Chronic kidney disease is a common complication and concomitant condition of diabetes mellitus. The treatment of patients with diabetes and chronic kidney disease, including intensive control of blood sugar and blood pressure, has been very similar for type 1 and type 2 diabetes patients. New therapeutic targets have shown promising results and may lead to more specific treatment options for patients with type 1 and type 2 diabetes.
Espen Nordheim and Trond Geir Jenssen
Tatsuya Kondo, Nobukazu Miyakawa, Sayaka Kitano, Takuro Watanabe, Rieko Goto, Mary Ann Suico, Miki Sato, Yuki Takaki, Masaji Sakaguchi, Motoyuki Igata, Junji Kawashima, Hiroyuki Motoshima, Takeshi Matsumura, Hirofumi Kai, and Eiichi Araki
Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities, but is deteriorated by chronic metabolic insults. Heat shock (HS) with appropriate mild electrical stimulation (MES) activates HSR, and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (2 times/week, n=10), patients with metabolic syndrome (4 times/week, n=40), and patients with T2DM (n=100; 4 times/week (n=40) and 2, 4, 7 times/week (n=20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.
H Vlaardingerbroek, E.l.t Van den Akker, and A.c.s Hokken-Koelega
Obesity is reaching endemic state and has a major impact on health and economy. In most cases obesity is caused by life style factors. However, the risk of becoming obese differs highly between people. Individual differences in life style, genetic, and neuroendocrine factors play a role in satiety, hunger and regulation of body weight. In a small percentage of children and adults with obesity, an underlying hormonal or genetic cause can be found. The aim of this review is to present and compare data on the extreme ends of the obesity and undernutrition spectrum in patients with Prader-Willi syndrome (PWS), Bardet-Biedl syndrome (BBS), acquired hypothalamic obesity in craniopharyngioma patients, and anorexia nervosa. This may give more insight in the role of neuroendocrine factors and might give direction for future research in conditions of severe obesity and underweight.
Lei Hu, Xiao Liu, Chong Pei, Li Xie, and Nianan He
Objective: We evaluated the diagnostic accuracy of perinodular stiffness, four risk stratification systems (RSSs) (KWAK-TIRADS, ACR-TIRADS, EU-TIRADS, and C-TIRADS), and the combination of perinodular stiffness and these four RSSs in differentiating malignant from benign thyroid nodules (TNs).
Methods: A total of 788 TNs in 726 patients were examined with conventional ultrasound (US) examination and sound touch elastography (STE). All TNs were classified by each of the four RSSs. The stiffness inside (E) the TNs was measured by STE. The stiffness of the 2.0mm perinodular region (Eshell) was measured with the Shell measurement function of STE. The diagnostic performances of four RSSs, the E values, and the Eshell values were evaluated. All TNs were further divided into subgroups based on size (≤ 10 mm group and > 10 mm group).
Results: Ninety-six TNs were classified as benign and 692 as malignant. Among the single-method approaches, ACR-TIRADS showed the highest AUC (0.77) for differentiating malignant from benign TNs for all TNs included. Eshell showed the highest AUC (0.75) in differentiating malignant from benign TNs for TNs with sizes ≤ 10 mm, and there were no significant differences in AUC among all single methods for diagnosis of TNs with sizes > 10 mm (P > 0.05). The combination of C-TIRADS and Eshell/E yielded the highest AUC for all TNs (0.83) and for TNs with size ≤ 10 mm (0.85) compared with other combinations.
Conclusions: Eshell/E combined with conventional US improves the diagnostic accuracy in TNs, and may reduce unnecessary fine needle aspiration.
Yun Cai, Jieni Yan, Yong Gu, Heng Chen, Yang Chen, Xinyu Xu, Mei Zhang, Liping Yu, Xuqin Zheng, and Tao Yang
Objective: The most common coexisting organ-specific autoimmune disease in patients with type 1 diabetes mellitus (T1DM) is autoimmune thyroid disease (AITD). However, there have been little clinical reports based on large population about the prevalence of zinc transporter 8 autoantibody (ZnT8A) and other islet autoantibodies in AITD patients. We aimed to explore the presence of islet autoantibodies, ZnT8A, glutamic acid decarboxylase autoantibodies (GADA) and insulinoma-associated antigen 2 autoantibodies (IA-2A) compared with thyroid autoantibodies, thyroid peroxidase autoantibodies (TPOAb) and thyroglobulin autoantibodies (TGAb) and thyrotropin receptor autoantibodies (TRAb) in patients with Graves’ disease (GD), Hashimoto’s thyroiditis (HT) and T1DM patients with AITD.
