Significant Improvement In Insulin Sensitivity Research Articles

Effects of L-carnitine on Polycystic Ovary Syndrome

Objective:Polycystic ovary syndrome (PCOS) is a common disorder in women of reproductive age. This study investigated the effects of L-carnitine on the clinical and laboratory findings of women with PCOS.Methods:Eighty women diagnosed with PCOS between 2017 and 2018 by the Rotterdam Criteria were enrolled in the study; six were lost during the study. The participants were given L-carnitine 3 g daily (Pursinapharma, Iran) for three months. Blood samples were taken after overnight fasting at baseline and three months into the study to assess the levels of fasting glucose, insulin, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL), free testosterone, dehydroepiandrosterone (DHEA), and the insulin resistance index (HOMA-IR). The patients were weighed before and after treatment and had their body mass index (BMI) calculated. Menstrual cycles and manifestations of hirsutism were also assessed.Results:The data showed a significant improvement in insulin sensitivity and decreases in serum LDL levels and the BMI after three months of treatment. There was a significant increase in serum HDL levels. More regular menstrual cycles and decreased hirsutism were also observed.Conclusion:It appears that treatment with L-carnitine might decrease the risk of cardiovascular events by normalizing metabolic profiles and the BMI.

Improvement in insulin sensitivity and serum leptin concentration after the switch from a ritonavir-boosted PI to raltegravir or dolutegravir in non-diabetic HIV-infected patients.

An observational, prospective, cohort study was performed to assess changes in insulin sensitivity and serum leptin level after a switch from a ritonavir-boosted PI (PI/r) to raltegravir or dolutegravir in HIV-infected adults on stable combination ART (cART). Non-diabetic HIV-infected patients receiving suppressive cART including tenofovir disoproxil fumarate/emtricitabine plus one PI/r, who underwent a switch from the PI/r to raltegravir (group A) or dolutegravir (group B), were enrolled in the study. Serum levels of insulin, leptin and the homeostasis model assessment of insulin resistance (HOMA) index were evaluated during a 12 month follow-up. Overall, 86 patients were enrolled: 45 patients were included in group A and 41 were included in group B. The mean age was 45.7 years and 74 (86%) patients were male. After 12 months of follow-up, a significant reduction in the mean concentration of leptin and insulin was reported both in group A [-0.61 ng/mL (P < 0.001) and -2.5 mIU/L (P = 0.008), respectively] and in group B [-0.54 ng/mL (P = 0.005) and -2.1 mIU/L (P = 0.017), respectively], without a significant difference between the groups. A significant and comparable reduction in the mean HOMA index was reported both in group A [-0.55 (P = 0.004)] and in group B [-0.49 (P < 0.001)], as well as a significant decrease in lipid levels. In HIV-positive subjects on suppressive cART, the switch from a PI/r to raltegravir or dolutegravir led to a significant and comparable reduction in both HOMA index and serum leptin level, reflecting a similar and significant improvement in insulin sensitivity.

Efficacy of Metformin Treatment with Respect to Weight Reduction in Children and Adults with Obesity: A Systematic Review.

Obesity and its related complications are increasing health issues. Since generally only minor weight loss is obtained with lifestyle intervention, additional pharmacological therapies such as metformin are often used. We conducted a systematic review to provide an overview of the efficacy of ≥ 6months of metformin treatment in children and adults with respect to weight, insulin resistance, and progression toward type 2 diabetes mellitus (T2DM). In September 2018, we searched PubMed, Embase, and the Cochrane Library for studies published in English using the keywords metformin, obesity/overweight, and weight loss. Prospective studies reporting weight/body mass index (BMI) as a primary or secondary outcome in patients with overweight/obesity with ≥ 6months' metformin treatment were included. Included subjects were children and adults with overweight/obesity who received ≥ 6months of metformin and/or lifestyle intervention, and/or placebo and/or lifestyle intervention, and/or standard care. Studies were independently screened by two reviewers. Data were extracted by one and verified by the other reviewer, and both reviewers assessed the risk of bias using the Cochrane risk-of-bias tool. Our review includes 15 pediatric and 14 adult studies. In children, after 6months, more than half the studies reported a greater reduction in BMI with metformin versus controls. Only six studies had an intervention of > 6months, and these studies found no further improvement in BMI in the metformin users, though their BMI was lower than that of controls. Three studies showed a significant improvement in insulin sensitivity in the metformin versus the control group. Adults using metformin experienced and maintained small decreases in weight irrespective of duration of intervention. In 11 of 14 studies, a greater reduction in weight/BMI was observed with metformin than with placebo. Progression toward T2DM was significantly reduced in adults using metformin, ranging from 7 to 31%. The safety and tolerability of metformin, withdrawal of participants, and comparison with other drugs were not taken into account. The effects of metformin on weight/BMI vary, with smaller reductions in children than in adults. This could be because of differences in adherence, daily dosage, and insulin status. Metformin significantly reduced the progression toward T2DM in adults. Therefore, metformin should be considered as a treatment for obesity and its related complications.

