ENPP1 Affects Insulin Action and Secretion: Evidences from In Vitro Studies

The aim of this study was to deeper investigate the mechanisms through which ENPP1, a negative modulator of insulin receptor (IR) activation, plays a role on insulin signaling, insulin secretion and eventually glucose metabolism. ENPP1 cDNA (carrying either K121 or Q121 variant) was transfected in HepG2 liver-, L6 skeletal muscle- and INS1E beta-cells. Insulin-induced IR-autophosphorylation (HepG2, L6, INS1E), Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 phosphorylation (HepG2, L6), PEPCK mRNA levels (HepG2) and 2-deoxy-D-glucose uptake (L6) was studied. GLUT 4 mRNA (L6), insulin secretion and caspase-3 activation (INS1E) were also investigated. Insulin-induced IR-autophosphorylation was decreased in HepG2-K, L6-K, INS1E-K (20%, 52% and 11% reduction vs. untransfected cells) and twice as much in HepG2-Q, L6-Q, INS1E-Q (44%, 92% and 30%). Similar data were obtained with Akt-Ser473, ERK1/2-Thr202/Tyr204 and GSK3-beta Ser9 in HepG2 and L6. Insulin-induced reduction of PEPCK mRNA was progressively lower in untransfected, HepG2-K and HepG2-Q cells (65%, 54%, 23%). Insulin-induced glucose uptake in untransfected L6 (60% increase over basal), was totally abolished in L6-K and L6-Q cells. GLUT 4 mRNA was slightly reduced in L6-K and twice as much in L6-Q (13% and 25% reduction vs. untransfected cells). Glucose-induced insulin secretion was 60% reduced in INS1E-K and almost abolished in INS1E-Q. Serum deficiency activated caspase-3 by two, three and four folds in untransfected INS1E, INS1E-K and INS1E-Q. Glyburide-induced insulin secretion was reduced by 50% in isolated human islets from homozygous QQ donors as compared to those from KK and KQ individuals. Our data clearly indicate that ENPP1, especially when the Q121 variant is operating, affects insulin signaling and glucose metabolism in skeletal muscle- and liver-cells and both function and survival of insulin secreting beta-cells, thus representing a strong pathogenic factor predisposing to insulin resistance, defective insulin secretion and glucose metabolism abnormalities

Prevalence of hepatic steatosis in patients with type 2 diabetes and response to glucose-lowering treatments. A multicenter retrospective study in Italian specialist care

Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI

Influence of the Mediterranean and Ketogenic Diets on cognitive status and decline:a narrative review

Abstract Alzheimer’s disease (AD) is the most common form of senile dementia, accounting for up to 70% of dementia cases. AD is a slowly progressive disease, which causes global mental deterioration by affecting various cognitive areas. A growing body of evidence has demonstrated that lifestyle habits and nutritional patterns could delay the natural course of the neurodegeneration process. There is no single dietary pattern unequivocally proven to prevent AD. Nevertheless, epidemiological data suggest that by adopting several dietary habits, especially if accompanied with a healthy lifestyle, the negative consequences of AD could potentially be delayed. Alongside with others, two specific eating patterns have been well investigated concerning their potential beneficial effect on cognitive status: the Mediterranean diet (MedDi) and the Ketogenic Diet (KD). Despite the different underlying mechanisms, both of them have demonstrated a fairly profitable role in reducing or delaying cognitive impairment. The aim of the present narrative review is to overview the existing research on the efficacy of MedDi and KD against AD-related cognitive decline, focusing on the proposed protective mechanisms of action. Although the current knowledge on this complex topic does not allow us, at this point, to make exhaustive conclusions, this information could be of help in order to better characterize the possible role of MedDi and KD as nonpharmacological therapies in the treatment of AD and, more generically, of neurodegenerative disorders

Association of personalised care plans with monitoring and control of clinical outcomes, prescription of medication and utilisation of primary care services in patients with type 2 diabetes:an observational real-world study

Abstract Objective: To study the association of personalised care plans with monitoring and controlling clinical outcomes, prescription of cardiovascular and antihyperglycaemic medication and utilisation of primary care services in patients with type 2 diabetes (T2D). Patients: Primary care T2D outpatients from the Rovaniemi Health Centre. Setting: The municipal health centre, Rovaniemi, Finland. Design: A cross-sectional, observational, retrospective register-based study. The patients were divided into three groups: ‘no care plan entries’ (usual care); ‘1–2 care plan entries’; and ‘3 or more care plan entries’. Main outcome measures: Monitoring of clinical and biochemical measures, achievement of treatment targets, prescription of cardiovascular and antihyperglycemic medication, and use of primary care services. Results: A total of 5104 patients with T2D (mean age 65.5 years (SD 12.4)), of which 67% had at least one care plan entry. Compared to usual care, the establishment of a care plan (either care plan group) was associated with better monitoring of glycosylated haemoglobin A1c, low-density-lipoprotein cholesterol, systolic blood pressure (sBP), and renal function, and there was more frequent prescription of all cardiovascular and antihyperglycemic medication. Patients in either care plan group were more likely to achieve sBP target (p < 0.05). Patients without a care plan had more unplanned primary care physician contacts compared to patients in care plan groups (p <0.001). Conclusion: Establishment of a care plan is associated with more intensive and focussed care of patients with T2D. The appropriate use of primary care resources is essential and personalised care plans may contribute to the treatment of patients with T2D

Implementation of a personalized care plan for patients with type 2 diabetes is associated with improvements in clinical outcomes:an observational real-world study

Abstract Objective: To analyze the clinical outcomes of patients with type 2 diabetes (T2D) before and after implementation of a personalized care plan in the primary health care setting. Design: Observational, retrospective, real-world study. Setting: All T2D patients with a care plan in Rovaniemi Health Center, Rovaniemi, Finland, for whom data were available from a baseline visit (in 2013–2015 during which the care plan was written) and from a follow-up visit, including an updated care plan by the year 2017. Subjects: In total, 447 patients were included. Mean age was 66.9 (SD 10.1) years, 58.8% were male, 15.4% were smokers, 33.1% had vascular disease, and 17.0% were receiving insulin treatment. The mean follow-up time was 14.4 months. Main Outcome Measures: Glycosylated hemoglobin A1 (HbA1c), low-density lipoprotein (LDL), blood pressure (BP), and body mass index (BMI). Clinical values were taken at both baseline and follow-up. Results: LDL decreased by 0.2 mmol/L, systolic blood pressure by 2.2 mm Hg, diastolic blood pressure by 1.5 mm Hg, and BMI by 0.5 kg/m² (P < 0.05 for each). The decrease in HbA1c was 0.8 mmol/mol (P = 0.07). Conclusion: We observed statistically significant decreases in LDL, BP, and BMI. Our results indicate that, over 14 months of follow-up, implementation of a written care plan was associated with small improvements in the clinical outcomes of T2D patients in a primary health care study population in a real-world setting

Prevalence and clinical characteristics of children and adolescents with metabolically healthy obesity:role of insulin sensitivity

Abstract Obesity represents a major risk factor for metabolic disorders, but some individuals, “metabolically healthy” (MHO), show less clinical evidence of these complications, in contrast to “metabolically unhealthy” (MUO) individuals. The aim of this cross-sectional study is to assess the prevalence of the MHO phenotype in a cohort of 246 overweight/obese Italian children and adolescents, and to evaluate their characteristics and the role of insulin resistance. Homeostasis model assessment–insulin resistance (HOMA-IR), insulin sensitivity index (ISI), insulinogenic index (IGI) and disposition index (DI) were all calculated from the Oral Glucose Tolerance Test (OGTT). MHO was defined by either: (1) HOMA-IR < 2.5 (MHO-IRes), or (2) absence of the criteria for metabolic syndrome (MHO-MetS). The MHO prevalence, according to MHO-MetS or MHO-IRes criteria, was 37.4% and 15.8%, respectively. ISI was the strongest predictor of the MHO phenotype, independently associated with both MHO-IRes and MHO-MetS. The MHO-MetS group was further subdivided into insulin sensitive or insulin resistant on the basis of HOMA-IR (either < or ≥ 2.5). Insulin sensitive MHO-MetS patients had a better metabolic profile compared to both insulin resistant MHO-MetS and MUO-MetS individuals. These data underscore the relevance of insulin sensitivity to identifying, among young individuals with overweight/obesity, the ones who have a more favorable metabolic phenotype

Highlights from "Italian Standards of care for Diabetes Mellitus 2009-2010"

The Italian Standards for the Treatment of Diabetes Mellitus represent a consensus document of the two Italian scientific diabetes societies (AMD and SID), providing specific recommendations for the diagnosis and treatment of diabetes and its complications. The level of scientific evidence behind every recommendation has been classified in accordance with the National Guidelines Plan. An original processing system was employed: the document prepared by the Editorial Team was published online for 20 days, and the suggestions and criticisms of about 30 persons were evaluated and integrated to those provided by a panel of diabetologists and members of other healthcare professions dedicated to diabetes care, as well as lay members. Lastly, the document was approved by AMD and SID National Steering Committees. In this version, some highlights of the full document (www.siditalia.it; www.aemmedi.it) concerning the main and most representative recommendations on diagnosis and treatment of diabetes and its complications as well as on diabetes care in some specific contexts, are reported

Phenotyping normal kidney function in elderly patients with type 2 diabetes: a cross-sectional multicentre study

AIMS: Type 2 diabetes (T2D) accelerates the decline in glomerular function; however, some individuals do not develop chronic kidney disease despite advanced age and long-lasting T2D. We aimed to phenotype patients with T2D aged 80 years or older who presented with a fully preserved kidney function. METHODS: From an Italian population of 281,217 T2D outpatients, we collected data on demographics, anthropometrics, diabetes duration, HbA1c, fasting plasma glucose, lipids, liver enzymes, estimated glomerular filtration rate (eGFR), albumin excretion rate (AER), chronic complications, and medication use. We primarily compared patients with a fully preserved kidney function (eGFR\u2009>\u200990 ml/min/1.73 m2 and AER\u2009<\u200930 mg/24 h, or G1A1) with those with mild kidney impairment (eGFR 60-90 ml/min/1.73 m2 and AER\u2009<\u200930 mg/24 h, or G2A1). RESULTS: N\u2009=\u2009113,860 had available data for eGFR and AER, 21,648 of whom were aged\u2009 65\u200980. G1A1 (n\u2009=\u2009278) and G2A1 (n\u2009=\u20096647) patients represented 1.3 and 30.7% of aged T2D patients, respectively, with an average diabetes duration of 16 years. Differences between the G1A1 and G2A1 groups were entered in a multiple logistic regression analysis with and without imputation of missing data. After adjustment and in both imputed and non-imputed datasets, younger age, lower BMI and lower triglycerides were associated with fully preserved versus mildly impaired kidney function. The comparison between G1A1 and G1A2/3 yielded different results. CONCLUSIONS: In a rare population of patients with a fully preserved kidney function despite old age and long-lasting diabetes, lower BMI and triglycerides suggest that protection from lipotoxicity may preserve kidney function over time