Skip to main content
Erschienen in: Diabetologia 7/2004

01.07.2004 | Article

Loss of beta cell function as fasting glucose increases in the non-diabetic range

verfasst von: I. F. Godsland, J. A. R. Jeffs, D. G. Johnston

Erschienen in: Diabetologia | Ausgabe 7/2004

Einloggen, um Zugang zu erhalten

Abstract

Aims/hypothesis

Our aim was to define the level of glycaemia at which pancreatic insulin secretion, particularly first-phase insulin release, begins to decline.

Methods

Plasma glucose and insulin concentrations were measured during an IVGTT in 553 men with non-diabetic fasting plasma glucose concentrations. In 466 of the men C-peptide was also estimated. IVGTT insulin secretion in first and late phases was assessed by: (i) the circulating insulin response; (ii) population parameter deconvolution analysis of plasma C-peptide concentrations; and (iii) a combined model utilising both insulin and C-peptide concentrations. Measurements of insulin sensitivity and elimination were also derived by modelling analysis.

Results

As fasting plasma glucose (FPG) increased, IVGTT first-phase insulin secretion declined by 73%, 71% and 68% for the three methods respectively. The FPG values at which this decline began, determined by change point regression, were 4.97, 5.16 and 5.42 mmol/l respectively. The sensitivity of late-phase insulin secretion to glucose declined at FPG concentrations above 6.0 mmol/l. Insulin elimination, but not insulin sensitivity, varied with FPG.