Intermittent administration of a fasting-mimicking diet intervenes in diabetes progression, restores \u03b2 cells and reconstructs gut microbiota in mice

Fasting and especially intermittent fasting have been shown to be an effective intervention in many diseases, such as obesity and diabetes. The fasting-mimicking diet (FMD) has recently been found to ameliorate metabolic disorders. To investigate the effect of a new type of low-protein low-carbohydrate FMD on diabetes, we tested an FMD in db/db mice, a genetic model of type 2 diabetes. The diet was administered every other week for a total of 8 weeks. The intermittent FMD normalized blood glucose levels in db/db mice, with significant improvements in insulin sensitivity and β cell function. The FMD also reduced hepatic steatosis in the mice. Deterioration of pancreatic islets and the loss of β cells in the diabetic mice were prevented by the FMD. The expression of β cell progenitor marker Ngn3 was increased by the FMD. In addition, the FMD led to the reconstruction of gut microbiota. Intermittent application of the FMD increased the genera of Parabacteroides and Blautia while reducing Prevotellaceae, Alistipes and Ruminococcaceae. The changes in these bacteria were also correlated with the fasting blood glucose levels of the mice. Furthermore, intermittent FMD was able to reduce fasting blood glucose level and increase β cells in STZ-induced type 1 diabetic mouse model. In conclusion, our study provides evidence that the intermittent application of an FMD is able to effectively intervene in the progression of diabetes in mice.

Mangosteen Extract Shows a Potent Insulin Sensitizing Effect in Obese Female Patients: A Prospective Randomized Controlled Pilot Study.

There is a widely acknowledged association between insulin resistance and obesity/type 2 diabetes (T2DM), and insulin sensitizing treatments have proved effective in preventing diabetes and inducing weight loss. Obesity and T2DM are also associated with increased inflammation. Mangosteen is a tropical tree, whose fruits—known for their antioxidant properties—have been recently suggested having a possible further role in the treatment of obesity and T2DM. The objective of this pilot study has been to evaluate safety and efficacy of treatment with mangosteen extract on insulin resistance, weight management, and inflammatory status in obese female patients with insulin resistance. Twenty-two patients were randomized 1:1 to behavioral therapy alone or behavioral therapy and mangosteen and 20 completed the 26-week study. The mangosteen group reported a significant improvement in insulin sensitivity (homeostatic model assessment-insulin resistance, HOMA-IR −53.22% vs. −15.23%, p = 0.004), and no side effect attributable to treatment was reported. Given the positive preliminary results we report and the excellent safety profile, we suggest a possible supplementary role of mangosteen extracts in the treatment of obesity, insulin resistance, and inflammation.

1012: Are changes in post-delivery glucose metabolism related to changes in cytokines, adipokines or lipids in women with gestational diabetes mellitus?

