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1.
Clin Endocrinol (Oxf) ; 96(4): 539-548, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-34580897

RESUMEN

OBJECTIVE: Type 2 diabetes mellitus (T2DM) and hypertension commonly coexist; however, underlying primary aldosteronism (PA) can lead to worsening of hypertension, glycemia and cardiovascular risk. We aim to screen patients with T2DM and hypertension for PA by conducting a prospective monocentric study from Western India, which included adults with T2DM and hypertension from the outpatient diabetes clinic. DESIGN: Prospective study. PATIENTS AND MEASUREMENTS: Patients with an aldosterone renin ratio of ≥1.6 ng/dl/µIU/ml with plasma aldosterone concentration (PAC) ≥ 10 ng/dl were considered to be positive on a screening test. A PAC ≥ 6 ng/dl on seated saline suppression test (SST) was used to confirm the diagnosis of PA. RESULTS: Four hundred and eighty-six patients were included in this study. Seventy-six (15.6%, 95% confidence interval [CI]: 12.7%-19.1%) patients had a positive screening test with positive confirmatory test in 20 of the 36 (55.5%, 95% CI: 39.3%-71.7%) screen-positive patients who underwent SST. Patients with positive screening test had a higher proportion of females (65.8% vs. 50%; p = .011), frequent history of hypertensive crises (21.1% vs. 8%; p = .001), uncontrolled blood pressure (51.3% vs. 34.6%; p = .006), diagnosis of hypertension before diabetes (32.9% vs. 21.7%; p = .035) and higher systolic (137.6 ± 6.9 vs. 131.2 ± 17.8 mmHg; p = .004) and diastolic (85.3 ± 11.1 vs. 81.7 ± 10.7 mmHg; p = .007) blood pressures. Patients with positive confirmatory test had longer duration of diabetes (108 [60-162] vs. 42 [24-87] months; p = .012), hypertension (84 [42-153] vs. 36 [15-81] months; p = .038) and higher creatinine (1.16 [1.02-1.42] vs. 0.95 [0.84-1.12] mg/dl; p = .021). CONCLUSIONS: PA is prevalent (at least 4.1%) in Asian Indian patients with T2DM and hypertension. Further studies are needed to assess the cost-effectiveness of routine screening.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hiperaldosteronismo , Hipertensión , Adulto , Aldosterona , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Hiperaldosteronismo/complicaciones , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiología , Hipertensión/diagnóstico , India/epidemiología , Prevalencia , Estudios Prospectivos , Renina
2.
Pituitary ; 23(6): 701-715, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32894409

RESUMEN

CONTEXT: Regional variation in prevalence of genetic mutations in growth hormone deficiency (GHD) is known. AIM: Study phenotype and prevalence of mutations in GH1, GHRHR, POU1F1, PROP1 genes in GHD cohort. METHODS: One hundred and two patients {Isolated GHD (IGHD): 79; combined pituitary hormone deficiency (CPHD): 23} with orthotopic posterior pituitary were included. Auxologic, hormonal and radiological details were studied. All four genes were analysed in IGHD patients. POU1F1 and PROP1 were studied in CPHD patients. RESULTS: Of 102, 19.6% were familial cases. Height SDS, mean (SD) was - 5.14 (1.63). Peak GH, median (range) was 0.47 ng/ml (0-6.59), 72.5% patients had anterior pituitary hypoplasia (APH). Twenty mutations (novel: 11) were found in 43.1% patients (n = 44, IGHD-36, CPHD-8). GHRHR mutations (n = 32, p.Glu72* = 24) were more common than GH1 mutations (n = 4) in IGHD cohort. POU1F1 mutations (n = 6) were more common than PROP1 mutations (n = 2) in CPHD cohort. With few exceptions, this prevalence pattern is contrary to most studies in world-literature. No patients with peak GH > 4 ng/ml had mutations, signifying it as negative predictor. While many parameters were significant on univariate analysis, only positive family history and lower median peak GH levels were significant predictors of mutations on multivariate analysis in IGHD patients. CONCLUSION: At variance with world literature, we found reverse predominance of GHRHR over GH1 mutations, POU1F1 over PROP1 mutations and predominance of GHRHR p.Glu72* mutations thus re-affirming the regional diversity in GHD genetics. We report positive and negative predictors of mutations in GHD.


