MARRIAGE: A Randomized Trial of Moxonidine Versus Ramipril or in Combination With Ramipril in Overweight Patients With Hypertension and Impaired Fasting Glucose or Diabetes Mellitus. Impact on Blood Pressure, Heart Rate and Metabolic Parameters.

BACKGROUND: Moxonidine, an imidazoline I1 receptor agonist, is an effective antihypertensive drug that was shown to improve insulin sensitivity. RAAS-blockers are recommended as first-line therapy in patients with diabetes, alone or in combination with a calcium-channel antagonist or a diuretic. AIMS: This study compared the effects of moxonidine and ramipril on blood pressure (BP) and glucose metabolism in overweight patients with mild-to-moderate hypertension and impaired fasting glucose or type 2 diabetes. METHODS: Treatment-naïve patients for hypertension and dysglycemia were randomized to 12 weeks of double-blind moxonidine 0.4 mg or ramipril 5 mg once-daily treatment. At 12 weeks, for a further 12 weeks non-responders received combination of mox/ram, while responders continued blinded treatment. RESULTS: Moxonidine and ramipril were equivalent in lowering SiDBP and SiSBP at the end of the first 12 weeks. The responder rate was approximately 50% in both groups, with a mean SiDBP and SiSBP decrease of 10 and 15 mm Hg in the responders, respectively. The normalization rate (SiDBP < 85 mm Hg) was non significantly different between treatments groups. Moxonidine reduced heart rate (HR) (average -3.5 bpm, p = 0.017) during monotherapy, and when added to ramipril. HbA1c decreased significantly at Week 12 in both groups. Neither drug affected glucose or insulin response to the oral glucose tolerance test. In non-responders, moxonidine/ramipril combination further reduced BP without compromising metabolic parameters. CONCLUSION: Moxonidine 0.4 mg and ramipril 5 mg were equally effective on BP lowering and were well tolerated and mostly metabolically neutral either as monotherapies or in combination. HR was lowered on moxonidine treatment.

Does type 2 diabetes duration influence the effectiveness of an aerobic exercise intervention: Results from the INTENSITY study.

BACKGROUND: Studies suggest that longer durations of T2DM increase the risk of T2DM complications and premature mortality. However, whether T2DM duration impacts the efficacy of an aerobic exercise intervention is unclear. OBJECTIVE: The purpose of this study was: 1) to compare changes in body composition, cardiorespiratory fitness, and glycemia between individuals with short- and long-duration T2DM after aerobic exercise and 2) to determine whether these changes were associated with changes in glycemia by T2DM duration. METHODS: A secondary analysis of the INTENSITY study (NCT03787836), including thirty-four adults (≥19 years) with T2DM who participated in 28 weeks of aerobic exercise training for 150 minutes per week at a moderate-to-vigorous intensity (4.5 to 6.0 metabolic equivalents (METs)). Using pre-established cut-points, participants were categorized into two groups 1) short-duration T2DM (<5 years) or 2) long-duration T2DM (≥5 years). Glycemia was measured by glycated hemoglobin (HbA1c), body composition by BodPod, and cardiorespiratory fitness by a measure of peak oxygen consumption (VO2peak). All measurements were performed at baseline, 16 weeks, and 28 weeks. RESULTS: Participants in the short-duration T2DM group experienced decreases in fat mass (kg) (p = 0.03), HbA1c (p = 0.05), and an increased relative VO2peak (p = 0.01). Those with long-duration T2DM experienced decreases in fat mass (kg) (p = 0.02) and HbA1c (p <0.001) and increased fat-free mass (p = 0.02). No significant differences were observed between groups in any outcomes. Changes in fat mass (r = 0.54, p = 0.02), and body fat percentage (r = 0.50, p = 0.02) were significantly associated with the change in HbA1c in those with a long-duration T2DM only. CONCLUSION: Our results suggest T2DM duration did not differently impact the efficacy of a 28-week aerobic exercise intervention. However, changes in body composition were associated with better glycemia in individuals with longer T2DM duration only.

