Switching to a fixed-ratio combination of insulin degludec/liraglutide (IDegLira) is associated with improved glycaemic control in a real-world population with type 2 diabetes mellitus in the United Arab Emirates: Results from the multicentre, prospective INTENSIFY study.

AIM: Investigate the effectiveness of IDegLira, a fixed-ratio combination of insulin degludec/liraglutide, in a real-world setting in patients with type 2 diabetes mellitus in the United Arab Emirates. METHODS: This non-interventional study enrolled adults switching to IDegLira from basal insulin (BI) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) with/without concomitant oral antidiabetic drugs (OADs). Primary endpoint was change in HbA1c from baseline, assessed using a mixed model for repeated measurements. RESULTS: Among 263 patients (BI ± OADs, n = 206; GLP-1 RA ± OADs, n = 57), mean baseline HbA1c was 9.29 % (78 mmol/mol). After 26 weeks, HbA1c was significantly reduced (BI ± OADs, -0.83 % [-9.0 mmol/mol] and GLP-1 RA ± OADs, -1.24 % [-13.5 mmol/mol]; both p < 0.0001). Fasting plasma glucose (FPG) was significantly reduced (-39.48 mg/dL [BI ± OADs] and -82.49 mg/dL [GLP-1 RA ± OADs]; both p < 0.0001). Before treatment initiation, 3/263 patients experienced ≥ 1 severe hypoglycaemic episode and 7/263 patients experienced ≥ 1 non-severe hypoglycaemic episode compared with 1/263 patients who had ≥ 1 severe and 1/263 who had ≥ 1 non-severe episode at end of study. Body weight decreased significantly among patients switching from BI ± OADs (-1.05 kg [p < 0.0001]). Treatment was well tolerated. CONCLUSIONS: IDegLira significantly reduced HbA1c and FPG in this real-world setting, along with less frequent episodes of hypoglycaemia. Switching to IDegLira offers effective treatment intensification for type 2 diabetes patients with inadequate glycaemic control.

Lack of secondary hyperparathyroidism in sub-group of vitamin D deficient postmenopausal women: Is VDR gene polymorphism behind this mystery?

BACKGROUND AND AIMS: We aimed to determine the cause of non-secondary hyperparathyroidism (Non-SHPT) in Indian postmenopausal women. MATERIALS & METHODS: 334 apparently healthy postmenopausal women were assessed for bone mineral homeostaisis including Vitamin D, PTH and VDR polymorphism. RESULTS: 83% of the subjects had vitamin D deficiency further associated with VDR gene polymorphism (P 0.000). A sizable number of subjects (N = 83) did evoke SHPT despite low vitamin D levels. We observe that VDR gene polymorphism was strongly associated in the sub-group of non-SHPT. CONCLUSION: lack of SHPT warrants researchers to study the pathophysiology of non-SHPT in detail to substantiate our findings.

COVID-19 infection, inception and immunity: Observations and recommendations in the light of vitamin D?

Responsive immunity plays an important role fighting against infections. Worldwide, Vitamin D deficiency is a major concern not only for musculoskeletal health but also affecting the immunity status in population. Amidst COVID-19 pandemic, it is imperative to establish the role of vitamin D in destruction of pathogens. Vitamin D awareness program at school level might be an effective health governance policy to educate populations for the importance of vitamin D in overall health.

COVID-19 and Clinical Trials: Current Challenges and Future Directions.

BACKGROUND: The outbreak of coronavirus disease (COVID-19) has posed a major threat to people's lives across the globe. It has drastically changed the way we perceive this world. A paradigm shift was observed globally as the world's emphasis shifted to testing, diagnosis, treatment, and developing a coronavirus cure. Clinical trials were also not untouched by this. The coronavirus pandemic has abhorrently affected the day-to-day clinical trial activities at sites. METHODS: The status of various ongoing clinical trials was assessed through a literature search, which also includes clinical trial portals. Our evaluations were based on these observations. RESULTS: Multiple challenges were present in clinical trials as recruitment, retention, the safety of trial subjects, protocol compliance, and this made the world to re-think to incorporate newer strategies and to cope with this untoward situation. CONCLUSION: Digitalization of clinical trials as virtual management of adverse events, remote monitoring visits, and web-based consulting with trial subjects are potential directions that can be applied to better manage clinical trials worldwide.

