Prevalence and clinical determinants of rapid eGFR decline among patients with newly diagnosed type 2 diabetes.

BACKGROUND: Diabetic kidney disease is the most common cause of end-stage kidney disease (ESKD) in the western world. Rapid estimated glomerular filtration rate (eGFR) decline is an independent predictor of ESKD and death in the general population and in subjects with type 2 diabetes mellitus (T2D). AIM: We investigated in a large sample of subjects with newly diagnosed T2D the prevalence and clinical determinants of fast eGFR decline, taking advantage from the dataset of the Associazione Medici Diabetologi (AMD) Annals initiative. METHODS: The eGFR trajectories were evaluated by applying a linear mixed model for repeated measures (LMMRM) and rapid eGFR decline defined as an eGFR decline greater than 5 mL/min/1.73 m2 per year at 3 years. RESULTS: Among 105,163 (57.7% M) subjects with newly diagnosed T2D, 13,587 (12.9 %) subjects showed a rapid eGFR loss. The independent significant predictors were age, female gender, HbA1c, smoking, high baseline eGFR, albuminuria and retinopathy. CONCLUSION: Our study demonstrates that a significant percentage of newly diagnosed T2D subjects have a rapid eGFR decline. Given the association between dynamic changes in eGFR and the risk of ESKD or death, we suggest to include this variable in the definition of CKD.

Profiles of sulfonylurea use in Diabetes Mellitus type 2: an analysis of clinical practice over the last 10 years.

AIMS: Describing the evolution over time in the use of sulfonylureas (SUs) and the characteristics of patients at first prescription and at interruption of treatment with SUs. METHODS: Retrospective evaluation of data from the Italian Association of Diabetologists (AMD) Annals registry (2010-2020), about T2D patients who started treatment with SUs. The longitudinal probability of remaining on SUs was estimated by Kaplan Meier survival curves. RESULTS: SU prescription decreased from 30.7 % (2010) to 12.9 % (2020). Patients started on SU were 68.2 ± 11.2 years old, mostly males (55.5 %), with diabetes duration = 10.1 ± 8.3 years, BMI = 29.7 ± 5.5 kg/m2, and HbA1c = 8.3 ± 1.7 % [67 mmol/mol]. After one year, the probability of staying on SU was 85.4 %, 75.9 % after two years, 68.2 % after 3 years, 56.6 % after 5 years. Patients who discontinued SUs had higher BMI and HbA1c, were younger, more often males and treated with insulin. Over time, the percentage of subjects switched to metformin, DPP4i, SGLT2i, and GLP1RA increased, whereas use of glinides, glitazones, acarbose and insulin declined. CONCLUSIONS: These data suggest a consensus, slowly, but increasingly aligning with the current National indications of dismissing SUs for the treatment of T2D. The new drugs for diabetes should represent a preferable choice in all patients who do not have specific contraindications.

The Burden of Obesity in Type 1 Diabetic Subjects: A Sex-specific Analysis From the AMD Annals Initiative.

OBJECTIVE: Obesity is a growing emergency in type 1 diabetes (T1D). Sex differences in obesity prevalence and its clinical consequences in adult T1D subjects have been poorly investigated. The aim of this study was to investigate the prevalence of obesity and severe obesity, clinical correlates, and potential sex differences in a large cohort of T1D subjects participating to the AMD (Associazione Medici Diabetologi) Annals Initiative in Italy. RESEARCH DESIGN AND METHODS: The prevalence of obesity [body mass index(BMI) ≥30 kg/m2] and severe obesity (BMI ≥ 35 kg/m2) according to sex and age, as well as obesity-associated clinical variables, long-term diabetes complications, pharmacological treatment, process indicators and outcomes, and overall quality of care (Q-score) were evaluated in 37 436 T1D subjects (45.3% women) attending 282 Italian diabetes clinics during 2019. RESULTS: Overall, the prevalence of obesity was similar in the 2 sexes (13.0% in men and 13.9% in women; mean age 50 years), and it increased with age, affecting 1 out of 6 subjects ages >65 years. Only severe obesity (BMI >35 kg/m2) was more prevalent among women, who showed a 45% higher risk of severe obesity, compared with men at multivariate analysis. Cardiovascular disease risk factors (lipid profile, glucose, and blood pressure control), and the overall quality of diabetes care were worse in obese subjects, with no major sex-related differences. Also, micro- and macrovascular complications were more frequent among obese than nonobese T1D men and women. CONCLUSIONS: Obesity is a frequent finding in T1D adult subjects, and it is associated with a higher burden of cardiovascular disease risk factors, micro- and macrovascular complications, and a lower quality of care, with no major sex differences. T1D women are at higher risk of severe obesity.

