Abstract
Introduction
This year, we screened 957 potentially eligible titles on lifestyle-related research in diabetes published between July 1, 2022, and June 30, 2023, using various search strategies including PubMed and Google Scholar. We shortlisted 48 original peer-reviewed manuscripts that focused on “exercise” and/or “nutrition” in diabetes mellitus and selected 10 papers to represent this broad and important research field. In general, these papers represent the continued focus on how exercise and/or nutrition modify the disease etiology and/or the disease progression/management.
Key Articles Reviewed
Legaard GE, Lyngbæk MPP, Almdal TP, Karstoft K, Bennetsen SL, Feineis CS, Nielsen NS, Durrer CG, Liebetrau B, Nystrup U, Østergaard M, Thomsen K, Trinh B, Solomon TPJ, Van Hall G, Brønd JC, Holst JJ, Hartmann B, Christensen R, Pedersen BK, Ried-Larsen M
Riddell MC, Li Z, Gal RL, Calhoun P, Jacobs PG, Clements MA, Martin CK, Doyle Iii FJ, Patton SR, Castle JR, Gillingham MB, Beck RW, Rickels MR, for the T1DEXI Study Group
Aronson R, Riddell MC, Conoscenti V, Junaidi MK
Igudesman D, Crandell J, Corbin KD, Zaharieva DP, Addala A, Thomas JM, Casu A, Kirkman MS, Pokaprakarn T, Riddell MC, Burger K, Pratley RE, Kosorok MR, Maahs DM, Mayer-Davis EJ, for the ACTION Study Group
Andriessen C, Fealy CE, Veelen A, van Beek SMM, Roumans KHM, Connell NJ, Mevenkamp J, Moonen-Kornips E, Havekes B, Schrauwen-Hinderling VB, Hoeks J, Schrauwen P
Strain T, Dempsey PC, Wijndaele K, Sharp SJ, Kerrison N, Gonzales TI, Li C, Wheeler E, Langenberg C, Brage S, Wareham N
Coomans de Brachène A, Scoubeau C, Musuaya AE, Costa-Junior JM, Castela A, Carpentier J, Faoro V, Klass M, Cnop M, Eizirik DL
Obermayer A, Tripolt NJ, Pferschy PN, Kojzar H, Aziz F, Müller A, Schauer M, Oulhaj A, Aberer F, Sourij C, Habisch H, Madl T, Pieber T, Obermayer-Pietsch B, Stadlbauer V, Sourij H
Mosquera-Lopez C, Ramsey KL, Roquemen-Echeverri V, Jacobs PG
Liu X, Johnson SB, Lynch KF, Cordan K, Pate R, Butterworth MD, Lernmark Å, Hagopian WA, Rewers MJ, McIndoe RA, Toppari J, Ziegler AG, Akolkar B, Krischer JP, Yang J, and the TEDDY Study Group
Effects of Different Doses of Exercise and Diet-induced Weight Loss on Beta-Cell Function in Type 2 Diabetes (DOSE-EX): A Randomized Clinical Trial
Legaard GE1, Lyngbæk MPP1, Almdal TP2,3, Karstoft K1,4, Bennetsen SL1, Feineis CS1, Nielsen NS1, Durrer CG1, Liebetrau B1, Nystrup U1, Østergaard M1, Thomsen K1, Trinh B1, Solomon TPJ5, Van Hall G6,7, Brønd JC8, Holst JJ9, Hartmann B9, Christensen R10,11, Pedersen BK1, Ried-Larsen M1,8
1Centre for Physical Activity Research, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 2Department of Endocrinology PE, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 3Department of Immunology & Microbiology, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 4Department of Clinical Pharmacology, Bispebjerg-Frederiksberg Hospital, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 5Blazon Scientific, London, UK; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 6Biomedical Sciences, Faculty of Health & Medical Science, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 7Clinical Metabolomics Core Facility, Clinical Biochemistry, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 8Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, Odense, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 9Department of Biomedical Sciences and the Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 10Section for Biostatistics and Evidence-Based Research, the Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; Department of Clinical Research, University of Southern Denmark, Odense, Denmark; 11Research Unit of Rheumatology, Department of Clinical Research, University of Southern Denmark, Odense, Denmark
The progressive loss of normal β-cell function is a hallmark in the development of type 2 diabetes (T2D). Regular exercise can help delay T2D onset by enhancing insulin sensitivity, but it is currently unclear if exercise impacts β-cell function and/or the capacity for the cells to secrete insulin under a glucose load in individuals who are recently diagnosed with T2D. This study examined the impact of different volumes of exercise, done over 16 weeks, on insulin sensitivity and β-cell function in adults recently diagnosed with T2D.
Methods
This four-armed randomized control trial enrolled a total of 82 persons (35% females; mean age 58 ± 10 years) with newly diagnosed T2D (< 7 years). The participants were randomly allocated to standard care (n = 20; CON), calorie restriction (25% energy reduction; n = 21; DCON), calorie restriction plus exercise three times per week (n = 20; MED), or calorie restriction and exercise six times per week (n = 21; HED) for 16 weeks. The type of exercise done in MED and HED included both aerobic and resistance training but differed in the total volume of exercise done per week (i.e., ∼150–160 min/wk vs 300–330 min/wk). The primary outcome was β-cell function, as measured by the late-phase disposition index (DI: insulin secretion × insulin sensitivity) at steady-state hyperglycemia during a hyperglycemic clamp. Secondary outcomes included glucose-stimulated insulin secretion and sensitivity during the clamp as well as the measurement of these same things during a liquid meal tolerance test.
Results
The late-phase DI, as measured during the last 30-minute phase of the hyperglycemic clamp, a marker of β-cell function, increased more in DCON (by 58% [95% CI, 16–116]) MED (by 105% [95% CI, 49–182]), and HED (by 137% [95% CI, 73–225]), relative to the changes observed in CON, with improvements more marked in the two exercise groups (MED and HED), which followed a linear dose-response relationship to the volume of exercise done (P < 0.001). The dose–response relationship observed for the late-phase DI was also reflected in the late-phase glucose-stimulated insulin sensitivity index (ISI) (P < 0.001), where both MED and HED increased more than CON; however, the difference in ISI between DCON and CON was less pronounced and not statistically different. The DI derived from a mixed meal tolerance test confirmed that oral DI increased more in all intervention groups relative to CON, with the MED and HED groups increasing more than DCON but similarly to each other.
