Insulin degludec in Japanese patients with type 1 diabetes mellitus: A randomized controlled trial

Introduction

Insulin degludec is an ultra‐long‐acting insulin with a flat time‐action profile and duration of action >42 h. Data from several studies have shown insulin degludec to have a favorable therapeutic profile in type 1 and type 2 diabetes.

Materials and Methods

This was a 6‐week, parallel‐group, randomized controlled trial carried out in 65 Japanese patients with type 1 diabetes, previously treated with mealtime insulin aspart and either insulin glargine or neutral protamine Hagedorn insulin. Patients were randomized to receive either insulin degludec or insulin detemir, each once daily and at the same unit dose as pretrial basal insulin. During the trial, basal insulin was titrated according to a prespecified algorithm in order to achieve a fasting plasma glucose target of 80–109 mg/dL.

Results

No severe hypoglycemia occurred; there was no significant difference in confirmed hypoglycemia rates with insulin degludec and insulin detemir (rate ratio degludec/detemir 0.78; 95% confidence interval 0.45–1.34). The rate of nocturnal confirmed hypoglycemia was 69% lower with insulin degludec than with insulin detemir (rate ratio 0.31; 95% confidence interval 0.13–0.78). Final fasting plasma glucose levels were similar (insulin degludec 147 mg/dL, insulin detemir 136 mg/dL), despite differing baseline fasting plasma glucose levels.

Conclusions

In conclusion, no concerns relating to hypoglycemia or general safety were observed when initiating insulin degludec in Japanese patients with type 1 diabetes at the same unit dose as previous basal insulin. This trial was registered with ClinicalTrials.gov (no. NCT00841087).     

The effect of home-based resistance exercise training in people with type 2 diabetes: A randomized controlled trial

Aims

To evaluate the effects of pragmatic home-based resistance exercise training on glycated haemoglobin (HbA1c) as well as muscle strength and body composition in people with type 2 diabetes.

Materials and Methods

People with type 2 diabetes were randomized (1:1) to usual care or usual care plus home-based resistance exercise for 32 weeks. The changes in HbA1c, body composition, physical function, quality of life, continuous glucose monitoring and liver fat were compared by randomized group using linear regression.

Results

This study recruited 120 participants (female: n = 46 [38%], age 60.2 (9.4) years, BMI 31.1 (5.4) kg.m⁻²), 64 to intervention and 56 to usual care. Intention to treat analysis revealed no effect on HbA1c (difference in difference: −0.4 mmol/mol, 95% confidence interval [CI]: −3.26, 2.47; p = 0.78) but the intervention increased the number of push-ups (3.6 push-ups, 95% CI: 0.8, 6.4), arm lean mass (116 g, 95% CI: 6, 227) and leg lean mass (438 g, 95% CI 65, 810) and decreased liver fat (−1.27%, 95% CI -2.17, −0.38), with no differences in other outcomes. Per-protocol analysis revealed similar results.

Conclusions

Home-based resistance exercise is unlikely to lower HbA1c in people with type 2 diabetes but may be of benefit for maintaining muscle mass and function and reducing liver fat.     

Effects of resveratrol therapy on glucose metabolism,insulin resistance,inflammation, and renal function in the elderly patients with type 2 diabetes mellitus: A randomized controlled clinical trial protocol

