Cardiac Diastolic Dysfunction and Regional Body Fat Distribution in Insulin Resistant Peripubertal Obese Males.

BACKGROUND: To evaluate presence of diastolic dysfunction in obese peripubertal males (8-18 years of age). To correlate diastolic dysfunction with insulin resistance, insulin levels and omental and epicardial fat. METHODS: Obese males (n=46) and age matched healthy lean controls (n=50) in the age group of 8-18 years were included in this study. Anthropometric measurements were recorded. Investigations done: Fasting blood sugar and serum insulin levels, lipid profile, 2-D Echocardiography to assess left ventricular diastolic function and epicardial fat, abdominal CT scan to measure omental fat and ultrasound for NAFLD. RESULTS: Isovolumetric relaxation time (IVRT) above 100 msec seen in 18/46, E/A ratio of 0.75 seen in 4/46 cases. Left ventricular mass > 125gm seen in 10/46 cases. All the left ventricular diastolic function parameters were within normal range in controls. Significant difference in LVM (p=0.00099), LVPW(d) (p=0.0018), IVS(d) (p=0.007), E/A ratio (p=0.043), epicardial fat (p=0.0000) were seen in cases as compared to controls. Correlation of visceral fat with HOMA-IR, insulin levels and left ventricular diastolic parameters in cases was as follows HOMA vs omental fat (p=0.0008), Insulin vs omental fat (p=0.0015), E/A vs omental fat (p=0.015), LVM vs omental fat (p=0.0000), IVRT vs omental fat (p-=0.005). HOMA vs epicardial fat (p=0.0000), insulin vs epicardial fat (p=0.0000), E/A vs epicardial fat (p=0.09), LVM vs epicardial fat (p=0.006), IVRT vs epicardial fat (p=0.011). CONCLUSIONS: Left ventricular hypertrophy and diastolic derangements start early in obese peripubertal males with positive correlation between left ventricular diastolic dysfunction and HOMA-IR and insulin levels. Epicardial fat mass and visceral fat show positive correlation with diastolic dysfunction.

A multicentre, multinational, randomized, placebo-controlled, double-blind, phase 3 trial to evaluate the efficacy and safety of gemigliptin (LC15-0444) in patients with type 2 diabetes.

AIM: This study was designed to assess the efficacy and safety of the dipeptidyl peptidase IV inhibitor gemigliptin (LC15-0444) 50 mg versus placebo in patients with type 2 diabetes. METHODS: We conducted a 24-week, randomized, double-blind, placebo-controlled phase III trial in 182 patients (74 from Korea and 108 from India) with type 2 diabetes. After an initial 2 weeks of a diet and exercise programme followed by 2 weeks of a single-blind placebo run-in period, eligible patients were randomized to gemigliptin 50 mg or placebo, receiving the assigned treatment for 24 weeks. HbA1c and fasting plasma glucose (FPG) were measured periodically, and oral glucose tolerance test was performed at baseline and weeks 12 and 24. RESULTS: At week 24, gemigliptin treatment led to significant reductions in HbA1c measurements compared to placebo (adjust mean after subtracting the placebo effect size: -0.71%, 95% confidence interval: -1.04 to -0.37%). A significantly greater proportion of patients achieved an HbA1c <7% with gemigliptin than with placebo. The placebo-subtracted FPG change from baseline at week 24 was -19.80 mg/dl. The overall incidence rates for adverse events were similar in the gemigliptin and placebo groups. CONCLUSIONS: This study showed the efficacy and safety of gemigliptin 50 mg administered once daily as a monotherapy for type 2 diabetes patients.

Fine-needle aspiration of the thyroid: rate and causes of cytohistopathologic discordance.

