Peroxisome proliferator-activated receptors (PPARs): from metabolic control to epidermal wound healing.

Peroxisome proliferator-activated receptors control many cellular and metabolic processes. They are transcription factors belonging to the family of ligand-inducible nuclear receptors. Three isotypes called PPARalpha, PPARbeta/delta and PPARgamma have been identified in lower vertebrates and mammals. They display differential tissue distribution and each of the three isotypes fulfills specific functions. PPARalpha and PPARgamma control energy homoeostasis and inflammatory responses. Their activity can be modulated by drugs such as the hypolipidaemic fibrates and the insulin sensitising thiazolidinediones (pioglitazone and rosiglitazone). Thus, these receptors are involved in the control of chronic diseases such as diabetes, obesity, and atherosclerosis. Little is known about the main function of PPARbeta, but it has been implicated in embryo implantation, tumorigenesis in the colon, reverse cholesterol transport, and recently in skin wound healing. Here, we present recent developments in the PPAR field with particular emphasis on both the function of PPARs in lipid metabolism and energy homoeostasis (PPARalpha and PPARgamma), and their role in epidermal maturation and skin wound repair (PPARalpha and PPARbeta).

Potential of education-based insulin therapy for achievement of good metabolic control: a real-life experience.

Diabet. Med. 28, 539-542 (2011) ABSTRACT: Aims  Achievement of good metabolic control in Type 1 diabetes is a difficult task in routine diabetes care. Education-based flexible intensified insulin therapy has the potential to meet the therapeutic targets while limiting the risk for severe hypoglycaemia. We evaluated the metabolic control and the rate of severe hypoglycaemia in real-life clinical practice in a centre using flexible intensified insulin therapy as standard of care since 1990. Methods  Patients followed for Type 1 diabetes (n = 206) or those with other causes of absolute insulin deficiency (n = 17) in our outpatient clinic were analysed in a cross-sectional study. Mean age (± standard deviation) was 48.9 ± 15.7 years, with diabetes duration of 21.4 ± 14.4 years. Outcome measures were HbA(1c) and frequency of severe hypoglycaemia. Results  Median HbA(1c) was 7.1% (54 mmol/mol) [interquartile range 6.6-7.8 (51-62 mmol/mol)]; a good or acceptable metabolic control with HbA(1c) < 7.0% (53 mmol/mol) or 7.5% (58 mmol/mol) was reached in 43.5 and 64.6% of the patients, respectively. The frequency of severe hypoglycaemic episodes was 15 per 100 patient years: 72.3% of the patients did not experience any such episodes during the past 5 years. Conclusions  Good or acceptable metabolic control is achievable in the majority of patients with Type 1 diabetes or other causes of absolute insulin deficiency in routine diabetes care while limiting the risk for severe hypoglycaemia.

Training in flexible intensive insulin therapy improves quality of life, decreases the risk of hypoglycaemia and ameliorates poor metabolic control in patients with type 1 diabetes.

AIM: Intensified insulin therapy has evolved to be the standard treatment of type 1 diabetes. However, it has been reported to increase significantly the risk of hypoglycaemia. We studied the effect of structured group teaching courses in flexible insulin therapy (FIT) on psychological and metabolic parameters in patients with type 1 diabetes. METHODS: We prospectively followed 45 type 1 diabetic patients of our outpatient clinic participating in 5 consecutive FIT teaching courses at the University Hospital of Basel. These courses consist of 7 weekly ambulatory evening group sessions. Patients were studied before and 1, 6, and 18 months after the course. Main outcome measures were glycated haemoglobin (HbA1c), severe hypoglycaemic events, quality of life (DQoL), diabetes self-control (IPC-9) and diabetes knowledge (DWT). RESULTS: Quality of life, self-control and diabetes knowledge improved after the FIT courses (all p<0.001). The frequency of severe hypoglycaemic events decreased ten-fold from 0.33 episodes/6 months at baseline to 0.03 episodes/6 months after 18 months (p<0.05). Baseline HbA1c was 7.2+/-1.1% and decreased in the subgroup with HbA1c > or = 8% from 8.4% to 7.8% (p<0.05). CONCLUSIONS: In an unselected, but relatively well-controlled population of type 1 diabetes, a structured, but not very time consuming FIT teaching programme in the outpatient setting improves psychological well-being and metabolic parameters.

