The 27th annual European Group for the Study of Insulin Resistance meeting was held in Lisbon, birthplace of Ernesto Roma, founder of the worlds oldest diabetes association ‘Associação Protetora dos Diabéticos de Portugal’ (Association for the Protection of Poor Diabetics) in 1926. Although he graduated in medicine (psychiatry) in Lisbon, it was in Boston (1922), where he witnessed the revolution of insulin. On his return to Portugal, he vowed to make this treatment available to everyone with diabetes, regardless of his or her capacity to pay. He immediately introduced diabetes education enabling people with diabetes to make lifestyle modifications (self-injections and an adequate diet). This concept of patient empowerment through education has since become the hallmark of diabetes associations around the world. The 27th meeting of the group was hosted by Dr. John Jones and Dr. Maria Paula Macedo (Coimbra and Lisboa, Portugal) with the overall theme of ‘New Voyages of Discovery Towards Understanding Insulin Actions.’
The first session focused on glucoregulatory hormones and the central nervous system. Dr. Sara Silva (Portugal) commenced by discussing that the hypothalamus plays a determinant role in overall insulin sensitivity. Thereafter, she suggested that finding new players of hypothalamic physiology might provide strategies for potential therapeutic approaches for diabetes. Ataxin-2 is a ubiquitous protein, decreased in the hypothalamus of obese mice. The modulation of ataxin-2 in this region impacts directly on insulin sensitivity. The silencing of ataxin-2 promotes insulin resistance, while its overexpression prevents diet-induced impairment on insulin sensitivity. This effect of hypothalamic ataxin-2 is partly mediated through the its potential of maintenance of circadian rhythm, which upon disruption can promote insulin resistance.
There followed abstracts on the prevalence of neuropathy in pre-diabetic individuals versus healthy volunteers, where sudomotor function was quantitatively assessed (Rafael Gabriel, Spain). This was followed by a study on adipose tissue browning, mediating the beneficial effects of carotid sinus nerve resection on obesity and glucose homeostasis (Bernadete Melo, Portugal). Dr. Joao Duarte (Sweden) presented his recent work on brain energy metabolism in diabetes. Using Goto-Kakizaki diabetic rats, which also show spatial memory impairments, he revealed that insulin resistance is associated to brain glucose hypometabolism, which he suggested to be associated with impaired astrocytic glycogen metabolism, reduced neuronal oxidative metabolism, decreased glutamine synthesis, and glutamate-glutamine cycling between neurons and astrocytes, thus demonstrating a dysregulation of metabolic interactions between astrocytes and neurons in the insulin-resistant brain.
After three further abstracts, Carlo Dieguez (Spain) ended by giving a keynote lecture summarizing his pioneering work on energy sensors, glucoregulatory hormones and the central nervous system.
Taking to the streets, delegates made their way to the emblematic and highly regarded Varanda de Lisboa restaurant, which features a terrace with stunning panoramic city and São Jorge Castle views for local gastronomy courtesy of the hosts.
The following morning was kicked off by Maria Paula Macedo (Portugal) who discussed the overarching hypothesis that hepatic subclinical inflammatory states, derived from diet-induced changes in intestinal microbiota, originates a sustained suppression on hepatic insulin clearance leading to persistent hyperinsulinemia, as the liver is responsible for 50–70% of the insulin clearance. In turn, this primary hyperinsulinemia leads to insulin resistance resulting in mild hyperglycemia against which the pancreas responds by increasing insulin secretion and thereby escalating the hyperinsulinemic state, insulin resistance, and diabetes.
Sonia Najjar (United States) then presented interesting data on impaired insulin clearance, which occurs with insulin resistance. Interestingly, the cause-effect relationship has not been well delineated. Professor Najjar has shown that Carcinoembryonic antigen related cell adhesion molecule 1 gene promotes hepatic insulin clearance and that by targeting this gene in liver using loss- or gain-of-function mouse models, she has shown that impaired insulin clearance can cause insulin resistance and not just a consequence thereof. This was followed by three abstracts and invited talk by Roberto Bizzotto (Italy) who discussed how to derive endogenous insulin clearance at standardized levels of insulin secretion, and further proposed that this quantity is strongly associated to insulin sensitivity but not to BMI nor to oral glucose stimulation. Markus Muhlemann (France) then turned the spotlight on pancreatic alpha cells, thus reaffirming that although heterogeneously expressed, alpha-cell specific sodium glucose co-transporter-2 (SGLT2) protein directly regulates glucagon secretion in humans. In line with this, Ana Acosta (France) provided data showing that mutations in hepatocyte nuclear factor 1-alpha, a key regulator of SGLT2 cause hyperglucagonemia in mice.
After a traditional Portuguese style buffet washed down by local wine, President of the group, Amalia Gastaldelli (Texas, USA; Pisa Italy) took to the floor to present data on the cross-talk between liver-pancreas-gut focusing on the effect of these combined metabolic organs on hepatic glucose metabolism. After further abstract presentations, Andrea Natali (Italy) discussed the recent data on SGLT2 inhibition and cardiorenal protection. In the final invited talk, Maria Joao Pereira (Sweden) then spoke on the effects of glucagon on human adipocytes.
In summary, European Group for the study of Insulin Resistance delegates were rewarded with memorable discussions in metabolic science with leading figures in the field. The European Group for the study of Insulin Resistance group has now become an official study group of the European Association for the Study of Diabetes and is embedded within a number of multicenter European projects. The next meeting will be held in Greece on May 2020, hosted by Professor Asimina Mitrakou (University of Athens, Greece). New members are always welcome (https://www.easd.org/egirstudy-group.html).