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Clinical focus: Cardiometabolic Conditions - Review

Beta-cell failure in type 2 diabetes: mechanisms, markers, and clinical implications

ORCID Icon & ORCID Icon
Pages 676-686 | Received 02 Dec 2019, Accepted 15 May 2020, Published online: 16 Jun 2020

References

  • Cerf ME. Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne). 2013;4:37.
  • Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nat Rev Endocrinol. 2018 Feb;14(2):88–98.
  • Kendall DM, Cuddihy RM, Bergenstal RM. Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. Am J Med. 2009 Jun;122(6 Suppl):S37–50.
  • Ferrannini E, Nannipieri M, Williams K, et al. Mode of onset of type 2 diabetes from normal or impaired glucose tolerance. Diabetes. 2004 Jan;53(1):160–165.
  • Ahlqvist E, Storm P, Käräjämäki A, et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018 May;6(5):361–369.
  • Khunti S, Khunti K, Seidu S. Therapeutic inertia in type 2 diabetes: prevalence, causes, consequences and methods to overcome inertia. Ther Adv Endocrinol Metab. 2019;10:2042018819844694.
  • Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000 Aug 12;321(7258):405–412.
  • Carls G, Huynh J, Tuttle E, et al. Achievement of glycated hemoglobin goals in the US remains unchanged through 2014. Diabetes Ther. 2017 8;Aug(4):863–873.
  • NCQA. Comprehensive diabetes care (CDC); [ cited 2019 Oct 2]. Available from: https://www.ncqa.org/hedis/measures/comprehensive-diabetes-care/.
  • Kahn SE. Clinical review 135: the importance of beta-cell failure in the development and progression of type 2 diabetes. J Clin Endocrinol Metab. 2001 Sep;86(9):4047–4058.
  • UKPDS. U.K. Prospective diabetes study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. U.K. Prospective diabetes study group. Diabetes. 1995 Nov;44(11):1249–1258.
  • Holman RR. Assessing the potential for alpha-glucosidase inhibitors in prediabetic states. Diabetes Res Clin Pract. 1998 Jul;40(Suppl):S21–25.
  • Bretzel RG, Eckhard M, Landgraf W, et al. Initiating insulin therapy in type 2 diabetic patients failing on oral hypoglycemic agents: basal or prandial insulin? The APOLLO trial and beyond. Diabetes Care. 2009 Nov;32(Suppl 2):S260–265.
  • Ferrannini E. The stunned beta cell: a brief history. Cell Metab. 2010 May 5;11(5):349–352.
  • Ferrannini E, Natali A, Bell P, et al. Insulin resistance and hypersecretion in obesity. European Group for the Study of Insulin Resistance (EGIR). J Clin Invest. 1997 Sep 1;100(5):1166–1173.
  • Fonseca VA. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009 Nov;32(Suppl 2):S151–156.
  • Weyer C, Bogardus C, Mott DM, et al. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest. 1999 Sep;104(6):787–794.
  • Swisa A, Glaser B, Dor Y. Metabolic stress and compromised identity of pancreatic beta cells. Front Genet. 2017;8:21.
  • Clark A, Wells CA, Buley ID, et al. Islet amyloid, increased A-cells, reduced B-cells and exocrine fibrosis: quantitative changes in the pancreas in type 2 diabetes. Diabetes Res. 1988 Dec;9(4):151–159.
  • Butler AE, Janson J, Bonner-Weir S, et al. Beta-cell deficit and increased beta-cell apoptosis in humans with type 2 diabetes. Diabetes. 2003 Jan;52(1):102–110.
  • Rahier J, Guiot Y, Goebbels RM, et al. Pancreatic beta-cell mass in European subjects with type 2 diabetes. Diabetes Obes Metab. 2008 Nov;10(Suppl 4):32–42.
  • Tabák AG, Jokela M, Akbaraly TN, et al. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet. 2009 Jun 27;373(9682):2215–2221.
