Fragility fractures are increasingly recognized as a complication of both type 1 and type 2 diabetes, with fracture risk that increases with disease duration and poor glycemic control. Yet the ...identification and management of fracture risk in these patients remains challenging. This review explores the clinical characteristics of bone fragility in adults with diabetes and highlights recent studies that have evaluated bone mineral density (BMD), bone microstructure and material properties, biochemical markers, and fracture prediction algorithms (i.e., FRAX) in these patients. It further reviews the impact of diabetes drugs on bone as well as the efficacy of osteoporosis treatments in this population. We finally propose an algorithm for the identification and management of diabetic patients at increased fracture risk.
Inflammation plays a central role in the etiology of diabetic nephropathy, a global health issue. We observed a significant reduction in the renal expression of fibroblast growth factor 1, a known ...mitogen and insulin sensitizer, in patients with diabetic nephropathy and in mouse models implying that fibroblast growth factor 1 possesses beneficial anti-inflammatory and renoprotective activities in vivo. To test this possibility, we investigated the effects of chronic intraperitoneal administration of fibroblast growth factor 1 into both the streptozotocin-induced type 1 diabetes and db/db type 2 diabetes models. Indeed, recombinant fibroblast growth factor 1 significantly suppressed renal inflammation (i.e., cytokines, macrophage infiltration), glomerular and tubular damage, and renal dysfunction in both type 1 and type 2 diabetes mice. Fibroblast growth factor 1 was able to correct the elevated blood glucose levels in type 2 but not in type 1 diabetic mice, suggesting that the anti-inflammatory effect of fibroblast growth factor 1 was independent of its glucose-lowering activity. The mechanistic study demonstrated that fibroblast growth factor 1–mediated inhibition of the renal inflammation in vivo was accompanied by attenuation of the nuclear factor κB and c-Jun N-terminal kinase signaling pathways, further validated in vitro using cultured glomerular mesangial cells and podocytes. Thus, fibroblast growth factor 1 holds great promise for developing new treatments for diabetic nephropathy through countering inflammatory signaling cascades in injured renal tissue.
Aims/hypothesis
The aim was to conduct a systematic review and meta-analysis of randomised controlled clinical trials assessing the effect of probiotic, prebiotic or synbiotic supplementation on gut ...microbiota and glucose control and lipid levels in individuals with diabetes.
Methods
MEDLINE, EMBASE and the Cochrane Library were searched. The eligibility criteria for the studies was involvement of participants with a diagnosis of type 1 or type 2 diabetes. Metabolic outcomes (glucose control, insulinaemia, and lipid profile) of any probiotic, prebiotic or synbiotic supplementation related to modification of gut microbiota (prebiotics, probiotics and synbiotics) were analysed. We provided a narrative synthesis and meta-analysis of the findings on metabolic outcomes from the studies. Metabolic outcomes were extracted post-intervention and expressed as mean differences (MDs) and 95% CIs between treatment and comparator groups. We pooled the results using a random-effects meta-analysis. The meta-analysis was conducted using Review Manager (RevMan) software.
Results
After the removal of duplicates and ineligible studies, 5219 studies were retained for review of titles and abstracts. The number of articles was reduced to 130 by review, for which the full-text articles were obtained and reassessed, 38 of which were included in the final meta-analysis. Overall, the use of prebiotics, probiotics or synbiotics reduced HbA
1c
levels, but did not reach the threshold for significance (−2.17 mmol/mol, 95% CI −4.37, 0.03;
p
= 0.05, −0.20%, 95% CI −0.40 to 0.00;
p
= 0.05,
I
2
= 66%) and had no effect on LDL-cholesterol levels (−0.05 mmol/l; 95% CI −0.14, 0.05,
p
= 0.35,
I
2
= 37%). However, their consumption decreased levels of fasting blood glucose (−0.58 mmol/l; 95% CI −0.86, −0.30;
p
< 0.01,
I
2
= 60%), total cholesterol (−0.14 mmol/l; 95% CI −0.26, −0.02,
p
= 0.02,
I
2
= 39%), triacylglycerols (−0.11 mmol/l; 95% CI −0.20, −0.02,
p
= 0.01,
I
2
= 21%) and insulinaemia (−10.51 pmol/l; 95% CI −16.68,−4.33,
p
< 0.01,
I
2
= 74%), and increased HDL-cholesterol levels (0.04 mmol/l; 95% CI 0.01, 0.07,
p
< 0.01,
I
2
= 24%).
