Prevalence and Incidence of Medication-Treated Diabetes and Pattern of Glucose-Lowering Treatment During the COVID-19 Pandemic: Real-World Data from the Electronic Greek Prescription Database.

OBJECTIVES: This study aimed to investigate the prevalence and incidence of medication-treated diabetes mellitus and the evolving patterns of glucose-lowering treatments the year before and during the first two years of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Data from the Greek electronic prescription database were analyzed for 2019, 2020, and 2021. The study population included individuals with active social security numbers. Prevalence and incidence rates were calculated based on the dispensing of glucose-lowering medications according to their unique anatomical therapeutic chemical (ATC) code. RESULTS: The study population comprised 10,289,140 individuals in 2019, 10,630,726 in 2020, and 11,246,136 in 2021. Diabetes prevalence rates were 8.06%, 6.89%, and 7.91%, and incidence rates were 16.8/1000, 8.6/1000, and 13.4/1000 individuals, respectively. Metformin was the most prescribed medication, and newer classes, like sodium-glucose cotransporter-2 inhibitors 2 (SGLT-2) inhibitors and glucagon like peptide-1 (GLP-1) receptor agonists exhibited increasing trends. CONCLUSIONS: The study identified a decrease in medication-prescribed diabetes prevalence and incidence during the initial year of the COVID-19 pandemic, attributed to healthcare access restrictions. Subsequently, figures returned close to baseline levels. Glucose-lowering medication trends reflected adherence to local and international guidelines, with metformin as the cornerstone, and increasing preference for newer classes such as GLP-1 receptor agonists and SGLT-2 inhibitors.

Effect of heterozygous beta thalassemia on HbA1c levels in individuals without diabetes mellitus: A cross sectional study.

AIMS: To investigate the effect of heterozygous ß-thalassemia on HbA1c levels in a population without diabetes mellitus (DM). METHODS: Using a cross-sectional design, HbA1c levels were compared between two groups of 100 consecutive carriers of ß-thalassemia and 100 healthy controls matched for age, gender and BMI, taking into account fasting serum glucose and fructosamine levels. The effect of hemoglobin concentration on HbA1c was also examined. RESULTS: The mean HbA1c level was almost identical in the two groups (33.6 mmol/mol [5.23%] vs. 33.6 mmol/mol [5.22%], p = 0.857). Within the group of ß-thalassemia, there was a positive correlation between HbA1c and hemoglobin concentration (r = 0.455, p < 0.001), which was not observed in controls. ß-thalassemia carriers without anemia had slightly higher HbA1c levels compared to those with anemia (34.9 mmol/mol [5.35%] vs. 32.5 mmol/mol [5.12%] p < 0.001, absolute difference (2.4 mmol/mol [0.23%]). In multivariable analysis, hemoglobin concentration, BMI and 1st degree family history of T2DM were significant predictors of HbA1c, while ß-thalassemia carrier state was non-significant (p = 0.07). CONCLUSIONS: In individuals without DM, heterozygous ß-thalassemia has a borderline effect on HbA1c levels, while the impact of ß-thalassemia trait-associated anemia on HbA1c is of negligible clinical significance. These findings advocate for the clinical use of HbA1c as a diagnostic criterion for diabetes mellitus in this population.

Baseline osteocalcin levels and incident diabetes in a 3-year prospective study of high-risk individuals.

AIM: Experimental evidence suggests that osteocalcin is a key messenger that affects both adipocytes and insulin-producing ß cells. Epidemiological cross-sectional studies have shown a negative association between plasma levels of osteocalcin and glucose. For this reason, the hypothesis that lower baseline osteocalcin plasma levels are associated with diabetes was prospectively tested. METHODS: The study population consisted of individuals at high risk for type 2 diabetes who were screened for participation in the Greek arm of a European type 2 diabetes prevention study (the DE-PLAN study). All participants were free of diabetes at baseline and underwent a second evaluation 3 years later. Diabetes status was defined according to an oral glucose tolerance test. RESULTS: A total of 307 subjects were included in the present analysis. The population, including 154 men (50.3%), was middle-aged (54.4 ± 10.2 years) and overweight (BMI: 29.5 ± 4.9 kg/m(2)). At baseline, mean total plasma osteocalcin was lower in those with impaired fasting glucose and/or impaired glucose tolerance compared with those with normal glucose tolerance (6.0 ± 3.1 ng/mL vs. 7.3 ± 4.0 ng/mL, respectively; P = 0.01). After 3 years, 36 subjects had developed diabetes. In the prospective evaluation, there was no association between baseline osteocalcin levels and diabetes (OR: 1.04 per 1 ng/mL, 95% CI: 0.93-1.15; P = 0.49) on multivariable logistic regression analysis, nor was there any correlation with changes in plasma glucose after 3 years (r = 0.09, P = 0.38). CONCLUSION: Our prospective results show that lower levels of circulating osteocalcin do not predict future diabetes development and, in contrast to most cross-sectional published data so far, suggest that this molecule may not be playing a major role in glucose homoeostasis in humans.

