Diabetes Metab J.  2012 Apr;36(2):108-115. 10.4093/dmj.2012.36.2.108.

Alcoholism and Diabetes Mellitus

• Kim SJ
• Kim DJ

• KMID: 2281412
• DOI: http://doi.org/10.4093/dmj.2012.36.2.108

Abstract

Chronic use of alcohol is considered to be a potential risk factor for the incidence of type 2 diabetes mellitus (T2DM), which causes insulin resistance and pancreatic beta-cell dysfunction that is a prerequisite for the development of diabetes. However, alcohol consumption in diabetes has been controversial and more detailed information on the diabetogenic impact of alcohol seems warranted. Diabetes, especially T2DM, causes dysregulation of various metabolic processes, which includes a defect in the insulin-mediated glucose function of adipocytes, and an impaired insulin action in the liver. In addition, neurobiological profiles of alcoholism are linked to the effects of a disruption of glucose homeostasis and of insulin resistance, which are affected by altered appetite that regulates the peptides and neurotrophic factors. Since conditions, which precede the onset of diabetes that are associated with alcoholism is one of the crucial public problems, researches in efforts to prevent and treat diabetes with alcohol dependence, receives special clinical interest. Therefore, the purpose of this mini-review is to provide the recent progress and current theories in the interplay between alcoholism and diabetes. Further, the purpose of this study also includes summarizing the pathophysiological mechanisms in the neurobiology of alcoholism.

Keyword

Alcohol; Diabetes mellitus; Glucose; Insulin

MeSH Terms

Adipocytes
Alcohol Drinking
Alcoholism
Appetite
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose
Homeostasis
Incidence
Insulin
Insulin Resistance
Liver
Nerve Growth Factors
Neurobiology
Peptides
Risk Factors
Glucose
Insulin
Nerve Growth Factors
Peptides

Reference

1. Hodge AM, Dowse GK, Collins VR, Zimmet PZ. Abnormal glucose tolerance and alcohol consumption in three populations at high risk of non-insulin-dependent diabetes mellitus. Am J Epidemiol. 1993. 137:178–189.

2. Wannamethee SG, Shaper AG, Perry IJ, Alberti KG. Alcohol consumption and the incidence of type II diabetes. J Epidemiol Community Health. 2002. 56:542–548.

3. Wan Q, Liu Y, Guan Q, Gao L, Lee KO, Zhao J. Ethanol feeding impairs insulin-stimulated glucose uptake in isolated rat skeletal muscle: role of Gs alpha and cAMP. Alcohol Clin Exp Res. 2005. 29:1450–1456.

4. Koppes LL, Dekker JM, Hendriks HF, Bouter LM, Heine RJ. Moderate alcohol consumption lowers the risk of type 2 diabetes: a meta-analysis of prospective observational studies. Diabetes Care. 2005. 28:719–725.

5. Wei M, Gibbons LW, Mitchell TL, Kampert JB, Blair SN. Alcohol intake and incidence of type 2 diabetes in men. Diabetes Care. 2000. 23:18–22.

6. Kao WH, Puddey IB, Boland LL, Watson RL, Brancati FL. Alcohol consumption and the risk of type 2 diabetes mellitus: atherosclerosis risk in communities study. Am J Epidemiol. 2001. 154:748–757.

7. Green CA, Perrin NA, Polen MR. Gender differences in the relationships between multiple measures of alcohol consumption and physical and mental health. Alcohol Clin Exp Res. 2004. 28:754–764.

8. Howard AA, Arnsten JH, Gourevitch MN. Effect of alcohol consumption on diabetes mellitus: a systematic review. Ann Intern Med. 2004. 140:211–219.

9. McKinlay J, Marceau L. US public health and the 21st century: diabetes mellitus. Lancet. 2000. 356:757–761.

10. Nealon WH, Townsend CM Jr, Thompson JC. The time course of beta cell dysfunction in chronic ethanol-induced pancreatitis: a prospective analysis. Surgery. 1988. 104:1074–1079.

11. Ikai E, Ishizaki M, Suzuki Y, Ishida M, Noborizaka Y, Yamada Y. Association between hepatic steatosis, insulin resistance and hyperinsulinaemia as related to hypertension in alcohol consumers and obese people. J Hum Hypertens. 1995. 9:101–105.

12. Nikkila EA, Taskinen MR. Ethanol-induced alterations of glucose tolerance, postglucose hypoglycemia, and insulin secretion in normal, obese, and diabetic subjects. Diabetes. 1975. 24:933–943.

13. Singh SP, Kumar Y, Snyder AK, Ellyin FE, Gilden JL. Effect of alcohol on glucose tolerance in normal and noninsulin-dependent diabetic subjects. Alcohol Clin Exp Res. 1988. 12:727–730.

14. de la Monte SM, Ganju N, Tanaka S, Banerjee K, Karl PJ, Brown NV, Wands JR. Differential effects of ethanol on insulin-signaling through the insulin receptor substrate-1. Alcohol Clin Exp Res. 1999. 23:770–777.

