A psycho-educational intervention for the prevention of foot lesions in people with diabetes: Report of a clinical audit.

BACKGROUND AND AIMS: Motivational approaches may help target the psychological aspects of self-care, improving adherence to good practices in individuals with diabetes. The present study was designed to test the feasibility and effectiveness of a psychoeducational program for diabetic foot prevention or disease progression. METHODS AND RESULTS: Eighty-one subjects with or at high risk of foot ulcer development entered a program consisting of six 120-min group sessions, conducted by a podiatrist and an expert in psycho-education. Occurrence/recurrence of lesions in a 3-year follow-up was compared with 172 cases with similar risk score (IWGDF score 2019), receiving education at any 6-month podiatric visit (standard-of-care). Motivation to self-care and competence were assessed by specific questionnaires. The experimental program increased adherence to follow-up. The prevalence of foot lesions was higher at baseline and was remarkably reduced at any time-point in patients attending the psychoeducational program, whereas it remained relatively stable in standard care (around 10% of cases). The cumulative incidence was lower in the psychoeducational program (13.2, 95% CI 9.2-18.0 per 100 patient-year vs. 26.1; 95% CI 22.1-30.2); time to new lesions was increased (P = 0.022). Cox proportional hazard analysis confirmed an overall reduction of lesions in the psychoeducational program (HR 0.34; 95% CI 0.18-0.66; P < 0.001), after adjustment for confounders. The program was associated with significant changes in competence and motivation to self-care. CONCLUSION: A psychoeducational approach is both feasible and effective to support patients with diabetes at high risk of first or recurrent foot lesions, increasing their adherence to self-care practices.

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.

Estimating the risk of severe hypoglycemic event related to glucose-lowering treatment among Italian patients with diabetes: the HYPOTHESIS database.

The primary objective of this study was to estimate 1) the annual risk of undergoing a severe hypoglycemic event in Italian patients with diabetes and 2) the risk of hospitalization following such event. From the HYPOTHESIS database, powered by 46 emergency departments covering a 12-million-odd population, data were extracted of 1,922 hypoglycemic events occurring in patients with diabetes in 2011. The mean age was 71.5 (standard deviation 16.8) years, 50.1% were men, and blood glucose at the time of the event was 44.2 (26.5) mg/dL. Patients were being treated with insulin alone (55%) or in combination with oral hypoglycemic agents (OHA, 15%), or with OHA alone, either in monotherapy (14%) or in multiple therapy (16%). Comorbidities were recorded in 71.8% of the patients. Based on the rates of glucose-lowering drug use in Italian patients with diabetes, the annual risk of undergoing a serious hypoglycemic event was estimated at 1.27% for subjects treated with insulin alone, the highest (p<0.00001) as compared with insulin + OHA (0.41%) or OHA alone, either in monotherapy or in multiple therapy (0.1% and 0.17%, respectively). The risk of being hospitalized following the hypoglycemic event was the least (27.6%) for subjects treated with insulin alone (p<0.0083). Subjects treated with insulin + OHA showed a lower risk (34.2%) as compared with that for subjects treated with OHA (p<0.02). Death occurs in 7% of hospitalized patients. Older age (p<0.0001) and comorbidities (p<0.0001) were risk factors for hypoglycemia-related hospitalization. Treatments with insulin alone (p<0.005) or in combination (p<0.049) were negatively associated with hospital admission. Severe hypoglycemic events associated with the use of oral glucose-lowering agents carry the highest risk of hospital treatment. As such, they are also likely to generate higher tangible and intangible costs.

Occurrence over time and regression of nonalcoholic fatty liver disease in type 2 diabetes.

BACKGROUND: This analysis was aimed to assess the incidence, regression, and correlated factors of nonalcoholic fatty liver disease (NAFLD) in type 2 diabetes, which are poorly known. METHODS: Nonalcoholic fatty liver disease (defined as fatty liver index [FLI] score ≥ 60) in patients with type 2 diabetes, and related factors was investigated in a nationwide database containing information from the Italian network of diabetes clinics. A 10% variation of FLI was the cut-off considered in the analyses of a cohort of 5030 patients, which was separately conducted for those who developed, maintained, or recovered from FLI-assessed NAFLD (FLI-NAFLD) over a 3-year period. RESULTS: At baseline, FLI-NAFLD was diagnosed in 61.3% of patients. Within the 3-year study period, FLI-NAFLD occurred in 313 patients and remitted in 410. The FLI score remained unchanged in 4307. Body-mass index (odds ratio, 1.45 95%; confidence interval, 1.35-1.55), abdominal obesity (2.11; 1.64-2.72), low HDL cholesterol levels (1.38; 1.02-1.87), and triglycerides (1.20; 1.12-1.28) all emerged as notable negative prognostic factors for the development or maintenance of FLI-NAFLD. The regression rate of FLI-NAFLD was higher among patients who managed to partially control these factors. Male sex and established organ damage, especially kidney function (1.64; 1.12-2.42), were independent risk predictors. Unlike other diabetes complications, FLI-NAFLD was more frequent among younger patients or those with a shorter duration of diabetes. CONCLUSIONS: FLI-assessed NAFLD is a dynamic condition, with about 5% of diabetic patients entering or leaving the status every year. Younger male patients with insulin resistance or organ damage have a higher risk of presenting with FLI-NAFLD at baseline, developing FLI-NAFLD within 3 years, and a lower probability of regression.

The Burden of NAFLD and Its Characteristics in a Nationwide Population with Type 2 Diabetes.

OBJECTIVE: We studied the prevalence of nonalcoholic fatty liver disease (NAFLD) and its clinical correlates in a population of patients with type 2 diabetes mellitus (T2DM). METHODS: Clinical data of 94,577 T2DM patients were retrieved from 160 diabetes clinics in Italy in a standardized format and centrally analyzed anonymously. After exclusion of 5967 cases (high or uncertain alcohol intake), in 38,880 the Fatty Liver Index (FLI) was used as a proxy for the diagnosis of NAFLD. Factors associated with FLI assessed NAFLD (FLI-NAFLD) were evaluated through multivariate analysis. RESULTS: FLI-NAFLD was present in 59.6% of patients. Compared to non-NAFLD, FLI-NAFLD was associated with impairment in renal function, higher albumin excretion, HbA1c and blood pressure, lower HDL cholesterol, and poorer quality of care. ALT was within normal limits in 73.6% of FLI-NAFLD patients (45.6% if the updated reference values were used). The prevalence of FLI-NAFLD did not differ if the whole sample (94,577 cases) was examined, irrespective of alcohol intake. CONCLUSIONS: FLI-NAFLD was present in the majority of T2DM patients of our sample and metabolic derangement, not alcohol consumption, was mainly associated with the disease. FLI-NAFLD patients have a worse metabolic profile. ALT levels are not predictive of NAFLD.

A standard ballroom and Latin dance program to improve fitness and adherence to physical activity in individuals with type 2 diabetes and in obesity.

OBJECTIVE: To test the effectiveness of a dance program to improve fitness and adherence to physical activity in subjects with type 2 diabetes and obesity. RESEARCH DESIGN AND METHODS: Following a motivational interviewing session, 100 subjects with diabetes and/or obesity were enrolled either in a dance program (DP, n = 42) or in a self-selected physical activity program (SSP, n = 58), according to their preferences. Outcome measures were reduced BMI/waist circumference, improved metabolic control in type 2 diabetes (-0.3% reduction of HbA1c) and improved fitness (activity expenditure >10 MET-hour/week; 10% increase in 6-min walk test (6MWT)). Target achievement was tested at 3 and 6 months, after adjustment for baseline data (propensity score). RESULTS: Attrition was lower in DP. Both programs significantly decreased body weight (on average, -2.6 kg; P < 0.001) and waist circumference (DP, -3.2 cm; SSP, -2.2; P < 0.01) at 3 months, and the results were maintained at 6 months. In DP, the activity-related energy expenditure averaged 13.5 ± 1.8 MET-hour/week in the first three months and 14.1 ± 3.0 in the second three-month period. In SSP, activity energy expenditure was higher but highly variable in the first three-month period (16.5 ± 13.9 MET-hour/week), and decreased in the following three months (14.2 ± 12.3; P vs. first period < 0.001). At three months, no differences in target achievement were observed between groups. After six months the odds to attain the MET, 6MWT and A1c targets were all significantly associated with DP. CONCLUSION: Dance may be an effective strategy to implement physical activity in motivated subjects with type 2 diabetes or obesity (Clinical trial reg. no.NCT02021890, clinicaltrials.gov).

The management of severe hypoglycemia by the emergency system: the HYPOTHESIS study.