Asunto(s)
Enanismo Hipofisario/genética , Mutación/genética , Adulto , Pueblo Asiatico , Biomarcadores , Femenino , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Aprendizaje Automático , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad
3.
Diabetes Obes Metab ; 20(6): 1535-1541, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29436761

RESUMEN

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.


Asunto(s)
Diabetes Mellitus Tipo 2/prevención & control , Inhibidores de la Dipeptidil-Peptidasa IV/administración & dosificación , Hipoglucemiantes/administración & dosificación , Metformina/administración & dosificación , Piperidonas/administración & dosificación , Pirimidinas/administración & dosificación , Fosfato de Sitagliptina/administración & dosificación , Anciano , Diabetes Mellitus Tipo 2/sangre , Inhibidores de la Dipeptidil-Peptidasa IV/efectos adversos , Método Doble Ciego , Esquema de Medicación , Sustitución de Medicamentos , Femenino , Hemoglobina Glucada/efectos de los fármacos , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/efectos adversos , Masculino , Metformina/efectos adversos , Persona de Mediana Edad , Piperidonas/efectos adversos , Pirimidinas/efectos adversos , Fosfato de Sitagliptina/efectos adversos , Resultado del Tratamiento
4.
Clin Endocrinol (Oxf) ; 87(2): 201-206, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28273382

RESUMEN

CONTEXT: The relative recurrence risk ratio (λR ) for Hashimoto's thyroiditis (HT) has not been widely studied. The age at which thyroid function evaluation should be initiated for relatives of HT patients remains unclear. OBJECTIVE: To study λR and age-related prevalence of HT in first-degree relatives of HT patients. METHODS: First-degree relatives (n = 861) of 264 HT patients were evaluated for goitre, thyroid function tests, thyroid antibodies (TAb) and urinary iodide concentration (UIC). HT was defined as TAb positivity and hypothyroidism (subclinical/overt). λR was calculated as {number of index patients whose relatives (of particular subtype) had HT/number of index patients having relatives of same subtype}÷ population prevalence of HT (5·1%). The age-related prevalence of HT was studied using Kaplan-Meier method. RESULTS: A total of 861 relatives (205 parents, 336 siblings and 320 offspring) participated in the study. About 38·3% were TAb positive. The prevalence of HT was 16·7% (22·9% in parents, 19·6% in siblings and 9·6% in offspring). TAb positivity (48·3% vs 33·1%) and HT (23·5% vs 13·6%) were significantly more common in the goitrous group (n = 267) vs nongoitrous group. The median UIC for the study population was 182·5 µg/l. Computed λR was 9·1 for any one relative being affected, 5·9 for parents, 6·3 for siblings and 3·1 for offspring. The prevalence of HT increased with age and exceeded the adult population prevalence of 5·1% at 20 years in females and 27 years in males. CONCLUSIONS: Relatives of HT patients have a ninefold increased risk for developing HT as compared to the general population. The risk of developing HT exceeds that of the general population at 20 years in females and 27 years in males.


Asunto(s)
Salud de la Familia , Enfermedad de Hashimoto/epidemiología , Adolescente , Adulto , Factores de Edad , Anticuerpos/sangre , Niño , Susceptibilidad a Enfermedades , Femenino , Enfermedad de Hashimoto/diagnóstico , Enfermedad de Hashimoto/patología , Humanos , Masculino , Oportunidad Relativa , Prevalencia , Recurrencia , Factores Sexuales , Glándula Tiroides/inmunología , Adulto Joven
5.
Clin Endocrinol (Oxf) ; 85(1): 100-9, 2016 07.
Artículo en Inglés | MEDLINE | ID: mdl-26708526

