Clinical Characteristics and Diagnostic Criteria of Maturity-Onset Diabetes Of The Young (MODY) due to Molecular Anomalies of the HNF1A Gene

Context: The diagnosis of maturity-onset diabetes of the young type 3 (MODY3), associated with HNF1A molecular abnormalities, is often missed.Objective: The objective of the study was to describe the phenotypes of a large series of MODY3 patients and to reassess parameters that may improve its diagnosis. Design, Setting, and Patients: This retrospective multicenter study included 487 unrelated patients referred because of suspicion of MODY3. Genetic analysis identified 196 MODY3 and 283 non-MODY3 cases. Criteria associated with MODY3 were assessed by multivariate analysis. The capacity of the model to predict MODY3 diagnosis was assessed by the area under the receiver-operating characteristic curve and was further validated in an independent sample of 851 patients (165 MODY3 and 686 non-MODY3). Results: In the MODY3 patients, diabetes was revealed by clinical symptoms in 25% of the cases and was diagnosed by screening in the others. Age at diagnosis of diabetes was more than 25 yr in 40% of the MODY3 patients. There was considerable variability and overlap of all assessed parameters in MODY3 and non-MODY3 patients. The best predictive model was based on criteria available at diagnosis of diabetes, including age, body mass index, number of affected generations, presence of diabetes symptoms, and geographical origin. The area under the curve of the receiver-operating characteristic analysis was 0.81. When sensitivity was set to 90%, specificity was 49%. Conclusions: Differential diagnosis between MODY3 and early-onset type 2 diabetes remains difficult. Whether the proposed model will improve the pick-up rate of MODY3 diagnosis needs to be confirmed in independent populations

Cardiac adipose tissue volume assessed by computed tomography is a specific and independent predictor of early mortality and critical illness in COVID-19 in type 2-diabetic patients

Abstract Background Patients with type 2-diabetes mellitus (T2D), are characterized by visceral and ectopic adipose tissue expansion, leading to systemic chronic low-grade inflammation. As visceral adiposity is associated with severe COVID-19 irrespective of obesity, we aimed to evaluate and compare the predictive value for early intensive care or death of three fat depots (cardiac, visceral and subcutaneous) using computed tomography (CT) at admission for COVID-19 in consecutive patients with and without T2D. Methods Two hundred and two patients admitted for COVID-19 were retrospectively included between February and June 2020 and distributed in two groups: T2D or non-diabetic controls. Chest CT with cardiac (CATi), visceral (VATi) and subcutaneous adipose tissue (SATi) volume measurements were performed at admission. The primary endpoint was a composite outcome criteria including death or ICU admission at day 21 after admission. Threshold values of adipose tissue components predicting adverse outcome were determined. Results One hundred and eight controls [median age: 76(IQR:59–83), 61% male, median BMI: 24(22–27)] and ninety-four T2D patients [median age: 70(IQR:61–77), 70% male, median BMI: 27(24–31)], were enrolled in this study. At day 21 after admission, 42 patients (21%) had died from COVID-19, 48 (24%) required intensive care and 112 (55%) were admitted to a conventional care unit (CMU). In T2D, CATi was associated with early death or ICU independently from age, sex, BMI, dyslipidemia, CRP and coronary calcium (CAC). (p = 0.005). Concerning T2D patients, the cut-point for CATi was  &gt; 100 mL/m2 with a sensitivity of 0.83 and a specificity of 0.50 (AUC = 0.67, p = 0.004) and an OR of 4.71 for early ICU admission or mortality (p = 0.002) in the fully adjusted model. Other adipose tissues SATi or VATi were not significantly associated with early adverse outcomes. In control patients, age and male sex (OR = 1.03, p = 0.04) were the only predictors of ICU or death. Conclusions Cardiac adipose tissue volume measured in CT at admission was independently predictive of early intensive care or death in T2D patients with COVID-19 but not in non-diabetics. Such automated CT measurement could be used in routine in diabetic patients presenting with moderate to severe COVID-19 illness to optimize individual management and prevent critical evolution. </jats:sec

Cost-effectiveness of 82-Rubidium PET myocardial perfusion imaging for the diagnosis of myocardial ischemia depending on the prevalence of coronary artery disease