Conclusions/interpretation
In individuals with diabetes mellitus, supplementation with probiotics, prebiotics or synbiotics improved metabolic variables, although the magnitude of this effect is low. Our results suggest that consumption of probiotics, prebiotics or synbiotics may be a potential adjuvant treatment for improving metabolic outcomes.
Registration
PROSPERO ID CRD42017080071.
Graphical abstract
In healthy individuals, the incretin hormone glucagon-like peptide 1 (GLP1) potentiates insulin release and suppresses glucagon secretion in response to the ingestion of nutrients. GLP1 also delays ...gastric emptying and increases satiety. In patients with type 2 diabetes mellitus (T2DM), supraphysiological doses of GLP1 normalize the endogenous insulin response during a hyperglycaemic clamp. Owing to the short plasma half-life of native GLP1, several GLP1 receptor agonists (GLP1RAs) with longer half-lives have been developed for the treatment of T2DM. These compounds vary in chemical structure, pharmacokinetics and size, which results in different clinical effects on hyperglycaemia and body weight loss; these variations might also explain the difference in cardiovascular effect observed in large-scale cardiovascular outcome trials, in which certain GLP1RAs were shown to have a positive effect on cardiovascular outcomes. Owing to their metabolic effects, GLP1RAs are also considered for the treatment of several other lifestyle-induced conditions, such as obesity, prediabetes and liver disease. This Review provides insights into the physiology of GLP1 and its involvement in the pathophysiology of T2DM and an overview of the currently available and emerging GLP1RAs. Furthermore, we review the results from the currently available large-scale cardiovascular outcome trials and the use of GLP1RAs for other indications.
Diabetes mellitus is an important risk factor for atrial fibrillation (AF) development. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors are used for the treatment of type 2 diabetes mellitus ...(T2DM). Their cardioprotective effects have been reported but whether they prevent AF in T2DM patients are less well-explored. We tested the hypothesis that the SGLT-2 inhibitor, empagliflozin, can prevent atrial remodeling in a diabetic rat model.
High-fat diet and low-dose streptozotocin (STZ) treatment were used to induce T2DM. A total of 96 rats were randomized into the following four groups: (i) control (ii) T2DM, (iii) low-dose empagliflozin (10 mg/kg/day)/T2DM; and (iv) high-dose empagliflozin (30 mg/kg/day)/T2DM by the intragastric route for 8 weeks.
Compared with the control group, left atrial diameter, interstitial fibrosis and the incidence of AF inducibility were significantly increased in the DM group. Moreover, atrial mitochondrial respiratory function, mitochondrial membrane potential, and mitochondrial biogenesis were impaired. Empagliflozin treatment significantly prevented the development of these abnormalities in DM rats, likely via the peroxisome proliferator-activated receptor-c coactivator 1α (PGC-1α)/nuclear respiratory factor-1 (NRF-1)/mitochondrial transcription factor A (Tfam) signaling pathway.
Empagliflozin can ameliorate atrial structural and electrical remodeling as well as improve mitochondrial function and mitochondrial biogenesis in T2DM, hence may be potentially used in the prevention of T2DM-related atrial fibrillation.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The purpose of this review is to provide an update on the changing face of paediatric type 1 diabetes and type 2 diabetes. Paediatric diabetes is on the rise, with extensive research dedicated to ...understanding its pathophysiology, comorbidities and complications. As obesity continues to increase among all youth, differentiating between type 1 diabetes and type 2 diabetes has become increasingly difficult but remains important for optimising treatment, anticipating complications and predicting disease risk. Novel treatments are emerging, with the ultimate goal being to achieve glycaemic control, limit weight gain, improve quality of life and reduce comorbidities. In this review, we focus on updates regarding the epidemiology, clinical presentation, comorbidities and complications of paediatric type 1 diabetes and type 2 diabetes and conclude with current and emerging treatments.
A summary of the latest evidence‐based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, ...and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes‐related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non‐nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted ‘GRADE’ methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines.
What's new?
These updated guidelines, based on recently published studies, provide evidence‐based recommendations for the prevention and management of diabetes.
The focus is on food, rather than nutrients, and an individualized, flexible approach to nutritional management is recommended.
New guidelines for remission of Type 2 diabetes and considerations for ethnic minorities are included.
Guidelines are assessed using adapted ‘GRADE’ methodology.
