Physician experts in diabetes are natural team leaders for managing diabetic patients with foot complications. A position statement from the Italian diabetic foot study group.

Diabetic foot syndrome (DFS) is a complex disease. The best outcomes are reported with the multi-disciplinary team (MDT) approach, where each member works collaboratively according to his/her expertise. However, which health provider should act as the team leader (TL) has not been determined. The TL should be familiar with the management of diabetes, related complications and comorbidities. He/she should be able to diagnose and manage foot infections, including prompt surgical treatment of local lesions, such as abscesses or phlegmons, in an emergent way in the first meeting with the patient. According to the Organization for Economic Co-operation and Development (OECD) reports, Italy is one of countries with a low amputation rate in diabetic patients. Many factors might have contributed to this result, including 1)the special attention directed to diabetes by the public health system, which has defined diabetes as a "protected disease", and accordingly, offers diabetic patients, at no charge, the best specialist care, including specific devices, and 2)the presence of a network of diabetic foot (DF) clinics managed by diabetologists with medical and surgical expertise. The health care providers all share a "patient centred model" of care, for which they use their internal medicine background and skills in podiatric surgery to manage acute or chronic needs in a timely manner. Therefore, according to Italian experiences, which are fully reported in this document, we believe that only a skilled diabetologist/endocrinologist should act as a TL. Courses and university master's degree programmes focused on DF should guarantee specific training for physicians to become a TL.

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.

Treatment of peripheral arterial disease in diabetes: a consensus of the Italian Societies of Diabetes (SID, AMD), Radiology (SIRM) and Vascular Endovascular Surgery (SICVE).

Diabetic foot (DF) is a chronic and highly disabling complication of diabetes. The prevalence of peripheral arterial disease (PAD) is high in diabetic patients and, associated or not with peripheral neuropathy (PN), can be found in 50% of cases of DF. It is worth pointing out that the number of major amputations in diabetic patients is still very high. Many PAD diabetic patients are not revascularised due to lack of technical expertise or, even worse, negative beliefs because of poor experience. This despite the progress obtained in the techniques of distal revascularisation that nowadays allow to reopen distal arteries of the leg and foot. Italy has one of the lowest prevalence rates of major amputations in Europe, and has a long tradition in the field of limb salvage by means of an aggressive approach in debridement, antibiotic therapy and distal revascularisation. Therefore, we believe it is appropriate to produce a consensus document concerning the treatment of PAD and limb salvage in diabetic patients, based on the Italian experience in this field, to share with the scientific community.

Outcome of pregnancy in type 1 diabetic patients treated with insulin lispro or regular insulin: an Italian experience.

Some studies have shown that fetal outcome observed in patients using insulin lispro is much the same as in pregnant women using regular insulin. This study aims to analyze the Italian data emerging from a multinational, multicenter, retrospective study on mothers with type 1 diabetes mellitus before pregnancy, comparing those treated with insulin lispro for at least 3 months before and 3 months after conception with those treated with regular insulin. The data collected on pregnant women with diabetes attending 15 Italian centers from 1998 to 2001 included: HbA1c at conception and during the first and third trimesters, frequency of severe hypoglycemic episodes, spontaneous abortions, mode and time of delivery, fetal malformations and mortality. Seventy-two diabetic pregnancies treated with lispro and 298 treated with regular insulin were analyzed, revealing a trend towards fewer hypoglycemic episodes in the former, who also had a significantly greater reduction in HbA1c during the first trimester. The rate of congenital malformations was similar in the offspring of the two groups of women treated with insulin lispro or regular insulin. These findings suggest that insulin lispro could be useful for the treatment of hyperglycemia in type 1 diabetic pregnant women.

Effects of troglitazone on insulin action and cardiovascular risk factors in patients with non-insulin-dependent diabetes.

