Diabetes, Obesity and Metabolism Now最新文献

The changes to inpatient diabetes services brought about as a result of the current COVID-19 pandemic may result in long-term improvement to the outcomes of inpatients with diabetes.

The intensive use of telehealth improves glycaemic control among rural patients with type 2 diabetes, according to a recent study presented at the American Diabetes Association's 80th Virtual Conference.

Previous phase II randomised controlled trials have shown that teplizumab (an Fc receptor–nonbinding anti-CD3 monoclonal antibody) was able to delay progression to type 1 diabetes in high-risk patients.

The study enrolled 76 participants (55 children and 21 adults) who were the relatives of people with type 1 diabetes and did not have diabetes themselves, but were at high risk for developing the condition. At the end of the trial, 53% of the teplizumab-treated group did not have type 1 diabetes, compared to 28% in the placebo group.

New follow up data, presented at the American Diabetes Association's virtual meeting in 2020 have showed sustained reduction in the onset of type 1 diabetes - a delay of as much as three years, compared to placebo.

In addition, people who were treated with teplizumab showed a significant reversal in C-peptide decline in the six months following treatment, after which C-peptide levels seemed to stabilize. These findings provide early evidence for the potential of this therapy to prevent type 1 diabetes in high risk patients, and an FDA decision could be expected by mid-2021.

A study presented at this year's American Diabetes Association's Virtual Conference showed a dramatic drop in ketoacidosis rates after FreeStyle Libre system initiation in people with type 1 and type 2 diabetes.

Studies using univariate analysis from China, Italy and the USA, as well as multivariate analysis from USA and UK have shown that people with diabetes have a higher risk of more adverse outcomes from COVID-19 compared with people without diabetes. However, the differential risks between type 1 versus type 2 diabetes remains unreported. Using data from the COVID patient notification system, UK investigators have studied the relative and absolute risk of in-hospital related death with COVID-19 in people with type 1 and type 2 diabetes. There were 23,804 hospital deaths with COVID-19 in England reported to 11th May 2020. Overall, one third of these deaths occurred in people with diabetes. Adjusted for age, sex, deprivation, ethnicity and geographical regions, people with type 1 and type 2 diabetes had 3.5 and 2.03 times the relative risk of dying in hospital from COVID-19 compared to those without diabetes. To put this into context however, age appears to be a major factor for people with diabetes at risk of death with COVID-19. Mean age of death in type 1 diabetes was 72 years and type 2 diabetes was 77.9 years. Moreover, the odd ratio for death in people <40 years was 0.01, whereas for people >80 years was 9.14 (both relative to reference age group of 60-69 years. Additional important risk factors which adjusted and increases the risk of in-patient death with COVID-19 in people with type 1 and type 2 diabetes are social deprivation, British Asian Minority ethnic (BAME) group and presence of comorbidities such as coronary heart disease, cerebrovascular disease and heart failure.

Roux-en-Y gastric bypass is one of the most widely performed bariatric surgical procedure worldwide, but an important complication of this procedure is the occurrence of reactive hypoglycaemia following surgery – also known as the late dumping syndrome. This is characterised by symptoms of dizziness, fatigue, weakness, and diaphoresis, 1–3 hours after meal ingestion and is due to the rapid insulin response to carbohydrate ingestion resulting from rapid absorption of simple sugars from the proximal small intestine. For many patients, these symptoms can be quite severe and debilitating putting patients at risk for seizures, altered mental status, loss of consciousness, cognitive dysfunction, disability, and death. The current mainstay of treatment for late dumping is nutritional and lifestyle modification but for many patients whose symptoms persists, pharmacological therapy such as acarbose, diazoxide and somatostatin injections may sometimes be necessary, with variable and in many cases, limited success. In severe resistant cases, late dumping may also require continuous enteral feeding or the reversal of surgical procedure (Gastric bypass). Significant interest has emerged in the development of more effective therapy to manage reactive hypoglycaemia associated with late dumping syndrome. Eiger biopharmaceutical has acquired an exclusive license to a targeted therapeutic for treating post-bariatric hypoglycaemia with Avexitide – a GLP-1 receptor antagonist. Avexitide is a 31 amino acid peptide fragment of Exenatide, and has never been approved or commercialized for any indication. Early phase 1 (Infusion studies) and phase 2 (subcutaneous injection studies) have demonstrated in a proof-of-concept exploratory clinical study with Avexitide that pharmacologic blockade of GLP-1 prevents hypoglycemia in post-bariatric surgical patients and may represent the first targeted medical treatment for patients with post-bariatric hypoglycemia. The long-term efficacy and safety of Avexitide have not been established yet. A Phase 2, Multicenter, Randomized, SinglE-Blind, Placebo-Controlled, Cross-oVer Study to Assess the Efficacy and Safety of ExeNdin 9-39 in PaTients with Postbariatric Hypoglycemia (PREVENT) is currently underway.

