Schizophrenia and type 2 diabetes mellitus.

Schizophrenia is associated with increased risk for type 2 diabetes mellitus, resulting in elevated cardiovascular risk and limited life expectancy, translated into a weighted average of 14.5 years of potential life lost and an overall weighted average life expectancy of 64.7 years. The exact prevalence of type 2 diabetes among people with schizophrenia varies across studies and ranges 2-5fold higher than in the general population, whereas the aetiology is complex and multifactorial. Besides common diabetogenic factors, applied similarly in the general population, such as obesity, hyperlipidemia, smoking, hypertension, poor diet and limited physical activity, the co-occurrence of schizophrenia and diabetes is also attributed to unique conditions. Specifically, excessive sedentary lifestyle, social determinants, adverse effects of antipsychotic drugs and limited access to medical care are considered aggravating factors for diabetes onset and low quality of diabetes management. Schizophrenia itself is further proposed as causal factor for diabetes, given the observed higher prevalence of diabetes in young patients, newly diagnosed with schizophrenia and unexposed to antipsychotics. Furthermore, studies support genetic predisposition to diabetes among people with schizophrenia, suggesting shared genetic risk and disclosing a number of overlapped risk loci. Therefore, special attention should be paid in preventing diabetes in people with schizophrenia, through intervention in all possible modifiable risk factors. Implementation of careful antipsychotic prescription, provision of adequate motivation for balanced diet and physical activity and facilitating access to primary health care, could serve in reducing diabetes prevalence. On the other hand, increasing calls are made for early diagnosis of diabetes, application of the appropriate anti-diabetic therapy and strict inspection of therapy adherence, to limit the excess mortality due to cardiovascular events in people with schizophrenia. Moreover, population health programs could help counseling and preventing diabetes risk, additionally to early screening and diagnosis set, aiming to reduce disparities in populations. Finally, mental health-care providers might greatly promote offered health services to patients with schizophrenia, through a holistic individualized approach, considering additionally the physical health of the patients and working closely, preventively and therapeutically, in collaboration with the physicians and diabetologists.

Relation of the Mediterranean diet with the incidence of gestational diabetes.

BACKGROUND/OBJECTIVES: Some studies document relationships of the incidence of gestational diabetes mellitus (GDM) with individual components of the diet, but studies exploring relationships with patterns of eating are lacking. This observational study aimed to explore a possible relationship between the incidence of GDM and the Mediterranean diet (MedDiet) pattern of eating. SUBJECTS/METHODS: In 10 Mediterranean countries, 1076 consecutive pregnant women underwent a 75-g OGTT at the 24th-32nd week of gestation, interpreted both by the ADA_2010 and the International Association of the Diabetes and Pregnancy Study Groups (IADPSG)_2012 criteria. The dietary habits were assessed by a previously validated questionnaire and a Mediterranean Diet Index (MDI) was computed, reflecting the degree of adherence to the MedDiet pattern of eating: a higher MDI denoting better adherence. RESULTS: After adjustment for age, BMI, diabetes in the family, weight gain and energy intake, subjects with GDM, by either criterion, had lower MDI (ADA_2010, 5.8 vs 6.3, P=0.028; IADPSG_2012, 5.9 vs 6.4, P<0.001). Moreover, the incidence of GDM was lower in subjects with better adherence to the MedDiet (higher tertile of MDI distribution), 8.0% vs 12.3%, OR=0.618, P=0.030 by ADA_2010 and 24.3% vs 32.8%, OR=0.655, P=0.004 by IADPSG_2012 criteria. In subjects without GDM, MDI was negatively correlated with both fasting plasma glucose and AUC glucose, P<0.001 for both. CONCLUSIONS: Adherence to a MedDiet pattern of eating is associated with lower incidence of GDM and better degree of glucose tolerance, even in women without GDM. The possibility to use MedDiet for the prevention of GDM deserves further testing with intervention studies.

Study comparing the effect of pioglitazone in combination with either metformin or sulphonylureas on lipid profile and glycaemic control in patients with type 2 diabetes (ECLA).

