Skip to main content
Top
Published in: Current Diabetes Reports 3/2013

01-06-2013 | Macrovascular Complications in Diabetes (PD Reaven, Section Editor)

Do Statins Cause Diabetes?

Authors: Mark R. Goldstein, Luca Mascitelli

Published in: Current Diabetes Reports | Issue 3/2013

Login to get access

Abstract

A wealth of evidence has established that cholesterol-lowering statin drugs, widely used for the prevention of cardiovascular disease, do increase the risk of new-onset diabetes, possibly by impairing pancreatic beta cell function and decreasing peripheral insulin sensitivity. Groups at particular risk include the elderly, women, and Asians. The diabetogenic effect of statins appear directly related to statin dose and the degree of attained cholesterol lowering. Statins can cause hyperinsulinemia even in the absence of hyperglycemia and the potential mitogenic effects and implications of prolonged hyperinsulinemia are discussed. Suggestions are made as to how physicians might avert the hyperinsulinemic and diabetogenic effects of statin therapy in clinical practice, and modulate the detrimental effects of these drugs on exercise performance. Finally, long-term studies are needed to determine if the deleterious hyperinsulinemic and diabetogenic effects of statin therapy undermine the beneficial cardiovascular disease risk outcomes in various segments of the population.
Literature
1.
go back to reference Gotto AM, Moon JE. Management of cardiovascular risk: the importance of meeting lipid targets. Am J Cardiol. 2012;110(Suppl):3A–14A.PubMedCrossRef Gotto AM, Moon JE. Management of cardiovascular risk: the importance of meeting lipid targets. Am J Cardiol. 2012;110(Suppl):3A–14A.PubMedCrossRef
2.
go back to reference Metz SA, Rabaglia ME, Stock JB, Kowluru A. Modulation of insulin secretion from normal rat islets by inhibitors of the post-translational modifications of GTP-binding proteins. Biochem J. 1993;295:31–40.PubMed Metz SA, Rabaglia ME, Stock JB, Kowluru A. Modulation of insulin secretion from normal rat islets by inhibitors of the post-translational modifications of GTP-binding proteins. Biochem J. 1993;295:31–40.PubMed
3.
go back to reference Ohrvall M, Lithell H, Johansson J, Vessby B. A comparison between the effects of gemfibrozil and simvastatin on insulin sensitivity in patients with noninsulin dependent diabetes mellitus and hyperlipoproteinemia. Metabolism. 1995;44:212–7.PubMedCrossRef Ohrvall M, Lithell H, Johansson J, Vessby B. A comparison between the effects of gemfibrozil and simvastatin on insulin sensitivity in patients with noninsulin dependent diabetes mellitus and hyperlipoproteinemia. Metabolism. 1995;44:212–7.PubMedCrossRef
4.
go back to reference Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, et al. For the JUPITER Study Group. N Engl J Med. 2008;359:2195–207. Ridker PM, Danielson E, Fonseca FAH, Genest J, Gotto AM, Kastelein JJP, et al. For the JUPITER Study Group. N Engl J Med. 2008;359:2195–207.
5.
go back to reference Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380:565–71.PubMedCrossRef Ridker PM, Pradhan A, MacFadyen JG, Libby P, Glynn RJ. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. Lancet. 2012;380:565–71.PubMedCrossRef
6.
go back to reference Steinberg D. Earlier intervention in the management of hypercholesterolemia: what are we waiting for? J Am Coll Cardiol. 2010;56:627–9.PubMedCrossRef Steinberg D. Earlier intervention in the management of hypercholesterolemia: what are we waiting for? J Am Coll Cardiol. 2010;56:627–9.PubMedCrossRef
7.
go back to reference Pletcher MJ, Hulley SB. Statin therapy in young adults: ready for prime time? J Am Coll Cardiol. 2010;56:637–40.PubMedCrossRef Pletcher MJ, Hulley SB. Statin therapy in young adults: ready for prime time? J Am Coll Cardiol. 2010;56:637–40.PubMedCrossRef
8.
go back to reference Petersen LK, Christensen K, Kragstrup J. Lipid-lowering treatment to the end? A review of observational studies and RCTs on cholesterol and mortality in 80+-year olds. Age Aging. 2010;39:674–80.CrossRef Petersen LK, Christensen K, Kragstrup J. Lipid-lowering treatment to the end? A review of observational studies and RCTs on cholesterol and mortality in 80+-year olds. Age Aging. 2010;39:674–80.CrossRef
9.
go back to reference Simons LA, Simons J, Friedlander Y, McCallum J. Predictors of long-term mortality in the elderly: the Dubbo Study. Intern Med J. 2011;41:555–60.PubMedCrossRef Simons LA, Simons J, Friedlander Y, McCallum J. Predictors of long-term mortality in the elderly: the Dubbo Study. Intern Med J. 2011;41:555–60.PubMedCrossRef
10.
