Diet-Induced Weight Loss Is Associated with an Improvement in β-Cell Function in Older Men

Abstract Although weight loss in older subjects has been shown to improve insulin sensitivity, it is unclear what effect this lifestyle intervention has on β-cell function. To determine whether diet-induced weight loss can improve β-cell function in older subjects, we studied 19 healthy male subjects (age, 65.4 ± 0.9 yr; body mass index, 30.9 ± 0.6 kg/m2; mean ± sem) before and after a 3-month 1200-kcal/d diet. The insulin sensitivity index (SI) was quantified using Bergman’s minimal model. The acute insulin response to glucose (AIRg) and the maximal glucose-potentiated insulin response (AIRmax) were determined and then adjusted for SI (SI × AIRg and SI × AIRmax), thus providing measures of β-cell function. Subjects demonstrated significant weight loss (95.6 ± 2.4 to 86.1 ± 2.5 kg; P < 0.001). Both fasting plasma glucose [97.3 ± 1.6 to 95.1 ± 1.3 mg/dl (5.4 ± 0.09 to 5.3 ± 0.07 mm); P = 0.05] and insulin [18.5 ± 1.3 to 12.2 ± 1.0 μU/ml (110.9 ± 7.7 to 73.5 ± 5.9 pm); P < 0.001] levels decreased. With weight loss, SI increased [1.59 ± 0.24 to 2.49 ± 0.32 × 10−4 min−1/(μU/ml) (2.65 ± 0.4 to 4.15 ± 0.5 × 10−5 min−1/pm); P < 0.001], whereas both AIRg [63.4 ± 13.4 to 51.0 ± 10.7 μU/ml (380 ± 80 to 306 ± 64 pm); P < 0.05] and AIRmax [314 ± 31.4 to 259.9 ± 33.4 μU/ml (1886 ± 188 to 1560 ± 200 pm); P < 0.05] decreased. Overall β-cell function improved (SI × AIRg, 9.63 ± 2.28 to 12.78 ± 2.58 × 10−3 min−1, P < 0.05; and SI × AIRmax, 51.01 ± 9.2 to 72.69 ± 13.4 × 10−3 min−1, P < 0.05). Thus, the weight loss-associated improvements in both insulin sensitivity and β-cell function may explain the beneficial effects of a lifestyle intervention on delaying the development of diabetes in older subjects.

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Improved β-cell function after standardized weight reduction in severely obese subjects

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00325.2002 ◽

2003 ◽

Vol 284 (3) ◽

pp. E557-E565 ◽

Cited By ~ 73

Author(s):

Marie Guldstrand ◽

Bo Ahrén ◽

Ulf Adamson

Keyword(s):

Insulin Sensitivity ◽

Weight Reduction ◽

Cell Function ◽

Insulin Response ◽

Insulin Level ◽

Glucagon Secretion ◽

Obese Women ◽

Β Cell ◽

Β Cell Function ◽

Severely Obese

Islet function was examined in 13 severely obese women [body mass index 46.4 ± 5.5 (SD) kg/m2] before and after standardized 15 and 25% weight reduction (WR) instituted by bariatric surgery. The insulin response to arginine at fasting (AIR1), at 14 mmol/l, and at >25 mmol/l glucose was reduced by 37–50% after 15 and 25% WR ( P ≤ 0.05). Insulin sensitivity was determined as the amount of glucose infused to reach 14 mmol/l divided by the insulin level (M/I), a measure showing a linear correlation with insulin sensitivity during euglycemic hyperinsulinemic clamps ( r = 0.74, P < 0.001) and a hyperbolic relation to AIR1 ( r = −0.63, P < 0.001) in 169 healthy subjects. M/I was increased by 318 ± 182% after 15% ( P = 0.004) and by 489 ± 276% after 25% WR ( P = 0.007). The reduction in insulin secretion was not as large as anticipated from the increased insulin sensitivity, which resulted in an increased disposition index (DI; AIR1 × M/I). Thus DI increased by 95 ± 24% after 15% ( P = 0.018) and by 176 ± 35% after 25% WR ( P = 0.011). This improved β-cell function correlated independently with reduced glucose, triglycerides, and leptin and increased adiponectin levels and was associated with a reduced proinsulin-to-insulin ratio. In contrast, glucagon secretion was not significantly affected by WR. We conclude that WR results in improved β-cell function when related to insulin sensitivity.