BACKGROUND AND AIMS: Severe hypoglycemia is not rare in diabetes and markedly impacts on health resource use. We aimed to describe the characteristics of patients attending emergency departments (EDs) following a severe episode of hypoglycemia, the factors associated with the management of events and the final outcome. METHODS AND RESULTS: We carried out a retrospective analysis of cases attending 46 Italian EDs for hypoglycemia from January 2011 to June 2012. A total of 3753 records were retrieved from the databases of the participating centers, part of a network repeatedly involved in collaborative studies; 3516 episodes occurred in subjects with diabetes (median age, 76 years; range, 1-102). Comorbidities were recorded in 2320 (65.9%) diabetes cases; association with trauma or road accidents in 287 (8.2%) and 47 (1.3%), respectively. Patients were treated with insulin (49.8%), oral agents (31.4%), or combination treatment (15.1%). The event required assistance by the out-of-hospital Emergency services in 1821 cases (51.8%). Following the ED visit, admission to hospital departments was deemed necessary in 1161 cases (33.1%). Diabetes treatment (oral agents: OR, 1.63; 95% confidence interval (CI), 1.37-1.94), increasing age (OR, 1.39; 95% CI, 1.31-1.48) and the number of comorbidities (OR, 1.51; 95% CI, 1.38-1.66) were the main drivers of admission. The in-hospital death rate was 10%, associated with the number of comorbidities (OR, 1.28; 95%CI, 1.01-1.63). CONCLUSION: Severe hypoglycemia requiring referral to EDs is associated with a significant work-up of the Emergency services and a remarkable in-hospital death rate in frail individuals with diabetes.

A psychological support program for individuals with Type 1 diabetes.

We aimed to test the effects of a psychological support program on the psychological distress, mood, and quality of life of well-educated individuals with type 1 diabetes. A newly developed support program was offered to 60 patients with type 1 diabetes on intensive insulin treatment, previously enrolled in group-care educational programs. Thirty-three subjects participated (experimental group, in groups of 8-12 subjects); 22, who postponed their entry, were used as controls. The program consisted of 7 weekly work sessions of 2 hours chaired by a psychologist and covered aspects of daily living with diabetes using role-playing, metaplan, and problem solving. At baseline and approximately 6 months later, all participants completed a battery of questionnaires, and the differences between the experimental and the control group were analyzed by repeated-measurements ANOVA. In response to the psychological support program, subjects in the experimental group reduced their depressive mood (Beck Depression Inventory and depression scales of the Psychological Well-Being Index) and anxiety (Self-rating Anxiety Scale), improved disease-specific quality of life (Symptom and Well-Being scales of the Well-Being Enquiry for Diabetes), increased their internal and decreased their external locus of control. These changes were accompanied by a 0.3% decrease in glycosylated hemoglobin, whereas no significant changes were observed in the control group (ANOVA, P = 0.032). These results underline the importance of psychological aspects in individuals with type 1 diabetes; treating the psychological aspects related to the disease may be as important as medical control in order to improve living with diabetes.

Insulin resistance: mechanism and implications for carcinogenesis and hepatocellular carcinoma in NASH.

INTRODUCTION: The effects of insulin resistance in human diseases are of paramount importance. Since the original proposal by the WHO indicating insulin resistance as the common substrate of the metabolic syndrome, large data are now available on its significance in cardiovascular diseases, nonalcoholic fatty liver disease and cancer risk. MATERIALS AND METHODS: We reviewed the evidence linking hyperinsulinemia to insulin resistance and ultimately to increased cancer risk. Insulin resistance, by reducing substrate flux along the PI3-K pathway, is followed by compensatory hyperinsulinemia, considered a potential stimulus for cancerogenesis along the MAP-K pathway. Adaptive mechanisms of fat storage, promoted by insulin resistance, chronically maintained in an obesiogenic environment, may lead to oxidative stress and inflammation and modify the immune responses, further increasing the carcinogenic potential. The increased cancer risk associated with obesity, type 2 diabetes and nonalcoholic fatty liver may thus be fueled by hyperinsulinemia. Insulin secretagogs and insulin treatment, by raising circulating insulin levels, further increase cancer risk, whereas insulin sensitizers are associated with decreased cancer risk (all sites) and specifically decrease hepatocellular carcinoma. Likewise, drugs related to the incretin system, which are weight neutral or even reduce whole-body and hepatic fat, improve insulin sensitivity and potentially reduce the cancer risk. CONCLUSION: New diabetes treatments might thus help decrease the future burden of diabetes-associated cancer and particularly of hepatocellular carcinoma.

HBV and HCV infection in type 2 diabetes mellitus: a survey in three diabetes units in different Italian areas.

