Anil Bhansali

Background: there are dearths of studies describing the effect of autologous bone marrow derived stem cell transplantation (ABMSCT) through targeted approach in Type 2 Diabetes Mellitus.This study reports the efficacy and safety of super-selective injection of ABMSCT in T2DM. Materials and Methods: Ten patients (8 men and 2 women) with T2DM, with duration of disease >5 years and with documented triple drug failure receiving insulin (0.7 U/Kg/day), metformin and pioglitazone underwent super-selective injection of stem cells into superior pancreaticoduodenal artery under fluoroscopic guidance. The primary outcome measure was decrease in insulin requirement by ≥50% (defined as responders), while secondary endpoints were improvement in glucagon stimulated C-peptide levels, changes in weight, HbA1c, lipid profile and quality of life (QOL) at the end of 15 months. Results: Six patients (60%) were 'responders' at 15 months of follow-up showing a reduction in mean insulin requirement by 74% as compared to baseline and one patient was off-insulin till the end of the study. Mean HbA1c reduction in 'responders' was 1.1% (8.1 ± 0.5% to 7.0 ± 0.6%, P = 0.03), accompanied with a significant improvement in glucagon stimulated C-peptide levels (P = 0.03), Homeostasis Model Assessment -β (P = 0.03) and QOL scores. However, 'non-responders' did not show any significant alterations in these parameters. No serious adverse events were noted. Conclusion: Our observations indicate that ABMSCT is effective in management of T2DM and its efficacy is maintained over a period of 15 months without any adverse events. However, more number of patients and longer duration of follow-up are required to substantiate these observations.

Electrolyte imbalance and acute diabetes insipidus (DI) are the most common complications in patients undergoing craniopharyngioma surgery. Improper management of water and electrolyte imbalance is common cause of morbidity and mortality. Data is sparse and controversial regarding the choice of fluid therapy in this population during perioperative period. In this retrospective-prospective study involving 73 patients (58 retrospective), the type of fluid therapy was correlated with occurrence of hypernatremia, hyponatremia, DI, morbidity, and mortality. In the retrospective study, 48 patients received normal saline and 10 received mixed fluids as per the prevailing practice. In the prospective group, five patients each received normal saline, half normal saline, and 5% dextrose randomly. The sodium values were significantly higher in first 48 h in the group that received normal saline compared with other groups (P < 0.001). The use of normal saline was associated with higher incidence of hypernatremia, DI, and mortality (P = 0.05), while the group that received 5% dextrose was associated with hyponatremia, hypoglycemia, and seizures. There was no perioperative hypotension with use of any of the fluids. Our results indicate half normal saline was fluid of choice with diminished incidence of water and electrolyte abnormalities without increase in mortality during postoperative period.

Objectives: Thyroid antibody positivity during pregnancy has been associated with adverse outcomes including miscarriage and preterm delivery. The aim of the study is to evaluate the obstetric outcome in pregnant women with recurrent miscarriage and their response to levothyroxine (l-T₄) therapy.Study design and methods: All pregnant and non-pregnant women between 21 and 35 years of age with a history of two or more consecutive miscarriages were included in the study. A third group comprising 100 pregnant women without a history of miscarriage were taken as healthy controls. Thyroid autoimmunity, prevalence of subclinical hypothyroidism and maternal and foetal complications were analysed in all the groups with appropriate statistical methods.Results: The mean age of the patients included in the study was 27.0±3.1 years. Of 100 pregnant patients with previous recurrent miscarriage, thyroid autoimmunity (thyroid peroxidase antibody (TPOAb⁺) >34 U/ml) was found in 31% of the cases. The incidence of subclinical hypothyroidism was higher in TPOAb⁺ group than in TPOAb⁻ group (52 vs 16%; P=0.0002). There was no difference in the prevalence of miscarriage or obstetric outcomes between recurrent miscarriage and healthy pregnant women group irrespective of TPO status.Conclusions: The prevalence of thyroid autoimmunity was higher in pregnant women with a history of recurrent abortion compared with healthy pregnant control population. Following l-T₄ treatment, there was no difference in prevalence of miscarriage between hypothyroid and euthyroid individuals in TPOAb⁺ women.