To compare changes in maternal insulin sensitivity (IS), insulin response (IR) and disposition index (DI) from late pregnant (PP0:34-37 weeks) to early postpartum (PP1: 1-5 days after delivery) and late postpartum (PP2: 6-12 weeks after delivery) and to correlate the results to changes in maternal lipids, adipokines and lipids over the same time interval in women with gestational diabetes (GDM). This is a secondary analysis from a previously reported cohort of 27 women with GDM. Subjects were eligible with a singleton pregnancy ≥34 weeks, no pre-existing diabetes, evidence of infection, or medication for glucose control post-partum. Subjects underwent an OGTT at three points (PP0, PP1, PP2) with assessment of fasting lipids (cholesterol, LDL, HDL, VLDL, triglycerides), cytokines (IL6, IL8, CRP, TNFα), adiponectin and leptin. Maternal serum for insulin and glucose were collected for measures of IS (ISogtt), IR (Stumvoll method) and DI (IS*IR). The IS, IR and DI were compared at PP0, PP1 and PP2. The correlation between changes in IS, IR and DI and lipid/cytokine measures were made at PP0 vs. PP1 and PP0 vs. PP2. The changes in IS, IR and DI over time and are shown in Figure 1. Changes in maternal lipids and cytokines are in Table 1.There were significant correlations between changes in IR and Leptin from PP0 to PP1 (r=-0.37, p=0.05) and changes in IS and Triglyceride from PP0 to PP2 (r=-0.40, p=0.04). There is a significant improvement in IS and DI and decrease in IR immediately PP. The changes in glucose metabolism are independent of changes in lipids and cytokines and maternal weight. The placental factors relating to changes in glucose metabolism in GDM pregnancy remain largely unknown. CDC, Battelle Memorial Institute (200-2008-27956, Task Order 23) and CTSC at Case Western Reserve University.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

The effects of trans-resveratrol on insulin resistance, inflammation, and microbiota in men with the metabolic syndrome: a pilot randomized, placebo controlled clinical trial

The metabolic syndrome (MetS) is a pathological condition comprised of abdominal obesity, insulin resistance, hypertension, and hyperlipidemia. It has become a major threat globally, resulting in rapidly increasing rates of diabetes, coronary heart disease, and stroke. The polyphenol resveratrol (RES) is believed to improve glucose homeostasis and insulin resistance by activating sirtuin, which acetylates and coactivates downstream targets and affects glucose and lipid homeostasis in the liver, insulin secretion in the pancreas, and glucose uptake in skeletal muscle. We studied the effects of RES on insulin resistance, glucose homeostasis, and concomitant effects on adipose tissue metabolism and fecal microbiota in insulin-resistant subjects with the MetS. A total of 28 obese men with the MetS were studied during a 35-day stay in the Rockefeller University Hospital metabolic unit. Subjects were randomized to receive RES 1 g orally twice daily or placebo while kept weight stable and consuming a western-style diet. At baseline, and after 30 days of RES or placebo administration, subjects underwent testing that included a euglycemic, hyperinsulinemic clamp, 2-h oral glucose tolerance test (GTT), resting energy expenditure, daily blood pressure monitoring, abdominal adipose tissue biopsy, and fecal and blood collections. RES induced no changes in insulin resistance but reduced the 120-min time point and the area under the curve for glucose concentration in the 2-h GTT. In post-hoc analysis, Caucasian subjects showed a significant improvement in insulin sensitivity and glucose homeostasis after GTT, whereas non-Caucasians showed no similar effects. Levels of fasting plasma RES and its primary metabolite dihydroresveratrol were variable and did not explain the racial differences in glucose homeostasis. RES administration to Caucasian subjects leads to an increase in several taxa including Akkermansia muciniphila. RES 2 g administered orally to obese men with MetS and insulin resistance marginally altered glucose homeostasis. However, in a small group of Caucasians, insulin resistance and glucose homeostasis improved. No concomitant changes in adipose tissue metabolism occurred, but fecal microbiota showed RES-induced changes. The MetS increases the risk of diabetes, heart disease, and stroke. A major component of the syndrome is insulin resistance, resulting in systemic inflammation and hyperinsulinemia. The primary treatment consists of lifestyle changes, improved diet, and increased physical activity. This is often unsuccessful. In this study, RES was well tolerated. In Caucasian men, it significantly improved insulin sensitivity and glucose homeostasis. Similar results were found in studies that consisted exclusively of Caucasian men. However, RES presents a novel addition to the current treatment of the MetS and its sequelae.

Effect of Mediterranean Diet and Antioxidant Formulation in Non-Alcoholic Fatty Liver Disease: A Randomized Study.