Viral infections and the metabolic syndrome may coexist in several individuals, due to the large prevalence of obesity and type 2 diabetes mellitus (T2DM). Antiviral therapy has changed the natural history of chronic viral hepatitis, but viral infection may remain undiagnosed in the absence of systematic screening. We determined the prevalence of HBV and/or HCV infection in an Italian cohort with T2DM (859 consecutive patients, 413 females) in three Italian centers: Turin, Bologna, and Naples. Screening for viral disease was coupled with the determination of parameters of metabolic syndrome. Fourteen patients were HBsAg-positive, 51 anti-HCV with a prevalence of genotype-1 infection in 58% of cases. Thirty cases had newly diagnosed viral markers, only one-third had already-diagnosed liver disease, 16 were being followed-up by a Liver Unit, and 9 cases had received antiviral treatment. Patients with viral markers had higher liver enzyme levels in comparison with virus-negative patients (P < 0.0001), whereas the prevalence of the metabolic syndrome was similar in the 2 groups. A positive correlation between BMI and alanine aminostransferase levels was only present in virus-negative cases, where the probability of enzyme levels above the upper limit of normal increased by 5% for unit of increase in BMI (OR: 1.05; 95% CI: 1.003-1.100, P = 0.037). In conclusion, the prevalence of HBV and HCV is non-negligible in patients with T2DM, but these cases may long remain undiagnosed. Elevated liver enzymes might be frequently disregarded in diabetes Units and ascribed to metabolic syndrome, thus excluding T2DM patients from specific disease-modifying antiviral treatment for hepatitis.

Double heterozygous mutations involving both HNF1A/MODY3 and HNF4A/MODY1 genes: a case report.

OBJECTIVE: We describe a maturity-onset diabetes of the young (MODY) case with mutations involving both HNF4A and HNF1A genes. RESEARCH DESIGN AND METHODS: A male patient was diagnosed with diabetes at age 17; the metabolic control rapidly worsened to insulin requirement. At that time no relatives were known to be affected by diabetes, which was diagnosed years later in both the parents (father at age 50 years, mother at age 54 years) and the sister (at age 32 years, during pregnancy). RESULTS: The genetic screening showed a double heterozygosity for the mutation p.E508K in the HNF1A/MODY3 gene and the novel variant p.R80Q in the HNF4A/MODY1 gene. The genetic testing of the family showed that the father carried the MODY3 mutation while the mother, the sister, and her two children carried the MODY1 mutation. CONCLUSIONS: MODY1 and MODY3 mutations may interact by chance to give a more severe form of diabetes (younger age at presentation and early need of insulin therapy to control hyperglycemia).

Obesity-associated liver disease.

CONTEXT: In the last few years, several data have accumulated suggesting that obesity may be associated with liver disease and disease progression. Accordingly, the worldwide epidemic of obesity is likely to become a relevant source of morbidity and mortality in the general population. EVIDENCE ACQUISITION: We reviewed the literature on two main issues: 1) the evidence that obesity carries out an increased risk of liver disease, both in the general population and in selected cohorts; and 2) the evidence that obesity is a risk factor for nonalcoholic fatty liver disease and its progression in a series observed in liver units. EVIDENCE SYNTHESIS: The presence of obesity increases the risk of elevated liver enzymes by a factor of two to three, whereas the risk of steatosis at ultrasonography is increased by a factor of 3 in the presence of overweight and peaks at a factor of approximately 15 in the presence of obesity. Both cirrhosis (cryptogenic cirrhosis) and hepatocellular carcinoma are also associated with obesity in the general population. In patients with nonalcoholic fatty liver disease observed in liver units, obesity and weight gain are systematically associated with advanced fibrosis and fibrosis progression. CONCLUSION: Liver disease of metabolic origin, associated with obesity, is now recognized as the most prevalent liver disease in Western countries. Strategies are needed to approach obesity-associated liver disease by behavior programs, motivating people to adopt a healthier lifestyle. Such programs should be coupled with public policies at a societal level to obtain the maximum effects in lifestyle changes.

Insulin glargine improves glycemic control and health-related quality of life in type 1 diabetes.

BACKGROUND AND AIMS: Glargine improves glucose control and reduces the risk of nocturnal hypoglycemia compared with neutral protamine Hagedorn (NPH) insulin. To date, only one study has measured the effects of glargine on health-related quality of life (HRQL); the aim of this study was therefore to confirm the beneficial effects of glargine on disease-specific HRQL in type 1 diabetes. METHODS AND RESULTS: Forty-seven patients (mean age, 46 range, 25-74; males, 54%) with diabetes of at least 1-year duration, and with suboptimal glucose control under intensive insulin treatment (IIT), were switched from NPH to glargine. Forty patients maintained on IIT were used as controls. Diabetes-related HRQL was assessed using the Well-being Enquiry for Diabetics (WED), before and after a 6- to 8-month switch to glargine. An 11-item questionnaire based upon diabetes-specific issues was used to assess treatment satisfaction and perceived changes after switching. On glargine, the mean glycosylated hemoglobin decreased by 0.7% (treatment vs. baseline, P<0.0001) and several WED scores improved (discomfort, P=0.020; impact, P=0.0002; total score, P=0.0005). WED changes were associated with a lower perceived risk of hypoglycemia and less problems in daily life on glargine. CONCLUSIONS: The results of this study show that the beneficial effect of glargine is not limited to better metabolic control; the burden of type 1 diabetes mellitus on everyday life is also reduced.

Disease management of the metabolic syndrome in a community: study design and process analysis on baseline data.

BACKGROUND: A comprehensive lifestyle approach is suggested as first-line treatment for the individual features of the metabolic syndrome, but the results in community medicine are usually discouraging. No study has tested the feasibility of an integrated approach between general practitioners (GPs) and specialist centers. METHODS: We report the process analysis on baseline data of a randomized study based on the integration between GPs, selecting patients on the basis of a pre-defined grid and specific targets, and a specialist center, providing informative material and arranging courses of counseling and cognitive-behavioral therapy, using a shared database. After initial visits by GPs for clinical assessment and motivation to treatment, patients were randomly assigned to: (a) prescriptive diet, managed by GPs; (b) counseling (four group lessons); (c) cognitive-behavioral treatment (12 group lessons), both managed by specialist center. Data of the first 503 subjects were compared with those of 139 cases self-referring to the specialist center for the treatment of obesity. RESULTS: Subjects enrolled by GPs were more frequently males, had lower obesity grades, and a higher number of features of metabolic syndrome, compared with the control group. Only 10% of subjects randomized to counseling and 27% randomized to behavior declined participation in the intensive treatments; attendance at sessions averaged 90%. GPs were satisfied with their participation and reported that treatments met patients' needs. CONCLUSIONS: An integrated approach to lifestyle changes between GPs and a specialist center is feasible in the metabolic syndrome and may be cost-effective, considering the high burden of disease.

Is liver disease a threat to patients with metabolic disorders?

The association of metabolic disorders with liver disease is receiving increasing attention in the gastroenterological community. Cohort studies have shown that advanced liver disease may stem from metabolic disorders, via fatty liver, non-alcoholic steatohepatitis, cryptogenic cirrhosis, and eventually hepatocellular carcinoma. In both obesity and diabetes, deaths from cirrhosis are higher than expected, mainly in subjects with no or moderate alcohol consumption, but high rates of fatty liver disease have been associated with all features of the metabolic syndrome. Also the risk of hepatocellular carcinoma is higher than normal, being dependent on body mass index (BMI) in obesity, and independent of age, BMI, gender and race in diabetes. Finally, metabolic liver disease may interact with hepatitis C virus infection, increasing the risk of steatosis and liver disease progression, as well as reducing the chances of an effective antiviral treatment. There is evidence that treatments aimed at reducing insulin resistance are also effective in improving liver histology. Although cardiovascular disease remains the major cause of increased morbidity and excess mortality in metabolic disorders, the risk of progressive liver disease should no longer be underestimated, being a threat to millions of people at risk in the present epidemics of obesity and diabetes, and therapeutic strategies need to be tested.

Non-alcoholic steatohepatitis in patients cared in metabolic units.

The clinical significance of liver disease is frequently underestimated in patients with metabolic disorders. In patients followed up in a metabolic unit for diabetes, obesity or hyperlipidemia (n=147), we studied the prevalence and the severity of liver disease, and its relationship with the metabolic syndrome (MS). Cases cared for in a liver unit (n=179) were used as controls. Patients in the metabolic series were older and had a higher prevalence of coronary heart disease. Criteria for the metabolic syndrome were fulfilled in 64% and 22% of cases, respectively (P<0.0001). Liver biopsy was obtained in 44 and 66% of cases. Metabolic patients had a more severe steatosis score (P<0.0001), whereas the scores of fibrosis and necroinflammation were less severe (P=0.0059 and 0.0007, respectively). Histological criteria for non-alcoholic steatohepatitis (NASH) were present in 82% of metabolic cases and 68% cases in the liver series (P=0.057). Liver disease in patients routinely cared for in metabolic units is similar to that observed in patients cared for in liver units, and potentially may progress to terminal liver failure. Liver biopsy is recommended for diagnostic and prognostic purposes, as well as for testing treatment effects in controlled trials.