Abstract Background 82-Rubidium-Positron emission tomography myocardial perfusion imaging (Rb-PET-MPI) offers higher diagnostic performance for the detection of myocardial ischemia compared to Tc-SPECT-MPI. The aim of this economic evaluation was to perform a cost-effectiveness analysis of Rb-PET-MPI versus Tc-SPECT-MPI in patients with suspected myocardial ischemia according to pretest probabilities (PTP) of obstructive coronary artery disease based on the results of the RUBIS Trial. Methods Costs and effectiveness were calculated for all patients over 1 year and an incremental analysis of differences in costs and effectiveness in terms of diagnostic accuracy was performed. The uncertainty of the results was estimated using bootstrap. The analysis was conducted from the perspective of the French health care system with a time horizon of 12 months. Results The average cost of a Rb-PET-MPI-based strategy for the detection of myocardial ischemia was €219 lower than a SPECT-MPI-based strategy (€1192 (± 1834) vs €973 (± 1939), p &lt; 0.01). The one-year incremental cost-effectiveness ratio was negative: − €2730 (money saved per additional accurate diagnosis) in patients presenting PTP &gt; 15% for the Rb-PET-MPI vs. Tc-SPECT-MPI strategy. Analysis of the joint distribution of costs and outcomes found that the Rb-PET-MPI strategy had a 92% probability to be dominant (cost-saving and outcome-improving). Conclusions Rb-PET-MPI is cost-effective compared to Tc-SPECT-MPI for the detection of myocardial ischemia in patients with PTP &gt; 15% of obstructive coronary artery disease. Trial registration RUBIS Trial registration: NCT01679886, Registered 03 September 2012, https://clinicaltrials.gov/ct2/show/NCT01679886. </jats:sec

Long-term Metabolic and Socioeducational Outcomes of Transient Neonatal Diabetes: A Longitudinal and Cross-sectional Study

OBJECTIVE Transient neonatal diabetes mellitus (TNDM) occurs during the 1st year of life and remits during childhood. We investigated glucose metabolism and socioeducational outcomes in adults. RESEARCH DESIGN AND METHODS We included 27 participants with a history of TNDM currently with (n = 24) or without (n = 3) relapse of diabetes and 16 non-TNDM relatives known to be carriers of causal genetic defects and currently with (n = 9) or without (n = 7) diabetes. Insulin sensitivity and secretion were assessed by hyperinsulinemic-euglycemic clamp and arginine-stimulation testing in a subset of 8 TNDM participants and 7 relatives carrying genetic abnormalities, with and without diabetes, compared with 17 unrelated control subjects without diabetes. RESULTS In TNDM participants, age at relapse correlated positively with age at puberty (P = 0.019). The mean insulin secretion rate and acute insulin response to arginine were significantly lower in TNDM participants and relatives of participants with diabetes than in control subjects (median 4.7 [interquartile range 3.7–5.7] vs. 13.4 [11.8–16.1] pmol/kg/min, P &amp;lt; 0.0001; and 84.4 [33.0–178.8] vs. 399.6 [222.9–514.9] µIU/mL, P = 0.0011), but were not different between participants without diabetes (12.7 [10.4–14.3] pmol/kg/min and 396.3 [303.3–559.3] µIU/mL, respectively) and control subjects. Socioeducational attainment was lower in TNDM participants than in the general population, regardless of diabetes duration. CONCLUSIONS Relapse of diabetes occurred earlier in TNDM participants compared with relatives and was associated with puberty. Both groups had decreased educational attainment, and those with diabetes had lower insulin secretion capacity; however, there was no difference in insulin resistance in adulthood. These forms of diabetes should be included in maturity-onset diabetes of the young testing panels, and relatives of TNDM patients should be screened for underlying defects, as they may be treated with drugs other than insulin. </jats:sec

Islet-reactive CD8 ⁺ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors

Islet-reactive CD8 + T cells are common in the periphery, but home to the pancreas preferentially in the context of type 1 diabetes. </jats:p

The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19)

International audienceAbstract Background It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. Methods We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020—October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. Results Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83–2.45 with an I 2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29–1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31–0.75], I 2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40–0.68], I 2 37%) were significantly lower for people with previous macrovascular disease. Conclusions This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup