Assessment of pancreatic β-cell function: Review of methods and clinical applications

Current Diabetes Reviews

Volumn 10, Issue 1, 2014, Pages 2-42

  Cersosimo, Eugenio ^a   Solis Herrera, Carolina ^a   Trautmann, Michael E ^b   Malloy, Jaret ^c   Triplitt, Curtis L ^a  

^a UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

^b Amylin Pharmaceuticals LLC ^*  (Germany)

^c AMYLIN PHARMACEUTICALS INC   (United States)

Author keywords

DPP 4 inhibitor; Euglycemic hyperinsulinemic clamp; GLP 1 receptor agonist; Glucose tolerance test; Hyperglycemic clamp; Meal tolerance test; cell function

Indexed keywords

ALOGLIPTIN; ARGININE; DIPEPTIDYL PEPTIDASE IV INHIBITOR; EXENDIN 4; GLUCAGON LIKE PEPTIDE 1 RECEPTOR AGONIST; GLUCOSE; INSULIN; INSULIN SENSITIZING AGENT; SAXAGLIPTIN; SITAGLIPTIN; VILDAGLIPTIN;

CELL FUNCTION; CLINICAL TRIAL (TOPIC); DIET RESTRICTION; GLUCOSE BLOOD LEVEL; GLUCOSE METABOLISM; GLUCOSE TOLERANCE; HOMEOSTASIS; HYPERGLYCEMIA; IMPAIRED GLUCOSE TOLERANCE; INSULIN BLOOD LEVEL; INSULIN CLEARANCE; INSULIN RELEASE; INSULIN RESISTANCE; INSULIN RESPONSE; INSULIN SENSITIVITY; INTRAVENOUS GLUCOSE TOLERANCE TEST; LIFESTYLE; NON INSULIN DEPENDENT DIABETES MELLITUS; ORAL GLUCOSE TOLERANCE TEST; PANCREAS ISLET BETA CELL; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; TEST MEAL;

BLOOD GLUCOSE; DIABETES MELLITUS, TYPE 2; DIPEPTIDYL-PEPTIDASE IV INHIBITORS; FEMALE; GLUCOSE CLAMP TECHNIQUE; GLUCOSE TOLERANCE TEST; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPERGLYCEMIA; INSULIN RESISTANCE; INSULIN-SECRETING CELLS; MALE; MODELS, THEORETICAL; RECEPTORS, GLUCAGON;

EID: 84897467088     PISSN: 15733998     EISSN: 18756417     Source Type: Journal    
DOI: 10.2174/1573399810666140214093600     Document Type: Review

References (185)