go back to reference Carter BL, Einhorn PT, Brands M, He J, Cutler JA, Whelton PK, et al. Thiazide-induced dysglycemia: call for research from a working group from the National Heart, Lung, and Blood Pressure Institute. Hypertension. 2008;52:30–6. Carter BL, Einhorn PT, Brands M, He J, Cutler JA, Whelton PK, et al. Thiazide-induced dysglycemia: call for research from a working group from the National Heart, Lung, and Blood Pressure Institute. Hypertension. 2008;52:30–6.
11.
go back to reference Goldberg RB, Jacabson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc. 2008;83:470–8.PubMedCrossRef Goldberg RB, Jacabson TA. Effects of niacin on glucose control in patients with dyslipidemia. Mayo Clin Proc. 2008;83:470–8.PubMedCrossRef
12.
go back to reference Cooper-DeHoff RM, Pacanowski MA, Pepine CJ. Cardiovascular therapies and associated glucose homeostasis: implications across the dysglycemia continuum. J Am Coll Cardiol. 2009;53:S28–34.PubMedCrossRef Cooper-DeHoff RM, Pacanowski MA, Pepine CJ. Cardiovascular therapies and associated glucose homeostasis: implications across the dysglycemia continuum. J Am Coll Cardiol. 2009;53:S28–34.PubMedCrossRef
13.
go back to reference Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet. 2011;378:169–81.PubMedCrossRef Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet. 2011;378:169–81.PubMedCrossRef
14.
go back to reference Mascitelli L, Goldstein MR. Long-standing statin therapy and the risk of new-onset diabetes in the elderly: collateral damage caused by preventive medicine? Drugs Aging. 2010;29:9–13.CrossRef Mascitelli L, Goldstein MR. Long-standing statin therapy and the risk of new-onset diabetes in the elderly: collateral damage caused by preventive medicine? Drugs Aging. 2010;29:9–13.CrossRef
15.
go back to reference •• Campbell PT, Jacobs EJ, Newton CC, Gapstur SM, Patel AV. Diabetes and cause-specific mortality in a prospective cohort of one million U.S. adults. Diabetes Care. 2012;35:1835–44. This very large 26-year observational study shows that diabetes is associated with an increased mortality from a variety of cancers in both men and women.PubMedCrossRef •• Campbell PT, Jacobs EJ, Newton CC, Gapstur SM, Patel AV. Diabetes and cause-specific mortality in a prospective cohort of one million U.S. adults. Diabetes Care. 2012;35:1835–44. This very large 26-year observational study shows that diabetes is associated with an increased mortality from a variety of cancers in both men and women.PubMedCrossRef
16.
go back to reference Barone BB, Yeh H-C, Snyder CF, Peairs KS, Stein KB, Derr RL, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA. 2008;300:2754–64. Barone BB, Yeh H-C, Snyder CF, Peairs KS, Stein KB, Derr RL, et al. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA. 2008;300:2754–64.
17.
go back to reference Freeman DJ, Norrie J, Sattar N, Neely DG, Cobbe SM, Ford I, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001;103:357–62. Freeman DJ, Norrie J, Sattar N, Neely DG, Cobbe SM, Ford I, et al. Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation. 2001;103:357–62.
18.
go back to reference Keech A, Hague W, Colquhoun D, Beller E, Best J, Arulchelvam M, et al. For the LIPID Study Group. Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial. Diabetes Care. 2003;26:2713–21. Keech A, Hague W, Colquhoun D, Beller E, Best J, Arulchelvam M, et al. For the LIPID Study Group. Secondary prevention of cardiovascular events with long-term pravastatin in patients with diabetes or impaired fasting glucose: results from the LIPID trial. Diabetes Care. 2003;26:2713–21.
19.
go back to reference Shepherd J, Blauw MB, Murphy MB, Bollen ELEM, Buckley BM, Cobbe SM, et al. On behalf of the PROSPER Study Group. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomized controlled trial. Lancet. 2002;360:1623–30. Shepherd J, Blauw MB, Murphy MB, Bollen ELEM, Buckley BM, Cobbe SM, et al. On behalf of the PROSPER Study Group. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomized controlled trial. Lancet. 2002;360:1623–30.
20.
go back to reference Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet. 2010;375:735–42. Sattar N, Preiss D, Murray HM, Welsh P, Buckley BM, de Craen AJM, et al. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. Lancet. 2010;375:735–42.
21.
