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1.  The predictive value of sonographic images of follicular lesions – a comparison with nodules unequivocal in FNA – single centre prospective study 
Background
To determine the diagnostic efficacy of ultrasonographic malignancy risk features (UMRFs) in follicular lesions (FL) in a population with low risk of malignancy in FL and to compare it with a similar analysis in a group of patients with unequivocal cytology (UC): benign lesion (BL) or malignant neoplasm (MN).
Methods
Presence of UMRFs (hypoechogenicity, solid echostructure, taller-than-wide shape, pathological vascularization, irregular margins, microcalcifications and macrocalcifications) and their sets were assessed in 322 FL: 202 follicular lesions of undetermined significance (FLUS) and 120 suspicious for follicular neoplasm (SFN) and 300 nodules with UC: 200 BL and 100 MN, subsequently evaluated histopathologically.
Results
Cancers were confirmed in 100% nodules in MN group (89.0% of them were papillary carcinomas - PTC), in 6.4% FLUS nodules (69.2% PTC), and in 10.8% SFN nodules (30.8% PTC). In the UC group all UMRFs occurred more frequently in cancers than in benign lesions. In the FL group only calcifications were found in cancers more frequently – macro and microcalcifications together: 34.6 vs. 11.5% (p = 0.001) and isolated macrocalcifications: 26.0 vs. 6.8% (p = 0.001); the presence of those features increased the basic risk of malignancy in FL more than 2 times. The presence of at least 2 of the following URMFs: hypoechogenicity, solid echostructure, any type of calcifications and suspected shape, additionally improved sensitivity.
Conclusions
Evaluation of UMRFs in FLs is less effective than in nodules with UC, and its effectiveness decreases parallel to the decrease in percentage of PTCs among malignant neoplasms and to the increase of the percentage of adenomas among benign nodules. The presence of macrocalcifications in such FLs significantly increases the basic risk of malignancy in these nodules.
doi:10.1186/s12902-016-0151-5
PMCID: PMC5131422  PMID: 27903245
Thyroid; Ultrasonography; Fine needle aspiration biopsy; Follicular lesions; Cancer; FLUS; SFN
2.  Effect of sitagliptin on blood glucose control in patients with type 2 diabetes mellitus who are treatment naive or poorly responsive to existing antidiabetic drugs: the JAMP study 
Background
To investigate the ameliorating effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood glucose control in patients with type 2 diabetes mellitus who were previously untreated with or who have a poor responsive to existing antidiabetic drugs.
Methods
Sitagliptin (50 mg/day) was added on to the pre-existing therapy for type 2 diabetes and changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline and performed exploratory analysis.
Results
HbA1c levels were significantly decreased after 1 month of treatment compared to baseline, with a mean change in HbA1c level from baseline of −0.73% (range, −0.80 to −0.67) in the entire study population at 3 months. Patients who received a medium dose of glimepiride showed the least improvement in HbA1c levels. The percentage of patients who achieved an HbA1c level of <7.0% significantly increased after 1 month of treatment, reaching 53.1% at 3 months. The percentage of patients who achieved a fasting blood glucose level of <130 mg/dL significantly increased after 1 month of treatment, reaching 50.9% at 3 months.
Conclusions
Sitagliptin improved the HbA1c level and rate of achieving the target control levels in patients with type 2 diabetes mellitus who were previously untreated with, or poorly responsive to, existing antidiabetic drugs. Thus, sitagliptin is expected to be useful in this patient group. However, the additional administration of sitagliptin in patients treated with medium-dose glimepiride only slightly improved blood glucose control when corrected for baseline HbA1c level.
Electronic supplementary material
The online version of this article (doi:10.1186/s12902-016-0149-z) contains supplementary material, which is available to authorized users.
doi:10.1186/s12902-016-0149-z
PMCID: PMC5133763  PMID: 27905912
Sitagliptin; Diabetes mellitus; DPP-4 inhibitor; HbA1c; Glimepiride
3.  Prevalence and factors associated with diabetes mellitus and impaired fasting glucose level among members of federal police commission residing in Addis Ababa, Ethiopia 
Background
The prevalence of diabetes mellitus and factors associated with it, nowadays, are increasing in alarming rates among different occupational groups. Of these occupational groups are Police officers that, often, are exposed to unique life styles and stressful situations which may lead to diabetes mellitus and other cardiovascular diseases. Due to this reason, the present study was conducted to assess the prevalence and factors associated with diabetes mellitus and impaired fasting glucose level among members of federal police commission residing in Addis Ababa, Ethiopia.
Methods
A cross-sectional study design was conducted from April to May 2015. Multistage and systematic random sampling techniques were employed to select the study participants. The study population was federal police commission members living in Addis Ababa and served for at least a year. The data were collected using structured questionnaire, physical examinations and blood samples, based on the WHO stepwise approach. Data were entered in to SPSS version 20.0 and descriptive statistics and logistics regression were used for analysis.
Results
Out of the 1003 eligible subjects, 936 (93.3%) police officers have participated in this study. The prevalence of overall impaired glucose homeostasis (IGH) was 120 (13%) of which 47 (5%) were diabetes and 73 (8%) were impaired fasting glucose. Whereas police rank, history of first degree relative who suffered from diabetes, hypertension and waist hip ratio showed a statistical significance with prevalence of diabetes mellitus, age, family history, hypertension, BMI and waist hip ratio were found to be associated with impaired fasting glucose.
Conclusion
The study identified a high prevalence of IGH among the police officers. A priority should be given on preventive strategies of diabetes mellitus, as that of communicable diseases, by Federal Police Commission Health Service Directorate, Federal Ministry of Health and other concerned partners.
doi:10.1186/s12902-016-0150-6
PMCID: PMC5126814  PMID: 27894278
Associated factors; Diabetes mellitus; Federal Police Commission; Impaired fasting glucose; Impaired glucose homeostasis; Prevalence
4.  A randomised, open-labelstudy of insulin glargine or neutral protamine Hagedorn insulin in Chinese paediatric patients with type 1 diabetes mellitus 
Background
We aimed to describe the safety and efficacy of insulin glargine in Chinese paediatric patients with type 1 diabetes mellitus (T1DM). Neutral protamine Hagedorn (NPH) insulin was the reference therapy.