Conclusions
All lifestyle-related interventions increased β-cell function relative to standard care in newly diagnosed patients with T2D. However, the addition of exercise in modest or high-volume amounts increased β-cell function to a higher degree than dietary restriction alone. The enhancement of β-cell function, as measured by the DI, by the addition of moderate and high-volume exercise appeared to be related to the activity-induced enhancement of insulin sensitivity.
Comments
Previous studies in humans with type 2 diabetes (T2D) have suggested that exercise training (aerobic) may enhance both first-phase and late-phase insulin responses (1,2), but a direct effect of exercise on β-cell function and insulin secretion is difficult to prove because exercise also increases insulin sensitivity and thus often reduces insulin needs. Directly measuring exercise effects on β-cell function is difficult in humans, but a number of indirect assessments can be made from frequent blood sampling and the measurements of circulating insulin and glucose levels after either a mixed meal challenge or a glucose clamp.
Both moderate- and high-volume exercise appeared to benefit overall glycemia, as did dietary restriction alone, but the mechanisms for improvement were not all the same. The authors speculated that the dietary restriction protocol used in this study to improve glycemia in individuals living with T2D resulted in enough weight loss (∼7.5%) to re-establish late-phase insulin secretion rate, and that the addition of exercise resulted in no further rise in insulin secretion capacity but did result in improvements in insulin index, a marker of insulin sensitivity. In other words, weight loss helps with insulin secretion whereas exercise training appears to primarily drive improvement in insulin sensitivity.
This new study conflicts with earlier work, however, where individuals with T2D, who had at least a moderate capacity to secrete insulin during a hyperglycemic clamp at baseline as measured by C-peptide levels, tended to have a significant improvement in C-peptide secretion after 3 months of intensive training (3). This does suggest that exercise can improve both insulin sensitivity and secretion capacity. In any event, the end result for glycemia is clear: combining regular exercise with dietary restriction results in better glucose management through adaptive changes in the pancreas and peripheral tissues.
One additional interesting observation in this new study is that adding exercise training to dietary restriction lowered the first-phase insulin response rather than increasing it, particularly in the group undergoing calorie restriction and exercise six times per week (HED). This may be because HED was associated with a greater improvement in insulin sensitivity and a higher level of glucose effectiveness (i.e., greater ability of glucose itself to enhance its own disposal and suppress its own endogenous glucose production rate under basal insulin conditions). Based on this study, we suggest that regular exercise should be encouraged during dietary-induced weight loss for people with early T2D with the expectation that an enhancement of β-cell function should occur.
Examining the Acute Glycemic Effects of Different Types of Structured Exercise Sessions in Type 1 Diabetes in a Real-World Setting: The Type 1 Diabetes and Exercise Initiative (T1DEXI)
Riddell MC1, Li Z2, Gal RL2, Calhoun P2, Jacobs PG3, Clements MA4, Martin CK5, Doyle Iii FJ6, Patton SR7, Castle JR8, Gillingham MB9, Beck RW2, Rickels MR10 for the T1DEXI Study Group
1Muscle Health Research Centre, York University, Toronto, Canada; University of Pennsylvania, Philadelphia, PA; 2Jaeb Center for Health Research, Tampa, FL; University of Pennsylvania, Philadelphia, PA; 3Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR; University of Pennsylvania, Philadelphia, PA; 4Children's Mercy Hospital, Kansas City, MO; University of Pennsylvania, Philadelphia, PA; 5Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA; University of Pennsylvania, Philadelphia, PA; 6Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, University of Pennsylvania, Philadelphia, PA; 7Nemours Children's Health, Jacksonville, FL; University of Pennsylvania, Philadelphia, PA; 8Harold Schnitzer Diabetes Health Center, Oregon Health & Science University, Portland, OR; University of Pennsylvania, Philadelphia, PA; 9Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR; University of Pennsylvania, Philadelphia, PA; 10Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
This manuscript is also discussed in DIA-2024-2502, page S-14.
Our knowledge of the typical blood glucose responses to different forms of exercise in people with type 1 diabetes (T1D) is largely based on a number of relatively small but carefully constructed clinical studies in highly controlled environments. From these studies and clinical experiences, it is well established that aerobic exercise tends to cause glucose levels to drop, while resistance and interval exercise can have variable effects, with some individuals potentially having a rise in glucose or only a small drop (4). Measuring the glucose responses in real-world activities in T1D has not been done to any large extent. The Type 1 Diabetes Exercise Initiative (T1DEXI) was a real-world study of spontaneous physical activity and structured exercise sessions in adults living with T1D who were randomized to supplementary sessions (∼30 minutes) of at-home aerobic, interval, or resistance exercise led by instructional videos.
Methods
The Type 1 Diabetes Exercise Initiative (T1DEXI) was a real-world study of at-home exercise. Adult participants were randomly assigned to complete six structured aerobic, interval, or resistance exercise sessions over 4 weeks. Participants self-reported study and nonstudy exercise, food intake, and insulin dosing (multiple daily injection [MDI] users) using a custom smartphone application and provided pump (pump users), heart rate, and continuous glucose monitoring data.
Results
Mean (± SD) change in sensor-glucose level during assigned exercise was −18 ± 39, −14 ± 32, and −9 ± 36 mg/dL for aerobic, interval, and resistance, respectively (P < 0.001), with similar results for hybrid closed-loop, standard pump, and MDI users. On average, time in target range (TIR: 70–180 mg/dL or 3.9–10.0 mmol/L) was six percentage points higher during the 24 hours after study-assigned exercise than in any 24-hour period without activity (mean, 76% ± 20% SD vs 70% ± 23% SD; P < 0.001).