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide, characterized by liver fatty acid accumulation and fibrosis, not due to excessive alcohol consumption. Notably, nutritional habits have been reported to be implicated in the onset and severity of the hepatic damage, while the Mediterranean diet has shown beneficial effects on NAFLD. Free radicals and oxidative stress were suggested to be involved in the pathogenesis and progression of NAFLD, and several data highlighted the efficacy of antioxidant supplementation in its treatment. The aim of this study was to compare the effects of the Mediterranean diet, with or without an antioxidant complex supplement, in overweight patients suffering from NAFLD. In this prospective study, fifty Caucasian overweight patients were randomized into three groups (Groups A–C). A personalized moderately hypocaloric Mediterranean diet was prescribed to all patients included in the A and B groups. In addition to the diet, Group B was administered antioxidant supplementation daily and for the period of six months. Group C did not have any type of treatment. The study proved that the Mediterranean diet alone or in association with the antioxidant complex improved anthropometric parameters, lipid profile and reduced hepatic fat accumulation and liver stiffness. However, Group B patients, in which the diet was associated with antioxidant intake, showed not only a significant improvement in insulin sensitivity, but also a more consistent reduction of anthropometric parameters when compared with Group A patients. Taken together, these results support the benefit of antioxidant supplementation in overweight patients with NAFLD.

Effects of Roux-en-Y gastric bypass on insulin secretion and sensitivity, glucose homeostasis, and diabetic control: A prospective cohort study in Chinese patients

To report on the effects of Roux-en-Y gastric bypass operation for obesity on measures of adiposity, insulin secretion and sensitivity, glucose homeostasis, and improvement in diabetic control in Chinese patients. This was a prospective cohort study of 152 participants (81% with diabetes) who were recruited for bariatric operation. Mean body mass index was decreased by 18.1% from 30.31±5.38kg/m2 at baseline to 24.45±3.79kg/m2 at 2years (P<.001). Indices of insulin secretion, including serum c-peptide (both fasted and at various time points during an oral glucose tolerance test) improved at the 3-year follow-up, with a significant improvement in insulin sensitivity and glucose homeostasis. The effects of Roux-en-Y gastric bypass 3years postoperative on adiposity were paralleled by a significant improvement in insulin secretion and sensitivity, and glucose tolerance.

Inflammation Improves Glucose Homeostasis through IKKβ-XBP1s Interaction

It is widely believed that inflammation associated with obesity has an important role in the development of type 2 diabetes. IκB kinase beta (IKKβ) is a crucial kinase that responds to inflammatory stimuli such as tumor necrosis factor α (TNF-α) by initiating a variety of intracellular signaling cascades and is considered to be a key element in the inflammation-mediated development of insulin resistance. We show here, contrary to expectation, that IKKβ-mediated inflammation is a positive regulator of hepatic glucose homeostasis. IKKβ phosphorylates the spliced form of X-Box Binding Protein 1 (XBP1s) and increases the activity of XBP1s. We have used three experimental approaches to enhance the IKKβ activity in the liver of obese mice and observed increased XBP1s activity, reduced ER stress, and a significant improvement in insulin sensitivity and consequently in glucose homeostasis. Our results reveal a beneficial role of IKKβ-mediated hepatic inflammation in glucose homeostasis.

Pathogenetic role of intestinal dysbiosis in obesity and type 2 diabetes mellitus

The article decribes the up-to-date view on the role of intestinal dysbiosis in obesity and type 2 diabetes mellitus. Particularly, these metabolic disorders are associated with changes in the composition of the intestinal microbiota, and the gut microbiome in obese individuals seems to be more efficient in harvesting energy from the diet. Such differences in gut microbiota composition might function as early diagnostic markers for the development of type 2 diabetes mellitus in high-risk patients. Lean male donor fecal microbiota transplantation in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains, that may induce beneficial metabolic effects.

Light-intensity and high-intensity interval training improve cardiometabolic health in rats

Physical activity has the potential to reduce cardiometabolic risk factors but evaluation of different intensities of physical activity and the mechanisms behind their health effects still need to be fully established. This study examined the effects of sedentary behaviour, light-intensity training, and high-intensity interval training on biometric indices, glucose and lipid metabolism, inflammatory and oxidative stress markers, and vascular and cardiac function in adult rats. Rats (12 weeks old) were randomly assigned to 1 of 4 groups: control (CTL; no exercise), sedentary (SED; no exercise and housed in small cages to reduce activity), light-intensity trained (LIT; four 30-min exercise bouts/day at 8 m/min separated by 2-h rest period, 5 days/week), and high-intensity interval trained (HIIT, four 2.5-min work bouts/day at 50 m/min separated by 3-min rest periods, 5 days/week). After 12 weeks of intervention, SED had greater visceral fat accumulation (p < 0.01) and slower cardiac conduction (p = 0.04) compared with the CTL group. LIT and HIIT demonstrated beneficial changes in body weight, visceral and epididymal fat weight, glucose regulation, low-density lipoprotein cholesterol, total cholesterol, and mesenteric vessel contractile response compared with the CTL group (p < 0.05). LIT had significant improvements in insulin sensitivity and cardiac conduction compared with the CTL and SED groups whilst HIIT had significant improvements in systolic blood pressure and endothelium-independent vasodilation to aorta and mesenteric artery compared with the CTL group (p < 0.05). LIT and HIIT induce health benefits by improving traditional cardiometabolic risk factors. LIT improves cardiac health while HIIT promotes improvements in vascular health.