Effect of high dose vitamin d supplementation on vitamin d nutrition status of pre-pubertal children on anti-epileptic drugs - A randomized controlled trial.

BACKGROUND AND AIMS: Patients on long term anti-epileptic drug therapy are prone for Vitamin D deficiency for a myriad of reasons. The aim of this research was to study the effect of high dose vitamin D supplementation on vitamin D nutrition status of children newly started on anti-epileptic drug therapy. MATERIALS: This randomized controlled trial was conducted in a tertiary care Children's Hospital at New Delhi from November 2011 to March 2013. Eighty three children in the age group 5-10 years newly started on anti-epileptic drugs (AED) were randomized into two groups; group A - the intervention group, to whom 60,000 IU vitamin D3 was given orally/month under direct supervision along with AED for a period of 6 months, and group B- the control group, to whom AED without vitamin D3 was given. Serum 25(OH)D, ionized calcium (iCa), total calcium (tCa), inorganic phosphate (iP), alkaline phosphatase (ALP) and parathyroid hormone (PTH) levels were assayed at baseline and at the end of 6 months and were compared within and between the two groups. RESULTS: The mean 25(OH)D in Group A was maintained at 6 months follow up [ 26 ng/ml, 95% CI 20-34 ng/ml] compared to baseline [25 ng/ml, 95% CI -19 to 33 ng/ml] [ p = 0.83]. In group B, there was a significant decrease in 25(OH)D levels at 6 months [13 ng/ml (95% CI 9 ng/ml-17 ng/ml)] compared to baseline [18 ng/ml (95% CI 13-24 ng/ml)] [p = 0.01]. At 6 months, mean serum 25(OH)D was significantly higher in group A as compared to group B (p = 0.005). CONCLUSION: To conclude, oral administration of 60,000 IU vitamin D3/month is sufficient to maintain serum 25(OH)D level and prevent development of vitamin D deficiency in children newly started on AED over a period of 6 months. Non supplementation leads to the lowering of serum 25(OH)D in these children. TRIAL REGISTRATION NUMBER: CTRI/2017/08/009234.

All 25-hydroxyvitamin D-deficient Indian postmenopausal women do not have secondary hyperparathyroidism.

This study shows a high 25-hydroxyvitamin D deficiency among postmenopausal women accompanying secondary hyperparathyroidism. However, a sizable number of subjects did not have secondary hyperparathyroidism despite having low 25-hydroxyvitamin D levels. This condition arises a research question in clinical practice needed to be addressed in the future. PURPOSE: The present study was attempted to determine the prevalence of secondary hyperparathyroidism and also to analyze the mean value (cutoff) of 25-hydroxyvitamin D from where the PTH begins to rise in Indian postmenopausal women. METHODS: A cross-sectional study including 334 postmenopausal women attending the outpatient department (MOPD) of Lok Nayak Hospital, New Delhi, between July 2008 and June 2010. Institutional ethical approval was obtained for this study. The apparently healthy postmenopausal women and attendees of the patients were included in the study. Post-thyroidectomy, thyroid illness, pregnant women, subjects taking drugs that can affect bone mineral metabolism, such as glucocorticoids, antitubercular therapy, antiepileptic, and 25-hydroxyvitamin D supplement were excluded from the study. BMD parameters such as PTH and 25(OH)D were measured by using commercial kits from DiaSorin, USA, and blood chemistry was evaluated by standard methods from the central facility of the center. Dietary calcium was analyzed by applying a food frequency questionnaire by a trained dietician. RESULTS: Mean (SD) age of the subjects was 56.4 ± 7.7 years. The mean BMI was 24.7 ± 5.5 kg/m2. The baseline biochemical investigations such as total bilirubin, liver function test (LFT), kidney function test (KFT), calcium, phosphorous, total protein, and serum albumin were in reference range except alkaline phosphatase (ALP). The mean values of 25(OH)D and PTH were 12.95 ± 8.08 ng/ml and 91.60 ± 75.56 pg/ml respectively. The 24-h dietary calcium intake was 487.06 ± 239.36 mg/24 h. 25-hydroxyvitamin D deficiency was found in 277 subjects (82.93%) and was inversely related to PTH. Forty-three subjects had 25-hydroxyvitamin D levels between 20 and 29 ng/ml (12.87%), and only 14 subjects (4.19%) had optimum 25-hydroxyvitamin D levels. Secondary hyperparathyroidism was found in 235 (70.35%) subjects; however, it was not found in 30%. CONCLUSIONS: Majority of postmenopausal women of India had 25-hydroxyvitamin D deficiency with raised PTH levels. The cutoff point of 25-hydroxyvitamin D at which PTH began to rise was found at 25 ng/ml which seems similar to that of the Caucasians.

