Type 2 Diabetes Mellitus. From the start – combination therapy

Modern treatment of T2DM requires a shift in paradigm with appropriate intensification of therapy from the very first time of diabetes diagnosis. This is supported by data showing how even a moderate delay in achieving good glycemic control can translate into a later increased risk of developing diabetic complications. The recognition of the complexity of the pathogenesis of T2DM leads to the appreciation of the importance of attacking the disease from different angles, i.e. simultaneous tackling of multiple mechanisms contributing to hyperglycemia. From the turn of century a growing number of new anti-hyperglycemic agents have been made available. As compared to the older ones, these new medicines have a more targeted mechanism of action as they act at the level of the specific pathophysiologic disturbances accounting the development and progression of hyperglycemia. Because of that drugs can be use in combination taking advantage of their complementary mechanisms of action and synergistic. If introduced earlier in the natural history of the disease combination therapy may contribute avoiding undesirable exposure to even mild chronic hyperglycemia and provide early benefits. With respect to that in this review we will discuss advantages, disadvantages and still unanswered questions related to the use of early combination therapy in type 2 diabetes

SIRT1 rs7896005 polymorphism affects major vascular outcomes, not all-cause mortality, in Caucasians with type 2 diabetes: A 13-year observational study

Aims SIRT1 exerts effects on ageing and lifespan, as well cardiovascular (CV) disease risk. SIRT1 gene is very polymorph with a few tagging single nucleotide polymorphisms (SNPs) so far identified. Some SNPs, including rs7896005, were associated with type 2 diabetes (T2DM). We aimed to ascertain whether this SNP may be associated with CV disease at baseline as well with these same outcomes and all-cause mortality over a 13-year follow-up. Materials and Methods Genotypes of SIRT1 gene were determined using TaqMan SNP assay. Results Out of 905 T2DM, 9.1% had the AA genotype, 43.2% the AG, and 47.7% the GG. Hardy-Weinberg Equilibrium was met (minor allele frequency 0.306; p = 0.8899). At baseline, there was no difference across genotypes for sex, age, diabetes duration, CV risk factors, treatments, and microangiopathy. Major CV outcomes, myocardial infarction (MI), any coronary heart disease (CHD), and peripheral artery disease (PAD) were more frequent in GG than in AA/AG (p from 0.013 to 0.027), with no association with cerebrovascular events. By fully adjusted regression, GG remained independently related to major CV outcomes, MI, CHD, and PAD. Over follow-up, we recorded 258 major CV events (28.5%; AA/AG 25.2%, GG 32.2%; p = 0.014) with an adjusted hazard ratio (HR) of GG versus AA/AG of 1.296 (95% CI 1.007-1.668, p = 0.044); 169 coronary events (18.7%; AA/AG 15.4%, GG 22.2%; p = 0.006) with HR 1.522 (1.113-2.080, p = 0.008); 79 (8.7%) hospitalisation for heart failure (AA/AG 7.0%, GG 10.6%; p = 0.045) and HR 1.457 (0.919-2.309, p = 0.109); 36 PAD (4.0%; AA/AG 2.3%, GG 5.8%; p = 0.007) with HR 2.225 (1.057-4.684, p = 0.035). No association was found with cerebrovascular events, end stage renal disease, and all-cause mortality. Conclusions The rs7896005 SNP of SIRT1 might play a role in cardiovascular disease, mainly CHD risk in T2DM. Results call for larger association studies as well as studies to ascertain mechanisms by which this variant confers increased risk

Monitoraggio in continuo del glucosio e controllo glicemico in soggetti con diabete in emodialisi: risultati di uno studio pilota

Background: La malattia renale cronica è ancora oggi una delle complicanze a maggiore impatto negli individui con diabete ed la principale causa di ricorso alla terapia dialitica. La stima del controllo glicemico nei soggetti con diabete in terapia emodialitica ha diverse criticità, in quanto i marcatori tradizionali quali l'emoglobina glicata (HbA1c) hanno dimostrato di avere una scarsa accuratezza. In questo contensto, il monitoraggio in continuo della glicemia con flash glucose monitoring (FGM) sembrerebbe essere clinicamente accettabile ma i dati sull'impatto a medio termine nei soggetti con diabete in emodialisi sono ancora scarsi. Materiali e metodi: in questo studio pilota di tipo osservazionale, prospettico, monocentrico, sono stati reclutati 13 soggetti con diabete tipo 1 e 2 in emodialisi [maschi 11/13 (84.6%) ; età media 64±12.6 anni; BMI 26.1±6.4 kg/m2; età dialitica 2.4±1.4 anni]. A tutti i soggetti è stato applicato un sensore FGM (Freestyle Libre, Abbott, USA) ed osservati per 12 settimane. Il sensore è stato sostituito ogni 2 settimane. Al momento dell'arruolamento e a cadenza bisettimanale sono stati eseguiti prelievi ematici per il dosaggio di glicemia a digiuno, HbA1c, fruttosamina. Tutti i soggetti sono stati istruiti ad eseguire stick digitale per la stima della glicemia capillare (SMBG) nel corso della giornata come da normale pratica clinica, e di eseguire a distanza di massimo 2 minuti dallo stick anche una scansione del sensore FGM. Abbiamo valutato l'accuratezza delle misurazioni FGM confrontandole con quelle ottenute con SMBG. Abbiamo inoltre valutato se l'utilizzo dell'FGM si associasse ad un miglioramento del controllo glicemico. Risultati: abbiamo documentato una buona correlazione tra le misurazioni effettuate con SMBG ed FGM (n=540, r=0.88; P 36%) valutata con FGM. Conclusione: nei soggetti con diabete in emodialisi, le misurazioni del glucosio interstiziale ottenute con FGM sono accurate e clinicamente accettabili. L'utilizzo di tale tecnologia sembrerebbe inoltre associarsi ad una riduzione del tempo in ipoglicemia. Studi più ampi e con follow-up più lungo sono necessari per validare il dato