A Novel Partial PPARα/γ Dual Agonist SN159 Improves Insulin Sensitivity

We here demonstrate that (E)‐1‐(3‐aminophenyl)‐3‐(5‐bromo‐4‐hydroxy‐2‐methoxyphenyl)prop‐2‐en‐1‐one (SN159) is a novel peroxisome proliferator‐activated receptor (PPAR) partial agonist that improves insulin sensitivity. SN159 interacted directly with PPARα and PPARγ, which were confirmed by LanthaScreen ligand binding assay and molecular docking study. SN159 treatment leads to a significant improvement of insulin sensitivity, resulting in enhancing glucose uptake in muscle cells. SN159 stimulated adipogenic differentiation of 3T3‐L1 preadipocytes, however, the effects were much weaker than those of PPARγ agonist troglitazone. In parallel, SN159 increased weakly the transcriptional activities of PPARα/γ, compared to the positive control. Furthermore, PPARγ activation and adipogenic differentiation by troglitazone were significantly reduced by treatment with SN159, indicating that SN159 is a partial agonist of PPARs. SN159 was able to enhance fatty acid oxidation and glucose utilization through the dual activation of PPARα/γ. Taken together, these results suggest that SN159 is a novel PPAR partial agonist, which can be used as potential therapeutic agents against type 2 diabetes and related metabolic disorders by enhancing glucose and lipid metabolism.

The Effect of Regular Exercise on Insulin Sensitivity in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

The purpose of this study was to examine the effect of regular exercise training on insulin sensitivity in adults with type 2 diabetes mellitus (T2DM) using the pooled data available from randomised controlled trials. In addition, we sought to determine whether short-term periods of physical inactivity diminish the exercise-induced improvement in insulin sensitivity. Eligible trials included exercise interventions that involved ≥3 exercise sessions, and reported a dynamic measurement of insulin sensitivity. There was a significant pooled effect size (ES) for the effect of exercise on insulin sensitivity (ES, –0.588; 95% confidence interval [CI], –0.816 to –0.359; P<0.001). Of the 14 studies included for meta-analyses, nine studies reported the time of data collection from the last exercise bout. There was a significant improvement in insulin sensitivity in favour of exercise versus control between 48 and 72 hours after exercise (ES, –0.702; 95% CI, –1.392 to –0.012; P=0.046); and this persisted when insulin sensitivity was measured more than 72 hours after the last exercise session (ES, –0.890; 95% CI, –1.675 to –0.105; P=0.026). Regular exercise has a significant benefit on insulin sensitivity in adults with T2DM and this may persist beyond 72 hours after the last exercise session.

Clearance of Hepatitis C Virus Improves Insulin Resistance During and After Peginterferon and Ribavirin Therapy.

Patients with chronic hepatitis C virus (HCV) infection are at a greater risk of developing insulin resistance (IR). However, little is known about when insulin sensitivity may improve during or after treatment for hepatitis C. In this study, we examined the effect of combination therapy with pegylated interferon-α and ribavirin on IR in patients with chronic HCV infection. We also analyzed factors associated with changes in insulin sensitivity. IR was estimated by homeostasis model assessment (HOMA-IR). HOMA-IR was measured before therapy, during therapy (12 and 24 weeks), and at the end of therapy (EOT; 24 or 48 weeks). We analyzed 78 HCV patients receiving combination therapy. Twenty-two patients (28.2%) exhibited pretreatment IR (HOMA-IR >2.5). In all patients, HOMA-IR was not significantly different from baseline values at 12 weeks (P = 0.823), 24 weeks (P = 0.417), or at EOT (P = 0.158). In patients with pretreatment IR, a significant decrease in HOMA-IR was observed at 12 weeks (P = 0.023), 24 weeks (P = 0.008), and at EOT (P = 0.002). Multivariate analysis using a logistic regression model showed that baseline HOMA-IR is the only factor associated with the decline in HOMA-IR during and after therapy. The eradication of HCV infection was associated with improved insulin sensitivity among patients with pretreatment IR. This significant improvement in insulin sensitivity may occur as early as 12 weeks after the initiation of antiviral therapy.