Wearable laser Doppler flowmetry for non-invasive assessment of diabetic foot microcirculation: methodological considerations and clinical implications.

Significance: Type 2 diabetes mellitus (T2DM) is a global health concern with significant implications for vascular health. The current evaluation methods cannot achieve effective, portable, and quantitative evaluation of foot microcirculation. Aim: We aim to use a wearable device laser Doppler flowmetry (LDF) to evaluate the foot microcirculation of T2DM patients at rest. Approach: Eleven T2DM patients and twelve healthy subjects participated in this study. The wearable LDF was used to measure the blood flows (BFs) for regions of the first metatarsal head (M1), fifth metatarsal head (M5), heel, and dorsal foot. Typical wavelet analysis was used to decompose the five individual control mechanisms: endothelial, neurogenic, myogenic, respiratory, and heart components. The mean BF and sample entropy (SE) were calculated, and the differences between diabetic patients and healthy adults and among the four regions were compared. Results: Diabetic patients showed significantly reduced mean BF in the neurogenic (p=0.044) and heart (p=0.001) components at the M1 and M5 regions (p=0.025) compared with healthy adults. Diabetic patients had significantly lower SE in the neurogenic (p=0.049) and myogenic (p=0.032) components at the M1 region, as well as in the endothelial (p<0.001) component at the M5 region and in the myogenic component at the dorsal foot (p=0.007), compared with healthy adults. The SE in the myogenic component at the dorsal foot was lower than at the M5 region (p=0.050) and heel area (p=0.041). Similarly, the SE in the heart component at the dorsal foot was lower than at the M5 region (p=0.017) and heel area (p=0.028) in diabetic patients. Conclusions: This study indicated the potential of using the novel wearable LDF device for tracking vascular complications and implementing targeted interventions in T2DM patients.

Balance performance, falls-efficacy and social participation in patients with type 2 diabetes mellitus with and without vestibular dysfunction.

Background: The performance of balance is an important factor to perform activities. The complications of type 2 diabetes mellitus (T2DM), especially vestibular dysfunction (VD), could decrease balance performance and falls-efficacy (FE) which consequently impacts social participation and quality of life (QoL). Purpose: This study aimed to compare balance performance, FE, social participation and QoL between individuals with T2DM with and without VD. Methods: The participants comprised 161 T2DM with VD and 161 without VD. Three clinical tests used for confirming VD included the Head Impulse Test (HIT), the Dix Hallpike Test (DHT) and the Supine Roll Test (SRT). The scores of static and dynamic balances, FE, social participation and QoL were compared between groups. Results: The balance performance, FE, social participation and QoL were lower in the group with VD. The number of patients who had severe social restriction was higher in T2DM with VD than without VD (58.4% vs 48.4%). Moreover, all domains of QoL (physical, psychological, social relationships and environmental) were lower in T2DM with VD than without VD. Conclusion: The presence of VD in T2DM patients was associated with decreased physical balance performances and increased social and QoL disengagement. Comprehensive management related to balance and FE, as well as the monitoring to support social participation and QoL, should be emphasized in patients with T2DM with VD.

Sarcopenia prevalence using handgrip strength or chair stand performance in adults living with type 2 diabetes mellitus.

