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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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Effects of exenatide on urinary albumin in overweight/obese patients with T2DM: a randomized clinical trial.
Kang, C, Qiao, Q, Tong, Q, Bai, Q, Huang, C, Fan, R, Wang, H, Kaliannan, K, Wang, J, Xu, J
Scientific reports. 2021;(1):20062
Abstract
In this study, we investigated the effect of exenatide (EXE), a glucagon-like peptide (GLP)-1 receptor agonist, on kidney function, obesity indices, and glucose control in overweight/obese patients with type 2 diabetes mellitus (T2DM). A total of 159 overweight/obese patients with T2DM were randomized to the EXE group or insulin glargine (GLAR) control group for a total treatment period of 24 weeks. EXE intervention significantly reduced the urine albumin concentration (UAC) at week 12 and 24 endpoints (P < 0.001 at week 12 and 24). The levels of the anthropometric, glucose and lipid parameters (TG and HDL-c), and inflammation biomarkers (CRP and TNF-α) in the EXE group were improved at 12 weeks or 24 weeks, respectively. Meanwhile, a comparison between two groups showed significant changes in anthropometric parameters, glucose parameters, lipid parameters (TG and HDL-c), and Inflammation biomarkers (CRP, IL-6, and TNF-α). Serum fibroblast growth factor 21 (FGF21) was increased in the EXE group (P = 0.005) at week 24, and the change was significantly improved compared with GLAR group (P = 0.003). Correlation network analysis showed that FGF21 had a more central role in improving metabolism in the EXE group, and the change of FGF 21 was significantly negatively correlated with UAC at week 12 and week 24, respectively (r = - 0.297, P = 0.010; r = - 0.294, P = 0.012). Our results showed that EXE could help patients improve UAC, glycemic levels, and inflammatory biomarkers after a follow-up period of 24 weeks intervention. These EXE effects may be partly mediated by FGF 21, indicating that EXE is an effective and safe way to control albuminuria in overweight/obese patients with T2DM.
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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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Prophylactic metformin after antenatal corticosteroids (PROMAC): a double blind randomized controlled trial.
Hong, JGS, Tan, PC, Kamarudin, M, Omar, SZ
BMC pregnancy and childbirth. 2021;(1):138
Abstract
BACKGROUND Antenatal corticosteroids (ACS) are increasingly used to improve prematurity-related neonatal outcome. A recognized and common adverse effect from administration of antenatal corticosteroid is maternal hyperglycemia. Even normal pregnancy is characterized by relative insulin resistance and glucose intolerance. Treatment of maternal hyperglycemia after ACS might be indicated due to the higher risk of neonatal acidosis which may coincide with premature birth. Metformin is increasingly used to manage diabetes mellitus during pregnancy as it is effective and more patient friendly. There is no data on prophylactic metformin to maintain euglycemia following antenatal corticosteroids administration. METHODS A double blind randomized trial. 103 women scheduled to receive two doses of 12-mg intramuscular dexamethasone 12-hour apart were separately randomized to take prophylactic metformin or placebo after stratification according to their gestational diabetes (GDM) status. First oral dose of allocated study drug was taken at enrolment and continued 500 mg twice daily for 72 hours if not delivered. Six-point blood sugar profiles were obtained each day (pre- and two-hour post breakfast, lunch and dinner) for up to three consecutive days. A hyperglycemic episode is defined as capillary glucose fasting/pre-meal ≥ 5.3 mmol/L or two-hour post prandial/meal ≥ 6.7 mmol/L. Primary outcome was hyperglycemic episodes on Day-1 (first six blood sugar profile points) following antenatal corticosteroids. RESULTS Number of hyperglycemic episodes on the first day were not significantly different (mean ± standard deviation) 3.9 ± 1.4 (metformin) vs. 4.1 ± 1.6 (placebo) p = 0.64. Hyperglycemic episodes markedly reduced on second day in both arms to 0.9 ± 1.0 (metformin) vs. 1.2 ± 1.0 (placebo) p = 0.15 and further reduced to 0.6 ± 1.0 (metformin) vs. 0.7 ± 1.0 (placebo) p = 0.67 on third day. Hypoglycemic episodes during the 3-day study period were few and all other secondary outcomes were not significantly different. CONCLUSIONS In euglycemic and diet controllable gestational diabetes mellitus women, antenatal corticosteroids cause sustained maternal hyperglycemia only on Day-1. The magnitude of Day-1 hyperglycemia is generally low. Prophylactic metformin does not reduce antenatal corticosteroids' hyperglycemic effect. TRIAL REGISTRATION The trial is registered in the ISRCTN registry on May 4 2017 with trial identifier https://doi.org/10.1186/ISRCTN10156101 .