1. American Diabetes Association. Standards of medical care-2013. Diabetes Care 2013; 36 (Suppl 1): S11-66.
2. DeFronzo RA. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 2009; 58: 773-95.
3. International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009; 32: 1327-34.
4. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RL. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-9.
5. UK Prospective Diabetes Study Group. UK Prospective Diabetes Study (UKPDS) VIII. Study design, progress and performance. Diabetologia 1991; 34: 877-90.
6. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diabetes Care 2004; 27: 1487-95.
7. Levy JC, Matthews CR, Hermans MP. Correct homeostasis model assessment (HOMA) evaluation uses the computer program. Diabetes Care 1998; 21: 2191-2.
8. The Diabetes Trials Unit. The Oxford Centre for Diabetes, Endocrinology and Metabolism. HOMA calculator home page. Accessed at http://www.dtu.ox.ac.uk/homacalculator.
9. Polonsky KS, Gumbiner B, Ostrega D, Griver K, Tager H, Henry RR. Alterations in immunoreactive proinsulin and insulin clearance induced by weight loss in NIDDM. Diabetes 1994; 43: 871-7.
10. Polonsky KC, Licinio-Paixao J, Given BD, et al. Use of biosyn-thetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type 1 diabetic patients. J Clin Invest 1986; 77: 98-105.
11. Eaton RP, Allen RC, Schade DS, Erickson KM, Standefer J. Pre-hepatic insulin production in man: kinetic analysis using peripheral connecting peptide behavior. J Clin Endocrinol Metab 1980; 51: 520-8.
12. Van Cauter E, Mestrez F, Sturis J, Polonsky KS. Estimation of insulin secretion rates from C-peptide levels: comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 1992; 41: 368-77.
13. Polonsky KS. Lilly lecture 1994. The β-cell in diabetes: from molecular genetics to clinical research. Diabetes 1995; 44: 705-17.
14. Tura A, Pacini G, Kautzky-Willer A, et al. Estimation of prehepatic insulin secretion: comparison between standardized C-peptide and insulin kinetic models. Metab Clin Exp 2012; 61: 434-43.
15. Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man. Measurement of insulin sensitivity and β-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest 1981; 68: 1456-67.
16. Bergman RN. Lilly lecture 1989. Toward physiological understanding of glucose tolerance: minimal-model approach. Diabetes 1989; 38: 1512-27.
17. Seltzer HS, Allen EW, Herron AL, Brennan MT. Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest 1967; 46: 323-35.
18. Seltzer HS, Smith WL. Plasma insulin activity after glucose. An index of insulinogenic reserve in normal and diabetic man. Diabetes 1959; 8: 417-24.
19. Saad MF, Anderson RL, Laws A, et al. For the Insulin Resistance Atherosclerosis Study. A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Diabetes 1994; 43: 1114-21.
20. Tura A, Sbrignadello S, Succurro E, Groop L, Sesti G, Pacini G. An empirical index of insulin sensitivity from short IVGTT: validation against the minimal model and glucose clamp indices in patients with different clinical characteristics. Diabetologia 2010; 53: 144-52.
21. Cobelli C, Toffolo GM, Dalla Man C, et al. Assessment of β-cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests. Am J Physiol Endocrinol Metab 2007; 293: E1-15.
22. Breda E, Cavaghan MK, Toffolo G, Polonsky KS, Cobelli C. Oral glucose tolerance test minimal model indexes of β-cell function and insulin sensitivity. Diabetes 2001; 50: 150-8.
23. Cretti A, Lehtorvirta M, Bonora E, et al. Assessment of β-cell function during the oral glucose tolerance test by a minimal model of insulin secretion. Eur J Clin Invest 2001; 31: 405-16.
24. Dalla Man C, Caumo A, Basu R, Rizza R, Toffolo G, Cobelli C. Measurement of selective effect of insulin on glucose disposal from labeled glucose oral test minimal model. Am J Physiol Endocrinol Metab 2005; 289: E909-14.
25. Dalla Man C, Yarasheski KE, Caumo A, et al. Insulin sensitivity by oral glucose minimal models: validation against clamp. Am J Physiol Endocrinol Metab 2005; 289: E954-9.
26. Dalla Man C, Caumo A, Basu R, Rizza R, Toffolo G, Cobelli C. Minimal model estimation of glucose absorption and insulin sensitivity from an oral test: validation with a tracer method. Am J Physiol Endocrinol Metab 2004; 287: E637-43.
27. Matsuda M, De Fronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglyce-mic glucose clamp. Diabetes Care 1999; 22: 1462-70.
28. Matsuda M. Measuring and estimating insulin resistance in clinical and research settings. Nutr Metab Cardiovasc Dis 2010; 20: 79-86.
29. Elrick H, Stimmler L, Hlad CJ, Arai Y. Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab 1964; 24: 1076-82.
30. Triplitt C, Chiquette E. Exenatide: from the gila monster to the pharmacy. J Am Pharm Assoc 2006; 46: 44-55.
31. Hovorka R, Chassin L, Luzio SD, Playle R, Owens DR. Pancreatic β-cell responsiveness during meal tolerance test: model assessment in normal subjects and subjects with newly diagnosed noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1998; 83: 744-50.
