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.

Quality of care and clinical inertia in the management of cardiovascular risk factors in patients with type 1 and type 2 diabetes: data from AMD annals.

BACKGROUND: Cardiovascular disease is the leading cause of morbidity and mortality among patients with diabetes, and for this reason, all guidelines for CV risk management provide the same targets in controlling traditional CV risk factors in patients with type 1 or type 2 diabetes at equal CV risk class. Aim of our study was to evaluate and compare CV risk management in patients with type 1 and type 2 diabetes included in AMD Annals Database paying particular attention to indicators of clinical inertia. METHODS: This was a multicenter, observational, retrospective study of AMD Annals Database during year 2022. Patients with diabetes were stratified on the basis of their cardiovascular risk, according to ESC-EASD guidelines. The proportion of patients not treated with lipid-lowering despite LDL cholesterol > to 100 mg/dl or the proportion of patients not treated with antihypertensive drug despite BP > 140/90 mmhg and proportion of patients with proteinuria not treated with angiotensin converting enzyme inhibitors or angiotensinogen receptor blockers (ACE/ARBs) were considered indicators of clinical inertia. The proportion of patients reaching at the same time HbA1c < 7% LDL < 70 mg/dl and BP < 130/80 mmhg were considered to have good multifactorial control. Overall quality of health care was evaluated by the Q-score. RESULTS: Using the inclusion criteria and stratifying patients by ESC/EASD Cardiovascular Risk categories, we included in the analysis 118.442 patients at High Cardiovascular risk and 416.246 patients at Very High Cardiovascular risk. The proportion of patients with good multifactorial risk factor control was extremely low in both T1D and T2D patients in each risk class. At equal risk class, the patients with T1D had lower proportion of subjects reaching HbA1c, LDL, or Blood Pressure targets. Indicators of clinical inertia were significantly higher compared with patients with T2D at equal risk class. Data regarding patients with albuminuria not treated with RAAS inhibitors were available only for those at Very High risk and showed that the proportion of patients not treated was again significantly higher in patients with T1DM. CONCLUSIONS: In conclusion, this study provides evidence of wide undertreatment of traditional cardiovascular risk factors among patients with diabetes included in AMD Annals Database. Undertreatment seems to be more pronounced in individuals with T1D compared to those with T2D and is frequently due to clinical inertia.

Diabetes management in cancer patients. An Italian Association of Medical Oncology, Italian Association of Medical Diabetologists, Italian Society of Diabetology, Italian Society of Endocrinology and Italian Society of Pharmacology multidisciplinary consensus position paper.

Cancer management has significantly evolved in recent years, focusing on a multidisciplinary team approach to provide the best possible patient care and address the various comorbidities, toxicities, and complications that may arise during the patient's treatment journey. The co-occurrence of diabetes and cancer presents a significant challenge for health care professionals worldwide. Management of these conditions requires a holistic approach to improve patients' overall health, treatment outcomes, and quality of life, preventing diabetes complications and cancer treatment side-effects. In this article, a multidisciplinary panel of experts from different Italian scientific societies provide a critical overview of the co-management of cancer and diabetes, with an increasing focus on identifying a novel specialty field, 'diabeto-oncology', and suggest new co-management models of cancer patients with diabetes to improve their care. To better support cancer patients with diabetes and ensure high levels of coordinated care between oncologists and diabetologists, 'diabeto-oncology' could represent a new specialized field that combines specific expertise, skills, and training.

MiRNA dysregulation underlying common pathways in type 2 diabetes and cancer development: an Italian Association of Medical Oncology (AIOM)/Italian Association of Medical Diabetologists (AMD)/Italian Society of Diabetology (SID)/Italian Society of Endocrinology (SIE)/Italian Society of Pharmacology (SIF) multidisciplinary critical view.

