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Update on diagnosis, pathogenesis and management of ketosis-prone Type 2 diabetes mellitus.

ABSTRACT: Diabetic ketoacidosis (DKA) has been considered a key clinical feature of Type 1 diabetes mellitus; however, increasing evidence indicates that DKA is also a common feature of Type 2 diabetes (T2DM). Many cases of DKA develop under stressful conditions such as trauma or infection but an increasing number of cases without precipitating cause have been reported in children and adults with T2DM. Such patients present with severe hyperglycemia and ketosis as in Type 1 diabetes mellitus but can discontinue insulin after a few months and maintain acceptable glycemic control on diet or oral agents. This subtype of diabetes has been referred to as ketosis-prone T2DM. In this article, we reviewed the literature on ketosis-prone T2DM and summarized the epidemiology, putative pathophysiology and approaches to management.

SUBMITTER: Smiley D

PROVIDER: S-EPMC3351851 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Update on diagnosis, pathogenesis and management of ketosis-prone Type 2 diabetes mellitus.

Smiley Dawn D Chandra Prakash P Umpierrez Guillermo E GE

Diabetes management (London, England) 20111101 6

Diabetic ketoacidosis (DKA) has been considered a key clinical feature of Type 1 diabetes mellitus; however, increasing evidence indicates that DKA is also a common feature of Type 2 diabetes (T2DM). Many cases of DKA develop under stressful conditions such as trauma or infection but an increasing number of cases without precipitating cause have been reported in children and adults with T2DM. Such patients present with severe hyperglycemia and ketosis as in Type 1 diabetes mellitus but can disco ...[more]

PMID: 22611441

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Project description:Background:A-? + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible ? cell dysfunction of unknown etiology. Plasma metabolomic analysis indicates that abnormal arginine metabolism may be involved. Objective:The objective of this study was to determine the relation between gut microbiome and arginine metabolism and the relation between arginine availability and ? cell function in KPD patients compared with control participants. Methods:Kinetics of arginine and related metabolites were measured with stable isotope tracers, and insulin secretory responses to arginine and glucose were determined under euglycemic and hyperglycemic conditions in 6 KPD patients and 6 age-, gender-, and body mass index-matched control participants. Glucose potentiation of arginine-induced insulin secretion was performed in a different set of 6 KPD and 3 control participants. Results:Arginine availability was higher in KPD patients during euglycemia [53.5 ± 4.3 (mean ± SEM) compared with 40.3 ± 2.4 ?mol · kg lean body mass (LBM)-1 · h-1, P = 0.03] but declined more in response to hyperglycemia (? 10.15 ± 2.6 compared with ? 3.20 ± 1.3 ?mol · kg LBM-1 · h-1, P = 0.041). During hyperglycemia, ornithine flux was not different between groups but after an arginine bolus, plasma ornithine AUC trended higher in KPD patients (3360 ± 294 compared with 2584 ± 259 min · ?mol · L-1, P = 0.08). In both euglycemia and hyperglycemia, the first-phase insulin responses to glucose stimulation were lower in KPD patients (euglycemic insulin AUC 282 ± 108 compared with 926 ± 257 min · ?U · mL-1, P = 0.02; hyperglycemic insulin AUC 358 ± 79 compared with 866 ± 292 min · ?U · mL-1, P = 0.05), but exogenous arginine restored first-phase insulin secretion in KPD patients to the level of control participants. Conclusion:Compared with control participants, KPD patients have increased arginine availability in the euglycemic state, indicating a higher requirement. This is compromised during hyperglycemia, with an inadequate supply of arginine to sustain metabolic functions such as insulin secretion. Exogenous arginine administration restores a normal insulin secretory response.

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Update on diagnosis, pathogenesis and management of ketosis-prone Type 2 diabetes mellitus.

Publications

Update on diagnosis, pathogenesis and management of ketosis-prone Type 2 diabetes mellitus.

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