32. Dalla Man C, Caumo A, Cobelli C. The oral glucose minimal model: estimation of insulin sensitivity from a meal test. IEEE Trans Biomed Eng 2002; 49: 419-29.
33. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979; 237: E214-23.
34. Nauck MA, Helmesaat MM, Ørskov C, Holst JJ, Ebert R, Creutzfeldt. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest 1993; 91: 301-7.
35. Bonadonna RC, Stumvoll M, Fritsche A, et al. Altered homeostatic adaptation of first- and second-phase β-cell secretion in the offspring of patients with type 2 diabetes: studies with a minimal model to assess β-cell function. Diabetes 2003; 52: 470-80.
36. Mari A, Schmitz O, Gastaldelli A, Oestergaard T, Nyholm B, Fer-rannini E. Meal and oral glucose tests for assessment of β-cell function: modeling analysis in normal subjects. Am J Physiol Endocrinol Metab 2002; 283: E1159-66.
37. Mari A, Nielsen L, Nanayakkara N, DeFronzo R, Ferrannini E, Halseth A. Mathematical modeling shows exenatide improved β-cell function in patients with type 2 diabetes treated with metformin or metformin and a sulfonylurea. Horm Metab Res 2006; 38: 838-44.
38. Center for Disease Control and Prevention (CDC). National diabetes fact sheet, 2011. Available from: http://www.cdc.gov/diabe-tes/pubs/pdf/ndfs_2011.pdf. Accessed March 2013.
39. DeFronzo RA, Abdul-Ghani A. Preservation of β-cell function: a key to diabetes prevention. J Clin Endocrinol Metab 2011; 96: 2354-66.
40. Zhang X, Gregg EW, Williamson DF, et al. A1C level and future risk of diabetes: a systematic review. Diabetes Care 2010; 33: 1665-73.
41. Kanat M, Winnier D, Norton L, et al. The relationship between β-cell function and glycated hemoglobin: results from the Veterans Administration Genetic Epidemiology Study. Diabetes Care 2011; 34: 1006-10.
42. DREAM (Diabetes Reduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators. Effect of rosiglita-zone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomized controlled trial. Lancet 2006; 368: 1096-105.
43. DeFronzo RA, Banerji MA, Bray GA, et al. For the ACT NOW Study Group. Determinants of glucose tolerance in impaired glucose tolerance at baseline in the Actos Now for Prevention of Diabetes (ACT NOW) study. Diabetologia 2010; 53: 435-45.
44. Astrup A, Carraro R, Finer N, et al. On behalf of the NN8022-1807 Investigators. Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Int J Obesity 2012; 36: 843-54.
45. Ferrannini E, Camastra S, Gastaldelli A, et al. β-cell function in obesity: effects of weight loss. Diabetes 2004; 53(Suppl 3): S26-33.
46. Foster-Schubert K. Hypoglycemia complicating bariatric surgery: incidence and mechanisms. Curr Opin Endocrinol Diab Obes 2011; 18: 129-33.
47. World Health Organization (WHO). Global status report on NCDs 2010, chapter 1. Available from: http://www.who.int/nmh/publications/ncdreportchapter1.pdf. Accessed April 2013.
48. World Health Organization (WHO). Diabetes fact sheet Sept 2012. Available from: http://www.who.int/mediacentre/factsheets/fs312/en/index.html#. Accessed April 2013.
49. Maggio CA, Pi-Sunyer FX. Obesity and type 2 diabetes. Endocrinol Metab Clin North Am 2003; 32: 805-22.
50. Williamson DF, Thompson TJ, Thun M, Flanders D, Pamuk E, Byers T. Intentional weight loss and mortality among overweight individuals with diabetes. Diabetes Care 2000; 23: 1499-504.
51. Juang JH, Wang PW, Huang MJ. Effect of dietary therapy on pancreatic beta cell function in noninsulin-dependent diabetes mellitus. J Formosan Med Assoc 1990; 89: 672-6.
52. Escalante-Pulido M, Escalante-Herrera A, Milke-Najar ME, Alpi-zar-Salazar M. Effects of weight loss on insulin secretion and in vivo insulin sensitivity in obese diabetic and non-diabetic subjects. Diab Nutr Metab 2003; 16: 277-83.
53. Levy J, Atkinson AB, Bell PM, McCance DR, Hadden DR. Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study. Diabet Med 1998; 15: 290-6.
54. Gumbiner B, Polonsky KS, Beltz WF, et al. Effects of weight loss and reduced hyperglycemia on the kinetics of insulin secretion in obese non-insulin dependent diabetes mellitus. J Clin Endocrinol Metab 1990; 70: 1594-602.
55. Malandrucco I, Pasqualetti P, Giordani I, et al. Very-low-calorie diet: a quick therapeutic tool to improve (5 cell function in morbidly obese patients with type 2 diabetes. Am J Clin Nutr 2012; 95: 609-13.
56. Rachman J, Levy JC, Barrow BA, Manley SE, Turner RC. Relative hyperproinsulinemia of NIDDM persists despite the reduction of hyperglycemia with insulin or sulfonylurea therapy. Diabetes 1997; 46: 1557-62.
57. Look AHEAD Research Group. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 2007; 30: 1374-83.
58. UK Prospective Diabetes Study (UKPDS) Group. UK Prospective Diabetes Study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. UK Prospective Diabetes Study Group. Diabetes 1995; 44: 1249-58.
59. UK Prospective Diabetes Study (UKPDS) Group. United Kingdom Prospective Diabetes Study 24: A 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. Ann Intern Med 1998; 128: 165-75.
60. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998; 352: 837-53.
