Abstract

BACKGROUND Aging and type-2 diabetes (T2D) are the most important risk factors for cognitive impairment and Alzheimer's disease. Exercise training is an effective, safe, and practical intervention in improving glucose metabolism, physical function, and cognitive disorders. This pilot study investigated the feasibility and preliminary efficacy of high-intensity low-volume (HIFT) vs. low-intensity high-volume (LIFT) functional training in elderly T2D patients with cognitive impairment. METHODS Forty-eight elderly T2D patients (31 female, 17 male, age 67.5 ± 5.8 years, MMSE score 18.8 ± 2.6, FBG 209.5 ± 37.9) were randomly assigned to HIFT, LIFT and control groups. Cognitive impairment was diagnosed with MMSE ≤ 23 based Iranian society. The SDMT, CVLT-II, BVMT-R, and Stroop tests were used to evaluated processing speed, learning, memory and attention respectively. Physical fitness tests include: tandem stance and walk test; TUG; 6MWT, 10MWT; SSST; 5TSTS; and hand grip was used to evaluated static and dynamic balance, agility, walking endurance, gait speed, lower limb function and lower and upper body strength respectively. As well as, Biochemical (FBG, insulin, HOMA-IR, HbA1c) and physiological outcomes (SBP, and DBP) were assessed. The HIFT group performed six weeks of functional training (three sessions per week) with 120-125% of the lactate threshold. The LIFT group performed six weeks of functional training (five sessions per week) with a 70-75% lactate threshold. Feasibility, safety, and acceptability of exercise programs were assessed at the end of the study. RESULT HIFT showed a higher adherence rate (91% vs. 87.5%), safety, and acceptability compared to LIFT. MMSE and Stroop scores, 6MWT, FBG, insulin, HOMA-IR, HbA1c, SBP, and DBP significantly improved in HIFT (all, P ≤ 0.004) and LIFT (all, P ≤ 0.023). Changes in 6MWT, FBG, insulin, HOMA-IR, and HbA1c in HIFT (all, P ≤ 0.001) and LIFT (all, P ≤ 0.008) were significant compared to the control group. Changes in Stroop scores were significant only in the HIFT group compared to the control group (P = 0.013). SDMT, CVLT-II, BVMT-R, balance test, 10MWT, SSST, TUG and hang grip significantly improved only in HIFT (all, P ≤ 0.038). CONCLUSION HIFT vs. LIFT is a safe, feasible, and effective approach for improving some aspects of physical, biochemical, and cognitive function in elderly T2D patients with cognitive impairment. This pilot study provides initial proof-of-concept data for the design and implementation of an appropriately powered randomised controlled trial (RCT) of HIFT vs. LIFT in a larger sample of elderly T2D patients with cognitive impairment. TRIAL REGISTRATION Randomized controlled trial (RCT) (Iranian Registry of Clinical Trials, trial registration number: IRCT20230502058055N1. Date of registration: 11/06/2023.

Abstract

BACKGROUND & AIMS Continuous glucose monitoring (CGM) provides data on short-term glycemic variability (GV). GV is associated with adverse outcomes in individuals with diabetes. Whether GV is associated with cardiometabolic risk in individuals without diabetes is unclear. We systematically reviewed the literature to assess whether GV is associated with cardiometabolic risk markers or outcomes in individuals without diabetes. METHODS Searches were performed in PubMed/Medline, Embase and Cochrane from inception through April 2022. Two researchers were involved in study selection, data extraction and quality assessment. Studies evaluating GV using CGM for ≥24 h were included. Studies in populations with acute and/or critical illness were excluded. Both narrative synthesis and meta-analyzes were performed, depending on outcome. RESULTS Seventy-one studies were included; the majority were cross-sectional. Multiple measures of GV are higher in individuals with compared to without prediabetes and GV appears to be inversely associated with beta cell function. In contrast, GV is not clearly associated with insulin sensitivity, fatty liver disease, adiposity, blood lipids, blood pressure or oxidative stress. However, GV may be positively associated with the degree of atherosclerosis and cardiovascular events in individuals with coronary disease. CONCLUSION GV is elevated in prediabetes, potentially related to beta cell dysfunction, but less clearly associated with obesity or traditional risk factors. GV is associated with coronary atherosclerosis development and may predict cardiovascular events and type 2 diabetes. Prospective studies are warranted, investigating the predictive power of GV in relation to incident disease. GV may be an important risk measure also in individuals without diabetes.