Methods
This open-label, randomised, Phase III study was conducted at 10 sites in China. Children aged ≥6 to <18 years with T1DM were randomised (2:1) to insulin glargine or NPH insulin asbasal insulinfor a 24-week treatment period. For all patients, insulin aspart was given as bolus insulin. The primary endpoint was absolute change in glycated haemoglobin(HbA1c) from baseline to Week 24. Secondary endpoints included the percentage of patients reaching HbA1c <7.5% (<58.5 mmol/mol), and safety. The study was registered at clinicaltrials.gov (NCT01223131).
Results
In total,196 patients were screened, and 162 were randomised (107 and 55 patients were randomised to insulin glargine and NPH insulin, respectively). The mean ± SD of absolute change in HbA1c was–0.25 ± 1.68% (–2.69 ± 18.32 mmol/mol) in the insulin glargine group and –0.54 ± 1.67% (–5.55 ± 20.32 mmol/mol) in the NPH insulin group. At Week 24, 18.7 and 21.6% of patients in the insulin glargine and NPH insulin groups achieved HbA1c <7.5% (<58.5 mmol/mol). Both treatments were generally well tolerated. A numerically lower rate of symptomatic hypoglycaemia per patient year was observed for insulin glargine versus NPH insulin (24.3 ± 45.8 versus32.3 ± 43.2); severe hypoglycaemia was rare (<2%).
Conclusions
Initiation of insulin glargine can aid Chinese paediatric patients with T1DM to safely reduce their HbA1c levels.
Electronic supplementary material
The online version of this article (doi:10.1186/s12902-016-0146-2) contains supplementary material, which is available to authorized users.
doi:10.1186/s12902-016-0146-2
PMCID: PMC5124261  PMID: 27887605
Chinese paediatric patients; Insulin glargine; NPH insulin; Type 1 diabetes mellitus
5.  Administration of anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody for the treatment of osteoporosis was associated with amelioration of hepatitis in a female patient with growth hormone deficiency: a case report 
Background
Growth hormone deficiency (GHD) is associated with non-alcoholic fatty liver disease (NAFLD). A recent animal study showed that hepatocyte-specific receptor activator of nuclear factor-kappa B (RANK) knockout mice had significantly lower liver fat content compared with control mice concomitant with a decrease in production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) from hepatocytes and kupffer cells. The role of anti-RANK ligand (RANKL) antibody for osteoporosis on hepatitis in patients with aGHD is still unknown.
Case presentation
A forty-seven-year-old female patient was referred to our hospital to investigate chronic hepatitis caused by unknown etiology. She had past history of craniopharyngioma treated with craniotomy and post-surgical radiotherapy. She was for the first time diagnosed as panhypopituitarism including growth hormone deficiency and osteoporosis by endocrine examinations and bone mineral densitometry, respectively. In addition, non-alcoholic steatohepatitis (NASH) was histologically confirmed by liver biopsy in this time. Sixty mg anti-RANKL antibody, which was subcutaneously injected to treat the osteoporosis every six months after replacement of 5 mg hydrocortisone and 30 μg oral desmopressin, rapidly decreased the levels of her liver enzymes (ALT and γGTP were 133 to 72 U/L and 284 to 99 U/L at 16 months after the beginning of the treatment, respectively). Additional amelioration of liver dysfunction was not observed after growth hormone replacement.
Conclusions
The clinical course of the present case suggested that RANKL-RANK signaling may be a key pathological mechanism in establishment or development of NAFLD or NASH in patients with panhypopituitarism including GHD.
doi:10.1186/s12902-016-0148-0
PMCID: PMC5122017  PMID: 27881164
Growth hormone deficiency (GHD); Non-alcoholic fatty liver disease (NAFLD); Non-alcoholic steatohepatitis (NASH); Receptor activator of nuclear factor-kappa B ligand (RANKL); Denosumab
6.  Diabetes screening intervals based on risk stratification 
Background
Guidelines for frequency of Type 2 diabetes mellitus (DM) screening remain unclear, with proposed screening intervals typically based on expert opinion. This study aims to demonstrate that HbA1c screening intervals may differ substantially when considering individual risk for diabetes.
Methods
This was a multi-institutional retrospective open cohort study. Data were collected between April 1999 to March 2014 from one urban and one rural cohort in Japan. After categorization by age, we stratified individuals based on cardiovascular disease risk (Framingham 10-year cardiovascular risk score) and body mass index (BMI). We adapted a signal-to-noise method for distinguishing true HbA1c change from measurement error by constructing a linear random effect model to calculate signal and noise of HbA1c. Screening interval for HbA1c was defined as informative when the signal-to-noise ratio exceeded 1.
Results
Among 96,456 healthy adults, 46,284 (48.0%) were male; age (range) and mean HbA1c (SD) were 48 (30–74) years old and 5.4 (0.4)%, respectively. As risk increased among those 30–44 years old, HbA1c screening intervals for detecting Type 2 DM consistently decreased: from 10.5 (BMI <18.5) to 2.4 (BMI > 30) years, and from 8.0 (Framingham Risk Score <10%) to 2.0 (Framingham Risk Score ≥20%) years. This trend was consistent in other age and risk groups as well; among obese 30–44 year olds, we found substantially shorter intervals compared to other groups.
Conclusion
HbA1c screening intervals for identification of DM vary substantially by risk factors. Risk stratification should be applied when deciding an optimal HbA1c screening interval in the general population to minimize overdiagnosis and overtreatment.
doi:10.1186/s12902-016-0139-1
PMCID: PMC5120442  PMID: 27876036
Diabetes mellitus; Screening interval; Accuracy of testing
7.  Foot insensitivity is associated with renal function decline in patients with type 2 diabetes: a cohort study 
Background
Identifying patients with diabetes at increased risk of chronic kidney disease (CKD) is essential to prevent/slow the progression to end-stage renal disease (ESRD). CKD and diabetic peripheral neuropathy (DPN) share common mechanisms. Hence, we aimed to examine the relationship between foot insensitivity and CKD in patients with Type 2 diabetes.
Methods
A prospective observational cohort study in adults with Type 2 diabetes. Patients with ESRD were excluded. Foot insensitivity was assessed using the 10-g monofilament test. Renal function was assessed using estimated glomerular filtration rate (eGFR) based on the MDRD equation. Albuminuria was defined as the presence of urinary albumin/creatinine ratio (ACR) >3.4 mg/mmol.
Results
Two hundred and twenty eight patients were recruited and followed-up for 2.5 years. One hundred and ninety patients (83.4%) had eGFR ≥ 60 ml/min/1.73 m2. Seventy six (33.3%) patients had foot insensitivity (i.e. abnormal monofilament test). Patients with foot insensitivity had lower eGFR and higher prevalence of albuminuria compared to patients with normal monofilament test. After adjustment for age, gender, ethnicity, diabetes duration, HbA1c, body mass index, insulin treatment, number of anti-hypertensives, history of peripheral vascular disease, and baseline eGFR (R2 0.87), baseline foot insensitivity was associated with study-end eGFR (B = −3.551, p = 0.036).
Conclusions
Patients with Type 2 diabetes and foot insensitivity are at increased risk of eGFR decline. Identifying these patients offers an opportunity to intensify metabolic and blood pressure control to prevent/retard the development of CKD. Future studies of larger sample size and longer follow up from multiple centres are needed to assess the diagnostic performance of our findings in predicting CKD development, and to compare the performance of the monofilament test with albuminuria.
doi:10.1186/s12902-016-0147-1
PMCID: PMC5120531  PMID: 27876022
Diabetic neuropathy; Chronic kidney disease; Diabetic nephropathy; Albuminuria; Estimated glomerular filtration rate; Foot insensitivity; 10 g monofilament
8.  Erratum to: Adrenal fatigue does not exist: a systematic review 
doi:10.1186/s12902-016-0132-8
PMCID: PMC5112686  PMID: 27852255
9.  The course of diabetes in children, adolescents and young adults: does the autoimmunity status matter? 
Background
Initial classification of diabetes of young may require revision to improve diagnostic accuracy of different forms of diabetes.
The aim of our study was to examine markers of beta-cell autoimmunity in a cohort of young (0–25 years) patients with type 1 diabetes and compare the presentation and course of the disease according to the presence of pancreatic antibodies.
Methods
Cross-sectional population-based study was performed covering 100% of pediatric (n = 860) and 70% of 18–25 years old adult patients (n = 349) with type 1 diabetes in Lithuania.
Results
No antibodies (GAD65, IA-2, IAA and ICA) were found in 87 (7.5%) cases. Familial history of diabetes was more frequent in those with antibodies-negative diabetes (24.1 vs. 9.4%, p < 0.001). Gestational age, birth weight and age at diagnosis was similar in both groups. Ketosis at presentation was more frequent in patients with autoimmune diabetes (88.1 vs. 73.5%, p < 0.05). HbA1c at the moment of investigation was 8.6 (3) vs. 8.7 (2.2)% in antibodies-negative and antibodies-positive diabetes groups, respectively, p > 0.05. In the whole cohort, neuropathy was found in 8.8% and nephropathy - in 8.1% of cases, not depending on autoimmunity status. Adjusted for age at onset, disease duration and HbA1c, retinopathy was more frequent in antibodies-negative subjects (13.8 vs. 7.8%, p < 0.05).
Conclusion
Antibodies-negative pediatric and young adult patients with type 1 diabetes in this study had higher incidence of family history of diabetes, higher frequency of retinopathy, less frequent ketosis at presentation, but similar age at onset, HbA1c, incidence of nephropathy and neuropathy compared to antibodies-positive patients.
doi:10.1186/s12902-016-0145-3
PMCID: PMC5109672  PMID: 27842589
Type 1 diabetes; Children; Adolescents; Young adults; Pancreatic antibodies
10.  Acute glycaemic effects of co-trimoxazole at prophylactic dose in healthy adults 
Background
Cases of severe hypoglycaemia were reported in HIV/AIDS patients receiving high dose of the sulfonylurea co-trimoxazole for opportunistic infections. Whether co-trimoxazole at prophylactic dose would induce similar side effects is unknown. We aimed to investigate the acute effects of co-trimoxazole at prophylactic dose on glucose metabolism in healthy adults.
Methods
We enrolled 20 healthy volunteers (15 males and 5 females) aged 23.0 (SD 2.0) years, with mean BMI of 22.3 (SD 3.6) Kg/m2 with normal glucose tolerance, hepatic and renal function. We performed a 75-g oral glucose tolerance test (OGTT) with and without concomitant oral co-trimoxazole administered 60 min before the test. Blood glucose response was measured using a capillary test at baseline and at 30, 60, 90, 120 and 180 min following oral glucose load on the two occasions. C-peptide response was also measured. Absolute values of blood glucose and C-peptide with and without co-trimoxazole were compared using the Wilcoxon test.
Results
During the OGTT without co-trimoxazole (control) vs. the OGTT with co-trimoxazole (test), the glycaemia varied from 4.83 (SD 0.39) mmol/l vs. 4.72 (SD 0.28) mmol/l at T0 (P = 0.667), to 8.00 (SD 1.11) mmol/l vs. 7.44 (SD 0.78) mmol/l at T30 (P = 0.048), 8.00 (SD 1.17) mmol/l vs. 7.67 (SD 1.00) mmol/l at T60 (P = 0.121), 7.33 (SD 0.94) mmol/l vs. 7.11 (SD 0.83) mmol/l at T90 (P = 0.205), 6.78 (SD 1.00) mmol/l vs. 6.67 (SD 1.00) mmol/l at T120 (P = 0.351) and 4.72 (SD 1.39) mmol/l vs. 4.72 (SD 1.56) mmol/l at T180 (P = 0.747). The ratio of area under the glycaemia curve during the control and test investigation was 96.7 %, thus a 3.3 decreased glycaemic response (p = 0.062). A decrease of glycaemia by more than 10 % occurred in 6/20 participants at T30, 7/20 participants at T60 and 1/20 participant at T30 and T60. None of the volunteers experienced co-trimoxazole-induced hypoglycaemia. At the same time, the C-peptide response during the control vs. the test investigation varied from 278.1 (SD 57.5) pmol/l vs. 242.8 (SD 42.5) pmol/l at T0 (P = 0.138), to 1845.6 (SD 423.6) pmol/l vs. 2340.6 (SD 701.3) pmol/l at T60 (P = 0.345) and 1049.8 (SD 503.1) pmol/l vs. 1041.63 (SD 824.21) pmol/l at T180 (P = 0.893).
Conclusion
Ninety minutes after its administration, co-trimoxazole induced a significant reduction of the early glycaemic response to oral glucose in parallel with a 27-% increase in insulin secretory response. Co-trimoxazole induced within 120 min a more than 10-% blood glucose reduction in 2/3 of participants. However none of the volunteers experienced hypoglycaemia.
doi:10.1186/s12902-016-0142-6
PMCID: PMC5143444  PMID: 27927207
Co-trimoxazole; Glycaemia; Adults
11.  Obesity and diabetes mellitus association in rural community of Katana, South Kivu, in Eastern Democratic Republic of Congo: Bukavu Observ Cohort Study Results 
Background
Factual data exploring the relationship between obesity and diabetes mellitus prevalence from rural areas of sub-Saharan Africa remain scattered and are unreliable. To address this scarceness, this work reports population study data describing the relationship between the obesity and the diabetes mellitus in the general population of the rural area of Katana (South Kivu in the Democratic Republic of the Congo).
Methods
A cohort of three thousand, nine hundred, and sixty-two (3962) adults (>15 years old) were followed between 2012 and 2015 (or 4105 person-years during the observation period), and data were collected using the locally adjusted World Health Organization’s (WHO) STEPwise approach to Surveillance (STEPS) methodology. The hazard ratio for progression of obesity was calculated. The association between diabetes mellitus and obesity was analyzed with logistic regression.
Results
The diabetes mellitus prevalence was 2.8 % versus 3.5 % for obese participants and 7.2 % for those with metabolic syndrome, respectively. Within the diabetes group, 26.9 % had above-normal waist circumference and only 9.8 % were obese. During the median follow-up period of 2 years, the incidence of obesity was 535/100,000 person-years. During the follow-up, the prevalence of abdominal obesity significantly increased by 23 % (p <0.0001), whereas the increased prevalence of general obesity (7.8 %) was not significant (p = 0.53). Finally, diabetes mellitus was independently associated with age, waist circumference, and blood pressure but not body mass index.
Conclusion
This study confirms an association between diabetes mellitus and abdominal obesity but not with general obesity. On the other hand, the rapid increase in abdominal obesity prevalence in this rural area population within the follow-up period calls for the urgent promoting of preventive lifestyle measures.
doi:10.1186/s12902-016-0143-5
PMCID: PMC5105280  PMID: 27835951
Obesity; Diabetes mellitus; Democratic Republic of the Congo; Sub-Saharan Africa
12.  Gastric bypass surgery reveals independency of obesity and diabetes melitus type 2 
Background
Roux-en-Y gastric bypass surgery is widely applied to ameliorate morbid obesity, including diabetes in people with type 2 diabetes. The latter vanish a few days after surgery for many, but not in all patients before any weight reduction has occurred. The explanation for this change in metabolic status is poorly understood, but the observation may suggest that the fate obesity and diabetes is only partly linked after surgery.
Methods
The trajectories of weight reduction measured as reduced body mass index (BMI) in 741obese subjects with and without diabetes were evaluated. Evaluation was performed on three groups: 1) subjects that were non-diabetic before and after surgery; 2) subjects that were diabetics before surgery but non-diabetics after surgery; and 3) subjects that were diabetics before surgery and remained diabetics after surgery. The diabetic state was established at HbA1c above 48 mmol/mol.
Results
The trajectories differ significantly between groups and any sub-populations of groups, the latter identified by the distance between individual trajectories using a k-means procedure. The results suggest that different domains in the enormous genetic network governing basic metabolism are perturbed in obesity and diabetes, and in fact some of the patients are affected by two distinct diseases: obesity and diabetes mellitus type 2.
Conclusion
Although RYGB “normalized” many glycaemic parameters in some of the diabetic subjects apparently converting to a non-diabetics state, other diabetic subjects stay diabetic in the context of the new gut anatomy after surgery. Thus, the obesity part of the glycaemic derangement may have been ameliorated, but some defects of the diabetic state had not.
Electronic supplementary material
The online version of this article (doi:10.1186/s12902-016-0140-8) contains supplementary material, which is available to authorized users.
doi:10.1186/s12902-016-0140-8
PMCID: PMC5103622  PMID: 27829412
13.  Case report of whole genome sequencing in the XY female: identification of a novel SRY mutation and revision of a misdiagnosis of androgen insensitivity syndrome 
Background
The 46,XY female is characterised by a male karyotype and female phenotype arising due to any interruption in the sexual development pathways in utero. The cause is usually genetic and various genes are implicated.
Case presentation
Herein we describe a 46,XY woman who was first diagnosed with androgen insensitivity syndrome (testicular feminisation) at 18 years; however, this was later questioned due to the presence of intact Müllerian structures. The clinical phenotype suggested several susceptibility genes including SRY, DHH, NR5A1, NR0B1, AR, AMH, and AMHR2. To study candidate genes simultaneously, we performed whole genome sequencing. This revealed a novel and likely pathogenic missense variant (p.Arg130Pro, c.389G>C) in SRY, one of the major genes implicated in complete gonadal dysgenesis, hence securing this condition over androgen insensitivity syndrome as the cause of the patient’s disorder of sexual development.
Conclusion
This case highlights the emerging clinical utility of whole genome sequencing as a tool in differentiating disorders of sexual development.
doi:10.1186/s12902-016-0141-7
PMCID: PMC5100246  PMID: 27821113
Disorders of sexual development; Androgen insensitivity syndrome; Gonadal dysgenesis; Whole genome sequencing; Next generation sequencing; SRY; Case report
14.  The effect of lifestyle intervention in obesity on the soluble form of activated leukocyte cell adhesion molecule 
Background
The aim of this study was to investigate the effect of a lifestyle intervention in obesity on the soluble form of the activated leukocyte cell adhesion molecule (sALCAM) and its association with metabolic parameters.