go back to reference •• Mora S, Glynn RJ, Hsia J, MacFadyen JG, Genest J, Ridker PM. Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia: results from the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) and meta-analysis of women from primary prevention trials. Circulation. 2010;121:1069–77. This post-hoc analysis of the JUPITER trial is notable for the women in the rosuvastatin group exhibiting a significant absolute increase in new-onset diabetes equal to the absolute decrease in the composite primary endpoint of cardiovascular disease events. •• Mora S, Glynn RJ, Hsia J, MacFadyen JG, Genest J, Ridker PM. Statins for the primary prevention of cardiovascular events in women with elevated high-sensitivity C-reactive protein or dyslipidemia: results from the Justification for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) and meta-analysis of women from primary prevention trials. Circulation. 2010;121:1069–77. This post-hoc analysis of the JUPITER trial is notable for the women in the rosuvastatin group exhibiting a significant absolute increase in new-onset diabetes equal to the absolute decrease in the composite primary endpoint of cardiovascular disease events.
22.
go back to reference Fugh-Berman A. Rosuvastatin in patients with elevated C-reactive protein. N Engl J Med. 2009;360:1038–9.PubMedCrossRef Fugh-Berman A. Rosuvastatin in patients with elevated C-reactive protein. N Engl J Med. 2009;360:1038–9.PubMedCrossRef
24.
go back to reference Chan JCN, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon K-H, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA. 2009;301:2129–40. Chan JCN, Malik V, Jia W, Kadowaki T, Yajnik CS, Yoon K-H, et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA. 2009;301:2129–40.
25.
go back to reference Culver AL, Ockene IS, Balasubramanian R, Olendzki BC, Sepavich DM, Wactawski-Wende J, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Woman’s Health Initiative. Arch Intern Med. 2012;172:144–52. Culver AL, Ockene IS, Balasubramanian R, Olendzki BC, Sepavich DM, Wactawski-Wende J, et al. Statin use and risk of diabetes mellitus in postmenopausal women in the Woman’s Health Initiative. Arch Intern Med. 2012;172:144–52.
26.
go back to reference Zaharan NL, Williams D, Bennet K. Statins and risk of treated incident diabetes in a primary care population. Br J Clin Pharmacol. 2012. [Epub ahead of print]. Zaharan NL, Williams D, Bennet K. Statins and risk of treated incident diabetes in a primary care population. Br J Clin Pharmacol. 2012. [Epub ahead of print].
27.
go back to reference Rajpathak SN, Barzilai N, Kumbhani DJ, Alderman M, Crandall J, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32:1924–9. Rajpathak SN, Barzilai N, Kumbhani DJ, Alderman M, Crandall J, Ridker PM. Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care. 2009;32:1924–9.
28.
go back to reference • Preiss D, Seshasai SRK, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy; a meta-analysis. JAMA. 2011;305:2556–64. This large meta-analysis shows that intensive compared with moderate-dose statin therapy is associated with a significantly greater risk of new-onset diabetes. • Preiss D, Seshasai SRK, Welsh P, Murphy SA, Ho JE, Waters DD, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy; a meta-analysis. JAMA. 2011;305:2556–64. This large meta-analysis shows that intensive compared with moderate-dose statin therapy is associated with a significantly greater risk of new-onset diabetes.
29.
go back to reference Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Park JB, et al. Differential metabolic effects of pravastatin and simvastatin in hypercholesterolemic patients. Atherosclerosis. 2009;204:483–90. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Park JB, et al. Differential metabolic effects of pravastatin and simvastatin in hypercholesterolemic patients. Atherosclerosis. 2009;204:483–90.
30.
go back to reference Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK. Atorvastatin causes insulin resistance and increases ambient glycaemia in hypercholesterolemic patients. J Am Coll Cardiol. 2010;55:1209–16. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK. Atorvastatin causes insulin resistance and increases ambient glycaemia in hypercholesterolemic patients. J Am Coll Cardiol. 2010;55:1209–16.
31.
go back to reference •• Moutzouri E, Liberopoulos E, Mikhailidis DP, Kostapanos MS, Kei AA, Milionis H, et al. Comparison of the effects of simvastatin vs rosuvastatin vs simvastatin/ezetimibe on parameters of insulin resistance. Int J Clin Pract. 2011;65:1141–8. This study demonstrates that statin therapy can significantly increase fasting insulin levels without having an effect on fasting glucose or glycosylated hemoglobin levels. •• Moutzouri E, Liberopoulos E, Mikhailidis DP, Kostapanos MS, Kei AA, Milionis H, et al. Comparison of the effects of simvastatin vs rosuvastatin vs simvastatin/ezetimibe on parameters of insulin resistance. Int J Clin Pract. 2011;65:1141–8. This study demonstrates that statin therapy can significantly increase fasting insulin levels without having an effect on fasting glucose or glycosylated hemoglobin levels.
