RESUMEN
A mutation in the steroidogenic acute regulatory protein (STAR) gene, which encodes a protein that plays a crucial role in steroid hormone synthesis, causes a severe form of congenital adrenal hyperplasia (CAH) known as lipoid CAH (LCAH). LCAH presents with primary adrenal insufficiency (PAI) as well as atypical genitalia. Individuals with LCAH require adrenal steroid hormone supplements for survival. Masculinization in males with STAR deficiency varies from incomplete to normal virilization. Radiological examinations reveal enlarged and lipid-laden adrenals. A 10-year-old boy born of second-degree consanguinity presented with weight gain and hyperpigmentation for 1 year. He was diagnosed with PAI at age 7 months and treated with hydrocortisone and fludrocortisone. Dynamic adrenal gland testing revealed undetectable hormone reserves. Imaging detected hypoplastic adrenals and a small testis with testicular adrenal rests (TART). Genetic analysis indicated a novel homozygous pathogenic variant of STAR in exon 7, c.814C > G(pArg272Gly) associated with LCAH (OMIM No. 201710). Testing revealed that asymptomatic family members and relatives were heterozygotes for the variant. The patient was diagnosed with nonclassic LCAH with hypoplastic adrenals and TART. Adequate hormone supplementation resulted in TART regression. This genetic variation is reported for the first time.
RESUMEN
Calcium and vitamin D are inseparable nutrients required for bone health. In the past half a century, the dietary calcium intake of rural, tribal, and urban India has declined. Though India is the largest producer of milk and cereals, the major source of calcium in India is through non-dairy products. The highest intake of cereals and lowest intake of milk & milk products was observed in rural and tribal subjects whereas, the intake of cereals, milk & milk products were similar in both urban and metropolitan subjects. One of the reasons for lower calcium intake was the proportion of calcium derived from dairy sources. Over the past half a century, the average 30-day consumption of cereals in the rural and urban population has declined by 30%. The Per Capita Cereal Consumption (PCCC)has declined despite sustained raise in Monthly Per capita Consumption Expenditure (MPCE) in both rural and urban households. The cereal consumption was the highest in the lowest income group, despite spending smaller portion of their income, as cereals were supplied through public distribution system (PDS). About 85% of the Indian population are vitamin D deficient despite abundant sunlight. Dietary calcium deficiency can cause secondary vitamin D deficiency. Though India as a nation is the largest producer of milk, there is profound shortage of calcium intake in the diet with all negative consequences on bone health. There is a decline in dietary calcium in the background of upward revision of RDI/RDA. There is a gap in the production-consumption-supply chain with respect to dietary calcium. To achieve a strong bone health across India, it is imperative to have population based strategies addressing different segments including supplementing dietary/supplemental calcium in ICDS, mid-day-meals scheme, public distribution system, educational strategies. Other measures like mass food fortification, biofortification, bioaddition, leveraging digital technologies, investments from corporate sector are some measures which can address this problem. India is a vast country with diverse social, cultural and dietary habits. No single measure can address this problem and requires a multi-pronged strategic approach to tackle the dietary calcium deficiency to achieve strong bone health while solving the problem of nutritional deficiency.
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Trastornos del Metabolismo del Calcio/epidemiología , Calcio/deficiencia , Trastornos del Metabolismo del Calcio/sangre , Trastornos del Metabolismo del Calcio/dietoterapia , Calcio de la Dieta/administración & dosificación , Femenino , Alimentos Fortificados/estadística & datos numéricos , Alimentos Fortificados/provisión & distribución , Historia del Siglo XX , Historia del Siglo XXI , Humanos , India/epidemiología , Masculino , Estado Nutricional/fisiología , Ingesta Diaria Recomendada , Estudios Retrospectivos , Vitamina D/administración & dosificación , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Deficiencia de Vitamina D/dietoterapia , Deficiencia de Vitamina D/epidemiologíaRESUMEN
Vitamin D and calcium are essential nutrients for bone health, to achieve peak bone mass and to preserve bone as age advances. A deficiency in these nutrients casts a long shadow in later life in the form of short/long latency diseases-rickets/osteomalacia/osteoporosis. There is scant review available about the trend of these nutrients in India. For over past half a century, the intake of dietary calcium, milk, milk products, and cereals has declined drastically in the background of upward revision of RDA/RDI in modern India. This is attributed to changing lifestyle, inadequate milk consumption across various socio-economic strata, and shift in dietary intake from cereals to rice and wheat. There is a clear rural-urban divide in consumption of milk, milk products and cereals, a change in dietary habits which magnify the calcium and vitamin D deficiency. Revisiting of RDA guidelines for calcium along with public health measures is required to tackle the morbidity arising due to the deficiency in these nutrients. Any measure to addresses this issue in isolation, without achieving the desired benefits, is a disservice to the population. Population based educational strategies, government measures, leveraging technology, adequate sun exposure and food fortification help in tackling the twin nutrient deficiencies in this diverse country.
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The vitamin D endocrine system in now recognized as subserving a wide range of fundamental biological functions in cell differentiation, inhibition of cell growth as well as immunomodulation. Both forms of immunity, namely adaptive and innate, are regulated by 1,25(OH)2D3. The immune-modulatory properties of vitamin D suggest that it could play a potential therapeutic role in prevention of type 1 diabetes mellitus (T1DM). It is postulated that large doses of vitamin D supplementation may influence the pattern of immune regulation and subsequent progression to T1DM in a genetically susceptible individual. More studies are required to substantiate the relation between T1DM and vitamin D/vitamin D analogues in the pattern of immune regulations in susceptible individuals. In type 2 diabetes mellitus (T2DM), vitamin D may influence both insulin secretion and sensitivity. An inverse relationship between T2DM and vitamin D is postulated from cross-sectional and prospective studies, though conclusive proof is as yet lacking. Available studies differ in their design and in the recommended daily allowances (RDA) of vitamin D in non-skeletal diseases and ß-cell function. Large, well designed, controlled, randomized interventional studies on the potential role of vitamin D and calcium in prevention and management of T2DM are required to clarify the relationship between vitamin D and glucose homeostasis in T2DM.
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Diabetes Mellitus Tipo 1/prevención & control , Diabetes Mellitus Tipo 2/prevención & control , Suplementos Dietéticos , Células Secretoras de Insulina/efectos de los fármacos , Vitamina D/uso terapéutico , Animales , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/inmunología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/inmunología , Humanos , Insulina/sangre , Células Secretoras de Insulina/inmunología , Células Secretoras de Insulina/metabolismo , Pronóstico , Factores de Riesgo , Vitamina D/metabolismoRESUMEN
OBJECTIVE: There are varied reports on the effect of vitamin D supplementation on ß-cell function and plasma glucose levels. The objective of this study was to examine the effect of vitamin D and calcium supplementation on ß-cell function and plasma glucose levels in subjects with vitamin D deficiency. METHODS: Nondiabetic subjects (N = 48) were screened for their serum 25-hydroxyvitamin D (25-OHD), albumin, creatinine, calcium, phosphorus, alkaline phosphatase, and intact parathyroid hormone (PTH) status. Subjects with 25-OHD deficiency underwent a 2-hour oral glucose tolerance test. Cholecalciferol (9,570 international units [IU]/day; tolerable upper intake level, 10,000 IU/day; according to the Endocrine Society guidelines for vitamin D supplementation) and calcium (1 g/day) were supplemented. RESULTS: Thirty-seven patients with 25-OHD deficiency participated in the study. The baseline and post-vitamin D/calcium supplementation and the difference (corrected) were: serum calcium, 9 ± 0.33 and 8.33 ± 1.09 mg/dL (-0.66 ± 1.11 mg/dL); 25-OHD, 8.75 ± 4.75 and 36.83 ± 18.68 ng/mL (28.00 ± 18.33 ng/mL); PTH, 57.9 ± 29.3 and 36.33 ± 22.48 pg/mL (-20.25 ± 22.45 pg/mL); fasting plasma glucose, 78.23 ± 7.60 and 73.47 ± 9.82 mg/dL (-4.88 ± 10.65 mg/dL); and homeostasis model assessment-2-percent ß-cell function C-peptide secretion (HOMA-2-%B C-PEP), 183.17 ± 88.74 and 194.67 ± 54.71 (11.38 ± 94.27). Significant differences were observed between baseline and post-vitamin D/calcium supplementation serum levels of corrected calcium (Z, -3.751; P<.0001), 25-OHD (Z, -4.9; P<.0001), intact PTH (Z, -4.04; P<.0001), fasting plasma glucose (Z, -2.7; P<.007), and HOMA-2-%B C-PEP (Z, -1.923; P<.05) as determined by Wilcoxon signed rank test. Insulin resistance as measured by HOMA was unchanged. CONCLUSION: Optimizing serum 25-OHD concentrations and supplementation with calcium improves fasting plasma glucose levels and ß-cell secretory reserve. Larger randomized control studies are needed to determine if correction of 25-OHD deficiency will improve insulin secretion and prevent abnormalities of glucose homeostasis.
