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Effectiveness of carbohydrate counting and Dietary Approach to Stop Hypertension dietary intervention on managing Gestational Diabetes Mellitus among pregnant women who used metformin: A randomized controlled clinical trial.
Allehdan, S, Basha, A, Hyassat, D, Nabhan, M, Qasrawi, H, Tayyem, R
Clinical nutrition (Edinburgh, Scotland). 2022;(2):384-395
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) is one of the most common complication of pregnancy that has significant impacts on both mother and her offspring health. The present study aimed to examine the effect of carbohydrate counting, carbohydrate counting combined with DASH, and control dietary interventions on glycemic control, and maternal and neonatal outcomes. METHODS A total of 75 pregnant women with GDM at 24th - 30th week of gestation were enrolled and randomized to follow one of the three diets: control or carbohydrate counting, or carbohydrate counting combined with Dietary Approach to Stop Hypertension (DASH). Only 70 of them completed the study until delivery. Fasting blood samples were taken at baseline and the end of the study to measure fasting blood glucose (FBG), fasting insulin, glycated hemoglobin (HbA1c), and fructosamine. Homeostatic model assessment-insulin resistance (HOMA-IR) score was calculated using HOMA2 calculator program. The participants recorded at least four blood glucose readings per day. Maternal and neonatal outcomes were collected from medical records. Dietary intake was assessed by three-day food records at the baseline and the end of the study. RESULTS Adherence to the three dietary interventions, resulted in decreased FBG levels significantly among all the participants (P < 0.05). Consumption of the carbohydrate counting combined with the DASH diet showed significant reduction in serum insulin levels and HOMA-IR score compared to carbohydrate counting group and control group. Means of fructosamine and HbA1c did not differ significantly among the three intervention diet groups. Overall mean of 1-h postprandial glucose (1 h PG) level was significantly lower in the carbohydrate counting combined with DASH group compared with that in the carbohydrate counting group and the control group (P < 0.001). The number of women who were required to commence insulin therapy after dietary intervention was significantly lower in carbohydrate counting group and carbohydrate counting combined with DASH group (P = 0.026). There were no significant differences in other maternal and neonatal outcomes among the three dietary intervention groups. CONCLUSIONS The carbohydrate counting and the carbohydrate counting combined with DASH dietary interventions resulted in beneficial effects on FBG and 1 h PG compared with the control diet. The three dietary interventions produced similar maternal and neonatal outcomes in women with GDM. TRIAL REGISTRATION This trial was registered on ClinicalTrials.gov under the identification code: NCT03244579. https://clinicaltrials.gov/ct2/show/NCT03244579.
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A Randomized Controlled Clinical Trial of Lifestyle Intervention and Pioglitazone for Normalization of Glucose Status in Chinese with Prediabetes.
Luo, Y, Wang, H, Zhou, X, Chang, C, Chen, W, Guo, X, Yang, J, Ji, L, Paul, SK
Journal of diabetes research. 2022;:2971382
Abstract
AIMS: Prediabetes has been proved as an important risk factor of both diabetes and cardiovascular disease (CVD). Previous studies have shown that both lifestyle intervention and pioglitazone may delay the development of diabetes in patients with prediabetes. However, no study has ever explored whether these interventions could revert prediabetes to normal glycemic status as the primary outcome. Interventions that may revert prediabetes back to normal glucose status would be of great clinical importance. MATERIALS AND METHODS We conducted a randomized, multicenter, 2 × 2 factorial designed study to examine whether intensive lifestyle intervention and/or pioglitazone could revert prediabetes to normal glucose tolerance. The participants were followed up for three years unless they reverted to normal glucose state or developed diabetes at the annual oral glucose tolerance test (OGTT). Reversion to normal glucose tolerance was confirmed on the basis of the results of OGTT. RESULTS In our study, 1945 eligible patients were ultimately randomized into four groups. In this three-year follow-up study, overall, 60.0%, 50.3%, 56.6% and 65.1% reverted back to normoglycemic state over 3 years of follow-up in the conventional lifestyle intervention plus placebo, intensive lifestyle intervention plus placebo, conventional lifestyle intervention plus pioglitazone, and intensive lifestyle intervention plus pioglitazone groups, respectively. Compared to the conventional lifestyle intervention plus placebo group, all the other three groups did not show any significant benefit in terms of reverting back to normoglycemic state. CONCLUSION In our study, for patients with prediabetes, neither intensive lifestyle intervention nor pioglitazone had led to a higher reversion rate to normal glucose state. Trail registration.http://www.chictr.org.cn: ChiCTR-PRC-06000005.