Metabolic control in cancer cells.

An important hallmark of cancer cells is a profound change in metabolism. Indeed, most tumor cells are characterized by higher rates of glycolysis, lactate production, and biosynthesis of lipids and other macromolecules. Our group, among others, has previously demonstrated a close relationship between metabolic responses and proliferative stimuli, showing that cell cycle regulators have a major role in the control of metabolism. Changes in this coordinated response might lead to abnormal metabolic changes during tumor development and cancer progression. In this paper we review the dual role of cell cycle regulators in the control of both proliferation and metabolism in normal and in cancer cells. We show participation of the E2F1-CDK4 axis in the modulation of oxidative metabolism, in the positive regulation of lipid synthesis, and the regulation glycolysis. These three metabolic pathways are, interestingly fundamental in providing synthetic processes, energy production and cell signaling events, which are crucial factors for cancer cell survival.

Fetal hemoglobin levels are related to metabolic control in diabetic subjects

We have investigated the relationship between fetal hemoglobin (HbF) levels and metabolic control in subjects with insulin-dependent (N = 79) and non-insulin-dependent diabetes mellitus (N = 242). HbF and hemoglobin A1c (HbA1c) levels were increased in subjects with type 1 and type 2 diabetes as compared to levels in nondiabetic individuals (P<0.0001), and were significantly higher in type 1 than in type 2 diabetes subjects. Lower levels of HbA1c and HbF were observed in type 2 diabetes subjects treated by diet, intermediate levels in those treated with oral hypoglycemic agents, and higher levels in those treated with insulin. HbF and HbA1c levels were correlated in type 1 diabetes (R2 = 0.57, P<0.0001) and type 2 diabetes (R2 = 0.58, P<0.0001) subjects. Following intense treatment, twelve diabetic patients showed significant improvement both in HbA1c and HbF values. We conclude that increased HbF levels reflect poor metabolic control in subjects with diabetes mellitus.

Effect of metabolic control on parathyroid hormone secretion in diabetic patients

The metabolic derangement caused by diabetes mellitus may potentially affect bone mineral metabolism. In the present study we evaluated the effect of diabetes metabolic control on parathyroid hormone (PTH) secretion during stimulation with EDTA infusion. The study was conducted on 24 individuals, 8 of them normal subjects (group N: glycated hemoglobin - HbA1C = 4.2 ± 0.2%; range = 3.5-5.0%), 8 patients with good and regular metabolic control (group G-R: HbA1C = 7.3 ± 0.4%; range = 6.0-8.5%), and 8 patients with poor metabolic control (group P: HbA1C = 12.5 ± 1.0%; range: 10.0-18.8%). Blood samples were collected at 10-min intervals throughout the study (a basal period of 30 min and a 2-h period of EDTA infusion, 30 mg/kg body weight) and used for the determination of ionized calcium, magnesium, glucose and intact PTH. Basal ionized calcium levels were slightly lower in group P (1.19 ± 0.01 mmol/l) than in group N (1.21 ± 0.01 mmol/l) and group G-R (1.22 ± 0.01 mmol/l). After EDTA infusion, the three groups presented a significant fall in calcium, but with no significant difference among them at any time. Basal magnesium levels and levels determined during EDTA infusion were significantly lower (P<0.01) in group P than in group N. The induction of hypocalcemia caused an elevation in PTH which was similar in groups N and G-R but significantly higher than in group P throughout the infusion period (+110 min, N = 11.9 ± 2.1 vs G-R = 13.7 ± 1.6 vs P = 7.5 ± 0.7 pmol/l; P<0.05 for P vs N and G-R). The present results show that PTH secretion is impaired in patients with poorly controlled diabetes.