Background:Diabetes mellitus is a spectrum of metabolic disorders characterized by hyperglycemia and shows a growing global public health problem in the elderly. Resveratrol presents antiaging, anti-inflammatory, antitumor antioxidant, and cardioprotective activities. The purpose of this study was to investigate the ameliorative effects of resveratrol on blood glucose, insulin metabolism, lipid profile, renal function, inflammation, and nutrient sensing systems in the elderly patients with type 2 diabetes mellitus.Methods:The study is a single-blind, parallel-group, randomized controlled clinical trial consisting of a 6-month treatment period. A total of 472 elderly patients with type 2 diabetes mellitus were enrolled, and included participants will be randomized into 2 groups: resveratrol (n = 242) and placebo (n = 230). The clinical efficacy and changes in clinical parameters in each group will be measured at the indicated time. Clinical parameters included blood glucose, insulin resistance index, blood lipid index, proinflammatory cytokines, renal function, and nutrient sensing systems.Results:Resveratrol treatment greatly improved glucose metabolism, insulin tolerance, and insulin metabolism compared to placebo. Resveratrol relieved symptoms through enhancing nutrient sensing systems, which in turn reduced production and activity of glucose-6-phosphatase. Compared with placebo, resveratrol treatment significantly decreased proinflammatory cytokines glycated hemoglobin/hemoglobin A1c, interleukin-6, tumor necrosis factor-alpha, and interleukin-1beta in the elderly diabetes. Resveratrol treatment decreased blood glucose parameters, improved the lipid profile (total cholesterol, low-density lipoprotein, high-density lipoprotein, and triglycerides), and renal function compared to placebo.Conclusion:In conclusion, resveratrol treatment improves inflammation, renal function, blood glucose parameters, inflammation, insulin resistance, and nutrient sensing systems in the elderly patients with type 2 diabetes mellitus, indicating resveratrol may be a potential therapeutic drug for the treatment of the elderly patients with type 2 diabetes mellitus.     

妊娠早期糖脂代谢对妊娠糖尿病发病及不良妊娠结局的影响

目的探讨妊娠早期糖脂代谢与妊娠糖尿病（GDM）发生的关系以及对妊娠结局的影响。方法回顾性分析2000年7月至2009年12月在解放军第三。六医院妇产科分娩的3923名初产孕妇的早孕空腹血糖、血脂、超敏c反应蛋白（sCRP）、尿酸（uA）对妊娠24—32周口服葡萄糖耐量试验（OGTT）血糖结果和妊娠结局的影响。将所有人组孕妇按WHO及国际糖尿病与妊娠研究组诊断标准分为GDM组与糖耐量正常组,比较GDM组与糖耐量正常组妊娠早期空腹血糖、血脂、sCRP和uA的差异,根据妊娠结局将所有孕妇分为妊娠高血压综合征组、先兆子痫／子痫组、剖宫产组、巨大儿组、低出生体重儿组、新生儿窒息组、GDM组,比较妊娠早期代谢指标与妊娠结局关系,采用Pearson相关分析及logistie回归分析探讨妊娠早期空腹血糖、血脂、sCRP和UA对GDM发生及不良妊娠结局的影响。结果GDM组早期空腹血糖[（4．4±0．6）VS（4．2±0．4）mmol／L,t=-6．91,P〈0．05]、甘油三酯（TG）[（1．9±0．7）VS（1．7±0．8）mmol／L,t=-3．30,P〈0．05]及sCRP[（2．4±1．6）VS（2．1±1．7）mg／L,t=-2．65,P〈0．05]高于糖耐量正常组。妊娠早期空腹血糖、TG及sCRP与OGTT0、60、120min血糖水平均呈显著正相关（空腹血糖：r值分别为0．43、0．17、0．20;TG：r值分别为0．12、0．07、0．11;sCRP：r值分别为0．07、0．08、0．08;均P〈0．05）,妊娠早期空腹血糖与新生儿出生后1、5、10rain阿氏评分均呈显著负相关（r值分别为-0．121、-0．096、-0．076,均P〈0．05）。随着妊娠早期空腹血糖、TG及sCRP的升高,剖宫产率也增加。校正年龄后,妊娠早期血糖、TG及sCRP水平升高导致GDM以及不良妊娠结局的OR（95％CI）值分别为：GDM组2．07（1．59～2．69,P〈0．05）、1．25（1．07～1．46,P〈0．05）、1．09（1．02～1．16,P〈0．05）;新生儿窒息组为2．13（1．43～3．16,P〈0．05）、0．73（0．45～1．18,P〉0．05）、1．01（0．87—1．19,P〉0．05）;巨大儿组（〉4000g）为1．45（1．09—1．92,P〈0．05）、1．18（0．97—1．44,P〉0．05）、1．06（0．98～1．14,P〉0．05）;低体重出生儿组（〈2500g）为0．97（0．62～1．52,P〉0．05）、1．35（1．06—1．70,P〈0．05）、0．97（0．83—1．13,P〉0．05）。结论GDM患者妊娠早期糖脂代谢指标虽仍处于正常范围,却显著高于糖耐量正常孕妇。妊娠早期空腹血糖、TG及sCRP水平上升,可能增加GDM的发生及妊娠不良结局的风险。     