RESUMEN

BACKGROUND: Congenital isolated hypogonadotropic hypogonadism (IHH) is caused due to defect in GnRH neuronal development, migration and action. Although genetic aetiology of IHH is increasingly being studied, Asian Indian data on phenotypic spectrum and genetic basis are scarce. OBJECTIVE: To investigate the phenotypic and genotypic spectrum of IHH in Asian Indian subjects. DESIGN, SETTING AND SUBJECTS: A cohort of 135 IHH probands were characterized phenotypically for reproductive and nonreproductive features and screened for rare sequence variations (RSVs) in five genes KAL1, FGFR1, FGF8, GNRHR and KISS1R. RESULT: Of 135 probands [56 normosmic IHH (nIHH) and 79 Kallmann syndrome (KS)], 20 were familial cases. KS group had more male dominance (M:F ratio of 8:1) as compared to nIHH group (M:F ratio of 1·5:1). Complete absence of puberty was more prevalent in KS probands (81% in KS vs 46% in nIHH). The prevalence of MRI abnormalities was more in anosmic group (92·8%) as compared to hyposmic (37·5%) and normosmic groups (15·4%). No particular nonreproductive phenotypic predominance was seen in any group. Genotyping revealed rare sequence variation (RSV) detection rate of 15·5% in five genes studied: (KAL1 - 4·4%, FGFR1 - 4·4%, GNRHR - 6·7%, oligogenicity - 1·5%). Prevalence of RSV was more common in familial cases (35%) as compared to sporadic (12·2%). GNRHR RSV p.C279Y (not reported in patients of ethnicities other than south Asians) was recurring in four unrelated patients. CONCLUSION: In our cohort, 60% were KS with majority of males and a severe reproductive phenotype as against nIHH. Contribution of the genetic burden for the five genes studied was 15·5%. RSV p.C279Y in GNRHR may have a founder effect originating from south Asia. This study provides a model for molecular and phenotypic representation of Asian Indian subjects with IHH.


Asunto(s)
Genotipo , Hipogonadismo/genética , Síndrome de Kallmann/genética , Fenotipo , Asia/etnología , Secuencia de Bases , Salud de la Familia , Femenino , Efecto Fundador , Variación Genética , Humanos , Hipogonadismo/patología , India/epidemiología , Síndrome de Kallmann/patología , Masculino , Epidemiología Molecular , Linaje , Reproducción
6.
Endocr Pract ; 21(2): 158-64, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25297662

RESUMEN

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.


Asunto(s)
Hidrocortisona/análisis , Hipersecreción de la Hormona Adrenocorticotrópica Pituitaria (HACT)/diagnóstico , Saliva/química , Adulto , Femenino , Humanos , Técnicas para Inmunoenzimas , Masculino , Estudios Prospectivos , Reproducibilidad de los Resultados
7.
JCEM Case Rep ; 2(1): luad155, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38148762

RESUMEN

Pancreatitis is a very rare complication of methimazole and carbimazole therapy. We describe a case of possible carbimazole-associated pancreatitis. A 41-year-old Asian man (with no comorbidities) reported to the hospital with atrial fibrillation and a fast ventricular rate. He was diagnosed with hyperthyroidism due to Graves disease. His rhythm was reverted with amiodarone, and carbimazole was initiated at 15 mg daily for the medical management of Graves disease. Fifteen days later, he presented with acute severe abdominal pain and vomiting with elevated serum amylase 387 U/L (reference range, 28-100 U/L) and lipase levels 206 U/L (reference range, 13-60 U/L). Magnetic resonance imaging showed a bulky pancreas with extensive extrapancreatic fat stranding suggestive of acute pancreatitis. Considering the possibility of carbimazole-related pancreatitis, the drug was withheld. He was managed conservatively, and his pancreatic enzymes normalized within 1 week. The observation suggests that the pancreatitis was a consequence of the therapy with carbimazole. Although it is a rare occurrence, patients taking carbimazole who report abdominal discomfort and vomiting should be evaluated for pancreatitis.

8.
Indian J Pharmacol ; 55(3): 179-184, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37555413

RESUMEN

Human paraoxonase 1 (PON1) enzyme protects against atherosclerosis by preventing low-density lipoprotein from oxidative modification. Upregulation of PON1 enzymatic activity is suggested to contribute to atheroprotective potential of statins. Glutamine (Q) to arginine (R) at site 192 and leucine (L) to methionine (M) substitution at site 55 polymorphisms influence the PON1 activity. The study assessed the role of PON1 polymorphisms on lipid-lowering and PON1-modulating activity of statins in a Western Indian cohort of patients with dyslipidemia. Lipid profile and PON1 activity were determined at baseline and 3 months after initiation of statin treatment. PON1 genotypes (QQ, QR, RR; LL, LM, and MM) were determined by PCR-RFLP. Paraoxon was used as a substrate for assessing PON1 activity by spectrophotometry. A total of 140 statin-naïve patients were enrolled; of them, 116 were available for final analysis. Fifty-seven (50%) had QQ, 39 (35%) had QR, and 17 (15%) had RR genotypes. Seventy-six (67%) patients had LL, 35 (31%) had LM, and 2 (2%) had MM genotypes. We observed no impact of PON1 polymorphisms on lipid parameters posttreatment. A significant increase was observed in the serum PON1 activity from a median (range) of 47.92 U/L (9.03-181.25) to 72.22 U/L (7.64-244.44) (P < 0.05) following statin treatment, which was independent from high-density lipoprotein (HDL) concentration. This increase was significantly greater in QQ compared to QR and RR genotypes (P = 0.01). To conclude, the important antioxidant properties of statins are exerted via the rise in serum PON1 activity, independent of HDL cholesterol concentrations. The increase was greater in individuals with QQ genotype. Future large-scale studies will validate the premise that QQ homozygotes see added benefits from statin treatment compared to R carriers. In the meantime, PON1 enzymatic activity remains an important marker to be measured while assessing pleotropic effects of statins in CAD.


