Data regarding hyperglycemia-related factors were scarce in people without diabetes. Fifty males (age 50-65 years) with overweight/obesity but without diagnosis of diabetes were recruited. After excluding participants with the 2 h plasma glucose value during a 75 g oral glucose tolerance test ≥200 mg/dL, continuous glucose monitoring (CGM) was performed for 6 days. Subjects with ≥1800 CGM readings were included ( = 36). The CGM indices of hyperglycemia were significantly associated with disposition index and snacking frequency. In receiver-operating characteristic analysis for predicting the maximal CGM glucose ≥200 mg/dL, the area under curves of disposition index, snacking frequency, and minimal daily step counts during the study were 0.69, 0.63, and 0.68, whereas the cutoff values were 1.57, once daily, and 2499 steps, respectively. After adjustments, the lower disposition index (≤1.57), higher snacking frequency (≥1 per day), and lower minimal step (≤2499 steps per day) categories conferred 14.5, 14.5, and 6.6-fold increased probabilities for having the maximum level ≥ 200 mg/dL, respectively. In addition, the snacking habits were significantly associated with insulin resistance and compensatory hyperinsulinemia. In conclusion, in middle aged males with overweight/obesity but without diabetes, snacking and physical inactivity serve as the major drivers of postprandial hyperglycemia independently of β-cell function.

BACKGROUND:Regular physical activity (PA) is associated with a lower risk of several types of cancers. However, two-thirds of overweight/obese adults are not sufficiently active; this, in combination with the unfavorable effect of excess body weight, puts them at a greater risk for cancer. One reason that these individuals do not engage in enough PA may be their lack of motivation to change their current behavior due to the perception of putting in effort for possible future gain without obvious short-term benefits. There is a need for innovative ways to help individuals recognize the immediate health benefits of PA and thus increase their motivation. METHODS:This pilot intervention tested a PA education module that included a one-on-one counseling session highlighting the acute effects of PA on glucose patterns, followed by a 10-day self-monitoring period with a continuous glucose monitor (CGM) and a Fitbit tracker. Participants rated the acceptability of the education module on a 5-point Likert scale and completed surveys assessing stages of change for motivational readiness. RESULTS:Nineteen overweight/obese adults (84% female) completed the study. Participants gave high ratings to the counseling session for improving their PA-related knowledge (mean = 4.22), increasing motivation (mean = 4.29), and providing personally relevant information (mean = 4.35). The summary acceptability scores for the self-monitoring period were 4.46 for CGM and 4.51 for Fitbit. Participants reported a significant decrease in the precontemplation stage and an increase in the action stage ( < 0.05). CONCLUSIONS:CGM is a feasible tool for PA interventions. IMPACT:Information from CGM could be used as biological-based feedback to motivate PA.

INTRODUCTION:Emerging evidence suggests us of real-time continuous glucose monitoring systems (RT-CGM), can assist to improve glucose control in Type 2 Diabetes (T2D) treatment, however the impact of these devices on patients' stress levels and behaviour is poorly understood. This study aimed to examine the effects of RT-CGM on tolerance and acceptability of device wear, stress and diabetes management and motivation to change. METHODS:Twenty adults (10 men, 10 women) with T2D (aged 60.6 ± 8.4 years, BMI 34.2 ± 4.7 kg/m), were randomised to a low-carbohydrate lifestyle plan whilst wearing a RT-CGM or an 'offline-blinded' (Blinded-CGM) monitoring system continuously for 12 weeks. Outcomes were glycaemic control (HbA1c), weight (kg) perceived stress scale (PSS), CGM device intolerance, acceptability, motivation to change and diabetes management behaviour questionnaires. RESULTS:Both groups experienced significant reductions in body weight (RT-CGM -7.4 ± 4.5 kg vs. Blinded-CGM -5.5 ± 4.0 kg) and HbA1c (-0.67 ± 0.82% vs. -0.68 ± 0.74%). There were no differences between groups for perceived stress (P = 0.47) or device intolerance at week 6 or 12 (both P > 0.30). However, there was evidence of greater acceptance of CGM in the RT-CGM group at week 12 (P = 0.03), improved blood glucose monitoring behaviour in the RT-CGM group at week 6 and week 12 (P ≤ 0.01), and a significant time x group interaction (P = 0.03) demonstrating improved diabetes self-management behaviours in RT-CGM. CONCLUSION:This study provides preliminary evidence of improved behaviours that accompany RT-CGM in the context of diabetes management and glucose self-monitoring. RT-CGM may provide an alternative approach to glucose management in individuals with T2D without resulting in increased disease distress.