OBJECTIVE: To explore whether the improvement of lipid profile and glycaemic control observed in randomized control trials with pioglitazone (PIO) is replicated under conditions of general clinical practice. RESEARCH DESIGN AND METHODS: We studied 2388 patients with type 2 diabetes (T2DM) not adequately controlled by monotherapy on either metformin (MET) or sulphonylurea (SU). Addition of a second drug, according to the treating physician's choice, resulted in three groups, PIO + MET, PIO + SU and MET + SU, followed for twelve months, while efficacy and safety parameters were measured at baseline, at six and at twelve months. RESULTS: A total of 2116 (88.6%) patients completed the study. Diabetic control and lipid profile improved in all three groups, but the improvement was always greater in the two PIO groups. At 12 months PIO + SU and PIO + MET groups compared to SU + MET showed greater increase in HDL cholesterol (8.3% and 9.2 versus 4.3% p < 0.001) and greater decrease in HbA1c (1.53% and 1.46% versus 0.97%, p < 0.001 for both), in triglycerides (20.7% and 21.5% versus 15.2%, p < 0.001) and in LDL cholesterol (15.2% and 14.6% versus 11.3%, p < 0.001 and p < 0.01, respectively). All changes were greater in patients already taking hypolipidaemic drugs. As ECLA was an observational study, the major limitation is the introduction of confounding bias which, however, was accounted for in the statistical analysis. CONCLUSIONS: Since improvement of both glycaemic control and lipid profile are considered main targets in the management of the diabetic patient, the results of the present study, conducted under conditions of everyday clinical practice, show that pioglitazone may be considered a potential choice for the treatment of type 2 diabetes, when lifestyle and metformin fail.

Evidence that even "normal" albuminuria may denote incipient GFR reduction in patients with type 2 diabetes mellitus.

AIMS: In patients with diabetes and microalbuminuria, small changes of GFR could have been missed, due to the lack of sensitive methodology for GFR determination in clinical practice (creatinine based calculations). Therefore we explored the relation of the degree of albumin excretion with Cystatin C, which has been recently proved to be a better marker of GFR, compared to serum creatinine. METHODS: We studied 179 patients with type 2 diabetes, in whom renal function and microalbuminuria were evaluated. RESULTS: In patients with normal renal function, GFR/MDRD>or=60 ml/min/1.73 m(2), (n=79), urinary albumin concentration (UAC) was significantly correlated with Cystatin C, both in patients with normoalbuminuria (r=0.547, p<0.023) or microalbuminuria (r=0.305, p<0.035), while it was not correlated either with serum creatinine or calculated creatinine clearance. In patients with GFR/MDRD<60 ml/min/1.73 m(2), (n=100), UAC was significantly correlated with Cystatin C, also both in patients with normoalbuminuria (r=0.536, p<0.032) or microalbuminuria (r=0.340, p<0.016), while it was significantly correlated with serum creatinine and calculated creatinine clearance only in those with microalbuminuria. CONCLUSIONS: Subtle changes in renal function, as judged by Cystatin C concentration, may parallel the degree of albuminuria, even in the normoalbuminuric stage. This finding needs further confirmation by more appropriate methodology in prospective follow up studies.

Epidemiological evidence for the non-random clustering of the components of the metabolic syndrome: multicentre study of the Mediterranean Group for the Study of Diabetes.

OBJECTIVE: To determine: (a) whether the components of metabolic syndrome (MetS) cluster more frequently than predicted by chance alone and (b) whether increased risk for MetS is associated also with values of each component below, but close to the cutoff points defining MetS. RESEARCH DESIGN AND METHODS: Anthropometrical and biochemical measurements were performed and a dietary questionnaire was filled-in in 1833 randomly selected non-diabetic subjects, 916 men and 917 women, 20-74 years old, in nine centres in five Mediterranean countries. The prevalence of MetS and of possible combinations of its individual components was measured. The expected frequencies of the above combinations were calculated according to the mathematical formula of probabilities. RESULTS: The overall prevalence of MetS was 27.2%, but varied greatly among countries, from 5.8% in Algeria to 37.3% in Greece. The observed prevalence of each combination diagnostic of MetS was higher than the expected by chance. Thus, the observed overall prevalence of MetS was also higher than the expected, 27.2 vs 24.0%, P=0.03. Furthermore, for each individual component (except high-density lipoprotein), as values in the normal range, approached the cutoff point, the risk of having MetS (i.e. clustering of the other components) increased significantly (odds ratio 2.2-4.6, P<0.001). CONCLUSIONS: The MetS is not related to the Mediterranean type of diet and its prevalence varies greatly among five Mediterranean countries. The clustering of the components defining the MetS is not due to chance and moreover even 'high normal' levels of each component confer increased risk for the syndrome.

The ORLIstat and CArdiovascular risk profile in patients with metabolic syndrome and type 2 DIAbetes (ORLICARDIA) Study.

BACKGROUND: Metabolic syndrome (MetSyn) is associated with a marked increase in the risk of cardiovascular disease, especially in patients with type 2 diabetes mellitus (DM). AIM: To investigate the effect of orlistat plus hypocaloric diet (HCD) vs HCD alone on the cardiovascular risk profile in patients with both MetSyn (National Cholesterol Educational Program--NCEP--Adult Treatment Panel III definition) and type 2 DM. METHODS: This was a prospective, multicentre, open-label, randomized, controlled study. One hundred and twenty-six patients, free of cardiovascular disease at baseline, were included in the final analysis. Ninety-four (73%) patients were treated with orlistat (360 mg/day) and HCD for a 6-month period, while 34 (27%) were on HCD alone. Analysis of covariance was used to assess differences between the treatment groups over time. MAIN OUTCOME MEASURES: Components of the MetSyn criteria assessed were: waist circumference; systolic and diastolic blood pressure; fasting glucose, triglycerides; high-density lipoprotein cholesterol (HDL-C) plus body mass index; glycosylated haemoglobin (HbA1C); homeostasis model for assessment of insulin resistance (HOMA) index; and total and low-density lipoprotein cholesterol (LDL-C). RESULTS: By protocol, all patients had MetSyn at baseline. After a 6 month treatment period there were significant differences between the orlistat plus HCD vs the HCD-alone groups in body weight (p = 0.0001), waist circumference (p < 0.0001), fasting glucose (p < 0.0001), HbA(1C) (p < 0.0001), systolic blood pressure (p = 0.024), total cholesterol (p < 0.0001), LDL-C (p = 0.034), and HOMA index (p = 0.022), while there were no significant differences in triglycerides and HDL-C. Orlistat was well tolerated. By the end of the study, 65% of the patients on orlistat plus HCD were still meeting the MetSyn criteria and 41% had four to five MetSyn components vs 91% (p < 0.0001) and 53% (p = 0.017), respectively, of those on HCD alone. CONCLUSIONS: Orlistat plus HCD favourably modified several cardiovascular risk factors in patients with both MetSyn and type 2 DM. These effects might partly offset the excess cardiovascular risk and improve outcome in this patient population.

Nutritional habits of subjects with Type 2 diabetes mellitus in the Mediterranean Basin: comparison with the non-diabetic population and the dietary recommendations. Multi-Centre Study of the Mediterranean Group for the Study of Diabetes (MGSD).

AIMS/HYPOTHESIS: The aim of this study was to compare the nutritional habits of Type 2 diabetic patients among Mediterranean countries and also with those of their background population and with the nutritional recommendations of the Diabetes and Nutrition Study Group. METHODS: We did a cross-sectional study of 1833 non-diabetic subjects and 1895 patients with Type 2 diabetes, in nine centres in six Mediterranean countries. A dietary questionnaire validated against the 3-Day Diet Diary was used. RESULTS: In diabetic patients the contribution of proteins, carbohydrates and fat to the energy intake varied greatly among centres, ranging from 17.6% to 21.0% for protein, from 37.7% to 53.0% for carbohydrates and from 27.2% to 40.8% for fat, following in every centre the trends of the non-diabetic population. Furthermore, diabetic patients compared to the corresponding background population had: (i). lower energy intake, (ii). lower carbohydrate and higher protein contribution to the energy intake, (iii). higher prevalence of obesity, ranging from 9 to 50%. The adherence to the nutritional recommendations for proteins, carbohydrate and fat was very low ranging from 1.4 to 23.6%, and still decreased when fibre was also considered. CONCLUSION/INTERPRETATION: In diabetic patients of the Mediterranean area: (i). dietary habits vary greatly among countries, according to the same trends of the background population; (ii). the prevalence of obesity is much lower than the 80% reported for patients with diabetes in Western countries; (iii). Carbohydrate intake is decreased with a complementary increase of protein and fat consumption, resulting to a poor compliance with the nutritional recommendations.

Nutritional habits in the Mediterranean Basin. The macronutrient composition of diet and its relation with the traditional Mediterranean diet. Multi-centre study of the Mediterranean Group for the Study of Diabetes (MGSD).

