Hospitalisation for herpes zoster in people with and without diabetes: A 10-year-observational study.

AIMS: This study explores the association between Herpes Zoster (HZ) hospitalizations and diabetes in Piedmont, Italy from 2010 to 2019. Focusing on the burden of HZ hospitalizations in diabetic and non-diabetic groups, it aims to identify risk factors in diabetics to enhance prevention strategies. METHODS: In a two-phase study, we first compared age-standardized HZ hospitalization rates between diabetic and non-diabetic individuals from 2010 to 2019. We then examined hospitalization risk factors for HZ within a diabetic patient cohort managed by regional diabetes clinics. RESULTS: Of 3,423 HZ hospitalizations in 2010-2019, 17.9 % (613 cases) were diabetic patients, who exhibited higher hospitalization rates (15.9 to 6.0 per 100,000) compared to non-diabetese individuals. Among diabetics subjects risk factors for HZ hospitalization included age over 65, obesity (BMI > 30), and poor glycemic control (HbA1c > 8.0 %). These patients had a 40 % increased rehospitalization risk and a 25 % higher risk of severe complications, such as stroke and myocardial infarction, post-HZ. CONCLUSIONS: Diabetes markedly increases HZ hospitalization rates, rehospitalization, and complication risks. These findings underscore the need for preventive strategies, especially improved glycemic control among high-risk diabetic patients, to inform public health policies and clinical practices aimed at mitigating HZ's impact on this population.

Hepatocellular carcinoma in a large cohort of type 2 diabetes patients.

AIMS: To elucidate the current burden of hepatocellular carcinoma (HCC) in type 2 diabetes (DM2) with a focus on the associated clinical determinants. METHODS: Incidence of HCC between 2009 and 2019 in the diabetic and general population was calculated from regional administrative and hospital databases. Potential determinants of the disease were evaluated with a follow-up study. RESULTS: In the DM2 population, the incidence resulted in 8.05 cases per 10,000 yearly. This rate was three times higher than that of the general population. 137,158 patients with DM2 and 902 HCC were found for the cohort study. The survival of HCC patients was 1/3 of that of cancer-free diabetic controls. Age, male sex, alcohol abuse, previous viral hepatitis B and C, cirrhosis, low platelet count, elevated GGT/ALT, higher BMI and HbA1c levels were associated with HCC occurrence. Diabetes therapy was not adversely associated with HCC development. CONCLUSION: Incidence of HCC in DM2 is more than tripled compared to the general population with high mortality. These figures are higher than those expected from the previous evidence. In parallel with known risk factors for liver disease, such as viruses and alcohol, insulin-resistance characteristics are associated with a higher probability of HCC.

Hepatic fibrosis of any origin in a large population of type 2 diabetes patients.

BACKGROUND AND AIMS: Excess morbidity and mortality from chronic liver disease in type 2 diabetes (T2DM) is recognized; however, the clinical features associated with liver fibrosis (LF) of any origin are poorly known. Metabolic status and/or coexisting complications over time may play a role. METHODS AND RESULTS: We interrogated the database of the diabetes unit network of Piedmont (Italy) (71,285 T2DM patients) and calculated a fibrosis-4 score (FIB-4) from data recorded between 2006 and 2019. Comorbidities were obtained by linkage with hospital data. The study population was subdivided by aetiology of LF (alcoholic, viral, metabolic). Associations between upper level of FIB-4 and demographic and clinical variables were evaluated separately for each group using robust Poisson models and presented as prevalence ratios. Nearly one-quarter (24%) of T2DM patients had some form of LF: viral (0.44%) and alcoholic (0.53%) forms were far less frequent than metabolic ones (22.7%). Only 1 out of 5 of these patients had a history of known cirrhosis. Age, male sex, duration of diabetes, coronary disease, hyperuricemia, renal failure, and features of liver failure (e.g., lower body-mass index, lipid and HbA1c levels) were positively associated with metabolic LF. More intensive treatments with insulin and segretagogue emerged as a significant predictive indicators of LF of metabolic origin. CONCLUSION: A sizeable proportion of T2DM patients has some degree of LF, mainly of metabolic origin and often undiagnosed. There is a need to clarify whether the link between insulin therapy and advanced LF is causal or not.

From swab testing to health outcomes within the T2DM population: Impact of diabetes background on COVID19 progression.

