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Bodyweight threshold for sudden onset of ketosis might exist in ketosis-prone type 2 diabetes patients.

ABSTRACT: Ketosis-prone type 2 diabetes is recognized as atypical diabetes. These patients are often male, characterized by obesity, sudden onset of ketosis and a transient decrease in insulin secretion capacity that can be recovered with temporal insulin therapy. Here, we report a male patient with ketosis-prone type 2 diabetes who was followed up for 8 years. During the follow-up period, his bodyweight fluctuated and he experienced four episodes of critical ketosis recurrence in association with bodyweight gain. He discontinued insulin therapy after each ketosis episode within the first 4 years, but thereafter, he had to continue insulin therapy because of decreased insulin secretion capacity. Interestingly, his peak bodyweight just before the repeated ketosis episode gradually decreased, and the insulin secretion capacity after the recovery from repeated ketosis decreased in parallel with his peak bodyweight. This long-term clinical course might be a clue to understand the pathophysiology of ketosis-prone type 2 diabetes.

SUBMITTER: Satomura A

PROVIDER: S-EPMC7078091 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Bodyweight threshold for sudden onset of ketosis might exist in ketosis-prone type 2 diabetes patients.

Satomura Atsushi A Oikawa Yoichi Y Haisa Akifumi A Inoue Ikuo I Noda Mitsuhiko M Shimada Akira A

Journal of diabetes investigation 20190814 2

Ketosis-prone type 2 diabetes is recognized as atypical diabetes. These patients are often male, characterized by obesity, sudden onset of ketosis and a transient decrease in insulin secretion capacity that can be recovered with temporal insulin therapy. Here, we report a male patient with ketosis-prone type 2 diabetes who was followed up for 8 years. During the follow-up period, his bodyweight fluctuated and he experienced four episodes of critical ketosis recurrence in association with bodywei ...[more]

PMID: 31339666

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Project description:ObjectiveTo evaluate the clinical value of glycosylated hemoglobin (HbA1c) in newly diagnosed ketosis-prone type 2 diabetes (KPD).MethodsA total of 330 patients with newly diagnosed type 2 diabetes (T2DM) hospitalized in our department with an average age of 48.72 ± 13.07 years old were selected and divided into T2DM group (193 cases) and KPD group (137 cases) according to whether they were combined with ketosis. According to the quartile level of HbA1c, they were divided into group A (HbA1c < 8.90%, 84 cases), group B (8.90%≤HbA1c < 10.70%, 86 cases), group C (10.70%≤HbA1c ≤ 12.40%, 85 cases) and group D (HbA1c > 12.40%, 75 cases). The general clinical features, laboratory indicators and islet function of each group were compared. Spearman correlation analysis was used to explore the correlation between HbA1c and β- Hydroxybutyric acid (β- HB) and islet function. ROC curve was used to analyze the sensitivity and specificity of HbA1c in diagnosing KPD, and the optimal tangent point was obtained.ResultsHbA1c, β-HB, FFA, RBG, insulin dosage, GSP, OGTT (0, 0.5, 1, 2, 3h) in KPD group were significantly higher than those in T2DM group (P< 0.001). HDL-C, IRT (0, 0.5, 1, 2, 3h), HOMA-β, HOMA-IR, HOMA-IS, ΔC30/ΔG30, AUC insulin were significantly lower than those in T2DM group (P< 0.001). With the increase of HbA1c level, the incidence of ketosis, β-HB, FFA and insulin dosage increased, while IRT (0, 0.5, 1, 2, 3h), ΔC30/ΔG30, AUC insulin, HOMA-β and HOMA-IS decreased accordingly (P< 0.001). In all newly diagnosed T2DM patients, Spearman correlation analysis showed that HbA1c was positively correlated with β-HB (r=0.539, P < 0.001), and was negatively correlated with HOMA-β (r=-0.564, P < 0.001), HOMA-IS (r=-0.517, P < 0.01, P < 0.001), HOMA-IR (r=-0.177, P < 0.001), ΔC30/ΔG30 (r=-0.427, P < 0.01) and AUC insulin (r=-0.581, P < 0.001). In ROC curve analysis, the optimal threshold for the diagnosis of KPD was 10.15%, Youden index was 0.616, area under the curve (AUC) was 0.882, sensitivity = 92.70%, specificity = 70.50%.ConclusionIn newly diagnosed T2DM patients, if HbA1c > 10.15%, it is more likely to develop KPD. Monitoring HbA1c level is conducive to timely detection of high-risk individuals with KPD and taking appropriate measures to prevent the occurrence and development of the disease.

