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Extending the Overnight Fast: Sex Differences in Acute Metabolic Responses to Breakfast.
S Atkinson, F, A Heruc, G, M H Tan, V, Petocz, P, C Brand-Miller, J
Nutrients. 2020;(8)
Abstract
Fasting for over 24 h is associated with worsening glucose tolerance, but the effect of extending the overnight fast period (a form of time-restricted feeding) on acute metabolic responses and insulin sensitivity is unclear. The aim of this pilot study was to determine the acute impact of an increased fasting period on postprandial glycaemia, insulinemia, and acute insulin sensitivity responses to a standard meal. Twenty-four lean, young, healthy adults (12 males, 12 females) consumed a standard breakfast after an overnight fast of 12, 14, and 16 h. Each fast duration was repeated on three separate occasions (3 × 3) in random order. Postprandial glucose and insulin responses were measured at regular intervals over 2 h and quantified as incremental area under the curve (iAUC). Insulin sensitivity was determined by homeostatic modelling assessment (HOMA). After 2 h, ad libitum food intake at a buffet meal was recorded. In females, but not males, insulin sensitivity improved (HOMA%S +35%, p = 0.016, marginally significant) with longer fast duration (16 h vs. 12 h), but paradoxically, postprandial glycaemia was higher (glucose iAUC +37%, p = 0.002). Overall, males showed no differences in glucose or insulin homeostasis. Both sexes consumed more energy (+28%) at the subsequent meal (16 h vs. 12 h). Delaying the first meal of the day by 4 h by extending the fasting period may have adverse metabolic effects in young, healthy, adult females, but not males.
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E-health education interventions on HbA1c in patients with type 1 diabetes on intensive insulin therapy: A systematic review and meta-analysis of randomized controlled trials.
Feigerlová, E, Oussalah, A, Zuily, S, Sordet, S, Braun, M, Guéant, JL, Guerci, B
Diabetes/metabolism research and reviews. 2020;(6):e3313
Abstract
AIMS: Patient-centered education improves glycemic control in subjects with type 1 diabetes (T1D). E-health technologies are widely used to support medical decision-making, patient advising or teleconsultations; however, the active participation of a patient is missing. Challenges remain whether e-health education can be effectively incorporated into clinical pathways. The purpose of the study was to examine the effects of e-health education, compared to standard care, on HbA1c. MATERIAL AND METHODS We conducted a literature search (EMBASE, MEDLINE, The Cochrane Library and Web of Science) up to February 2018 for randomized controlled trials (RCTs) of Internet-/ mobile application-based educational interventions, with the active involvement of patients, provided in addition to, or substituting usual care in patients with T1D on intensive insulin therapy. The primary outcome was the standardized difference in means (SDM) of HbA1c change from baseline between intervention and comparator groups. RESULTS Eight RCTs involving 757 subjects were included on 6335 screened citations. After excluding two trials with a high risk of bias from the meta-analysis, the HbA1c change from baseline did not significantly differ between intervention and comparator groups (SDM = -0.154, 95% CI: -0.335 to 0.025; P = 0.01, random-effect model). The number of studies is limited with a relatively short duration. Reporting of educational outcomes was not rigorous. CONCLUSIONS The effect of e-health educational interventions on HbA1c in patients with T1D is comparable to the standard care. This review highlights the need for further well-designed RCTs that will investigate the opportunities of incorporating e-health education into clinical pathways.
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Long-term (52-week) efficacy and safety of ipragliflozin add-on therapy to insulin in Japanese patients with type 1 diabetes mellitus: An uncontrolled, open-label extension of a phase III study.
Kaku, K, Isaka, H, Sakatani, T, Toyoshima, J
Journal of diabetes investigation. 2020;(3):662-671
Abstract
INTRODUCTION The aim of the present study was to assess the long-term (52-week) efficacy and safety of ipragliflozin in insulin-treated Japanese patients with type 1 diabetes mellitus and inadequate glycemic control. MATERIALS AND METHODS In this 28-week, open-label extension of a multicenter, randomized, placebo-controlled, 24-week phase III study, ipragliflozin recipients continued treatment (50 mg, once daily), and placebo recipients were switched to once-daily 50 mg ipragliflozin at the start of the extension period. The ipragliflozin dose could be increased to 100 mg if warranted. The primary end-point was change in glycated hemoglobin; secondary end-points were change in insulin dose and bodyweight. Safety outcomes were monitored as treatment-emergent adverse events. RESULTS A total of 53 (placebo switched to ipragliflozin) and 108 (ipragliflozin) patients completed the open-label extension (treatment period 2), with 24 and 44 patients, respectively, receiving dose increases. From baseline to end of treatment, the overall mean change (standard deviation [SD]) in glycated hemoglobin was -0.33% (0.72; -3.7 mmol/mol [7.9]), with changes in basal, bolus and total insulin doses of -3.76 IU (SD 3.85 IU), -2.51 IU (SD 7.08 IU) and -6.27 IU (SD 8.16 IU), respectively. No serious drug-related treatment-emergent adverse events or deaths were reported. Treatment-emergent adverse events leading to study discontinuation occurred in zero and three (2.6%) patients in the placebo switched to ipragliflozin and ipragliflozin groups, respectively; all were considered drug-related. There were no cases of severe hypoglycemia or diabetic ketoacidosis, and no safety concerns related to dose increase. CONCLUSIONS The efficacy and safety of 50 mg, once-daily ipragliflozin in insulin-treated type 1 diabetes mellitus patients were confirmed in this long-term, open-label extension study. No safety concerns were attributed to a dose increase to 100 mg.