BACKGROUND: We aimed to study the impact of diabetes background on COVID-19 progression from swab testing to health outcomes in type 2 diabetes (T2DM). METHODS: From the database of the diabetes units of Piedmont-Italy we extracted records of T2DM patients, which were linked with the swab-testing-database, and the database of hospital discharges. Five outcomes (PCR testing, PCR testing positivity, hospitalization, Intensive Care Unit (ICU), death) were evaluated using robust Poisson models. RESULTS: Among 125,021 T2DM patients, 1882 had a positive PCR test. Of these patients, 49.4% were hospitalized within 30 days, 11.8% were admitted to an ICU, and 27.1% died. Greater probability of death was associated with age, male sex, liver and renal impairment, Hba1c above 8%, and former smoking. Hospitalization and ICU admission were mainly affected by age, male sex, hypertension, and metabolic control. Notably, ICU admissions were reduced in very elderly people. No outcomes were associated with educational level. CONCLUSIONS: Hospitalization and ICU admission are heavily affected by age and local triage policy. A key finding was that men who were > 75 years old and poorly compensated were highly vulnerable patients. Renal and/or hepatic impairment are additional factors. This information may be useful for addressing intervention priorities.

Incretin-based therapy and risk of cholangiocarcinoma: a nested case-control study in a population of subjects with type 2 diabetes.

BACKGROUND AND AIMS: One cohort and several basic science studies have raised suspicion about an association between incretin therapies and cholangiocarcinoma. Our aim was to verify the occurrence of CC in relation to incretin-based medication use versus any antidiabetic treatment in an unselected population of diabetic patients. METHODS: A population-based matched case-control study was conducted using administrative data from the Region of Piedmont (4,400,000 inhabitants), Italy. From a database of 312,323 patients treated with antidiabetic drugs, we identified 744 cases hospitalized for cholangiocarcinoma from 2010 to 2016 and 2976 controls matched for gender, age and initiation of antidiabetic therapy; cases and controls were compared for exposure to incretin-based medications. All analyses were adjusted for risk factors for CC, as ascertained by hospital discharge records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by fitting a conditional logistic model. RESULTS: The mean age of the sampled population (cases and controls, 75 years) was very high, with no gender prevalence. Five per cent was treated with incretin-based medications. After adjusting for possible confounders, we found no increased risk of cholangiocarcinoma associated with the use of either DPP4i (OR 0.98, 95% CI 0.75-1.29: p = 0.89) or GLP-1-RA (OR 1.09, 95% CI 0.63-1.89; p = 0.76) in the 24 months before hospital admission. Neither the duration of the therapy nor the dose modified the risk of cholangiocarcinoma. CONCLUSIONS: Our findings suggest that, in an unselected population, the use of both classes of incretin-based medications is not associated with an increased risk of cholangiocarcinoma.

Ten-year comparative analysis of incidence, prognosis, and associated factors for dialysis and renal transplantation in type 1 and type 2 diabetes versus non-diabetes.

AIMS: To study the incidence of and the factors associated with renal dialysis and transplantation in type 1 (T1DM) and type 2 diabetes (T2DM). METHODS: Data on individuals who had received dialysis treatment or renal transplant between 1 January 2004 and 31 December 2013 were extracted from the regional administrative database (Piedmont, Italy), and the crude (cumulative) incidence of dialysis was calculated. Overall cumulative survival was estimated using the Kaplan-Meier method and compared using the log-rank test. Poisson regression was used to estimate adjusted rate ratios for potential predictors of renal transplant or death. RESULTS: A total of 7401 persons started dialysis treatment during the decade, with a 10-year cumulative crude incidence of 16.8/100,000. Incidence was stable and consistently eightfold higher in persons with T2DM (tenfold higher in T1DM) compared to those without diabetes. The risk of dialysis in T1DM was about double that of T2DM. The mortality rate was significantly higher in diabetics than in non-diabetes (241.4/1000 vs. 153.99/1000 person-years). During the decade 2004-2013, 893 patients underwent a kidney transplant. Transplantation rates were significantly lower for diabetics than non-diabetics (16.5/1000 vs. 42.9/1000 person-years). CONCLUSIONS: In the past decade, the incidence of dialysis has stabilized in both the general population and in diabetics in whom it remains far higher by comparison. Also mortality rates are higher, with a worse prognosis for T1DM. Diabetes poses a barrier to allotransplantation, and efforts should be made to overcome this limitation.

Trend over time in hepatic fibrosis score in a cohort of type 2 diabetes patients.

