Ketosis-prone Atypical Diabetes Research Articles

Atypical diabetes with spontaneous remission associated with systemic lupus erythematosus in an adolescent girl of African ancestry, a case report

BackgroundNew-onset diabetes in youth encompasses type 1 diabetes, type 2 diabetes, monogenic diabetes, and rarer subtypes like Type B insulin resistance syndrome and ketosis-prone atypical diabetes in African populations. Some cases defy classification, posing management challenges. Here, we present a case of a unique, reversible diabetes subtype.Case presentationWe describe an adolescent African girl recently diagnosed with systemic lupus erythematosus. At age 15, she presented with ketoacidosis, HbA1c of 108.7 mmol/mol (12.1%), and positive anti-insulin antibodies. Initially diagnosed with type 1 diabetes, insulin was prescribed. Due to the presence of obesity and signs of insulin resistance, we added metformin. Concurrently, she received treatment for lupus with hydroxychloroquine, mycophenolate mofetil, and prednisone. After discharge, she stopped insulin due to cultural beliefs. Five months later, her glycemia and HbA1c normalized (37 mmol/mol or 5.5%) without insulin, despite corticosteroid therapy and weight gain. Autoantibodies normalized, and lupus activity decreased. Genetic testing for monogenic diabetes was negative, and the type 1 genetic risk score was exceptionally low.ConclusionsWe present a complex, reversible diabetes subtype. Features suggest an autoimmune origin, possibly influenced by overlapping HLA risk haplotypes with lupus. Lupus treatment or immunomodulation may have impacted diabetes remission. Ancestry-tailored genetic risk scores are currently designed to improve diagnostic accuracy.

Acute phase ketosis-prone atypical diabetes is associated with a pro-inflammatory profile: a case-control study in a sub-Saharan African population.

It is unknown whether inflammation plays a role in metabolic dysfunction on ketosis-prone diabetes (KPD). We aimed to assess the inflammatory profile in sub-Saharan African patients with KPD during the acute ketotic phase as well as during non-ketotic hyperglycemic crises.We studied 72 patients with non-autoimmune diabetes: 23 with type 2 diabetes mellitus (T2D), and 49 with KPD, all admitted in hyperglycemic crisis (plasma glucose ≥250 mg/dl). The T2D and KPD groups were matched by sex, age, and Body Mass Index. KPD was sub-classified into new-onset ketotic phase (n = 34) or non-ketotic phase (n = 15). We measured TNF-α, MCP-1, MIP1-α, IL-8, MIP1-β, and VEGF in the serum of all participants.TNF-α and IL-8 were higher in participants with KPD compared to those with T2D (p = 0.02 TNF-α; p = 0.03 IL-8). TNF-α and IL-8 were also higher in the ketotic phase KPD group compared to the T2D group (p = 0.03 TNF-α; p < 0.001 IL-8) while MIP1-α was lower in people with ketotic phase KPD compared to their T2D counterparts (p = 0.03). MIP1-α was lower in the ketotic phase KPD group compared to the non-ketotic phase KPD group (p = 0.04). MCP-1 was lower in non-ketotic phase KPD compared to T2D (p = 0.04), and IL-8 was higher in non-ketotic phase KPD compared to T2D (p = 0.02).Participants with KPD had elevated pro-inflammatory cytokines compared to their T2D counterparts. Ketotic phase KPD is associated with a different pro-inflammatory profile compared to non-ketotic phase KPD, and the inflammatory profile appears to be comparable between non-ketotic phase KPD and T2D patients.

Use of capillary ketones monitoring in treatment of mild ketotic crisis in adults with ketosis prone atypical diabetes

Introduction : the utility of capillary ketones monitoring is known in the management of type 1 diabetes and severe diabetic ketoacidosis, but not in adults with ketosis-prone atypical diabetes (KPD) or mild ketosis. The objective was to assess the potential reduction in duration of intensive diabetic ketoacidosis treatment in adults with KPD when using capillary versus urinary ketones. Methods : from February to end March 2015, a total of 20 (9/20 newly diagnosed) patients, aged 46 ±12 years and classified as KPD presented at the National Obesity Center of the Yaounde Central Hospital with marked hyperglycemia and significant ketosis (ketonuria ≥ ++) requiring intensive insulin treatment. The mean plasma glucose and urinary ketones levelon admission was 22.8±5mmol/L and 2.9± 2.7 mmol/L respectively. No patient had severe acidosis (HCO3 Results : the time-to-normalization of ketonuria ranged between 2 and 14 hours, and that of ketonemia between 1 and 10 hours. The mean time-to-disappearance of ketonuria was 6.3 ± 3.6 hours with a median time of 5 hours, while the mean time-to-normalization of capillary β-hydroxybutyrate was 4.2± 2.7 hours with the median of 4 hours (p = 0.0002). The absolute difference in time-to-normalization of ketonuria versus ketonemia was 2[1-3] hours (median [interquartile difference]) and relative time reduction of treatment to 32.5±18.0%. Conclusion : the use of capillary ketones versus ketonuria would allow a significant reduction in duration of intensive insulin treatment by one third in adults with ketosis prone diabetes and therefore reduce admission rates and costs.