Hyperprolactinemia occurs in 15–20 % of women with menstrual disturbances and 30–40 % of infertile women and it can adversely affect the fertility. High molecular weight prolactin (macroprolactin) has long been known in hyperprolactinemic fertile women. However, the prevalence of macroprolactinemia in hyperprolactinemic infertile women is not known. This cross-sectional study was carried out during the period of June 2010 and June 2011 at a single tertiary care centre. All women who attended the infertility clinic during this period were screened for hyperprolactinemia and only women with hyperprolactinemia and infertility were further studied for the presence of macroprolactin by polyethylene glycol precipitation assay. We compared the clinical, hormonal profile and fertility outcome of infertile women with true hyperprolactinemia and macroprolacinemia using appropriate statistical tests. Of 1,163 infertile women, 183 (15.7 %) had hyperprolactinemia [134 (73 %) had primary infertility and 49 (27 %) had secondary infertility]. Out of these 183 women with hyperprolactinemia, one had microadenoma, 161 had true idiopathic hyperprolactinemia and 21 (11.5 %) women had macroprolactinemia. The prevalence of oligomenorrhea and galactorrhea were significantly higher in patients with true hyperprolactinemia than macroprolactinemia (46 vs. 14 %, p < 0.008 and 30 vs. 5 %, p = 0.01 respectively). Twenty-two patients (13.5 %) of true hyperprolactinemia and two (9 %) in macroprolactinemia became pregnant during the study period. Prolactin measurement should be a part of routine evaluation of couples referred to infertility clinics. Macroprolactin screening is mandatory when clinical features and serum PRL assay results are conflicting. Patients with macroprolactinemia should be investigated for causes of infertility other than hyperprolactinemia.

Summary: Objectives: Pioglitazone is an insulin sensitizer used for the management of type 2 diabetes mellitus (T2DM). It has been shown to reduce testosterone level in patients with polycystic ovarian syndrome. However, its effect on testosterone in men has not been studied.Research design and methods: A randomized, double‐blind, placebo‐controlled trial with 6 months follow‐up. Fifty (25 in each group) eugonadal men (well virilized and total testosterone ≥12 nm) with T2DM, aged 30–55 year and HbA1c of ≤7·5% were randomly assigned to receive pioglitazone 30 mg per day or placebo along with existing glimepiride and metformin therapy.Results: As compared to placebo, 6 months of pioglitazone therapy in patients with T2DM resulted in significant reduction in mean total testosterone level (16·1 to 14·9 vs 17·1 to 17·0 nm; P = 0·031), calculated free testosterone (P = 0·001) and bioavailable testosterone (P = 0·000) despite significant increase in sex hormone‐binding globulin (P = 0·000). Plasma androstenedione (∆⁴) level increased (1·5 to 1·9 vs 1·7 to 1·7 ng/ml; P = 0·051) following pioglitazone therapy. The decrease in testosterone was independent of change in body weight, body fat and HbA1c.Conclusion: Pioglitazone therapy significantly decreases total, free and bioavailable testosterone in eugonadal men with T2DM. The effects of these alterations need to be determined by further long‐term studies.

Hyperthyroidism is associated with increased food intake, energy expenditure and altered body composition. This study was aimed to evaluate the role of adipocytokines in weight homeostasis in patients with hyperthyroidism. Patients (n=27, 11men) with hyperthyroidism (20 Graves’ disease, 7 toxic multinodular goiter) with mean age of 31.3±4.2 yr and 28 healthy age and body mass index (BMI) matched controls were studied. They underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids. Patients were re-evaluated after 3 months of treatment as by that time all of them achieved euthyroid state with carbimazole therapy. The LBM was higher (P<0.001) in healthy controls as compared to hyperthyroid patients even after adjustment for body weight (BW), whereas total body fat was comparable between the two groups. Serum leptin levels were higher in patients with hyperthyroidism than controls (22.3±3.7 and 4.1±0.34 ng/ml, P<0.001), whereas adiponectin levels were comparable. Plasma acylated ghrelin was higher in patients than in controls (209.8±13.3 vs 106.2±8.2 pg/ml, P<0.05). Achievement of euthyroidism was associated with significant weight gain (P<0.001) and significant increase in lean body mass (P<0.001). The total body fat also increased but insignificantly from 18.4±1.8 to 19.9±1.8 kg. There was significant decrease (P<0.05) in serum leptin and acylated ghrelin but adiponectin levels remained unaltered after treatment. Serum leptin positively correlated with TBF and this correlation persisted even after adjustment for BW, BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin did not correlate with the presence or absence of hyperphagia. Patients with hyperthyroidism predominantly had decreased lean body mass which increased after achievement of euthyroidism with carbimazole. The hyperphagia and the alterations in weight homeostasis associated with hyperthyroidism were independent of circulating leptin and ghrelin levels.