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Weight Loss Improves β-Cell Function in People With Severe Obesity and Impaired Fasting Glucose: A Window of Opportunity

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz189 ◽

2019 ◽

Vol 105 (4) ◽

pp. e1621-e1630

Author(s):

Amy E Rothberg ◽

William H Herman ◽

Chunyi Wu ◽

Heidi B IglayReger ◽

Jeffrey F Horowitz ◽

...

Keyword(s):

Weight Loss ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Impaired Fasting Glucose ◽

Severe Obesity ◽

Cell Function ◽

Fasting Glucose ◽

Β Cell ◽

Obese People ◽

Β Cell Function

Abstract Background In people with obesity, β-cell function may adapt to insulin resistance. We describe β-cell function in people with severe obesity and normal fasting glucose (NFG), impaired fasting glucose (IFG), and type 2 diabetes (T2DM), as assessed before, 3 to 6 months after, and 2 years after medical weight loss to describe its effects on insulin sensitivity, insulin secretion, and β-cell function. Methods Fifty-eight participants with body mass index (BMI) ≥ 35 kg/m2 (14 with NFG, 24 with IFG, and 20 with T2DM) and 13 normal weight participants with NFG underwent mixed meal tolerance tests to estimate insulin sensitivity (S[I]), insulin secretion (Φ), and β-cell function assessed as model-based Φ adjusted for S(I). All 58 obese participants were restudied at 3 to 6 months and 27 were restudied at 2 years. Results At 3 to 6 months, after a 20-kg weight loss and a decrease in BMI of 6 kg/m2, S(I) improved in all obese participants, Φ decreased in obese participants with NFG and IFG and tended to decrease in obese participants with T2DM, and β-cell function improved in obese participants with NFG and tended to improve in obese participants with IFG. At 2 years, β-cell function deteriorated in participants with NFG and T2DM but remained significantly better in participants with IFG compared to baseline. Conclusions Short-term weight loss improves β-cell function in participants with NFG and IFG, but β-cell function tends to deteriorate over 2 years. In participants with IFG, weight loss improves longer-term β-cell function relative to baseline and likely relative to no intervention, suggesting that obese people with IFG are a subpopulation whose β-cell function is most likely to benefit from weight loss.

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Association between Genetic Polymorphisms of β-Cell Differentiation Genes and Insulin Resistance (β-Cell Dysfunction) in Childhood Acute Lymphoblastic Leukemia (ALL) Survivors.

Blood ◽

10.1182/blood.v110.11.4281.4281 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4281-4281

Author(s):

Pacharapan Surapolchai ◽

Suradej Hongeng ◽

Samart Pakakasama ◽

Pat Mahachoklertwattana ◽

Angkana Winaichatsak ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Glucose Tolerance ◽