Risk factors and epidemiological profile of hip fractures in Indian population: A case-control study.

OBJECTIVES: This analytic retrospective case-control study was designed to analyze risk factors and the epidemiological profile of hip fractures among the Indian population with special importance to the mechanism of injuries. METHODS: Patients of hip fractures (n = 41) and age- and sex-matched healthy volunteers (n = 41) were interviewed by a questionnaire regarding the occurrence of the fracture, past history of diseases and long-term medication usage, past and physical activity, supplements, smoking, and alcohol intake. The data were tabulated using descriptive statistics and logistic regression was used to determine significant risk factors. RESULTS: Age group 60-69 was found to be most affected by hip fractures, though an early onset of fractures was noted in males. Falls due to slipping indoors from standing position was found very commonly. However, an increasing trend of falls was noted from lying down position in the older age groups which was more common during the morning and night hours. Logistic regression analysis for the detection of risk factors was applied to the various variables in the questionnaire. Active status in the past was inversely related (odds ratio [OR], 0.33; P < 0.05) to fracture risk while alternative medication usage in the past 1 year (OR, 4.086; P < 0.05) and significant alcohol consumption were directly associated with fracture risk (OR, 5.484; P < 0.05). A potential inverse relation of use of calcium supplements in the past 3 months and fracture risk (OR, 0.872) was seen, although this was not significant. A potential positive relation of smoking with hip fractures was also seen, but not found significant (OR, 2.204). CONCLUSIONS: Hip fractures in the elderly population are on a rising trend especially in the Indian subcontinent due to a number of factors both hereditary and acquired. Simple measures like routine usage of bedside railing, wall-side railings at an appropriate height, high friction tiles inside rooms and washrooms, and adequate lighting indoors can play a significant role in reducing falls and hip fractures among the elderly.

Prevalence of hypothyroidism in pregnancy: An epidemiological study from 11 cities in 9 states of India.

BACKGROUND: A previous hospital based study from Delhi revealed a high prevalence of hypothyroidism in pregnant women. Several other studies with small sample size also indicate a rising trend of prevalence of hypothyroidism during pregnancy in India. OBJECTIVE: To assess prevalence of hypothyroidism in pregnant women from various states/cities across India. MATERIALS AND METHODS: This was a cross-sectional multicenter study conducted at Allahabad (Uttar Pradesh), Bengaluru (Karnataka), Chennai (Tamil Nadu), Kolkata (West Bengal), Hyderabad (Telangana), Nasik (Maharashtra), Rohtak (Haryana), Pune (Maharashtra), New Delhi (Delhi), Srinagar (Kashmir), and Vizag (Andhra Pradesh) enrolling 2599 pregnant women. Estimation of thyroid stimulating hormone (TSH), free T4, and antithyroid peroxidase (TPO) antibodies was carried out using Roche modular kit using ECLIA technology in a central laboratory. RESULTS: We found in our study population that 13.13% of pregnant women have hypothyroidism (n = 388), using a cutoff TSH level of 4.5 µIU/ml. This prevalence was much higher using the American Thyroid Association criteria. Anti-TPO antibodies were positive in 20.74% of all pregnant women (n = 613), whereas 40% (n = 155) of hypothyroid pregnant women were positive for anti-TPO antibodies. CONCLUSION: This study concludes that there is a high prevalence of hypothyroidism (13.13%), majority being subclinical in pregnant women during the first trimester from India and universal screening of hypothyroidism may be desirable in our country.

