Tag: alcohol

Alcohol’s effect on body systems

Alcohol on it’s own can have negative effects on the body but the effects on some one with diabetes can be augmented by the interaction of alcohol and medications. Patients with diabetes should be counselled regarding the negative effects of alcohol on diabetes and possible interactions. Alcohol in diabetes should be avoided and patients should be advised of abstaining from alcohol.

Cardiovascular and Gastro Intestinal

Chronic alcohol use is associated with negative cardiac health events including:
● nonischemic dilated cardiomyopathy (3)
● ventricular dysfunction (3)
● atrial fibrillation (5)
● hypertension (4)
● increased caloric intake and weight gain (4)
Interestingly, alcohol exhibits a “J”-shaped dosing curve for many of these events, where lower risk is observed at approximately 2 drinks/day, but steeply rises beyond this (8) Chronic alcohol is associated with negative GI health events, including:
● injury to gastric mucosa, leading to an increased risk of GI bleeds (12)

Liver/Pancreas

Chronic alcohol is associated with negative hepatic and pancreatic health events, including:
● increased triglyceride secretion which increases the risk of pancreatitis(7)

●increased TGs (>1000 mg/dL) are associated with increased chylomicrons which can obstruct pancreatic capillaries, supporting ischemia and inflammation (16)
● promoting hepatic fibrosis and cirrhosis via fatty acid breakdown mechanisms (8)
● increasing hepatic production of LDL (8)
● decreasing atheroprotective efficacy of produced HDL (8)

Managing Diabetes:  Chronic alcohol use dramatically limits the ability to use ADA recommended antidiabetic agents.

Metformin

Mechanism: AMP kinase activation, decreasing hepatic glucose production Problems raised with chronic alcohol use:
● Both metformin and alcohol have individually demonstrated a risk of causing lactic acidosis (10,11)
● Concurrent use of metformin and alcohol has demonstrated an increased risk of developing lactic acidosis (9). Limiting use in patients with chronic or binging alcohol intake.
● Would probably think twice about starting metformin in this patient given the risk of lactic acidosis, but if other medication classes are problematic, the patient will still need at least some therapy to manage diabetes.

Sulfonylureas

Mechanism: Blocks K+ channels on pancreatic beta cell membranes, increasing insulin secretion Problems raised with chronic alcohol use:
● Concurrent use of alcohol and sulfonylureas is associated with an increased risk of delayed hypoglycemia (19)
● Chronic alcohol use is associated with decreased insulin secretion response in the presence of elevated blood glucose levels (2)      Use in these patients?
● Probably not, given the added risk of delayed hypoglycemia
● Additionally, starting a medication in this class might not be very effective in managing chronic diabetes anyway, given the decreased insulinogenic response.

Thiazolidinediones

Mechanism: PPAR-gamma activation, increasing insulin sensitivity and glucose uptake in peripheral tissues Problems raised with chronic alcohol use:
● Pioglitazone has been reported in post-marketing surveillance to cause hepatic failure, but actual risk remains unknown (18)
● Chronic alcohol use is known to be associated with hepatic injury.  Use in these patients?
● Probably not, given multiple risk factors for liver injury
● If given, would have to closely monitor hepatic function tests

DPP4 Inhibitors

Mechanism: Inhibits DPP enzyme, prolonging effects of endogenous GLP1/GIP to increase insulin secretion and decrease glucagon secretion Problems raised with chronic alcohol use:
● Sitagliptin has been reported in post-marketing surveillance to cause acute pancreatitis, but actual risk remains unknown (0.1 per 100 patient years in both study and placebo) (17)  ○ Pancreatitis was reversible

● Chronic alcohol use is known to be associated with increased risk of pancreatitis via increased triglyceride levels (16) Use in these patients?
● Probably not, considering multiple risk factors for pancreatitis, but possible with monitoring
● Also, the value of this class (post-prandial control) in a patient with an A1c close to 9% would seem limited.

SGLT2 Inhibitors

Mechanism: Inhibits SGLT2 in nephrons, reducing renal glucose reabsorption Problems raised with chronic alcohol use:
● Empagliflozin can induce diabetic ketoacidosis even at glucose levels

GLP1 Receptor Agonists

Mechanism: Activates GLP 1 receptors to increase insulin secretion, decrease glucagon secretion, slow gastric emptying and promote longer satiety Problems raised with chronic alcohol use:
● Liraglutide has been observed to cause more cases of pancreatitis than control groups (2.2 vs. 0.6 cases per 1000 patient-years), but this has not been fully studied (17) ○ Pancreatitis was reversible, however
● Chronic alcohol use is known to be associated with increased risk of pancreatitis via increased triglyceride levels (16) Use in these patients?
● considering multiple risk factors such as pancreatitis,  possible with monitoring

Insulin

Mechanism: supplements endogenous insulin production Problems raised with chronic alcohol use:
● Concurrent use of alcohol and insulin is associated with an increased risk of delayed hypoglycemia (1)
● Chronic alcohol use is associated with decreased insulin secretion response in the presence of elevated blood glucose levels( (2) Use in this patient?
● patients  already on insulin, are more likely to grow more resistant to insulin as doses increase – higher doses and/or adding bolus dosing might temporarily improve glycemic control, but also contribute to weight gain
● Additionally, compliance with bolus dosing may be unlikely

Statins

Mechanism: inhibits function of HMG-CoA reductase, increasing hepatic LDL breakdowns. Also reduces endothelial inflammation. Problems raised with chronic alcohol use:
● Although statins are rarely causative in hepatic injury or failure (Out of 1188 cases reported to the US Drug Induced Liver Injury Network, only 22 cases could be clearly linked to hepatic injury), a fatality was associated with alcoholic liver disease and statin use (20)  Use in this patient?
●  a statin but is indicated per ADA guidelines for CV mortality reduction. Chronic alcohol use and possible hepatic injury would warrant caution if this class were used, but still possible.

