Diet-induced weight loss alters hepatic glucocorticoid metabolism in type 2 diabetes mellitus

Context: Altered tissue-specific glucocorticoid metabolism has been described in uncomplicated obesity and type 2 diabetes. We hypothesized that weight loss induced by diet and exercise, which has previously been shown to reverse abnormal cortisol metabolism in uncomplicated obesity, also normalizes cortisol metabolism in patients with type 2 diabetes. Objective: Test the effects of a diet intervention with added exercise on glucocorticoid metabolism. Design: Two groups followed a Paleolithic diet (PD) for 12 weeks with added 180 min of structured aerobic and resistance exercise per week in one randomized group (PDEX). Setting: Umea University Hospital. Participants: Men and women with type 2 diabetes treated with lifestyle modification +/- metformin were included. Twenty-eight participants (PD, n = 15; PDEX, n = 13) completed measurements of glucocorticoid metabolism. Main outcome measures: Changes in glucocorticoid metabolite levels in 24-h urine samples, expression of HSD1181 mRNA in s.c. adipose tissue and conversion of orally administered cortisone to cortisol measured in plasma. Body composition and insulin sensitivity were measured using a hyperinsulinemic-euglycemic clamp, and liver fat was measured by magnetic resonance spectroscopy. Results: Both groups lost weight and improved insulin sensitivity. Conversion of orally taken cortisone to plasma cortisol and the ratio of 5 alpha-THF + 5 beta-THF/THE in urine increased in both groups. Conclusions: These interventions caused weight loss and improved insulin sensitivity with concomitant increases in the conversion of cortisone to cortisol, which is an estimate of hepatic HSD11B1 activity. This suggests that dysregulation of liver glucocorticoid metabolism in these patients is a consequence rather than a cause of metabolic dysfunction

Трансоральная тиреоид- и паратиреоидэктомия: серия наблюдений

ЩИТОВИДНОЙ ЖЕЛЕЗЫ БОЛЕЗНИПАРАЩИТОВИДНЫХ ЖЕЛЕЗ БОЛЕЗНИОКОЛОЩИТОВИДНЫХ ЖЕЛЕЗ БОЛЕЗНИЭНДОКРИННЫЕ ХИРУРГИЧЕСКИЕ ОПЕРАЦИИХИРУРГИЯ ЭНДОКРИННЫХ ЖЕЛЕЗТИРЕОИДЭКТОМИЯЭНДОСКОПИЧЕСКАЯ ТЕХНИКАПАРАТИРЕОИДЭКТОМИЯОКОЛОЩИТОВИДНОЙ ЖЕЛЕЗЫ УДАЛЕНИЕТРАНСОРАЛЬНЫЙ ДОСТУПТРАНСОРАЛЬНАЯ ХИРУРГИЯ ШЕИДЕРМАТОЛОГИЧЕСКИЙ ИНДЕКСКАЧЕСТВО ЖИЗНИЦель. Представить результаты собственной серии трансоральных операций у пациентов с заболеваниями щитовидной и околощитовидных желез. Материал и методы. Трансоральная операция выполнена 20 женщинам и 1 мужчине. Все пациенты оперированы по поводу первичного заболевания и соответствовали критериям отбора на основании ультразвукового и цитологического исследований, гормонального фона, соматического статуса. Показаниями к операции в 17 случаях явился узловой зоб, в 2 случаях – диффузный токсический зоб, в 2 случаях – первичный гиперпаратиреоз, аденома околощитовидной железы. Хирургическая техника включала в себя трехпортовый доступ в нижнем своде преддверия рта и газовый способ поддержания рабочей полости. Для операции использовались стандартные лапароскопические инструменты и ультразвуковое энергетическое устройство. В послеоперационном периоде пациенты прошли тест по субъективной оценке эстетического результата операции с использованием опросника дерматологического индекса качества жизни. Результаты. Тиреоидэктомия выполнена 4 пациентам, 15 пациентам – гемитиреоидэктомия и 2 пациентам – паратиреоидэктомия. У одной пациентки трансоральная паратиреоидэктомия выполнена в составе симультанной операции по поводу синдрома множественной эндокринной неоплазии 1 типа. У двух пациентов после операции верифицирован папиллярный рак T1N0M0. Среднее время операции составило 196,1 мин (диапазон 110 – 300 мин). Средняя кровопотеря 39,5 мл (диапазон 10 – 300 мл). На девятой по счету операции потребовалась конверсия вследствие неконтролируемого кровотечения. В одном случае отмечен преходящий парез возвратного гортанного нерва, в одном случае гематома. После операции медиана и среднее значение дерматологического индекса качества жизни составили 1 (0; 4) и 2,05 соответственно, что свидетельствует о незначительном влиянии на качество жизни. Заключение. Трансоральная эндоскопическая операция на щитовидной и околощитовидных железах перспективна в отношении оптимального выбора у пациентов, желающих избежать рубца на шее.Objective. To present the results of the author’s own series of transoral operations in patients with pathology of the thyroid and parathyroid glands. Methods. Transoral surgery was performed in women (n=20) and man (n=1). All patients were operated on for the primary disease and met the selection criteria based on ultrasound and cytological examinations, hormonal levels, and somatic status. Indications for surgery were: nodular goiter in 17 cases, diffuse toxic goiter – in 2 cases, parathyroid adenoma – in 2 cases. The surgical technique included a three-port approach in the lower fornix of the vestibule of the mouth and a gas technique for maintaining the working cavity. Standard laparoscopic instruments and an energy based ultrasonic device were used for the operation. In the postoperative period, patients underwent a test for subjective assessment of the aesthetic result of the operation using the survey of the dermatology life quality index. Results. Thyroidectomy was performed in 4 patients, hemithyroidectomy – in 15 patients and parathyroidectomy – in 2 patients. In one patient, transoralparathyroidectomy was performed as a part of a simultaneous operation for multiple endocrine neoplasia type 1 syndrome. Papillary cancer T1N0M0 was verified in two patients after surgery. The mean operation time was 196.1 min (range 110 – 300 min). Average blood loss – 39.5 ml (range 10 – 300 ml). The nineth operation required the conversion due to severe bleeding. In one case, the temporary recurrent laryngeal nerve (RLN) injury was reported, in one case – hematoma. After surgery, the median and average values of the dermatology life quality index were 1 (IQR 0-4) and 2.05, respectively, which indicates an insignificant effect on the quality of life. Conclusion. Transoral endoscopic surgery on the thyroid and parathyroid glands would be the promising optimal choice in patients to avoid scarring on the neck

