Role of telemedicine during COVID-19 pandemic in type 2 diabetes outpatients: The AMD annals initiative.

AIMS: Telemedicine is advocated as a fundamental tool in modern clinical management. However, data on the effects of telemedicine vs face-to-face consultation on clinical outcomes in type 2 diabetes (T2DM) are still uncertain. This paper describes the use of telemedicine during the 2020 COVID-19 emergency and compares volume activity and quality indicators of diabetes care between face-to-face vs telemedicine counseling in the large cohort of T2DM patients from the AMD Annals Initiative. METHODS: Demographic and clinical characteristics, including laboratory parameters, rate of the screening of long-term complications, current therapies and the Q-score, a validated score that measures the overall quality of care, were compared between 364,898 patients attending face-to-face consultation and 46,424 on telemedicine, during the COVID-19 pandemic. RESULTS: Patients on telemedicine showed lower HbA1c levels (7.1 ± 1.2 % vs 7.3 ± 1.3 %, p < 0.0001), and they were less frequently treated with metformin, GLP1-RAs and SGLT2i and more frequently with DPP4i. The telemedicine group showed reduced monitoring of the various parameters considered as process indicators, especially, eye and foot examination. The proportion of patients with a good quality of care (Q score > 25) was higher among those receiving face-to-face consultation. Moreover, in the telemedicine group, all major clinical outcomes remained stable when further compared to those collected in the year 2019, when the same patients underwent a regular face-to-face consultation, suggesting that the care provided through telemedicine did not negatively affect the most important parameters. CONCLUSIONS: During the COVID-19 pandemic, telemedicine provided an acceptable quality of diabetes care, comparable to that of patients attending face-to-face consultation, although a less frequent screening of complications seems to have occurred in subjects consulted by telemedicine.

Management of patients with chronic heart failure and type 2 diabetes mellitus: the SCODIAC-II study.

SCODIAC was a pilot study which revealed an increasing use of SGLT2i in 123 outpatients affected with Heart Failure (HF) and Type 2 Diabetes Mellitus. SCODIAC-II study, the second phase of the program, has been carried out to determine diagnostic and therapeutic pathways in a larger group of patients and to verify whether the use of innovative antidiabetic therapies could modify echocardiographic parameters and cardiovascular therapies. 406 HF-diabetic patients, referred to Cardiologists and Diabetologists of pertaining healthcare districts in Campania, were enrolled in this retrospective study and divided in Group A, composed of 136 patients with preserved Ejection Fraction (HF-pEF)(> 45%) and Group B, formed of 270 patients with reduced EF (HF-rEF)(≤ 45%). All patients had performed periodic clinical and echocardiographic evaluations. The antidiabetic therapies resulted modified after 1 year with a greater use of GLP1-AR, gliptins and SGLT2i. Cardiovascular therapies resulted also modified with a greater use of sacubitril/valsartan and a reduction of ACEi and ARBs in HF-rEF patients. Echocardiography E velocity, A velocity and E/e' ratio resulted markedly reduced in 25 HF-pEF and in 60 HF-rEF patients treated with SGLT2i, in respect to both the whole sample of subjects at beginning and the other diabetic patients. LAVi resulted reduced only in HF-pEF patients and EF increased only in HF-rEF patients. The approach to the patients with HF and diabetes must necessarily take place in the healthcare districts, be multidisciplinary and integrated. SGLT2i could improve left ventricular function in HF-rEF patients and modify cardiovascular therapies, almost in this setting of patients.Trial registration The protocol was approved by the University of Naples Federico II Ethics Committee and registered at ClinicalTrial.gov (CT04375943). The principles outlined in the Declaration of Helsinki were followed.

The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes.

