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Retinal oxygen saturation is associated with HbA1c but not with short-term diabetes control, internal environment, smoking and mild retinopathy - ROXINEGLYD study.
Mlčák, P, Chlup, R, Kudlová, P, Krystyník, O, Král, M, Kučerová, V, Spurná, J, Titzová, S, Hübnerová, P, Vláčil, O, et al
Acta ophthalmologica. 2022;(1):e142-e149
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Abstract
PURPOSE Purpose of this prospective uncontrolled single-centre pilot study was to find an association of retinal oxygen saturation (SatO2 ) with acid-base balance (ABB), carboxyhaemoglobin concentration, current plasma glucose concentration (PG), mean PG and PG variability over the last 72 hr, haemoglobin A1c (HbA1c), and other conditions. METHODS Forty-one adults (17 men) with type 1 (N = 14) or type 2 (N = 27) diabetes mellitus, age 48.6 ± 13.5 years, diabetes duration 9 (0.1-36) years, BMI 29.4 ± 6.3 kg/m2 , and HbA1c 52 ± 12.7 mmol/mol completed the study. The 4-day study comprised two visits (Day l, Day 4) including 72 hr of continuous glucose monitoring (CGM) by iPro® 2 Professional CGM (Medtronic, MiniMed, Inc., Northridge, CA, USA). Retinal oximeter Oxymap T1 (Oxymap ehf., Reykjavik, Iceland) was used to assess SatO2 . RESULTS Wilcoxon signed-rank test showed no SatO2 difference between eyes and visits. Spearman's correlation analysis revealed a significant correlation between arterial SatO2 and PG variability in type 2 diabetes mellitus, a positive correlation of venous SatO2 with HbA1c and with finger pulse oximetry. However, no correlation of SatO2 with ABB, carboxyhaemoglobin, current PG, mean PG over the 72 hr, age, diabetes duration, BMI, lipoproteinaemia, body temperature, systolic and diastolic blood pressure, heart rate, central retinal thickness and retinal nerve fibre layer thickness was found. CONCLUSION This study confirmed the association of venous SatO2 with long-term but not with short-term diabetes control, ABB and other conditions. The increased SatO2 and questionable impact of PG variability on retinal SatO2 is a research challenge.
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Understanding inhaled Technosphere Insulin: Results of an early randomized trial in type 1 diabetes mellitus.
McGill, JB, Weiss, D, Grant, M, Jones, MC, Kendall, DM, Hoogwerf, BJ
Journal of diabetes. 2021;(2):164-172
Abstract
BACKGROUND Technosphere Insulin (TI) is an inhaled insulin. Studies comparing TI with short-acting insulin analogues provide important insights on efficacy, dosing, and time course of action. METHODS Planned enrollment of 230 subjects was limited to 138 due to premature study discontinuation. The primary efficacy endpoint was a noninferiority of glycosylated hemoglobin (HbA1c) of 0.4% for TI compared with insulin lispro (LIS) in a 16-week phase 3 randomized clinical trial in type 1 diabetes mellitus. RESULTS HbA1c values were similar in the TI and LIS groups at the beginning of the trial (7.8% and 7.6%, respectively) and at trial endpoint (7.7% and 7.6%, respectively). Least squares mean changes from baseline were similar between study groups. Glucose values after a standard meal were significantly lower with TI in the first 90 minutes post meal compared with LIS. Mild or moderate hypoglycemia event rates were also significantly lower with TI compared with LIS (5.97 vs 8.01, respectively; P = .0269). Cough was the most commonly reported adverse event with TI. Pulmonary function as measured by forced expiratory volume in 1 second was not different between groups at baseline, 16 weeks, or 4 weeks off study drug. CONCLUSIONS HbA1c was unchanged and overall glucose control was comparable between groups. Treatment with TI resulted in improved post-meal glucose and a lower risk of hypoglycemia compared with LIS.
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Improved HbA1c and reduced glycaemic variability after 1-year intermittent use of flash glucose monitoring.