A rare case of autoimmune hypophysitis presenting as temperature dysregulation.

Autoimmune hypophysitis is a rare cause of pan-hypopituitarism. Hypothalamic involvement in autoimmune hypophysitis is rare and usually manifests as central diabetes insipidus due to antibodies against arginine vasopressin. Temperature dysregulation is occasionally seen with suprasellar tumours but has never been reported with hypophysitis. We report a case of a middle aged man who presented to us with the complaints of documented body temperature fluctuations since two months followed gradually by hoarseness of voice, sexual dysfunction and syncope. Examination was remarkable for postural hypotension, dry coarse skin and delayed ankle reflexes. Patient's hormone profile revealed pan-hypopituitarism and elevated titre of anti-TPO antibodies. Patient's work up for secondary causes of hypopituitarism was negative. MRI brain revealed typical findings of hypophysitis. Patient was suspected as a case of autoimmune hypophysitis and was immediately treated with prednisolone along with hormone replacement. Rapid response within 30 days was observed in the form of subsidence of temperature fluctuations, improvement in general well being, sexual function and repeat MRI done after one month which revealed a partial empty sella. Autoimmune hypophysitis as a potentially treatable cause of temperature dysregulation has been highlighted in this case.

Hormonal profile in children with isolated hypospadias associates better with comprehensive score of local anatomical factors as compared to meatal location or degree of chordee.

BACKGROUND: To evaluate if hormonal profile of children with isolated hypospadias (IH) associates better with comprehensive local anatomical factor score (LAFS) than with clinically adjudged urethral meatus location or severity of chordee/k.j. MATERIAL AND METHODS: Ninety-nine children with IH were enrolled, as per inclusion criteria. Meatal location was recorded at first clinical examination in OPD; while LAFS was computed per-operatively using indigenously devised scale, except for neonates. Hypospadiacs were first classified into three standard meatal based groups and subsequently into LAFS based two groups (≤19, >19). For all participants, pre HCG and post HCG (96 hour post- injection) estimation of serum gonadotropins, DHEA-S, estrogen (E), progesterone (P), testosterone (T) and Dihydrotestosterone (DHT) was done. Statistical tests were applied to assess significance of hormonal levels with respect to meatal location, chordee and LAFS. RESULTS: Only FSH levels differed significantly among meatal based groups; while among LAFS groups, multiple hormonal differences were noted; with poor LAFS associated significantly with higher FSH, LH and lower E, T/DHT. Children with severe degree of chordee had poorer T output and a significantly lower LAFS as compared to those with moderate/mild chordee. CONCLUSION: Serotoli cell dysfunction, indirectly indicated by high FSH was found among midpenile hypospadiacs and those with poorer LAFS. Since groups based on LAFS revealed multiple intergroup hormonal differences than what was seen for meatal/chordee based groups; LAFS should be considered a better guide for prognostication and for deciding about hormonal supplementation. Lower androgenic output was particularly noted in children with severe chordee.

Recurrent hypoglycaemia: a delayed presentation of Sheehan syndrome.

Sheehan syndrome is a rare but potentially serious complication of postpartum haemorrhage. The diagnosis can often be delayed by many years as symptoms may be subtle. We report the case of a 45-year-old woman who presented to the medical emergency unit with acute onset altered sensorium. On further evaluation she was found to have severe hypoglycaemia which was corrected by giving intravenous dextrose. On detailed clinical evaluation, she had a history of agalactia and amenorrhoea following her last pregnancy which was 15 years ago. She had a history of excessive postpartum bleeding during her last delivery. MRI of the brain showed empty sella and hormonal evaluation revealed adenohypophyseal insufficiency as evident from decreased levels of cortisol, thyroid-stimulating hormone, triiodothyronine, free thyroxine, follicle-stimulating hormone, luteinising hormone and prolactin. Based on clinical, radiological and laboratory parameters her final diagnosis was Sheehan syndrome with hypoglycaemia.

