Insufficient vitamin D status and increased renin-angiotensin system (RAS) activity have been associated with renal-vascular disease and nephropathy in diabetes. Accumulating evidence indicates that vitamin D receptor (VDR) activation lowers unfavorable RAS activity; however, more human intervention studies evaluating whether this mechanism could influence diabetic kidney disease are needed. We previously reported that both vitamin D levels and genetic variation at the VDR predict human RAS activity, and that vitamin D therapy can lower RAS activity in non-diabetics. The VALIDATE-D study is a randomized, placebo-controlled, intervention study designed to extend these findings by evaluating whether direct VDR activation in diabetes lowers circulating and local renal-vascular tissue RAS activity (Aims 1 and 2) in a manner similar to the action of ACE inhibitors (Aim 3).
Forty subjects with type 2 diabetes, microalbuminuria, and without chronic kidney disease will be recruited to undergo detailed assessment of the RAS before and after randomization to calcitriol 0.75 mcg/day or placebo. Primary analyses will evaluate whether calcitriol therapy reduces circulating and renal-vascular tissue-RAS activity in comparison to placebo. All subjects will thereafter be treated with lisinopril and followed for 3.5 months to evaluate whether combination therapy (calcitriol + lisinopril vs. placebo + lisinopril) additively or synergistically improves renal-vascular function, and lowers proteinuria.
The VALIDATE-D study is the first human intervention study to evaluate whether direct VDR activation can lower the human RAS in diabetes, compared to the effect of an ACE inhibitor, and whether this mechanism can translate to clinically relevant endpoints for diabetic kidney disease. The outcomes of VALIDATE-D will have major implications for the recommendation of vitamin D supplementation for the primary prevention of kidney complications in diabetes.
Vitamin D; Calcitriol; Renin; Angiotensin; Diabetes; Kidney
The interaction of advanced glycation end products (AGEs) and its receptor (RAGE) has played an important role in the pathogenesis of diabetes and its complications. A soluble form of RAGE (sRAGE) has been reported as a decoy receptor for AGEs. Oxidative stress is demonstrated in pathological condition such as atherosclerosis and diabetes mellitus. It has been suggested to be involved in the pathogenesis of both macro- and microvascular complications. This study was designed to evaluate the effect of glycemic control on sRAGE and oxidative stress markers in type 2 diabetic patients.
Seventy patients with type 2 diabetes and 20 healthy subjects were recruited into the study. Blood glutathione (GSH) and plasma total nitric oxide (NOx) levels were measured using commercially available colorimetric kits, blood superoxide dismutase (SOD) activity was measured by the method of Marklund and Marklund, and plasma C-peptide, oxidized LDL (ox-LDL), sRAGE, and VCAM-1 levels were measured using competitive ELISA kits.
Plasma sRAGE levels were significantly lower (p < 0.05) while VCAM-1 levels were significantly higher (p < 0.05) in poorly controlled diabetic patients compared with healthy control. Blood GSH levels were significantly lower in diabetic patients compared with healthy control (p < 0.05). Plasma C-peptide, NOx, ox-LDL levels, and SOD activity were not significantly different in diabetic patients compared with healthy control. Plasma levels of sRAGE were negatively associated with circulating VCAM-1 levels in diabetic patients.
Poor glycemic control decreases plasma sRAGE and increases VCAM-1 levels while good glycemic control improves these abnormalities which provides benefit to diabetic patients.
sRAGE; Oxidative stress; HbA1c; Type 2 DM
Sub-clinical hypothyroid dysfunction, a relatively understudied disorder in the Kingdom of Saudi Arabia (KSA), has significant clinical implications if not properly monitored. Also from KSA, more than 50% of the population suffer from hypovitaminosis D (<50 nmol/l). In this cross-sectional case-control study, we described the differences and associations in the metabolic patterns of adult Saudis with and without hypothyroid dysfunction in relation to their vitamin D status, PTH, calcium and lipid profile.
A total of 94 consenting adult Saudis [52 controls (without subclinical hypothyroidism), 42 cases (previously diagnosed subjects)] were included in this cross-sectional study. Anthropometrics were obtained and fasting blood samples were taken for ascertaining lipid and thyroid profile, as well as measuring PTH, 25(OH) vitamin D and calcium.
Cases had a significantly higher body mass index than the controls (p < 0.001). Circulating triglycerides was also significantly higher in cases than the controls (p = 0.001). A significant positive association between HDL-cholesterol and PTH (R = 0.56; p = 0.001), as well as a negative and modestly significant negative association between LDL-cholesterol and PTH (R = - 20.0; p = 0.04) were observed. FT3 was inversely associated with circulating 25 (OH) vitamin D (R = -0.25; p = 0.01).
Patients with hypothyroid dysfunction possess several cardiometabolic risk factors that include obesity and dyslipidemia. The association between PTH and cholesterol levels as well as the inverse association between vitamin D status and FT3 needs to be reassessed prospectively on a larger scale to confirm these findings.