Zhang, W, Liu, Y, Sun, B, Shen, Y, Li, M, Peng, L, Duan, H, Su, X, Lu, S, Tian, X, et al
Scientific reports. 2021;(1):23950
Abstract
Flash glucose monitoring (FGM) was introduced in China in 2016, and it might improve HbA1c measurements and reduce glycaemic variability during T1DM therapy. A total of 146 patients were recruited from October 2018 to September 2019 in Liaocheng. The patients were randomly divided into the FGM group or self-monitoring blood glucose (SMBG) group. Both groups wore the FGM device for multiple 2-week periods, beginning with the 1st, 24th, and 48th weeks for gathering data, while blood samples were also collected for HbA1c measurement. Dietary guidance and insulin dose adjustments were provided to the FGM group patients according to their Ambulatory Glucose Profile (AGP) and to the SMBG group patients according to their SMBG measurements taken 3-4 times daily. All of the participants underwent SMBG measurements on the days when not wearing the FGM device. At the final visit, HbA1c, time in range (TIR), duration of hypoglycaemia and the number of diabetic ketoacidosis (DKA) events were taken as the main endpoints. There were no significant difference in the baseline characteristics of the two groups. At 24 weeks, the HbA1c level of the FGM group was 8.16 ± 1.03%, which was much lower than that of the SMBG group (8.68 ± 1.01%) (p = 0.003). The interquartile range (IQR), mean blood glucose (MBG), and the duration of hypoglycaemia in the FGM group also showed significant declines, compared with the SMBG group (p < 0.05), while the TIR increased in the FGM group [(49.39 ± 17.54)% vs (42.44 ± 15.49)%] (p = 0.012). At 48 weeks, the differences were more pronounced (p < 0.01). There were no observed changes in the number of episodes of DKA by the end of the study [(0.25 ± 0.50) vs (0.28 ± 0.51), p = 0.75]. Intermittent use of FGM by T1DM patients can improve their HbA1c and glycaemic control without increasing the hypoglycaemic exposure in insulin-treated individuals with type 1 diabetes in an developing country.
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Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome.
Kaur, V, Dimitriadis, GK, Pérez-Pevida, B, Bansi, DS, Jayasena, C, Bate, D, Houghton, R, Fielding, BA, Balfoussia, D, Webber, L, et al
Metabolism: clinical and experimental. 2021;:154908
Abstract
BACKGROUND Duodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans. METHODS Thirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention. RESULTS A small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion. CONCLUSIONS These findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.
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Insulin Secretion Predicts the Response to Antidiabetic Therapy in Patients With New-onset Diabetes.
Abdelgani, S, Puckett, C, Adams, J, Triplitt, C, DeFronzo, RA, Abdul-Ghani, M
The Journal of clinical endocrinology and metabolism. 2021;(12):3497-3504
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CONTEXT The results of the present study demonstrate that beta cell function in newly diagnosed T2DM patients is the key predictor of response to glucose lowering medications and provides a practical tool (C-Pep120 /C-Pep0) to guide the choice of glucose lowering agent. OBJECTIVE This work aims to identify predictors for individualization of antidiabetic therapy in patients with new-onset type 2 diabetes mellitus (T2DM). METHODS A total of 261 drug-naive participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study, with new-onset diabetes, were randomly assigned in a single-center study to receive 1) metformin followed by glipizide and then insulin glargine on failure to achieve glycated hemoglobin A1c (HbA1c) less than 6.5%, or 2) initial triple therapy with metformin/pioglitazone/exenatide. Each patient received a 75-g oral glucose tolerance test (OGTT) prior to start of therapy. Factors that predicted response to therapy were identified using the area under the receiver operating characteristic curve method. RESULTS Thirty-nine patients started and maintained the treatment goal (HbA1c < 6.5%) on metformin only, and did not require intensification of antihyperglycemic therapy; 54 patients required addition of glipizide to metformin; and 47 patients required insulin addition to metformin plus glipizide for glucose control. The plasma C-peptide concentration (C-Pep)120/C-Pep0 ratio during the OGTT was the strongest predictor of response to therapy. Patients with a ratio less than 1.78 were more likely to require insulin for glucose control, whereas patients with a ratio greater than 2.65 were more likely to achieve glucose control with metformin monotherapy. In patients started on initial triple therapy, the HbA1c decreased independently of the C-Pep120/C-Pep0 ratio. CONCLUSION The increase in C-Pep above fasting following glucose load predicts the response to antihyperglycemic therapy in patients with new-onset diabetes. C-Pep120/C-Pep0 provides a useful tool for the individualization of antihyperglycemic therapy in patients with new-onset T2DM.
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Effects of canagliflozin compared with placebo on major adverse cardiovascular and kidney events in patient groups with different baseline levels of HbA1c, disease duration and treatment intensity: results from the CANVAS Program.