61. Glucophage® (metformin hydrochloride) tablets and Glucophage® XR (metformin hydrochloride) extended-release tablets prescribing information. Princeton, NJ: Bristol-Myers Squibb Company; January 2009.
62. Kahn SE, Haffner SM, Heise MA, et al. ADOPT Study Group. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006; 355: 2427-43.
63. Glucotrol® (glipizide) tablets prescribing information. Sellersville, PA: Teva Pharmaceuticals USA; February 2011.
64. Amaryl (glimepiride) tablets prescribing information. Bridgewater, NJ: Sanofi-aventis U.S., LLC; 1995.
65. Micronase (glyburide) tablets, USP for oral use prescribing information. New York, NY: Pfizer/Pharmacia & Upjohn Company; May 2010.
66. Starlix (nateglinide tablets) prescribing information. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2013.
67. Prandin (repaglinide tablets) prescribing information. Princeton, NJ: Novo Nordisk; September 2011.
68. Avandia (rosiglitazone maleate) tablets prescribing information. Research Triangle Park, NC: GlaxoSmithKline; May 2011.
69. Actos (pioglitazone) tablets for oral use prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; August 2012.
70. Tan MH, Baksi A, Krahulec B, Kubalski P, Stankiewicz A, Urqu-hart R, Edwards G, Johns D, for the GLAL Study Group. Comparison of pioglitazone and gliclazide in sustaining glycemic control over 2 years in patients with type 2 diabetes. Diabetes Care 2005; 28: 544-50.
71. Miyazaki Y, Matsuda M, DeFronzo RA. Dose-response effect of pioglitazone on insulin sensitivity and insulin secretion in type 2 diabetes. Diabetes Care 2002; 25: 517-23.
72. Nesina (alogliptin) tablets prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; January 2013.
73. Kasano (alogliptin and metformin HCl) tablets for oral administration prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; January 2013.
74. Oseni (alogliptin and pioglitazone) tablets prescribing information. Deerfield, IL: Takeda Pharmaceuticals America, Inc.; January 2013.
75. Tradjenta (linagliptin) tablets prescribing information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; September 2012.
76. Jentadueto (linagliptin and metformin hydrochloride) tablets prescribing information. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc.; January 2012.
77. Onglyza (saxagliptin) tablets prescribing information. Princeton, NJ: Bristol-Myers Squibb Company and Wilmington, DE: Astra-Zeneca Pharmaceuticals LP; December 2011.
78. Kombiglyze (saxagliptin and metformin HCl extended-release) tablets prescribing information. Princeton, NJ: Bristol-Myers Squibb Company and Wilmington, DE: AstraZeneca Pharmaceuticals LP; March 2012.
79. Januvia® (sitagliptin) tablets prescribing information. Whitehouse Station, NJ: Merck & Company; Revision April 2012.
80. Janumet (sitagliptin and metformin) prescribing information. Whitehouse Station, NJ: Merck & Company; Revision April 2012.
81. Juvisync (sitagliptin and simvastatin) prescribing information. Whitehouse Station, NJ: Merck & Company; 2011.
82. Victoza® (liraglutide [rDNA origin] injection), solution for subcutaneous use prescribing information. Bagsvaerd, Denmark: Novo Nordisk A/S; December 2012.
83. BYETTA® (exenatide) injection prescribing information. San Diego, CA: Amylin Pharmaceuticals LLC; December 2011.
84. BYDUREON™ (exenatide extended-release for injectable suspension) prescribing information. San Diego, CA: Amylin Pharmaceuticals LLC; January 2012.
85. Sanofi Press Release. Once daily Lyxumia (lixisenatide) approved for treatment of type 2 diabetes in Europe. February 4, 2013.
86. Barnett AH. Lixisenatide: evidence for its potential use in the treatment of type 2 diabetes. Core Evidence 2011; 6: 67-79.
87. Cersosimo E, Gastaldelli A, Cervera A, et al. Effect of exenatide on splanchnic and peripheral glucose metabolism in type 2 diabetic subjects. J Clin Endocrinol Metab 2011; 96: 1763-70.
88. Cervera A, Wajcberg E, Sriwijilkamol A, Fernandez M, Zuo P, Triplitt C, Musi N, DeFronzo RA, Cersosimo E. Mechanism of action of exenatide to reduce postprandial hyperglycemia in type 2 diabetes. Am J Physiol Endocrinol Metab 2008; 294: E846-52.
89. Mu PW, Petrov A, Eiermann GJ, et al. Inhibition of DPP-4 with sitagliptin improves glycemic control and restores islet cell mass and function in a rodent model of type 2 diabetes. Eur J Pharmacol 2009; 623: 148-54.
90. Inaba W, Mizukami H, Kamata K, Takahashi K, Tsuboi K, Yagi-hashi S. Effects of long-term treatment with the dipeptidyl pepti-dase-4 inhibitor vildagliptin on islet endocrine cells in non-obese type 2 diabetic Goto-Kakizaki rats. Eur J Pharmacol 2012; 691: 297-306.
91. Sato K, Nakamura A, Shirakawa J, et al. Impact of the dipeptidyl peptidase-4 inhibitor vildagliptin on glucose tolerance and β-cell function and mass in insulin receptor substrate-2-knockout mice fed a high-fat diet. Endocrinology 2012; 153: 1093-102.
92. Hamamoto S, Kanda Y, Shimoda M, Tatsumi F, Kohara K, Tawaramoto K. Vildagliptin preserves the mass and function of pancreatic (5 cells via the developmental regulation and suppression of oxidative and endoplasmic reticulum stress in a mouse model of diabetes. Diabetes Obes Metab 2013; 15: 153-63.
