Diabetes is very common in people over 75. A broad arsenal of treatments is now available. It is important, however, to choose the right treatment regimen to suit the patient\'s specific glycemic targets.

Hypertriglyceridemia-induced pancreatitis is a relatively common form of acute pancreatitis that may represent up to 10% of all etiologies of this condition. Due to its specific pathogenic mechanisms related to high serum triglyceride levels, different treatment options have been proposed, including insulin perfusion, heparin perfusion, and plasmapheresis. Although the superiority of plasmapheresis in this clinical setting has not been demonstrated in randomized clinical trials, many centers have reported its effectiveness and considered this as a possible alternative according to the current guidelines. We report a case of a young patient diagnosed with hypertriglyceridemia-induced pancreatitis that was successfully treated with plasmapheresis. Since complications associated with plasmapheresis are rare and other therapeutic options may not be so effective or safe, we believe that this should be a valid alternative treatment that may be offered to these patients. More studies are still needed to further evaluate its effectiveness and to elucidate if there is a subset of patients in whom treatment with plasmapheresis may be more beneficial.

In this study, we wanted to verify whether the effect of insulin on calcium homeostasis depends on the heart\'s development stage. Using a quantitative 3D confocal microscopy, we tested the effect of a high insulin concentration (100 µU) in freshly cultured ventricular cardiomyocytes from newborn and adult rats. Our results showed that the cytosolic basal level of calcium was higher in newborn cardiomyocytes with no change in the nuclear basal calcium level compared with the adult cardiomyocytes; in addition, insulin induced a slow increase of cytosolic and nuclear calcium in newborn ventricular cardiomyocytes, followed by two phases. However, the first phase of slow cytosolic and nuclear calcium increase was absent in adult rat ventricular cardiomyocytes. Furthermore, the time to the onset of increase of cytosolic and nuclear calcium was longer in newborn cardiomyocytes compared with adults. Moreover, the time to peak of the calcium transient was shorter in newborns than in adult cardiomyocytes. These results demonstrate that insulin differently regulates calcium homeostasis in newborns than in adult cardiomyocytes. Thus, newborn rat cardiomyocytes, commonly used in research as a model for adult cardiomyocytes, should be used with caution when dealing with insulin in normal and disease conditions.

OBJECTIVE: Depression in patients with diabetes mellitus is common and associated with poorer outcomes. This study aims to identify demographic, socioeconomic and medical factors associated with the initiation of antidepressant medication after a diagnosis of diabetes in adult patients without a previous prescription for antidepressants. We also examined frequency of primary care visits in the year after antidepressant initiation compared with the year before treatment began.
METHODS: This was a retrospective cohort study using routinely collected electronic medical record data spanning January 2011 to December 2019 from the University of Toronto Practice-based Research Network (UTOPIAN) Data Safe Haven. Our primary outcome was a first prescription for an antidepressant in patients with diabetes. We used a mixed-effects logistic regression model to identify sociodemographic and medical factors associated with this event.
RESULTS: Among 22,750 patients with diabetes mellitus, 3,055 patients (13.4%) began taking an antidepressant medication. Increased odds of antidepressant initiation were observed in younger patients (odds ratio [OR], 1.77; 95% confidence interval [CI], 1.39 to 2.26), females (OR, 1.60; 95% CI, 1.46 to 1.7), those receiving insulin treatment (OR, 1.59; 95% CI, 1.43 to 1.78) and cases of polypharmacy (OR, 3.67; 95% CI, 3.29 to 4.11). There was an increase in the mean number of primary care visits from 4.6 to 5.9 per year after antidepressant initiation.
CONCLUSIONS: In patients with diabetes, age, sex and medical characteristics were associated with the initiation of antidepressants. These patients accessed primary care more frequently. Screening and prevention of depression, particularly in these subgroups, could reduce its personal and systemic burdens.