Conclusions/interpretation

The range of FPG over which progressive loss of the first-phase response begins may be as low as 5.0 to 5.4 mmol/l, with late-phase insulin responses declining at FPG concentrations above 6.0 mmol/l.
Literatur
1.
Zurück zum Zitat Gerich JE (1998) The genetic basis of Type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocrine Rev 19:491–503CrossRef Gerich JE (1998) The genetic basis of Type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocrine Rev 19:491–503CrossRef
2.
Zurück zum Zitat Pratley RE, Weyer C (2001) The role of impaired early insulin secretion in the pathogenesis of type II diabetes mellitus. Diabetologia 44:929–945CrossRefPubMed Pratley RE, Weyer C (2001) The role of impaired early insulin secretion in the pathogenesis of type II diabetes mellitus. Diabetologia 44:929–945CrossRefPubMed
3.
Zurück zum Zitat Straub SG, Sharp GWG (2002) Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab Res Rev 18:451–463CrossRefPubMed Straub SG, Sharp GWG (2002) Glucose-stimulated signaling pathways in biphasic insulin secretion. Diabetes Metab Res Rev 18:451–463CrossRefPubMed
4.
Zurück zum Zitat Lillioja S, Mott DM, Spraul M et al. (1993) Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 329:1988–1992CrossRefPubMed Lillioja S, Mott DM, Spraul M et al. (1993) Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med 329:1988–1992CrossRefPubMed
5.
Zurück zum Zitat Haffner SM, Miettinen H, Gaskill SP, Stern MP (1995) Decreased insulin secretion and increased insulin resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans. Diabetes 44:1386–1391CrossRefPubMed Haffner SM, Miettinen H, Gaskill SP, Stern MP (1995) Decreased insulin secretion and increased insulin resistance are independently related to the 7-year risk of NIDDM in Mexican-Americans. Diabetes 44:1386–1391CrossRefPubMed
6.
Zurück zum Zitat Gerich JE (2002) Is reduced first-phase insulin release the earliest detectable abnormality in individuals destined to develop type 2 diabetes. Diabetes 51 [Suppl 1]:S117–S121 Gerich JE (2002) Is reduced first-phase insulin release the earliest detectable abnormality in individuals destined to develop type 2 diabetes. Diabetes 51 [Suppl 1]:S117–S121
7.
Zurück zum Zitat Zethelius B, Byberg L, Hales CN, Lithell H, Berne C (2003) Proinsulin and acute insulin response independently predict type 2 diabetes mellitus in men—report from 27 years of follow-up study. Diabetologia 46:20–26CrossRefPubMed Zethelius B, Byberg L, Hales CN, Lithell H, Berne C (2003) Proinsulin and acute insulin response independently predict type 2 diabetes mellitus in men—report from 27 years of follow-up study. Diabetologia 46:20–26CrossRefPubMed
8.
Zurück zum Zitat Pimenta W, Korytkowski M, Mitrakou A et al. (1995) Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. Evidence from studies in normal glucose-tolerant individuals with first-degree NIDDM relative. JAMA 273:1855–1861CrossRefPubMed Pimenta W, Korytkowski M, Mitrakou A et al. (1995) Pancreatic beta-cell dysfunction as the primary genetic lesion in NIDDM. Evidence from studies in normal glucose-tolerant individuals with first-degree NIDDM relative. JAMA 273:1855–1861CrossRefPubMed
9.
Zurück zum Zitat Vølund A, Polonsky K, Bergman R (1987) Calculated pattern of intraportal insulin appearance without independent assessment of C-peptide kinetics. Diabetes 36:1195–1202CrossRef Vølund A, Polonsky K, Bergman R (1987) Calculated pattern of intraportal insulin appearance without independent assessment of C-peptide kinetics. Diabetes 36:1195–1202CrossRef
10.
Zurück zum Zitat Cobelli C, Pacini G (1988) Insulin secretion and hepatic extraction in humans by minimal modelling of C-peptide and insulin kinetics. Diabetes 37:223–231CrossRefPubMed Cobelli C, Pacini G (1988) Insulin secretion and hepatic extraction in humans by minimal modelling of C-peptide and insulin kinetics. Diabetes 37:223–231CrossRefPubMed
11.
Zurück zum Zitat Ferrannini E, Cobelli C (1987) The kinetics of insulin in man. II. Role of the liver. Diabetes Metab Rev 3:365–397CrossRefPubMed Ferrannini E, Cobelli C (1987) The kinetics of insulin in man. II. Role of the liver. Diabetes Metab Rev 3:365–397CrossRefPubMed
12.
Zurück zum Zitat Gower BA, Granger WM, Franklin F, Shewchuk RM, Goran MI (2002) Contribution of insulin secretion and clearance to glucose-induced insulin concentration in African-American and Caucasian children. J Clin Endocrinol Metab 87:18–24CrossRef Gower BA, Granger WM, Franklin F, Shewchuk RM, Goran MI (2002) Contribution of insulin secretion and clearance to glucose-induced insulin concentration in African-American and Caucasian children. J Clin Endocrinol Metab 87:18–24CrossRef
13.
Zurück zum Zitat Goran MI, Bergman RN, Cruz ML, Watanabe R (2002) Insulin resistance and associated compensatory responses in African-American and Hispanic children. Diabetes Care 25:2184–2190CrossRefPubMed Goran MI, Bergman RN, Cruz ML, Watanabe R (2002) Insulin resistance and associated compensatory responses in African-American and Hispanic children. Diabetes Care 25:2184–2190CrossRefPubMed
14.
Zurück zum Zitat The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. (1997) Report of the Expert Committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 20:1183–1197CrossRef The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. (1997) Report of the Expert Committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 20:1183–1197CrossRef
15.
Zurück zum Zitat Alberti KGM, Zimmet PZ, for the WHO Consultation (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Provisional Report of a WHO Consultation. Diabetic Med 15:539–553CrossRefPubMed Alberti KGM, Zimmet PZ, for the WHO Consultation (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus. Provisional Report of a WHO Consultation. Diabetic Med 15:539–553CrossRefPubMed
16.
Zurück zum Zitat Charles MA, Fontbonne A, Thibult N, Warnet J-M, Rosselin GE, Eschwege E (1991) Risk factors for NIDDM in white population: Paris Prospective Study. Diabetes 40:796–799CrossRefPubMed Charles MA, Fontbonne A, Thibult N, Warnet J-M, Rosselin GE, Eschwege E (1991) Risk factors for NIDDM in white population: Paris Prospective Study. Diabetes 40:796–799CrossRefPubMed
17.
Zurück zum Zitat Coutinho M, Gerstein HC, Wang Y, Yusuf S (1999) The relationship between glucose and incident cardiovascular events. Diabetes Care 22:233–240CrossRefPubMed Coutinho M, Gerstein HC, Wang Y, Yusuf S (1999) The relationship between glucose and incident cardiovascular events. Diabetes Care 22:233–240CrossRefPubMed
18.
Zurück zum Zitat Shaw JE, Zimmet PZ, Hodge AM et al. (2000) Impaired fasting glucose: how low should it go? Diabetes Care 23:34–39CrossRefPubMed Shaw JE, Zimmet PZ, Hodge AM et al. (2000) Impaired fasting glucose: how low should it go? Diabetes Care 23:34–39CrossRefPubMed
19.
Zurück zum Zitat Brunzell JD, Robertson RP, Lerner RL et al. (1976) Relationship between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance. J Clin Endocrinol Metab 42:222–229CrossRefPubMed Brunzell JD, Robertson RP, Lerner RL et al. (1976) Relationship between fasting plasma glucose levels and insulin secretion during intravenous glucose tolerance. J Clin Endocrinol Metab 42:222–229CrossRefPubMed
20.
Zurück zum Zitat Van Haeften TW, Pimenta W, Mitrakou A et al. (2000) Relative contributions of beta-cell function and tissue insulin sensitivity to fasting and postglucose-load glycaemia. Metabolism 49:1318–1325CrossRef Van Haeften TW, Pimenta W, Mitrakou A et al. (2000) Relative contributions of beta-cell function and tissue insulin sensitivity to fasting and postglucose-load glycaemia. Metabolism 49:1318–1325CrossRef
21.
Zurück zum Zitat Godsland IF, Leyva F, Worthington M, Walton C, Stevenson JC (1998) Associations of smoking, alcohol and physical activity with risk factors for coronary heart disease and diabetes in the first follow-up cohort of the HDDRISC Study (HDDRISC-1). J Intern Med 244:33–41CrossRefPubMed Godsland IF, Leyva F, Worthington M, Walton C, Stevenson JC (1998) Associations of smoking, alcohol and physical activity with risk factors for coronary heart disease and diabetes in the first follow-up cohort of the HDDRISC Study (HDDRISC-1). J Intern Med 244:33–41CrossRefPubMed
22.
Zurück zum Zitat Godsland IF, Rosankiewicz JR, Proudler AJ, Johnston DG (2001) Plasma total homocysteine concentrations are unrelated to insulin sensitivity and components of the metabolic syndrome in healthy men. J Clin Endocrinol Metab 86:719–723PubMed Godsland IF, Rosankiewicz JR, Proudler AJ, Johnston DG (2001) Plasma total homocysteine concentrations are unrelated to insulin sensitivity and components of the metabolic syndrome in healthy men. J Clin Endocrinol Metab 86:719–723PubMed
23.
24.
