Advertisement

Calcium channel blocker use is associated with lower fasting serum glucose among adults with diabetes from the REGARDS study

Published:January 15, 2016DOI:https://doi.org/10.1016/j.diabres.2016.01.021

      Highlights

      • Diabetes does not have a definitive treatment, but in recent studies of mouse models of type 1 diabetes, verapamil, a commonly used medication for a variety of conditions, decreased β-cell apoptosis and restored insulin levels, essentially rescuing mice from the disease.
      • The role of verapamil as a possible anti-diabetic agent in humans is highly novel and unexplored.
      • Verapamil use was associated with significantly lower fasting blood glucose levels among participants with diabetes from a population-based cohort, controlling for a host of covariates.

      Abstract

      Background

      Ca2+ channel blockers (CCB) and verapamil in particular prevented β-cell apoptosis and enhanced endogenous insulin levels in recent studies of mouse models of diabetes. Verapamil's effect on serum glucose levels in humans with diabetes is not described.

      Methods

      We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS), a national cohort study of community-dwelling middle-aged and older adults, enrolled between 2003 and 2007 from the continental United States. We examined associations of CCB and verapamil use with fasting serum glucose among 4978 adults with diabetes, controlling for covariates in generalized linear models (GLM).

      Findings

      The sample included 1484 (29.6%) CCB users, of which 174 (3.4%) were verapamil users. In fully adjusted GLMs, CCB users had 5 mg/dL lower serum glucose compared to non-users. Verapamil users had on average 10 mg/dL lower serum glucose compared to CCB non-users with substantially greater differences among insulin users: 24 mg/dL lower serum glucose among users of insulin in combination with oral agents and 37 mg/dL lower among users of insulin alone.

      Interpretation

      CCB and in particular verapamil use was associated with lower fasting blood glucose levels among REGARDS participants with diabetes.

      Funding

      UO1NS041588 from the National Institute of Neurological Disorders and Stroke, NIH; K24HL111154 and R01HL080477 from the National Heart, Lung, and Blood Institute.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Diabetes Research and Clinical Practice
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Cnop M.
        • Welsh N.
        • Jonas J.C.
        • Jorns A.
        • Lenzen S.
        • Eizirik D.L.
        Mechanisms of pancreatic beta-cell death in type 1 and type 2 diabetes: many differences, few similarities.
        Diabetes. 2005; 54: S97-S107
        • Halban P.A.
        • Polonsky K.S.
        • Bowden D.W.
        • Hawkins M.A.
        • Ling C.
        • Mather K.J.
        • et al.
        Beta-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment.
        Diabetes Care. 2014; 37: 1751-1758
        • Mandrup-Poulsen T.
        Beta-cell apoptosis: stimuli and signaling.
        Diabetes. 2001; 50: S58-S63
        • Xu G.
        • Chen J.
        • Jing G.
        • Shalev A.
        Preventing beta-cell loss and diabetes with calcium channel blockers.
        Diabetes. 2012; 61: 848-856
        • Chen J.
        • Cha-Molstad H.
        • Szabo A.
        • Shalev A.
        Diabetes induces and calcium channel blockers prevent cardiac expression of proapoptotic thioredoxin-interacting protein.
        Am J Physiol Endocrinol Metab. 2009; 296: E1133-E1139
        • Howard V.J.
        • Cushman M.
        • Pulley L.
        • Gomez C.R.
        • Go R.C.
        • Prineas R.J.
        • et al.
        The reasons for geographic and racial differences in stroke study: objectives and design.
        Neuroepidemiology. 2005; 25: 135-143
        • Gillett S.R.
        • Boyle R.H.
        • Zakai N.A.
        • McClure L.A.
        • Jenny N.S.
        • Cushman M.
        Validating laboratory results in a national observational cohort study without field centers: the Reasons for Geographic and Racial Differences in Stroke cohort.
        Clin Biochem. 2014; 47: 243-246
        • Morisky D.E.
        • Green L.W.
        • Levine D.M.
        Concurrent and predictive validity of a self-reported measure of medication adherence.
        Med Care. 1986; 24: 67-74
        • Peralta C.A.
        • Shlipak M.G.
        • Judd S.
        • Cushman M.
        • McClellan W.
        • Zakai N.A.
        • et al.
        Detection of chronic kidney disease with creatinine, cystatin C, and urine albumin-to-creatinine ratio and association with progression to end-stage renal disease and mortality.
        JAMA. 2011; 305: 1545-1552
        • Elliott W.J.
        • Ram C.V.
        Calcium channel blockers.
        J Clin Hypertens. 2011; 13: 687-689
        • Akhtar M.
        • Tchou P.
        • Jazayeri M.
        Use of calcium channel entry blockers in the treatment of cardiac arrhythmias.
        Circulation. 1989; 80: IV31-IV39
        • Capobianco D.J.
        • Dodick D.W.
        Diagnosis and treatment of cluster headache.
        Semin Neurol. 2006; 26: 242-259
        • Pelzer N.
        • Stam A.H.
        • Haan J.
        • Ferrari M.D.
        • Terwindt G.M.
        Familial and sporadic hemiplegic migraine: diagnosis and treatment.
        Curr Treat Opt Neurol. 2013; 15: 13-27
        • Cooper-Dehoff R.
        • Cohen J.D.
        • Bakris G.L.
        • Messerli F.H.
        • Erdine S.
        • Hewkin A.C.
        • et al.
        Predictors of development of diabetes mellitus in patients with coronary artery disease taking antihypertensive medications (findings from the INternational VErapamil SR-Trandolapril STudy [INVEST]).
        Am J Cardiol. 2006; 98: 890-894
        • Cooper-DeHoff R.M.
        • Aranda Jr., J.M.
        • Gaxiola E.
        • Cangiano J.L.
        • Garcia-Barreto D.
        • Conti C.R.
        • et al.
        Blood pressure control and cardiovascular outcomes in high-risk Hispanic patients—findings from the International Verapamil SR/Trandolapril Study (INVEST).
        Am Heart J. 2006; 151: 1072-1079
        • Chen J.
        • Hui S.T.
        • Couto F.M.
        • Mungrue I.N.
        • Davis D.B.
        • Attie A.D.
        • et al.
        Thioredoxin-interacting protein deficiency induces Akt/Bcl-xL signaling and pancreatic beta-cell mass and protects against diabetes.
        FASEB J. 2008; 22 (official publication of the Federation of American Societies for Experimental Biology): 3581-3594
        • Chen J.
        • Saxena G.
        • Mungrue I.N.
        • Lusis A.J.
        • Shalev A.
        Thioredoxin-interacting protein: a critical link between glucose toxicity and beta-cell apoptosis.
        Diabetes. 2008; 57: 938-944
        • Jing G.
        • Westwell-Roper C.
        • Chen J.
        • Xu G.
        • Verchere C.B.
        • Shalev A.
        Thioredoxin-interacting protein promotes islet amyloid polypeptide expression through miR-124a and FoxA2.
        J Biol Chem. 2014; 289: 11807-11815
        • Sherifali D.
        • Nerenberg K.
        • Pullenayegum E.
        • Cheng J.E.
        • Gerstein H.C.
        The effect of oral antidiabetic agents on A1C levels: a systematic review and meta-analysis.
        Diabetes Care. 2010; 33: 1859-1864