Effekter av livsstilsförändring på hjärnfunktion och stresshormoner vid fetma och typ 2 diabetes

Background Obesity and associated metabolic dysregulation are linked to impaired cognitive function and alterations in brain structure, which increases the risk of age-related dementia. Increased glucocorticoid (GC) exposure may be a potential mediator of these negative effects on the brain. Methods and results In paper 1, we tested the relationship between cortisol levels, brain morphology and cognitive function in 200 women and men. Salivary cortisol levels were negatively related to cortical surface areas in prefrontal brain regions in both sexes. In participants with type 2 diabetes, high salivary cortisol levels were associated with lower memory performance. In paper 2, we tested in 70 overweight women the effects on tissue-specific GC metabolism of a Paleolithic diet or a diet following the Nordic nutrition recommendations. The 24-month interventions led to decreased expression of the GC-activating enzyme 11βHSD1 in adipose tissue, interpreted as a normalization of an obesity-related disturbance in GC metabolism. Furthermore, GC metabolism by 5α-reductase increased substantially after 2 years, an unexpected and novel result. The outcomes did not differ by diet. In paper 3, 20 women included in paper 2 were examined with functional magnetic resonance imaging (fMRI) while performing a memory task at baseline and after 6 months. Memory performance improved and functional brain responses increased in the hippocampus. Once again, the results were similar in both diet groups. In paper 4, 24 overweight participants with type 2 diabetes were examined with fMRI, using the same memory test as in paper 3, at baseline and after 12 weeks of intervention with a Paleolithic diet with or without exercise training. Functional brain response increased in the hippocampus, but memory was not improved. The addition of physical exercise did not alter the results. Conclusion Cortisol levels are linked to prefrontal brain structure and, at least in type 2 diabetes, lower memory performance. Furthermore, the dysregulated GC metabolism in obesity can be reversed by long-term diet- induced weight loss. Finally, dietary interventions with associated metabolic improvements alter functional brain responses during memory testing, including increased activation of the hippocampus. Whether these changes are linked to alterations in GC exposure and mediate improved cognition requires further study.