A Randomized controlled trial on safety and efficacy of single intramuscular versus staggered oral dose of 600 000IU Vitamin D in treatment of nutritional rickets.

OBJECTIVE: Comparison of efficacy and safety of two different regimens of vitamin D-600 000 IU as a single intramuscular dose, and 60 000IU orally once a week for 10 weeks-in treatment of nutritional rickets. METHODS: Children with nutritional rickets (age: 0.5-5 years, n = 61) were randomized to receive either 60 000IU vitamin D orally once a week for 10 weeks or 600 000IU single intramuscular injection. Serum calcium, phosphate, alkaline phosphatase, urinary calcium/creatinine ratio, serum 25 hydroxy vitamin D and radiological score were compared at 12-week follow-up. RESULTS: No difference was found in efficacy of the two regimens on comparing biochemical and radiological parameters. Serum 25 hydroxy vitamin D >100 ng/ml was found in two children in the oral group and one child in the intramuscular group. No child developed hypercalcemia or hypercalciuria after starting treatment. CONCLUSION: Staggered oral and one-time intramuscular administrations of 600 000IU vitamin D are equally effective and safe in treatment of nutritional rickets.

Successful treatment of acquired pure red cell aplasia with oral corticosteroids in a patient with B-cell CLL.

We present the case of a 57-year-old male patient diagnosed with chronic lymphoid leukaemia (CLL) B-cell type along with moderate anaemia. On follow-up investigations the aetiology of anaemia turned out to be pure red cell aplasia (PRCA) on trephine bone biopsy with an elevated serum erythropoietin level. The patient received blood transfusion support. He showed remarkable improvement on oral corticosteroids (prednisolone 60 mg/daily dose) with no further requirement of blood transfusion over next 3 months. However, when the dose of steroid was tapered down to 10 mg/day, the anaemia reappeared. An increase in the dose of steroid brought the haemoglobin level back to normal. Anaemia in CLL can be due to many reasons, of which PRCA is an uncommon association occurring in only around 1% of patients with CLL and usually refractory to the conventional treatment with steroids. This PRCA secondary to CLL is considered to be immune in origin and a response to combination of immunosuppressive therapy such as steroids, cyclosporine, rituximab is anticipated. Our case responded completely to oral steroids alone.

Recurrent symptomatic hypoglycaemia with pancytopenia as a delayed presentation of Sheehan's syndrome with complete recovery after hormone replacement.

A 38-year-old woman presented to our hospital emergency section in altered sensorium and with blood pressure of 80/60 mm Hg. She gave a history of recurrent episodes of loss of consciousness for 15-20 days, generalised body swelling and generalised weakness for the past 5-6 years. On further evaluation she was found to have severe hypoglycaemic episodes. In view of history of pregnancy and significant blood loss during surgery and long history of lethargy, asthaenia and generalised anasarca, the patient was evaluated for Sheehan's syndrome. Her serum cortisol levels were very low and she was found to have central hypothyroidism. MRI of the brain also revealed small sella turcica and small pituitary gland suggestive of hypopituitarism. The patient was started on high-concentration dextrose drips, steroids and thyroid hormone replacement. The patient showed a marked improvement within 1 week of treatment. And she was discharged with an advice to follow-up at our outpatient department.

MEN2B syndrome presenting as an acute respiratory emergency.

An 18-year-old girl presented to the emergency department with a history of noisy breathing and breathlessness progressively increasing for few days. The patient had stridor and tachypnoea. She was tall with a long thin face, wrist sign and high-arched palate suggestive of marfanoid features. X-ray of the neck revealed critical tracheal narrowing. Emergency tracheostomy was performed as a lifesaving procedure. Non-contrast CT neck revealed extratracheal compression by a mass surrounding it. Contrast-enhanced CT scan of the neck revealed heterogeneous mass arising from the right lobe of the thyroid and tracheal deviation with narrowing. Fine-needle aspiration cytology of the mass revealed medullary carcinoma of the thyroid, positive for calcitonin. Calcitonin levels were raised. Apart from the marfanoid features she had localised swellings over the lips, lower eyelid and the lateral aspects of the tongue, clinically suggestive of neuromas. A clinical diagnosis of multiple endocrine neoplasia type 2B syndrome was made. The patient underwent total thyroidectomy with central lymphnode dissection. This case highlights an unusual presentation of a rare disease.

