Sanofi - Discussing diabetes to better manage highs and lows
Although essential phospholipids EPL from soybean are often used in membrane-associated disorders and diseases, their high quality of purification and effects on prevalent liver diseases, especially on fatty liver diseases FLDs of different origin, are still widely unknown and a matter of continuous active research. Database research was carried out on Medline, Embase, Cochrane Library, country-specific journals, and follow-up literature citations Essentiale bei Diabetes relevant Essentiale bei Diabetes articles published between and EPL has a well-established mode of action, therapeutic effectiveness, and lack of toxicity, which ensures clinically relevant efficacy-to-safety ratio.
It influences membrane- dependent cellular functions and shows anti-inflammatory, antioxidant, antifibrogenic, anti apoptotic, membrane-protective, and lipid-regulating effects. Due to its positive effects on Essentiale bei Diabetes composition and functions, it accelerates the improvement or normalization of subjective symptoms; pathological, clinical, and Essentiale bei Diabetes findings; hepatic imaging; and liver histology. It is justified to administer EPL together with other therapeutic measurements in the liver.
Nonalcoholic fatty liver disease NAFLD and alcoholic liver disease ALD are one and the same fatty liver disease FLD with an underlying multicausal origin, such as obesity, alcohol drinking, and diabetes mellitus, 1 which are important public health problems, for which an established therapy Essentiale bei Diabetes not yet available. This is a medical challenge as progressive course from simple steatosis to steatohepatitis and possible cirrhosis with Essentiale bei Diabetes of liver cancer is known.
Diet and physical exercise are recommended as a basic universal approach. Some pharmacological agents show promising results, although on the basis of recent clinical trials no firm conclusions can yet be drawn. Phospholipids Essentiale bei Diabetes known to form the double layer of cellular and subcellular membranes and precondition their fluidity and biological activity.
The efficacy of EPL in the therapy of liver Essentiale bei Diabetes is confirmed not only by the ability of DLPC to be incorporated into damaged sections of membranes, Essentiale bei Diabetes improves hepatic regeneration and replaces endogenous, less unsaturated PC molecules but also by its ability to increase membrane fluidity and functioning.
With regard to in vitro and animal investigations, EPL influences membrane-dependent cellular functions and shows antioxidant, anti-inflammatory, antifibrotic, apoptosis-modulating, regenerative, membrane-repairing and -protective, cell-signaling and receptor-influencing, and lipid-regulating effects.
In a two-step process, we first used combinations of keywords including NAFLD, ALD, essentiale, ESLs, polyenylphosphatidylcholine, polyene phosphatidylcholine, dilinoleoylphosphatidylcholine, phosphatidylcholine, and therapy. Studies with less purified PC from soybean or with PC from other provenience were excluded. All papers that were reported in different languages other than English were completely Essentiale bei Diabetes into English. Of the 83 clinical studies in total, 25 representative ones regarding the causes of FLD, study design, and investigated variables were selected, including one case report study and seven double-blind studies Table 1.
Twenty-eight, mostly randomized studies, were open controlled and three double-blind. Dosage of EPL and treatment duration varied as a rule between 1. Therapy started in some studies with —1, mg EPL iv over 10 days to 4 weeks, before continuing with oral EPL administration; one study was done with mg EPL iv Essentiale bei Diabetes 30 days only.
According to the available studies, analysis of subjective symptoms, clinical findings, biochemical and imaging data, and histology was possible. In the first clinical study from Japan, six nonalcoholic and nondiabetic patients with fatty liver due to obesity were successfully treated with a low-calorie diet, physical exercise, and 1.
Cairella et al 10 from Italy evaluated the efficacy of EPL in therapy of hepatobiliary dysfunction when administering 1. The study group and control comprised 20 cases each with a body mass index of In the EPL group, the ultrasonographic picture clearly improved in 14 and normalized in six cases, while it only slightly changed in three cases of the control group. Koga et al 11 confirmed the continuous, EPL-induced improvement or normalization of the ultrasonic picture in 39 patients with fatty liver due to obesity.
Bright liver was reduced, and decrement of backward echocardiogram and the obscurity of the intrahepatic venogram were decreased. Ina randomized double-blind study by Li et al 12 reported about the positive influence of 1.
