Temporal trends in the starting of insulin therapy in type 2 diabetes in Italy: data from the AMD Annals initiative.

AIMS: Opportunities and needs for starting insulin therapy in Type 2 diabetes (T2D) have changed overtime. We evaluated clinical characteristics of T2D subjects undergoing the first insulin prescription during a 15-year-observation period in the large cohort of the AMD Annals Initiative in Italy. METHODS: Data on clinical and laboratory variables, complications and concomitant therapies and the effects on glucose control after 12 months were evaluated in T2D patients starting basal insulin as add-on to oral/non-insulin injectable agents, and in those starting fast-acting in add-on to basal insulin therapy in three 5-year periods (2005-2019). RESULTS: We evaluated data from 171.688 T2D subjects who intensified therapy with basal insulin and 137.225 T2D patients who started fast-acting insulin. Overall, intensification with insulin occurred progressively earlier over time in subjects with shorter disease duration. Moreover, the percentage of subjects with HbA1c levels > 8% at the time of basal insulin initiation progressively decreased. The same trend was observed for fast-acting formulations. Clinical characteristics of subjects starting insulin did not change in the three study-periods, although all major risk factors improved overtime. After 12 months from the starting of basal or fast-acting insulin therapy, mean HbA1c levels decreased in all the three investigated time-periods, although mean HbA1c levels remained above the recommended target. CONCLUSIONS: In this large cohort of T2D subjects, a progressively earlier start of insulin treatment was observed during a long observation period, suggesting a more proactive prescriptive approach. However, after 12 months from insulin prescription, in many patients, HbA1c levels were still out-of-target.

The AMD ANNALS: A continuous initiative for the improvement of type 2 diabetes care.

AIMS: Since 2006, the Italian AMD (Associations of Medical Diabetologists) Annals Initiative promoted a continuous monitoring of the quality of diabetes care, that was effective in improving process, treatment and outcome indicators through a periodic assessment of standardized measures. Here, we show the 2022 AMD Annals data on type 2 diabetes (T2D). METHODS: A network involving ∼1/3 of diabetes centers in Italy periodically extracts anonymous data from electronic clinical records, by a standardized software. Process, treatment and outcome indicators, and a validated score of overall care, the Q-score, were evaluated. RESULTS: 295 centers provided the annual sample of 502,747 T2D patients. Overall, HbA1c value ≤7.0% was documented in 54.6% of patients, blood pressure <130/80 mmHg in 23.0%, and LDL-cholesterol levels <70 mg/dl in 34.3%, but only 5.2% were at- target for all the risk factors. As for innovative drugs, 29.0% of patients were on SGLT2-i, and 27.5% on GLP1-RAs. In particular, 59.7% were treated with either GLP1-RAs or SGLT2-i among those with established cardiovascular disease (CVD), 26.6% and 49.3% with SGLT2-i among those with impaired renal function and heart failure, respectively. Notably, only 3.2% of T2D patients showed a Q score <15, which correlates with a 80% higher risk of incident CVD events compared to scores >25. CONCLUSIONS: The 2022 AMD Annals data show an improvement in the use of innovative drugs and in the overall quality of T2D care in everyday clinical practice. However, additional efforts are needed to reach the recommended targets for HbA1c and major CVD risk factors.

Epidemiology, course, and outcomes of Sars-CoV-2 infection in patients with acromegaly and Cushing's disease: a monocentric experience in Southern Italy.

PURPOSE: Acromegaly (AC) and Cushing's disease (CD) increase morbidity and mortality due to cardio-metabolic alterations, and overall cause frailty in the affected patients, potentially making them more susceptible to infective diseases. However, up to now, very few studies evaluated the course of COVID-19 disease in this setting. METHODS: We investigated epidemiology, course, and outcomes of COVID-19 disease in patients with AC or CD, managed in the Endocrine Unit of a Sicilian University Hospital during 2 years of pandemic outbreak. RESULTS: We enrolled 136 patients with AC or CD (74 and 62 cases, respectively, 39 males) from Sicily and Calabria regions. Incidence of Sars-CoV-2 infection in these subjects was lower than in the general population, becoming quite similar after vaccines introduction (11%). No difference was observed concerning prevalence. Mean age of infected patients (IPs) was significantly lower than the unaffected ones (p < 0.02). No differences were found for sex, BMI, disease control, occurrence of diabetes mellitus, OSAS, cardiomyopathy, and hypopituitarism. The rate of IPs was similar in AC and CD patients' groups. None of them died. CONCLUSIONS: In conclusion, we did not find a significantly different incidence of Sars-CoV-2 infection in AC or CD patients compared to the general population. IPs were younger than the unaffected patients, but sex, BMI, or diabetes mellitus were not risk factors for infection/worse outcomes. Nevertheless, these results could have been biased by a safer behavior probably adopted by older and more complicated patients.