93. Shimizu S, Hosooka T, Matsuda T, et al. DPP4 inhibitor vildagliptin preserves β-cell mass through amelioration of endoplasmic reticulum stress in C/EBPB transgenic mice. J Mol Endocrinol 2012; 49: 125-35.
94. Van Genugten RE, van Raalte DH, Diamant M. Dipeptidyl pepti-dase-4 inhibitors and preservation of pancreatic islet-cell function: a critical appraisal of the evidence. Diabetes Obes Metab 2012; 14: 101-11.
95. Hermansen K, Kipnes M, Luo E, Fanurik D, Khatami H, Stein P. Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sita-gliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin. Diabetes Obes Metab 2007; 9: 733-45.
96. Rosenstock J, Sankoh S, List JF. Glucose-lowering activity of the dipeptidyl peptidase-4 inhibitor saxagliptin in drug-naive patients with type 2 diabetes. Diabetes Obes Metab 2008; 10: 376-86.
97. Hollander P, Li J, Allen E, Chen R. Or the CV181-013 Investigators. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Clin Endocrinol Metab 2009; 94: 4810-9.
98. Jadzinsky M, Pfützner A, Paz-Pacheco E, Xu Z, Allen E, Chen R. For the CV181-039 Investigators. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab 2009; 11: 611-22.
99. Rosenstock J, Aguilar-Salinas C, Klein E, Nepal S, List J, Chen R. For the CV181-011 Study Investigators. Effect of saxagliptin monotherapy in treatment-naive patients with type 2 diabetes. Curr Med Res Opin 2009; 10: 2401-11.
100. Aaboe K, Knop FK, Vilsbøll T, Deacon CF, Holst JJ, Madsbad S. Twelve weeks treatment with the DPP-4 inhibitor, sitagliptin, prevents degradation of peptide YY and improves glucose and non-glucose induced insulin secretion in patients with type 2 diabetes mellitus. Diabetes Obes Metab 2010; 12: 323-33.
101. Foley JE, Bunck MC, Möller-Goede K, et al. Beta cell function following 1 year vildagliptin or placebo treatment and after 12 week washout in drug-naive patients with type 2 diabetes and mild hy-perglycaemia: a randomised controlled trial. Diabetologia 2011; 54: 1985-91.
102. Mari A, Sallas WM, He YL, et al. Vildagliptin, a dipeptidyl pepti-dase-IV inhibitor improves model-assessed β-cell function in patients with type 2 diabetes. J Clin Endocrinol Metab 2005; 90: 4888-94.
103. Parkes DG, Mace KF, Trautmann ME. Discovery and development of exenatide: the first antidiabetic agent to leverage the multiple benefits of the incretin hormone, GLP-1. Expert Opin Drug Discov 2013; 8: 219-44.
104. Vilsbøll T. The effects of glucagon-like peptide-1 on the beta cell. Diabetes Obes Metab 2009; 11(Suppl 3): 11-8.
105. Gedulin BR, Nikoulina SE, Smith PA, Gedulin G, Nielsen LL, Baron AD. Exenatide (exendin-4) improves insulin sensitivity and β-cell mass in insulin-resistant obese fa/fa Zucker rats independent of glycemia and body weight. Endocrinology 2005; 146: 2069-76.
106. Soria B. In-vitro differentiation of pancreatic β-cells. Differentiation 2001; 68: 205-19.
107. Nielsen LL, Young AA, Parkes D. Pharmacology of exenatide (synthetic exendin-4): A potential therapeutic for improved glycemic control of type 2 diabetes. Regul Pept 2004; 117: 77-88.
108. Moretto TJ, Milton DR, Ridge TD, MacConell LA, Okerson T, Wolka AM. Efficacy and tolerability of exenatide monotherapy over 24 weeks in antidiabetic drug-naive patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, parallel-group study. Clin Ther 2008; 30: 1448-60.
109. Fineman MS, Bicsak TA, Shen LZ, Taylor K, Gaines E, Varns A. Effect on glycemic control of synthetic exendin-4 (synthetic exendin-4) additive to existing metformin and/or sulfonylurea treatment in patients with type 2 diabetes. Diabetes Care 2003; 26: 2370-7.
110. Preumont V, Hermans MP, Brichard S, Buysschaert M. Six-month exenatide improves HOMA hyperbolic product in type 2 diabetic patients mostly by enhancing beta-cell function rather than insulin sensitivity. Diab Metab 2010; 36: 293-8.
111. Buse JB, Klonoff DC, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Maggs DG, Wintle ME. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther 2007; 29: 139-153.
112. Vilsbøll T, Zdravkovic M, Le-Thi T, et al. Liraglutide, a long-acting human glucagon-like peptide-1 analog, given as monother-apy significantly improves glycemic control and lowers body weight without risk of hypoglycemia in patients with type 2 diabetes. Diabetes Care 2007; 30: 1608-10.
113. Buse JB, Rosenstock J, Sesti G, Schmidt WE, Montanya E, Brett JH. For the LEAD-6 Study Group. Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week, randomised, parallel-group, multinational, open-label trial (LEAD-6). Lancet 2009; 374: 39-47.
114. Russell-Jones D, Vaag A, Schmitz O, et al. On behalf of the lira-glutide effect and action in diabetes 5 (LEAD-5) met+SU Study Group. Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes melli-tus (LEAD-5 met+SU): a randomised controlled trial. Diabetologia 2009; 52: 2046-55.