Denervation of the renal arteries in metabolic syndrome: the DREAMS-study.

Chronic elevation of sympathetic nervous system is a key factor in metabolic syndrome. Because renal denervation (RDN) is thought to modulate sympathetic activity, we performed the Denervation of the Renal Arteries in Metabolic Syndrome (DREAMS)-study to investigate the effects of RDN on insulin sensitivity and blood pressure (BP) in patients with metabolic syndrome. Twenty-nine patients fulfilling the criteria for metabolic syndrome and who used a maximum of 1 antihypertensive or 1 antidiabetic drug or 1 of both gave informed consent and were treated by RDN. Glucose tolerance tests and 24-hour ambulatory BP measurements were performed at baseline, at 6 and 12 months of follow-up. Moreover, we performed self-monitored BP measurements at home every month. To assess sympathetic activity, we performed muscle sympathetic nerve activity and heart rate variability measurements at baseline and follow-up. The majority of the included patients was men (57%), mean body mass index was 31±5 kg/m(2). Median insulin sensitivity as assessed by the Simple Index assessing Insulin Sensitivity oral glucose tolerance test did not change at 6- and 12-month follow-up (P=0.60 and P=0.77, respectively). Mean 24-hour BP decreased by 6±12/5±7 mm Hg 12 months after RDN (P=0.04/0.01). However, self-monitored BP measurements data showed no reduction over time. Measurements of sympathetic activity showed no reduction in systemic sympathetic activity. In conclusion, RDN did not lead to a significant improvement of insulin sensitivity ≤12 months after treatment. Although a significant reduction in ambulatory BP was observed in this nearly drug-naïve population, the self-monitored BP measurements data suggest that this may be explained by regression to the mean. Moreover, no effect in systemic sympathetic activity was observed.

Metabolic and physiologic effects from consuming a hunter-gatherer (Paleolithic)-type diet in type 2 diabetes.

The contemporary American diet figures centrally in the pathogenesis of numerous chronic diseases--'diseases of civilization'--such as obesity and diabetes. We investigated in type 2 diabetes whether a diet similar to that consumed by our pre-agricultural hunter-gatherer ancestors ('Paleolithic' type diet) confers health benefits. We performed an outpatient, metabolically controlled diet study in type 2 diabetes patients. We compared the findings in 14 participants consuming a Paleo diet comprising lean meat, fruits, vegetables and nuts, and excluding added salt, and non-Paleolithic-type foods comprising cereal grains, dairy or legumes, with 10 participants on a diet based on recommendations by the American Diabetes Association (ADA) containing moderate salt intake, low-fat dairy, whole grains and legumes. There were three ramp-up diets for 7 days, then 14 days of the test diet. Outcomes included the following: mean arterial blood pressure; 24-h urine electrolytes; hemoglobin A1c and fructosamine levels; insulin resistance by euglycemic hyperinsulinemic clamp and lipid levels. Both groups had improvements in metabolic measures, but the Paleo diet group had greater benefits on glucose control and lipid profiles. Also, on the Paleo diet, the most insulin-resistant subjects had a significant improvement in insulin sensitivity (r = 0.40, P = 0.02), but no such effect was seen in the most insulin-resistant subjects on the ADA diet (r = 0.39, P = 0.3). Even short-term consumption of a Paleolithic-type diet improved glucose control and lipid profiles in people with type 2 diabetes compared with a conventional diet containing moderate salt intake, low-fat dairy, whole grains and legumes.

Effects of continuous positive airway pressure therapy on glycaemic control, insulin sensitivity and body mass index in patients with obstructive sleep apnoea and type 2 diabetes: a systematic review and meta-analysis.