Association of HLA class II markers with autoantibody-negative ketosis-prone atypical diabetes compared to type 2 diabetes in a population of sub-Saharan African patients

AimWe investigated the association of HLA DRB1 and DQB1 alleles, haplotypes and genotypes with unprovoked antibody-negative ketosis-prone atypical diabetes (A− KPD) in comparison to type 2 diabetes (T2D). MethodsA− KPD and T2D sub-Saharan African patients aged 19–63 years were consecutively recruited. Patients positive for cytoplasmic islet cell, insulin, glutamic acid decarboxylase or islet antigen-2 autoantibodies were excluded. Odds ratios were obtained via logistic regression after considering alleles with a minimum frequency of 5% in the study population. Bonferroni correction was used in the case of multiple comparisons. ResultsAmong the 130 participants, 35 (27%) were women and 57 (44%) were A− KPD. DRB1 and DQB1 allele frequencies were similar for both A− KPD and T2D patients; they did not confer any substantial risk even after considering type 1 diabetes susceptibility and resistance alleles. We found no association between A− KPD and the derived DRB1*07-DQB1*02:02 (OR: 0.55 [95%CI: 0.17–1.85], P=0.336); DRB1*11-DQB1*03:01 (OR: 2.42 [95%CI: 0.79–7.42], P=0.123); DRB1*15-DQB1*06:02 (OR: 0.87 [95%CI: 0.39–1.95], P=0.731) and DRB1*03:01-DQB1*02:01 (OR: 1.48 [95%CI: 0.55–3.96], P=0.437) haplotypes. Overall, we did not find any evidence of susceptibility to ketosis associated with DRB1 and DQB1 genotypes (all P>0.05) in A− KPD compared to T2D. Similar results were obtained after adjusting the analysis for age and sex. ConclusionFactors other than DRB1 and DQB1 genotype could explain the propensity to ketosis in A− KPD. These results need to be confirmed in a larger population with the perspective of improving the classification and understanding of the pathophysiology of A− KPD.

Ketosis-Prone Atypical Diabetes: Glucagon Is There, Too

As stated by Zimmet et al. (1) in the initial chapter of a classical textbook on diabetes, the major requirement for orderly epidemiologic, genetic, and clinical research on diabetes and glucose intolerance, and indeed for their clinical management, is an appropriate classification. Furthermore, a hallmark in the process of understanding the etiology of a disease and studying its natural history is the ability to identify and differentiate its various forms and place them into a rational etio-pathologic framework. In 1984, Ahren and Corrigan (2) reported the existence of a subgroup of diabetic patients observed in Tanzania where the need for insulin replacement therapy fluctuates with time, waxes and wanes, and transient ketoacidosis develops. This subtype of diabetes is not unusual in African Americans and sub-Saharan Africans and currently recognized under the term of ketosis-prone atypical diabetes (KPD) (review in ref. 3). Classifying KPD in relation with the other more frequent forms of diabetes is not easy. At the onset, KPD often appears as type 1 diabetes with acute hyperglycemia and ketosis or ketoacidosis and the obvious need for insulin therapy but the signs of autoimmunity against islet β-cells are absent. In contrast, during near-normoglycemic remission, patients with KPD usually display multisite insulin resistance similar to that seen in type 2 diabetes (4,5). In 2008, Sobngwi et al. (6) hypothesized that KPD is a subtype of type 2 diabetes with acute onset at diagnosis as the result of an environmental factor such as a human herpes virus infection that would severely impair glucose-stimulated insulin secretion and favor ketogenesis. In this issue of Diabetes Care , Choukem et al. (7) present original data on the islet dysfunction present in KPD during remission. Previous studies have shown severe insulin secretory deficiency during the acute ketotic phase of KPD while during …

β- and α-Cell Dysfunctions in Africans With Ketosis-Prone Atypical Diabetes During Near-Normoglycemic Remission