Effect of device-guided breathing exercises on blood pressure in hypertensive patients with type 2 diabetes mellitus: a randomized controlled trial

OBJECTIVE: In patients with type 2 diabetes mellitus (DM2), it is hard to reach treatment objectives for blood pressure (BP) with classical treatment options. Recently, reducing breathing frequency has been advocated as a method to reduce BP. We examined if an electronic device such as Resperate, by reducing breathing frequency, would lead to BP reduction in a population of patients with DM2 and hypertension. Our secondary objective was to study the effect of this device on quality of life (QOL). METHODS: A randomized, single-blind, controlled trial was conducted over a period of 8 weeks to evaluate the effect of this therapy on BP and QOL. The control group listened to music and used no other therapeutic device. BP and QOL changes were studied in 30 patients with DM2 and hypertension. RESULTS: There was no significant difference in change in BP between groups; -7.5 [95% confidence interval (CI) -12.7, -2.3]/-1.0 (95% CI -5.5, 3.6) mmHg in the intervention group and -12.2 (95% CI -17.4, -7.0)/-5.5 (95% CI -9.7, -1.4) mmHg in the control group. Whether or not the target breathing frequency of 10 breaths/min was reached did not affect BP. There were no significant changes in QOL. CONCLUSIONS: The effects of Resperate on BP and QOL were not significantly different from those found in the control group. Furthermore, 40% of patients did not reach the target breathing frequency, making this device less suitable for clinical practice in patients with DM2.     

Effects of flash glucose monitoring on glycemic control in participants with diabetes mellitus: A meta-analysis of randomized controlled trials

BackgroundWith the introduction of flash glucose monitoring (FGM) into the international market in 2014, academics worldwide are exploring whether this device improves glycemic control in participants with diabetes mellitus.ObjectiveA study was conducted in which participants were evaluated to determine the effect of FGM on glycemic control.MethodsFrom inception to April 9, 2022, we searched the Cochrane Library, PubMed, SinoMed, Embase, Web of Science, MEDLINE, CNKI, Wan Fang Data, and VIP databases to collect randomized controlled trials (RCTs) related to the effect of FGM on glycemic control in participants with diabetes mellitus. Outcomes included glycated hemoglobin, the occurrence of hypoglycemic events, fasting plasma glucose (FPG), and 2-h postprandial glucose (2hPG) levels. The statistical analysis was performed using R 4.1.3 software.ResultsWe included 19 studies involving 2013 participants, all of which were RCTs. Meta-analysis results revealed that compared to self-monitoring of blood glucose (SMBG), FGM significantly reduced glycated hemoglobin levels in participants with type 2 diabetes mellitus [mean difference = ?0.74 [95 % CI-1.16, ?0.32], P < 0.01] and type 1 diabetes mellitus combined with type 2 diabetes mellitus [mean difference = ?1.14 [95 % CI-3.14, 0.87], P < 0.01], with a greater effect in participants aged ≤65 years with type 2 diabetes mellitus (mean difference = ?1.38 [95 % CI-2.05, ?0.72], P < 0.01). However, there was no effect of FGM on the improvement of glycated hemoglobin levels in patients with type 1 diabetes mellitus [P = 0.45]. Furthermore, fasting plasma glucose levels and 2-h postprandial glucose levels were significantly lower in FGM than SMBG, and the number of hypoglycemic events was also significantly lower.ConclusionComparing SMBG with FGM indicated that FGM improves fasting plasma glucose levels, 2-h postprandial glucose levels, and glycated hemoglobin levels, and it reduces the number of hypoglycemic events.     