BACKGROUND: The updated European Working Group on Sarcopenia in Older People (EWGSOP2) recommends handgrip strength (HGS) and the chair stand test (CST) to assess muscle strength, with the CST being a convenient proxy for lower limb strength. However, adiposity may differentially influence these strength criteria and produce discrepant sarcopenia prevalence. OBJECTIVE: To determine the prevalence of sarcopenia using HGS or the CST, and to investigate the associations between these strength criteria and adiposity in adults with type 2 diabetes mellitus. METHODS: The EWGSOP2 definition was used to assess the prevalence of probable (low muscle strength), confirmed (plus low muscle mass) and severe (plus poor physical performance) sarcopenia. Linear regression models were used to study the association between different measures of muscle strength and adiposity. RESULTS: We used data from 732 adults with type 2 diabetes mellitus (35.7% female, aged 64 ± 8 years, body mass index 30.7 ± 5.0 kg/m2). Using the CST compared with HGS produced a higher prevalence of probable (31.7% vs. 7.1%), confirmed (5.6% vs. 1.6%) and severe (1.0% vs. 0.3%) sarcopenia, with poor agreement between strength criteria to identify probable sarcopenia. CST performance, but not HGS, was significantly associated with all measures of adiposity in unadjusted and adjusted models. CONCLUSIONS: Higher levels of adiposity may impact CST performance, but not HGS, resulting in a higher prevalence of sarcopenia in adults with type 2 diabetes mellitus. Consideration should be paid to the most appropriate measure of muscle function in this population.

Impaired Sensitivity to Thyroid Hormones Is Associated With the Change of Abdominal Fat in Euthyroid Type 2 Diabetes Patients: A Retrospective Cohort Study.

Background and Aims: This study is aimed at investigating the potential correlation of thyroid hormone sensitivity with visceral fat area (VFA), subcutaneous fat area (SFA), and body mass index (BMI) among euthyroid type 2 diabetes mellitus (T2DM) subjects. Methods: Thyroid hormone sensitivity indices were calculated by thyroid feedback quantile-based index (TFQI), TSH index (TSHI), thyrotropin thyroxine resistance index (TT4RI), and free thyroxine (fT4)/free triiodothyronine (fT3) ratio. These indices were then categorized into quartiles for analysis. The outcomes were the change rates in VFA, SFA, and BMI among the participants. Result: The present study included 921 patients, with a median follow-up of 2.2 years. In multivariate linear regression, when compared to the first quartile, SFA demonstrated a notable decline in the fourth quartile of TFQI, TSHI, and TT4RI (ß coefficient = -5.78, -7.83, and - 6.84 cm2 per year), while it significantly increased in the fourth quartile of fT4/fT3 ratio (ß coefficient = 6.13 cm2 per year). Similarly, in the fourth quartile of TFQI, TSHI, and TT4RI, VFA decreased significantly, evidenced by ß coefficients of -5.14, -4.80, and -4.08 cm2 per year. Yet, among the quartiles of the fT4/fT3 ratio, no discernible trend in VFA was observed. There was no significant association between indices of thyroid hormone sensitivity and change in BMI. Conclusion: Impaired central sensitivity to thyroid hormones was significantly associated with the reduction of VFA and SFA, while impaired peripheral sensitivity was associated with an increase of SFA in euthyroid individuals with T2DM.

A High Fibrosis-4 Index is Associated with a Reduction in the Estimated Glomerular Filtration Rate in Non-obese Japanese Patients with Type 2 Diabetes Mellitus.

Liver fibrosis is associated with non-alcoholic fatty liver disease (NAFLD), and one of the most important risk factors for NAFLD is type 2 diabetes (T2DM). The Fibrosis-4 (FIB-4) index, a noninvasive liver fibrosis score, has been found to be useful for estimating liver fibrosis. Because individuals with non-obese NAFLD were recently reported to be metabolically unhealthy and have a higher risk of T2DM than individuals with obese NAFLD, we hypothesized that the clinical factors related to a high FIB-4 index would differ between non-obese and obese Japanese T2DM patients. Accordingly, we examined the relationship between clinical factors and the FIB-4 index in non-obese and obese Japanese patients with T2DM. We divided 265 patients into two groups by BMI level - a non-obese group (n = 149) and an obese group (n = 116) - and examined the correlation between the FIB-4 index and clinical parameters. Single regression analysis revealed that a high FIB-4 index was correlated with a reduction in the estimated glomerular filtration rate and hypertension in the non-obese group. Importantly, multiple regression analysis showed that only a reduction in the estimated glomerular filtration rate was significantly associated with a high FIB-4 index in the non-obese group. These results demonstrated that non-obese T2DM patients with a high FIB-4 index might be at risk of kidney dysfunction. Our findings may enable the more appropriate treatment of T2DM patients based on BMI level.