OBJECTIVE: Insulin resistance is a potential target for pharmacologic intervention in non-insulin-dependent diabetes. Troglitazone is being evaluated as an insulin enhancer in insulin resistant states. RESEARCH DESIGN AND METHODS: We randomized 40 patients with non-insulin-dependent diabetes to diet plus placebo (n = 15) or diet plus troglitazone (n = 25; 200 mg/day) treatment for 8 weeks. Fasting endogenous glucose production (EGP, by the stable isotope technique) and whole-body insulin sensitivity (by the insulin suppression test) were measured at baseline and on days 3, 7, 14, 28, and 56 of treatment. RESULTS: By day 56, fasting plasma glucose had risen from 12.0 +/- 0.9 to 12.8 +/- 1.2 mmol/L in the placebo group and had fallen from 12.4 +/- 0.6 to 11.3 +/- 0.6 mmol/L in the troglitazone group (p = 0.03). This was the result of small improvements in whole-body insulin sensitivity (steady-state plasma glucose during the insulin suppression test: from 11.09 +/- 1.1 to 10.3 +/- 0.8 mmol/L versus 13.8 +/- 1.0 to 10.0 +/- 0.9 mmol/L, placebo versus troglitazone; p = 0.01) and EGP (from 103% +/- 3% versus 96% +/- 2% of baseline, placebo versus troglitazone; p = 0.09). The time course of insulin action showed an early (first week of treatment) decrease in EGP in the troglitazone group that was maintained throughout, whereas steady-state plasma glucose levels began to diverge toward the end of treatment. The effects of insulin on plasma free fatty acid and potassium concentrations were not different between placebo and troglitazone. The cardiovascular risk profile (heart rate; serum triglycerides; total, low-density lipoprotein, and high-density lipoprotein cholesterol; proinsulin; uric acid; plasminogen activator inhibitor-1 antigen and activity; 24-hour blood pressure monitoring and urinary albumin excretion) was unaltered by troglitazone treatment. CONCLUSIONS: Troglitazone as monotherapy for typical non-insulin-dependent diabetes had a modest anti-hyperglycemic effect and, at the dose used in this study, had no effect on cardiovascular risk factors.

Plasma and platelet taurine are reduced in subjects with insulin-dependent diabetes mellitus: effects of taurine supplementation.

Plasma and platelet taurine concentrations were assayed in 39 patients with insulin-dependent diabetes mellitus (IDDM) and in 34 control subjects matched for age, sex, and both total and protein-derived daily energy intake. Platelet aggregation induced by arachidonic acid in vitro at baseline and after oral taurine supplementation (1.5 g/d) for 90 d was also studied. Plasma and platelet taurine concentrations (mean +/- SEM) were lower in diabetic patients (65.6 +/- 3.1 mumol/L, or 0.66 +/- 0.07 mol/g protein) than in control subjects (93.3 +/- 6.3 mumol/L, or 0.99 +/- 0.16 mol/g protein, P < 0.01). After oral supplementation, both plasma and platelet taurine concentrations increased significantly in the diabetic patients, reaching the mean values of healthy control subjects. The effective dose (mean +/- SEM) of arachidonic acid required for platelets to aggregate was significantly lower in diabetic patients than in control subjects (0.44 +/- 0.07 mmol compared with 0.77 +/- 0.02 mmol, P < 0.001, whereas after taurine supplementation it equaled the mean value for healthy control subjects (0.72 +/- 0.04 mmol). In in vitro experiments, taurine reduced platelet aggregation in diabetic patients in a dose-dependent manner, whereas 10 mmol taurine/L did not modify aggregation in healthy subjects.

Urinary albumin excretion in normal subjects and in diabetic patients measured by a radioimmunoassay: methodological and clinical aspects.

We have developed a radioimmunoassay method (RIA) to measure urinary albumin excretion. We determined the albumin excretion rate (AER) (micrograms/min) of 122 healthy subjects and 145 diabetic patients (115 type I, 30 type II). The results indicate that the RIA is sensitive (0.39 +/- 0.08 mg/L), precise (CV 5-8%), and gives reliable results on previously frozen urine samples. The distribution of the AER values in healthy subjects and diabetic patients was not normal. It was normalized by log or square-root transformation of the data. Seventy-three percent of diabetic patients lay within the normal range (0.6-10.6 micrograms/min). Twenty percent could be considered "at risk" to develop overt diabetic nephropathy because their albuminuria exceeded a threshold level of 15 micrograms/min chosen previously as the cutoff value for microalbuminuria. We found no correlation between AER and glycated hemoglobin, and only a weak correlation between AER and diabetes duration in type I diabetic patients.

Relationship between metabolic glycaemic control and platelet content of glutathione and its related enzymes, in insulin-dependent diabetes mellitus.