OBJECTIVE: To compare the nutritional habits among six Mediterranean countries and also with the various official recommendations and the 'Mediterranean diet' as originally described. DESIGN: Cross-sectional study. SETTINGS: Three centres in Greece, two in Italy and one in Algeria, Bulgaria, Egypt and Yugoslavia. SUBJECTS: Randomly selected non-diabetic subjects from the general population, of age 35-60, not on diet for at least 3 months before the study. INTERVENTIONS: A dietary questionnaire validated against the 3-Day Diet Diary was used. Demographic data were collected and anthropometrical measurements done. RESULTS: All results were age adjusted. Energy intake varied in men, from 1825 kcal/day in Italy-Rome to 3322 kcal/day in Bulgaria and in women, from 1561 kcal/day in Italy-Rome to 2550 kcal/day in Algeria. Protein contribution (%) to the energy intake varied little, ranging from 13.4% in Greece to 18.5% in Italy-Rome, while fat ranged from 25.3% in Egypt to 40.2% in Bulgaria and carbohydrates from 41.5% in Bulgaria to 58.6% in Egypt. Fibre intake, g/1000 kcal, ranged from 6.8 in Bulgaria to 13.3 in Egypt and the ratio of plant to animal fat from 1.2 in Bulgaria to 2.8 in Greece. The proportion of subjects following the WHO and the Diabetes and Nutrition Study Group (DNSG) of the EASD recommendations for carbohydrates, fat and protein ranged from 4.2% in Bulgaria to 75.7% in Egypt. Comparison with the Mediterranean diet, as defined in the seven Country Study, showed significant differences especially for fruit, 123-377 vs 464 g/day of the Mediterranean diet, meat, 72-193 vs 35 g/day, cheese, 15-79 vs 13 g/day, bread, 126-367 vs 380 g/day. CONCLUSIONS: (a) Dietary habits of the 'normal' population vary greatly among the Mediterranean countries studied. (b) Egypt is closest to the DNSG recommendations. (c) Significant differences from the originally described Mediterranean diet are documented in most Mediterranean countries, showing a Westernization of the dietary habits.

Maximal post-prandial triglyceride increase reflects post-prandial hypertriglyceridaemia and is associated with the insulin resistance syndrome.

AIMS: To assess the value of maximal post-prandial triglyceride increase after a high fat, low carbohydrate (CHO) test meal, as index of post-prandial hypertriglyceridaemia and its relation with insulin resistance. METHODS: Fifty non-diabetic subjects, 22 male and 28 female, aged 52.1+/-4.5 and 56.9+/-3.8 years, were studied. Glucose, insulin and triglycerides were measured fasting and 1, 2, 3 and 4 h after a meal consisting of 40 g fat, 19 g protein and 10 g CHO. Insulin resistance was calculated according to the HOMA model. RESULTS: The maximal triglyceride increment occurred during the 4th hour. Its absolute value (delta-TG) and the per cent increase over the fasting value (PTI), were considered appropriate for the evaluation of the post-prandial triglyceride response. Both delta-TG and PTI were strongly correlated with triglycerides incremental area in males and females, r = 0.797 and r = 0.700, P<0.01 and r = 0.805 and r = 0.774, P<0.001, respectively, and thus they can be used as indices of the post-prandial triglyceride response. No correlation was found between fasting triglyceride and triglyceride incremental area or delta-TG. Thus, post-prandial hypertriglyceridaemia can occur irrespectively of the fasting triglyceride concentrations. A weak correlation was found between PTI and insulin resistance in females, r = 0.384, P<0.05, but not in males, r = 0.224, P>0.05. However further analysis by quartiles of PTI showed similar insulin resistance levels in the first three quartiles and a significant increase in the 4th, both for males and females, 4th vs. 3rd quartile 7.4+/-3.6 vs. 2.2+/-0.7 and 6.4+/-2.4 vs. 2.2+/-0.6, respectively. The 4th quartile corresponds to a PTI > or =80%. CONCLUSIONS: PTI after the high fat, low CHO test meal used, consistently reflects post-prandial hypertriglyceridaemia, is easily measured and it is not predicted by fasting triglycerides. A PTI > or = 80% is associated with a significant increase of insulin resistance, and might therefore be considered the cut-off point for an abnormal post-prandial hypertriglyceridaemic response, at least in relation with insulin resistance. Such response could be added to the abnormalities of the insulin resistance syndrome, as an independent parameter.