OBJECTIVE: Evidence suggests that glucose levels in menstruating females with type 1 diabetes change throughout the menstrual cycle, reaching a peak during the luteal phase. The Type 1 Diabetes Exercise Initiative (T1DEXI) study provided the opportunity to assess glycemic metrics between early and late phases of the menstrual cycle, and whether differences could be explained by exercise, insulin, and carbohydrate intake.
METHODS: One hundred seventy-nine women were included in our analysis. Glycemic metrics, carbohydrate intake, insulin requirements, and exercise habits during the early vs late phases of their menstrual cycles (i.e. 2 to 4 days after vs 2 to 4 days before reported menstruation start date) were compared.
RESULTS: Mean glucose increased from 8.2±1.5 mmol/L (148±27 mg/dL) during the early follicular phase to 8.6±1.6 mmol/L (155±29 mg/dL) during the late luteal phase (p<0.001). Mean percent time-in-range (3.9 to 10.0 mmol/L [70 to 180 mg/dL]) decreased from 73±17% to 70±18% (p=0.002), and median percent time >10.0 mmol/L (>180 mg/dL) increased from 21% to 23% (p<0.001). Median total daily insulin requirements increased from 37.4 units during the early follicular phase to 38.5 units during the late luteal phase (p=0.02) and mean daily carbohydrate consumption increased slightly from 127±47 g to 133±47 g (p=0.05); however, the difference in mean glucose during early follicular vs late luteal phase was not explained by differences in exercise duration, total daily insulin units, or reported carbohydrate intake.
CONCLUSIONS: Glucose levels during the late luteal phase were higher than those of the early follicular phase of the menstrual cycle. These glycemic changes suggest that glucose management for women with type 1 diabetes may need to be fine-tuned within the context of their menstrual cycles.

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.

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.

Benefits of pulse consumption on glycemic control are well established; however, research examining the effects of pulse fractions incorporated into extruded products is limited. In a randomized, repeated-measures crossover study, adults (n = 26) consumed cereals made with oat flour (control), oat flour and pea starch (starch), oat flour and pea protein (protein), oat flour, pea starch and pea protein (starch+protein), oat flour, pea fibre and pea protein (fibre+protein), and pea fibre, pea starch and pea protein (fibre+starch+protein). Blood glucose (BG) and insulin concentrations, and appetite incremental area under the curve (iAUC) were calculated before (0-120 min) and after (120-200 min) the ad libitum meal for measurement of food intake. Pre-meal, overall mean BG and iAUC were lower following the protein, starch+protein, protein+fibre, and the fibre+starch+protein cereals compared with the starch and control. For pre-meal overall mean insulin concentrations, fibre+protein led to a lower response compared with control, starch+protein, and protein cereals. Fibre+starch+protein also led to lower insulin compared with protein cereal. Pre-meal insulin iAUC was lower following fibre+protein compared with control and protein cereals. The inclusion of yellow pea protein and fibre in oat-based breakfast cereal reduces postprandial glycemia; however this effect is dependent on fraction type. ClinicalTrials.gov: NCT02366572. Novelty: Inclusion of pulse protein and fibre in oat flour-based breakfast cereal reduces postprandial glucose response. The glycemic benefits of whole pulses are at least somewhat retained in some pulse fractions.

Research indicates that the postprandial glycemic benefits of consuming whole pulses are retained when consumed in a mixed meal, pureed, and ground into flours. The glycemic benefits of pulse flours when incorporated into extruded products are unknown. In a randomized, repeated-measures crossover study, adults (n = 26) consumed extruded corn snacks made with the addition of 40% pulse flour from either whole yellow pea, split yellow pea, green lentil, chickpea, or pinto bean. The control snack was 100% corn. Food intake was measured with an ad libitum meal consumed at 120 min. Blood glucose (BG), insulin and appetite were measured regularly before (pre-meal, 0-120 min) and after (post-meal, 140-200 min) the meal. Pinto bean and chickpea snacks led to lower (p < 0.05) pre-meal BG incremental area under the curve (iAUC), compared with control, whole yellow pea and green lentil snacks. Pinto bean snack also led to lower (pre-meal BG (p < 0.05) and insulin (p < 0.05) iAUC compared with control, whole yellow pea, and split yellow pea snacks. There were no differences in food intake or appetite. These findings indicate that effects of replacing corn with pulse flours in extruded snacks on BG, and insulin are dependent on pulse type. ClinicalTrials.gov Identifier: NCT02402504. Registered on 30 March 2015. Novelty: The incorporation of pinto bean and chickpea flour into extruded corn snacks improves postprandial glycemic response. Pulse containing snacks were equally as palatable as the corn snacks. The incorporation of pulses into corn snacks increased the protein and fibre content.

