Cost of screening, out-of-pocket expenditure & quality of life for diabetes & hypertension in India

Background & objectives: The Government of India has initiated a population based screening (PBS) for noncommunicable diseases (NCDs). A health technology assessment agency in India commissioned a study to assess the cost-effectiveness of screening diabetes and hypertension. The present study was undertaken to estimate the cost of PBS for Type II diabetes and hypertension. Second, out-of-pocket expenditure (OOPE) for outpatient care and health-related quality of life (HRQoL) among diabetes and hypertension patients were estimated. Methods: Economic cost of PBS of diabetes and hypertension was assessed using micro-costing methodology from a health system perspective in two States. A total of 165 outpatients with diabetes, 300 with hypertension and 497 with both were recruited to collect data on OOPE and HRQoL. Results: On coverage of 50 per cent, the PBS of diabetes and hypertension incurred a cost of ? 45.2 per person screened. The mean OOPE on outpatient consultation for a patient with diabetes, hypertension and both diabetes and hypertension was ? 4381 (95% confidence interval [CI]: 3786-4976), ? 1427 (95% CI: 1278-1576) and ? 3932 (95% CI: 3614-4250), respectively. Catastrophic health expenditure was incurred by 20, 1.3 and 14.8 per cent of patients with diabetes, hypertension and both diabetes and hypertension, respectively. The mean HRQoL score of patients with diabetes, hypertension and both was 0.76 (95% CI: 0.72-0.8), 0.89 (95% CI: 0.87-0.91) and 0.68 (95% CI: 0.66-0.7), respectively. Interpretations & conclusions: The findings of our study are useful for assessing cost-effectiveness of screening strategies for diabetes and hypertension.

Anthropometric and Pubertal Outcomes in Girls With Classical Congenital Adrenal Hyperplasia

Objective: To evaluate the anthropometric and pubertal outcomes, over a spectrum of treatment regimens and compliance. Methods: We reviewed records of the patients with classical CAH seen at the endocrinology clinic of a tertiary care center between 1995 and 2016. Results: 25 females were included in the study, the majority (80%) with simple virilizing variant. All patients had genital ambiguity since birth, yet 40% (10/25) presented much later with menstrual complaints. All patients received hydrocortisone, but some switched to dexamethasone (n=7) or prednisolone (n=4). 7/9 (77.9%) girls who achieved target height, were on hydrocortisone. Menarche occurred with corticosteroid treatment in 60% (15/25) patients at a median (IQR) age of 16 (12-22) years. Conclusion: Hydrocortisone seems to have a beneficial effect on linear growth. Once target height is achieved, dexamethasone may be considered as an alternative.

Differential loss of fat in polycystic ovary syndrome: A welcome or warning sign?

Lipodystrophy syndrome is a rare disorder characterized by selective deficiency of adipose tissue and severe insulin resistance resulting in metabolic complications. Its presentation as polycystic ovary disease (PCOD) is even rarer. We present a 23-year-old woman who came with complaints of oligomenorrhoea and hirsutism. When specifically asked, she accepted noticing loss of fat from some areas of her body. Examination showed loss of fat from the face, buttocks and thighs. Her investigations revealed deranged blood sugars, transaminitis, dyslipidaemia and elevated serum testosterone; ultrasonography showed fatty liver and polycystic ovary. Fat composition measurement revealed loss of fat from lower limbs and increased ratio of trunk-to-leg fat. Based on these findings, a diagnosis of lipodystrophy was made. She was started on metformin, statins and ursodeoxycholic acid. Blood sugars, lipid profile and dyslipidaemia improved over a period of 6 months. We suggest that in lean patients with PCOD, lipodystrophy becomes a differential diagnosis, so attention should be paid to body fat distribution in them. Despite normal body mass index (BMI), these patients tend to develop metabolic complications as in our patient (BMI 21.5). This diagnosis has long-term implications in view of its association with metabolic complications.

Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1) gene with diabetic nephropathy in north Indians.

