Download PDF
Exp Clin Endocrinol Diabetes 2021; 129(06): 443-448
DOI: 10.1055/a-0919-4525
Article

Association Between Glycaemic Control and the Intake of Thiazide Diuretics, Beta Blockers and Levothyroxine in People Without Diabetes

Johannes Roth
1   Department of Anesthesia and Intensive Care, Jena University Hospital, Jena, Germany
2   Jena University Hospital, Department of Internal Medicine III, Division of Endocrinology and Metabolic Diseases, Jena, Germany
,
Nicole Müller
2   Jena University Hospital, Department of Internal Medicine III, Division of Endocrinology and Metabolic Diseases, Jena, Germany
,
Nadine Kuniss
2   Jena University Hospital, Department of Internal Medicine III, Division of Endocrinology and Metabolic Diseases, Jena, Germany
,
Gunter Wolf
2   Jena University Hospital, Department of Internal Medicine III, Division of Endocrinology and Metabolic Diseases, Jena, Germany
,
Ulrich Alfons Müller
2   Jena University Hospital, Department of Internal Medicine III, Division of Endocrinology and Metabolic Diseases, Jena, Germany
› Author Affiliations
› Further Information
Also available at
    Permissions and Reprints

Abstract

Objective The pharmacological additional information for many medications includes warnings stating that the blood sugar control may be worsened by the intake of certain drugs. However a quantification of the effects is missing. This may result in confusion for patients as well as for their physicians. The aim of this study was to assess a potential association between medication (beta blockers, thiazides, levothyroxine) and HbA1c in people without diabetes.

Methods In this cross-sectional study we analysed data from 2 921 people (7 699 visits) without diabetes (age 46.6 y; 69.1% women; BMI 27.6±6.4 kg/m²; HbA1c 5.2%) who had at least one HbA1c determination and a complete documentation of their drug intake. An oral glucose tolerance test was not performed. The participants were divided in 8 groups (no regular drug intake, levothyroxine alone, beta blockers alone, thiazides alone, combination 2 of 3, combination of all 3). Patients with known distorting influences of the HbA1c were excluded.

Results People with no regular drug intake had an HbA1c of 5.4% [35.8 mmol/mol]. The HbA1c of the group that took all 3 drugs in combination was 5.6% [38.2 mmol/mol]. A multiple linear mixed model showed an increase in HbA1c for thiazides (β=0.0558, p=0.025) and a decrease for combination of levothyroxine and thiazide (β=−0.0765, p=0.010).

Conclusion Thiazides and the combination of levothyroxine and thiazides were associated with slight changes in HbA1c. In this study there was no association between the intake of beta blockers and HbA1c. At least for people without diabetes these effects seem to be of minor importance.

Key words

HbA1c - metabolic control - medication - beta blockers - thiazides - levothyroxine


