Cited by 431Diabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic DiseasesDiet, Metabolism, and Disease

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Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects.

Santomauro, A T, Boden, G, Silva, M E, Rocha, D M, Santos, R F, Ursich, M J, Strassmann, P G, Wajchenberg, B L·1999·Diabetes

DOI 10.2337/diabetes.48.9.1836

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Abstract

Obesity is commonly associated with elevated plasma free fatty acid (FFA) levels, as well as with insulin resistance and hyperinsulinemia, two important cardiovascular risk factors. What causes insulin resistance and hyperinsulinemia in obesity remains uncertain. Here, we have tested the hypothesis that FFAs are the link between obesity and insulin resistance/hyperinsulinemia and that, therefore, lowering of chronically elevated plasma FFA levels would improve insulin resistance/hyperinsulinemia and glucose tolerance in obese nondiabetic and diabetic subjects. Acipimox (250 mg), a long-acting antilipolytic drug, or placebo was given overnight (at 7:00 P.M., 1:00 A.M., 7:00 A.M.) to 9 lean control subjects, 13 obese nondiabetic subjects, 10 obese subjects with impaired glucose tolerance, and 11 patients with type 2 diabetes. Euglycemic-hyperinsulinemic clamps and oral glucose tolerance tests (75 g) were performed on separate mornings after overnight Acipimox or placebo treatment. In the three obese study groups, Acipimox lowered fasting levels of plasma FFAs (by 60-70%) and plasma insulin (by approximately 50%). Insulin-stimulated glucose uptake during euglycemic-hyperinsulinemic clamping was more than twofold higher after Acipimox than after placebo. Areas under the glucose and insulin curves during oral glucose tolerance testing were both approximately 30% lower after Acipimox administration than after placebo. We conclude that lowering of elevated plasma FFA levels can reduce insulin resistance/hyperinsulinemia and improve oral glucose tolerance in lean and obese nondiabetic subjects and in obese patients with type 2 diabetes.

