Goals of Treatment for Type 2 Diabetes: β-Cell preservation for glycemic control

Piero Marchetti; Roberto Lupi; Silvia Del Guerra; Marco Bugliani; Valentina D'Aleo; Margherita Occhipinti; Ugo Boggi; Lorella Marselli; Matilde Masini

doi:10.2337/dc09-S306

Diabetes Progression, Prevention, and Treatment

Goals of Treatment for Type 2 Diabetes

β-Cell preservation for glycemic control

Piero Marchetti, MD, PHD,
Roberto Lupi, BS,
Silvia Del Guerra, BS,
Marco Bugliani, PHD,
Valentina D'Aleo, BS,
Margherita Occhipinti, MD,
Ugo Boggi, MD,
Lorella Marselli, MD and
Matilde Masini, MD

From the Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.

Corresponding author: Piero Marchetti, marchant{at}immr.med.unipi.it.

Diabetes Care 2009 Nov; 32(suppl 2): S178-S183. https://doi.org/10.2337/dc09-S306

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Figure 1
Percentage of subjects with fasting plasma glucose higher than 100 mg/dl in relation to β-cell volume (lower or greater than 1.1%). Case subjects were obese and nondiabetic either with IFG or with diabetes. A higher percentage of individuals with increased glucose values had reduced β-cell volume. Adapted from Ritzel RA, Butler AE, Rizza RA, Veldhuis JD, Butler PC: Relationship between β-cell mass and fasting blood glucose concentration in humans. Diabetes Care 2006;29:717–718.
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Figure 2
Volume density of mature and immature insulin granules and its ratio in β-cells from type 2 diabetic subjects before and after ex vivo metformin exposure. Treatment caused significant increase of mature granules, decrease of immature granules, and higher ratio. Adapted from Marchetti P, Del Guerra S, Marselli L, Lupi R, Masini M, Pollera M, Bugliani M, Boggi U, Vistoli F, Mosca F, Del Prato S: Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J Clin Endocrinol Metab 2004;89:5535–5541.

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Table 1

Measures of β-cell function during hypeglycemic clamp and ratio to pretreatment in the groups of type 2 diabetic patients treated with exenatide or insulin glargine

	Pretreatment	End of treatment	Off-drug	End of treatment ratio to pretreatment (geometric mean)	End of treatment ratio to pretreatment (between group difference)	End of treatment ratio to pretreatment (P)	Off-drug ratio to pretreatment (geometric mean)	Off-drug ratio to pretreatment (between group difference)	Off-drug ratio to pretreatment (P)
First-phase C-peptide response to glucose
Glargine	5.4 ± 0.6	6.1 ± 0.5	6.1 ± 0.6	1.17 ± 0.06			1.13 ± 0.05
Exenatide	5.4 ± 0.6	9.4 ± 1.0	5.0 ± 0.6	1.78 ± 0.11	1.53 ± 0.11	<0.0001	1.00 ± 0.05	0.90 ± 0.06	0.11
Second-phase C-peptide response to glucose
Glargine	77.4 ± 8.8	80.7 ± 6.9	86.2 ± 9.1	1.08 ± 0.05			1.10 ± 0.05
Exenatide	78.5 ± 8.3	235.6 ± 23.0	79.5 ± 9.1	3.05 ± 0.22	2.85 ± 0.22	<0.0001	1.01 ± 0.04	0.92 ± 0.06	0.19
C-peptide response to arginine at 15 mM glucose
Glargine	20.0 ± 2.5	24.8 ± 2.2	21.4 ± 2.5	1.31 ± 0.07			1.03 ± 0.08
Exenatide	19.7 ± 2.1	62.2 ± 7.0	22.0 ± 2.6	3.19 ± 0.24	2.46 ± 0.20	<0.0001	1.12 ± 0.06	1.08 ± 0.10	0.40

Data are means ± SD. Table adapted from Bunck MC, Diamant M, Cornér A, Eliasson B, Malloy JL, Shaginian RM, Deng W, Kendall DM, Taskinen MR, Smith U, Yki-Järvinen H, Heine RJ: One-year treatment with exenatide improves β-cell function, compared with insulin glargine, in metformin-treated type 2 diabetes patients: a randomized, controlled trial. Diabetes Care 2009;32:762–768.