A prediction model to assess the risk of egfr loss in patients with type 2 diabetes and preserved kidney function: The amd annals initiative.

OBJECTIVE: To develop and validate a model for predicting 5-year eGFR-loss in type 2 diabetes mellitus (T2DM) patients with preserved renal function at baseline. RESEARCH DESIGN AND METHODS: A cohort of 504.532 T2DM outpatients participating to the Medical Associations of Diabetologists (AMD) Annals Initiative was splitted into the Learning and Validation cohorts, in which the predictive model was respectively developed and validated. A multivariate Cox proportional hazard regression model including all baseline characteristics was performed to identify predictors of eGFR-loss. A weight derived from regression coefficients was assigned to each variable and the overall sum of weights determined the 0 to 8-risk score. RESULTS: A set of demographic, clinical and laboratory parameters entered the final model. The eGFR-loss score showed a good performance in the Validation cohort. Increasing score values progressively identified a higher risk of GFR loss: a score ≥ 8 was associated with a HR of 13.48 (12.96-14.01) in the Learning and a HR of 13.45 (12.93-13.99) in the Validation cohort. The 5 years-probability of developing the study outcome was 55.9% higher in subjects with a score ≥ 8. CONCLUSIONS: In the large AMD Annals Initiative cohort, we developed and validated an eGFR-loss prediction model to identify T2DM patients at risk of developing clinically meaningful renal complications within a 5-years time frame.

Resistin levels and inflammatory and endothelial dysfunction markers in obese postmenopausal women with type 2 diabetes mellitus.

BACKGROUND: Obesity-associated coronary heart disease (CHD) risk is higher in women than in men with type 2 diabetes (T2DM). Resistin, an adipokine secreted by adispose tissue, may contribute to this higher risk. AIMS: To explore the relationships among resistin levels and common inflammatory and endothelial dysfunction markers and CHD risk in obese post-menopausal T2DM women. METHODS: Serum levels of resistin, hsCRP, IL-6, Soluble vascular cell adhesion molecule (sVCAM), homocysteine (tHcy), HOMA-IR and metabolic parameters were determined in a group of 132 T2DM women with and without documented CHD and in 55 non-diabetic women. RESULTS: Resistin, sVCAM, IL-6 and tHcy levels were comparable in T2DM and controls. CHD women showed higher resistin, sVCAM and tHcy levels than those without CHD, and for resistin this difference remained significant after age-adjustment (P = 0.013); conversely hsCRP were ~ 2X higher in T2DM women than in controls (P = 0.0132) without any difference according to CHD history. At univariate analysis resistin levels were significantly associated with age, waist circumference, hypertension, tHcy, hsPCR, sVCAM, IL-6, HDL-cholesterol, triglycerides and creatinine levels, but only creatinine, triglycerides, hsCRP, IL-6 and sVCAM were independently associated to resistin levels at stepwise regression analysis. Resistin levels were independently associated to CHD, increasing the risk by 1.15 times (0.986-1.344 95% CI), together with age, tHcy, LDL-C and hypertension. CONCLUSIONS: Circulating resistin levels were comparable in obese/overweight T2DM and control women. In T2DM women, resistin levels correlated with markers of renal function, systemic inflammation and endothelial dysfunction and were independently associated with a higher CHD risk.

Incretin-based therapy and acute cholecystitis: a review of case reports and EudraVigilance spontaneous adverse drug reaction reporting database.

WHAT IS KNOWN AND OBJECTIVE: Glucagon-like peptide-1 (GLP-1) receptor agonists delay gastric and bowel emptying. A similar inhibitory effect of GLP-1 on gallbladder motility has been suggested, possibly leading to an increased risk of cholecystitis related to incretin-based medications, which include GLP-1 antagonists. Our objective was to review evidence in EudraVigilance, the European spontaneous reporting database and the scientific literature on this issue. COMMENT: Increasing evidence suggests an association of incretins with gallbladder adverse events. Pharmacovigilance data from EudraVigilance includes 200 serious ADR reports concerning cholecystitis related to the use of incretin-based therapies. Several mechanisms may explain this increased risk of cholecystitis, including rapid weight loss, inhibition of gallbladder contraction and emptying, reduced bile acids production, modulation of inflammation. WHAT IS NEW AND CONCLUSIONS: The available data suggest the possibility of gallbladder disease in diabetic subjects treated with incretins and highlight the importance of evaluating risk factors for cholelithiasis and gallbladder diseases in patients with diabetes before starting this therapy.