Zurück zum Zitat Albano JDM, Ekins RP, Maritz G, Turner RC (1972) A sensitive, precise radioimmunoassay of serum insulin relying on charcoal separation of bound and free hormone moieties. Acta Endocrinol 70:487–509PubMed Albano JDM, Ekins RP, Maritz G, Turner RC (1972) A sensitive, precise radioimmunoassay of serum insulin relying on charcoal separation of bound and free hormone moieties. Acta Endocrinol 70:487–509PubMed
25.
Zurück zum Zitat Bergman RN, Ider YZ, Bowden CR, Cobelli C (1979) Quantitative estimation of insulin sensitivity. Am J Physiol 236:E667–E677PubMed Bergman RN, Ider YZ, Bowden CR, Cobelli C (1979) Quantitative estimation of insulin sensitivity. Am J Physiol 236:E667–E677PubMed
26.
Zurück zum Zitat Bergman R (1989) Lilly Lecture 1989. Towards physiological understanding of glucose tolerance: minimal model approach. Diabetes 38:1512–1527CrossRefPubMed Bergman R (1989) Lilly Lecture 1989. Towards physiological understanding of glucose tolerance: minimal model approach. Diabetes 38:1512–1527CrossRefPubMed
27.
Zurück zum Zitat Walton C, Godsland IF, Proudler AJ, Felton C, Wynn V (1992) Evaluation of four mathematical models of glucose and insulin dynamics with analysis of the effects of age and obesity. Am J Physiol 262:E755–E762PubMed Walton C, Godsland IF, Proudler AJ, Felton C, Wynn V (1992) Evaluation of four mathematical models of glucose and insulin dynamics with analysis of the effects of age and obesity. Am J Physiol 262:E755–E762PubMed
28.
Zurück zum Zitat Swan J, Walton C, Godsland IF (1994) Assessment of insulin sensitivity in man: a comparison of minimal model and euglycaemic clamp derived measures in health and heart failure. Clin Sci 86:317–322CrossRefPubMed Swan J, Walton C, Godsland IF (1994) Assessment of insulin sensitivity in man: a comparison of minimal model and euglycaemic clamp derived measures in health and heart failure. Clin Sci 86:317–322CrossRefPubMed
29.
Zurück zum Zitat Horwitz D, Starr J, Mako M, Blackard W, Rubenstein A (1975) Proinsulin, insulin and C-peptide concentrations in human portal and peripheral blood. J Clin Invest 55:1278–1283CrossRefPubMedPubMedCentral Horwitz D, Starr J, Mako M, Blackard W, Rubenstein A (1975) Proinsulin, insulin and C-peptide concentrations in human portal and peripheral blood. J Clin Invest 55:1278–1283CrossRefPubMedPubMedCentral
30.
Zurück zum Zitat Van Cauter E, Mestrez F, Sturis J, Polonsky K (1992) Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 41:368–377CrossRef Van Cauter E, Mestrez F, Sturis J, Polonsky K (1992) Estimation of insulin secretion rates from C-peptide levels. Comparison of individual and standard kinetic parameters for C-peptide clearance. Diabetes 41:368–377CrossRef
31.
Zurück zum Zitat Watanabe R, Vølund A, Roy S, Bergman R (1989) Prehepatic beta-cell secretion during the intravenous glucose tolerance test in humans: Application of a combined model of insulin and C-peptide kinetics. J Clin Endocrinol Metab 69:790–797CrossRefPubMed Watanabe R, Vølund A, Roy S, Bergman R (1989) Prehepatic beta-cell secretion during the intravenous glucose tolerance test in humans: Application of a combined model of insulin and C-peptide kinetics. J Clin Endocrinol Metab 69:790–797CrossRefPubMed
32.
Zurück zum Zitat Tranberg K, Dencker H (1978) Modeling of plasma disappearance of unlabelled insulin in man. Am J Physiol 235:E577–E585PubMed Tranberg K, Dencker H (1978) Modeling of plasma disappearance of unlabelled insulin in man. Am J Physiol 235:E577–E585PubMed
33.
Zurück zum Zitat Watanabe RM, Steil GM, Bergman RN (1998) Critical evaluation of the combined model approach for estimation of prehepatic insulin secretion. Am J Physiol 274:E172–E183PubMed Watanabe RM, Steil GM, Bergman RN (1998) Critical evaluation of the combined model approach for estimation of prehepatic insulin secretion. Am J Physiol 274:E172–E183PubMed
34.
Zurück zum Zitat Julious SA (2001) Inference and estimation in changepoint regression. J Royal Stat Soc 50:51–62 Julious SA (2001) Inference and estimation in changepoint regression. J Royal Stat Soc 50:51–62
35.
Zurück zum Zitat Finegood DT, Tzur D (1996) Reduced glucose effectiveness associated with reduced insulin release: an artifact of the minimal–model method. Am J Physiol 271:E485–E495PubMed Finegood DT, Tzur D (1996) Reduced glucose effectiveness associated with reduced insulin release: an artifact of the minimal–model method. Am J Physiol 271:E485–E495PubMed