32.
go back to reference Koh KK, Ahn JY, Quon MJ, Kim SJ, Han SH, Koh Y, et al. Simvastatin improves flow-mediated dilation but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients. Diabetes Care. 2008;31:776–82. Koh KK, Ahn JY, Quon MJ, Kim SJ, Han SH, Koh Y, et al. Simvastatin improves flow-mediated dilation but reduces adiponectin levels and insulin sensitivity in hypercholesterolemic patients. Diabetes Care. 2008;31:776–82.
33.
go back to reference Meier JJ. Beta cell mass in diabetes: a realistic therapeutic target? Diabetologia. 2008;51:701–13.CrossRef Meier JJ. Beta cell mass in diabetes: a realistic therapeutic target? Diabetologia. 2008;51:701–13.CrossRef
34.
go back to reference Defronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care. 2009;32:S157–63.PubMedCrossRef Defronzo RA, Tripathy D. Skeletal muscle insulin resistance is the primary defect in type 2 diabetes. Diabetes Care. 2009;32:S157–63.PubMedCrossRef
35.
go back to reference Xia F, Xie L, Mihic A, Gao X, Chen Y, Gaisano HY, et al. Inhibition of cholesterol biosynthesis impairs insulin secretion and voltage-gated calcium channel function in pancreatic β-cells. Endocrinology. 2008;149:5136–45. Xia F, Xie L, Mihic A, Gao X, Chen Y, Gaisano HY, et al. Inhibition of cholesterol biosynthesis impairs insulin secretion and voltage-gated calcium channel function in pancreatic β-cells. Endocrinology. 2008;149:5136–45.
36.
go back to reference • Brown JE. The ageing pancreas. Br J Diabetes Vasc Dis. 2012;12:141–5. This interesting paper notes that the aging pancreas is associated with impaired beta cell function, implies that the elderly might be particularly sensitive to statin induced beta cell dysfunction.CrossRef • Brown JE. The ageing pancreas. Br J Diabetes Vasc Dis. 2012;12:141–5. This interesting paper notes that the aging pancreas is associated with impaired beta cell function, implies that the elderly might be particularly sensitive to statin induced beta cell dysfunction.CrossRef
37.
go back to reference •• Kwak H-B, Thalacker-Mercer A, Anderson EJ, Lin C-T, Kane DA, Lee N-S, et al. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes. Free Radic Biol Med. 2012;52:198–207. This paper shows how simvastatin results in skeletal muscle mitochondrial dysfunction. •• Kwak H-B, Thalacker-Mercer A, Anderson EJ, Lin C-T, Kane DA, Lee N-S, et al. Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes. Free Radic Biol Med. 2012;52:198–207. This paper shows how simvastatin results in skeletal muscle mitochondrial dysfunction.
38.
go back to reference Galtier F, Mura T, de Mauverger ER, Chevassus H, Farret A, Gagnol J-P, et al. Effect of high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers. Toxicol Appl Pharmacol. 2012;263:281–6. Galtier F, Mura T, de Mauverger ER, Chevassus H, Farret A, Gagnol J-P, et al. Effect of high dose of simvastatin on muscle mitochondrial metabolism and calcium signaling in healthy volunteers. Toxicol Appl Pharmacol. 2012;263:281–6.
39.
go back to reference • Hoeks J, Schrauwen P. Muscle mitochondria and insulin resistance: a human perspective. Trends Endocrinol Metab. 2012;23:444–50. This interesting paper connects skeletal muscle mitochondrial dysfunction with insulin resistance.PubMedCrossRef • Hoeks J, Schrauwen P. Muscle mitochondria and insulin resistance: a human perspective. Trends Endocrinol Metab. 2012;23:444–50. This interesting paper connects skeletal muscle mitochondrial dysfunction with insulin resistance.PubMedCrossRef
40.
go back to reference Kusminski CM, Scherer PE. Mitochondrial dysfunction in white adipose tissue. Trends Endocrinol Metab. 2012;23:435–43.PubMedCrossRef Kusminski CM, Scherer PE. Mitochondrial dysfunction in white adipose tissue. Trends Endocrinol Metab. 2012;23:435–43.PubMedCrossRef
41.
go back to reference • Supale S, Li N, Brun T, Maechler P. Mitochondrial dysfunction in pancreatic β cells. Trends Endocrinol Metab. 2012;23:477–87. This paper suggests pancreatic beta cell mitochondrial dysfunction leads to beta cell apoptosis and cell death.PubMedCrossRef • Supale S, Li N, Brun T, Maechler P. Mitochondrial dysfunction in pancreatic β cells. Trends Endocrinol Metab. 2012;23:477–87. This paper suggests pancreatic beta cell mitochondrial dysfunction leads to beta cell apoptosis and cell death.PubMedCrossRef
42.