Thyroid dysfunction; Obesity; Dyslipidemia; Saudi
To examine the association of anthropometry indices with gout and to compare the performance of indices to predict gout in Taiwanese men.
There were 1443 male subjects aged more than 20 years who participated in the Nutrition and Health Survey in Taiwan (NAHSIT, 1993–1996). Anthropometric evaluation consisted of weight, height, hip and waist circumference (WC) with later body mass index (BMI), waist to height (WHtR) and waist to hip (WHR) estimations. We conducted 4 logistic models to determine the relationships between anthropometric indices and gout. Receiver operating characteristic (ROC) curve were used to compare the predictive performance and to identify the optimal cut-off points, sensitivity and specificity of these indices for gout in men.
After controlling for other covariables, the adjusted odds ratios for the mid and top tertiles of WHtR were 2.55 (95% CI: 1.16, 5.59) and 3.01 (95% CI: 1.13, 7.99), respectively, but no linear association was found for BMI, WHR and WC. In ROC curve, the greatest area under curve was 0.684 for WHtR and the cut-off point of WHtR was 0.57.
WHtR had a significant linear association with gout in Taiwanese men and was superior to BMI, WHR and WC.
Gout; Anthropometry; Waist to height ratio
Sorafenib can be considered as the effective option of treatment in patients with metastatic radioiodine refractory differentiated thyroid cancers. The cutaneous manifestations of Sorafenib include rash, desquamation, hand foot skin reactions, pruritus, alopecia and erythema. We report the first case of hypopigmentation related to sorafenib therapy.
We report the case of a middle aged gentleman with metastatic papillary carcinoma of thyroid diagnosed in 2005. He was managed with total thyroidectomy, radioactive iodine and TSH suppressive therapy. Despite receiving radioactive iodine 530 mci cumulative dose, patient had persistant disease with lung metastasis. Therefore a TKI, sorafenib, was started. He developed hypopigmentation of the skin more prominent on face six weeks after starting sorafenib treatment.He also developed diarrhea, desquamation of hands and feet, hair loss over scalp, eye brows and moustache. Sorafenib treatment was discontinued. His diarrhea stopped in one week and after four weeks his skin became normalized whereas he regained his hairs in six weeks.
To our knowledge, hypopigmentation in our patient appears to be the first reported of its kind in the literature to date. Sorafenib is used in Renal cell carcinoma, Hepatcellular carcinoma and radioactive iodine refractory thyroid carcinoma therefore it is very important to be aware of hypopigmentation as a potential side effect for both physicians and patients.
Thyroid Carcinoma; Sorafenib; Hypopigmentation
Being an intermediate stage in the development of diabetes, pre-diabetics were estimated as high as 14% to 63% in China and one to three quarters of them will develop into diabetes within 10 years. It is well established that the risk of diabetes progression can be modified substantially and a whole range of proven guidelines, protocols and methodologies are available. Unfortunately, most proven interventions are seldom used in daily practice and this is especially true in resource poor rural China. This project aims at demonstrating that an evolutionary intervention package featuring low cost, integration with routine services, cultural sensitization and self-optimization, is effective and sustainable in preventing diabetes.
This project utilizes a quasi cluster randomized controlled trial and a batched implementation strategy in which villages are recruited in 7 blocks within 7 consecutive years respectively. Block 0 involves 3 villages and provides an opportunity for piloting and refining primitive intervention methodologies and protocols. The following 6 blocks consist of 14 villages each and serve as intervention arm; while all the villages not yet started intervention form the control arm. For each block, measurement happens at baseline and every 12 months (for plasma glucose) or monthly (for body weight and blood pressure) after baseline. These arrangements enable documentation of up to 6 years of consecutive measures and detection of lower incidence of progression into diabetes, improved body max index and blood pressure, and increased service use and involvement in healthy dietary and physical activities among pre-diabetics receiving the experimental intervention compared to themselves at baseline or those in the delayed-intervention control condition.
China has a long history of separating disease prevention and treatment systems and there is a clear need to leverages key success factors in a synergetic way toward integrated and sustainable diabetes prevention. This project is owned and managed by local health authorities and utilizes available resources. It introduces a package of long-term incentives, establishes ongoing mechanisms for continuous capacity building and quality improvement, and builds up an operational cycle for catalyzing similar efforts in the local prefecture even throughout rural China.
Current Controlled Trials: ISRCTN66772711.
Hypothyroidism, commonly induced in preparation for radioiodine treatment of differentiated thyroid cancer, is a text-book cause for hyponatremia. Nausea, stress, and increased fluid intake associated with the treatment are expected to exacerbate hyponatremia.
We prospectively studied 212 (80% females) consecutive thyroid cancer patients for the incidence of hypothyroidism-induced hyponatremia and associated risk factors.
Mean(SD) age was 39.7(14.1) year, creatinine 82.0(20.8) μmol/l, TSH 141.6(92.0) mU/l, pre- and post-isolation sodium 139.5(2.3) and 137.8(3.0) mEq/l, respectively, and estimated fluid intake during isolation 9.7(6.2) L. Mild hyponatremia (≥130 mEq/l) was present in 18 patients (8.5%) and moderate hyponatremia (≥120 mEq/l) in 4(1.9%), 3 of the latter had elevated creatinine concentration and 2 were on diuretics. There was no significant correlation between post-isolation sodium concentration and TSH concentration (r = 0.03, p = 0.69) or estimated fluid intake (r = 0.10, p =0.17). There was significant correlation between post-isolation sodium concentration and age (r = −0.24, p < 0.0001) and creatinine concentration (r = −0.22, p = 0.001). Pre-post-isolation drop in sodium concentration was more in females (mean difference 1.21, p = 0.02). Compared to eunatremic patients, hyponatremic patients were more likely to have pre-isolation hyponatremia (9% vs. 0.5%, p = 0.03), elevated creatinine concentration (36% vs. 13%, p = 0.008), and to be on diuretics (23% vs. 1%, p = 0.0001).
In the setting of acute severe hypothyroidism: 1) clinically-important hyponatremia is uncommon; sodium concentration may not need to be monitored unless patients have impaired renal function or are on diuretics, 2) age and female gender are associated with lower sodium concentration. Uncomplicated acute severe hypothyroidism didn’t cause clinically-important hyponatremia/SIADH in this cohort of patients.
Hyponatremia; Hypothyroidism; Differentiated thyroid cancer; Radioiodine therapy
The abnormality of interleukin-21 (IL-21)-IL-21-receptor (IL-21R) system has been found in many autoimmune diseases including autoimmune thyroid diseases (AITDs). In this study, we investigated whether polymorphisms of the IL-21 and IL-21R are associated with Graves’ disease (GD) and Hashimoto’s thyroiditis (HT), two major forms of AITDs, among a Chinese population.
Rs907715, rs4833837, rs2221903 and rs2055979 of the IL-21 gene and rs3093301 and rs2285452 of the IL-21R gene were explored in a case–control study including 405 GD, 228 HT patients and 242 controls. These genes were genotyped by the PCR and restriction fragment length polymorphism (RFLP) analysis and the MASS spectrometry method.
For IL-21 gene, we identified and confirmed a higher prevalence of A alleles of rs2221903 (P = 0.018, OR = 1.50 95% CI = 1.07-2.09) in GD patients. We also found a significant association between rs2221903 and HT (allele: P = 0.009, OR = 1.69 95% CI = 1.13-2.51; genotype: recessive P = 0.021, OR = 11.72 95% CI = 1.46-94.13). For the IL-21R gene, compared with controls, the genotype frequencies of rs3093301 and rs2285452 were significantly different in HT patients using dominant genetic model (P = 0.023, OR = 1.61 95% CI = 1.07-2.42; P = 0.031, OR = 1.71 95% CI = 1.05-2.80, respectively). Furthermore, the haplotype AA containing the major alleles of rs4833837 and rs2221903 was associated with increased susceptibility to GD with an OR of 1.50(95% CI =1.08-2.09, P = 0.016), and to HT with an OR of 1.69(95% CI =1.14-2.52, P = 0.009).
Our results indicated that the SNPs of the IL-21 gene is associated with the development of GD. In addition, we found that individuals with the SNPs of the common IL-21 and IL-21R may have higher risk of HT.
Interleukin-21 (IL-21); Interleukin-21 receptor (IL-21R); Graves’ disease; Hashimoto’s thyroiditis; Single nucleotide polymorphism (SNP)
Diabetes distress is a general term that refers to the emotional burdens, anxieties, frustrations, stressors and worries that stem from managing a severe, complex condition like Type 1 diabetes. To date there has been limited research on diabetes-related distress in younger people with Type 1 diabetes. This qualitative study aimed to identify causes of diabetes distress in a sample of young adults with Type 1 diabetes.
Semi-structured interviews with 35 individuals with Type 1 diabetes (23–30 years of age).
This study found diabetes related-distress to be common in a sample of young adults with Type 1 diabetes in the second phase of young adulthood (23–30 years of age). Diabetes distress was triggered by multiple factors, the most common of which were: self-consciousness/stigma, day-to-day diabetes management difficulties, having to fight the healthcare system, concerns about the future and apprehension about pregnancy. A number of factors appeared to moderate distress in this group, including having opportunities to talk to healthcare professionals, attending diabetes education programmes and joining peer support groups. Young adults felt that having opportunities to talk to healthcare professionals about diabetes distress should be a component of standard diabetes care.
Some aspects of living with diabetes frequently distress young adults with Type 1 diabetes who are in their twenties. Clinicians should facilitate young adults’ attendance at diabetes education programmes, provide them with opportunities to talk about their diabetes-related frustrations and difficulties and, where possible, assist in the development of peer-support networks for young adults with diabetes.