Effects of temporal changes in resting heart rate on future diabetes-related outcomes.

Background and aims: Most studies have analyzed the relationship between resting heart rate (RHR) measured at only one time point and future clinical events. The current study aims to investigate the impact of long-term RHR changes on future clinical outcomes in a decade-long cohort with type 2 diabetes mellitus (T2DM). Methods: The two-staged follow-up involved 2,513 T2DM participants. The first stage (2008-2014) intended to identify levels and trends in RHR changes, while the second stage (2014-2018) attempted to collect new occurrence records of clinical results. Cox proportional hazards models were applied to predict hazard ratios (HRs), along with 95% confidence interval (CI) for the correlation between RHR changes and future events. Results: There is no significant correlation between baseline RHR levels and long-term clinical events. According to the range of RHR change, compared with the stable RHR group, the adjusted HRs for cardiovascular events and all-cause death in the large increase group were 3.40 (95% CI: 1.33-8.71, p=0.010) and 3.22 (95% CI: 1.07-9.64, p=0.037), respectively. While the adjusted HRs for all-cause death and major adverse cardiac and cerebrovascular events (MACCE) in the moderate decrease group were 0.55 (95% CI: 0.31-0.96, p=0.037) and 0.51 (95% CI: 0.26-0.98, p=0.046). According to the trend of RHR, compared with the normal-normal group, the adjusted HRs for composite endpoint events and cerebrovascular events in the normal-high group were 1.64 (95% CI: 1.00-2.68, p=0.047) and 2.82 (95% CI: 1.03-7.76, p=0.043), respectively. Conclusion: Changes in RHR had predictive value for long-term clinical events in diabetic populations. Individuals with significantly elevated RHR over a particular period of time showed an increased risk of adverse events.

The Relationship between the Ewing Test, Sudoscan Cardiovascular Autonomic Neuropathy Score and Cardiovascular Risk Score Calculated with SCORE2-Diabetes.

Background and Objectives: Cardiac autonomic neuropathy (CAN) is a severe complication of diabetes mellitus (DM) strongly linked to a nearly five-fold higher risk of cardiovascular mortality. Patients with Type 2 Diabetes Mellitus (T2DM) are a significant cohort in which these assessments have particular relevance to the increased cardiovascular risk inherent in the condition. Materials and Methods: This study aimed to explore the subtle correlation between the Ewing test, Sudoscan-cardiovascular autonomic neuropathy score, and cardiovascular risk calculated using SCORE 2 Diabetes in individuals with T2DM. The methodology involved detailed assessments including Sudoscan tests to evaluate sudomotor function and various cardiovascular reflex tests (CART). The cohort consisted of 211 patients diagnosed with T2DM with overweight or obesity without established ASCVD, aged between 40 to 69 years. Results: The prevalence of CAN in our group was 67.2%. In the study group, according SCORE2-Diabetes, four patients (1.9%) were classified with moderate cardiovascular risk, thirty-five (16.6%) with high risk, and one hundred seventy-two (81.5%) with very high cardiovascular risk. Conclusions: On multiple linear regression, the SCORE2-Diabetes algorithm remained significantly associated with Sudoscan CAN-score and Sudoscan Nephro-score and Ewing test score. Testing for the diagnosis of CAN in very high-risk patients should be performed because approximately 70% of them associate CAN. Increased cardiovascular risk is associated with sudomotor damage and that Sudoscan is an effective and non-invasive measure of identifying such risk.

Sleep duration and its association with constipation in patients with diabetes: The fukuoka diabetes registry.