Background & objectives: CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the rate-limiting enzyme in hydrolysis of carnosine to β-alanine and L-histidine. Linkage of CTG trinucleotide (leucine) repeat polymorphism in CNDP1 gene with diabetic nephropathy has been observed in several populations. However, this association is conflicting and population-dependent. We investigated this association in type 2 diabetes mellitus (T2DM) patients with and without nephropathy in north India. Methods: A total of 564 individuals [199 T2DM without nephropathy (DM), 185 T2DM with nephropathy (DN) and 180 healthy individuals (HC)] were enrolled. CNDP1 CTG repeat analysis was done by direct sequencing of a 377 base pair fragment in exon 2. Results: The most frequent leucine (L) repeats were 5L-5L, 6L-5L and 6L-6L. 5L-5L genotype frequency was reduced in DN (24.3%) as compared to DM (34.7%, P=0.035) and HC (38.4%, P=0.005). Similarly, 5L allele frequency was lower in DN (46.8%) as compared to DM (57.3%, P=0.004) and HC (60.5%, P<0.001). The genotype and allelic frequencies were similar in DM and HC groups. No gender specific difference was observed in the genotype or allelic frequencies between groups. Interpretation & conclusions: Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population.

Prevalence of generalized & abdominal obesity in urban & rural India- the ICMR-INDIAB study (Phase-I) [ICMR-INDIAB-3].

Background & objectives: Overweight and obesity are rapidly increasing in countries like India. This study was aimed at determining the prevalence of generalized, abdominal and combined obesity in urban and rural India. Methods: Phase I of the ICMR-INDIAB study was conducted in a representative population of three states [Tamil Nadu (TN), Maharashtra (MH) and Jharkhand (JH)] and one Union Territory (UT)[Chandigarh (CH)] of India. A stratified multi-stage sampling design was adopted and individuals ≥20 yr of age were included. WHO Asia Pacific guidelines were used to define overweight [body mass index (BMI) ≥23 kg/m2 but <25 kg/m2], generalized obesity (GO, BMI≥25kg/m2), abdominal obesity (AO, waist circumference ≥90 cm for men and ≥80cm for women) and combined obesity (CO, GO plus AO). Of the 14,277 participants, 13,800 subjects (response rate, 96.7%) were included for the analysis (urban: n=4,063; rural: n=9737). Results: The prevalence of GO was 24.6, 16.6, 11.8 and 31.3 per cent among residents of TN, MH, JH and CH, while the prevalence of AO was 26.6, 18.7, 16.9 and 36.1 per cent, respectively. CO was present in 19.3, 13.0, 9.8 and 26.6 per cent of the TN, MH, JH and CH population. The prevalence of GO, AO and CO were significantly higher among urban residents compared to rural residents in all the four regions studied. The prevalence of overweight was 15.2, 11.3, 7.8 and 15.9 per cent among residents of TN, MH, JH and CH, respectively. Multiple logistic regression analysis showed that female gender, hypertension, diabetes, higher socio-economic status, physical inactivity and urban residence were significantly associated with GO, AO and CO in all the four regions studied. Age was significantly associated with AO and CO, but not with GO. Interpretation & conclusions: Prevalence of AO as well as of GO were high in India. Extrapolated to the whole country, 135, 153 and 107 million individuals will have GO, AO and CO, respectively. However, these figures have been estimated from three States and one UT of India and the results may be viewed in this light.

Effect of mesenchymal stem cells transplantation on glycaemic profile & their localization in streptozotocin induced diabetic Wistar rats.

Background & objectives: Bone marrow is a rich source of adult stem cells that can differentiate into various cell types. Administration of mesenchymal stem cells (MSCs) in irradiated diabetic rat model has transiently shown to decrease blood glucose level. This study examines the effect of high dose and multiple injections of MSCs on glycemic profile, their localization and regeneration of islet in diabetic Wistar rat. Methods: The study was carried out in male Wistar rats categorized into three groups (n=6, in each group): Group 1 as control, group 2 streptozotocin (STZ) (50 mg/kg) induced diabetic group and group 3 experimental group; 5-bromo-2-deoxyuridine (BrdU) labelled allogenic MSCs were injected in the non-irradiated diabetic rat of the experimental group through tail vein. The blood glucose profile was subsequently monitored at regular intervals. Rats were sacrificed on day 45 and pancreas was examined for localization of BrdU labelled stem cells by immunofluorescence and islet-neogenesis by immunohistochemistry . Results: There was a significant reduction in blood glucose level after administration of MSCs in the experimental group (p<0.001). The presence of BrdU labelled MSCs in islet suggested their localization in the pancreas. Co-expression of anti-BrdU and anti-insulin antibody indicated trans-differentiation / fusion into insulin producing cells evidenced by significant increase in total number of islet (p=0.004) and insulin positive cells (p<0.0001) in experimental group. Interpretation & conclusions: Our results showed that the MSCs administration in non-irradiated diabetic Wistar rat reduced hyperglycaemia and was accompanied by increased islet-neogenesis, possibly through trans- differentiation/fusion.