go back to reference Chamberlain LH. Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. FEBS Lett. 2001;507:357–61.PubMedCrossRef Chamberlain LH. Inhibition of isoprenoid biosynthesis causes insulin resistance in 3T3-L1 adipocytes. FEBS Lett. 2001;507:357–61.PubMedCrossRef
43.
go back to reference Nakata M, Nagasaka S, Kusaka I, Matsuoka H, Ishibashi S, Yada T. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycemic control. Diabetologia. 2006;49:1881–92. Nakata M, Nagasaka S, Kusaka I, Matsuoka H, Ishibashi S, Yada T. Effects of statins on the adipocyte maturation and expression of glucose transporter 4 (SLC2A4): implications in glycemic control. Diabetologia. 2006;49:1881–92.
44.
go back to reference Shepherd PR, Kahn BB. Glucose transporters and insulin action: implications for insulin resistance and diabetes mellitus. N Engl J Med. 1999;341:248–57.PubMedCrossRef Shepherd PR, Kahn BB. Glucose transporters and insulin action: implications for insulin resistance and diabetes mellitus. N Engl J Med. 1999;341:248–57.PubMedCrossRef
45.
go back to reference Chidlow Jr JH, Sessa WC. Caveolae, caveolins, and cavins; complex control of cellular signaling and inflammation. Cardiovasc Res. 2010;86:219–25.PubMedCrossRef Chidlow Jr JH, Sessa WC. Caveolae, caveolins, and cavins; complex control of cellular signaling and inflammation. Cardiovasc Res. 2010;86:219–25.PubMedCrossRef
46.
go back to reference Breen MR, Camps M, Carvalho-Simoes F, Zorzano A, Pilch PF. Cholesterol depletion in adipocytes causes caveolae collapse concomitant with proteosomal degradation of cavin-2 in a switch-like fashion. PLoS One. 2012;7:e34516. Breen MR, Camps M, Carvalho-Simoes F, Zorzano A, Pilch PF. Cholesterol depletion in adipocytes causes caveolae collapse concomitant with proteosomal degradation of cavin-2 in a switch-like fashion. PLoS One. 2012;7:e34516.
47.
go back to reference González-Muñoz E, López-Iglesias C, Calvo M, Palacin M, Zorzano A, Camps M. Caveolin-1 loss of function accelerates glucose transporter 4 and insulin receptor degradation in 3T3-L1 adipocytes. Endocrinology. 2009;150:3493–502. González-Muñoz E, López-Iglesias C, Calvo M, Palacin M, Zorzano A, Camps M. Caveolin-1 loss of function accelerates glucose transporter 4 and insulin receptor degradation in 3T3-L1 adipocytes. Endocrinology. 2009;150:3493–502.
48.
go back to reference Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 2001;409:729–33. Abel ED, Peroni O, Kim JK, Kim YB, Boss O, Hadro E, et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature. 2001;409:729–33.
49.
go back to reference • Rosenbaum D, Dallongeville J, Sabouret P, Bruckert E. Discontinuation of statin therapy due to muscular side effects: a survey in real life. Nutr Metab Cardiovasc Dis. 2012. [Epub ahead of print]. This important study shows that muscular side effects from average doses of statins in real-life clinical situations are much more common than what has been seen in clinical trials. • Rosenbaum D, Dallongeville J, Sabouret P, Bruckert E. Discontinuation of statin therapy due to muscular side effects: a survey in real life. Nutr Metab Cardiovasc Dis. 2012. [Epub ahead of print]. This important study shows that muscular side effects from average doses of statins in real-life clinical situations are much more common than what has been seen in clinical trials.
50.
go back to reference Fernandez G, Spatz ES, Jablecki C, Phillips PS. Statin myopathy: a common dilemma not reflected in clinical trials. Cleve Clin J Med. 2011;78:393–403.PubMedCrossRef Fernandez G, Spatz ES, Jablecki C, Phillips PS. Statin myopathy: a common dilemma not reflected in clinical trials. Cleve Clin J Med. 2011;78:393–403.PubMedCrossRef
51.
go back to reference Draeger A, Monastyrskaya K, Mohaupt M, Hoppeler H, Savolainen H, Allemann C, et al. Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia. J Pathol. 2006;210:94–102. Draeger A, Monastyrskaya K, Mohaupt M, Hoppeler H, Savolainen H, Allemann C, et al. Statin therapy induces ultrastructural damage in skeletal muscle in patients without myalgia. J Pathol. 2006;210:94–102.
52.
go back to reference Golomb BA, Evans MA, Dimsdale JE, White HL. Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial. Arch Intern Med. 2012;172:1180–2.PubMed Golomb BA, Evans MA, Dimsdale JE, White HL. Effects of statins on energy and fatigue with exertion: results from a randomized controlled trial. Arch Intern Med. 2012;172:1180–2.PubMed
53.
go back to reference Scott D, Blizzard L, Fell J, Jones G. The epidemiology of sarcopenia in community living older adults: what role does lifestyle play? J Cachex Sarcopenia Muscle. 2011;2:125–34.CrossRef Scott D, Blizzard L, Fell J, Jones G. The epidemiology of sarcopenia in community living older adults: what role does lifestyle play? J Cachex Sarcopenia Muscle. 2011;2:125–34.CrossRef
