HLA Class II Alleles Specify Phenotypes of Ketosis-Prone Diabetes

Nalini, Ramaswami; Gaur, Lakshmi K.; Maldonado, Mario; Hampe, Christiane S.; Rodríguez, Luisa M.; Garza, Gilberto; Lernmark, Åke; Balasubramanyam, Ashok

doi:10.2337/dc07-1971

Cited by 22 publications

(23 citation statements)

References 40 publications

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“…Hence, absence of GAD65 or IA-2 Abs, even in patients with long-standing diabetes, is probably quite reliable in classifying them as AϪ. To limit further the possibility of misclassifying Aϩ␤Ϫ KPD patients as AϪ␤Ϫ, we have performed extensive HLA typing (1,27) and have found that the frequencies of major class II alleles associated with susceptibility to autoimmune type 1 diabetes are not significantly higher in AϪ␤Ϫ KPD patients than in ethnicmatched population controls, whereas they are significantly higher in Aϩ␤Ϫ KPD patients.…”

Section: B Aϫ␤ϫmentioning

confidence: 99%

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Syndromes of Ketosis-Prone Diabetes Mellitus

et al. 2008

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Ketosis-prone diabetes (KPD) is a widespread, emerging, heterogeneous syndrome characterized by patients who present with diabetic ketoacidosis or unprovoked ketosis but do not necessarily have the typical phenotype of autoimmune type 1 diabetes. Multiple, severe forms of beta-cell dysfunction appear to underlie the pathophysiology of KPD. Until recently, the syndrome has lacked an accurate, clinically relevant and etiologically useful classification scheme. We have utilized a large, longitudinally followed, heterogeneous, multiethnic cohort of KPD patients to identify four clinically and pathophysiologically distinct subgroups that are separable by the presence or absence of beta-cell autoimmunity and the presence or absence of beta-cell functional reserve. The resulting "Abeta" classification system of KPD has proven to be highly accurate and predictive of such clinically important outcomes as glycemic control and insulin dependence, as well as an aid to biochemical and molecular investigations into novel causes of beta-cell dysfunction. In this review, we describe the current state of knowledge in regard to the natural history, pathophysiology, and treatment of the subgroups of KPD, with an emphasis on recent advances in understanding their immunological and genetic bases.

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Section: B Aϫ␤ϫmentioning

confidence: 99%

“…The longitudinal Houston cohort comprises over 500 multiethnic patients (44% African-American, 40% Hispanic, 15% Caucasian, 1% Asian), including 185 patients who have been followed for a mean of 5.5 yr (27). A comprehensive database compiles information on the natural history of all four groups of KPD.…”

Section: A Houstonmentioning

confidence: 99%

Syndromes of Ketosis-Prone Diabetes Mellitus

et al. 2008

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“…Several reports from sub-Saharan Africa [18-21] and the U.S. African-American population [22-25] have described atypical ketosis-prone "African" diabetes. While this clinical entity remains poorly defined, the common characteristics appear to include acute onset, often with ketoacidosis, in often obese adolescents or young adults with no islet autoantibodies and HLA genotypes inconsistent with T1aD.…”

Section: Ketosis-prone T1bdmentioning

confidence: 99%

Challenges in Diagnosing Type 1 Diabetes in Different Populations

Rewers

2012

Diabetes Metab J

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Diabetes affects today an estimated 366 million people world-wide, including 20 million to 40 million of patients with type 1 diabetes (T1D). While T1D accounts for 5% to 20% of those with diabetes, it is associated with higher morbidity, mortality and health care cost than the more prevalent type 2 diabetes. Patients with T1D require exogenous insulin for survival and should be identified as soon as possible after diagnosis to avoid high morbidity due to a delay in insulin treatment. It is also important to present to the patient correct prognosis that differs by the type of diabetes. From the research point of view, correct classification should help to identify the etiologies and to develop specific prevention for T1D. This review summarizes evidence that may be helpful in diagnosing T1D in various ethnic groups. Challenges in interpretation of results commonly used to determine the type of diabetes are highlighted.

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“…Initial insulin therapy for type 2 diabetes patients is unusual unless the patient is markedly hyperglycemic and/or symptomatic [3,9,10,12]. Patients with ketosis prone diabetes (KPD) are in the category of those who present with ketocidosis but after initial insulin therapy can stop insulin and revert to tablet treatment [19]. The ORIGIN trial failed to find a role for low-dose insulin therapy early in the course of type 2 diabetes, in that insulin treatment did not reduce cardiovascular risk [20].…”

Section: Discussionmentioning

confidence: 99%

Personalizing guidelines for diabetes management: twilight or dawn of the expert?

Paschou

Leslie

2013

BMC Med

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BackgroundThis opinion article on the management of type 2 diabetes considers the old and new format of guidelines and critical changes in the character of such guidelines. We highlight limitations of the guidelines and make recommendations for how treatment can be more personalised.DiscussionPublished guidelines for the management of adult-onset non-insulin requiring diabetes have adopted a formulaic approach to patient management that can be overseen centrally and delivered by personnel with limited training. Recently, guidelines have taken a patient-centered, multiple risk-factor approach. Importantly, local funding issues are considered, but drive the final action and not the decision-making process. The nature of the disease can be determined by laboratory tests, including screening for diabetes-associated autoantibodies. The strategy remains step-up, with intensification of drug or insulin dose. As with past guidelines, there is an assumption that in each patient with type 2 diabetes, metformin is used initially, but targets and therapies then veer in different directions to create a matrix of options based on the features and responses of each individual. Factors to consider include: (A)ge, (B)ody weight, (C)omplications and co-morbidities, Diabetes (D)uration and (E)xpense, but also patient preference and patient response.SummaryGuidelines for the management of type 2 diabetes have important limitations and a patient-centered, multiple target, multiple therapy approach is proposed.

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HLA Class II Alleles Specify Phenotypes of Ketosis-Prone Diabetes

Cited by 22 publications

References 40 publications

Syndromes of Ketosis-Prone Diabetes Mellitus

Syndromes of Ketosis-Prone Diabetes Mellitus

Challenges in Diagnosing Type 1 Diabetes in Different Populations

Personalizing guidelines for diabetes management: twilight or dawn of the expert?

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