Two Decades of Gla-100-Reflections from the Pivotal Clinical Trials.

The progressive nature of type 2 diabetes mellitus (T2DM) renders the shifting of patients from oral drugs to insulin therapy an inevitability in most patients especially in those with long duration of diabetes. At the turn of the last millennium, neutral protamine Hagedorn (NPH) insulin was still the only long-acting insulin available for people with diabetes. The advent of the first truly long-acting basal insulin, i.e. insulin glargine 100 U/mL (Gla-100) brought to the table a remarkably long duration of action and a very minimal risk of hypoglycemia by due to less pronounced peaks in their action profile. Further, in trying to achieve fasting normoglycemia, Gla-100 has demonstrated remarkably more holistic glucose-lowering efficacy in several pivotal trials compared to other insulin formulations, such as premixed insulin and coformulations-apart from NPH insulin. This article delineates clinical data on the effectiveness of Gla-100 vs. other insulin formulations in the context of T2DM.

Serum CCL 18 Levels in Women with Polycystic Ovarian Syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common metabolic disorders seen in women of the reproductive age group, with the majority of them having insulin resistance. There is a need to identify sensitive markers of insulin resistance. CC chemokine ligand 18 (CCL 18) secreted from white adipose tissue is upregulated in individuals with insulin resistance. OBJECTIVES: To study the correlation between serum CCL 18 levels and insulin resistance in PCOS. MATERIALS AND METHODS: This case-control study included 45 PCOS women and an equal number of age and body mass index (BMI) matched controls. Estimation of serum CCL 18, serum testosterone, fasting plasma glucose, fasting insulin, HbA1c, and ultrasonography of abdomen and pelvis was done and HOMA IR was calculated. RESULTS: Serum CCL 18 level was higher in women with PCOS when compared to controls. The mean level of serum CCL 18 (ng/mL) in the PCOS group and control group was 28.32 ± 4.17 and 11.90 ± 4.91, respectively (P < 0.001). Blood pressure, waist circumference, waist-hip ratio, modified Ferriman Gallway score (FG) score serum total testosterone, fasting serum insulin, and HOMA IR showed a relationship with serum CCL 18 levels. Serum CCL 18 was an independent predictor of PCOS (P < 0.05). A serum CCL 18 cutoff level of 18.84 ng/mL showed 93.3% sensitivity and 91.7% specificity in distinguishing PCOS subjects from healthy individuals. CONCLUSION: There is a significant correlation of serum CCL 18 level with insulin resistance in PCOS subjects and serum CCL levels can be considered as a marker of PCOS.

Serum Fibroblast Growth Factor 21 Levels in Patients with Hyperthyroidism and its Association with Body Fat Percentage.

BACKGROUND: Most of the actions of thyroid hormone (TH) on body metabolisms like maintenance of basal metabolic rate (BMR) and body fat are similar to that of fibroblast growth factor 21 (FGF21). We hypothesized that in patients with hyperthyroidism, the pathological changes in the BMR, body fat are mediated by TH through FGF21. OBJECTIVES: To study the association of serum FGF21 levels with hyperthyroidism and correlate body fat percentage with serum FGF21 levels in hyperthyroid patients. STUDY DESIGN: Case-control prospective follow-up study. METHODOLOGY: A total of 68 hyperthyroid patients and age, sex-matched healthy controls who fulfilled the inclusion and exclusion criteria were studied. Among them, 45 cases were followed up at 3 to 6 months after the achievement of euthyroidism. Body fat percentage was calculated from Jackson and Pollock 3 site equation and Siri equation. BMR percentage was calculated by the Gale formula. RESULTS: The mean age in years in the cases was similar to that of controls (36.14 ± 10.01 vs. 36.57 ± 10.53, P = 0.81). The serum FGF21 levels at baseline were significantly elevated in patients with hyperthyroidism compared to controls [median 406.6 pg/ml (interquartile range, 262.9-655.6) vs. 252.3 (125.1-341) P < 0.001] and declined dramatically following treatment with anti-thyroid drugs [405 (275.5-680.4) vs. 203.6 (154.6-230.6) P < 0.001]. Serum FGF21 levels negatively correlated with body fat percentage (r = -0.268, P = 0.002). After adjusting to various confounding factors, serum FGF21 was independently associated with hyperthyroidism and was significant. (OR [95%CI] 3.78 (1.046-13.666) P = 0.043). CONCLUSION: Serum FGF21 levels were elevated in hyperthyroid patients and decreased following treatment with anti-thyroid drugs. It was independently associated with hyperthyroidism. There may be a future therapeutic role of FGF21 inhibition in the reversal of these changes in addition to anti-thyroid drugs in patients with hyperthyroidism.

