Associated autoimmunity in Type 1 Diabetes and latent autoimmune diabetes of adults: The role of glutamic-acid decarboxylase autoantibodies.

AIMS: To determine the prevalence of Associated Autoimmune Diseases (AADs) in Latent Autoimmune Diabetes of Adults (LADA) versus autoimmune Type 1 Diabetes (T1D) and the role of glutamic-acid decarboxylase antibodies (GADA) and other factors. METHODS: Adults with autoimmune diabetes mellitus (DM) were recruited from the Diabetes Center of Nikaia-Piraeus Hospital. Demographic and clinical parameters were recorded and anti-pancreatic and organ-specific antibodies were measured. RESULTS: Of 160 patients, 33.75% had one AAD and 24.37% had two or more. Patients with LADA had higher overall prevalence of AADs, mainly autoimmune thyroiditis and gastritis. Celiac disease was present only in T1D. GADA positive patients had higher prevalence of AADs and multiple autoimmunity, especially thyroiditis and gastritis. Patients with LADA had higher rates of positive GADA or islet-cell antibodies (ICA). After controlling for LADA, GADA remained a significant predictor of AADs. Female gender and chronological age were also significant predictors of AADs. CONCLUSIONS: AADs were present in 58.13% of patients. Patients with LADA were more prone to a generalized autoimmune disorder than those with T1D. AADs development was significantly associated with female sex, older age and positive GADA, which proved an independent marker of associated autoimmunity.

Dryness of Foot Skin Assessed by the Visual Indicator Test and Risk of Diabetic Foot Ulceration: A Prospective Observational Study.

Research Question: Previous cross-sectional studies have shown an association between sudomotor dysfunction and diabetic foot ulceration (DFU). The aim of this prospective multicenter study was to determine the role of dryness of foot skin and of established neurological modalities in the prediction of risk for foot ulceration in a cohort of individuals with diabetes mellitus (DM). Design: The study was conducted from 2012 to 2017. A total of 308 subjects with DM without history of DFU or critical limb ischemia completed the study. Diabetic neuropathy was assessed using the neuropathy symptom score (NSS) and neuropathy disability score (NDS). In a subset of participants, vibration perception threshold (VPT) was evaluated. Dryness of foot skin was assessed by the visual indicator plaster method (IPM). The diagnostic performance of the above neurological modalities for prediction of DFU was tested by receiver operating characteristic curve (ROC) analysis. Results: During the 6-year follow-up, 55 patients (annual ulceration incidence 2.97%) developed DFU. Multivariate Cox-regression analysis after controlling for the effect of age, gender, and DM duration demonstrated that the risk (hazard ratio, 95% confidence intervals) of DFU increased significantly with either abnormal IPM (3.319, 1.460-7.545, p = 0.004) or high (≥6) NDS (2.782, 1.546-5.007, p = 0.001) or high (≥25 volts) VPT (2.587, 1.277-5.242, p = 0.008). ROC analysis showed that all neurological modalities could discriminate participants who developed DFU (p < 0.001). IPM testing showed high sensitivity (0.86) and low specificity (0.49), while high vs. low NDS and VPT showed low sensitivity (0.40 and 0.39, respectively) and high specificity (0.87 and 0.89, respectively) for identification of patients at risk for DFU. Conclusion: Dryness of foot skin assessed by the IPM predicts the development of DFU. IPM testing has high sensitivity, whereas high NDS and VPT have high specificity in identifying subjects at risk for DFU. The IPM can be included in the screening methods for identification of the foot at risk.

Adherence to the National Guidelines for Follow-Up Protocol in Subjects with Type 2 Diabetes Mellitus in Greece: The GLANCE Study.

