Ketosis-prone Type 2 Diabetes Research Articles

Enhancing outcome prediction by applying the 2019 WHO DM classification to adults with hyperglycemic crises: A single-center cohort in Thailand

Background and aimsHyperglycemic crisis is a metabolic catastrophe which can occur in any type of diabetes. In 2019, the World Health Organization (WHO) revised the classification of diabetes mellitus (DM) and established two new hybrid forms, latent autoimmune diabetes in adults (LADA) and ketosis-prone type 2 diabetes (T2D). This study aimed to determine clinical outcomes after a hyperglycemic crisis event in people with diabetes classified subtypes by 2019 WHO DM classification. MethodsA five-year (2015–2019) retrospective study of adult patients admitted with hyperglycemic crises was conducted. Types of diabetes were recategorized based on the 2019 WHO DM classification. Clinical characteristics, in-admission treatment and complications, long-term follow-up outcomes, and mortality were collected, analyzed, and compared. ResultsA total of 185 admissions occurred in 136 patients. The mean age was 50.6 ± 18.4 years (49.3 % men). The annual average incidence of hyperglycemic crises was 5.2 events/1000 persons. The proportion of type 1 diabetes, T2D, LADA, ketosis-prone T2D, and pancreatic DM were 15.4 %, 69.1 %, 2.2 %, 11 %, and 2.2 %, respectively. In-hospital mortality was 3.7 % while cumulative mortality totaled 19.1 %. During the 24-month follow-up, ketosis-prone T2D had the highest success of insulin discontinuation (HR 6.59; 95 % CI 6.69–319.4; p < 0.001), while T2D demonstrated the highest mortality compared to others (HR, 2.89; 95%CI 1.15–6.27; p = 0.02). ConclusionThe reclassification of diabetes based on 2019 WHO DM classification helped elucidate differences in long-term outcomes and mortality among DM types. The new classification, which separates ketosis-prone T2D from standard T2D, should be encouraged in clinical practice for precise and individualized management.

The clinical value of glycosylated hemoglobin level in newly diagnosed ketosis-prone type 2 diabetes.

To evaluate the clinical value of glycosylated hemoglobin (HbA1c) in newly diagnosed ketosis-prone type 2 diabetes (KPD). A 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. HbA1c, 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%. In 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.

High Atherogenic Risk in Ketosis-Prone Type 2 Diabetic Individuals with Ketosis Episodes: A Cross-Sectional Study.

Diabetes is an important contributor to the progression of atherosclerosis (AS). We aimed to investigate the correlation between ketosis episodes and lipid-related parameters in patients with new-onset ketosis-prone type 2 diabetes (KPT2D), further attempting to assess the impact of ketosis episodes on AS. A cross-sectional study of 147 subjects with new-onset diabetes was performed, including 65 KPT2D subjects (KPT2D group) and 82 non-ketotic type 2 diabetes (T2D) (T2D group) subjects. Anthropometric and biochemical parameters were measured in all subjects. Calculation of atherogenic index of plasma (AIP) by traditional lipid parameters. The AIP (P = 0.008) level and the percentage of AIP ≥ 0.24 (P = 0.026) in subjects with KPT2D were higher than in subjects with T2D. The apoA1 (P = 0.001) levels were significantly lower in patients with KPT2D than in patients with T2D. In the KPT2D group, plasma ketones were positively correlated with AIP (P = 0.023) and negatively correlated with apoA1 (P = 0.002). Univariate logistic regression suggested that plasma ketone (OR = 1.704, P = 0.040) was an important related factor for the AS in subjects with KPT2D. Multiple linear regression suggested plasma ketone was significantly positive with AIP (β = 0.437, P = 0.020). In multiple linear regression analysis suggests that apolipoprotein A1 (β = -0.335, P = 0.033) is strongly associated with ketotic episodes in newly diagnosed ketosis-prone type 2 diabetic patients. Ketosis episodes in patients with KPT2D were significantly and positively associated with elevated AIP levels and reduced apoA1 levels. Frequent ketosis episodes may accelerate the progression of AS.