Asunto(s)
Arildialquilfosfatasa , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Humanos , Arildialquilfosfatasa/genética , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Antioxidantes , Estudios Prospectivos , Genotipo , Lipoproteínas HDL , Fenotipo
9.
J Clin Densitom ; 15(2): 152-8, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22402119

RESUMEN

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.


Asunto(s)
Absorciometría de Fotón , Pueblo Asiatico , Densidad Ósea/fisiología , Adulto , Fosfatasa Alcalina/sangre , Biomarcadores/sangre , Calcio/sangre , Dieta , Femenino , Fémur/diagnóstico por imagen , Humanos , India , Vértebras Lumbares/diagnóstico por imagen , Masculino , Hormona Paratiroidea/sangre , Fósforo/sangre , Valor Predictivo de las Pruebas , Análisis de Regresión , Vitamina D/sangre
10.
Diabetes Metab Syndr ; 16(5): 102483, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35483209

RESUMEN

BACKGROUND AND AIMS: Airborne Low Intensity Multi frequency Ultrasound (ALIMFUS) uses thermal and non thermal principal of ultrasound to facilitate transportation of drugs into the cells and it's metabolism. This is randomized, multi-center, Double Blind, Interventional, Placebo Controlled Study to evaluate efficacy and safety of ALIMFUS as an Add-on therapy to Oral Hypoglycemic Agent (OHA) in Type 2 DM. METHODS: Total 103/186 subjects completed the study and received 10 min either ALIMFUS therapy on alternate day for 90 days or placebo. Baseline and end of the study Lab parameters like HbA1c, blood sugars, Lipid Profile, Serum Hs-CRP, Serum Interleukin-6, Serum TNF-α, Serum homocysteine, Serum Vitamin D, Serum Leptin, Serum Adiponectin and Quality of Life score were assessed. RESULTS: At the end of study ALIMFUS group achieved greater (0.77 ± 1.13 vs 0.48 ± 0.79) but non-significant reduction in HbA1c. More subjects in ALIMFUS group (30.76% vs 27.45%) achieved HbA1c < 7%. Significant reduction in fasting and postprandial glucose noted in both groups whose baseline HbA1c was ≥8%. Significant reduction in lipid profile noted in ALIMFUS group compared to placebo. Insulin, adiponectin, CRP and homocysteine and quality of life were significantly better in ALMFUS group compared to baseline; but non-significant compared to placebo. No adverse events were associated with ALIMFUS. CONCLUSIONS: Thus, ALIMFUS could be novel technology in diabetes management for patient unable to achieve glycemic targets on combination therapy. However further exploratory long term studies are required to demonstrate its effective role as add-on therapy in diabetes management.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemiantes , Terapia por Ultrasonido , Adiponectina/sangre , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/terapia , Método Doble Ciego , Hemoglobina Glucada/metabolismo , Control Glucémico , Humanos , Hipoglucemiantes/uso terapéutico , Metabolismo de los Lípidos , Calidad de Vida
11.
Postgrad Med J ; 87(1030): 514-8, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21508424

RESUMEN

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.


Asunto(s)
Conservadores de la Densidad Ósea/administración & dosificación , Calcio de la Dieta/administración & dosificación , Ácido Fítico/administración & dosificación , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/epidemiología , Vitamina D/administración & dosificación , Adulto , Calcio/sangre , Estudios Transversales , Dieta , Conducta Alimentaria , Femenino , Humanos , India/epidemiología , Masculino , Actividad Motora , Estado Nutricional , Ácido Fítico/metabolismo , Estaciones del Año , Luz Solar , Salud Urbana , Vitamina D/análogos & derivados , Vitamina D/análisis , Vitamina D/sangre , Vitamina D/metabolismo , Adulto Joven
12.
Diabetes Metab J ; 45(4): 606-612, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33081425

RESUMEN

The purpose of this extension study was to assess the long-term efficacy and safety of gemigliptin 50 mg in patients with type 2 diabetes mellitus (T2DM). Patients with T2DM who had completed the initial 24-week study comparing gemigliptin monotherapy with placebo were eligible to enrol. In the open-label, 28-week extension study, all enrolled patients received gemigliptin, regardless of the treatment received during the initial 24-week study period. The mean reduction±standard deviation (SD) in glycosylated hemoglobin (HbA1c) observed after 24 weeks of treatment (-0.6%±1.1%) was further decreased for the gemi-gemi group and the mean change in HbA1c at week 52 from baseline was -0.9%±1.2% (P<0.0001). For the pbo-gemi group, HbA1c decreased after they were switched to gemigliptin, and the mean change in HbA1c at week 52 from baseline was -0.7%±1.2% (P<0.0001). Furthermore, the overall incidence of adverse events demonstrated that gemigliptin was safe and well tolerated up to 52 weeks.


Asunto(s)
Diabetes Mellitus Tipo 2 , Piperidonas , Pirimidinas , Glucemia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/uso terapéutico , Piperidonas/efectos adversos , Piperidonas/uso terapéutico , Pirimidinas/efectos adversos , Pirimidinas/uso terapéutico
13.
J Pediatr Endocrinol Metab ; 30(5): 575-581, 2017 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-28432847

RESUMEN

BACKGROUND: Data on genotype-phenotype correlation in children is limited. Hence, we studied the prevalence of germline mutations and genotype-phenotype correlation in children with pheochromocytoma (PCC)/paraganglioma (PGL) and compared it with adult PCC/PGL cohort. METHODS: A total of 121 consecutive, unrelated, index PCC/PGL patients underwent genetic testing for five PCC/PGL susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) and were evaluated for clinical diagnosis of neurofibromatosis type1 (NF1). RESULTS: Thirty patients (12 boys, 18 girls) presented at ≤20 years of age (mean age of 15.9±3.8 years). Children were more frequently symptomatic and more frequently had bilateral PCC than adults. Fourteen (46.7%) PCC/PGL children had germline mutations (VHL 10 [33.3%], SDHB 2 [6.6%], and SDHD 2 [6.6%]). Overall germline mutations (46.7% vs. 26.4%, p=0.04) and VHL mutations (33.3% vs. 10.9%, p=0.026) were significantly more common in children than in adults. In children with VHL mutations, bilateral PCC were more frequent than in adults with VHL mutations. Within the paediatric cohort, bilateral PCC (60% vs. 5%, p=0.002), PCC+sPGL (30% vs. 0%, p=0.03) and occurrence of a second PCC/PGL (30% vs. 0%, p=0.03) were significantly more frequent among children with VHL mutations than others. CONCLUSIONS: All PCC/PGL children should be screened for germline mutations with first priority for VHL gene testing. Paediatric PCC/PGL patients with VHL mutations should be thoroughly evaluated for bilateral PCC and PCC+sPGL at initial presentation and closely followed up for occurrence of a second PCC/PGL.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/genética , Marcadores Genéticos , Mutación , Paraganglioma/genética , Feocromocitoma/genética , Adolescente , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Niño , Estudios de Cohortes , Femenino , Estudios de Asociación Genética , Humanos , India , Masculino , Paraganglioma/patología , Feocromocitoma/patología , Adulto Joven
14.
J Diabetes Investig ; 2017 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-28921919

RESUMEN

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.