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Calcio de la Dieta/administración & dosificación , Células Secretoras de Insulina/fisiología , Deficiencia de Vitamina D/tratamiento farmacológico , Vitamina D/administración & dosificación , Adulto , Glucemia/análisis , Suplementos Dietéticos , Femenino , Humanos , Masculino , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/fisiopatologíaRESUMEN
BACKGROUND: Little if any cutaneous production of vitamin D3 occurs at latitudes above and below 35° N and 35° S during the winter months. It was postulated that those residing in tropics synthesize enough vitamin D3 year round. Several studies have documented the effect of latitude, season and time of the day on the cutaneous production of vitamin D3 in an ampoule model. Studies from India have shown high prevalence of vitamin D deficiency despite abundant sunshine. METHODS: We studied the influence of season and time of the day on synthesis of previtamin D3 in an ampoule model in Tirupati, (latitude 13.40° N and longitude 77.2° E) south India, between May 2007 to August 2008. Sealed borosilicate glass ampoules containing 50 µg of 7-DHC in 1 ml of methanol were exposed to sunlight hourly from 8 a.m. until 4 p.m. The percent conversion of 7-DHC to previtamin D3 and its photoproducts and the percent of previtamin D3 and vitamin D3 formed was estimated and related to solar zenith angle. RESULTS: The percent conversion of 7-DHC to previtamin D3 and its photoproducts and formation of previtamin D3 and vitamin D3 was maximal between 11 a.m. to 2 p.m. of the day during the entire year (median 11.5% and 10.2% respectively at 12.30 p.m.). CONCLUSIONS: Therefore at this latitude exposure to sunlight between the hours of 11 a.m. and 2 p.m. will promote vitamin D production in the skin year round.
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INTRODUCTION: Polycystic ovarian syndrome (PCOS) is common among women of reproductive age. Although traditional cardiac risk factors are known to be altered and improved with short-term metformin therapy, not much is known about novel cardiac risk factors. OBJECTIVE: The aim of this study was to evaluate the effects of lifestyle modification and short-term metformin therapy on the fasting serum lipids, homeostasis model assessment of insulin resistance (HOMA-IR), serum high-sensitivity C-reactive protein (hsCRP), and serum homocysteine. METHODS: Native overweight [body mass index (BMI) >23 kg/m(2)] Indian women diagnosed with PCOS were evaluated and subjected to an oral glucose tolerance test and determination of insulin, homocysteine, hsCRP, and fasting lipids levels. They were started on maximally tolerated doses of metformin along with lifestyle modification. Following 3 months of therapy, they were resampled. RESULTS: Out of 36 consecutive patients included, 25 women completed 3 months of metformin treatment and were eligible for repeat evaluation. The age of study group was 22.2 ± 5 years. Twenty-two (61%) women were obese (BMI >25 kg/m(2)). Improvement was seen in body weight, BMI, serum total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C), hsCRP, and serum testosterone on metformin therapy. However, no improvement was seen in serum fasting insulin, HOMA-IR, or homocysteine. CONCLUSION: Serum hsCRP improved with lifestyle modification and metformin therapy for 3 months in overweight subjects from India with PCOS, along with serum total cholesterol, triglycerides, and HDL-C. However, markers of insulin resistance and serum homocysteine did not improve.