AIMS: Shorter and longer sleep durations are associated with adverse health consequences. However, available evidence on the association of sleep duration with constipation is limited, especially in patients with diabetes, who are at a high risk of both conditions. This study aimed to examine the association between sleep duration and constipation in patients with type 2 diabetes. METHODS: A total of 4,826 patients with type 2 diabetes were classified into six groups according to sleep duration: <4.5, 4.5-5.4, 5.5-6.4, 6.5-7.4, 7.5-8.4, and ≥8.5 hours/day. The odds ratios for the presence of constipation, defined as a defecation frequency <3 times/week and/or laxative use, were calculated using a logistic regression model. RESULTS: Shorter and longer sleep durations were associated with a higher likelihood of constipation than an intermediate duration (6.5-7.4 hours/day). This U-shaped association persisted after adjusting for confounding factors, including lifestyle behavior, measures of obesity and glycemic control, and comorbidities. Broadly identical findings were observed when decreased defecation frequency and laxative use were individually assessed. CONCLUSIONS: This study shows a U-shaped association between sleep duration and constipation in patients with type 2 diabetes, and highlights the importance of assessing sleep duration in daily clinical practice.

Is GFR decline induced by SGLT2 inhibitor of clinical importance?

BACKGROUND: Use of sodium-glucose-cotransporter-2 (SGLT2) inhibitors often causes an initial decline in glomerular filtration rate (GFR). This study addresses the question whether the initial decline of renal function with SGLT2 inhibitor treatment is related to vascular changes in the systemic circulation. METHODS: We measured GFR (mGFR) and estimated GFR (eGFR) in 65 patients with type 2 diabetes (T2D) at baseline and after 12 weeks of treatment randomized either to a combination of empagliflozin and linagliptin (SGLT2 inhibitor based treatment group) (n = 34) or metformin and insulin (non-SGLT2 inhibitor based treatment group) (n = 31). mGFR was measured using the gold standard clearance technique by constant infusion of inulin. In addition to blood pressure (BP), we measured pulse wave velocity (PWV) under standardized conditions reflecting vascular compliance of large arteries, as PWV is considered to be one of the most reliable vascular parameter of cardiovascular (CV) prognosis. RESULTS: Both mGFR and eGFR decreased significantly after initiating treatment, but no correlation was found between change in mGFR and change in eGFR in either treatment group (SGLT2 inhibitor based treatment group: r=-0.148, p = 0.404; non-SGLT2 inhibitor based treatment group: r = 0.138, p = 0.460). Noticeably, change in mGFR correlated with change in PWV (r = 0.476, p = 0.005) in the SGLT2 inhibitor based treatment group only and remained significant after adjustment for the change in systolic BP and the change in heart rate (r = 0.422, p = 0.018). No such correlation was observed between the change in eGFR and the change in PWV in either treatment group. CONCLUSIONS: Our main finding is that after initiating a SGLT2 inhibitor based therapy an exaggerated decline in mGFR was related with improved vascular compliance of large arteries reflecting the pharmacologic effects of SGLT2 inhibitor in the renal and systemic vascular bed. Second, in a single patient with T2D, eGFR may not be an appropriate parameter to assess the true change of renal function after receiving SGLT2 inhibitor based therapy. TRIAL REGISTRATION: clinicaltrials.gov (NCT02752113).

Association between A/G ratio and arterial stiffness among Chinese type 2 diabetics: A cross-sectional study.

BACKGROUND: The android-to-gynoid fat ratio (A/G ratio), an emerging indicator of obesity independent of body mass index (BMI), has yet to be conclusively associated with arterial stiffness in type 2 diabetes mellitus (T2DM). This study aimed to construct a nomogram to estimate arterial stiffness risk in diabetics and explore the interaction effect between A/G ratio and traditional obesity indicators on arterial stiffness. METHODS: 1313 diabetics were divided into 2 groups based on arterial stiffness identified by brachial ankle pulse wave velocity (baPWV), and demographic and clinical features were measured. The LASSO and multivariate logistics regression were used to develop the nomogram. Calibration curve, decision curve analysis (DCA) and receiver operating characteristic (ROC) were applied to assess calibration and clinical usefulness. Interaction effect analysis was performed to quantify the interactive relationship of A/G ratio and obesity indicators on arterial stiffness. RESULTS: 6 independent predictors (age, gender, A/G ratio, SBP, LDL-C and HbA1C) were screened to construct a nomogram prediction model. The calibration curve demonstrated satisfactory agreement between predicted and actual probability, and the nomogram exhibited clinical beneficial at the threshold between 8 % and 95 % indicated by DCA. The area under curve (AUC) was 0.918 and 0.833 for training and external set, respectively. Further investigation revealed A/G ratio and BMI acted positively synergistically towards arterial stiffness, and in BMI-based subgroup analysis, elevated A/G ratio was a significant risk factor for arterial stiffness, especially in normal BMI. CONCLUSIONS: A/G ratio showed a substantial association with arterial stiffness, and the nomogram, incorporating age, gender, A/G ratio, SBP, LDL-C, and HbA1c, exhibited high predictive value. A/G ratio measurement in BMI-normal individuals assisted in identifying cardiovascular diseases early.