Development and validation of a novel nomogram for prediction of ketosis-prone type 2 diabetes.

Ketosis-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. In 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). 4 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. In 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.

Association Between Serum Vitamin D Levels and Ketosis Episodes in Hospitalized Patients with Newly Diagnosed Ketosis-Prone Type 2 Diabetes.

This study aimed to investigate the relationship between 25-hydroxyvitamin D (25OHD) and the onset of ketosis in newly diagnosed patients with ketosis-prone type 2 diabetes (KPT2D). A total of 162 patients with non-autoimmune newly diagnosed diabetes mellitus were included in this cross-sectional study. Patients were classified into KPT2D (n = 71) or non-ketotic type 2 diabetes (NKT2D, n = 91). Anthropometric parameters, islet functions, biochemical parameters, and body composition were determined in both KPT2D and NKT2D groups. Correlation analysis was performed to determine the associations between 25OHD and plasma ketones. The risk factors associated with ketosis episodes in patients with new-onset KPT2D were evaluated using binary logistic regression analysis. Vitamin D deficiency was observed in both patients with KPT2D and NKT2D. Compared with the NKT2D group, serum 25OHD values were lower in the participants of the KPT2D group [14.20 (10.68, 19.52) vs 16.98 (13.54,2.96) ng/mL, P = 0.011]. Serum 25OHD was associated with plasma ketones (R = -0.387). Serum 25OHD is an independent protective factor for ketosis or ketoacidosis episodes in patients with new onset of KPT2D (P = 0.037, OR = 0.921). Vitamin D levels are associated with ketosis episodes in patients with KPT2D. Serum 25OHD is an independent protective factor for ketosis episodes in patients with KPT2D.

Clinical features, biochemistry, and HLA-DRB1 status in youth-onset type 1 diabetes in Mali.

Limited information is available regarding youth-onset diabetes in Mali. We investigated demographic, clinical, biochemical, and genetic features in new diabetes cases in children and adolescents. The study was conducted at Hôpital du Mali in Bamako. A total of 132 recently-diagnosed cases <21 years were enrolled. Demographic characteristics, clinical information, biochemical parameters (blood glucose, HbA1c, C-peptide, glutamic acid decarboxylase-65 (GAD-65) and islet antigen-2 (IA2) autoantibodies) were assessed. DNA was genotyped for HLA-DRB1 using high-resolution genotyping technology. A total of 130 cases were clinically diagnosed as type 1 diabetes (T1D), one with type 2 diabetes (T2D), and one with secondary diabetes. A total of 66 (50.8%) T1D cases were males and 64 (49.2%) females, with a mean age at diagnosis of 13.8 ± 4.4 years (range 0.8-20.7 years) peak onset of 15 years. 58 (44.6%) presented in diabetic ketoacidosis; with 28 (21.5%) IA2 positive, 76 (58.5%) GAD-65 positive, and 15 (11.5%) positive for both autoantibodies. HLA was also genotyped in 195 controls without diabetes. HLA-DRB1 genotyping of controls and 98 T1D cases revealed that DRB1*03:01, DRB1*04:05, and DRB1*09:01 alleles were predisposing for T1D (odds ratios [ORs]: 2.82, 14.76, and 3.48, p-values: 9.68E-5, 2.26E-10, and 8.36E-4, respectively), while DRB1*15:03 was protective (OR=0.27; p-value=1.73E-3). No significant differences were observed between T1D cases with and without GAD-65 and IA2 autoantibodies. Interestingly, mean C-peptide was 3.6 ± 2.7ng/ml (1.2 ± 0.9nmol/L) in T1D cases at diagnosis. C-peptide values were higher than expected in those diagnosed as T1D and autoantibody rates lower than in European populations. It is quite possible that some cases have an atypical form of T1D, ketosis-prone T2D, or youth-onset T2D. This study will help guide assessment and individual management of Malian diabetes cases, potentially enabling healthier outcomes.