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Insulin-mimetic compound hexaquis (benzylammonium) decavanadate is antilipolytic in human fat cells
Carpéné, C., García‐Vicente, S., Serrano, M., Marti, L., Belles, C., Royo, M., Galitzky, J., Zorzano, A., & Testar, X. (2017) · World Journal of Diabetes · doi:10.4239/wjd.v8.i4.143 · Cited by 26
“This adds an alternative to classical antilipolytic agents proposed to limit lipotoxicity, such as nicotinic acid (Acipimox) [12] , or lipase inhibitors [5] .”
Sleep Apnea and Metabolic Dysfunction: Cause or Co-Relation?
Aurora, R. N., & Punjabi, N. M. (2007) · Sleep Medicine Clinics · doi:10.1016/j.jsmc.2007.03.006 · Cited by 27
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“Pharmacological treatment with acipimox to reduce plasma FFAs improves insulin sensitivity in obese and diabetic subjects.(29) FFAs can directly induce insulin resistance in skeletal muscle, adipocytes and liver through increased production of fatty acid intermediates (diacylglyceride, ceramide, and long-chain acyl-Co…”
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“Therefore, a diminution of the lipid profile could improve insulin resistance [4,13–17] and possibly decrease the risk for diabetes.”
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“24 28-30 Together, these studies suggest a strong causal relationship between the elevation of FFA levels in obesity and metabolic dysfunction (Fig.”
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“Furthermore, lowering of fasting free fatty acids using acipimox over night improves insulin resistance acutely in humans [35].”
Background
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“[27] Santomauro AT, Boden G, Silva ME, et al.”
Background
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Background
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Background
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“ously as being effective in in vitro studies (27).”
Background
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Background
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Background
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Background
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Background
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Background
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Ichimori, S., Shimoda, S., Goto, R., Matsuo, Y., Maeda, T., Furukawa, N., Kawashima, J., Kodama, S., Sekigami, T., Isami, S., et al. (2011) · Journal of Diabetes Investigation · doi:10.1111/j.2040-1124.2011.00147.x · Cited by 15
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Telle‐Hansen, V. H., Narverud, I., Retterstøl, K., Wesseltoft-Rao, N., Mosdøl, A., Granlund, L., Christiansen, K. F., Lamglait, A., Halvorsen, B. L., Holven, K. B., et al. (2012) · Journal of Nutritional Science · doi:10.1017/jns.2012.18 · Cited by 15
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Background
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Background
GLUT4 expression in human muscle fibres is not correlated with intracellular triglyceride (TG) content. Is TG a maker or a marker of insulin resistance?
Gaster, M., Ottosen, P. D., Vach, W., CHRISTIANSEN, H., Stæhr, P., Beck‐Nielsen, H., & Schrøder, H. D. (2003) · Apmis · doi:10.1034/j.1600-0463.2003.1110207.x · Cited by 15
“(28) found that FFA accounted for the entire insulin resistance in obese non-diabetic subjects and about 50% of insulin resistance in obese with impaired glucose tolerance or type 2 diabetic subjects.”
BackgroundInfluential
Metabolic and Molecular Pathogenesis of Type 2 Diabetes Mellitus
DeFronzo, R. A., Mandarino, L. J., & Ferrannini, E. (2003) · Wiley eBooks · doi:10.1002/0470862092.d0310 · Cited by 15
Alterations in plasma non-esterified fatty acid (NEFA) kinetics and relationship with insulin resistance in polycystic ovary syndrome
Ezeh, U. I., Arzumanyan, Z., Lizneva, D., Mathur, R., Chen, Y., Boston, R. C., Chen, Y. I., & Azziz, R. (2018) · Human Reproduction · doi:10.1093/humrep/dey356 · Cited by 14
Coagulanolide modulates hepatic glucose metabolism in C57BL/KsJ- db/db mice
Singh, A. B., Singh, N., Akanksha, A., Jayendra, J., Maurya, R., & Srivastava, A. (2012) · Human & Experimental Toxicology · doi:10.1177/0960327112438289 · Cited by 14
“Therefore, a reduction in the circulating FFA and TGs would be expected to improve hyperglycemia and strengthen insulin response by suppressing glucose production while increasing glucose utilization.(27) The reesterification of FFA in adipocytes is defective in obese and diabetic patients, leading to increased circul…”
Background
Factors regulating subcutaneous adipose tissue storage, fibrosis, and inflammation may underlie low fatty acid mobilization in insulin-sensitive obese adults
Pelt, D. W. V., Pitchford, L. M., Wang, A. Y., & Horowitz, J. F. (2017) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00084.2017 · Cited by 15
“Conversely, drugs that lower systemic fatty acid availability in obese adults can reverse insulin resistance (3, 41).”
Background
Beneficial metabolic effects of nateglinide versus acarbose in patients with newly-diagnosed type 2 diabetes
Gao, H., Xie, C., Wang, H., Yu-jing, L. I. N., & Hong, T. (2007) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2007.00534.x · Cited by 13
Impact of Acipimox Therapy on Free Fatty Acid Efflux and Endothelial Function in the Metabolic Syndrome: A Randomized Trial
Aday, A. W., Goldfine, A. B., Gregory, J. M., & Beckman, J. A. (2019) · Obesity · doi:10.1002/oby.22602 · Cited by 13
“Acipimox acutely reduces FFA mobilization from adipose tissue and improves insulin sensitivity in individuals with type 2 diabetes mellitus (11,12).”
Background
Metabolic and Endocrine Consequences of Acute Suppression of FFAs by Acipimox in Polycystic Ovary Syndrome
Ciampelli, M., Muzj, G., Leoni, F., Romualdi, D., Belosi, C., Cento, R. M., & Lanzone, A. (2001) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.86.11.8060 · Cited by 12
“It could be hypothesized that this disagreement could be ascribed to different dosages or length of treatment; indeed, both the investigator groups (28, 29) chose an overnight FFA inhibition with a 3-fold administration of acipimox (250 mg orally) within a 12-h period, whereas in our study the same drug was administer…”
Result
The Effect of Long-Term Pharmacological Antilipolysis on Substrate Metabolism in Growth Hormone (GH)-Substituted GH-Deficient Adults
Nielsen, S., Møller, N., Pedersen, S. B., Christiansen, J. S., & Jørgensen, J. O. L. (2002) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.87.7.8597 · Cited by 13
Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat
Vickers, M. H., Hofman, P. L., Gluckman, P. D., Lobie, P. E., & Cutfield, W. S. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00614.2005 · Cited by 13
“Acipimox, a potent long-acting nicotinic acid derivative, lowers non-esterified fatty acids and triglyceride levels, reduces lipid oxidation rate and increases glucose oxidation rate (8; 25; 33).”
Background
Insulin's stimulation of endothelial superoxide generation may reflect up-regulation of isoprenyl transferase activity that promotes rac translocation
