Search for other papers by Rama Lakshman in
Google Scholar
PubMed
Cambridge University Hospitals NHS Foundation Trust, Wolfson Diabetes and Endocrine Clinic, Cambridge, UK
Search for other papers by Charlotte Boughton in
Google Scholar
PubMed
Search for other papers by Roman Hovorka in
Google Scholar
PubMed
Automated insulin delivery systems, also known as closed-loop or ‘artificial pancreas’ systems, are transforming the management of type 1 diabetes. These systems consist of an algorithm which responds to real-time glucose sensor levels by automatically modulating insulin delivery through an insulin pump. We review the rapidly changing landscape of automated insulin-delivery systems over recent decades, from initial prototypes to the different hybrid closed-loop systems commercially available today. We discuss the growing body of clinical trials and real-world evidence demonstrating their glycaemic and psychosocial benefits. We also address future directions in automated insulin delivery such as dual-hormone systems and adjunct therapy as well as the challenges around ensuring equitable access to closed-loop technology.
Search for other papers by Merlin C Thomas in
Google Scholar
PubMed
Search for other papers by Brendon L Neuen in
Google Scholar
PubMed
Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW, Australia
Search for other papers by Stephen M Twigg in
Google Scholar
PubMed
Search for other papers by Mark E Cooper in
Google Scholar
PubMed
Department of Renal Medicine, St George Hospital, Sydney, NSW, Australia
Faculty of Medicine and Health, University of New South Wales, Sydney, NSW, Australia
Search for other papers by Sunil V Badve in
Google Scholar
PubMed
Sodium‐glucose co-transporter 2 (SGLT2) inhibitors have recently emerged as an effective means to protect kidney function in people with type 2 diabetes and chronic kidney disease (CKD). In this review, we explore the role of SGLT2 inhibition in these individuals. SGLT2 inhibitors specifically act to inhibit sodium and glucose reabsorption in the early proximal tubule of the renal nephron. Although originally developed as glucose-lowering agents through their ability to induce glycosuria, it became apparent in cardiovascular outcome trials that the trajectory of kidney function decline was significantly slowed and the incidence of serious falls in kidney function was reduced in participants receiving an SGLT2 inhibitor. These observations have recently led to specific outcome trials in participants with CKD, including DAPA-CKD, CREDENCE and EMPA-KIDNEY, and real-world studies, like CVD-REAL-3, that have confirmed the observation of kidney benefits in this setting. In response, recent KDIGO Guidelines have recommended the use of SGLT2 inhibitors as first-line therapy in patients with CKD, alongside statins, renin–angiotensin–aldosterone system inhibitors and multifactorial risk factor management as indicated. However, SGLT2 inhibitors remain significantly underutilized in the setting of CKD. Indeed, an inertia paradox exists, with patients with more severe disease less likely to receive an SGLT2 inhibitor. Concerns regarding safety appear unfounded, as acute kidney injury, hyperkalaemia, major acute cardiovascular events and cardiac death in patients with CKD appear to be lower following SGLT2 inhibition. The first-in-class indication of dapagliflozin for CKD may begin a new approach to managing kidney disease in type 2 diabetes.
Search for other papers by Yinqiong Huang in
Google Scholar
PubMed
Department of Endocrinology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, China
Search for other papers by Zhaozhao Zhu in
Google Scholar
PubMed
Search for other papers by Zhiqin Huang in
Google Scholar
PubMed
Search for other papers by Jingxiong Zhou in
Google Scholar
PubMed
Background
Diabetic kidney disease (DKD) has become a major cause of chronic kidney disease. However, early diagnosis of DKD is challenging. Trimethylamine oxide (TMAO) is an intestinal microbial metabolite which might be associated with diabetes complications. The aim of this study was to investigate the correlation between TMAO and DKD.
Methods
A cross-sectional study was conducted. A total of 108 T2DM patients and 33 healthy subjects were enrolled in this study. Multiple logistic regression analyses and area under receiver operating characteristic curves (AUROC) were performed to evaluate the correlation between serum TMAO and DKD.