Publication History

Received: 31 January 2019
Received: 22 April 2019

Accepted: 14 May 2019

Article published online:
01 July 2019

© 2019. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Goffrier B, Schulz M, Bätzing-Feigenbaum J. Administrative Prävalenzen und Inzidenzen des Diabetes mellitus von 2009 bis 2015. 10.20364/VA-17.03. Available at http://www.versorgungsatlas.de/themen/alle-analysen-nach-datum-sortiert/?tab=6&uid=79 (last accessed 13 September 2017)
  • 2 Luijks H, Schermer T, Bor H. et al. Prevalence and incidence density rates of chronic comorbidity in type 2 diabetes patients: An exploratory cohort study. BMC Med 2012; Oct 29 10: 128
    CrossrefPubMedSearch in Google Scholar
  • 3 Chamberlain JJ, Rhinehart AS, Shaefer Jr CF. et al. Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med 2016; Apr 19 164: 542-552
    CrossrefPubMedSearch in Google Scholar
  • 4 Diabetes-in-Control. Drugs that can affect blood glucose levels. 2016. Available at http://www.diabetesincontrol.com/images/tools/druglistaffectingbloodglucose.pdf (last accessed 13 September 2017
  • 5 Tsujimoto T, Sugiyama T, Shapiro MF. et al. Risk of Cardiovascular Events in Patients With Diabetes Mellitus on β-Blockers. Hypertension. 07/2017; 70: 103-110
    CrossrefPubMedSearch in Google Scholar
  • 6 Rote Liste.. Drug information Database for Germany. Available at https://online.rote-liste.de (last accessed 14 September 2017
  • 7 Barron AJ, Zaman N, Cole GD. et al. Systematic review of genuine versus spurious side-effects of beta-blockers in heart failure using placebo control: Recommendations for patient information. Int J Cardiol 2013; 168: 3572-3579
    CrossrefPubMedSearch in Google Scholar
  • 8 Park C, Yang I, Woo J. et al. Acute hyperglycemia and activation of the beta-adrenergic system exhibit synergistic inhibitory actions on growth hormone (GH) releasing hormone-induced GH release. Eur J Endocrinol 2003; 148: 635-640
    CrossrefPubMedSearch in Google Scholar
  • 9 Horev A, Haim A, Zvulunov A. Propranolol induced hypoglycemia. Pediatr Endocrinol Rev 2015; Mar 12: 308-310
    PubMedSearch in Google Scholar
  • 10 The ADVANCE Collaborative Group Action in Diabetes and Vascular Disease. Modified-Release Controlled Evaluation. N Engl J Med 2008; 358: 2560-2572
    CrossrefPubMedSearch in Google Scholar
  • 11 Curb JD, Pressel SL, Cutler JA. et al. Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. Systolic Hypertension in the Elderly Program Cooperative Research. Group. JAMA 1996; 276: 1886-1892
    CrossrefPubMedSearch in Google Scholar
  • 12 Kostis JB, Wilson AC, Freudenberger RS. et al. Long-term effect of diuretic-based therapy on fatal outcomes in subjects with isolated systolic hypertension with and without diabetes. Am J Cardiol 2005; 95: 29-35
    CrossrefPubMedSearch in Google Scholar
  • 13 Zhang X, Zhao Q. Association of Thiazide-Type Diuretics With Glycemic Changes in Hypertensive Patients: A Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials. J ClinHypertens (Greenwich) 2016; Apr 18: 342-351
    CrossrefPubMedSearch in Google Scholar
  • 14 Natali A, Quiñones Galvan A, Santoro D. et al. Relationship between insulin release, antinatriuresis and hypokalaemia after glucose ingestion in normal and hypertensive man. Clin Sci (Lond) 10/1993; 85: 327-335
    CrossrefPubMedSearch in Google Scholar
  • 15 Iwen KA, Schröder E, Brabant G. Thyroid hormones and the metabolic syndrome.Eur. Thyroid J 2013; Jun 2: 83-92
    CrossrefPubMedSearch in Google Scholar
  • 16 Lambadiari V, Mitrou P, Maratou E. et al. Thyroid hormones are positively associated with insulin resistance early in the development of type 2 diabetes. Endocrine 02/2011; 39: 28-32
    CrossrefPubMedSearch in Google Scholar
  • 17 Szkudelski T, Michalski W, Szkudelska K. The effect of thyroid hormones on blood insulin level and metabolic parameters in diabetic rats. J Physiol Biochem 2003; Jun 59: 71-76
    CrossrefPubMedSearch in Google Scholar