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Determinants of glycaemic outcome in the current practice of care for young people up to 21 years old with type 1 diabetes under real-life conditions.
Kordonouri, O, Lange, K, Biester, T, Datz, N, Kapitzke, K, von dem Berge, T, Weiskorn, J, Danne, T
Diabetic medicine : a journal of the British Diabetic Association. 2020;(5):797-804
Abstract
AIM: To determine factors influencing the success of treatment for type 1 diabetes, defined as HbA1c < 58 mmol/mol (<7.5%), in a large paediatric cohort under real-life conditions. METHODS This is a monocentric observational study analysing the determinants of glycaemic outcome (sex, age, comorbidities, sociodemographic factors, diabetes technology) in an entire cohort of people with diabetes aged up to 21 years. Glycaemic outcome was defined as an individual's median HbA1c and the prevalence of acute complications over this period. RESULTS Of 700 young people with type 1 diabetes [age 13.6 years (range: 1.4-20.9 years); diabetes duration 5.8 years (range: 0.1-18.3 years)], 63% were using an insulin pump and 32% any type of continuous glucose monitoring. Mean HbA1c was 61 mmol/mol [95% confidence interval (CI) 60-62; 7.7%, 95% CI 7.5-7.8]. Some 63% of children aged < 12 years reached HbA1c (58 mmol/mol (<7.5%) compared with 43% of older participants. The prevalence of severe hypoglycaemia was 2.41 events and that of diabetic ketoacidosis 1.4 events per 100 person-years. Neither type of insulin therapy nor use of continuous glucose monitoring, sex or comorbidity with coeliac disease or thyroiditis was significantly associated with glycaemic outcome. However, age, diabetes duration, having a father not born in Germany, psychiatric comorbidities and family structure were associated with HbA1c . CONCLUSIONS Current technologies and a multidisciplinary team approach allow high numbers of children and adolescents to realize tight glycaemic control with a low prevalence of acute complications. However, age-related challenges, sociodemographic factors and psychological comorbidities are barriers to achieving best possible glycaemic outcome.
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Glycemic Monitoring and Management in Advanced Chronic Kidney Disease.
Galindo, RJ, Beck, RW, Scioscia, MF, Umpierrez, GE, Tuttle, KR
Endocrine reviews. 2020;(5):756-74
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Abstract
Glucose and insulin metabolism in patients with diabetes are profoundly altered by advanced chronic kidney disease (CKD). Risk of hypoglycemia is increased by failure of kidney gluconeogenesis, impaired insulin clearance by the kidney, defective insulin degradation due to uremia, increased erythrocyte glucose uptake during hemodialysis, impaired counterregulatory hormone responses (cortisol, growth hormone), nutritional deprivation, and variability of exposure to oral antihyperglycemic agents and exogenous insulin. Patients with end-stage kidney disease frequently experience wide glycemic excursions, with common occurrences of both hypoglycemia and hyperglycemia. Assessment of glycemia by glycated hemoglobin (HbA1c) is hampered by a variety of CKD-associated conditions that can bias the measure either to the low or high range. Alternative glycemic biomarkers, such as glycated albumin or fructosamine, are not fully validated. Therefore, HbA1c remains the preferred glycemic biomarker despite its limitations. Based on observational data for associations with mortality and risks of hypoglycemia with intensive glycemic control regimens in advanced CKD, an HbA1c range of 7% to 8% appears to be the most favorable. Emerging data on the use of continuous glucose monitoring in this population suggest promise for more precise monitoring and treatment adjustments to permit fine-tuning of glycemic management in patients with diabetes and advanced CKD.
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Effect of Exercise Duration on Postprandial Glycaemic and Insulinaemic Responses in Adolescents.