Methods: Totally, 389 patients with GD, 334 patients with HT, 108 T1DM patients with AITD and 115 healthy controls (HC) were recruited in the study. Islet autoantibodies (ZnT8A, GADA and IA-2A) were detected by radioligand binding assay. Thyroid autoantibodies, TPOAb and TGAb were detected by chemiluminescence assay, and TRAb was detected by radioimmunoassay.
Results: The prevalence of ZnT8A, GADA and IA-2A was higher in GD and HT patients than that of HC (ZnT8A: GD 8.48%, HT 10.8% vs HC 1.74%; GADA: GD 7.46%, HT 7.74% vs HC 0.870%; IA-2A: GD 4.88%, HT 3.59% vs HC 0%; All P<0.05); but lower than that of T1DM subjects with AITD (ZnT8A: 42.6%; IA-2A: 44.4%; GADA: 74.1%; all P<0.0001).
Conclusions: An increased prevalence of ZnT8A as well as GADA and IA-2A was found in both GD and HT patients, indicating that there is a potential link between thyroid autoimmunity and islet autoimmunity.
David C Llewellyn, Rajaventhan Srirajaskanthan, Royce P Vincent, Catherine Guy, Eftychia E Drakou, Simon J B Aylwin, Ashley B Grossman, John K Ramage, and Georgios K Dimitriadis
Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.
Jia Liu, Lin Zhang, Jing Fu, Qiu Wang, and Guang Wang
Prolactin (PRL) has been demonstrated as a metabolic hormone to regulate energy metabolism recently. The present study aims to investigate the association between PRL and metabolic alterations in different obesity phenotypes.
A total of 451 drug-naive participants were recruited, comprising 351 obese patients and 100 age- and sex-matched healthy participants with normal weight. PRL, anthropometric, and clinical parameters were measured.
In the obesity group, 15.1% (53/351) were categorized as 'metabolically healthy obesity (MHO)'. Besides favorable blood pressure, glucose, and lipids profiles, the MHO group exhibited increased PRL, and lower levels of high-sensitivity C-reactive protein (hsCRP), homeostasis model assessment of insulin resistance (HOMA-IR), and adipose tissue insulin resistance (adipo-IR) than the metabolically unhealthy obesity (MUHO) group (PRL, HOMA-IR, and adipo-IR: P < 0.01; hsCRP: P < 0.05). The severe MUHO group showed significantly decreased PRL levels than the mild MUHO group (P < 0.05). Multivariate linear regression analysis indicated that fasting plasma glucose (FBG) and adipo-IR were significantly associated with PRL (FBG: β = −0.263, P < 0.05; adipo-IR: β = −0.464, P < 0.01). Multivariable logistic regression analysis showed that hsCRP (OR = 0.824) and PRL (OR = 1.211) were independent predictors of MHO (all P < 0.01).
The MHO group had significantly increased circulating PRL levels when compared with the control and MUHO groups, and multivariable logistic regression analysis showed that PRL was independent predictors of MHO. Our findings suggested that increased circulating PRL might be a compensatory response for favoring energy metabolism during obesity.
Henghai Huang, Qijian Ding, XiaoCao Lin, DeLin Li, Jingjing Zeng, and Weijin Fu
Background: Adrenal schwannomas (AS) are extremely rare neoplasms. This study shares our experience regarding the diagnosis and operative management of AS.
Methods: Clinical details, radiologic, laboratory, and pathologic findings as well as follow-up data were analyzed retrospectively for 13 AS patients who accepted surgery at a tertiary referral hospital in China between January 1, 1996, and December 31, 2017.
Results: The mean age of the patients at diagnosis was 44.7 ± 13.7 years (range 19–62 years; male: female ratio, 1:1.16), of whom 7 patients had unilateral AS on the right side, and the remaining 6 on the left side. None of the cases were hormonally active. None of the 13 cases were diagnosed as AS by computed tomography imaging before the operation. Among the patients, 10 were asymptomatic. The mean preoperative size was 7.1 ± 3.2 cm (range 1.6–12.6 cm). All patients underwent surgery, with open adrenalectomy in 5 patients and laparoscopy in 8 patients. The mean tumor size on pathologic examination was 6.8 ± 3.0 cm (range 3.0–11.7 cm). The surgical specimens were confirmed by pathological examination. During a median follow-up of 60.8 ± 17.7 months, no patients showed recurrence or metastasis.