INTRODUCTION: Physician adherence, or lack therefore, to diabetes care and follow-up guidelines may be linked to the rates of achieving suboptimal glycaemic, blood pressure and lipid targets in people with type 2 diabetes mellitus (T2DM). In this cross-sectional study we evaluated physician adherence to the patient follow-up protocol (PFP) of the 2017 Hellenic Diabetes Association (HDA) guidelines and also assessed glycated haemoglobin (HbA1c), blood pressure and lipid control achievement rates in the routine care setting in Greece. METHODS: Eligible subjects were adults with T2DM receiving oral hypoglycaemic agents (OHAs) for ≥ 1 year who had ≥ 2 HbA1c measurements in the previous year and an HbA1c target < 7%. Overall adherence at the subject level was defined as the percentage of the 62 HDA PFP items that had been met during the past year. RESULTS: Between June and December 2018, 601 eligible subjects (54.6% men; mean age 65.2 years; median T2DM duration 5.9 years, of whom 96.5% had ≥ 1 medical condition/comorbidity), were enrolled into the study by 53 hospital- and office-based endocrinologists, internists and general practitioners. The main OHAs prescribed at enrolment were metformin (91.0%), dipeptidyl peptidase-4 inhibitors (60.7%), sodium-glucose co-transporter-2 inhibitors (23.5%) and sulphonylureas (16.3%). Mean overall physician adherence to the PFP was 43.6%. Predictors of greater higher physicans' adherence were female sex (p = 0.026), > 3 medical conditions/comorbidities (p = 0.043) and diabetic complications (p < 0.001). HbA1c, low-density lipoprotein-cholesterol, systolic/diastolic blood pressure and composite metabolic targets were achieved by 82.1, 57.0, 42.6 and 21.6% of subjects, respectively. CONCLUSIONS: In Greek routine care, physician adherence to the PFP of the 2017 HDA guidelines is suboptimal. Future efforts should focus on identifying the barriers to an adequate adherence by physicians to the full PFP, with the aim to provide optimal patient care.

Left ventricular anatomical and functional changes with ageing in type 2 diabetic adults.

AIMS: Previous studies indicate that diabetic patients show evidence of coexisting systolic and diastolic myocardial dysfunction when examined by new echocardiographic techniques. Yet, there is no systematic investigation of the serial age-related changes of left ventricular anatomy and function in this patient population. METHODS AND RESULTS: One hundred and sixty type 2 diabetic patients and 110 non-diabetic controls, all with no evidence of heart disease, were studied. The participants were stratified into four distinct age-groups (A: <46, B: 46-60, C: 61-75, and D: >75 years) and underwent full echocardiographic examination. Conventional systolic and diastolic parameters were similar between the study groups. However, tissue Doppler imaging examination revealed an impaired systolic and diastolic longitudinal myocardial function in diabetic patients vs. controls, although these differences were not noticed within the youngest age-group. Diastolic dysfunction was established concomitantly in both diabetic and control subjects in age-group B. In contrast, diabetic patients showed an earlier induction of myocardial systolic dysfunction, evidenced by significantly lower average systolic longitudinal myocardial velocity in age-group B. Independent predictors of systolic myocardial dysfunction were age, glycated haemoglobin, and systemic blood pressure. CONCLUSION: Type 2 diabetic patients demonstrate an early and concomitant induction of systolic and diastolic myocardial dysfunction as a preclinical manifestation of diabetic cardiomyopathy.

Postprandial glucose response after the consumption of three mixed meals based on the carbohydrate counting method in adults with type 1 diabetes. A randomized crossover trial.

BACKGROUND & AIMS: People on intensive insulin therapy usually calculate their premeal insulin dose based on the total amount of consumed carbohydrates. However, arguments have been expressed supporting that also the protein and fat content of the meals should be considered when estimating premeal insulin dose. We examined the effectiveness of the carbohydrate counting method after consumption of mixed meals, and we further explored the effects of added extra virgin olive oil in these mixed meals, in adults with type 1 diabetes. METHODS: Twenty adults (35.0 ± 8.9 years, BMI 27 ± 5 kg/m2) with diabetes duration 17 ± 11 years, on intensive insulin therapy with multiple injections, consumed 3 mixed meals (pasticcio, chicken with vegetables and baked giant beans), with and without the addition of 11 ml extra virgin olive oil (total of 6 meals), in random order, with the insulin dose determined by using the carbohydrate counting method. Capillary blood glucose was measured at premeal (baseline) and 30, 60, 90, 120, 150 and 180 min after meal consumption. At every visit, participants were assessed for anthropometric parameters and subjective stress. RESULTS: Participants had mean HbA1c 7.5 ± 1.2%, mean carbohydrate to insulin ratio 9:1 IU and stable body weight, waist circumference and subjective stress throughout the study. The mean glucose concentration, for all 6 meals, 120 min postprandially was within target (<180 mg/dl) in nearly 80% of the sample. Addition of olive oil produced sustained increased postprandial glucose concentrations only to pasticcio meal, although within target, and no significant differences were noticed for the grilled chicken with vegetables or the baked giant beans (legume) meals. CONCLUSIONS: The carbohydrate-counting method was effective for achieving postprandial glucose levels within target threshold up to 3 h postprandially. Moreover, adding small amounts of dietary fat (extra virgin olive oil) to low fat meals does not significantly alter the postprandial response within the first 3 h, whereas caused a sustained increase in postprandial blood glucose concentrations to the high energy density meal (i.e. the pasticcio meal).