Temporal trends in intensification of glucose-lowering therapy for type 2 diabetes in Italy: Data from the AMD Annals initiative and their impact on clinical inertia.

AIMS: Clinical inertia negatively affects type 2 diabetes (T2DM) management. We evaluated changes in prescription patterns of hypoglycemic drugs during a 15 year-observation period in a large population of T2DM outpatients and their effect on metabolic control. METHODS: Data on all T2DM patients attending 258 Italian diabetes clinics between 2005 and 2019 were collected and analyzed for three 5-years periods. The addition of a second drug to metformin and the addition of a third agent to dual therapy were evaluated. RESULTS: During the observation period, 437.179 patients added a second drug to metformin. The intensification occurred earlier over time: patients had a shorter duration of disease and a better cardiovascular risk profile in the last five years, compared to previous periods. During the same period, 208.767 patients added a third agent to dual therapy. Duration of diabetes at the time of intensification decreased, and cardiovascular risk profile improved over time. Also HbA1c levels at the time of intensification decreased over time. CONCLUSIONS: in this large cohort of T2MD subjects during a long observation period an earlier treatment intensification and a better metabolic control were observed, suggesting an improved approach to clinical inertia.

As Time Goes by: Anxiety Negatively Affects the Perceived Quality of Life in Patients With Type 2 Diabetes of Long Duration.

INTRODUCTION: Age-related medical conditions are increasing worldwide. Type 2 Diabetes mellitus (T2DM) represents a chronic disease, which affects a large amount of general population, accounting for over 90% of diabetes mellitus (DM) cases. PURPOSE: As psychopathological symptoms frequently occur in medical conditions, our study aimed at exploring whether psychological factors and metabolic control may affect health related quality of life (HRQoL). METHODS: Forty five patients with T2DM were consecutively recruited and assessed with a psychodiagnostic battery: Hamilton Anxiety Rating Scale (HAM-A), Beck Depression Inventory II edition (BDI-II) and the 36-Item Short Form Health Survey (SF-36), including indexes Physical and Mental Component Summary (PCS, MCS). Moreover, time since DM diagnosis and glycated hemoglobin (HbA1c) values were detected. RESULTS: Participants (mean age 65.3 ± 5.9 years) had a mean time since diagnosis of 11.6 ± 6.7 years, and showed a good metabolic control as highlighted by mean HbA1c values 7.1 ± 0.9%. Median HAM-A score [25(20.7-30.6)], represented high prevalence of anxious symptoms. A moderate expression of depressive symptoms was observed [BDI-II score: 13(8.3-21.4)]. A multiple regression analysis, after correcting for age, BMI, HbA1c value and BDI-II score, showed the perceived quality of life relative to PCS was significantly related to both disease duration (ß = -0.55, p = 0.03, SE = 0.25) and HAM-A scores (ß = -0.52, p = 0.04, SE = 0.24). Moreover, both HAM-A (ß = -0.67, p = 0.01, SE = 0.26) and BDI-II (ß = -0.48, p = 0.02, SE = 0.20) scores were independently predictive of MCS. Metabolic control, instead, was not a significant predictor. CONCLUSION: Our study suggests a predictive role of both anxiety levels and time since diagnosis in perceived HRQoL in T2DM patients. PCS was associated with anxiety and time since diagnosis and MCS was associated with anxiety and depressive symptoms but not with diabetes duration or metabolic control. These data could be useful to plan T2DM training programs focused on psychological health concerns, possibly leading to a healthy self-management and a better perceived HRQoL, even assisting patients in reducing the negative effect due to the chronicization of T2DM.

