Microvascular complications burden (nephropathy, retinopathy and peripheral polyneuropathy) affects risk of major vascular events and all-cause mortality in type 1 diabetes: a 10-year follow-up study.

BACKGROUND: Microvascular complications (MC) have been claimed to increase the risk for cardiovascular disease in diabetic subjects. However, the effect of MC burden on the risk of major vascular outcomes and all-cause mortality in type 1 diabetes is still poorly explored. We evaluated the relationship between microvascular complications burden and incidence of major cardiovascular events and all-cause mortality in subjects with type 1 diabetes. METHODS: We recruited 774 participants with type 1 diabetes in a single-center observational study over a follow-up of 10.8 ± 2.5 years. Hazard ratios (HR) for cardiovascular outcomes and all-cause death associated with microvascular complications were determined by unadjusted and adjusted Cox regression analysis. RESULTS: Out of 774 individuals, 54.9% had no-MC, 32.3% 1 MC, 9.7% 2 MC and 3.1% 3 MC. A total of 54 deaths (7.0%) occurred. Death rate increased from no-MC 2.1% (Ref) to 1 MC 7.2% (HR 3.54 [95% CI 1.59-7.87]), 2 MC 14.7% (HR 6.41 [95% CI 2.65-15.49]) and 3 MC 66.7% (HR 41.73 [95% CI 18.42-94.57], p < 0.0001). After adjustments, HRs were: 1 MC 2.05 (95% CI 0.88-4.76), 2 MC 1.98 (95% CI 0.75-5.21), 3 MC 7.02 (95% CI 2.44-20.20, p = 0.002). Forty-nine subjects (6.7%) had at least one cardiovascular event, and cumulative incidence went from no-MC 2.2% (Ref) to 1 MC 5.0%; (HR 2.27 [95% CI 0.96-5.38]), 2 MC 26.8% (HR 12.88 [95% CI 5.82-28.50]) and 3 MC 40.9% (HR 29.34 [95% CI 11.59-74.25], p < 0.0001). Upon adjustments, HRs were: 1 MC 1.59 (95% CI 0.65-3.88), 2 MC 4.33 (95% CI 1.75-10.74), 3 MC 9.31 (95% CI 3.18-27.25, p < 0.0001). Thirty-five individuals (4.8%) had at least one coronary event, which cumulative incidence increased with MC burden (p < 0.0001). CONCLUSIONS: In type 1 diabetes, microvascular complications burden increases in an independent dose-dependent manner the risk of major cardiovascular outcomes and all-cause mortality. The presence and number of microvascular complications should be considered in stratifying overall cardiovascular risk in type 1 diabetes.

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.

Type 1 diabetes and COVID-19: The "lockdown effect".

AIMS: The aim of this study was to evaluate the effect the lockdown imposed during COVID-19 outbreak on the glycemic control of people with Type 1 diabetes (T1D) using Continuous (CGM) or Flash Glucose Monitoring (FGM). MATERIALS AND METHODS: We retrospectively analyzed glucose reading obtained by FGM or CGM in T1D subjects. Sensor data from 2 weeks before the lockdown (Period 0, P0), 2 weeks immediately after the lockdown (period 1, P1), in mid-lockdown (Period 2, P2) and immediately after end of lockdown (Period 3, P3) were analyzed. RESULTS: The study included 63 T1D patients, (FGM: 52, 82%; CGM:11, 18%). Sensor use (91%) were slightly reduced. Despite this reduction, Time in Range increased in P1 (62%), P2 (61%) and P3 (62%) as compared to P0 (58%, all p < 0.05 or less) with concomitant reduction in the Time Above Range (P0: 38%; P1: 34%, P2: 34%, P3: 32%, all p < 0.05 or less vs. P0). Average glucose and GMI improved achieving statistical difference in P3 (165 vs. 158 mg/dl, p = 0.040 and 7.2% (55 mmol/mol) vs. 7.0% (53 mmol/mol), p = 0.016) compared to P0. Time Below Range (TBR) and overall glucose variability remained unchanged. Bi-hourly analysis of glucose profile showed an improvement particularly in the early morning hours. CONCLUSIONS: In T1D subjects with good glycemic control on CGM or FGM, the lockdown had no negative impact. Rather a modest but significant improvement in glycemic control has been recorded, most likely reflecting more regular daily life activities and reduces work-related distress.