Fine-needle aspiration (FNA) of the thyroid gland is a widely utilized, sensitive, specific, and cost-effective method for the evaluation of thyroid nodules. The purpose of this study was to evaluate the accuracy of thyroid FNA and causes of cytohistological discordance in our institution. Six hundred twenty-five thyroid FNAs obtained from 503 females (mean age, 54) and 122 males (mean age, 51) in whom histopathologic follow-up material was available for review, were analyzed. FNAs were classified as: nondiagnostic, negative, intermediate, and positive for malignancy, and the histopathologic material was categorized as benign or malignant. The review revealed 93% sensitivity and 96% specificity for the FNA diagnoses. The FNA results were diagnostic in 87%, indeterminate in 6%, and nondiagnostic in 7% of the cases. Cytohistologic correlation was achieved in 88% of the cases. The false-negative rate was 4% and the false-positive rate was 8%. The most common pitfalls for false-negative diagnoses consisted of suboptimal material and underdiagnosis of papillary carcinoma due to cystic degeneration. The most common pitfall for false-positive cases was overdiagnosis of follicular neoplasms. Our study confirmed that FNA of thyroid nodules can be performed with high sensitivity and specificity by experienced clinicians or pathologists. The application of strict specimen adequacy rules for FNA interpretation is likely to decrease the rate of false-negative and false-positive diagnoses.

Two years of intensive glycemic control and left ventricular function in the Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM).

OBJECTIVE: The Veterans Affairs Cooperative Study in Type 2 Diabetes Mellitus (VA CSDM) was a multicenter randomized prospective study of 153 male type 2 diabetic patients to assess the ability to sustain clinically significant glycemic separation between intensive and standard treatment arms. A trend toward an excess of combined cardiovascular events in the intensive treatment arm of this trial was reported earlier. The present analysis was done to evaluate the effect of 2 years of intensive glycemic control on the left ventricular (LV) function. RESEARCH DESIGN AND METHODS: The patients were randomized to intensive step treatment with insulin alone or with sulfonylurea (intensive treatment arm [INT], n = 75) or to standard once-daily insulin injection (standard treatment arm [STD], n = 78) treatment. A total of 136 patients (standard treatment arm [STD], n = 70; INT, n = 66) had radionuclide ventriculography at entry and at 24 months for the assessment of LV function. RESULTS: There was no difference in the mean LV ejection fraction (at entry: STD 57.1+/-9.51%; INT 58.1+/-8.7%; at 24 months: STD 57.3+/-10.8%, INT 59.5+/-10.7%), peak filling rate (at entry: STD 2.6+/-0.7 end diastolic volume per second, INT 2.4+/-0.8 end diastolic volume per second; at 24 months: STD 2.7+/-1.0 end diastolic volume per second, INT 2.5+/-0.7 end diastolic volume per second), or time to peak filling rate (at entry: STD 195.3+/-69.5 ms, INT 185.6 +/-62.4 ms; at 24 months: STD 182.6+/-64.8 ms, INT 179.2+/-61.2 ms) between the 2 treatment arms. A subgroup analysis of 104 patients (STD, n = 53; INT, n = 51) that omitted individuals with intervening cardiac events/revascularization or a change in cardioactive medications also showed no difference in the LV function at entry and at 24 months between the 2 groups. Abnormal LV ejection fraction at baseline predicted cardiac events (interval between cardiac beats [RR] = 2.5). CONCLUSIONS: Two years of intensive glycemic control does not affect the LV systolic or diastolic function in patients with type 2 diabetes.

Brain metastases from medullary thyroid carcinoma in a patient with multiple endocrine neoplasia type 2A.

Medullary thyroid carcinoma (MTC) is an uncommon thyroid cancer occurring in less than 10% of patients with thyroid cancer. Brain metastasis from MTC is exceedingly rare. Only six cases of brain metastasis from MTC have been reported in the literature and none had MTC as a part of multiple endocrine neoplasia (MEN) syndrome. We report a 42-year-old Caucasian male with MEN 2A who presented with neurological symptoms 25 years after total thyroidectomy with lymphadenectomy for MTC metastatic to local lymph nodes. A brain magnetic resonance imaging (MRI) showed a 4-cm cystic mass and a 1-cm nodule in the left frontal-parietal lobe in addition to a 0.8-cm cystic mass in the left frontal lobe and multiple tiny cerebellar metastatic lesions. Partial resection of the cerebral metastasis followed by whole brain radiotherapy resulted in resolution of the neurological symptoms. However, the patient had multiple systemic metastasis from the MTC and he died of systemic complications due to metastatic MTC. To our knowledge this is the first report of brain metastases from MTC in a patient with MEN 2A.