54.
go back to reference Khamseh ME, Malek M, Aghili R, Emami Z. Sarcopenia and diabetes: pathogenesis and consequences. Br J Diabetes Vasc Dis. 2011;11:230–4.CrossRef Khamseh ME, Malek M, Aghili R, Emami Z. Sarcopenia and diabetes: pathogenesis and consequences. Br J Diabetes Vasc Dis. 2011;11:230–4.CrossRef
55.
go back to reference •• Zhou XH, Qiao Q, Zethelius B, Pyörälä K, Söderberg S, Pajak A, et al, for the DECODE Study Group. Diabetes, prediabetes and cancer mortality. Diabetologia. 2010;53:1867–76. This large observational study shows that pre-diabetes and diabetes are risk factors for cancer mortality in men and women irrespective of body mass index. •• Zhou XH, Qiao Q, Zethelius B, Pyörälä K, Söderberg S, Pajak A, et al, for the DECODE Study Group. Diabetes, prediabetes and cancer mortality. Diabetologia. 2010;53:1867–76. This large observational study shows that pre-diabetes and diabetes are risk factors for cancer mortality in men and women irrespective of body mass index.
56.
go back to reference Noto H, Tsujimoto T, Noda M. Significantly increased risk of cancer in diabetes mellitus patients: a meta-analysis of epidemiological evidence in Asians and non-Asians. J Diabetes Invest. 2012;3:24–33.CrossRef Noto H, Tsujimoto T, Noda M. Significantly increased risk of cancer in diabetes mellitus patients: a meta-analysis of epidemiological evidence in Asians and non-Asians. J Diabetes Invest. 2012;3:24–33.CrossRef
57.
go back to reference Tsugane S, Inoue M. Insulin resistance and cancer: epidemiological evidence. Cancer Sci. 2010;101:1073–9.PubMedCrossRef Tsugane S, Inoue M. Insulin resistance and cancer: epidemiological evidence. Cancer Sci. 2010;101:1073–9.PubMedCrossRef
58.
go back to reference Johnson JA, Pollak M. Insulin, glucose and the increased risk of cancer in patients with type 2 diabetes. Diabetologia. 2010;53:2086–8.PubMedCrossRef Johnson JA, Pollak M. Insulin, glucose and the increased risk of cancer in patients with type 2 diabetes. Diabetologia. 2010;53:2086–8.PubMedCrossRef
59.
go back to reference Cowie CC, Williams DE, Rust KF, Gregg EW, Ford ES, Bainbridge KE, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005–2006. Diabetes Care. 2009;32:287–94. Cowie CC, Williams DE, Rust KF, Gregg EW, Ford ES, Bainbridge KE, et al. Full accounting of diabetes and pre-diabetes in the U.S. population in 1988-1994 and 2005–2006. Diabetes Care. 2009;32:287–94.
60.
go back to reference Simard EP, Ward EM, Siegel R, Jemal A. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin. 2012;62:118–28.CrossRef Simard EP, Ward EM, Siegel R, Jemal A. Cancers with increasing incidence trends in the United States: 1999 through 2008. CA Cancer J Clin. 2012;62:118–28.CrossRef
61.
go back to reference DeSantis C, Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA Cancer J Clin. 2011;61:409–18.PubMedCrossRef DeSantis C, Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA Cancer J Clin. 2011;61:409–18.PubMedCrossRef
62.
63.
go back to reference • Pollak M. The insulin and insulin-like growth factor family in neoplasia: an update. Nat Rev Cancer. 2012;12:159–69. This is a great review on the mechanisms of hyperinsulinemia and insulin growth factor signaling in oncogenesis.PubMed • Pollak M. The insulin and insulin-like growth factor family in neoplasia: an update. Nat Rev Cancer. 2012;12:159–69. This is a great review on the mechanisms of hyperinsulinemia and insulin growth factor signaling in oncogenesis.PubMed
64.
go back to reference Giovannucci E, Habel LA, Harlan DM, Pollak M, Archer MC, Regensteiner JG, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33:1674–85. Giovannucci E, Habel LA, Harlan DM, Pollak M, Archer MC, Regensteiner JG, et al. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33:1674–85.
65.
go back to reference Wanders D, Plaisance EP, Judd RL. Pharmacological effects of lipid-lowering drugs on circulating adipokines. World J Diabetes. 2010;1:116–28.PubMedCrossRef Wanders D, Plaisance EP, Judd RL. Pharmacological effects of lipid-lowering drugs on circulating adipokines. World J Diabetes. 2010;1:116–28.PubMedCrossRef
66.
go back to reference Jardé T, Perrier S, Vasson M-P, Caldefie-Chézet F. Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer. 2011;47:33–43.PubMedCrossRef Jardé T, Perrier S, Vasson M-P, Caldefie-Chézet F. Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer. 2011;47:33–43.PubMedCrossRef
67.