Hyperglycemia at Hospital Admission Is Associated With Severity of the Prognosis in Patients Hospitalized for COVID-19: The Pisa COVID-19 Study.

OBJECTIVE: To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: Hospitalized COVID-19 patients (N = 271) were subdivided based on at-admission glycemic status: 1) glucose levels <7.78 mmol/L (NG) (N = 149 [55.0%]; median glucose 5.99 mmol/L [range 5.38-6.72]), 2) known diabetes mellitus (DM) (N = 56 [20.7%]; 9.18 mmol/L [7.67-12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N = 66 [24.3%]; 8.57 mmol/L [8.18-10.47]). RESULTS: Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27-3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92-3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03-3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46-8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91-5.96, P = 0.079) vs. Q1. CONCLUSIONS: Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.

The beneficial effects of pancreas transplant alone on diabetic nephropathy.

OBJECTIVE: Pancreas transplant alone can be effective in significantly improving the quality of life of type 1 diabetic patients, and it can also eliminate acute diabetes complications, such as hypoglycemic and/or hyperglycemic episodes. The effects of pancreas transplant alone on long-term complications of diabetes, including nephropathy, are still not settled. We evaluated whether restoration of long-lasting normoglycemia by pancreas transplant alone might have beneficial action on diabetic nephropathy. RESEARCH DESIGN AND METHODS: A total of 32 type 1 diabetic patients were evaluated before and 1 year after successful pancreas transplant alone, together with 30 matched nontransplanted type 1 diabetic subjects. Several metabolic and kidney function parameters were measured, including plasma glucose, glycohemoglobin (A1C), C-peptide, plasma lipids, blood pressure, creatinine, creatinine clearance, and urinary protein excretion. RESULTS: Pancreas transplant alone restored sustained normoglycemia, without exogenous insulin administration, and improved plasma lipid levels. Blood pressure decreased significantly. Creatinine concentrations and clearances did not differ before and after transplantation. Urinary protein excretion decreased significantly after pancreas transplant alone, with four microalbuminuric and three macroalbuminuric patients who became normoalbuminuric. None of these changes occurred in the nontransplanted group. CONCLUSIONS: Successful pancreas transplant alone, through restoration of sustained normoglycemia, improves diabetic nephropathy in type 1 diabetic patients.

Pancreas transplant alone determines early improvement of cardiovascular risk factors and cardiac function in type 1 diabetic patients.

BACKGROUND: The effects of pancreas transplant alone (PTA) on cardiovascular risk factors (CRF) and cardiac function in type 1 diabetes mellitus (T1DM) patients are still unsettled. METHODS: We studied 13 T1DM patients who received PTA with portal drainage and 11 matched control patients. Parameters of glucose and lipid metabolism and several additional classic CRF were assessed before and up to 6 months posttransplant. Cardiac morphology and function were assessed by Doppler echocardiographic examination. RESULTS: Insulin independence was promptly achieved and then maintained after PTA. Total and low-density lipoprotein cholesterol levels were significantly lower after transplantation, whereas high-density lipoprotein cholesterol and triglyceride concentrations did not change. Both systolic and diastolic blood pressure values and fibrinogen levels improved significantly. In addition, PTA determined a significant amelioration of several morphologic and functional cardiac indices. None of the measured parameters changed in the control patients. CONCLUSIONS: PTA with portal drainage induces an early improvement of CRF and ameliorates cardiac function in patients with T1DM.

Long-term (5 years) efficacy and safety of pancreas transplantation alone in type 1 diabetic patients.