15. Umeki S, Hisamoto N, Hara Y. Study on background factors associated with impaired glucose tolerance and/or diabetes mellitus. Acta Endocrinol (Copenh). 1989. 120:729–734.

16. Jung KI, Ju A, Lee HM, Lee SS, Song CH, Won WY, Jeong JS, Hong OK, Kim JH, Kim DJ. Chronic ethanol ingestion, type 2 diabetes mellitus, and brain-derived neurotrophic factor (BDNF) in rats. Neurosci Lett. 2011. 487:149–152.

17. Saltiel AR, Pessin JE. Insulin signaling pathways in time and space. Trends Cell Biol. 2002. 12:65–71.

18. Gillespie KM. Type 1 diabetes: pathogenesis and prevention. CMAJ. 2006. 175:165–170.

19. Foulis AK, McGill M, Farquharson MA. Insulitis in type 1 (insulin-dependent) diabetes mellitus in man: macrophages, lymphocytes, and interferon-gamma containing cells. J Pathol. 1991. 165:97–103.

20. Mauvais-Jarvis F, Kahn CR. Understanding the pathogenesis and treatment of insulin resistance and type 2 diabetes mellitus: what can we learn from transgenic and knockout mice? Diabetes Metab. 2000. 26:433–448.

21. DeFronzo RA. Pathogenesis of type 2 (non-insulin dependent) diabetes mellitus: a balanced overview. Diabetologia. 1992. 35:389–397.

22. Cryer PE. Hypoglycemia: still the limiting factor in the glycemic management of diabetes. Endocr Pract. 2008. 14:750–756.

23. Lin Y, Sun Z. Current views on type 2 diabetes. J Endocrinol. 2010. 204:1–11.

24. Wauters M, Considine RV, Yudkin JS, Peiffer F, De Leeuw I, Van Gaal LF. Leptin levels in type 2 diabetes: associations with measures of insulin resistance and insulin secretion. Horm Metab Res. 2003. 35:92–96.

25. Rosengren A, Wilhelmsen L, Wedel H. Separate and combined effects of smoking and alcohol abuse in middle-aged men. Acta Med Scand. 1988. 223:111–118.

26. Kahn SE. Clinical review 135: the importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab. 2001. 86:4047–4058.

27. Blaak EE, Wagenmakers AJ, Glatz JF, Wolffenbuttel BH, Kemerink GJ, Langenberg CJ, Heidendal GA, Saris WH. Plasma FFA utilization and fatty acid-binding protein content are diminished in type 2 diabetic muscle. Am J Physiol Endocrinol Metab. 2000. 279:E146–E154.

28. Boden G. Free fatty acids, insulin resistance, and type 2 diabetes mellitus. Proc Assoc Am Physicians. 1999. 111:241–248.

29. Phielix E, Mensink M. Type 2 diabetes mellitus and skeletal muscle metabolic function. Physiol Behav. 2008. 94:252–258.

30. Hurt RD, Patten CA. Treatment of tobacco dependence in alcoholics. Recent Dev Alcohol. 2003. 16:335–359.

31. Ju A, Cheon YH, Lee KS, Lee SS, Lee WY, Won WY, Park SI, Kim WH, Kim DJ. The change of plasma ghrelin and leptin levels by the development of type 2 diabetes mellitus in patients with alcohol dependence. Alcohol Clin Exp Res. 2011. 35:905–911.

32. Irako T, Akamizu T, Hosoda H, Iwakura H, Ariyasu H, Tojo K, Tajima N, Kangawa K. Ghrelin prevents development of diabetes at adult age in streptozotocin-treated newborn rats. Diabetologia. 2006. 49:1264–1273.

33. Anderwald C, Brabant G, Bernroider E, Horn R, Brehm A, Waldhausl W, Roden M. Insulin-dependent modulation of plasma ghrelin and leptin concentrations is less pronounced in type 2 diabetic patients. Diabetes. 2003. 52:1792–1798.

34. Sun Y, Asnicar M, Smith RG. Central and peripheral roles of ghrelin on glucose homeostasis. Neuroendocrinology. 2007. 86:215–228.

35. Yada T, Dezaki K, Sone H, Koizumi M, Damdindorj B, Nakata M, Kakei M. Ghrelin regulates insulin release and glycemia: physiological role and therapeutic potential. Curr Diabetes Rev. 2008. 4:18–23.

36. Cohen B, Novick D, Rubinstein M. Modulation of insulin activities by leptin. Science. 1996. 274:1185–1188.

37. Aas AM, Hanssen KF, Berg JP, Thorsby PM, Birkeland KI. Insulin-stimulated increase in serum leptin levels precedes and correlates with weight gain during insulin therapy in type 2 diabetes. J Clin Endocrinol Metab. 2009. 94:2900–2906.

38. Sweeney G, Keen J, Somwar R, Konrad D, Garg R, Klip A. High leptin levels acutely inhibit insulin-stimulated glucose uptake without affecting glucose transporter 4 translocation in l6 rat skeletal muscle cells. Endocrinology. 2001. 142:4806–4812.

