Skip to main content
Top
Published in: Diabetologia 5/2012

01-05-2012 | Article

Pancreatic diabetes manifests when beta cell area declines by approximately 65% in humans

Authors: J. J. Meier, T. G. K. Breuer, R. C. Bonadonna, A. Tannapfel, W. Uhl, W. E. Schmidt, H. Schrader, B. A. Menge

Published in: Diabetologia | Issue 5/2012

Login to get access

Abstract

Aims/hypothesis

Diabetes frequently develops in patients with pancreatic disorders. We aimed to determine the lower threshold of beta cell area for diabetes manifestation as well as the impact of insulin sensitivity on glucose homoeostasis in patients with pancreatic diabetes.

Methods

Eighty-two patients undergoing pancreatic surgery underwent pre-operative oral glucose challenge. Fractional pancreatic beta cell area was determined, and indices of insulin sensitivity and beta cell function were calculated.

Results

HbA1c and glucose levels were similar in patients with high and intermediate beta cell area, but were significantly higher in those with the lowest beta cell area (p < 0.0001). Insulin secretion was reduced only in patients with the lowest beta cell area (p < 0.001). The relative beta cell deficits at the onset of diabetes and impaired glucose tolerance were 64% and 21%, respectively, based on 2 h glucose levels. Deteriorating insulin sensitivity was associated with a small increase in the incidence of diabetes.