  • 18 Yang L, Shen X, Yan S. et al. HbA1c in the diagnosis of diabetes and abnormal glucose tolerance in patients with Graves' hyperthyroidism. Diabetes Res Clin Pract 07/2013; 101: 28-34
    CrossrefPubMedSearch in Google Scholar
  • 19 Wintergerst KA, Rogers ES, Foster MB. Hyperthyroidism presenting with hyperglycemia in an adolescent female. J Pediatr Endocrinol Metab 2011; 24: 385-387
    CrossrefPubMedSearch in Google Scholar
  • 20 Roubsanthisuk W, Watanakejorn P, Tunlakit M. et al. Hyperthyroidism induces glucose intolerance by lowering both insulin secretion and peripheral insulin sensitivity. J Med Assoc Thai 11/2006; 89 Suppl 5 S133-S140
    PubMedSearch in Google Scholar
  • 21 Schwabe U, Paffrath D. (Hrsg) Arzneimittelverordnungs-Report. 2014: p 982. Springer Verlag Berlin Heidelberg: 2014.
  • 22 Han C, He X, Xia X. et al. Subclinical Hypothyroidism and Type 2 Diabetes. A Systematic Review and Meta-Analysis. PLoSOne 2015; Aug 13 10: e0135233
    PubMedSearch in Google Scholar
  • 23 Schumann M.. Electronic Medical Information System for long-term documentation of chronic diseases (EMIL). 2013; Available at http://cleverdoku.de (last accessed 25 January 2018)
  • 24 Halwachs-Baumann G, Katzensteiner S, Schnedl W. et al. Comparative evaluation of three assay systems for automated determination of hemoglobin A1c. Clin Chem. 1997; 43: 511-517
    CrossrefPubMedSearch in Google Scholar
  • 25 Chapelle JP, Teixeira J, Maisin D. et. al. Multicentre evaluation of the TosohHbA1cG8analyser. Clin Chem Lab Med 2010; 48: 365-371
    CrossrefPubMedSearch in Google Scholar
  • 26 The WHO. Haemoglobin concentrations for the diagnosis of anaemia and assessment of severity. Available at http://www.who.int/vmnis/indicators/haemoglobin.pdf (last accessed 14 September 2017
  • 27 Pani LN, Korenda L, Meigs JB. et al. Effect of aging on A1C levels in individuals without diabetes. Evidence from the Framingham Offspring Study and the National Health and Nutrition Examination Survey 2001–2004. Diabetes Care 2008; 31: 1991-1996
    CrossrefPubMedSearch in Google Scholar
  • 28 Roth J, Müller N, Lehmann T. et al. HbA1c and age in non-diabetic subjects: An ignored association?. Exp Clin Endocrinol Diabetes 2016; 124: 637-642
    PubMedSearch in Google Scholar
  • 29 The DESIR Study Group. HbA1c, fasting and 2 h plasma glucose in current, ex- and never-smokers: A meta-analysis. Diabetologia 2014; Jan 57: 30-39
    CrossrefPubMedSearch in Google Scholar
  • 30 Pottegård A, Pedersen SA, Schmidt SAJ. et al. Association of Hydrochlorothiazide Use and Risk of Malignant Melanoma. JAMA. Intern Med 01.08.2018; 178: 1120-1122
    PubMedSearch in Google Scholar
  • 31 Pedersen SA, Johannesdottir Schmidt SA. et al. Hydrochlorothiazide use and risk for Merkel cell carcinoma and malignant adnexal skin tumors: A nationwide case-control study. J Am Acad Dermatol 02/2019; 80: 460-465
    CrossrefPubMedSearch in Google Scholar
  • 32 Savage PJ, Pressel SL, Curb JD. et al. Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group. Arch Intern Med 13.04.1998; 158: 741-751
    CrossrefPubMedSearch in Google Scholar
  • 33 Moser M. Why are physicians not prescribing diuretics more frequently in the management of hypertension?. JAMA 1998; Jun 10 279: 1813-1816
    CrossrefPubMedSearch in Google Scholar
  • 34 Hirst JA, Farmer AJ, Feakins BG. et al. Quantifying the effects of diuretics and β-adrenoceptor blockers on glycaemic control in diabetes mellitus - a systematic review and meta-analysis. Br J Clin Pharmacol 05/2015; 79: 733-743
    CrossrefPubMedSearch in Google Scholar
  • 35 Majumdar SR. Beta-blockers for the treatment of hypertension in patients with diabetes: exploring the contraindication myth. Cardiovasc Drugs Ther 1999; Sep 13: 435-439
    CrossrefPubMedSearch in Google Scholar
  • 36 Masuch A, Friedrich N, Roth J. et al. Preventing misdiagnosis of diabetes in the elderly: Age-dependent HbA1c reference intervals derived from two population-based study cohorts. BMC Endocr Disord 12.02.2019; 19: 20
    CrossrefPubMedSearch in Google Scholar