Aspirin

Mechanism: inhibits platelet COX 1 and 2, reducing platelet aggregation and prostaglandin effects Problems raised with chronic alcohol use:
● Aspirin has demonstrated an increased risk of GI bleeds (22)
● Alcohol causing injury to gastric mucosa, leading to an increased risk of GI bleeds (12) Use in these patients?
● aspirin for primary CV prevention, but could be considered per ADA guidelines, considering hypertension and dyslipidemia.
● However, the multiple risk factors for bleeding (including concomitant use of NSAIDS such as naproxen or ibuprofen) would probably make aspirin a poor choice.

References

1. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care 2017; 40 Suppl 1: S1-S135.
2. Nguyen, Lee, & Nyomba. (2011). Ethanol causes endoplasmic reticulum stress and impairment of insulin secretion in pancreatic β-cells. Alcohol, 46(1), 89-99.
3. Mozaffarian, D. (2016). Dietary and Policy Priorities for Cardiovascular Disease, Diabetes, and Obesity A Comprehensive Review. Circulation, 133(2), 187-225.
4. Núñez-Córdoba, J., Valencia-Serrano, F., Toledo, E., Alonso, A., & Martínez-González, M. (2009). The Mediterranean diet and incidence of hypertension: The Seguimiento Universidad de Navarra (SUN) Study. American Journal of Epidemiology, 169(3), 339-46.
5. Larsson, Drca, & Wolk. (2014). Alcohol Consumption and Risk of Atrial Fibrillation: A Prospective Study and Dose-Response Meta-Analysis: A Prospective Study and Dose-Response Meta-Analysis. Journal of the American College of Cardiology, 64(3), 281-289.
6. Sacks, F., Svetkey, L., Vollmer, W., Appel, L., Bray, G., Harsha, D., . . . Cutler, J. (2001). Effects on Blood Pressure of Reduced Dietary Sodium and the Dietary Approaches to Stop Hypertension (DASH) Diet. The New England Journal of Medicine, 344(1), 3-10.
7. Berglund, Lars, Brunzell, John D, Goldberg, Anne C, Goldberg, Ira J, Sacks, Frank, Murad, Mohammad Hassan, & Stalenhoef, Anton F H. (2012). Evaluation and treatment of hypertriglyceridemia: An Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism,97(9), 2969-89.
8. Brinton, E. (2010). Effects of ethanol intake on lipoproteins and atherosclerosis. Current Opinion In Lipidology, 21(4), 346-351.
9. Krzymień, J., & Karnafel, W. (2013). Lactic acidosis in patients with diabetes. Polskie Archiwum Medycyny Wewnetrznej, 123(3), 91-7.
10. Müssig, Schleicher, Häring, & Riessen. (2008). Satisfactory Outcome After Severe Ethanol-Induced Lactic Acidosis and Hypoglycemia. Journal of Emergency Medicine, 34(3), 337-338.
11. Glucophage (metformin). [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; August 2008. 17
12. Macmath, T. (1990). Alcohol and gastrointestinal bleeding. Emergency Medicine Clinics of North America,8(4), 859-72.
13. Handelsman, Y., Henry, R., Bloomgarden, Z., Dagogo-Jack, S., Defronzo, R., Einhorn, D., . . . Weir, M. (2016). AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY POSITION STATEMENT ON THE ASSOCIATION OF SGLT-2 INHIBITORS AND DIABETIC KETOACIDOSIS. Endocrine Practice, 22(6), 753-762.
14. Kitabchi, A., Umpierrez, G., Miles, J., & Fisher, J. (2009). Hyperglycemic crises in adult patients with diabetes. Diabetes Care, 32(7), 1335-43.
15. Mcguire, L., Cruickshank, A., & Munro, P. (2006). Alcoholic ketoacidosis. Emergency Medicine Journal, 23(6), 417-420.
16. Yadav, D., & Pitchumoni, C. (2003). Issues in hyperlipidemic pancreatitis. Journal Of Clinical Gastroenterology, 36(1), 54-62.
17. Januvia (sitagliptin). [prescribing information]. Whitehouse Station, NJ: Merck & Co. Inc.; August 2018.
18. Actos (pioglitazone). [prescribing information]. Deerfield, IL: Takeda Pharmaceuticals America; July 2011.
19. Glucotrol (glipizide). [prescribing information]. New York, NY: Pfizer Inc.; October 2016.
20. Victoza (liraglutide). [prescribing information]. Princeton, NJ: Novo Nordisk Inc.; January 2010.
21. Russo, M., Hoofnagle, J., Gu, J., Fontana, R., Barnhart, H., Kleiner, D., . . . Bonkovsky, H. (2014). Spectrum of statin hepatotoxicity: Experience of the drug‐induced liver injury network. Hepatology,60(2), 679-686.
22. Pignone, M., Alberts, M., Colwell, J., Cushman, M., Inzucchi, S., Mukherjee, D., . . . Kirkman, M. (2010). Aspirin for primary prevention of cardiovascular events in people with diabetes: A position statement of the American Diabetes Association, a scientific statement of the American Heart Association, and an expert consensus document of the American College of Cardiology Foundation. Diabetes Care, 33(6), 1395-1402.