Project description:BackgroundKetosis-prone type 2 diabetes (KPD), as a unique emerging clinical entity, often has no clear inducement or obvious clinical symptoms at the onset of the disease. Failure to determine ketosis in time may lead to more serious consequences and even death. Therefore, our study aimed to develop and validate a novel nomogram to predict KPD.MethodsIn this retrospective study, clinical data of a total of 398 newly diagnosed type 2 diabetes in our hospital who met our research standards with an average age of 48.75 ± 13.86 years years old from January 2019 to December 2022 were collected. According to the occurrence of ketosis, there were divided into T2DM groups(228 cases)with an average age of 52.19 ± 12.97 years, of whom 69.74% were male and KPD groups (170cases)with an average age of 44.13 ± 13.72 years, of whom males account for 80.59%. Univariate and multivariate logistic regression analysis was performed to identify the independent influencing factors of KPD and then a novel prediction nomogram model was established based on these independent predictors visually by using R4.3. Verification and evaluation of predictive model performance comprised receiver-operating characteristic (ROC) curve, corrected calibration curve, and clinical decision curve (DCA).Results4 primary independent predict factors of KPD were identified by univariate and multivariate logistic regression analysis and entered into the nomogram including age, family history, HbA1c and FFA. The model incorporating these 4 predict factors displayed good discrimination to predict KPD with the area under the ROC curve (AUC) of 0.945. The corrected calibration curve of the nomogram showed good fitting ability with an average absolute error =0.006 < 0.05, indicating a good accuracy. The decision analysis curve (DCA) demonstrated that when the risk threshold was between 5% and 99%, the nomogram model was more practical and accurate.ConclusionIn our novel prediction nomogram model, we found that age, family history, HbA1c and FFA were the independent predict factors of KPD. The proposed nomogram built by these 4 predictors was well developed and exhibited powerful predictive performance for KPD with high discrimination, good accuracy, and potential clinical applicability, which may be a useful tool for early screening and identification of high-risk population of KPD and therefore help clinicians in making customized treatment strategy.

Project description:Background:A-β + ketosis-prone diabetes (KPD) is a subset of type 2 diabetes in which patients have severe but reversible β 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 β 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 μmol · kg lean body mass (LBM)-1 · h-1, P = 0.03] but declined more in response to hyperglycemia (Δ 10.15 ± 2.6 compared with Δ 3.20 ± 1.3 μmol · 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 · μmol · 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 · μU · mL-1, P = 0.02; hyperglycemic insulin AUC 358 ± 79 compared with 866 ± 292 min · μU · 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.

Project description:BackgroundRecent literature suggests a bi-directional relationship between COVID-19 infection and diabetes mellitus, with an increasing number of previously normoglycemic adults with COVID-19 being admitted with new-onset diabetic ketoacidosis (DKA). However, the possibility of COVID-19 being a potential trigger for A-β + ketosis-prone diabetes (KPD) in these patients needs elucidation. Our study aimed at analyzing such a cohort of patients and determining their natural course of β-cell recovery on serial follow-up.MethodsAfter initial screening, n = 42 previously non-diabetic patients with new-onset DKA and RT-PCR positive COVID-19, were included in our ten-month follow-up study. Of these, n = 22 were negative (suspected A-β + KPD) and n = 20 were positive (Type 1A DM) for autoantibodies (GAD/IA-2/ZnT8). Subsequently, n = 19 suspected KPD and n = 18 Type 1A DM patients were followed-up over ten months with serial assessments of clinical, biochemical and β-cell secretion. Amongst the former, n = 15 (79%) patients achieved insulin independence, while n = 4 (21%) continued to require insulin at ten-months follow-up.ResultsOn comparison, the suspected KPD patients showed significantly greater BMI, age, Hba1c, IL-6 and worse DKA parameters at presentation. Serial C-peptide estimations demonstrated significant β-cell recovery in KPD group, with complete recovery seen in the 15 patients who became insulin independent on follow-up. Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were associated with poorer recovery of β-cell secretion at ten-month follow-up amongst the KPD patients, CONCLUSIONS: This is the first prospective study to demonstrate progressive recovery of β-cell secretion in new-onset A-β + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM. Given their significant potential for β-cell recovery, meticulous follow-up involving C-peptide estimations can help guide treatment and avoid injudicious use of insulin.

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Bodyweight threshold for sudden onset of ketosis might exist in ketosis-prone type 2 diabetes patients.

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Bodyweight threshold for sudden onset of ketosis might exist in ketosis-prone type 2 diabetes patients.

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