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Erectile function in men with type 2 diabetes treated with dulaglutide: an exploratory analysis of the REWIND placebo-controlled randomised trial.
Bajaj, HS, Gerstein, HC, Rao-Melacini, P, Basile, J, Colhoun, H, Conget, I, Cushman, WC, Dagenais, GR, Franek, E, Hanefeld, M, et al
The lancet. Diabetes & endocrinology. 2021;(8):484-490
Abstract
BACKGROUND Diabetes is a major risk factor for erectile dysfunction, however, the effect of GLP-1 receptor agonists on erectile dysfunction is unknown. We aimed to assess the incidence, prevalence, and progression of erectile dysfunction in men treated with dulaglutide compared with placebo, and to determine whether dulaglutide's effect on erectile dysfunction was consistent with its effect on other diabetes-related outcomes. METHODS The Researching Cardiovascular Events with a Weekly Incretin in Diabetes (REWIND) trial was a double-blind, placebo-controlled randomised trial of the effect of dulaglutide on cardiovascular outcomes. REWIND was done at 371 sites in 24 countries. Men and women aged older than 50 years with type 2 diabetes, who had either a previous cardiovascular event or cardiovascular risk factors, were randomly assigned (1:1) to receive either dulaglutide or placebo. Participating men were offered the opportunity to complete the standardised International Index of Erectile Function (IIEF) questionnaire at baseline, 2 years, 5 years, and study end. We did an exploratory analysis, in which we included participants who completed a baseline and at least 1 follow-up IIEF questionnaire. The primary outcome for these analyses was the first occurrence of moderate or severe erectile dysfunction following randomisation, assessed by the erectile function subscores on IIEF. This analysis was part of the REWIND trial, which is registered with ClinicalTrials.gov, NCT01394952. FINDINGS Between Aug 18, 2011, and Aug 14, 2013, 3725 (70·1%) of 5312 male participants with a mean age of 65·5 years (SD 6·4 years) were analysed, of whom 1487 (39·9%) had a history of cardiovascular disease, and 2104 (56·5%) had moderate or severe erectile dysfunction at baseline. The incidence of erectile dysfunction following randomisation was 21·3 per 100 person-years in the dulaglutide group and 22·0 per 100 person-years in the placebo group (HR 0·92, 95% CI 0·85-0·99, p=0·021). Men in the dulaglutide group also had a lesser fall in erectile function subscore compared with the placebo group, with a least square mean difference of 0·61 (95% CI 0·18-1·05, p=0·006). INTERPRETATION Long-term use of dulaglutide might reduce the incidence of moderate or severe erectile dysfunction in men with type 2 diabetes. FUNDING Eli Lilly and Company.
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Effect of Dietary Supplementation with a Natural Extract of Sclerocarya birrea on Glycemic Metabolism in Subjects with Prediabetes: A Randomized Double-Blind Placebo-Controlled Study.