Young adult; Distress; Qualitative; Type 1 diabetes; Emerging adulthood
In randomized controlled trials (RCTs), colesevelam HCI, added to other anti-diabetic therapy, reduced hemoglobin A1C by approximately 0.3% to 0.4% over 16- to 26-weeks compared with an increase of approximately 0.1% to 0.2% for placebo, for a placebo-adjusted treatment effect of approximately 0.5%. Evidence on real-world effectiveness is unknown. This retrospective cohort study examined A1C changes following colesevelam HCL initiation in patients with diabetes, regardless of concomitant anti-diabetic medication use.
2000–2011 GE Centricity electronic medical records data were used to identify patients with type 2 diabetes mellitus (T2DM) aged 18 or older initiating colesevelam HCL. The sample was further restricted to uncontrolled patients with database activity ≥ 395 days before and after colesevelam HCL initiation, A1C > 7% during 90 days prior to starting colesevelam HCL, without prior use of bile acid sequestrants, and with at least one A1C result between 42 to 210 days after initiation. Three overlapping time intervals were created for A1C measurement, including 16-weeks, 26-weeks, and 52-weeks following therapy initiation. The last observed A1C lab measurement during each interval was used to define change from baseline. Mean change in A1C was examined using paired t-tests. Sensitivity analyses considered only patients who remained on colesevelam HCL through each respective measurement period, as well as the effect of concomitant diabetes medications.
Of 1,709,393 patients in the GE database with T2DM, 1,747 met inclusion criteria. The cohort was 58% female, 38% age ≥ 65, and the majority was white. For the 16-week endpoint (N = 1,385), A1C dropped from a mean of 8.22% to 7.75% (mean change −0.47%; P < 0.0001). For the 26- and 52-week endpoints (N = 1,747), A1C dropped from a mean of 8.25% to 7.81% (mean change −0.44%; P < 0.0001) and 8.25% to 7.79% (mean change −0.46%; P < 0.0001), respectively. Sensitivity analyses showed that A1C reductions were of similar direction and magnitude for patients who remained on treatment, and for the subgroups of patients stratified by receipt of concomitant T2DM treatments.
The 0.44% to 0.47% A1C reduction observed in this study was similar to the reduction observed in RCTs, supporting the real-world effectiveness of colesevelam HCL in reducing A1C.
Infection is the most common precipitating factor and cause of death in patients with hyperglycemic crises. Treating infection-precipitated hyperglycemic crises includes using empiric antibiotics early; correcting dehydration, hyperglycemia, and electrolyte imbalances; and frequent monitoring. Intensive care unit admission, broad-spectrum antibiotics, and even novel therapy for infection may be beneficial for patients with a high risk of mortality. However, these management options are costly and not beneficial for every patient. Selecting high-risk patients who would most likely benefit is more appropriate. We investigated the independent mortality predictors of patients with infection-precipitated hyperglycemic crises to facilitate clinical decision making.
This study was conducted in a university-affiliated medical center. Consecutive adult patients (> 18 years old) visiting the Emergency Department between January 2004 and December 2010 were enrolled when they met the criteria of an infection-precipitated hyperglycemic crisis. Thirty-day mortality was the primary endpoint.
One hundred forty-two patients were enrolled. The infection source did not predict mortality. The presenting variables that were independently associated with 30-day mortality in a multiple logistic regression model were cancer history (odds ratio [OR], 7.4; 95% confidence interval [CI], 2.4-23.2), bandemia (OR, 7.0; 95% CI, 1.6-30.3), and serum creatinine (OR, 1.4; 95% CI, 1.1-1.8). The common sources of infection were the lower respiratory tract (30.3%), urinary tract (49.3%), skin or soft tissue (12.0%), and intra-abdominal (6.3%).
Cancer history, bandemia, and serum creatinine level are three independent mortality predictors for patients with infection-precipitated hyperglycemic crises. These predictors are both readily available and valuable for physicians making decisions about risk stratification, treatment, and disposition.
Hyperglycemic crises; Hyperosmolality; Infection; Mortality; Predictor
Down syndrome (DS) has been described as one of the main contributors for low bone mineral density (BMD). Physical activity (PA) is a key factor in skeletal health and thus, PA levels might be associated to the risk of developing osteoporosis. Therefore, the aims were (1) to describe PA patterns in adolescents with DS compared to their counterparts and (2) to determine the relationships between PA and the risk of having low bone mass in adolescents with DS.
Nineteen adolescents (10 girls) with DS and 14 without disabilities (7 girls) participated in the study. Minutes in different PA intensities were objectively assessed with accelerometers (ActiTrainer). Moreover adolescents with DS were classified into PA tertiles taking into account the amount of total minutes of PA at any intensity, resulting in those performing low, medium or high of PA (lowPA, medPA and highPA). BMD was measured at the whole body, hip and lumbar spine with dual-energy X-ray absorptiometry and the BMD Z-score was calculated for each region taking into account age- and sex-matched reference data. Student’s unpaired t-tests and analysis of covariance were used to compare variables between different conditions (DS vs. control) and PA levels (low, medium and high).