Conclusions
Adults with T1D have the largest drop in glucose level with ∼30 minutes of structured aerobic exercise, and considerably less of a drop if they do interval or resistance activity for the same duration. The acute changes in glycemia caused by all three major forms of exercise do not appear to be impacted significantly by insulin delivery modality. Nonetheless, days with structured at-home exercise sessions appear to contribute to clinically meaningful improvement in glucose TIR, while only marginally increasing glucose time below range.
Comments
This is the largest study to date on the effects of physical activity on glycemia in adults with T1D. The overarching goal of the T1DEXI study was to observe the acute effects of different forms of at-home activity, including planned and structured exercise sessions that last about 30 minutes, which is typical of an average “workout.” This first study is only the tip of the iceberg. Riddell and colleagues provide considerable data on the various patient-specific and event-level factors that appear to impact the change in glucose caused by exercise, including sex, recent glycated hemoglobin (HbA1c) level, pre-exercise glucose concentration, glucose trends before exercise, insulin on board, exercise time of day, and baseline heart rate (a good proxy for aerobic fitness). In another “big data” paper from the T1DEXI working group, the team published an exercise hypoglycemia prediction model using repeated measures random forest plot analyses (5). Taken together, these publications should help to improve decision support for exercise and glucose management in T1D. The full T1DEXI dataset is openly available on the Vivli platform (
Effect of Mini-dose Ready-to-Use Liquid Glucagon on Preventing Exercise-associated Hypoglycemia in Adults with Type 1 Diabetes
Aronson R1, Riddell MC1, Conoscenti V2, Junaidi MK2
1LMC Diabetes & Endocrinology, Toronto, Ontario, Canada; Inc., Chicago, IL; 2Xeris Pharmaceuticals, Inc., Chicago, IL
Prolonged moderate-to-vigorous intensity exercise causes glucose levels to drop in individuals with type 1 diabetes (T1D). To help limit the risk for hypoglycemia during and after exercise, individuals are instructed to reduce insulin delivery and/or consume extra carbohydrates, but both strategies have limitations. Lowering insulin requires careful consideration as to what insulin to reduce (basal or bolus) and when to reduce it. Consuming extra carbohydrates works to limit the drop in glucose, but this can sometimes cause hyperglycemia, and it may be undesirable for the individual if weight loss is a goal. A third option may be to administer a small amount of glucagon (∼150 μg, called a mini-dose) just before exercise. This study investigated the efficacy and safety of mini-dose glucagon (MDG) in active adults with T1D in real-world settings.
Methods
Adults with T1D on continuous subcutaneous insulin infusion (CSII) were randomly assigned to an outpatient crossover design study that included prolonged exercise (self-selected activities that lasted between 30 and 75 minutes) using (A) MDG plus a 50% basal rate reduction (BRR) before exercise, (B) placebo treatment plus a 50% BRR before exercise, or (C) MDG with no insulin adjustments. Glucose data were analyzed for incidence of level 1 hypoglycemia (as the primary end point) based on self-monitoring blood glucose (SMBG).
Results
Forty-five adults (22 female) completed the outpatient study. For all exercise sessions in the outpatient phase (n = 795), the incidence of level 1 hypoglycemia was lower in both MDG arms (A: 12% [P < 0.0001]; C: 16% [P = 0.0032]) than in the placebo arm with a 50% BRR (B: 39%). Carbohydrate intake tended to be less with MDG use than with placebo use, but the differences did not reach statistical significance (P = 0.12). The percent time below range, time in range, and time above range from 0 to 300 minutes using continuous glucose monitoring analyses (as secondary end points) did not differ among treatment arms.
Conclusions
Ready-to-use, liquid-stable MDG, with or without 50% BRR, given just before prolonged moderate-to-vigorous exercise effectively decreases the incidence rate of level 1 hypoglycemia in adults with T1D as compared with a 50% BRR alone. Time-in-range metrics do not appear to be negatively or positively impacted by the frequent use of MDG for exercise at home.
Comments
This is another excellent study demonstrating that a small amount of subcutaneously delivered glucagon, with or without BRR, before exercise is a simple and viable approach to prevent exercise-induced hypoglycemia in active adults with T1D. Unlike a previous study showing similar efficacy with in-clinic exercise (6), this research team used the liquid-stable form of glucagon (Xeris Pharmaceuticals), which makes the procedure quick and convenient. This study also used an in-clinic visit to train the participants on withdrawing MDG from a syringe and vial with instructions on how and when to deliver the hormone to help prevent exercise-induced hypoglycemia. This was likely valuable because one should not use glucagon for all forms of exercise or when the glucose level before exercise is already elevated above what appears to be the ideal target range for exercise (∼90–180 mg/dL or 5–10 mmol/L) (7). Although the expense of this approach for exercise may become an issue (MDG will be more expensive than sugar), the efficacy and tolerability should not be questioned based on this study: the incidence of hypoglycemia dropped from ∼40% when a BRR was used to only ∼15% when MDG was used. Moreover, the risk for side effects with MDG for exercise are low because the amount of glucagon used is about one-tenth of a hypoglycemia treatment dose.
Weight Management in Young Adults with Type 1 Diabetes: The Advancing Care for Type 1 Diabetes and Obesity Network Sequential Multiple Assignment Randomized Trial Pilot Results
Igudesman D1,2, Crandell J3, Corbin KD2, Zaharieva DP4, Addala A4, Thomas JM1, Casu A2, Kirkman MS5, Pokaprakarn T3, Riddell MC6, Burger K1, Pratley RE2, Kosorok MR3, Maahs DM4, Mayer-Davis EJ1,5, for the ACTION Study Group
1Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC; York University, Toronto, Ontario, Canada; 2AdventHealth Translational Research Institute, Orlando, FL; York University, Toronto, Ontario, Canada; 3Department of Biostatistics, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC; York University, Toronto, Ontario, Canada; 4Department of Pediatrics, Division of Endocrinology, Stanford University, Stanford, CA; York University, Toronto, Ontario, Canada; 5Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC; York University, Toronto, Ontario, Canada; 6School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada
More than two-thirds of adults with type 1 diabetes (T1D) are overweight or obese, and this percentage has increased about twofold over the last 30 years. For many individuals with diabetes, the simultaneous management of weight and glycemia poses a challenge, particularly in the context of T1D. The present study assessed the impact of three distinct diets—a hypocaloric low-carbohydrate diet, a hypocaloric moderately low-fat diet, and a Mediterranean diet without calorie restriction—on weight and glycemia among young adults with T1D and overweight or obesity.