The relationship between glycaemic metabolic control and intracellular concentration of reduced glutathione (GSH) and related enzymes GSH-peroxidase (GSH-Px), GSH-reductase (GSH-Red), GSH-transferase (GSH-Tr), glucose-6-P-dehydrogenase (G6PDH), and thioltransferase (TT) in patients with insulin-dependent diabetes mellitus (IDDM) is controversial. Choosing platelets as cell model (as commonly done in previous studies), the aim of this study was to relate the platelet content of GSH and related enzymes to glycaemic metabolic control, expressed as glycated haemoglobin (HbA1c), as well as to presence of retinopathy and nephropathy in 114 IDDM patients. As compared to controls, both GSH and GSH-Red (geometric means (95% CI)) were significantly increased in platelets of diabetic patients: 3.3 (0.7-9.6) vs. 2.4 (0.8-7.6) mmol 10(-9) platelets; P=0.01 for GSH, and 30.6 (14.7-61.6) vs. 22.2 (8.7-52.2) mU 10(-9) platelets, P=0.0002 for GSH-Red, and TT activity was marginally decreased in the IDDM group (P=0.06). While no clear relationship was present between GSH-related enzymes and HbA1c, a trend was present toward a non-linear relation between HbA1c and GSH, being significantly related by a parabolic curve (P=0.002). As compared to patients with normoalbuminuria (n=88), diabetic patients with increased urinary albumin excretion rate (n=26) had a significant decrease in platelet TT concentration (3.2 (0.9-6.7) vs. 5.1 (1.9-18.7) mU 10(-9) platelets; P=0.0002), whereas retinopathy was not associated to modifications in GSH or in the enzymatic pattern. In summary: (a) platelet GSH and GSH-Red are increased in IDDM, while other enzymes are unmodified; (b) GSH seems to be related to metabolic control according to non-linear parabolic curve; (c) presence of increased albuminuria is associated to a selective decrease in platelet TT content.

Platelet antioxidant enzymes in insulin-dependent diabetes mellitus.

BACKGROUND: The measurement of the peroxidase scavenging system represented by the activities of superoxide dismutase (SOD), catalase and glutathione peroxidase (GSH-Px) in blood cells of diabetic patients has, in the past, given equivocal results. Likewise, the role of these intracellular enzymatic scavengers against the oxidative stress of diabetes-associated microangiopathic complications is unknown. METHODS: Choosing platelets as cell model (as commonly done in previous studies), the aim of this study was to relate the platelet content of SOD, catalase and GSH-Px to the presence of diabetes, as well as to the presence of nephropathy and retinopathy in 35 insulin-dependent diabetic patients, as compared to 10 age-matched control subjects. RESULTS: The enzymatic activities were not changed in diabetic patients in comparison with healthy controls. After stratifying patients according to presence of nephropathy (24-h urinary albumin excretion rate persistently > or =20 microg min(-1)) or retinopathy, the group of albuminuric patients was characterized by a significant decrease in SOD activity as compared to those in the normoalbuminuric range (4.36+/-1.06 vs. 6.81+/-2.26 mU 10(-9) platelets; p=0.01). Catalase and GSH-Px did not change. No modification in platelet enzyme activities has been found in diabetic subjects with retinopathy. CONCLUSIONS: These results suggest that diabetic nephropathy, at least in its early stage, may be related to an altered redox state of platelets, as tested by the reduction in SOD activity, thus, indicating that the renal damage in these patients may be associated to a selective increase in platelet susceptibility to variation in the redox state.

Raised erythrocyte polyamine levels in non-insulin-dependent diabetes mellitus with great vessel disease and albuminuria.

Erythrocyte content of polyamines has been previously found increased in insulin-dependent diabetes mellitus with microalbuminuria. Since increased urinary albumin excretion (AER) is associated with the presence of vascular diseases in non-insulin-dependent diabetes mellitus (NIDDM) the aim of this study was to verify the hypothesis that the presence of increased urinary albumin excretion (AER), and of macroangiopathy in NIDDM would be related to a significant modification in polyamine erythrocyte levels. The erythrocyte content of spermine and spermidine was measured by a HPLC method in 39 patients affected with NIDDM and in 24 age- and sex-matched healthy control subjects, evaluating the relationship between erythrocyte polyamines of NIDDM patients with the presence of macroangiopathy as well as with retinopathy or increased AER (> or = 20 micrograms/ml). Both spermidine and spermine were not modified in the group of NIDDM patients while the presence of raised urinary AER was characterised by an increase in erythrocyte spermine (11 +/- 1.7 vs. 7.7 +/- 1.7 nmol/ml packed erythrocytes; P = 0.04) and spermidine (18.9 +/- 1.7 vs. 12.6 +/- 1.5 nmol/ml packed erythrocytes; P = 0.02), being both polyamines significantly related to AER and to metabolic control. Erythrocyte spermidine and spermine were moreover significantly higher in the group of patients with macroangiopathy (22.8 +/- 1.5 vs. 12.3 +/- 1.5 nmol/ml; P = 0.0001 and 11.5 +/- 1.7 vs. 7.8 +/- 1.7 nmol/l packed erythrocytes; P = 0.04) and being, moreover, erythrocyte spermidine augmented in patients with retinopathy (24.2 +/- 1.5 vs. 12.2 +/- 1.5 nmol/ml packed erythrocytes; P = 0.009). In conclusion the levels of erythrocyte spermine and spermidine are both associated with the presence of albuminuria and macroangiopathy in NIDDM, while spermidine is on the average increased in the group of diabetic patients with retinopathy.