The ASSIST trial: Acute effects of manipulating strength exercise volume on insulin sensitivity in obese adults: A protocol for a randomized controlled, crossover, clinical trial.

Type 2 diabetes mellitus is a disease in which insulin action is impaired, and an acute bout of strength exercise can improve insulin sensitivity. Current guidelines for strength exercise prescription suggest that 8 to 30 sets could be performed, although it is not known how variations in exercise volume impact insulin sensitivity. Additionally, this means an almost 4-fold difference in time commitment, which might directly impact an individual's motivation and perceived capacity to exercise. This study will assess the acute effects of high- and low-volume strength exercise sessions on insulin sensitivity. After being thoroughly familiarized, 14 obese individuals of both sexes (>40 year old) will undergo 3 random experimental sessions, with a minimum 4-day washout period between them: a high-volume session (7 exercises, 3 sets per exercise, 21 total sets); a low-volume session (7 exercises, 1 set per exercise, 7 total sets); and a control session, where no exercise will be performed. Psychological assessments (feeling, enjoyment, and self-efficacy) will be performed after the sessions. All sessions will be held at night, and the next morning, an oral glucose tolerance test will be performed in a local laboratory, from which indexes of insulin sensitivity will be derived. We believe this study will aid in strength exercise prescription for individuals who claim not to have time to exercise or who perceive high-volume strength exercise intimidating to adhere to. This trial was prospectively registered (ReBEC #RBR-3vj5dc5 https://ensaiosclinicos.gov.br/rg/RBR-3vj5dc5).

MAFLD and glomerular hyperfiltration in subjects with normoglycemia, prediabetes and type 2 diabetes: A cross-sectional population study.

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD, 2020 diagnostic criteria) and glomerular hyperfiltration share common risk factors, including obesity, insulin resistance, impaired glucose tolerance, diabetes, dyslipidemia, and hypertension. AIMS: To assess the prevalence of MAFLD and its association with glomerular hyperfiltration and age-related worsening of kidney function in subjects with normoglycemia, prediabetes and type 2 diabetes mellitus (T2DM). METHODS: We analysed data recorded during occupational health visits of 125,070 Spanish civil servants aged 18-65 years with a de-indexed glomerular filtration rate (GFR) estimated with the chronic-kidney-disease-epidemiological (CKD-EPI) equation (estimated glomerular filtration rate [eGFR]) ≥60 mL/min. Subjects were categorised according to fasting plasma glucose levels <100 mg/dL (normoglycemia), ≥100 and ≤ 125 mg/dL (prediabetes), or ≥126 mg/dL and/or antidiabetic treatment (T2DM). The association between MAFLD and glomerular hyperfiltration, defined as a de-indexed eGFR above the age- and gender-specific 95th percentile, was assessed by multivariable logistic regression. RESULTS: In the whole study group, MAFLD prevalence averaged 19.3%. The prevalence progressively increased from 14.7% to 33.2% and to 48.9% in subjects with normoglycemia, prediabetes and T2DM, respectively (p < 0.001 for trend). Adjusted odds ratio (95% CI) for the association between MAFLD and hyperfiltration was 9.06 (8.53-9.62) in the study group considered as a whole, and 8.60 (8.03-9.21), 9.52 (8.11-11.18) and 8.31 (6.70-10.30) in subjects with normoglycemia, prediabetes and T2DM considered separately. In stratified analyses, MAFLD amplified age-dependent eGFR decline in all groups (p < 0.001). CONCLUSIONS: MAFLD prevalence increases across the glycaemic spectrum. MAFLD is significantly associated with hyperfiltration and amplifies the age-related eGFR decline.