  • Garofano A, Czernichow P, Bréant B. In utero undernutrition impairs rat beta-cell development. Diabetologia. 1997 Oct;40(10):1231–1234.
  • Petrik J, Reusens B, Arany E, et al. A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II. Endocrinology. 1999 Oct;140(10):4861–4873.
  • Meier JJ. Linking the genetics of type 2 diabetes with low birth weight: a role for prenatal islet maldevelopment? Diabetes. 2009 Jun;58(6):1255–1256.
  • Kaneto H, Kajimoto Y, Miyagawa J, et al. Beneficial effects of antioxidants in diabetes: possible protection of pancreatic beta-cells against glucose toxicity. Diabetes. 1999 Dec;48(12):2398–2406.
  • Kaneto H, Xu G, Fujii N, et al. Involvement of c-Jun N-terminal kinase in oxidative stress-mediated suppression of insulin gene expression. J Biol Chem. 2002 Aug 16;277(33):30010–30018.
  • Krauss S, Zhang CY, Scorrano L, et al. Superoxide-mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest. 2003 Dec;112(12):1831–1842.
  • Robertson R, Zhou H, Zhang T, et al. Chronic oxidative stress as a mechanism for glucose toxicity of the beta cell in type 2 diabetes. Cell Biochem Biophys. 2007;48(2–3):139–146.
  • Robertson RP, Harmon J, Tran PO, et al. Glucose toxicity in beta-cells: type 2 diabetes, good radicals gone bad, and the glutathione connection. Diabetes. 2003 Mar;52(3):581–587.
  • Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev. 2008 May;29(3):351–366.
  • Lenzen S. Oxidative stress: the vulnerable beta-cell. Biochem Soc Trans. 2008 Jun;36(Pt 3):343–347.
  • Halban PA, Polonsky KS, Bowden DW, et al. Beta-cell failure in type 2 diabetes: postulated mechanisms and prospects for prevention and treatment. Diabetes Care. 2014 Jun;37(6):1751–1758.
  • Back SH, Kaufman RJ. Endoplasmic reticulum stress and type 2 diabetes. Annu Rev Biochem. 2012;81:767–793.
  • Evans-Molina C, Hatanaka M, Mirmira RG. Lost in translation: endoplasmic reticulum stress and the decline of beta-cell health in diabetes mellitus. Diabetes Obes Metab. 2013 Sep;15(Suppl 3):159–169.
  • Pinnick K, Neville M, Clark A, et al. Reversibility of metabolic and morphological changes associated with chronic exposure of pancreatic islet beta-cells to fatty acids. J Cell Biochem. 2010 Mar 1;109(4):683–692.
  • Cruzat VF, Keane KN, Scheinpflug AL, et al. Alanyl-glutamine improves pancreatic beta-cell function following ex vivo inflammatory challenge. J Endocrinol. 2015 Mar;224(3):261–271.
  • Lim EL, Hollingsworth KG, Aribisala BS, et al. Reversal of type 2 diabetes: normalisation of beta cell function in association with decreased pancreas and liver triacylglycerol. Diabetologia. 2011 Oct;54(10):2506–2514.
  • Steven S, Hollingsworth KG, Al-Mrabeh A, et al. Very low-calorie diet and 6 months of weight stability in type 2 diabetes: pathophysiological changes in responders and nonresponders. Diabetes Care. 2016 May;39(5):808–815.
  • Talchai C, Xuan S, Lin HV, et al. Pancreatic beta cell dedifferentiation as a mechanism of diabetic beta cell failure. Cell. 2012 Sep 14;150(6):1223–1234.
  • Laybutt DR, Hawkins YC, Lock J, et al. Influence of diabetes on the loss of beta cell differentiation after islet transplantation in rats. Diabetologia. 2007 Oct;50(10):2117–2125.
