Impact of excluding hyperglycemia from international diabetes federation metabolic syndrome diagnostic criteria on prevalence of the syndrome and its association with microvascular complications, in adult patients with type 1 diabetes.

BACKGROUND: We aimed to determine, in patients with type 1 diabetes (T1DM), the impact of excluding hyperglycemia as a criterion from the International Diabetes Federation (IDF) definition of the metabolic syndrome (MetS), both on its prevalence and on its association with micro and macrovascular complications and markers of subclinical inflammation. METHODS: A cross-sectional design, including 280 patients with T1DM. We defined MetS by three different models: (i) the standard IDF criteria, (ii) a modification consisting of excluding of hyperglycemia as a criterion (modified IDF criteria) and (iii) a modification consisting in changing the hyperglycemia by insulin resistance (MetS + IR model) defined by the estimated glucose disposal rate. Microvascular complications and cardioautonomic neuropathy were assessed. We measured an inflammatory panel including high sensitivity C reactive protein, erythrocyte sedimentation rate, homocysteine, and fibrinogen concentrations. RESULTS: After excluding hyperglycemia, the prevalence of MetS was 6.4% (95%CI: 4.1 to 9.9) compared with 20.7% (95%CI: 16.3 to 25.8) using standard IDF criteria. After adjusting for duration of diabetes, all three MetS definitions increased the odds for having microvascular complications [OR: 6.012 (2.208-16.307) for modified definition; OR: 5.176 (2.555-10.486) for standard definition and [OR: 3.374 (1.649-8.456) for MetS+IR model]. However, the both modified IDF models for MetS showed better predictive performance than standard criteria for suffering from neuropathy, nephropathy, cardiovascular disease and were associated with markers of subclinical inflammation. CONCLUSIONS: The prevalence of MetS significantly varies as a function whether or not hyperglycemia is included as a diagnostic criterion. The subset of patients fulfilling the modified MetS definitions may reflect better the concept of metabolic syndrome in T1DM. These modified definitions were accompanied by a poorer metabolic control and lipid profile, showing the worse inflammatory biomarker profiles and higher odds for micro- and macrovascular complications. In patients with T1DM, the inclusion of insulin resistance instead of hyperglycemia as a criterion of MetS may be of interest in routine clinical practice.

Efficacy and Safety of SGLT2 Inhibitors in Type 1 Diabetes After the Introduction of an Off-Label Use Protocol for Clinical Practice.

Aims: We evaluated the real-life efficacy and safety of empagliflozin in combination with optimized insulin therapy in patients with type 1 diabetes (T1D). Methods: This was a prospective study, including 27 patients with T1D treated with insulin therapy to whom empagliflozin was added according to an off-label protocol approved for use in clinical practice. The primary end point was the change in HbA1c 52 weeks after the addition of empagliflozin to insulin therapy. Blood pressure (BP), weight, and safety were also assessed. Results: At week 52, the addition of empagliflozin significantly reduced HbA1c from 8.0% ± 0.7% to 7.2% ± 0.8% (P < 0.001). The mean percentage of time in range for capillary glucose monitoring increased from 50% to 62% (P = 0.008) in parallel to a -0.08 IU/(kg·day) reduction in insulin requirements (P = 0.031). There was also a reduction in the body weight (-8 kg) and in systolic BP from 134 to 127 mmHg (P < 0.001). The most commonly reported adverse events were genitourinary infections (10 episodes in 52 weeks of follow-up). One patient developed an episode of mild diabetic ketoacidosis that motivated empagliflozin withdrawal. No severe hypoglycemic events were registered. Conclusions: Our results suggested that the use of empagliflozin following a strict off-label protocol may represent an effective and safe option in real life among patients with T1D, improving metabolic control, and ameliorating some cardiovascular risk factors.

Association of Cardiovascular Autonomic Dysfunction With Peripheral Arterial Stiffness in Patients With Type 1 Diabetes.

