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2. The role of pioglitazone in the fight against insulin resistance, atherosclerosis, cardiovascular disease, and non-alcoholic fatty liver disease

Author

N. A. Petunina, E. V. Goncharova, I. A. Kuzina, L. V. Nedosugova, N. S. Martirosyan, and M. Е. Теlnova

Subjects
thiazolidinediones, glitazones, pioglitazone, insulin resistance, insulin signal transmission pathways, Nutritional diseases. Deficiency diseases, RC620-627
Abstract

Modern strategies for the treatment of type 2 diabetes mellitus involve the use of pathogenetically based approaches aimed at achieving optimal glycemic control and its long-term retention. Timely and rational use of 9 classes of hypoglycemic drugs, including as part of combination therapy, makes it possible to achieve significant success in diabetes therapy. One of the fundamental principles in the treatment of type 2 diabetes mellitus is the effect on insulin resistance. For this purpose, two groups of drugs are used: biguanides and thiazolidinediones (glitazones). The action of glitazones is directly related to an increase in the sensitivity of insulin-dependent tissues to insulin and a pronounced decrease in hyperinsulinemia in patients with type 2 diabetes. Of particular interest are the pathways of insulin signal transduction, the mechanisms of insulin resistance, and the possibilities of pathogenetic therapy with thiazolidinediones. Pioglitazone is currently the only available member of the thiazolidinedione class in the world, allowing to expand the management of diabetes mellitus by reducing insulin resistance in muscle and adipose tissue and glucose production by the liver. Its use can have a number of pleiotropic effects, including on cardiovascular diseases and non-alcoholic fatty liver disease, which expands the priorities for choosing hypoglycemic therapy in patients with type 2 diabetes at various stages of therapy.

Published
2022
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5. Individual serum saturated fatty acids and markers of chronic subclinical inflammation: the Insulin Resistance Atherosclerosis Study

Author

Ingrid D. Santaren, Steven M. Watkins, Angela D. Liese, Lynne E. Wagenknecht, Marian J. Rewers, Steven M. Haffner, Carlos Lorenzo, Andreas Festa, Richard P. Bazinet, and Anthony J. Hanley

Subjects
metabolic disease, epidemiology, diet and dietary lipids, cohort study, Biochemistry, QD415-436
Abstract

Recent evidence has documented distinct effects of individual saturated FAs (SFAs) on cardiometabolic outcomes, with potential protective effects from odd- and very long-chain SFAs (VLSFAs). Cross-sectional and prospective associations of individual serum SFAs (12:0, 14:0, 15:0, 16:0, 18:0, 20:0, 22:0, and total SFA) with proinflammatory biomarkers and adiponectin were investigated in 555 adults from the IRAS. Principal component analysis (PCA) of proinflammatory markers yielded three clusters: principal component (PC) 1: fibrinogen, white cell count, C-reactive protein; PC 2: plasminogen activator inhibitor-1 (PAI-1), TNF-α, IL-18; PC 3: IL-6 and IL-8. Cross-sectional analyses on proinflammatory PCs and adiponectin, and prospective analyses on 5 year PAI-1 and fibrinogen concentrations were conducted with multiple regression. Total SFA and 16:0 were positively associated with PC 1 and PC 2, and negatively associated with adiponectin. The 14:0 was positively associated with PC 1 and negatively associated with adiponectin. In contrast, 15:0, 20:0, and 22:0 were negatively associated with PC 2, and 20:0 and 22:0 were positively associated with adiponectin. The 18:0 was negatively associated with PC 3. Prospectively, 15:0, 18:0, 20:0, and 22:0 were negatively associated with 5 year PAI-1 concentrations. The results demonstrate that individual SFAs have distinct roles in subclinical inflammation, highlighting the unique metabolic impacts of individual SFAs.

Published
2017
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42. Intensity and amount of physical activity in relation to insulin sensitivity: the Insulin Resistance Atherosclerosis Study

Author

Mayer-Davis, Elizabeth J., D'Agostino, Ralph, Jr., Karter, Andrew J., Haffner, Steven M., Rewers, Marian J., Saad, Mohammed, and Bergman, Richard N.

Subjects
Insulin resistance -- Prevention, Exercise -- Physiological aspects
Abstract

Physical activity can improve insulin sensitivity to glucose, which could reduce the risk of non-insulin-dependent, or type 2, diabetes mellitus (NIDDM). Researchers estimated energy expenditure and gave glucose tolerance tests to 1,467 men and women, some of whom had mild NIDDM. Those who exercised five or more times a week had higher insulin sensitivity than those who did not. This was true of vigorous and non-vigorous activities. Many physicians recommend 30 minutes of activity every day of the week., Context.--Exercise training is associated with improved insulin sensitivity ([S.sub.I]), but the potential impact of habitual, nonvigorous activity is uncertain. Objective.--To determine whether habitual, nonvigorous physical activity, as well as vigorous and overall activity, is associated with better [S.sub.I]. Design.--A multicultural epidemiologic study. Setting.--The Insulin Resistance Atherosclerosis Study, conducted in Oakland, Calif; Los Angeles, Calif; the San Luis Valley, Colo; and San Antonio, Tex. Participants.--A total of 1467 men and women of African American, Hispanic, and non-Hispanic white ethnicity, aged 40 to 69 years, with glucose tolerance ranging from normal to mild non-insulin-dependent diabetes mellitus. Main Outcome Measure.--Insulin sensitivity as measured by an intravenous glucose tolerance test. Results.--The mean [S.sub.I] for individuals who participated in vigorous activity 5 or more times per week was 1.59 [min.sup.-1] [multiplied by] [micro][U.sup.-1] [multiplied by] [mL.sup.-1] [multiplied by] [10.sup.-4] (95% confidence interval [Cl], 1.39-1.79) compared with 0.90 (95% Cl, 0.83-0.97) for those who rarely or never participated in vigorous activity, after adjusting for potential confounders (P [is less than] .001). When habitual physical activity (estimated energy expenditure [EEE]) was assessed by 1-year recall of activities, the correlation coefficient between [S.sub.I] and total EEE was 0.14 (P [is less than] .001). After adjustment for confounders, vigorous and nonvigorous levels of EEE (metabolic equivalent levels [is greater than or equal to] 6.0 and [is less than] 6.0, respectively) were each positively and independently associated with [S.sub.I] (P [is less than or equal to] 5.01 for each). The association was attenuated after adjustment for the potential mediators, body mass index (a measure of weight in kilograms divided by the square of the height in meters), and waist-to-hip ratio. Results were similar for subgroups of sex, ethnicity, and diabetes. Conclusions.--Increased participation in nonvigorous as well as overall and vigorous physical activity was associated with significantly higher [S.sub.I]. These findings lend further support to current public health recommendations for increased moderate-intensity physical activity on most days. JAMA. 1998;279:669-674

Published
1998

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