IDF21-0243 Clinical characteristics and outcomes in adult patients with hyperglycemic crises based on WHO classification 2019

Background: Hyperglycemic crises composed of diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are metabolic catastrophes and could occur in any type of diabetes. Recently, the World Health Organization (WHO) revised the classification of diabetes and established the hybrid forms of diabetes mellitus, latent autoimmune diabetes in adults (LADA) and ketosis-prone type 2 diabetes (KPD). Although many clinical trials demonstrated the clinical characteristics and outcomes of hyperglycemic crises, few studies investigated the outcome of care in patients with hyperglycemic crises using the new WHO diabetic classification. Aim: To examine the clinical characteristics, outcomes of hyperglycemic crisis treatment, and post-discharged diabetic complications in the referral hospital in Bangkok, Thailand, of which diabetic subtypes were re-classified by the WHO diabetic classification 2019. Method: A retrospective study of patients with hyperglycemic crisis over 5 years (2015-2019) was done. Patients were re-classified into new DM subtypes according to the WHO diabetic classification 2019. The clinical characteristics, laboratory data, in-hospital outcomes, and long-term macrovascular and microvascular diabetic complications were collected and analyzed. Results: A total of 185 hyperglycemic crisis episodes in 138 patients with diabetes were included. DKA occurred more frequently than HHS and overlapped DKA and HHS (88.4%, 5.1%, and 6.1%, respectively). The mean age was 50.7±18.3 years old (51.4% female). The baseline A1c was 11.9±3.4%. Subjects were classified as follows: T1DM 15.9%, T2DM 68.8%, LADA 2.2%, KPD 10.9%, and pancreatic DM 2.2%. The most common precipitating causes of hyperglycemic crises were different among subtypes, i.e. medication noncompliance for T1DM, first diagnosis of DM for KPD, and infection for T2DM, LADA, and pancreatic DM (p=0.013). Forty-seven percent of all subjects developed hypokalemia during hyperglycemic crisis management, which was no different among DM subtypes. Five T2DM patients expired due to infection, the precipitating cause, which accounted for a mortality rate of 3.62% in our study. By the median follow-up of 25 months, insulin therapy had successfully been discontinued up to 71.4% in KPM and 24.4% in T2DM. The median time at insulin discontinuation was 7.2±4.3 months after hospital discharge. The last follow-up A1c was lowest in KPM, 6.5±1.4% (p=0.02). The new-onset macrovascular diabetic complications occurred in only T2DM and KPD, of which 55.5% occurred beyond 12 months. The microvascular complication occurred in all subtypes, of which 67.4% occurred within 12 months. Discussion: The KPD and LADA, the new hybrid subtypes of DM, accounted for 13% of hyperglycemic crisis patients in our center. Among diabetic subtypes, the acute outcomes of care were comparable but the long-term consequences were different. The KPD patients were more successful in discontinuing insulin therapy and had better glycemic control than other diabetic types. However, all DM subtypes were not different in developing macrovascular and microvascular complications. We encourage using the WHO diabetic classification 2019 to predict long-term clinical outcomes and insulin management in patients presenting with hyperglycemic crises.

A Cross-Sectional Study of Atherosclerosis in Newly Diagnosed Patients with Ketosis-Prone Type 2 Diabetes.

PurposeTo investigate the prevalence, clinical and metabolic characteristics of atherosclerosis (AS) in newly diagnosed patients with ketosis-prone type 2 diabetes (KPT2D) or non-ketotic type 2 diabetes (NKPT2D).Patients and MethodsAbout 1072 subjects with non-autoimmune new-onset diabetes were included in the cross-sectional study. Patients were classified as non-ketotic type 2 diabetes (NKPT2D, n = 662) or ketosis-prone type 2 diabetes (KPT2D, n = 410). Blood samples were collected to determine the levels of glucose, HbA1c, insulin and C-peptide. Routine liver and kidney function tests were also performed. AS was determined by vascular ultrasonography.ResultsThe levels of fasting blood glucose and HbA1c were significant higher in the KPT2D group when compared to the NKPT2D group (P<0.001). The levels of fasting C-peptide, 2 h C-peptide and HOMA-β were lower in the KPT2D group than those in NKPT2D group (P<0.001). However, no significant difference was observed for HOMA-IR between the two groups. The onset age of the patients with KPT2D was significantly lower compared to NKPT2D patients (38±13 vs 49±14, P<0.001). After adjusting age of the two groups, the KPT2D patients had a higher prevalence of AS compared to the NKPT2D patients (31.4% vs 21.1%, P=0.005). In both groups, age and gender were independent risk factors for AS, whereas estimated glomerular filtration rate (eGFR) was an independent risk factor in the NKPT2D patients and 2-h postprandial plasma glucose (2h-PPG) was an independent risk factor in the KPT2D patients.ConclusionAS was more prevalent in KPT2D patients compared to the NKPT2D cohort, which was independent of age and gender. These data suggest that KPT2D patients may have a higher risk of macrovascular complications compared to NKPT2D of the same age.