Experience with EPL in patients suffering from maturity- onset diabetes mellitus and fatty liver started with a randomized, placebo-controlled double-blind study. There were five patients in the placebo and seven patients in the EPL group who were treated with 1.
Half of the patients were additionally given 1. During the 6-month treatment phase, liver size hardly changed in the patients of the placebo group, but there was a significant reduction in liver size in the EPL group. The histological examination of the liver biopsy yielded corresponding results: marked improvement was observed in four patients treated with EPL and only in one patient of the placebo group.
Although no fatty infiltration was seen in the posttreatment liver biopsy of this patient, he developed the feature of progression to cirrhosis. Also in one patient treated with EPL, whose fatty infiltration was more pronounced at the second biopsy, morphological features of developing discrete fibrosis in portal tract were observed. Altogether, there were seven patients in the EPL group and four under placebo including the patient with developing cirrhosis, whose steatosis improved histologically during the study.
Additionally, y-GT was Essentiale bei Diabetes lowered after 1 month, 3 months, and 6 months of EPL therapy, whereas in the control group, the deviations were not statistically significant. Transaminases and bilirubin were within normal range throughout the study. Since this double-blind trial, seven further clinical studies confirmed the influence of EPL on diabetes mellitus-associated fatty liver. Alanine aminotransferase ALTserum TC, and TG, low-density lipoprotein- and high-density lipoprotein-cholesterol had significantly improved or normalized within the Essentiale bei Diabetes group, the lipid variables also between the groups.
The improvements were seen in Fasting blood sugar values improved in both groups, but the difference between Essentiale bei Diabetes groups was not significant. Twenty-two patients from the study of Poongothai et al 15 received, besides a standard diet, antidiabetics depending on the severity of the glycemic level: EPL 2.
Ultrasonographic improvement was seen in Transaminases and y-GT improved too. Ohbayashi et al 16 treated a female patient with NASH with nateglinide as insulin secretagogue for 7 months, followed by an additional 1. The Homeostasis Model Assessment, an index of insulin resistance normalized, same as hepatorenal echo contrast, transaminases, y-GT, and ferritin.
The beneficial effect continued over the 24 months of study. During the last 8 years, three studies investigated the combination of metformin and EPL on patients with diabetes, and the authors observed the same positive effects on aspartate aminotransferase, y-GT, blood lipids, and ultrasonic Essentiale bei Diabetes. Besides the abovementioned study, Ohbayashi 20 and Ohbayashi et al 21 confirmed with further 18 and eight patients with NASH that long-term administration of EPL continues to improve hepatic function until completion of the study.
First, significantly decreased transaminase levels were seen within 4-week treatment and continued over a month therapy. The randomized, open controlled studies compared EPL to Gynostemma pentaphyllum gypenosides, to an extract from red yeast rice Xuezhikang; each capsule contains 2. Compared to the gypenosides of G. EPL showed obvious effects in However, EPL was more effective on serum lipid levels and fatty liver severity than diammonium glycyrrhizinate.
Especially, the proportion of serious fatty liver changed significantly in the EPL group from 23 to nine patients versus 15 to 12 patients in the control group. The abovementioned randomized, open controlled studies 22 — 25 are added by a double-blind one, which compared 3-month therapy of 1. Patients with cardiovascular disease, liver disease other than hepatosteatosis, complications of diabetes including ketoacidosis, pregnant and lactating women, and patients with a history of alcohol consumption were Essentiale bei Diabetes from the study.
Intake of all other medications was stopped during the evaluation period. There were no major differences in the response of the diabetic and obese subgroups. Twelve, partly randomized studies were open controlled, one single-blind, and two double-blind.
In most studies, patients were advised to stop alcohol Essentiale bei Diabetes during the observation period. With the exception of two clinical trials for more details see laterdosage of EPL Essentiale bei Diabetes 1. All studies compared the effects to placebo. Two studies were in the frame of our database research, 3031 two were older, 3233 and in two studies patients suffered from NAFLD. Only one study reported on mortality rate, which was A meta-analysis of the four studies showed an efficacy rate of Additionally, a total of patients in three trials could be included for analysis of histology.
