Skip to main content
Erschienen in: Endocrine 1/2017

03.09.2016 | Original Article

Diabetic ketosis during hyperglycemic crisis is associated with decreased all-cause mortality in patients with type 2 diabetes mellitus

verfasst von: Ivan Kruljac, Miroslav Ćaćić, Petra Ćaćić, Vedran Ostojić, Mario Štefanović, Aljoša Šikić, Milan Vrkljan

Erschienen in: Endocrine | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Patients with type 2 diabetes mellitus have impaired ketogenesis due to high serum insulin and low growth hormone levels. Evidence exists that ketone bodies might improve kidney and cardiac function. In theory, improved ketogenesis in diabetics may have positive effects. We aimed to assess the impact of diabetic ketosis on all-cause mortality in patients with type 2 diabetes mellitus presenting with hyperglycemic crisis. We analyzed 486 patients with diabetic ketosis and 486 age and sex-matched patients with non-ketotic hyperglycemia presenting to the emergency department. Cox proportional hazard models were used to analyze the link between patient characteristics and mortality. During an observation time of 33.4 months, death of any cause occurred in 40.9 % of the non-ketotic hyperglycemia group and 30.2 % of the DK group (hazard ratio in the diabetic ketosis group, 0.63; 95 % confidence interval 0.48–0.82; P = 0.0005). Patients with diabetic ketosis had a lower incidence of symptomatic heart failure and had improved renal function. They used less furosemide and antihypertensive drugs, more metformin and lower insulin doses, all of which was independently associated with decreased mortality. Plasma glucose and glycated hemoglobin levels were similar in both groups. Patients with hyperglycemic crisis and diabetic ketosis have decreased all-cause mortality when compared to those with non-ketotic hyperglycemia. diabetic ketosis might be a compensatory mechanism rather than a complication in patients with hyperglycemic crises, but further prospective studies are warranted.
Literatur
1.
Zurück zum Zitat A. Avogaro, A. Valerio, L. Gnudi, A. Maran, M. Zolli, E. Duner, A. Riccio, S. Del Prato, A. Tiengo, R. Nosadini, Ketone body metabolism in NIDDM. Effect of sulfonylurea treatment. Diabetes 41, 968–974 (1992)CrossRefPubMed A. Avogaro, A. Valerio, L. Gnudi, A. Maran, M. Zolli, E. Duner, A. Riccio, S. Del Prato, A. Tiengo, R. Nosadini, Ketone body metabolism in NIDDM. Effect of sulfonylurea treatment. Diabetes 41, 968–974 (1992)CrossRefPubMed
2.
Zurück zum Zitat N. Geidenstam, P. Spégel, H. Mulder, K. Filipsson, M. Ridderstråle, A.P.H. Danielsson, Metabolite profile deviations in an oral glucose tolerance test-a comparison between lean and obese individuals. Obesity (Silver Spring) 22, 2388–2395 (2014)CrossRef N. Geidenstam, P. Spégel, H. Mulder, K. Filipsson, M. Ridderstråle, A.P.H. Danielsson, Metabolite profile deviations in an oral glucose tolerance test-a comparison between lean and obese individuals. Obesity (Silver Spring) 22, 2388–2395 (2014)CrossRef
3.
Zurück zum Zitat M. Beylot, Regulation of in vivo ketogenesis: role of free fatty acids and control by epinephrine, thyroid hormones, insulin and glucagon. Diabetes Metab. 22, 299–304 (1996)PubMed M. Beylot, Regulation of in vivo ketogenesis: role of free fatty acids and control by epinephrine, thyroid hormones, insulin and glucagon. Diabetes Metab. 22, 299–304 (1996)PubMed
4.
Zurück zum Zitat J.A. Edge, D.A. Harris, P.E. Phillips, B.R. Pal, D.R. Matthews, D.B. Dunger, Evidence for a role for insulin and growth hormone in overnight regulation of 3-hydroxybutyrate in normal and diabetic adolescents. Diabetes Care 16, 1011–1018 (1993)CrossRefPubMed J.A. Edge, D.A. Harris, P.E. Phillips, B.R. Pal, D.R. Matthews, D.B. Dunger, Evidence for a role for insulin and growth hormone in overnight regulation of 3-hydroxybutyrate in normal and diabetic adolescents. Diabetes Care 16, 1011–1018 (1993)CrossRefPubMed
5.
Zurück zum Zitat M. Beylot, S. Picard, C. Chambrier, H. Vidal, M. Laville, R. Cohen, A. Cotisson, R. Mornex, Effect of physiological concentrations of insulin and glucagon on the relationship between nonesterified fatty acids availability and ketone body production in humans. Metabolism 40, 1138–1146 (1991)CrossRefPubMed M. Beylot, S. Picard, C. Chambrier, H. Vidal, M. Laville, R. Cohen, A. Cotisson, R. Mornex, Effect of physiological concentrations of insulin and glucagon on the relationship between nonesterified fatty acids availability and ketone body production in humans. Metabolism 40, 1138–1146 (1991)CrossRefPubMed
6.
Zurück zum Zitat G.E. Umpierrez, D. Smiley, A.E. Kitabchi, Narrative review: ketosis-prone type 2 diabetes mellitus. Ann. Intern. Med. 144, 350–357 (2006)CrossRefPubMed G.E. Umpierrez, D. Smiley, A.E. Kitabchi, Narrative review: ketosis-prone type 2 diabetes mellitus. Ann. Intern. Med. 144, 350–357 (2006)CrossRefPubMed
7.
Zurück zum Zitat B. Zinman, C. Wanner, J.M. Lachin, D. Fitchett, E. Bluhmki, S. Hantel, M. Mattheus, T. Devins, O.E. Johansen, H.J. Woerle, U.C. Broedl, S.E. Inzucchi, EMPA-REG OUTCOME Investigators Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N. Engl. J. Med. 373, 2117–2128 (2015)CrossRefPubMed B. Zinman, C. Wanner, J.M. Lachin, D. Fitchett, E. Bluhmki, S. Hantel, M. Mattheus, T. Devins, O.E. Johansen, H.J. Woerle, U.C. Broedl, S.E. Inzucchi, EMPA-REG OUTCOME Investigators Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N. Engl. J. Med. 373, 2117–2128 (2015)CrossRefPubMed
8.
Zurück zum Zitat E. Ferrannini, S. Baldi, S. Frascerra, B. Astiarraga, T. Heise, R. Bizzotto, A. Mari, T.R. Pieber, E. Muscelli, Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. Diabetes 65, 1190–1195 (2016)CrossRefPubMed E. Ferrannini, S. Baldi, S. Frascerra, B. Astiarraga, T. Heise, R. Bizzotto, A. Mari, T.R. Pieber, E. Muscelli, Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. Diabetes 65, 1190–1195 (2016)CrossRefPubMed
9.
Zurück zum Zitat Y. Kao, C.-C. Hsu, S.-F. Weng, H.-J. Lin, J.-J. Wang, S.-B. Su, C.-C. Huang, H.-R. Guo, Subsequent mortality after hyperglycemic crisis episode in the non-elderly: a national population-based cohort study. Endocrine 51, 72–82 (2016)CrossRefPubMed Y. Kao, C.-C. Hsu, S.-F. Weng, H.-J. Lin, J.-J. Wang, S.-B. Su, C.-C. Huang, H.-R. Guo, Subsequent mortality after hyperglycemic crisis episode in the non-elderly: a national population-based cohort study. Endocrine 51, 72–82 (2016)CrossRefPubMed
10.
Zurück zum Zitat C.L. Morgan, J. Mukherjee, S. Jenkins-Jones, S.E. Holden, C.J. Currie, Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality. Diabetes. Obes. Metab. 16, 977–983 (2014)CrossRefPubMed C.L. Morgan, J. Mukherjee, S. Jenkins-Jones, S.E. Holden, C.J. Currie, Combination therapy with metformin plus sulphonylureas versus metformin plus DPP-4 inhibitors: association with major adverse cardiovascular events and all-cause mortality. Diabetes. Obes. Metab. 16, 977–983 (2014)CrossRefPubMed
11.
Zurück zum Zitat U. Anyanwagu, J. Mamza, R. Mehta, R. Donnelly, I. Idris Cardiovascular events and all-cause mortality with insulin versus glucagon-like peptide-1 analogue in type 2 diabetes. Heart. (2016). U. Anyanwagu, J. Mamza, R. Mehta, R. Donnelly, I. Idris Cardiovascular events and all-cause mortality with insulin versus glucagon-like peptide-1 analogue in type 2 diabetes. Heart. (2016).
12.
Zurück zum Zitat C.A. Bannister, S.E. Holden, S. Jenkins-Jones, C.L. Morgan, J.P. Halcox, G. Schernthaner, J. Mukherjee, C.J. Currie, Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes. Obes. Metab. 16, 1165–1173 (2014)CrossRefPubMed C.A. Bannister, S.E. Holden, S. Jenkins-Jones, C.L. Morgan, J.P. Halcox, G. Schernthaner, J. Mukherjee, C.J. Currie, Can people with type 2 diabetes live longer than those without? A comparison of mortality in people initiated with metformin or sulphonylurea monotherapy and matched, non-diabetic controls. Diabetes. Obes. Metab. 16, 1165–1173 (2014)CrossRefPubMed
13.
Zurück zum Zitat W.W. Winder, D.G. Hardie, AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am. J. Physiol 277, E1–E10 (1999)PubMed W.W. Winder, D.G. Hardie, AMP-activated protein kinase, a metabolic master switch: possible roles in type 2 diabetes. Am. J. Physiol 277, E1–E10 (1999)PubMed
14.
Zurück zum Zitat C. Wolfrum, E. Asilmaz, E. Luca, J.M. Friedman, M. Stoffel, Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. Nature 432, 1027–1032 (2004)CrossRefPubMed C. Wolfrum, E. Asilmaz, E. Luca, J.M. Friedman, M. Stoffel, Foxa2 regulates lipid metabolism and ketogenesis in the liver during fasting and in diabetes. Nature 432, 1027–1032 (2004)CrossRefPubMed
15.
Zurück zum Zitat G. Aubert, O.J. Martin, J.L. Horton, L. Lai, R.B. Vega, T.C. Leone, T. Koves, S.J. Gardell, M. Krüger, C.L. Hoppel, E.D. Lewandowski, P.A. Crawford, D.M. Muoio, D.P. Kelly, The Failing Heart Relies on Ketone Bodies as a Fuel. Circulation 133, 698–705 (2016)PubMed G. Aubert, O.J. Martin, J.L. Horton, L. Lai, R.B. Vega, T.C. Leone, T. Koves, S.J. Gardell, M. Krüger, C.L. Hoppel, E.D. Lewandowski, P.A. Crawford, D.M. Muoio, D.P. Kelly, The Failing Heart Relies on Ketone Bodies as a Fuel. Circulation 133, 698–705 (2016)PubMed
16.
Zurück zum Zitat Y.-C. Tsai, Y.-C. Chou, A.-B. Wu, C.-M. Hu, C.-Y. Chen, F.-A. Chen, J.-A. Lee, Stereoselective effects of 3-hydroxybutyrate on glucose utilization of rat cardiomyocytes. Life Sci 78, 1385–1391 (2006)CrossRefPubMed Y.-C. Tsai, Y.-C. Chou, A.-B. Wu, C.-M. Hu, C.-Y. Chen, F.-A. Chen, J.-A. Lee, Stereoselective effects of 3-hydroxybutyrate on glucose utilization of rat cardiomyocytes. Life Sci 78, 1385–1391 (2006)CrossRefPubMed
17.
Zurück zum Zitat P. Fioretto, R. Trevisan, M. Velussi, A. Cernigoi, C. De Riva, M. Bressan, A. Doria, N. Pauletto, P. Angeli, C. De Donà, Glomerular filtration rate is increased in man by the infusion of both D,L-3-hydroxybutyric acid and sodium D,L-3-hydroxybutyrate. J. Clin. Endocrinol. Metab. 65, 331–338 (1987)CrossRefPubMed P. Fioretto, R. Trevisan, M. Velussi, A. Cernigoi, C. De Riva, M. Bressan, A. Doria, N. Pauletto, P. Angeli, C. De Donà, Glomerular filtration rate is increased in man by the infusion of both D,L-3-hydroxybutyric acid and sodium D,L-3-hydroxybutyrate. J. Clin. Endocrinol. Metab. 65, 331–338 (1987)CrossRefPubMed
18.
Zurück zum Zitat T. Wei, W. Tian, F. Liu, G. Xie, Protective effects of exogenous β-hydroxybutyrate on paraquat toxicity in rat kidney. Biochem. Biophys. Res. Commun. 447, 666–671 (2014)CrossRefPubMed T. Wei, W. Tian, F. Liu, G. Xie, Protective effects of exogenous β-hydroxybutyrate on paraquat toxicity in rat kidney. Biochem. Biophys. Res. Commun. 447, 666–671 (2014)CrossRefPubMed
19.
Zurück zum Zitat R. Trevisan, R. Nosadini, P. Fioretto, A. Avogaro, E. Duner, E. Jori, A. Valerio, A. Doria, G. Crepaldi, Ketone bodies increase glomerular filtration rate in normal man and in patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30, 214–221 (1987)CrossRefPubMed R. Trevisan, R. Nosadini, P. Fioretto, A. Avogaro, E. Duner, E. Jori, A. Valerio, A. Doria, G. Crepaldi, Ketone bodies increase glomerular filtration rate in normal man and in patients with type 1 (insulin-dependent) diabetes mellitus. Diabetologia 30, 214–221 (1987)CrossRefPubMed
20.
21.
Zurück zum Zitat C. Wanner, S.E. Inzucchi, J.M. Lachin, D. Fitchett, M. von Eynatten, M. Mattheus, O.E. Johansen, H.J. Woerle, U.C. Broedl, B. Zinman, EMPA-REG OUTCOME Investigators empagliflozin and progression of kidney disease in type 2 diabetes. N. Engl. J. Med. (2016) C. Wanner, S.E. Inzucchi, J.M. Lachin, D. Fitchett, M. von Eynatten, M. Mattheus, O.E. Johansen, H.J. Woerle, U.C. Broedl, B. Zinman, EMPA-REG OUTCOME Investigators empagliflozin and progression of kidney disease in type 2 diabetes. N. Engl. J. Med. (2016)
Metadaten
Titel
Diabetic ketosis during hyperglycemic crisis is associated with decreased all-cause mortality in patients with type 2 diabetes mellitus
verfasst von
Ivan Kruljac
Miroslav Ćaćić
Petra Ćaćić
Vedran Ostojić
Mario Štefanović
Aljoša Šikić
Milan Vrkljan
Publikationsdatum
03.09.2016
Verlag
Springer US
Erschienen in
Endocrine / Ausgabe 1/2017
Print ISSN: 1355-008X
Elektronische ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-016-1082-7

Weitere Artikel der Ausgabe 1/2017

Endocrine 1/2017 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

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