None of the adolescents with DS achieved the minimum of 60 min of daily moderate to vigorous PA (VPA) intensity recommended by PA guidelines; adolescents with DS group spent less time in sedentary and in VPA and more time in light PA than those without DS (p < 0.05). Adolescents with DS showed lower BMD Z-score values than those without (p < 0.05). Those adolescents with DS allocated in the lowPA tertile showed significant lower BMD Z-score at the hip and a general tendency towards lower BMD Z-score was found at whole body and lumbar spine compared to those in highPA tertile and (p < 0.05).
Adolescents with DS in the highPA tertile showed lower risk of developing future osteoporosis by having higher BMD Z-score at the hip. This data provides an idea regarding the importance of accumulated minutes of PA, and not only moderate or vigorous in the bone health in adolescents with DS.
Osteoporosis; Osteopenia; Accelerometer; Dual energy x-ray; Actitrainer; Body composition
Chronic insulin resistance, exacerbated in the course of pregnancy, is an important pathophysiologic mechanism of gestational diabetes mellitus (GDM). We hypothesise that the degree of insulin resistance, assessed at diagnosis of GDM, is a parameter of its pathophysiologic heterogeneity and/or severity. Thus, it offers potential to open new avenues for the personalization of therapy in affected women.
1254 Polish Caucasian women with GDM were recruited into the study. The following parameters were assessed in the course of the study: body mass index (BMI), parity, weight gain during pregnancy, glycated haemoglobin, glucose level during an oral glucose tolerance test (OGTT), insulin, insulin resistance and insulin secretion. The severity of GDM was assessed based on insulin use and daily insulin dose during gestation. In order to evaluate insulin secretion and insulin resistance the homeostatic method was used (HOMA-B and HOMA-IR, respectively). We compared all the metabolic parameters and methods of treatment of GDM in women subdivided by quartiles of insulin resistance.
The HOMA-IR in the whole population ranged from 0.34 to 20.39. The BMI, fasting insulin, fasting glucose and insulin dose per day increased along with increasing quartiles (HOMA-IR > 1.29). We observed a decrease of HOMA-B in the third quartile (1.92-2.89) compared with the first quartile (0.34-1.29). Insulin treatment was associated with HOMA-IR (<1.29 vs. >2.89), OR: 3.37, fasting glucose (≤6.11 vs. >6.11 mmol/dl), OR: 2.61, age (≤30 vs. >30 y. o.), OR: 1.54, and BMI (<25 vs. ≥25 kg/m2), OR: 1.45. Maximum insulin dose was associated with HOMA-IR, OR: 2.00, after adjustment for family history of diabetes, and 2-h OGTT glucose.
Insulin resistance assessed by the HOMA index at diagnosis is associated with the severity and pathophysiological heterogeneity of GDM. A HOMA-IR >1.29 points to the major role of insulin resistance, indicating the need for a treatment aimed at improving tissue sensitivity to insulin. A HOMA-IR 1.29-2.89 suggests reduced insulin secretion, which is an indication for the introduction of insulin therapy. A HOMA-IR >2.89 indicates insufficient compensation for insulin resistance, which suggests the need for a treatment aimed at improving susceptibility of tissues to insulin combined with insulin therapy.
Gestational Diabetes; Pathophysiology; Gestational Diabetes; Treatment; Gestational Diabetes; Insulin Resistance; Gestational Diabetes; HOMA
Type 2 diabetes is a common and costly illness, associated with significant morbidity and mortality. Despite this, there is relatively little information on the ‘real-world’ medication utilization patterns for patients with type 2 diabetes initiating exenatide BID or glargine. The objective of this study was to evaluate the ‘real-world’ medication utilization patterns in patients with type 2 diabetes treated with exenatide BID (exenatide) versus insulin glargine (glargine).
Adult patients( ≥18 years of age) with type 2 diabetes who were new initiators of exenatide or glargine from October 1, 2006 through March 31, 2008 with continuous enrollment for the 12 months pre- and 18 months post-index period were selected from the MarketScan® Commercial and Medicare Databases. To control for selection bias, propensity score matching was used to complete a 1:1 match of glargine to exenatide patients. Key study outcomes (including the likelihood of overall treatment modification, discontinuation, switching, or intensification) were analyzed using survival analysis.
A total of 9,197 exenatide- and 4,499 glargine-treated patients were selected. Propensity score matching resulted in 3,774 matched pairs with a mean age of 57 years and a mean Deyo Charlson Comorbidity Index score of 1.6; 54% of patients were males. The 18-month treatment intensification rates were 15.9% and 26.0% (p < 0.0001) and the discontinuation rates were 38.3% and 40.0% (p = 0.14) for exenatide and glargine, respectively. Alternatively, 14.9% of exenatide-treated patients switched therapies, compared to 10.0% of glargine-treated patients (p < 0.0001). Overall, glargine-treated patients were more likely to modify their treatment [hazard ratio (HR) = 1.33, p < 0.0001] with shorter mean time on treatment until modification (123 vs. 159 days, p < 0.0001). Compared to exenatide-treated patients, glargine-treated patients were more likely to discontinue [hazard ratio (HR) = 1.25, p < 0.0001] or intensify therapy (HR = 1.72, p < 0.0001) but less likely to switch (HR = 0.71, p < 0.0001) the index therapy.