Serious adverse events were not reported in the six studies. The randomized, prospective double-blind trials from Panos et al 30 and Lieber et al 31 were both performed according to Good Clinical Practice and differed from the older double-blind studies 3233 by the attempt to increase the efficacy of EPL by increasing dosage and duration of treatment.
In the study by Panos et al, 30 53 patients received 6 g EPL daily and 51 patients a corresponding placebo over a period of 2 years.
Patients with Child Pugh B score usually carry a higher death risk than those in classification Essentiale bei Diabetes. The mean survival in this subgroup was Two-year biopsy was completed in patients. Accordingly, there was Essentiale bei Diabetes more progression of the fibrosis and therefore no way to test whether EPL could oppose such a progression except in a subgroup of patients who were still consuming six or more drinks a day and showed beneficial effects against Essentiale bei Diabetes.
Ascites, an important secondary clinical measure of liver disease, was also less frequently observed during follow-up of EPL-treated patients. Furthermore, improvements in aminotransferases Essentiale bei Diabetes bilirubin favoring EPL were seen at some time points in the subgroups of drinkers who were positive for hepatitis C virus and in nondrinkers. In a randomized single-blind clinical study from Sas et al, 35 86 patients with uncomplicated ALD were adequately controlled by diet and abstinent from alcohol and followed a basic treatment scheme, including diet, physical regimen, and abstinence from alcohol.
Fifty-six of these patients were additionally treated with 1. Basic treatment plus vitamin E led to less reduction of transaminase levels than basic treatment plus EPL. Essentiale bei Diabetes, the mean value of disease activity Essentiale bei Diabetes by Metavir scale was after treatment A1 mild activity in the EPL group and A3 severe activity in the control group.
Ultrasound studies revealed significant improvement in the hepatic echo-structure in 49 of the 56 patients of the investigational group. Essentiale bei Diabetes biopsy and Fibromax test showed that the additional EPL administration significantly slowed the progress of hepatic fibrosis to F1 portal fibrosis without septa versus F3 numerous septa without cirrhosis in the control group. Steatosis significantly increased in the vitamin E group and decreased in the EPL group. Additionally, the authors reported about significant reduction of glucose, insulin levels, and insulin resistance index.
Not much therapeutic options for NAFLD are accepted Essentiale bei Diabetes today besides correction of obesity with hypocaloric diets and physical exercise and controlling hyperglycemia with diet, insulin, or oral hypoglycemic agents.
Therefore, any therapeutic intervention that targets fat accumulation in the liver and ameliorates hepatic histology would be of great benefit.
EPL is able to re-improve this disturbed ratio. As mentioned, besides low-calorie diets and physical loads, therapy of NAFLD should be directed at treating components of metabolic syndrome, which may be additionally Essentiale bei Diabetes for the liver.
However, clinically EPL is not as well investigated as pharmacologically. Though the authors found four double-blind and one single-blinded studies for analysis, two are older ones and two were done with significantly higher doses than recommended in the marketed form. Apart Essentiale bei Diabetes that, it Essentiale bei Diabetes been shown that the compliance of patients with ALD can be increased by a good intervention approach, which leads to alcohol abstinence or at least clear reduction of the alcohol consumption, with corresponding improvements of the hepatic status.
As there was a trend for higher survival of the patients with acute alcoholic hepatitis under EPL, especially of those with Child Pugh B disease severity, 30 a further promising double-blind study is recommended with such patients Essentiale bei Diabetes this time with a lower daily dosage of EPL and a shorter duration of treatment, for example, with 1.
The slower progression rate was supposed to be related to the reduction in drinking that occurred. Therefore, most patients did not meet the protocol entry definition of heavy drinking six or Essentiale bei Diabetes drinks per day during Essentiale bei Diabetes follow-up.
A second drawback was that more than double the rate of Essentiale bei Diabetes anticipated in the sample size adjustment withdrew or were lost to follow-up before the month biopsy. On the other hand, most of the analyzed clinical studies on EPL in NAFLD and ALD have their shortcomings: too low number of patients, incomplete methodological description including unclear statistical evaluation, varying dosages of EPL, data published in secondary papers, or others.
Therefore, further randomized double-blind clinical studies with higher number of patients and of comparable histology or imaging status are necessary to regard the administration of EPL as a standard treatment.