International Journal of Clinical Pharmacy

, Volume 34, Issue 6, pp 863–870 | Cite as

Optimisation of glycaemic control during episodes of severe/acute hyperglycaemia in patients with type 2 diabetes mellitus

  • Hasniza Zaman HuriEmail author
  • Mohd Makmor-Bakry
  • Rosnani Hashim
  • Norlaila Mustafa
  • Wan Zurinah Wan Ngah
Research Article


Background Patients with type 2 diabetes mellitus (T2DM) are frequently admitted to the hospital with severe or acute hyperglycaemia secondary to an acute illness or disease. Uncontrolled glycaemia is a significant problem during severe or acute hyperglycaemia. Objective This study sought to identify demographic, clinical, and genetic factors that may contribute to increased insulin resistance or worsening of glycaemic control in patients with T2DM. Setting This prospective cohort study included 156 patients with T2DM and severe or acute hyperglycaemia who were treated with insulin at any medical ward of the National University of Malaysia Medical Centre. Method Insulin resistance was determined using the homeostatic model assessment–insulin resistance index. Glycaemic control during the episode of hyperglycaemia was assessed as the degree to which the patient achieved the target glucose levels. The polymerase chain reaction–restriction fragment length polymorphism method was used to identify polymorphisms in insulin receptor substrate (IRS) genes. Main outcome measure Identification of possible predictors (demographic, clinical, or genetic) for insulin resistance and glycaemic control during severe/acute hyperglycaemia. Results A polymorphism in IRS1, r.2963 G>A (p.Gly972Arg), was a significant predictor of both insulin resistance [odds ratios (OR) 4.48; 95 % confidence interval (CI) 1.2–16.7; P = 0.03) and worsening of glycaemic control (OR 6.04; 95 % CI 0.6–64.6; P = 0.02). The use of loop diuretics (P < 0.05) and antibiotics (P < 0.05) may indirectly predict worsening of insulin resistance or glycaemic control in patients with severe/acute hyperglycaemia. Conclusion Clinical and genetic factors contribute to worsening of insulin resistance and glycaemic control during severe/acute hyperglycaemia in patients with T2DM. Early identification of factors that may influence insulin resistance and glycaemic control may help to achieve optimal glycaemic control during severe/acute hyperglycaemia.


Acute hyperglycaemia Genetics Glycaemic control Insulin resistance Malaysia Predictive models Predictors Type 2 diabetes 



The authors would like to thank the National University of Malaysia, University of Malaya, Malaysia, and the Ministry of Higher Education, Malaysia, for financial and technical support.

Conflicts of interest

The authors have no conflict of interest to report.