Insulin regimens have been evolving for a century. The schemes used for type 1 (T1D) and type 2 (T2D) diabetes differ due to differences in pathophysiology but share important features. Insulin is required for both types of diabetes when other means of controlling glucose are insufficient. For T1D this requires multiple daily injections or continuous subcutaneous infusion assisted by CGM, whereas in early T2D basal insulin together with oral agents or GLP-1RA is usually effective. In both cases current schemes typically maintain HbA1c levels between 7 and 8%, a range that limits but does not eliminate the long-term complications of diabetes, but do not restore glycemic control to a fully protective level. Inability to control postprandial hyperglycemia without problematic weight gain and hypoglycemia is a leading obstacle in both T1D and long-duration T2D. A greater share of prandial dosing decisions will have to be provided by smart electronic systems. Further changes in the structure or formulation of insulin are of uncertain potential, but schemes including delivery of amylin, GLP-1, and glucagon show promise. More reliable access to insulins, delivery devices, and capable medical advisors will be needed to optimize replacement of this essential hormone.

Due to its simplicity, time-limited eating (TLE) may represent a more feasible approach for treating adolescents with obesity compared to other caloric restriction regimens. This pilot study examines the feasibility and safety of TLE combined with continuous glucose monitoring (CGM) in adolescents. Fifty adolescents with BMI ≥95th percentile were recruited to complete a 12-week study. All received standard nutritional counseling, wore a CGM daily, and were randomized to: (1) Prolonged eating window: 12 h eating/12 h fasting + blinded CGM; (2) TLE (8 h eating/16 h fasting, 5 days per week) + blinded CGM; (3) TLE + real-time CGM feedback. Recruitment, retention, and adherence were recorded as indicators of feasibility. Weight loss, dietary intake, physical activity, eating behaviors, and quality of life over the course of the intervention were explored as secondary outcomes. Forty-five participants completed the study (16.4 ± 1.3 years, 64% female, 49% Hispanic, 75% public insurance). There was high adherence to prescribed eating windows (TLE 5.2 d/wk [SD 1.1]; control 6.1 d/wk [SD 1.4]) and daily CGM wear (5.85 d/wk [SD 4.8]). Most of the adolescents (90%) assigned to TLE reported that limiting their eating window and wearing a CGM was feasible without negative impact on daily functioning or adverse events. There were no between-group difference in terms of weight loss, energy intake, quality of life, physical activity, or eating behaviors. TLE combined with CGM appears feasible and safe among adolescents with obesity. Further investigation in larger samples, with a longer intervention duration and follow-up assessments are needed.

INTRODUCTION:There have been many recent advances in the treatment of type 1 diabetes (T1D) including in insulin formulations, continuous glucose monitoring (CGM) technology and automated insulin delivery. However, long-term optimal glycemic control is still only achieved in a minority. AREAS COVERED:Adjunct therapy - the use of therapeutic agents other than insulin - is one strategy aimed at improving outcomes. An ideal adjunct agent would improve glycemic control, reduce weight (or weight gain), reduce insulin requirement and prevent complications (e.g. cardiorenal) without increasing hypoglycemia. The amylin analogue pramlintide has been licensed in the USA, while the sodium glucose co-transporter-2 inhibitor (SGLT2i) dapagliflozin, was briefly (2019 - 2021) licensed for type 1 diabetes in Europe and the UK. However, other agents from the type 2 diabetes (T2D) arena including metformin, other SGLT2is, glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-IV (DPP-4) inhibitors have been investigated. EXPERT OPINION:As evidence emerges for cardiorenal protection by SGLT2is and GLP-1RAs in T2D, it has become increasingly important to know whether people with T1D can also benefit. Here, we review recent trials of adjunct agents in T1D and discuss the efficacy and safety of these agents (alone and in combination) in an era in which continuous glucose monitoring is becoming standard of care.

CONTEXT:Use of continuous glucose monitoring (CGM) is increasing for insulin-requiring patients with diabetes. Although data on glycemic profiles of healthy, nondiabetic individuals exist for older sensors, assessment of glycemic metrics with new-generation CGM devices is lacking. OBJECTIVE:To establish reference sensor glucose ranges in healthy, nondiabetic individuals across different age groups using a current generation CGM sensor. DESIGN:Multicenter, prospective study. SETTING:Twelve centers within the T1D Exchange Clinic Network. PATIENTS OR PARTICIPANTS:Nonpregnant, healthy, nondiabetic children and adults (age ≥6 years) with nonobese body mass index. INTERVENTION:Each participant wore a blinded Dexcom G6 CGM, with once-daily calibration, for up to 10 days. MAIN OUTCOME MEASURES:CGM metrics of mean glucose, hyperglycemia, hypoglycemia, and glycemic variability. RESULTS:A total of 153 participants (age 7 to 80 years) were included in the analyses. Mean average glucose was 98 to 99 mg/dL (5.4 to 5.5 mmol/L) for all age groups except those over 60 years, in whom mean average glucose was 104 mg/dL (5.8 mmol/L). The median time between 70 to 140 mg/dL (3.9 to 7.8 mmol/L) was 96% (interquartile range, 93 to 98). Mean within-individual coefficient of variation was 17 ± 3%. Median time spent with glucose levels >140 mg/dL was 2.1% (30 min/d), and median time spent with glucose levels <70 mg/dL (3.9 mmol/L) was 1.1% (15 min/d). CONCLUSION:By assessing across age groups in a healthy, nondiabetic population, normative sensor glucose data have been derived and will be useful as a benchmark for future research studies.

BACKGROUND:Combining the GLP-1 receptor agonist semaglutide with the long-acting amylin analogue cagrilintide has weight-loss benefits; the impact on glycated haemoglobin (HbA) is unknown. This trial assessed the efficacy and safety of co-administered semaglutide with cagrilintide (CagriSema) in participants with type 2 diabetes. METHODS:This 32-week, multicentre, double-blind, phase 2 trial was conducted across 17 sites in the USA. Adults with type 2 diabetes and a BMI of 27 kg/m or higher on metformin with or without an SGLT2 inhibitor were randomly assigned (1:1:1) to once-weekly subcutaneous CagriSema, semaglutide, or cagrilintide (all escalated to 2·4 mg). Randomisation was done centrally using an interactive web response system and was stratified according to use of SGLT2 inhibitor treatment (yes vs no). The trial participants, investigators, and trial sponsor staff were masked to treatment assignment throughout the trial. The primary endpoint was change from baseline in HbA; secondary endpoints were bodyweight, fasting plasma glucose, continuous glucose monitoring (CGM) parameters, and safety. Efficacy analyses were performed in all participants who had undergone randomisation, and safety analyses in all participants who had undergone randomisation and received at least one dose of the trial medication. This trial is registered on ClinicalTrials.gov (NCT04982575) and is complete. FINDINGS:Between Aug 2 and Oct 18, 2021, 92 participants were randomly assigned to CagriSema (n=31), semaglutide (n=31), or cagrilintide (n=30). 59 (64%) participants were male; the mean age of participants was 58 years (SD 9). The mean change in HbA from baseline to week 32 (CagriSema: -2·2 percentage points [SE 0·15]; semaglutide: -1·8 percentage points [0·16]; cagrilintide: -0·9 percentage points [0·15]) was greater with CagriSema versus cagrilintide (estimated treatment difference -1·3 percentage points [95% CI -1·7 to -0·8]; p<0·0001), but not versus semaglutide (-0·4 percentage points [-0·8 to 0·0]; p=0·075). The mean change in bodyweight from baseline to week 32 (CagriSema: -15·6% [SE 1·26]; semaglutide: -5·1% [1·26]; cagrilintide: -8·1% [1·23]) was greater with CagriSema versus both semaglutide (p<0·0001) and cagrilintide (p<0·0001). The mean change in fasting plasma glucose from baseline to week 32 (CagriSema: -3·3 mmol/L [SE 0·3]; semaglutide: -2·5 mmol/L [0·4]; cagrilintide: -1·7 mmol/L [0·3]) was greater with CagriSema versus cagrilintide (p=0·0010) but not versus semaglutide (p=0·10). Time in range (3·9-10·0 mmol/L) was 45·9%, 32·6%, and 56·9% at baseline and 88·9%, 76·2%, and 71·7% at week 32 with CagriSema, semaglutide, and cagrilintide, respectively. Adverse events were reported by 21 (68%) participants in the CagriSema group, 22 (71%) in the semaglutide group, and 24 (80%) in the cagrilintide group. Mild or moderate gastrointestinal adverse events were most common; no level 2 or 3 hypoglycaemia was reported. No fatal adverse events were reported. INTERPRETATION:In people with type 2 diabetes, treatment with CagriSema resulted in clinically relevant improvements in glycaemic control (including CGM parameters). The mean change in HbA with CagriSema was greater versus cagrilintide, but not versus semaglutide. Treatment with CagriSema resulted in significantly greater weight loss versus semaglutide and cagrilintide and was well tolerated. These data support further investigation of CagriSema in this population in longer and larger phase 3 studies. FUNDING:Novo Nordisk.