McCarty, M. F. (2002) · Medical Hypotheses · doi:10.1054/mehy.2001.1455 · Cited by 13
Modelling age-related metabolic disorders in the mouse
Goldsworthy, M. E., & Potter, P. K. (2014) · Mammalian Genome · doi:10.1007/s00335-014-9539-6 · Cited by 12
“Lowering FFA levels overnight normalises insulin sensitivity in obese non-diabetic individuals and significantly improves insulin sensitivity in obese diabetic patients (Santomauro et al. 1999).”
Background
Effect of augmented glycation in mobilization of plasma free fatty acids in type 2 diabetes mellitus
Chandra, K., Jain, V. K., Azhar, M., Khan, W., Alam, O., Ahmad, S., & Jain, S. K. (2020) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2020.07.028 · Cited by 11
Effects of acipimox on the lipolysis rate in subcutaneous adipose tissue of obese subjects
Flechtner‐Mors, M., Jenkinson, C. P., Alt, A., Adler, G., & Ditschuneit, H. H. M. (2001) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.219 · Cited by 11
“Furthermore, NEFA are involved in the regulation of whole-body glucose uptake [6] and elevated NEFA concentrations may contribute to insulin resistance [7].”
Background
Plasma free fatty acids do not provide the link between obesity and insulin resistance or β‐cell dysfunction: results of the Reading, Imperial, Surrey, Cambridge, Kings ( RISCK ) study
Johns, I., Goff, L. M., Bluck, L. J. C., Griffin, B. A., Jebb, S. A., Lovegrove, J. A., Sanders, T. A. B., Frost, G. S., & Dornhorst, A. (2014) · Diabetic Medicine · doi:10.1111/dme.12550 · Cited by 11
Toxicity and Safety Concerns in Orlistat Therapy for Obesity: A Critical Evaluation
Nwobodo, N. N. (2015) · Asian journal of biomedical and pharmaceutical sciences · doi:10.15272/ajbps.v5i47.725 · Cited by 11
Hepatothermic therapy of obesity: rationale and an inventory of resources
McCarty, M. F. (2001) · Medical Hypotheses · doi:10.1054/mehy.2000.1322 · Cited by 11
Association of endotoxaemia with serum free fatty acids in metabolically healthy and unhealthy abdominally obese individuals: a case–control study in northwest of Iran
Saghafi‐Asl, M., Amiri, P., Naghizadeh, M., Ghavami, S. M., & Karamzad, N. (2017) · BMJ Open · doi:10.1136/bmjopen-2017-015910 · Cited by 10
Acute reduction of lipolysis reduces adiponectin and IL-18: evidence from an intervention study with acipimox and insulin
Lindegaard, B., Ditlevsen, S., Plomgaard, P., Mittendorfer, B., & Pedersen, B. K. (2013) · Diabetologia · doi:10.1007/s00125-013-2964-3 · Cited by 10
“The timing of acipimox treatment and the euglycaemic clamp in relation to fasting was chosen according to previous studies [24, 25].”
Method
Relationship between plasma 12,13-diHOME level and nonalcoholic fatty liver disease in patients with type 2 diabetes and obesity
Wang, S., Sun, W., Cheng, Y., Wang, L., Ma, S., Jing, F., Zhang, X., & Zhou, X. (2021) · Minerva Endocrinology · doi:10.23736/s2724-6507.21.03424-6 · Cited by 12
Free Fatty Acid Impairs Myogenic Differentiation through the AMPK α -MicroRNA 206 Pathway
Jiang, A., Guo, H., Zhang, L., Jiang, X., Zhang, X., Wu, W., & Liu, H. (2021) · Molecular and Cellular Biology · doi:10.1128/mcb.00327-21 · Cited by 10
The eSS rat, a nonobese model of disordered glucose and lipid metabolism and fatty liver
Daniele, S. M., Montenegro, S. M., Tarrés, M. C., Picena, J. C., & Martínez, S. M. (2010) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-2-15 · Cited by 9
“Because elevated plasmatic NEFA levels has been implied as a causative factor of insulin resistance by interfering with glucose cellular uptake and by stimulating the hepatic neoglucogenesis [18,19], attention should be exerted in the elevated NEFA concentrations verified in eSS rats.”
Background
Acetogenic fibers reduce fasting glucose turnover but not peripheral insulin resistance in metabolic syndrome patients
Pouteau, E. B., Ferchaud‐Roucher, V., Zaïr, Y., Paintin, M., Enslen, M., Auriou, N., Macé, K., Godin, J., Ballèvre, O. P., & Krempf, M. (2010) · Clinical Nutrition · doi:10.1016/j.clnu.2010.05.006 · Cited by 10
A pilot study of the long-term effects of acipimox in polycystic ovarian syndrome
Ciampelli, M., Leoni, F., Lattanzi, F., Guido, M., Apa, R., & Lanzone, A. (2002) · Human Reproduction · doi:10.1093/humrep/17.3.647 · Cited by 9
Acipimox attenuates atherosclerosis and enhances plaque stability in ApoE-deficient mice fed a palmitate-rich diet
Jin, F., Jiang, S., Yang, D., Zhang, X., Yang, Y. C., Zhang, Y., Li, K., Yang, Y., & Ma, S. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.10.011 · Cited by 9
Impact of Sleep and Circadian Disturbances on Glucose Metabolism and Type 2 Diabetes
Reutrakul, S., Punjabi, N. M., & Cauter, E. V. (2018) · Cited by 9
Fat Metabolism and Diabetes: 2003 American Diabetes Association Postgraduate Course
Bloomgarden, Z. T. (2003) · Diabetes Care · doi:10.2337/diacare.26.7.2198 · Cited by 9
“In contrast, overnight FFA lowering using the drug acipimox increases peripheral glucose uptake in lean and obese individuals without diabetes, as well as in persons with IGT and with diabetes, although the latter groups remain insulin resistant (37).”
Background
Chronic intestinal electrical stimulation improves glucose intolerance and insulin resistance in diet‐induced obesity rats
Li, S., Zhu, W., Zhang, S., & Chen, J. D. Z. (2017) · Obesity · doi:10.1002/oby.21852 · Cited by 9
“well as subjects with obesity, was reported to improve insulin sensitivity (32,33).”
Background
Acipimox Acutely Increases GLP-1 Concentrations in Overweight Subjects and Hypopituitary Patients
Vestergaard, E. T., Hjelholt, A. J., Kuhre, R. E., Møller, N., Larraufie, P., Gribble, F. M., Reimann, F. M., Jessen, N., Holst, J. J., & Jørgensen, J. O. L. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-02503 · Cited by 9
“Grants and fellowships: The study was supported by a postdoctoral research fellow grant (11-105283) from the Danish Council for Independent Research (Medical Sciences) and grants from the Riisfort Fonden, and the A.”
Background
A shift in myocardial substrate, improved endothelial function, and diminished sympathetic activity may contribute to the anti-anginal impact of very-low-fat diets
McCarty, M. F. (2003) · Medical Hypotheses · doi:10.1016/s0306-9877(03)00232-9 · Cited by 9
Free Fatty Acids, A Major Link Between Obesity, Insulin Resistance, Inflammation, and Atherosclerotic Vascular Disease
Boden, G. H. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-141-3_4 · Cited by 8
Self-citation
Combined effects of moderate exercise and short-term fasting on markers of immune function in healthy human subjects
Mooren, F. C., Krueger, K., Ringseis, R., Eder, K., Liebisch, G., Conrad, K. D., Alack, K., & Maleki, B. H. (2020) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00341.2019 · Cited by 10
The metabolic syndrome: evolving evidence that thiazolidinediones provide rational therapy
Wyne, K. L. (2006) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2005.00522.x · Cited by 8
Concepts of Insulin Resistance
Bloomgarden, Z. T. (2005) · Metabolic Syndrome and Related Disorders · doi:10.1089/met.2005.3.284 · Cited by 8
“Determinants of postprandial lipemia include the amount of dietary fat and endogenous triglyceride production as well as the rates of triglyceride-rich lipoproteins.”