Discovery of insulin. If the symptoms of diabetes have been known since Antiquity, it is at the end of the 19th century that several investigators searched for the active substance of the pancreas and endeavoured to produce extracts that lowered blood and urine glucose and decreased polyuria in pancreatectomized dogs. The breakthrough came 100 years ago when the team of Frederick Banting, Charles Best and James Collip, working in the Department of Physiology, headed by John MacLeod at the University of Toronto, managed to obtain pancreatic extracts that could be used to treat patients and rescue them from the edge of death by starvation, the only treatment then available. This achievement was quickly recognized by the Nobel Prize in Physiology or Medicine to Banting and MacLeod in 1923. The discovery has had important scientific, industrial and clinical developments still efficient nowadays.
UNASSIGNED: La découverte de l’insuline 1921–1922 : un saut dans la recherche biomédicale.
UNASSIGNED: Si les symptômes du diabète ont été décrits depuis l’Antiquité et caractérisés par la présence de sucre dans les urines et une soif intense, ce n’est qu’à la fin du xixe siècle que les travaux de plusieurs équipes aboutissent à rechercher la substance active de la sécrétion interne du pancréas dans des extraits susceptibles de diminuer le glucose dans le sang et les urines chez le chien diabétique. C’est à l’Université de Toronto, au Canada, il y a 100 ans, entre 1921 et 1922, que Frederick Banting, Charles Best et James Collip, travaillant dans le département de physiologie dirigé par John MacLeod, obtiennent des extraits pancréatiques suffisamment purifiés qui permettent de traiter de jeunes patients diabétiques. Cette découverte de l’insuline est très vite reconnue et saluée par l’attribution du Prix Nobel de Physiologie ou Médecine en 1923 à Frederick Banting et John MacLeod. Cette découverte a eu d’importantes retombées scientifiques, industrielles et cliniques, toujours d’actualité.

OBJECTIVE: The objective of this study was to compare initiation of a fixed-ratio combination of insulin glargine and lixisenatide (iGlarLixi) vs insulin glargine U100 (iGlar) along with gliclazide, exclusively in people of South Asian origin with type 2 diabetes (T2D).
METHODS: The Variability of glucose Assessed in a Randomized trial comparing the Initiation of A Treatment approach with biosimilar basal Insulin analog Or a titratable iGlarLixi combinatioN in type 2 diabetes among South Asian participants (VARIATION 2 SA) trial (ClinicalTrials.gov identifier: NCT03819790) randomized insulin-naïve adults with T2D having glycated hemoglobin (A1C) 7.1% to 11% to initiate either iGlarLixi or iGlar + gliclazide. Insulin doses were titrated similarly to a prebreakfast glucose target of 4.0 to 5.5 mmol/L. Average time in range (TIR) on a masked continuous glucose monitor (CGM), A1C, fasting plasma glucose (FPG) and weight were assessed at the end of the 12-week treatment period.
RESULTS: Mean baseline characteristics for the 104 randomized participants were similar between treatment groups, including the following: age, 59±11 years; diabetes duration, 13.7±7.3 years; and A1C, 8.5%±1.2%. Coprimary outcomes of average TIRs within 24- and 12-h (6 am to 6 pm) periods at the end of trial were 70.5%±16.8% and 72.9%±17.6% for iGlarLixi, whereas these TIRs were 65.6%±21.6% and 67.3%±20.7% for the iGlar + gliclazide regimen, respectively, with no significant differences between groups (p=0.35 for 24-h TIR and p=0.14 for 12-h TIR). No significant difference in secondary outcomes was observed between treatment groups. Self-reported hypoglycemic events throughout the trial period and CGM-reported hypoglycemia (<4 and <3 mmol/L) were similar between randomized treatments.
CONCLUSIONS: Initiation of iGlarLixi resulted in similar TIR, A1C, FPG, weight and hypoglycemia compared with the more affordable option of starting iGlar + gliclazide in adults of South Asian origin with T2D.

OBJECTIVE: In the management of diabetic patients on insulin therapy, adherence to medication is a key element for avoiding chronic complications. The purpose of this study was to evaluate diabetic patients\' ability to translate glycemic results into an appropriate insulin dose and thus, adherence to insulins.
METHODS: This was an observational, retrospective, monocentric pilot study. Diabetic patients on insulin therapy being followed at the metabolic and endocrine diseases department were divided into two groups depending on their mode of glycemic control at home: capillary glycemia (Notebook group) or interstitial glycemia using the FreeStyle Libre® flash system (FSL group). Adherence was assessed based on the rate of compliance in adapting insulin doses to the prescribed protocols (depending on type of insulin, glycemic targets, and patients\' characteristics) by a pharmacy resident and a senior diabetologist. Good adherence was defined as a minimum rate of 80% of conforming insulin injections for each patient.
RESULTS: A total of 50 patients were included, 35 in the Notebook group and 15 in the FSL group. Two-thirds of patients were non-adherent to insulin. Dose adjustment errors mainly concerned rapid-acting insulin with 51.1% of non- conformities, 10.0% of which were due to underdosing in the Notebook group and 21.7% to overdosing in the FSL group. Hyperglycemia was predominant in both populations with a median time in range of 19.0% in the FSL group and well below recommendations (>70%).
CONCLUSIONS: Despite the use of increasingly efficient, easy-to-use devices in diabetes monitoring, insulin non-adherence and glycemic imbalance are unresolved major issues. Diabetic patients require reinforced medical follow-up for optimal insulin management.