  • Blum B, Roose AN, Barrandon O, et al. Reversal of beta cell de-differentiation by a small molecule inhibitor of the TGFbeta pathway. Elife. 2014 Sep;16(3):e02809.
  • Brereton MF, Iberl M, Shimomura K, et al. Reversible changes in pancreatic islet structure and function produced by elevated blood glucose. Nat Commun. 2014 Aug;22(5):4639.
  • Wang Z, York NW, Nichols CG, et al. Pancreatic beta cell dedifferentiation in diabetes and redifferentiation following insulin therapy. Cell Metab. 2014 May 6;19(5):872–882.
  • Kahn SE. The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of type 2 diabetes. Diabetologia. 2003 Jan;46(1):3–19.
  • Cernea S, Dobreanu M. Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. Biochem Med (Zagreb). 2013;23(3):266–280.
  • Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004 Jun;27(6):1487–1495.
  • Cersosimo E, Solis-Herrera C, Trautmann ME, et al. Assessment of pancreatic beta-cell function: review of methods and clinical applications. Curr Diabetes Rev. 2014 Jan;10(1):2–42.
  • Russo GT, Giorda CB, Cercone S, et al. Beta cell stress in a 4-year follow-up of patients with type 2 diabetes: a longitudinal analysis of the BetaDecline Study. Diabetes Metab Res Rev. 2018 Sep;34(6):e3016.
  • Russo GT, Giorda CB, Cercone S, et al. Factors associated with beta-cell dysfunction in type 2 diabetes: the BETADECLINE study. PLoS One. 2014;9(10):e109702.
  • Matthews DR, Cull CA, Stratton IM, et al. UKPDS 26: sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK prospective diabetes study (UKPDS) group. Diabet Med. 1998 Apr;15(4):297–303.
  • Hou X, Liu J, Song J, et al. Relationship of hemoglobin A1c with beta cell function and insulin resistance in newly diagnosed and drug naive type 2 diabetes patients. J Diabetes Res. 2016;2016:8797316.
  • Fang FS, Cheng XL, Gong YP, et al. Association between glycemic indices and beta cell function in patients with newly diagnosed type 2 diabetes. Curr Med Res Opin. 2014 Aug;30(8):1437–1440.
  • White MG, Shaw JA, Taylor R. Type 2 diabetes: the pathologic basis of reversible beta-cell dysfunction. Diabetes Care. 2016 Nov;39(11):2080–2088.
  • Ohashi K, Fujii M, Uda S, et al. Increase in hepatic and decrease in peripheral insulin clearance characterize abnormal temporal patterns of serum insulin in diabetic subjects. NPJ Syst Biol Appl. 2018;4:14.
  • Røder ME, Porte D Jr., Schwartz RS, et al. Disproportionately elevated proinsulin levels reflect the degree of impaired B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab. 1998 Feb;83(2):604–608.
  • Loopstra-Masters RC, Haffner SM, Lorenzo C, et al. Proinsulin-to-C-peptide ratio versus proinsulin-to-insulin ratio in the prediction of incident diabetes: the Insulin Resistance Atherosclerosis Study (IRAS). Diabetologia. 2011 Dec;54(12):3047–3054.
  • Leighton E, Sainsbury CA, Jones GC. A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017 Jun;8(3):475–487.
  • Polonsky KS, Licinio-Paixao J, Given BD, et al. Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type I diabetic patients. J Clin Invest. 1986 Jan;77(1):98–105.
  • Luzi L, Zerbini G, Caumo A. C-peptide: a redundant relative of insulin? Diabetologia. 2007 Mar;50(3):500–502.
  • American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2020. Diabetes Care. 2020 Jan;43(Suppl1):S14–S31.
  • Palmer JP, Fleming GA, Greenbaum CJ, et al. C-peptide is the appropriate outcome measure for type 1 diabetes clinical trials to preserve beta-cell function: report of an ADA workshop, 21-22 October 2001. Diabetes. 2004 Jan;53(1):250–264.