Increasing evidence suggests that patients with diabetes, particularly type 2 diabetes (T2D), are characterized by an increased risk of developing different types of cancer, so cancer could be proposed as a new T2D-related complication. On the other hand, cancer may also increase the risk of developing new-onset diabetes, mainly caused by anticancer therapies. Hyperinsulinemia, hyperglycemia, and chronic inflammation typical of T2D could represent possible mechanisms involved in cancer development in diabetic patients. MicroRNAs (miRNAs) are a subset of non-coding RNAs, ⁓22 nucleotides in length, which control the post-transcriptional regulation of gene expression through both translational repression and messenger RNA degradation. Of note, miRNAs have multiple target genes and alteration of their expression has been reported in multiple diseases, including T2D and cancer. Accordingly, specific miRNA-regulated pathways are involved in the pathogenesis of both conditions. In this review, a panel of experts from the Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), and Italian Society of Pharmacology (SIF) provide a critical view of the evidence about the involvement of miRNAs in the pathophysiology of both T2D and cancer, trying to identify the shared miRNA signature and pathways able to explain the strong correlation between the two conditions, as well as to envision new common pharmacological approaches.

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.

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.

Predictors of treatment response to liraglutide in type 2 diabetes in a real-world setting.

AIMS: There is an unmet need among healthcare providers to identify subgroups of patients with type 2 diabetes who are most likely to respond to treatment. METHODS: Data were taken from electronic medical records of participants of an observational, retrospective study in Italy. We used logistic regression models to assess the odds of achieving glycated haemoglobin (HbA1c) reduction ≥ 1.0% point after 12-month treatment with liraglutide (primary endpoint), according to various patient-related factors. RECursive Partitioning and AMalgamation (RECPAM) analysis was used to identify distinct homogeneous patient subgroups with different odds of achieving the primary endpoint. RESULTS: Data from 1325 patients were included, of which 577 (43.5%) achieved HbA1c reduction ≥ 1.0% point (10.9 mmol/mol) after 12 months. Logistic regression showed that for each additional 1% HbA1c at baseline, the odds of reaching this endpoint were increased 3.5 times (95% CI: 2.90-4.32). By use of RECPAM analysis, five distinct responder subgroups were identified, with baseline HbA1c and diabetes duration as the two splitting variables. Patients in the most poorly controlled subgroup (RECPAM Class 1, mean baseline HbA1c > 9.1% [76 mmol/mol]) had a 28-fold higher odds of reaching the endpoint versus patients in the best-controlled group (mean baseline HbA1c ≤ 7.5% [58 mmol/mol]). Mean HbA1c reduction from baseline was as large as - 2.2% (24 mol/mol) in the former versus - 0.1% (1.1 mmol/mol) in the latter. Mean weight reduction ranged from 2.5 to 4.3 kg across RECPAM subgroups. CONCLUSIONS: Glycaemic response to liraglutide is largely driven by baseline HbA1c levels and, to a lesser extent, by diabetes duration.

Sex differences in food choices, adherence to dietary recommendations and plasma lipid profile in type 2 diabetes - The TOSCA.IT study.

BACKGROUND AND AIMS: Diabetic women have a more adverse plasma lipid profile than men. Sex differences in dietary habits may play a role, but are little investigated. The study evaluates the quality of diet, adherence to the nutritional recommendations of the Diabetes and Nutrition Study Group and their relation with plasma lipid in men and women with diabetes. METHODS AND RESULTS: We studied 2573 people, aged 50-75, enrolled in the TOSCA.IT study (clinicaltrials.gov; NCT00700856). Plasma lipids were measured centrally. Diet was assessed with a semi-quantitative food frequency questionnaire. Women had a more adverse plasma lipid profile than men. Women consumed significantly more legumes, vegetables, fruits, eggs, milk, vegetable oils, and added sugar, whereas men consumed more starchy foods, soft drinks and alcoholic beverages. This stands for a higher proportion (%) of energy intake from saturated fat and added sugar (12.0 ± 2.4 vs 11.5 ± 2.5 and 3.4 ± 3.2 vs 2.3 ± 3.2, P < 0.04), and a higher intake of fiber (11.2 ± 2.8 vs 10.4 ± 2.6 g/1000 Kcal/day) in women. Adherence to the recommendations for saturated fat and fiber consumption was associated with significantly lower LDL-cholesterol regardless of sex. Adherence to the recommendations for added sugars was associated with significantly lower triglycerides and higher HDL-cholesterol in men and women. CONCLUSIONS: Men and women with diabetes show significant differences in adherence to nutritional recommendations, but sex differences in plasma lipid profile are unlikely to be explained by nutritional factors. Adherence to the nutritional recommendations is associated with a better plasma lipid profile regardless of sex, thus reinforcing the importance of substituting saturated for unsaturated fat sources, increasing fiber and reducing added sugar intake.