OBJECTIVE: Cross-sectional studies suggest the association between diabetic nephropathy and the PPARγ2 Pro12Ala polymorphism of the peroxisome proliferator-activated receptor γ2 (PPARγ2). Prospective data are limited to microalbuminuria and no information on renal function is available to date. The present study evaluates the association between the Pro12Ala polymorphism of PPARγ2 and the progression of albuminuria and decay in glomerular filtration rate (GFR) in type 2 diabetes. PATIENTS AND MEASUREMENTS: We studied 256 patients with an average 5-year follow-up. Among others, urinary albumin excretion rate (UAER) was measured on spot sample, GFR was estimated with the CKD-EPI Equation. RESULTS: Baseline UAER and GFR were similar for carriers or non-carriers of the polymorphism. At follow-up no significant changes from baseline were observed for UAER or eGFR in carriers of the Pro12Ala polymorphism whereas a significant increase in UAER [17 (11.3-37.9) versus 24.5 (13.8-49.9) µg/mg, p < 0.006)] and a significant reduction in the eGFR (82.8 ± 14.5 versus 80.3 ± 17.3 ml/min/1.73, m(2) p = 0.02), were observed in non carriers of the Pro12Ala polymorphism. Progression of nephropathy - defined according to a combined end point of UAER and eGFR- i.e. doubling of baseline UAER to at least 100 µg/mg, or new onset microalbuminuria, or progression from micro to macroalbuminuria, or 25% reduction of eGFR, or annualized eGFR decline >3 ml/min/year - was significantly less frequent in Ala carriers than non carriers (11.4% vs 35.8%; p < 0.01); HR adjusted for baseline age, AER, eGFR, HbA1c, diabetes duration and blood pressure was 0.32 (0.12-0.80). CONCLUSIONS: This study found that among patients with type 2 diabetes, the PPARγ2 Pro12Ala polymorphism is protective against progression of nephropathy and decay of renal function independent of major confounders.

Interaction between Pro12Ala polymorphism of PPARγ2 and diet on adiposity phenotypes.

The aim of this report is to perform a systematic review and qualitative synthesis of the literature to address whether, and to what extent, diet modulates the effects of the Pro12Ala polymorphism of peroxisome proliferator-activated receptor gamma 2 (PPARγ2) on body weight and other measures of adiposity. A systematic search of the literature was conducted, wherein both observational and experimental studies of adults were reviewed. Overall, the results of the observational studies show little consistency. Methodological differences in their design, conduct and analysis may largely account for the apparently discrepant findings. This notwithstanding, the main picture that emerges is that the energy content and composition of the diet may affect BMI, body composition and metabolic parameters in Ala allele carriers more than in Pro/Pro homozygotes. In most studies, carriers of the Ala allele with an obesogenic lifestyle (i.e. high-energy, high-carbohydrate and, to some extent, high-fat diets) are more obese than Pro homozygotes. Well-designed intervention studies with a sufficiently large sample size consistently show that carriers of the Ala allele are more prone to weight loss when exposed to a healthy lifestyle; however, these individuals do not seem to retain these benefits when returning to a sedentary lifestyle and inadequate dieting behaviours. Some key questions in this area of research have emerged. Carefully designed and adequately powered studies are needed, particularly involving the development and validation of standardized tools for the assessment of dietary exposure, including the use of biomarkers, to move the field forward.

Iron deficiency and cardiovascular disease: an updated review of the evidence.

Body iron status has been suggested to be related to the development of cardiovascular disease (CVD). Biologically plausible mechanisms for this association have been described, however epidemiological studies on iron status and CVD risk have provided conflicting results. The lack of consistency is likely explained by differences in the study design, the measures used for the assessment of iron status, the definition of outcomes, and adjustment for confounders. To help clarify the available evidence, we report a systematic review of published cross-sectional, longitudinal, and intervention studies evaluating the relationship between different measures of iron status and CVD risk. The most likely scenario that emerges from the available studies is that, in the reference range, iron status has a neutral effect. Extreme conditions of iron deficiency, as well as of iron overload, are associated with modestly increased CVD risk, although with different proposed mechanisms.

Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review.

AIMS/HYPOTHESIS: Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association between metformin and risk of cancer and cancer mortality in patients with diabetes. DATA SOURCE: MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers. RESULTS: Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death [6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80], all malignancies [18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88], liver [8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60] colorectal [12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74-0.92], pancreas [9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36-0.86], stomach [2 studies, 100701 patients, OR:0.83, 95%CI: 0.76-0.91], and esophagus cancer [2 studies, 100694 patients, OR:0.90, 95%CI: 0.83-0.98]. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma. CONCLUSIONS/INTERPRETATION: Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.

Fasting apolipoprotein B48 is associated with asymptomatic peripheral arterial disease in type 2 diabetic subjects: a case-control study.

OBJECTIVE: To test whether there is an association between fasting ApoB48 level, a marker of the residual presence of intestinally derived TRLs lipoproteins, thought to be highly atherogenic, and peripheral artery disease (PAD) in type 2 diabetic patients independent of fasting plasma lipids. METHODS: We studied 87 patients with type 2 diabetes: 34 with asymptomatic PAD (ankle/brachial index < 0.9) and 53 without PAD matched on age (±2 years), gender and BMI (±2 kg/m(2)). The plasma fasting ApoB48 was measured by ELISA. RESULTS: Patients with PAD had significantly higher ApoB48 levels (1.529 ± 1.253 vs 1.095 ± 0.667 µg/ml p = 0.04) than those without PAD independent of major confounders, such as duration of diabetes, smoking status, HbA1c, systolic blood pressure and fasting plasma lipids. CONCLUSIONS: Fasting ApoB48 was independently associated with asymptomatic PAD in patients with type 2 diabetes.