BACKGROUND: Although combined pancreas and kidney transplantation is an established procedure for the treatment of type 1 diabetes (T1D) in patients with end-stage renal disease, the role of pancreas transplant alone (PTA) in the therapy of T1D subjects with preserved kidney function is still matter of debate. METHODS: We report our single-center experience of PTA in 71 consecutive T1D patients all with a posttransplant follow-up of 5 years. Patient and pancreas (normoglycemia in the absence of any antidiabetic therapy) survivals were determined, and several clinical parameters (including risk factors for cardiovascular diseases) were assessed. Cardiac evaluation and Doppler echocardiographic examination were also performed, and renal function and proteinuria were evaluated. RESULTS: Actual patient and pancreas survivals at 5 years were 98.6% and 73.2%, respectively. Relaparotomy was needed in 18.3% of cases. Restoration of endogenous insulin secretion was accompanied by sustained normalization of fasting plasma glucose concentrations and HbA1c levels as well as significant improvement of total cholesterol, low-density lipoprotein-cholesterol, and blood pressure. An improvement of left ventricular ejection fraction was also observed. Proteinuria (24 hours) decreased significantly after transplantation. One patient developed end-stage renal disease. In the 51 patients with sustained pancreas graft function, kidney function (serum creatinine and glomerular filtration rate) decreased over time with a slower decline in recipients with pretransplant glomerular filtration rate less than 90 mL/min. CONCLUSIONS: PTA was an effective and reasonably safe procedure in this single-center cohort of T1D patients.

Results of pancreas transplantation alone with special attention to native kidney function and proteinuria in type 1 diabetes patients.

We report on our single-center experience with pancreas transplantation alone (PTA) in 71 patients with type 1 diabetes, and a 4-year follow-up. Portal insulin delivery was used in 73.2% of cases and enteric drainage of exocrine secretion in 100%. Immunosuppression consisted of basiliximab (76%), or thymoglobulin (24%), followed by mycophenolate mofetil, tacrolimus, and low-dose steroids. Actuarial patient and pancreas survival at 4 years were 98.4% and 76.7%, respectively. Relaparatomy was needed in 18.3% of patients. Restored endogenous insulin secretion resulted in sustained normalization of fasting plasma glucose levels and HbA1c concentration in all technically successful transplantations. Protenuria (24-hour) improved significantly after PTA. Renal function declined only in recipients with pretransplant glomerular filtration rate (GFR) greater than 90 ml/min, possibly as a result of correction of hyperfiltration following normalization of glucose metabolism. Further improvements were recorded in several cardiovascular risk factors, retinopathy, and neuropathy. We conclude that PTA was an effective and reasonably safe procedure in this single-center experience.

Effects of pancreas-kidney transplantation on diabetic retinopathy.

The effects of pancreas transplantation (PTx) on diabetic retinopathy (DR) are still debated. We studied the course of DR in 48 patients (age: 40 +/- 7 years; males/females 26/22, body mass index (BMI): 23.0 +/- 2.4 kg/m2, duration of diabetes: 24 +/- 8 years) bearing a successful PTx (combined with a kidney). Follow-up ranged 6-60 months (median: 17 months). Before transplantation, according to the Eurodiab Study classification, 12 patients (25%) had nonproliferative retinopathy (NPDR; mild, moderate or severe), and 36 patients (75%) had laser-treated and/or proliferative retinopathy (LT/PDR). During the follow-up, in the NPDR group improvement/deterioration was defined as regression/progression to a lower/higher retinopathy grade; in the LT/PTD group, stabilization was defined as no new neo-vessel formation or development of new lesions requiring laser-treatment. In the NPDR group, five (41.7%) patients improved of one or more lesion grading, three (25%) patients showed no change, and four (33.3%) patients progressed of one grade. In the LT/PDR group, the post-transplant data were: stabilization in 35 (97%) patients, and worsening in one (3%) patient. The number of improved/stabilized patients was significantly higher in the transplanted than in a control group of nontransplanted type 1 diabetic patients. In conclusion, despite a relatively short follow-up period, successful PTx in our cohort of patients was associated with improvement and/or stabilization of DR in the majority of recipients.