15.
Endocr Connect ; 5(6): 89-97, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27852633

RESUMEN

BACKGROUND AND AIMS: Malignant transformation of pheochromocytomas/paragangliomas (PCC/PGL) is a rare occurrence, and predictive factors for the same are not well understood. This study aims to identify the predictors of malignancy in patients with PCC/PGL. MATERIALS AND METHODS: We performed a retrospective analysis of 142 patients with either PCC or PGL registered at our institute between 2000 and 2015. Records were evaluated for clinical parameters like age, gender, familial/syndromic presentation, symptomatic presentation, biochemistry, size, number and location of tumours and presence of metastases and mode of its diagnosis. RESULTS: Twenty patients were found to have metastases; 13 had metastases at diagnosis and seven during follow-up. Metastases were detected by radiology (CT-neck to pelvis) in 11/20 patients (5/13 synchronous and 6/7 metachronous), 131I-metaiodobenzylguanidine in five (2/12 synchronous and 3/6 metachronous) patients and 18F-flurodeoxyglucose PET/CT in 15 (12/12 synchronous and 3/3 metachronous) patients. Malignant tumours were significantly larger than benign tumours (8.3 ± 4.1 cm, range: 3-22 cm vs 5.7 ± 2.3 cm, range: 2-14 cm, P = 0.0001) and less frequently metanephrine secreting. On linear regression analysis, tumour size and lack of metanephrine secretion were the independent predictors of malignancy. CONCLUSIONS: Patients with primary tumour size >5.7 cm and lack of metanephrine secretory status should be evaluated for possible malignancy not only at diagnosis but also in the postoperative period. As compared to CT and 131I-MIBG scan, 18F-flurodeoxyglucose PET/CT analyses are better (sensitivity: 100%) for the diagnosis of metastases in our study.

16.
Eur J Endocrinol ; 175(4): 311-23, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27539324

RESUMEN

BACKGROUND: Genetic aetiology of pheochromocytoma (PCC) and paraganglioma (PGL) is increasingly being studied; however, Asian Indian data on this aspect are scarce. OBJECTIVE: To study the prevalence of germline mutations and genotype-phenotype correlation in Asian Indian PCC/PGL patients. DESIGN: In this study, 150 index patients (M:F, 73:77) with PCC/PGL were evaluated. Phenotypic data were collected. Germline mutations in five susceptibility genes (RET, VHL, SDHB, SDHD and SDHC) were tested by sequencing and NF1 was diagnosed according to phenotype. RESULT: Of the total population, 49 (32.7%) PCC/PGL patients had germline mutations (VHL: 23 (15.3%), RET: 13 (8.7%), SDHB: 9 (6%), SDHD: 2 (1.3%) and NF1: 2 (1.3%)). Amongst the 30 patients with familial and/or syndromic presentation, all had germline mutations (VHL: 14 (46.7%), RET: 13 (43.3%), SDHB: 1 (3.3%) and NF1: 2 (6.7%)). Out of 120 patients with apparently sporadic presentation, 19 (15.8%) had a germline mutation (VHL: 9 (7.5%), SDHB: 8 (6.7%) and SDHD: 2 (1.7%)). Mutation carriers were younger (29.9 ± 14.5 years vs 36.8 ± 14.9; P = 0.01) and had a higher prevalence of bilateral PCC (26.5% vs 2.9%, P < 0.001) and multifocal tumours (12.2% vs 0.96%, P = 0.06). Based on syndromic features, metastasis, location and number of tumours, around 96% mutations in our cohort could be detected by appropriately selected single gene testing. CONCLUSION: Asian Indians with PCC/PGL differ from Western cohorts in having preponderance of VHL mutations in multifocal tumours and apparently sporadic unilateral PCC. Syndromic presentation, metastasis, location and number of PCC/PGL can be effectively used for guiding genetic prioritisation.


Asunto(s)
Neoplasias de las Glándulas Suprarrenales/genética , Mutación de Línea Germinal , Paraganglioma/genética , Feocromocitoma/genética , Neoplasias de las Glándulas Suprarrenales/patología , Adulto , Factores de Edad , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Paraganglioma/patología , Feocromocitoma/patología , Proteínas Proto-Oncogénicas c-ret/genética , Succinato Deshidrogenasa/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Adulto Joven
18.
Endocr Connect ; 4(4): 242-8, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26420669

RESUMEN

Variable prevalence of subclinical Cushing's syndrome (SCS) has been reported in patients with type 2 diabetes mellitus (T2DM), making the need for screening in this population uncertain. It is unknown if this variability is solely due to study-related methodological differences or a reflection of true differences in ethnic predisposition. The objective of this study is to explore the prevalence of SCS in Asian Indian patients with T2DM. In this prospective single center study conducted in a tertiary care referral center, 993 T2DM outpatients without any discriminatory clinical features (easy bruising, facial plethora, proximal muscle weakness, and/or striae) of hypercortisolism underwent an overnight 1 mg dexamethasone suppression test (ODST). ODST serum cortisol ≥1.8 µg/dl was considered positive, and those with positive results were subjected to 48 h, 2 mg/day low dose DST (LDDST). A stepwise evaluation for endogenous hypercortisolism was planned for patients with LDDST serum cortisol ≥1.8 µg/dl. Patients with positive ODST and negative LDDST were followed up clinically and re-evaluated a year later for the development of clinically evident Cushing's syndrome (CS). In this largest single center study reported to date, we found 37 out of 993 (3.72%) patients had ODST serum cortisol ≥1.8 µg/dl. None of them had LDDST cortisol ≥1.8 µg/dl, nor did they develop clinically evident CS over a follow-up period of 1 year. Specificity of ODST for screening of CS was 96.3% in our cohort. None of the T2DM outpatients in our cohort had SCS, hence cautioning against routine biochemical screening for SCS in this cohort. We suggest screening be based on clinical suspicion only.