A resistance exercise program improves functional capacity of patients with psoriatic arthritis: a randomized controlled trial

The objective of this study is to assess the effectiveness of resistance training in patients with psoriatic arthritis (PsA). The study is a randomized controlled trial with 41 patients aged between 18 and 65 years with diagnosis of psoriatic arthritis (PsA). The patients were randomized into the following: intervention group (IG) and control group (CG). The IG underwent resistance exercise twice a week, for 12 weeks. The CG remained with the conventional drug therapy. The outcome measurements were the following: BASFI and HAQ-S for functional capacity, one maximum repetition test (1RM) for muscle strength, SF-36 questionnaire for general quality of life, and BASDAI and DAS-28 for disease activity. The evaluations were done by a blinded evaluator at baseline (T0) after 6 (T6) and 12 weeks (T12). At baseline, the groups were homogeneous regarding clinical and demographic characteristics. The IG significantly improved functional capacity measured by HAQ-S and disease activity measured by BASDAI, compared to CG, at week 12. Regarding quality of life, the IG improved the domains “pain” and “general health status” compared to CG (p?<?0.05). There was improvement in muscular strength in almost all exercises in IG, except in the exercise for biceps. However, there were statistical differences between groups only on exercise “leg extension” in IG compared to CG. Resistance training is effective in improving functional capacity, disease activity, and quality of life of patients with psoriatic arthritis. The clinical improvements were not coupled to significant changes in muscular strength.     

Effects of moderate-intensity exercise on physiological, behavioral, and emotional responses to family caregiving: a randomized controlled trial.

BACKGROUND: The study objective was to determine the health and quality-of-life effects of moderate-intensity exercise among older women family caregivers. METHODS: This 12-month randomized controlled trial involved a volunteer sample of 100 women aged 49 to 82 years who were sedentary, free of cardiovascular disease, and caring for a relative with dementia. Participants were randomized to 12 months of home-based, telephone-supervised, moderate-intensity exercise training or to an attention-control (nutrition education) program. Exercise consisted of four 30- to 40-minute endurance exercise sessions (brisk walking) prescribed per week at 60% to 75% of heart rate reserve based on peak treadmill exercise heart rate. Main outcomes were stress-induced cardiovascular reactivity levels, rated sleep quality, and reported psychological distress. RESULTS: Compared with nutrition participants (NU), exercise participants (EX) showed significant improvements in the following: total energy expenditure (baseline and post-test means [SD] for EX = 1.4 [1.9] and 2.2 [2.2] kcal/kg/day; for NU = 1.2 [1.7] and 1.2 [1.6] kcal/kg/day; p <.02); stress-induced blood pressure reactivity (baseline and post-test systolic blood pressure reactivity values for EX = 21.6 [12.3] and 12.4 [11.2] mm Hg; for NU = 17.9 [10.2] and 17.7 [13.8] mm Hg; p <.024); and sleep quality (p <.05). NU showed significant improvements in percentages of total calories from fats and saturated fats relative to EX (p values <.01). Both groups reported improvements in psychological distress. Conclusions. Family caregivers can benefit from initiating a regular moderate-intensity exercise program in terms of reductions in stress-induced cardiovascular reactivity and improvements in rated sleep quality.     

Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus

We have determined prehepatic insulin secretion rates (ISRs) in seven patients with gestational diabetes mellitus (GDM) and in eight age- and weight-matched nondiabetic pregnant women during late gestation (third trimester) and again postpartum. Plasma glucose concentrations were raised to approximately 8.9 mM with iv glucose (hyperglycemic clamping), and ISRs were determined by deconvolution of peripheral C-peptide concentrations using C-peptide kinetic parameters that were obtained in every patient during late gestation and again postpartum. Plasma insulin levels were measured by RIA with an antibody with minimal (<0.2%) cross-reactivity with proinsulin. During late gestation, women with GDM were more insulin resistant than nondiabetic controls and had significantly lower ISRs (689 vs. 849 pmol/min, P < 0.05) and glucose uptake rates (30.6 vs. 49.4 micromol/kg.min, P < 0.05) in response to hyperglycemia. Postpartum, ISRs and insulin resistance decreased in women with GDM and controls (ISR by 43% and 43%, respectively, and insulin resistance by 75% and 118%, respectively), and both groups had similar ISRs (352 vs. 408 pmol/min, nonsignificant). Women with GDM, however, continued to be more insulin resistant than controls. In summary, patients with GDM during late pregnancy not only had severe deficiencies in ISR but, in addition, were more insulin resistant than controls. Postpartum, insulin resistance and ISRs (and plasma insulin levels) improved in both groups, and ISRs (and plasma insulin levels) were no longer significantly different in patients with GDM and controls. Insulin resistance, however, remained higher in women with GDM, and their glucose uptake remained lower. We concluded that the women with GDM had a major ss-cell defect that made it impossible for them to compensate for their increased level of insulin resistance, which occurred during late pregnancy.     