Methods
This 9-month pilot study using a sequential, multiple assignment, randomized trial approach enrolled individuals aged 19–30 years with a T1D diagnosis for at least 1 year and a body mass index (BMI) between 27 and 39.9 kg/m2. Reassignment to different diets occurred at the 3- and 6-month period if the initially assigned diet was deemed unsatisfactory or ineffective. The present findings are from the initial 3-month dietary phase along with the reassignment data that were collected before the COVID-19 pandemic began. The study focused on primary outcomes, including weight, hemoglobin A1c (HbA1c) levels, and the percentage of time spent below range (< 70 mg/dL). Secondary outcomes included body fat percentage, the percentage of time in range (70–180 mg/dL), and the percentage of time below range (< 54 mg/dL). Statistical models were adjusted for study design, demographic characteristics, and clinical variables and tested changes in outcomes and differences in diet.
Results
The adjusted values for weight and HbA1c (n = 38) demonstrated changes of −2.7 kg ([95% CI, −3.8 to −1.5], P < 0.0001) and −0.91 percentage points ([95% CI, −1.5 to −0.30], P < 0.005), respectively. Conversely, the adjusted average body fat percentage remained relatively stable (P = 0.21). Even after adjustments, there was no significant difference in hypoglycemia (n = 28, P > 0.05). There was considerable variability across all outcomes, including weight change, with 57.9% of participants being rerandomized due to weight loss < 2%. None of the outcomes varied by diets tested.
Conclusions
This study demonstrated that over a 3-month period young adults with T1D achieved modest weight loss (∼2 kg) without compromising HbA1c levels or increasing hypoglycemia risk, regardless of macronutrient distribution or caloric restriction.
Comments
There is growing concern regarding the increasing prevalence of overweight and obesity among individuals with type 1 diabetes (T1D), particularly in the United States (8). Obesity rates have risen drastically from 3.4% (1986–1988) to 22.7% (2007) and 36.8% (2018). This is particularly concerning given the increased cardiovascular disease risk in T1D. There seems to be no universal consensus on the “right” dietary approach or the “right” weight loss approach, particularly for individuals with T1D. This may be in part due to the various ways in which T1D affects individuals, the complexities of managing glycemia, and the unique interplay of factors such as genetics, metabolism, insulin needs, and overall patient goals. As such, coming up with a one-size-fits-all weight loss or dietary approach that works for everyone is an oversimplification.
The present study by Igudesman and colleagues was a sequential, multiple-assignment, randomized trial approach that implemented three evidence-based diets: hypocaloric low carbohydrate, hypocaloric moderate low fat (Look AHEAD), and Mediterranean diet without calorie restriction (9). The objective was to find acceptable and effective dietary approaches for weight and glycemic optimization in young adults with T1D and overweight or obesity. The study uncovered the potential for modest weight reduction (∼2 kg) while sustaining or improving HbA1c levels. As we know, diet and exercise often complement each other to drive positive lifestyle changes and improvements in overall well-being. As such, Muntis et al. (10) conducted an ancillary study within the Advancing Care for Type 1 Diabetes and Obesity Network (ACT1ON) that focused on the relationship between moderate-to-vigorous physical activity (MVPA) and glycemic outcomes. These findings surprisingly demonstrated that among young adults with T1D and overweight or obesity, increased MVPA was associated with worsened glycemia. The higher percent time in hyperglycemia (> 180 mg/dL) and lower percent time in range (TIR, 70–180 mg/dL) in the 24 hours following days with more physical activity could indicate possible changes in dietary habits or self-management behaviors related to T1D.
Collectively, these studies demonstrate the complexity and challenges around optimizing weight and glycemic management together in young adults with T1D and overweight or obesity. Although increasing physical activity has been shown in prior studies (11,12) to improve TIR and lower mean glucose in youth and adults with T1D, those participants were generally more lean and physically active at baseline compared with the present study. As such, more research is needed to understand the obstacles impeding glycemic control during and after physical activity in young adults with T1D and overweight or obesity.
Three Weeks of Time-restricted Eating Improves Glucose Homeostasis in Adults with Type 2 Diabetes but Does Not Improve Insulin Sensitivity: A Randomised Crossover Trial
Andriessen C1, Fealy CE1, Veelen A1, van Beek SMM1, Roumans KHM1, Connell NJ1, Mevenkamp J1,2, Moonen-Kornips E1, Havekes B3, Schrauwen-Hinderling VB1,2, Hoeks J1, Schrauwen P1
1Department of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands; Division of Endocrinology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands; 2Department of Radiology and Nuclear Medicine, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands; Division of Endocrinology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands; 3Department of Internal Medicine, Division of Endocrinology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands
The current eating habits of many people is disrupting their metabolic rhythmicity and leading to a lack of a true overnight fast due to individuals consuming much of their daily “nutrition” within a 14-hour period. Time-restricted eating (TRE) has shown beneficial effects in some metabolic studies in humans, such as increased lipid oxidation (13), decreased plasma glucose levels (14), and improved insulin sensitivity (15). These benefits can be valuable for people with type 2 diabetes (T2D). This study explored the metabolic effects of TRE in free-living conditions in this population, focusing on some of the mechanistic changes that might help explain clinical outcomes.
Methods
This randomized crossover study, consisting of 3 weeks of control (CON) and 3 weeks of TRE intervention, which restricted food intake to a 10-hour window per day, enrolled 14 participants with T2D (50% female; mean age: 67.5 ± 5.2; mean body mass index [BMI]: 30.5 ± 4.2; mean baseline fasting glucose: 7.9 ± 1.3 mmol/L). Hepatic glycogen levels, insulin sensitivity, and glucose homeostasis were assessed using 13C-MRS, two-step hyperinsulinemic-euglycemic clamp, and continuous glucose monitoring, respectively.