36.
Zurück zum Zitat Seltzer H, Allen E, Herron A Jr, Brennan M (1967) Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest 46:323–335CrossRefPubMedPubMedCentral Seltzer H, Allen E, Herron A Jr, Brennan M (1967) Insulin secretion in response to glycemic stimulus: relation of delayed initial release to carbohydrate intolerance in mild diabetes mellitus. J Clin Invest 46:323–335CrossRefPubMedPubMedCentral
37.
Zurück zum Zitat Perley M, Kipinis D (1967) Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 46:1954–1962CrossRefPubMedPubMedCentral Perley M, Kipinis D (1967) Plasma insulin responses to oral and intravenous glucose: studies in normal and diabetic subjects. J Clin Invest 46:1954–1962CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Cerasi E (1967) An analogue computer model for the insulin response to glucose infusion. Acta Endocrinol 55:163–183PubMed Cerasi E (1967) An analogue computer model for the insulin response to glucose infusion. Acta Endocrinol 55:163–183PubMed
39.
Zurück zum Zitat DeFronzo RA (1988) Lilly lecture 1987: the triumvirate: beta cell, muscle, liver: a collusion responsible for NIDDM. Diabetes 37:667–687CrossRefPubMed DeFronzo RA (1988) Lilly lecture 1987: the triumvirate: beta cell, muscle, liver: a collusion responsible for NIDDM. Diabetes 37:667–687CrossRefPubMed
40.
Zurück zum Zitat Ozaki K, Okubo M, Mori H, Mito K, Hara H, Kohno N (2002) Decreased insulin secretion and dyslipidemia coexist in subjects with impaired fasting glucose. Diabetes Res Clin Pract 55:159–164CrossRefPubMed Ozaki K, Okubo M, Mori H, Mito K, Hara H, Kohno N (2002) Decreased insulin secretion and dyslipidemia coexist in subjects with impaired fasting glucose. Diabetes Res Clin Pract 55:159–164CrossRefPubMed
41.
Zurück zum Zitat Mittelman SD, van Citters GW, Kim SP et al. (2000) Longitudinal compensation for fat-induced insulin resistance includes reduced insulin clearance and enhanced beta-cell response. Diabetes 49:2116–2125CrossRefPubMed Mittelman SD, van Citters GW, Kim SP et al. (2000) Longitudinal compensation for fat-induced insulin resistance includes reduced insulin clearance and enhanced beta-cell response. Diabetes 49:2116–2125CrossRefPubMed
42.
Zurück zum Zitat Eaton R, Allen R, Schade D, Erickson K, Standefer J (1980) Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behaviour. J Clin Endocrinol Metab 51:520–528CrossRefPubMed Eaton R, Allen R, Schade D, Erickson K, Standefer J (1980) Prehepatic insulin production in man: kinetic analysis using peripheral connecting peptide behaviour. J Clin Endocrinol Metab 51:520–528CrossRefPubMed
43.
Zurück zum Zitat Polonsky K, Licinio-Paixao J, Given B et al. (1986) Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type 1 diabetic patients. J Clin Invest 77:98–105CrossRefPubMedPubMedCentral Polonsky K, Licinio-Paixao J, Given B et al. (1986) Use of biosynthetic human C-peptide in the measurement of insulin secretion rates in normal volunteers and type 1 diabetic patients. J Clin Invest 77:98–105CrossRefPubMedPubMedCentral
44.
Zurück zum Zitat Kjems LL, Volund A, Madsbad S (2001) Quantification of beta-cell function during IVGTT in type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods. Diabetologia 44:1339–1348CrossRefPubMed Kjems LL, Volund A, Madsbad S (2001) Quantification of beta-cell function during IVGTT in type II and non-diabetic subjects: assessment of insulin secretion by mathematical methods. Diabetologia 44:1339–1348CrossRefPubMed
45.
Zurück zum Zitat Walton C, Godsland I, Proudler A, Felton C, Wynn V (1992) An apparently anomalous relationship between insulin and C-peptide concentrations in their initial response to intravenous glucose. Metabolism 41:1210–1214CrossRefPubMed Walton C, Godsland I, Proudler A, Felton C, Wynn V (1992) An apparently anomalous relationship between insulin and C-peptide concentrations in their initial response to intravenous glucose. Metabolism 41:1210–1214CrossRefPubMed
Metadaten
Titel
Loss of beta cell function as fasting glucose increases in the non-diabetic range
verfasst von
I. F. Godsland
J. A. R. Jeffs
D. G. Johnston
Publikationsdatum
01.07.2004
Verlag
Springer Berlin Heidelberg
Erschienen in
Diabetologia / Ausgabe 7/2004
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-004-1454-z

Weitere Artikel der Ausgabe 7/2004

Diabetologia 7/2004 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.