Patients treated for type 2 diabetes with exenatide BID or insulin glargine differ in their adherence to therapy. Exenatide-treated patients were less likely to discontinue or modify treatment but more likely to switch therapy compared to glargine-treated patients.
Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia in hospitalized patients and is often described in patients with small-cell carcinoma of the lung. In this report, we described both Castleman’s disease and lymphoma coexisting in one patient with SIADH.
A 70-year-old Chinese woman with a history of diabetes mellitus and insulin therapy had severe hyponatremia and gastrointestinal symptoms. Through a series of examinations, common causes such as pulmonary carcinoma were excluded. An abdominal mass was detected by computed tomography. Although the peripheral lymph node biopsy showed the pathological result as Castleman’s disease, the pathology of the abdominal lymph node revealed diffuse large B-cell lymphoma. After chemotherapy, the hyponatremia was treated during a period of follow-up.
This patient presented with the rare clinical condition of inappropriate antidiuretic hormone secretion alongside Castleman’s disease and lymphoma. Asymptomatic hyponatremia may persist for some time suggesting that clinical physicians should pay attention to the mild cases of hyponatremia. We also hypothesized that Castleman’s disease is a condition of pre-lymphoma with both having the ability to cause SIADH. The possibility of lymphoma as well as Castleman’s disease triggering the development of SIADH should also be taken into consideration for conducting recurrent biopsies.
Castleman’s disease; Hyponatremia; Lymphoma; Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
The aim was to study the glycaemic control of type 2 diabetic patients, and to identify factors associated with unacceptable glycaemic control (defined as HbA1c >8.0%).
Analysis of data collected in a cross-sectional survey of type 2 diabetic patients in eight SingHealth Polyclinics in January 2009. HbA1c value was measured on the day of the survey, while information on patient and diabetic characteristics was obtained through a questionnaire. Odds ratio of having unacceptable glycaemic control was estimated for selected variables using multiple logistic regression models.
A total of 688 patients were included in the analysis. The mean (± standard deviation) and median (range) HbA1c levels were 7.6% (± 1.35) and 7.3% (5.0% to 14.0%), respectively. 25.4% of the patients had an unacceptable HbA1c level of >8.0% and the odds of this were higher (p < 0.05) in patients with the following characteristics: younger age, longer diabetes duration, presence of insulin treatment, and poorer compliance to medication.
Younger adult patients were found to have poorer glycaemic control, and hence targeted educational and behaviour modification programmes would be required to effectively manage this group of patients.
Diabetes mellitus type 2; Hemoglobin A glycosylated; Primary health care; Singapore
Autoimmune thyroid diseases including Graves’ disease and Hashimoto’s thyroiditis are caused by immune response to self-thyroid antigens. The rare situation of hyperthyroidism with Graves’ disease in twins has been reported in a very few case reports in literature.
We present monozygotic female twins developing consecutively Graves’ disease within five years. One year before the diagnosis of Graves’ disease was established in the first twin, the mother developed a toxic thyroid nodule with hyperthyroidism leading to hemi thyroidectomy. Both the mother and the twins were cigarette smokers. The twins were treated with carbamizole and this therapy led to normalization of thyroid stimulating hormone and thyroxine.
This case report supports the hypothesis that a genetic factor as well as an environmental factor (cigarette smoking) might be of great importance in the aetiology of Graves’ disease.
Marine-Lenhart syndrome is defined as the co-occurrence of Graves’ disease and functional nodules. The vast majority of autonomous adenomas are benign, whereas functional thyroid carcinomas are considered to be rare. Here, we describe a case of simultaneous occurrence of Marine-Lenhart syndrome and a papillary microcarcinoma embedded in a functional nodule.
A 55 year-old, caucasian man presented with overt hyperthyroidism (thyrotropin (TSH) <0.01 μIU/L; free thyroxine (FT4) 3.03 ng/dL), negative thyroid peroxidase and thyroglobulin autoantibodies, but elevated thyroid stimulating hormone receptor antibodies (TSH-RAb 2.6 IU/L). Ultrasound showed a highly vascularized hypoechoic nodule (1.1 × 0.9 × 2 cm) in the right lobe, which projected onto a hot area detected in the 99mtechnetium thyroid nuclear scan. Overall uptake was increased (4.29%), while the left lobe showed lower tracer uptake with no visible background-activity, supporting the notion that both Graves’ disease and a toxic adenoma were present. After normal thyroid function was reinstalled with methimazole, the patient underwent thyroidectomy. Histological work up revealed a unifocal papillary microcarcinoma (9 mm, pT1a, R0), positively tested for the BRAF V600E mutation, embedded into the hyperfunctional nodular goiter.
Neither the finding of an autonomously functioning thyroid nodule nor the presence of Graves’ disease rule out papillary thyroid carcinoma.
