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

References

• Cerf ME. Beta cell dysfunction and insulin resistance. Front Endocrinol (Lausanne). 2013;4:37.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Web of Science ®Google Scholar
• NCQA. Comprehensive diabetes care (CDC); [ cited 2019 Oct 2]. Available from: https://www.ncqa.org/hedis/measures/comprehensive-diabetes-care/.
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Holman RR. Assessing the potential for alpha-glucosidase inhibitors in prediabetic states. Diabetes Res Clin Pract. 1998 Jul;40(Suppl):S21–25.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Ferrannini E. The stunned beta cell: a brief history. Cell Metab. 2010 May 5;11(5):349–352.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Fonseca VA. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009 Nov;32(Suppl 2):S151–156.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Swisa A, Glaser B, Dor Y. Metabolic stress and compromised identity of pancreatic beta cells. Front Genet. 2017;8:21.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Garofano A, Czernichow P, Bréant B. In utero undernutrition impairs rat beta-cell development. Diabetologia. 1997 Oct;40(10):1231–1234.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Poitout V, Robertson RP. Glucolipotoxicity: fuel excess and beta-cell dysfunction. Endocr Rev. 2008 May;29(3):351–366.
   PubMed Web of Science ®Google Scholar
• Lenzen S. Oxidative stress: the vulnerable beta-cell. Biochem Soc Trans. 2008 Jun;36(Pt 3):343–347.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Back SH, Kaufman RJ. Endoplasmic reticulum stress and type 2 diabetes. Annu Rev Biochem. 2012;81:767–793.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   Google Scholar
• 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.
   Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Cernea S, Dobreanu M. Diabetes and beta cell function: from mechanisms to evaluation and clinical implications. Biochem Med (Zagreb). 2013;23(3):266–280.
   PubMed Web of Science ®Google Scholar
• Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care. 2004 Jun;27(6):1487–1495.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Leighton E, Sainsbury CA, Jones GC. A practical review of C-peptide testing in diabetes. Diabetes Ther. 2017 Jun;8(3):475–487.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Luzi L, Zerbini G, Caumo A. C-peptide: a redundant relative of insulin? Diabetologia. 2007 Mar;50(3):500–502.
   PubMed Web of Science ®Google Scholar
• American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes-2020. Diabetes Care. 2020 Jan;43(Suppl1):S14–S31.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Jane Ellis M, Livesey JH, Evans MJ. Hormone stability in human whole blood. Clin Biochem. 2003 Mar;36(2):109–112.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• American Diabetes Association [Internet]. Understanding A1C; [ cited 2019 Sep 12]. Available from: https://www.diabetes.org/a1c
   Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• American DiabetesAssociation. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020. Diabetes Care. 2020 Jan;43(Suppl 1)):S98–S110.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012 Dec;8(12):728–742.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar