PubMed · 12173921
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F John Service. How did we get here?. https://pubmed.ncbi.nlm.nih.gov/12173921/
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Glucocorticoids are known to increase blood glucose levels, and an impairment of glucose tolerance is a common side effect of glucocorticoid therapy and a central feature of Cushing's disease. A major pathophysiological event in this process is an increased glucose production of the liver on the basis of glucocorticoid-induced insulin resistance resulting in an increment in hepatic gluconeogenesis. Both, glucocorticoids and insulin are known to affect the expression of the two gluconeogenic key enzymes, phosphoenolpyruvate-carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). While glucocorticoids are known to stimulate the expression of the PEPCK- and G6Pase gene, insulin decreases hepatic glucose production through an inhibition of PEPCK- and G6Pase gene expression. Recently, considerable progress has been made in the understanding of the signal transduction involved in the glucocorticoid- and insulin-dependent regulation of hepatic gluconeogenesis. In this article, we will review the most recent advances and assemble the current knowledge into a clinically relevant pathophysiological model.
CONTEXT: Low-carbohydrate diets have been popularized without detailed evidence of their efficacy or safety. The literature has no clear consensus as to what amount of carbohydrates per day constitutes a low-carbohydrate diet. OBJECTIVE: To evaluate changes in weight, serum lipids, fasting serum glucose, and fasting serum insulin levels, and blood pressure among adults using low-carbohydrate diets in the outpatient setting. DATA SOURCES: We performed MEDLINE and bibliographic searches for English-language studies published between January 1, 1966, and February 15, 2003, with key words such as low carbohydrate, ketogenic, and diet. STUDY SELECTION: We included articles describing adult, outpatient recipients of low-carbohydrate diets of 4 days or more in duration and 500 kcal/d or more, and which reported both carbohydrate content and total calories consumed. Literature searches identified 2609 potentially relevant articles of low-carbohydrate diets. We included 107 articles describing 94 dietary interventions reporting data for 3268 participants; 663 participants received diets of 60 g/d or less of carbohydrates--of whom only 71 received 20 g/d or less of carbohydrates. Study variables (eg, number of participants, design of dietary evaluation), participant variables (eg, age, sex, baseline weight, fasting serum glucose level), diet variables (eg, carbohydrate content, caloric content, duration) were abstracted from each study. DATA EXTRACTION: Two authors independently reviewed articles meeting inclusion criteria and abstracted data onto pretested abstraction forms. DATA SYNTHESIS: The included studies were highly heterogeneous with respect to design, carbohydrate content (range, 0-901 g/d), total caloric content (range, 525-4629 kcal/d), diet duration (range, 4-365 days), and participant characteristics (eg, baseline weight range, 57-217 kg). No study evaluated diets of 60 g/d or less of carbohydrates in participants with a mean age older than 53.1 years. Only 5 studies (nonrandomized and no comparison groups) evaluated these diets for more than 90 days. Among obese patients, weight loss was associated with longer diet duration (P =.002), restriction of calorie intake (P =.03), but not with reduced carbohydrate content (P =.90). Low-carbohydrate diets had no significant adverse effect on serum lipid, fasting serum glucose, and fasting serum insulin levels, or blood pressure. CONCLUSIONS: There is insufficient evidence to make recommendations for or against the use of low-carbohydrate diets, particularly among participants older than age 50 years, for use longer than 90 days, or for diets of 20 g/d or less of carbohydrates. Among the published studies, participant weight loss while using low-carbohydrate diets was principally associated with decreased caloric intake and increased diet duration but not with reduced carbohydrate content.
Alterations in the intermediary metabolism respectively a "metabolic maladaptation" to the modern lifestyle represents an important risk factor for most chronic diseases, especially also for cardiovascular risk. An increased concentration of free fatty acids plays a central role in the pathophysiological sequence of events. Overweight and obesity represent one important cause for the increase in free fatty acids and are thus potentially preventable causes. It seems that the metabolic syndrome represents the result of our genetic predisposition as a response to the modern lifestyle characterized by physical inactivity and a increase in the duration of the postprandial status.