Periodontitis and diabetes: a two-way relationship.

Periodontitis is a common chronic inflammatory disease characterised by destruction of the supporting structures of the teeth (the periodontal ligament and alveolar bone). It is highly prevalent (severe periodontitis affects 10-15% of adults) and has multiple negative impacts on quality of life. Epidemiological data confirm that diabetes is a major risk factor for periodontitis; susceptibility to periodontitis is increased by approximately threefold in people with diabetes. There is a clear relationship between degree of hyperglycaemia and severity of periodontitis. The mechanisms that underpin the links between these two conditions are not completely understood, but involve aspects of immune functioning, neutrophil activity, and cytokine biology. There is emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control. Incidences of macroalbuminuria and end-stage renal disease are increased twofold and threefold, respectively, in diabetic individuals who also have severe periodontitis compared to diabetic individuals without severe periodontitis. Furthermore, the risk of cardiorenal mortality (ischaemic heart disease and diabetic nephropathy combined) is three times higher in diabetic people with severe periodontitis than in diabetic people without severe periodontitis. Treatment of periodontitis is associated with HbA(1c) reductions of approximately 0.4%. Oral and periodontal health should be promoted as integral components of diabetes management.

Cardiac autonomic function correlates with arterial stiffness in the early stage of type 1 diabetes.

Arterial stiffness is increased in type 1 diabetes (T1D), before any clinical complications of the disease are evident. The aim of the present paper was to investigate the association between cardiac autonomic function and arterial stiffness in a cohort of young T1D patients, without history of hypertension and any evidence of macrovascular and/or renal disease. Large artery stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV). Cardiac autonomic function was assessed by the cardiovascular tests proposed by Ewing and Clarke. Patients with a high cardiac autonomic neuropathy score (≥4) had significantly higher PWV than those with a low score (0-1). A negative, heart rate-independent, correlation between PWV and heart rate variation during respiration was observed (r = -0.533, P < 0.001). In multivariable analysis, E/I index was the strongest correlate of PWV (ß-coefficient = -0.326, P = 0.002). Cardiac parasympathetic function is a strong predictor of large arterial stiffness, in young T1D patients free of macrovascular and renal complications.

Validation of the Finnish diabetes risk score (FINDRISC) questionnaire for screening for undiagnosed type 2 diabetes, dysglycaemia and the metabolic syndrome in Greece.

AIM: The present study aimed to validate the Finnish Type 2 Diabetes Risk Score (FINDRISC) questionnaire for its ability to predict the presence of any glucose homoeostasis abnormalities and the metabolic syndrome (MetS) in the Greek population. METHODS: Validation was performed on a sample of individuals who had agreed to participate in a screening program for type 2 diabetes (T2D) prevention (the Greek part of the DE-PLAN study), using both FINDRISC and oral glucose tolerance tests (OGTT). Impaired fasting glucose (IFG) was defined as a fasting plasma glucose level of 6.1-6.9 mmol/L, and impaired glucose tolerance (IGT) as a 2-h plasma glucose of 7.8-11.0 mmol/L. The predictive value of the FINDRISC was cross-sectionally evaluated using the area under the receiver operating characteristic (AUROC) curve method. RESULTS: A total of 869 individuals (379 men, aged 56.2 ± 10.8 years) were screened from the general population living in the city and suburbs of Athens. OGTT revealed the presence of unknown diabetes in 94 cases (10.8%), IFG in 85 (9.8%) and IGT in 109 (12.6%). The sensitivity of a FINDRISC score greater or equal to 15 (45% of the population) to predict unknown diabetes was 81.9% and its specificity was 59.7%. The AUROC curve for detecting unknown diabetes was 0.724 (95% CI: 0.677-0.770). For any dysglycaemia, the AUROC curve was 0.716 (0.680-0.752) while, for detection of the MetS, it was 0.733 (0.699-0.767). CONCLUSION: The FINDRISC questionnaire performed well as a screening tool for the cross-sectional detection of unknown diabetes, IFG, IGT and the MetS in the Greek population.

Implementation and effectiveness of the first community lifestyle intervention programme to prevent Type 2 diabetes in Greece. The DE-PLAN study.

AIMS: To report our experience of implementing the first community-based lifestyle intervention programme to detect high-risk individuals and prevent the development of Type 2 diabetes mellitus (T2DM) in a general population sample in Athens, Greece (the DE-PLAN Study). METHODS: The Finnish Type 2 Diabetes Risk Score (FINDRISC) questionnaire was distributed to 7900 people at workplaces and primary-care centres. High-risk individuals were invited to receive an oral glucose tolerance test (OGTT) and, after excluding persons with diabetes, to participate in a 1-year intervention programme, based on bimonthly sessions with a dietitian. RESULTS: Three thousand, two hundred and forty questionnaires were returned; 620 high-risk individuals were identified and 191 agreed to participate. Recruitment from workplaces was the most successful strategy for identifying high-risk persons, enrolling and maintaining them throughout the study. The 125 participants who fully completed the programme (66 did not return for a second OGTT) lost on average 1.0+/-4.7 kg (P=0.022). Higher adherence to the intervention sessions resulted in more significant weight loss (1.1+/-4.8 vs. 0.6+/-4.6 kg for low adherence). Persons with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) at baseline lost more weight than those with normal glucose tolerance (1.5+/-4.8 vs. -0.2+/-4.5 kg). The percentage of people with any type of dysglycaemia (IFG/IGT) was lower after the intervention (68.0% at baseline vs. 53.6% 1 year later, P=0.009); 5.6% developed diabetes. CONCLUSIONS: The implementation of a lifestyle intervention programme to prevent T2DM in the community is practical and feasible, accompanied by favourable lifestyle changes. Recruitment from workplaces was the most successful strategy.

Vinegar reduces postprandial hyperglycaemia in patients with type II diabetes when added to a high, but not to a low, glycaemic index meal.

BACKGROUND/OBJECTIVES: Earlier studies have shown that the addition of vinegar in a carbohydrate-rich meal lowers glucose and insulin response in healthy individuals. The mechanism of how this is accomplished, however, remains unclear. The aim of this study is to examine the effect of vinegar on glucose and insulin response in patients with type II diabetes (T2D) in relation to the type of carbohydrates consumed in a meal. SUBJECTS/METHODS: Sixteen patients with T2D were divided into two groups, matched for age, gender and HbA(1c). Patients in the first group (group A) were given a high-glycaemic index (GI) meal (mashed potatoes and low-fat milk) on two different days, with and without the addition of vinegar, respectively. In the second group (group B), patients were given an isocaloric meal with the same nutrient composition, but low GI (whole grain bread, lettuce and low-fat cheese). Postprandial plasma glucose and insulin values were measured every 30 min for 2 h. RESULTS: In group A, the incremental area under the curve of glucose (GiAUC(120)) was lower after the addition of vinegar (181+/-78 mmol min/l vs 311+/-124 mmol min/l, P=0.04). The iAUC of insulin (IiAUC(120)) was also reduced, but the difference was of marginal statistical significance (2368+/-1061 microU min/ml vs 3545+/-2586 microU min/ml, P=0.056). In group B, the addition of vinegar did not affect either the GiAUC(120) (229+/-38 mmol min/l vs 238+/-25 mmol min/l, P=0.56) or the IiAUC(120) (2996+/-1302 microU min/ml vs 3007+/-1255 microU min/ml, P=0.98). CONCLUSIONS: We conclude that the addition of vinegar reduces postprandial glycaemia in patients with T2D only when it is added to a high-GI meal.

A European evidence-based guideline for the prevention of type 2 diabetes.

BACKGROUND: The prevalence and socioeconomic burden of type 2 diabetes (T2DM) and associated co-morbidities are rising worldwide. AIMS: This guideline provides evidence-based recommendations for preventing T2DM. METHODS: A European multidisciplinary consortium systematically reviewed the evidence on the effectiveness of screening and interventions for T2DM prevention using SIGN criteria. RESULTS: Obesity and sedentary lifestyle are the main modifiable risk factors. Age and ethnicity are non-modifiable risk factors. Case-finding should follow a step-wise procedure using risk questionnaires and oral glucose tolerance testing. Persons with impaired glucose tolerance and/or fasting glucose are at high-risk and should be prioritized for intensive intervention. Interventions supporting lifestyle changes delay the onset of T2DM in high-risk adults (number-needed-to-treat: 6.4 over 1.8-4.6 years). These should be supported by inter-sectoral strategies that create health promoting environments. Sustained body weight reduction by >or= 5 % lowers risk. Currently metformin, acarbose and orlistat can be considered as second-line prevention options. The population approach should use organized measures to raise awareness and change lifestyle with specific approaches for adolescents, minorities and disadvantaged people. Interventions promoting lifestyle changes are more effective if they target both diet and physical activity, mobilize social support, involve the planned use of established behaviour change techniques, and provide frequent contacts. Cost-effectiveness analysis should take a societal perspective. CONCLUSIONS: Prevention using lifestyle modifications in high-risk individuals is cost-effective and should be embedded in evaluated models of care. Effective prevention plans are predicated upon sustained government initiatives comprising advocacy, community support, fiscal and legislative changes, private sector engagement and continuous media communication.