Methods
Twenty-nine obese subjects selected from the OPTIFAST®52 program. This program consisted into 2 crucial phases: an initial 12-week active weight reduction phase, followed by a 40-week weight maintenance phase. At baseline, after 12 weeks and at the end of the program, fasting glucose and insulin, total cholesterol, LDL-C, HDL-C, triglycerides, adiponectin, leptin, high sensitivity CRP, sALCAM, homeostasis model assessment-estimated insulin resistance (HOMA-IR) and leptin-to-adiponectin-ratio were determined. Oral glucose tolerance test (OGTT) was performed when indicated.
Results
At baseline, the serum concentration of sALCAM was increased and correlated positively with HOMA-IR and negatively with age. At the end of the program, sALCAM concentrations decreased significantly. Multivariate analysis showed that sALCAM significantly correlated with age, glucose concentration after 2 h OGTT and the HOMA-IR. A higher decrease of HOMA-IR during the study was observed in subjects with higher concentration of sALCAM at baseline.
Conclusions
sALCAM might be a novel biomarker in obesity that correlates and predicts insulin sensitivity improvement and that can be affected by lifestyle intervention.
doi:10.1186/s12902-016-0138-2
PMCID: PMC5064930  PMID: 27737658
Obesity; Lifestyle intervention; Insulin resistance; sALCAM; Cell adhesion molecule
15.  Arterial stiffness in hypertensive and type 2 diabetes patients in Ghana: comparison of the cardio-ankle vascular index and central aortic techniques 
Background
Diabetes and hypertension increase arterial stiffness and cardiovascular events in all societies studied so far; sub-Saharan African studies are sparse. We investigated factors affecting arterial function in Ghanaians with diabetes, hypertension, both or neither.
Method
Testing the hypothesis that arterial stiffness would progressively increase from controls to multiply affected patients, 270 participants were stratified into those with diabetes or hypertension only, with both, or without either. Cardio-ankle vascular index (CAVI), heart–ankle pulse wave velocity (haPWV), aortic PWV (PWVao) by Arteriograph, aortic and brachial blood pressures (BP), were measured.
Results
In patients with both diabetes and hypertension compared with either alone, values were higher of CAVI (mean ± SD, 8.3 ± 1.2 vs 7.5 ± 1.1 and 7.4 ± 1.1 units; p < 0.05), PWVao (9.1 ± 1.4 vs 8.7 ± 1.9 and 8.1 ± 0.9 m/s; p < 0.05) and haPWV (8.5 ± 1 vs 7.9 ± 1 and 7.2 ± 0.7 m/s; p < 0.05) respectively. In multivariate analysis, age, having diabetes or hypertension and BMI were independently associated with CAVI in all participants (β = 0.49, 0.2, 0.17 and -0.2 units; p < 0.01, respectively). Independent determinants of PWVao were heart rate, systolic BP and age (β = 0.42, 0.27 and 0.22; p < 0.01), and for haPWV were systolic BP, age, BMI, diabetes and hypertension status (β = 0.46, 0.32, -0.2, 0.2 and 0.11; p < 0.01).
Conclusion
In this sub-Saharan setting with lesser atherosclerosis than the western world, arterial stiffness is significantly greater in patients with coexistent diabetes and hypertension but did not differ between those with either diabetes or hypertension only. Simple, reproducibly measured PWV/CAVI may offer effective and efficient targets for intervention.
Electronic supplementary material
The online version of this article (doi:10.1186/s12902-016-0135-5) contains supplementary material, which is available to authorized users.
doi:10.1186/s12902-016-0135-5
PMCID: PMC5041289  PMID: 27680212
Cardio-ankle vascular index; Arterial stiffness; Aortic pulse wave velocity; Diabetes; Hypertension; Ghana
16.  Neonatal and obstetric outcomes in diet- and insulin-treated women with gestational diabetes mellitus: a retrospective study 
Background
To evaluate the neonatal and obstetric outcomes of pregnancies complicated by gestational diabetes mellitus (GDM). Screening and treatment – diet-only versus additional insulin therapy – were based on the 2010 national Dutch guidelines.
Methods
Retrospective study of the electronic medical files of 820 singleton GDM pregnancies treated between January 2011 and September 2014 in a university and non-university hospital. Pregnancy outcomes were compared between regular care treatment regimens –diet-only versus additional insulin therapy- and pregnancy outcomes of the Northern region of the Netherlands served as a reference population.
Results
A total of 460 women (56 %) met glycaemic control on diet-only and 360 women (44 %) required additional insulin therapy. Between the groups, there were no differences in perinatal complications (mortality, birth trauma, hyperbilirubinaemia, hypoglycaemia), small for gestational age, large for gestational age (LGA), neonate weighing >4200 g, neonate weighing ≥4500 g, Apgar score <7 at 5 min, respiratory support, preterm delivery, and admission to the neonatology department. Neonates born in the insulin-group had a lower birth weight compared with the diet-group (3364 vs. 3467 g, p = 0.005) and a lower gestational age at birth (p = 0.001). However, birth weight was not different between the groups when expressed in percentiles, adjusted for gestational age, gender, parity, and ethnicity. The occurrence of preeclampsia and gestational hypertension was comparable between the groups. In the insulin-group, labour was more often induced and more planned caesarean sections were performed (p = 0.001). Compared with the general obstetric population, the percentage of LGA neonates was higher in the GDM population (11.0 % vs.19.9 %, p = <0.001).
Conclusions
Neonatal and obstetric outcomes were comparable either with diet-only or additional insulin therapy. However, compared with the general obstetric population, the incidence of LGA neonates was significantly increased in this GDM cohort.
doi:10.1186/s12902-016-0136-4
PMCID: PMC5041294  PMID: 27680327
Diet; Gestational diabetes mellitus; Insulin; Pregnancy outcomes; Treatment
17.  Single-dose acarbose decreased glucose-dependent insulinotropic peptide and glucagon levels in Chinese patients with newly diagnosed type 2 diabetes mellitus after a mixed meal 
Background
Acarbose slows down the intestinal absorption of carbohydrates, but its effects on the secretion of incretins are still poorly known. This study aimed to examine the effects of single-dose acarbose on the secretion of incretins in patients with newly diagnosed type 2 diabetes mellitus (T2DM).