Abstract

AIMS/HYPOTHESIS Continuous glucose monitoring (CGM) is increasingly used in the treatment of type 2 diabetes, but the effects on glycaemic control are unclear. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the effect of CGM on glycaemic control in adults with type 2 diabetes. METHODS We performed a systematic review using Embase, MEDLINE, Web of Science, Scopus and ClinicalTrials.gov from inception until 2 May 2023. We included RCTs investigating real-time CGM (rtCGM) or intermittently scanned CGM (isCGM) compared with self-monitoring of blood glucose (SMBG) in adults with type 2 diabetes. Studies with an intervention duration <6 weeks or investigating professional CGM, a combination of CGM and additional glucose-lowering treatment strategies or GlucoWatch were not eligible. Change in HbA1c and the CGM metrics time in range (TIR), time below range (TBR), time above range (TAR) and glycaemic variability were extracted. We evaluated the risk of bias using the Cochrane risk-of-bias tool version 2. Data were synthesised by performing a meta-analysis. We also explored the effects of CGM on severe hypoglycaemia and micro- and macrovascular complications. RESULTS We found 12 RCTs comprising 1248 participants, with eight investigating rtCGM and four isCGM. Compared with SMBG, CGM use (rtCGM or isCGM) led to a mean difference (MD) in HbA1c of -3.43 mmol/mol (-0.31%; 95% CI -4.75, -2.11, p<0.00001, I2=15%; moderate certainty). This effect was comparable in studies that included individuals using insulin with or without oral agents (MD -3.27 mmol/mol [-0.30%]; 95% CI -6.22, -0.31, p=0.03, I2=55%), and individuals using oral agents only (MD -3.22 mmol/mol [-0.29%]; 95% CI -5.39, -1.05, p=0.004, I2=0%). Use of rtCGM showed a trend towards a larger effect (MD -3.95 mmol/mol [-0.36%]; 95% CI -5.46 to -2.44, p<0.00001, I2=0%) than use of isCGM (MD -1.79 mmol/mol [-0.16%]; 95% CI -5.28, 1.69, p=0.31, I2=64%). CGM was also associated with an increase in TIR (+6.36%; 95% CI +2.48, +10.24, p=0.001, I2=9%) and a decrease in TBR (-0.66%; 95% CI -1.21, -0.12, p=0.02, I2=45%), TAR (-5.86%; 95% CI -10.88, -0.84, p=0.02, I2=37%) and glycaemic variability (-1.47%; 95% CI -2.94, -0.01, p=0.05, I2=0%). Three studies reported one or more events of severe hypoglycaemia and macrovascular complications. In comparison with SMBG, CGM use led to a non-statistically significant difference in the incidence of severe hypoglycaemia (RR 0.66, 95% CI 0.15, 3.00, p=0.57, I2=0%) and macrovascular complications (RR 1.54, 95% CI 0.42, 5.72, p=0.52, I2=29%). No trials reported data on microvascular complications. CONCLUSIONS/INTERPRETATION CGM use compared with SMBG is associated with improvements in glycaemic control in adults with type 2 diabetes. However, all studies were open label. In addition, outcome data on incident severe hypoglycaemia and incident microvascular and macrovascular complications were scarce. REGISTRATION This systematic review was registered on PROSPERO (ID CRD42023418005).