Increased plasma ghrelin levels in chronic renal failure are not associated with hemodynamic parameters.

BACKGROUND/AIMS: Hardly anything is known about the effect of renal function on plasma ghrelin levels. Ghrelin is an orexigenic hormone with important hemodynamic effects. We examined differences in plasma ghrelin levels between chronic renal failure (CRF) patients and healthy subjects, and ghrelin's relationship with indices of left ventricular (LV) function. METHODS: Fasting total plasma ghrelin levels were measured in 122 CRF patients (57 on, 65 not on hemodialysis) and 57 control subjects. Indices of LV function were evaluated using echocardiography. RESULTS: Total plasma ghrelin levels were higher in patients with CRF compared to controls, but were not different between patients on and those not on hemodialysis. In a multivariate linear regression model, presence of kidney dysfunction explained 41 % of the variability of ghrelin values. The etiology of renal failure (diabetic nephropathy or not) had no influence on ghrelin levels in the renal patients. Ghrelin levels were not associated with indices of LV systolic function or blood pressure in these patients. CONCLUSION: Fasting plasma ghrelin concentrations are higher in CRF patients regardless of their need for hemodialysis compared to controls. The etiology of renal failure does not have any effect on plasma ghrelin levels. In addition, ghrelin levels are not associated with hemodynamic parameters in patients with CRF.

The J-shape effect of alcohol intake on the risk of developing acute coronary syndromes in diabetic subjects: the CARDIO2000 II Study.

AIMS: To identify the threshold of alcohol consumption above which the balance of risk and benefit becomes adverse in diabetic subjects. METHODS: We studied demographic, lifestyle, dietary and clinical information in 216 hospitalized diabetic patients (171 men, 63 +/- 9 years old, 45 women, 67 +/- 5 years old) with a first event of an acute coronary syndrome (ACS) and 196 frequency matched (age-sex) diabetic controls, without any clinical evidence of coronary heart disease. Alcohol consumption was quantified and a measure for the comparisons was predetermined to be a wine glass (100 ml of wine, 12 g of ethanol) and its alcohol equivalents. RESULTS: Alcohol consumption was associated with an age-adjusted J-shape relationship with total cholesterol, blood pressure and smoking (all P < 0.001). A J-shape association was also found between alcohol intake and the risk of ACS (OR = 2.54-2.43 x (alcohol intake) + 0.80 x (alcohol intake)2, R2 = 0.96, P < 0.001), adjusted for several risk factors and interactions between alcohol intake and smoking status, job and familial stress, and low income. In particular, low alcohol consumption (< 12 g/day) was associated with a 47% (OR = 0.53, 95% CI 0.28-0.97) reduction of the prevalence of ACS, while a higher intake (12-24 and > 24 g/day) increased the prevalence by 2.7-fold (OR = 2.72, 95% CI 1.39-5.38) and 5.4-fold (OR = 5.44, 95% CI 1.21-24.55), respectively. CONCLUSIONS: Alcohol intake is a significant predictor of coronary events. Low-to-moderate intake seems to be associated with a reduction in the prevalence of ACS in diabetes, whereas higher consumption is associated with an increase in lipids and blood pressure levels, and also the risk of developing ACS.

Plasma adiponectin concentrations in patients with chronic renal failure: relationship with metabolic risk factors and ischemic heart disease.