Results
Serum TMAO levels were significantly higher in DKD patients than healthy control group and the NDKD (T2DM without combined DKD) group (P < 0.05). TMAO levels were negatively correlated with eGFR and positively correlated with urea nitrogen, ACR and DKD (P < 0.05). Logistic regression analysis indicated that serum TMAO was one of the independent risk factors for DKD patients (P < 0.05). In the diagnostic model, the AUROC of TMAO for the diagnosis of DKD was 0.691.
Conclusion
Elevated levels of serum TMAO levels were positively associated with the risk of DKD in T2DM patients, which might be a potential biomarker for DKD.
Search for other papers by Yansu Wang in
Google Scholar
PubMed
Search for other papers by Yun Shen in
Google Scholar
PubMed
Search for other papers by Tingting Hu in
Google Scholar
PubMed
Search for other papers by Yufei Wang in
Google Scholar
PubMed
Search for other papers by Xiaojing Ma in
Google Scholar
PubMed
Search for other papers by Haoyong Yu in
Google Scholar
PubMed
Search for other papers by Yuqian Bao in
Google Scholar
PubMed
Objective
Clusterin is closely correlated with insulin resistance and its associated comorbidities. This study aimed to investigate the correlation between serum clusterin levels and non-alcoholic fatty liver disease (NAFLD) and further explore the mediating role of insulin resistance in this relationship.
Methods
This study enrolled 195 inpatients (41 males and 154 females) aged 18–61 years. Twenty-four patients were followed up for 12 months after bariatric surgery. Serum clusterin levels were measured using a sandwich enzyme-linked immunosorbent assay. Fatty liver disease was diagnosed on the basis of liver ultrasonography. The fatty liver index (FLI) was calculated to quantify the degree of hepatic steatosis. The mediating role of homeostasis model assessment-insulin resistance (HOMA-IR) was assessed using mediation analysis.
Results
Participants with NAFLD had significantly higher serum clusterin levels than those without NAFLD (444.61 (325.76–611.52) mg/L vs 294.10 (255.20–373.55) mg/L, P < 0.01). With increasing tertiles of serum clusterin levels, the prevalence of NAFLD displayed an upward trend (P < 0.01). Multivariate linear regression analysis showed that serum clusterin levels were a positive determinant of FLI (standardized β = 0.271, P < 0.001) after adjusting for multiple metabolic risk factors. Serum clusterin levels significantly decreased after bariatric surgery (298.77 (262.56–358.10) mg/L vs 520.55 (354.94–750.21) mg/L, P < 0.01). In the mediation analysis, HOMA-IR played a mediating role in the correlation between serum clusterin levels and FLI; the estimated percentage of the total effect was 17.3%.
Conclusion
Serum clusterin levels were associated with NAFLD. In addition, insulin resistance partially mediated the relationship between serum clusterin levels and FLI.
Search for other papers by Jared G Friedman in
Google Scholar
PubMed
Search for other papers by Kasey Coyne in
Google Scholar
PubMed
Search for other papers by Grazia Aleppo in
Google Scholar
PubMed
Search for other papers by Emily D Szmuilowicz in
Google Scholar
PubMed
Hemoglobin A1c (HbA1c) has long been considered a cornerstone of diabetes mellitus (DM) management, as both an indicator of average glycemia and a predictor of long-term complications among people with DM. However, HbA1c is subject to non-glycemic influences which confound interpretation and as a measure of average glycemia does not provide information regarding glucose trends or about the occurrence of hypoglycemia and/or hyperglycemia episodes. As such, solitary use of HbA1c, without accompanying glucose data, does not confer actionable information that can be harnessed to guide targeted therapy in many patients with DM. While conventional capillary blood glucose monitoring (BGM) sheds light on momentary glucose levels, in practical use the inherent infrequency of measurement precludes elucidation of glycemic trends or reliable detection of hypoglycemia or hyperglycemia episodes. In contrast, continuous glucose monitoring (CGM) data reveal glucose trends and potentially undetected hypo- and hyperglycemia patterns that can occur between discrete BGM measurements. The use of CGM has grown significantly over the past decades as an ever-expanding body of literature demonstrates a multitude of clinical benefits for people with DM. Continually improving CGM accuracy and ease of use have further fueled the widespread adoption of CGM. Furthermore, percent time in range correlates well with HbA1c, is accepted as a validated indicator of glycemia, and is associated with the risk of several DM complications. We explore the benefits and limitations of CGM use, the use of CGM in clinical practice, and the application of CGM to advanced diabetes technologies.
