Active clinical trials for "Diabetes Mellitus, Type 2"

In Singapore, the Ministry of Health has declared a "War on Diabetes" and major efforts will be made to develop and deploy programs to prevent diabetes. One of the cornerstones of diabetes management involves dietary modifications to reduce postprandial hyperglycaemia. However, implementation of a low GI diet is highly complex requiring the individual to choose foods from a long list which are primarily based on western consumption patterns. Many foods in the Asian diet, which largely consist of carbohydrates such as white rice, noodles and other flour-based products, are not represented. An alternative solution will require innovative ways to alter commonly available food products that will not only help reduce postprandial glycaemia but also preserve the sensory characteristics of the foods to create a new generation of food products both functional and palatable.

Large interindividual variability exists in the glycemic response to exercise program, resulting in a subset of individuals known as exercise non-responders (NRs). Increasing the intensity of an exercise intervention has been proposed as one method for rescuing NRs by producing beneficial changes. However, this theory has not been tested on NRs classified using glycemic outcomes. This study will evaluate if increasing the intensity of an exercise intervention will elicit a response within previous exercise NRs.

The objective of this study is to compare two metabolically distinct diets, WFKD vs Med-Plus, in order to examine the potential benefits, and unintended consequences, of going beyond a focus on maximally avoiding added sugars and refined grains, to also avoiding legumes, fruits, and whole grains.

ABSTRACT Introduction: There is no current data about the effects of non-nutritive sweeteners (NNS) about important factors, such as the energy intake, appetite and its relationship in people with diabetes when tasting sweet. It is highly relevant to compare the effects of NNS intake, such as, stevia (steviol glycosides) and sucralose, previous to a mixed food on glycemic response, insulin and plasmatic concentrations of Glucagon-like peptide type 1 (GLP-1) and ghrelin in subjects with type 2 diabetes mellitus (T2DM). Objective: To compare the effects of non-nutritive sweeteners intake: stevia (steviol glyco-sides) and sucralose previous to mixed food on appetite, glycemia, insulin, ghrelin,incretin plasmatic concentrations GLP-1 in people with T2DM. Methods: Seventeen subjects with T2DM were studied in 3 different moments and they received 3 treatments: pre-load of water or sucralose or stevia and then offered to consume mixed food as a test, which provided 332 Kcal and 75 grams of available carbohydrates. Blood samples were obtained to measure the dependent variables, glycemic and insulin at times -10, 0, 30, 60, 90, 120, 150 and 180 minutes and GLP-1 with ghrelin, at times -10, 0, 30, 90, and 180 minutes. The analogue visual scale questionnaires (VAS) was conducted every 30 minutes in order to obtain the results of the depend variables: appetite and wish of specific type of food in a subjective way; appetite, satiety, relax, wish to eat any food, craving for something sweet, craving for something salty, something tasty, something fatty. Through food provided ad libi-tum (objective appetite), were obtained the results of: energy, carbohydrates, proteins and lipid intakes. The statistical analysis applied included the Shapiro-Wilk's Normality test, repeated measures ANOVA to assess differences among treatments, Friedman's test followed by Wilcoxon test corrected by Bonferroni as needed. The degree of association between variables was conducted using the Pearson's or Spearman's correlation coefficient tests, as requested. A probability value p <0.05 was considered significant.

The sodium-glucose cotransporter 2 (SGLT2) inhibitors are an exciting new class of antidiabetic drugs that cause a modest reduction in high blood pressure and large reductions in the risk of cardiovascular disease (CVD) outcomes and renal outcomes in patients with advanced type 2 diabetes and very high CVD risk. However, the mechanistic underpinning of these CVD benefits is not well understood. Mechanistic studies are needed to define specific biologic targets and thus optimize therapeutic benefits. Type 2 diabetes mellitus is firmly established as a state of sympathetic neural overactivity, which may contribute to coexistent hypertension, heart failure, sudden cardiac death, macro- and micro-vascular complications of diabetes, and diabetic nephropathy. In patients recently diagnosed with Type 2 diabetes, microelectrode recordings of sympathetic nerve activity (SNA) targeted to the skeletal muscle circulation have shown both: abnormally high resting (ambient) levels of sympathetic nerve activity; and greatly exaggerated increases in sympathetic nerve activity during isometric (static) handgrip exercise. The purpose of the proposed study is to determine if Ertugliflozin, a SGLT2 inhibitor, constitutes an effective countermeasure against sympathetic overactivity in patients with diagnosed hypertension and recently diagnosed type 2 diabetes by normalizing the high resting level of muscle sympathetic nerve activity (SNA) as measured by intraneural microelectrodes in the peroneal nerve. Thus, an effective countermeasure is an urgent unmet medical need. The SGLT2 inhibitors hold exciting promise to address this need.