Results
The hepatic glycogen level was not different between the TRE and CON interventions after a standardized 11-hour fast (P = 0.88). Insulin sensitivity, as assessed by M value during hyperinsulinemic-euglycemic clamp, was also not different between the two interventions (P = 0.1). However, insulin-induced nonoxidative glucose disposal was higher in the TRE group (from baseline to high insulin) than the CON group (4.3 ± 1.1 vs 1.5 ± 1.7 μmol kg−1 min−1, P = 0.04). Time spent in normal glycemia (defined as 4.4–7.2 mmol/L) was higher in the TRE group than the CON group (15.1 ± 0.8 hours vs 12.2 ± 1.1 hours; P = 0.01). TRE reduced the mean 24-hour glucose (6.8 ± 0.2 vs 7.6 ± 0.3 mmol/L; P < 0.01) and fasting glucose (7.6 ± 0.4 vs 8.6 ± 0.4 mmol/L; P = 0.03). Both interventions had a similar 24-hour energy expenditure and 24-hour respiratory exchange ratio; however, carbohydrate oxidation was reduced with TRE (260.2 ± 7.6 vs 277.8 ± 10.7 g/day; P = 0.04).
Conclusions
TRE resulted in decreased glucose levels and better time in range for people with T2D, suggesting improved glucose homeostasis. However, these improvements were not associated with changes in hepatic glycogen, insulin sensitivity, mitochondrial function, or 24-hour substrate oxidation rates.
Comments
Previous studies in nondiabetic, overweight/obese individuals showed the beneficial metabolic effects of time-restricted eating (TRE), but most of these studies were done under controlled conditions (6- to 8-hour eating window) (13 –16). This study showed the benefits of TRE with a more feasible 10-hour eating window in free-living conditions for people with T2D, though the underlying mechanisms were not fully apparent. The improved glucose homeostasis could be driven by nocturnal glucose levels and/or hepatic glycogen changes that can be further explored in future studies. Furthermore, this study demonstrated the safety of TRE for people with T2D who are on diabetes medication (10 out of 14 participants using metformin) because no adverse events were reported. Based on this small study, we cautiously suggest that TRE could be another tool for people with T2D to decrease hyperglycemia by decreasing their daily eating window from 14 hours to 10 hours a day.
Quantifying the Relationship between Physical Activity Energy Expenditure and Incident Type 2 Diabetes: A Prospective Cohort Study of Device-measured Activity in 90,096 Adults
Strain T1, Dempsey PC1,2, Wijndaele K1, Sharp SJ1, Kerrison N1, Gonzales TI1, Li C1, Wheeler E1, Langenberg C1, Brage S1, Wareham N1
1MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK; College of Life Sciences, University of Leicester, Leicester, UK; 2Diabetes Research Centre, College of Life Sciences, University of Leicester, Leicester, UK
The dose–response relationship between habitual physical activity levels and the development of type 2 diabetes (T2D) is unclear, particularly because the measurement of activity levels is often based on self-report or because the volume and intensity of exercise is highly controlled (fixed) in most randomized control trials without much of a range in exercise volume or intensity. Physical activity energy expenditure (PAEE) can be estimated with wearable technology, thereby allowing for larger datasets to be collected to help determine the optimal dose of activity to prevent or treat T2D. This study investigated the association between accelerometer-derived PAEE and incident T2D in a large (n = 90,096) cohort of middle-aged adults without known diabetes at baseline using the UK Biobank prospective study.
Methods
Volunteers were interviewed in person, completed an online questionnaire, and had a baseline anthropometric assessment. A subsample (n = 103,670) was invited to wear a wrist-worn accelerometer (AX3; Axivity monitor) for 7 days, approximately 5 years after initial recruitment. An equation was used to convert activity counts into PAEE units, expressed as kilojoules per kilogram body mass per day. Time spent in moderate-to-vigorous physical activity (MVPA) was also estimated from these data. Diabetes at follow-up was assessed based on self-report of a diagnosis, hospital episode statistics, medication use, and/or blood tests. The relationship between PAEE and incident T2D was examined with model adjustments for potential confounders and effect modifiers.
Results
PAEE was inversely associated with incident T2D in a linear fashion with no observable attenuation in the association even at extreme PAEE levels (> 70 kJ · kg−1 · day−1). The odds of developing T2D were reduced by 19% (95% CI, 17–21) for every increase in PAEE by 5 kJ · kg−1 · day−1 without adjustment for body mass index (BMI), and were estimated to be reduced by 11% (9 –13) with BMI adjustment. The association was stronger in men than women and weaker in those with obesity and higher genetic susceptibility to obesity. There was no evidence of effect modification by genetic susceptibility to T2D or insulin resistance. For a given level of PAEE, the odds of T2D were lower among those engaging in more moderate-to-vigorous activity.
Conclusions
A strong linear relationship likely exists between PAEE and incident T2D. A difference in PAEE equivalent to an additional 20-minute brisk walk per day is associated with 19% lower odds of developing T2D.
Comments
The bottom line of this impactful study is that some exercise is good, but more is better with respect to T2D prevention. It was impressive to us that the protective effects of regular exercise (with some exercise good, but with more being better) is maintained in all subgroup analyses (sex, BMI status, genetic susceptibility to obesity, etc.), albeit the strength of the association differed somewhat in a few of these subgroups. Another interesting finding was that accumulating the same volume of PAEE through higher intensity effort was associated with lower odds of T2D than accumulating it through lower intensity activity. One odd thing to us is that physical activity levels were only measured once during a 7-day activity monitor wear time, which suggests that activity patterns must be largely consistent within an individual over a given period of time. In any event, it will be valuable to track activity levels in a large cohort of people to confirm that more exercise is better than some exercise for T2D prevention.