Dring, KJ, Cooper, SB, Williams, RA, Morris, JG, Sunderland, C, Nevill, ME
Nutrients. 2020;(3)
Abstract
High-intensity intermittent exercise (HIIE) is a potential intervention to manage hyperglycaemia and insulin resistance in adolescents. The aim of this study was to determine the optimum duration of HIIE to reduce postprandial glycaemic and insulinaemic responses in adolescents and the longevity of the response. Thirty-nine participants (12.4 ± 0.4 year) completed a 30- and 60-min exercise trial (Loughborough Intermittent Shuttle Test) and a rested control trial in a randomised crossover design. Capillary blood samples were taken at baseline, immediately and 1-h post-exercise; and 30, 60 and 120 min following a standardised lunch (day one) and a standardised breakfast 24-h post-exercise. Plasma insulin total area under the curve (tAUC) following lunch was lower following 60-min HIIE (21754 ± 16861 pmol·L-1 × 120 min, p = 0.032) and tended to be lower following 30-min HIIE (24273 ± 16131 pmol·L-1 × 120 min, p = 0.080), when compared with the resting condition (26931 ± 21634 pmol·L-1 × 120 min). Blood glucose concentration was lower 1-h post-exercise following 30-min HIIE (3.6 ± 0.6 mmol·L-1) when compared to resting (4.1 ± 0.9 mmol·L-1, p = 0.001). Blood glucose and plasma insulin concentration did not differ across trials on day two. Shorter bouts of HIIE (30-min), as well as a 60-min bout, reduced the postprandial insulinaemic response to lunch, an ecologically valid marker of insulin sensitivity. As the beneficial effects of HIIE were limited to 3 h post-exercise, adolescents are recommended to engage daily HIIE to enhance metabolic health.
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Effects of Sodium-Glucose Cotransporter Inhibitor/Glucagon-Like Peptide-1 Receptor Agonist Add-On to Insulin Therapy on Glucose Homeostasis and Body Weight in Patients With Type 1 Diabetes: A Network Meta-Analysis.
Kim, YJ, Hwang, SD, Lim, S
Frontiers in endocrinology. 2020;:553
Abstract
Many patients with type 1 diabetes (T1D) do not achieve the glycemic target goal with insulin treatment. In this study, we aimed to evaluate the efficacy and safety of add-on to insulin therapy in patients with T1D. We conducted direct and indirect network meta-analyses using Bayesian models and ranked hypoglycemic agents via mixed treatment comparison, using data from the CENTRAL, MEDLINE, EMBASE, and Science Citation Index Expanded databases. Randomized controlled trials (RCTs) involving patients with T1D treated with insulin and add-on metformin or sodium-glucose cotransporter inhibitors or glucagon-like peptide-1 receptor agonists from January 1970 to September 2019 were included in this study. Twenty-three RCTs with 5,151 subjects were divided into the following groups: insulin alone, insulin+metformin, insulin+canagliflozin, insulin+dapagliflozin, insulin+empagliflozin, insulin+sotagliflozin, insulin+liraglutide, and insulin+exenatide. HbA1c level in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group (mean difference: -0.43, 95% credible interval: -0.62 to -0.23). Total daily insulin dose in the insulin+sotagliflozin group was significantly lower than that in the insulin alone group. Compared with that in the insulin alone group, body weight in the groups treated with insulin+add-on canagliflozin, sotagliflozin, and exenatide was significantly decreased by 4.5, 2.8, and 5.1 kg, respectively. Hypoglycemic episodes did not differ among the groups. In patients with T1D, insulin+sotagliflozin decreased the HbA1c level, daily insulin dose, and body weight without hypoglycemia compared with insulin monotherapy. Insulin+canagliflozin or insulin+exenatide was effective in reducing body weight compared with insulin alone. In conclusion, sotagliflozin treatment decreased not only the HbA1c levels and insulin dose but also the body weight without causing hypoglycemia in patients with T1D. Treatment with canagliflozin and exenatide effectively reduced body weight in patients with T1D. However, ketoacidosis associated with the use of SGLT inhibitors should be considered in these patients. Thus, our results suggest that sotagliflozin has a high probability of being ranked first as an adjunctive therapy to insulin in patients with T1D.
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GLP-1 and insulin regulation of skeletal and cardiac muscle microvascular perfusion in type 2 diabetes.