19.
Growth Horm IGF Res ; 24(6): 227-32, 2014 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-25153028

RESUMEN

CONTEXT: Cohort specific mutations in the growth hormone (GH1) and growth hormone-releasing hormone receptor (GHRHR) genes have been reported worldwide in isolated growth hormone deficiency (IGHD) patients. However, limited data is available on ethnically diverse Indian IGHD patients. OBJECTIVE: The aim of the study was to find GH1 and GHRHR gene mutations in Indian IGHD patients from two unrelated non-consanguineous families. DESIGN: The 5' and 3' untranslated regions (UTRs) and coding regions with splice sites of the GH1 and GHRHR genes were sequenced for all patients (n=6). Family members and 20 controls were evaluated for the sequence variants identified in the index patients. Online bioinformatics tools were used to confirm mutations and their pathogenicity. RESULTS: GHRHR gene mutations were observed in all patients. Interestingly, a novel indel g.30999250_31006943delinsAGAGATCCA was observed in both the unrelated families. Three patients were homozygous for the novel indel, two were homozygous for the previously reported p.E72X mutation and one was compound heterozygous with both the mutations (indel and p.E72X) in the GHRHR gene. The novel indel has resulted in the loss of 5' regulatory region and exon 1 of the GHRHR gene impairing the GHRHR expression. All the normal family members were heterozygous either for the indel or p.E72X mutation. None of the patients had GH1 gene mutations. CONCLUSIONS: We describe a novel gross indel in the GHRHR gene resulting in the loss of 5' regulatory region and GHRHR exon 1 in four IGHD IB patients from two unrelated non-consanguineous Indian families.


Asunto(s)
Enanismo Hipofisario/genética , Hormona de Crecimiento Humana/deficiencia , Mutación INDEL/genética , Receptores de Neuropéptido/genética , Receptores de Hormona Reguladora de Hormona Hipofisaria/genética , Adulto , Secuencia de Bases , Niño , Preescolar , Enanismo Hipofisario/epidemiología , Exones/genética , Femenino , Heterocigoto , Humanos , India/epidemiología , Masculino , Datos de Secuencia Molecular , Linaje
20.
Indian J Endocrinol Metab ; 18(6): 831-7, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25364679

RESUMEN

OBJECTIVE: To assess bone mineral density (BMD) in type 2 diabetes mellitus (T2DM) patients and its relation, if any, to clinical, hormonal and metabolic factors. MATERIALS AND METHODS: A prospective evaluation of 194 T2DM patients (97 men and 97 women) was carried out. BMD was done with dual energy X-ray absorptiometry (DXA) at the lumbar spine and total hip. Physical activity, nutritional intake and sunlight exposure were calculated. Biochemical and hormonal tests included serum 25 hydroxy vitamin D [25(OH) D], parathyroid hormone, estrogen, testosterone and urinary calcium-creatinine ratio. Glycosylated hemoglobin and complete lipid profiles were done in patients with diabetes. Five hundred and seventy one non-diabetic controls (262 males and 309 females) were evaluated for BMD alone. RESULTS: BMD was normal (Z score > -2) in 156 (80.5%) and low (Z score ≤ -2) in 38 (19.5%) patients in the diabetes study group. BMD in the diabetes group was significantly higher than the control group in both sexes at the hip and spine. The difference was no longer significant on analysis of a BMI matched control subgroup. Weight and BMI showed significant correlation to BMD. Duration of T2DM, degree of glycemic control, use of drugs like statins and thiazolidinediones, 25(OH) D levels, calcium intake, sunlight exposure and physical activity did not significantly affect BMD in this cohort of individuals with diabetes. CONCLUSIONS: Bone mineral density of Asian Indian T2DM subjects was similar to that of healthy volunteers in this study.

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