Background:Evidence suggests that 15–30% of individuals with obstructive sleep apnoea (OSA) have type 2 diabetes mellitus (T2DM), and that OSA is an independent risk factor for T2DM. There is considerable interest in ascertaining whether OSA treatment improves glycaemic control and insulin sensitivity in patients with OSA and T2DM.Aims:To assess the effects of continuous positive airway pressure (CPAP) therapy on glycosylated haemoglobin (HbA1c) level, insulin sensitivity and body mass index (BMI) in patients with OSA and T2DM.Methods:MEDLINE, EMBASE and the Cochrane Library were searched to identify prospective studies involving patients with OSA and T2DM who had received CPAP, and data on primary outcome (change in HbA1c) and/or secondary outcomes (changes in insulin sensitivity and BMI) were reported. All relevant studies published before 31 January 2014 were included.Results:Six studies were included in the systematic review and meta-analysis. The numbers of patients ranged from 9 to 44 (total=128), and mean age ranged from 50.7 to 66.1 years. For the change in HbA1c (six studies, 128 patients), the combined standardised paired difference revealed no significant effect of CPAP (−0.071, 95% confidence interval (CI)=−0.245, 0.103; P=0.421). Similarly, there was no significant effect of CPAP on the change in BMI (−0.102, 95% CI=−0.296, 0.092; P=0.302; five studies, 103 patients). In contrast, there was a significant effect of CPAP on the change (improvement) in insulin sensitivity (0.330, 95% CI=0.001, 0.658; P=0.049; three studies, 39 patients).Conclusion:The limited available evidence from randomised controlled trials and prospective observational studies suggests that CPAP does not decrease HbA1c level or BMI in patients with OSA and T2DM but may improve insulin sensitivity.

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review.

To study the clinical efficacy and safety of Fecal microbiota transplantation (FMT). We systematically reviewed FMT used as clinical therapy. We searched MEDLINE, EMBASE, the Cochrane Library and Conference proceedings from inception to July, 2013. Treatment effect of FMT was calculated as the percentage of patients who achieved clinical improvement per patient category, on an intention-to-treat basis. We included 45 studies; 34 on Clostridium difficile-infection (CDI), 7 on inflammatory bowel disease, 1 on metabolic syndrome, 1 on constipation, 1 on pouchitis and 1 on irritable bowel syndrome (IBS). In CDI 90% resolution of diarrhea in 33 case series (n = 867) was reported, and 94% resolution of diarrhea after repeated FMT in a randomized controlled trial (RCT) (n = 16). In ulcerative colitis (UC) remission rates of 0% to 68% were found (n = 106). In Crohn's disease (CD) (n = 6), no benefit was observed. In IBS, 70% improvement of symptoms was found (n = 13). 100% Reversal of symptoms was observed in constipation (n = 3). In pouchitis, none of the patients (n = 8) achieved remission. One RCT showed significant improvement of insulin sensitivity in metabolic syndrome (n = 10). Serious adverse events were rare. FMT is highly effective in CDI, and holds promise in UC. As for CD, chronic constipation, pouchitis and IBS data are too limited to draw conclusions. FMT increases insulin sensitivity in metabolic syndrome.

Insights into the role of the microbiome in obesity and type 2 diabetes.

The worldwide prevalence of obesity and type 2 diabetes mellitus (T2DM) continues to rise at an alarming pace. Recently the potential role of the gut microbiome in these metabolic disorders has been identified. Obesity is associated with changes in the composition of the intestinal microbiota, and the obese microbiome seems to be more efficient in harvesting energy from the diet. Lean male donor fecal microbiota transplantation (FMT) in males with metabolic syndrome resulted in a significant improvement in insulin sensitivity in conjunction with an increased intestinal microbial diversity, including a distinct increase in butyrate-producing bacterial strains. Such differences in gut microbiota composition might function as early diagnostic markers for the development of T2DM in high-risk patients. Products of intestinal microbes such as butyrate may induce beneficial metabolic effects through enhancement of mitochondrial activity, prevention of metabolic endotoxemia, and activation of intestinal gluconeogenesis via different routes of gene expression and hormone regulation. Future research should focus on whether bacterial products (like butyrate) have the same effects as the intestinal bacteria that produce it, in order to ultimately pave the way for more successful interventions for obesity and T2DM. The rapid development of the currently available techniques, including use of fecal transplantations, has already shown promising results, so there is hope for novel therapies based on the microbiota in the future.