Search for other papers by Patricia Arroyo Tardio in
Google Scholar
PubMed
Search for other papers by Gabriela Baldini in
Google Scholar
PubMed
University Clinic of Medicine, Cantonal Hospital Baselland, Liestal, Switzerland
Search for other papers by Eleonora Seelig in
Google Scholar
PubMed
Objective
Hypercortisolism is a risk factor for obesity. Cortisol increases in response to food intake in lean subjects. In obese subjects, disturbances of the food-induced cortisol peak were reported, but data from sufficiently powered and well-controlled trials are lacking. Understanding the cortisol response to food is essential as amplified or recurrent cortisol surges could lead to hypercortisolism and contribute to obesity. Therefore, we investigate the cortisol response to food in lean and obese subjects.
Design
This is a non-randomized, open-label study.
Methods
We assessed serum cortisol values after a high-calorie meal in lean and obese male subjects. Cortisol levels were frequently assessed before and for 3 h after food intake.
Results
A total of 36 subjects (18 lean and 18 obese) were included. There was no difference in overall cortisol levels between both groups during the study (area under the curve (AUC) obese: 55,409 ± 16,994, lean: 60,334 ± 18,001, P = 0.4). Total cortisol levels reached peak concentrations 20 min after food intake in both groups; the maximum cortisol increase was similar in both groups (cortisol increase obese: 69.6 ± 135.5 nmol/L, lean: 134.7 ± 99.7 nmol/L; P = 0.1). There was no correlation between body mass index and baseline cortisol values (R 2 = 0.001, P = 0.83), cortisol increase (R 2 = 0.05, P = 0.17), or cortisol AUC (R 2 = 0.03, P = 0.28).
Conclusions
This study demonstrates that high-calorie food intake causes an immediate and substantial cortisol response in lean and obese subjects and is independent of body weight.
Significance statement
This study demonstrates that high-calorie food intake causes an immediate and substantial cortisol response in lean and obese subjects, independent of body weight. In contrast to the current literature, our findings show that the physiological cortisol response to food is intact in obesity. The substantial and prolonged increase further supports the hypothesis that frequent high-calorie meals cause hypercortisolism and aggravate weight gain.
Search for other papers by Felix Reschke in
Google Scholar
PubMed
Search for other papers by Torben Biester in
Google Scholar
PubMed
Search for other papers by Thekla von dem Berge in
Google Scholar
PubMed
Search for other papers by Dagmar Jamiolkowski in
Google Scholar
PubMed
Search for other papers by Laura Hasse in
Google Scholar
PubMed
Search for other papers by Francesca Dassie in
Google Scholar
PubMed
Search for other papers by Pietro Maffei in
Google Scholar
PubMed
Search for other papers by Katharina Klee in
Google Scholar
PubMed
Search for other papers by Olga Kordonouri in
Google Scholar
PubMed
Search for other papers by Hagen Ott in
Google Scholar
PubMed
Search for other papers by Thomas Danne in
Google Scholar
PubMed
As the most visible and vulnerable organ of the human organism, the skin can provide an impression of its state of health. Rare forms of diabetes and endocrinopathies are often diagnosed late or primarily misinterpreted due to their rarity. Skin peculiarities associated with these rare diseases may be indicative of the underlying endocrinopathy or form of diabetes. At the same time, rare skin changes in diabetes or endocrinopathies can also be a major challenge for dermatologists, diabetologists and endocrinologists in optimal patient and therapy management. Active collaboration between these different specialist groups can therefore lead to increased patient safety, better therapeutic success and more targeted diagnostics.