Observational studies have shown that the presence of diabetes and hypertension are associated with an increased risk of mortality from COVID-19, but whether the increased risk of death occurred independent of concurrent drugs that patients are taking is unclear. Relevant to this is the speculation that ACE and ARB – drugs widely used in people with diabetes and hypertension - maybe deleterious to COVID-19 outcome due to the propensity of the virus to bind to cellular ACE-2 receptors. In the absence of clear evidence, guideline from national and international hypertension societies have recommended that patients should not discontinue these drugs in the event of COVID-19 infection. A recent study from the USA, published in the New England Journal of Medicine, have provided some reassurance of the safety of these classes of drugs during COVID-19 infection. The study investigated clinical outcomes of 8910 patients admitted to hospital with COVID-19. After adjusting for confounders, they identified that age above 65 years old, having cardiovascular disease, COPD and being a current smoker was associated with a significant doubling of mortality rate. However, reassuringly, the use of ACE and ARB was not associated with an increased risk of mortality. NEJM (doi:10.1056/NEJMoa2007621).

Loss of mean muscle mass and function is associated with type 2 diabetes. A recent study have utilized grip strength to develop cut points relative to body weight, gender, and age group to predict type 2 diabetes in a large nationally representative sample of participants pre-screened for comorbid conditions such as hypertension. In this study, researchers analyzed survey data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Survey to establish normalized grip strength (grip strength relative to body weight) cut points for type 2 diabetes risk. Portable handgrip dynamometer devices were used to determine hand and forearm strength. After adjusting for sociodemographics (i.e., race/ethnicity, education, poverty, sex, and age), lifestyle factors (i.e., sedentary behavior, alcohol use, and smoking status), and waist circumference, the investigators identified the grip strength levels of at-risk patients who were otherwise healthy. These levels are presented with age- and sex-specific grip strength cut points that correspond to varying body weights to increase the ease of use for practitioners as indicators of when further diabetes diagnostic testing is warranted. The investigators suggested that the use of the normalized grip strength cut points could be used in routine health screenings to identify at-risk patients and improve diagnosis and outcome.

American Journal of Preventive Medicine, 2020; DOI: 10.1016/j.amepre.2020.01.016.

Amylin is a small peptide hormone excreted alongside insulin by pancreatic beta cells. Amylin acts centrally to slow gastric emptying, suppress postprandial glucagon secretion, and decrease food intake, thus complementing the action of insulin to regulate blood glucose levels. In people with type 1 diabetes, amylin production is completely absent. Studies for many years using the stable Amylin, pramlitide have shown that treatment of diabetes with a combination of insulin and amylin analogues at meal times are more effective than insulin alone. However its clinical development is limited due to the impracticality of administering insulin and amylin analogues as two separate injections (since these proteins can't be co-formulated). More recently, investigators from Stanford University have developed a novel formulation which enabled insulin (Humalog Lisipro; Eli Lilly) and Symlin (pramlitide; AstraZeneca) to be given as a single injection. The novel formulation developed by the researchers involves a molecular wrapper made out of polyethylene glycol, engineered to selectively bind to amylin and insulin molecules. This protective element shields the two compounds until they are injected into a body, at which point they unbind from the wrapper and function as normal. The formulation has been tested on animal models and shown to be effective in mimicking the body's endogenous co-secretions of these two important hormones. The formulation has also been found to be stable for over 100 hours, meaning it could be effectively stored and administered by an implanted insulin pump. Further clinical studies are therefore required to show its efficacy in people with type 1 or type 2 diabetes. This recent study on the co-formulation of insulin and Amylin was published in the journal Nature Biomedical Engineering.

Use of an experimental drug with Rosiglitazone shown to reduce similar degree of insulin sensitization without the known adverse effects of Rosiglitazone.