46 XX, SRY Negative Ovotesticular DSD.

46 XX ovotesticular DSD is a rare disorder. It presents with cryptorchidism, hypospadias or ambiguous genitalia at birth, gynaecomastia in adolescent stage or infertility in adult age. We report here a 20 year old phenotypically male who presented with gynaecomastia and found to have testis on right side and left inguinoscrotal swelling consisting of ovary, uterus and fallopian tubes. Evaluation revealed SRY negative 46 XX karyotype. He underwent surgical removal of ovary and mullerian structures. The highlight of case is development of testicular tissue in absence of SRY gene.

Serum adiponectin levels in gestational diabetes mellitus.

INTRODUCTION: Gestational diabetes mellitus (GDM) is defined as any degree of glucose intolerance with onset or first recognition during pregnancy.[1] Pregnancy is a unique situation in which there is a physiological temporary increase in insulin resistance (IR). The mechanisms responsible for the gestational-induced IR are not completely understood. The current study was undertaken to compare adiponectin levels during 24-28 weeks period of gestation in drug-naive newly diagnosed GDM women with a cohort of normoglycemic pregnant women. SUBJECTS AND METHODS: A total of 47 pregnant women in the age group of 18-40 years were included in this cross-sectional study, of which 13 were GDM cases and 34 were normoglycemic controls. Serum adiponectin level was analyzed by enzyme-linked immunosorbent assay. RESULTS: The mean adiponectin level was 16.92 ng/ml (standard deviation [SD] = 2.78) and 19.38 ng/ml (SD = 2.71) in case and control groups, respectively, and the difference was found to be statistically significant (P = 0.008). CONCLUSION: Our study demonstrated decreased serum adiponectin levels in women with GDM when compared with age- and body mass index-matched euglycemic pregnant women.

Adult hypopituitarism: Are we missing or is it clinical lethargy?

Hypopituitarism, a disease of varied etiologies, is a serious endocrine illness that requires early recognition and prompt treatment to avoid its severe deleterious effects. In adults it is often missed due to non-specific symptoms of growth hormone deficiency and hypogonadism or mild deficiencies of other pituitary hormones. In some it may present with acute onset of symptoms suggestive of acute adrenal (corticotropin) insufficiency or symptoms due to mass lesion in/or around pituitary. High index of suspicion is required to seek hypopituitarism in patients with non-specific symptoms such as fatigue and malaise. Treatment of isolated hormone deficiency, partial or panhypopituitarism, has gratifying results although they require lifelong treatment and follow-up.

Parathyroid Neoplasms: The Army Hospital (Research & Referral) Experience.

BACKGROUND: Neoplasms of the parathyroid are common but parathyroid carcinoma is exceptionally rare. In contrast to most other malignant endocrine tumours that are usually less hormonally active, malignant parathyroid tumours are hyper functional. Malignant parathyroid tumours pose a diagnostic dilemma for the pathologist. OBJECTIVE: To study the clinicopathological profile of a case series of parathyroid neoplasms and determine features which facilitate a malignant diagnosis. METHODS: A retrospective analysis of seven cases of surgically treated parathyroid tumours over a three-year period at a single centre was done. Clinical, haematological, biochemical, and radiological data was accrued from medical records. The histopathology slides were reviewed along with the clinicopathological profile in an attempt to delineate markers of malignancy. RESULTS: Patients ranged from 30 to 58 years of age. Males and females were approximately equal. Weakness and bone pain were the commonest presenting symptoms. Over 50% had significant hypercalcaemia and all had elevated serum parathormone. Clinically apparent mass was seen in only one. All tumours were successfully localised using CT scan and MRI. Thick fibrous capsule and broad septal fibrosis was seen in both the carcinomas; these were thin in the adenomas. Mitotic counts of 1-3 per high power field (HPF), capsular invasion and nodal metastasis were noted in the malignant tumours. CONCLUSION: Elevated serum calcium and parathormone values point to a parathyroid neoplasm. Current imaging modalities are successful in localising the tumour preoperatively. Markedly elevated serum calcium, broad fibrous bands, mitotic counts and capsular invasion are indicators of malignancy.