  1. 1.
    Shaw J, Sicree R, Zimmet P. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010;87(1):4–14.PubMedCrossRefGoogle Scholar
  2. 2.
    WHO 2011. Diabetes. Accessed 15 June 2012.
  3. 3.
    West KM, Kalbfleisch JM. Glucose tolerance, nutrition, and diabetes in Uruguay, Venezuela, Malaya, and East Pakistan. Diabetes. 1966;15:9–18.PubMedGoogle Scholar
  4. 4.
    Mustaffa BE. Diabetes mellitus in peninsular Malaysia: ethnic differences in prevalence and complications. Ann Acad Med Singap. 1985;14:272–6.PubMedGoogle Scholar
  5. 5.
    Khalid BA, Usha R, Ng ML, Norella Kong CT, Tariq AR. Prevalence of diabetes, hypertension and renal disease amongst railway workers in Malaysia. Med J Malaysia. 1990;45:8–13.PubMedGoogle Scholar
  6. 6.
    Letchuman GR, Wan Nazaimoon WM, Wan Mohamad WB, Chandran LR, Tee GH, Jamaiyah H, et al. Prevalence of diabetes in the Malaysian National Health Morbidity Survey III 2006. Med J Malaysia. 2010;65(3):173–9.Google Scholar
  7. 7.
    Huri HZ, Min YS, Pendek R. Episodes of hypoglycemia and hyperglycemia during the use of sliding scale insulin in hospitalized diabetes patients. Asian biomed. 2007;1(3):307–11.Google Scholar
  8. 8.
    Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care. 2009;32(7):1335–43.PubMedCrossRefGoogle Scholar
  9. 9.
    ADA. Standard of medical care in diabetes 2012. Diabetes Care. 2012;35(1):S11–63.CrossRefGoogle Scholar
  10. 10.
    Burgering BM, Coffer PJ. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature. 1985;376:599–602.CrossRefGoogle Scholar
  11. 11.
    Zhao L, Sun D, Cao F, Yin T, Wang H. Can insulin resistance be reversed by insulin therapy? Med Hypotheses. 2009;72:34–5.PubMedCrossRefGoogle Scholar
  12. 12.
    Aileen JM, Edward PF, Ronald K. Human insulin receptor substrate-1 (IRS-1) polymorphism G972R causes IRS-1 to associate with the insulin receptor and inhibit receptor autophosphorylation. J Biol Chem. 2005;280(8):6441–6.CrossRefGoogle Scholar
  13. 13.
    Yiqing S, JoAnn EM, Lesley T, Barbara VH, Lewis HK, Lauren N, et al. Insulin sensitivity and insulin secretion determined by homeostasis model assessment (HOMA) and risk of diabetes in a multiethnic cohort of women: the women’s health initiative observational study. Diabetes Care. 2007;30(7):1747–52.CrossRefGoogle Scholar
  14. 14.
    Li Y, Xu W, Liao Z, Yao B, Chen X, Huang Z, et al. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients is associated with improvement of beta-cell function. Diabetes Care. 2004;27(11):2597–602.PubMedCrossRefGoogle Scholar
  15. 15.
    Elkeles R, Godsland IF, Feher MD, Rubens MB, Roughton M, Nugara F, PREDICT Study Group, et al. Coronary calcium measurement improves prediction of cardiovascular events in asymptomatic patients with type 2 diabetes: the PREDICT study. Eur Heart J. 2008;29(18):2244–51.PubMedCrossRefGoogle Scholar
  16. 16.
    Chen HS, Wu TE, Jap TS, Hsiao LC, Lee SH, Lin HD. Beneficial effects of insulin on glycemic control and beta-cell function in newly diagnosed type 2 diabetes with severe hyperglycemia after short-term intensive insulin therapy. Diabetes Care. 2008;31(10):1927–32.PubMedCrossRefGoogle Scholar
  17. 17.
    Marenzi G, De Metrio M, Rubino M, Lauri G, Cavallero A, Assanelli E, et al. Acute hyperglycemia and contrast-induced nephropathy in primary percutaneous coronary intervention. Am Heart J. 2010;160(6):1170–7.PubMedCrossRefGoogle Scholar
  18. 18.
    WMA. Declaration of Helsinki. Ethical principles for medical research involving human subjects. 59th WMA General Assembly, Seoul 2008. Accessed 15 Nov 2011.
  19. 19.
    Green S. How many subjects does it take to do a regression analysis? Multivariate Behav Res. 1991;26:499–510.CrossRefGoogle Scholar
  20. 20.
    Harris RJ. A primer of multivariate statistics. 2nd ed. New York: Academic Press; 1985.Google Scholar
  21. 21.
    Hsieh FY, Bloch DA, Larsen MD. A simple method of sample size calculation for linear and logistic regression. Stat Med. 1998;17:1623–34.PubMedCrossRefGoogle Scholar
  22. 22.
    Inzucchi SE. Management of hyperglycemia in the hospital setting. New Engl J Med. 2006;355(18):1903–11.PubMedCrossRefGoogle Scholar
  23. 23.
    Marfella R, Verrazzo G, Acampora R, La Marca C, Giunta R, Lucarelli C, et al. Glutathione reverses systemic hemodynamic changes induced by acute hyperglycemia in healthy subjects. Am J Physiol. 1995;268(6):E1167–73.PubMedGoogle Scholar
  24. 24.
    AGS. Physician consortium for performance improvement®, National Committee for Quality Assurance. Geriatrics physician performance measurement set. Chicago, IL: American Medical Association (AMA); 2009.Google Scholar
  25. 25.
    Muniyappa R, Lee S, Chen H, Quon MJ. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am J Physiol Endocrinol Metab. 2008;294:E15–26.PubMedCrossRefGoogle Scholar
  26. 26.
    Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412–9.PubMedCrossRefGoogle Scholar
  27. 27.