Diabetic neuropathy is not associated with homocysteine, folate, vitamin B12 levels, and MTHFR C677T mutation in type 2 diabetic outpatients taking metformin.

BACKGROUND: Hyperhomocysteinemia and vitamin B12 deficiency may be involved in the development of diabetic peripheral neuropathy (DPN). Metformin therapy may reduce vitamin B12 plasma levels, thus contributing to DPN. AIM AND METHODS: The purposes of this cross-sectional study were to assess (1) the potential associations of DPN with serum levels of homocysteine (tHcy), B-vitamins, and/or the common methylenetetrahydrofolate reductase (MTHFR) C677T mutation; (2) the influence of chronic treatment with metformin on tHcy and B-vitamins concentrations and, finally, (3) to evaluate whether, by this influence, metformin is a risk factor for DPN in a group of type 2 diabetic outpatients. RESULTS: Our data showed that fasting tHcy, folate, and vitamin B12 levels and the MTHFR C677T genotype distribution were comparable between subjects with (n = 79, 30 %) and without DPN (n = 184, 70 %). Metformin-treated subjects (n = 124, 47 %) showed significantly lower levels of vitamin B12 (P < 0.001), but the prevalence of DPN was not different when compared to those not treated with this drug (33 vs. 27 %, P = NS). At univariate regression analysis, DPN was associated with age, duration of diabetes, HbA1c, creatinine levels, and the presence of coronary heart disease (CHD), and negatively with HDL-C concentrations (P < 0.05 all), but at multivariate regression analysis, high creatinine levels (P = 0.06), low HDL-C levels (P = 0.013), and a higher prevalence of CHD (P = 0.001) were the only variables independently associated with DPN in this population. CONCLUSIONS: In conclusion, in these type 2 diabetic outpatients circulating levels of tHcy, folate, and the MTHFR C677T mutation are not associated with DPN, which was predicted by creatinine levels, CHD, and dyslipidemia. Metformin therapy is associated with a mild vitamin B12 level reduction, but not with DPN.

Twelve-month treatment with Liraglutide ameliorates Visceral Adiposity Index and common cardiovascular risk factors in type 2 diabetes outpatients.

AIM: In addition to the effects on glycemic control and body weight, GLP-1 receptor agonists may favorably affect other major cardiovascular disease (CVD) risk factors, although currently available data are still sparse. In this retrospective study, we evaluated the effects of 12-month treatment with liraglutide on major CVD risk factors in 115 type 2 diabetes outpatients (60 men and 55 women), on stable hypoglycemic, anti-hypertensive and/or lipid-lowering therapy. METHODS: Clinical and anthropometric data, metabolic and lipid profile, as well as the Visceral Adiposity Index (VAI), an obesity-related CVD risk factor, were measured in all participants at baseline and after 12-month treatment. RESULTS: Treatment with liraglutide was associated with a significant reduction from baseline values of fasting blood glucose (-42.1 mg/dl, P < 0.05), HbA1c (-1.5 %, -17 mmol/mol, P < 0.05), body weight (-7.1 kg, P < 0.05), waist circumference (-6.8 cm, P < 0.001), total-cholesterol (-27.4 mg/dl, P < 0.05), LDL-cholesterol (-25.4 mg/dl, P < 0.05), triglycerides (-56.1 mg/dl, P < 0.05), and non-HDL-C (-36.6 mg/dl, P < 0.05) and an increase of HDL-cholesterol concentrations (+9.3 mg/dl, P < 0.001), a significant reduction in both systolic and diastolic blood pressure (-14.7 mmHg, P < 0.001 and -9.0 mmHg, P < 0.05, respectively) and a decrease of VAI values (-1.6, P < 0.001). All these differences were independent of changes in BMI and comparable in men and women. CONCLUSIONS: In conclusion, 12-month treatment with liraglutide in add-on to on-going hypoglycemic therapy significantly ameliorates all major CVD risk factors and reduces cardiometabolic risk, as estimated by VAI values.

Lipid and non-lipid cardiovascular risk factors in postmenopausal type 2 diabetic women with and without coronary heart disease.