Overcoming the struggle of living with type 2 diabetes - diabetes specialist nurses and patients perspectives on digital interventions

BackgroundDiabetes self-management education and support (DSMES) is a cornerstone in the treatment of type 2 diabetes mellitus (T2DM). It is unclear whether delivering DSMES as a digital health intervention (DHI) might meet the needs experienced by patients with T2DM and diabetes specialist nurses (DSN) of the primary health care system in Sweden.MethodsFourteen patients with T2DM and four DSN participated in three separate focus groups: two groups comprised patients and one group comprised DSN. The patients discussed the questions: "What needs did you experience after your T2DM diagnosis?" and "How might these needs be met with a DHI?" The DSN discussed the questions: "What needs do you experience when treating a patient with newly diagnosed T2DM?" and "How might these needs be met with a DHI?". Furthermore, data were collected in the form of field notes from group discussions at a meeting including 18 DSNs working with T2DM in PHCCs. The discussions from focus groups were transcribed verbatim and analyzed together with the field notes from the meeting using inductive content analysis.ResultsThe analysis yielded the overall theme: "Overcoming the struggle of living with T2DM", which was summarized in two categories: "learning and being prepared" and "giving and receiving support". Important findings were that, for success, a DHI for DSMES must be integrated into routine care, provide structured, high-quality information, suggest tasks to stimulate behavioral changes, and provide feedback from the DSN to the patient.ConclusionThis study highlighted several important aspects, from the perspectives of both the patient with T2DM and the DSN, which should be taken into consideration for the successful development and use of a DHI for DSMES

Sex and age differences in the incidence of acute myocardial infarction during the COVID-19 pandemic in a Swedish health-care region without lockdown : a retrospective cohort study

Background The incidence of acute myocardial infarction has decreased during the COVID-19 pandemic, but sex and age differences in this change in incidence have not been tested. Thus, we aimed to compare the incidence of acute myocardial infarction in a health-care region in Sweden during the COVID-19 pandemic with previous years and to evaluate sex and age differences. Methods We did a retrospective, observational cohort study using data from a national registry of patients admitted to coronary care units in Sweden. All patients admitted to one of three hospitals in Region Jonkoping County with a diagnosis of acute myocardial infarction during the COVID-19 pandemic (March 1 to July 31, 2020) or reference period (March 1 to July 31, 2017-19) were included. The incidence of acute myocardial infarction (ST-elevation and non-ST-elevation) was calculated for both study periods. Participants were grouped according to sex and age (<70 years vs >= 70 years). The incidence and the incidence rate ratio (IRR) between the two study periods was calculated for each group and compared between groups using the Breslow-Day test. Findings The study included 1088 participants, 846 who were admitted for acute myocardial infarction during the reference period and 242 who were admitted during the COVID-19 pandemic period. The IRR of acute myocardial infarction for the COVID-19 period compared with the reference period was 0.85 (95% CI 0.73-0.98). The IRR for acute myocardial infarction was significantly lower among women aged 70 years or older (0.56 [0.40-0.78]) than among men aged 70 years or older (0.97 [0.77-1.23]; p=0.0074). Interpretation The incidence of acute myocardial infarction decreased predominantly among women aged 70 years or older during the COVID-19 pandemic. This highlights potential sex differences in health effects of the COVID-19 pandemic, which should be further elucidated. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd

Using a paleo ratio to assess adherence to paleolithic dietary recommendations in a randomized controlled trial of individuals with type 2 diabetes