Abstract

AIMS/HYPOTHESIS Hypomagnesaemia has been associated with insulin resistance and an increased risk of type 2 diabetes. Whether magnesium supplementation improves insulin sensitivity in people with type 2 diabetes and a low serum magnesium level is unknown. METHODS Using a randomised, double-blind (both participants and investigators were blinded to the participants' treatment sequences), placebo-controlled, crossover study design, we compared the effect of oral magnesium supplementation (15 mmol/day) for 6 weeks with that of matched placebo in individuals with insulin-treated type 2 diabetes (age ≥18 years, BMI 18-40 kg/m2, HbA1c <100 mmol/mol [11.3%], serum magnesium ≤0.79 mmol/l). Participants were recruited from the outpatient clinic and through advertisements. Randomisation to a treatment sequence order was done using a randomisation list. We used block randomisation and the two possible treatment sequences were evenly distributed among the trial population. The primary outcome was the mean glucose infusion rate during the final 30 min of a hyperinsulinaemic-euglycaemic clamp (i.e. M value). Secondary outcomes included variables of glucose control, insulin need, BP, lipid profile and hypomagnesaemia-related symptoms during follow-up. RESULTS We recruited 14 participants (50% women, 100% White, mean ± SD age 67±6 years, BMI 31±5 kg/m2, HbA1c 58±9 mmol/mol [7.4±0.9%]) with insulin-treated type 2 diabetes. Magnesium supplementation increased both mean ± SEM serum magnesium level (0.75±0.02 vs 0.70±0.02 mmol/l, p=0.016) and urinary magnesium excretion (magnesium/creatinine ratio, 0.23±0.02 vs 0.15±0.02, p=0.005), as compared with placebo. The M value of the glucose clamp did not differ between the magnesium and placebo study arms (4.6±0.5 vs 4.4±0.6 mg kg-1 min-1, p=0.108). During the 6 weeks of treatment, continuous glucose monitoring outcomes, HbA1c, insulin dose, lipid profile and BP also did not differ, except for a lower HDL-cholesterol concentration after magnesium compared with placebo (1.14±0.08 vs 1.20±0.09 mmol/l, p=0.026). Symptoms potentially related to hypomagnesaemia were similar for both treatment arms. CONCLUSIONS/INTERPRETATION Despite an albeit modest increase in serum magnesium concentration, oral magnesium supplementation does not improve insulin sensitivity in people with insulin-treated type 2 diabetes and low magnesium levels. TRIAL REGISTRATION EudraCT number 2021-001243-27. FUNDING This study was supported by a grant from the Dutch Diabetes Research Foundation (2017-81-014).

Abstract

AIMS: Although conventional interventions for people at high risk of developing type 2 diabetes are usually conducted face-to-face, such interventions are burdensome for health care providers. We developed a lifestyle intervention program combining lifestyle coaching via a smartphone application augmented by intermittently scanned continuous glucose monitoring without burdening health care providers. Its effectiveness for glycemic control and body weight reduction in people at risk of type 2 diabetes was investigated. MATERIALS AND METHODS For this 12-week randomized unblinded trial with offline recruitment, participants with a hemoglobin A1c level of 5.6% to 6.4% or a fasting blood glucose of 110 to 125 mg/dL and body mass index (BMI) >23 kg/m2 but <40 kg/m2 were randomly assigned to the intervention group (App) and control group (C). The primary endpoint was the difference in time in range of blood glucose between 70 and 140 mg/dL (3.9-7.8 mmol/L) before and after the study period between the 2 groups. RESULTS Among 168 patients (mean age, 48.1 years; mean BMI, 26.6 kg/m2; and male, 80.4%), 82 and 86 were assigned to the App group and C group, respectively. After 12 weeks, time in range of blood glucose at 70 to 140 mg/dL significantly improved in the App group compared with the C group (-2.6 minutes/day vs +31.5 minutes/day, P = .03). Changes in time above range did not differ, whereas time below range (blood glucose <70 mg/dL; +23.5 minutes/day vs -8.9 minutes/day, P = .02) improved in the App group. BMI (-0.26 vs -0.59, P = .017) was reduced in the App group compared with the C group. CONCLUSION Intervention with a smartphone app and intermittently scanned continuous glucose monitoring increased glycemic control accompanied by decreased carbohydrate intake and weight loss. Further trials are needed to confirm whether these interventions can reduce incident type 2 diabetes.