The α-cell in diabetes mellitus Gromada, Jesper; Chabosseau, Pauline; Rutter, Guy A
Nature reviews. Endocrinology,
12/2018, Letnik:
14, Številka:
12
Journal Article
Recenzirano
Findings from the past 10 years have placed the glucagon-secreting pancreatic α-cell centre stage in the development of diabetes mellitus, a disease affecting almost one in every ten adults ...worldwide. Glucagon secretion is reduced in patients with type 1 diabetes mellitus, increasing the risk of insulin-induced hypoglycaemia, but is enhanced in type 2 diabetes mellitus, exacerbating the effects of diminished insulin release and action on blood levels of glucose. A better understanding of the mechanisms underlying these changes is therefore an important goal. RNA sequencing reveals that, despite their opposing roles in the control of blood levels of glucose, α-cells and β-cells have remarkably similar patterns of gene expression. This similarity might explain the fairly facile interconversion between these cells and the ability of the α-cell compartment to serve as a source of new β-cells in models of extreme β-cell loss that mimic type 1 diabetes mellitus. Emerging data suggest that GABA might facilitate this interconversion, whereas the amino acid glutamine serves as a liver-derived factor to promote α-cell replication and maintenance of α-cell mass. Here, we survey these developments and their therapeutic implications for patients with diabetes mellitus.
Diabetes is not a single homogeneous disease but composed of many diseases with hyperglycaemia as a common feature. Four factors have, historically, been used to identify this diversity: the age at ...onset; the severity of the disease, i.e. degree of loss of beta cell function; the degree of insulin resistance and the presence of diabetes-associated autoantibodies. Our broad understanding of the distinction between the two major types, type 1 diabetes mellitus and type 2 diabetes mellitus, are based on these factors, but it has become apparent that they do not precisely capture the different disease forms. Indeed, both major types of diabetes have common features, encapsulated by adult-onset autoimmune diabetes and maturity-onset diabetes of the young. As a result, there has been a repositioning of our understanding of diabetes. In this review, drawing on recent literature, we discuss the evidence that autoimmune type 1 diabetes has a broad clinical phenotype with diverse therapeutic options, while the term non-autoimmune type 2 diabetes obscures the optimal management strategy because it encompasses substantial heterogeneity. Underlying these developments is a general progression towards precision medicine with the need for precise patient characterisation, currently based on clinical phenotypes but in future augmented by laboratory-based tests.
Key points
• The need to clarify diabetes classification, which is currently imprecise in distinguishing major disease types, using laboratory tests
• The importance of predictors of disease progression, including genetic, immune and metabolic features
• The potential for predicting therapeutic responses to provide a more personalised approach to therapy
AbstractObjectiveTo estimate the prevalence of diagnosed total diabetes, type 1 diabetes, and type 2 diabetes in the US general population and the proportions of each among US adults with a diagnosis ...of diabetes.DesignNationwide, population based, cross sectional survey.SettingNational Health Interview Survey, 2016 and 2017.ParticipantsAdults aged 20 years or older (n=58 186), as a nationally representative sample of the civilian, non-institutionalized US population.Main outcome measuresPrevalence of diagnosed diabetes, type 1 diabetes, and type 2 diabetes in the US general population, and the proportions of each subtype in participants with a diagnosis of diabetes.ResultsAmong the 58 186 included adults, 6317 had received a diagnosis of diabetes. The weighted prevalence of diagnosed diabetes, type 1 diabetes, and type 2 diabetes among US adults was 9.7% (95% confidence interval 9.4% to 10.0%), 0.5% (0.5% to 0.6%), and 8.5% (8.2% to 8.8%), respectively. Type 1 diabetes was more prevalent among adults with lower education level, and type 2 diabetes was more prevalent among older adults, men, and those with lower educational level, lower family income level, and higher body mass index (BMI). Among adults with a diagnosis of diabetes, the weighted percentage of type 1 and type 2 diabetes was 5.6% (4.9% to 6.4%) and 91.2% (90.4% to 92.1%), respectively. The percentage of type 1 diabetes was higher among younger adults (age 20-44 years), non-Hispanic white people, those with higher education level, and those with lower BMI, whereas the percentage of type 2 diabetes was higher among older adults (age ≥65 years), non-Hispanic Asians, those with lower education level, and those with higher BMI.ConclusionThis study provided benchmark estimates on the national prevalence of diagnosed type 1 diabetes (0.5%) and type 2 diabetes (8.5%) among US adults. Among US adults with diagnosed diabetes, type 1 and type 2 diabetes accounted for 5.6% and 91.2%, respectively.
PDF