Young, TK, Li, JW, Kang, A, Heerspink, HJL, Hockham, C, Arnott, C, Neuen, BL, Zoungas, S, Mahaffey, KW, Perkovic, V, et al
Diabetologia. 2021;(11):2402-2414
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AIMS/HYPOTHESIS Type 2 diabetes mellitus can manifest over a broad clinical range, although there is no clear consensus on the categorisation of disease complexity. We assessed the effects of canagliflozin, compared with placebo, on cardiovascular and kidney outcomes in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program over a range of type 2 diabetes mellitus complexity, defined separately by baseline intensity of treatment, duration of diabetes and glycaemic control. METHODS We performed a post hoc analysis of the effects of canagliflozin on major adverse cardiovascular events (MACE) according to baseline glucose-lowering treatments (0 or 1, 2 or 3+ non-insulin glucose-lowering treatments, or insulin-based treatment), duration of diabetes (<10, 10 to 16, >16 years) and HbA1c (≤53.0 mmol/mol [<7.0%], >53.0 to 58.5 mmol/mol [>7.0% to 7.5%], >58.5 to 63.9 mmol/mol [>7.5 to 8.0%], >63.9 to 69.4 mmol/mol [8.0% to 8.5%], >69.4 to 74.9 mmol/mol [>8.5 to 9.0%] or >74.9 mmol/mol [>9.0%]). We analysed additional secondary endpoints for cardiovascular and kidney outcomes, including a combined kidney outcome of sustained 40% decline in eGFR, end-stage kidney disease or death due to kidney disease. We used Cox regression analyses and compared the constancy of HRs across subgroups by fitting an interaction term (p value for significance <0.05). RESULTS At study initiation, 5095 (50%) CANVAS Program participants were treated with insulin, 2100 (21%) had an HbA1c > 74.9 mmol/mol (9.0%) and the median duration of diabetes was 12.6 years (interquartile interval 8.0-18 years). Canagliflozin reduced MACE (HR 0.86 [95% CI 0.75, 0.97]) with no evidence that the benefit differed between subgroups defined by the number of glucose-lowering treatments, the duration of diabetes or baseline HbA1c (all p-heterogeneity >0.17). Canagliflozin reduced MACE in participants receiving insulin with no evidence that the benefit differed from other participants in the trial (HR 0.85 [95% CI 0.72, 1.00]). Similar results were observed for other cardiovascular outcomes and for the combined kidney outcome (HR for combined kidney outcome 0.60 [95% CI 0.47, 0.77]), with all p-heterogeneity >0.37. CONCLUSIONS/INTERPRETATION In people with type 2 diabetes mellitus at high cardiovascular risk, there was no evidence that cardiovascular and renal protection with canagliflozin differed across subgroups defined by baseline treatment intensity, duration of diabetes or HbA1c.
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Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus: The SIMPLE Trial.
Jürgens, M, Schou, M, Hasbak, P, Kjær, A, Wolsk, E, Zerahn, B, Wiberg, M, Brandt-Jacobsen, NH, Gæde, P, Rossing, P, et al
Journal of the American Heart Association. 2021;(15):e020418
Abstract
Background Sodium-glucose cotransporter 2 inhibitors reduce hospitalizations for heart failure and cardiovascular death, although the underlying mechanisms have not been resolved. The SIMPLE trial (The Effects of Empagliflozin on Myocardial Flow Reserve in Patients With Type 2 Diabetes Mellitus) investigated the effects of empagliflozin on myocardial flow reserve (MFR) reflecting microvascular perfusion, in patients with type 2 diabetes mellitus at high cardiovascular disease risk. Methods and Results We randomized 90 patients to either empagliflozin 25 mg once daily or placebo for 13 weeks, as add-on to standard therapy. The primary outcome was change in MFR at week 13, quantified by Rubidium-82 positron emission tomography/computed tomography. The secondary key outcomes were changes in resting rate-pressure product adjusted MFR, changes to myocardial flow during rest and stress, and reversible cardiac ischemia. Mean baseline MFR was 2.21 (95% CI, 2.08-2.35). There was no change from baseline in MFR at week 13 in either the empagliflozin: 0.01 (95% CI, -0.18 to 0.21) or placebo groups: 0.06 (95% CI, -0.15 to 0.27), with no treatment effect -0.05 (95% CI, -0.33 to 0.23). No effects on the secondary outcome parameters by Rubidium-82 positron emission tomography/computed tomography was observed. Treatment with empagliflozin reduced hemoglobin A1c by 0.76% (95% CI, 1.0-0.5; P<0.001) and increased hematocrit by 1.69% (95% CI, 0.7-2.6; P<0.001). Conclusions Empagliflozin did not improve MFR among patients with type 2 diabetes mellitus and high cardiovascular disease risk. The present study does not support that short-term improvement in MFR explains the reduction in cardiovascular events observed in the outcome trials. Registration URL: https://clinicaltrialsregister.eu/; Unique identifier: 2016-003743-10.
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Insulin resistance in type 1 diabetes managed with metformin (INTIMET): Study protocol of a double-blind placebo-controlled, randomised trial.