AIMS: The prevalence and progression of hepatic fibrosis and its correlated factors in type 2 diabetes (T2DM) are poorly known. We aimed to define the percentage of T2DM patients who progress to fibrosis and the factors associated with disease progression. METHODS: Data from the electronic health records of 1527 patients with diagnosed T2DM and nonalcoholic fatty liver disease (NAFLD), as diagnosed by the Fatty Liver Index, were extracted from the AMD Annals database, which collects data from the Italian network of diabetes clinics. For the main analysis, we evaluated variables associated with Fibrosis 4 [FIB-4] score at baseline and at 3-year follow-up to determine their role in predicting FIB-4 at 3 years and the risk of hepatic fibrosis in T2DM. RESULTS: High-risk of advanced fibrosis was detected in 13.1% of patients at baseline and in 18.1% at 3 years, LDL cholesterol, and body-mass index, correlated negatively with baseline FIB-4 scores, whereas gamma glutamil transerasi correlated positively . The FIB-4 score at 3 years was associated with lower values of baseline renal function, LDL, and BMI; however, the baseline FIB-4 score was the strongest predictor for the FIB-4 score at 3 years. CONCLUSIONS: The prevalence of and progression to hepatic fibrosis within 3 years in patients with T2DM is not negligible. Patients with a higher likelihood of liver scarring differ from those with hepatic steatosis. Differently from NAFLD, the FIB-4 score is inversely correlated with insulin resistance and appears to increase independent of classic metabolic factors.

Prevalence, incidence and associated comorbidities of treated hypothyroidism: an update from a European population.

OBJECTIVE: Estimates of the prevalence of hypothyroidism in unselected populations date from the late 1990s. We present an update on the prevalence and incidence of overt hypothyroidism in Piedmont, northwest Italy and examine the association between hypothyroidism and multiple chronic comorbidities. DESIGN AND METHODS: Data were obtained from drug prescription and hospital discharge databases. Individuals who had received at least two levothyroxine prescriptions in 2012 were defined as having hypothyroidism; those who had undergone thyroidectomy or I131 irradiation in the previous 5 years were defined as having iatrogenic hypothyroidism and those who had either obtained exemption from treatment co-payment or had been discharged from hospital with a chronic comorbidity (diabetes and connective tissue diseases) were identified as having one of these conditions. RESULTS: The overall crude prevalence was 31.1/1000 (2.3/1000 for iatrogenic hypothyroidism) and the overall crude incidence was 7/1000. The average daily dose of thyroxine (122 µg) roughly corresponded to 1.7 µg/kg. There was a strong association between hypothyroidism and diabetes (type 1, type 2 or gestational) and with autoimmune diseases, with the odds ratio ranging from 1.43 (1.02-1.99) for psoriatic arthritis to 4.99 (3.06-8.15) for lupus erythematosus. CONCLUSIONS: As compared with previous estimates, the prevalence of hypothyroidism rose by about 35%, driven mainly by non-iatrogenic forms. The increase may be due to either population aging or improved diagnostic capability or both. The frequent co-occurrence of hypothyroidism with other multiple chronic conditions characterizes it more as a comorbidity rather than an isolated chronic disease.

Hospitalisation for heart failure and mortality associated with dipeptidyl peptidase 4 (DPP-4) inhibitor use in an unselected population of subjects with type 2 diabetes: a nested case-control study.

OBJECTIVE: The SAVOR TIMI-53 study reported a significant increase in the risk of hospitalisation for heart failure (HF) in patients treated with a DPP-4 inhibitor (DPP-4i) in comparison with placebo. A recent case-control study in part confirmed this risk signal. Our aim was to compare the occurrence of HF in relation to DPP-4i use versus any antidiabetic treatment. DESIGN: Population-based matched case-control study conducted using administrative data. SETTING: The Italian Region of Piedmont (4.4 million inhabitants). PARTICIPANTS: From a database of 282,000 patients treated with antidiabetic drugs, we identified 14,613 hospitalisations for HF, 7212 incident cases, and 1727 hospital re-admissions between 2008 and 2012; each case was matched for gender, age and antidiabetic therapy with 10 controls; cases and controls were compared for exposure to DPP-4i. OUTCOME MEASURES: ORs and 95% CIs were calculated by fitting a conditional logistic model. All analyses were adjusted for available risk factors for HF. RESULTS: We found no increased risk of hospitalisation for HF associated with the use of DPP-4i (OR for admission for HF 1.00 (0.94 to 1.07), incident HF1.01 (0.92 to 1.11), recurrent HF 1.02 (0.84 to 1.22)). All-cause mortality was 6% lower in DPP-4i users (p<0.001), whereas insulin users showed an excess of risk for any type of hospital admission (19%) and death (20%) (p<0.001). CONCLUSIONS: Our findings suggest that, in an unselected population of diabetic patients, the use of DPP-4i is not associated with an increased risk of HF. The favourable impact on all-cause mortality should be viewed with caution and also other explanations investigated.

Incretin therapies and risk of hospital admission for acute pancreatitis in an unselected population of European patients with type 2 diabetes: a case-control study.