Victoria-Montesinos, D, Sánchez-Macarro, M, Gabaldón-Hernández, JA, Abellán-Ruiz, MS, Querol-Calderón, M, Luque-Rubia, AJ, Bernal-Morell, E, Ávila-Gandía, V, López-Román, FJ
Nutrients. 2021;(6)
Abstract
A randomized, double-blind, placebo-controlled study was conducted with the primary objective of assessing the effect of a natural extract of Sclerocarya birrea on glucose metabolism in subjects with prediabetes. The duration of the study was 90 days. Thirty-three subjects assigned to the experimental group (daily ingestion of 100 mg of the nutraceutical product) and 34 assigned to the placebo group completed the study. There were 36 men and 31 women with a mean age of 32.3 ± 14.1 years. In the area under the curve (AUC) of the oral glucose tolerance test (OGTT), statistically significant decreases in the experimental group at 40 and 90 days as compared with baseline were found, whereas significant changes in the placebo group were not observed. Within-group differences were statistically significant in favor of the experimental group for glucose peak at OGTT, serum insulin, insulin resistance markers, and flow-mediated dilation. Changes in lipid and anthropometric parameters were not observed, although there was a trend for lower cholesterol levels and a decrease in body weight in the experimental group. Decreases in systolic blood pressure were also higher among subjects in the experimental group. This exploratory study confirms the antidiabetic activity of Sclerocarya birrea in prediabetes. Further studies using better measurements of beta-cell function are needed to clarify the underlying mechanisms of the hypoglycemic effect of this natural compound.
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Islet Function and Insulin Sensitivity in Latent Autoimmune Diabetes in Adults Taking Sitagliptin: A Randomized Trial.
Yang, L, Liang, H, Liu, X, Wang, X, Cheng, Y, Zhao, Y, Liu, L, Huang, G, Wang, X, Zhou, Z
The Journal of clinical endocrinology and metabolism. 2021;(4):e1529-e1541
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CONTEXT The long-term effects of dipeptidyl peptidase-4 inhibitors on β-cell function and insulin sensitivity in latent autoimmune diabetes in adults (LADA) are unclear. OBJECTIVE To investigate the effects of sitagliptin on β-cell function and insulin sensitivity in LADA patients receiving insulin. DESIGN AND SETTING A randomized controlled trial at the Second Xiangya Hospital. METHODS Fifty-one patients with LADA were randomized to sitagliptin + insulin (SITA) group or insulin alone (CONT) group for 24 months. MAIN OUTCOME MEASURES Fasting C-peptide (FCP), 2-hour postprandial C-peptide (2hCP) during mixed-meal tolerance test, △CP (2hCP - FCP), and updated homeostatic model assessment of β-cell function (HOMA2-B) were determined every 6 months. In 12 subjects, hyperglycemic clamp and hyperinsulinemic euglycemic clamp (HEC) tests were further conducted at 12-month intervals. RESULTS During the 24-month follow-up, there were no significant changes in β-cell function in the SITA group, whereas the levels of 2hCP and △CP in the CONT group were reduced at 24 months. Meanwhile, the changes in HOMA2-B from baseline were larger in the SITA group than in the CONT group. At 24 months, first-phase insulin secretion was improved in the SITA group by hyperglycemia clamp, which was higher than in the CONT group (P < .001), while glucose metabolized (M), insulin sensitivity index, and M over logarithmical insulin ratio in HEC were increased in the SITA group (all P < .01 vs baseline), which were higher than in the CONT group. CONCLUSION Compared with insulin intervention alone, sitagliptin plus insulin treatment appeared to maintain β-cell function and improve insulin sensitivity in LADA to some extent.
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Is the stepping-down approach a better option than multiple daily injections in obese patients with poorly controlled Type 2 diabetes on advanced insulin therapy?