  • McDonald TJ, Perry MH, Peake RW, et al. EDTA improves stability of whole blood C-peptide and insulin to over 24 hours at room temperature. PLoS One. 2012;7(7):e42084.
  • Oddoze C, Lombard E, Portugal H. Stability study of 81 analytes in human whole blood, in serum and in plasma. Clin Biochem. 2012 Apr;45(6):464–469.
  • Jane Ellis M, Livesey JH, Evans MJ. Hormone stability in human whole blood. Clin Biochem. 2003 Mar;36(2):109–112.
  • Yosten GL, Maric-Bilkan C, Luppi P, et al. Physiological effects and therapeutic potential of proinsulin C-peptide. Am J Physiol Endocrinol Metab. 2014 Dec 1;307(11):E955–968.
  • Saisho Y. Postprandial C-peptide to glucose ratio as a marker of beta cell function: implication for the management of type 2 diabetes. Int J Mol Sci. 2016 May 17;17(5):E744.
  • McDonald TJ, Knight BA, Shields BM, et al. Stability and reproducibility of a single-sample urinary C-peptide/creatinine ratio and its correlation with 24-h urinary C-peptide. Clin Chem. 2009 Nov;55(11):2035–2039.
  • Jones AG, Hattersley AT. The clinical utility of C-peptide measurement in the care of patients with diabetes. Diabet Med. 2013 Jul;30(7):803–817.
  • Besser RE, Ludvigsson J, Jones AG, et al. Urine C-peptide creatinine ratio is a noninvasive alternative to the mixed-meal tolerance test in children and adults with type 1 diabetes. Diabetes Care. 2011 Mar;34(3):607–609.
  • Bowman P, McDonald TJ, Shields BM, et al. Validation of a single-sample urinary C-peptide creatinine ratio as a reproducible alternative to serum C-peptide in patients with type 2 diabetes. Diabet Med. 2012 Jan;29(1):90–93.
  • Covic AM, Schelling JR, Constantiner M, et al. Serum C-peptide concentrations poorly phenotype type 2 diabetic end-stage renal disease patients. Kidney Int. 2000 Oct;58(4):1742–1750.
  • Saisho Y, Kou K, Tanaka K, et al. Postprandial serum C-peptide to plasma glucose ratio as a predictor of subsequent insulin treatment in patients with type 2 diabetes. Endocr J. 2011;58(4):315–322.
  • Saisho Y, Kou K, Tanaka K, et al. Postprandial serum C-peptide to plasma glucose ratio predicts future insulin therapy in Japanese patients with type 2 diabetes. Acta Diabetol. 2013 Dec;50(6):987–988.
  • Berger B, Stenström G, Sundkvist G. Random C-peptide in the classification of diabetes. Scand J Clin Lab Invest. 2000 Dec;60(8):687–693.
  • American Diabetes Association [Internet]. Understanding A1C; [ cited 2019 Sep 12]. Available from: https://www.diabetes.org/a1c
  • Duckworth WC, Abraira C, Moritz TE, et al. The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA Diabetes Trial. J Diabetes Complications. 2011 Nov-Dec;25(6):355–361.
  • Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006 Dec 7;355(23):2427–2443.
  • Kahn SE, Lachin JM, Zinman B, et al. Effects of rosiglitazone, glyburide, and metformin on beta-cell function and insulin sensitivity in ADOPT. Diabetes. 2011 May;60(5):1552–1560.
  • Garber A, Henry RR, Ratner R, et al. Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes. Diabetes Obes Metab. 2011 Apr;13(4):348–356.
  • Gallwitz B, Guzman J, Dotta F, et al. Exenatide twice daily versus glimepiride for prevention of glycaemic deterioration in patients with type 2 diabetes with metformin failure (EUREXA): an open-label, randomised controlled trial. Lancet. 2012 Jun 16;379(9833):2270–2278.