Effects of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in patients with type 2 diabetes mellitus: a randomised controlled trial

Aims/hypothesis

The aim of the present study was to investigate the effect of blood pressure lowering and intensive glucose control on the incidence and progression of retinopathy in type 2 diabetic patients.

Methods

The Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) Retinal Measurements study, a substudy of ADVANCE, is a randomised (using a central, computer-based procedure) controlled 2?×?2 factorial trial comprising a double-blind comparison of blood pressure lowering with perindopril–indapamide vs placebo, and an open comparison of standard vs intensive glucose control targeting a HbA_1c of?≤?6.5% in 1,602 diabetic patients from ADVANCE centres with access to retinal cameras conducted from 2001 to 2008. At baseline and the final visit, seven-field stereoscopic retinal photographs were taken and graded by blinded readers (gradeable baseline and final photographs from 1,241 patients). Progression of ≥2 steps in the Early Treatment of Diabetic Retinopathy Study classification (using the eye with worst grading) was the primary outcome.

Results

Retinopathy progressed in 59 (4.8%) patients and developed in 128 (10.3%) patients over 4.1 years. Fewer patients on blood pressure-lowering treatment (n?=?623) experienced incidence or progression of retinopathy compared with patients on placebo (n?=?618), but the difference was not significant (OR 0.78; 95% CI 0.57–1.06; p?=?0.12). Blood pressure-lowering treatment reduced the occurrence of macular oedema (OR 0.50; 95% CI 0.29–0.88; p?=?0.016) and arteriovenous nicking compared with placebo (OR 0.60; 95% CI 0.38–0.94; p?=?0.025). Compared with standard glucose control (n?=?611), intensive glucose control (n?=?630) did not reduce (p?=?0.27) the incidence and progression of retinopathy (OR 0.84; 95% CI 0.61–1.15). Lower, borderline significant risks of microaneurysms, hard exudates and macular oedema were observed with intensive glucose control, adjusted for baseline retinal haemorrhages. These effects of the two treatments were independent and additive. Adverse events in the ADVANCE study are reported elsewhere.

Conclusions/interpretation

Blood pressure lowering or intensive glucose control did not significantly reduce the incidence and progression of retinopathy, although consistent trends towards a benefit were observed, with significant reductions in some lesions observed with both interventions.

Trial registration:

ClinicalTrials.gov ID no. NCT00145925.

Funding:

Grants from Servier and the National Health and Medical Research Council of Australia     

The blood glucose lowering effects of exercise and glibenclamide in patients with Type 2 diabetes mellitus

Physical exercise is associated with a fall in serum insulin levels, whereas sulphonylurea administration increases insulin release. To date, the opposing effects of exercise and sulphonylurea administration have not been systematically studied in Type 2 diabetic patients, who are not infrequently treated with sulphonylureas. In this study nine patients with Type 2 diabetes mellitus were subjected to four treatments in random order on separate days: (A) endurance exercise after the administration of 3.5 mg glibenclamide; (B) as A but given only 1.75 mg glibenclamide; (C) as A but with placebo; (D) rest and administration of 1.75 mg glibenclamide. Exercise and placebo resulted in only a small decrease in glycaemia. Rest and administration of 1.75 mg glibenclamide led to a moderate but steady fall in blood glucose concentrations. If glibenclamide administration and exercise were combined, blood glucose concentrations declined more markedly. Serum insulin concentrations showed a physiological decrease during exercise and placebo administration. If patients rested after administration of glibenclamide serum insulin levels rose and remained elevated. When exercise and glibenclamide were combined the rise in serum insulin levels was blunted and insulin levels fell once exercise was begun. Thus, exercise attenuates the glibenclamide induced increase in serum insulin in moderately hyperglycaemic Type 2 diabetic patients. Nevertheless, exercise has a substantial hypoglycaemic effect in glibenclamide treated Type 2 diabetic patients. © 1998 John Wiley & Sons, Ltd.