Toxic adenoma; Graves’ disease; Marine-Lenhart syndrome; Papillary carcinoma; Hyperthyroidism
This study compares annual ambulatory care expenditures per patient with type 2 diabetes mellitus (T2DM) in France according to treatment phase and renal function status.
Records from patients with T2DM were extracted from a health insurance database. Patients were classified in subgroups, by treatment phase: oral/GLP1 monotherapy, double therapy, triple therapy or insulin therapy, and according to renal function status (identified using pharmacy, lab and consultation claims). Annual ambulatory expenditures were estimated from the national insurance perspective by year (from 2005 to 2010) and subgroup.
The number of patients ranged from 9,682 to 11,772 between 2005 and 2010. The average annual expenditure per individual in 2010 ranged from €3,017 (standard deviation: €3,829) for monotherapy to €3,609 ± €3,801 for triple therapy, and €7,398 ± €5,487 with insulin (adjusted ratio insulin therapy/monotherapy: 2.36, p < 0.001). Similar differences between treatement stages were found in previous years. Additional costs for insulin were mainly related to nursing care (multiplied by 18.42, p < 0.001), medical devices and pharmacy costs. DM-attributable drug costs were mainly related to antidiabetic drugs (28% for monotherapy to 71% for triple therapy), but also to cardiovascular system drugs (21% for monotherapy to 51% with insulin) and nervous system drugs (up to 8% with insulin). Declining renal function was associated with an increase in expenses by 12% to 53% according to treatment stage.
Overall, ambulatory care expenditures increase with treatment escalation and declining renal function amongst patients with T2DM. Insulin therapy is associated with substantially increased costs, related to pharmacy, nursing care and medical device costs.
Cost analysis; Type 2 diabetes mellitus; Oral antidiabetics; Insulin; Renal function
HIV patients on HAART are prone to metabolic abnormalities, including insulin resistance, lipodystrophy and diabetes. This study purports to investigate the relationship of ethnicity and CD4+ T cell count attained after stable highly-active antiretroviral treatment (HAART) with glucose metabolism in hyperrtriglyceridemic HIV patients without a history of diabetes.
Demographic, anthropometric, clinical, endocrinologic, energy expenditure and metabolic measures were obtained in 199 multiethnic, healthy but hypertriglyceridemic HIV-infected patients [46% Hispanic, 17% African-American, 37% Non-Hispanic White (NHW)] on stable HAART without a history of diabetes. The relationship of glucose and insulin responses to ethnicity, CD4 strata (low (<300/cc) or moderate-to-high (≥ 300/cc)), and their interaction was determined.
African-Americans had significantly greater impairment of glucose tolerance (P < 0.05) and HbA1c levels (P < .001) than either Hispanics or NHWs. In multivariate models, after adjusting for confounders (age, sex, HIV/HAART duration, smoking, obesity, glucose, insulin and lipids), African-Americans and Hispanics had significantly higher HbA1c and 2-hour glucose levels than NHW’s. Demonstrating a significant interaction between ethnicity and CD4 count (P = 0.023), African Americans with CD4 <300/cc and Hispanics with CD4 ≥300/cc had the most impaired glucose response following oral glucose challenge.
Among hypertriglyceridemic HIV patients on HAART, African-Americans and Hispanics are at increased risk of developing diabetes. Ethnicity also interacts with CD4+ T cell count attained on stable HAART to affect post-challenge glycemic response.
African American; Hispanic; Impaired glucose tolerance; HbA1c; Dyslipidemia
To investigate potential associations of serum prolactin concentration (PRL) with metabolic syndrome (MetS) and type 2 diabetes mellitus (T2DM), previously observed in small and selected study samples, in a large population-based cohort.
Data from 3,993 individuals (2,027 women) aged 20-79 years from the population-based Study of Health of Pomerania (SHIP) were used to analyse cross-sectional and longitudinal associations of PRL with MetS and T2DM risk in age- and multivariable-adjusted Poisson regression models. PRL were log-transformed and modelled as continuous (per standard deviation (SD) increase) and categorical predictor (sex-specific quartiles) variable, separately for men and woman.
Cross-sectional analyses showed an inverse association between low PRL concentrations and prevalent T2DM risk in men and women after multivariable-adjustment (men: Q1 vs. Q4: relative risk (RR), 1.55; 95% confidence interval (CI), 1.13 – 2.14; women: Q1 vs. Q4: RR, 1.70; 95% CI, 1.10 – 2.62). Likewise, higher PRL concentrations were associated with significantly lower T2DM risk (RR per SD increase in log-PRL: 0.83; 95% CI, 0.72 – 0.95 in men, and 0.84; 95% CI, 0.71 – 0.98 in women, respectively). An inverse association between PRL and MetS risk was not retained after multivariable adjustment. Longitudinal analyses yielded no association of PRL with incident MetS or T2DM.
The present study is the first large population-based study reporting a cross-sectional inverse association between PRL and prevalent T2DM in both genders. But the absent longitudinal associations do not support a causal role of PRL as a risk factor of incident MetS or T2DM.
