Clinical Characteristics and Long-term Follow-up of Ketosis-prone Diabetes in Thai Patients

Abstract

Introduction: Diabetes presenting with ketoacidosis is a heterogeneous disorder. The purpose of this study was to determine whether ketosis-prone diabetes (KPDM) in Thai patients were different from type1 diabetes by assessment of the beta-cell response to a standardized mixed meal and pancreatic autoantibodies.

Material and Methods: 20 patients who were categorized as ketosis-prone diabetes based on the occurrence of unprovoked DKA after the age of 30 years were compared with 12 type1 diabetic patients. The beta-cell function and pancreatic autoantibodies were followed after resolution of DKA every 6 months for 2 years.

Results: Mean (±SD) age at presentation was 38.8±11.5 and 26.7+10.3 years in KPDM and type1 DM, respectively (p<0.05). Median (IQR) fasting plasma C-peptide obtained after resolution of DKA within 2 weeks was 0.90 ng/dl ­(0.20–1.30) in KPDM compared with 0.10 ng/dl (0.10–0.45) in type1 diabetes and median peak stimulated plasma C-peptide was 6.80 ng/dl (0.90–9.80) compared with 0.10 ng/dl (0.10–0.75). Based on Aβ classification, 4 patients were classified as A+β−, 12 patients were classified as A−β+, and 4 patients were classified as A−β−. No patient was classified as A+β+ in this study. At the median time of 31 months follow-up (range from 8–44 months), 11 patients from 12 A−β+ KPDM (92%) could be withdrawn from insulin treatment successfully at median time of 5 months after admission.

Conclusions: Thai KPDM patients had variable clinical course which were different from typical type1 DM. The Aβ classification was proven to be useful predictors for consideration of insulin withdrawal after resolution of DKA.