Abstract

AIMS: Management of blood glucose fluctuation is essential for diabetes. Exercise is a key therapeutic strategy for diabetes patients, although little is known about determinants of glycemic response to exercise training. We aimed to investigate the effect of combined aerobic and resistance exercise training on blood glucose fluctuation in type 2 diabetes patients and explore the predictors of exercise-induced glycemic response. MATERIALS AND METHODS Fifty sedentary diabetes patients were randomly assigned to control or exercise group. Participants in the control group maintained sedentary lifestyle for 2 weeks, and those in the exercise group specifically performed combined exercise training for 1 week. All participants received dietary guidance based on a recommended diet chart. Glycemic fluctuation was measured by flash continuous glucose monitoring. Baseline fat and muscle distribution were accurately quantified through magnetic resonance imaging (MRI). RESULTS Combined exercise training decreased SD of sensor glucose (SDSG, exercise-pre vs exercise-post, mean 1.35 vs 1.10 mmol/L, p = .006) and coefficient of variation (CV, mean 20.25 vs 17.20%, p = .027). No significant change was observed in the control group. Stepwise multiple linear regression showed that baseline MRI-quantified fat and muscle distribution, including visceral fat area (β = -0.761, p = .001) and mid-thigh muscle area (β = 0.450, p = .027), were significantly independent predictors of SDSG change in the exercise group, as well as CV change. CONCLUSIONS Combined exercise training improved blood glucose fluctuation in diabetes patients. Baseline fat and muscle distribution were significant factors that influence glycemic response to exercise, providing new insights into personalized exercise intervention for diabetes.

Abstract

(1) Background: The effect of garlic on glucose and lipid metabolism in humans remains controversial. The aim of this study was to investigate the effects of garlic on blood lipid levels and glucose levels in humans through a systematic review and meta-analysis. (2) Methods: We extensively searched four databases, including PubMed, Web of Science, Embase, and the Cochrane Library, up to February 2024. To assess the collective impact of garlic and its supplements on fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG), an analysis was conducted using a random effects model. Subgroup analyses were performed when I2 < 50%. (3) Result: We found that the garlic intervention was effective in controlling FBG (mean difference = -7.01; 95% CI: -8.53, -5.49, p < 0.001), HbA1c (mean deviation = -0.66; 95% CI: -0.76, -0.55, p < 0.001, I2 = 62.9%), TC (mean difference = -14.17; 95% CI: -19.31, -9.03, p < 0.001), and LDL-C (mean difference = -8.20; 95% CI: -15.58, -0.81, p = 0.03); moreover, it also increased the level of HDL-C in humans (mean difference = 2.06; 95% CI: 1.54, 2.59; p < 0.001). Nonetheless, the intervention involving garlic did not yield a substantial impact on triglyceride (TG) levels. (4) Conclusion: The intervention of garlic is beneficial to control blood glucose and blood lipids in humans.

Abstract

This systematic review and meta-analysis evaluated the combined effects of clinician-led and community-based group exercise interventions on a range of health outcomes in adults with type 2 diabetes mellitus. Our literature search spanned Medline, Scopus, PubMed, Embase, and CINAHL databases, focusing on peer-reviewed studies published between January 2003 and January 2023. We included studies involving participants aged 18 years and older and articles published in English, resulting in a dataset of eight studies with 938 participants. Spanning eight peer-reviewed studies with 938 participants, the analysis focused on the interventions' impact on glycemic control, physical fitness, and anthropometric and hematological measurements. Outcomes related to physical fitness, assessed through the six-minute walk test, the 30 s sit-to-stand test, and the chair sit-and-reach test, were extracted from five studies, all of which reported improvements. Anthropometric outcomes from seven studies highlighted positive changes in waist circumference and diastolic blood pressure; however, measures such as body mass index, systolic blood pressure, weight, and resting heart rate did not exhibit significant changes. Hematological outcomes, reviewed in four studies, showed significant improvements in fasting blood glucose, triglycerides, and total cholesterol, with glycemic control evidenced by reductions in HbA1c levels, yet LDL and HDL cholesterol levels remained unaffected. Ten of the fifteen outcome measures assessed showed significant enhancement, indicating that the intervention strategies implemented may offer substantial health benefits for managing key type 2 diabetes mellitus-related health parameters. These findings in combination with further research, could inform the refinement of physical activity guidelines for individuals with type 2 diabetes mellitus, advocating for supervised group exercise in community settings.