De-intensification of basal-bolus insulin regimen after initiation of a GLP-1 RA improves glycaemic control and promotes weight loss in subjects with type 2 diabetes

Aims To evaluate the impact of adding a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in people with type 2 diabetes (T2D) in basal-bolus (BB) insulin regimen, on insulin requirement, HbA1c, weight loss up to 24 months. Methods Data on subjects with T2D on BB who initiated a GLP-1 RA have been retrospectively collected. HbA1c, body weight, and insulin dose were recorded at baseline, 6, 12, and 24 months after initiation of GLP-1 RA therapy. A linear mixed model for repeated measures was used to evaluate the changes in HbA1c, body weight, and insulin requirement over time. Results We included 156 subjects (63.5% males; age 62 +/- 11 years, HbA1c 70 +/- 22.0 mmol/mol; 8.6 +/- 4.2%). Compared to baseline, HbA1c and body weight were significantly lower at 6 months after introducing a GLP-1RA and remained stable up to 24 months (all p < 0.0001 vs. baseline). At 24 months, 81% of subjects discontinued prandial insulin, while 38.6% discontinued basal insulin as well. Insulin requirement at baseline (aOR 0.144; 95% CI, 0.046-0.456; P = 0.001) was the only significant predictor of prandial insulin discontinuation. Conclusions Replacing prandial insulin with GLP-1 RA is a valuable strategy to simplify the BB insulin regimen while improving glycaemic control and promoting weight loss in subjects with T2D

Bilateral testicular metastases of MTC in an adult male with MEN2A syndrome: case report and review of literature

Introduction: Medullary thyroid cancer (MTC) is a rare endocrine tumor, which can be sporadic or familial, as a component of multiple endocrine neoplasia 2 (MEN2). Overall, 10% of MTC cases has already developed at presentation or will develop metastasis during follow-up. Testicular metastases are exceptional and only one case of unilateral testis' involvement by metastatic MTC has been already reported in literature. We described the first known case of asymptomatic bilateral testicular MTC metastases, discovered incidentally at testicular ultrasound performed for unrelated reasons. Case presentation: A Latin-American 32-year-old man with MEN 2A syndrome and metastatic MTC underwent andrological and urological examination due to premature ejaculation. Ultrasound imaging showed two symmetrical hypoecoic lesions involving both testis. Suspecting a bilateral testicular cancer, the patient underwent excision biopsy of both testicular lesions. Histopathology and immunoistochemical exams documented metastatic MTC of both testicular lesions. Conclusion: Beyond its rarity, testis should be considered as potential metastatic site of MTC, especially in patients with advanced disease

Impact of COVID-19 lockdown on glucose control of elderly people with type 2 diabetes in Italy

Aims: to evaluate the effect of home confinement related to COVID-19 lockdown on metabolic control in subjects with T2DM in Italy. Methods: we evaluated the metabolic profile of 304 individuals with T2DM (65% males; age 69 ± 9 years; diabetes duration 16 ± 10 years) attending our Diabetes Unit early at the end of lockdown period (June 8 to July 7, 2020) and compared it with the latest one recorded before lockdown. Results: There was no significant difference in fasting plasma glucose (8.6 ± 2.1 vs 8.8 ± 2.5 mmol/L; P = 0.353) and HbA1c (7.1 ± 0.9 vs 7.1 ± 0.9%; P = 0.600) before and after lockdown. Worsening of glycaemic control (i.e., ΔHbA1c ≥ 0.5%) occurred more frequently in older patients (32.2% in > 80 years vs 21.3% in 61-80 years vs 9.3% in < 60 years; P = 0.05) and in insulin users (28.8 vs 16.5%; P = 0.012). On multivariable analysis, age > 80 years (OR 4.62; 95%CI: 1.22-16.07) and insulin therapy (OR 1.96; 95%CI: 1.10-3.50) remained independently associated to worsening in glycaemic control. Conclusions: Home confinement related to COVID-19 lockdown did not exert a negative effect on glycaemic control in patients with T2DM. However, age and insulin therapy can identify patients at greatest risk of deterioration of glycaemic control