Sensitivity and specificity of nonmydriatic digital imaging in screening diabetic retinopathy in Indian eyes.

Background: Nonmydriatic digital imaging (NMDI) is ideal for screening diabetic retinopathy (DR), but its use in Indian eyes has not been evaluated. Aim: The aim was to evaluate the sensitivity and specifi city of NMDI as a screening tool in detecting DR in Indian eyes. Design: A prospective, nonrandomized, noncomparative, noninterventional study. Materials and Methods: A total of 500 diabetic patients visiting the endocrinology clinic (September 2008-June 2010) underwent NMDI (Zeiss Procam), followed by routine dilated fundus photography (FP; Zeiss Visupac 450+) of 345° retinal fi elds (1) optic disc and macula, (2) superotemporal, and (3) nasal to optic disc. Two-masked retina specialists graded the images for quality and severity of DR, and compared between NMDI and dilated FP. Statistical Analysis: SPSS Windows 17 for version. Results: Mean age was 52.97 ± 13.46 years (306 males: 194 females). The rate of ungradable images was 30.6% and 31% by the two observers. By observer 1, the sensitivity and specifi city of detecting any DR was 58.8% and 69.1%, respectively, ( = 0.608) and sight-threatening DR (STDR) was 63.1% and 68.9%, respectively, ( = 0.641). By observer 2, the sensitivity and specifi city was 57.3% and 68.3%, respectively, for any DR ( = 0.593) and 62.8% and 68.3%, respectively, for STDR ( = 0.637). The level of agreement between two observers was high ( = 0.96). Conclusion: A high rate of poor quality photographs and low sensitivity limited the use of NMDI as a perfect screening system, particularly in dark iris population with diabetes as seen in Indian eyes.

Predictors of atypical femoral fractures during long term bisphosphonate therapy: A case series & review of literature.

Background & objectives: Bisphosphonates (BPs) are the most widely prescribed medicines for the treatment of osteoporosis because of their efficacy and favourable safety profile. There have been, several reports on an increased incidence of atypical femoral fractures after long term treatment with BPs. The objective of this study was to evaluate the clinical presentation including prodromal symptoms, skeletal radiograph findings, type and duration of BPs received and treatment outcome of patients who developed atypical femoral fractures during bisphosphonate therapy. Methods: In this retrospective study, eight patients with atypical femoral fractures were analysed based on clinical features, biochemical and radiological investigations. Results: Of the eight patients, who sustained atypical femoral fractures, six were on alendronate and two were on zoledronate therapy before the fractures. In addition to BPs, two patients were on long term corticosteroid therapy for rheumatoid arthritis and Addison’s disease. Three patients had bilateral atypical femoral fractures. Except one, all of them had prodromal symptoms prior to fracture. Skeletal radiograph showed cortical thickening, pointed (beaking of) cortical margin and transverse fracture in meta-diaphyseal location. Serum calcium, phosphate, alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) concentrations were within the reference range in all patients. Interpretation & conclusions: Long term bisphosphonate therapy may increase the risk of atypical femoral fractures. Presence of prodromal pain, thickened cortex with cortical beaking may be an early clue for predicting the atypical fractures. High risk patients need periodical skeletal survey and a close follow up for early detection of cases.

Changes in clinical & biochemical presentations of primary hyperparathyroidism in India over a period of 20 years.

