietary intake of calcium and phytates in healthy adult volunteers from a city in the western part of India. METHODS: This cross-sectional study was conducted at a tertiary care centre in western India. A total of 1137 young (age: 25-35 years), healthy volunteers of both sexes were included in the study. All subjects were assessed for sun exposure, dietary intake of energy, protein, fat, calcium and phytates. Biochemical investigations included calcium, inorganic phosphorus, alkaline phosphatase, 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (iPTH), total proteins, albumin and creatinine in serum and spot urinary calcium to creatinine ratio. RESULTS: The serum 25(OH)D concentration for the whole study population was low (17.4±9.1 ng/ml), and that for men and women were 18.9±8.9 ng/ml and 15.8±9.1 ng/ml, respectively. Seventy per cent of the study population had hypovitaminosis D (25(OH)D <20 ng/ml) with a slightly higher prevalence in women (76%). Mean dietary calcium intake of the study population was 322.92±135.17 mg/day and was very low when compared with the recommended dietary allowance (400 mg/day for adults of both sexes) issued by the Indian Council of Medical Research. Dietary phytate was much higher than calcium intake with a dietary phytate to calcium ratio of 2.25±0.76. Serum iPTH had significant negative correlation with 25(OH)D (r=-0.23, p<0.001). CONCLUSION: Hypovitaminosis D, low dietary calcium and high phytate consumption are highly prevalent among young healthy adults in the western part of India.

Oral glucose lowering with linagliptin and metformin compared with linagliptin alone as initial treatment in Asian patients with newly diagnosed type 2 diabetes and marked hyperglycemia: Subgroup analysis of a randomized clinical trial.

AIMS/INTRODUCTION: Type 2 diabetes mellitus is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enroll predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed type 2 diabetes mellitus patients in Asia with marked hyperglycemia. MATERIALS AND METHODS: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed type 2 diabetes mellitus patients with glycated hemoglobin A1c (HbA1c) 8.5-12.0% were randomized to double-blind oral treatment with linagliptin/metformin or linagliptin monotherapy. The primary end-point was the change from baseline in HbA1c at week 24. We evaluated data for the 125 participants from Asian countries. RESULTS: After 24 weeks, the mean ± standard error reduction from baseline in HbA1c (mean 10.0%) was -2.99 ± 0.18% with linagliptin/metformin and -1.84 ± 0.18% with linagliptin; a treatment difference of -1.15% (95% confidence interval -1.65 to -0.66, P < 0.0001). HbA1c <7.0% was achieved by 60% of participants receiving linagliptin/metformin. The mean bodyweight change after 24 weeks was -0.45 ± 0.41 kg and 1.33 ± 0.45 kg in the linagliptin/metformin and linagliptin groups, respectively (treatment difference -1.78 kg [95% confidence interval -2.99 to -0.57, P = 0.0043]). Drug-related adverse events occurred in 9.7% of participants receiving linagliptin/metformin and 4.8% of those receiving linagliptin. Hypoglycemia occurred in 6.5% and 4.8% of the linagliptin/metformin and linagliptin groups, respectively, with no severe episodes. Gastrointestinal disorders occurred in 12.9% and 12.7% of the linagliptin/metformin and linagliptin groups, respectively, with no associated treatment discontinuations. CONCLUSIONS: In people from Asia with newly diagnosed type 2 diabetes mellitus and marked hyperglycemia, the initial combination of linagliptin and metformin substantially improved glycemic control without weight gain and with infrequent hypoglycemia. Initial oral combination therapy might be a viable treatment for such individuals.

Pilot study to evaluate the effect of short-term improvement in vitamin D status on glucose tolerance in patients with type 2 diabetes mellitus.

OBJECTIVE: To study the effect of improvement in vitamin D status on glucose tolerance in Asian Indian patients with moderately controlled type 2 diabetes mellitus (T2DM). METHODS: This randomized, double-blind, placebo-controlled pilot study was conducted in 28 Asian Indian patients with T2DM. Study participants were randomly assigned to a vitamin D-treated group (group D) or a placebo group (group P). Serum 25-hydroxyvitamin D, hemoglobin A1c, and serum fructosamine levels were measured, and an oral glucose tolerance test (OGTT) was performed in all patients at baseline and 4 weeks after intervention. During the OGTT, plasma glucose and serum insulin levels were measured at 0, 30, 60, 90, and 120 minutes. The unpaired t test was used to compare the groups at baseline and to compare the differences in changes from baseline to 4 weeks between the 2 study groups. RESULTS: Group D and group P were similar with respect to their fasting plasma glucose and serum insulin concentrations, post-OGTT plasma glucose and serum insulin levels, and hemoglobin A1c and fructosamine values at baseline. Serum 25-hydroxyvitamin D levels increased significantly in group D at 4 weeks. No significant differences were found between the groups at baseline and 4 weeks with respect to serum fructosamine, fasting plasma glucose and serum insulin, post-OGTT plasma glucose and serum insulin levels, and homeostasis model assessment of insulin resistance. CONCLUSION: In this study, short-term improvement in vitamin D status was not associated with improvement in glucose tolerance, insulin secretion, or insulin sensitivity in Asian Indian patients with moderately controlled T2DM.

Prevalence of hypogonadism in patients with type 2 diabetes mellitus in an Asian Indian study group.

OBJECTIVE: To determine the prevalence of hypogonadism in Asian Indian patients with type 2 diabetes mellitus (T2DM) and to correlate it with components of the metabolic syndrome and microvascular complications of T2DM. METHODS: One hundred consecutive male patients with T2DM between 25 and 50 years of age and 50 age-matched healthy adults without diabetes underwent assessment. Calculated free testosterone was derived by using serum total testosterone and sex hormone-binding globulin. Those patients with 2 calculated free testosterone values less than 64.8 pg/mL were diagnosed as having hypogonadism. RESULTS: Of the 100 patients with T2DM, 15 (15%) were found to have hypogonadism-7 of 29 (24%) between 31 and 40 years of age and 8 of 67 (12%) between 41 and 50 years old. None of the 4 patients between 25 and 30 years old had hypogonadism. Eleven patients (73%) had hypogonadotropic hypogonadism, and 4 (27%) had hypergonadotropic hypogonadism. Among the control subjects, the prevalence of hypogonadism was 10%. In comparison with Western data, we found a higher prevalence of hypogonadism in patients with T2DM, especially in those in the 4th decade of life. The prevalence of hypogonadism was higher in obese patients, although it did not reach statistical significance. No statistically significant correlation was observed between hypogonadism and age, duration of diabetes, glycemic control, androgen deficiency symptoms, or microvascular complications. CONCLUSION: The prevalence of hypogonadism was higher in the patients with diabetes than in the control subjects, although the difference did not reach statistical significance. There was no correlation of hypogonadism with components of the metabolic syndrome or microvascular complications of diabetes mellitus.