  • Xu W, Li YB, Deng WP, et al. Remission of hyperglycemia following intensive insulin therapy in newly diagnosed type 2 diabetic patients: a long-term follow-up study. Chin Med J (Engl). 2009 Nov 5;122(21):2554–2559.
  • Kramer CK, Zinman B, Retnakaran R. Short-term intensive insulin therapy in type 2 diabetes mellitus: a systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2013 Sep;1(1):28–34.
  • Hanefeld M. Use of insulin in type 2 diabetes: what we learned from recent clinical trials on the benefits of early insulin initiation. Diabetes Metab. 2014 Dec;40(6):391–399.
  • American DiabetesAssociation. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020. Diabetes Care. 2020 Jan;43(Suppl 1)):S98–S110.
  • Nauck MA, Kemmeries G, Holst JJ, et al. Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans. Diabetes. 2011 May;60(5):1561–1565.
  • Marathe CS, Rayner CK, Jones KL, et al. Relationships between gastric emptying, postprandial glycemia, and incretin hormones. Diabetes Care. 2013 May;36(5):1396–1405.
  • Guo XH. The value of short- and long-acting glucagon-like peptide-1 agonists in the management of type 2 diabetes mellitus: experience with exenatide. Curr Med Res Opin. 2016;32(1):61–76.
  • Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012 Dec;8(12):728–742.
  • Jones AG, McDonald TJ, Shields BM, et al. Markers of beta-cell failure predict poor glycemic response to GLP-1 receptor agonist therapy in type 2 diabetes. Diabetes Care. 2016 Feb;39(2):250–257.
  • Thong KY, McDonald TJ, Hattersley AT, et al. The association between postprandial urinary C-peptide creatinine ratio and the treatment response to liraglutide: a multi-centre observational study. Diabet Med. 2014 Apr;31(4):403–411.
  • Seufert J, Bailey T, Barkholt Christensen S, et al. Impact of diabetes duration on achieved reductions in glycated haemoglobin, fasting plasma glucose and body weight with liraglutide treatment for up to 28 weeks: a meta-analysis of seven phase III trials. Diabetes Obes Metab. 2016 Jul;18(7):721–724.
  • Yabe D, Ambos A, Cariou B, et al. Efficacy of lixisenatide in patients with type 2 diabetes: a post hoc analysis of patients with diverse beta-cell function in the GetGoal-M and GetGoal-S trials. J Diabetes Complications. 2016 Sep-Oct;30(7):1385–1392.
  • Bonadonna RC, Blonde L, Antsiferov M, et al. Lixisenatide as add-on treatment among patients with different β-cell function levels as assessed by HOMA-β index. Diabetes Metab Res Rev. 2017 Sep;33(6):e2897.
  • RISE Consortium. Lack of durable improvements in beta-cell function following withdrawal of pharmacological interventions in adults with impaired glucose tolerance or recently diagnosed type 2 diabetes. Diabetes Care. 2019 Jun 9;42(9):1742–1751.
  • Bunck MC, Diamant M, Cornér A, et al. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. 2009 May;32(5):762–768.
  • van Raalte DH, Bunck MC, Smits MM, et al. Exenatide improves beta-cell function up to 3 years of treatment in patients with type 2 diabetes: a randomised controlled trial. Eur J Endocrinol. 2016 Oct;175(4):345–352.
  • van Raalte DH, Verchere CB. Improving glycaemic control in type 2 diabetes: stimulate insulin secretion or provide beta-cell rest? Diabetes Obes Metab. 2017 Sep;19(9):1205–1213.
  • Garber AJ, Abrahamson MJ, Barzilay JI, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm - 2019 Executive summary. Endocr Pract. 2019 Jan;25(1):69–100.
  • Nathan DM, Buse JB, Kahn SE, et al. Rationale and design of the glycemia reduction approaches in diabetes: a comparative effectiveness study (GRADE). Diabetes Care. 2013 Aug;36(8):2254–2261.