Worldwide, diabetic kidney disease (DKD) is the most common cause of chronic and end stage kidney disease. Large-sized prospective randomized clinical trials indicate that intensified glucose and blood pressure control, the latter especially by using agents that interfere with the renin-angiotensin-aldosterone system (RAS), halts the onset and (particularly) the progression of DKD, in both type 1 Diabetes Mellitus (T1DM) and type 2 Diabetes Mellitus (T2DM) patients. However, despite the wide use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), a considerable amount of patients develop DKD (20-40%), indicating an unmet need for renoprotective therapies as DKD largely causes the increased mortality risk from cardiovascular disease (CVD) in people with diabetes. Sodium-glucose linked transporters (SGLT-2) inhibitors are a relatively novel glucose-lowering drug for the treatment of T2DM as they lower plasma glucose levels by blocking renal glucose reabsorption. In addition, these agents exert pleiotropic actions beyond glucose control. As such, SGLT-2 inhibitors decrease proximal sodium reabsorption, reduce blood pressure, body weight and uric acid. In large trials and likely through these pleiotropic effects, SGLT2 inhibitors reduce cardiovascular mortality, hospitalization for heart failure and reduce end stage kidney disease. At this point in time, the renoprotective mechanisms involved with SGLT-2 inhibition still remain speculative, though a consistent finding is that SGLT-2 inhibitors reduce estimated eGFR after first dosing, which is reversible after treatment cessation. This "dip" indicates a renal hemodynamic phenomenon reminiscent of the RAS blockers and is thought to reflect a reduction in intraglomerular pressure. The mechanisms of this observation have only been partially investigated by us and others. From studies in peolpe with T1DM it is hypothesized that SGLT-2 inhibition increases sodium chloride delivery to the macula densa, which in turn augments the afferent arteriolar resistances, known as tubuloglomerular feedback (TGF), consequently reducing glomerular (hyper)filtration and hydrostatic pressure. Recently a trial has been conducted in humans with T2DM to investigate if this also holds true in these patients. Suprisingly, this study showed that the renohemodynamic actions of SGLT-2 inhibition in T2DM are not due to afferent vasoconstriction but rather efferent vasodilation [van Bommel/van Raalte Kidney International 2019 in press]. The investigators realized that the SGLT-2 associated dip in eGFR remains insufficient understood. The increase in sodium excretion following SGLT-2 inhibition peaks at day 2-3 after which it normalizes. It is unknown whether this drop in eGFR is related to this peak in sodium excretion, as the drop remains after normalization of sodium excretion. Therefore it might be possible that glucosuria, by inducing osmotic diuresis, is the main driver of the reduction in intraglomerular pressure more than sodium, since SGLT-2 inhibitors cause persisting glucosuria. Furthermore, it is known that SGLT-2 induced glucosuria and possibly sodium excretion is dependent of renal function and HbA1c and consequently is diminished in people with CKD or without T2DM. However, the renoprotective effects in T2DM are also observed in patients with impaired kidney function and seem statistically independent of glucose levels. Until now it has not been investigated whether or not the SGLT-2 induced eGFR alterations occur in people with CKD with or without T2DM. It is clinically relevant to understand the renal hemodynamics of SGLT-2 inhibitors in these populations since then it is possible to interpret the results from the ongoing trials in people with CKD without T2DM, such as EMPA-KIDNEY and DAPA-CKD. Recently, potential mediators of renal arterole tone, such as adenosine, have been measured to gain more insight into mechanisms of SGLT-2 inhibitor-induced changes in renal hemodynamics. Adenosine is known to augment preglomerular arteriolar resistance. Adenosine was significantly increased after SGLT-2 inhibition, as was also observed in patients with type 1 diabetes. However, it can also induce postglomerular vasodilation via A2aR activation in the presence of RAS blockade. One study in T1DM rats has shown that increased adenosine generation by the macula densa in response to SGLT-2 inhibition suppresses hyperfiltration, as the improvements in preglomerular arteriolar resistance were abolished after adenosine antagonist administration. To date, this has not been investigated in T2DM humans. Therefore, this trial will assess TGF responses with and without adenosine blockade by caffeine.