Methods
In this pilot study, twenty-three patients diagnosed with T2DM were randomly assigned to the oral glucose tolerance test (OGTT) group (n = 11) and the mixed meal test (MMT) group (n = 12). Fourteen subjects with normal OGTT were included as controls. Plasma glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic peptide (GIP) were measured at 0 (fasting), 15, 30, 60, 90, and 120 min after nutrient load. A week later, controls underwent MMT, the OGTT group underwent OGTT receiving 100 mg acarbose, and the MMT group underwent MMT receiving 100 mg acarbose. The same blood markers were measured again.
Results
No significant difference was observed in the OGTT group before and after administering acarbose. In the MMT group, postprandial levels of glucose (P < 0.01), insulin (P < 0.01), glucagon at 15 min (P < 0.05), glucagon area under the curve (AUC) (P < 0.05), GIP levels at 30 min (P < 0.05), and GIP AUC (P < 0.05) were decreased after receiving acarbose with a mixed meal, but GLP-1 levels and GLP-1 AUC did not change.
Conclusions
Single-dose acarbose could reduce the secretion of GIP and glucagon after a mixed meal in patients with newly diagnosed T2DM. The influence of acarbose on incretin levels could be related to the types of carbohydrate being consumed.
Trial registration
This study was registered with the Chinese Clinical Trial Registry (Registration Number: ChiCTR-TRC-14004260, Date of Registration: 2014-01-19).
doi:10.1186/s12902-016-0133-7
PMCID: PMC5041397  PMID: 27686734
Acarbose; Glucagon-like peptide-1; Glucose-dependent insulinotropic peptide; Glucagon; Type 2 diabetes mellitus
18.  Gender-modulated risk of coronary heart disease, diabetes and coronary mortality among Turks for three major risk factors, and residual adiposity risk 
Background
We determined the proportion of the effects of body mass index (BMI) or its categories on cardiometabolic outcomes mediated through systolic blood pressure (SBP), total cholesterol and fasting glucose.
Methods
Cox regression analyses were performed for incident outcomes among Turkish Adult Risk Factor study participants in whom the three mediators had been determined (n = 2158, age 48.5 ± 11 years). Over a mean 10.2-years’ follow-up, new coronary heart disease (CHD) developed in 406, diabetes in 284 individuals, and 149 CHD deaths occurred.
Results
Hazard ratios (HR) of BMI for incident diabetes were no more than marginally attenuated by the 3 mediators including glucose, irrespective of gender. Compared to “normal-weight”, sex- and age-adjusted RRs for incident CHD of overweight and obesity were 1.40 and 2.24 (95 % CI 1.68; 2.99), respectively, in gender combined. Only three-tenths of the excess risk was retained by BMI in men, six-tenths in women. No mediation of glycemia was discerned in males, in contrast to greatest mediation in females. HR of age-adjusted continuous BMI was a significant but modest contributor to CHD mortality in each gender. While the BMI risk of CHD death was abolished by mediation of SBP in men, HR strengthened to over two-fold in women through mediation of fasting glucose.
Conclusions
Mediation of adiposity by 3 traditional factors exhibited among Turkish adults strong gender dependence regarding its magnitude for CHD risk and the mediation by individual risk factors. Retention of the large part of risk for diabetes in each sex and for CHD in women likely reflects underlying autoimmune activation.
Electronic supplementary material
The online version of this article (doi:10.1186/s12902-016-0134-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s12902-016-0134-6
PMCID: PMC5041572  PMID: 27680100
Autoimmune activation; Body mass index; Coronary heart disease; Coronary mortality; Type-2 diabetes; Gender difference
19.  Plantar pressures are higher in cases with diabetic foot ulcers compared to controls despite a longer stance phase duration 
Background
Current international guidelines advocate achieving at least a 30 % reduction in maximum plantar pressure to reduce the risk of foot ulcers in people with diabetes. However, whether plantar pressures differ in cases with foot ulcers to controls without ulcers is not clear. The aim of this study was to assess if plantar pressures were higher in patients with active plantar diabetic foot ulcers (cases) compared to patients with diabetes without a foot ulcer history (diabetes controls) and people without diabetes or a foot ulcer history (healthy controls).
Methods
Twenty-one cases with diabetic foot ulcers, 69 diabetes controls and 56 healthy controls were recruited for this case-control study. Plantar pressures at ten sites on both feet and stance phase duration were measured using a pre-established protocol. Primary outcomes were mean peak plantar pressure, pressure-time integral and stance phase duration. Non-parametric analyses were used with Holm’s correction to correct for multiple testing. Binary logistic regression models were used to adjust outcomes for age, sex and body mass index. Median differences with 95 % confidence intervals and Cohen’s d values (standardised mean difference) were reported for all significant outcomes.
Results
The majority of ulcers were located on the plantar surface of the hallux and toes. When adjusted for age, sex and body mass index, the mean peak plantar pressure and pressure-time integral of toes and the mid-foot were significantly higher in cases compared to diabetes and healthy controls (p < 0.05). The stance phase duration was also significantly higher in cases compared to both control groups (p < 0.05). The main limitations of the study were the small number of cases studied and the inability to adjust analyses for multiple factors.
Conclusions
This study shows that plantar pressures are higher in cases with active diabetic foot ulcers despite having a longer stance phase duration which would be expected to lower plantar pressure. Whether plantar pressure changes can predict ulcer healing should be the focus of future research. These results highlight the importance of offloading feet during active ulceration in addition to before ulceration.
Electronic supplementary material
The online version of this article (doi:10.1186/s12902-016-0131-9) contains supplementary material, which is available to authorized users.
doi:10.1186/s12902-016-0131-9
PMCID: PMC5024422  PMID: 27629263
Diabetic foot disease; Biomechanics; Plantar ulcers; Peripheral diabetic neuropathy; Foot ulceration; Plantar pressure; Offloading
20.  Familial early puberty: presentation and inheritance pattern in 139 families 
BMC Endocrine Disorders  2016;16(1):50.