Natural history and risk factors for diabetic kidney disease in patients with T2D: lessons from the AMD-annals.

The Associazione Medici Diabetologi (AMD) annals initiative is an ongoing observational survey promoted by AMD. It is based on a public network of about 700 Italian diabetes clinics, run by specialists who provide diagnostic confirmation and prevention and treatment of diabetes and its complications. Over the last few years, analysis of the AMD annals dataset has contributed several important insights on the clinical features of type-2 diabetes kidney disease and their prognostic and therapeutic implications. First, non-albuminuric renal impairment is the predominant clinical phenotype. Even though associated to a lower risk of progression compared to overt albuminuria, it contributes significantly to the burden of end-stage renal disease morbidity. Second, optimal blood pressure control provides significant but incomplete renal protection. It reduces albuminuria but there may be a J curve phenomenon with eGFR at very low blood pressure values. Third, hyperuricemia and diabetic hyperlipidemia, namely elevated triglycerides and low HDL cholesterol, are strong independent predictors of chronic kidney disease (CKD) onset in diabetes, although the pathogenetic mechanisms underlying these associations remain uncertain. Fourth, the long-term intra-individual variability in HbA1c, lipid parameters, uric acid and blood pressure plays a greater role in the appearance and progression of CKD than the absolute value of each single variable. These data help clarify the natural history of CKD in patients with type 2 diabetes and provide important clues for designing future interventional studies.

Multiple fractures and impaired bone metabolism in Wolfram syndrome: a case report.

Wolfram Syndrome (WS) is a rare and lethal disease characterized by optic atrophy, diabetes mellitus, diabetes insipidus, and hearing loss. To date, osteoporotic related fractures have not been reported in affected patients. Here, we describe the case of a man affected by WS complicated by several bone fragility fractures. A 50-year-old Caucasian man was hospitalized because of tibia and fibula fractures. His clinical features included diabetes mellitus, diabetes insipidus, optic atrophy and deafness that were consistent with an unrecognized WS diagnosis, which was confirmed by the identification of a specific mutation in gene WFS1 encoding wolframin. Bone mineral density by phalangeal quantitative ultrasound demonstrated severe osteoporosis, with high serum levels of surrogate markers of bone turn-over. Previously unidentified rib fractures were also detected. To the best of our knowledge, this is the first report of osteoporotic related fractures in a patient affected by WS. Although no effective treatments are currently available to delay the progression of the disease, this case report suggests to evaluate fracture risk in the diagnostic work-up of WS.

Visceral adiposity index as an indicator of cardiometabolic risk in patients treated for craniopharyngioma.

PURPOSE: Craniopharyngioma is associated with metabolic alterations leading to increased cardiovascular mortality. Recently, the visceral adiposity index has been proposed as a marker of visceral adipose tissue dysfunction and of the related cardiometabolic risk. The role of the visceral adiposity index has never been explored in craniopharyngioma patients. We assessed the cardiometabolic risk on the basis of the visceral adiposity index in craniopharyngioma patients. METHODS: We evaluated data of 24 patients treated for craniopharyngioma in a single-centre. We investigated the relationship among patients' clinical and biochemical features, cardiovascular risk -assessed by the Framingham and the atherosclerotic cardiovascular disease risk scores-, visceral adiposity index and adipose tissue dysfunction severity. RESULTS: Increased visceral adiposity index was found in 8 patients (33%). Adipose tissue dysfunction resulted to be severe, moderate or mild in 5, 2 and 1 cases. Increased visceral adiposity index significantly correlated with the occurrence of metabolic syndrome (p 0.027), IRI (p 0.001), triglycerides (p < 0.001), HOMA-IR (p < 0.001) and with lower ISI-Matsuda (p 0.005) and HDL-cholesterol (p < 0.001). Higher degree of adipose tissue dysfunction associated with increased insulin resistance. No gender difference was found for visceral adiposity index, adipose tissue dysfunction severity, and cardiovascular risk scores. Patients with adulthood onset craniopharyngioma showed higher Framingham risk score (p 0.004), atherosclerotic cardiovascular disease 10-year (p < 0.001) and lifetime (p 0.018) risk scores than those with childhood onset disease. CONCLUSIONS: Visceral adiposity index is increased in one third of our patients with craniopharyngioma, even if metabolic syndrome does not occur. Increased visceral adiposity index and adipose tissue dysfunction severity correlate with insulin sensitivity parameters, do not correlate with Framingham or atherosclerotic cardiovascular disease risk scores, and are not influenced by gender and age of disease onset.