Conclusion: The preoperative diagnosis of AS remains difficult despite the advances in imaging examinations. After complete resection, the prognosis of AS is excellent.
Johanna Christina Penell, Mark M. Kushnir, Lars Lind, Jonatan Bergquist, Jonas Bergquist, P. Monica Lind, and Tord Naessen
Objectives: Circulating concentrations of endogenous steroids have systemic implications for health in elderly. However, population-based age- and ethnicity-specific data are scarce. The aim was to report sex-specific plasma concentrations of endogenous sex- and adrenal steroids in elderly Swedish Caucasians, to examine the impact of BMI, and to present concentrations in apparently healthy subjects.
Methods: A population-based observational study of 70-year olds, including 684 community-dwelling men and women enrolled in the PIVUS study, Sweden. Median plasma concentrations were determined using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for pregnenolone, 17-OH-pregnenolone, 17-OH-progesterone, 11-deoxycortisol, dehydroepiandrosterone, androstenedione, testosterone, estrone and estradiol.
Results: Plasma concentrations were significantly higher in men (n=452) than in women (n=232) for estradiol: median 61.3 pmol/L (95% CI, 11.4, 142.7) vs. 18.4 (4.0, 127.3), for estrone: 92.8 (33.3, 206) vs 71.6 (17.8, 209) pmol/L, and for testosterone 13.8 (5.7, 28.0) vs. 0.7 (0.2, 2.0) nmol/L. Higher concentrations of estrone and estradiol were observed in obese than non-obese women. Compared to non-obese men, obese men had lower concentrations of testosterone and its precursors: 17-OH-pregnenolone, 17-OH-progesterone, androstenedione and dehydroepiandrosterone. The subgroup of apparently healthy individuals had median values >20% lower for estrone and estradiol in women but slightly higher for testosterone in both sexes.
Conclusions: Concentrations of estradiol, estrone and testosterone were higher in 70-year old men than in women. BMI associated positively to estradiol and estrone in women and negatively to testosterone in men. Apparently healthy women had lower median concentrations of estradiol and estrone and men higher median testosterone compared to all individuals.
Punith Kempegowda, Eka Melson, Agnes Johnson, Lucy Wallett, Lucretia Thomas, Dengyi Zhou, Catherine Holmes, Agata Juszczak, Mohammed Ali Karamat, Sandip Ghosh, Wasim Hanif, Parth Narendran, and Srikanth Bellary
COVID-19 in people with diabetes is associated with a disproportionately worse prognosis. DKA is an acute complication of diabetes with a mortality rate of approximately 0.67%. Little is known about the natural history of DKA in the presence of COVID-19. This study aimed to explore the effects of COVID-19 on presentation, clinical course and outcome in patients presenting with DKA.
Retrospective cohort study.
All patients treated for DKA between 1 March 2020 and 30 May 2020 were included. Patients were categorised as COVID-positive or COVID-negative based on the swab test. A pre-COVID group was established using data from 01 March 2019 to 30 May 2019 as external control. Data regarding demographics, diabetes type, pH, bicarbonate, lactate, glucose, DKA duration, complications and outcome were collected.
A total of 88 DKA episodes were included in this study. There was no significant difference in the severity or duration of DKA between the three groups. COVID-positive T1DM were more hyperglycaemic on admission compared to COVID-negative and pre-COVID patients. There was an over representation of T2DM in COVID-positive patients with DKA than in pre-COVID or COVID-negative groups.
COVID-19 appears to influence the natural history of DKA differently in T1DM and T2DM. Patients with T1DM and COVID-19 presented with more hyperglycaemia (60 mmol/L (35.9–60.0) vs 31.4 mmol/L (28.0–39.1) vs 24 mmol/L (20.2–33.75), respectively). Patients with T2DM were unusually presenting in DKA when infected with COVID-19 with greater ICU need and higher mortality rates. A collaborative, multi-centre study is needed to provide more definitive results.