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Gabriele Forlani

Bio: Gabriele Forlani is an academic researcher from University of Bologna. The author has contributed to research in topics: Diabetes mellitus & Nonalcoholic fatty liver disease. The author has an hindex of 20, co-authored 37 publications receiving 7512 citations.

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Journal ArticleDOI
TL;DR: The presence of multiple metabolic disorders is associated with a potentially progressive, severe liver disease and the increasing prevalence of obesity, coupled with diabetes, dyslipidemia, hypertension, and ultimately the metabolic syndrome puts a very large population at risk of forthcoming liver failure in the next decades.

2,538 citations

Journal ArticleDOI
01 Aug 2001-Diabetes
TL;DR: It is concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity.
Abstract: Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU m(-2) min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2) Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs -84% in control subjects; P = 0003) Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs 84% in control subjects (P = 0002) Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance

2,367 citations

Journal ArticleDOI
TL;DR: Nonalcoholic fatty liver disease is associated with insulin resistance and hyperinsulinemia even in lean subjects with normal glucose tolerance, and genetic factors that reduce insulin sensitivity and increase serum triglyceride levels may be responsible for its development.

1,488 citations

Journal ArticleDOI
TL;DR: Liver disease of metabolic origin, associated with obesity, is now recognized as the most prevalent liver disease in Western countries and strategies are needed to approach obesity-associated liver disease by behavior programs, motivating people to adopt a healthier lifestyle.
Abstract: Context: In the last few years, several data have accumulated suggesting that obesity may be associated with liver disease and disease progression. Accordingly, the worldwide epidemic of obesity is likely to become a relevant source of morbidity and mortality in the general population. Evidence Acquisition: We reviewed the literature on two main issues: 1) the evidence that obesity carries out an increased risk of liver disease, both in the general population and in selected cohorts; and 2) the evidence that obesity is a risk factor for nonalcoholic fatty liver disease and its progression in a series observed in liver units. Evidence Synthesis: The presence of obesity increases the risk of elevated liver enzymes by a factor of two to three, whereas the risk of steatosis at ultrasonography is increased by a factor of 3 in the presence of overweight and peaks at a factor of approximately 15 in the presence of obesity. Both cirrhosis (cryptogenic cirrhosis) and hepatocellular carcinoma are also associated wi...

455 citations

Journal ArticleDOI
Olga Vaccaro1, Maria Masulli1, Antonio Nicolucci, Enzo Bonora  +375 moreInstitutions (19)
TL;DR: In this long-term, pragmatic trial, incidence of cardiovascular events was similar with sulfonylureas and pioglitazone as add-on treatments to metformin, although piog litazone was associated with fewer hypoglycaemia events.

212 citations


Cited by
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Paul Angulo1
TL;DR: Nonalcoholic fatty liver disease is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is present in up to one third of the general population and in the majority of patients with metabolic risk factors such as obesity and diabetes. Insulin resistance is a key pathogenic factor resulting in hepatic fat accumulation. Recent evidence demonstrates NAFLD in turn, exacerbates hepatic insulin resistance and often precedes glucose intolerance. Once hepatic steatosis is established, other factors including oxidative stress, mitochondrial dysfunction, gut-derived lipopolysaccharide and adipocytokines, may promote hepatocellular damage, inflammation and progressive liver disease. Confirmation of the diagnosis of NAFLD can usually be achieved by imaging studies, however staging the disease requires a liver biopsy. NAFLD is associated with an increased risk of all-cause death, probably because of complications of insulin resistance such as vascular disease, as well as due to cirrhosis and hepatocellular carcinoma, which occurs in a minority of patients. NAFLD is also now recognized to account for a substantial proportion of patients previously diagnosed with 'cryptogenic cirrhosis'. Diabetes, obesity and the necroinflammatory form of NAFLD known as non-alcoholic steatohepatitis, are risk factors for progressive liver disease. Current treatment relies on weight loss and exercise, although various insulin-sensitizing medications appear promising. Further research is needed to identify which patients will achieve the most benefit from therapy.

4,705 citations

Journal ArticleDOI
TL;DR: The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice and form the subject of this review.
Abstract: Lipid homeostasis in vertebrate cells is regulated by a family of membrane-bound transcription factors designated sterol regulatory element–binding proteins (SREBPs). SREBPs directly activate the expression of more than 30 genes dedicated to the synthesis and uptake of cholesterol, fatty acids, triglycerides, and phospholipids, as well as the NADPH cofactor required to synthesize these molecules (1–4). In the liver, three SREBPs regulate the production of lipids for export into the plasma as lipoproteins and into the bile as micelles. The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice. These studies form the subject of this review.

4,406 citations

Journal ArticleDOI
TL;DR: The present report has been written to focus attention on the issue and to urge policy-makers to consider taking action before it is too late.
Abstract: Ten per cent of the world’s school-aged children are estimated to be carrying excess body fat (Fig. 1), with an increased risk for developing chronic disease. Of these overweight children, a quarter are obese, with a significant likelihood of some having multiple risk factors for type 2 diabetes, heart disease and a variety of other co-morbidities before or during early adulthood. The prevalence of overweight is dramatically higher in economically developed regions, but is rising significantly in most parts of the world. In many countries the problem of childhood obesity is worsening at a dramatic rate. Surveys during the 1990s show that in Brazil and the USA, an additional 0.5% of the entire child population became overweight each year. In Canada, Australia and parts of Europe the rates were higher, with an additional 1% of all children becoming overweight each year. The burden upon the health services cannot yet be estimated. Although childhood obesity brings a number of additional problems in its train – hyperinsulinaemia, poor glucose tolerance and a raised risk of type 2 diabetes, hypertension, sleep apnoea, social exclusion and depression – the greatest health problems will be seen in the next generation of adults as the present childhood obesity epidemic passes through to adulthood. Greatly increased rates of heart disease, diabetes, certain cancers, gall bladder disease, osteoarthritis, endocrine disorders and other obesityrelated conditions will be found in young adult populations, and their need for medical treatment may last for their remaining life-times. The costs to the health services, the losses to society and the burdens carried by the individuals involved will be great. The present report has been written to focus attention on the issue and to urge policy-makers to consider taking action before it is too late. Specifically, the report:

3,953 citations