OBJECTIVE: Hypoglycemia is a common adverse event for people with type 1 and type 2 diabetes mellitus. In this article, we explore the specific roles that individuals assume to prevent or treat hypoglycemia.
METHODS: A descriptive qualitative study from the UnderstandINg the impact of HYPOglycemia on Diabetes Management Study (InHypo-DM) research program. A purposive sample of people with type 1 and type 2 diabetes were recruited for semistructured interviews. There were 16 participants (women and men), who were, on average, 53 years old. Average time since diagnosis was 15 (type 1) and 21 (type 2) years; all patients had at least 1 hypoglycemic event in the past year. Individual and team analysis of interviews were conducted to identify overarching themes.
RESULTS: Participants articulated 4 roles in preventing or treating hypoglycemia. The first role was being a manager by assuming ownership and accountability for their own glycemic control. The second role, being a technician, used both subjective and objective information and employed specific strategies to respond to hypoglycemic events. The third role, educator, extended beyond self-management to increase others\' awareness of hypoglycemia. The fourth role, advocate, involved championing one\'s own needs during a hypoglycemic event. These 4 roles were, in turn, influenced by the contexts of work, social settings, exercise and travel.
CONCLUSIONS: These findings demonstrate that strategies that individuals use to avoid or reduce the severity of a hypoglycemic event extend beyond merely making impromptu decisions during events. Instead, these 4 roles of manager, technician, educator and advocate, embedded in specific contexts, enhanced their mastery in managing hypoglycemia in daily life.

This study aimed to determine the effect of pure forms of sucralose and aspartame, in doses reflective of common consumption, on glucose metabolism. Healthy participants consumed pure forms of a non-nutritive sweetener (NNS) that were mixed with water and standardized to doses of 14% (0.425 g) of the acceptable daily intake (ADI) for aspartame and 20% (0.136 g) of the ADI for sucralose every day for 2 weeks. Blood samples were collected and analyzed for glucose, insulin, active glucagon-like peptide-1 (GLP-1), and leptin. Seventeen participants (10 females and 7 males; age, 24 ± 6.8 years; body mass index, 22.9 ± 2.5 kg/m2) participated in the study. The total area under the curve values of glucose, insulin, active GLP-1 and leptin were similar for the aspartame and sucralose treatment groups compared with the baseline values in healthy participants. There was no change in insulin sensitivity after NNS treatment compared with the baseline values. These findings suggest that daily repeated consumption of pure sucralose or aspartame for 2 weeks had no effect on glucose metabolism among normoglycaemic adults. However, these results need to be tested in studies with longer durations. Novelty Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on glucose metabolism. Daily consumption of pure aspartame or sucralose for 2 weeks had no effect on insulin sensitivity among healthy adults.

This randomized crossover study assessed the acute effects of almonds on postprandial glycemic, hormonal, and appetite responses in a sample of 7 men with type 2 diabetes (T2D). Participants completed 2 experimental visits during which a control (white bread, butter, cheese) and a test (white bread, almonds) meal were ingested. Energy, available carbohydrate, total lipid, and protein content were the same in both meals. Blood samples were collected in fasting state as well as 15, 30, 60, 90, 120, and 240 min postprandially for quantifying blood glucose, as well as insulin and glucagon-like peptide-1 (GLP-1) serum concentrations. Subjective appetite sensations were assessed using visual analog scales at the same time-points. Within this sample of participants, the test meal was found to be associated with lower postprandial glycemia and insulinemia, higher GLP-1 serum concentrations, decreased hunger and desire to eat, and increased fullness. The test meal was also associated with an increased estimated glucose metabolic clearance rate, indicating higher postprandial insulin sensitivity. Overall, results suggest that almonds\' macronutrient subtype profile could have a beneficial impact on postprandial glycemic, hormonal, and appetite responses in men with T2D. Studies with larger sample sizes are warranted to confirm these findings. Novelty A meal containing almonds (vs. isocaloric macronutrient-matched control) induced lower glycemic and insulinemic responses. A meal containing almonds (vs. isocaloric macronutrient-matched control) induced a greater elevation in postprandial GLP-1 serum concentrations. A meal containing almonds (vs. isocaloric macronutrient-matched control) induced more favourable postprandial appetite responses.

OBJECTIVE: Diabetic ketoacidosis (DKA) is a common acute complication of diabetes mellitus and is associated with significant morbidity and mortality. There is currently a paucity of data concerning the Canadian experience with DKA. We aimed to characterize the acute management and course of DKA at several Canadian hospitals.
METHODS: We performed a retrospective cohort study of patients admitted to 3 teaching hospitals in Edmonton, Canada. We extracted clinical and laboratory data from the medical charts of patients admitted to general internal medicine wards or intensive care units with moderate or severe DKA.
RESULTS: We included 103 admissions (84 patients) in our study. The majority (68.9%) had type 1 diabetes and presented with severe DKA (60.2%). In the first 24 h, the median (interquartile range) intravenous fluid received was 7.0 (5.5 to 8.8) litres; 23.3% received a priming insulin bolus, 24.3% received bicarbonate and 91.3% received potassium. Hypoglycemia was relatively rare (5.8%), but hypokalemia was common (41.7%). The median time to anion gap ≤12 mmol/L was 8.8 (6.0 to 12.3) h. In 27.1% of cases, intravenous insulin was stopped prior to subcutaneous insulin administration, with a median of 95 (30 to 310) min elapsing before subcutaneous insulin was given. DKA-related mortality was 2.9%.
CONCLUSIONS: The acute management of DKA was generally aligned with clinical guidelines. Areas for improvement include preventing hypokalemia by proactively increasing potassium repletion, reducing initial insulin boluses, administering subcutaneous insulin before stopping intravenous insulin and administering sodium bicarbonate judiciously. Protocols and preprinted order sets may be helpful, especially in smaller centres.