Osteocalcin (OC) is a bone-specific protein produced primarily by osteoblasts during bone formation. Besides its role in bone formation, osteocalcin may play a role in the regulation of energy metabolism and male fertility. To interpret serum OC data, reference intervals adapted to a specific laboratory method are needed.
A healthy reference population was selected from the first follow-up of the Study of Health in Pomerania. Serum OC concentrations were measured with the IDS-iSYS N-Mid Osteocalcin assay on the IDS-iSYS Automated System (Immunodiagnostic Systems, Frankfurt am Main, Germany). The reference interval was defined as the central 95% range (2.5th-97.5th percentile). Age-specific reference intervals were calculated by quantile regression for 1107 men (25–79 years) and 545 premenopausal women (25–54 years). The reference interval for 498 postmenopausal women (50–79 years) was calculated irrespective of age.
Median (1st-3rd quartile) serum OC concentrations were 15.4 ng/mL (12.0-19.4 ng/mL) in men, 14.4 ng/mL (11.3-18.5 ng/mL) in premenopausal women, and 18.6 ng/mL (13.6-25.6 ng/mL) in postmenopausal women. Serum OC concentrations were highest in men and premenopausal women aged 25–29 years, were stable during midlife, and rose again after 65 years of age in men and at transition to menopause in women. Serum OC concentrations were lower in women taking oral contraceptives or who were under hormone replacement therapy after menopause and in subjects with diabetes mellitus or with body mass index < 18 or > 30 kg/m2 than in subjects without these conditions.
We established sex-specific adult reference intervals for the serum OC concentration measured by the IDS-iSYS N-Mid Osteocalcin assay.
Reference interval; Serum osteocalcin concentration; Healthy adult men and women
The editors of BMC Endocrine Disorders would like to thank all our reviewers who have contributed to the journal in Volume 12 (2012).
Diabetic patients with positive glutamic acid decarboxylase antibody (GAD-Ab) could be classified as autoimmune diabetes, which is discriminated into acute-onset classical type 1 diabetes (T1DM) and latent autoimmune diabetes in adults (LADA). However, whether the decay rate of beta cell function is relevant with the mode of onset (acute or latent-onset) is unclear. We aimed to investigate whether initial C peptide levels could help differentiate variation of C peptide decay rate.
Five hundred and twenty-seven newly diagnosed GAD-Ab positive diabetic patients were followed up to assess the natural course of beta cell function. Beta cell function failure was defined as fasting C peptide and postprandial C peptide levels less than 100 pmol/L and 150 pmol/L respectively.
All these diabetic patients were discriminated according to initial fasting C peptide of 300 pmol/L, that is B+ (larger than 300 pmol/L) and B- (less than 300 pmol/L) group. The proportion of developing beta cell function failure was 13.1% in B+ group and 90.5% in B- group, which suggested that fasting C peptide levels made a good distinction of the heterogeneity in autoimmune diabetes. Receiver operator characteristic (ROC) analysis suggested that the fasting C peptide level of 300 pmol/L was optimal for determining beta cell function failure with sensitivity of 90.5% and specificity of 86.9%.
Initial level of fasting C peptide is a good indicator for predicting beta cell function failure in GAD-Ab positive diabetic patients.
The glycated haemoglobin A1c (HbA1c) level may be used for screening for type 2 diabetes and prediabetes instead of a more burdensome oral glucose tolerance test (OGTT). However, among the high-risk South Asian population, little is known about the overlap of the methods or about the metabolic profiles of those disconcordantly diagnosed.
We included 944 South Asians (18–60 years old), whom we screened with the HbA1c level and the OGTT in The Hague, the Netherlands. We calculated the area under the receiver-operator characteristic curve (AUROC) with a 95% confidence interval of HbA1c using the American Diabetes Association classifications, and determined the sensitivity and specificity with 95% confidence intervals at different thresholds. Moreover, we studied differences in metabolic characteristics between those identified by HbA1c and by the OGTT alone.
The overlap between HbA1c and OGTT classifications was partial, both for diabetes and prediabetes. The AUROC of HbA1c for OGTT defined diabetes was 0.86 (0.79–0.93). The sensitivity was 0.46 (0.29–0.63); the specificity 0.98 (0.98–0.99). For prediabetes, the AUROC was 0.73 (0.69–0.77). Each of the 31 individuals with diabetes and 353 with prediabetes identified with the HbA1c level had a high body mass index, large waist circumference, high blood pressure, and low insulin sensitivity, all of which were similar to the values shown by those among the 19 with diabetes or 62 with prediabetes who only met the OGTT criteria, but not the HbA1c criteria.
The HbA1c level identified a partially different group than the OGTT did. However, both those identified with the HbA1c level and those identified with the OGTT alone were at increased metabolic risk.
Dutch Trial Register:
Type 2 Diabetes; Prediabetes; South Asian Populations; Screening; HbA1c; OGTT