This study is a secondary analysis of a randomized controlled trial using Paleolithic diet and exercise in individuals with type 2 diabetes. We hypothesized that increased adherence to the Paleolithic diet was associated with greater effects on blood pressure, blood lipids and HbA1c independent of weight loss. Participants were asked to follow a Paleolithic diet for 12 weeks and were randomized to supervised exercise or general exercise recommendations. Four-day food records were analyzed, and food items characterized as “Paleolithic” or “not Paleolithic”. Foods considered Paleolithic were lean meat, poultry, fish, seafood, fruits, nuts, berries, seeds, vegetables, and water to drink; “not Paleolithic” were legumes, cereals, sugar, salt, processed foods, and dairy products. A Paleo ratio was calculated by dividing the Paleolithic calorie intake by total calorie intake. A mul-tiple regression model predicted the outcome at 12 weeks using the Paleo ratio, group affiliation, and outcome at baseline as predictors. The Paleo ratio increased from 28% at baseline to 94% after the intervention. A higher Paleo ratio was associated with lower fat mass, BMI, waist circumference, sys-tolic blood pressure, and serum triglycerides at 12 weeks, but not with lower HbA1c levels. The Paleo ratio predicted triglyceride levels independent of weight loss (p = 0.046). Moreover, an increased monounsaturated/saturated fatty acids ratio and an increased polyunsaturated/saturated fatty acids ratio was associated with lower triglyceride levels independent of weight loss. (p = 0.017 and p = 0.019 respectively). We conclude that a higher degree of adherence to the Paleolithic diet recommendations improved fat quality and was associated with improved triglyceride levels independent of weight loss among individuals with type 2 diabetes

A Paleolithic Diet with and without Combined Aerobic and Resistance Exercise Increases Functional Brain Responses and Hippocampal Volume in Subjects with Type 2 Diabetes

Type 2 diabetes is associated with impaired episodic memory functions and increased risk of different dementing disorders. Diet and exercise may potentially reverse these impairments. In this study, sedentary individuals with type 2 diabetes treated by lifestyle ± metformin were randomized to a Paleolithic diet (PD, n = 12) with and without high intensity exercise (PDEX, n = 12) for 12 weeks. Episodic memory function, associated functional brain responses and hippocampal gray matter volume was measured by magnetic resonance imaging. A matched, but not randomized, non-interventional group was included as a reference (n = 6). The PD included a high intake of unsaturated fatty acids and protein, and excluded the intake of dairy products, grains, refined sugar and salt. The exercise intervention consisted of 180 min of supervised aerobic and resistance exercise per week. Both interventions induced a significant weight loss, improved insulin sensitivity and increased peak oxygen uptake without any significant group differences. Furthermore, both interventions were associated with increased functional brain responses within the right anterior hippocampus, right inferior occipital gyrus and increased volume of the right posterior hippocampus. There were no changes in memory performance. We conclude that life-style modification may improve neuronal plasticity in brain areas linked to cognitive function in type 2 diabetes. Putative long-term effects on cognitive functions including decreased risk of dementing disorders await further studies. Clinical trials registration number: Clinicaltrials. gov NCT01513798

Oral glucose tolerance testing as a complement to fasting plasma glucose in screening for type 2 diabetes : population-based cross-sectional analyses of 146 000 health examinations in Västerbotten, Sweden

OBJECTIVE: To assess the effect of adding an oral glucose tolerance test (OGTT) to fasting plasma glucose (FPG) in terms of detection of type 2 diabetes (T2D) and impaired glucose tolerance (IGT). DESIGN: Retrospective analysis of serial cross-sectional screening study. SETTING: Population-based health examinations within primary care in Västerbotten County, Sweden. PARTICIPANTS: Individuals aged 40- 50 and 60 years with participation from 1985 to 2017. Those with previously diagnosed diabetes and FPG≥7 mmol/L were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Prevalence of hyperglycaemia on the OGTT (IGT and T2D defined as 2-hour postload capillary plasma glucose of 8.9-12.1 mmol/L and ≥12.2 mmol/L, respectively). Analyses were further stratified by age, sex and risk factor burden to identify groups at high or low risk of IGT and T2D on testing. The numbers needed to screen (NNS) to prevent one case of T2D through detection and treatment of IGT was estimated, combining prevalence numbers with average progression rates and intervention effects from previous meta-analyses. RESULTS: The prevalence of IGT ranged from 0.9% (95% CI 0.7% to 1.1%) to 29.6% (95% CI 27.4% to 31.7%), and the prevalence of T2D ranged from 0.06% (95% CI 0.02% to 0.11%) to 7.0% (95% CI 5.9% to 8.3%), depending strongly on age, sex and risk factor burden. The estimated NNS to prevent one case of T2D through detection and lifestyle treatment of IGT ranged from 1332 among 40-year-old men without risk factors, to 39 among 60-year-old women with all risk factors combined. CONCLUSIONS: The prevalence of hyperglycaemia on OGTT is highly dependent on age, sex and risk factor burden; OGTT should be applied selectively to high-risk groups to avoid unnecessary testing in the general population