Cell Function ◽

Sensitivity Index ◽

Insulin Sensitivity Index ◽

Β Cell ◽

Childhood All ◽

Cell Dysfunction ◽

Β Cell Function

Abstract Background: The purposes of the study were to determine β-cell function and insulin sensitivity after ALL therapy cessation and the association between genetic polymorphisms of β-cell differentiation genes, TCF7L2 and PAX4, with insulin resistance (β-cell dysfunction) in childhood ALL survivors. Methods: Childhood ALL patients diagnosed during 1997–2004 finished the treatment for at least 6 months. The oral glucose tolerance test and lipid screening were performed. Impaired glucose tolerance and diabetes mellitus (DM) were defined according to WHO criteria. β-cell function was estimated by homeostasis model assessment β-cell (HOMA β-cell) and insulinogenic index (IGI) and insulin sensitivity was estimated by whole body insulin sensitivity index (WBISI). The polymorphisms of TCF7L2 (rs12255372 and rs7903146) and PAX4 (A1186C) were genotyped and assessed for the association between these polymorphisms and the β-cell function and the insulin sensitivity. Results: 126 patients were studied (52 females, 74 males and age at the time of study; 4–20 yrs). 116 patients (92%) had normal glucose tolerance (NGT) while the others 10 patients (8%) had impaired glucose tolerance (IGT). Comparing between IGT and NGT groups respectively, we found statistically significant differences in age at the diagnosis (7.5 and 5.2 yrs, p=0.041), age at the study (14 and 10.3 yrs, p=0.001), the duration of post ALL therapy cessation (43 and 26 months, p=0.015), and insulin sensitivity index (WBISI) (5.75 and 9.52, p<0.001). HOMA β-cell and IGI were not different between NGT and IGT group (190.8 and 139.5, p=0.332; 23.6 and 15.8, p=0.310, respectively). Moreover, 32 of 126 patients (25%) had insulin resistance (modified from the criteria of WBISI in obese children and adolescents). These 32 patients who had insulin resistance demonstrated significant pictures of metabolic syndrome i.e. hypertriglyceridemia (116.6 and 85.4 mg/dL, p=0.036), low HDL-C (43.0 and 48.3 mg/dL, p=0.015), obesity (BMI SDS 1.03 and 0.38, p=0.044) and were also older age at the study (12.8 and 9.9 yrs, p<0.001). The genotype frequencies and allele frequencies of polymorphisms of TCF7L2 and PAX4 genes between IGT and NGT groups and between insulin resistance and nonresistance were not difference (p>0.05). Conclusion: The childhood ALL survivors who had IGT were associated with the longer duration of ALL therapy cessation, the older age at diagnosis and at the time of study, and insulin resistance while β-cell function was still relatively preserved. Long-term childhood ALL survivors have potential risks of IGT, insulin resistance and metabolic syndrome. Our findings with such small representatives are not yet applicable to associate TCF7L2 and PAX4 polymorphisms with the insulin resistance (β-cell dysfunction) in the childhood ALL survivors.

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Estimation of β-cell function from the data of the oral glucose tolerance test

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00341.2006 ◽

2007 ◽

Vol 292 (6) ◽

pp. E1575-E1580 ◽

Cited By ~ 9

Author(s):

Shinji Sakaue ◽

Shinji Ishimaru ◽

Daisuke Ikeda ◽

Yoshinori Ohtsuka ◽

Toshiro Honda ◽

...

Keyword(s):

Insulin Sensitivity ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Cell Function ◽

Tolerance Test ◽

Oral Glucose ◽

Sensitivity Index ◽

Β Cell ◽

Β Cell Function ◽

The Relationship

Although a hyperbolic relationship between insulin secretion and insulin sensitivity has been shown, the relationship has been often questioned. We examined the relationship using oral glucose tolerance test (OGTT)-derived indexes. A total of 374 Japanese subjects who had never been given a diagnosis of diabetes underwent a 75-g OGTT. In subjects with normal glucose tolerance (NGT), the ln [insulinogenic index (IGI)] was described by a linear function of ln ( x) ( x, insulin sensitivity index) in regression analysis when the reciprocal of the insulin resistance index in homeostasis model assessment, Matsuda's index, and oral glucose insulin sensitivity index were used as x. Because the 95% confidence interval of the slope of the regression line did not necessarily include −1, the relationships between IGI and x were not always hyperbolic, but power functions IGI × xα = a constant. We thought that IGI × xα was an appropriate β-cell function estimate adjusted by insulin sensitivity and referred to it as β-cell function index (BI). When Matsuda's index was employed as x, the BI values were decreased in subjects without NGT. Log BI had a better correlation with fasting plasma glucose (PG; FPG) and 2-h PG in non-NGT subjects than in NGT subjects. In subjects with any glucose tolerance, log BI was linearly correlated with 1-h PG and glucose spike (the difference between maximum PG and FPG). In conclusion, the relationship between insulin secretion and insulin sensitivity was not always hyperbolic. The BI is a useful tool in the estimation of β-cell function with a mathematical basis.