Clinical Significance of Insulin Peptide-specific Interferon-γ-related Immune Responses in Ketosis-prone Type 2 Diabetes.

Unprovoked A-β+ ketosis-prone type 2 diabetes (KPD) is characterized by the sudden onset of diabetic ketosis/ketoacidosis (DK/DKA) without precipitating factors, negative anti-islet autoantibodies ("A-"), and preservation of β-cell function ("β+") after recovery from DKA. Although this phenotype often appears with acute hyperglycemia and DK/DKA just like acute-onset type 1 diabetes (AT1D), the involvement of anti-islet immune responses remains unknown. We sought to clarify the immunological role of insulin-associated molecules in unprovoked A-β+ KPD. In this cross-sectional study, blood samples from 75 participants (42 with AT1D and 33 with KPD) were evaluated for interferon (IFN)-γ-secreting peripheral blood mononuclear cells (PBMCs) reactive to 4 insulin B-chain amino acid 9-23-related peptides (B:9-23rPep) using an enzyme-linked immunospot (ELISpot) assay. Overall, 36.4% (12/33) of KPD participants showed positive IFN-γ ELISpot assay results; the positivity rate in KPD was similar to that in AT1D (38.1%; 16/42) and statistically significantly higher than the previously reported rate in type 2 diabetes (8%; 2/25; P < .0167). Moreover, B:9-23rPep-specific IFN-γ-producing PBMC frequency was negatively correlated with age and ad lib serum C-peptide levels in all KPD participants and positively correlated with glycated hemoglobin A1c level in KPD participants with positive IFN-γ ELISpot results. These findings suggest the involvement of B:9-23rPep-specific IFN-γ-related immunoreactivity in the pathophysiology of some unprovoked A-β+ KPD. Moreover, increased immunoreactivity may reflect transiently decreased β-cell function and increased disease activity at the onset of DK/DKA, thereby playing a key role in DK/DKA development in this KPD phenotype.

Elevated Serum Triglycerides are Associated with Ketosis-Prone Type 2 Diabetes in Young Individuals.

PurposeKetosis-prone type 2 diabetes (KPT2D) is increasingly recognized in young adults. However, the role of blood lipids in KPT2D, especially serum triglycerides (TGs), is not yet clearly understood.Patients and MethodsWe retrospectively evaluated 409 young patients diagnosed with KPT2D or classical type 2 diabetes (T2D) attending an academic tertiary hospital. Clinical characteristics and laboratory findings were compared between KPT2D and T2D patients. ANOVA or a non-parametric test analyses were used to evaluate differences in clinical characteristics and laboratory findings. Multivariate regression analyses and stratified analyses were used to further investigate differences in serum TGs levels between KPT2D and T2D individuals.ResultsKPT2D is a subtype of T2D with traits of overweight or obesity. However, hyperglycemia and impaired β-cell functions were more severe in KPT2D patients. Serum TGs levels were significantly higher (P = 0.0003) in KPT2D individuals. Furthermore, the proportion of very high serum TGs levels was 6-fold higher (P < 0.0001) in KPT2D than in T2D patients. Elevated serum TGs were associated with young KPT2D patients.ConclusionLifestyle changes as well as lipid-lowering treatments might be effective in lowering the incidence of ketosis as well as stabilizing disease progression.