Associations of between- and within-day patterns of physical activity accumulation with arterial stiffness and indices of microvascular health-Evidence from The Maastricht study.

While physical activity (PA) is understood to promote vascular health, little is known about whether the daily and weekly patterns of PA accumulation associate with vascular health. Accelerometer-derived (activPAL3) 6- or 7-day stepping was analyzed for 6430 participants in The Maastricht Study (50.4% women; 22.4% Type 2 diabetes mellitus (T2DM)). Multivariable regression models examined associations between stepping metrics (average step count, and time spent slower and faster paced stepping) with arterial stiffness (measured as carotid-femoral pulse wave velocity (cfPWV)), and several indices of microvascular health (heat-induced skin hyperemia, retinal vessel reactivity and diameter), adjusting for confounders and moderators. PA pattern metrics were added to the regression models to identify associations with vascular health beyond that of stepping metrics. Analyses were stratified by T2DM status if an interaction effect was present. Average step count and time spent faster paced stepping was associated with better vascular health, and the association was stronger in those with compared to those without T2DM. In fully adjusted models a higher step count inter-daily stability was associated with a higher (worse) cfPWV in those without T2DM (std ß = 0.04, p = 0.007) and retinal venular diameter in the whole cohort (std ß = 0.07, p = 0.002). A higher within-day variability in faster paced stepping was associated with a lower (worse) heat-induced skin hyperemia in those with T2DM (std ß = -0.31, p = 0.008). Above and beyond PA volume, the daily and weekly patterns in which PA was accumulated were additionally associated with improved macro- and microvascular health, which may have implications for the prevention of vascular disease.

Circadian dysfunction and cardio-metabolic disorders in humans.

The topic of human circadian rhythms is not only attracting the attention of clinical researchers from various fields but also sparking a growing public interest. The circadian system comprises the central clock, located in the suprachiasmatic nucleus of the hypothalamus, and the peripheral clocks in various tissues that are interconnected; together they coordinate many daily activities, including sleep and wakefulness, physical activity, food intake, glucose sensitivity and cardiovascular functions. Disruption of circadian regulation seems to be associated with metabolic disorders (particularly impaired glucose tolerance) and cardiovascular disease. Previous clinical trials revealed that disturbance of the circadian system, specifically due to shift work, is associated with an increased risk of type 2 diabetes mellitus. This review is intended to provide clinicians who wish to implement knowledge of circadian disruption in diagnosis and strategies to avoid cardio-metabolic disease with a general overview of this topic.

Association of short-term changes in HbA1c with body composition and the importance of muscle maintenance in patients with Type 2 diabetes.

AIMS: This study aimed to investigate the relationship between changes in glucose metabolism and body composition in patients with diabetes. METHODS: We included 380 patients with type 2 diabetes, who underwent bioelectrical impedance analysis, in this longitudinal study. Changes in HbA1c (ΔHbA1c) levels and body composition indices were compared between baseline and 6 months. A multivariate analysis was performed to examine the relationship between ΔHbA1c and changes in body composition. RESULTS: HbA1c levels were significantly decreased at 6 months (P < 0.01), but there was no significant change in BMI. A linear multiple regression analysis showed that ΔHbA1c was negatively correlated with changes in muscle mass (ß = -0.18; P = 0.047) and bone mineral content (ß = -0.28; P < 0.001), but there was no significant association between ΔHbA1c levels and a change in body fat percentage. CONCLUSIONS: This study shows a limited association between short-term changes in glucose metabolism and changes in body composition in patients with type 2 diabetes. Therefore, interventions aimed at reducing adiposity may not affect glucose metabolism in the short term, while interventions focused on maintaining or enhancing muscle mass and bone mineral content may play an important role in diabetes management.