Exercise as a Non-pharmacological Intervention to Protect Pancreatic Beta Cells in Individuals with Type 1 and Type 2 Diabetes
Coomans de Brachène A1, Scoubeau C2, Musuaya AE1, Costa-Junior JM1, Castela A1, Carpentier J2, Faoro V3, Klass M2,4, Cnop M1,5, Eizirik DL3
1ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles, Brussels, Belgium; Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium; 2Laboratory for Biometry and Exercise Nutrition, Université Libre de Bruxelles, Brussels, Belgium; Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium; 3Cardiopulmonary Exercise Laboratory, Université Libre de Bruxelles, Brussels, Belgium; Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium; 4Laboratory of Applied Biology and Research Unit in Applied Neurophysiology, Université Libre de Bruxelles, Brussels, Belgium; Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium; 5Division of Endocrinology, Erasmus Hospital, Université Libre de Bruxelles, Brussels, Belgium
Both type 1 and type 2 diabetes (T1D and T2D) are characterized by a loss of pancreatic β-cells, and targeting this functional loss could offer a strategy to slow down the progression of diabetes. A proposed mechanism for pancreatic β-cell death is endoplasmic reticulum (ER) stress. A previous small study by this group had shown that serum from eight healthy participants who exercised for 8 weeks had attenuated β-cell apoptosis when donor β-cells were treated with thapsigargin (a chemical ER stressor). This study investigated whether serum from a diverse population undergoing a variety of exercise training could show the same beneficial effects.
Methods
To investigate the impact of different exercise training, 46 healthy individuals (56.5% female) were randomized into high-intensity interval training (HIIT), adapted sprint interval training (aSIP), vigorous-intensity continuous training (VICT), or high-intensity functional training performed at home (HIFT) for 8 to 12 weeks. To investigate the impact of diabetes status, 36 individuals (17 healthy, 8 T1D, and 11 T2D) were enrolled in a 12-week combined HIIT and strength training program. EndoC-βH1 (a precultured human β-cell line) were supplemented with serum from the participants from weeks 0, 4, 8, 12, or washout or clusterin and then treated with thapsigargin to evaluate β-cell apoptosis.
Results
HIIT, aSIP, and VICT significantly attenuated β-cell apoptosis at 4 weeks, and HIFT had significant protection after 8 weeks of exercise. Pooling all 46 healthy individuals showed a 28% and 35% decrease in apoptosis at 4 and 8 weeks, respectively. This protective effect remained for 2 months after the exercise training ended. Serum from both T1D and T2D participants also significantly reduced thapsigargin-induced apoptosis by 45% and 26%, respectively. Lastly, clusterin-treated cells (which the authors call an “exerkine” because it is a cellular “product” produced by the exercising organism) also had reduced apoptosis by 31%–42% (1 and 100 ng/mL) and significantly reduced DP5 (proapoptotic gene) expression at 100 ng/mL.
Conclusions
All exercise interventions protected β-cells against ER stress-induced apoptosis, and this benefit was irrespective of diabetes status, BMI, sex, age, or ancestry. This protection persisted after the end of the study, after 2 months of washout. The investigators suggest this could be explained by exercise-induced epigenetic changes. The exerkine clusterin replicates similar effects to the exercised serum.
Comments
Many studies focus on immunotherapies in T1D to protect β-cells. Nevertheless, ER stress has also been shown to impact β-cells in both T1D and T2D (17), and pharmaceutical therapies such as tauroursodeoxycholic acid and imatinib are currently undergoing testing with the aim of postponing the death of β-cells (18,19). This study demonstrated that serum from exercised individuals, which can carry all sorts of cellular products and signaling molecules (sometimes called exerkines), is able to protect β-cells against an ER stressor and apoptosis. This finding was particularly interesting because serum from people with T1D and T2D yielded similar effects if they did exercise. Exercise is recommended to all people with diabetes as it improves glycemic control, insulin sensitivity, and cardiovascular health (20). But this study adds to the story because exercise appears to produce chemical signals that promote β-cell health and longevity. Based on this novel work, exercise can potentially provide a safe strategy to delay diabetes onset and preserve endogenous insulin secretion, at least to a certain extent.
Efficacy and Safety of Intermittent Fasting in People with Insulin-treated Type 2 Diabetes (INTERFAST-2): A Randomized Controlled Trial
Obermayer A1,2, Tripolt NJ1,2, Pferschy PN1,2,3, Kojzar H1,2, Aziz F1,2, Müller A1,2, Schauer M2, Oulhaj A4,5, Aberer F1,2, Sourij C6, Habisch H7, Madl T7,8, Pieber T2,3, Obermayer-Pietsch B2,9, Stadlbauer V3,10, Sourij H1,2
1Interdisciplinary Metabolic Medicine Trials Unit, Medical University of Graz, Graz, Austria; Medical University of Graz, Graz, Austria; 2Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Medical University of Graz, Graz, Austria; 3CBmed - Center for Biomarker Research in Medicine, Graz, Austria; Medical University of Graz, Graz, Austria; 4College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates; Medical University of Graz, Graz, Austria; 5Research and Data Intelligence Support Center, Khalifa University, Abu Dhabi, United Arab Emirates; Medical University of Graz, Graz, Austria; 6Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria; Medical University of Graz, Graz, Austria; 7Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria; Medical University of Graz, Graz, Austria; 8BioTechMed-Graz, Graz, Austria; Medical University of Graz, Graz, Austria; 9Endocrinology Lab Platform, Division of Endocrinology and Diabetology, Department of Internal Medicine and Department of Gynecology and Obstetrics, Medical University of Graz, Graz, Austria; Medical University of Graz, Graz, Austria; 10Division of Gastroenterology and Hepatology, Medical University of Graz, Graz, Austria
The prevalence of type 2 diabetes (T2D) is increasing worldwide with a need for effective dietary strategies to enable therapeutic management of glucose levels, weight, and cardiovascular risk factors. To date, dietary modifications for individuals with T2D have focused on daily caloric restriction with resultant challenges in adherence. Intermittent fasting (IF) has been suggested as an alternative approach because it requires strict energy restriction on only certain days of the week; however, for those using insulin IF has potential to increase hypoglycemia risk. The present study investigated the impact of IF compared with standard care on change in hemoglobin A1c (HbA1c), weight reduction, and insulin dose reduction in adults with T2D on insulin therapy.