Effect of metabolic control on interferon-gamma and interleukin-10 production by peripheral blood mononuclear cells from type 1 and type 2 diabetic patients

The objective of the present study was to evaluate the production of cytokines, interferon-g (INF-g) and interleukin-10 (IL-10), in cultures of peripheral blood mononuclear cells (PBMC) from type 1 and type 2 diabetic patients and to correlate it with inadequate and adequate metabolic control. We studied 11 type 1 and 13 type 2 diabetic patients and 21 healthy individuals divided into two groups (N = 11 and 10) paired by sex and age with type 1 and type 2 diabetic patients. The PBMC cultures were stimulated with concanavalin-A to measure INF-g and IL-10 supernatant concentration by ELISA. For patients with inadequate metabolic control, the cultures were performed on the first day of hospitalization and again after intensive treatment to achieve adequate control. INF-g levels in the supernatants of type 1 diabetic patient cultures were higher compared to type 2 diabetic patients with adequate metabolic control (P < 0.001). Additionally, INF-g and IL-10 tended to increase the liberation of PBMC from type 1 and 2 diabetic patients with adequate metabolic control (P = 0.009 and 0.09, respectively). The increased levels of INF-g and IL-10 released from PBMC of type 1 and 2 diabetic patients with adequate metabolic control suggest that diabetic control improves the capacity of activation and maintenance of the immune response, reducing the susceptibility to infections.

Effect of periodontal treatment on metabolic control, systemic inflammation and cytokines in patients with type 2 diabetes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Role of metabolic control on diabetic nephropathy

OBJETIVO: Os autores relatam a influência do controle metabólico do diabetes, experimentalmente induzido no rato, sobre a nefropatia diabética. Eles observaram o efeito da insulina, da acarbose, um inibidor da glicosidase, e de dois agentes combinados sobre o controle metabólico e o desenvolvimento da expansão mesangial de glomérulos renais, no diabetes induzido pela aloxana no rato. MÉTODOS: Usando 5 grupos de ratos Wistar assim definidos: Normal(N), diabéticos não-tratados (D), diabéticos tratados com acarbose (AD); diabéticos tratados com insulina (ID) e diabéticos tratados com insulina associada à acarbose (IAD) foram avaliados os seguintes parâmetros: peso corporal, ingestão alimentar, ingestão hídrica, diurese, níveis de glicose sanguínea e urinária e as lesões renais: alargamento mesangial e vacuolização de células tubulares, usando contagem semi-quantitativa 1, 3, 6, 9 e 12 meses após a indução do diabetes. RESULTADOS: Houve acentuado aumento da glicemia, dos níveis de glicose na urina, da diurese, da ingestão hídrica e alimentar, e progressiva perda de peso nos ratos diabéticos, enquanto que os ratos diabéticos tratados exibiram melhora significativa destes parâmetros, sendo os ratos tratados com insulina + acarbose os que apresentaram controle metabólico mais satisfatório. Houve um significativo alargamento mesangial nos ratos diabéticos quando comparado ao observado nos ratos normais, desde o 3º até o 12º mês após a indução do diabetes, sendo observada diferença significativa entre os animais tratados com acarbose + insulina e os ratos diabéticos não-tratados. Não houve diferença significativa entre os animais tratados somente com acarbose ou com insulina quando comparados com ratos diabéticos não-tratados. CONCLUSÃO: Os autores discutem os resultados abordando o papel do controle metabólico do diabetes na prevenção da nefropatia diabética.

