Fatty liver index as a predictor for type 2 diabetes in subjects with normoglycemia in a nationwide cohort study.

Our aim was to evaluate whether fatty liver index (FLI) is associated with the risk of type 2 diabetes (T2DM) development within the Spanish adult population and according to their prediabetes status; additionally, to examine its incremental predictive value regarding traditional risk factors. A total of 2260 subjects (Prediabetes: 641 subjects, normoglycemia: 1619 subjects) from the Di@bet.es cohort study were studied. Socio-demographic, anthropometric, clinical data and survey on habits were recorded. An oral glucose tolerance test was performed and fasting determinations of glucose, lipids and insulin were made. FLI was calculated and classified into three categories: Low (< 30), intermediate (30-60) and high (> 60). In total, 143 people developed diabetes at follow-up. The presence of a high FLI category was in all cases a significant independent risk factor for the development of diabetes. The inclusion of FLI categories in prediction models based on different conventional T2DM risk factors significantly increase the prediction power of the models when all the population was considered. According to our results, FLI might be considered an early indicator of T2DM development even under normoglycemic condition. The data also suggest that FLI could provide additional information for the prediction of T2DM in models based on conventional risk factors.

Incidence of diabetes mellitus in Spain as results of the nation-wide cohort di@bet.es study.

Our aim was to determine the incidence of type 2 diabetes mellitus in a nation-wide population based cohort from Spain (di@bet.es study). The target was the Spanish population. In total 5072 people older than 18 years,were randomly selected from all over Spain). Socio-demographic and clinical data, survey on habits (physical activity and food consumption) and weight, height, waist, hip and blood pressure were recorder. A fasting blood draw and an oral glucose tolerance test were performed. Determinations of serum glucose were made. In the follow-up the same variables were collected and HbA1c was determined. A total of 2408 subjects participated in the follow-up. In total, 154 people developed diabetes (6.4% cumulative incidence in 7.5 years of follow-up). The incidence of diabetes adjusted for the structure of age and sex of the Spanish population was 11.6 cases/1000 person-years (IC95% = 11.1-12.1). The incidence of known diabetes was 3.7 cases/1000 person-years (IC95% = 2.8-4.6). The main risk factors for developing diabetes were the presence of prediabetes in cross-sectional study, age, male sex, obesity, central obesity, increase in weight, and family history of diabetes. This work provides data about population-based incidence rates of diabetes and associated risk factors in a nation-wide cohort of Spanish population.

Predictors of failure to respond to fluid restriction in SIAD in clinical practice; time to re-evaluate clinical guidelines?

BACKGROUND: Fluid restriction is recommended as first line therapy for Syndrome of Inappropriate Antidiuresis (SIAD), despite of lack of good evidence base to support its use, and poor efficacy in clinical practice and in the literature. AIM: We set out to determine how many patients with well-defined SIAD had pre-treatment criteria which would predict failure to fluid restriction. DESIGN AND METHODS: This was a consecutive, prospective evaluation of 183 patients with a diagnosis of SIAD in two different hospitals. Full ascertainment of the diagnostic criteria for SIAD was obtained in all patients. RESULTS: About 47% of patients had a urine volume <1500 ml in 24 h, 41% had initial urine osmolality > 500 mOsm/kg, 26% a Furst-equation ratio > 1. About 59% had one criterion predicting failure to respond to fluid restriction, 37% two criteria, and 3% three criteria. CONCLUSIONS: Our data suggest that up to 60% of patients with SIAD had criteria which recent clinical guidelines suggest would predict nonresponse to fluid restriction. This may explain why the recommended first line therapy for SIAD has been shown to be ineffective.

Olive oil has a beneficial effect on impaired glucose regulation and other cardiometabolic risk factors. Di@bet.es study.

BACKGROUND: Despite the marked increase in cardiovascular risk factors in Spain in recent years, the prevalence and incidence of cardiovascular diseases have not risen as expected. Our objective is to examine the association between consumption of olive oil and the presence of cardiometabolic risk factors in the context of a large study representative of the Spanish population. SUBJECTS AND METHODS: A population-based, cross-sectional, cluster sampling study was conducted. The target population was the whole Spanish population. A total of 4572 individuals aged ≥ 18 years in 100 clusters (health centers) were randomly selected with a probability proportional to population size. The main outcome measures were clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, body mass index, waist, hip and blood pressure) and oral glucose tolerance test (OGTT) (75 g). RESULTS: Around 90% of the Spanish population use olive oil, at least for dressing, and slightly fewer for cooking or frying. The preference for olive oil is related to age, educational level, alcohol intake, body mass index and serum glucose, insulin and lipids. People who consume olive oil (vs sunflower oil) had a lower risk of obesity (odds ratio (OR)=0.62 (95% confidence interval (CI)=0.41-0.93, P=0.02)), impaired glucose regulation (OR=0.49 (95% CI=0.28-0.86, P=0.04)), hypertriglyceridemia (OR=0.53 (95% CI=0.33-0.84, P=0.03)) and low HDL cholesterol levels (OR=0.40 (95% CI=0.26-0.59, P=0.0001)). CONCLUSIONS: The results show that consumption of olive oil has a beneficial effect on different cardiovascular risk factors, particularly in the presence of obesity, impaired glucose tolerance or a sedentary lifestyle.