Abstract

BACKGROUND About one in 11 adults worldwide suffers from diabetic disease with constantly increasing prevalence; from the 529 million patients registered in 2021, the number of people with diabetes was predicted to rise to approximately 1.31 billion in 2050. In Italy, 5.9% of the population is diabetic, with a higher prevalence with increasing age and in the South of the country. Yoga and Mindfulness could represent a valid support for the care of diabetic subjects especially in a stressful caring context such as the Covid-19 pandemic. STUDY DESIGN A scoping review was conducted to achieve the goals of the study. Yoga or Mindfulness interventions on diabetic subjects were specifically analyzed and qualitative-quantitative data collected in the selected randomized controlled trials were extensive for possible meta-analysis. METHODS The review was conducted by two independent practitioners and a third one was consulted in case of conflict. The PRISMA method was used for both the selection and reporting of the studies to be included. Specific PICOS and search strategies have been developed on PubMed, Embase and PsycINFO databases. Included in the review were: randomised controlled trials, full dissertation articles and papers in English with a time limit on May 31, 2022. RESULTS The Review included 22 studies; 12 on Mindfulness, 9 on Yoga and one about both disciplines; among these, one studied patients with Type 1 Diabetes, 14 with Type 2 Diabetes, 6 with both and one with Gestational Diabetes. Only one paper studied adolescent subjects while the other 21 focused on a range of adult subjects. The studies showed that Yoga and Mindfulness have strong potential not only on stress management, but also on clinical-metabolic parameters. CONCLUSIONS The recent Covid-19 pandemic has certainly redesigned a new way of treating and managing chronic diseases, such as diabetes. An increasingly fragile population, and with the growing need to reduce overall stress levels, could find alternative practices in Yoga and Mindfulness to support conventional therapies.

Abstract

BACKGROUND Chronic low-grade inflammatory profile (CLIP) is one of the pathways involved in type 2 diabetes (T2D). Currently, there is limited evidence for ameliorating effects of combined lifestyle interventions on CLIP in type 2 diabetes. We investigated whether a 13-week combined lifestyle intervention, using hypocaloric diet and resistance exercise plus high-intensity interval training with or without consumption of a protein drink, affected CLIP in older adults with T2D. METHODS In this post-hoc analysis of the PROBE study 114 adults (≥55 years) with obesity and type 2 (pre-)diabetes had measurements of C-reactive protein (CRP), pro-inflammatory cytokines interleukin (IL)-6, tumor-necrosis-factor (TNF)-α, and monocyte chemoattractant protein (MCP)-1, anti-inflammatory cytokines IL-10, IL-1 receptor antagonist (RA), and soluble tumor-necrosis-factor receptor (sTNFR)1, adipokines leptin and adiponectin, and glycation biomarkers carboxymethyl-lysine (CML) and soluble receptor for advanced glycation end products (sRAGE) from fasting blood samples. A linear mixed model was used to evaluate change in inflammatory biomarkers after lifestyle intervention and effect of the protein drink. Linear regression analysis was performed with parameters of body composition (by dual-energy X-ray absorptiometry) and parameters of insulin resistance (by oral glucose tolerance test). RESULTS There were no significant differences in CLIP responses between the protein and the control groups. For all participants combined, IL-1RA, leptin and adiponectin decreased after 13 weeks (p = 0.002, p < 0.001 and p < 0.001), while ratios TNF-α/IL-10 and TNF-α/IL-1RA increased (p = 0.003 and p = 0.035). CRP increased by 12 % in participants with low to average CLIP (pre 1.91 ± 0.39 mg/L, post 2.13 ± 1.16 mg/L, p = 0.006) and decreased by 36 % in those with high CLIP (pre 5.14 mg/L ± 1.20, post 3.30 ± 2.29 mg/L, p < 0.001). Change in leptin and IL-1RA was positively associated with change in fat mass (β = 0.133, p < 0.001; β = 0.017, p < 0.001) and insulin resistance (β = 0.095, p = 0.024; β = 0.020, p = 0.001). Change in lean mass was not associated with any of the biomarkers. CONCLUSION 13 weeks of combined lifestyle intervention, either with or without protein drink, reduced circulating adipokines and anti-inflammatory cytokine IL-1RA, and increased inflammatory ratios TNF-α/IL-10 and TNF-α/IL-1RA in older adults with obesity and T2D. Effect on CLIP was inversely related to baseline inflammatory status.