Improved beta-cell function after standardized weight reduction in severely obese subjects.

Islet function was examined in 13 severely obese women [body mass index 46.4 +/- 5.5 (SD) kg/m(2)] before and after standardized 15 and 25% weight reduction (WR) instituted by bariatric surgery. The insulin response to arginine at fasting (AIR(1)), at 14 mmol/l, and at >25 mmol/l glucose was reduced by 37-50% after 15 and 25% WR (P <or= 0.05). Insulin sensitivity was determined as the amount of glucose infused to reach 14 mmol/l divided by the insulin level (M/I), a measure showing a linear correlation with insulin sensitivity during euglycemic hyperinsulinemic clamps (r = 0.74, P < 0.001) and a hyperbolic relation to AIR(1) (r = -0.63, P < 0.001) in 169 healthy subjects. M/I was increased by 318 +/- 182% after 15% (P = 0.004) and by 489 +/- 276% after 25% WR (P = 0.007). The reduction in insulin secretion was not as large as anticipated from the increased insulin sensitivity, which resulted in an increased disposition index (DI; AIR(1) x M/I). Thus DI increased by 95 +/- 24% after 15% (P = 0.018) and by 176 +/- 35% after 25% WR (P = 0.011). This improved beta-cell function correlated independently with reduced glucose, triglycerides, and leptin and increased adiponectin levels and was associated with a reduced proinsulin-to-insulin ratio. In contrast, glucagon secretion was not significantly affected by WR. We conclude that WR results in improved beta-cell function when related to insulin sensitivity.

[1]  B. Ahrén,et al.  Failure to adequately adapt reduced insulin sensitivity with increased insulin secretion in women with impaired glucose tolerance , 1996, Diabetologia.

[2]  Philippe Froguel,et al.  Disruption of Adiponectin Causes Insulin Resistance and Neointimal Formation* , 2002, The Journal of Biological Chemistry.

[3]  M. Matsuda,et al.  Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 , 2002, Nature Medicine.

[4]  K. Petersen,et al.  Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy. , 2002, The Journal of clinical investigation.

[5]  M. Reitman,et al.  Leptin-replacement therapy for lipodystrophy. , 2002, The New England journal of medicine.

[6]  R. Bergman,et al.  Accurate Assessment of β-Cell Function: The Hyperbolic Correction , 2002 .

[7]  B. Ahrén,et al.  Quantification of insulin secretion in relation to insulin sensitivity in nondiabetic postmenopausal women. , 2002, Diabetes.

[8]  P. Havel.  Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin , 2002, Current opinion in lipidology.

[9]  R. Robertson,et al.  Minireview: Secondary β-Cell Failure in Type 2 Diabetes-A Convergence of Glucotoxicity and Lipotoxicity. , 2002, Endocrinology.

[10]  R. Robertson,et al.  Minireview: Secondary beta-cell failure in type 2 diabetes--a convergence of glucotoxicity and lipotoxicity. , 2002, Endocrinology.

[11]  J. McGarry.  Banting lecture 2001: dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. , 2002, Diabetes.

[12]  B. Ahrén,et al.  Impaired glucose tolerance (IGT) is associated with reduced insulin-induced suppression of glucagon concentrations , 2001, Diabetologia.

[13]  S. Kahn,et al.  The Importance of β-Cell Failure in the Development and Progression of Type 2 Diabetes , 2001 .

[14]  Y. Terauchi,et al.  The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity , 2001, Nature Medicine.

[15]  Xiao Man Yang,et al.  Physiological increase in plasma leptin markedly inhibits insulin secretion in vivo. , 2001, Diabetes.

[16]  J. McGarry.  Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes , 2001 .

[17]  A. Yates,et al.  Stimulus-secretion coupling of arginine-induced insulin release: comparison between the cationic amino acid and its methyl ester. , 2000, Endocrine.

[18]  R. Rizza,et al.  Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus. , 2000, The Journal of clinical endocrinology and metabolism.

[19]  E. Hultman,et al.  Body Composition and Muscle Constituents During Weight Loss: Studies in obese patients following gastroplasty , 2000, Obesity surgery.