Influence of dietary fat and carbohydrates proportions on plasma lipids, glucose control and low-grade inflammation in patients with type 2 diabetes-The TOSCA.IT Study.

PURPOSE: The optimal macronutrient composition of the diet for the management of type 2 diabetes is debated, particularly with regard to the ideal proportion of fat and carbohydrates. The aim of the study was to explore the association of different proportions of fat and carbohydrates of the diet-within the ranges recommended by different guidelines-with metabolic risk factors. METHODS: We studied 1785 people with type 2 diabetes, aged 50-75, enrolled in the TOSCA.IT Study. Dietary habits were assessed using a validated food-frequency questionnaire (EPIC). Anthropometry, fasting lipids, HbA1c and C-reactive protein (CRP) were measured. RESULTS: Increasing fat intake from <25 to ≥35 % is associated with a significant increase in LDL-cholesterol, triglycerides, HbA1c and CRP (p < 0.05). Increasing carbohydrates intake from <45 to ≥60 % is associated with significantly lower triglycerides, HbA1c and CRP (p < 0.05). A fiber intake ≥15 g/1000 kcal is associated with a better plasma lipids profile and lower HbA1c and CRP than lower fiber consumption. A consumption of added sugars of ≥10 % of the energy intake is associated with a more adverse plasma lipids profile and higher CRP than lower intake. CONCLUSIONS: In people with type 2 diabetes, variations in the proportion of fat and carbohydrates of the diet, within the relatively narrow ranges recommended by different nutritional guidelines, significantly impact on the metabolic profile and markers of low-grade inflammation. The data support the potential for reducing the intake of fat and added sugars, preferring complex, slowly absorbable, carbohydrates.

Glucose Fluctuations during Gestation: An Additional Tool for Monitoring Pregnancy Complicated by Diabetes.

Continuous glucose monitoring (CGM) gives a unique insight into magnitude and duration of daily glucose fluctuations. Limited data are available on glucose variability (GV) in pregnancy. We aimed to assess GV in healthy pregnant women and cases of type 1 diabetes mellitus or gestational diabetes (GDM) and its possible association with HbA1c. CGM was performed in 50 pregnant women (20 type 1, 20 GDM, and 10 healthy controls) in all three trimesters of pregnancy. We calculated mean amplitude of glycemic excursions (MAGE), standard deviation (SD), interquartile range (IQR), and continuous overlapping net glycemic action (CONGA), as parameters of GV. The high blood glycemic index (HBGI) and low blood glycemic index (LBGI) were also measured as indicators of hyperhypoglycemic risk. Women with type 1 diabetes showed higher GV, with a 2-fold higher risk of hyperglycemic spikes during the day, than healthy pregnant women or GDM ones. GDM women had only slightly higher GV parameters than healthy controls. HbA1c did not correlate with GV indicators in type 1 diabetes or GDM pregnancies. We provided new evidence of the importance of certain GV indicators in pregnant women with GDM or type 1 diabetes and recommended the use of CGM specifically in these populations.

Pituitary autoimmunity in patients with diabetes mellitus and other endocrine disorders.

OBJECTIVE: Pituitary autoimmunity is often found in association with other endocrine autoimmune or non-autoimmune diseases. Aim of the study was to assess the prevalence of serum pituitary antibodies (PitAb) in patients with Type 1 diabetes mellitus (T1DM) or Type 2 diabetes mellitus (T2DM). RESEARCH DESIGN AND METHODS: In this casecontrol study 111 patients with T1DM, 110 patients with T2DM, and 214 healthy controls were enrolled in a tertiary referral center. Pituitary, thyroperoxidase, thyroglobulin, 21-hydroxylase, and parietal cell antibodies were assessed in all cases. Endocrine function was further assessed by basal hormone measurement and by dynamic tests, as well as a pituitary magnetic resonance imaging (MRI) was performed in those patients found positive for PitAb. RESULTS: PitAb prevalence was higher in T1DM (4 out of 111, 3.6%) than in T2DM (0 out of 110, p=0.045) and in healthy subjects (1 out of 214, 0.5% p=0.029). Prevalence of other autoimmune diseases was significantly higher in patients with T1DM (45 out of 111, 40.5%) when compared with patients with T2DM (18 out of 110 T2DM, 16.3%, p<0.001). Patients with T1DM and PitAb positivity were found with a pituitary lesion at MRI in 2 cases and pituitary dysfunction in one case. CONCLUSIONS: A significant association between pituitary autoimmunity and T1DM was found, in particular in subjects with one or more other endocrine autoimmune diseases.