39. Soppet D, Escandon E, Maragos J, Middlemas DS, Reid SW, Blair J, Burton LE, Stanton BR, Kaplan DR, Hunter T, Nikolics K, Parada LF. The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell. 1991. 65:895–903.

40. Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, Fischer CP, Lindegaard B, Petersen AM, Taudorf S, Secher NH, Pilegaard H, Bruunsgaard H, Pedersen BK. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007. 50:431–438.

41. Nakagawa T, Tsuchida A, Itakura Y, Nonomura T, Ono M, Hirota F, Inoue T, Nakayama C, Taiji M, Noguchi H. Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes. 2000. 49:436–444.

42. Gradman TJ, Laws A, Thompson LW, Reaven GM. Verbal learning and/or memory improves with glycemic control in older subjects with non-insulin-dependent diabetes mellitus. J Am Geriatr Soc. 1993. 41:1305–1312.

43. Naor M, Steingruber HJ, Westhoff K, Schottenfeld-Naor Y, Gries AF. Cognitive function in elderly non-insulin-dependent diabetic patients before and after inpatient treatment for metabolic control. J Diabetes Complications. 1997. 11:40–46.

44. Choeiri C, Staines W, Messier C. Immunohistochemical localization and quantification of glucose transporters in the mouse brain. Neuroscience. 2002. 111:19–34.

45. Awad N, Gagnon M, Messier C. The relationship between impaired glucose tolerance, type 2 diabetes, and cognitive function. J Clin Exp Neuropsychol. 2004. 26:1044–1080.

46. Yamanaka M, Itakura Y, Inoue T, Tsuchida A, Nakagawa T, Noguchi H, Taiji M. Protective effect of brain-derived neurotrophic factor on pancreatic islets in obese diabetic mice. Metabolism. 2006. 55:1286–1292.

47. Chao MV. Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat Rev Neurosci. 2003. 4:299–309.

48. Crews FT, Nixon K. Alcohol, neural stem cells, and adult neurogenesis. Alcohol Res Health. 2003. 27:197–204.

49. McGough NN, He DY, Logrip ML, Jeanblanc J, Phamluong K, Luong K, Kharazia V, Janak PH, Ron D. RACK1 and brain-derived neurotrophic factor: a homeostatic pathway that regulates alcohol addiction. J Neurosci. 2004. 24:10542–10552.

50. Goggi J, Pullar IA, Carney SL, Bradford HF. Modulation of neurotransmitter release induced by brain-derived neurotrophic factor in rat brain striatal slices in vitro. Brain Res. 2002. 941:34–42.

51. Jeanblanc J, He DY, McGough NN, Logrip ML, Phamluong K, Janak PH, Ron D. The dopamine D3 receptor is part of a homeostatic pathway regulating ethanol consumption. J Neurosci. 2006. 26:1457–1464.

52. Kovalchuk Y, Hanse E, Kafitz KW, Konnerth A. Postsynaptic induction of BDNF-mediated long-term potentiation. Science. 2002. 295:1729–1734.

53. Joe KH, Kim YK, Kim TS, Roh SW, Choi SW, Kim YB, Lee HJ, Kim DJ. Decreased plasma brain-derived neurotrophic factor levels in patients with alcohol dependence. Alcohol Clin Exp Res. 2007. 31:1833–1838.

54. Robinson TE, Berridge KC. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res Brain Res Rev. 1993. 18:247–291.

55. Biessels GJ, Kamal A, Ramakers GM, Urban IJ, Spruijt BM, Erkelens DW, Gispen WH. Place learning and hippocampal synaptic plasticity in streptozotocin-induced diabetic rats. Diabetes. 1996. 45:1259–1266.

56. Lu Y, Christian K, Lu B. BDNF: a key regulator for protein synthesis-dependent LTP and long-term memory? Neurobiol Learn Mem. 2008. 89:312–323.

57. Shonesy BC, Thiruchelvam K, Parameshwaran K, Rahman EA, Karuppagounder SS, Huggins KW, Pinkert CA, Amin R, Dhanasekaran M, Suppiramaniam V. Central insulin resistance and synaptic dysfunction in intracerebroventricular-streptozotocin injected rodents. Neurobiol Aging. 2012. 33:430.e5–430.e18.

58. Harper C, Matsumoto I. Ethanol and brain damage. Curr Opin Pharmacol. 2005. 5:73–78.

59. Min JA, Lee HR, Kim JI, Ju A, Kim DJ, Kaang BK. Impairment of long-term potentiation in the hippocampus of alcohol-treated OLETF rats. Neurosci Lett. 2011. 500:52–56.

60. Meaney MJ, O'Donnell D, Rowe W, Tannenbaum B, Steverman A, Walker M, Nair NP, Lupien S. Individual differences in hypothalamic-pituitary-adrenal activity in later life and hippocampal aging. Exp Gerontol. 1995. 30:229–251.