Indications of reduced pulmonary function in type 1 (insulin-dependent) diabetes mellitus.

Abnormalities of pulmonary function tests have been described in type 1 (insulin-dependent) diabetes mellitus (IDDM). To better characterise such abnormalities and to verify whether these latter are associated with the presence of diabetic microvascular disease we compared 23 non-smoking patients who had IDDM with 24 non-smoking healthy control subjects strictly matched for sex, age, and body mass index. Compared with controls, diabetic patients had a reduced forced vital capacity (FVC) (87.5 +/- 13.1% vs. 96.4 +/- 13.6% of the predicted; P = 0.03) and forced expiratory volume in 1 s (FEV1) (90.5 +/- 17.7% vs. 101.2 +/- 13.2% of the predicted; P = 0.02). While within the group of patients the presence of retinopathy and autonomic neuropathy were not associated with modifications of pulmonary function tests, those with altered urinary albumin excretion rate (AER > or = 20 micrograms/min; range 21-589) (n = 7) had a significantly lower pulmonary diffusion capacity (DLCO) than the 16 normoalbuminuric subjects (62.6 +/- 7.2% vs. 88.7 +/- 20.1% of the predicted; P = 0.01). Moreover, in the group of patients, DLCO was inversely related with AER (r = -0.43; P = 0.04). In conclusion, IDDM is characterised by reduced FVC and FEV1, while a significant decrease in DLCO may be considered as selectively associated with renal disease.

Plasma retinol and alpha-tocopherol concentrations in insulin-dependent diabetes mellitus: their relationship to microvascular complications.

Plasma alpha-tocopherol and retinol, both assayed by an HPLC method, have been evaluated in a group of 60 patients affected by insulin-dependent (type 1) diabetes mellitus, stratified according to the presence of retinopathy and nephropathy diagnosed by an urinary albumin excretion rate ranging between 20 and 200 micrograms/min (microalbuminaria) or > 200 micrograms/min (macroalbuminuria), all of whom were compared with 26 healthy controls strictly matched for age and sex. Plasma lipids and age were positively correlated with plasma retinol and alpha-tocopherol in both diabetic and control subjects. Either plasma retinol or its ratio to cholesterol were significantly and independently reduced in the younger subset of diabetics, as compared to controls, independently from other confounding variables, while plasma alpha-tocopherol was unchanged in diabetic subjects and in healthy controls. Retinopathy was not associated with altered levels of both plasma alpha-tocopherol or retinol. The presence of increased urinary albumin excretion was associated with higher plasma levels of alpha-tocopherol and, only for macroalbuminuria, of retinol. However, after processing the data by a multivariate model, nephropathy was characterized by an increase only in plasma alpha-tocopherol. In conclusion, according to our findings, plasma retinol is significantly decreased in younger insulin-dependent diabetic patients while alpha-tocopherol is significantly altered in diabetic patients with nephropathy.

Renal excretion of ascorbic acid in insulin dependent diabetes mellitus.

Serum ascorbic acid (AA) is reduced in diabetic patients. Aim of this study was 1) to verify whether such a decrease might be due to an altered urinary excretion of AA, and 2) whether this latter was modified in presence of early diabetic nephropathy with microalbuminuria (albumin excretion rate [AER] > 20 micrograms/min) in a group of 21 patients affected by insulin-dependent (type 1) diabetes mellitus (IDDM) as compared with 13 healthy controls matched for sex, age, dietary AA intake, and creatinine clearance per 1.73 m2 (CCl). Mean serum AA (+/- SD) was lower in diabetics (40.3 +/- 14 microM/l) than in controls (85.1 +/- 23.5 microM/l; p = 0.0001) and there was no difference between serum AA of patients with or without microalbuminuria. Urinary excretion of AA to creatinine x 100 (UAA/Cr) was higher in micro- (n = 6; 4.6 +/- 1.7) as compared to normoalbuminurics (n = 15; 1.6 +/- 0.9) or controls (1.5 +/- 1.2; p = 0.0001). For values exceeding renal threshold of tubular AA reabsorption (39 microM) the regression line of serum AA to UAA/Cr was significantly (p = 0.001) steeper in diabetics than in controls, suggesting an impaired tubular reabsorption of filtered AA in IDDM. The ratio of AA clearance to CCl was moreover related to AER (r = 0.48; p = 0.03) and to blood glucose (r = 0.51; p = 0.01), being unrelated to uric acid clearance, glycosuria and to urinary excretion of both alanine aminopeptidase and N-acetyl-beta-glucosaminidase.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of chronic ACE inhibition on glucose tolerance and insulin sensitivity in hypertensive type 2 diabetic patients.