Conclusions/interpretation

In conclusion, pancreatic diabetes probably develops after a reduction in beta cell area of ~65%. Post-challenge glucose excursions are much more closely related to pancreatic beta cell area than to fasting glycaemia, thereby underlining the usefulness of the OGTT in patients with pancreatic disorders.
Appendix
Available only for authorised users
Literature
1.
go back to reference Larsen S, Hilsted J, Tronier B, Worning H (1987) Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis. Metabolism 36:964–967PubMedCrossRef Larsen S, Hilsted J, Tronier B, Worning H (1987) Metabolic control and B cell function in patients with insulin-dependent diabetes mellitus secondary to chronic pancreatitis. Metabolism 36:964–967PubMedCrossRef
2.
go back to reference Larsen S, Hilsted J, Tronier B, Worning H (1988) Pancreatic hormone secretion in chronic pancreatitis without residual beta cell function. Acta Endocrinol 118:357–364PubMed Larsen S, Hilsted J, Tronier B, Worning H (1988) Pancreatic hormone secretion in chronic pancreatitis without residual beta cell function. Acta Endocrinol 118:357–364PubMed
3.
go back to reference Pannala R, Leibson CL, Rabe KG et al (2009) Temporal association of changes in fasting blood glucose and body mass index with diagnosis of pancreatic cancer. Am J Gastroenterol 104:2318–2325PubMedCrossRef Pannala R, Leibson CL, Rabe KG et al (2009) Temporal association of changes in fasting blood glucose and body mass index with diagnosis of pancreatic cancer. Am J Gastroenterol 104:2318–2325PubMedCrossRef
4.
go back to reference Pannala R, Basu A, Petersen GM, Chari ST (2009) New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol 10:88–95PubMedCrossRef Pannala R, Basu A, Petersen GM, Chari ST (2009) New-onset diabetes: a potential clue to the early diagnosis of pancreatic cancer. Lancet Oncol 10:88–95PubMedCrossRef
5.
go back to reference Schrader H, Menge BA, Schneider S et al (2009) Reduced pancreatic volume and beta cell area in patients with chronic pancreatitis. Gastroenterology 136:513–522PubMedCrossRef Schrader H, Menge BA, Schneider S et al (2009) Reduced pancreatic volume and beta cell area in patients with chronic pancreatitis. Gastroenterology 136:513–522PubMedCrossRef
6.
go back to reference Schrader H, Menge BA, Zeidler C et al (2010) Determinants of glucose control in patients with chronic pancreatitis. Diabetologia 53:1062–1069PubMedCrossRef Schrader H, Menge BA, Zeidler C et al (2010) Determinants of glucose control in patients with chronic pancreatitis. Diabetologia 53:1062–1069PubMedCrossRef
7.
go back to reference Schrader H, Menge BA, Belyaev O, Uhl W, Schmidt WE, Meier JJ (2009) Amino acid malnutrition in patients with chronic pancreatitis and pancreatic carcinoma. Pancreas 38:416–421PubMedCrossRef Schrader H, Menge BA, Belyaev O, Uhl W, Schmidt WE, Meier JJ (2009) Amino acid malnutrition in patients with chronic pancreatitis and pancreatic carcinoma. Pancreas 38:416–421PubMedCrossRef
8.
go back to reference Meier RF, Beglinger C (2006) Nutrition in pancreatic diseases. Best Pract Res Clin Gastroenterol 20:507–529PubMedCrossRef Meier RF, Beglinger C (2006) Nutrition in pancreatic diseases. Best Pract Res Clin Gastroenterol 20:507–529PubMedCrossRef
9.
go back to reference Figler RA, Wang G, Srinivasan S et al (2011) Links between insulin resistance, adenosine A2B receptors, and inflammatory markers in mice and humans. Diabetes 60:669–679PubMedCrossRef Figler RA, Wang G, Srinivasan S et al (2011) Links between insulin resistance, adenosine A2B receptors, and inflammatory markers in mice and humans. Diabetes 60:669–679PubMedCrossRef
10.
go back to reference Donath MY, Storling J, Maedler K, Mandrup-Poulsen T (2003) Inflammatory mediators and islet beta cell failure: a link between type 1 and type 2 diabetes. J Mol Med 81:455–470PubMedCrossRef Donath MY, Storling J, Maedler K, Mandrup-Poulsen T (2003) Inflammatory mediators and islet beta cell failure: a link between type 1 and type 2 diabetes. J Mol Med 81:455–470PubMedCrossRef
11.
go back to reference Meier JJ, Menge BA, Breuer TG et al (2009) Functional assessment of pancreatic beta cell area in humans. Diabetes 58:1595–1603PubMedCrossRef Meier JJ, Menge BA, Breuer TG et al (2009) Functional assessment of pancreatic beta cell area in humans. Diabetes 58:1595–1603PubMedCrossRef
12.
go back to reference Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta cell deficit and increased beta cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110PubMedCrossRef Butler AE, Janson J, Bonner-Weir S, Ritzel R, Rizza RA, Butler PC (2003) Beta cell deficit and increased beta cell apoptosis in humans with type 2 diabetes. Diabetes 52:102–110PubMedCrossRef
13.
go back to reference Butler AE, Cao-Minh L, Galasso R et al (2010) Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy. Diabetologia 53:2167–2176PubMedCrossRef Butler AE, Cao-Minh L, Galasso R et al (2010) Adaptive changes in pancreatic beta cell fractional area and beta cell turnover in human pregnancy. Diabetologia 53:2167–2176PubMedCrossRef
14.
go back to reference Bacos K, Bjorkqvist M, Petersen A et al (2008) Islet beta cell area and hormone expression are unaltered in Huntington's disease. Histochem Cell Biol 129:623–629PubMedCrossRef Bacos K, Bjorkqvist M, Petersen A et al (2008) Islet beta cell area and hormone expression are unaltered in Huntington's disease. Histochem Cell Biol 129:623–629PubMedCrossRef
15.
go back to reference In't Veld P, Lievens D, de Grijse J et al (2007) Screening for insulitis in adult autoantibody-positive organ donors. Diabetes 56:2400–2404PubMedCrossRef In't Veld P, Lievens D, de Grijse J et al (2007) Screening for insulitis in adult autoantibody-positive organ donors. Diabetes 56:2400–2404PubMedCrossRef
16.
go back to reference Buteau J, Spatz ML, Accili D (2006) Transcription factor FoxO1 mediates glucagon-like peptide-1 effects on pancreatic beta cell mass. Diabetes 55:1190–1196PubMedCrossRef Buteau J, Spatz ML, Accili D (2006) Transcription factor FoxO1 mediates glucagon-like peptide-1 effects on pancreatic beta cell mass. Diabetes 55:1190–1196PubMedCrossRef
17.
go back to reference Saisho Y, Butler AE, Meier JJ et al (2007) Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes. Clin Anat 20:933–942PubMedCrossRef Saisho Y, Butler AE, Meier JJ et al (2007) Pancreas volumes in humans from birth to age one hundred taking into account sex, obesity, and presence of type-2 diabetes. Clin Anat 20:933–942PubMedCrossRef