go back to reference Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review. Br J Cancer. 2006;94:1221–5.PubMedCrossRef Kelesidis I, Kelesidis T, Mantzoros CS. Adiponectin and cancer: a systematic review. Br J Cancer. 2006;94:1221–5.PubMedCrossRef
68.
go back to reference Duggan C, Irwin ML, Xiao L, Henderson KD, Smith AW, Baumgartner RN, et al. Associations of insulin resistance and adiponectin with mortality in women with breast cancer. J Clin Oncol. 2011;29:32–9. Duggan C, Irwin ML, Xiao L, Henderson KD, Smith AW, Baumgartner RN, et al. Associations of insulin resistance and adiponectin with mortality in women with breast cancer. J Clin Oncol. 2011;29:32–9.
69.
go back to reference Goldstein MR, Mascitelli L. Statin-induced diabetes: perhaps, it’s the tip of the iceberg. Q J Med. 2011;104:174–8.CrossRef Goldstein MR, Mascitelli L. Statin-induced diabetes: perhaps, it’s the tip of the iceberg. Q J Med. 2011;104:174–8.CrossRef
71.
go back to reference • Sniderman A, Thanassoulis G, Couture P, Williams K, Alam A, Furberg CD. Is lower and lower better and better? A re-evaluation of the evidence from the Cholesterol Treatment Trialists’ Collaboration meta-analysis for low-density lipoprotein lowering. J Clin Lipidol. 2012;6:303–9. This paper challenges the dogma that achieving ultra-low cholesterol levels with maximal doses of statins yields significantly better clinical results. • Sniderman A, Thanassoulis G, Couture P, Williams K, Alam A, Furberg CD. Is lower and lower better and better? A re-evaluation of the evidence from the Cholesterol Treatment Trialists’ Collaboration meta-analysis for low-density lipoprotein lowering. J Clin Lipidol. 2012;6:303–9. This paper challenges the dogma that achieving ultra-low cholesterol levels with maximal doses of statins yields significantly better clinical results.
72.
go back to reference Ferenczi EA, Asaria P, Hughes AD, Chaturvedi N, Francis DP. Can a statin neutralize the cardiovascular risk of unhealthy dietary choices? Am J Cardiol. 2010;106:587–92.PubMedCrossRef Ferenczi EA, Asaria P, Hughes AD, Chaturvedi N, Francis DP. Can a statin neutralize the cardiovascular risk of unhealthy dietary choices? Am J Cardiol. 2010;106:587–92.PubMedCrossRef
73.
go back to reference Mizuno K, Tajima Y, Ohashi Y, Nakamura H. Is the risk of new-onset diabetes by statins associated with diet adherence? Int J Cardiol. 2012. [Epub ahead of print]. Mizuno K, Tajima Y, Ohashi Y, Nakamura H. Is the risk of new-onset diabetes by statins associated with diet adherence? Int J Cardiol. 2012. [Epub ahead of print].
74.
go back to reference Perreault L, Pan Q, Mather KJ, Watson KE, Hamman RF, Kahn SE, for the Diabetes Prevention Program Research Group. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet. 2012;379:2243–51. Perreault L, Pan Q, Mather KJ, Watson KE, Hamman RF, Kahn SE, for the Diabetes Prevention Program Research Group. Effect of regression from prediabetes to normal glucose regulation on long-term reduction in diabetes risk: results from the Diabetes Prevention Program Outcomes Study. Lancet. 2012;379:2243–51.
75.
go back to reference Jula A, Marniemi J, Huupponen R, Virtanen A, Rastas M, Rönnemaa T. Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial. JAMA. 2002;287:598–605. Jula A, Marniemi J, Huupponen R, Virtanen A, Rastas M, Rönnemaa T. Effects of diet and simvastatin on serum lipids, insulin, and antioxidants in hypercholesterolemic men: a randomized controlled trial. JAMA. 2002;287:598–605.
77.
go back to reference Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, et al. Sugar-sweetened beverages and genetic risk of obesity. N Engl J Med. 2012;367:1387–96. Qi Q, Chu AY, Kang JH, Jensen MK, Curhan GC, Pasquale LR, et al. Sugar-sweetened beverages and genetic risk of obesity. N Engl J Med. 2012;367:1387–96.
78.
go back to reference Tappy L, Lê K-A. Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev. 2010;90:23–46.PubMedCrossRef Tappy L, Lê K-A. Metabolic effects of fructose and the worldwide increase in obesity. Physiol Rev. 2010;90:23–46.PubMedCrossRef
79.
go back to reference Port AM, Ruth MR, Istfan NW. Fructose comsumption and cancer: is there a connection? Curr Opin Endocrinol Diabetes Obes. 2012;19:367–74.PubMed Port AM, Ruth MR, Istfan NW. Fructose comsumption and cancer: is there a connection? Curr Opin Endocrinol Diabetes Obes. 2012;19:367–74.PubMed
80.
go back to reference Pomeranz JL, Brownell KB. Portion sizes and beyond—Government’s legal authority to regulate food industry practices. N Engl J Med. 2012;367:1383–5.PubMedCrossRef Pomeranz JL, Brownell KB. Portion sizes and beyond—Government’s legal authority to regulate food industry practices. N Engl J Med. 2012;367:1383–5.PubMedCrossRef