Authors: Santomauro, A. T., Boden, G., Silva, M. E., Rocha, D. M., Santos, R. F., Ursich, M. J., Strassmann, P. G., & Wajchenberg, B. L.
Affiliations: Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo (BR)
ORCID: Silva, M E
Rocha, D M
Santos, R F
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1999-09-01
Volume: 48
Issue: 9
Pages: 1836-1841
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.48.9.1836
OpenAlex: W2007405015
Cited by: 431
References: 0
Citations by year: 2026: 3 · 2025: 5 · 2024: 7 · 2023: 9 · 2022: 7 · 2021: 11 · 2020: 20 · 2019: 10 · 2018: 17 · 2017: 18 · 2016: 10 · 2015: 17 · 2014: 18 · 2013: 20 · 2012: 24
FWCI: 9.91
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ag007988-10, 5r01aa010221-03)
National Institute on Alcohol Abuse and Alcoholism (R01-AA-10221)
National Institute on Aging (R01-AG07988)
National Center for Research Resources (M01RR000349, RR-00349)
Topics: Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
Keywords: acipimox, free fatty acids, insulin resistance, hyperinsulinemia, glucose tolerance, obesity, type 2 diabetes, impaired glucose tolerance, insulin-stimulated glucose uptake, hyperinsulinemic-euglycemic clamp, oral glucose tolerance test
MeSH terms: Adult, Hypolipidemic Agents, Basal Metabolism, Diabetes Mellitus, Fatty Acids, Nonesterified, Female, Glucose Tolerance Test, Humans, Insulin Resistance, Male, Obesity, Oxidation-Reduction, Pyrazines, Glucose Clamp Technique

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Overnight lowering of free fatty acids with Acipimox improves insulin resistance and glucose tolerance in obese diabetic and nondiabetic subjects.

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