We studied 14 moderately overweight Type 2 diabetic patients with essential hypertension in stable metabolic control after a run-in period, and again after 3 months of antihypertensive treatment with the angiotensin-converting enzyme (ACE) inhibitor captopril. Glucose tolerance was tested with a 75g oral glucose load (OGTT) and insulin sensitivity was measured by the insulin suppression test (IST) while dietary and drug treatment of the hyperglycemia was maintained constant. In the whole group, mean blood pressure (MBP) fell progressively over 3 months from a baseline value of 123 +/- 3 mmHg (1 mmHg = 0.133 kpa) to a final value of 115 +/- 2 mmHg (P < 0.005). After treatment, fasting plasma glucose, insulin, free fatty acid (FFA), potassium, and glycosylated hemoglobin concentrations were unchanged from baseline. There were no significant differences in glucose tolerance and insulin sensitivity between pre- and post-treatment values. Neither endogenous (oral glucose) nor exogenous (IST) insulin caused any change in plasma potassium concentration. This resistance to the hypokalemic action of insulin was not affected by captopril.

Gender effect on the relation between diabetes and hospitalization for heart failure.

AIMS: Cardiovascular risk among diabetic patients is at least twice as much the one for non-diabetic individuals and even greater when diabetic women are considered. Heart failure (HF) is a common unfavorable outcome of cardiovascular disease in diabetes. However, since the comparison among sexes of heart failure prevalence in diabetic patients remains limited, this study is aimed at expanding the information about this point. METHODS: We have evaluated the association between diabetes and HF by reviewing the medical records of all subjects discharged from the Internal Medicine and Cardiology Units of all hospitals in the Tuscany region, Italy, during the period January 2002 through December 2008. In particular we sought concomitance of ICD-9-CM codes for diabetes and HF. RESULTS: Patients discharged by Internal Medicine were on average older, more represented by women, and had a lesser number of individuals coded as diabetic (p<0.05 for all). Relative risk for HF (95% CI) was significantly higher in patients with diabetes, irrespective of gender 1.39 (1.36-1.41) in males; 1.40 (1.37-1.42) in females. When the diabetes-HF association was analyzed according to decades of age, a "horse-shoe" pattern was apparent with an increased risk in 40-59 years old in female patients discharged by Internal Medicine. CONCLUSIONS: Although there is not a difference in the overall HF risk between hospitalized male and female diabetic patients, women have an excess risk at perimenopausal age.

Long term predictors of post-partum glucose metabolism in women with gestational diabetes mellitus.

AIMS: The question asked by this study was whether ß-cell function expressed by insulin secretion/sensitivity measured during pregnancy in women with gestational diabetes (GDM) predicts post-partum long-term derangement in glucose metabolism. METHODS: Seventy-four Caucasian women with previous GDM were retested through a 75 g-2-h-OGTT after 8 [6] years (median[interquartile range]) from index pregnancy, measuring at pregnancy and follow-up insulin sensitivity, insulin secretion (1-h-incremental-insulin-area/incremental-glucose-area: ΔAUC60 (I)/ΔAUC60 (G)) as well as the product of Stumvoll-first-phase - secretion x insulin sensitivity (insulin-secretion-sensitivity index (ISSI). RESULTS: At follow-up 47 women were normotelerant to glucose and 27 had altered glucose metabolism (AGM:10 with type 2 diabetes and 17 with IGT). Women progressed to AGM had at their index pregnancy higher mean 2-h-OGTT-glucose area (1.15±0.09 VS. 1.09±0.09 mol l 2-h (-1);p=0.014), and lower ΔAUC60 (I)/ΔAUC60 (median [interquantile range]) (54.4 [51.7] vs. 73.4 [60] pmol mmol (-1)) and ISSI (2 977 [766] vs. 3 708 [1 141]; p<0.05 for both), but similar insulin sensitivity index 2.9 [2.5] VS. 3.2 [2.2] ml min (-1) m (-2);p=NS). Two-h-OGTT-glucose area, or decrease in ΔAUC60 (I)/ΔAUC60 (G) and ISSI were significantly associated with glucose tolerance impairment and with raised adjusted risk for AGM while insulin sensitivity at pregnancy did no predict AGM development. CONCLUSIONS: In this group of women increased post-load plasma glucose and impaired ß-cell function assessed during GDM pregnancy predict long-term post-partum AGM, while insulin sensitivity measured at the same time does not.