Snaith, JR, Samocha-Bonet, D, Evans, J, Liu, Z, Kowalski, G, Bruce, C, Holmes-Walker, DJ, Greenfield, JR
Diabetic medicine : a journal of the British Diabetic Association. 2021;(9):e14564
Abstract
BACKGROUND Insulin resistance is an under-recognised metabolic defect and cardiovascular risk factor in Type 1 diabetes. Whether metformin improves hepatic, muscle or adipose tissue insulin sensitivity has not been studied in adults with Type 1 diabetes. We initiated the INTIMET study (INsulin resistance in Type 1 diabetes managed with METformin), a double-blind randomised, placebo-controlled trial to measure the effect of metformin on tissue-specific insulin resistance in adults with Type 1 diabetes. METHODS We will study 40 adults aged 20-55 years with Type 1 diabetes (HbA1c ≤ 80 mmol/mol [9.5%], fasting C-peptide <0.3 nmol/L) and 20 age-, gender- and body mass index (BMI)-matched controls. Insulin sensitivity will be determined by the two-step hyperinsulinaemic-euglycaemic clamp method with deuterated glucose to document liver, muscle and adipose insulin sensitivity. Subjects with Type 1 diabetes will be randomised to metformin extended-release 1500 mg daily or matched placebo for 26 weeks. The primary outcome is change in hepatic insulin sensitivity, assessed by change in basal rate of appearance (Ra) of glucose and suppression of endogenous glucose production (EGP) during the low-dose stage of the clamp. CONCLUSION The INTIMET study is the first clinical trial to quantify the impact of metformin on liver, muscle and adipose insulin resistance in adults with Type 1 diabetes. This study may identify factors that predict an individual's response to metformin in Type 1 diabetes. TRIAL REGISTRATION ACTRN12619001440112.
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Relaxation training significantly reduced blood glucose levels in patients with type 1 diabetes mellitus.
Paschali, AA, Peppou, LΕ, Benroubi, M
Hormones (Athens, Greece). 2020;(2):215-222
Abstract
PURPOSE/OBJECTIVE The present study was designed to test whether adding a relaxation training technique to the medical treatment of patients with type 1 diabetes mellitus could, adjusting for the non-specific factors of therapy, lead to an improvement in the patients' condition. METHOD Forty-six participants were randomly allocated either to an experimental (intervention) group, receiving weekly sessions of relaxation training, or to a control group (placebo) receiving weekly blood circulation training exercises. Measures included the State and Trait Anxiety Inventory, blood glucose levels, high-density lipoprotein levels, cholesterol levels, body weight, HbA1c levels, the Mood Adjective Checklist (MACL), a diary checklist, and urine glucose levels. Assessment of psychological and physiological parameters was conducted before and upon completion of the intervention (8 weeks). RESULTS Trait anxiety and the main metabolic measurement of blood glucose levels and HbA1C revealed significant differences over time, predominantly among patients in the intervention group. CONCLUSIONS Relaxation techniques as an adjunct to medical treatment are a useful tool for patients with type 1 diabetes mellitus.
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Effect of a Moderate Carbohydrate-Restricted Diet on DPP-4 Inhibitor Action among Individuals with Type 2 Diabetes Mellitus: A 6-Month Intervention Study.
Kobayashi, M, Miura, T, Miura, K, Hiroyama, N, Akashi, K
Journal of nutritional science and vitaminology. 2020;(2):114-118
Abstract
To decrease body weight and insulin resistance, a calorie-restricted diet-with minimal caloric intake required for daily activities-is the primary treatment strategy for patients with type 2 diabetes (T2D) in Japan. However, many patients cannot continue with this diet for long, because calorie restriction is difficult and nutritional balance is hard to understand. Carbohydrate-restricted diets are easier for patients than conventional calorie-restricted diet. In this study we aimed to elucidate the effects of a moderate carbohydrate-restricted diet on glucose metabolism and renal function in patients with T2D on dipeptidyl peptidase-4 (DPP-4) inhibitors. Nineteen outpatients with T2D continued on a moderate carbohydrate-restricted diet (targeting 50% of calories) for 6 mo. Meanwhile, 10 other outpatients with T2D on DPP-4 inhibitors had the conventional calorie-restricted diet using the food exchange table. No change in prescription drugs occurred for both groups during the study period. After the intervention, the carbohydrate content in dietary intake was lowered significantly from 56.8±8.3 to 46.8±10.1%, while the lipid concentration, primarily n-6 polyunsaturated fatty acids, was significantly increased. There was no significant change in protein intake. Hemoglobin A1c (HbA1c) fell from 7.22±0.74% to 6.95±0.72% (mean±SD). Furthermore, salt intake decreased significantly from 6.8±2.5 g prior to the intervention, to 5.7±1.9 g after the intervention. The estimated glomerular filtration rates (eGFR) decreased slightly, while serum creatinine levels did not change. These findings suggest that a moderate carbohydrate-restricted diet (50%) is effective in patients with T2D, without affecting kidney function.