Hand grip strength and its correlation with vitamin D in Indian patients with hip fracture.

UNLABELLED: This case-control study was performed to evaluate 25-hydroxyvitamin D [25(OH)D] deficiency and its correlation with hand grip strength in 95 Indian hip fracture subjects and 95 controls. 25(OH)D deficiency was found in 88.4 % of hip fracture subjects that was significantly higher as compared to controls. Hand grip strength as measured by hand held dynamometer was significantly lower in patients, and there was a significant positive correlation between 25(OH)D and hand grip strength. PURPOSE: The present study was conducted to assess correlation between 25(OH) D and hand grip strength in hip fracture subjects residing in North India. METHODS: Ninety-five patients with hip fracture and similar number of controls were enrolled in the study. Fasting venous samples were analyzed for 25(OH)D, intact parathyroid hormone (PTH), alkaline phosphatase, calcium, and phosphate. Hand grip strength of study subjects was measured using Jamar dynamometer. Correlation between vitamin D levels and hand grip strength was analyzed in study population. RESULTS: The mean age of hip fracture subjects was 61.4 ± 12.6 years which was comparable in men and women. Out of 95 subjects, 57 were men and 38 were women. Mean 25(OH)D levels were significantly lower whereas intact PTH levels were significantly higher in patient group compared controls (10.29 ± 6.53 vs 13.6 ± 4.01 ng/ml; 62.6 ± 59.3 vs 37.7 ± 28.8 pg/ml, respectively). The number of subjects with 25(OH)D deficiency and secondary hyperparathyroidism was significantly higher in hip fracture group. The mean hand grip strength among hip fracture subjects was significantly lower compared to that of controls (16.57 ± 5.74 vs 26.74 ± 5.23 kg). There was a significant positive correlation between 25(OH)D and hand grip strength ( r = 0.482, p value <0.01) in hip fracture population. CONCLUSION: Majority of hip fracture patients in India have vitamin D deficiency, secondary hyperparathyroidism, and lower hand grip strength compared to controls. Further, there is significant positive correlation between 25(OH)D and hand grip strength.

Evaluation of autonomic functions in subclinical hypothyroid and hypothyroid patients.

BACKGROUND: Autonomic dysfunction may contribute to cardiovascular morbidity in subclinical hypothyroid patients. It is controversial whether the abnormality exists in sympathetic or the parasympathetic function. It is also not known whether the severity of autonomic dysfunction is related to the degree of thyroid deficiency. DESIGN OF STUDY: Prospective case control. MATERIALS AND METHODS: Autonomic functions based on heart rate (HR) and blood pressure (BP) responses to various maneuvers were evaluated and scored in twenty two subclinical hypothyroid patients, 30-50 years and compared with twenty hypothyroid patients. Biochemical estimation of TSH, fT3, fT4, TPO antibody was done. RESULT: Sympathetic function abnormalities were seen in 82% subclinical hypothyroid patients and 85%hypothyroid patients when one test was abnormal. Parasympathetic dysfunction was also recorded in eight patients in both groups. When two abnormal tests were used as the selection criteria sympathetic function abnormality was observed in about 41% subclinical hypothyroid and 65% hypothyroid patients. There were no intergroup differences in autonomic functions, score and TPO levels. The TSH levels were not related to type or degree of autonomic dysfunction. Systolic BP in both groups and diastolic BP in hypothyroid patients were higher with lower thyroxine levels but the patients were normotensive. CONCLUSION: Autonomic dysfunction of comparable degree was seen in subclinical hypothyroid and hypothyroid patients. Sympathetic function abnormality was more common although decreased parasympathetic function reactivity was also present. These abnormalities were unrelated to TSH levels.