Background & objectives: With the advent of serum chemistry autoanalyzer and routine estimation of serum calcium as a part of annual physical examination, there has been a dramatic change in the presentation of primary hyperparathyroidism (PHPT) from symptomatic to asymptomatic disease in the United States. However, such trend has not been documented from India. We carried out this retrospective study to analyse the changes in clinical presentations of PHPT patients over a period of two decades in a tertiary care centre in north India. Methods: This retrospective study included patients with PHPT treated at a single centre of north India between March1990 and October 2010. Two decades were divided into four different time periods, i.e. 1990 to 1994, 1995 to 1999, 2000 to 2004 and 2005 to 2010. Clinical presentations, biochemical parameters and surgical outcomes were compared between different time periods using appropriate statistical methods. Results: Data of 202 patients with PHPT with male: female ratio of 3:7 were analyzed. There was a rise in the number of cases of PHPT diagnosed in the last decade compared to the previous decade (28 cases vs 174 cases, P<0.001). Change in the mean age, male: female ratio, lag time for the diagnosis of PHPT and clinical presentations of PHPT (predominance of bone and stone symptoms) did not differ across different time periods. Non-significant decrease in serum calcium levels at the time of diagnosis of PHPT and a significant, decline in the serum alkaline phosphatase levels (P<0.01) were found in the last decade, however, iPTH levels were higher in the last decade (pP<0.05). There was no change in the site and size of parathyroid adenoma in the two decades, however, postoperative symptomatic hypocalcemia was less frequent in the last decade. Interpretation & conclusions: The findings of this retrospective analysis show that the PHPT still remains symptomatic disease with increasing awareness over the last two decades in our center. There was not much change in the clinical presentation, in the past two decades.

Effect of gender, biochemical parameters & parathyroid surgery on gastrointestinal manifestations of symptomatic primary hyperparathyroidism.

Background & objectives: Information on gastrointestinal manifestations and then response after curative parathyroid surgery is scarce in symptomatic primary hyperparathyroidism (PHPT). This study was carried out to analyse gastrointestinal manifestations in patients with PHPT and their associations with biochemical parameters. Methods: This retrospective study included 153 patients with symptomatic primary hyperparathyroidism (PHPT). The signs and symptoms pertaining to gastrointestinal system were analyzed. The difference of symptoms between men and women and difference in biochemical parameters in presence of different symptoms were evaluated. The relationship between serum calcium, phosphate and parathyroid hormone (PTH) levels with presence of gallstone and pancreatitis was also studied. Result: Of the 153 patients, 46 (30%) were men. The mean age was 39.2 ± 13.9 yr. Nearly 80 per cent of PHPT patients had at least one symptom/ sign related to gastrointestinal system. The most common gastrointestinal manifestations were abdominal pain 66 (43%), constipation 55 (36%), and nausea/or vomiting 46 (30%). Nearly one-fourth 34 (22%) of patients had a history of either gallstone disease or cholecystectomy or both. The prevalence of gallstone disease was higher in women (P<0.05). Imaging and biochemical evidence of pancreatitis was found in 27 (18%) patients. Pancreatitis was more common in men compared to women (P<0.05) despite the higher prevalence of gallstones in women. Serum calcium, phosphate or PTH levels were not associated with high risk for gallstone disease, however, serum calcium (P<0.05) was associated with 1.3 times higher risk of developing pancreatitis. In majority of patients, gastrointestinal manifestations resolved within three months of curative parathyroidectomy. Except two patients, none had recurrence of pancreatitis. Interpretation & conclusions: The study revealed that the gastrointestinal symptoms were common in patients with symptomatic PHPT. There was not much gender difference in gastrointestinal symptoms except higher occurrence of gallstones in women and pancreatitis in men. There was no difference in biochemical profile between those who had and did not have gastrointestinal symptoms.

High prevalence of cardiovascular risk factors in Asian Indians: A community survey - Chandigarh Urban Diabetes Study (CUDS).

Background & objectives: Studies conducted to assess the prevalence of cardiovascular (CV) risk factors among different regions of the country show variation in risk factors in different age groups and urban and rural population. We undertook this study to determine the prevalence of cardiovascular risk factors among urban adults in a north Indian city. Methods: In a cross-sectional survey, 2227 subjects aged ≥ 20 yr were studied from April 2008 to June 2009 in Urban Chandigarh, a north Indian city. Demographic history, anthropometry and blood pressure were assessed. Fasting, and 2 h capillary plasma glucose after 75 g glucose load, HDL-C and triglycerides were estimated. Results: The most prevalent cardiovascular risk factors in the age group of 20-29 yr was sedentary lifestyle (63%), while from fourth decade and onwards, it was overweight/obesity (59-85%). The second most common prevalent cardiovascular risk factor in the age group of 20-29 yr was overweight/obesity, in 30-49 yr sedentary lifestyle, in 50-69 yr hypertension and in subjects ≥70 yr, it was hypertriglyceridaemia. The prevalence of overweight/obesity, hypertension, dysglycaemia and smoking was almost double in subjects in the fourth decade of life, as compared to those in the third decade of life. The prevalence of CV risk factors significantly increased with age irrespective of gender and prevalence of low HDL-C was significantly more common in women as compared to men. Interpretation & conclusions: Sedentary lifestyle, obesity and low HDL-C are the most prevalent CV risk factors in subjects in the third and fourth decade of life in this north Indian population and clustering of these cardiovascular risk factors increases with advancing age. Strategies need to be formulated to target this population to prevent the epidemic of cardiovascular disease.