81.
82.
go back to reference Lira VA, Benton CR, Yan Z, Bonen A. PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity. Am J Physiol Endocrinol Metab. 2010;299:E145–61.PubMed Lira VA, Benton CR, Yan Z, Bonen A. PGC-1α regulation by exercise training and its influences on muscle function and insulin sensitivity. Am J Physiol Endocrinol Metab. 2010;299:E145–61.PubMed
83.
go back to reference • Grontved A, Rimm EB, Willett WC, Anderson LB, Hu FB. A prospective study of weight training and risk of type 2 diabetes mellitus in men. Arch Intern Med. 2012;172:1306–12. This paper suggests that combined resistance and endurance exercise provide the best results in decreasing the risk of diabetes.PubMed • Grontved A, Rimm EB, Willett WC, Anderson LB, Hu FB. A prospective study of weight training and risk of type 2 diabetes mellitus in men. Arch Intern Med. 2012;172:1306–12. This paper suggests that combined resistance and endurance exercise provide the best results in decreasing the risk of diabetes.PubMed
84.
go back to reference Parker BA, Thompson PD. Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exerc Sport Sci Rev. 2012;40:188–94.PubMed Parker BA, Thompson PD. Effect of statins on skeletal muscle: exercise, myopathy, and muscle outcomes. Exerc Sport Sci Rev. 2012;40:188–94.PubMed
85.
go back to reference Deichmann R, Lavie C, Andrews S. Coenzyme Q10 and statin-induced mitochondrial dysfunction. Ochsner J. 2010;10:16–21.PubMed Deichmann R, Lavie C, Andrews S. Coenzyme Q10 and statin-induced mitochondrial dysfunction. Ochsner J. 2010;10:16–21.PubMed
86.
go back to reference Binkley N, Ramamurthy R, Krueger D. Low vitamin D status: definition, prevalence, consequences, and correction. Endocrinol Metab Clin N Am. 2010;39:287–301.CrossRef Binkley N, Ramamurthy R, Krueger D. Low vitamin D status: definition, prevalence, consequences, and correction. Endocrinol Metab Clin N Am. 2010;39:287–301.CrossRef
87.
go back to reference Borges MC, Martini LA, Rogero MM. Current perspectives on vitamin D, immune system, and chronic diseases. Nutrition. 2011;27:399–404.PubMedCrossRef Borges MC, Martini LA, Rogero MM. Current perspectives on vitamin D, immune system, and chronic diseases. Nutrition. 2011;27:399–404.PubMedCrossRef
88.
go back to reference Alvarez JA, Ashraf A. Role of vitamin D in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol. 2010;2010:351385.PubMed Alvarez JA, Ashraf A. Role of vitamin D in insulin secretion and insulin sensitivity for glucose homeostasis. Int J Endocrinol. 2010;2010:351385.PubMed
89.
go back to reference Ahmed W, Khan N, Glueck CJ, Pandey S, Wang P, Goldenberg N, et al. Low serum 25(OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients. Transl Res. 2009;153:11–6. Ahmed W, Khan N, Glueck CJ, Pandey S, Wang P, Goldenberg N, et al. Low serum 25(OH) vitamin D levels (<32 ng/mL) are associated with reversible myositis-myalgia in statin-treated patients. Transl Res. 2009;153:11–6.
90.
go back to reference Booth FW, Hargreaves M. Understanding multi-organ pathology from insufficient exercise. J Appl Physiol. 2011;111:1199–200.PubMedCrossRef Booth FW, Hargreaves M. Understanding multi-organ pathology from insufficient exercise. J Appl Physiol. 2011;111:1199–200.PubMedCrossRef
91.
go back to reference Thyfault JP, Krogh-Madsen R. Metabolic disruptions induced by reduced ambulatory activity in free-living humans. J Appl Physiol. 2011;111:1218–24.PubMedCrossRef Thyfault JP, Krogh-Madsen R. Metabolic disruptions induced by reduced ambulatory activity in free-living humans. J Appl Physiol. 2011;111:1218–24.PubMedCrossRef
Metadata
Title
Do Statins Cause Diabetes?
Authors
Mark R. Goldstein
Luca Mascitelli
Publication date
01-06-2013
Publisher
Current Science Inc.
Published in
Current Diabetes Reports / Issue 3/2013
Print ISSN: 1534-4827
Electronic ISSN: 1539-0829
DOI
https://doi.org/10.1007/s11892-013-0368-x

Other articles of this Issue 3/2013

Current Diabetes Reports 3/2013 Go to the issue

Pharmacologic Treatment of Type 2 Diabetes and Obesity (A Vella, Section Editor)

The Future of Thiazolidinedione Therapy in the Management of Type 2 Diabetes Mellitus

Diabetes and Other Diseases—Emerging Associations (D Aron, Section Editor)

Diabetes and Infections-Hepatitis C: Is There Type 2 Diabetes Excess in Hepatitis C Infection?

Macrovascular Complications in Diabetes (PD Reaven, Section Editor)

Is the Risk and Nature of CVD the Same in Type 1 and Type 2 Diabetes?

Diabetes and Other Diseases—Emerging Associations (D Aron, Section Editor)

Diabetes Mellitus and Osteoporosis

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.