Clinical correlates of persistently elevated liver enzymes in type 2 diabetic outpatients.

AIMS: To evaluate the prevalence and the clinical implication of persistently elevated liver enzymes in diabetic subjects, with no evidence of viral hepatitis infection or alcohol abuse. METHODS: Clinical, lifestyle, anthropometric data and laboratory test values were collected in 916 type 2 diabetic subjects, examined for alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltranspeptidase (γ-GT) levels at two different time points. RESULTS: Five hundred forty four patients (59.4%) showed normal (NLT group) and 182 (19.9%) persistently elevated (ELT group) liver tests in both determinations. ELT patients were prevalently men (P=0.016), younger (P<0.0001) and with a lower duration of diabetes (P=0.008). Adjusting for age and sex, ELT subjects had significantly higher BMI (P<0.001), waist circumference (P=0.010), systolic (P=0.017) and diastolic blood pressure (P<0.001), and higher levels of fasting blood glucose (P=0.023), and triglycerides (P<0.0001). Current hypoglycemic and/or hypolipidemic drugs were comparable between the two groups. At multivariate analysis, male gender (OR=3.017, P=0.012), worse metabolic control (HbA1c, OR=1.408, P=0.017), and a younger age (OR=1.054, P=0.007) predicted the presence of persistently elevated liver enzymes. CONCLUSIONS: Persistently elevated liver enzymes are a common finding in outpatient type 2 diabetic subjects, particularly in young men with suboptimal metabolic control and with the features of metabolic syndrome. The persistence of abnormal liver tests may be of potential utilization in clinical practice for the screening of patients at high risk of NAFLD.

Mild hyperhomocysteinemia, C677T polymorphism on methylenetetrahydrofolate reductase gene and the risk of macroangiopathy in type 2 diabetes: a prospective study.

The role of hyperhomocysteinemia as a risk factor for diabetic long-term complications has not been sufficiently evaluated in prospective studies, considering specific correlates of homocysteine (tHcy) concentration and traditional cardiovascular disease (CVD) risk factors. Fasting tHcy, vitamin B12 and folate plasma levels, the common methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism, as well as clinical and lifestyle information were assessed in 216 type 2 diabetic patients attending two outpatient clinics, who had a follow-up evaluation at 65 ± 9 months for the incidence of macroangiopathy. At basal evaluation, mild hyperhomocysteinemia (tHcy ≥ 15 µmol/l) was diagnosed in 21.3% of participants. At follow-up, hyperhomocysteinemia and the distribution of MTHFR C677T genotype did not significantly differ according to the incidence of macroangiopathy. Multiple variables adjusted ORs (95% CI) for CVD associated with mild hyperhomocysteinemia were 1.01 (0.37-2.82); P > 0.05; those associated with MTHFR TT genotype were 0.46 (0.15-1.38); P > 0.05. Although the prevalence of hyperhomocysteinemia was higher in diabetic men (26.9%) than in women (16.1%; P > 0.05), similar results were also observed in a separate sex-analysis. At the multivariate analysis, including in the model other potential CVD risk factors, only creatinine clearance was a significant risk factor for the development of macroangiopathy. In this cohort of diabetic subjects, mild hyperhomocysteinemia and the MTHFR TT genotype are not significant risk factors for the development of macroangiopathy; impaired renal function was confirmed as a significant predictor of this complication.