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Vigorous Physical Activity may be Important for the Insulin Sensitivity in Immigrants From the Middle East and Native Swedes

Journal of Physical Activity and Health ◽

10.1123/jpah.2013-0222 ◽

2015 ◽

Vol 12 (2) ◽

pp. 273-281 ◽

Cited By ~ 1

Author(s):

Daniel Arvidsson ◽

Ulf Lindblad ◽

Jan Sundquist ◽

Kristina Sundquist ◽

Leif Groop ◽

...

Keyword(s):

Physical Activity ◽

Insulin Sensitivity ◽

Sedentary Time ◽

Cell Function ◽

Vigorous Physical Activity ◽

Oral Glucose ◽

Sensitivity Index ◽

Β Cell ◽

Β Cell Function ◽

Activity Measures

Purpose:To compare physical activity measures and their associations with insulin sensitivity, β-cell function and body mass index (BMI) between Iraqi immigrants and native Swedes.Methods:A cross-sectional study of 493 Iraqis (58% men) and 469 Swedes (54% men) aged 30 to 75 years living in the city of Malmö, Sweden. Accelerometry was used for physical activity measures (sedentary time, breaks in sedentary time, moderate and vigorous physical activity, total counts). Insulin sensitivity index and oral disposal index were determined from an oral glucose tolerance test and BMI by body weight and height.Results:Iraqi men were less physically active than Swedish men, while the physical activity was more similar in the women. BMI was a strong predictor of insulin sensitivity and β-cell function and frequently associated with the physical activity measures. BMI modified the associations of insulin sensitivity and β-cell function with the physical activity measures to such extent that only VPA and total counts show direct associations with insulin sensitivity in addition to the indirect associations via BMI. Iraqi women demonstrated weaker associations compared with Swedish women.Conclusions:Physical activity and performed at vigorous intensity may be important mainly for the insulin sensitivity in Iraqi immigrants and native Swedes.

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Role of the Gut in the Temporal Changes of β-Cell Function After Gastric Bypass in Individuals With and Without Diabetes Remission

10.2337/figshare.16989505 ◽

2021 ◽

Author(s):

Malini Prasad ◽

Victoria Mark ◽

Chanel Ligon ◽

Roxanne Dutia ◽

Nandini Nair ◽

...

Keyword(s):

Weight Loss ◽

Gastric Bypass ◽

Insulin Sensitivity ◽

Cell Function ◽

Diabetes Remission ◽

Oral Glucose ◽

Β Cell ◽

Remission Status ◽

Β Cell Function

Objective: The role of the gut in diabetes remission after gastric bypass (RYGB) is incompletely understood. We therefore assessed the temporal change in insulin secretory capacity after RYGB, using oral and intravenous (IV) glucose, in individuals with type 2 diabetes. Research Design and Methods: Longitudinal, prospective measures of β-cell function after oral glucose and IV graded glucose infusion in individuals with severe obesity and diabetes studied at 0, 3 (n=29), 12 (n=24) and 24 (n=20) months after RYGB. Data were collected between 2015 and 2019 in an academic clinical research center. Results: The decreases in body weight, fat mass, waist circumference and insulin resistance after surgery (all p<0.001 at 12 and 24 months), did not differ according to diabetes remission status. In contrast, both the magnitude and temporal changes in β-cell glucose sensitivity after oral glucose differed by remission status (p=0.04): greater (6.5 fold, p<0.01) and sustained in full remitters, moderate and not sustained past 12 months in partial remitters (3.3 fold, p<0.001), minimal in non-remitters (2.7 fold, p=ns). The improvement in β-cell function after IV glucose was not apparent until 12 months, significant only in full remitters, and only ~1/3 of that observed after oral glucose. Pre-intervention β-cell function and its change after surgery predicted remission; weight loss and insulin sensitivity did not. Conclusion: Our data show the time course of changes in β-cell function after RYGB. The improvement in β-cell function after RYGB, but not changes in weight loss or insulin sensitivity, drives diabetes remission.

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Adipocyte Insulin Resistance in PCOS: Relationship With GLUT-4 Expression and Whole-Body Glucose Disposal and β-Cell Function

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa235 ◽

2020 ◽

Vol 105 (7) ◽

pp. e2408-e2420

Author(s):

Uche Ezeh ◽

Ida Y-D Chen ◽

Yen-Hao Chen ◽

Ricardo Azziz

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Cell Function ◽

Dynamic State ◽

Whole Body ◽

Sensitivity Index ◽

Β Cell ◽

Nonesterified Fatty Acids ◽

Glut 4 ◽

Β Cell Function

Abstract Context Impaired sensitivity to the antilipolytic action of insulin in adipose tissue (AT) may play a role in determining metabolic dysfunction in polycystic ovary syndrome (PCOS). Objectives To test the hypothesis that insulin resistance (IR) in AT is associated with whole-body insulin sensitivity and β-cell function in PCOS. Research Design and Setting Prospective cross-sectional study. Methods Eighteen participants with PCOS and 18-matched control participants underwent a modified frequently sampled intravenous glucose tolerance test (mFSIVGTT); subgroups underwent single-slice computed tomography scans determining AT distribution and adipocyte glucose transporter type 4 (GLUT-4) expression. Main Outcome Measures IR in AT in basal (by the adipose insulin resistance index [Adipo-IR]) and dynamic (mFSIVGTT-derived indices of insulin-mediated nonesterified fatty acids [NEFA] suppression [NEFAnadir, TIMEnadir, and %NEFAsupp]) states; whole-body insulin-mediated glucose uptake and insulin secretion in basal (by homeostatic model assessment [HOMA]-IR and HOMA-β%) and dynamic (mFSIVGTT-derived insulin sensitivity index [Si], acute insulin response to glucose [AIRg], and disposition index [Di]) states. Results Participants with PCOS had higher HOMA-IR and HOMA-β%, lower Si and Di, higher longer TIMEnadir, higher Adipo-IR and NEFAnadir, and a trend toward lower GLUT-4, than the control group participants. Adipo-IR was associated with dynamic state IR in AT (NEFAnadir TIMEnadir, and %NEFAsupp), but only in PCOS, and with HOMA-IR and HOMA-β% in both groups. NEFAnadir and TIMEnadir were negatively and %NEFAsupp positively associated with Si only in PCOS, but not with AIRg and Di, or GLUT-4 expression. Conclusion Women with PCOS demonstrated increased IR in AT, which is closely associated with whole-body IR but not with dynamic state β-cell function or adipocyte GLUT-4 gene expression.

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The increase in serum 25-hydroxyvitamin D following weight loss does not contribute to the improvement in insulin sensitivity, insulin secretion and β-cell function

British Journal Of Nutrition ◽

10.1017/s0007114515001610 ◽

2015 ◽

Vol 114 (2) ◽

pp. 161-168 ◽

Cited By ~ 3

Author(s):

Véronique Thibault ◽

Anne-Sophie Morisset ◽

Christine Brown ◽

André C. Carpentier ◽

Jean-Patrice Baillargeon ◽

...