Naing, S, Ramesh, G, Garcha, J, Poliyedath, A, Khandelwal, S, Mills, PK
Endocrinology, diabetes & metabolism. 2021;(2):e00204
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AIM: To determine whether de-escalating from advanced insulin therapy (AIT) to the combined use of metformin, an SGLT2 inhibitor, a GLP1 receptor agonist and basal insulin is the better option than multiple daily insulin injections (MDI) in obese patients with poorly controlled T2DM. METHODS This was a 16-week, prospective, randomized, controlled trial. Twenty-two obese patients with T2DM on AIT were randomized to intervention (step-down) or control (MDI) group. In the intervention group, all prandial insulin injections were discontinued, but the patient remained on basal insulin and metformin, to which an SGLT2i and a GLP1 RA were added. In the control group, the patient remained on MDI. RESULTS Compared to control group (n = 8), A1c was significantly lower at week 4 (9.54% vs 8.25%; p = .0088) and week 16 (9.7% vs 7.31%; p < .001) in intervention group (n = 10). In intervention group, compared to baseline, there was a significant decrease in weight (-16.38 pounds; p = .003), BMI (-3.06; p < .001), LDL cholesterol (-15.7 mg/dl; p = .0378), total cholesterol (-18.5 mg/dl; p = .0386), total daily insulin dose (-57.3 units; p < .001) and a significant improvement in DM-SAT patient satisfaction 0-100 scores: total score (+45.3; p < .001) and subscale scores (Convenience + 35.28, p = .019; Lifestyle + 35.8, p = .0052; Medical control + 51.3, p < .001; Wellbeing + 47.2, p = .0091) at week 16. CONCLUSION De-escalating from AIT to the combined use of metformin, SGLT2i, GLP1 RA and basal insulin in obese patients with poorly controlled T2DM on MDI resulted in significant improvement in glycaemic control, weight loss and significantly higher patient satisfaction. This stepping-down approach may be the better option than continuing MDI in these patients.
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Heterogeneity of Treatment Effects Among Patients With Type 2 Diabetes and Elevated Body Mass Index in a Study Comparing Group Medical Visits Focused on Weight Management and Medication Intensification.
Kobe, EA, Crowley, MJ, Jeffreys, AS, Yancy, WS, Zervakis, J, Edelman, D, Voils, CI, Maciejewski, ML, Coffman, CJ
Medical care. 2021;(11):1031-1038
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BACKGROUND Illuminating heterogeneity of treatment effect (HTE) within trials is important for identifying target populations for implementation. OBJECTIVE The aim of this study was to examine HTE in a trial of group medical visits (GMVs) for patients with type 2 diabetes and elevated body mass index. RESEARCH DESIGN AND MEASURES Participants (n=263) were randomized to GMV-based medication management plus low carbohydrate diet-focused weight management (WM/GMV; n=127) or GMV-based medication management alone (GMV; n=136) for diabetes control. We used QUalitative INteraction Trees, a tree-based clustering method, to identify subgroups with greater improvement in hemoglobin A1c (HbA1c) and weight from either WM/GMV or GMV. Subgroup predictors included 32 baseline demographic, clinical, and psychosocial factors. Internal validation was conducted to estimate bias in the range of mean outcome differences between arms. RESULTS QUalitative INteraction Trees analyses indicated that for patients who had not previously attempted weight loss, WM/GMV resulted in better glycemic control than GMV (mean difference in HbA1c improvement=1.48%). For patients who had previously attempted weight loss and had lower cholesterol and blood urea nitrogen, GMV was better than WM/GMV (mean difference in HbA1c improvement=1.51%). No treatment-subgroup effects were identified for weight. Internal validation resulted in moderate corrections in mean HbA1c differences between arms; however, differences remained in the clinically significant range. CONCLUSION This work represents a novel step toward targeting care approaches for patients to maximize benefit based on individual patient characteristics.
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Anti-interleukin-21 antibody and liraglutide for the preservation of β-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial.