PPARγ2 P12A polymorphism and albuminuria in patients with type 2 diabetes: a meta-analysis of case-control studies.

BACKGROUND: Insulin resistance has a role in diabetic nephropathy. The A12 variant of the PPARγ2 P121A polymorphism has been firmly associated with reduced risk of insulin resistance, while its role on the risk of albuminuria in patients with type 2 diabetes is uncertain. This study investigated whether the PPARγ2 P12A polymorphism modulates the risk of albuminuria in these patients. METHODS: We tested the association between the A12 variant and albuminuria in three new case-control studies in diabetic patients from Italy (n = 841, n = 623 and n = 714 patients, respectively) and then performed a meta-analysis of all studies available to date. The nine studies we meta-analysed (six previously published and three presented here) comprised a total of 2376 cases and 4188 controls. RESULTS: In none of the three new studies was a significant association observed with odds ratio (OR) [95% confidence intervals (95% CI)] being 1.115, 0.799 and 0.849 (P = 0.603, 0.358 and 0.518, respectively). At meta-analysis, the overall OR (95% CI) for association between A12 and albuminuria was 0.694 (0.528-0.912). A significant heterogeneity of the genetic effect was observed (P = 0.026), which was totally explained by the different method of urine collection and albuminuria definition utilized across the studies. In fact, most of the effect was observed in the four studies determining albumin excretion rate rather than in those using albumin concentration in a single spot (OR, 95% CI: 0.529, 0.397-0.706, P = 0.0000164 and 0.919, 0.733-1.153, P = 0.47, respectively). CONCLUSION: The present study shows that the PPARγ2 Ala12 variant is significantly associated with a reduced risk of albuminuria among patients with type 2 diabetes.

Uncoupling protein 2 G(-866)A polymorphism: a new gene polymorphism associated with C-reactive protein in type 2 diabetic patients.

BACKGROUND: This study evaluated the relationship between the G(-866)A polymorphism of the uncoupling protein 2 (UCP2) gene and high-sensitivity C reactive protein (hs-CRP) plasma levels in diabetic patients. METHODS: We studied 383 unrelated people with type 2 diabetes aged 40-70 years. Anthropometry, fasting lipids, glucose, HbA1c, and hs-CRP were measured. Participants were genotyped for the G (-866)A polymorphism of the uncoupling protein 2 gene. RESULTS: Hs-CRP (mg/L) increased progressively across the three genotype groups AA, AG, or GG, being respectively 3.0 ± 3.2, 3.6 ± 5.0, and 4.8 ± 5.3 (p for trend = 0.03). Since hs-CRP values were not significantly different between AA and AG genotype, these two groups were pooled for further analyses. Compared to participants with the AA/AG genotypes, homozygotes for the G allele (GG genotype) had significantly higher hs-CRP levels (4.8 ± 5.3 vs 3.5 ± 4.7 mg/L, p = 0.01) and a larger proportion (53.9% vs 46.1%, p = 0.013) of elevated hs-CRP (> 2 mg/L). This was not explained by major confounders such as age, gender, BMI, waist circumference, HbA1c, smoking, or medications use which were comparable in the two genotype groups. CONCLUSIONS: The study shows for the first time, in type 2 diabetic patients, a significant association of hs-CRP levels with the G(-866)A polymorphism of UCP2 beyond the effect of major confounders.

Abdominal adiposity is associated with elevated C-reactive protein independent of BMI in healthy nonobese people.