Influence of Supervised Disease Understanding and Diabetes Self-Management on Adherence to Oral Glucose-Lowering Treatment in Patients with Type 2 Diabetes.

INTRODUCTION: Systematic patient education has been reported to improve adherence to treatment, leading to better clinical outcomes. This cluster randomized real-world study investigated the effect of a systematic education program and telephone support on self-reported adherence to oral glucose-lowering treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: Centers were randomized (1:1) to provide either standard-of-care (control group) or standard-of-care along with the education program and telephone support (empowerment group). Adherence to treatment and satisfaction with treatment were assessed using the four-item Morisky Medication Adherence Scale (MMAS-4) and the Diabetes Treatment Satisfaction Questionnaire (DTSQ). The study population included 457 patients (258/199 male/female) with T2DM and non-optimal glycemic control, on oral antidiabetic treatment (age 62.7 [11.4]; disease duration 8.5 [6.5] years). RESULTS: MMAS-4 high adherence rates for the control and empowerment groups were increased by 3.8% and 16.8% at 4 months (Breslow-Day test p = 0.04) and by 8.5% and 18.8% at 8 months of follow-up, respectively (Breslow-Day test p = 0.09), compared to baseline. Intense physical activity was increased in both control and empowerment groups by 2.3% and 13.9% at 4 months (Breslow-Day test p = 0.082) and by 4.0% and 22.5% at 8 months of follow-up (Breslow-Day test p < 0.001). Baseline mean (SD) HbA1c was significantly lower in the control group compared with the empowerment group [7.7% versus 8.0%, p = 0.001] and decreased in both groups at 4 months by 0.7% and 0.9%, respectively. The change from baseline in the mean DTSQ status score at 4 months was greater in the empowerment group, and the effect was sustained at 8 months (control group: 29.1, 30.5, and 30.9; empowerment group: 25.0, 28.7, and 29.4 at baseline, 4 and 8 months, respectively, p < 0.001). CONCLUSION: Systematic education combined with telephone support delivered by physicians might be associated with improvement in treatment adherence and treatment satisfaction in patients with T2DM. FUNDING: MSD, Greece.

The Real-Life Effectiveness and Care Patterns of Type 2 Diabetes Management in Greece.

AIM: To investigate the prevalence of hypoglycaemia during sulfonylurea (SU) treatment of type 2 diabetes mellitus (T2DM) in Greece and its influence on glycaemic control, treatment adherence and quality of life (QoL). PATIENTS AND METHODS: This was a retrospective cross-sectional study. We included 383 T2DM patients ≥30 years old on treatment with SU in monotherapy or in combination with metformin for at least 6 months. Patients were requested to fill in retrospective questionnaires on hypoglycaemia experience, adherence, weight gain and lifestyle/behavioural factors along with QoL (EQ-5D-3L), treatment satisfaction (TSQM), and fear of hypoglycaemia (HFS-II Worry scale). RESULTS: HbA1c<7% was found in 161 (42.0%) patients. In total, 165 (43.1%) patients reported hypoglycaemic symptoms during the previous 6 months: 41.6% (67/161) of those with HbA1c <7% and 44.1% (98/222) of those with HbA1c ≥7%. Glycaemic control was achieved by 43.1% (94/218) of patients without hypoglycaemia and 50.0% (41/82), 36.8% (25/68) and 6.7% (1/15) of patients with mild, moderate or severe hypoglycaemia, respectively (p=0.013). In multivariate analysis, both occurrence (none vs. mild/moderate/severe) and severity (none vs. mild vs. moderate vs. severe) of hypoglycaemia were significantly associated with impaired global treatment satisfaction (p=0.002 and p<0.0001 respectively) and HFS-II Worry scale scores (both p<0.0001), while lower QoL (EQ-5D (UK) Index) was related to hypoglycaemia severity (p=0.024) only. Finally, treatment adherence was associated with increased (none/mild vs. moderate/severe) hypoglycaemia severity in univariate analysis (p=0.019). CONCLUSION: A high prevalence of patient treated with SU reported hypoglycaemia in Greek healthcare settings with negative effects on treatment satisfaction, patient worry and adherence. Severity of hypoglycaemic symptoms was associated with reduced glycaemic control.

Diabetes-dependent quality of life (ADDQOL) and affecting factors in patients with diabetes mellitus type 2 in Greece.