1796-P: A-ß+ Ketosis-Prone Diabetes (KPD) Patients Augment Insulin Response to Arginine but Not to Glucose after Sustained Hyperglycemia

We previously showed that patients with A-β+ KPD (“obese ketosis-prone type 2 diabetes”) have diminished intracellular arginine availability that may impair their ability to generate an adequate beta cell response in the face of hyperglycemia, and thus make them vulnerable to develop ketoacidosis (Mulukutla et al, J Nutr 2018). To investigate further their β cell responsiveness to exogenous arginine, we studied 9 recently diagnosed, stable, near-normoglycemic A-β+ KPD patients and 10 age-, sex- and BMI-matched nondiabetic controls with dynamic measures of insulin and C-peptide responses to glucose or arginine bolus under two conditions: in the euglycemic, fasting (basal) state and after a 5h hyperglycemic clamp. In the basal state, total and first phase insulin areas under the curve (AUC) in response to glucose were significantly greater in controls than KPD (total AUC 1756 ± 298 vs. 857 ± 126 min·µU/mL; P = 0.05); after hyperglycemia, AUC insulin response to glucose remained significantly greater in controls (total AUC 2470 ± 296 vs. 1512 ± 316 min·µU/mL; P = 0.04), and KPD patients mounted only a non-significant increase in total AUC insulin compared to the basal state (P = 0.12). In contrast, total and first phase AUC insulin in response to arginine in the basal state was similar in controls and KPD (total AUC 544 ± 85 vs. 337 ± 50 min·µU/mL; P = 0.75). After hyperglycemia, although AUC insulin response to arginine was greater in controls (total AUC 1854 ± 2227 vs. 1149 ± 207 min·µU/mL; P = 0.002), the KPD patients mounted a significant 70% increase in total AUC insulin compared to the basal state (P = 0.002). C-peptide responses mirrored those of insulin under all conditions. Thus, KPD patients exhibit a robust β cell response to arginine but not to glucose, both during fasting euglycemia and after sustained hyperglycemia. Exogenous arginine could augment insulin secretion during hyperglycemia and prevent the episodes of ketoacidosis that characterize A-β+ KPD. Disclosure J.W. Hsu: None. A.J. Cardenas: None. R. Gaba: None. M. Tosur: None. N. Ram: None. A.D. Gutierrez: Speaker’s Bureau; Self; AstraZeneca. K.M. Bohren: None. E.I. Caducoy: None. F. Jahoor: None. A. Balasubramanyam: None. Funding National Institutes of Health (R01DK101411)

Risperidone-induced type 2 diabetes presenting with diabetic ketoacidosis.

SummaryA 28-year-old male presented with 2 days of vomiting and abdominal pain, preceded by 2 weeks of thirst, polyuria and polydipsia. He had recently started risperidone for obsessive-compulsive disorder. He reported a high dietary sugar intake and had a strong family history of type 2 diabetes mellitus (T2DM). On admission, he was tachycardic, tachypnoeic and drowsy with a Glasgow Coma Scale (GCS) of 10/15. We noted axillary acanthosis nigricans and obesity (BMI 33.2 kg/m2). Dipstick urinalysis showed ketonuria and glycosuria. Blood results were consistent with diabetic ketoacidosis (DKA), with hyperosmolar state. We initiated our DKA protocol, with intravenous insulin, fluids and potassium, and we discontinued risperidone. His obesity, family history of T2DM, acanthosis nigricans and hyperosmolar state prompted consideration of T2DM presenting with ‘ketosis-prone diabetes’ (KPD) rather than T1DM. Antibody markers of beta-cell autoimmunity were subsequently negative. Four weeks later, he had modified his diet and lost weight, and his metabolic parameters had normalised. We reduced his total daily insulin dose from 35 to 18 units and introduced metformin. We stopped insulin completely by week 7. At 6 months, his glucometer readings and glycated haemoglobin (HbA1c) level had normalised.Learning points:Risperidone-induced diabetic ketoacidosis (DKA) is not synonymous with type 1 diabetes, even in young white patients and may be a manifestation of ‘ketosis-prone’ type 2 diabetes (KPD).KPD is often only confirmed after the initial presentation, when islet autoimmunity and cautious phasing out of insulin therapy have been assessed, and emergency DKA management remains the same.As in other cases of KPD, a family history of T2DM and presence of cutaneous markers of insulin resistance were important clinical features suggestive of an alternative aetiology for DKA.