von Herrath, M, Bain, SC, Bode, B, Clausen, JO, Coppieters, K, Gaysina, L, Gumprecht, J, Hansen, TK, Mathieu, C, Morales, C, et al
The lancet. Diabetes & endocrinology. 2021;(4):212-224
Abstract
BACKGROUND Type 1 diabetes is characterised by progressive loss of functional β-cell mass, necessitating insulin treatment. We aimed to investigate the hypothesis that combining anti-interleukin (IL)-21 antibody (for low-grade and transient immunomodulation) with liraglutide (to improve β-cell function) could enable β-cell survival with a reduced risk of complications compared with traditional immunomodulation. METHODS This randomised, parallel-group, placebo-controlled, double-dummy, double-blind, phase 2 trial was done at 94 sites (university hospitals and medical centres) in 17 countries. Eligible participants were adults aged 18-45 years with recently diagnosed type 1 diabetes and residual β-cell function. Individuals with unstable type 1 diabetes (defined by an episode of severe diabetic ketoacidosis within 2 weeks of enrolment) or active or latent chronic infections were excluded. Participants were randomly assigned (1:1:1:1), with stratification by baseline stimulated peak C-peptide concentration (mixed-meal tolerance test [MMTT]), to the combination of anti-IL-21 and liraglutide, anti-IL-21 alone, liraglutide alone, or placebo, all as an adjunct to insulin. Investigators, participants, and funder personnel were masked throughout the treatment period. The primary outcome was the change in MMTT-stimulated C-peptide concentration at week 54 (end of treatment) relative to baseline, measured via the area under the concentration-time curve (AUC) over a 4 h period for the full analysis set (intention-to-treat population consisting of all participants who were randomly assigned). After treatment cessation, participants were followed up for an additional 26-week off-treatment observation period. This trial is registered with ClinicalTrials.gov, NCT02443155. FINDINGS Between Nov 10, 2015, and Feb 27, 2019, 553 adults were assessed for eligibility, of whom 308 were randomly assigned to receive either anti-IL-21 plus liraglutide, anti-IL-21, liraglutide, or placebo (77 assigned to each group). Compared with placebo (ratio to baseline 0·61, 39% decrease), the decrease in MMTT-stimulated C-peptide concentration from baseline to week 54 was significantly smaller with combination treatment (0·90, 10% decrease; estimated treatment ratio 1·48, 95% CI 1·16-1·89; p=0·0017), but not with anti-IL-21 alone (1·23, 0·97-1·57; p=0·093) or liraglutide alone (1·12, 0·87-1·42; p=0·38). Despite greater insulin use in the placebo group, the decrease in HbA1c (a key secondary outcome) at week 54 was greater with all active treatments (-0·50 percentage points) than with placebo (-0·10 percentage points), although the differences versus placebo were not significant. The effects diminished upon treatment cessation. Changes in immune cell subsets across groups were transient and mild (<10% change over time). The most frequently reported adverse events included gastrointestinal disorders, in keeping with the known side-effect profile of liraglutide. The rate of hypoglycaemic events did not differ significantly between active treatment groups and placebo, with an exception of a lower rate in the liraglutide group than in the placebo group during the treatment period. No events of diabetic ketoacidosis were observed. One participant died while on liraglutide (considered unlikely to be related to trial treatment) in connection with three reported adverse events (hypoglycaemic coma, pneumonia, and brain oedema). INTERPRETATION The combination of anti-IL-21 and liraglutide could preserve β-cell function in recently diagnosed type 1 diabetes. The efficacy of this combination appears to be similar to that seen in trials of other disease-modifying interventions in type 1 diabetes, but with a seemingly better safety profile. Efficacy and safety should be further evaluated in a phase 3 trial programme. FUNDING Novo Nordisk.
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Liraglutide after diet-induced weight loss for pain and weight control in knee osteoarthritis: a randomized controlled trial.
Gudbergsen, H, Overgaard, A, Henriksen, M, Wæhrens, EE, Bliddal, H, Christensen, R, Nielsen, SM, Boesen, M, Knop, FK, Astrup, A, et al
The American journal of clinical nutrition. 2021;(2):314-323
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BACKGROUND Weight loss is critical for preventing and managing obesity-related diseases. There is a notable lack of valid and reliable means to manage patients with overweight/obesity and knee osteoarthritis (KOA). OBJECTIVE To determine the efficacy and safety of liraglutide in a 30 mg/d dosing in patients with overweight/obesity and KOA. METHODS The trial was designed as a randomized controlled trial including patients between the age of 18 and 74 y with KOA and a BMI ≥27 (measured in kg/m2).Patients underwent a pre-random assignment diet intervention (week -8 to 0). At week 0, patients having lost >5% of their body weight were randomly assigned to liraglutide 3 mg/d or placebo for 52 wk. The coprimary outcomes were changes in body weight and the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale from week 0 to 52. RESULTS In total, 168 patients enrolled and 156 were randomly assigned to receive liraglutide or placebo. Patients experienced a significant reduction in body weight and KOOS pain during the pre-random assignment dietary intervention period (week -8 to 0). From week 0 to 52 there was a significant difference in body weight between the liraglutide and placebo group (mean changes: -2.8 and +1.2 kg, respectively; group difference, 3.9 kg; 95% CI: -6.9, -1.0; P = 0.008). There was, however, no group difference in KOOS pain (mean changes: 0.4 and -0.6 points, respectively; group difference, 0.9 points; 95% CI: -3.9, 5.7; P = 0.71). Treatment-emergent adverse events related to the gastrointestinal system were experienced by 50.2% and 39.2% of patients in the liraglutide and placebo groups, respectively. CONCLUSIONS In patients with KOA and overweight/obesity liraglutide added after an 8-wk pre-random assignment diet induced a significant weight loss at >52 wk but did not reduce knee pain compared to placebo. This trial was registered at clinicaltrials.gov as NCT02905864.