Mediterranean diet adherence in individuals with prediabetes and unknown diabetes: the Di@bet.es Study.

BACKGROUND AND AIMS: Mediterranean diet (MedDiet) is causally related to diabetes and is a dietary pattern recommended to individuals with diabetes. We investigated MedDiet adherence in individuals with prediabetes and unknown (PREDM/UKDM) or known diabetes (KDM) compared to those with normal glucose metabolism (NORMAL). METHODS: This was a national, population-based, cross-sectional, cluster-sampling study. MedDiet adherence was scored (MedScore, mean ± SD 24 ± 5) using a qualitative food frequency questionnaire. Logistic regression was used to examine the association between MedScore and PREDM/UKDM or KDM versus control subjects. RESULTS: We evaluated 5,076 individuals. Mean age was 50 years, 57% were female, 826 (582/244) were PREDM/UKDM, 478 were KDM and 3,772 were NORMAL. Mean age increased across MedScore tertiles (46, 51 and 56 years, p < 0.0001). Higher age-adjusted adherence to MedDiet (5-unit increment in the MedScore) was associated with lower and nondifferent odds (OR, 95% CI) of prevalent PREDM/UKDM (0.88, 0.81-0.96, p = 0.001) and KDM (0.97, 0.87-1.07, p = 0.279), respectively, compared to individuals in the NORMAL group. CONCLUSIONS: In a representative sample of the whole Spanish population, MedDiet adherence is independently associated with PREDM/UKDM. Therapeutic intervention may be, in part, responsible for the lack of differences in adherence observed between the KDM and NORMAL groups. However, reverse causation bias cannot be ruled out in cross-sectional studies.

Evaluation of Health-Related Quality of Life according to Carbohydrate Metabolism Status: A Spanish Population-Based Study (Di@bet.es Study).

Objective. To evaluate the association between diabetes mellitus and health-related quality of life (HRQOL) controlled for several sociodemographic and anthropometric variables, in a representative sample of the Spanish population. Methods. A population-based, cross-sectional, and cluster sampling study, with the entire Spanish population as the target population. Five thousand and forty-seven participants (2162/2885 men/women) answered the HRQOL short form 12-questionnaire (SF-12). The physical (PCS-12) and the mental component summary (MCS-12) scores were assessed. Subjects were divided into four groups according to carbohydrate metabolism status: normal, prediabetes, unknown diabetes (UNKDM), and known diabetes (KDM). Logistic regression analyses were conducted. Results. Mean PCS-12/MCS-12 values were 50.9 ± 8.5/ 47.6 ± 10.2, respectively. Men had higher scores than women in both PCS-12 (51.8 ± 7.2 versus 50.3 ± 9.2; P < 0.001) and MCS-12 (50.2 ± 8.5 versus 45.5 ± 10.8; P < 0.001). Increasing age and obesity were associated with a poorer PCS-12 score. In women lower PCS-12 and MCS-12 scores were associated with a higher level of glucose metabolism abnormality (prediabetes and diabetes), (P < 0.0001 for trend), but only the PCS-12 score was associated with altered glucose levels in men (P < 0.001 for trend). The Odds Ratio adjusted for age, body mass index (BMI) and educational level, for a PCS-12 score below the median was 1.62 (CI 95%: 1.2-2.19; P < 0.002) for men with KDM and 1.75 for women with KDM (CI 95%: 1.26-2.43; P < 0.001), respectively. Conclusion. Current study indicates that increasing levels of altered carbohydrate metabolism are accompanied by a trend towards decreasing quality of life, mainly in women, in a representative sample of Spanish population.

Prevalence of diabetes mellitus and impaired glucose regulation in Spain: the Di@bet.es Study.