Background
The mechanism that initiates the onset of puberty is largely unknown but the age of onset is mainly under genetic control and influenced by environmental factors including nutrition. The coexistence in the same family of central precocious puberty and advanced puberty, both representing early puberty, suggests that they may represent a clinical spectrum of the same trait due to early activation of the GnRH pulse generator. We therefore evaluated the mode of inheritance of early puberty in a large series of familial cases.
Methods
A retrospective, single center study was carried out on 154 probands (116 girls and 38 boys), from 139 families seen for idiopathic central precocious puberty (onset before 8 years in girls and 9–10 years in boys, n = 93) and/or advanced puberty (onset between 8 and 10 years in girls and 10 and 11 years in boys, n = 61) seen over a period of 8 years.
Results
Of the 139 families, 111 (80.4 %) had at least one affected 1st degree relatives, 17 (12 %) had only 2nd, 5 (3.6 %) only 3rd and 3 (2.2 %) had both 2nd and 3rd degree affected individuals. In the two remaining families, the unaffected mother had affected girls from two unaffected fathers. In the majority of families the inheritance of the phenotype was consistent with autosomal dominant mode of transmission with incomplete penetrance. An exclusively maternal mode of transmission could be observed or inferred in 83 families, paternal in only 2 families (p < 0.0001) and both maternal and paternal modes in 15 families.
In the 139 families, 374 cases of early puberty were identified of whom 315 (84.2 %) were affected females and 59 (15.8 %) affected males (p < 0.0001). Twenty one percent of families had exclusively precocious puberty, 25 % had exclusively advanced puberty and 54 % had combinations of both.
Conclusions
The data confirm the high incidence of affected girls with familial early puberty. The mode of inheritance of the phenotype is predominantly maternal. More than half of the families included both precocious and advanced puberty suggesting similar genetic factors.
doi:10.1186/s12902-016-0130-x
PMCID: PMC5022170  PMID: 27624871
Advanced puberty; Autosomal inheritance; Bilineal inheritance; Central precocious puberty; Early puberty; Familial puberty; GnRH; Hypothalamic-pituitary-gonadal axis; Precocious puberty; Unilineal inheritance
21.  Increased skin autofluorescence of children and adolescents with type 1 diabetes despite a well-controlled HbA1c: results from a cohort study 
BMC Endocrine Disorders  2016;16(1):49.
Background
Early identification of children and adolescents with type 1 diabetes at high risk for development of complications is important, as early intervention may prevent further deterioration. Here we investigate the applicability of assessing skin advanced glycation end products (sAGEs) by skin autofluorescence (SAF) as a potential surrogate risk marker.
Methods
This study included a cross-sectional analysis of SAF in 77 patients with type 1 diabetes mellitus and 118 healthy controls across age categories (11–12, 13–14, 15–16, and 17–19 years old). In patients, the impact of current and historical glycated hemoglobin (HbA1c) values, age, and duration of diabetes on SAF was studied in a retrospective cohort study and analyzed with multivariable analyses.
Results
SAF was significantly and similarly higher in patients when compared with controls across all age categories (P ≤0.009). For patients, age, duration of diabetes, and current and historical HbA1c were associated with SAF in univariate analysis. Multivariate analysis showed no association between HbA1c and SAF. A subgroup of patients with a HbA1c-within-target (≤7.5 %/59 mmol/mol) were observed to have high SAF.
Conclusion
Children and adolescents with type 1 diabetes show higher SAF than controls. The presumed correlation of high HbA1c with high SAF does not exist in all patients. Thus, use of this non-invasive measure may provide a surrogate marker for diabetic complications, additional to HbA1c.
doi:10.1186/s12902-016-0129-3
PMCID: PMC5017065  PMID: 27613110
Pediatrics; Type 1 diabetes; Skin autofluorescence; Skin advanced glycation end products; Diabetic complications
22.  Adrenal fatigue does not exist: a systematic review 
BMC Endocrine Disorders  2016;16(1):48.
Background
The term “adrenal fatigue” (“AF”) has been used by some doctors, healthcare providers, and the general media to describe an alleged condition caused by chronic exposure to stressful situations. Despite this, “AF” has not been recognized by any Endocrinology society, who claim there is no hard evidence for the existence. The aim of this systematic review is to verify whether there is substantiation for “AF”.
Methods
A systematic search was performed at PUBMED, MEDLINE (Ebsco) and Cochrane databases, from the beginning of the data until April 22nd, 2016. Searched key words were: “adrenal” + “fatigue”, “adrenal” + “burnout”, “adrenal” + “exhaustion”, “hypoadrenia”, “burnout” + “cortisol”, “fatigue” + “cortisol”, “clinical” + “burnout”, “cortisol” + “vitalility”, “adrenal” + “vitality”, and “cortisol” + “exhaustion”. Eligibility criteria were: (1) articles written in English, (2) cortisol profile and fatigue or energy status as the primary outcome, (3) performed tests for evaluating the adrenal axis, (4) absence of influence of corticosteroid therapy, and (5) absence of confounding diseases. Type of questionnaire to distinct fatigued subjects, population studied, tests performed of selected studies were analyzed.
Results
From 3,470 articles found, 58 studies fulfilled the criteria: 33 were carried in healthy individuals, and 25 in symptomatic patients. The most assessed exams were “Direct Awakening Cortisol” (n = 29), “Cortisol Awakening Response” (n = 27) and “Salivary Cortisol Rhythm” (n = 26).
Discussion
We found an almost systematic finding of conflicting results derived from most of the studies methods utilized, regardless of the validation and the quality of performed tests. Some limitations of the review include: (1) heterogeneity of the study design; (2) the descriptive nature of most studies; (3) the poor quality assessment of fatigue; (4) the use of an unsubstantiated methodology in terms of cortisol assessment (not endorsed by endocrinologists); (5) false premises leading to an incorrect sequence of research direction; and, (6) inappropriate/invalid conclusions regarding causality and association between different information.
