Pro12Ala polymorphism in the PPARG gene contributes to the development of diabetic nephropathy in Chinese type 2 diabetic patients: comment on the study by Liu et al.

We read with interest the article by Liu et al. (1) showing that the Pro/Pro genotype of the peroxisome proliferator–activated receptor (PPAR)-γ2 is a significant independent predictor of the development of diabetic nephropathy in a large population of Chinese type 2 diabetic patients. The study confirms, in a different ethnic group, what has already been shown in relatively small studies conducted in Caucasian diabetic patients (i.e., a population with lower prevalence of diabetic nephropathy and higher frequency of Pro12Ala genotype than the Chinese population), although none of these studies provides a complete evaluation of renal function (2–4). We report data that confirm the association between the Pro12Ala polymorphism of PPAR-γ2 and urinary albumin excretion rate (AER) in

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

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

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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusions</p> <p>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.</p

β2-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/m(2 )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

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Interazione tra fattori ambientali e genetici nel determinismo di fenotipi clinici complessi come diabete mellito tipo 2 e complicanze, obesità e infiammazione subclinica

Il grasso intraddominale e sottocutaneo addominale correla più strettamente del grasso totale, espresso con l’Indice di massa corporea, con le complicanze metaboliche dell’obesità come l’insulino-resistenza, il diabete mellito, l’ipertensione arteriosa, la dislipidemia ed in ultima analisi con il rischio cardiovascolare globale. L’infiammazione subclinica rappresenta un possibile legame tra obesità, diabete mellito tipo 2 e rischio cardiovascolare. La genesi di queste condizioni è prettamente multifattoriale; sia fattori legati allo stile di vita, quali cattive abitudini alimentari e riduzione dell’attività fisica, sia il background genetico hanno un ruolo determinante nell’ influenzare la suscettibilità a queste malattie complesse. Attualmente non è ancora chiaro, per quanto riguarda l’ infiammazione subclinica, il ruolo della adiposità addominale indipendentemente dalla adiposità generale sui valori di CRP, il principale marcatore di infiammazione subclinica. Inoltre, anche se è noto che il 50% dei valori di CRP sono geneticamente determinati, pochi studi sono stati condotti per valutare l’associazione della CRP con polimorfismi di geni candidati alla regolazione dell’infiammazione. Sono invece molto numerosi gli studi che valutano l’associazione di determinati polimorfismi, in particolare il polimorfismo Pro12Ala di PPAR2, con l’obesità e le complicanze del diabete; tuttavia sono rari gli studi che valutano queste associazioni alla luce delle interazioni con i fattori ambientali e con altri geni. I lavori prodotti durante questo triennio di dottorato hanno dimostrato che il polimorfismo Pro12Ala di PPARg2, in soggetti con diabete tipo 2, è associato ad una riduzione dell’escrezione urinaria di albumina ed ad una funzione renale complessivamente migliore rispetto ai non portatori della mutazione, indipendentemente dai principali fattori confondenti analizzati. La funzione protettiva sulla microalbuminuria è stata altresì confermata in una metanalisi effettuata su 6564 pazienti. La combinazione dei genotipi ProPro di PPARg2 e di CT-TT di UCP3 è in grado di individuare soggetti che, a parità di dieta abituale, hanno un minore indice di massa corporea. L’ adiposità addominale è associata ad una maggiore infiammazione subclinica, indipendentemente dall’indice di massa corporea e questo può essere uno dei meccanismi che spiegano l’eccesso di rischio cardiovascolare associato all’adiposità addominale aldilà dei fattori di rischio tradizionali. Abbiamo, infine, per la prima volta, dimostrato l’associazione, significativa ed indipendente dai principali fattori ambientali, tra la CRP e il polimorfismo GG di UCP2 , gene fortemente canditato ad avere un ruolo nella infiammazione subclinica