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Effectiveness of a Female Community Health Volunteer-Delivered Intervention in Reducing Blood Glucose Among Adults With Type 2 Diabetes: An Open-Label, Cluster Randomized Clinical Trial.
Gyawali, B, Sharma, R, Mishra, SR, Neupane, D, Vaidya, A, Sandbæk, A, Kallestrup, P
JAMA network open. 2021;(2):e2035799
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IMPORTANCE Female community health volunteers (FCHVs) are frontline community health workers who have been a valuable resource in improving public health outcomes in Nepal, but their value is understudied in diabetes care. OBJECTIVE To assess whether an FCHV-delivered intervention is associated with reduced blood glucose levels among adults with type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS This community-based, open-label, 2-group, cluster randomized clinical trial with a 12-month delayed control group design was conducted in 14 clusters of a semiurban setting in Western Nepal. A total of 244 adults with type 2 diabetes were recruited between November 2016 and April 2017. The follow-up assessment was conducted at 12 months after enrollment. Data analysis was performed from January to February 2019. INTERVENTIONS Seven clusters were randomized to the FCHV-delivered intervention in which 20 FCHVs provided home visits 3 times a year (once every 4 months) for health promotion counseling and blood glucose monitoring. If participants had blood glucose levels of 126 mg/dL or higher, the FCHVs referred them to the nearest health facility, and if participants were taking antihyperglycemic medication, they were followed up by the FCHVs for adherence to their medication. Seven clusters were randomized to usual care (control group). MAIN OUTCOMES AND MEASURES The primary outcome was the change in mean fasting blood glucose from baseline to 12-month follow-up. Secondary outcomes included changes in mean systolic blood pressure, mean diastolic blood pressure, mean body mass index, percentage change in the proportion of low physical activity, harmful alcohol consumption, current smoking, low fruit and vegetable intake, and antihyperglycemic medication status. RESULTS Of 244 participants, 120 women (56.6%) and 92 men (43.4%) completed the trial. At baseline, the mean (SD) age was 51.71 (8.77) years; 127 participants were in the intervention group, and 117 participants were in the control group (usual care). At baseline, the mean (SD) fasting blood glucose level was 156.06 (44.48) mg/dL (158.48 [45.50] mg/dL in the intervention group and 153.43 [43.39] mg/dL in the control group). At 12-month follow-up, the mean fasting blood glucose decreased by 22.86 mg/dL in the intervention group, whereas it increased by 7.38 mg/dL in the control group. The mean reduction was 27.90 mg/dL greater with the intervention (95% CI, -37.62 to -18.18 mg/dL; P < .001). In secondary outcome analyses, there was a greater decline in mean systolic blood pressure in the intervention group than in the control group (-5.40 mm Hg; 95% CI, -8.88 to -1.92 mm Hg; P = .002). There was detectable difference in the intake of antihyperglycemic medication between the groups (relative risk, 1.35; 95% CI, 1.1 to 1.74; P = .02). CONCLUSIONS AND RELEVANCE These findings suggest that an FCHV-delivered intervention is associated with reduced blood glucose levels among adults with type 2 diabetes in a low-resource setting in Nepal. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03304158.