The study investigates the effects of a mindfulness intervention on sleep and subsequent cardio-metabolic risk in an adult Atlanta population aged 18 and older.

The study is a single site, prospective, open label, observational, single arm trial in 30 patients with type 2 diabetes with GI complaints using 1 or more oral or injectable anti-hyperglycemic agents to investigate if altering the microbiome though Pendulum T2D dietary supplementation can further enhance the efficacy of the current treatment while reducing the GI associated symptoms in patients with Type 2 diabetes.

Objectives: The aim of the study is evaluate the efficacy of a telephone assisted cognitive behavioral therapy for adherence (CBCBT) in type 2 diabetes. Hypothesis: CBCBT will primarily reduce depressive symptoms and improve glycemic control and secondarily, improve adherence and self-care and reduce diabetes-specific distress. Design and subjects: This is a prospective randomized two-armed intervention study. One hundred sixty eight participants will be recruited from five sites covering the following clusters: New Territories East, Kowloon East and Hong Kong West. Intervention: The CBT protocol (Safren et al., 2013) will be used in the intervention. Specific components include: 1) introducing CBT for behavior change, 2) increasing pleasurable activities and mood monitoring, 3) cognitive restructuring, 4) problem-solving in self-care and 5) relaxation training. To maximize accessibility, eight sessions will be delivered face-to-face in group setting and the other four sessions will be delivered by telephone. Three monthly follow-up telephone calls will be made to consolidate treatment gains. Main outcome measures: Primary outcomes include the Beck Depression Inventory and glycemic control. Secondary outcomes include self-care and diabetes-specific distress. Data analysis: Treatment outcomes will be assessed by Repeated Measures ANOVA and also Intention to Treat Analysis. Regression models will be used to estimate effect sizes and associations among variables. Expected results: CBCBT would significantly reduce depressive symptoms and improve glycemic control. With secondary outcomes, CBCBT will improve self-care and reduce diabetes-specific distress.

This is a randomized, placebo-controlled, four-arm, double-blind study. Subjects will be randomized (1:1:1:1) to receive either a daily oral placebo solution or a daily oral dose of 0.5 mg, 2.5 mg or 5.0 mg Foralumab Solution for 30 consecutive days. Subjects will record adverse events and daily administration of study medication in a subject diary. This will serve as a measure of compliance and record of safety and tolerability. Subjects will be followed up for 30 days following completion of treatment. Study visits performed on Days 14, 30 and 60 of the study, will monitor metabolic parameters (body mass index [BMI] and waist circumference), serum lipid profiles, immunological markers (c-reactive protein [CRP] and an array of cytokines), hepatic enzymes and functions (13C-methacetin breath test [MBT]) and liver steatosis/fibrosis, which will be compared to baseline levels (Day 1). The safety and tolerability of the treatment regimen will be determined by monitoring vital signs, laboratory values, adverse events and physical findings throughout the study. In addition, its efficacy will be established upon either reduced Day 30 serum alanine aminotransferase (ALT) levels, reduced hemoglobin A1c (HbA1c) or improved homeostasis model assessment (HOMA) or HOMA of insulin resistance (HOMA-IR) scores as compared to baseline (Day 1). In addition, to assess the efficacy of the tested Foralumab Solution regimen in improving overall subject status, a battery of exploratory metabolic, immunologic and hepatic markers will be evaluated on Days 30 and 60.