115. Zinman B, Gerich J, Buse J, et al. For the LEAD-4 Study Investigators. Efficacy and safety of the human glucagon-like peptide-1 analog liraglutide in combination with metformin and thiaxolidi-nenione in patients with type 2 diabetes mellitus (LEAD-4 Met + TZD). Diabetes Care 2009; 32: 1224-30.
116. Garber A, Henry R, Ratner R, et al. For the LEAD 3 (Mono) Study Group. Liraglutide versus glimepiride monotherapy for type 2 diabetes (LEAD-3 Mono): a randomised, 52-week, phase III, double-blind, parallel-treatment trial. Lancet 2009; 373: 473-81.
117. Marre M, Shaw J, Brändle M, et al. On behalf of the LEAD-1 SU Study Group. Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med 2009; 26: 268-78.
118. Diamant M, Van Gaal L, Stranks S, Northrup J, Cao D, Taylor K. Once weekly exenatide compared with insulin glargine titrated to target in patients with type 2 diabetes (DURATION-3): an open-label randomised trial. Lancet 2010; 375: 2234-43.
119. Russell-Jones D, Cuddihy RM, Hanefeld M, Kumar A, González JG, Chan M. On behalf of the DURATION-4 Study Group. Efficacy and safety of exenatide once weekly versus metformin, piogli-tazone, and sitagliptin used as monotherapy in drug-naive patients with type 2 diabetes (DURATION-4): A 26-week double-blind study. Diabetes Care 2012; 35: 252-8.
120. MacConell, Pencek R, Li Y, Maggs D, Porter L. Exenatide once weekly: sustained improvement in glycemic control and cardiome-tabolic measures through 3 years. Diabetes Metab Syndr Obes 2013; 6: 31-41.
121. Nauck MA, Duran S, Kim D, Johns D, Northrup J, Festa A. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: A non-inferiority study. Diabe-tologia 2007; 50: 259-67.
122. Zinman B, Hoogwerf BJ, Garcia SD, Milton DR, Giaconia JM, Kim DD. The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes. Ann Intern Med 2007; 146: 477-85.
123. Klonoff DC, Buse JB, Nielsen LL, Guan X, Bowlus CL, Holcombe JH. Exenatide effects on diabetes, obesity, cadiovascular risk factors, and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years. Curr Med Res Opin 2008; 24: 275-86.
124. Liutkus J, Rosas Guzman J, Norwood P, Pop L, Northrup J, Cao. A placebo-controlled trial of exenatide twice-daily added to thia-zolidinediones alone or in combination with metformin. Diabetes Obes Metab 2010; 12: 1058-65.
125. Kadowaki T, Namba M, Imaoka T, Yamamura A, Goto W, Boardman MK. Improved glycemic control and reduced body-weight with exenatide: a double-blind, randomized, phase 3 study in Japanese patients with suboptimally controlled type 2 diabetes over 24 weeks. J Diabetes Invest 2011; 2: 210-7.
126. Derosa G, Maffioli P, Salvadeo SA, et al. Exenatide versus gliben-clamide in patients with diabetes. Diabetes Technol Ther 2010; 12: 233-40.
127. Kolterman OG, Buse JB, Fineman MS, et al. Synthetic exendin-4 (AC2993) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab 2003; 88: 3082-9.
128. Kolterman OG, Kim DD, Shen L, Ruggles JA, Nielsen LL, Fine-man MS. Pharmacokinetics, pharmacodynamics, and safety of exenatide in patients with type 2 diabetes mellitus. Am J Health Sys Pharm 2005; 62: 173-81.
129. Kothare PA, Linnebjerg H, Isaka Y. Pharmacokinetics, pharmacodynamics, tolerability, and safety of exenatide in Japanese patients with type 2 diabetes mellitus. J Clin Pharmacol 2008; 48: 1389-99.
130. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD. For the Exenatide-113 Clinical Study Group. Effects of exenatide (ex-endin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care 2004; 27: 2628-35.
131. DeFronzo R, Ratner RE, Han J, Kim DD, Fineman MS, Baron AD. Effects of exenatide (exendin-4) on glycemic control and weight over 30 weeks in metformin-treated patients with type 2 diabetes mellitus. Diabetes Care 2005; 28: 1092-100.
132. Bunck M, Diamant M, Cornér A. 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; 32: 762-8.
133. Bunck M, Cornér A, Eliasson B. Effects of exenatide on measures of β-cell function after 3 years in metformin-treated patients with type 2 diabetes. Diabetes Care 2011; 34: 2041-7.
134. Vilsbøll T, Brock B, Perrild H. Liraglutide, a once-daily human GLP-1 analogue, improves pancreatic β-cell function and arginine-stimulated insulin secretion during hyperglycaemia in patients with type 2 diabetes mellitus. Diabet Med 2008; 25: 152-6.
135. DeFronzo RA, Okerson T, Viswanathan P, Guan X, Holcombe JH, MacConell L. Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin 2008; 24: 2943-52.
136. Bergman RN, Ider YZ, Bowden CR, Cobelli C. Quantitative estimation of insulin sensitivity. Am J Physiol 1979; 236: E667-77.
137. Abbasi F, Lamendola C, Reaven GM. What is the effect of rosigli-tazone treatment on insulin secretory function in insulin-resistant individuals? It depends on how you measure it. Metab Clin Exp 2011; 60: 57-62.
138. Abbink EJ, van der Wal PS, Sweep CGJ, Tack CJ. Compared to glibenclamide repaglinide treatment results in a more rapid fall in glucose level and beta-cell secretion after glucose stimulation. Diab Metab Res Rev 2004; 20:466-71.