Quality of Life, Wishes, and Needs in Women with Gestational Diabetes: Italian DAWN Pregnancy Study.

The DAWN (Diabetes Attitudes, Wishes and Needs) study is a survey promoted by the International Diabetes Federation to recognize the perceptions and attitudes of people suffering from diabetes mellitus. In this context, we evaluated the quality of life of Italian and immigrant women with gestational diabetes mellitus (GDM). Information was gathered using a structured questionnaire for patients' self-compilation. In a 3-month period, a 51-item questionnaire was submitted to 198 Italians and 88 immigrants (from 27 different foreign nationalities). Italian women were older and had higher education than the immigrants. 60% of the Italians and 38% of the immigrants had a family history of diabetes mellitus. In both groups, the diagnosis of GDM caused anxiety; one-third of women feared their child could contract diabetes at delivery and/or have congenital malformations. Some women had trouble in following treatment regimens: the major concern being dietary advice and blood glucose testing. Most women were satisfied (34%) or highly satisfied (60%) with the quality of care, although the degree of cooperation between diabetes specialists and gynaecologists was considered sometimes unsatisfactory. In order to optimize maternal and foetal outcomes, educational projects and improved communication between patients and the healthcare provider team are recommended.

Associations of Body Mass Index (Maternal BMI) and Gestational Diabetes Mellitus with Neonatal and Maternal Pregnancy Outcomes in a Multicentre European Database (Diabetes and Pregnancy Vitamin D and Lifestyle Intervention for Gestational Diabetes Mellitus Prevention).

Objective. Assess the impact of Gestational Diabetes Mellitus (GDM) and obesity on neonatal and maternal pregnancy outcomes. Methods. Cross-sectional data (3343 pregnancies) from seven European centres were included in a multilevel analysis of the association between GDM/obesity and caesarean section, macrosomia and neonatal morbidities. Results. Comparison of databases identified reporting differences between countries due to the inclusion of true population based samples or pregnancies from specialised tertiary centres, resulting in higher prevalences of GDM for some countries. The analysis showed that obesity and GDM were independent risk factors of perinatal complications. Only BMI had a dose-dependent effect on the risk of macrosomia and caesarean section. Both obesity (BMI > 30 kg/m(2)) and GDM were independent risk factors of neonatal morbidities. Conclusions. Obesity and GDM were independent risk factors of perinatal complications. The effect of the worldwide obesity and diabetes epidemic is extending to the next generation.

Glucagon-like peptide-1 secretion in women with gestational diabetes mellitus during and after pregnancy.