Characteristics of subjects with diabetes mellitus diagnosed before 35 years of age presenting to a tertiary diabetes clinic in Durban, South Africa, from 2003 to 2016

Background: Most patients diagnosed with diabetes mellitus < 35 years will have type 1 diabetes (T1D). The increase in youth-onset type 2 diabetes (T2D) parallels the obesity epidemic and in African subjects ketosis-prone type 2 diabetes (KPD) may occur in this age group.Objectives, setting and subjects: To evaluate the clinical, biochemical and immunologic characteristics of patients diagnosed with diabetes < 35 years presenting to a tertiary diabetes clinic in Durban, South Africa over 13 years.Design: A retrospective chart review of patients < 35 years diagnosed with diabetes was conducted. Data included clinical and laboratory variables, complications and follow-up status.Results: The study included 517 patients of whom 445 (86.1%) were diagnosed with T1D, 27 (5.2%) with T2D, 27 with KPD (5.2%) and 18 (3.5%) with other forms of diabetes. Mean age of the total group was 28 ± 10 years. Subjects with T1D were younger at diagnosis with a lower BMI than both T2D and KPD. HbA1c was higher in subjects with T1D. Overall mortality was low (3.5%) and follow-up was poor in all groups.Conclusion: The majority of young people with diabetes in KwaZulu-Natal, South Africa, have T1D, with small numbers of other types. Glucose control is poor with a high loss to follow-up.

Diabetic ketoacidosis: a challenging diabetes phenotype.

SummaryWe describe three patients presenting with diabetic ketoacidosis secondary to ketosis prone type 2, rather than type 1 diabetes. All patients were treated according to a standard DKA protocol, but were subsequently able to come off insulin therapy while maintaining good glycaemic control. Ketosis-prone type 2 diabetes (KPD) presenting with DKA has not been described previously in Irish patients. The absence of islet autoimmunity and evidence of endogenous beta cell function after resolution of DKA are well-established markers of KPD, but are not readily available in the acute setting. Although not emphasised in any current guidelines, we have found that a strong family history of type 2 diabetes and the presence of cutaneous markers of insulin resistance are strongly suggestive of KPD. These could be emphasised in future clinical practice guidelines.Learning points:Even in white patients, DKA is not synonymous with type 1 diabetes and autoimmune beta cell failure. KPD needs to be considered in all patients presenting with DKA, even though it will not influence their initial treatment.Aside from markers of endogenous beta cell function and islet autoimmunity, which in any case are unlikely to be immediately available to clinicians, consideration of family history of type 2 diabetes and cutaneous markers of insulin resistance might help to identify those with KPD and are more readily apparent in the acute setting, though not emphasised in guidelines.Consideration of KPD should never alter the management of the acute severe metabolic derangement of DKA, and phasing out of insulin therapy requires frequent attendance and meticulous and cautious surveillance by a team of experienced diabetes care providers.

Relationship between HHV8 infection markers and insulin sensitivity in ketosis-prone diabetes

Background and objectivesPeripheral tissue resistance to insulin action is a characteristic of type 2 diabetes mellitus (T2DM). It has also been reported that some chronic viral infections can contribute to insulin resistance. Human herpesvirus (HHV)-8 infection has been detected in T2DM patients in previous studies. Our study investigated whether the presence of the virus is associated with insulin resistance in patients with ketosis-prone type 2 diabetes (KPD), as reported with other viruses. Research design and methodsA total of 11 insulin-free KPD patients positive (+) and seven patients who were negative (−) for HHV-8 infection were recruited; the latter had KPD that was well controlled (HbA1c=6.2±0.7%). A two-step euglycaemic–hyperinsulinaemic clamp test coupled with deuterated [6,6-2H2]glucose was used to assess insulin sensitivity, non-esterified fatty acid (NEFA) suppression and endogenous glucose production. ResultsIn KPD patients, whether HHV-8+ or HHV-8−, there were no differences in NEFA release, endogenous glucose production or insulin sensitivity (M value). ConclusionAsymptomatic HHV-8 infection does not appear to be associated with decreased insulin sensitivity in diabetic patients. These results should now be confirmed in a larger sample population.