CONTEXT: Cardiovascular autonomic neuropathy (CAN) appears to contribute to peripheral arterial stiffness (AS) in type 1 diabetes. Whether CAN in patients with AS is associated with concomitant asymptomatic peripheral arterial disease (aPAD) remains unclear. OBJECTIVE: To assess the risk of CAN in patients with type 1 diabetes and AS and its potential association with atherosclerosis. DESIGN: Cross-sectional study. SETTING: Type 1 diabetes clinic in an academic hospital. PATIENTS: Two hundred sixty-four patients with type 1 diabetes. INTERVENTION: AS was defined as an ankle-brachial index (ABI) >1.2, aPAD by the toe-brachial index and Doppler sonography, and CAN by blood pressure and heart rate responses to active standing and Ewing and Clarke tests. MAIN OUTCOME MEASURES: Odds of having CAN among patients with AS. Odds for CAN were also calculated as a function of the presence of AS and concomitant aPAD. RESULTS: The study population's mean age was 35 ± 11 years, with a duration of disease of 19 ± 10 years and mean hemoglobin A1c of 7.5% ± 1.3%. Seventy-three patients (28%) had peripheral AS, of whom 28 showed aPAD. The prevalence of CAN among patients with AS was 48% but it was only 23% in subjects with normal ABI (OR: 3.1 [1.7; 5.4]). Concomitant aPAD increased the OR for CAN (OR: 4.5 [2.0; 10.1]). After adjustments for aPAD and relevant cardiovascular risk factors, AS remained associated with parasympathetic dysfunction. CONCLUSIONS: In type 1 diabetes, both peripheral AS and atherosclerosis were associated with CAN. A simple method, such as the ABI, may identify a subset of patients with undiagnosed dysautonomia.

The peripheral atherosclerotic profile in patients with type 1 diabetes warrants a thorough vascular assessment of asymptomatic patients.

AIMS: Epidemiological data on subclinical atherosclerotic disease in type 1 diabetes mellitus (DM1) are scarce. We aimed to estimate the subclinical atherosclerosis profile of asymptomatic patients with DM1 and an abnormal ankle-brachial index (ABI). MATERIAL AND METHODS: In a cross-sectional design (ClinicalTrials.gov Identifier: NCT02910271), we estimated ABI in 289 consecutive asymptomatic patients with DM1. An abnormal ABI led to measurements of toe-brachial index (TBI) and peripheral doppler ultrasound (DUS) to diagnose peripheral artery disease (PAD) and/or atherosclerotic carotid plaques (ACP). RESULTS: A reduced (≤0.9) or increased (>1.2) ABI was detected in 17 (6%) and 75 (26%) patients, respectively. PAD was confirmed by TBI and DUS in 9 (53%) patients with a reduced ABI and 28 (37%) patients with an increased ABI, resulting in a 12.8% (9.4-17.2) prevalence of asymptomatic PAD. Fourteen patients with an abnormal ABI also exhibited ACP [4.8% (2.9-7.9)], with 64% of these patients showing bilateral disease. Artery stenosis was mild or moderate in 21% and 29% of patients, respectively. Thus, 46 [16% (12-21)] patients showed asymptomatic PAD, ACP, or both. According to our data, we would have to explore three asymptomatic patients with DM1 and normal pulses to unmask one case of PAD, and seven asymptomatic patients showing abnormal ABI values to detect one carotid disease. CONCLUSIONS: Peripheral artery disease is often undiagnosed in asymptomatic patients with DM1. However, its presence may change medical management in a substantial percentage of cases, highlighting the potential benefit of a thorough vascular assessment on these patients.

Virilization of a postmenopausal woman by a mucinous cystoadenoma.

OBJECTIVE: To describe the case of the most hyperandrogenaemic ovarian mucinous cystadenoma reported to date. METHODS: We present the clinical, laboratory and radiologic findings in a patient with an unusual diagnosis according to age and the clinical behaviour of the tumour, as well as a review of relevant literature. RESULTS: A 77-year-old women came to our consult because of fronto-parietal alopecia and an augmentation of the abdominal perimeter since 1 year ago. Clitoromegaly was observed during the physical examination. Hormonal analysis showed elevated testosterone and dehydroepiandrostenerone-sulphate levels (659 ng/dL and 1950 ng/ml, respectively), and imaging examination described an andexal cystic mass dependent on the right ovary. Pathological diagnosis was "mucinous cystoadenoma". After surgery, clinical and analytical alterations were normalized. CONCLUSION: Although ovarian mucinous cystadenomas are classically classified as "nonfunctional" tumours, they exceptionally can act as functional, and produce testosterone levels as high as directly secreting hormones or germ cell tumours.