Diabetic ketosis during hyperglycemic crisis is associated with decreased all-cause mortality in patients with type 2 diabetes mellitus
- 662 Downloads
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.
KeywordsType 2 diabetes mellitus Ketosis Ketogenesis Mortality Heart failure Kidney disease
We wish to thank Dr. Lora S. Kirigin for English language editing. All authors fulfill the criteria for authorship: IK gave the idea for the study, performed statistical analysis, participated in manuscript drafting and gave the final approval. MĆ and PĆ performed the data acquisition, critically reviewed the manuscript and gave the final approval. VO and MŠ designed electronic databases, participated in manuscript drafting and gave their final approval. AŠ and MV gave advice regarding statistical analyses and data acquisition, critically reviewed the manuscript and gave the final approval.
This study did not receive any funding
Compliance with ethical standards
Conflict of interest
The authors declare that they have no competing interests.
- 5.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)CrossRefPubMedGoogle Scholar
- 7.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)CrossRefPubMedGoogle Scholar
- 8.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)CrossRefPubMedGoogle Scholar
- 10.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)CrossRefPubMedGoogle Scholar
- 11.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).Google Scholar
- 12.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)CrossRefPubMedGoogle Scholar
- 17.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)CrossRefPubMedGoogle Scholar
- 21.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)Google Scholar