OBJECTIVE: There is debate over the most appropriate adiposity markers of obesity-associated health risks. We evaluated the relationship between fat distribution and high-sensitivity C-reactive protein (hs-CRP), independent of total adiposity. RESEARCH DESIGN AND METHODS: We studied 350 people with abdominal adiposity (waist-to-hip ratio [WHR] > or =0.9 in male and > or =0.85 in female subjects) and 199 control subjects (WHR <0.9 in male and <0.85 in female subjects) matched for BMI and age. We measured hs-CRP and major cardiovascular risk factors. RESULTS: Participants with abdominal adiposity had BMI similar to that in control subjects (24.8 +/- 2.5 vs. 24.7 +/- 2.2 kg/m(2), respectively), but significantly higher waist circumference (96.4 +/- 6.0 vs. 83.3 +/- 6.7 cm; P < 0.01) and WHR (1.07 +/- 0.08 vs. 0.85 +/- 0.05; P < 0.001). Compared with the control subjects, participants with abdominal adiposity had an adverse cardiovascular risk factor profile, significantly higher hs-CRP (1.96 +/- 2.60 vs. 1.53 +/- 1.74 mg/dl; P < 0.01), and a twofold prevalence of elevated CRP values (>3 mg/dl). CONCLUSIONS: In nonobese people, moderate abdominal adiposity is associated with markers of subclinical inflammation independent of BMI.

Pro12Ala polymorphism of the PPARgamma2 locus modulates the relationship between energy intake and body weight in type 2 diabetic patients.

OBJECTIVE: We explore the relationship among BMI, habitual diet, and the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor (PPAR)gamma2. RESEARCH DESIGN AND METHODS: The Pro12Ala variant was characterized in 343 unrelated type 2 diabetic patients who were consecutively seen at the outpatient clinic of a health district of the province of Naples. Anthropometric and laboratory parameters were measured; habitual diet was assessed by a validated semiquantitative food frequency questionnaire. RESULTS: The overall frequency of Ala12 was 12% (n = 42). BMI was significantly higher in Ala carriers than non-Ala carriers, whereas total daily energy intake or macronutrient composition of the diet were similar in the two groups. For further analysis, participants were stratified according to genotype and sex-specific quartiles of energy intake. BMI increased in both genotype groups with increasing energy intake (P < 0.03). BMI was similar in Ala carriers and non-Ala carriers (30.0 vs. 30.1 kg/m2, P > 0.10) in the lower quartile of energy intake but significantly higher in Ala carriers in the upper quartile (36.0 vs. 32.1 kg/m2, P < 0.001). Average daily energy intake and diet composition were comparable within each quartile for carriers or noncarriers of the Ala allele. Relative to the noncarriers, Ala carriers had a significantly lower energy intake per kilogram body weight, thus suggesting that the Ala allele is associated with a higher food efficiency. The confounding role of medications, glucose control, and physical exercise was ruled out. CONCLUSIONS: This study provides evidence of a differential susceptibility to fat accumulation, and, hence, weight gain, in response to habitual high energy intake for Ala carriers compared with Pro/Pro homozygotes.

Beta2-adrenergic receptor and UCP3 variants modulate the relationship between age and type 2 diabetes mellitus.

BACKGROUND: It is widely accepted that Type 2 Diabetes Mellitus (T2DM) and other complex diseases are the product of complex interplay between genetic susceptibility and environmental causes. To cope with such a complexity, all the statistical and conceptual strategies available should be used. The working hypothesis of this study was that two well-known T2DM risk factors could have diverse effect in individuals carrying different genotypes. In particular, our effort was to investigate if a well-defined group of genes, involved in peripheral energy expenditure, could modify the impact of two environmental factors like age and obesity on the risk to develop diabetes. To achieve this aim we exploited a multianalytical approach also using dimensionality reduction strategy and conservative significance correction strategies. METHODS: We collected clinical data and characterised five genetic variants and 2 environmental factors of 342 ambulatory T2DM patients and 305 unrelated non-diabetic controls. To take in account the role of one of the major co-morbidity conditions we stratified the whole sample according to the presence of obesity, over and above the 30 Kg/m2 BMI threshold. RESULTS: By monofactorial analyses the ADRB2-27 Glu27 homozygotes had a lower frequency of diabetes when compared with Gln27 carriers (Odds Ratio (OR) 0.56, 95% Confidence Interval (CI) 0.36 - 0.91). This difference was even more marked in the obese subsample. Multifactor Dimensionality Reduction method in the non-obese subsample showed an interaction among age, ADRB2-16 and UCP3 polymorphisms. In individuals that were UCP3 T-carriers and ADRB2-16 Arg-carriers the OR increased from 1 in the youngest to 10.84 (95% CI 4.54-25.85) in the oldest. On the contrary, in the ADRB2-16 GlyGly and UCP3 CC double homozygote subjects, the OR for the disease was 1.10 (95% CI 0.53-2.27) in the youngest and 1.61 (95% CI 0.55-4.71) in the oldest. CONCLUSION: Although our results should be confirmed by further studies, our data suggests that, when properly evaluated, it is possible to identify genetic factors that could influence the effect of common risk factors.