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Policaptil Gel Retard in adult subjects with the metabolic syndrome: Efficacy, safety, and tolerability compared to metformin.
Guarino, G, Della Corte, T, Strollo, F, Gentile, S, ,
Diabetes & metabolic syndrome. 2021;(3):901-907
Abstract
BACKGROUND Policaptil Gel Retard® (PGR), is a new macromolecule complex based on polysaccharides slowing the rate of carbohydrate and fat absorption. It proved to significantly reduce body weight, acanthosis nigricans expression, HbA1c levels, and glucose metabolism abnormalities in obese, hyper-insulinemic adolescents. No such data are available for adults. AIM: to compare the effects of PGR vs. metformin in adult subjects with the Metabolic Syndrome (MS) and T2DM on a Low Glycemic Index diet. SUBJECTS AND METHODS This spontaneous clinical, longitudinal, single-blind, randomized study based on a per-protocol analysis enrolled 100 outpatients with MS and T2DM consecutively referring to our clinic for three months, and randomly assigned to either the active treatment (Group A:, 6 tablets/day) or the comparator (Group B: Metformin tablets, 1500-2000 mg/day in two divided doses during the two main meals, to minimize side effects) to be taken 30 min before each main meal in equally divided doses. Serum lipid profile, anthropometry, HOMA-IR index, and tolerability parameters were evaluated before and after a 6-month follow-up period. RESULTS all parameters improved at a similar rate in both groups but for the lipid profile, which got even better in Group A. Group A also experienced less prominent gastrointestinal side effects than its counterpart. CONCLUSION For the first time, we showed the non-inferiority of PGR compared to metformin in obese adult subjects with the MS and T2DM as for glycemic control and a clear-cut superiority of PGR in terms of both serum lipid-lowering capacity and tolerability.
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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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Effect of Dosage Reduction of Hypoglycemic Multidrug Regimens on the Incidences of Acute Glycemic Complications in People With Type 2 Diabetes Who Fast During Ramaḍān: A Randomized Controlled Trial.
Zaghlol, LY, Beirat, AF, Amarin, JZ, Hassoun Al Najar, AM, Hasan, YY, Qtaishat, A, Tierney, ME, Zaghlol, RY, Zayed, AA
Frontiers in endocrinology. 2021;:613826
Abstract
OBJECTIVE We aimed to investigate the effect of dosage reduction of four hypoglycemic multidrug regimens on the incidences of acute glycemic complications in people with type 2 diabetes who fast during Ramaḍān. METHODS We conducted an open-label, parallel-group, randomized controlled trial at a tertiary care center in Amman, Jordan. We recruited adults with type 2 diabetes who expressed an intention to fast during Ramaḍān and were adherent to one of four regimens-namely: metformin and glimepiride; metformin and vildagliptin; metformin and insulin glargine U100; or, metformin, insulin glargine U100, and human regular insulin. We randomly assigned participants in a 2:1 ratio to low- or regular-dosage therapy. The primary outcomes were the incidences of hypoglycemia and hyperglycemia during the 29 days of Ramaḍān 2017, and the secondary outcomes were the incidences of diabetic ketoacidosis and hyperosmolar hyperglycemic state during the same period. RESULTS We randomly assigned 687 participants to low-dosage therapy (n = 458) or regular-dosage therapy (n = 229) and included 678 (452 and 226, respectively) in the final analysis. The incidence of hypoglycemia was lower in the low-dosage group compared with the regular-dosage group (19 [4.2%] vs. 52 [23.0%], respectively; OR, 0.15 [95% CI, 0.08-0.26]; P < 0.001). The incidence of hyperglycemia did not differ between the low- and regular-dosage groups (319 [70.6%] vs. 154 [68.1%], respectively; OR, 1.12 [95% CI, 0.79-1.58]; P = 0.5). No participants experienced diabetic ketoacidosis or hyperosmolar hyperglycemic state. Each 1% decrease in the baseline HbA1c concentration was associated with a 19.9-fold (95% CI, 9.6-41.5; P < 0.001) increase in the odds of hypoglycemia, and each 1% increase in the baseline HbA1c concentration was associated with a 15.7-fold (95% CI, 10.0-24.6; P < 0.001) increase in the odds of hyperglycemia. CONCLUSION Dosage reduction decreases the incidence of hypoglycemia without a concomitant increase in the incidences of hyperglycemia, diabetic ketoacidosis, and hyperosmolar hyperglycemic state in people with type 2 diabetes who fast during Ramaḍān. CLINICAL TRIAL REGISTRATION www.ClinicalTrials.gov, identifier NCT04237493.