Key words

ketosis-prone diabetes - mixed meal tolerance test - long-term follow-up

• References

• 1 Banerji MA, Chaiken RL, Huey H et al. GAD antibody negative NIDDM in adult black subjects with diabetic ketoacidosis and increased frequency of human leukocyte antigen DR3 and DR4-Flatbush Diabetes. Diabetes 1994; 43: 741-745
• 2 Umpierrez GE, Casals MM, Gebhart SP et al. Diabetic ketoacidosis in obese African-Americans. Diabetes 1995; 44: 790-795
• 3 Balasubramanyam A, Nalini R, Hampe CS et al. Syndromes of ketosis-prone diabetes mellitus. Endocr Rev 2008; 29: 292-302
• 4 Aizawa T, Katakura M, Taguchi N et al. Ketoacidosis-onset noninsulin dependent diabetes in Japanese subjects. Am J Med Sci 1995; 310: 198-201
• 5 Yan SH, Sheu WH, Song YM et al. The occurrence of diabetic ketoacidosis in adults. Intern Med 2000; 39: 10-14
• 6 Li JK, Chan JC, Zimmet PZ et al. Young Chinese adults with new onset of diabetic ketoacidosis – clinical course, autoimmune status and progression of pancreatic beta-cell function. Diabet Med 2000; 17: 295-298
• 7 Hsin YuE, Guo HR, Wu TJ. Factors associated with discontinuing insulin therapy after diabetic ketoacidosis in adult diabetic patients. Diabet Med 2001; 18: 895-899
• 8 Ko S-H, Lee W-Y, Lee J-H et al. Clinical characteristics of diabetic ketoacidosis in Korea over the past two decades. Diabet Med 2005; 22: 466-469
• 9 Maldonado M, Hampe CS, Gaur LK et al. Ketosis-prone diabetes: dissection of a heterogeneous syndrome using an immunogenetic and beta-cell functional classification, prospective analysis, and clinical outcomes. J Clin Endocrinol Metab 2003; 88: 5090-5098
• 10 Nalini R, Ozer K, Maldonado M et al. Presence or absence of a known diabetic ketoacidosis precipitant defines distinct syndromes of “A-*beta++” ketosisprone diabetes based on long-term [beta]-cell function, human leukocyte antigen class II alleles, and sex predilection. Metabolism 2010; 59: 1448-1455
• 11 Maldonado MR, Otiniano ME, Cheema F et al. Factors associated with insulin discontinuation in subjects with ketosis-prone diabetes but preserved beta-cell function. Diabet Med 2005; 22: 1744-1750
• 12 Iwasaki Y, Hamamoto Y, Kawasaki Y et al. Japanese cases of acute onset diabetic ketosis without acidosis in the absence of glutamic acid decarboxylase autoantibody. Endocrine 2010; 37: 286-288
• 13 Matsui J, Tamasawa N, Tanabe J et al. Clinical characteristics of Japanese youth-onset type 2 diabetes with ketonuria. Diabetes Res Clin Pract 2005; 70: 235-238
• 14 Thewjitcharoen Y, Sunthornyothin S. Clinical Characteristics of Diabetic Ketoacidosis in Adult Patients. Diabetes Res Clin Pract 2010; 90: e43-e45
• 15 Greenbaum CJ, Harrison LC. Guidelines for intervention trials in subjects with newly diagnosed type 1 diabetes. Diabetes 2003; 52: 1059-1065
• 16 Greenbaum CJ, Mandrup-Poulsen T, McGee PF et al. Mixed-meal tolerance test versus glucagon stimulation test for the assessment of beta-cell function in therapeutic trials in type 1 diabetes. Diabetes Care 2008; 31: 1966-1971
• 17 Kim MK, Lee SH, Kim JH et al. Clinical characteristics of Korean patients with new-onset diabetes presenting with diabetic ketoacidosis. Diabetes Res Clin Pract 2009; 85: e8-e11
• 18 Yki-Jarvinen H. Glucose toxicity. Endocr Rev 1992; 13: 415-431
• 19 Balasubramanyam A, Nalini R, Hampe CS et al. Syndromes of ketosis-prone diabetes mellitus. Endocr Rev 2008; 29: 292-302
• 20 Sobngwi E, Gautier JF, Kevorkian JP et al. High prevalence of glucose-6-phosphate dehydrogenase deficiency without gene mutation suggests a novel genetic mechanism predisposing to ketosis-prone diabetes. J Clin Endocrinol Metab 2005; 90: 4446-4451
• 21 Galli-Tsinopoulou A, Nousia-Arvanitakis S. Glucose-6-phosphate dehydrogenase deficiency-induced hemolysis in newly diagnosed diabetic monozygot twins. J Pediatr Endocrinol Metab 2000; 13: 669-672
• 22 Sobngwi E, Choukem SP, Agbalika F et al. Ketosis-prone type 2 diabetes mellitus and human herpesvirus 8 infection in sub-Saharan Africans. JAMA 2008; 299: 2770-2776
• 23 Huiwen T, Chun W, Yerong Y. H1N1 Influenza: The Trigger of Diabetic Ketoacidosis in a Young Woman With Ketosis-Prone Diabetes. Am J Med Sci 2012; 343: 180-183
• 24 Patel SG, Hsu JW, Jahoor F et al. Pathogenesis of A-β+ ketosis-prone diabetes. Diabetes 2013; 62: 912-922
• 25 Chen CY, Fujimiya M, Laviano A et al. Modulation of ingestive behavior and gastrointestinal motility by ghrelin in diabetic animals and humans. J Chin Med Assoc 2010; 73: 225-229
• 26 Börner S, Derno M, Hacke S et al. Plasma ghrelin is positively associated with body fat, liver fat and milk fat content but not with feed intake of dairy cows after parturition. J Endocrinol 2013; 216: 217-229
• 27 Tong J, Prigeon RL, Davis HW et al. Ghrelin suppresses glucose-stimulated insulin secretion and deteriorates glucose tolerance in healthy humans. Diabetes 2010; 59: 2145-2151