Conclusion
This systematic review proves that there is no substantiation that “adrenal fatigue” is an actual medical condition. Therefore, adrenal fatigue is still a myth.
doi:10.1186/s12902-016-0128-4
PMCID: PMC4997656  PMID: 27557747
Adrenal depletion; Adrenal fatigue; Cortisol; Adrenal insufficiency; Burnout; Fatigue
23.  Pro inflammatory interleukins and thyroid function in Naswar (dipping tobacco) users: a case control study 
Background
Naswar is a type of finely ground, moistened smokeless dipping tobacco product being commonly used in Pakistan. Although, nicotine is the most important psychoactive agent present in Naswar, it also exerts immunosuppressive effects and could alter the levels of cytokines. Additionally, the effects of Naswar consumption on thyroid hormones are not known.
Methods
Eighty healthy males aged 16–43 years were selected for the study and were divided into a control group comprising 31 healthy subjects with no history of tobacco use in any form, with age matched test group comprising 49 exclusive Naswar users who were consuming Naswar for at least 1 year. Estimation of serum interleukin (IL)-1β, IL-6, free thyroxine (FT4), free triiodothyronine (FT3) and thyroid stimulating hormone (TSH) was carried out. The data was analyzed by statistical programme (SPSS) using student's independent samples t-test. One way Anova followed by post hoc Tukey test was applied to assess parameters in Naswar users grouped according to duration of Naswar usage. Pearson’s correlation coefficient was applied to assess correlations between parameters.
Results
IL-1β was found to be significantly lowered in Naswar users compared to the control group whereas serum FT3 and FT4 levels in Naswar users were significantly raised compared to the control group. However, no differences in the levels of serum IL-6 and TSH between Naswar users and the control group were found. Also, serum FT3 and FT4 were consistently raised whereas IL-1β was lowered in Naswar users irrespective of duration of Naswar consumption. IL-1β was negatively correlated with FT3 in Naswar users.
Conclusion
The findings suggest that Naswar users might be in an immune suppressive state as evident by the lowered levels of interleukin 1β. Additionally, alterations in the levels of thyroid hormones signify the impact of Naswar consumption on thyroid function.
doi:10.1186/s12902-016-0127-5
PMCID: PMC4982337  PMID: 27515932
Smokeless tobacco; Naswar; Interleukins; Free triiodothyronine; Free thyroxine; Thyroid stimulating hormone
24.  Prevalence of impaired glucose tolerance and other types of dysglycaemia among young twins and singletons in Guinea-Bissau 
Background
Twins may be at increased risk of dysglycaemic disorders due to adverse fetal conditions. Data from Africa regarding this association is limited. We studied impaired glucose tolerance (IGT) and other types of dysglycemia among twins and singletons in Guinea-Bissau.
Methods
The study was conducted from February 2011 until March 2012 at the Bandim Health Project, a health and demographic surveillance system site in the capital Bissau. Twins (n = 209) and singletons (n = 182) were recruited from a previously established cohort. Oral glucose tolerance tests (OGTT) were performed, along with anthropometrics and collection of clinical and dietary data.
Results
Median age was 16.6 and 14.2 years between twins and singletons, respectively (P = 0.08). Mean birth weight was 2410 vs. 3090 g, respectively (P < 0.001). Twins had higher median fasting- and two hour capillary plasma glucose, 5.4(3.2–8.2) vs. 5.0(3.2–11.5) mmol/L (P < 0.001) and 6.8(3.4–11.3) vs. 6.2(3.2–12.1) mmol/L (P < 0.001), respectively, compared to singletons. The prevalence of IGT was 2.5 % (5/209) vs. 3.5 % (6/182) (RR = 0.73, 95 % CI: 0.20–2.64). 12 % (25/209) of twins had impaired fasting glucose (IFG), compared to 3.5 % (6/182) of singletons (3.63, 1.53–8.62). Dysglycemia (IGT and/or IFG or overt diabetes) was found in 17 % (35/209) vs. 9 % (16/182) (1.90, 1.08–3.37), respectively.
Conclusions
Twins had higher glucose levels in both the fasting and postprandial state. This may indicate a detrimental effect of the twin fetal environment on glucose metabolism later in life, a result contrary to Scandinavian register studies. The IGT burden was low in this young age group and the risk was similar in twins and singletons.
Electronic supplementary material
The online version of this article (doi:10.1186/s12902-016-0126-6) contains supplementary material, which is available to authorized users.
doi:10.1186/s12902-016-0126-6
PMCID: PMC4973540  PMID: 27491662
Twins; Fetal origins hypothesis; Impaired glucose tolerance; Impaired fasting glucose; Diabetes; Sub-Saharan Africa; Low birth weight
25.  Utility of repeat cytological assessment of thyroid nodules initially classified as benign: clinical insights from multidisciplinary care in an Irish tertiary referral centre 
Background
Fine needle aspiration biopsy (FNAB) is the tool of choice for evaluating thyroid nodules with the majority classified as benign following initial assessment. However, concern remains about false negative results and some guidelines have recommended routine repeat aspirates. We aimed to assess the utility of routine repeat FNAB for nodules classified as benign on initial biopsy and to examine the impact of establishing a multidisciplinary team for the care of these patients.
Methods
We performed a retrospective review of 400 consecutive patients (413 nodules) who underwent FNAB of a thyroid nodule at our hospital between July 2008 and July 2011. Data recorded included demographic, clinical, histological and radiological variables.
Results
Three hundred and fifty seven patients (89 %) were female. Median follow-up was 5.5 years. Two hundred and fifty eight (63 %) nodules were diagnosed as benign. The rate of routine repeat biopsy increased significantly over the time course of the study (p for trend = 0.012). Nine Thy 2 nodules were classified differently on the basis of routine repeat biopsy; one patient was classified as malignant on repeat biopsy and was diagnosed with papillary thyroid carcinoma. Eight were classified as a follicular lesions on repeat biopsy—six diagnosed as benign following lobectomy; two declined lobectomy and were followed radiologically with no nodule size increase.
Conclusions
The false negative rate of an initial benign cytology result, from a thyroid nodule aspirate, is low. In the setting of an experienced multidisciplinary thyroid team, routine repeat aspiration is not justified.
doi:10.1186/s12902-016-0125-7
PMCID: PMC4969652  PMID: 27485324
Thyroid nodule; Fine needle aspiration; Thyroid cytology

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