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Enfermedades Cardiovasculares/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Estilo de Vida , Metformina/uso terapéutico , Sobrepeso/tratamiento farmacológico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Adolescente , Adulto , Proteína C-Reactiva/metabolismo , Femenino , Homeostasis , Homocisteína/sangre , Humanos , Insulina/sangre , Resistencia a la Insulina , Lípidos/sangre , Lípidos/química , Dosis Máxima Tolerada , Radioinmunoensayo/métodos , Factores de RiesgoRESUMEN
INTRODUCTION AND AIM OF THE STUDY: To document abnormalities on spirometry in patients with type1 diabetes mellitus (DM) and to study the determinants of these. MATERIAL AND METHODS: Thirty nine patients attending the type 1 DM clinic underwent spirometry. The absolute FEV1 and FVC were compared with the predicted ones and expressed as a percentage of the predicted. Additional information collected included gender, age, weight, height and the latest glycated hemoglobin. Data were presented as mean±SD.χ2 test was used to study differences in proportions and Pearson's coefficient was calculated for correlations. RESULTS: Twenty patients (51.2%) had pulmonary function abnormalities, of which 17 patients had a restrictive pattern on spirometry and 3 had an obstructive pattern. Of all the patients, 45.8% were stunted, i.e. had the height SDS <-2 SD while 25.7% were extremely stunted (height SDS < -3). Sevenof 9 (77.8%) patients with extreme stunting (Ht SDS <-3) had restrictive ventilatory disturbances, whereas only 8 of 26 (30.7%) persons with Ht SDS above -3 had the same (p <0.05). CONCLUSIONS: Spirometric abnormalities are common in type 1 DM and stunting is a significant determinant of the same.
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Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/fisiopatología , Espirometría/estadística & datos numéricos , Adolescente , Adulto , Edad de Inicio , Niño , Femenino , Humanos , Enfermedades Pulmonares/complicaciones , Enfermedades Pulmonares/diagnóstico , Masculino , Prevalencia , Adulto JovenRESUMEN
BACKGROUND: The effects of antiepileptic drugs (AED) on bone health are well documented. Inadequate dietary intake of calcium and vitamin D plays a vital role and further compromises the bone health. OBJECTIVE: To assess the dietary pattern with special reference to calcium and related minerals in people with epilepsy (PWE) on AED. MATERIALS AND METHODS: The dietary assessment in PWE was documented by dietary recall method. Patients were categorized according to age: group I: <14 years; group II: between 15-20 years; group III: between 21-45 years; group IV: >46 years. From the raw weights, total energy, dietary calcium, dietary phosphorous intake and phytate calcium ratio was calculated using a food composition table by Indian Council of Medical Research (ICMR) and analyzed statistically. RESULTS: A total of 362 patients with mean age of 29 + 15 years were studied. There were 190 women. The mean duration of AED treatment was 4 + 3 yrs, 64% on monotherapy 64% and 36% on polytherapy. The mean dietary intake of the total chohort was 2,007 + 211 Kcal/day, carbohydrate 335 + 33 gm/day; protein 31 + 7 gm/day; fat 18+2 gm/day; calcium 294 + 40 mg/day; phosphorus 557 + 102; phytates 179 + 30 mg/day; and phytate/calcium ratio 0.56+0.2. Milk and milk products were consumed by 42% of the total cohort. The daily dietary calcium (301 + 40 mg/day) intake of men was significantly higher than women (287 + 39 mg/day) (P < 0.001). This was more evident in group II (P < 0.01) and group III (P < 0.03). There was a positive correlation between dietary calcium and dietary phytates (P < 0.001), dietary proteins (P < 0.001), dietary fat (P < 0.001), and total energy (P < 0.001). CONCLUSIONS: The dietary consumption of calcium of all the patients was far below the recommended daily dietary allowance (RDA) by Indian Council of Medical Research (ICMR). Low dietary calcium could have a confounding effect on PWE on AED in all age groups. There is a need to formulate consensus guidelines to supplement dietary calcium to PWE.