AIMS/HYPOTHESIS: The Di@bet.es Study is the first national study in Spain to examine the prevalence of diabetes and impaired glucose regulation. METHODS: A population-based, cross-sectional, cluster sampling study was carried out, with target population being the entire Spanish population. Five thousand and seventy-two participants in 100 clusters (health centres or the equivalent in each region) were randomly selected with a probability proportional to population size. Participation rate was 55.8%. Study variables were a clinical and demographic structured survey, lifestyle survey, physical examination (weight, height, BMI, waist and hip circumference, blood pressure) and OGTT (75 g). RESULTS: Almost 30% of the study population had some carbohydrate disturbance. The overall prevalence of diabetes mellitus adjusted for age and sex was 13.8% (95% CI 12.8, 14.7%), of which about half had unknown diabetes: 6.0% (95% CI 5.4, 6.7%). The age- and sex-adjusted prevalence rates of isolated impaired fasting glucose (IFG), isolated impaired glucose tolerance (IGT) and combined IFG-IGT were 3.4% (95% CI 2.9, 4.0%), 9.2% (95% CI 8.2, 10.2%) and 2.2% (95% CI 1.7, 2.7%), respectively. The prevalence of diabetes and impaired glucose regulation increased significantly with age (p < 0.0001), and was higher in men than in women (p < 0.001). CONCLUSIONS/INTERPRETATION: The Di@bet.es Study shows, for the first time, the prevalence rates of diabetes and impaired glucose regulation in a representative sample of the Spanish population.

Efficacy and safety of vildagliptin monotherapy during 2-year treatment of drug-naïve patients with type 2 diabetes: comparison with metformin.

The present study was a 52-week extension of a previously published, multi-center, randomized, parallel-group study. The aim of this extension study was to compare the efficacy and tolerability of vildagliptin and metformin in drug-naïve patients with type 2 diabetes over 104 weeks. The extension population comprised 305 patients randomized to vildagliptin (100 mg daily) and 158 patients randomized to metformin (2 000 mg daily). Pioglitazone was added as rescue medication if fasting glucose was >10 mmol/l; data from patients receiving rescue medication were excluded from the primary analysis. Baseline HbA (1c) averaged 8.4+/-0.1% in patients randomized to vildagliptin and 8.8+/-0.1% in those randomized to metformin. The adjusted mean change from baseline to study endpoint was -1.0+/-0.1% in vildagliptin-treated patients and -1.5+/-0.1% in those receiving metformin (p<0.001 vs. vildagliptin). These results were similar to those reported after the 1-year core phase of the study. The adjusted mean changes in body weight from baseline to endpoint were 0.5+/-0.4 kg and -2.5+/-0.5 kg in the vildagliptin and metformin groups, respectively. One or more adverse event (AE) was reported by 82.2% of patients receiving vildagliptin and by 87.3% of those receiving metformin (p<0.001). Gastrointestinal AEs were more common in patients receiving metformin (45.6%) than in those receiving vildagliptin (25.0%, p<0.001 vs. metformin). One hypoglycemic event occurred after strenuous exercise in a single patient receiving vildagliptin (0.3%). In conclusion, both vildagliptin and metformin monotherapy provided clinically meaningful decreases in HbA (1c) over 2 years in drug-naïve patients with type 2 diabetes. Vildagliptin was weight neutral, while weight loss was observed with metformin; however, metformin was associated with significantly worse gastrointestinal tolerability.

Cardiovascular risk factor management is poorer in diabetic patients with undiagnosed peripheral arterial disease than in those with known coronary heart disease or cerebrovascular disease. Results of a nationwide study in tertiary diabetes centres.