Standard Modifiable Cardiovascular Risk Factors Mediate the Association Between Elevated Hair Cortisol Concentrations and Coronary Artery Disease

BackgroundIncreased cortisol exposure is a risk factor for coronary artery disease (CAD). It is not clear to what degree this risk is independent from the standard modifiable risk factors (SMuRFs) dyslipidemia, hypertension, and diabetes. AimTo use path analysis to test the direct and indirect association, mediated by SMuRFs, between long-term cortisol levels measured in hair cortisol concentration (HCC) and CAD. MethodsHair was sampled from patients admitted with acute myocardial infarction (n = 203) and a population-based sample without a diagnosis or symptoms of CAD (n = 3,134). The HCC was analyzed using radioimmunoassay and all the participants reported whether they were diagnosed with or treated for diabetes, hypertension, and hyperlipidemia. Path analysis was used to test to what degree the association between logarithmized (ln) HCC and CAD was direct or indirect, mediated by SMuRFs. ResultsParticipants with CAD had elevated HCC compared to those without elevated HCC [median interquartile range (IQR): 75.2 (167.1) vs. 23.6 (35.0) pg/mg, p < 0.0001]. Higher HCC was associated with diabetes, hypertension, and hyperlipidemia, which, in turn, were associated with CAD. In path models, 80% of the association between ln(HCC) and CAD were mediated by SMuRFs, while the direct path between ln(HCC) and CAD was not statistically significant. ConclusionThe SMuRFs diabetes, hyperlipidemia, and hypertension mediate the association between ln(HCC) and CAD. Some association between ln(HCC) and CAD did not operate via the SMuRFs considered and might have a pathway through atherosclerosis or inflammation

A heterogeneous response of liver and skeletal muscle fat to the combination of a Paleolithic diet and exercise in obese individuals with type 2 diabetes : a randomised controlled trial

Aims/hypothesis: The aim of the study was to investigate ectopic fat deposition and insulin sensitivity, in a parallel single-blinded randomised controlled trial, comparing Paleolithic diet alone with the combination of Paleolithic diet and exercise in individuals with type 2 diabetes. Methods: Thirty-two individuals with type 2 diabetes with BMI 25-40 kg/m(2) and 30-70 years of age followed a Paleolithic diet ad libitum for 12 weeks. In addition, study participants were randomised by computer program to either supervised combined exercise training (PD-EX group) or standard care exercise recommendations (PD group). Staff performing examinations and assessing outcomes were blinded to group assignment. Thirteen participants were analysed in each group: hepatic and peripheral insulin sensitivity were measured using the hyperinsulinaemic-euglycaemic clamp technique combined with [6,6-H-2(2)]glucose infusion, and liver fat was assessed by proton magnetic resonance spectroscopy; both analyses were secondary endpoints. Intramyocellular lipid (IMCL) content was measured by magnetic resonance spectroscopy as a secondary analysis. All examinations were performed at Umca University Hospital, Umca, Sweden. Results: Both study groups showed a median body weight loss of 7 kg. Fat mass decreased by 5.7 kg in the PD group and by 6.5 kg in the PD-EX group. Maximum oxygen uptake increased in the PD-EX group only. Liver fat showed a consistent reduction (74% decrease) in the PD group, while the response in the PD-EX group was heterogeneous (p < 0.05 for the difference between groups). IMCL content of the soleus muscle decreased by 40% in the PD group and by 22% in the PD-EX group (p < 0.05 for the difference between groups). Both groups improved their peripheral and adipose tissue insulin sensitivity, but not their hepatic insulin sensitivity. Plasma fetuin-A decreased by 11% in the PD group (p < 0.05) and remained unchanged in the PD-EX group. Liver fat changes during the intervention were correlated with changes in fetuin-A (r(S) = 0.63, p < 0.01). Participants did not report any important adverse events caused by the intervention. Conclusions/interpretation: A Paleolithic diet reduced liver fat and IMCL content, while there was a tissue-specific heterogeneous response to added exercise training