Search for other papers by Jan W Eriksson in
Google Scholar
PubMed
Search for other papers by Reem A Emad in
Google Scholar
PubMed
Search for other papers by Martin H Lundqvist in
Google Scholar
PubMed
Search for other papers by Niclas Abrahamsson in
Google Scholar
PubMed
Search for other papers by Maria C Kjellsson in
Google Scholar
PubMed
This study aimed to characterize how the dysregulation of counter-regulatory hormones can contribute to insulin resistance and potentially to diabetes. Therefore, we investigated the association between insulin sensitivity and the glucose- and insulin-dependent secretion of glucagon, adrenocorticotropic hormone (ACTH), and cortisol in non-diabetic individuals using a population model analysis. Data, from hyperinsulinemic–hypoglycemic clamps, were pooled for analysis, including 52 individuals with a wide range of insulin resistance (reflected by glucose infusion rate 20–60 min; GIR20–60min). Glucagon secretion was suppressed by glucose and, to a lesser extent, insulin. The GIR20–60min and BMI were identified as predictors of the insulin effect on glucagon. At normoglycemia (5 mmol/L), a 90% suppression of glucagon was achieved at insulin concentrations of 16.3 and 43.4 µU/mL in individuals belonging to the highest and lowest quantiles of insulin sensitivity, respectively. Insulin resistance of glucagon secretion explained the elevated fasting glucagon for individuals with a low GIR20–60min. ACTH secretion was suppressed by glucose and not affected by insulin. The GIR20–60min was superior to other measures as a predictor of glucose-dependent ACTH secretion, with 90% suppression of ACTH secretion by glucose at 3.1 and 3.5 mmol/L for insulin-sensitive and insulin-resistant individuals, respectively. This difference may appear small but shifts the suppression range into normoglycemia for individuals with insulin resistance, thus, leading to earlier and greater ACTH/cortisol response when the glucose falls. Based on modeling of pooled glucose-clamp data, insulin resistance was associated with generally elevated glucagon and a potentiated cortisol-axis response to hypoglycemia, and over time both hormonal pathways may therefore contribute to dysglycemia and possibly type 2 diabetes.
German Center for Diabetes Research (DZD), Neuherberg, Germany
Search for other papers by Marie Auzanneau in
Google Scholar
PubMed
German Center for Diabetes Research (DZD), Neuherberg, Germany
Search for other papers by Alexander J Eckert in
Google Scholar
PubMed
Department of Internal Medicine IV, University Hospital Tübingen, Germany
Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany
Search for other papers by Andreas Fritsche in
Google Scholar
PubMed
Division of Endocrinology and Diabetology, Department of Internal Medicine 1, University Hospital Ulm, Ulm, Germany
Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital Tübingen, Tübingen, Germany
Search for other papers by Martin Heni in
Google Scholar
PubMed
Institute of Health Services Research and Health Economics, Center for Health and Society, Faculty of Medicine, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Institute of Health Services Research and Health Economics, German Diabetes Center (DDZ), Leibniz Centre for Diabetes Research at Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
Search for other papers by Andrea Icks in
Google Scholar
PubMed
Department of Psychiatry and Psychotherapy II, University Hospital Ulm, Um, Germany
Search for other papers by Annabel S Mueller-Stierlin in
Google Scholar
PubMed
Search for other papers by Ana Dugic in
Google Scholar
PubMed
Search for other papers by Alexander Risse in
Google Scholar
PubMed
German Center for Diabetes Research (DZD), Neuherberg, Germany
Search for other papers by Stefanie Lanzinger in
Google Scholar
PubMed
German Center for Diabetes Research (DZD), Neuherberg, Germany
Search for other papers by Reinhard W Holl in
Google Scholar
PubMed
Objective
To analyze the proportion of diabetes among all hospitalized cases in Germany between 2015 and 2020.