Implementation of surface mechanomyography as a novel approach for objective evaluation of phasic muscle stretch reflexes in people with type 2 diabetes.

INTRODUCTION: Diabetic peripheral neuropathy is the most common complication of diabetes producing metabolic disruptions in the peripheral nervous system. Alteration in the predictable nature of tendon reflexes is the most common indicator suggesting the possibility of diabetic neuropathy. Evaluation of tendon reflexes is a part of various clinical scoring systems that assess neuropathy. The conventional reflex grading scales are subjective, lack temporal data, and have high inter-rater variability. Hence, an indigenous quantification tool was developed to evaluate the tendon reflexes in order to assess diabetic peripheral neuropathy. MATERIALS AND METHODS: A cross-sectional study was carried out in 140 healthy volunteers and 140 patients with type 2 diabetes. The mean age of controls and diabetics (49.1 ± 8.9, 50.7 ± 7.5) years, weight (66.9 ± 9.4, 69.8 ± 11.5) kilograms and BMI (24.5 ± 3.8, 26.1 ± 4.7), respectively. All of them are subjected to evaluation of tendon reflexes using the reflex quantification tool comprised of surface mechanomyography and electrogoniometry that can provide various static and dynamic variables of tendon reflex. RESULTS: The dynamic variables such as reflex amplitude, muscle velocity and angular velocity were significantly low in diabetic patients (p: <0.001) whereas latency and duration (p: <0.001) were prolonged. Furthermore, no significant difference was observed in the application of tendon striking force (p: 0.934) among the participants. CONCLUSION: The current study demonstrates that the proposed reflex quantification tool provides several dynamic variables of patellar tendon reflex, which are significantly affected and altered in diabetic patients suggesting the involvement of peripheral neurons.

Factors affecting the sodium-glucose cotransporter 2 inhibitors-related initial decline in glomerular filtration rate and its possible effect on kidney outcome in chronic kidney disease with type 2 diabetes: The Japan Chronic Kidney Disease Database.

AIM: Sodium-glucose cotransporter 2 (SGLT2) inhibitors often cause a transient decrease in glomerular filtration rate (GFR) shortly after the initiation, referred to as the 'initial drop'. However, the clinical significance of this initial drop in real-world practice remains unclear. MATERIALS AND METHODS: Using the nationwide Japan Chronic Kidney Disease Database, we examined factors that affected the initial drop, in patients with chronic kidney disease (CKD) and type 2 diabetes mellitus (T2DM). We also evaluated the effects of the initial drop on a composite kidney outcome (a decline in GFR of ≥50% or progression to end-stage kidney disease). RESULTS: Data from 2053 patients with CKD and T2DM newly prescribed an SGLT2 inhibitor were analysed. The follow-up period after SGLT2 inhibitor administration was 1015 days (interquartile range: 532, 1678). Multivariate linear regression models revealed that the concomitant use of the renin-angiotensin system inhibitors and diuretics, urinary protein levels ≥2+, and changes in GFR before the initiation of the SGLT2 inhibitor were associated with a larger initial GFR decline (ß = -0.609, p = .039; ß = -2.298, p < .001; ß = -0.936, p = .048; ß = -0.079, p < .001, respectively). Patients in the quartile with the largest initial GFR decline experienced a higher incidence of the subsequent composite kidney outcome than those in the other quartiles (p < .001). CONCLUSIONS: The concomitant use of renin-angiotensin system inhibitors and diuretics, higher urine protein levels and pre-treatment GFR changes were associated with a larger initial GFR decline. Of these factors, the use of a diuretic had the largest effect. Furthermore, patients with CKD and T2DM experiencing an excessive initial GFR drop might be at a higher risk of adverse kidney outcomes.