The Clinical And Metabolic Characteristics Of Young-Onset Ketosis-Prone Type 2 Diabetes In China

To investigate the prevalence and clinical characteristics of ketosis-prone type 2 diabetes (KPD) in Chinese patients with young-onset diabetes. A total of 238 young diabetic patients were recruited from our inpatient department from January 1, 2012, to December 28, 2014. KPD was defined as diabetes without precipitating illness and with the presence of ketosis or diabetic ketoacidosis in the absence of autoantibodies at the time of diagnosis. We reviewed the clinical characteristics and disease progression of this group of patients. Eighteen patients fulfilled the criteria for KPD, and the prevalence of patients with KPD was 7.6%. The mean (SD) age of the KPD group at the time of diagnosis of diabetes was 27.6 (4.85) years, and these patients were predominantly male (male to female ratio, 8:1) and had a high proportion of obesity and new-onset diabetes and a strong family history of diabetes. β-Cell function in the KPD group was intermediate between type 1 and type 2 diabetes. Patients with KPD had the highest levels of glycated hemoglobin, triglycerides, total cholesterol, and free fatty acids and the lowest levels of high-density lipoprotein. After 3 to 12 months of follow-up, 17 of 18 patients with KPD (94.4%) were able to discontinue insulin therapy, and 11 patients (61.1%) were managed with diet or exercise alone. KPD patients accounted for 7.6% of the diabetic patients requiring admission to a large urban hospital in China, with an age of onset of diabetes of ≤35 years. These patients are more likely to be male, have abnormal lipid metabolism, and have more reversible β-cell dysfunction.

Hyperglycaemia per se does not affect erythrocyte glucose-6-phosphate dehydrogenase activity in ketosis-prone diabetes

AimPreviously, we described patients with ketosis-prone type 2 diabetes (KPD) and glucose-6-phosphate dehydrogenase (G6PD) deficiency, but no mutation of the G6PD gene. Our present study used two complementary approaches to test whether hyperglycaemia might inhibit G6PD activity: (1) effect of acute hyperglycaemia induced by glucose ramping; and (2) effect of chronic hyperglycaemia using correlation between G6PD activity and HbA1c levels. MethodsIn the first substudy, 16 KPD patients were compared with 11 healthy, non-diabetic control subjects of the same geographical background. Erythrocyte G6PD activity and plasma glucose were assessed at baseline and every 40min during intravenous glucose ramping that allowed maintaining hyperglycaemia for more than 3h. In the second substudy, erythrocyte G6PD activity and HbA1c levels were evaluated in 108 consecutive African patients with either type 2 diabetes or KPD, and a potential correlation sought between the two variables. ResultsThe maximum plasma glucose level after 200min of glucose perfusion was 20.9±3.7mmol/L for patients and 10.7±2.3mmol/L for controls. There was no difference between baseline and repeated G6PD activity levels during acute hyperglycaemia in either KPD patients (P=0.94) or controls (P=0.57), nor was there any significant correlation between residual erythrocyte G6PD activity and HbA1c levels (r=−0.085, P=0.38). ConclusionNeither acute nor chronic hyperglycaemia affects erythrocyte G6PD activity. Thus, hyperglycaemia alone does not explain cases of G6PD deficiency in the absence of gene mutation as described earlier.