BACKGROUND: Diabetes mellitus type 2 (T2D) is a chronic metabolic disease with a great impact on health status and quality of life (QoL) in terms of physical, social, and psychological well-being. The aim of the present study was to measure diabetes-dependent QoL and affecting factors in patients with T2D. METHODS: Study population was consisted by 258 subjects with T2D attending diabetic outpatient clinics of General Hospitals of Piraeus "Tzaneio" and Nikaia "Ag.Panteleimon" during September-December 2014. The Audit of Diabetes-Dependent Quality of Life questionnaire was carried out in all study participants. RESULTS: Diabetes mellitus type 2 had a negative impact to QoL in 37.3 % of the study participants while 32.9 % believed that their life would have been better without the presence of T2D. Diabetes had negative impact on working life (-1.3 ± 0.6), health status (-1.3 ± 0.2), family (-1.3 ± 0.6) and sexual life (-1.3 ± 0.3), future perspectives (-1.3 ± 0.4) and dietary habits (-1.7 ± 0.2). The results of logistic regression analysis showed that QoL was related with age [odds ratio (OR) 0.94, 95 % confidence intervals (CIs) 0.91-1.98, P = 0.008] and marital status (OR 0.43, 95 %CIs 0.21-0.90, P = 0.03). CONCLUSIONS: The results of the present study showed that T2D per se has a negative impact to patient's QoL most of all affecting working life, health status, family and sexual life, future perspectives and dietary habits. Age and marital status were the only determinants of QoL.

Plasma glucose levels and white blood cell count are related with ankle brachial index in type 2 diabetic subjects.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major risk factor for peripheral arterial disease (PAD). A simple, noninvasive method for the estimation of PAD is ankle brachial index (ABI). The aim of the present study was to determine whether there is an association between ABI and cardiovascular risk factors in T2DM subjects without apparent macrovascular disease. METHODS: A total of 125 T2DM subjects (84 males, 41 females, mean age ± standard deviation 62.2 ± 9.1 years) who had no apparent macrovascular disease and who attended the Health Center of Erymantheia between January 2008 and June 2009 were recruited to the study. RESULTS: Of the study subjects 20% (n=25) had ABI <0.90. Univariate linear regression analysis showed that ABI was significantly associated with history of hypertension (p=0.02), fasting serum glucose levels (p=0.02), serum urea levels (p=0.005), serum uric acid levels (p=0.007) and white blood cell (WBC) count (p=0.04). Multivariate linear regression analysis demonstrated significant independent associations between ABI and fasting serum glucose levels (p=0.03) as well as WBC count (p=0.03). CONCLUSIONS: Elevated plasma glucose and WBC count increase the risk of PAD in asymptomatic diabetics.

Prevalence of asymptomatic bacteriuria in type 2 diabetic subjects with and without microalbuminuria.

BACKGROUND: Diabetic subjects, especially women, show high prevalence of asymptomatic bacteriuria (ASB). The aim of the present study was to evaluate the prevalence of ASB in subjects with type 2 diabetes mellitus (T2D) with and without microalbuminuria (MA). FINDINGS: A hundred diabetic subjects with MA (53 males/47 females, mean age +/- standard deviation: 65.5 +/- 11.1 years) and 100 diabetic subjects without MA (52 males/48 females, mean age +/- standard deviation: 65.4 +/- 11.3 years), consecutively attending the outpatient diabetes clinic of our hospital were recruited in the study. Subjects with overt diabetic nephropathy or nephropathy from other causes were excluded. In addition, subjects with symptoms of urinary track infection or use of antimicrobial drugs in the last 14 days were excluded by the study.Diabetic subjects with MA showed increased prevalence of ASB compared to diabetic subjects without MA (21% versus 8%, P < 0.001, respectively). Escherichia coli was the most prevalent pathogen isolated in diabetic subjects with and without MA (12% versus 3.0%, P = 0.01, respectively) followed by Proteus mirabilis (6% versus 5%, P = 0.75, respectively) and Klebsiella spp (5% versus 1%, P = 0.09, respectively). Univariate logistic analysis showed that ASB was associated with the presence of coronary artery disease [odds ratio (OR): 0.29, 95% Confidence Intervals (95% CI): 0.09-0.95, P = 0.04] and gender (OR: 0.09, 95% CI: 0.02-0.35, P < 0.001) in the diabetic study group with MA. CONCLUSIONS: ASB is more prevalent among T2D subjects with MA. Screening for ASB is warranted in diabetic patients especially if pyuria is detected in urine analysis since ASB has been found to be a risk factor for developing symptomatic urinary tract infection.