The first therapeutic benefits of insulin were recorded after the injection of pancreatic extract, given on January 23, 1922 in Toronto to a 14-year-old teenager. Until then, type I diabetes was always fatal, within weeks or months; the fatal outcome being delayed only at the cost of a drastic low-calorie diet. In previous decades, the importance of the pancreas in the development of diabetes had been pointed out, but all attempts to use a pancreatic extract had failed. It is with the objective of \"neutralizing\" the destructive effects of pancreatic juice (proteolytic) that the isolation of insulin was carried out by a research team which was totally improbable since it was headed by an orthopedic surgeon, Frederick Banting and a 22-year-old stagiaire, Charles Best. Their work was carried out in the university physiology laboratory of John Macleod and their outcome was made possible thanks to the skills of James Collip who purified the insulin preparation. Scientific reality invites us to emphasize that, Banting works, based on a wrong hypothesis, drew towards an historical discovery. Very quickly recognized as of major importance for medicine, the discovery was greeted by the attribution of the Nobel Prize in 1923. For a hundred years, insulin has not ceased to be an essential drug for tens of millions of patients in the world, but it has been a motor for scientific research: innovation in galenic pharmacy and biopharmacy, in fundamental chemistry as a subject for the study of the structure, analysis and synthesis of proteins, and finally, as a motor for the development of biotechnologies, since insulin was the first drug prepared by DNA-recombinant technology, and marketed in 1982.

A single bout of cycling or running performed in the evening can reduce postprandial lipaemia (PPL) the following morning, although this is currently unknown for upper-body exercise. The aim of this study was to determine if a bout of arm-crank exercise (high-intensity interval [HIIE] or moderate-intensity continuous [MICE]), can attenuate PPL in noninjured individuals. Eleven healthy and recreationally active participants (eight males, three females; age: 27 ± 7 years; body mass index: 23.5 ± 2.5 kg·m-2) volunteered to participate in three trials: HIIE (10 × 60 s at 80% peak power output), MICE (50% peak power output of isocaloric duration), and a no-exercise control condition. Each exercise bout was performed at 18:00, and participants consumed a standardised evening meal at 20:00. Following an overnight fast, a 5-h mixed-macronutrient tolerance test was performed at 08:00. There were no significant differences in triglyceride incremental area under the curve between HIIE (192 ± 94 mmol·L-1 per 300 min), MICE (184 ± 111 mmol·L-1 per 300 min), and the no-exercise condition (175 ± 90 mmol·L-1 per 300 min) (P = 0.46). There were no significant differences in incremental area under the curve for glucose (P = 0.91) or insulin (P = 0.59) between conditions. Upper-body MICE and HIIE performed in the evening do not influence PPL the following morning, in normotriglyceridemic individuals. Clinical Trials Registration: NCT04277091. Novelty: Arm-crank exercise has no effect on PPL when performed the evening prior to a mixed-macronutrient meal test. Upper-body sprint interval exercise should be investigated as a potential solution to reduce PPL.

OBJECTIVE: The oral glucose tolerance test (OGTT) classifies subjects as normal, glucose intolerant or diabetic depending on glycemia at 120 min (T120) post-test. Five insulin profiles associated with different incidences of diabetes over 10 years\' follow-up were previously described following OGTT. However, insulin measurement is sensitive to hemolysis, and can be replaced by C-peptide assay on hemolyzed samples. However, little is known about patterns of C-peptide response to OGTT.
METHODS: In total, 128 patients were included, to establish preliminary baseline C-peptide values and to evaluate C-peptide response to OGTT in comparison to insulin response, using the Liaison XL immunoanalyzer.
RESULTS: Hundred patients had a normal glycemic response, 19 were classified as glucose intolerant and 9 as diabetic. In normal subjects, median C-peptide values (nmol/L, with 5-95 percentiles) were 0.53 (0.23-1.37) at baseline, peaking at 2.36 (0.94-1.83) at T60, and decreasing to 2.09 (1.13-4.36) at T120. The C-peptide response pattern was similar but flatter than the insulin pattern because of different catabolism pathways. Nevertheless, C-peptide and insulin response profiles were discordant in only 9.4% of cases. Profile 3 (C-peptide peaking at T60) was the most prevalent in normal patients whereas profile 4 (peak at 120 min and lower level at T30 than at T60) was the most prevalent in glucose intolerant and diabetic patients.
CONCLUSIONS: In OGTT, C-peptide could replace insulin determination on hemolyzed blood samples to predict the risk of type 2 diabetes.