    Federici M, Petrone A, Porzio O, Bizzarri C, Lauro D, D’Alfonso R, et al. The Gly972Arg IRS-1 variant is associated with type 1 diabetes in continental Italy. Diabetes. 2003;52(3):887–90.PubMedCrossRefGoogle Scholar
  28. 28.
    Fritsche A, Madaus A, Renn W, Tschritter O, Teigeler A, Weisser M, et al. The prevalent Gly1057Asp polymorphism in the insulin receptor substrate-2 gene is not associated with impaired insulin secretion. JCEM. 2001;86:4822–5.PubMedGoogle Scholar
  29. 29.
    Clement S, Braithwaite SS, Magee MF, Ahmann A, Smith EP, Schafer RG, et al. American Diabetes Association Diabetes in Hospitals Writing Committee: management of diabetes and hyperglycemia in hospitals (Technical Review). Diabetes Care. 2004;27:553–97.PubMedCrossRefGoogle Scholar
  30. 30.
    Moghissi ES, Korytkowski MT, DiNardo M, Einhorn D, Hellman R, Hirsch IB, et al. American Association of Clinical Endocrinologists and ADA consensus statement on inpatient glycemic control. Diabetes Care. 2009;32(6):1119–31.PubMedCrossRefGoogle Scholar
  31. 31.
    Kim J, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: molecular and pathophysiological mechanisms. Circulation. 2006;113:1888–904.PubMedCrossRefGoogle Scholar
  32. 32.
    Almind K, Inoue G, Pedersen O, Kahn CR. A common amino acid polymorphism in insulin receptor substrate-1 causes impaired insulin signaling: evidence from transfection studies. J Clin Invest. 1996;97:2569–75.PubMedCrossRefGoogle Scholar
  33. 33.
    Yoshimura R, Araki E, Ura S, Todaka M, Tsurozoe K, Furukawa N, et al. Impact of natural IRS-1 mutations on insulin signals. Diabetes. 1997;46:929–36.PubMedCrossRefGoogle Scholar
  34. 34.
    Almind K, Bjorbaek C, Vestergaard H, Hansen T, Echwald SM, Pedersen O. Amino acid polymorphism in insulin receptor substrate-1 in non-insulin-dependent diabetes mellitus. Lancet. 1993;342:828–32.PubMedCrossRefGoogle Scholar
  35. 35.
    Imai Y, Fusco A, Suzuki Y, Lesniak M, D’Alfonso R, Sesti G, et al. Variant sequences of insulin receptor substrate-1 in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1994;79:1655–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Hager J, Zouali H, Velho G, Froguel P. Insulin receptor substrate-1 (IRS-1) polymorphisms in French NIDDM families. Lancet. 1993;342:1430.PubMedCrossRefGoogle Scholar
  37. 37.
    Mori H, Hashiramoto M, Kishimoto M, Kasuga M. Amino acid polymorphism of insulin receptor substrate-1 in Japanese noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1995;80:2822–6.PubMedCrossRefGoogle Scholar
  38. 38.
    Shimokawa K, Kadowaki H, Sakura H, Otabe S, Hagura R, Kosaka K, et al. Molecular scanning of the glycogen synthase and insulin receptor substrate-1 in Japanese subjects with non-insulin-dependent diabetes mellitus. Biochem Biophys Res Commun. 1994;202:463–9.PubMedCrossRefGoogle Scholar
  39. 39.
    Lee-Ming C, Chuen-Shiang L, Jih-I Y, Huey-Peir W, Tong-Yuan T, Boniface L. No association between the Gly972 Arg variant of the insulin receptor substrate-1 gene and NIDDM in Taiwanese population. Diabetes Care. 1996;19:446–9.CrossRefGoogle Scholar
  40. 40.
    Andersson C, Norgaard ML, Hansen PR, Fosbol EL, Schmiegelow M, Weeke P, et al. Heart failure severity as determined by loop diuretic dosages, predicts the risk of developing diabetes after myocardial infarction: a nationwide cohort study. Eur Heart J. 2010;12(12):1333–8.CrossRefGoogle Scholar
  41. 41.
    Feely J, O’Byrne S. Effects of drugs on glucose tolerance in non-insulin dependent diabetes. Drugs. 1990;40:6–18.PubMedCrossRefGoogle Scholar
  42. 42.
    Pollare T, Litchell M, Berne C. A comparison of the effects of hydrochlorothiazide and captopril on glucose and lipid metabolism in patients with hypertension. N Engl J Med. 1989;321:868–73.PubMedCrossRefGoogle Scholar
  43. 43.
    Joshi N, Caputo G, Weitekamp M, Karchmer A. Infections in patients with diabetes mellitus. N Engl J Med. 1999;341:1906–12.PubMedCrossRefGoogle Scholar
  44. 44.
    Pandit MK, Burke J, Gustafson AB, Minocha A, Peiris AN. Drug-induced disorders of glucose tolerance. Ann Int Med. 1993;118:529–40.PubMedGoogle Scholar
  45. 45.
    Magee MF. Insulin therapy for intensive glycemic control in hospital patients. Hosp Physician. 2006;38:17–27.Google Scholar
  46. 46.
    Pankaj S (2009). Glucocorticoid- induced diabetes mellitus. Mayo Clinic. Accessed 31 July 2012.

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Hasniza Zaman Huri
    • 1
    Email author
  • Mohd Makmor-Bakry
    • 2
  • Rosnani Hashim
    • 3
  • Norlaila Mustafa
    • 4
  • Wan Zurinah Wan Ngah
    • 5
  1. 1.Department of Pharmacy, Faculty of MedicineUniversity of MalayaKuala LumpurMalaysia
  2. 2.Faculty of PharmacyThe National University of MalaysiaKuala LumpurMalaysia
  3. 3.Faculty of PharmacyCyberjaya University College of Medical SciencesCyberjayaMalaysia
  4. 4.Department of Medicine, Faculty of MedicineThe National University of MalaysiaKuala LumpurMalaysia
  5. 5.Department of Biochemistry, Faculty of MedicineThe National University of MalaysiaKuala LumpurMalaysia

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