Efficacy & safety of continuous erythropoietin receptor activator (CERA) in treating renal anaemia in diabetic patients with chronic kidney disease not on dialysis.

Background & objectives: Chronic kidney disease (CKD) patients on dialysis regularly receive erythropoiesis stimulating agent (ESA) for treating renal anaemia during their dialysis unlike those who are not on dialysis. In such patients, the longer acting ESA can be helpful in reducing their frequent visits to the health care facilities and improving their compliance. This study was aimed to examine the efficacy and safety of continuous erythropoietin receptor activator (CERA), a long acting ESA in treating renal anaemia in patients with diabetic CKD not on dialysis. Methods: In this prospective, open-labelled, pilot clinical study, 35 adult type 2 diabetes patients with nephropathy and renal anaemia, who were not on dialysis nor receiving treatment with ESA were administered CERA subcutaneously once in two weeks for a period of 24 weeks. The primary efficacy end point was to evaluate the Hb response (Hb rise of ≥1 g/dl above the baseline or Hb level ≥11 g/dl) during the study period. Results: All patients showed Hb rise ≥1 g/dl during the study period and 80 per cent patients could achieve Hb value ≥11 g/dl. The maximum median Hb rise of 1.2 g/dl occurred in the initial 6 weeks after starting the treatment. The mean creatinine clearance (CrCl) improved by 2.8 ml/min, with mean Hb rise of 2.6 g/dl from the baseline after administration of CERA. Worsening of blood pressure (BP) control (42.9%) was the most common adverse event. Interpretation & conclusions: CERA once in two weeks was found to be efficacious in correcting anaemia in the ESA-naïve patients with diabetic nephropathy who are not on dialysis. However, regular monitoring of blood pressure is required while on treatment with CERA.

Weight homeostasis & its modulators in hyperthyroidism before & after treatment with carbimazole.

Background & objectives: 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. Methods: 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. Results: 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. Interpretation & conclusion: 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.

Macroorchidism: Consequence of Untreated Congenital Adrenal Hyperplasia.

Testicular adrenal rest tumors (TART) are consequences of delayed diagnosis and/or undertreatment in patients with congenital adrenal hyperplasia (CAH). We describe a case of CAH with TART who presented with bilateral macroorchidism. He was managed with glucocorticoids which led to decrease in testicular size without restoration of spermatogenesis.

Oro-mandibular manifestations of primary hyperparathyroidism.

Aims and Objective : To determine the effects of Primary Hyperparathyroidism on oral cavity in a symptomatic contemporary Indian population by taking note of the following parameters: (1) Radiological alteration of lamina dura, (2) mandibular cortical width, (3) prevalence of brown tumor, and (4) mandibular tori. Study Design : Twenty-six patients of Primary Hyperparathyroidism were examined clinically and radiologically for extra- and intraoral abnormalities. Loss of lamina dura, mandibular cortical width, presence of mandibular tori, and brown tumors were assessed and correlated with serum Calcium, Phosphate, Parathormone, and Alkaline phosphatase. The results were compared with twenty-six age- and gender-matched control subjects. The data was expressed as mean ± SD, and a probability (p) value of < 0.05 was considered significant. Pearson's statistical method was used to assess the significant correlation between radiological measurements and biochemical values. Results : Generalized absence of the lamina dura was the most consistent finding and there was a significant correlation between its loss and altered parathormone, alkaline phosphatase, and inorganic phosphate, but not with serum calcium or the duration of the disease. Mean values (in mm) for the cortical indices were significantly lower in the patients compared to the controls and correlated significantly with parathormone and alkaline phosphatase. None of the patients had mandibular tori and only one patient had a brown tumor. Conclusion : Loss of lamina dura, ground glass appearance, and mandibular cortical width reduction are common findings in primary hyperparathyroidism and these are significantly correlated with elevated parathormone and alkaline phosphatase. However, the presence of brown tumors and oral tori are less commonly encountered features.