[20]  B. Ahrén,et al.  Glucose intolerance is predicted by low insulin secretion and high glucagon secretion: outcome of a prospective study in postmenopausal Caucasian women , 2000, Diabetologia.

[21]  J. Habener,et al.  The adipoinsular axis: effects of leptin on pancreatic β-cells , 2000 .

[22]  C. Bogardus,et al.  The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. , 1999, The Journal of clinical investigation.

[23]  B. Ahrén,et al.  Relative hyperproinsulinemia as a sign of islet dysfunction in women with impaired glucose tolerance. , 1999, The Journal of clinical endocrinology and metabolism.

[24]  B. Ahrén,et al.  Leptin inhibits insulin secretion induced by cellular cAMP in a pancreatic B cell line ( INS-1 cells ) , 1999 .

[25]  J. McGarry,et al.  Fatty acids, lipotoxicity and insulin secretion , 1999, Diabetologia.

[26]  B. Ahrén,et al.  Glucose-dependent arginine stimulation test for characterization of islet function: studies on reproducibility and priming effect of arginine , 1998, Diabetologia.

[27]  N. Barzilai,et al.  Leptin selectively decreases visceral adiposity and enhances insulin action. , 1997, The Journal of clinical investigation.

[28]  G. Pacini,et al.  Impaired adaptation of first-phase insulin secretion in postmenopausal women with glucose intolerance. , 1997, The American journal of physiology.

[29]  G. Mingrone,et al.  Reversibility of insulin resistance in obese diabetic patients: role of plasma lipids , 1997, Diabetologia.

[30]  R. Bergman,et al.  Causal linkage between insulin suppression of lipolysis and suppression of liver glucose output in dogs. , 1996, The Journal of clinical investigation.

[31]  B. Ahrén,et al.  Islet dysfunction in obese women with impaired glucose tolerance. , 1996, Metabolism: clinical and experimental.

[32]  R. Bergman,et al.  Free Fatty Acid as a Link in the Regulation of Hepatic Glucose Output by Peripheral Insulin , 1995, Diabetes.

[33]  G. Berglund,et al.  Glucose modulation of insulin and glucagon secretion is altered in impaired glucose tolerance. , 1995, The Journal of clinical endocrinology and metabolism.

[34]  G. Berglund,et al.  Fasting blood glucose in determining the prevalence of diabetes in a large, homogeneous population of Caucasian middle‐aged women , 1995, Journal of internal medicine.

[35]  R. Bergman,et al.  Quantification of the Relationship Between Insulin Sensitivity and β-Cell Function in Human Subjects: Evidence for a Hyperbolic Function , 1993, Diabetes.

[36]  G. Dohm,et al.  Surgical treatment of obesity and its effect on diabetes: 10-y follow-up. , 1992, The American journal of clinical nutrition.

[37]  D. Grace.  Gastric restriction procedures for treating severe obesity. , 1992, The American journal of clinical nutrition.

[38]  D. Kelley,et al.  Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. , 1992, The New England journal of medicine.

[39]  R. Brolin.  Gastrointestinal surgery for severe obesity. , 1996, Consensus statement. National Institutes of Health Consensus Development Conference.

[40]  P. Bennett,et al.  Disproportionately elevated proinsulin in Pima Indians with noninsulin-dependent diabetes mellitus. , 1990, The Journal of clinical endocrinology and metabolism.

[41]  S. Kahn,et al.  Hyperproinsulinemia and Amyloid in NIDDM: Clues to Etiology of Islet β-Cell Dysfunction? , 1989, Diabetes.

[42]  A. Golay,et al.  Documentation of hyperglucagonemia throughout the day in nonobese and obese patients with noninsulin-dependent diabetes mellitus. , 1987, The Journal of clinical endocrinology and metabolism.

[43]  K. Norris,et al.  A new approach for the estimation of body composition: infrared interactance. , 1984, The American journal of clinical nutrition.

[44]  J. Halter,et al.  Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus. , 1984, The Journal of clinical investigation.

[45]  E. Mason.  Vertical banded gastroplasty for obesity. , 1982, Archives of surgery.

[46]  R. Bergman,et al.  Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. , 1981, The Journal of clinical investigation.

[47]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.