UNLABELLED: Gestational diabetes mellitus (GDM) predisposes women to future development of Type 2 diabetes mellitus (DM2) and the two conditions share similar metabolic alterations. Recent observations suggest that a defective glucose stimulated insulin secretion by glucagon-like peptide-1 (GLP- 1) plays a role in the pathogenesis of DM2. Whether such a defect is impaired in GDM remains to be ascertained. AIM: We have determined GLP-1 secretion in response to oral glucose tolerance test (OGTT) in GDM and normal glucose tolerance (NGT) during and after pregnancy. MATERIALS AND METHODS: 100-g-3h OGTT was performed in 12 GDM and 16 NGT women at 27.3 ± 4.1 weeks of gestation, for determination of plasma GLP-1, glucose, insulin, and C-peptide. Insulin sensitivity (ISI) and insulin secretion (first and second phase); as well as ISI-secretion index (ISSI) were also derived. RESULTS: NGT and GDM women were comparable for age pre-pregnancy body mass index (BMI) and weight gain. GDM had higher glucose area under the curve (AUC): 27,575.5 ± 3448 vs 20,685.88 ± 2715 mg/dl min (p<0.01), but lower first-phase insulin secretion (993.12±367 vs 1376.61 ± 423, p<0.05) and ISSI compared to controls (3873.23 ± 1185 vs 6232.13 ± 1734, p<0.001). When we examined GLP-1 mean levels in relation to mean glycemic values, GLP-1 secretion was inappropriately low with respect to mean glycemic values in GDM compared to NGT. At follow-up, AUCGLP-1 was significantly lower in post-partum GDM compared to post-partum NGT women (2542 ± 273 vs 10,092 ± 7367 pmol·l-1·min-1, p<0.05, respectively). CONCLUSIONS: Our study suggests that GLP-1 secretion in GDM women is inadequate for the prevailing glycemic levels both in pregnancy and post partum. Moreover, we cannot exclude that other important aspects of the incretin effect may be involved in GDM development.

Type 1 diabetes control and pregnancy outcomes in women treated with continuous subcutaneous insulin infusion (CSII) or with insulin glargine and multiple daily injections of rapid-acting insulin analogues (glargine-MDI).

AIM: The best way to treat pregnant patients who have type 1 diabetes is still unclear. For this reason, the present study compared metabolic control and maternal-fetal outcomes in patients treated with continuous subcutaneous infusions of rapid-acting insulin analogues (CSII) or with insulin glargine and multiple daily injections of rapid-acting insulin analogues (glargine-MDI). METHODS: This retrospective multicentre study involved 144 women with type 1 diabetes, 100 of whom were using CSII and 44 glargine-MDI. Outcomes analyzed were metabolic control, diabetes complications, pregnancy outcome, perinatal morbidity and mortality, and fetal malformations. RESULTS: The two groups were comparable for age, prepregnancy BMI, primiparous rate and diabetes complications, although patients using CSII had longer duration of diabetes (P=0.03) and higher White classifications (P=0.04). In both groups, metabolic control improved during pregnancy, but good control was reached earlier among patients using CSII. At parturition, patients using CSII had lower HbA(1c) (6.2±0.7% vs 6.5±0.8%; P=0.02) and required less insulin (P<0.01). Weight gain was similar in both groups, and maternal-fetal outcomes did not differ. CONCLUSION: In pregnant patients with type 1 diabetes, MDI and CSII are equivalent in terms of metabolic control and fetal-maternal outcomes, although patients using CSII achieved good control earlier and with less insulin.

Prepregnancy BMI influences maternal and fetal outcomes in women with isolated gestational hyperglycaemia: a multicentre study.

AIM: This multicentre study analyzed the maternal and fetal outcomes of women who had one elevated 3-h oral glucose tolerance test (isolated gestational hyperglycaemia [IGH]). METHODS: From 1999 to 2003, data were collected for 606 IGH women from 31 Italian obstetric or diabetic centres, including time and mode of delivery, gestational hypertension, preeclampsia, eclampsia, congenital malformations, and neonatal mortality and morbidity, to compare them with the general pregnant Italian population. A prognostic model for the outcome of pregnancy was constructed, and the concurrence of certain specified conditions was considered a positive outcome, whereas pregnancies that failed to meet one or more of the stated conditions were classified as "complicated". RESULTS: Macrosomia was significantly more frequent in women with IGH than in the normal pregnant population (10.7 vs 7.4%, respectively; P=0.003). Stillbirth and neonatal mortality rates did not differ from those in normal pregnancies, while a slight rise in the frequency of major malformations was not statistically significant (1.48 vs 0.89%, respectively; P<0.11). Multivariate logistic analyses confirmed that the prepregnancy body mass index (BMI) was an independent predictor of a complicated pregnancy. As for fetal growth, multivariate logistic analyses according to BMI showed that being overweight or obese were strong predictors of macrosomia. CONCLUSION: These findings in a large cohort of Italian women with IGH confirm the detrimental effect of even minimally altered glucose tolerance on fetal outcome. Also, prepregnancy obesity plays an important role in raising the risk of adverse perinatal outcomes in such patients.