BACKGROUND: Coronary heart disease (CHD) is the leading cause of death in diabetic women. In addition to hyperglycemia, other factors may contribute to the excessive cardiovascular risk. AIM: In this study we evaluated common and emerging risk factors in a selected group of postmenopausal type 2 diabetic women with (n = 36) and without CHD (n = 59), not taking lipid-lowering medications. METHODS: Clinical and lifestyle data were collected, and metabolic and lipid profile, as well as fasting plasma levels of total homocysteine (tHcy), folate, vitamin B12, C-reactive protein (hsCRP), interleukin 6 (IL-6), and vascular cell adhesion molecule-1 (VCAM-1) were measured in all participants. RESULTS: Age, menopause and diabetes duration, family history for cardiovascular disease, prevalence of hypertension and current insulin use were greater in diabetic women with than without CHD (P < 0.05 for all comparisons). CHD women also showed higher levels of triglycerides, small dense LDL (sdLDL), remnant-like particle cholesterol, tHcy, and VCAM-1, and a lower creatinine clearance (P < 0.05 all). Conversely, the two groups were comparable for BMI, waist circumference, smoking habit, fasting plasma glucose, HbA1c, total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL cholesterol, folate, vitamin B12, hsCRP and IL-6 levels. At multivariate analysis, lower creatinine clearance (OR = 0.932, P = 0.017) and higher sdLDL serum concentration (OR = 1.224, P = 0.037) were the strongest risk factors associated with CHD in this population, whereas no significant association was noted with LDL-C. CONCLUSIONS: Our data suggest that beyond LDL-C, a lower creatinine clearance and more subtle alterations of LDL particles, together with a constellation of several well known and emerging cardiovascular risk factors, are stronger contributors to the high CHD risk of diabetic women.

Influence of high-normal serum TSH levels on major cardiovascular risk factors and Visceral Adiposity Index in euthyroid type 2 diabetic subjects.

Although several observations indicate that serum TSH levels in the high normal range are related to cardiovascular (CVD) risk factors in the general population, similar data are limited in diabetic subjects. The aim of this study was to investigate the potential associations between TSH serum levels within the normal range and major metabolic and non-metabolic CVD risk factors in a cohort of euthyroid type 2 diabetic subjects. Thyroid hormones, TSH levels, anthropometric parameters, lipid profile, glucose control, and blood pressure were measured in 490 euthyroid type 2 diabetic subjects, consecutively attending two outpatient diabetic units in Southern Italy. In all subjects, we also calculated the Visceral Adiposity Index (VAI), an obesity-related index associated with CVD risk. Diabetic women showed higher mean serum TSH levels and lower FT4 concentration than diabetic men, while FT3 levels were comparable in the two genders. Stratifying the study population according to quartiles of TSH levels, subjects in the highest TSH quartile were more likely to be female and younger, with higher values of BMI and waist circumference (P = 0.05 both), higher triglycerides (P = 0.002) and non-HDL cholesterol concentrations (P = 0.01), higher VAI values (P = 0.02), and lower FT4 levels (P = 0.05), when compared to those in the lowest quartile. At multivariate analysis, a younger age, female gender, triglycerides levels, and waist circumference were independently associated with higher TSH levels. In conclusion, in type 2 diabetic subjects with no evidence of thyroid disease, higher TSH concentrations within the normal range were more frequent in women and in younger subjects, and they were associated with visceral obesity and higher triglycerides concentrations, two well-known CVD risk factors.

Menopause modulates homocysteine levels in diabetic and non-diabetic women.

High total homocysteine (tHcy) plasma levels may contribute to the increased cardiovascular risk of Type 2 diabetic women. However, to date, data on factors modulating tHcy concentration in this population are scarce. Fasting tHcy, vitamin B12, folate plasma levels, and the methylene tetrahydrofolate reductase (MTHFR) C677T genotype as well as clinical, biochemical, and lifestyle variables were compared in 91 Type 2 diabetic and 91 matched non-diabetic women (40 pre- and 51 post-menopausal, in each group). Fasting tHcy concentration did not differ between diabetic and control women, even after multivariable adjustment. In both groups, tHcy levels increased after menopause, but the differences were weakened after multivariable adjustment. The MTHFR genotype distribution was in accordance with the Hardy-Weinberg equilibrium, with a similar TT frequency in diabetic (22.2 %) and control women (19.8%). Overall, tHcy plasma concentration was higher in TT homozygous compared to other genotypes. We found a menopause-genotype interaction on tHcy levels (p=0.068 for menopause*genotype interaction); overall, the increase of tHcy concentration in TT subjects was limited to pre-menopause (p<0.0001; adjusted p=0.024), and this was confirmed after considering diabetic and control women separately (p=0.001 and p=0.01, respectively). At multivariate analysis, menopause was an independent correlate of tHcy concentration, together with creatinine, folate and MTHFR genotype. Our data show that menopause has a strong influence on tHcy concentration even in Type 2 diabetic women and demonstrate, for the first time, that it may modulate the association between tHcy and the common MTHFR polymorphism both in diabetic and non-diabetic women.