Elisabeth Kugelberg

Diabetes: Betatrophin—inducing β-cell expansion to treat diabetes mellitus?

Betatrophin, a newly identified hormone, increases the production and expansion of insulin-secreting β cells in mice, research from Harvard University suggests. When insulin resistance develops, pancreatic β cells undergo an expansion in mass and proliferation to compensate for increasing insulin needs. To date, the mechanisms regulating β-cell replication are unclear. Yi et al. developed a mouse model of insulin resistance using the insulin receptor antagonist S961. Subcutaneous injections of the S961 peptide into mice led to dose-dependent, instant β-cell proliferation and hyperglycaemia. Microarray analysis revealed that a highly conserved mammalian gene, betatrophin, was upregulated fourfold in liver and threefold in white adipose tissue cells in response to the acute peripheral insulin resistance induced by S961. Yi and co-workers show that betatrophin DIABETES

Surgery: Altered gut microbiota trigger weight loss

Changes in the gut microbiota are partially responsible for the weight loss and reduced adiposity observed in mice following Roux-en-Y gastric bypass (RYGB) surgery, shows a recent study in Science Translational Medicine. RYGB surgery restricts food intake and alters metabolism. In addition, this procedure causes a shift in the gut microbiota, but the contribution of the altered microbial community to RYGB outcomes is unclear. Liou et al. hypothesized that because the gut microbiota and RYGB influence similar metabolic parameters, changes in gut microbiota could have a role in the metabolic benefits resulting from bariatric surgery. The investigators used an RYGB mouse model to examine whether changes in gut microbiota after RYGB are conserved among humans and rodents, and to identify the potential mechanisms underlying weight and adipose tissue loss. The researchers examined the gut microbial community before and weekly over 3 months after RYGB surgery and compared it with that of sham-operated ad-libitum-fed mice and with that of weight-matched sham-operated control mice. Analysis of faecal samples, by 16S ribosomal RNA gene sequencing, showed that RYGB led to a rapid (within 1 week) and sustained modification of the gut microbiota. A substantial increase in the amount of verrucomicrobia (Akkermansia) and gammaproteobacteria (Escherichia) was seen in faecal samples from RYGB-treated mice, which is similar to the microbial changes found in human patients after gastric bypass surgery. Transfer of caecal contents from RYGBtreated and control mice to nonoperated, germ-free mice led to a significant reduction in body weight and fat deposition in animals receiving the RYGB microbiota. Moreover, the RYGB-associated changes in gut microbiota were independent of dietary composition and weight change. The mechanisms behind the microbialinduced changes in metabolism are unclear, although the researchers suggest that by-products from microbial fermentation, short-chain fatty acids, could affect host physiology. Identifying the key metabolic pathways is the next important step to understanding how the gut microbiota shapes energy balance and the metabolic response to surgical intervention, the authors conclude.

Diabetes: Macrophages mediate β-cell loss in T2DM.

a combination of in vivo experiments in Zucker diabetic fatty rats to analyse hormonal and metabolic status related to T2DM. In addition, in vitro studies were used to explore the inflammatory mechanisms involved in β-cell death in pancreatic islets, macrophages and β cells isolated from humans and rodents,” explains George Kunos, one of the principal investigators. Blocking peripheral CB1 with JD5037, a non-brain-penetrant CB1 inverse agonist, resulted in decreased loss of β-cell function and delayed progression of T2DM. Immunohistochemical stains revealed that pancreatic islets from Zucker diabetic fatty rats were enlarged and infiltrated with CD68+ macrophages that expressed the Nlrp3 inflammasome, compared with islets from lean rats. Treatment with JD5037 led to reduced macrophage infiltration and inflammasome expression. Furthermore, β-cell loss and T2DM could be reversed by inducing macrophage apoptosis or by DIABETES

Diabetes: Regulation of hyperglycaemia--too much can be heart-breaking.

Concluding, the investigators do not recommend intensive insulin therapy in patients with ACS and elevated blood glucose levels; they propose that a “strict, but not too strict, glucose control”, as also recommended by the European Society of Cardiology guidelines, be the best practical approach. Further studies are needed to evaluate alternative strategies to obtain optimal glucose levels, especially in patients with ACS who have persistently increased glucose levels after percutaneous coronary intervention.

Reproductive endocrinology: ESR1 mutation causes estrogen resistance and puberty delay in women.

Reproductive endocrinology: ESR1 mutation causes estrogen resistance and puberty delay in women

Device therapy: Automatic insulin-pump suspension reduces hypoglycaemia

A novel ‘threshold-suspend’ feature of insulin pumps can safely and effectively reduce hypoglycaemia in patients with with type 1 diabetes mellitus (T1DM), a new study published in The New England Journal of Medicine reports. Hypoglycaemia is a common adverse effect of insulin therapy in people with T1DM, particularly during the night. Sensor-augmented insulin pumps, which integrate pumps with continuous glucose monitoring, provide a more effective therapy than multiple daily insulin injections. However, these pumps have not yet been proven to reduce the risk of hypoglycaemia. Bergenstal et al. investigated sensoraugmented insulin pumps containing a new threshold-suspend feature that automatically suspends basal insulin delivery when sensor glucose values reach a pre-set low level (≤3.9 mmol/l). In a randomized controlled 3-month study, the researchers assigned patients to receive sensor-augmented insulin-pump HbA1c level occurred in either group, and no adverse events were reported in the threshold-suspend group, whereas four patients in the control group experienced severe hypoglycaemia. The authors conclude that the threshold-suspend feature of sensoraugmented insulin pumps can safely reduce the frequency of hypoglycaemia, both diurnal and nocturnal, without any loss in overall glycaemic control.

Pain: Opioid use in patients undergoing bariatric surgery

systems, and people with a BMI <30 kg/m2 in the year before surgery were excluded. The patients were assessed 1 year before and at least 1 year after surgery. The database contained information on opioid dispensing, which was used to determine opioid usage. Chronic opioid users were defined as patients having ≥10 opioid dispensings over ≥90 days or at least a 120-day supply in the year prior to bariatric surgery. Before bariatric surgery, 56% of the patients did not use opioids, 36% used some opioids, and 8% were chronic opioid users. Among the chronic users, 77% continued opioid use after surgery. Moreover, in this group, the usage increased by 13% and 18% at 1 year and 3 years after surgery, respectively. “One possible explanation [for the increased use of opioids after surgery] is that some patients probably had pain unresponsive to weight loss but potentially responsive to opioids,” says Raebel. “This finding suggests the need for better pain Use of opioid medications to treat chronic pain does not decline after bariatric surgery for obesity, a new study published in JAMA shows. Indeed, many patients increase their opioid intake after surgery. The usage of opioids is increasing in North America, even though chronic use is associated with abuse, accidental overdose and death, and the long-term efficacy of these drugs remains unclear. People with obesity often suffer from chronic pain, such as knee osteoarthritis and back pain. Raebel et al. speculated that weight loss after bariatric surgery could be associated with reduced pain and opioid use. “To our knowledge, this is the first study evaluating chronic opioid use in the bariatric surgery population,” says lead investigator Marsha A. Raebel. In a retrospective cohort study, the researchers investigated 11,719 individuals aged ≥21 years who underwent bariatric surgery between 2005–2009. The study was conducted at 10 demographically and geographically varied US health-care Original article Raebel, M. A. et al. Chronic use of opioid medications before and after bariatric surgery. JAMA 310, 1369–1376 (2013) PAIN

Diabetes: have the gut(s) to test the risk of developing type 2 diabetes mellitus.

The risk of developing type 2 diabetes mellitus (T2DM) might be predicted by the gut metagenome, a new study suggests. Previous studies have shown that the gut microbiota can affect host metabolism, and Chinese patients with T2DM have an altered gut metagenome. Now, Karlsson et al. extended these findings to a European population and examined whether the microbiota composition can identify diabetes status. The researchers performed shotgun sequencing of DNA from faeces from 145 women aged 70 years (53 with T2DM, 49 with impaired glucose tolerance, 43 with normal glucose tolerance). “This [type of sequencing] provides us not only with taxonomical information but also functional insights, such as which microbial genes that are enriched in patients and controls”, explains senior investigator Fredrik Bäckhed. The researchers then developed a model that can differentiate DIABETES

Nutrition: Red meat consumption leads to a microbiota-dependent risk of cardiovascular disease

Nutrition: Red meat consumption leads to a microbiota-dependent risk of cardiovascular disease

Betatrophin—inducing β-cell expansion to treat diabetes mellitus?: Diabetes

Betatrophin, a newly identified hormone, increases the production and expansion of insulin-secreting β cells in mice, research from Harvard University suggests. When insulin resistance develops, pancreatic β cells undergo an expansion in mass and proliferation to compensate for increasing insulin needs. To date, the mechanisms regulating β-cell replication are unclear. Yi et al. developed a mouse model of insulin resistance using the insulin receptor antagonist S961. Subcutaneous injections of the S961 peptide into mice led to dose-dependent, instant β-cell proliferation and hyperglycaemia. Microarray analysis revealed that a highly conserved mammalian gene, betatrophin, was upregulated fourfold in liver and threefold in white adipose tissue cells in response to the acute peripheral insulin resistance induced by S961. Yi and co-workers show that betatrophin DIABETES