AIMS: To compare plasma adiponectin levels between healthy controls and patients with chronic renal failure and to examine for a relationship between plasma adiponectin levels and ischemic heart disease as well as aortic distensibility which is an early marker of atherosclerosis. METHODS: We included 89 patients with CRF (45 on and 44 not on hemodialysis) and 70 controls in a cross-sectional study. Plasma adiponectin levels were measured by radioimmunoassay. Aortic distensibility was assessed by high-resolution ultrasonography. RESULTS: Plasma adiponectin levels were significantly almost twice as high in patients with renal failure compared to controls (9.7 +/- 1.1 vs. 5.4 +/- 0.6 microg/ml, p < 0.0001). No significant differences were found between renal patients on hemodialysis and not on hemodialysis (p = 0.71). Multivariate linear regression analysis in the renal patient group demonstrated a significant negative relationship between plasma adiponectin levels and ischemic heart disease (p = 0.02). The same analysis in the control subjects group showed a significant, negative relationship between plasma adiponectin levels and body mass index (p = 0.02) and a highly significant positive relationship with the high density lipoprotein cholesterol (p < 0.0001). In the total study population, glomerular filtration rate was the only independent predictor of plasma adiponectin concentrations. Aortic distensibility was lower in renal patients than in controls at a high level of significance (p < 0.0001). However, no significant relationship could be found between plasma adiponectin and aortic distensibility in either the controls or the renal patients. CONCLUSIONS: Plasma adiponectin levels are almost twice as high in patients with chronic renal failure in comparison with healthy controls, but not different between renal patients on and those not on hemodialysis. In addition, low plasma adiponectin levels are strongly associated with ischemic heart disease, but not with aortic distensibility in chronic renal failure.

Acute respiratory distress syndrome due to miliary tuberculosis in a patient with rheumatoid arthritis under corticosteroid therapy.

We report the case of a 65-year-old woman with rheumatoid arthritis (RA) under corticosteroid therapy who presented with high fever and dyspnea and who, within 48 h, developed acute respiratory distress syndrome (ARDS) due to Mycobacterium tuberculosis (MTB). Miliary tuberculosis is a rare cause of ARDS; however, because of its ominous outcome, it should be included in the differential diagnosis of immunocompromised patients with rapidly worsening respiratory discomfort. A brief review of miliary tuberculosis as a cause of ARDS is presented.

Differential effects of high-fat and high-carbohydrate isoenergetic meals on cardiac autonomic nervous system activity in lean and obese women.

Food ingestion can influence autonomic nervous system activity. This study compares the effects of 2 different isoenergetic meals on sympathetic nervous system (SNS) activity, assessed by heart rate variability (HRV) and plasma norepinephrine (NE) levels, in lean and obese women. Fifteen lean and 15 obese healthy women were examined on 2 occasions: after a carbohydrate (CHO)-rich and after a fat-rich test meal. Measurements of blood pressure, heart rate, resting energy expenditure, plasma glucose, lipids, insulin, leptin, and NE, as well as spectral analysis of the HRV, were performed at baseline and every 1 hour for 3 hours after meals. At baseline, obese women had higher SNS activity than lean controls (higher values of low-to-high frequency ratio [LF/HF], 1.52 +/- 0.31 v 0.78 +/- 0.13, P=.04; and plasma NE levels, 405.6 +/- 197.9 v 240.5 +/- 95.8 pg/mL, P<.0001). After the CHO-rich meal a greater increase in LF/HF and in plasma NE levels was observed in lean, compared to obese women (1.21 +/- 0.6 v 0.32 +/- 0.06, P=.04; and 102.9 +/- 35.4 v 38.7 +/- 12.3 pg/mL, P=.01, respectively), while no differences were observed after the fat-rich meal. Meal-induced thermogenesis was higher after the CHO-rich as compared to the fat-rich meal and was comparable between lean and obese women. Changes in HRV were not associated with the thermogenic response to the test meals. In conclusion, consumption of a CHO-rich meal causes greater cardiac SNS activation in lean than in obese women, while fat ingestion does not result in any appreciable change in either group. SNS activation does not appear to influence the thermic effect of the food in either lean or obese women.

Diabetic hypertensive patients: improving their prognosis.

Diabetes is a devastating disease with multiple adverse effects on the vasculature. Moreover, hypertension is a prerequisite for patients with diabetes to progress to end-stage renal disease and to develop cardiovascular complications. Adequate control of blood glucose and blood pressure are the two most important factors that predict a favorable renal outcome. Recent studies have also shown that some classes of antihypertensive medications, such as the angiotensin-converting enzyme (ACE) inhibitors, may be ideal initial agents to control blood pressure in the hypertensive diabetic patient and thus to preserve renal function. In addition, nondihydropyridine calcium-channel blockers have been shown to retard the decline in renal function in patients with non-insulin-dependent diabetes mellitus (NIDDM) nephropathy who have lost at least 50% of their renal function. Retrospective analyses demonstrate that a reduction in blood pressure, especially to levels of <130/85 mg Hg in diabetic patients, retards the progression of renal disease. Reduction in arterial pressure to these low levels is probably more important than the agents used to achieve this goal. Because many of these patients require more than one medication to achieve these lower levels of arterial pressure, it is clear that fixed-dose combinations of such agents will both improve the likelihood of achieving a given blood pressure goal as well as medication compliance.