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Anticonvulsivantes/efectos adversos , Calcio de la Dieta/administración & dosificación , Deficiencia de Vitamina D/epidemiología , Adolescente , Adulto , Estudios de Cohortes , Ingestión de Energía/fisiología , Epilepsia/tratamiento farmacológico , Epilepsia/epidemiología , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Deficiencia de Vitamina D/inducido químicamente , Adulto JovenRESUMEN
OBJECTIVE: To determine if there was a genetic contribution to our patient's unusual clinical presentation of nephrolithiasis and nonhealing stress fracture. METHODS: We describe a 31-year-old man who had rickets as a child and developed a femur insufficiency fracture and recurrent nephrolithiasis as an adult after moving to the United States from India. The patient's clinical course and results from radiographic and biochemical analyses are described. Analysis of the SLC34A3 gene was performed using genomic DNA samples from the patient and his family members. RESULTS: Before referral to the Yale Bone Center, the patient was treated with calcitriol, ergocalciferol, and phosphate. Changing therapy to phosphate alone led to clinical improvement. Genetic analysis revealed that the patient is a compound heterozygote for mutations in the SLC34A3 gene. On 1 allele, he has a previously described missense mutation in exon 7: c.575C>T (p.Ser192Leu). The other allele carries a novel nonsense mutation in exon 3: c.145C>T (p.Gln49X). One unaffected sibling is a carrier of the missense mutation and 1 sister with a history of flank pain is a carrier of the novel mutation. CONCLUSIONS: Hereditary hypophosphatemic rickets with hypercalciuria is a rare metabolic disorder associated with mutations in SLC34A3, the gene that encodes the renal sodium phosphate cotransporter NaPi-IIc. Although hypercalciuria is a distinguishing feature of the disease, nephrolithiasis is rarely described. The patient's atypical clinical presentation illustrates that both environmental and genetic factors potentially affect phenotypic expression of SLC34A3 mutations.
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Fracturas del Cuello Femoral/genética , Fracturas del Cuello Femoral/patología , Hipofosfatemia/genética , Hipofosfatemia/patología , Cálculos Renales/genética , Cálculos Renales/patología , Proteínas Cotransportadoras de Sodio-Fosfato de Tipo IIc/genética , Adulto , Fracturas del Cuello Femoral/tratamiento farmacológico , Fracturas del Cuello Femoral/metabolismo , Humanos , Hipofosfatemia/tratamiento farmacológico , Hipofosfatemia/metabolismo , Cálculos Renales/tratamiento farmacológico , Cálculos Renales/metabolismo , Masculino , MutaciónRESUMEN
BACKGROUND: Data on the vitamin D status of the population in a tropical country such as India have seldom been documented. Vitamin D deficiency is presumed to be rare. OBJECTIVE: The objective was to document the dietary habits and concentrations of serum calcium, 25-hydroxyvitamin D [25(OH)D], and parathyroid hormone of Indian urban and rural populations. DESIGN: Healthy urban (n = 943) and rural (n = 205) subjects were studied for their dietary pattern and concentrations of serum calcium, phosphorus, alkaline phosphatase, 25(OH)D, and immunoreactive parathyroid hormone. RESULTS: The daily dietary calcium intake of both the urban and rural populations was low compared with the recommended dietary allowances issued by the Indian Council of Medical Research. Dietary calcium and phosphorous were significantly lower in rural adults than in urban adults (P < 0.0001). The dietary phytate-to-calcium ratio was higher in rural subjects than in urban subjects (P < 0.0001). The 25(OH)D concentrations of the rural subjects were higher than those of urban subjects (P < 0.001), both men and women. In the rural subjects, 25(OH)D-deficient (<20 ng/mL), -insufficient (20-30 ng/mL), and -sufficient (>30 ng/mL) states were observed in 44%, 39.5%, and 16.5% of the men and 70%, 29%, and 1% of the women, respectively. In the urban subjects, 25(OH)D-deficient, -insufficient, and -sufficient states were observed in 62%, 26%, and 12% of the men and 75%, 19%, and 6% of the women, respectively. CONCLUSIONS: Low dietary calcium intake and 25(OH)D concentrations were associated with deleterious effects on bone mineral homeostasis. Prospective longitudinal studies are required to assess the effect on bone mineral density, a surrogate marker for fracture risk and fracture rates.