OBJECTIVEKetosis-prone atypical diabetes (KPD) is a subtype of diabetes in which the pathophysiology is yet to be unraveled. The aim of this study was to characterize β- and α-cell functions in Africans with KPD during remission.RESEARCH DESIGN AND METHODSWe characterized β- and α-cell functions in Africans with KPD during remission. The cohort comprised 15 sub-Saharan Africans who had been insulin-free for a median of 6 months. Patients in remission were in good glycemic control (near-normoglycemic) and compared with 15 nondiabetic control subjects matched for age, sex, ethnicity, and BMI. Plasma insulin, C-peptide, and glucagon concentrations were measured in response to oral and intravenous glucose and to combined intravenous arginine and glucose. Early insulin secretion was measured during a 75-g oral glucose tolerance test. Insulin secretion rate and glucagon were assessed in response to intravenous glucose ramping.RESULTSEarly insulin secretion and maximal insulin secretion rate were lower in patients compared with control participants. In response to combined arginine and glucose stimulation, maximal insulin response was reduced. Glucagon suppression was also decreased in response to oral and intravenous glucose but not in response to arginine and insulin.CONCLUSIONSPatients with KPD in protracted near-normoglycemic remission have impaired insulin response to oral and intravenous glucose and to arginine, as well as impaired glucagon suppression. Our results suggest that β- and α-cell dysfunctions both contribute to the pathophysiology of KPD.

Characteristics of diabetic ketoacidosis in Chinese adults and adolescents – A teaching hospital-based analysis

ObjectiveTo investigate the diabetic ketoacidosis (DKA) episodes occurred in diabetic adults and adolescents. MethodsWe reviewed diabetic patients of admissions with DKA in West China Hospital in Chengdu from January 1, 2008 to December 31, 2008. Clinical and laboratory data including β-cell function and autoantibody status were collected respectively. Patients were classified as having type 1 or type 2 diabetes or atypical diabetes based on clinical diagnosis and treatment history. And groups were compared for differences in vital statistics and biochemical profiles at presentation. ResultsDetailed and accurate information was obtained in relation to 263 of patients accounted for the 287 admissions admitted for DKA, of whom 41 patients had type 1 diabetes (15.59%) meanwhile 178 patients were diagnosis as T2DM (67.68%), and 37 patients could not be “typed” were classified as atypical DM (14.07%). In addition, there were two gestational diabetes mellitus (GDM) and five patients with other specific types. Sixty admissions (22.81%) were newly diagnosed diabetes, of which 28 admissions (46.67%) were atypical diabetes. The most common contributing factor for DKA was infection (39.16%), followed by noncompliance with anti-diabetes treatment including omission of insulin (25.5%), unknown causes (25.86%) and other medical conditions (11.73%). Of note, these middle-age obese male patients with atypical diabetes often lapse into diabetic ketoacidosis without identifiable precipitating factors. ConclusionsDKA could occur not only in T1DM but also in patients with T2DM under infection or stress condition, furthermore without any identifiable precipitant. The prevalence of DKA and its clinical heterogeneity have significant implications for diagnosing and classification of diabetes. More attention and prevention strategies are needed in ketosis-prone atypical diabetes.

Le diabète sucré en Afrique : un enjeu de santé publique

W.H.O. predicts that there will be some 438 million diabetic patients in 2030, most of them living in developing countries. The IFD estimates that the prevalence of diabetes will rise by 98% in Africa during the next 20 years, with dramatic implications for public health and national budgets of the poorest countries. Type 2 diabetes is the most common form in Africa; type 1 is rarer than in western countries and tends to occur later. Two other forms seem specific to black Africans: ketosis-prone atypical diabetes, and tropical malnutrition-related diabetes. An increasing prevalence of obesity, diabetes and impaired glucose tolerance is observed in all parts of Africa. Several factors contribute to this situation, including aging, dietary transitions and lack of physical activity, all of which are related to rapid urbanization. In Africa, diabetes is associated with a high mortality rate, especially among insulin-dependent patients. Poor metabolic control can lead to severe ketosis and hypoglycemic accidents that carry a poor prognosis. Microvascular complications include retinopathy and nephropathy, and most patients cannot afford hemodialysis. Foot ulcers are frequent, due to trauma and neuropathies. Macrovascular complications are also increasing, with a high prevalence of hypertension. The poor prognosis of diabetes in Africa is related to late diagnosis, poor education, inadequate access to insulin, antidiabetic drugs and glycemia self-monitoring devices, absence of controlled diets, and difficult access to medical care in rural areas. Patient empowerment, knowledge and self-care must be improved. African governments must develop national prevention programs. Special attention must be paid to the prevention of obesity and diabetes. The urban environment, infrastructure, education, exercise and safe nutrition must be part of an overall policy designed to reduce the burden of chronic non transmissible diseases.