Methods
This was a 12-week randomized controlled trial with adults (mean age 63 years) with insufficiently controlled T2D (HbA1c > 7%), a body mass index (BMI) of > 30 kg/m2, and total daily insulin dose of > 0.3 IU/kg body weight. Forty-six participants were randomized to IF (n = 22) or usual care group (n = 24). All participants undertook dietary counseling and were provided with continuous glucose monitoring. The IF group undertook fasting 3 days per week reducing their calories on these days to 25% of recommended daily intake. On fasting days the participants were instructed to reduce their basal insulin by 20%. The co-primary end points were the change in HbA1c from baseline to 12 weeks and the difference in the number of participants achieving a combined end point (weight reduction ≥ 2%, insulin dose reduction ≥ 10% and HbA1c reduction ≥ 3 mmol/mol). Outcomes were analyzed using both unpaired t tests and linear mixed-effects model.
Results
After 12 weeks, HbA1c significantly decreased in the IF group compared with the standard care group (−7.3 ± 12.0 mmol/mol vs 0.1 ± 6.1 mmol/L, P = 0.012). The co-primary end point was achieved by eight participants in the IF group compared with none in the standard group (P < 0.001). At 12 weeks, the mean total insulin dose was significantly reduced in the IF group compared with the standard care group (9 ± 10 IU vs 4 ± 10 IU, P = 0.008). There was > 75% adherence to the fasting protocol (n = 20). No severe hypoglycemia occurred in either group.
Conclusions
In individuals with T2D using insulin therapy, IF is a feasible approach to improve glycemia and reduce body weight and total daily insulin dose. It can be employed safely in the short-term without significant hypoglycemia.
Comments
The implementation of therapeutic dietary approaches to lower glycemia and maintain healthy weight is critical for the successful management of T2D. Intermittent fasting, involving days of low-energy consumption coupled with days of normal eating patterns, has been proposed as a method to achieve weight loss outcomes in overweight and obese individuals without T2D (21). In individuals with T2D, intermittent fasting (IF) has also been shown to lead to improvements in glycemic outcomes (22). However, the effect of IF as a possible therapy option in individuals with T2D using insulin therapy has been controversial because of concerns regarding hypoglycemia and challenges in appropriate insulin adjustment protocols.
The current study implemented 12 weeks of IF in 22 older adults with long-standing T2D using insulin but above the target glycemia. The objective was to compare IF with a standard dietary intervention involving continuous energy restriction to assess the safety and efficacy for those using insulin. Importantly, on fasting days the participants were instructed to reduce their long-acting insulin by 20% and give prandial insulin only for glucose correctional reasons, a method that can readily be translated into the clinical setting. The study reported potential benefits of IF in terms of HbA1c and weight reduction, notably without any severe hypoglycemia.
These data extended the findings of other studies in T2D (23) that IF is a safe dietary option also for individuals using intensive insulin therapy. Thus, IF provides an alternative approach to continuous caloric restriction that potentially may be followed more easily by some individuals, although, like all dietary interventions, it should not be applied as an overarching recommendation for all. Close monitoring of insulin dose adjustments ideally coupled with continuous glucose monitoring use and awareness of emerging disordered eating behaviors, such as engagement in restriction and binge-eating patterns, is an important consideration for the safe and efficacious use of IF in the long-term management of insulin-treated T2D.
Modeling Risk of Hypoglycemia during and following Physical Activity in People with Type 1 Diabetes Using Explainable Mixed-Effects Machine Learning
Mosquera-Lopez C1, Ramsey KL2, Roquemen-Echeverri V1, Jacobs PG1
1Artificial Intelligence for Medical Systems (AIMS) Lab, Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR; Oregon Health & Science University, Portland, OR; 2Biostatistics and Design Program, Oregon Health & Science University, Portland, OR
Physical activity (PA) offers numerous health benefits for individuals with type 1 diabetes (T1D), such as improving glycemic management, cardiovascular fitness, and muscle strength and reducing diabetes-related complications. However, PA can also increase the risk of hypoglycemia during and after exercise. This study models the probability of hypoglycemia both during and after PA, identifying key factors influencing this risk in T1D.
Methods
This study used a real-world dataset from the Tidepool Big Data Donation Program that included glucose and PA data and insulin doses from 50 individuals with T1D (a total of 6448 sessions). This dataset was used to train and validate the machine-learning models. Additionally, data from the T1DEXI study, including glucose and PA data from 20 individuals with T1D (a total of 139 sessions), was used to independently assess the precision of the most successful model. To model hypoglycemia risk related to PA, mixed-effects logistic regression (MELR) and mixed-effects random forest (MERF) models were used. Odds ratios and partial dependence analysis were also used to determine hypoglycemia risk factors for the MELR and MERF models, respectively. The predictive accuracy was quantified using the area under the receiver operating characteristic curve (AUROC).
Results
The analysis successfully identified significant risk factors associated with hypoglycemia during and after PA in both the MELR and MERF models, including glucose and body exposure to insulin at PA onset, low blood glucose index 24 hours before PA, as well as the timing and intensity of PA. Both models demonstrated a distinct hypoglycemia risk peak 1 hour after PA and another one 5–10 hours later, aligning with the observed pattern in the training dataset. The impact of time after the activity on hypoglycemia risk varied across different types of physical activity. The MERF model's predictive accuracy for hypoglycemia was highest during the first hour after the onset of PA (AUROCValidation = 0.83, AUROCTesting = 0.86), and decreased for predicting hypoglycemia in the 24 hours after PA (AUROCValidation = 0.66, AUROCTesting = 0.68).
Conclusions
Hypoglycemia risk after the initiation of PA can be effectively captured through mixed-effects machine learning to identify risk factors that may be used in future decision support and insulin delivery systems. These models have been published online and made accessible to the general public to provide a population-level framework that others can employ.