BACKGROUND: Previous studies have yielded conflicting results about the association between incretin therapies and acute pancreatitis. We aimed to compare the occurrence of acute pancreatitis in a population of patients with type 2 diabetes who received incretins compared with those who received other antidiabetic treatment. METHODS: In our population-based matched case-control study, we extracted information from an administrative database from Piedmont, Italy (containing data for 4·4 million inhabitants). From a dataset of 282,429 patients receiving treatment with antidiabetic drugs for type 2 diabetes, we identified 1003 cases older than 41 years who had been admitted to hospital for acute pancreatitis between Jan 1, 2008, and Dec 31, 2012, and 4012 controls who were matched for sex, age, and time of start of antidiabetic therapy. We compared incretin exposure in cases and controls with a conditional logistic regression model, expressed as odds ratios (ORs [95% CI]). We adjusted all analyses for risk factors of acute pancreatitis, as ascertained by hospital discharge records, and concomitant use of metformin or glibenclamide. FINDINGS: The mean age of cases and controls (72·2 years [SD 11·1]) was high, as expected in an unselected diabetic population in Europe. After adjustment for available confounders, use of incretins in the 6 months before hospital admission was not associated with increased risk of acute pancreatitis (OR 0·98, 95% CI 0·69-1·38; p=0·8958). INTERPRETATION: Our findings suggest that, in an unselected population, use of incretins is not associated with an increased risk of acute pancreatitis. Larger studies are needed to clarify whether age or type of incretin therapy could affect the risk of acute pancreatitis in patients with type 2 diabetes. FUNDING: Chaira Medica Association, Chieri, Italy.

Pharmacokinetics, safety, and efficacy of DPP-4 inhibitors and GLP-1 receptor agonists in patients with type 2 diabetes mellitus and renal or hepatic impairment. A systematic review of the literature.

Renal or hepatic impairment, often encountered in patients with type 2 diabetes, influences the pharmacokinetics and bioavailability of antihyperglycemic agents. An emerging concern is whether pharmacotherapy with incretin-based agents, the most recent drug classes to be introduced for type 2 diabetes, can be safely used in patients with renal insufficiency or hepatic damage. This literature review examines the results of studies on these novel drug classes, with a view to provide the practitioner with a balanced, evidence-based position when considering incretin-based therapies in patients with type 2 diabetes and impaired kidney or liver function. All currently available dipeptidyl peptidase-4 (DPP-4) inhibitors appear to be appropriate pharmacotherapeutic choices in patients with declining renal function, with linagliptin affording the added advantage of not requiring dose adjustment or periodic monitoring of drug-related kidney function. In contrast, caution is warranted with the use of glucagon-like peptide-1 (GLP-1) receptor agonists in patients with moderate or severe renal impairment. The slightly wider evidence base for liraglutide than for exenatide or lixisenatide is not sufficient to support its use in severe renal impairment. What little evidence there is for incretin-based therapies in hepatic impairment has come from a few past hoc analysis of clinical trials, with most precautions and warnings reflecting the paucity of knowledge about incretin efficacy or safety in this condition.

The impact of adherence to screening guidelines and of diabetes clinics referral on morbidity and mortality in diabetes.

Despite the heightened awareness of diabetes as a major health problem, evidence on the impact of assistance and organizational factors, as well as of adherence to recommended care guidelines, on morbidity and mortality in diabetes is scanty. We identified diabetic residents in Torino, Italy, as of 1st January 2002, using multiple independent data sources. We collected data on several laboratory tests and specialist medical examinations to compare primary versus specialty care management of diabetes and the fulfillment of a quality-of-care indicator based on existing screening guidelines (GCI). Then, we performed regression analyses to identify associations of these factors with mortality and cardiovascular morbidity over a 4 year-follow-up. Patients with the lowest degree of quality of care (i.e. only cared for by primary care and with no fulfillment of GCI) had worse RRs for all-cause (1.72 [95% CI 1.57-1.89]), cardiovascular (1.74 [95% CI 1.50-2.01]) and cancer (1.35 [95% CI 1.14-1.61]) mortality, compared with those with the highest quality of care. They also showed increased RRs for incidence of major cardiovascular events up to 2.03 (95% CI 1.26-3.28) for lower extremity amputations. Receiving specialist care itself increased survival, but was far more effective when combined with the fulfillment of GCI. Throughout the whole set of analysis, implementation of guidelines emerged as a strong modifier of prognosis. We conclude that management of diabetic patients with a pathway based on both primary and specialist care is associated with a favorable impact on all-cause mortality and CV incidence, provided that guidelines are implemented.