Indian Journal of Endocrinology and Metabolism

LETTER TO THE EDITOR
Year
: 2017  |  Volume : 21  |  Issue : 5  |  Page : 788--789

Verapamil in diabetes


Resham Raj Poudel1, Nisha Kusum Kafle2,  
1 Department of Internal Medicine, Western Reserve Health Education, Youngstown, OH, USA
2 Department of Public Health, Institute of Medicine, Kathmandu, Nepal

Correspondence Address:
Resham Raj Poudel
Western Reserve Health Education, Youngstown, OH
USA




How to cite this article:
Poudel RR, Kafle NK. Verapamil in diabetes.Indian J Endocr Metab 2017;21:788-789


How to cite this URL:
Poudel RR, Kafle NK. Verapamil in diabetes. Indian J Endocr Metab [serial online] 2017 [cited 2019 Dec 11 ];21:788-789
Available from: http://www.ijem.in/text.asp?2017/21/5/788/214779


Full Text



Sir,

Loss of pancreatic β cells is a pathological hallmark of both type 1 and type 2 diabetes mellitus; however, no specific therapy targeting this defect is yet available. A paradigm shift with such a molecule has always been awaited. Verapamil – a nondihydropyridine calcium channel blocker used in the treatment of hypertension, angina, and tachyarrhythmias, particularly atrial fibrillation – has been observed to show some hope in preventing β cell loss in diabetics by inhibiting thioredoxin-interacting protein (TXNIP).

TXNIP was first cloned in 1994 and the relation with β cells was elucidated in 2002. Pancreatic β cells have a poor antioxidant system and are highly susceptible to oxidative stress. TXNIP inhibits thioredoxin – a redox protein/antioxidant system [Figure 1],[1] and thereby induces oxidative stress. β cells TXNIP expression is strongly induced by glucose and is increased in diabetes. The overexpression of TXNIP in β cells has been shown to promote β cell apoptosis and reduce insulin production,[2] as shown in [Figure 1].[1] Genetic deletion or pharmacological inhibition of TXNIP seems to be protective against diabetes. In animal studies, the calcium channel blocker verapamil has been shown to prevent β cell apoptosis in streptozocin-induced diabetic mice; it supposedly promotes β cell survival and improves glucose homeostasis by inhibiting TXNIP expression.[2],[3]{Figure 1}

Recently, verapamil has also been shown to decrease fasting plasma glucose in diabetic patients in an observational study of 4978 patients – REasons for Geographic And Racial Differences in Stroke (REGARDS). Type 1 diabetics, and type 2 diabetics on insulin with or without oral drugs, who also received verapamil had fasting serum glucose levels that were 24 mg/dL lower than those who did not receive verapamil (P = 0.039),[4] correlating with approximately 1% reduction in glycated hemoglobin. In another study of patients with no prior diabetes, oral verapamil use was associated with a lower incidence of type 2 diabetes (6.41 vs. 8.07 per 1000 per year) compared with other calcium channel blockers.[5] Following REGARDS observation, a randomized controlled trial (NCT02372253) is ongoing to study the effect of verapamil in β cell survival in type 1 diabetics focusing on functional β cell mass, exogenous insulin requirements, glycemic control, and TXNIP expression in peripheral blood monocytes.[6] The future of clinical studies holds prospect for verapamil as well as other TXNIP inhibitors to come up as β cell saviors in preventing and treating diabetes. If it proves for clinical significance, the use of verapamil can hit two targets in diabetics – hyperglycemia and hypertension.

References

1Muoio DM. TXNIP links redox circuitry to glucose control. Cell Metab 2007;5:412-4.
2Shalev A. Minireview: Thioredoxin-interacting protein: Regulation and function in the pancreatic ß-cell. Mol Endocrinol 2014;28:1211-20.
3Xu G, Chen J, Jing G, Shalev A. Preventing ß-cell loss and diabetes with calcium channel blockers. Diabetes 2012;61:848-56.
4Khodneva Y, Shalev A, Frank SJ, Carson AP, Safford MM. Calcium channel blocker use is associated with lower fasting serum glucose among adults with diabetes from the REGARDS study. Diabetes Res Clin Pract 2016;115:115-21.
5Yin T, Kuo SC, Chang YY, Chen YT, Wang KK. Verapamil use is associated with reduction of newly diagnosed diabetes mellitus. J Clin Endocrinol Metab 2017. doi: 10.1210/jc.2016-3778. [Epub ahead of print].
6Verapamil for Beta Cell Survival Therapy in Type 1 Diabetes – Full Text View – ClinicalTrials.gov; 2017. Available from: https://www.clinicaltrials.gov/ct2/show/NCT02372253. [Last cited on 2017 May 05].