Love, KM, Liu, J, Regensteiner, JG, Reusch, JEB, Liu, Z
Journal of diabetes. 2020;(7):488-498
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Abstract
Muscle microvasculature critically regulates skeletal and cardiac muscle health and function. It provides endothelial surface area for substrate exchange between the plasma compartment and the muscle interstitium. Insulin fine-tunes muscle microvascular perfusion to regulate its own action in muscle and oxygen and nutrient supplies to muscle. Specifically, insulin increases muscle microvascular perfusion, which results in increased delivery of insulin to the capillaries that bathe the muscle cells and then facilitate its own transendothelial transport to reach the muscle interstitium. In type 2 diabetes, muscle microvascular responses to insulin are blunted and there is capillary rarefaction. Both loss of capillary density and decreased insulin-mediated capillary recruitment contribute to a decreased endothelial surface area available for substrate exchange. Vasculature expresses abundant glucagon-like peptide 1 (GLP-1) receptors. GLP-1, in addition to its well-characterized glycemic actions, improves endothelial function, increases muscle microvascular perfusion, and stimulates angiogenesis. Importantly, these actions are preserved in the insulin resistant states. Thus, treatment of insulin resistant patients with GLP-1 receptor agonists may improve skeletal and cardiac muscle microvascular perfusion and increase muscle capillarization, leading to improved delivery of oxygen, nutrients, and hormones such as insulin to the myocytes. These actions of GLP-1 impact skeletal and cardiac muscle function and systems biology such as functional exercise capacity. Preclinical studies and clinical trials involving the use of GLP-1 receptor agonists have shown salutary cardiovascular effects and improved cardiovascular outcomes in type 2 diabetes mellitus. Future studies should further examine the different roles of GLP-1 in cardiac as well as skeletal muscle function.
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A Sensitive Plasma Insulin Immunoassay to Establish the Diagnosis of Congenital Hyperinsulinism.
Siersbæk, J, Larsen, AR, Nybo, M, Christesen, HT
Frontiers in endocrinology. 2020;:614993
Abstract
BACKGROUND The diagnosis of congenital hyperinsulinism (CHI) may be hampered by a plasma (p-) insulin detection limit of 12-18 pmol/L (2-3 mU/L). OBJECTIVE To evaluate the diagnostic performance of a sensitive insulin immunoassay and to find the optimal p-insulin cut-off for the diagnosis of CHI. METHODS Diagnostic fasting tests, performed without medication or i.v.-glucose, were investigated in children with a clinical diagnosis of CHI, or idiopathic ketotic hypoglycemia (IKH). The CHI diagnosis was either clinical or by the alternative, p-insulin-free criteria; hypoglycemia plus disease-causing genetic mutations and/or CHI-compatible pancreatic histopathology. We included diagnostic p-insulin samples with simultaneous p-glucose <3.2 mmol/L and used a sensitive insulin assay (Cobas e411 immunoassay analyzer; lower detection limit 1.2 pmol/L; normal range 15.1-147.1 pmol/L). Receiver operating characteristics area under the curve (ROC AUC) values and optimal cut-offs were analyzed for the performance of p-insulin to diagnose CHI. RESULTS In 61 CHI patients, the median (range) p-insulin was 76.5 (17-644) pmol/L compared to 1.5 (1.5-7.7) pmol/L in IKH patients (n=15). The ROC AUC was 1.0 for the diagnosis of CHI defined both by the clinical diagnosis (n=61) and by alternative criteria (n=57). The optimal p-insulin cut-offs were 12.3 pmol/L, and 10.6 pmol/L, at p-glucose <3.2 mmol/L (n=61), and <3.0 mmol/L (n=49), respectively. CONCLUSIONS The sensitive insulin assay performed excellent in diagnosing CHI with optimal p-insulin cut-offs at 12.3 pmol/L (2.0 mU/L), and 10.6 pmol/L (1.8 mU/L), at p-glucose <3.2 mmol/L, and <3.0 mmol/L, respectively. A sensitive insulin assay may serve to simplify the diagnosis of CHI.
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Utilization of anthropometric parameters as a novel tool for detection of insulin resistance.
Chao, YP, Kao, TW, Chang, YW, Peng, TC, Chen, WL, Wu, LW
Clinical nutrition (Edinburgh, Scotland). 2020;(8):2571-2579
Abstract
BACKGROUND Anthropometric parameters have been widely applied in evaluating muscle mass, insulin resistance (IR), and cardiometabolic diseases. Arm circumference (AC) and calf circumference (CC) are used as informative markers for sarcopenia. However, few studies concern the correlation between AC, CC and IR. The aim of the present survey is to investigate the relationship between AC, CC and homeostatic model assessment of insulin resistance (HOMA-IR). METHODS This cross-sectional observational study included 11,527 participants aged 40-85 years from the National Health and Nutrition Examination Survey (NHANES), 1999 to 2006. We divided the participants into male and female groups. Each group was then divided into four subgroups depending on their AC and CC levels. RESULTS After adjustment for multiple covariates, we observed a significant negative correlation between the CC and HOMA-IR. This study showed a significant positive correlation between the AC and HOMA-IR after multiple adjustments. Subjects in the highest CC quartiles tended to have the lowest HOMA-IR in both male and female group (P for trend <0.001 in all models). CONCLUSIONS CC may be a novel tool to guide public health policy and clinical predictor of IR in middle-aged and older people.