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Effect of 26 Weeks of Liraglutide Treatment on Coronary Artery Inflammation in Type 2 Diabetes Quantified by [64Cu]Cu-DOTATATE PET/CT: Results from the LIRAFLAME Trial.
Jensen, JK, Zobel, EH, von Scholten, BJ, Rotbain Curovic, V, Hansen, TW, Rossing, P, Kjaer, A, Ripa, RS
Frontiers in endocrinology. 2021;:790405
Abstract
BACKGROUND Quantification of coronary artery inflammation and atherosclerosis remains a challenge in high-risk individuals. In this study we sought to investigate if the glucagon like peptide-1 receptor agonist liraglutide has a direct anti-inflammatory effect in the coronary arteries using positron emission tomography (PET) with a radioactive tracer targeting activated macrophages in the vessel-wall. METHODS Thirty randomly selected participants with type 2 diabetes from the placebo-controlled trial LIRAFLAME were enrolled in this sub-study. Participants were, prior to enrollment in this sub-study, randomized to either treatment with daily liraglutide (n=15) or placebo (n=15). Both groups underwent a combined [64Cu]Cu-DOTATATE positron emission tomography and computed tomography scan of the heart at baseline and after 26 weeks of treatment. Coronary artery uptake of [64Cu]Cu-DOTATATE were measured as maximum standardized uptake values (SUVmax); and means of the maximum values (mSUVmax), both values were calculated at the level of each participant and each individual coronary-segment. RESULTS SUVmax and mSUVmax values decreased significantly in the liraglutide group both at the participant level (SUVmax: p=0.013; mSUVmax: p=0.004) and at the coronary-segment level (SUVmax: p=0.001; mSUVmax: p<0.0001). No change was observed in the placebo group neither at the participant level (SUVmax: p=0.69; mSUVmax: p=0.67) or at the coronary-segment level (SUVmax: p=0.49; mSUVmax: p=0.30). When comparing the mean change in uptake values between the two groups at both the participant level (SUVmax: p=0.076; mSUVmax: p=0.077) and the coronary segment level (SUVmax: p=0.13; mSUVmax: p=0.11) a borderline significant difference was observed. Baseline SUVmax [64Cu]Cu-DOTATATE uptake values showed a weak positive correlation with the inflammatory biomarker high-sensitivity c-reactive protein (τ =0.26, p=0.045). CONCLUSION Liraglutide treatment for 26-weeks caused a significant reduction in [64Cu]Cu-DOTATATE uptake in the coronary arteries whereas this was not seen in the placebo treated group. In addition, [64Cu]Cu-DOTATATE PET/CT as a marker of coronary inflammation correlated with the systemic inflammation marker hs-CRP.
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Distinct effects of carbohydrate ingestion timing on glucose fluctuation and energy metabolism in patients with type 2 diabetes: a randomized controlled study.
Enyama, Y, Takeshita, Y, Tanaka, T, Sako, S, Kanamori, T, Takamura, T
Endocrine journal. 2021;(10):1225-1236
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This randomized, open-label, and parallel-group study aimed to investigate the effects of altering the timing of carbohydrate intake at breakfast or dinner on blood glucose fluctuations and energy metabolism. A total of 43 participants with type 2 diabetes were assigned to either the breakfast or dinner group. Participants were provided an isocaloric carbohydrate-restricted diet constituting 10% carbohydrate only at breakfast or dinner for 2 days during the study. Glucose fluctuations were compared using a continuous glucose monitoring system (iPro2) and body composition, energy expenditure, blood biochemistry, and endocrine function changes. The carbohydrate restriction either at breakfast or dinner significantly decreased postprandial glucose excursion and mean 24-h blood glucose levels. The incremental blood glucose area under the curve (AUC) for 2 h (iAUC0-2h) at lunch significantly increased in the breakfast group, whereas no significant differences were observed in the iAUC0-2h between breakfast and lunch in the dinner group. Carbohydrate restriction reduced diet-induced thermogenesis at breakfast (intragroup comparison; 223 ± 117 to 109 ± 104 kcal, p = 0.002) but did not affect diet-induced thermogenesis at dinner. However, fasting plasma free fatty acids were comparable in both groups, prelunch free fatty acids increased significantly only in the breakfast group (0.20 ± 0.09 to 0.63 ± 0.19 mEq/L, p < 0.001). Carbohydrate restriction in the diet once daily decreases mean 24-h blood glucose levels and exerts unique metabolic effects depending on the timing.