AIMS: To assess whether patients with Type 2 diabetes mellitus and unrecognized peripheral arterial disease (PAD), detected by the ankle-brachial index (ABI), have poorer cardiovascular risk factor management (CVRFs) and receive fewer medications than patients previously diagnosed with coronary heart disease (CHD) or cerebrovascular disease (CVD). METHODS: In 31 diabetes centres throughout Spain, 1303 patients with Type 2 diabetes mellitus were screened for PAD using the ABI. Patient history of CHD and CVD and treatment and control of CVRFs were recorded. RESULTS: Forty-one patients had an ABI > 1.30 and were excluded, leaving 1262 patients (age 65.3 +/- 7.7 years) for the study. Of those screened, 790 patients had a normal ABI (ABI > 0.9) and no known history of CHD or CVD (no CHD/CVD/PAD group), 194 had unrecognized PAD (ABI < or = 0.9) with no known history of CHD or CVD (undiagnosed PAD group) and 278 had a known history of CHD and/or CVD (CHD/CVD group). The undiagnosed PAD group had higher low-density lipoprotein (LDL) cholesterol (2.9 +/- 0.83 vs. 2.4 +/- 0.84 mmol/l; P < 0.001) and systolic blood pressure (150 +/- 20 vs. 145 +/- 21 mmHg; P < 0.001) compared with the CHD/CVD group. They were less likely to take statins (56.9 vs. 71.6%; P < 0.001), anti-hypertensive agents (75.9 vs. 90.1%, P = 0.001), and anti-platelet agents (aspirin, 28.7 vs. 57.2%; P < 0.001; clopidogrel, 5.6 vs. 20.9%; P < 0.001) and more likely to smoke (21.0 vs. 9.2%; P < 0.001). Higher LDL in the undiagnosed PAD group was associated with the underutilization of statins. CONCLUSIONS: Measurement of ABI detected a significant number of patients with PAD, who did not have CHD or CVD, but whose CVRFs were under treated and poorly controlled compared with subjects with CHD and/or CVD.

Comparison of peripheral arterial reconstruction in diabetic and non-diabetic patients: a prospective clinic-based study.

UNLABELLED: To assess the efficacy and safety of lower extremity arterial reconstruction in diabetic and non-diabetic subjects during a 3-year period. A prospective clinic-based study between 1994-1999 in Area 7, Madrid, with a population of 569307 and an estimated diabetic population of 37932 (15505 men and 22427 women). The level of arterial reconstruction and associated risk factors were ascertained. RESULTS: A total of 588 peripheral revascularization surgical procedures were performed in 481 patients. The diabetic patients (n=174, 36.2%) underwent 222 surgical procedures (including 48 follow-on operations, 21.6%), and 307 non-diabetic subjects underwent 366 surgical procedures (59 follow-on operations, 16.1%). The numbers of surgical procedures per 100000 people at risk and year were 18.8 and 1.8 for non-diabetic men and women, respectively, and 145.1 and 29.0 for men and women with diabetes mellitus (7.7- and 16.2-fold, respectively). Age at reconstruction surgery was 2 and 5 years earlier in non-diabetic than in diabetic men and women, respectively. Diabetic patients had a higher neuropathy score (P<0.05) and were less frequently smokers (P<0.05) than non-diabetic subjects. Diabetic subjects more frequently had distal reconstruction while proximal arterial reconstruction was more often performed in non-diabetic subjects. Between 64.6 and 80.4% of people with diabetes and 82.3 and 88.9% of non-diabetic subjects had no complications during their in-hospital stay. Distal amputation simultaneous to arterial reconstruction was the most frequent morbidity of people with diabetes during the study (P<0.05). Despite a graft occlusion rate after femoropopliteal revascularization significantly higher than in non-diabetic people (P<0.05), diabetic people more often required lower extremity amputations (LEAs) for the same level of bypass (P<0.01). Cumulative limb salvage rates were lower in diabetic patients than in non-diabetic subjects at femoropopliteal (49.2 vs. 89.7%; P<0.001), femorodistal (73.5 vs. 95.2%; P<0.01), and distal reverse (77.9 vs. 87.3%; P<0.05) arterial reconstruction, at the end of the third year, but similar after aorto-iliac reconstruction (93.1 vs. 97.5%). A higher neuropathy score and the presence of foot ulcers were associated to significantly lower limb salvage in diabetic patients (P<0.05), but not in non-diabetic people. Survival rates after 3 years were similar between diabetic and non-diabetic populations after aorto-iliac (93.1 vs. 97.5%), femoropopliteal (97.2 vs. 90.3%), and distal reverse (93.2 vs. 98.1%) revascularization, and slightly lower in diabetic compared to non-diabetic patients after femorodistal revascularization (82.1 vs. 96.3%; P<0.05). CONCLUSION: Although limb salvage after arterial reconstruction is lower in diabetic than in non-diabetic subjects, particularly in those with a higher neuropathy score, this surgical approach can be applied in both diabetic and non-diabetic subjects with otherwise similar outcome.

Nontraumatic lower extremity amputations in diabetic and non-diabetic subjects in Madrid, Spain.