18.
go back to reference Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care 22:1462–1470PubMedCrossRef Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing. Diabetes Care 22:1462–1470PubMedCrossRef
19.
go back to reference Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and ß-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419PubMedCrossRef
20.
go back to reference Bonadonna RC, Heise T, Arbet-Engels C et al (2010) Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: a mechanistic study. J Clin Endocrinol Metab 95:5028–5036PubMedCrossRef Bonadonna RC, Heise T, Arbet-Engels C et al (2010) Piragliatin (RO4389620), a novel glucokinase activator, lowers plasma glucose both in the postabsorptive state and after a glucose challenge in patients with type 2 diabetes mellitus: a mechanistic study. J Clin Endocrinol Metab 95:5028–5036PubMedCrossRef
21.
go back to reference Cobelli C, Toffolo GM, Dalla Man C et al (2007) Assessment of beta cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests. Am J Physiol Endocrinol Metab 293:E1–E15PubMedCrossRef Cobelli C, Toffolo GM, Dalla Man C et al (2007) Assessment of beta cell function in humans, simultaneously with insulin sensitivity and hepatic extraction, from intravenous and oral glucose tests. Am J Physiol Endocrinol Metab 293:E1–E15PubMedCrossRef
22.
go back to reference Mari A, Camastra S, Toschi E et al (2001) A model for glucose control of insulin secretion during 24 h of free living. Diabetes 50(Suppl 1):S164–S168PubMedCrossRef Mari A, Camastra S, Toschi E et al (2001) A model for glucose control of insulin secretion during 24 h of free living. Diabetes 50(Suppl 1):S164–S168PubMedCrossRef
23.
go back to reference Saisho Y, Butler AE, Manesso E et al (2009) Relationship between fractional pancreatic beta cell area and fasting plasma glucose concentration in monkeys. Diabetologia 53:111–114PubMedCrossRef Saisho Y, Butler AE, Manesso E et al (2009) Relationship between fractional pancreatic beta cell area and fasting plasma glucose concentration in monkeys. Diabetologia 53:111–114PubMedCrossRef
24.
go back to reference Larsen MO, Rolin B, Sturis J et al (2005) Measures of insulin responses as predictive markers of pancreatic beta cell mass in normal and beta cell reduced lean and obese Gottingen minipigs in vivo. Am J Physiol Endocrinol Metab 8:8 Larsen MO, Rolin B, Sturis J et al (2005) Measures of insulin responses as predictive markers of pancreatic beta cell mass in normal and beta cell reduced lean and obese Gottingen minipigs in vivo. Am J Physiol Endocrinol Metab 8:8
25.
go back to reference Finegood DT, Weir GC, Bonner-Weir S (1999) Prior streptozotocin treatment does not inhibit pancreas regeneration after 90% pancreatectomy in rats. Am J Physiol 276:E822–E827PubMed Finegood DT, Weir GC, Bonner-Weir S (1999) Prior streptozotocin treatment does not inhibit pancreas regeneration after 90% pancreatectomy in rats. Am J Physiol 276:E822–E827PubMed
26.
go back to reference Liu YQ, Nevin PW, Leahy JL (2000) Beta cell adaptation in 60% pancreatectomy rats that preserves normoinsulinemia and normoglycemia. Am J Physiol Endocrinol Metab 279:E68–E73PubMed Liu YQ, Nevin PW, Leahy JL (2000) Beta cell adaptation in 60% pancreatectomy rats that preserves normoinsulinemia and normoglycemia. Am J Physiol Endocrinol Metab 279:E68–E73PubMed
27.
go back to reference Menge BA, Tannapfel A, Belyaev O et al (2008) Partial pancreatectomy in adult humans does not provoke beta cell regeneration. Diabetes 57:142–149PubMedCrossRef Menge BA, Tannapfel A, Belyaev O et al (2008) Partial pancreatectomy in adult humans does not provoke beta cell regeneration. Diabetes 57:142–149PubMedCrossRef
28.
go back to reference Rankin MM, Kushner JA (2009) Adaptive beta cell proliferation is severely restricted with advanced age. Diabetes 58:1365–1372PubMedCrossRef Rankin MM, Kushner JA (2009) Adaptive beta cell proliferation is severely restricted with advanced age. Diabetes 58:1365–1372PubMedCrossRef
29.
go back to reference Tschen SI, Dhawan S, Gurlo T, Bhushan A (2009) Age-dependent decline in beta cell proliferation restricts the capacity of beta cell regeneration in mice. Diabetes 58:1312–1320PubMedCrossRef Tschen SI, Dhawan S, Gurlo T, Bhushan A (2009) Age-dependent decline in beta cell proliferation restricts the capacity of beta cell regeneration in mice. Diabetes 58:1312–1320PubMedCrossRef
31.
go back to reference Rizza RA (2010) Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: implications for therapy. Diabetes 59:2697–2707PubMedCrossRef Rizza RA (2010) Pathogenesis of fasting and postprandial hyperglycemia in type 2 diabetes: implications for therapy. Diabetes 59:2697–2707PubMedCrossRef
32.
go back to reference Ritzel RA, Butler AE, Rizza RA, Veldhuis JD, Butler PC (2006) Relationship between beta cell mass and fasting blood glucose concentration in humans. Diabetes Care 29:717–718PubMedCrossRef Ritzel RA, Butler AE, Rizza RA, Veldhuis JD, Butler PC (2006) Relationship between beta cell mass and fasting blood glucose concentration in humans. Diabetes Care 29:717–718PubMedCrossRef
33.
go back to reference Marchetti P, del Guerra S, Marselli L et al (2004) Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J Clin Endocrinol Metab 89:5535–5541PubMedCrossRef Marchetti P, del Guerra S, Marselli L et al (2004) Pancreatic islets from type 2 diabetic patients have functional defects and increased apoptosis that are ameliorated by metformin. J Clin Endocrinol Metab 89:5535–5541PubMedCrossRef
34.
go back to reference Reaven GM (1988) Banting Lecture: role of insulin resistance in human disease. Diabetes 37:1593–1607 Reaven GM (1988) Banting Lecture: role of insulin resistance in human disease. Diabetes 37:1593–1607
Metadata
Title
Pancreatic diabetes manifests when beta cell area declines by approximately 65% in humans
Authors
J. J. Meier
T. G. K. Breuer
R. C. Bonadonna
A. Tannapfel
W. Uhl
W. E. Schmidt
H. Schrader
B. A. Menge
Publication date
01-05-2012
Publisher
Springer-Verlag
Published in
Diabetologia / Issue 5/2012
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-012-2466-8

Other articles of this Issue 5/2012

Diabetologia 5/2012 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.