Diabetes Mellitus tipo 2 con tendencia a la cetosis: Caso clínico

Ketosis prone type 2 diabetes (KPD) is presently a well-defined clinical entity, characterized by a debut with severe hyperglycemia and ketoacidosis similar to the presenting form of Type 1 diabetes mellitus (DM1). However, it appears in subjects with Type 2 diabetes mellitus (DM2) phenotype. This situation is caused by an acute, reversible dysfunction of the beta cell in individuals with insulin resistance. Once the acute stage subsides, patients behave as having a DM2 and do not require insulin treatment. They should be kept on a diet and oral hypoglycemic drugs due to their susceptibility to have recurrent acute ketotic decompensations.

Diabetes mellitus and glucose-6-phosphate dehydrogenase deficiency: From one crisis to another

Aim Epidemiological data suggest that glucose-6-phosphate dehydrogenase (G6PD) deficiency may be a risk factor for diabetes. Also, the occurrence of haemolysis in the context of diabetes crises has been reported in patients with G6PD deficiency. A unifying hypothesis could explain these associations. Methods We report two patients in whom haemolytic crises occurred soon after acute diabetes decompensation, and revealed G6PD deficiency. We have reviewed the mechanisms that may link the two diseases. Results One patient was admitted for decompensated ketosis-prone type-2 diabetes (KPT2D), but no acidosis, and was treated with insulin, then metformin and glibenclamide. The second patient had type-1 diabetes and ketoacidosis treated with insulin. Haemolytic crises were recognized 8 and 4 days after admission, respectively, and G6PD deficiency was confirmed in both patients. These patients and the other published cases share, as a unique characteristic, the occurrence of haemolysis after diabetes decompensation, whatever the treatment or associated conditions. Experimental data show that hyperglycaemia can reduce expression of the G6PD gene and activity of the enzyme. Conversely, G6PD deficiency can promote oxidative stress and impairment of insulin secretion by beta cells. Conclusion In patients at risk of G6PD deficiency, the possibility of haemolysis should be explored in case of diabetes crisis. In African patients with KPT2D diabetes, potentially oxidative hypoglycaemic agents should be avoided in the remission phase of the disease. G6PD deficiency and diabetes can aggravate each other, and diabetes could be aetiologically associated with G6PD deficiency.

Effects of Intravenous Glucose Load on Insulin Secretion in Patients With Ketosis-Prone Diabetes During Near-Normoglycemia Remission

OBJECTIVEMost patients with ketosis-prone type 2 diabetes (KPD) discontinue insulin therapy and remain in near-normoglycemic remission. The aim of this study was to determine the effect of glucotoxicity on β-cell function during remission in obese patients with KPD.RESEARCH DESIGN AND METHODSAge- and BMI-matched obese African Americans with a history of KPD (n = 8), severe hyperglycemia but without ketosis (ketosis-resistant type 2 diabetes, n = 7), and obese control subjects (n = 13) underwent intravenous infusion of 10% dextrose at a rate of 200 mg per m2/min for 20 h. β-Cell function was assessed by changes in insulin and C-peptide concentrations during dextrose infusion and by changes in acute insulin response (AIR) and first-phase insulin release (FPIR) to arginine stimulation before and after dextrose infusion.RESULTSThe mean ± SD time to discontinue insulin therapy was 7.1 ± 1.7 weeks in KPD and 9.6 ± 2.3 weeks in ketosis-resistant type 2 diabetes (NS). During a 20-h dextrose infusion, changes in insulin, C-peptide, and the C-peptide–to–glucose ratio were similar among diabetic and control groups. During dextrose infusion, subjects with ketosis-resistant type 2 diabetes had greater areas under the curve for blood glucose than subjects with KPD and control subjects (P < 0.05). The AIR and FPIR to arginine stimulation as well as glucose potentiation to arginine assessed before and after dextrose infusion were not different among the study groups.CONCLUSIONSNear-normoglycemia remission in obese African American patients with KPD and ketosis-resistant type 2 diabetes is associated with a remarkable recovery in basal and stimulated insulin secretion. At near-normoglycemia remission, patients with KPD displayed a pattern of insulin secretion similar to that of patients with ketosis-resistant type 2 diabetes and obese nondiabetic subjects.