The purpose of this study was to determine the incidence of non-traumatic lower extremity amputations (LEAs) in diabetic and non-diabetic subjects in Madrid, Spain, and their direct cost. All patients who underwent LEAs between the 1st of January 1994 and the 31st of December 1996, and who had lived in area 7 of the city (569,307 inhabitants) for at least the last 6 months, were identified through operating theatre records cross-checked with Vascular Surgery Department discharge records. In addition, the direct cost of LEAs per year was estimated, taking into account the length of the hospital stay, the period of rehabilitation in the outpatient clinic after discharge, and the use of artificial limbs and their maintenance. The incidence of LEAs was 1.6 (95% CI: 1.1-2.2) per 10(5) non-diabetic subjects and 46.1 (95% CI: 34.5-57.6) per 10(5) diabetic patients. Relative risk was 28. Total direct costs associated with LEAs per year were US$ 56,131 in the diabetic population and US$ 30,765 in the non-diabetic population. Thus, potential cost savings associated with excess amputations in the diabetic population was estimated at US$ 541,353 per year of US$ 94,736 per 10(5) inhabitants. It is concluded that the incidence of LEAs in both diabetic and non-diabetic populations in area 7 is the lowest reported in European countries. The potential cost savings per 10(5) inhabitants and per year is estimated at US$ 94,736.

Changes in nutritional pattern, insulin sensitivity and glucose tolerance during weight loss in obese patients from a Mediterranean area.

In order to study the nutritional pattern in obese subjects living in an area with a Mediterranean diet, as well as the modifications in nutritional behaviour, cardiovascular risk factors and insulin sensitivity induced by changes in nutritional pattern, 54 obese patients completed a 20-week behaviour programme. They prospectively fulfilled a food records diary in order to ascertain their nutritional pattern. Weight, body mass index (BMI). waist-to-hip ratio (WHR), blood pressure (BP), cholesterol, HDL-c, LDL-c, triglycerides, fasting and 2 h-post glucose load plasma glucose were determined at the onset and at the end of the study. Insulin sensitivity index (SI), and glucose effectiveness (Sg) were assessed by using the modified FSIVGTT. The usual diet in obese patients living in a Mediterranean country is low in carbohydrates (35%) and high in fats (43%), 55% of the latter being monounsaturated fatty acids (MUFAs), especially olive oil. After the educational programme they decreased the caloric intake to slightly over 700 Kcal/day, with a reduction of 36% in carbohydrates consumption, 18% in proteins and 43% in fats (46% in MUFAs). These modifications resulted in a decrease in weight, BMI, WHR, BP, and fasting and 2 h-post glucose load plasma glucose (all p < 0.05), whereas the lipoprotein profile did not change. In a similar way SI and Kg (glucose disappearance rate) increased, while fasting plasma insulin (FPI) decreased (p < 0.05) and Sg and I1+3 remained unaffected. Our results indicate that weight loss induced by caloric restriction improves insulin sensitivity rather insulin secretory capacity or glucose effectiveness, and all the cardiovascular risk factors but lipoproteic profile, that remains unchanged, probably because of the lower MUFAs consumption. These facts should be taken into account when recommending changes in the diet of obese patients with a Mediterranean-style diet.

Comparison between acarbose, metformin, and insulin treatment in type 2 diabetic patients with secondary failure to sulfonylurea treatment.

The purpose of this study was to determine the most suitable treatment for Type 2 (non-insulin-dependent) diabetic patients with secondary failure to sulfonylureas (SFS). In a four-month comparative study, 36 Type 2 diabetic patients given SFS were allocated to three treatment groups: A (n = 12, M/F 6/6, HbAlc 9.1 +/- 1.6%) received 0.3 IU/Kg body weight (BW) of insulin-Zn between 10 and 11 p.m.; B (n = 12, M/F 6/6, HbAlc 9.2 +/- 1.6%) SFS plus 850 mg/day of metformin; and C (n = 12, M/F 6/6, HbAlc 9.5 +/- 2.4%) SFS plus acarbose 3 x 100 mg daily. Modifications in HbAlc, BW, blood pressure (BP), lipoprotein profile and insulin sensitivity were evaluated. HbAlc decreased in the three groups (A: 17.9 +/- 13.5%; B: 18.2 +/- 4.5%; C: 7.6 +/- 16.8%; all p < 0.05; A and B vs C = p < 0.05). BW increased in group A and decreased in the other groups. BP decreased statistically in group B. HDL-cholesterol increased (1.26 +/- 0.46 vs 1.49 +/- 0.36 mmol/L; p < 0.05) and triglyceride levels decreased (1.68 +/- 0.85 vs 1.16 +/- 0.43 mmol/L; p < 0.05) in group A. There were no significant changes in the other studied parameters. We conclude that, for Type 2 diabetic patients given SFS, both insulin and metformin plus SFS provided better glycaemic control than acarbose plus SFS. Metformin combined with SFS offered further advantages for the control of BW and BP.