Impact of diabetes mellitus and metabolic control on bone healing around osseointegrated implants: Removal torque and histomorphometric analysis in rats

Objectives: To evaluate bone healing around dental implants with established osseointegration in experimental diabetes mellitus (DM) and insulin therapy by histomorphometric and removal torque analysis in a rat model. Materials and methods: A total of 80 male Wistar rats received a titanium implant in the tibiae proximal methaphysis. After a healing period of 60 days, the rats were divided into four groups of 20 animals each: a 2-month control group, sacrificed at time (group A), a diabetic group (group D), an insulin group (group I), and a 4-month control group (group C), subdivided half for removal torque and half for histomorphometric analysis. In the D and I groups the DM was induced by a single injection of 40 mg/kg body weight streptozotocin (STZ). Two days after DM induction, group I received subcutaneous doses of insulin twice a day, during 2 months. Groups C and D received only saline. Two months after induction of DM, the animals of groups D, C and I were sacrificed. The plasmatic levels of glucose (GPL) were monitored throughout the experiment. Evaluation of the percentages of bone-to-implant contact and bone area within the limits of the implant threads was done by histomorphometric and mechanical torque analysis. Data were analyzed by anova at significant level of 5%. Results: The GPL were within normal range for groups A, C and I and higher for group D. The means and standard deviations (SD) for histomorphometric bone area showed significant difference between group D (69.34 ± 5.00%) and groups C (78.20 ± 4.88%) and I (79.63 ± 4.97%). Related to bone-to-implant contact there were no significant difference between the groups D (60.81 + 6.83%), C (63.37 + 5.88%) and I (66.97 + 4.13%). The means and SD for removal torque showed that group D (12.91 ± 2.51 Ncm) was statistically lower than group I (17.10 ± 3.06 Ncm) and C (16.95 ± 5.39 Ncm). Conclusions: Diabetes mellitus impaired the bone healing around dental implants with established osseointegration because the results presented a lower percentage of bone area in group D in relation to groups C and I resulting in a lowest torque values for implant removal. Moreover, insulin therapy prevents the occurrence of bone abnormalities found in diabetic animals and osseointegration was not compromised. © 2012 John Wiley & Sons A/S.

Microbiological changes after periodontal therapy in diabetic patients with inadequate metabolic control

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Relationship among social support, treatment adherence and metabolic control of diabetes mellitus patients

This cross-sectional and quantitative study aimed to analyze the relationship among social support, adherence to non-pharmacological (diet and physical exercise) and pharmacological treatments (insulin and/or oral anti-diabetic medication) and clinical and metabolic control of 162 type 2 diabetes mellitus patients. Data were collected through instruments validated for Brazil. Social support was directly correlated with treatment adherence. Adherence to non-pharmacological treatment was inversely correlated with body mass index, and medication adherence was inversely correlated with diastolic blood pressure. There were no associations between social support and clinical and metabolic control variables. Findings indicate that social support can be useful to achieve treatment adherence. Studies with other designs should be developed to broaden the analysis of relations between social support and other variables.

Assessment of metabolic control among patients in a capillary glucose self-monitoring program

OBJECTIVE: To assess the metabolic control of diabetes mellitus patients registered in a capillary glucose self-monitoring program at home. METHODS: In this longitudinal retrospective study, 97 subjects at four health institutions in a Brazilian city were followed during 37 months between 2005 and 2008. The health files were analyzed of patients selected to register the evolution of variables related to capillary glucose self-monitoring at home and metabolic control of diabetes mellitus. RESULTS: During the assessment, both mean and monthly percentages of capillary blood glucose measurements at home decreased from 34.1 (65.1%) to 33.6 (64.8%), respectively (p <0.001). Mean HbA1c levels dropped from 9.20% to 7.94% (p<0.001). HDL cholesterol decreased from 51 mg/dl to 47 mg/dl (p=0.001). CONCLUSION: Patients' metabolic control improved, characterized by a significant reduction in HbA1C.

Metabolic control of type 1 diabetic patients followed at the University Children's Hospital in Berne: Have we reached the goal?

In type 1 diabetes (T1DM), a good metabolic control is important to reduce and/or postpone complications. Guidelines regarding how to achieve this goal are published by the American Diabetes Association (ADA) and the International Society of Paediatric and Adolescence Diabetes (ISPAD). The aims of this study were to determine the current level of metabolic control in T1DM patients on different treatment regimens, followed at the diabetes outpatient unit of the University Children's Hospital Bern, Switzerland, and to compare it with both the reported data from ten years ago (1998) and with the current guidelines of the ADA and ISPAD.