139. Ahrén B, Pacini G, Foley JE, Schweizer A. Improved meal-related beta-cell function and insulin sensitivity by the dipeptidyl pepti-dase-IV inhibitor vildagliptin in metformin-treated patients with type 2 diabetes over 1 year. Diabetes Care 2005; 28: 1936-40.
140. Balas B, Baig MR, Watson C, et al. The dipeptidyl peptidase IV inhibitor vildagliptin suppresses endogenous glucose production and enhance islet function after single-dose administration in type 2 diabetic patients. J Clin Endocrinol Metab 2007; 92: 1249-55.
141. β-cell) without hyperinsulinemia in patients with type 2 diabetes mellitus. Am J Ther 2007; 14: 194-202.
142. Bruce S, Park JS, Fiedorek FT, Howlett HCS. Beta-cell response to metformin-glibenclamide combination tablets (Glucovance) in patients with type 2 diabetes. Int J Clin Pract 2006; 60: 783-90.
143. Byrne MM, Gliem K, Wank U, Arnold R, Katschinski M, Polonsky KS. Glucagon-like peptide 1 improves the ability of the beta-cell to sense and respond to glucose in subjects with impaired glucose tolerance. Diabetes 1998; 47: 1259-65.
144. Cavaghan MK, Ehrmann DA, Byrne MM, Polonsky KS. Treatment with the oral antidiabetic agent troglitazone improves beta cell responses to glucose in subjects with impaired glucose tolerance. J Clin Invest 1997; 100: 530-7.
145. Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J. For the CV181-040 Investigators. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Practice 2009; 63: 1395-406.
146. Charpentier G, Halimi S. On behalf of the F-PIO-100 Study Investigators. Earlier triple therapy with pioglitazone in patients with type 2 diabetes. Diabetes Obes Metab 2009; 11: 844-54.
147. Chang AM, Jakobsen G, Sturis J, Smith MJ, Bloem CJ, An B. The GLP-1 derivative NN2211 restores β-cell sensitivity to glucose in type 2 diabetic patients after a single dose. Diabetes 2003; 52: 1786-91.
148. Clark HE, Matthews DR. The effect of glimepiride on pancreatic beta-cell function under hyperglycaemic clamp and hyperinsu-linaemic euglycaemic clamp conditions in non-insulin-dependent diabetes mellitus. Horm Metab Res 1996; 28: 445-50.
149. Cozma LS, Luzio SD, Dunseath GJ, Underwood PM, Owens DR. Beta-cell response during a meal test: a comparative study of incremental doses of repaglinide in type 2 diabetic patients. Diabetes Care 2005; 28: 1001-7.
150. De Fronzo RA, Hissa MN, Garber AJ, Gross JL, Duan RY, Ravichandran S, Chen RS. For the Saxagliptin 014 Study Group. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin alone. Diabetes Care 2009; 32: 1649-55.
151. DeFronzo RA, Triplitt C, Qu Y, Lewis MS, Maggs D, Glass LC. Effects of exenatide plus rosiglitazone on beta-cell function and insulin sensitivity in subjects with type 2 diabetes on metformin. Diabetes Care 2010; 33: 951-7.
152. DeFronzo RA, Burant CF, Fleck P, Wilson C, Mekki Q, Pratley RE. Efficacy and tolerability of the DPP-4 inhibitor alogliptin combined with pioglitazone, in metformin-treated patients with type 2 diabetes. J Clin Endocrinol Metab 2012; 97: 1615-22.
153. Della Casa L, Del Rio G, Glaser B, Cerasi E. Effect of 6-month gliclazide treatment on insulin release and sensitivity to endogenous insulin in NIDDM: role of initial continuous subcutaneous insulin infusion-induced normoglycemia. Am J Med 1991; 90 (Suppl 6A): 37-45.
154. Del Prato S, Barnett AH, Huisman H, Neubacher D, Woerle HJ, Dugi KA. Effect of linagliptin monotherapy on glycaemic control and markers of beta-cell function in patients with inadequately controlled type 2 diabetes: a randomized controlled trial. Diabetes Obes Metab 2011; 13: 258-67.
155. Derosa G, Carbone A, Franzetti I, et al. Effects of a combination of sitagliptin plus metformin vs metformin monotherapy on glycemic control, beta-cell function and insulin resistance in type 2 diabetic patients. Diabetes Res Clin Pract 2012; 98: 51-60.
156. Derosa G, Ragonesi PD, Carbone A, Fogari E, Bianchi L, Bona-ventrua A. Vildagliptin added to metformin on beta-cell function after a euglycemic hyperinsulinemic and hyperglycemic clamp in type 2 diabetes patients. Diabetes Tech Ther 2012; 14: 475-84.
157. Derosa G, Franzetti G, Querci F, Carbone A, Ciccarelli L, Piccinni MN. Exenatide plus metformin compared with metformin alone on β-cell function in patients with type 2 diabetes. Diabet Med 2012; 29: 1515-23.
158. Drucker DJ, Buse JB, Taylor K, Kendall DM, Trautmann M, Zhuang D. For the DURATION-1 Study Group. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet 2008; 372: 1240-50.
159. Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. Beta cell function in subjects spanning the range from normal glucose tolerance to overt diabetes mellitus: a new analysis. J Clin Endocrinol Metab 2005; 90: 493-500.
160. Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, DeFronzo RA. Beta cell dysfunction and glucose intolerance: results from the San Antonio Metabolism (SAM) study. Diabetologia 2004; 47: 31-9.
161. Gastaldelli A, Ferrannini E, Miyazaki Y, Matsuda M, Mari A, DeFronzo RA. Thiazolidinediones improve beta-cell function in type 2 diabetic patients. Am J Physiol Endocrinol Metab 2007; 292: E871-83.