Comments
Even with advancements in diabetes technology (e.g., hybrid closed-loop systems) and faster-acting insulin formulations (e.g., fast-acting insulin aspart), one of the ongoing challenges and barriers to regular physical activity (PA) and exercise is the heightened risk of hypoglycemia for individuals with T1D. So can we not just predict when hypoglycemia would occur during exercise? Well, yes and no. Thanks to large-scale and ongoing research studies, we can do a better job at predicting hypoglycemia risk now that we understand what factors play the biggest role. The present study by Mosquera-Lopez and colleagues revealed that the key risk factors significantly associated with hypoglycemia included glucose and body exposure to insulin at PA onset, the low blood glucose index in the 24 hours before PA, and the intensity and timing of the PA (24). Additional work by Bergford et al. (5) identified similar yet different hypoglycemia risk factors, including lower starting pre-exercise glucose levels, decreasing glucose levels before exercise, and higher levels of insulin on board or active insulin pre-exercise. I suppose if we had to combine both these studies and consider optimal strategies for reducing the risk of exercise-associated hypoglycemia, one might consider five key factors: (1) the intensity and timing of PA, (2) hypoglycemia in the 24 hours before exercise, (3) pre-exercise insulin on board, (4) starting glucose concentrations, and (5) glucose trends before exercise. Simple, right?!
Physical Activity and the Development of Islet Autoimmunity and Type 1 Diabetes in 5- to 15-Year-Old Children Followed in the TEDDY Study
Liu X1, Johnson SB2, Lynch KF1, Cordan K3, Pate R3, Butterworth MD1, Lernmark Å4, Hagopian WA5, Rewers MJ6, McIndoe RA7, Toppari J8,9, Ziegler AG10, Akolkar B11, Krischer JP1, Yang J1, and the TEDDY Study Group
1Health Informatics Institute, Morsani College of Medicine, University of South Florida, Tampa, FL; Bethesda, MD; 2Department of Behavioral Sciences and Social Medicine, Florida State University College of Medicine, Tallahassee, FL; Bethesda, MD; 3Department of Exercise Science, Arnold School of Public Health, University of South Carolina, Columbia, SC; Bethesda, MD; 4Department of Clinical Sciences, Lund University/CRC, Skåne University Hospital SUS, Malmo, Sweden; Bethesda, MD; 5Pacific Northwest Research Institute, Seattle, WA; Bethesda, MD; 6Barbara Davis Center for Childhood Diabetes, University of Colorado, Aurora, CO; Bethesda, MD; 7Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Augusta University, Augusta, GA; Bethesda, MD; 8Department of Pediatrics, Turku University Hospital, Turku, Finland; Bethesda, MD; 9Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, University of Turku, Turku, Finland; Bethesda, MD; 10Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany; Bethesda, MD; 11National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD
The Environmental Determinants of Diabetes in the Young (TEDDY), a large multicenter study investigating the environmental factors that could affect the development of islet autoantibodies (IAs) and type 1 diabetes (T1D), recruited and followed infants for 15 years. This group has reported that the type of first-appearing autoantibody impacts the environmental predictors of seroconversion and diabetes progression. Furthermore, because exercise has demonstrated a direct positive effect on the autoimmune process in other autoimmune conditions (25,26), this study investigated how physical activity (PA) impacts the progression of T1D.
Methods
The TEDDY study recruited 8678 children aged ≤ 4.5 months. At 5 years old the children were asked to wear accelerometers. Only 4653 remained in this study (120 ineligible HLA genotype, 54 indeterminate IAs, and 3849 lacked activity data). Three risk groups were identified: (1) 3869 IA negative children (157 became single IA positive); (2) 302 single IA positive (73 became multiple IA positive); and (3) 294 multiple IA positive (148 developed T1D). To examine the relationship between daily time spent in moderate to vigorous PA and the three risk groups, a time-to-event analysis using Cox proportional hazards (PH) model was used. The analysis was adjusted for several covariates such as type of first IA (particularly glutamate decarboxylase [GADA]), IA risk factors, and age-adjusted PA minutes. The magnitude of association is reported as hazard ratios (HRs).
Results
In risk group 1, the risk of developing a single IA was not associated with daily moderate plus vigorous (mod+vig) PA time (HR, 1.038). No association was also observed in risk group 2 (HR, 0.926). In risk group 3, mod+vig PA significantly reduced the progression of T1D (HR, 0.920) per 10 minutes of PA increase (P = 0.021). The subgroup analysis demonstrated a similar association for children who had GADA as their first IA (HR, 0.883; P = 0.043), but not when insulin autoantibodies (HR, 0.917; P = 0.161) and insulinoma-associated protein 2 or multiple IAs were the first IA (HR, 0.972; P = 0.696).
Conclusions
This study concluded that increased time spent doing moderate-to-vigorous PA could slow down the progression of T1D for children with multiple IAs. Children with multiple IAs had an 8% reduced risk of T1D progression for every 10-minute increase in moderate-to-vigorous daily PA. Notably, the risk reduction was increased to 12% for children who had GADA as their first IA.
Comments
The etiology of T1D has been an area of research focus, but we still do not have a full understanding of the environmental triggers of T1D progression and IA seroconversion. The TEDDY study set out to examine these genetic-environmental interactions. Specifically, this study revealed that PA was associated with a reduced risk of developing T1D for children with multiple IAs. Considering the results of this study, along with the study by Coomans de Brachène et al. (27) that revealed using serum from exercised individuals protected β-cell from ER stress-induced apoptosis, we suggest exercise should be an essential therapy for children who are at high risk of developing T1D. The TEDDY study is still ongoing, and the data collected can tell us more about the association of exercise and T1D progression and other factors such as nutrition and dietary exposure.
Footnotes
Author Disclosure Statement
MCR serves on advisory boards for Eli Lilly, Indigo, Insulet, Supersapiens, and Zucara Therapeutics and has given industry-supported lectures for Eli Lilly, Insulet, Novo Nordisk, and Sanofi. DPZ has received honoraria for speaking engagements from Ascensia Diabetes, Insulet Canada, and Medtronic Diabetes and is on an advisory board for Dexcom. DPZ has received research support from the Leona M. and Harry B. Helmsley Charitable Trust (G-2002-04251-2) and the ISPAD-JDRF Research Fellowship. CEM has received honoraria for speaking engagements from Medtronic Diabetes, Novo Nordisk, and Sanofi. No other potential conflicts of interest relevant to this article were reported.