Methods
Using the nationwide Diagnosis-Related-Groups statistics, we identified among all inpatient cases aged ≥ 20 years all types of diabetes in the main or secondary diagnoses based on ICD-10 codes, as well all COVID-19 diagnoses for 2020.
Results
From 2015 to 2019, the proportion of cases with diabetes among all hospitalizations increased from 18.3% (3.01 of 16.45 million) to 18.5% (3.07 of 16.64 million). Although the total number of hospitalizations decreased in 2020, the proportion of cases with diabetes increased to 18.8% (2.73 of 14.50 million). The proportion of COVID-19 diagnosis was higher in cases with diabetes than in those without in all sex and age subgroups. The relative risk (RR) for a COVID-19 diagnosis in cases with vs without diabetes was highest in age group 40–49 years (RR in females: 1.51; in males: 1.41).
Conclusions
The prevalence of diabetes in the hospital is twice as high as the prevalence in the general population and has increased further with the COVID-19 pandemic, underscoring the increased morbidity in this high-risk patient group. This study provides essential information that should help to better estimate the need for diabetological expertise in inpatient care settings.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Pernille H Hellmann in
Google Scholar
PubMed
Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
Search for other papers by Jonatan I Bagger in
Google Scholar
PubMed
Search for other papers by Katrine R Carlander in
Google Scholar
PubMed
Search for other papers by Katrine B Hansen in
Google Scholar
PubMed
Search for other papers by Julie L Forman in
Google Scholar
PubMed
Search for other papers by Joachim Størling in
Google Scholar
PubMed
Search for other papers by Elizaveta Chabanova in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens Holst in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
Search for other papers by Tina Vilsbøll in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Filip K Knop in
Google Scholar
PubMed
Objectives
Preclinically, curcumin has been shown to protect against glucocorticoid-induced insulin resistance. We evaluated the effect of curcumin administered with prednisolone in healthy overweight or obese men.
Methods
In a double-blind, parallel-group trial, 24 overweight/obese non-diabetic men were randomised to one of three intervention groups (A) prednisolone placebo+curcumin placebo, (B) prednisolone (50 mg/day)+curcumin placebo or (C) prednisolone and curcumin (400 mg/day). Curcumin or curcumin placebo treatment started 1 day prior to 10-day prednisolone or prednisolone placebo treatment. The primary endpoint was change in prednisolone-induced insulin resistance assessed by homeostatic model assessment of insulin resistance (HOMA2-IR). Other endpoints included anthropometric measurements, magnetic resonance spectroscopy-assessed hepatic fat content, blood pressure, circulating metabolic markers and continuous glucose monitoring measures.
Results
Baseline characteristics (mean ± s.d): age 44.2 ± 13.7 years, BMI 30.1 ± 3.5 kg/m2, HbAlc 33.3 ± 3.2 mmol/mol, HOMA2-IR 1.10 ± 0.45 and fasting plasma glucose 5.2 ± 0.4 mmol/L. Prednisolone significantly increased HOMA2-IR (estimated treatment difference 0.36 (95% CI 0.16; 0.57)). Co-treatment with curcumin had no effect on HOMA2-IR (estimated treatment difference 0.08 (95% CI −0.13; 0.39)). Prednisolone increased HbAlc, insulin, C-peptide, glucagon, blood pressure, mean interstitial glucose, time spent in hyperglycaemia and glucose variability, but no protective effect of curcumin on any of these measures was observed.
Conclusions
In this double-blind, placebo-controlled parallel-group study involving 24 overweight or obese men randomised to one of three treatment arms, curcumin treatment had no protective effect on prednisolone-induced insulin resistance or other glucometabolic perturbations.