Keyword(s):

Weight Loss ◽

Insulin Secretion ◽

Insulin Sensitivity ◽

Cell Function ◽

Disposition Index ◽

Model Assessment ◽

Β Cell ◽

Hydroxyvitamin D ◽

Β Cell Function ◽

25 Hydroxyvitamin D

Serum 25-hydroxyvitamin D (25(OH)D) concentrations have been reported to increase following weight loss. Moreover, both weight loss and higher serum 25(OH)D concentrations have been associated with a lower risk of developing type 2 diabetes. The objective of the present study was to determine whether the increase in serum 25(OH)D concentration following weight loss is associated with improved insulin sensitivity, insulin secretion and disposition index (β-cell function). Data from two prospective lifestyle modification studies had been combined. Following a lifestyle-modifying weight loss intervention for 1 year, eighty-four men and women with prediabetes and a BMI ≥ 27 kg/m2 were divided based on weight loss at 1 year: < 5 % (non-responders, n 56) and ≥ 5 % (responders, n 28). The association between the change in serum 25(OH)D concentration and changes in insulin sensitivity (homeostasis model assessment of insulin sensitivity (HOMA%S) and Matsuda), insulin secretion (AUC of C-peptide) and disposition index after adjustment for weight loss was examined. Participants in the responders' group lost on average 9·5 % of their weight when compared with non-responders who lost only 0·8 % of weight. Weight loss in responders resulted in improved insulin sensitivity (HOMA%S, P= 0·0003) and disposition index (P= 0·02); however, insulin secretion remained unchanged. The rise in serum 25(OH)D concentration following weight loss in responders was significantly higher than that in non-responders (8·9 (sd 12·5) v. 3·6 (sd 10·7) nmol/l, P= 0·05). However, it had not been associated with amelioration of insulin sensitivity and β-cell function, even after adjustment for weight loss and several confounders. In conclusion, the increase in serum 25(OH)D concentration following weight loss does not contribute to the improvement in insulin sensitivity or β-cell function.

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The Macrophage Activation Marker Soluble CD163 is Longitudinally Associated With Insulin Sensitivity and β-cell Function

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz166 ◽

2019 ◽

Vol 105 (3) ◽

pp. e285-e294 ◽

Cited By ~ 1

Author(s):

Zhila Semnani-Azad ◽

Philip W Connelly ◽

Luke W Johnston ◽

Ravi Retnakaran ◽

Stewart B Harris ◽

...

Keyword(s):

Type 2 Diabetes ◽

Insulin Sensitivity ◽

Cell Function ◽

Sensitivity Index ◽

Insulinogenic Index ◽

Β Cell ◽

Soluble Cd163 ◽

Β Cell Function ◽

Longitudinal Associations

Abstract Context Chronic inflammation arising from adipose tissue macrophage (ATM) activation may be central in type 2 diabetes etiology. Our objective was to assess the longitudinal associations of soluble CD163 (sCD163), a novel biomarker of ATM activation, with insulin sensitivity, β-cell function, and dysglycemia in high-risk subjects. Methods Adults at risk for type 2 diabetes in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) study had 3 assessments over 6 years (n = 408). Levels of sCD163 were measured using fasting serum. Insulin sensitivity was assessed by HOMA2-%S and the Matsuda index (ISI). β-cell function was determined by insulinogenic index (IGI) over HOMA-IR and insulin secretion-sensitivity index-2 (ISSI-2). Incident dysglycemia was defined as the onset of impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes. Generalized estimating equations (GEE) evaluated longitudinal associations of sCD163 with insulin sensitivity, β-cell function, and incident dysglycemia adjusting for demographic and lifestyle covariates. Areas under receiver-operating-characteristic curve (AROC) tested whether sCD163 improved dysglycemia prediction in a clinical model. Results Longitudinal analyses showed significant inverse associations between sCD163 and insulin sensitivity (% difference per standard deviation increase of sCD163 for HOMA2-%S (β = −7.01; 95% CI, −12.26 to −1.44) and ISI (β = −7.60; 95% CI, −11.09 to −3.97) and β-cell function (ISSI-2 (β = −4.67; 95 %CI, −8.59 to −0.58) and IGI/HOMA-IR (β = −8.75; 95% CI, −15.42 to −1.56)). Increased sCD163 was associated with greater risk for incident dysglycemia (odds ratio = 1.04; 95% CI, 1.02-1.06; P < 0.001). Adding sCD163 data to a model with clinical variables improved prediction of incident dysglycemia (AROC=0.6731 vs 0.638; P < 0.05). Conclusions sCD163 was longitudinally associated with core disorders that precede the onset of type 2 diabetes.