162. Groop LC, Ratheiser K, Luzi L, et al. Effect of sulphonylurea on glucose-stimulated insulin secretion in healthy and non-insulin dependent diabetic subjects: a dose-response study. Acta Diabetol 1991; 28: 162-8.
163. Henry RR, Smith SR, Schwartz SL, et al. Effects of saxagliptin on beta-cell stimulation and insulin secretion in patients with type 2 diabetes. Diabetes Obes Metab 2011; 13: 850-8.
164. Home PD, Jones NP, Pocock SJ, et al. For the RECORD Study Group. Rosiglitazone RECORD study: glucose control outcomes at 18 months. Diabet Med 2007; 24: 626-34.
165. Juhl CB, Hollingdal M, Pørksen N, Prange A, Lönnqvist F, Schmitz O. Influence of rosiglitazone treatment on beta-cell function in type 2 diabetes: evidence of an increased ability of glucose to entrain high-frequency insulin pulsatility. J Clin Endocrinol Metab 2003; 88: 3794-800.
166. Kahn SE, Montgomery B, Howell W, et al. Importance of early phase insulin secretion to intravenous glucose tolerance in subjects with type 2 diabetes mellitus. J Clin Endocrinol Metab 2001; 86: 5824-9.
167. Kahn SE, Lachin JM, Zinman B, et al. Effects of rosiglitazone, glyburide, and metformin on β-cell function and insulin sensitivity in ADOPT. Diabetes 2011; 60: 1552-60.
168. Kjems LL, Holst JJ, Vølund A, Madsbad S. The influence of GLP-1 on glucose-stimulated insulin secretion: effects on beta-cell sensitivity in type 2 and nondiabetic subjects. Diabetes 2003; 52: 380-6.
169. Li J, Tian H, Li Q, et al. Improvement of insulin sensitivity and beta-cell function by nateglinide and repaglinide in type 2 diabetic patients - a randomized controlled double-blind and double-dummy multicentre clinical trial. Diabetes Obes Metab 2007; 9: 558-65.
170. Lim S, Jyun An J, Shin H, et al. Factors predicting therapeutic efficacy of combination treatment with sitagliptin and metformin in type 2 diabetic patients: the COSMETIC study. Clin Endocrinol 2012; 77: 215-23.
171. Mari A, Scherbaum WA, Nilsson PM, et al. Characterization of the influence of vildagliptin on model-assessed β-cell function in patients with type 2 diabetes and mild hyperglycemia. J Clin Endocrinol Metab 2008; 93: 103-9.
172. Osei K, Gaillard T, Schuster D. Thiazolidinediones increase hepatic insulin extraction in African Americans with impaired glucose tolerance and type 2 diabetes mellitus. A pilot study of rosiglitazone. Metab Clin Exp 2007; 56: 24-9.
173. Ovalle F, Bell DSH. Effect of rosiglitazone versus insulin on the pancreatic β-cell function of subjects with type 2 diabetes. Diabetes Care 2004; 27: 2585-9.
174. Pratley RE, Schweizer A, Rosenstock J, Foley JE, Banerji MA, Pi-Sunyer FX. Robust improvements in fasting and prandial measures of beta-cell function with vildagliptin in drug-naive patients: analysis of pooled vildagliptin monotherapy database. Diabetes Obes Metab 2008; 10: 931-8.
175. Quddusi S, Vahl TP, Hanson K, Prigeon RL, D'Allesio DA. Differential effects of acute and extended infusions of glucagon-like peptide-1 on first- and second-phase insulin secretion in diabetic and nondiabetic humans. Diabetes Care 2003; 26: 791-8.
176. Rachman J, Gribble FM, Barrow BA, Levy JC, Buchanan KD, Turner RC. Normalization of insulin responses to glucose by overnight infusion of glucagon-like peptide 1 (7-36) amide in patients with NIDDM. Diabetes 1996; 45: 1524-30.
177. Taverna MJ, Pacher N, Bruzzo F, Slama G, Selam JL. Beta-cell function evaluated by HOMA as a predictor of secondary sulphon-ylurea failure in type 2 diabetes. Diabet Med 2001; 18: 584-8.
178. Van der Wal PS, Draeger KE, van Iperen AM, Martini C, Aarsen M, Heine RJ. Beta cell response to oral glimepiride administration during and following a hyperglycaemic clamp in NIDDM patients. Diabet Med 1997; 14: 556-63.
179. Wajchenberg BL, Tereza A, Santomauro MG, Giannella-Neto D, Borghi VC, Porrelli RN. Short- and long-term gliclazide effects on pancreatic islet cell function and hepatic insulin extraction in non-insulin-dependent diabetes mellitus. Diabetes Res Clin Pract 1992; 17: 89-97.
180. Wallace TM, Levy JC, Matthews DR. An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomized study. Diabet Med 2004; 21: 568-76.
181. Weng J, Yanbing L, Wen X, et al. Effect of intensive insulin therapy on β-cell function and glycaemic control in patients with newly diagnosed type 2 diabetes: a multicentre randomised parallel-group trial. Lancet 2008; 371: 1753-60.
182. Williams-Herman D, Xu L, Teng R, et al. Effect of initial combination therapy with sitagliptin and metformin on beta-cell function in patients with type 2 diabetes. Diabetes Obes Metab 2012; 14: 67-76.
183. Zander M, Madsbad S, Madsen JL, Holst JJ. Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet 2002; 359: 824-30.
184. Ahrén B, Pratley RE, Soubt M, Dunning BE, Foley JE. Clinical measures of islet function: usefulness to characterize defects in diabetes. Curr Diabetes Rev 2008; 4: 129-45.
185. Simonson GD, Kendall DM. Diagnosis of insulin resistance and associated syndromes: the spectrum from the metabolic syndrome to type 2 diabetes mellitus. Coron Artery Dis 2005; 16: 465-72.