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Impact of short-term exercise training intensity on β-cell function in older obese adults with prediabetes

Journal of Applied Physiology ◽

10.1152/japplphysiol.00680.2018 ◽

2018 ◽

Vol 125 (6) ◽

pp. 1979-1986 ◽

Cited By ~ 4

Author(s):

Steven K. Malin ◽

Monique E. Francois ◽

Natalie Z. M. Eichner ◽

Nicole M. Gilbertson ◽

Emily M. Heiston ◽

...

Keyword(s):

Skeletal Muscle ◽

Weight Loss ◽

Insulin Sensitivity ◽

Exercise Training ◽

Glucose Tolerance ◽

Cell Function ◽

Β Cell ◽

Short Term ◽

Β Cell Function ◽

High Intensity Interval

The effect of work-matched exercise intensity on β-cell function is unknown in people with prediabetes before clinical weight loss. We determined if short-term moderate continuous (CONT) vs. high-intensity interval (INT) exercise increased β-cell function. Thirty-one subjects (age: 61.4 ± 2.5 yr; body mass index: 32.1 ± 1.0 kg/m2) with prediabetes [American Diabetes Association criteria, 75-g oral glucose tolerance test (OGTT)] were randomized to work-matched CONT (70% HRpeak) or INT (3 min 90% HRpeak and 3 min 50% HRpeak) exercise for 60 min/day over 2 wk. A 75-g 2-h OGTT was conducted after an overnight fast, and plasma glucose, insulin, C-peptide, and free fatty acids were determined for calculations of skeletal muscle [oral minimal model (OMM)], hepatic (homeostatic model of insulin resistance), and adipose (Adipose-IR) insulin sensitivity. β-Cell function was defined from glucose-stimulated insulin secretion (GSIS, deconvolution modeling) and the disposition index (DI). Glucagon-like polypeptide-1 [GLP-1(active)] and glucose-dependent insulinotropic polypeptide (GIP) were also measured during the OGTT, along with peak oxygen consumption and body composition. CONT and INT increased skeletal muscle- but not hepatic- or adipose-derived DI ( P < 0.05). Although both treatments tended to reduce fasting GLP-1(active) ( P = 0.08), early phase GLP-1(active) increased post-CONT and INT training ( P < 0.001). Interestingly, CONT exercise increased fasting GIP compared with decreases in INT ( P = 0.02). Early and total-phase skeletal muscle DI correlated with decreased total glucose area under the curve ( r = −0.52, P = 0.002 and r = −0.50, P = 0.003, respectively). Independent of intensity, short-term training increased pancreatic function adjusted to skeletal muscle in relation to improved glucose tolerance in adults with prediabetes. Exercise also uniquely affected GIP and GLP-1(active). Further work is needed to elucidate the dose-dependent mechanism(s) by which exercise impacts glycemia. NEW & NOTEWORTHY Exercise is cornerstone for reducing blood glucose, but whether high-intensity interval training is better than moderate continuous exercise is unclear in people with prediabetes before weight loss. We show that 2 wk of exercise training, independent of intensity, increased pancreatic function in relation to elevated glucagon-like polypeptide-1 secretion. Furthermore, β-cell function, but not insulin sensitivity, was also correlated with improved glucose tolerance. These data suggest that β-cell function is a strong predictor of glycemia regardless of exercise intensity.

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